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Reticulate acropigmentation of Kitamura Other namesRAK[1] SpecialtyDermatology Reticulate acropigmentation of Kitamura consists of linear palmar pits and pigmented macules 1 to 4 mm in diameter on the volar and dorsal aspects of the hands and feet, usually inherited in an autosomal-dominant fashion.[2]:856[3][4] ## Contents * 1 Genetics * 2 See also * 3 References * 4 External links ## Genetics[edit] This condition is associated with mutations in the a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) gene. This association was first shown in 2013. ## See also[edit] * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Reticulate acropigmentation of Kitamura". www.orpha.net. Retrieved 23 April 2019. 2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 4. ^ Vasudevan B, Verma R, Badwal S, Pragasam V, Moorchung N, Badad A (2014). "A case of reticulate acropigmentation of kitamura: dowling degos disease overlap with unusual clinical manifestations". Indian J Dermatol. 59 (3): 290–2. doi:10.4103/0019-5154.131408. PMC 4037953. PMID 24891663. ## External links[edit] Classification D * ICD-10: L81.8 * OMIM: 615537 * MeSH: C562924 External resources * Orphanet: 178307 This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Reticulate acropigmentation of Kitamura	c0406811	30,500	wikipedia	https://en.wikipedia.org/wiki/Reticulate_acropigmentation_of_Kitamura	2021-01-18T18:50:25	{"mesh": ["C562924"], "umls": ["C0406811"], "orphanet": ["178307"], "wikidata": ["Q7316721"]}
pregnancy-related tumours Gestational trophoblastic disease Micrograph of intermediate trophoblast, decidua and a hydatidiform mole (bottom of image). H&E stain. SpecialtyOncology Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumours. These tumours are rare, and they appear when cells in the womb start to proliferate uncontrollably. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to form the placenta during pregnancy. There are several different types of GTD. Hydatidiform moles are benign in most cases, but sometimes may develop into invasive moles, or, in rare cases, into choriocarcinoma, which is likely to spread quickly,[1][2] but which is very sensitive to chemotherapy, and has a very good prognosis. Gestational trophoblasts are of particular interest to cell biologists because, like cancer, these cells invade tissue (the uterus), but unlike cancer, they sometimes "know" when to stop.[citation needed] GTD can simulate pregnancy, because the uterus may contain fetal tissue, albeit abnormal. This tissue may grow at the same rate as a normal pregnancy, and produces chorionic gonadotropin, a hormone which is measured to monitor fetal well-being.[3] While GTD overwhelmingly affects women of child-bearing age, it may rarely occur in postmenopausal women.[4] ## Contents * 1 Types * 2 Cause * 3 Diagnosis * 3.1 Differential diagnosis * 4 Treatment * 4.1 Follow up * 5 Prognosis * 5.1 Becoming pregnant again * 5.2 Risk of a repeat GTD * 5.3 Persistent trophoblastic disease * 5.4 GTD coexisting with a normal fetus, also called "twin pregnancy" * 6 Epidemiology * 7 Terminology * 8 See also * 9 References * 10 External links ## Types[edit] GTD is the common name for five closely related tumours (one benign tumour, and four malignant tumours):[5] * The benign tumour * Hydatidiform mole Here, first a fertilised egg implants into the uterus, but some cells around the fetus (the chorionic villi) do not develop properly. The pregnancy is not viable, and the normal pregnancy process turns into a benign tumour. There are two subtypes of hydatidiform mole: complete hydatidiform mole, and partial hydatidiform mole. * The four malignant tumours * Invasive mole * Choriocarcinoma * Placental site trophoblastic tumour * Epithelioid trophoblastic tumour All five closely related tumours develop in the placenta. All five tumours arise from trophoblastic cells. The trophoblast is the membrane that forms the wall of the blastocyst in the early development of the fetus. In a normal pregnancy, trophoblastic cells aid the implantation of the fertilised egg into the uterine wall. But in GTD, they develop into tumour cells.[citation needed] ## Cause[edit] Two main risk factors increase the likelihood for the development of GTD: 1) The woman being under 20 years of age, or over 35 years of age, and 2) previous GTD.[6][7][8] Although molar pregnancies affect women of all ages, women under 16 and over 45 years of age have an increased risk of developing a molar pregnancy.[9]Being from Asia/of Asian ethnicity is an important risk factor.[10] Hydatidiform moles are abnormal conceptions with excessive placental development. Conception takes place, but placental tissue grows very fast, rather than supporting the growth of a fetus.[11][12][13] Complete hydatidiform moles have no fetal tissue and no maternal DNA, as a result of a maternal ovum with no functional DNA. Most commonly, a single spermatozoon duplicates and fertilises an empty ovum. Less commonly, two separate spermatozoa fertilise an empty ovum (dispermic fertilisation). Partial hydatidiform moles have a fetus or fetal cells. They are triploid in origin, containing one set of maternal haploid genes and two sets of paternal haploid genes. They almost always occur following dispermic fertilisation of a normal ovum.Malignant forms of GTD are very rare. About 50% of malignant forms of GTD develop from a hydatidiform mole.[citation needed] ## Diagnosis[edit] Cases of GTD can be diagnosed through routine tests given during pregnancy, such as blood tests and ultrasound, or through tests done after miscarriage or abortion.[14] Vaginal bleeding, enlarged uterus, pelvic pain or discomfort, and vomiting too much (hyperemesis) are the most common symptoms of GTD. But GTD also leads to elevated serum hCG (human chorionic gonadotropin hormone). Since pregnancy is by far the most common cause of elevated serum hCG, clinicians generally first suspect a pregnancy with a complication. However, in GTD, the beta subunit of hCG (beta hCG) is also always elevated. Therefore, if GTD is clinically suspected, serum beta hCG is also measured.[citation needed] The initial clinical diagnosis of GTD should be confirmed histologically, which can be done after the evacuation of pregnancy (see «Treatment» below) in women with hydatidiform mole.[15] However, malignant GTD is highly vascular. If malignant GTD is suspected clinically, biopsy is contraindicated, because biopsy may cause life-threatening haemorrhage. Women with persistent abnormal vaginal bleeding after any pregnancy, and women developing acute respiratory or neurological symptoms after any pregnancy, should also undergo hCG testing, because these may be signs of a hitherto undiagnosed GTD. There might be some signs and symptoms of hyperthyroidism as well as an increase in the levels of thyroid hormones in some patients. The proposed mechanism is attaching hCG to TSH receptors and acting like TSH weakly.[16]https://www.thyroid.org/patient-thyroid-information/ct-for-patients/vol-4-issue-9/vol-4-issue-9-p-5/</ref> ### Differential diagnosis[edit] * These are not GTD, and they are not tumours[17] * Exaggerated placental site * Placental site nodule Both are composed of intermediate trophoblast, but their morphological features and clinical presentation can differ significantly. Exaggerated placental site is a benign, non cancerous lesion with an increased number of implantation site intermediate trophoblastic cells that infiltrate the endometrium and the underlying myometrium. An exaggerated placental site may occur with normal pregnancy, or after an abortion. No specific treatment or follow up is necessary. Placental site nodules are lesions of chorionic type intermediate trophoblast, usually small. 40 to 50% of placental site nodules are found in the cervix. They almost always are incidental findings after a surgical procedure. No specific treatment or follow up is necessary. ## Treatment[edit] Treatment is always necessary.[citation needed] The treatment for hydatidiform mole consists of the evacuation of pregnancy.[18][19][20][21][22] Evacuation will lead to the relief of symptoms, and also prevent later complications. Suction curettage is the preferred method of evacuation. Hysterectomy is an alternative if no further pregnancies are wished for by the female patient. Hydatidiform mole also has successfully been treated with systemic (intravenous) methotrexate.[23] The treatment for invasive mole or choriocarcinoma generally is the same. Both are usually treated with chemotherapy. Methotrexate and dactinomycin are among the chemotherapy drugs used in GTD.[24][25][26][27] In women with low risk gestational trophoblastic neoplasia, a review has found that Actinomycin D is probably more effective as a treatment and more likely to achieve a cure in the first instance than methotrexate.[28] Only a few women with GTD suffer from poor prognosis metastatic gestational trophoblastic disease. Their treatment usually includes chemotherapy. Radiotherapy can also be given to places where the cancer has spread, e.g. the brain.[29] Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment. These women also are likely to have an earlier menopause. It has been estimated by the Royal College of Obstetricians and Gynaecologists that the age at menopause for women who receive single agent chemotherapy is advanced by 1 year, and by 3 years for women who receive multi agent chemotherapy. ### Follow up[edit] Follow up is necessary in all women with gestational trophoblastic disease, because of the possibility of persistent disease, or because of the risk of developing malignant uterine invasion or malignant metastatic disease even after treatment in some women with certain risk factors.[30][31] The use of a reliable contraception method is very important during the entire follow up period, as patients are strongly advised against pregnancy at that time. If a reliable contraception method is not used during the follow-up, it could be initially unclear to clinicians as to whether a rising hCG level is caused by the patient becoming pregnant again, or by the continued presence of GTD. In women who have a malignant form of GTD, hCG concentrations stay the same (plateau) or they rise. Persistent elevation of serum hCG levels after a non molar pregnancy (i.e., normal pregnancy [term pregnancy], or preterm pregnancy, or ectopic pregnancy [pregnancy taking place in the wrong place, usually in the fallopian tube], or abortion) always indicate persistent GTD (very frequently due to choriocarcinoma or placental site trophoblastic tumour), but this is not common, because treatment mostly is successful. In rare cases, a previous GTD may be reactivated after a subsequent pregnancy, even after several years. Therefore, the hCG tests should be performed also after any subsequent pregnancy in all women who had had a previous GTD (6 and 10 weeks after the end of any subsequent pregnancy). ## Prognosis[edit] Women with a hydatidiform mole have an excellent prognosis. Women with a malignant form of GTD usually have a very good prognosis.[citation needed] Choriocarcinoma, for example, is an uncommon, yet almost always curable cancer. Although choriocarcinoma is a highly malignant tumour and a life-threatening disease, it is very sensitive to chemotherapy. Virtually all women with non-metastatic disease are cured and retain their fertility; the prognosis is also very good for those with metastatic (spreading) cancer, in the early stages, but fertility may be lost. Hysterectomy (surgical removal of the uterus) can also be offered[32] to patients > 40 years of age or those for whom sterilisation is not an obstacle. Only a few women with GTD have a poor prognosis, e.g. some forms of stage IV GTN. The FIGO staging system is used.[33] The risk can be estimated by scoring systems such as the Modified WHO Prognostic Scoring System, wherein scores between 1 and 4 from various parameters are summed together:[34]</ref> Modified WHO Prognostic Scoring System[34] 0 1 2 4 Age <40 ≥40 – – Antecedent pregnancy mole abortion term – Interval months from index pregnancy <4 4–6 7–12 >12 Pretreatment serum hCG (IU/L) <103 103–104 104–105 >105 Largest tumor size (including uterus) <3 3–4 cm ≥5 cm – Site of metastases lung spleen, kidney gastrointestinal liver, brain Number of metastases – 1–4 5–8 >8 Previous failed chemotherapy – – single drug ≥2 drugs In this scoring system, women with a score of 7 or greater are considered at high risk. It is very important for malignant forms of GTD to be discovered in time. In Western countries, women with molar pregnancies are followed carefully; for instance, in the UK, all women who have had a molar pregnancy are registered at the National Trophoblastic Screening Centre.[35] There are efforts in this direction in the developing countries too, and there have been improvements in these countries in the early detection of choriocarcinoma, thereby significantly reducing the mortality rate also in developing countries.[36][37][38] ### Becoming pregnant again[edit] Most women with GTD can become pregnant again and can have children again. The risk of a further molar pregnancy is low. More than 98% of women who become pregnant following a molar pregnancy will not have a further hydatidiform mole or be at increased risk of complications. In the past, it was seen as important not to get pregnant straight away after a GTD. Specialists recommended a waiting period of 6 months after the hCG levels become normal. Recently, this standpoint has been questioned. New medical data suggest that a significantly shorter waiting period after the hCG levels become normal is reasonable for approximately 97% of the patients with hydatidiform mole.[39] ### Risk of a repeat GTD[edit] The risk of a repeat GTD is approximately 1 in 100, compared with approximately 1 in 1000 risk in the general population. Especially women whose hCG levels remain significantly elevated are at risk of developing a repeat GTD.[40] ### Persistent trophoblastic disease[edit] The term «persistent trophoblastic disease» (PTD) is used when after treatment of a molar pregnancy, some molar tissue is left behind and again starts growing into a tumour. Although PTD can spread within the body like a malignant cancer, the overall cure rate is nearly 100%.[citation needed] In the vast majority of patients, treatment of PTD consist of chemotherapy. Only about 10% of patients with PTD can be treated successfully with a second curettage.[41][42] ### GTD coexisting with a normal fetus, also called "twin pregnancy"[edit] In some very rare cases, a GTD can coexist with a normal fetus. This is called a "twin pregnancy". These cases should be managed only by experienced clinics, after extensive consultation with the patient. Because successful term delivery might be possible, the pregnancy should be allowed to proceed if the mother wishes, following appropriate counselling. The probability of achieving a healthy baby is approximately 40%, but there is a risk of complications, e.g. pulmonary embolism and pre-eclampsia. Compared with women who simply had a GTD in the past, there is no increased risk of developing persistent GTD after such a twin pregnancy.[43][44][45][46][47][48] In few cases, a GTD had coexisted with a normal pregnancy, but this was discovered only incidentally after a normal birth.[49] ## Epidemiology[edit] Overall, GTD is a rare disease. Nevertheless, the incidence of GTD varies greatly between different parts of the world. The reported incidence of hydatidiform mole ranges from 23 to 1299 cases per 100,000 pregnancies. The incidence of the malignant forms of GTD is much lower, only about 10% of the incidence of hydatidiform mole.[50] The reported incidence of GTD from Europe and North America is significantly lower than the reported incidence of GTD from Asia and South America.[51][52][53][54] One proposed reason for this great geographical variation is differences in healthy diet in the different parts of the world (e.g., carotene deficiency).[55] However, the incidence of rare diseases (such as GTD) is difficult to measure, because epidemiologic data on rare diseases is limited. Not all cases will be reported, and some cases will not be recognised. In addition, in GTD, this is especially difficult, because one would need to know all gestational events in the total population. Yet, it seems very likely that the estimated number of births that occur at home or outside of a hospital has been inflated in some reports.[56] ## Terminology[edit] Gestational trophoblastic disease (GTD) may also be called gestational trophoblastic tumour (GTT).Hydatidiform mole (one type of GTD) may also be called molar pregnancy.[citation needed] Persistent disease; persistent GTD: If there is any evidence of persistence of GTD, usually defined as persistent elevation of beta hCG (see «Diagnosis» below), the condition may also be referred to as gestational trophoblastic neoplasia (GTN).[57] ## See also[edit] * Trophoblastic neoplasms ## References[edit] 1. ^ Seckl MJ, Sebire NJ, Berkowitz RS (August 2010). "Gestational trophoblastic disease". Lancet. 376 (9742): 717–29. doi:10.1016/S0140-6736(10)60280-2. PMID 20673583. S2CID 32138190. 2. ^ Lurain JR (December 2010). "Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole". American Journal of Obstetrics and Gynecology. 203 (6): 531–9. doi:10.1016/j.ajog.2010.06.073. PMID 20728069. 3. ^ Gestational trophoblastic disease: Epidemiology, clinical manifestations and diagnosis. Chiang JW, Berek JS. In: UpToDate [Textbook of Medicine]. Basow, DS (Ed). Massachusetts Medical Society, Waltham, Massachusetts, USA, and Wolters Kluwer Publishers, Amsterdam, The Netherlands. 2010. 4. ^ Chittenden B, Ahamed E, Maheshwari A (August 2009). "Choriocarcinoma in a postmenopausal woman". Obstetrics and Gynecology. 114 (2 Pt 2): 462–5. doi:10.1097/AOG.0b013e3181aa97e7. PMID 19622962. S2CID 35996436. 5. ^ Gestational trophoblastic disease: Pathology. Kindelberger DW, Baergen RN. In: UpToDate [Textbook of Medicine]. Basow, DS (Ed). Massachusetts Medical Society, Waltham, Massachusetts, USA, and Wolters Kluwer Publishers, Amsterdam, The Netherlands. 2010. 6. ^ Kohorn EI (2007). "Dynamic staging and risk factor scoring for gestational trophoblastic disease". International Journal of Gynecological Cancer. 17 (5): 1124–30. doi:10.1111/j.1525-1438.2007.00898.x. PMID 17386047. S2CID 31319545. 7. ^ Kohorn EI (June 2002). "Negotiating a staging and risk factor scoring system for gestational trophoblastic neoplasia. A progress report". The Journal of Reproductive Medicine. 47 (6): 445–50. PMID 12092012. 8. ^ Kohorn EI (2001). "The new FIGO 2000 staging and risk factor scoring system for gestational trophoblastic disease: description and critical assessment". International Journal of Gynecological Cancer. 11 (1): 73–7. doi:10.1046/j.1525-1438.2001.011001073.x. PMID 11285037. 9. ^ "Gestational Trophoblastic Disease". 10. ^ Gestational Trophoblastic Disease 11. ^ Lipata F, Parkash V, Talmor M, Bell S, Chen S, Maric V, Hui P (April 2010). "Precise DNA genotyping diagnosis of hydatidiform mole". Obstetrics and Gynecology. 115 (4): 784–94. doi:10.1097/AOG.0b013e3181d489ec. PMID 20308840. S2CID 41305866. 12. ^ Alifrangis C, Seckl MJ (December 2010). "Genetics of gestational trophoblastic neoplasia: an update for the clinician". Future Oncology. 6 (12): 1915–23. doi:10.2217/fon.10.153. PMID 21142864. 13. ^ Azuma C, Saji F, Tokugawa Y, Kimura T, Nobunaga T, Takemura M, Kameda T, Tanizawa O (January 1991). "Application of gene amplification by polymerase chain reaction to genetic analysis of molar mitochondrial DNA: the detection of anuclear empty ovum as the cause of complete mole". Gynecologic Oncology. 40 (1): 29–33. doi:10.1016/0090-8258(91)90080-O. PMID 1671219. 14. ^ "Gestational Trophoblastic Tumors Treatment - National Cancer Institute". 1980-01-01. Retrieved 2010-03-21. 15. ^ Sebire NJ (2010). "Histopathological diagnosis of hydatidiform mole: contemporary features and clinical implications". Fetal and Pediatric Pathology. 29 (1): 1–16. doi:10.3109/15513810903266138. PMID 20055560. S2CID 21384533. 16. ^ Walkington L, Webster J, Hancock BW, Everard J, Coleman RE (May 2011). "Hyperthyroidism and human chorionic gonadotrophin production in gestational trophoblastic disease". British Journal of Cancer. 104 (11): 1665–9. doi:10.1038/bjc.2011.139. PMC 3111156. PMID 21522146. 17. ^ Shih IM, Seidman JD, Kurman RJ (June 1999). "Placental site nodule and characterization of distinctive types of intermediate trophoblast". Human Pathology. 30 (6): 687–94. doi:10.1016/S0046-8177(99)90095-3. PMID 10374778. 18. ^ Gerulath AH, Ehlen TG, Bessette P, Jolicoeur L, Savoie R (May 2002). "Gestational trophoblastic disease". Journal of Obstetrics and Gynaecology Canada. 24 (5): 434–46. doi:10.1016/S1701-2163(16)30408-X. PMID 12196865. 19. ^ Lurain JR (January 2011). "Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia". American Journal of Obstetrics and Gynecology. 204 (1): 11–8. doi:10.1016/j.ajog.2010.06.072. PMID 20739008. 20. ^ Sebire NJ, Seckl MJ (August 2008). "Gestational trophoblastic disease: current management of hydatidiform mole". BMJ. 337: a1193. doi:10.1136/bmj.a1193. PMID 18708429. S2CID 30372260. 21. ^ Berkowitz RS, Goldstein DP (April 2009). "Clinical practice. Molar pregnancy". The New England Journal of Medicine. 360 (16): 1639–45. doi:10.1056/NEJMcp0900696. PMID 19369669. 22. ^ Gestational trophoblastic disease: Management of hydatidiform mole. Garner EIO. In: UpToDate [Textbook of Medicine]. Basow, DS (Ed). Massachusetts Medical Society, Waltham, Massachusetts, USA, and Wolters Kluwer Publishers, Amsterdam, The Netherlands. 2010. 23. ^ De Vos M, Leunen M, Fontaine C, De Sutter P (2009). "Successful Primary Treatment of a Hydatidiform Mole with Methotrexate and EMA/CO". Case Reports in Medicine. 2009: 1–3. doi:10.1155/2009/454161. PMC 2729468. PMID 19707478. 24. ^ Chalouhi GE, Golfier F, Soignon P, Massardier J, Guastalla JP, Trillet-Lenoir V, Schott AM, Raudrant D (June 2009). "Methotrexate for 2000 FIGO low-risk gestational trophoblastic neoplasia patients: efficacy and toxicity". American Journal of Obstetrics and Gynecology. 200 (6): 643.e1–6. doi:10.1016/j.ajog.2009.03.011. PMID 19393597. 25. ^ Abrão RA, de Andrade JM, Tiezzi DG, Marana HR, Candido dos Reis FJ, Clagnan WS (January 2008). "Treatment for low-risk gestational trophoblastic disease: comparison of single-agent methotrexate, dactinomycin and combination regimens". Gynecologic Oncology. 108 (1): 149–53. doi:10.1016/j.ygyno.2007.09.006. PMID 17931696. 26. ^ Malignant gestational trophoblastic disease: Staging and treatment. Garner EIO. In: UpToDate [Textbook of Medicine]. Basow, DS (Ed). Massachusetts Medical Society, Waltham, Massachusetts, USA, and Wolters Kluwer Publishers, Amsterdam, The Netherlands. 2010. 27. ^ Kang WD, Choi HS, Kim SM (June 2010). "Weekly methotrexate (50mg/m(2)) without dose escalation as a primary regimen for low-risk gestational trophoblastic neoplasia". Gynecologic Oncology. 117 (3): 477–80. doi:10.1016/j.ygyno.2010.02.029. PMID 20347479. 28. ^ Lawrie TA, Alazzam M, Tidy J, Hancock BW, Osborne R (June 2016). "First-line chemotherapy in low-risk gestational trophoblastic neoplasia". The Cochrane Database of Systematic Reviews (6): CD007102. doi:10.1002/14651858.cd007102.pub4. PMC 6768658. PMID 27281496. 29. ^ Lurain JR, Singh DK, Schink JC (2010). "Management of metastatic high-risk gestational trophoblastic neoplasia: FIGO stages II-IV: risk factor score > or = 7". The Journal of Reproductive Medicine. 55 (5–6): 199–207. PMID 20626175. 30. ^ Kohorn EI (July 2009). "Long-term outcome of placental-site trophoblastic tumours". Lancet. 374 (9683): 6–7. doi:10.1016/S0140-6736(09)60791-1. PMID 19552947. S2CID 7147283. 31. ^ Hoekstra AV, Lurain JR, Rademaker AW, Schink JC (August 2008). "Gestational trophoblastic neoplasia: treatment outcomes". Obstetrics and Gynecology. 112 (2 Pt 1): 251–8. doi:10.1097/AOG.0b013e31817f58ae. PMID 18669719. S2CID 1746731. 32. ^ Lurain JR, Singh DK, Schink JC (October 2006). "Role of surgery in the management of high-risk gestational trophoblastic neoplasia". The Journal of Reproductive Medicine. 51 (10): 773–6. PMID 17086805. 33. ^ FIGO Committee on Gynecologic Oncology (April 2009). "Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia". International Journal of Gynaecology and Obstetrics. 105 (1): 3–4. doi:10.1016/j.ijgo.2008.12.015. PMID 19322933. S2CID 41395844. 34. ^ a b "Stage Information for Gestational Trophoblastic Tumors and Neoplasia". The National Cancer Institute (NCI). U.S. National Institutes of Health (NIH). 1980-01-01. in turn citing: FIGO Committee on Gynecologic Oncology (April 2009). "Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia". International Journal of Gynaecology and Obstetrics. 105 (1): 3–4. doi:10.1016/j.ijgo.2008.12.015. PMID 19322933. S2CID 41395844. 35. ^ "Molar Pregnancy". 2017-10-19. 36. ^ Izhar R (2003). "Prognosis of gestational choriocarcinoma at Khyber Teaching Hospital Peshawar". Journal of Ayub Medical College, Abbottabad. 15 (2): 45–8. PMID 14552249. 37. ^ Yang JJ, Xiang Y, Wan XR, Yang XY (August 2008). "Prognosis of malignant gestational trophoblastic neoplasia: 20 years of experience". The Journal of Reproductive Medicine. 53 (8): 600–7. PMID 18773625. 38. ^ Lok CA, Ansink AC, Grootfaam D, van der Velden J, Verheijen RH, ten Kate-Booij MJ (November 2006). "Treatment and prognosis of post term choriocarcinoma in The Netherlands". Gynecologic Oncology. 103 (2): 698–702. doi:10.1016/j.ygyno.2006.05.011. PMID 16790263. 39. ^ Wolfberg AJ, Feltmate C, Goldstein DP, Berkowitz RS, Lieberman E (September 2004). "Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy". Obstetrics and Gynecology. 104 (3): 551–4. doi:10.1097/01.AOG.0000136099.21216.45. PMID 15339768. S2CID 1172620. 40. ^ Garrett LA, Garner EI, Feltmate CM, Goldstein DP, Berkowitz RS (July 2008). "Subsequent pregnancy outcomes in patients with molar pregnancy and persistent gestational trophoblastic neoplasia". The Journal of Reproductive Medicine. 53 (7): 481–6. PMID 18720922. 41. ^ van Trommel NE, Massuger LF, Verheijen RH, Sweep FC, Thomas CM (October 2005). "The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey". Gynecologic Oncology. 99 (1): 6–13. doi:10.1016/j.ygyno.2005.06.032. PMID 16085294. 42. ^ Gillespie AM, Kumar S, Hancock BW (April 2000). "Treatment of persistent trophoblastic disease later than 6 months after diagnosis of molar pregnancy". British Journal of Cancer. 82 (8): 1393–5. doi:10.1054/bjoc.1999.1124. PMC 2363366. PMID 10780516. 43. ^ Lee SW, Kim MY, Chung JH, Yang JH, Lee YH, Chun YK (February 2010). "Clinical findings of multiple pregnancy with a complete hydatidiform mole and coexisting fetus". Journal of Ultrasound in Medicine. 29 (2): 271–80. doi:10.7863/jum.2010.29.2.271. PMID 20103799. S2CID 24528503. 44. ^ Suri S, Davies M, Jauniaux E (2009). "Twin pregnancy presenting as a praevia complete hydatidiform mole and coexisting fetus complicated by a placental abscess". Fetal Diagnosis and Therapy. 26 (4): 181–4. doi:10.1159/000253272. PMID 19864876. S2CID 7720159. 45. ^ Dolapcioglu K, Gungoren A, Hakverdi S, Hakverdi AU, Egilmez E (March 2009). "Twin pregnancy with a complete hydatidiform mole and co-existent live fetus: two case reports and review of the literature". Archives of Gynecology and Obstetrics. 279 (3): 431–6. doi:10.1007/s00404-008-0737-x. PMID 18679699. S2CID 20825878. 46. ^ Vandenhove M, Amant F, van Schoubroeck D, Cannie M, Dymarkowski S, Hanssens M (May 2008). "Complete hydatidiform mole with co-existing healthy fetus: a case report". The Journal of Maternal-Fetal & Neonatal Medicine. 21 (5): 341–4. doi:10.1080/14767050801925156. PMID 18446663. S2CID 6552298. 47. ^ True DK, Thomsett M, Liley H, Chitturi S, Cincotta R, Morton A, Cotterill A (September 2007). "Twin pregnancy with a coexisting hydatiform mole and liveborn infant: complicated by maternal hyperthyroidism and neonatal hypothyroidism". Journal of Paediatrics and Child Health. 43 (9): 646–8. doi:10.1111/j.1440-1754.2007.01145.x. PMID 17688651. S2CID 45319678. 48. ^ Behtash N, Behnamfar F, Hamedi B, Ramezanzadeh F (April 2009). "Term delivery following successful treatment of choriocarcinoma with brain metastases, a case report and review of literature". Archives of Gynecology and Obstetrics. 279 (4): 579–81. doi:10.1007/s00404-008-0753-x. PMID 18726607. S2CID 24481680. 49. ^ Ganapathi KA, Paczos T, George MD, Goodloe S, Balos LL, Chen F (September 2010). "Incidental finding of placental choriocarcinoma after an uncomplicated term pregnancy: a case report with review of the literature". International Journal of Gynecological Pathology. 29 (5): 476–8. doi:10.1097/PGP.0b013e3181d81cc2. PMID 20736774. 50. ^ Altieri A, Franceschi S, Ferlay J, Smith J, La Vecchia C (November 2003). "Epidemiology and aetiology of gestational trophoblastic diseases". The Lancet. Oncology. 4 (11): 670–8. doi:10.1016/S1470-2045(03)01245-2. PMID 14602247. 51. ^ Savage P, Williams J, Wong SL, Short D, Casalboni S, Catalano K, Seckl M (2010). "The demographics of molar pregnancies in England and Wales from 2000-2009". The Journal of Reproductive Medicine. 55 (7–8): 341–5. PMID 20795349. 52. ^ Soares PD, Maestá I, Costa OL, Charry RC, Dias A, Rudge MV (2010). "Geographical distribution and demographic characteristics of gestational trophoblastic disease". The Journal of Reproductive Medicine. 55 (7–8): 305–10. PMID 20795343. 53. ^ Chauhan A, Dave K, Desai A, Mankad M, Patel S, Dave P (2010). "High-risk gestational trophoblastic neoplasia at Gujarat Cancer and Research Institute: thirteen years of experience". The Journal of Reproductive Medicine. 55 (7–8): 333–40. PMID 20795348. 54. ^ Kashanian M, Baradaran HR, Teimoori N (October 2009). "Risk factors for complete molar pregnancy: a study in Iran". The Journal of Reproductive Medicine. 54 (10): 621–4. PMID 20677481. 55. ^ Berkowitz RS, Cramer DW, Bernstein MR, Cassells S, Driscoll SG, Goldstein DP (August 1985). "Risk factors for complete molar pregnancy from a case-control study". American Journal of Obstetrics and Gynecology. 152 (8): 1016–20. doi:10.1016/0002-9378(85)90550-2. PMID 4025447. 56. ^ Palmer JR (March 1994). "Advances in the epidemiology of gestational trophoblastic disease". The Journal of Reproductive Medicine. 39 (3): 155–62. PMID 8035370. 57. ^ "Gestational Trophoblastic Disease (Green-top 38)" (PDF). Royal College of Obstetricians and Gynaecologists guideline 2010. 2010-03-04. Archived from the original (PDF) on 2010-07-10. ## External links[edit] Classification D * MeSH: D031901 * DiseasesDB: 2602 External resources * MedlinePlus: 001496 * eMedicine: article/279116 * Orphanet: 254685 * v * t * e Germ cell tumors Germinomatous * Germinoma * Seminoma * Dysgerminoma Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor/Yolk sac tumor * Teratoma: Fetus in fetu * Dermoid cyst * Struma ovarii * Strumal carcinoid * Trophoblastic neoplasm: Gestational trophoblastic disease * Hydatidiform mole * Choriocarcinoma * Placental site trophoblastic tumor * Polyembryoma * Gonadoblastoma * v * t * e Tumors of the female urogenital system Adnexa Ovaries Glandular and epithelial/ surface epithelial- stromal tumor CMS: * Ovarian serous cystadenoma * Mucinous cystadenoma * Cystadenocarcinoma * Papillary serous cystadenocarcinoma * Krukenberg tumor * Endometrioid tumor * Clear-cell ovarian carcinoma * Brenner tumour Sex cord–gonadal stromal * Leydig cell tumour * Sertoli cell tumour * Sertoli–Leydig cell tumour * Thecoma * Granulosa cell tumour * Luteoma * Sex cord tumour with annular tubules Germ cell * Dysgerminoma * Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma/Struma ovarii * Choriocarcinoma Fibroma * Meigs' syndrome Fallopian tube * Adenomatoid tumor Uterus Myometrium * Uterine fibroids/leiomyoma * Leiomyosarcoma * Adenomyoma Endometrium * Endometrioid tumor * Uterine papillary serous carcinoma * Endometrial intraepithelial neoplasia * Uterine clear-cell carcinoma Cervix * Cervical intraepithelial neoplasia * Clear-cell carcinoma * SCC * Glassy cell carcinoma * Villoglandular adenocarcinoma Placenta * Choriocarcinoma * Gestational trophoblastic disease General * Uterine sarcoma * Mixed Müllerian tumor Vagina * Squamous-cell carcinoma of the vagina * Botryoid rhabdomyosarcoma * Clear-cell adenocarcinoma of the vagina * Vaginal intraepithelial neoplasia * Vaginal cysts Vulva * SCC * Melanoma * Papillary hidradenoma * Extramammary Paget's disease * Vulvar intraepithelial neoplasia * Bartholin gland carcinoma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Gestational trophoblastic disease	c2931618	30,501	wikipedia	https://en.wikipedia.org/wiki/Gestational_trophoblastic_disease	2021-01-18T18:37:59	{"gard": ["6498"], "mesh": ["D031901"], "umls": ["C2931618"], "orphanet": ["254685"], "wikidata": ["Q3433884"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant mental retardation-35 (MRD35) is caused by heterozygous mutation in the PPP2R5D gene (601646) on chromosome 6p21. Clinical Features The Deciphering Developmental Disorders Study (2015) identified 4 patients with intellectual disability and mutation in the PPP2R5D gene. The first patient was a girl with severe intellectual disability, hydrocephalus, chronic diarrhea, and hypoglycemia. The second was a boy with global developmental delay, seizures, ventriculomegaly, narrow forehead, downslanted palpebral fissures, pyloric stenosis, and macrocephaly. The third patient was a boy with global developmental delay, deeply set eyes, myopia, strabismus, and generalized hypotonia. The fourth was a girl with global developmental delay, congenital muscular torticollis, and congenital hip dislocation. Houge et al. (2015) reported 7 additional children with MRD35 confirmed by genetic analysis. All had neonatal and persistent hypotonia and delayed psychomotor development with poor speech. Most had increased head circumference, which was associated with hydrocephalus in at least 1 case. Dysmorphic facial features included hypotonic face with tented upper lip, mild hypertelorism with downslanting palpebral fissures, and frontal bossing. Loveday et al. (2015) reported 3 unrelated patients with MRD35 associated with overgrowth, mainly macrocephaly. Two patients had increased height. Molecular Genetics The Deciphering Developmental Disorders Study (2015) examined 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements. The authors discovered 12 novel genes associated with developmental disorders. The PPP2R5D gene was implicated in a gene-specific analysis (p = 6.01 x 10(-12)). The Deciphering Developmental Disorders Study (2015) identified 4 patients with intellectual disability who had heterozygous de novo missense mutations in the PPP2R5D gene. Three patients carried the same mutation (E198K; 601646.0001), and the fourth carried a different mutation (P201R; 601646.0002). In 7 unrelated patients with MRD35, Houge et al. (2015) identified 5 different de novo heterozygous missense mutations in the PPP2R5D gene (601646.0001-601646.0005). Three of the patients carried the same E198K mutation. The mutations were found by parent-child trio exome sequencing and confirmed by Sanger sequencing. All mutations clustered in a highly conserved acidic loop that faces the A and C subunits of the PP2A complex, except one (P52S; 601646.0003). In vitro functional expression studies in HEK293 cells showed that all mutations, except P53S, showed deficient holoenzyme formation of PP2A with decreased association of the mutant PPP2R5D subunit to the A or C subunits, consistent with a dominant-negative effect. Houge et al. (2015) suggested that disruption of normal phosphorylation in the brain may result in brain dysfunction, perhaps by having far-reaching consequences for regulation of localized signaling. Loveday et al. (2015) identified 2 different heterozygous missense mutations in the PPP2R5D gene (601646.0001 and 601646.0004) in 3 unrelated patients with MRD35 associated with overgrowth, including macrocephaly. Functional studies of the variants were not performed, but Loveday et al. (2015) postulated that they could plausibly alter the ability of PP2A to dephosphorylate target substrates. The first 2 patients were ascertained from a larger cohort of 111 parent-child trios with overgrowth syndrome, often associated with intellectual disability, who underwent exome sequencing. The third patient was ascertained from a cohort of 152 individuals with overgrowth phenotypes for whom parental DNA was not available. Loveday et al. (2015) postulated that the mutations may disrupt the PI3K (see 171834)/AKT1 (164730) growth regulatory cascade. INHERITANCE \- Autosomal dominant GROWTH Height \- Increased height (in some patients) HEAD & NECK Head \- Macrocephaly (in some patients) Face \- Broad, tall forehead \- Hypotonic facies Eyes \- Hypertelorism, mild Mouth \- Tented lip \- Open mouth NEUROLOGIC Central Nervous System \- Delayed psychomotor development, moderate to severe \- Poor or absent speech \- Hydrocephalus (in some patients) \- Seizures (in some patients) MISCELLANEOUS \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the protein phosphatase 2, regulatory subunit B (B56), delta gene (PPP2R5D, 601646.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	MENTAL RETARDATION, AUTOSOMAL DOMINANT 35	c4225354	30,502	omim	https://www.omim.org/entry/616355	2019-09-22T15:49:10	{"doid": ["0070065"], "omim": ["616355"], "orphanet": ["457279"], "synonyms": [], "genereviews": ["NBK536360"]}
## Description Congenital diaphragmatic hernia (CDH) refers to a group of congenital defects in the structural integrity of the diaphragm which are often associated with lethal pulmonary hypoplasia and pulmonary hypertension. Prevalence in newborns ranges from 1 in 2,500 to 1 in 4,000, and there is a 30 to 60% mortality rate (Langham et al., 1996; Harrison et al., 1994; Nobuhara et al., 1996). Most cases of congenital diaphragmatic hernia are sporadic. ### Genetic Heterogeneity of Diaphragmatic Hernia Congenital diaphragmatic hernia-1 (DIH1) maps to chromosome 15q26; DIH2 (222400) maps to chromosome 8p23; and DIH3 (610187) is associated with mutation in the ZFPM2 gene (603693). There is evidence for further genetic heterogeneity, including a possible X-linked form (306950). Congenital diaphragmatic hernia can also present with other congenital anomalies. Fryns syndrome (229850) may be the most common autosomal recessive syndrome with DIH as a cardinal feature (Slavotinek et al., 2005). See Holder et al. (2007) for a review of genetic factors in congenital diaphragmatic hernia. Pober (2008) reviewed genetic aspects of congenital diaphragmatic hernia, with emphasis on various syndromes in which CDH occurs along with other manifestations. Clinical Features There are several different types of CDH, including Bochdalek, Morgagni, and central (septum transversum) diaphragmatic hernia (Stokes, 1991). Approximately 70 to 90% of CDH cases are 'Bochdalek-type,' or posterolateral hernias, most often occurring on the left side. Morgagni CDH is less common and forms in the anterior retrosternal diaphragm. Central CDH occurs in the midline of the septum transversum and accounts for 1 to 2% of cases of CDH. The pathologic consequences of CDH result from the abdominal contents entering the thoracic cavity. Hypoplasia of the lung due to decreased thoracic volume results in compromised pulmonary capacity often resulting in neonatal death. Unilateral agenesis of the diaphragm is considered to be an extreme form of congenital diaphragmatic hernia (Baglaj et al., 1999). Enns et al. (1998) reviewed 60 patients with congenital diaphragmatic defects detected prenatally. In 29 of these, therapeutic or spontaneous abortion was the outcome of the pregnancy; anomalies in addition to diaphragmatic defects were present in 16 of 31 patients evaluated postnatally. Syndromes diagnosed postnatally in 7 of 16 patients included Fryns syndrome (229850) in 2, Simpson-Golabi-Behmel syndrome (312870) in 2, tetrasomy 12p (601803) in 1, Brachmann-de Lange syndrome (122470) in 1, and lethal multiple pterygium syndrome (253250) in 1. They were unable to make a specific diagnosis in 9 of 16 patients with multiple malformations. Using population-based data from ongoing studies in the California Birth Defects Monitoring Program, Slavotinek et al. (2007) compared additional clinical features of 38 (26%) patients with right-sided CDH and 108 (74%) with left-sided CDH. There were statistically significant differences in frequencies of atrial septal defect (1/38 right-CDH and 20/108 left-CDH cases; p = 0.015), bilateral pulmonary hypoplasia (22/108 left-CDH cases and 15/38 right-CDH cases; p = 0.029), abnormal skull or facial shape (17/108 left-CDH patients and 1/38 right-CDH cases; p = 0.043), assorted digital anomalies excluding syndactyly, polydactyly or absence of a digit (13/108 left-CDH patients and 0/38 right-CDH patients; p = 0.021), and assorted limb anomalies excluding limb reduction defects (18/108 left-CDH patients and 0/38 right-CDH patients; p = 0.004). Inheritance Passarge et al. (1968) reported unilateral agenesis of the diaphragm in a brother and sister and found 4 other reports of multiple affected sibs. A sibship with at least 3 affected was reported by Ten Kate and Anders (1970). Daentl and Passarge (1972) found that 2 or more sibs had been affected in 9 unrelated families and found probable consanguinity in 1, suggesting autosomal recessive inheritance. Wolff (1980) comprehensively reviewed 17 reports dealing with familial congenital diaphragmatic hernia and concluded that multifactorial inheritance is most likely. Arad et al. (1980) described congenital defects of the diaphragm in 2 female offspring of healthy Arab parents related as first cousins once removed, twice second cousins and second cousins once removed (F = 9/128). In 1 infant, the diaphragmatic defect took the form of a Bochdalek-type, posterolateral hernia. In the second, both diaphragms were almost completely lacking. Norio et al. (1984) reported 14 cases from 5 Finnish families affected with a life-threatening congenital diaphragmatic defect. Diaphragmatic defects occurred in 3 sibs and in the son of their half brother. Diaphragmatic defects probably occurred in all 4 offspring of a couple related as first cousins and second cousins. In the other Finnish families and most reported familial cases, only 2 sibs were affected. Norio et al. (1984) reviewed data on 53 previously reported familial cases, and presented a number of factors favoring multifactorial rather than recessive inheritance. The recurrence risk for sibs after the birth of one affected sib was judged to be about 2%. Schubert-Staudacher and Jauch (1984) reported bilateral eventration of the diaphragm in 2 offspring of nonconsanguineous parents. The authors quoted others who had pointed out that familial cases are more often bilateral than are sporadic cases. Czeizel and Kovacs (1985) described sibs with isolated congenital diaphragmatic defect of the Bochdalek type. Toriello et al. (1985) reported a male infant with unilateral pulmonary and diaphragmatic agenesis and his sister with bilateral pulmonary and diaphragmatic agenesis. Toriello et al. (1986) described 3 sisters with isolated unilateral agenesis of the diaphragm. Bocian et al. (1986) reported 2 families with multiple occurrence of congenital diaphragmatic defects. In one of the families, the lesion was detected in the fetus by ultrasound at 14 weeks. Segregation analysis of these families and of 17 other multiplex families from the literature led Bocian et al. (1986) to the conclusion that the autosomal recessive hypothesis 'cannot be rejected.' On the other hand, multifactorial determination was rejected by the data. Hubert and Toyama (1987) described a 'right thoracic stomach' in a 2-month-old boy whose mother had been operated on for the same abnormality at about the same age. Among the children of an Arab couple related as second cousins, Farag et al. (1989) observed 2 brothers, one with an extensive left-sided Bochdalek-type hernia, and the second with hemidiaphragmatic agenesis. Farag et al. (1994) described a Kuwaiti family and an Egyptian family in each of which 3 children of consanguineous parents had congenital diaphragmatic defects. Narayan et al. (1993) described congenital diaphragmatic hernia in a brother and sister and in a male first cousin. Mitchell et al. (1997) reported 4 cases of left-sided congenital diaphragmatic hernia in 2 generations of a consanguineous Pakistani family. Two children had associated cardiac abnormalities, but there were no other dysmorphic features. Pober et al. (2005) reviewed and classified 203 unrelated cases of Bochdalek-type hernia identified over a 28-year period through a hospital-based surveillance program. Phenotypically, 112 (55%) cases had an isolated defect, and 91 (45%) had a defect in association with additional malformations as part of a syndrome. Family histories showed that only 1 affected infant, who had an isolated defect, had a previous sib who also had an isolated defect, for a recurrence rate of 0.9%. However, 4% of all sibs had a major malformation other than CDH, including cleft lip and palate, hydronephrosis, renal agenesis/dysgenesis, anencephaly, and congenital heart defects. There were 8 twin pairs, including 5 monozygotic pairs, all of whom were discordant for CDH; in 2 cases the cotwin had other malformations. Pober et al. (2005) presented a detailed review of the literature, and suggested that previous studies may have overestimated the concordance for CDH among twins. Pober et al. (2005) hypothesized that de novo dominant mutations or epigenetic factors likely contribute to the development of CDH. Cytogenetics ### Chromosome 15q Although most cases of congenital diaphragmatic hernia are idiopathic, chromosomal abnormalities have been implicated in approximately 15% of cases. Biggio et al. (2004) cited numerous reports of either de novo deletion or unbalanced translocations involving the 15q24-q26 region, suggesting that this region is critical to normal development of the diaphragm. They described a patient with deletion of 15q26.1, the smallest isolated chromosomal aberration on distal 15q that had been reported to that time. In addition to diaphragmatic hernia, coarctation of the aorta and dysmorphic features were present. Biggio et al. (2004) noted that the myocyte-specific enhancer factor-2 (MEF2) proteins play a critical role in the control of muscle differentiation and development. They proposed MEF2A (600660), a member of the MEF2 gene family mapping to 15q26, as a candidate gene. By array CGH, Slavotinek et al. (2005) screened patients with DIH and additional phenotypic anomalies consistent with Fryns syndrome for cryptic chromosomal aberrations. They identified submicroscopic chromosome deletions in 3 probands who had previously been diagnosed with Fryns syndrome and had normal karyotyping with G-banded chromosome analysis. Two female infants were found to have microdeletions involving 15q26.2, and 1 male infant had a deletion in band 8p23.1. ### Chromosome 1q41-q42 Youssoufian et al. (1988) reported an infant with a diaphragmatic hernia and a de novo interstitial deletion of chromosome 1q32.3-q42.3. The patient died at age 8 hours. The patient had other abnormal clinical features, including low-set ears, mild webbing of the neck, undescended testes, hypospadias, equinovarus, and flexion contractures of the fingers. Smith et al. (1994) reported a 9-year-old boy with multiple congenital anomalies, including diaphragmatic hernia, bilateral clinical anophthalmia, and tetralogy of Fallot who had an apparently balanced reciprocal translocation t(1;15)(q41;q21.2). These patients had a phenotype that may be consistent with a contiguous gene deletion syndrome involving 1q41-q42 (612530), of which CDH is a feature. Kantarci et al. (2006) reported a newborn female with Fryns syndrome (229850) associated with a de novo approximately 5-Mb deletion of chromosome 1q41-q42.12. She died at 1 hour of age of respiratory insufficiency and congenital diaphragmatic hernia. Kantarci et al. (2006) concluded that there may be a possible locus for Fryns syndrome at 1q41-q42, and more specifically that this region may harbor one or more genes required for normal diaphragmatic development. In further analysis of the patient reported by Kantarci et al. (2006), Kantarci et al. (2010) used multiplex ligation-dependent probe amplification (MLPA) to extend the minimally deleted region to approximately to 6.1 to 6.2 Mb spanning from the EPRS gene (138295) to the ACBD3 gene (606809). Slavotinek et al. (2006) identified a de novo interstitial deletion of 1q32.3-q42.2 in a male with CDH and pulmonary hypoplasia with multiple other congenital anomalies suggestive of Fryns syndrome. The authors referred to the reports of Youssoufian et al. (1988) and Kantarci et al. (2006). Using MLPA analysis, Kantarci et al. (2010) found that 2 of 179 patients with CDH had deletions at chromosome 1q41-q42. One patient had previously been reported by Kantarci et al. (2006), and the other was reported for the first time. The second patient had multiple congenital anomalies, including pulmonary hypoplasia, talipes equinovarus, undescended testes and dysmorphic facial features; he died at age 1 month. The deletion extended from the BPNT1 gene (604053) on chromosome 1q41 to the PSEN2 gene (600759) on chromosome 1q41.13. Wat et al. (2011) identified a de novo deletion at chromosome 1q41-q42 in 1 of 45 unrelated patients with CDH. This patient had multiple congenital anomalies and developmental delay. The deletion breakpoints in the patient reported by Wat et al. (2011) allowed definition of a new 2.2-Mb minimal deleted region for congenital diaphragmatic hernia on 1q41-q42 (223,073,839 to 225,318,623, GRCh37), which contains 15 genes including DISP1 (607502), but not including HLX (142995). ### Chromosome 11q Klaassens et al. (2006) reported 2 brothers with partial trisomy 11q, 1 of whom had left-sided posterolateral CDH. Array-based comparative genomic hybridization and FISH enabled mapping of the duplication to a 19-Mb region on 11q23.3-qter, suggesting that duplication of a gene within this region may predispose to the development of CDH. Wat et al. (2011) reported a patient with multiple congenital anomalies, including CDH, who had an unbalanced maternal translocation between chromosome 13q and 11q, resulting in a 47,XX,+der(13)t(11;13)(q23;q12.3). She was trisomic for a part of chromosome 13q12.3 and a part of chromosome 11q23-qter. Mapping ### DIH1 Locus on Chromosome 15q To define candidate regions for CDH, Klaassens et al. (2005) analyzed cytogenetic data collected on 200 CDH cases, of which 7% and 5% showed numerical and structural abnormalities, respectively. The authors focused on the most frequent structural anomaly found: a deletion on 15q. They analyzed material from 3 of their patients and from 4 previously reported patients with CDH and a 15q deletion. Using array-based comparative genomic hybridization and FISH to determine the boundaries of the deletions and by including data from 2 individuals with terminal 15q deletions but without CDH, they were able to exclude a substantial portion of the telomeric region from the genetic etiology of this disorder. Moreover, 1 patient with CDH harbored a small interstitial deletion. Together these findings allowed them to define a minimal deletion region of approximately 5 Mb at chromosome 15q26.1-q26.2. This region contained 4 known genes, of which 2--NR2F2 (107773) and CDH2 (114020)--were considered particularly intriguing gene candidates for CDH. Castiglia et al. (2005) also examined the probable location of a gene involved in CDH by the study of a patient with a de novo deletion at 15q26.1-q26.2 without CDH. Klaassens et al. (2005) pointed out that 15q26.1-q26.2 is a gene-poor region and that haploinsufficiency of this region might not be completely penetrant. They still proposed NR2F2 as the most likely candidate gene for CDH. In a patient with CDH and multiple congenital anomalies, Bleyl et al. (2007) identified heterozygosity for a 2889C-G transversion in the PDGFRA gene (173490) predicting a leu967-to-val substitution. The change was not seen in 768 chromosomes. However, the patient's skin karyotype revealed 46,XX with 1 in 50 cells showing mosaicism for trisomy 15. The patient had left-sided CDH and multiple anomalies including pulmonary hypoplasia, congenital heart disease with a ventricular septal defect, secundum type atrial septal defect and tricuspid regurgitation, malrotation of the intestines, multicystic liver, neck webbing, dysmorphic facial features, and streaky skin hyperpigmentation. Bleyl et al. (2007) concluded that the physical anomalies could be related to trisomy 15 mosaicism, the PDGFRA alteration, or a combination of both. Although the patient had many phenotypic features typical of trisomy 15 and streaky skin hyperpigmentation supported mosaicism, the authors noted that diaphragmatic defects had not previously been described in patients with trisomy 15. Molecular Genetics ### Associations Pending Confirmation In a 6-year-old boy with multiple congenital anomalies, including congenital left-sided Bochdalek diaphragmatic hernia, ventricular septal defect and abnormal aorta, and left-sided cleft lip with bilateral cleft palate, Kantarci et al. (2010) identified mosaicism for a de novo heterozygous 4412C-G transversion in the DISP1 (607502) gene on chromosome 1q42, resulting in an ala1471-to-gly (A1471G) substitution. Studies of patient tissues showed that the mutant allele was present in 43% of lymphoblastoid cells, 12% of peripheral blood lymphocytes, and 4.5% in saliva. The patient had hypotonia but otherwise had normal development. No DISP1 mutations were found in 178 additional patients with congenital diaphragmatic hernia. In a 6-month-old boy of European descent with isolated congenital diaphragmatic hernia (CDH), and a 3-year-old girl with multiple congenital anomalies including CDH, Jordan et al. (2018) identified biallelic variants in the FREM2 gene (608945). Animal Model Yuan et al. (2003) described central diaphragmatic hernia in mice in whom a knockout of the Slit3 gene (603745) had been introduced. The central tendon region of the diaphragm failed to separate from liver tissue. The liver showed continuous growth into the thoracic cavity. You et al. (2005) generated tissue-specific Nr2f2 -/- mice and observed the development of dorsolateral Bochdalek-type congenital diaphragmatic hernias. The authors noted that in patients with a 5-Mb deletion on chromosome 15q26.1-q26.2, Klaassens et al. (2005) found left-sided Bochdalek-type hernias similar to those seen in the conditional knockout mice. You et al. (2005) suggested that NR2F2 is a likely contributor to the formation of CDH in patients with 15q deletions. Bleyl et al. (2007) observed that the homozygous Pgfra (173490)-null mouse had posterolateral diaphragmatic defects and concluded that the mouse is a model for human congenital diaphragmatic hernia. Thorax \- Familial congenital diaphragmatic hernia Inheritance \- Multifactorial \- ? some autosomal recessive cases ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	DIAPHRAGMATIC HERNIA, CONGENITAL	c0235833	30,503	omim	https://www.omim.org/entry/142340	2019-09-22T16:40:26	{"doid": ["3827"], "mesh": ["D065630"], "omim": ["142340"], "icd-10": ["Q79.0"], "orphanet": ["2140"], "synonyms": ["Alternative titles", "DIH", "HERNIA, CONGENITAL DIAPHRAGMATIC", "DIAPHRAGMATIC DEFECT, CONGENITAL", "DIAPHRAGM, UNILATERAL AGENESIS OF", "HEMIDIAPHRAGM, AGENESIS OF"], "genereviews": ["NBK1359"]}
A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by infantile onset of global developmental delay, severe intellectual disability, growth deficiency, microcephaly, strabismus, blue-gray sclerae, and extensive Mongolian spots. Some patients also present with epilepsy. Brain imaging may demonstrate variable abnormalities including cerebral atrophy, thin corpus callosum, ventriculomegaly, or arachnoid cysts. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome	c4310745	30,504	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=488627	2021-01-23T17:10:07	{"omim": ["617051"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Panniculitis" – news · newspapers · books · scholar · JSTOR (December 2018) Panniculitis Erythema induratum, a form of lobular panniculitis SpecialtyRheumatology Panniculitis is a group of diseases whose hallmark is inflammation of subcutaneous adipose tissue (the fatty layer under the skin – panniculus adiposus).[1] Symptoms include tender skin nodules, and systemic signs such as weight loss and fatigue. Restated, an inflammatory disorder primarily localized in the subcutaneous fat is termed a "panniculitis", a group of disorders that may be challenging both for the clinician and the dermatopathologist.[2]:487 The general term for inflammation of any adipose tissue is steatitis. ## Contents * 1 Signs and symptoms * 1.1 Associated conditions * 2 Diagnosis * 2.1 Classification * 2.1.1 Lobular * 2.1.1.1 With vasculitis * 2.1.1.2 Without vasculitis * 2.1.2 With needle-shaped clefts * 2.1.3 Septal * 2.1.3.1 Erythema nodosum * 2.1.3.2 A1AT-deficiency-associated * 3 Treatment * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] Panniculitis can also be classified based on the presence or absence of systemic symptoms. Panniculitis without systemic disease can be a result of trauma or cold.[3] Panniculitis with systemic disease can be caused by[citation needed]: * connective tissue disorders such as lupus erythematosus or scleroderma; * lymphoproliferative disease such as lymphoma or histiocytosis; * pancreatitis or pancreatic cancer; * sarcoidosis with cutaneous involvement (seen in up to 20 percent); * Alpha 1-antitrypsin deficiency * Crohn's disease This is not a complete list of possible causes. ### Associated conditions[edit] Lipoatrophy or lipodystrophy (the loss of subcutaneous adipose tissue) can occur in any of these conditions. ## Diagnosis[edit] ### Classification[edit] It can occur in any fatty tissue (cutaneous or visceral) and is often diagnosed on the basis of a deep skin biopsy, and can be further classified by histological characteristics based on the location of the inflammatory cells (within fatty lobules or in the septa which separate them) and on the presence or absence of vasculitis. There are thus four main histological subtypes:[4] 1. lobular panniculitis without vasculitis (acute panniculitis, previously termed Weber–Christian disease,[5] systemic nodular panniculitis) 2. lobular panniculitis with vasculitis 3. septal panniculitis without vasculitis 4. septal panniculitis with vasculitis #### Lobular[edit] ##### With vasculitis[edit] Erythema induratum, or "Bazin disease", is a panniculitis on the back of the calves.[6] It was formerly thought to be a reaction to the tuberculum bacillus. It is now considered a panniculitis that is not associated with a single defined pathogen.[7] Nodular vasculitis is a skin condition characterized by small, tender, reddened nodules on the legs, mostly on the calves and shins. Microscopically there are epithelioid granulomas and vasculitis in the subcutaneous tissue, making it a form of paniculitis. Most of these cases are now thought to be manifestation of tuberculosis and indeed they respond well to anti-tuberculous treatment.[citation needed] ##### Without vasculitis[edit] Non-vasculitis forms of panniculitis that may occur include: * Cytophagic histiocytic panniculitis was first described in 1980 by Winkelmann as a chronic histiocytic disease of the subcutaneous adipose tissue, which is characterized clinically by tender erythematous nodules, recurrent high fever, malaise, jaundice, organomegaly, serosal effusions, pancytopenia, hepatic dysfunction and coagulation abnormalities.[2]:494[8] CHP may occur either isolated or as part of cutaneous manifestations of hemophagocytic syndrome (HPS).[9] CHP is a rare and often fatal form of panniculitis with multisystem involvement. But it can also present in a benign form involving only the subcutaneous tissue, thus having a broad clinical spectrum. * Traumatic panniculitis is a panniculitis that occurs following trauma to the skin.[2]:492[10] * Cold panniculitis is a panniculitis occurring after exposure to cold, most often seen in infants and young children.[2]:491 This condition has been described in children who suck ice or popsicles, and therefore is sometimes referred to as "popsicle panniculitis."[2]:491[10] The term was coined when a patient with a rash of unknown origin on her cheek was taken to a dermatologist.[11] * Gouty panniculitis is a panniculitis caused by deposition of uric acid crystals in gout.[2]:494 * Pancreatic panniculitis (also known as enzymatic panniculitis, Pancreatic fat necrosis,[10] and subcutaneous fat necrosis) is a panniculitis most commonly associated with pancreatic carcinoma, and more rarely with anatomic pancreatic abnormalities, pseudocysts, or drug-induced pancreatitis.[2]:493 * Factitial panniculitis is a panniculitis that may be induced by the injection of organic materials, povidone, feces, saliva, vaginal fluid, and oils.[2]:492 #### With needle-shaped clefts[edit] Lipodermatosclerosis is a form of panniculitis associated with chronic venous insufficiency that presents with brown indurations on the front of the shins. It may be associated with pain and other signs of chronic venous insufficiency. The exact cause is unknown.[12] Other forms include: * Subcutaneous fat necrosis of the newborn, a form of panniculitis occurring in newborns that is usually self-resolving, that may be a result of hypoxic injury to relatively high levels of brown fat.[2]:492 * Sclerema neonatorum, affecting premature births.[2]:492 * Weber–Christian disease, a symmetrical form of the disease of unknown origin occurring in middle-aged women.[2]:492 * Lupus erythematosus panniculitis, panniculitis associated with lupus erythematosus.[13] * Forms associated with use of high doses of systemic corticosteroids during rapid corticosteroid withdrawal, and from the injection of silicone or mineral oils.[2]:492 #### Septal[edit] ##### Erythema nodosum[edit] Main article: Erythema nodosum Erythema nodosum is a form of panniculitis characterised by tender red nodules, 1–10 cm, associated with systemic symptoms including fever, malaise, and joint pain. Nodules may become bluish-purple, yellowing, and green, and subside over a period of 2–6 weeks without ulcerating or scarring. Erythema nodosum is associated with infections, including Hepatitis C, EBV and tuberculosis, Crohn's disease and sarcoidosis, pregnancy, medications including sulfonamides, and some cancers, including Non-Hodgkin lymphoma and pancreatic cancer.[14] ##### A1AT-deficiency-associated[edit] See also: Alpha-1 antitrypsin deficiency Alpha-1 antitrypsin deficiency panniculitis [13] is a panniculitis associated with a deficiency of the α1-antitrypsin enzyme.[2]:494 ## Treatment[edit] This section is empty. You can help by adding to it. (December 2017) ## See also[edit] * Panniculus carnosus * List of cutaneous conditions ## References[edit] 1. ^ "panniculitis" at Dorland's Medical Dictionary 2. ^ a b c d e f g h i j k l m James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 3. ^ "eMedicine - Cold Panniculitis : Article by Geromanta Baleviciene". Retrieved 2008-03-25. 4. ^ "Panniculitis. DermNet NZ". Retrieved 2010-05-17. 5. ^ "eMedicine - Weber-Christian Disease : Article by Moise L Levy". Retrieved 2008-03-25. 6. ^ "erythema induratum" at Dorland's Medical Dictionary[dead link] 7. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. p. 1265. ISBN 978-0-7216-0187-8. 8. ^ Winkelmann RK, Bowie EJ. Hemorrhagic diathesis associated with benign histiocytic cytophagic panniculitis and systemic histiocytosis. Arch Intern Med.1980; 140: 1460-3 9. ^ Smith K J, Skeleton H J, Yeagre J, Angritt P, Wagner K, James W. D., Giblin W. J., Lupton G. P. Cutaneous histopathological, immunohistochemical, and clinical manifestations inpatients with hemophagocytic syndrome. Military Medical old Consortium for Applied Retroviral Research (MMCARR). Arch Dermatol 1992; 128: 193-200 10. ^ a b c Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1515. ISBN 978-1-4160-2999-1. 11. ^ Epstein, Ervin and Oren, Mark, "Popsicle Panniculitis" "The New England Journal of Medicine", 282 (17) : 966-67, 1970 12. ^ Bruce AJ. et al., Lipodermatosclerosis: Review of cases evaluated at Mayo Clinic. J Am Acad Dermatol. 2002. 13. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 14. ^ Gilchrist, H; Patterson, JW (Jul–Aug 2010). "Erythema nodosum and erythema induratum (nodular vasculitis): diagnosis and management". Dermatologic Therapy. 23 (4): 320–7. doi:10.1111/j.1529-8019.2010.01332.x. PMID 20666819. ## External links[edit] * DermNet dermal-infiltrative/panniculitis * DermAtlas -639418194 Classification D * ICD-10: M79.3 * ICD-9-CM: 729.3 * MeSH: D015434 * DiseasesDB: 29081 * v * t * e Disorders of subcutaneous fat Panniculitis Lobular * without vasculitis * Cold * Cytophagic histiocytic * Factitial * Gouty * Pancreatic * Traumatic * needle-shaped clefts * Subcutaneous fat necrosis of the newborn * Sclerema neonatorum * Post-steroid panniculitis * Lipodermatosclerosis * Weber–Christian disease * Lupus erythematosus panniculitis * Sclerosing lipogranuloma * with vasculitis: Nodular vasculitis/Erythema induratum Septal * without vasculitis: Alpha-1 antitrypsin deficiency panniculitis * Erythema nodosum * Acute * Chronic * with vasculitis: Superficial thrombophlebitis Lipodystrophy Acquired * generalized: Acquired generalized lipodystrophy * partial: Acquired partial lipodystrophy * Centrifugal abdominal lipodystrophy * HIV-associated lipodystrophy * Lipoatrophia annularis * localized: Localized lipodystrophy Congenital * Congenital generalized lipodystrophy * Familial partial lipodystrophy * Marfanoid–progeroid–lipodystrophy syndrome * Poland syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Panniculitis	c0030326	30,505	wikipedia	https://en.wikipedia.org/wiki/Panniculitis	2021-01-18T18:28:52	{"mesh": ["D015434"], "umls": ["C0030326"], "wikidata": ["Q780629"]}
Robinow syndrome is a rare disorder that affects the bones as well as other parts of the body. Two forms of Robinow syndrome have been described: autosomal recessive Robinow syndrome, and the milder autosomal dominant Robinow syndrome. They are distinguished based on their modes of inheritance, symptoms, and severity. Autosomal recessive Robinow syndrome causes shortening of the long bones in the arms and legs; short fingers and toes; wedge-shaped spinal bones leading to kyphoscoliosis; fused or missing ribs; short stature; and distinctive facial features. Other features may include underdeveloped genitalia; dental problems; kidney or heart defects; or delayed development. This form is caused by mutations in the ROR2 gene. Autosomal dominant Robinow syndrome causes more mild, but similar, features. There are rarely spine and rib abnormalities, and short stature is less severe. A variant type of this form is additionally characterized by osteosclerosis. Autosomal dominant Robinow syndrome may be caused by a mutation in the WNT5A or DVL1 gene. In some cases, the underlying cause of Robinow syndrome is unknown. Management may include bracing or surgery for skeletal abnormalities and growth hormone to increase growth rate in affected children. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Robinow syndrome	c0265205	30,506	gard	https://rarediseases.info.nih.gov/diseases/312/robinow-syndrome	2021-01-18T17:57:52	{"mesh": ["C562492"], "omim": ["180700", "268310"], "umls": ["C0265205"], "orphanet": ["97360"], "synonyms": ["Robinow dwarfism", "Fetal face syndrome", "Acral dysostosis with facial and genital abnormalities", "Covesdem syndrome (formerly)", "Costovertebral segmentation defect with mesomelia (formerly)", "Mesomelic dwarfism-small genitalia syndrome", "Robinow-Silverman-Smith syndrome"]}
Sandifer syndrome is a paroxysmal dystonic movement disorder occurring in association with gastro-oesophageal reflux, and, in some cases, hiatal hernia. ## Epidemiology The prevalence is unknown. ## Clinical description Onset usually occurs during infancy or early childhood. The dystonic movements are characterised by abnormal posturing of the head and neck (torticollis) and severe arching of the spine. Episodes usually last for between 1-3 minutes and can occur up to 10 times a day, although they are usually associated with the ingestion of food. Vomiting, poor feeding, anaemia, epigastric discomfort, haematemesis and abnormal eye movements have also been reported. Reflux oesophagitis is common. ## Etiology The dystonic movements are clearly associated with gastro-oesophageal reflux but the pathophysiological mechanism is not clearly understood. Several studies have indicated that the dystonic posturing is a pathological reflex triggered in response to abdominal pain caused by gastroesophageal reflux and oesophagitis. Although conflicting results have been obtained, some authors have suggested that the dystonic posture provides relief from abdominal pain. ## Diagnostic methods Sandifer syndrome is diagnosed on the basis of the association of gastro-oesophageal reflux with the characteristic movement disorder. Neurological examination is usually normal. ## Differential diagnosis However, in the absence of clear indications of gastro-oesophageal reflux, misdiagnosis as infantile spasms, epilepsy or paroxysmal dystonia is common. ## Management and treatment Early diagnosis of the syndrome is essential, as effective treatment of the gastro-oesophageal reflux (by pharmacological therapy or surgical intervention) leads to resolution of the movement disorder. ## Prognosis The prognosis for patients is good. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Sandifer syndrome	c0338465	30,507	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=71272	2021-01-23T17:34:11	{"gard": ["9684"], "mesh": ["C537234"], "umls": ["C0338465"], "icd-10": ["G24.8"]}
A number sign (#) is used with this entry because this form of limb-girdle muscular dystrophy-dystroglycanopathy (type C3; MDDGC3), also known as LGMDR15 and LGMD2O, is caused by homozygous mutation in the gene encoding protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGNT1; 606822) on chromosome 1p34. Mutation in the POMGNT1 gene can also cause a severe congenital muscular dystrophy with brain and eye anomalies (type A3; MDDGA3; 253280) and congenital muscular dystrophy-dystroglycanopathy with mental retardation (type B3; MDDGB3; 613151). Description MDDGC3 is a rare form of autosomal recessive limb-girdle muscular dystrophy with normal cognition (Clement et al., 2008). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308). Clinical Features Clement et al. (2008) reported an Irish girl with limb-girdle muscular dystrophy. She first developed proximal limb muscle weakness at age 12 years, showing difficulty rising from a sitting position and climbing stairs. The weakness progressed rapidly; by the time the patient was 14 years old, it was more proximal than distal, with the neck, hip girdle, and shoulder abductor muscles particularly affected. She had positive Gowers sign and hypertrophy of the calves and quadriceps, with wasting of the hamstring and deltoid muscles. Other features included lordosis and tightening of the Achilles tendon. Muscle biopsy showed dystrophic changes with variable staining for glycosylated alpha-dystroglycan. She lost ambulation at age 19 years after a leg fracture. She also had myopia. Cognitive development and intelligence were normal. Clement et al. (2008) proposed the designation 'LGMD2M' for this phenotype. Raducu et al. (2012) reported an 11-year-old Belgian boy with limb-girdle muscular dystrophy without brain or eye anomalies. He had slightly delayed initial motor development and unsteady stance at age 2 years. Examination showed muscle weakness, slight generalized amyotrophy, a positive Gowers sign, and lack of reflexes. At age 7 to 8 years, he had lumbar hyperlordosis, difficulties in climbing stairs, and weakness of the shoulder muscles. Laboratory studies showed a mild elevation of serum creatine kinase, and muscle biopsy showed dystrophic changes and defects in alpha-dystroglycan staining. Ophthalmologic evaluation and brain MRI were normal. Molecular Genetics In an Irish girl with limb-girdle muscular dystrophy and normal intellect, Clement et al. (2008) identified a homozygous mutation in the POMGNT1 gene (D556N; 606822.0013). In an 11-year-old Belgian boy with limb-girdle muscular dystrophy without brain or eye anomalies, Raducu et al. (2012) identified a homozygous 9-bp duplication upstream of the transcriptional start site of the POMGNT1 gene (606822.0017). Transfection of the mutation in COS-7 and HEK293T cells resulted in a 75% decrease in promoter activity compared to wildtype. In vitro studies demonstrated that the mutation generated an additional binding site for the transcriptional repressor ZNF202 (603430), resulting in the downregulation of POMGNT1 gene expression and, ultimately, defective glycosylation. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Myopia (in 1 patient) SKELETAL Spine \- Lordosis Limbs \- Distal joint contractures MUSCLE, SOFT TISSUES \- Muscle weakness, proximal \- Gowers sign \- Difficulty climbing stairs \- Muscle hypertrophy \- Wasting of the proximal muscles \- Fatigue \- Biopsy shows dystrophic changes \- Decreased glycosylation of alpha-dystroglycan NEUROLOGIC Central Nervous System \- Delayed motor development (1 patient) Peripheral Nervous System \- Arflexia (1 patient) LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Two unrelated patients have been reported (last curated October 2012) \- Onset in infancy or early childhood \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1 gene (POMGNT1, 606822.0013 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 3	c3150417	30,508	omim	https://www.omim.org/entry/613157	2019-09-22T15:59:33	{"doid": ["0110292"], "omim": ["613157"], "orphanet": ["206564"], "synonyms": ["MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 15", "MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2O", "LGMD2O", "Alternative titles", "MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY, LIMB-GIRDLE, POMGNT1-RELATED"]}
## Description Multinodular goiter is a common disorder characterized by nodular enlargement of the thyroid gland (summary by Takahashi et al., 2001). For additional phenotypic information and a discussion of genetic heterogeneity of multinodular goiter, see MNG1 (138800). Clinical Features Takahashi et al. (2001) reported 2 unrelated Japanese multigeneration families with multinodular goiter with euthyroidism and high plasma thyroid-stimulating hormone. The propositi, 3- and 8-year-old girls, were found during a mass screening. The clinical examinations and testing suggested impaired hormonogenesis but excluded known defects in iodine transport and organification as well as deficiency of hydrogen peroxide and thyroid peroxidase. Inheritance The transmission pattern of multinodular goiter in 2 unrelated Japanese families was consistent with autosomal dominant inheritance (Takahashi et al., 2001). Mapping By linkage analysis in 2 unrelated Japanese families segregating multinodular goiter, Takahashi et al. (2001) found linkage of the disorder to D3S1618 (theta = 0.0) on chromosome 3q26.1-q26.3 with a 2-point lod score of 3.62 (1.81 for each family) and a multipoint lod score of 3.61 (1.80 for each family). Haplotype analysis delimited an 18-cM interval between D3S1565 and D3S3686. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	GOITER, MULTINODULAR 3	c1853686	30,509	omim	https://www.omim.org/entry/606082	2019-09-22T16:10:47	{"mesh": ["C565260"], "omim": ["606082"]}
Irritant folliculitis SpecialtyDermatology Irritant folliculitis is a cutaneous condition and usually occurs following the application of topical medications.[1] ## See also[edit] * Irritant diaper dermatitis * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Irritant folliculitis	None	30,510	wikipedia	https://en.wikipedia.org/wiki/Irritant_folliculitis	2021-01-18T18:51:58	{"wikidata": ["Q6073877"]}
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, variable degrees of intellectual disability, and facial dysmorphism (including high nasal bridge, deep-set eyes, and wide mouth), often associated with feeding difficulties and/or gastroesophageal reflux. Additional reported manifestations are seizures, hypotonia, autistic features, and joint laxity. Brain imaging may show non-specific features (such as cerebral atrophy). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	STAG1-related intellectual disability-facial dysmorphism-gastroesophageal reflux syndrome	c4539951	30,511	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=502434	2021-01-23T16:56:37	{"omim": ["617635"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Smith–Fineman–Myers syndrome" – news · newspapers · books · scholar · JSTOR (August 2010) (Learn how and when to remove this template message) Smith–Fineman–Myers syndrome Other namesX-linked mental retardation-hypotonic facies syndrome 1 (MRXHF1), Carpenter–Waziri syndrome, Chudley–Lowry syndrome, SFMS, Holmes–Gang syndrome and Juberg–Marsidi syndrome (JMS),[1][2] Smith–Fineman–Myers syndrome has an X-linked recessive pattern of inheritance. Smith–Fineman–Myers syndrome (SFMS1) is a congenital disorder that causes birth defects. This syndrome was named after Richard D. Smith, Robert M. Fineman and Gart G. Myers who discovered it around 1980.[3] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatments * 5 History * 6 References * 7 External links ## Signs and symptoms[edit] Facial deformities with Smith-Fineman-Myers syndrome SFMS affects the skeletal and nervous system. This syndrome's external signs would be an unusual facial appearance with their heads being slightly smaller and unusually shaped, a narrow face which is also called dolichocephaly, a large mouth with a drooping lower lip that are held open, protruding upper jaw, widely spaced upper front teeth, an underdeveloped chin, cleft palate and exotropied-slanted eyes with drooping eyelids. Males who have SFMS have short stature and a thin body build. Also skin is lightly pigmented with multiple freckles. They may have scoliosis and chest abnormalities. Affected boys have reduced muscle tone as infants and young children. X-rays sometimes show that their bones are underdeveloped and show characteristics of younger bones of children. Boys usually under the age of 10 have reduced muscle tone but later, patients with SFMS over the age of 10 have increased muscle tone and reflexes that cause spasticity. Their hands are short with unusual palm creases with short, shaped fingers and foot abnormalities are shortened and have fused toes and usually mild. They have an absent of a spleen and the genitals may also show undescended testes ranging from mild to severe that leads to female gender assignment. People who have SFMS have severe mental retardation. They are sometimes restless, behavior problems, seizures and severe delay in language development. They are self-absorbed with reduced ability to socialize with others around them. They also have psychomotor retardation which is the slowing-down of thoughts and a reduction of physical movements. They have cortical atrophy or degeneration of the brain's outer layer. Cortical atrophy is usually founded in older affected people.[4] ## Genetics[edit] SFMS is an X-linked disease by chromosome Xq13. X-linked diseases map to the human X chromosome because this syndrome is an X chromosome linked females who have two chromosomes are not affected but because males only have one X chromosome, they are more likely to be affected and show the full clinical symptoms. This disease only requires one copy of the abnormal X-linked gene to display the syndrome. Since females have two X chromosomes, the effect of one X chromosome is recessive and the second chromosome masks the affected chromosome.[5] Affected fathers can never pass this X-linked disease to their sons but affected fathers can pass the X-linked gene to their daughters who has a 50% chance to pass this disease-causing gene to each of her children. Since females who inherit this gene do not show symptoms, they are called carriers. Each of the female's carrier's son has a 50% chance to display the symptoms but none of the female carrier's daughters would display any symptoms.[4] Some patients with SFMS have been founded to have a mutation of the gene in the ATRX on the X chromosome, also known as the Xq13 location. ATRX is a gene disease that is associated with other forms of X-linked mental retardation like Alpha-thalassemia/mental retardation syndrome, Carpenter syndrome, Juberg-Marsidi syndrome, and soastic paraplegia. It is possible that patients with SFMS have Alpha-thalassemia/mental retardation syndrome without the affected hemoglobin H that leads to Alphathalassemia/ mental retardation syndrome in the traditionally recognized disease.[5] ## Diagnosis[edit] The assessment for Smith-Finemen-Myers syndrome like any other mental retardation includes a detailed family history and physical exam that tests the mentality of the patient. The patient also gets a brain and skeletal imaging though CT scans or x-rays. They also does a chromosome study and certain other genetic biochemical tests to help figure out any other causes for the mental retardation. The diagnosis of SFMS is based on visible and measurable symptoms. Until 2000, SFMS was not known to be associated with any particular gene. As of 2001, scientists do not yet know if other genes are involved in this rare disease. Generic analysis of the ATRX gene may prove to be helpful in diagnosis of SFMS.[6] ## Treatments[edit] Treatments are usually based on the individuals symptoms that are displayed. The seizures are controlled with anticonvulsant medication. For the behavior problems, the doctors prescribe a few medications and behavioral modification routines that involve therapists and other types of therapy. Even if mental retardation is severe, it does not seem to shorten the lifespan of the patient or to get worse with age. ## History[edit] On September 15, 1991 in Sydney, Australia at the Prince of Wales Children's Hospital, reported on two brothers with a distinct facial appearance, severe mental retardation, short stature, cryptorchidism (undescended testicle), asplenia in one (absent spleen), dramatic failure to thrive, early hypotonia, and later hypertonia, all suggestive of the Smith–Fineman–Myers syndrome. All five of the reported cases have been males, suggesting X-linked inheritance.[7] On September 23, 1998 at the Hospital Injury Research and Rehabilitation at the University of São Paulo in Bauru, Brazil report on two boys, monozygotic twins born to normal and non consanguineous parents, presenting with an unusual facial appearance, cortical atrophy, dolichocephaly, short stature, cleft palate, micrognathia, prominent upper central incisors, bilateral Sidney line, minor foot deformities, unstableness in walking, early hypotonia, hyperreflexia, hyperactivity, psychomotor retardation, and severe delay in language development. These symptoms resemble those previously described in the Smith–Fineman–Myers syndrome.[8] ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 309580 2. ^ Saugier-Veber P, Abadie V, Moncla A, et al. (June 1993). "The Juberg-Marsidi syndrome maps to the proximal long arm of the X chromosome (Xq12-q21)". American Journal of Human Genetics. 52 (6): 1040–5. PMC 1682258. PMID 8503439. 3. ^ http://www.whonamedit.com/synd.cfm/2227.html[full citation needed] 4. ^ a b http://health.yahoo.net/galecontent/smith-fineman-myers-syndrome[full citation needed] 5. ^ a b http://www.bookrags.com/research/smith-fineman-myers-syndrome-wog/[full citation needed] 6. ^ http://www.rightdiagnosis.com/s/smith_fineman_myers_syndrome_1/tests.htm[full citation needed] 7. ^ Adès LC, Kerr B, Turner G, Wise G (September 1991). "Smith-Fineman-Myers syndrome in two brothers". American Journal of Medical Genetics. 40 (4): 467–70. doi:10.1002/ajmg.1320400419. PMID 1684092. 8. ^ Guion-Almeida ML, Tabith A, Kokitsu-Nakata NM, Zechi RM (September 1998). "Smith-Fineman-Myers syndrome in apparently monozygotic twins". American Journal of Medical Genetics. 79 (3): 205–8. doi:10.1002/(SICI)1096-8628(19980923)79:3<205::AID-AJMG11>3.0.CO;2-L. PMID 9788563. ## External links[edit] Classification D * OMIM: 309580 * MeSH: C537445 * DiseasesDB: 32665 * SNOMED CT: 719212004 External resources * Orphanet: 93974 * v * t * e X-linked disorders X-linked recessive Immune * Chronic granulomatous disease (CYBB) * Wiskott–Aldrich syndrome * X-linked severe combined immunodeficiency * X-linked agammaglobulinemia * Hyper-IgM syndrome type 1 * IPEX * X-linked lymphoproliferative disease * Properdin deficiency Hematologic * Haemophilia A * Haemophilia B * X-linked sideroblastic anemia Endocrine * Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy * KAL1 Kallmann syndrome * X-linked adrenal hypoplasia congenita Metabolic * Amino acid: Ornithine transcarbamylase deficiency * Oculocerebrorenal syndrome * Dyslipidemia: Adrenoleukodystrophy * Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency * Pyruvate dehydrogenase deficiency * Danon disease/glycogen storage disease Type IIb * Lipid storage disorder: Fabry's disease * Mucopolysaccharidosis: Hunter syndrome * Purine–pyrimidine metabolism: Lesch–Nyhan syndrome * Mineral: Menkes disease/Occipital horn syndrome Nervous system * X-linked intellectual disability: Coffin–Lowry syndrome * MASA syndrome * Alpha-thalassemia mental retardation syndrome * Siderius X-linked mental retardation syndrome * Eye disorders: Color blindness (red and green, but not blue) * Ocular albinism (1) * Norrie disease * Choroideremia * Other: Charcot–Marie–Tooth disease (CMTX2-3) * Pelizaeus–Merzbacher disease * SMAX2 Skin and related tissue * Dyskeratosis congenita * Hypohidrotic ectodermal dysplasia (EDA) * X-linked ichthyosis * X-linked endothelial corneal dystrophy Neuromuscular * Becker's muscular dystrophy/Duchenne * Centronuclear myopathy (MTM1) * Conradi–Hünermann syndrome * Emery–Dreifuss muscular dystrophy 1 Urologic * Alport syndrome * Dent's disease * X-linked nephrogenic diabetes insipidus Bone/tooth * AMELX Amelogenesis imperfecta No primary system * Barth syndrome * McLeod syndrome * Smith–Fineman–Myers syndrome * Simpson–Golabi–Behmel syndrome * Mohr–Tranebjærg syndrome * Nasodigitoacoustic syndrome X-linked dominant * X-linked hypophosphatemia * Focal dermal hypoplasia * Fragile X syndrome * Aicardi syndrome * Incontinentia pigmenti * Rett syndrome * CHILD syndrome * Lujan–Fryns syndrome * Orofaciodigital syndrome 1 * Craniofrontonasal dysplasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Smith–Fineman–Myers syndrome	c0796159	30,512	wikipedia	https://en.wikipedia.org/wiki/Smith%E2%80%93Fineman%E2%80%93Myers_syndrome	2021-01-18T19:05:46	{"gard": ["81"], "mesh": ["C537445"], "umls": ["C0796159"], "orphanet": ["93974"], "wikidata": ["Q7545701"]}
A number sign (#) is used with this entry because OKT4 epitope deficiency is caused by a polymorphism in the CD4 gene (186940). Clinical Features The OKT monoclonal antibodies are widely used for the analysis of human peripheral blood T lymphocytes. OKT3 reacts with virtually all peripheral T cells; OKT4 with T-helper/inducer cells; and OKT8 with T-cytotoxic/suppressor cells. Bach et al. (1981) described 2 black Americans whose lymphocytes were unreactive with OKT4. Karol et al. (1984) described 2 unrelated black persons whose lymphocytes showed virtual absence of the OKT4 epitope. Neither had manifestations of defective Th function. The parents and children of affected individuals showed about 50% of the normal number of OKT4 sites on their lymphocytes. Fukuda et al. (1984) studied 2 families in which OKT4-positive T cells were absent. In each family 3 sibs had complete lack of OKT4-positive cells. In all children of such persons studied, the percentage of OKT4-positive cells was normal, but these cells showed half-normal intensity of immunofluorescence. Responses to phytohemagglutinin and pokeweed antigen were normal. No autoantibodies to OKT4 were found in the serum of the presumed homozygotes. The probands had Graves disease (see 275000); they were discovered in the course of a study of surface markers on lymphocytes of patients with autoimmune thyroid disease. Polymorphism of the T4 epitope was recognized by Fuller et al. (1984), Karol et al. (1984), Sato et al. (1984), and Stohl and Kunkel (1984). OKT4 epitope deficiency is inherited in a codominant manner. To the time of the report by Stohl et al. (1985), it had been detected only in blacks. Stohl and Kunkel (1984) presented evidence suggesting that deficiency of the T4 epitope in homozygous state predisposes to systemic lupus erythematosus with lymphadenopathy as a particular clinical feature (see 152700). Gill et al. (1985) found absent OKT4 lymphocyte antigen in 2 black sibs. There was no defect in binding of Leu 3a/3b antibody, and the sibs had no unusual frequency of infections. They cited 5 other reports; 4 were also in blacks and 1 was in Japanese. Takenaka et al. (1993) studied a large Japanese family in which some members were homozygous or heterozygous for OKT4 epitope deficiency. The deficiency was transmitted as an autosomal codominant trait. The OKT4 epitope was not needed for internalization of CD4 molecules, and IL2 (147680) production was similar in homozygote, heterozygote, and normal individuals. Hughes et al. (1994) used flow cytometry analysis to study OKT4 epitope deficiency in healthy black South African children. They concluded that there is considerable risk of underestimating the number of CD4-positive cells in black South Africans if the OKT4 monoclonal antibody is used. Mapping OKT4 epitope deficiency is caused by a polymorphism in the CD4 gene, which Gross (2011) mapped to chromosome 12p13.31. Molecular Genetics In African American, Caucasian, and Japanese individuals with OKT4 epitope deficiency, Hodge et al. (1991) identified a C-to-T change at nucleotide 868 of the CD4 gene, resulting in an arg240-to-trp (R240W; 186940.0001) substitution. Independently, Lederman et al. (1991) and Takenaka et al. (1993) identified the R240W substitution as the cause of OKT4 epitope deficiency. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	OKT4 EPITOPE DEFICIENCY	c3151379	30,513	omim	https://www.omim.org/entry/613949	2019-09-22T15:57:00	{"omim": ["613949"], "synonyms": ["Alternative titles", "T4 EPITOPE DEFICIENCY"]}
Spastic diplegia cerebral palsy is a form of cerebral palsy, a neurological condition that usually appears in infancy or early childhood, and permanently affects muscle control and coordination. Affected people have increased muscle tone which leads to spasticity (stiff or tight muscles and exaggerated reflexes) in the legs. The arm muscles are generally less affected or not affected at all. Other signs and symptoms may include delayed motor or movement milestones (i.e. rolling over, sitting, standing); walking on toes; and a "scissored" gait (style of walking). As with other types of cerebral palsy, spastic diplegia is usually caused by brain damage, which generally happens before, during, or shortly after birth. Babies born prematurely and with low birth weight are at a higher risk of developing cerebral palsy. The exact cause is often unknown; however, the condition has been associated with genetic abnormalities; congenital brain malformations; maternal infections or fevers; and/or injury before, during or shortly after birth. There is no cure, and treatment options vary depending on the signs and symptoms present in each person and the severity of the condition, and may include physical, occupational and speech therapy, medication and surgery. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Spastic diplegia cerebral palsy	c0270804	30,514	gard	https://rarediseases.info.nih.gov/diseases/9637/spastic-diplegia-cerebral-palsy	2021-01-18T17:57:39	{"mesh": ["C537945"], "synonyms": ["Cerebral palsy spastic diplegic"]}
Achalasia microcephaly Chest x-ray of an individual with achalasia. The arrows point to the areas of extreme esophageal dilation. SymptomsManifestation of achalasia: regurgitation, vomiting and dysphagia, alongside diagnosis of microcephaly: abnormally small head size below the third percentile as well as mild to moderate mental retardation. Frequency9 children between 1980-2017 Achalasia microcephaly syndrome is a rare condition whereby achalasia in the oesophagus manifests alongside microcephaly and mental retardation. This is a rare constellation of symptoms with a predicted familial trend.[1] The main signs of achalasia microcephaly syndrome involve the manifestation of each individual disease associated with the condition. Microcephaly can be primary, where the brain fails to develop properly during pregnancy, or secondary, where the brain is normal sized at birth but fails to grow as the child ages.[2] Abnormalities will be observed progressively after birth whereby the child will display stunted growth and physical and cognitive development. The occipital-frontal circumference will be at or near the extreme lower end, the third percentile, indicating microcephaly.[3] There are both genetic and behavioural causes of microcephaly.[2] Achalasia, or oesophageal achalasia, is a disorder occurring in the lower oesophageal sphincter (LES). The LES fails to relax completely, resulting in frequent vomiting and regurgitation, usually one to two hours after meals.[4][3] If untreated, the long-term health of the individual will be compromised, leading to the development of dysphagia, weight loss and chronic aspiration.[4] It is very rare in children, especially siblings.[3] Mortality, specifically in young children, can occur.[3] Due to the nature of the individual diseases, there is no cure for achalasia microcephaly. Treatment for achalasia involves drugs and surgical intervention, such as heller myotomy, with the goal of relieving LES pressure and its symptoms. Management of these symptoms are important for the maintenance of the quality of life of the child and the prevention of the progression to more serious complications. These include organ perforation, aspiration pneumonia and death.[4][5][6] Similarly, there is no cure for microcephaly and instead, early intervention, such as speech and physical therapy is recommended[7] Families who have a genetic predisposition to microcephaly can involve genetic counselling in their planning for pregnancy[8] As of 2017, there are 5 reported cases of achalasia microcephaly syndrome, all of which involve children.[6] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Mechanism * 4 Diagnosis * 4.1 Achalasia * 4.1.1 Barium swallow * 4.1.2 Oesophageal manometry * 4.2 Microcephaly * 5 Management * 5.1 Achalasia * 5.2 Microcephaly * 6 Epidemiology * 7 Research * 8 See also * 9 References ## Signs and symptoms[edit] A comparison between the approximate head size of a baby with microcephaly (left) and a normal disposition (right). The main symptoms of achalasia microcephaly syndrome are the progressive manifestation of the major symptoms associated with the individual diseases, in young children. Achalasia causes dysphagia, which leads to difficulties when eating, frequent vomiting after meals and possible respiratory arrest due to chronic aspiration.[4][9][6] Symptoms can manifest at ages as young as six weeks.[6] Alongside prominent dysphagia, the child will have microcephaly, which is characterised by an abnormally small head. Mild scaphocephaly may also be observed.[3] This can manifest upon or after birth.[2] Slow cognitive and fine motor development as well as delayed speech will be observed.[3][6] Craniofacial dysmorphism, such as a globular-shaped nose, micrognathia and a flattened forehead may also be involved, but is not observed in all cases.[9][6] Camptodactyly of some fingers can also manifest.[10] ## Cause[edit] Achalasia microcephaly has only been reported in children, despite achalasia being associated as an adult disease.[3] The first case involved an affected family of four children, three sisters and one brother, from northwest Mexico.[11][12] All three sisters underwent the Heller procedure in order to relieve vomiting and regurgitation due to achalasia. The brother passed away at four and a half years old,[12] due to the improper diagnosis of recurrent vomiting and resultant malnourishment. All siblings had slow to moderate cognitive development within the mentally retarded criteria.[12] Both parents were unaffected and were from the same small village. The second case involved two affected brothers, aged seven and nine, from Libya, in a family of six children.[3] By the age of two, both children were vomiting and regurgitating recurrently, had slow development and suffered from pneumonitis. They also displayed mild micrognathia and scaphocephaly.[3] The elder son underwent a modified Heller's operation at age six. Their parents were first cousins, however, chromosomal studies did not observe any abnormalities.[3] The third examined case was an affected nine-year-old boy born to unaffected parents who were from the same north-western Mexican area as the first reported case.[10] It is denied but implicated that the parents were closely related. Abnormalities in motor function, physical appearance and difficulties during feeding manifested after birth.[10] By eight months, psychomotor retardation was prominent and at nine months, malnourishment was extreme and so oesophagomyotomy (Heller myotomy) was performed.[10] At eighteen months, microcephaly was revealed.[10] The fourth case study involved an affected German child.[9] Unlike previous cases, the condition was attributed to the anti-malaria drug, Mefloquine, which was prescribed during pregnancy. There is no apparent genetic correlation between parents.[9] At eight weeks, the child was officially diagnosed with microcephaly and displayed craniofacial dysmorphism and muscular hypotonia similar to previous cases. Vomiting, seizures and respiratory arrest were common. It was noted that only 5.4% of pregnancies under the medication of Mefloquine experienced abnormalities.[9] This is the first case involving a person of European descent. The fifth, most recent case, involved a girl born to consanguineous parents from Pakistan. There was no history of abnormalities or genetic disorders in previous children in the family.[6] Gestational diabetes during the pregnancy did not cause any significant complications. Feeding difficulties and recurrent vomiting began to occur at six weeks, resulting in severe weight loss.[6] The girl received surgery and repeated balloon dilatations by the age of two for severe achalasia. She was diagnosed with microcephaly at age six after concerns for her delayed fine motor skills and limited understanding of speech.[6] ## Mechanism[edit] Achalasia is a neurodegenerative disease characterised by the degeneration of neurones of the myenteric plexus which are responsible for the motility of the digestive tract.[13] It is extremely rare in children and normally affects the lower oesophageal sphincter (LES).[6][13] LES contraction prevents acid reflux while relaxation allows food to enter the stomach.[13] Impaired LES relaxation therefore leads to dysphagia, as the oesophagus cannot be emptied.[13] Familial achalasia, whereby achalasia manifests among siblings, is noted in families displaying consanguinity or inbreeding as the disease can be passed on as an autosomal recessive trait.[14] Microcephaly can manifest due to a variety of reasons, these include: TORCH infections, chromosomal and biochemical abnormalities and can be transmitted as an autosomal recessive, dominant or X-linked disorder.[12] It is most commonly caused by congenital infections due to viruses such as cytomegalovirus, herpes simplex virus and Zika virus.[15] The severe reduction of neural progenitors and neurones as a result of cell cycle arrest and neural progenitor death due to viral infection leads to microcephaly.[15] There are two types of microcephaly, primary, occurring before thirty-two weeks of gestation or secondary, after birth.[2] A reduced production of neurones is attributed to primary microcephaly whilst decreased dendritic connection is thought to cause secondary microcephaly, all amounting to an estimated brain size that is significantly smaller than average.[2] Further, the cerebral cortex occupies 55% of the human brain, therefore, most microcephalic people are mentally retarded.[2][4] Developmental delay in motor and communication skills will result.[4] Congenital microcephaly has also been attributed to serine deficiencies that cause defects in two known enzymes: 3-phosphogycerate dehydrogenase and 3-phosphoserine phosphatase, leading to severe neurological abnormalities[16] Like familial achalasia, microcephaly has an autosomal recessive predisposition.[15] Although no disease-causing gene has been identified, studies suggest that due to the consanguinity or close relatedness of parents observed in four out of five cases, achalasia microcephaly might be inherited via an autosomal recessive gene.[1][10] ## Diagnosis[edit] Barium swallow procedure commonly used for the diagnosis of achalasia. Symptoms of achalasia can be detected by fluoroscopy during barium swallow or oesophageal manometry.[4] ### Achalasia[edit] #### Barium swallow[edit] A positive barium swallow will display the narrowing of the distal oesophagus in a ‘bird beak’ or ‘champagne class’ fashion, aperistalsis, minimal LES opening and oesophageal dilation as the main indicator of the disease.[4][5] Minimal barium will be present in the stomach.[5] However, these diagnostic findings are not always present in the early onset of the disease and so a normal oesophagogram is not an indication of a lack of disease.[5] #### Oesophageal manometry[edit] Patients who suffer from the vigorous achalasia variant of the disease, do not express dilation.[4] Manometry is the best, most sensitive method in these cases as it can diagnose abnormalities related to achalasia based on basal pressure, without the need for the manifestation of dilation.[4][5] Aperistalsis and a poorly relaxed and hypertensive LES is required for a positive diagnosis.[5] ### Microcephaly[edit] Prenatal diagnosis of microcephaly is difficult due to the variability present in the causes of the disease.[8] Early detection, however, is important for consanguineous parents as an autosomal recessive inheritance is highly implicated for microcephaly.[12][8] Anomaly scans during pregnancy can be used to calculate the ratio between the head/abdominal circumference and head circumference/femur length which are used calculate and diagnose microcephaly.[8] Ultrasound scans have also led to the accidental discovery of microcephaly, however this occurrence is an anomaly.[8] Women who are at risk of contracting TORCH infections or exposure to Zika virus are recommended to undergo screening as most resultant infections are asymptomatic.[17] This includes testing sera and saliva for viral antigens.[17] Prenatal diagnosis is further complicated when microcephaly manifests with achalasia as it is only possible to detect symptoms shortly after the first trimester and early into the second.[8] Consequently, microcephaly is usually diagnosed after the onset of achalasia by eighteen months or older.[10] An occipital-frontal head circumference of less than three standard deviations is an indication of microcephaly.[2] Radiography and NMR imaging of the skull can also be utilised.[9] A physical examination of height and weight proportions as well as IQ and motor development is implemented for further confirmation as not all children with microcephaly have abnormal development[3][15] A positive test will show normal to abnormal proportions, a low IQ and slow motor development. ## Management[edit] There is currently no treatment to reverse the neuropathology of achalasia or the effects of microcephaly. Instead, treatment focuses on the management of associated symptoms. ### Achalasia[edit] There are no medical interventions that allow the restoration of neurons in the myenteric plexus.[5] Thus, early diagnosis of achalasia is crucial for the prevention of the progression of the disease to severe stages of aspiration pneumonia and organ perforation.[5] Current treatment for achalasia symptoms focuses on the reduction of LES pressure to relieve dysphagia and therefore prevent further regurgitation, vomiting and aspiration.[4] These include drugs such as anticholinergics and calcium channel blockers, mechanical dilation with a balloon dilator, or heller myotomy surgery.[4][5][6] Botulinum toxin injections have been most successful in patients with vigorous achalasia and for those with unclear diagnosis.[5] Follow up treatment involving re-dilatation or barium swallow is essential to monitor and prevent progression of disease severity.[5] ### Microcephaly[edit] Early intervention involving speech pathology and occupational therapy can assist in addressing associated motor and speech dysfunction displayed by the child.[7] Genetic counselling is utilised by families who are concerned or at a high risk of carrying genes for microcephaly.[8] Congenital microcephaly due to serine deficiency can be treated by L-serine or L-serine with glycine in order to improve debilitating symptoms such as seizures and psychomotor retardation.[16] Exogenous growth hormones can be used to boost development in microcephalic patients.[18] ## Epidemiology[edit] Familial achalasia alone is scarce, especially in paediatric cases.[19] Consequently, achalasia microcephaly, which has a familial predisposition, is an extremely rare syndrome. Current cases of achalasia microcephaly have only implicated children in its pathogenesis and there are only five, separate, known cases as of 2017. These cases involve a total of nine children, where each case refers to individual affected families. All cases, except for one, involves consanguineous parents. ## Research[edit] Knowledge of genes directly associated with achalasia microcephaly are unknown. However, genetic research is targeted towards the disease causing genes implicated in the manifestation of the individual diseases that arise alongside achalasia.[1] These include recent breakthroughs that implicate 3-phosphoglycerate dehydrogenase in causing congenital microcephaly, severe retardation and seizures.[16] Treatment with L-serine coupled with early diagnosis have shown favourable outcomes.[16] Studies implicate that biological disturbances in the pathways downstream of these candidate genes can lead to the development of achalasia.[1] It is suggested that the disease has roots in neurological dysfunction due to the co-occurrence of microcephaly, the progressive narrowing of the oesophagus in the early stages of life and intellectual disability.[6] Whole-exosome and whole-genome sequencing is proposed for the discovery of the underlying genetic cause of achalasia microcephaly.[6] The familial trend of disease manifestation between siblings along with consanguinity in majority of cases is consistent with an autosomal recessive inheritance.[12][3] ## See also[edit] * Esophageal achalasia * Microcephaly ## References[edit] 1. ^ a b c d Gockel HR, Schumacher J, Gockel I, Lang H, Haaf T, Nöthen MM (October 2010). "Achalasia: will genetic studies provide insights?". Human Genetics. 128 (4): 353–64. doi:10.1007/s00439-010-0874-8. PMID 20700745. S2CID 583462. 2. ^ a b c d e f g Woods CG (February 2004). "Human microcephaly". Current Opinion in Neurobiology. 14 (1): 112–7. doi:10.1016/j.conb.2004.01.003. PMID 15018946. S2CID 30096852. 3. ^ a b c d e f g h i j k l Khalifa MM (October 1988). "Familial achalasia, microcephaly, and mental retardation. Case report and review of literature". Clinical Pediatrics. 27 (10): 509–12. doi:10.1177/000992288802701009. PMID 3048841. S2CID 40020496. 4. ^ a b c d e f g h i j k l Spiess, A.E; Kahrilas, P.J (1998). "Treating achalasia: from whalebone to laparoscope". Journal of the American Medical Association. 280 (7): 638–642. doi:10.1001/jama.280.7.638. PMID 9718057. 5. ^ a b c d e f g h i j k Pohl, D; Tutuian, R (2007). "Achalasia: an Overview of Diagnosis and Treatment". Journal of Gastrointestinal and Liver Diseases. 16 (3): 297–303. PMID 17925926. 6. ^ a b c d e f g h i j k l m Wafik M, Kini U (July 2017). "Achalasia-microcephaly syndrome: a further case report". Clinical Dysmorphology. 26 (3): 190–192. doi:10.1097/MCD.0000000000000181. PMID 28471776. 7. ^ a b "Microcephaly Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". 2016-03-11. Archived from the original on 2016-03-11. Retrieved 2019-05-27. 8. ^ a b c d e f g Hollander, N.S.D.; Wessels, M.W.; Los, F.J.; Ursem, N.T.C.; Niermeijer, M.F.; Wladimiroff, J.W. (2000). "Congenital microcephaly detected by prenatal ultrasound: genetic aspects and clinical significance". Ultrasound in Obstetrics and Gynecology. 15 (4): 282–287. doi:10.1046/j.1469-0705.2000.00092.x. ISSN 0960-7692. PMID 10895445. 9. ^ a b c d e f Kreuz FR, Nolte-Buchholtz S, Fackler F, Behrens R (October 1999). "Another case of achalasia-microcephaly syndrome". Clinical Dysmorphology. 8 (4): 295–7. doi:10.1097/00019605-199910000-00012. PMID 10532181. 10. ^ a b c d e f g Hernández A, Reynoso MC, Soto F, Quiñones D, Nazará Z, Fragoso R (December 1989). "Achalasia microcephaly syndrome in a patient with consanguineous parents: support for a.m. being a distinct autosomal recessive condition". Clinical Genetics. 36 (6): 456–8. doi:10.1111/j.1399-0004.1989.tb03376.x. PMID 2591072. S2CID 2186970. 11. ^ Williams JJ, Sandlin CS, Dumars KW (1978). "New syndrome: microcephaly associated with achalasia". American Journal of Human Genetics. 30: 106. 12. ^ a b c d e f Dumars KW, Williams JJ, Steele-Sandlin C (1980). "Achalasia and microcephaly". American Journal of Medical Genetics. 6 (4): 309–14. doi:10.1002/ajmg.1320060408. PMID 7211947. 13. ^ a b c d Gockel I, Müller M, Schumacher J (March 2012). "Achalasia--a disease of unknown cause that is often diagnosed too late". Deutsches Ärzteblatt International. 109 (12): 209–14. doi:10.3238/arztebl.2012.0209. PMC 3329145. PMID 22532812. 14. ^ Monnig PJ (June 1990). "Familial achalasia in children". The Annals of Thoracic Surgery. 49 (6): 1019–22. doi:10.1016/0003-4975(90)90897-f. PMID 2369177. 15. ^ a b c d Devakumar D, Bamford A, Ferreira MU, Broad J, Rosch RE, Groce N, Breuer J, Cardoso MA, Copp AJ, Alexandre P, Rodrigues LC, Abubakar I (January 2018). "Infectious causes of microcephaly: epidemiology, pathogenesis, diagnosis, and management" (PDF). The Lancet. Infectious Diseases. 18 (1): e1–e13. doi:10.1016/s1473-3099(17)30398-5. PMID 28844634. 16. ^ a b c d de Koning, T.J.; Duran, M; van Maldergem, L; Pineda, M; Dorland, L; Gooskens, R; Jaeken, J; Poll-The, B.T (2002). "Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: Outcome of treatment with amino acids". Journal of Inherited Metabolic Disease. 25 (2): 119–125. doi:10.1023/A:1015624726822. PMID 12118526. S2CID 24655366. 17. ^ a b Baud, D; Van Mieghem, T; Musso, D; Truttmann, A.C; Panchaud, A; Vouga, M (2016). "Clinical management of pregnant women exposed to Zika virus". The Lancet Infectious Diseases. 16 (5): 523. doi:10.1016/S1473-3099(16)30008-1. PMID 27056096. 18. ^ Spadoni GL, Cianfarani S, Bernardini S, Fabrizio V, Galasso C, Boscherini B (November 1989). "Growth hormone treatment in children with sporadic primary microcephaly". American Journal of Diseases of Children. 143 (11): 1282–3. doi:10.1001/archpedi.1989.02150230040019. PMID 2816854. 19. ^ Polonsky, L; Guth, P.H (1970). "Familial achalasia". The American Journal of Digestive Diseases. 15 (3): 291–295. doi:10.1007/BF02233464. ISSN 0002-9211. PMID 5435950. 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A number sign (#) is used with this entry because of evidence that the corner fracture type of spondylometaphyseal dysplasia (SMDCF) is caused by heterozygous mutation in the fibronectin gene (FN1; 135600) on chromosome 2q35. Description The corner fracture type of spondylometaphyseal dysplasia is characterized by flake-like, triangular, or curvilinear ossification centers at the edges of irregular metaphyses that simulate fractures. These 'corner fractures,' which involve the distal tibia, the ulnar aspect of the distal radius, the proximal humerus, and the proximal femur, represent irregular ossification at the growth plates and secondary ossification centers. They become larger in older children and disappear after growth has stopped. In addition, severe scoliosis has been observed in FN1-associated SMDCF, whereas developmental coxa vara is less often seen, and odontoid abnormalities have not been reported (Lee et al., 2017). Clinical Features In 11 patients, including a father and daughter and a mother and 2 children, Langer et al. (1990) described an apparently unique skeletal dysplasia associated with short stature and developmental coxa vara. Progressive hip deformity usually resulted in a significant disability requiring surgical correction. The diagnostic constellation comprised coxa vara, simulated 'corner fractures' of long tubular bones, and vertebral body abnormalities. They pictured x-rays of patients with large triangular fragments situated laterally in the distal tibial metaphyses on the ulnar aspect of the distal radius and in the proximal humerus. The vertebral body endplates were more convex than usual for the patient's age. Some hypoplasia of the anterior part of the bodies created an appearance of anterior wedging. By the time a gait disturbance was identified, at about 2 years of age, characteristic radiographic changes were present in the hips. Continued slippage of the femoral capital epiphysis resulted in an angle between the long axis of the femoral capital epiphysis and the femoral shaft of 90 degrees or less. This type of deformity is referred to as developmental coxa vara. Also called the Sutcliffe type of spondylometaphyseal dysplasia (SMD) (Sutcliffe, 1966), cases of SMD 'corner fractures' type were described by Felman et al. (1974), Langer et al. (1990), Kozlowski et al. (1992), and Currarino et al. (2000). The features of these cases were proportional short stature, mild vertebral abnormalities, developmental coxa vara in most cases, metaphyseal abnormalities that included flakelike, triangular, or curvilinear ossification centers at the edges of the metaphyses (corner fractures), and deficiency or absence of ossification of the odontoid process. Mild short stature in childhood was a feature. This type of SMD differs from the Kozlowski type (184252) by the presence of corner fractures, absence of marked platyspondyly, absence of kyphoscoliosis, and milder involvement of short tubular bones (Langer et al., 1990). Sutton et al. (2005) reported a mother and 2 sons with a dominantly inherited SMD with corner fractures and severe, congenital scoliosis but neither coxa vara nor odontoid abnormalities, which are usually found with the corner fracture type of SMD. Severe congenital scoliosis and short stature were present in all members of this family, suggesting that the disorder may represent a different dominantly inherited SMD. Lee et al. (2017) studied patients from 7 families with SMD and corner fractures who had mutations in the FN1 gene (see MOLECULAR GENETICS), including the family originally reported by Sutton et al. (2005). Noting that 7 of the 9 mutation-positive patients exhibited severe scoliosis and that developmental coxa vara was only observed in 3, Lee et al. (2017) suggested that these patients might represent a subtype of the classic Sutcliffe-type SMD. Molecular Genetics Using exome sequencing, Lee et al. (2017) identified heterozygous variants in the FN1 gene in 3 of 13 individuals with SMD and corner fractures (SMDCF). Mutations included C87P (135600.0004) in a mother a 2 sons (family 1), originally reported by Sutton et al. (2005), and Y240D (135600.0005) in a mother and daughter (family 4). Subsequently, they identified 4 more patients with de novo FN1 mutations, including C123R (135600.0006) in 2 patients (families 2 and 7). All of the FN1 variants involved highly conserved residues, and none was found in the ExAC database. Noting that FN1 mutations had previously been associated with glomerulopathy (GFND2; 601894), Lee et al. (2017) stated that none of the SMDCF patients showed any evidence of renal disease. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature CHEST Ribs Sternum Clavicles & Scapulae \- Pectus carinatum (in some patients) SKELETAL Spine \- Scoliosis \- Ovoid vertebral bodies Pelvis \- Coxa vara, developmental (in some patients) Limbs \- Irregular metaphyses \- Corner fractures \- Genu varum (in some patients) MOLECULAR BASIS \- Caused by mutation in the fibronectin-1 gene (FN1, 135600.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	SPONDYLOMETAPHYSEAL DYSPLASIA, CORNER FRACTURE TYPE	c0432221	30,516	omim	https://www.omim.org/entry/184255	2019-09-22T16:34:22	{"mesh": ["C535793"], "omim": ["184255"], "orphanet": ["93315"], "synonyms": ["Alternative titles", "SPONDYLOMETAPHYSEAL DYSPLASIA, SUTCLIFFE TYPE"]}
Aortopulmonary septal defect SpecialtyCardiology Aortopulmonary septal defect is a rare congenital heart disorder accounting for only 0.1-0.3% of congenital heart defects worldwide.[1] It is characterized by a communication between the aortic and pulmonary arteries, with preservation of two normal semilunar valves. It is the result of an incomplete separation of the aorticopulmonary trunk that normally occurs in early fetal development with formation of the spiral septum.[2] Aortopulmonary septal defects occur in isolation in about half of cases, the remainder are associated with more complex heart abnormalities.[3] ## Contents * 1 Causes * 2 Diagnosis * 2.1 Subtypes * 3 Management * 4 References * 5 External links ## Causes[edit] This section is empty. You can help by adding to it. (March 2017) ## Diagnosis[edit] ### Subtypes[edit] There are numerous types, differentiated by the extent of the defect.[3] These types are: * Type I: simple defects leading to communication between the ascending aorta and pulmonic trunk * Type II: defects that extend to the origin of the right pulmonary artery * Type III: anomalous origin of the right pulmonary artery from the ascending aorta It is also classified as simple or complex. Simple defects are those that do not require surgical repair, occur with no other defects, or those that require minor stright-forward repair (ductus arteriosus, atrial septal defect). Complex defects are those that occur with other anatomical anomalies or require non-standard repair. ## Management[edit] This section is empty. You can help by adding to it. (July 2017) ## References[edit] 1. ^ Love, Barry (5 February 2015). "Aortopulmonary Septal Defect". Medscape. 2. ^ Burakovsky, V. I., Falkovsky, G. E., & Ivanitsky, A. V. (1984). Surgical repair of truncus arteriosus. Pediatric cardiology, 5(2), 111-114. 3. ^ a b McElhinney DB, Reddy VM, Tworetzky W, Silverman NH, Hanley FL (January 1998). "Early and late results after repair of aortopulmonary septal defect and associated anomalies in infants <6 months of age". Am. J. Cardiol. 81 (2): 195–201. doi:10.1016/S0002-9149(97)00881-3. PMID 9591904. ## External links[edit] Classification D * ICD-10: Q20.0-Q20.3, Q21.4 * ICD-9-CM: 745.0-745.1 * MeSH: D001028 * SNOMED CT: 17024001 * v * t * e Congenital heart defects Heart septal defect Aortopulmonary septal defect * Double outlet right ventricle * Taussig–Bing syndrome * Transposition of the great vessels * dextro * levo * Persistent truncus arteriosus * Aortopulmonary window Atrial septal defect * Sinus venosus atrial septal defect * Lutembacher's syndrome Ventricular septal defect * Tetralogy of Fallot Atrioventricular septal defect * Ostium primum Consequences * Cardiac shunt * Cyanotic heart disease * Eisenmenger syndrome Valvular heart disease Right * pulmonary valves * stenosis * insufficiency * absence * tricuspid valves * stenosis * atresia * Ebstein's anomaly Left * aortic valves * stenosis * insufficiency * bicuspid * mitral valves * stenosis * regurgitation Other * Underdeveloped heart chambers * right * left * Uhl anomaly * Dextrocardia * Levocardia * Cor triatriatum * Crisscross heart * Brugada syndrome * Coronary artery anomaly * Anomalous aortic origin of a coronary artery * Ventricular inversion This cardiovascular system article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Aortopulmonary septal defect	c0003516	30,517	wikipedia	https://en.wikipedia.org/wiki/Aortopulmonary_septal_defect	2021-01-18T18:38:13	{"mesh": ["D001028"], "icd-9": ["745.1", "745.0"], "icd-10": ["Q21.4", "Q20.0", "Q20.3"], "wikidata": ["Q4778774"]}
Cortical depression in the posterolateral head of the humerus Hill–Sachs lesion Other namesHill–Sachs fracture Anterior shoulder dislocation on X-ray with a large Hill–Sachs lesion SpecialtyOrthopedics A Hill–Sachs lesion, or Hill–Sachs fracture, is a cortical depression in the posterolateral head of the humerus. It results from forceful impaction of the humeral head against the anteroinferior glenoid rim when the shoulder is dislocated anteriorly. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 Incidence * 5 Eponym * 6 See also * 7 References * 8 External links ## Causes[edit] The lesion is associated with anterior shoulder dislocation.[1] When the humerus is driven from the glenoid cavity, its relatively soft head impacts against the anterior edge of the glenoid. The result is a divot or flattening in the posterolateral aspect of the humeral head, usually opposite the coracoid process. The mechanism which leads to shoulder dislocation is usually traumatic but can vary, especially if there is history of previous dislocations. Sports, falls, seizures, assaults, throwing, reaching, pulling on the arm, or turning over in bed can all be causes of anterior dislocation. ## Diagnosis[edit] MRI of shoulder after dislocation with Hill–Sachs lesion and labral Bankart's lesion Hill–Sachs lesion post-shoulder dislocation X-ray at left shows anterior dislocation in a young man after trying to get up from his bed. X-ray at right shows same shoulder after reduction and internal rotation, revealing both a Bankart lesion and a Hill-Sachs lesion. Diagnosis can be suspected by history and physical examination which is usually followed by imaging. Because of the mechanism of injury, apprehension of anterior dislocation is common with provocative maneuvers. Hill–Sachs lesions have been classified as "engaging" or "non-engaging", with engaging lesions defined by the ability of the glenoid to sublux into the humeral head defect during abduction and external rotation. Engaging dislocations have a higher risk of recurrent anterior dislocation, and their presence can help guide surgical management.[2] Imaging diagnosis conventionally begins with plain film radiography. Generally, anteroposterior (AP) radiographs of the shoulder with the arm in internal rotation offer the best yield while axillary views and AP radiographs with external rotation tend to obscure the defect. However, pain and tenderness in the injured joint make appropriate positioning difficult and in a recent study of plain film x-ray for Hill–Sachs lesions, the sensitivity was only about 20%. i.e. the finding was not visible on plain film x-ray about 80% of the time.[3] By contrast, studies have shown the value of ultrasonography in diagnosing Hill–Sachs lesions. In a population with recurrent dislocation using findings at surgery as the gold standard, a sensitivity of 96% was demonstrated.[4] In a second study of patients with continuing shoulder instability after trauma, and using double contrast CT as a gold standard, a sensitivity of over 95% was demonstrated for ultrasound.[5] It should be borne in mind that in both those studies, patients were having continuing problems after initial injury, and therefore the presence of a Hill–Sachs lesion was more likely. Nevertheless, ultrasonography, which is noninvasive and free from radiation, offers important advantages. MRI has also been shown to be highly reliable for the diagnosis of Hill-Sachs (and Bankart) lesions. One study used challenging methodology. First of all, it applied to those patients with a single, or first time, dislocation. Such lesions were likely to be smaller and therefore more difficult to detect. Second, two radiologists, who were blinded to the surgical outcome, reviewed the MRI findings, while two orthopedic surgeons, who were blinded to the MRI findings, reviewed videotapes of the arthroscopic procedures. Coefficiency of agreement was then calculated for the MRI and arthroscopic findings and there was total agreement ( kappa = 1.0) for Hill-Sachs and Bankart lesions.[6] ## Treatment[edit] The decision to repair of the Hill–Sachs lesion is based on its association with continuing symptoms and instability. This is particularly important in patients below 25 year of age and in throwing athletes. The role of the Hill-Sachs in continuing symptoms, in turn, may be related to its width and depth, particularly if involving greater than 20% of the articular surface. Associated bony lesions or fractures may coexist in the glenoid such as the bony Bankart lesion. In such scenarios, surgical repair may include bony augmentation, a common example of which is the Latarjet procedure. Additional lesions such as a Bankart, SLAP tear, or biceps injury may also be present.[7] ## Incidence[edit] The incidence of Hill–Sachs lesion is not known with certainty. It has been reported to be present in 40% to 90% of patients presenting with anterior shoulder instability, that is subluxation or dislocation.[8][9] In those who have recurrent events, it may be as high as 100%.[10] Its presence is a specific sign of dislocation and can thus be used as an indicator that dislocation has occurred even if the joint has since regained its normal alignment. Large, engaging Hill-Sachs fractures can contribute to shoulder instability and will often cause painful clicking, catching, or popping.[citation needed] The average depth of Hill–Sachs lesion has been reported as 4.1 mm.[11] ## Eponym[edit] The lesion is named after Harold Arthur Hill (1901–1973) and Maurice David Sachs (1909–1987), two radiologists from San Francisco, USA. In 1940, they published a report of 119 cases of shoulder dislocation and showed that the defect resulted from direct compression of the humeral head. Before their paper, although the fracture was already known to be a sign of shoulder dislocation, the precise mechanism was uncertain.[12] ## See also[edit] * Bankart lesion * Terms for anatomical location ## References[edit] 1. ^ Calandra, Joseph (December 1989). "The incidence of Hill-Sachs lesions in initial anterior shoulder dislocations". The Journal of Arthroscopic & Related Surgery. 5 (4): 254–257. doi:10.1016/0749-8063(89)90138-2. PMID 2590322. 2. ^ Burkhart, SS; De Beer, JF (October 2000). "Traumatic glenohumeral bone defects and their relationship to failure of arthroscopic Bankart repairs: significance of the inverted-pear glenoid and the humeral engaging Hill-Sachs lesion". Arthroscopy. 16 (7): 677–94. doi:10.1053/jars.2000.17715. PMID 11027751. 3. ^ Auffarth A, Mayer M, Kofler B, Hitzl W, Bogner R, Moroder P, Korn G, Koller H, Resch H (Nov 2013). "The interobserver reliability in diagnosing osseous lesions after first-time anterior shoulder dislocation comparing plain radiographs with computed tomography scans". J Shoulder Elbow Surg. 22 (11): 1507–13. doi:10.1016/j.jse.2013.04.020. PMID 23790679. 4. ^ Cicak N, Bilić R, Delimar D (Sep 1998). "Hill-Sachs lesion in recurrent shoulder dislocation: sonographic detection". J Ultrasound Med. 17 (9): 557–60. doi:10.7863/jum.1998.17.9.557. PMID 9733173. 5. ^ Pancione L, Gatti G, Mecozzi B (Jul 1997). "Diagnosis of Hill-Sachs lesion of the shoulder. Comparison between ultrasonography and arthro-CT". Acta Radiol. 38 (4): 523–6. doi:10.1080/02841859709174380. PMID 9240671. 6. ^ Kirkley A, Litchfield R, Thain L, Spouge A (May 2003). "Agreement between magnetic resonance imaging and arthroscopic evaluation of the shoulder joint in primary anterior dislocation of the shoulder". Clin J Sport Med. 13 (3): 148–51. doi:10.1097/00042752-200305000-00004. PMID 12792208. S2CID 42695994. 7. ^ Streubel PN, Krych AJ, Simone JP, Dahm DL, Sperling JW, Steinmann SP, O'Driscoll SW, Sanchez-Sotelo J (May 2014). "Anterior glenohumeral instability: a pathology-based surgical treatment strategy". J Am Acad Orthop Surg. 22 (5): 283–94. doi:10.5435/JAAOS-22-05-283. PMID 24788444. 8. ^ Taylor DC, Arciero RA (May–Jun 1997). "Pathologic changes associated with shoulder dislocations. Arthroscopic and physical examination findings in first-time, traumatic anterior dislocations". Am J Sports Med. 25 (3): 306–11. doi:10.1177/036354659702500306. PMID 9167808. 9. ^ Calandra JJ, Baker CL, Uribe J (1989). "The incidence of Hill-Sachs lesions in initial anterior shoulder dislocations". Arthroscopy. 5 (4): 254–7. doi:10.1016/0749-8063(89)90138-2. PMID 2590322. 10. ^ Yiannakopoulos CK, Mataragas E, Antonogiannakis E (Sep 2007). "A comparison of the spectrum of intra-articular lesions in acute and chronic anterior shoulder instability". Arthroscopy. 23 (9): 985–90. doi:10.1016/j.arthro.2007.05.009. PMID 17868838. 11. ^ Horst, K; Von Harten, R; Weber, C; Andruszkow, H; Pfeifer, R; Dienstknecht, T; Pape, HC (February 2014). "Assessment of coincidence and defect sizes in Bankart and Hill-Sachs lesions after anterior shoulder dislocation: a radiological study". The British Journal of Radiology. 87 (1034): 20130673. doi:10.1259/bjr.20130673. PMC 4064539. PMID 24452107. 12. ^ Hill HA, Sachs MD (1940). "The grooved defect of the humeral head: a frequently unrecognized complication of dislocations of the shoulder joint". Radiology. 35: 690–700. doi:10.1148/35.6.690. ## External links[edit] Classification D * Hill-Sachs lesions (frontal X-ray) \- szote.u-szedeg.hu. * http://www.shoulderus.com/ultrasound-of-the-shoulder/proximal-humerus-fracture-ultrasound-hill-sachs-lesion [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Hill–Sachs lesion	None	30,518	wikipedia	https://en.wikipedia.org/wiki/Hill%E2%80%93Sachs_lesion	2021-01-18T19:01:42	{"icd-10": ["S42.21", "S43.0", "S42.291"], "wikidata": ["Q839219"]}
A number sign (#) is used with this entry because of evidence that intellectual developmental disorder with cardiac arrhythmia (IDDCA) is caused by homozygous or compound heterozygous mutation in the GNB5 gene (604447) on chromosome 15q21. Biallelic missense mutation in the GNB5 gene can cause language delay and attention deficit-hyperactivity disorder/cognitive impairment with or without cardiac arrhythmia (LADCI; 617182), a less severe disorder with overlapping features. Description Intellectual developmental disorder with cardiac arrhythmia is an autosomal recessive multisystem disorder characterized by delayed psychomotor development, severe intellectual disability with poor or absent speech, and bradycardia and/or cardiac sinus arrhythmias. Additional features include visual abnormalities, seizures, hypotonia, and gastric reflux (summary by Lodder et al., 2016). Clinical Features Lodder et al. (2016) reported 6 patients from 4 unrelated families of various ethnic backgrounds with a complex multisystem disorder apparent from infancy or early childhood. The patients ranged in age from 6 to 22 years, and the families originated from Italy, Jordan, Puerto Rico, and India. The patients had delayed psychomotor development with severe intellectual disability, poor or absent speech, severe hypotonia, often without head control, and nystagmus. All also had cardiac abnormalities, most commonly sick sinus syndrome with bradycardia, escape beats, and other arrhythmias in the absence of structural abnormalities, except for a patent foramen ovale in 1 patient. Two sibs had a pacemaker implanted. Visual abnormalities were variable: 2 sibs had retinal degeneration, another patient had no eye contact, and 3 patients had abnormal electroretinograms. Four patients had seizures, including 1 patient with refractory seizures and hypsarrhythmia, and 5 patients had pathologic gastric reflux. Brain imaging was basically normal. Inheritance The transmission pattern of IDDCA in the families reported by Lodder et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In 6 patients from 4 unrelated families with IDDCA, Lodder et al. (2016) identified homozygous or compound heterozygous truncating mutations in the GNB5 gene (604447.0001-604447.0005). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Functional studies of the variants were not performed; studies of patient cells, performed only in 1 family (family A) with compound heterozygous truncating variants, demonstrated that both alleles were subject to nonsense-mediated mRNA, consistent with a complete loss of function. These patients were part of a cohort of 9 patients from 6 families who were found to have GNB5 mutations: those with truncating mutations had a more severe phenotype than those with a missense mutation (LADCI), suggesting a genotype/phenotype correlation. Animal Model Lodder et al. (2016) used CRISPR/Cas9 genome editing to generate complete loss of gnb5 function in zebrafish; mutant zebrafish had impaired swimming activity, remained small, and died 7 to 14 days postfertilization, likely due to an inability to feed. Treatment of mutant larvae with carbachol, a parasympathomimetic compound that activates the GNB5/RGS/GIRK (G protein-coupled inward rectifier potassium) channel pathway, resulted in a strong decrease in heart rate compared to controls. Treatment with a sympathetic agonist resulted in an increased heart rate similar to controls. These findings indicated that loss of gnb5 caused a loss of negative regulation of the cardiac GIRK channel and parasympathetic control, without effects on sympathetic control. Mutant larvae were predominantly unresponsive to repeated tactile stimulation, apparently due to neurologic deficits, not muscle dysfunction, and showed impaired optokinetic responses, also with normal eye muscle function. The findings indicated that Gnb5 is important for neuronal signaling and autonomic function. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus \- Retinal degeneration \- Abnormal electroretinogram CARDIOVASCULAR Heart \- Sick sinus syndrome \- Bradycardia \- Arrhythmias ABDOMEN Gastrointestinal \- Gastric reflux MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Speech delay \- Seizures (in some patients) MISCELLANEOUS \- Onset in early childhood \- Some patients are severely affected with no head control, visual contact, or speech MOLECULAR BASIS \- Caused by mutation in the guanine nucleotide-binding protein, beta-5 gene (GNB5, 604447.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	INTELLECTUAL DEVELOPMENTAL DISORDER WITH CARDIAC ARRHYTHMIA	c4310682	30,519	omim	https://www.omim.org/entry/617173	2019-09-22T15:46:38	{"omim": ["617173"]}
Prothrombin (or factor II) deficiency is a blood disorder that affects the ability of the blood to clot properly. Symptoms of the deficiency include prolonged bleeding, especially after an injury or after surgery. Women with prothrombin deficiency may have heavy menstrual bleeding. The severity of the disease can vary, with some people experiencing severe bleeding without any known cause, and others only experiencing increased bleeding after a surgery or serious injury. Prothrombin deficiency is caused by changes (mutations) in the F2 gene. There are two types of inherited prothrombin deficiency. Type I or hypoprothrombinemia and type II or dysprothrombinemia. Inheritance of both types is autosomal recessive. Diagnosis is based on laboratory test results that are consistent with the deficiency. Treatment includes IV therapy using plasma, which is the part of the blood that contains the blood clotting factors. The blood product that is used is called fresh frozen plasma. A form of the disease that is not inherited (acquired) can be caused by vitamin K deficiency, liver disease, or an autoimmune response. The underlying cause of acquired factor II deficiency should be treated in order to relieve symptoms of the disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Prothrombin deficiency	c0272317	30,520	gard	https://rarediseases.info.nih.gov/diseases/2926/prothrombin-deficiency	2021-01-18T17:58:07	{"mesh": ["C562724"], "omim": ["613679"], "umls": ["C0272317"], "orphanet": ["325"], "synonyms": ["Hypoprothrombinemia, inherited", "Congenital factor II deficiency", "Dysprothrombinemia", "Inherited prothrombin deficiency", "Inherited hypoprothrombinemia", "Factor II deficiency"]}
Chronic mucocutaneous candidiasis can have many causes, e.g., (1) failure of lymphocytes to transform in response to antigen, either because of an intrinsic defect (247450) or because of an inhibiting serum factor (247430); (2) failure of production of lymphokine; or (3) unresponsiveness of monocytes to lymphokine (252250). Deficient production of lymphokine despite normal lymphoblastic transformation was demonstrated by Lehner et al. (1972). Inheritance \- Autosomal recessive Lab \- Failure of production of lymphokine \- Normal lymphoblastic transformation Skin \- Chronic mucocutaneous candidiasis ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	LYMPHOKINE DEFICIENCY	c0006845	30,521	omim	https://www.omim.org/entry/247650	2019-09-22T16:25:45	{"mesh": ["D002178"], "omim": ["247650"], "orphanet": ["1334"]}
Adult polyglucosan body disease (APBD) is a condition that affects the nervous system. People with APBD typically first experience signs and symptoms related to the condition between ages 35 and 60. Initial symptoms of the disorder include numbness and tingling in the legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). As a result, affected individuals can have an unsteady gait, poor balance, and an increased risk of falling. Damage to the nerves that control bladder function, a condition called neurogenic bladder, is another feature that often occurs early in the course of APBD. Affected individuals have increasing difficulty starting or stopping the flow of urine. Eventually, most people with APBD lose the ability to control their bladder and bowel functions and their limbs. Damage to the autonomic nervous system, which controls body functions that are mostly involuntary, leads to problems with blood pressure, heart rate, breathing rate, digestion, temperature regulation, and sexual response, and results in daily bouts of exhaustion. About half of people with APBD experience a decline in intellectual function (dementia). ## Frequency APBD is a rare condition, although its exact prevalence is unknown. Approximately 200 affected individuals have been diagnosed worldwide. Recently these have included younger individuals who have not yet experienced signs or symptoms but who are diagnosed in the course of genetic screening when considering parenthood. Researchers suspect that the disorder may be underdiagnosed. ## Causes Mutations in the GBE1 gene cause APBD. The GBE1 gene provides instructions for making the glycogen branching enzyme. This enzyme is involved in the production of a complex sugar called glycogen, which is a major source of stored energy in the body. Most GBE1 gene mutations that cause APBD result in a shortage (deficiency) of the glycogen branching enzyme, which leads to the production of abnormal glycogen molecules. These abnormal glycogen molecules, called polyglucosan bodies, accumulate within cells and cause damage. Nerve cells (neurons) appear to be particularly vulnerable to the accumulation of polyglucosan bodies in people with this disorder, leading to impaired neuronal function. Some mutations in the GBE1 gene that cause APBD do not result in a shortage of glycogen branching enzyme. In people with these mutations, the activity of this enzyme is normal. How mutations cause the disease in these individuals is unclear. Other people with APBD do not have identified mutations in the GBE1 gene. In these individuals, the cause of the disease is unknown. ### Learn more about the gene associated with Adult polyglucosan body disease * GBE1 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Adult polyglucosan body disease	c1849722	30,522	medlineplus	https://medlineplus.gov/genetics/condition/adult-polyglucosan-body-disease/	2021-01-27T08:24:40	{"gard": ["108"], "mesh": ["C564878"], "omim": ["263570"], "synonyms": []}
Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by renal magnesium (Mg) and calcium (Ca) wasting, nephrocalcinosis, kidney failure and, in some cases, severe ocular impairment. Two subtypes of FHHNC are described: FHHNC with severe ocular involvement (FHHNCOI) and without severe ocular involvement (FHHN) (see these terms). ## Epidemiology To date, approximately 200 cases have been reported in the literature. ## Clinical description The median age of onset ranges from 1 to 8 years. The most common presenting features are recurrent urinary tract infections, nephrolithiasis, nephrocalcinosis, polyuria, polydipsia, enuresis, hematuria and pyuria. Additional manifestations include failure to thrive, seizures, abdominal pain, muscular tetany and, rarely, rickets. Patients develop chronic kidney disease (CKD) that progresses to end-stage renal disease (ESRD). Two subtypes of FHHNC have been described: FHHNCOI and FHHN. Both forms share identical renal manifestations. By contrast, severe ocular involvement (macular coloboma, pigmentary retinitis, nystagmus, or visual loss) has been described in FHHNCOI, while mild nonspecific ocular involvement (myopia, astigmatism, hypermetropia, or strabismus) has been reported in some cases of FHHN. ## Etiology The disease is caused by mutations in the genes CLDN16 (3q28) and CLDN19 (1p34.2), encoding claudin-16 and claudin-19 respectively. Both proteins are expressed in the thick ascending limb of Henle's loop where they interact to form heteromultimers and play a role in the paracellular reabsorption of Mg and Ca. Inactivating mutations in either gene results in urinary loss of Mg and Ca. Ocular involvement occurs in patients with the CLDN19 mutation as claudin-19 is expressed in retinal pigment epithelium. ## Diagnostic methods Diagnosis is based on the triad of hypomagnesemia, hypercalciuria and nephrocalcinosis. Hypocalcemia, hyperuricemia, incomplete distal renal tubular acidosis and hypocitraturia are supportive findings. Parathyroid hormone levels are high before onset of CKD. High fractional urinary excretion of Mg is found while serum level is inappropriately low. Ocular abnormalities are detected by fundoscopy and optical coherence tomography (OCT). Diagnosis is confirmed by genetic screening of CLDN16 and CLDN19. ## Differential diagnosis Differential diagnosis includes Bartter syndrome, autosomal dominant hypocalcemia, Dent disease, hereditary hypophosphatemic rickets with hypercalciuria, distal renal tubular acidosis and other tubular disorders causing early nephrocalcinosis (like primary hyperoxaluria) (see these terms). ## Genetic counseling Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child. ## Management and treatment Management is mainly supportive and includes administration of Mg supplements in high doses and thiazide diuretics to reduce urinary Ca excretion and the progression of nephrocalcinosis. Indomethacin may be used to increase Ca reabsorption. Therapies aimed at delaying progression of CKD should be provided as well as conventional management strategies for kidney stones. Renal transplantation is the optimal treatment for ESRD. Lens implantation can be proposed to patients suffering from severe ocular abnormalities. ## Prognosis Progression to ESRD is frequent (50% of patients at 20 years). Follow-up data in one of the described cohorts suggested that patients harboring CLDN19 mutations have a higher risk of progression to CKD than patients with CLDN16 mutations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis	None	30,523	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=306516	2021-01-23T18:42:36	{"icd-10": ["E83.4"], "synonyms": ["FHHNC", "Michellis-Castrillo syndrome"]}
A number sign (#) is used with this entry because congenital disorder of glycosylation type IIk (CDG2K) is caused by homozygous or compound heterozygous mutation in the TMEM165 gene (614726) on chromosome 4q12. Description CDG2K is an autosomal recessive disorder with a variable phenotype. Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Serum transferrin analysis shows a CDG type II pattern (summary by Foulquier et al., 2012). For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066). Clinical Features Foulquier et al. (2012) reported 5 patients from 4 families with CDG2K. The first family contained 2 affected sibs, born of Georgian Jewish parents. The 19-year-old boy had psychomotor retardation and severe growth retardation. He also had midface hypoplasia, muscle weakness, fat excess, joint laxity, and hepatosplenomegaly with increased serum transaminases. Laboratory studies showed increased creatine kinase and partial growth hormone deficiency. Skeletal anomalies included osteoporosis and epiphyseal, metaphyseal, and diaphyseal dysplasia. Brain MRI showed white matter abnormalities and hypoplasia of the pituitary gland. His sister, who had similar clinical features, also had recurrent, unexplained fever episodes; she died at 14 months of age from an acute infectious shock. Another Georgian Jewish child with similar features, including unexplained fever, also had transient epilepsy, dwarfism, and unexplained restrictive lung pathology. A Turkish boy had delayed psychomotor development and mild rhizomelia, but no significant skeletal anomalies. An American girl had short stature, facial dysmorphism, wrinkled skin, abnormal fat distribution, and dysplastic toenails. She had amelogenesis imperfecta and multiple skeletal abnormalities, including osteoporosis, anterior beaking of vertebrae, dysplastic vertebrae and ribs, dysplastic fourth metacarpals and metatarsals, hypoplasia of femoral heads, and kyphoscoliosis. Serum transferrin analysis of the patients showed a CDG type II pattern, and patient cells showed an N-glycosylation defect and abnormal Golgi morphology. Zeevaert et al. (2013) provided a detailed clinical summary of the 3 Georgian Ashkenazi Jewish patients with CDG2K reported by Foulquier et al. (2012). Additional dysmorphic features noted in the Georgian Jewish boy included dense hair, long and dense eyelashes, delayed dentition, and hoarse voice. He also had a waddling gait and muscular hypotrophy. Laboratory abnormalities included a moderate decrease in certain clotting factors and low levels of certain pubertal hormones at age 16. His younger sister also had some dysmorphic features, including ptosis, strabismus, low-set ears, long philtrum, high-arched palate, short and broad neck, broad thorax, sacral dimple, and absent second toenails. The unrelated boy had macrocephaly, tongue protrusion, downslanting palpebral fissures, flat nose, and posteriorly rotated ears. All 3 patients had radiologic evidence of skeletal dysplasia, which Zeevaert et al. (2013) noted was a distinctive feature in this form of CDG. Molecular Genetics In 5 patients from 4 families with CDG2K, Foulquier et al. (2012) identified homozygous or compound heterozygous mutations in the TMEM165 gene (614726.0001-614726.0004). The mutations were found by autozygosity mapping followed by gene expression profiling. Silencing of the TMEM165 gene in HEK cells resulted in disturbed N-glycosylation in the terminal Golgi. The findings suggested an important role for TMEM165 in Golgi glycosylation and Golgi morphology maintenance. INHERITANCE \- Autosomal recessive GROWTH Weight \- Short stature Other \- Failure to thrive \- Growth retardation HEAD & NECK Head \- Microcephaly, acquired Face \- Dysmorphic features \- Midface hypoplasia (1 patient) Ears \- Low-set ears \- Posteriorly rotated ears Eyes \- Eye abnormalities Teeth \- Amelogenesis imperfecta (1 patient) CHEST Ribs Sternum Clavicles & Scapulae \- Dysplastic ribs (1 patient) ABDOMEN Liver \- Hepatomegaly Gastrointestinal \- Feeding problems in infancy SKELETAL \- Joint laxity \- Osteoporosis Spine \- Dysplastic vertebrae \- Kyphoscoliosis Limbs \- Epiphyseal dysplasia \- Metaphyseal dysplasia \- Diaphyseal dysplasia \- Hypoplasia of the femoral heads (1 patient) Hands \- Dysplastic fourth metacarpals (1 patient) Feet \- Dysplastic fourth metatarsals (1 patient) MUSCLE, SOFT TISSUES \- Muscle weakness \- Hypotonia \- Abnormal fat distribution NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- White matter abnormalities \- Seizures (1 patient) METABOLIC FEATURES \- Unexplained fevers (2 patients) HEMATOLOGY \- Thrombocytopenia LABORATORY ABNORMALITIES \- Abnormal liver enzymes \- Increased serum creatine kinase \- N-glycosylation defect \- Decreased levels of certain coagulation factors MISCELLANEOUS \- Onset in early childhood \- Variable phenotype \- Five patients have been reported (last curated December 2014) MOLECULAR BASIS \- Caused by mutation in the transmembrane protein 165 gene (TMEM165, 614726.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIk	c3553571	30,524	omim	https://www.omim.org/entry/614727	2019-09-22T15:54:22	{"doid": ["0070263"], "omim": ["614727"], "orphanet": ["314667"], "synonyms": ["CDG syndrome type IIk", "CDG-IIk", "Congenital disorder of glycosylation type 2k", "Alternative titles", "CDG2K", "CDG IIk", "Carbohydrate deficient glycoprotein syndrome type IIk", "Congenital disorder of glycosylation type IIk"], "genereviews": ["NBK1332"]}
Autosomal dominant inheritance was suggested by Billard et al. (1994) as the basis of some cases of developmental dysphasia. This disorder is characterized by a specific and severe delay in the development of spoken language. This results in impaired or completely absent language in a normal social environment without other abnormalities such as mental retardation, emotional or communication disabilities, deafness, cerebral palsy, or brain lesions on CT scan. A genetic component had been suggested because of similarities with dyslexia (127700) where a genetic basis had been recognized for many years. Family studies (Gopnik, 1990; Hurst et al., 1990) and a twin study (Borges-Osorio and Salzano, 1985) have been reported. Billard et al. (1994) reported on 6 families. Four generations were affected in 1, 3 generations in 2, and 2 generations in the other 3. Five of the 6 families had instances of male-to-male transmission. The coexistence in the same family of completely normal and severely impaired sibs suggested a genetic rather than a familial socio-linguistic cause. See SPCH1 (602081) for discussion of a similar disorder. Neuro \- Developmental dysphasia \- Specific severe delayed spoken language development Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	DYSPHASIA, FAMILIAL DEVELOPMENTAL	c1838630	30,525	omim	https://www.omim.org/entry/600117	2019-09-22T16:16:42	{"mesh": ["C563997"], "omim": ["600117"], "orphanet": ["1799"]}
Alternariosis A 69-year-old female with alternariosis in her left forearm and electron micrograph of her skin showing sporangiophores of Lichtheimia corymbifera[citation needed] SpecialtyDermatology, infectious disease Alternariosis is an infection by Alternaria, presenting cutaneously as focal, ulcerated papules and plaques.[1]:330 Treatment with itraconazole has been reported.[2] ## See also[edit] * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 2. ^ Matson DR, Eudy JD, Matson SC (January 2010). "Cutaneous alternariosis in an adolescent patient". Pediatr Dermatol. 27 (1): 98–100. doi:10.1111/j.1525-1470.2009.01056.x. PMID 20199426. ## External links[edit] Classification D * MeSH: D060487 This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Alternariosis	c3178963	30,526	wikipedia	https://en.wikipedia.org/wiki/Alternariosis	2021-01-18T19:10:42	{"mesh": ["D060487"], "wikidata": ["Q4736375"]}
Presumed ocular histoplasmosis syndrome Retinal photograph of ocular histoplasmosis SpecialtyOphthalmology Presumed ocular histoplasmosis syndrome (POHS) is a syndrome affecting the eye, which is characterized by peripheral atrophic chorioretinal scars, atrophy or scarring adjacent to the optic disc and maculopathy. The loss of vision in POHS is caused by choroidal neovascularization. ## Contents * 1 Presentation * 2 Causes * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Presentation[edit] The diagnosis of POHS is based on the clinical triad of multiple white, atrophic choroidal scars, peripapillary pigment changes (dark spots around optic disc of the eye), and a maculopathy caused by choroidal neovascularization. Completely distinct from POHS, acute ocular histoplasmosis may rarely occur in immunodeficiency.[1][2] ## Causes[edit] Despite its name, the "presumed" relationship of POHS to Histoplasma capsulatum is controversial and has been questioned by a number of medical professionals.[3][4][5] The fungus has rarely been isolated from cases with POHS,[6][medical citation needed] the condition has also been found in locations where histoplasmosis is rare,[7] and there appears to be a relationship with tobacco smoking.[medical citation needed] ## Diagnosis[edit] Fluorescein angiography is usually performed for diagnosis and follow-up of patients with POHS. ## Treatment[edit] Treatment requires careful consideration of angiographic findings when a choroidal neovascular membrane is suspected which is a condition that responds to treatment. A vitreo-retinal specialist (an ophthalmologist specialized in treatment of retinal diseases) should be consulted for proper management of the case.[citation needed] Presumed ocular histoplasmosis syndrome and age-related macular degeneration (AMD) have been successfully treated with laser, anti-vascular endothelial growth factors and photodynamic therapy. Ophthalmologists are using anti-vascular endothelial growth factors to treat AMD and similar conditions since research indicates that vascular endothelial growth factor (VEGF) is one of the causes for the growth of the abnormal vessels that cause these conditions.[citation needed] ## See also[edit] * Uveitis ## References[edit] 1. ^ Macher A, Rodrigues MM, Kaplan W, Pistole MC, McKittrick A, Lawrinson WE, Reichert CM (1985). "Disseminated bilateral chorioretinitis due to Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome". Ophthalmology. 92 (8): 1159–64. doi:10.1016/s0161-6420(85)33921-0. PMID 2413418. 2. ^ Gonzales, C. A.; Scott, I. U.; Chaudhry, N. A.; Luu, K. M.; Miller, D; Murray, T. G.; Davis, J. L. (2000). "Endogenous endophthalmitis caused by Histoplasma capsulatum var. Capsulatum: A case report and literature review". Ophthalmology. 107 (4): 725–9. doi:10.1016/s0161-6420(99)00179-7. PMID 10768335. 3. ^ Thuruthumaly C; Yee D. C.; Rao P. K. (2014). "Presumed ocular histoplasmosis". Current Opinion in Ophthalmology. 25 (6): 508–12. doi:10.1097/ICU.0000000000000100. PMID 25237930. 4. ^ Nielsen J. S.; Fick T. A.; Saggau D. D.; Barnes C. H. (2012). "Intravitreal anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to ocular histoplasmosis syndrome". Retina. 32 (3): 468–72. doi:10.1097/IAE.0b013e318229b220. PMID 21817958. 5. ^ Woods AC; Wahlen HE (1959). "The probable role of benign histoplasmosis in the etiology of granulomatous uveitis". Transactions of the American Ophthalmological Society. 57: 318–347. PMC 1316339. PMID 16693576. 6. ^ [1] Presumed Ocular Histoplasmosis Syndrome 7. ^ Stefan Dithmar; Frank Gerhard Holz (28 April 2008). Fluorescence Angiography in Ophthalmology. Springer. pp. 168–. ISBN 978-3-540-78359-6. Retrieved 29 June 2010. 8. ^ Ehrlich R, Ciulla TA, Maturi R, et al. (2009). "Intravitreal bevacizumab for choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome". Retina (Philadelphia, Pa.). 29 (10): 1418–23. doi:10.1097/IAE.0b013e3181babdf1. PMID 19898179. ## External links[edit] Classification D External resources * eMedicine: article/1224400 * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Presumed ocular histoplasmosis syndrome	c0153278	30,527	wikipedia	https://en.wikipedia.org/wiki/Presumed_ocular_histoplasmosis_syndrome	2021-01-18T18:49:39	{"umls": ["C0153278"], "wikidata": ["Q7242093"]}
A number sign (#) is used with this entry because of evidence that X-linked spondyloepimetaphyseal dysplasia (SEMDX) is caused by mutation in the BGN gene (301870) on chromosome Xq28. Clinical Features Camera et al. (1994) described what they suggested might represent a new form of spondyloepimetaphyseal dysplasia with X-linked inheritance. Eight males in 6 sibships in 4 generations were affected. The authors examined 3 of the adults and studied the skeletal radiologic aspects of one of these patients at 2.5 and 9 years of age. The main clinical features were severe short-trunk dwarfism, brachydactyly, normal facies, and normal intelligence. Radiologically, the diaphyses of all the long bones were short and broad. Epiphyses of the distal portion of the femurs and those of the proximal and distal portions of the tibias were embedded in their metaphyses, and there was marked narrowing of the intercondylar groove. There was moderate platyspondyly. Several vertebrae showed an anterior tongue in infancy and severe irregularities of the upper and lower surfaces in adulthood. The eleventh or twelfth thoracic vertebra was wedge shaped. The pelvis was narrow. The distal ulnas and fibulas were disproportionately long. The hands showed radial deviation and brachydactyly was present in the hands and feet. The disorder was not detectable at birth and appeared to be distinct from X-linked spondyloepiphyseal dysplasia tarda (313400). Cho et al. (2016) studied 3 families with X-linked SEMD, including the Italian family reported by Camera et al. (1994), a Korean family in which 2 brothers, their maternal grandfather, and 2 maternal great-uncles were affected, and an Indian family with 1 affected boy. Birth weights and lengths were normal, but all presented between 12 and 24 months of age due to growth retardation with body disproportion, with mesomelic shortening of the limbs and a short limbs-to-trunk ratio. Affected individuals showed significant bowing of the legs, a waddling gait with lumbar lordosis, and brachydactyly. In adulthood, they walked without support, enjoyed hiking and bicycling, and had no symptoms or signs of early arthritis or neurologic issues. A 46-year-old Italian man, who had nearly normal stature and gait and could swim, had undergone 15 surgical interventions since adolescence to lengthen his femora and tibiae. Radiographs of the Korean and Indian boys showed platyspondyly with central protrusion of the anterior vertebral bodies, kyphotic angulation, and increased lumbar lordosis, as well as flared ilia with horizontal and irregular acetabular roofs, and long and constricted femoral necks. The long bones were very short with dysplastic epiphyses and flared, irregular, and cupped metaphyses. Uniform shortening of the metacarpals and phalanges with coning at the metacarpals was seen in both children and adults. Cho et al. (2016) noted that these findings were similar to those reported by Camera et al. (1994). Molecular Genetics In an Italian family with X-linked SEMD, previously reported by Camera et al. (1994), and a similarly affected Korean family, both negative for mutation in genes known to be associated with skeletal dysplasia and severe short stature, Cho et al. (2016) performed whole-exome sequencing and identified missense mutations in the BGN gene: K147E (301870.0001) in the Korean patients and G259V (301870.0002) in the Italian patients. An affected Indian boy was found to have the K147E variant as a de novo mutation. Both mutations segregated fully with disease in the families, and neither was found in 904 Korean or 800 Japanese control chromosomes or in the ExAC database. INHERITANCE \- X-linked recessive GROWTH Height \- Severe short-trunked dwarfism (identifiable in early childhood) HEAD & NECK Face \- Normal facies CHEST Ribs Sternum Clavicles & Scapulae \- Pectus carinatum \- Posterior rib cupping \- Short clavicles SKELETAL \- Spondyloepimetaphyseal dysplasia Skull \- Mild maxillary hypoplasia Spine \- Mild odontoid hypoplasia \- Platyspondyly \- Anterior vertebral tongue (infancy) \- Wedge-shaped 11th or 12th thoracic vertebrae \- Kyphosis \- Lumbar lordosis Pelvis \- Narrow pelvis \- Hypoplastic iliac bones \- Flared iliac wings \- Horizontal acetabular roof \- Femoral neck hypoplasia \- Coxa valga Limbs \- Moderate limitation of elbow extension \- Short, broad long bone diaphyses \- Disproportionately long ulnae \- Disproportionately long fibulae \- Prominent ulnar styloid process \- Irregular metaphyses \- Metaphyseal flaring of lower extremities \- Underossified epiphyses \- Cone-shaped epiphyses (distal radii) \- Cone-shaped epiphyses fused within their metaphyses (distal femora, proximal and distal tibiae) Hands \- Brachydactyly \- Radial deviation of hands \- Short hands \- Delayed carpal bone age \- Short, broad metacarpals and phalanges \- Cone-shaped epiphyses (metacarpals and proximal phalanges) Feet \- Short feet NEUROLOGIC Central Nervous System \- Normal intelligence MISCELLANEOUS \- Pectus carinatum present in obligate carrier mothers \- Dwarfism not detectable at birth ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	SPONDYLOEPIMETAPHYSEAL DYSPLASIA, X-LINKED	c1848097	30,528	omim	https://www.omim.org/entry/300106	2019-09-22T16:20:52	{"mesh": ["C564714"], "omim": ["300106"], "orphanet": ["93349"], "synonyms": ["Alternative titles", "SEMD, X-LINKED"]}
"GEFS" redirects here. For the online flight simulator, see GEFS-Online. "SMEB" redirects here. For the League of Legends player, see Smeb. This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (October 2013) (Learn how and when to remove this template message) This article possibly contains original research. Please improve it by verifying the claims made and adding inline citations. Statements consisting only of original research should be removed. (October 2013) (Learn how and when to remove this template message) (Learn how and when to remove this template message) GEFS+ SpecialtyNeurology Generalized epilepsy with febrile seizures plus (GEFS+) is a syndromic autosomal dominant disorder where afflicted individuals can exhibit numerous epilepsy phenotypes.[1] GEFS+ can persist beyond early childhood (i.e., 6 years of age). GEFS+ is also now believed to encompass three other epilepsy disorders: severe myoclonic epilepsy of infancy (SMEI), which is also known as Dravet's syndrome, borderline SMEI (SMEB), and intractable epilepsy of childhood (IEC).[2][3] There are at least six types of GEFS+, delineated by their causative gene. Known causative genes are the sodium channel α subunit genes SCN1A, an associated β subunit SCN1B, and a GABAA receptor γ subunit gene, GABRG2 and there is another gene related with calcium channel the PCDH19 which is also known as Epilepsy Female with Mental Retardation.[4] Penetrance for this disorder is estimated at approximately 60%.[5] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 2.1 Type 1 * 2.2 Type 2 * 2.3 Type 3 * 2.4 SCN2A mutations * 3 Management * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] Individuals with GEFS+ present with a range of epilepsy phenotypes. These include febrile seizures that end by age 6 (FS), such seizures extending beyond age 6 that may include afebrile tonic-clonic, myoclonic, absence, atonic seizures and myoclonic-astatic epilepsy. Individuals may also present with SMEI, characterized by generally tonic-clonic seizures, impaired psychomotor development, myoclonic seizures, ataxia, and poor response to many anticonvulsants.[1][6] ## Pathophysiology[edit] ### Type 1[edit] Figure 1. Schematic structure of SCN1B with GEFS+ type 1 mutations shown in red. The single red spot is the C121W mutant at the disulfide bond (black) and the stretch of red the I70_E74del mutation. GEFS+ type 1 is a subtype of GEFS+ in which there are mutations in SCN1B, a gene encoding a sodium channel β subunit. The β subunit is required for proper channel inactivation. There are two known mutations in SCN1B that lead to GEFS+ (Figure 1). The first and best characterized of these mutations is C121W. This mutation alters a cysteine involved in a disulfide bond in the extracellular N-terminus of the protein. This extracellular region is similar to the cell adhesion molecule contactin and other cell adhesion molecules. It is believed that the disulfide bond disrupted by the C121W mutation is required for the proper folding of this N-terminus motif. Coexpression of SCN1B with sodium channel α subunits in oocytes and other cells results in channels that inactivate more slowly. Expression of C121W mutant along with wild-type α subunits produces current indistinguishable from that through α subunits alone.[5][7] Further investigation of this mutation has indicated that it results in decreased frequency dependent rundown and, thus, likely hyperexcitability when compared to cells expressing the wild-type subunit. This mutation also disrupts the subunit's ability to induce cellular aggregation. The importance of this last fact is unclear, though it is presumed that proper channel aggregation within cells and cell-cell contact are required for normal neuronal function.[8][9] A second mutation has been found in one kindred with GEFS+ type 1. This mutation is in a splice acceptor site of exon 3\. The loss of this acceptor site reveals a downstream cryptic acceptor site and a protein missing 5 amino acids in the N-terminus (I70_E74del). This mutation has not been further characterized.[10] ### Type 2[edit] A second subtype of GEFS+, type 2, is the result of mutations in SCN1A, a gene encoding a sodium channel α subunit. There are currently almost 90 known mutations in the SCN1A gene throughout the entirety of the channel (see table 1). These mutations result in almost any imaginable mutation type in the gene, short of duplications. The results of these mutations are highly variable, some producing functional channels while others result in non-functional channels. Some functional channels result in membrane hyperexcitability while others result in hypoexcitability. Most of the functional mutant channels result in hyperexcitability due to decreased frequency dependent rundown. An example of this is the D188V mutation. A 10 Hz stimulation of wild-type channels causes current to decrease to approximately 70% of maximum whereas the same stimulation of mutant channels results in rundown to 90% of maximum. This is caused by an expedited recovery from inactivation for mutant channels versus wild-type. The D188V mutant, for example, recovers to 90% maximal current in 200ms while wild-type channels are unable to recover to this degree in >1000ms.[11] Some other functional mutations that lead to hyperexcitability do so by other means, such as decreasing the rate of entrance into the slow inactivated state.[citation needed] Some of the other functional mutations are believed to result in hypoexcitability. The R859C mutation, for example, has a more depolarized voltage dependence of activation, meaning that the membrane must be more depolarized for the channel to open. This mutant also recovers more slowly from inactivation.[12] The nonfunctional channels are believed to produce similar changes in cell excitability. Likewise, many of the nonsense mutations likely result in nonfunctional channels and hypoexcitability, though this has yet to be tested. It is also unclear how this membrane hypoexcitability leads to the GEFS+ phenotype.[citation needed] Table 1. Summary of mutations found in patients diagnosed with GEFS+ type 2 Mutation Region Functional? Excitability Prediction References R101Q N-Terminus [13] S103G N-Terminus [14] T112I N-Terminus [14] V144fsX148 D1S1 [13] G177fsX180 D1S2-S3 [14] D188V D1S2-S3 Yes Hyperexcitable [11][15] F190R D1S3 [13] S219fsX275 D1S4 [16] R222X D1S4 [13][16] G265W D1S5 [14] G343E D1S5-S6 [14] E435X D1-2 [13] R613X D1-2 [17] R701X D1-2 [13] P707fsX715 D1-2 [17] R712X D1-2 [14] Q732fsX749 D1-2 [14] Y779C D2S1 [18] T808S D2S2 Yes Hyperexcitable [6][14] R859C D2S4 Yes Hypoexcitability [12] T875M D2S4 Yes Hyperexcitable* [19][20][21][22][23] F902C D2S5 No Hypoexcitable [24] S914fsX934 D2S5-6 [17] M924I D2S5-6 [13] V934A D2S5-6 [13] R936C D2S5-6 [13] R936H D2S5-6 [13] W942X D2S5-6 [13] R946fsX953 D2S5-6 [14] W952X D2S5-6 [14] D958fsX973 D2S5-6 [14] M960V D2S5-6 [14] G979R D2S6 No Hypoexcitable [6][14] V983A D2S6 Yes Hyperexcitable [6][14] N985I D2S6 [14] L986F D2S6 No Hypoexcitable [16][25] N1011I D2-3 Yes Hyperexcitable [6][14] K1100fsX1107 D2-3 [16] L1156fsX1172 D2-3 [13] W1204R D2-3 Yes Hyperexcitable [2][23][26] W1204X D2-3 [14] R1213X D2-3 [14] S1231R D3S1 [14] S1231T D3S1 [17] F1263L D3S2 [14] W1284X D3S3 [14] L1345P D3S5 [13] V1353L D3S5 No Hypoexcitable [15][25] Splice Exon 4 [14][16] R1397X D3S5-6 [13] R1407X D3S5-6 [14] W1408X D3S5-6 [14] V1428A D3S6 [27][28] S1516X D3-4 [14] R1525X D3-4 [17] M1549del D4S1 [13] V1611F D4S3 Yes Hyperexcitable [6][14] P1632S D4S3 Yes Hyperexcitable [6][14] R1635X D4S4 [13] R1648C D4S4 Yes Hyperexcitable [24] R1648H D4S4 Yes Hyperexcitable [20][22][23][29][30] I1656M D4S4 Yes [15][25] R1657C D4S4 Yes Hypoexcitable [25][30][31] F1661S D4S4 Yes Hyperexcitable [24] L1670fsX1678 D4S4-5 [14][16] G1674R D4S4-5 No Hypoexcitable [24] F1682S D4S5 [13] Y1684C D4S5 [13] A1685V D4S5 No Hypoexcitable [25][27][28] A1685D D4S5 [14] T1709I D4S5-6 No Hypoexcitable [6][14] D1742G D4S5-6 [32] G1749E D4S6 Yes Hypoexcitable [24] F1756del D4S6 [13] F1765fsX1794 D4S6 [14] Y1771C D4S6 [13] 1807delMFYE C-Terminus [14] F1808L C-Terminus Yes Hyperexcitable [6][14] W1812G C-Terminus [14] F1831S C-Terminus [14] M1841T C-Terminus [18] S1846fsX1856 C-Terminus [16][17] R1882X C-Terminus [13] D1886Y C-Terminus Yes Hyperexcitable [33] R1892X C-Terminus [14] R1902X C-Terminus [13] Q1904fsX1945 C-Terminus [14] * Results are dependent on experimental paradigm ### Type 3[edit] Patients with GEFS+ type 3 have mutations in the GABRG2 gene, which encodes the GABAA γ2 subunit (figure 2). The first mutation discovered in GABRG2 was K289M, in the extracellular region linking membrane-spanning domains M2 and M3. Oocytes injected with α1, β2, and γ2 subunits produce large GABA inducible currents whereas those injected with K289M mutant instead of wild-type subunits produce currents much smaller (about 10% of wild-type). This abnormal current is not the result of non-incorporation of mutant subunits since mutant containing receptors are still sensitive to benzodiazepines, a property for which functional γ subunits are required. Because of these results, it is believed that the GEFS+ phenotype in these individuals is a result of hyperexcitability.[34] Concurrent with the previous mutation, a second group found a second mutation in GABRG2 associated with GEFS+. This mutation, R43Q, is located in the one of two benzodiazepine binding-sites located in the extracellular N-terminus. Benzodiazepines, such as Diazepam, potentiate GABA induced current. This potentiation is abolished in cells expressing the R43Q mutant subunit instead of the wild-type γ subunit. This mutation does not affect the subunit's ability to coassemble into function receptors as it still confers resistance to GABA current blockade by zinc. As with the previous mutation, this mutation is expected to result in neuronal hyperexcitability.[35][36] The final known GEFS+ type 3 mutation is a nonsense mutation, Q351X, located in the intracellular region linking the third and fourth membrane spanning segments. When this mutant subunit is expressed in cells with wild-type α and β subunits it produces non-functional receptors. Since wild-type α and β subunits expressed alone are able to produce GABA inducible current this indicates that the mutation either prevents both coassembly of the mutant and wild-type subunits but also coassembly of the wild-type α and β subunits or prevents proper trafficking of the formed receptor to the membrane. Fusion of GFP onto this mutated subunit has indicated that it is localized to the endoplasmic reticulum instead of the cell membrane. As with other known GEFS+ type 3 mutation, Q351X likely results in neuronal hyperexcitability.[37] ### SCN2A mutations[edit] Figure 3. Schematic structure of SCN2A with GEFS+ associated mutation positions indicated by red dots. The final type of GEFS+ is caused by mutations in the SCN2A gene, which encodes a sodium channel α subunit. The first associated mutation in this gene is R187W, located on the intracellular region linking membrane spanning units two and three in the first domain (D1S2-S3, figure 3). Patients with this mutation have both febrile and afebrile seizures. Electrophysiological examination of this mutant revealed that it increases the time constant for inactivation, presumably increasing sodium current and leading to hyperexcitability. However, this mutation also yields channels that inactivate at more hyperpolarized potentials relative to wild-type channels, indicative of hypoexcitability. Whether the end result on membrane excitability of this mutation is hyperexcitability or hypoexcitability is, as yet, unclear.[28][38] The second known mutation in SCN2A associated with GEFS+ is R102X. This mutation is located in the intracellular N-terminus (figure 3) and results in SMEI in patients. The result of this mutation is completely non-functional channels and membrane hypoexcitability. The truncated mutant protein also seems to cause wild-type channels to inactivate at more hyperpolarized potentials, indicating that it also acts in a dominant negative manner.[39] ## Management[edit] Long term management is by use of anticonvulsant medication, principally valproate, stiripentol, topiramate or clobazam.[40] Ketogenic diet has also been found useful in certain cases [41] Management of breakthrough seizures is by benzodiazepine such as midazolam.[citation needed] ## See also[edit] * Febrile seizures * Idiopathic generalized epilepsy * Dravet Syndrome Foundation * International Dravet Epilepsy Action League ## References[edit] 1. ^ a b Scheffer I, Berkovic S (1997). "Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes". Brain. 120 (3): 479–90. doi:10.1093/brain/120.3.479. PMID 9126059. 2. ^ a b Spampanato J, Escayg A, Meisler M, Goldin A (2003). "Generalized epilepsy with febrile seizures plus type 2 mutation W1204R alters voltage-dependent gating of Na(v)1.1 sodium channels". Neuroscience. 116 (1): 37–48. doi:10.1016/S0306-4522(02)00698-X. PMID 12535936. 3. ^ Singh R, Andermann E, Whitehouse W, Harvey A, Keene D, Seni M, Crossland K, Andermann F, Berkovic S, Scheffer I (2001). "Severe myoclonic epilepsy of infancy: extended spectrum of GEFS+?". Epilepsia. 42 (7): 837–44. doi:10.1046/j.1528-1157.2001.042007837.x. PMID 11488881. 4. ^ Scheffer, Ingrid; et al. (2007). "Epilepsy and mental retardation limited to females: an under-recognized disorder". Brain. 131 (4): 918–927. doi:10.1093/brain/awm338. PMID 18234694. 5. ^ a b Wallace R, Wang D, Singh R, Scheffer I, George A, Phillips H, Saar K, Reis A, Johnson E, Sutherland G, Berkovic S, Mulley J (1998). "Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B". Nat Genet. 19 (4): 366–70. doi:10.1038/1252. 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"An epilepsy mutation in the beta1 subunit of the voltage-gated sodium channel results in reduced channel sensitivity to phenytoin". Epilepsy Res. 64 (3): 77–84. doi:10.1016/j.eplepsyres.2005.03.003. PMID 15922564. 10. ^ Audenaert D, Claes L, Ceulemans B, Löfgren A, Van Broeckhoven C, De Jonghe P (2003). "A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy". Neurology. 61 (6): 854–6. doi:10.1212/01.wnl.0000080362.55784.1c. PMID 14504340. 11. ^ a b Cossette P, Loukas A, Lafrenière R, Rochefort D, Harvey-Girard E, Ragsdale D, Dunn R, Rouleau G (2003). "Functional characterization of the D188V mutation in neuronal voltage-gated sodium channel causing generalized epilepsy with febrile seizures plus (GEFS)". Epilepsy Res. 53 (1–2): 107–17. doi:10.1016/S0920-1211(02)00259-0. PMID 12576172. 12. ^ a b Barela A, Waddy S, Lickfett J, Hunter J, Anido A, Helmers S, Goldin A, Escayg A (2006). "An epilepsy mutation in the sodium channel SCN1A that decreases channel excitability". J Neurosci. 26 (10): 2714–23. doi:10.1523/JNEUROSCI.2977-05.2006. PMC 6675156. PMID 16525050. 13. ^ a b c d e f g h i j k l m n o p q r s t u v Fukuma G, Oguni H, Shirasaka Y, Watanabe K, Miyajima T, Yasumoto S, Ohfu M, Inoue T, Watanachai A, Kira R, Matsuo M, Muranaka H, Sofue F, Zhang B, Kaneko S, Mitsudome A, Hirose S (2004). "Mutations of neuronal voltage-gated Na+ channel alpha 1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB)". Epilepsia. 45 (2): 140–8. doi:10.1111/j.0013-9580.2004.15103.x. PMID 14738421. 14. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak Fujiwara T, Sugawara T, Mazaki-Miyazaki E, Takahashi Y, Fukushima K, Watanabe M, Hara K, Morikawa T, Yagi K, Yamakawa K, Inoue Y (2003). "Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures". Brain. 126 (Pt 3): 531–46. doi:10.1093/brain/awg053. PMID 12566275. 15. ^ a b c Wallace R, Scheffer I, Barnett S, Richards M, Dibbens L, Desai R, Lerman-Sagie T, Lev D, Mazarib A, Brand N, Ben-Zeev B, Goikhman I, Singh R, Kremmidiotis G, Gardner A, Sutherland G, George A, Mulley J, Berkovic S (2001). "Neuronal Sodium-Channel α1-Subunit Mutations in Generalized Epilepsy with Febrile Seizures Plus". Am J Hum Genet. 68 (4): 859–65. doi:10.1086/319516. PMC 1275639. PMID 11254444. 16. ^ a b c d e f g Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P (2001). "De Novo Mutations in the Sodium-Channel Gene SCN1A Cause Severe Myoclonic Epilepsy of Infancy". Am J Hum Genet. 68 (6): 1327–32. doi:10.1086/320609. PMC 1226119. PMID 11359211. 17. ^ a b c d e f Kearney J, Wiste A, Stephani U, Trudeau M, Siegel A, RamachandranNair R, Elterman R, Muhle H, Reinsdorf J, Shields W, Meisler M, Escayg A (2006). "Recurrent de novo mutations of SCN1A in severe myoclonic epilepsy of infancy". Pediatr Neurol. 34 (2): 116–20. doi:10.1016/j.pediatrneurol.2005.07.009. PMID 16458823. 18. ^ a b Annesi G, Gambardella A, Carrideo S, Incorpora G, Labate A, Pasqua A, Civitelli D, Polizzi A, Annesi F, Spadafora P, Tarantino P, Cirò Candiano I, Romeo N, De Marco E, Ventura P, LePiane E, Zappia M, Aguglia U, Pavone L, Quattrone A (2003). "Two novel SCN1A missense mutations in generalized epilepsy with febrile seizures plus". Epilepsia. 44 (9): 1257–8. doi:10.1046/j.1528-1157.2003.22503.x. PMID 12919402. 19. ^ Moulard B, Guipponi M, Chaigne D, Mouthon D, Buresi C, Malafosse A (1999). "Identification of a New Locus for Generalized Epilepsy with Febrile Seizures Plus (GEFS+) on Chromosome 2q24-q33". Am J Hum Genet. 65 (5): 1396–400. doi:10.1086/302621. PMC 1288292. PMID 10521305. 20. ^ a b Escayg A, MacDonald B, Meisler M, Baulac S, Huberfeld G, An-Gourfinkel I, Brice A, LeGuern E, Moulard B, Chaigne D, Buresi C, Malafosse A (2000). "Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2". Nat Genet. 24 (4): 343–5. doi:10.1038/74159. PMID 10742094. 21. ^ Alekov A, Rahman M, Mitrovic N, Lehmann-Horn F, Lerche H (2001). "Enhanced inactivation and acceleration of activation of the sodium channel associated with epilepsy in man". Eur J Neurosci. 13 (11): 2171–6. doi:10.1046/j.0953-816x.2001.01590.x. PMID 11422459. 22. ^ a b Spampanato J, Escayg A, Meisler M, Goldin A (2001). "Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2" (PDF). J Neurosci. 21 (19): 7481–90. doi:10.1523/JNEUROSCI.21-19-07481.2001. PMID 11567038. 23. ^ a b c Lossin C, Wang D, Rhodes T, Vanoye C, George A (2002). "Molecular basis of an inherited epilepsy". Neuron. 34 (6): 877–84. doi:10.1016/S0896-6273(02)00714-6. PMID 12086636. 24. ^ a b c d e Rhodes T, Lossin C, Vanoye C, Wang D, George A (2004). "Noninactivating voltage-gated sodium channels in severe myoclonic epilepsy of infancy". Proc Natl Acad Sci USA. 101 (30): 11147–52. Bibcode:2004PNAS..10111147R. doi:10.1073/pnas.0402482101. PMC 503754. PMID 15263074. 25. ^ a b c d e Lossin C, Rhodes T, Desai R, Vanoye C, Wang D, Carniciu S, Devinsky O, George A (2003). "Epilepsy-associated dysfunction in the voltage-gated neuronal sodium channel SCN1A". J Neurosci. 23 (36): 11289–95. doi:10.1523/JNEUROSCI.23-36-11289.2003. PMC 6740520. PMID 14672992. 26. ^ Escayg A, Heils A, MacDonald B, Haug K, Sander T, Meisler M (2001). "A Novel SCN1A Mutation Associated with Generalized Epilepsy with Febrile Seizures Plus—and Prevalence of Variants in Patients with Epilepsy". Am J Hum Genet. 68 (4): 866–73. doi:10.1086/319524. PMC 1275640. PMID 11254445. 27. ^ a b Ito M, Nagafuji H, Okazawa H, Yamakawa K, Sugawara T, Mazaki-Miyazaki E, Hirose S, Fukuma G, Mitsudome A, Wada K, Kaneko S (2002). "Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A". Epilepsy Res. 48 (1–2): 15–23. doi:10.1016/S0920-1211(01)00313-8. PMID 11823106. 28. ^ a b c Ito M, Yamakawa K, Sugawara T, Hirose S, Fukuma G, Kaneko S (2006). "Phenotypes and genotypes in epilepsy with febrile seizures plus". Epilepsy Res. 70 (2–3 Suppl): 199–205. doi:10.1016/j.eplepsyres.2005.11.028. PMID 16884893. 29. ^ Baulac S, Gourfinkel-An I, Picard F, Rosenberg-Bourgin M, Prud'homme J, Baulac M, Brice A, LeGuern E (1999). "A Second Locus for Familial Generalized Epilepsy with Febrile Seizures Plus Maps to Chromosome 2q21-q33". Am J Hum Genet. 65 (4): 1078–85. doi:10.1086/302593. PMC 1288241. PMID 10486327. 30. ^ a b Vanoye C, Lossin C, Rhodes T, George A (2006). "Single-channel Properties of Human NaV1.1 and Mechanism of Channel Dysfunction in SCN1A-associated Epilepsy". J Gen Physiol. 127 (1): 1–14. doi:10.1085/jgp.200509373. PMC 2151481. PMID 16380441. 31. ^ Nagao Y, Mazaki-Miyazaki E, Okamura N, Takagi M, Igarashi T, Yamakawa K (2005). "A family of generalized epilepsy with febrile seizures plus type 2-a new missense mutation of SCN1A found in the pedigree of several patients with complex febrile seizures". Epilepsy Res. 63 (2–3): 151–6. doi:10.1016/j.eplepsyres.2004.11.005. PMID 15715999. 32. ^ Pineda-Trujillo N, Carrizosa J, Cornejo W, Arias W, Franco C, Cabrera D, Bedoya G, Ruíz-Linares A (2005). "A novel SCN1A mutation associated with severe GEFS+ in a large South American pedigree". Seizure. 14 (2): 123–8. doi:10.1016/j.seizure.2004.12.007. PMID 15694566. 33. ^ Spampanato J, Kearney J, de Haan G, McEwen D, Escayg A, Aradi I, MacDonald B, Levin S, Soltesz I, Benna P, Montalenti E, Isom L, Goldin A, Meisler M (2004). "A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for beta subunit interaction". J Neurosci. 24 (44): 10022–34. doi:10.1523/JNEUROSCI.2034-04.2004. PMC 6730248. PMID 15525788. 34. ^ Baulac S, Huberfeld G, Gourfinkel-An I, Mitropoulou G, Beranger A, Prud'homme J, Baulac M, Brice A, Bruzzone R, LeGuern E (2001). "First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene". Nat Genet. 28 (1): 46–8. doi:10.1038/88254. PMID 11326274. 35. ^ Wallace R, Marini C, Petrou S, Harkin L, Bowser D, Panchal R, Williams D, Sutherland G, Mulley J, Scheffer I, Berkovic S (2001). "Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures". Nat Genet. 28 (1): 49–52. doi:10.1038/88259. PMID 11326275. 36. ^ Marini C, Harkin L, Wallace R, Mulley J, Scheffer I, Berkovic S (2003). "Childhood absence epilepsy and febrile seizures: a family with a GABA(A) receptor mutation". Brain. 126 (Pt 1): 230–40. doi:10.1093/brain/awg018. PMID 12477709. 37. ^ Harkin L, Bowser D, Dibbens L, Singh R, Phillips F, Wallace R, Richards M, Williams D, Mulley J, Berkovic S, Scheffer I, Petrou S (2002). "Truncation of the GABAA-Receptor γ2 Subunit in a Family with Generalized Epilepsy with Febrile Seizures Plus". Am J Hum Genet. 70 (2): 530–6. doi:10.1086/338710. PMC 384926. PMID 11748509. 38. ^ Sugawara T, Tsurubuchi Y, Agarwala K, Ito M, Fukuma G, Mazaki-Miyazaki E, Nagafuji H, Noda M, Imoto K, Wada K, Mitsudome A, Kaneko S, Montal M, Nagata K, Hirose S, Yamakawa K (2001). "A missense mutation of the Na+ channel αII subunit gene Nav1.2 in a patient with febrile and afebrile seizures causes channel dysfunction". Proc Natl Acad Sci USA. 98 (11): 6384–9. Bibcode:2001PNAS...98.6384S. doi:10.1073/pnas.111065098. PMC 33477. PMID 11371648. 39. ^ Kamiya K, Kaneda M, Sugawara T, Mazaki E, Okamura N, Montal M, Makita N, Tanaka M, Fukushima K, Fujiwara T, Inoue Y, Yamakawa K (2004). "A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline". J Neurosci. 24 (11): 2690–8. doi:10.1523/JNEUROSCI.3089-03.2004. PMC 6729532. PMID 15028761. 40. ^ British National Formulary for Children (May 2014) 41. ^ "Search Results \| Great Ormond Street Hospital". ## External links[edit] Classification D * ICD-10: G40.3 * OMIM: 604233 609800 607208 * MeSH: C565809 * v * t * e Diseases of ion channels Calcium channel Voltage-gated * CACNA1A * Familial hemiplegic migraine 1 * Episodic ataxia 2 * Spinocerebellar ataxia type-6 * CACNA1C * Timothy syndrome * Brugada syndrome 3 * Long QT syndrome 8 * CACNA1F * Ocular albinism 2 * CSNB2A * CACNA1S * Hypokalemic periodic paralysis 1 * Thyrotoxic periodic paralysis 1 * CACNB2 * Brugada syndrome 4 Ligand gated * RYR1 * Malignant hyperthermia * Central core disease * RYR2 * CPVT1 * ARVD2 Sodium channel Voltage-gated * SCN1A * Familial hemiplegic migraine 3 * GEFS+ 2 * Febrile seizure 3A * SCN1B * Brugada syndrome 6 * GEFS+ 1 * SCN4A * Hypokalemic periodic paralysis 2 * Hyperkalemic periodic paralysis * Paramyotonia congenita * Potassium-aggravated myotonia * SCN4B * Long QT syndrome 10 * SCN5A * Brugada syndrome 1 * Long QT syndrome 3 * SCN9A * Erythromelalgia * Febrile seizure 3B * Paroxysmal extreme pain disorder * Congenital insensitivity to pain Constitutively active * SCNN1B/SCNN1G * Liddle's syndrome * SCNN1A/SCNN1B/SCNN1G * Pseudohypoaldosteronism 1AR Potassium channel Voltage-gated * KCNA1 * Episodic ataxia 1 * KCNA5 * Familial atrial fibrillation 7 * KCNC3 * Spinocerebellar ataxia type-13 * KCNE1 * Jervell and Lange-Nielsen syndrome * Long QT syndrome 5 * KCNE2 * Long QT syndrome 6 * KCNE3 * Brugada syndrome 5 * KCNH2 * Short QT syndrome * KCNQ1 * Jervell and Lange-Nielsen syndrome * Romano–Ward syndrome * Short QT syndrome * Long QT syndrome 1 * Familial atrial fibrillation 3 * KCNQ2 * BFNS1 Inward-rectifier * KCNJ1 * Bartter syndrome 2 * KCNJ2 * Andersen–Tawil syndrome * Long QT syndrome 7 * Short QT syndrome * KCNJ11 * TNDM3 * KCNJ18 * Thyrotoxic periodic paralysis 2 Chloride channel * CFTR * Cystic fibrosis * Congenital absence of the vas deferens * CLCN1 * Thomsen disease * Myotonia congenita * CLCN5 * Dent's disease * CLCN7 * Osteopetrosis A2, B4 * BEST1 * Vitelliform macular dystrophy * CLCNKB * Bartter syndrome 3 TRP channel * TRPC6 * FSGS2 * TRPML1 * Mucolipidosis type IV Connexin * GJA1 * Oculodentodigital dysplasia * Hallermann–Streiff syndrome * Hypoplastic left heart syndrome * GJB1 * Charcot–Marie–Tooth disease X1 * GJB2 * Keratitis–ichthyosis–deafness syndrome * Ichthyosis hystrix * Bart–Pumphrey syndrome * Vohwinkel syndrome) * GJB3/GJB4 * Erythrokeratodermia variabilis * Progressive symmetric erythrokeratodermia * GJB6 * Clouston's hidrotic ectodermal dysplasia Porin * AQP2 * Nephrogenic diabetes insipidus 2 See also: ion channels [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Generalized epilepsy with febrile seizures plus	c1858672	30,529	wikipedia	https://en.wikipedia.org/wiki/Generalized_epilepsy_with_febrile_seizures_plus	2021-01-18T18:57:57	{"mesh": ["C565809"], "umls": ["C1858672"], "orphanet": ["36387"], "wikidata": ["Q16909671"]}
Superfetation occurs as a result of continuing ovulation and implantation after the initiation of another pregnancy. This rare phenomenon, leading to an unusual form of fraternal twinning, was reported as an autosomal dominant trait by Rhine and Nance (1976). The gene is transmitted by males as well as females, suggesting that it is primarily expressed at the level of the placenta rather than at the level of the mother's hypothalamus or the ovary. By some mechanism, the placenta, under the influence of a dominant gene, permits further ovulation and implantation. In the family reported by Rhine and Nance (1976), all the twin pairs showed marked discordance in birth weight and gestational age. In 5 of the 6 pairs, 1 twin was normal while the other was either a macerated fetal mass or a stillbirth, or died of prematurity in the neonatal period. The single twin pair that survived was dizygotic and showed a 21% discrepancy in body weight. Nance et al. (1978) pictured the pedigree of an Italian kindred with 9 sets of twins in 4 generations. Nance (1986) knew of additional families. INHERITANCE \- Autosomal dominant MISCELLANEOUS \- Superfetation twinning \- Continuing ovulation and implantation after initiation of another pregnancy ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	TWINNING DUE TO SUPERFETATION	c1860645	30,530	omim	https://www.omim.org/entry/191250	2019-09-22T16:32:14	{"mesh": ["C566018"], "omim": ["191250"], "synonyms": ["Alternative titles", "SUPERFETATION TWINNING"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive nonsyndromic deafness-31 (DFNB31) is caused by homozygous mutation in the whirlin gene (WHRN; 607928) on chromosome 9q32. Clinical Features Mustapha et al. (2002) described a consanguineous Palestinian family from Jordan in which 6 members had profound prelingual nonsyndromic hearing loss. Tlili et al. (2005) reported a consanguineous Tunisian family in which 4 sibs had congenital profound hearing loss (greater than 90 dB) but were otherwise healthy with no dysmorphic or other abnormal findings indicative of syndromic deafness. No vestibular defects were detected. Mapping By homozygosity mapping in a consanguineous Palestinian family from Jordan with autosomal recessive neurosensory hearing loss, Mustapha et al. (2002) mapped a locus for the deafness (DFNB31) to chromosome 9q32-q34. A genomewide screening showed linkage to marker D9S1776 (2-point lod score of 4.98 at theta of zero). The homozygous region common to the 6 affected individuals extended between markers D9S1824 and D9S1682, a region of 15.1 cM. The murine region showing homology of synteny to the DFNB31 interval is located on chromosome 4, which contains the locus for the recessive deafness mutant 'whirler' (wi). The whirler mutation in the mouse causes, in the homozygous adult, the shaker-waltzer syndrome: deafness and circling with tossing of the head (Fleming et al., 1994). Mustapha et al. (2002) proposed that DFNB31 and whirler may result from orthologous gene defects. Molecular Genetics Mburu et al. (2003) pointed out that in the whirler mouse mutant, ultrastructural analysis of sensory hair cells in the organ of Corti of the inner ear indicated that the gene encodes a protein involved in the elongation and maintenance of stereocilia in both inner hair cells and outer hair cells. BAC-mediated transgene correction of the mouse phenotype and mutation analysis identified the causative gene as encoding a novel PDZ protein, which the authors designated whirlin. They suggested that this PDZ domain-containing molecule acts as an organizer of submembranous molecular complexes that control the coordinated actin polymerization and membrane growth of stereocilia. In affected members of the Palestinian family with nonsyndromic deafness reported by Mustapha et al. (2002), Mburu et al. (2003) identified homozygosity for an arg778-to-ter mutation in the WHRN gene (607928.0001). In affected members of a consanguineous Tunisian family with autosomal recessive nonsyndromic deafness showing linkage to the DFNB31 region, Tlili et al. (2005) identified a homozygous frameshift mutation in the WHRN gene (607928.0006). The mutation segregated with the phenotype in the family. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural (bilateral, profound, and prelingual) MISCELLANEOUS \- Based on reports of a consanguineous Jordanian family and a Tunisian family (last curated August 2015) MOLECULAR BASIS \- Caused by mutation in the whirlin gene (WHRN, 607928.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	DEAFNESS, AUTOSOMAL RECESSIVE 31	c1846839	30,531	omim	https://www.omim.org/entry/607084	2019-09-22T16:09:43	{"doid": ["0110490"], "mesh": ["C564629"], "omim": ["607084"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive non-syndromic neurosensory deafness type DFNB", "WHIRLER, MOUSE, HOMOLOG OF", "Alternative titles", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive isolated neurosensory deafness type DFNB"], "genereviews": ["NBK1434"]}
Immune suppression may be merely the 'other side of the coin' from immune response. Sasazuki et al. (1980) proposed linkage between HLA and a dominant gene at a locus Is (immune suppression), which suppresses in vitro lymphoproliferative response to streptococcal cell wall antigen. A lod score of +3.2 was observed in 7 families for linkage of the postulated locus with HLA. Although no recombinants were observed, pleiotropism was considered unlikely because no significant association between low responders and HLA specificities was found in the random population. The gene presumably controls the generation of suppressor T cells. The existence of such cells was demonstrated in man by McMichael and Sasazuki (1977), using the mixed lymphocyte response (MLR) system; Engleman et al. (1978) demonstrated a soluble factor that can replace the suppressor T cell. Nishimura and Sasazuki (1983) further demonstrated that the gene controls the generation of the antigen-specific suppressor T cell. Immunology \- Immune suppression \- Control of suppressor T cell generation Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	IMMUNE SUPPRESSION	c1840264	30,532	omim	https://www.omim.org/entry/146850	2019-09-22T16:39:36	{"omim": ["146850"], "synonyms": ["Alternative titles", "STREPTOCOCCAL CELL WALL ANTIGEN, SUPPRESSION OF IMMUNE RESPONSE TO", "ISCW"]}
## Clinical Features Progressive bifocal chorioretinal atrophy is a rare, autosomal dominant congenital chorioretinal dystrophy. The disorder is characterized by progressive macular and nasal retinal atrophic lesions, nystagmus, myopia, and poor vision (Douglas et al., 1968). Invariably, there are 2 distinct foci of atrophy, a temporal focus that is present at birth and a nasal focus that appears early in life. Retinal detachment is an additional complication of the disease. Mapping Kelsell et al. (1995) performed linkage analysis on a large 5-generation family based in Dundee, Scotland, with progressive bifocal chorioretinal atrophy. As 2 macular dystrophy genes had already been mapped to the region 6q11-q16.2, Stargardt disease-3 (600110) and the North Carolina type of macular dystrophy (136550), they chose to concentrate their linkage analysis first on that region. Two-point linkage analysis showed significant linkage with 9 microsatellite markers mapping to 6q. Multipoint analysis gave a maximum lod score of 11.8 (theta = 0.05) between D6S249 and D6S283, in the region 6q14-q16.2. This region overlaps with that to which the North Carolina macular dystrophy gene had been assigned. The range of differences in phenotype between the 2 retinal disorders led Kelsell et al. (1995) to conclude, however, that 'different mutation mechanisms are responsible for each disease.' Unlike PBCRA, the North Carolina macular dystrophy is nonprogressive and the vision tends to be good, unless complicated by the presence of choroidal neovascularization. Molecular Genetics In patients from 6q-linked multigenerational families diagnosed with PBCRA or MCDR1 (136550), as well as in a single patient from an autosomal dominant STGD family unlinked to STGD2 or STGD3 loci on 13q or 6q (see 600110), respectively, Gehrig et al. (1998) found no disease-associated mutations in the IMPG1 (602870) gene. Eyes \- Progressive bifocal chorioretinal atrophy \- Congenital chorioretinal dystrophy \- Progressive macular and nasal retinal atrophic lesions \- Nystagmus \- Myopia \- Poor vision \- Congenital temporal atrophy \- Retinal detachment Inheritance \- Autosomal dominant (6q) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	CHORIORETINAL ATROPHY, PROGRESSIVE BIFOCAL	c1833321	30,533	omim	https://www.omim.org/entry/600790	2019-09-22T16:15:55	{"mesh": ["C535356"], "omim": ["600790"], "orphanet": ["75373"], "synonyms": ["Alternative titles", "CRAPB", "PROGRESSIVE BIFOCAL CHORIORETINAL ATROPHY"]}
For a phenotypic description and a discussion of genetic heterogeneity of bipolar disorder, see 125480. Mapping Jamra et al. (2007) presented the first genomewide interaction and locus heterogeneity linkage scan in bipolar affective disorder (BPAD), using a large linkage dataset (52 families of European descent; 448 participants and 259 affected individuals). The results provided the strongest evidence of interaction between BPAD genes on chromosome 2q22-q24 (MAFD5; 611535) and 6q23-q24 (MAFD6), which was observed symmetrically in both directions; nonparametric lod (NPL) scores of 7.55 on 2q and 7.63 on 6q; P less than 0.0001 and P = 0.0001, respectively, after a genomewide permutation procedure. With use of a 1-lod interval, the underlying BPAD gene on 6q23-q24 is located between 131 and 148 cM corresponding to approximately 132 and 147 Mb, respectively, according to NCBI36. Jamra et al. (2007) noted that the BPAD locus on 6q23-q24 identified by them overlapped the most significant implicated BPAD locus in the linkage metaanalysis by McQueen et al. (2005). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	MAJOR AFFECTIVE DISORDER 6	c1970945	30,534	omim	https://www.omim.org/entry/611536	2019-09-22T16:03:09	{"mesh": ["C567075"], "omim": ["611536"], "synonyms": ["Alternative titles", "BIPOLAR AFFECTIVE DISORDER"]}
Hepatocellular adenoma (HA) is a rare benign tumor of the liver. ## Epidemiology Annual incidence is estimated at one case per million. ## Clinical description Mean age at diagnosis is 34 years (ranging from 15 to 64 years). HA rarely occurs in children. Most patients with HA are asymptomatic and lesions are found incidentally during laparotomy or radiologic studies performed for other reasons. Pain or discomfort in the right upper quadrant or epigastric region is common, but not always related to the adenoma. HA may be revealed by spontaneous rupture or hemorrhage (leading to acute abdominal pain and possibly progressing to hemorrhagic shock, hypotension and even death). These complications are estimated to occur in 30% of patients with an adenoma over 5 cm in diameter. HA patients have normal liver function and no elevation of serum tumor markers. Serum aminotransferases and gamma-glutamyl transpeptidase may be mildly elevated. HA is typically solitary, although multiple lesions have been reported under the denomination `hepatocellular adenomatosis'. Size varies from about 1 cm (the detection limit for usual imaging methods) to over 20 cm. There appears to be a zero risk of complications for patients with a HA below 5 cm in diameter. In rare cases, and more frequently in males, the largest tumors may harbor malignant features. Histologically, adenoma cells are larger than normal hepatocytes but do not show cytonuclear atypia. Few or no portal tracts, central veins or bile ducts are present but there are isolated arteries. Kupffer cells are less numerous or absent. ## Etiology In most cases, adenomas develop for unclear reasons in an otherwise healthy liver. Some predisposing conditions have been identified: prolonged oral contraceptive use, glycogenosis type III and IV, congenital portocaval shunt and, in males, use of anabolic steroids. Molecular analysis has disclosed specific mutations in adenomatous cells, each associated with specific histological features: HNF1 mutations are associated with fatty hepatocytes, and mutations in beta-catenin are associated with dysplasia and malignant transformation. An additional type of hepatic adenoma has recently been characterized as telangiectatic adenoma. This type of adenoma features sinusoidal dilatation and inflammatory infiltrates. ## Diagnostic methods Diagnosis is made by a characteristic pattern of enhancement after injection of intravascular contrast medium, using contrast enhanced ultrasound, multiphasic computed tomography, or gadolinium-enhanced MRI. Biopsy and/or resection may be necessary to confirm the diagnosis. ## Differential diagnosis Differential diagnosis includes some forms of angiomas, focal nodular hyperplasia, hepatocellular carcinoma (see these terms), and certain types of liver metastases. ## Management and treatment Oral contraceptives are contraindicated and should be stopped. Surgical resection is advocated in most patients with a HA greater than 5 cm in diameter. When diagnosis is certain, and the tumor is less than 5 cm in diameter and asymptomatic, it can be left in place but surveillance is required. ## Prognosis Malignant transformation is rare and the long-term prognosis is good. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Hepatocellular adenoma	c0206669	30,535	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=54272	2021-01-23T18:08:54	{"mesh": ["D018248"], "umls": ["C0206669"], "icd-10": ["D13.4"]}
Inflammation of the membranes around the brain and spinal cord Meningitis Meninges of the central nervous system: dura mater, arachnoid mater, and pia mater. SpecialtyInfectious disease, neurology SymptomsFever, headache, neck stiffness[1] ComplicationsDeafness, epilepsy, hydrocephalus, cognitive deficits[2][3] CausesViral, bacterial, other[4] Diagnostic methodLumbar puncture[1] Differential diagnosisEncephalitis, brain tumor, lupus, Lyme disease, seizures, neuroleptic malignant syndrome,[5] naegleriasis[6] PreventionVaccination[2] MedicationAntibiotics, antivirals, steroids[1][7][8] Frequency10.6 million (2017)[9] Deaths288,000 (2017)[10] Meningitis is an acute inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges.[2] The most common symptoms are fever, headache, and neck stiffness.[1] Other symptoms include confusion or altered consciousness, vomiting, and an inability to tolerate light or loud noises.[1] Young children often exhibit only nonspecific symptoms, such as irritability, drowsiness, or poor feeding.[1] If a rash is present, it may indicate a particular cause of meningitis; for instance, meningitis caused by meningococcal bacteria may be accompanied by a characteristic rash.[2][3] The inflammation may be caused by infection with bacteria, other microorganisms, or viruses, and less commonly by certain drugs.[4] Meningitis can be life-threatening because of the inflammation's proximity to the brain and spinal cord; therefore, the condition is classified as a medical emergency.[2][8] A lumbar puncture, in which a needle is inserted into the spinal canal to collect a sample of cerebrospinal fluid (CSF), can diagnose or exclude meningitis.[1][8] Some forms of meningitis are preventable by immunization with the meningococcal, mumps, pneumococcal, and Hib vaccines.[2] Giving antibiotics to people with significant exposure to certain types of meningitis may also be useful.[1] The first treatment in acute meningitis consists of promptly giving antibiotics and sometimes antiviral drugs.[1][7] Corticosteroids can also be used to prevent complications from excessive inflammation.[3][8] Meningitis can lead to serious long-term consequences such as deafness, epilepsy, hydrocephalus, or cognitive deficits, especially if not treated quickly.[2][3] In 2017, meningitis occurred in about 10.6 million people worldwide.[9] This resulted in 288,000 deaths—down from 464,000 deaths in 1990.[11][12] With appropriate treatment the risk of death in bacterial meningitis is less than 15%.[1] Outbreaks of bacterial meningitis occur between December and June each year in an area of sub-Saharan Africa known as the meningitis belt.[13] Smaller outbreaks may also occur in other areas of the world.[13] The word meningitis comes from the Greek μῆνιγξ meninx, "membrane", and the medical suffix -itis, "inflammation".[14][15] ## Contents * 1 Signs and symptoms * 1.1 Clinical features * 1.2 Early complications * 2 Causes * 2.1 Bacterial * 2.2 Viral * 2.3 Fungal * 2.4 Parasitic * 2.5 Non-infectious * 3 Mechanism * 4 Diagnosis * 4.1 Lumbar puncture * 4.2 Postmortem * 5 Prevention * 5.1 Behavioral * 5.2 Vaccination * 5.3 Antibiotics * 6 Management * 6.1 Bacterial meningitis * 6.1.1 Antibiotics * 6.1.2 Steroids * 6.2 Viral meningitis * 6.3 Fungal meningitis * 7 Prognosis * 8 Epidemiology * 9 History * 10 References * 11 External links ## Signs and symptoms[edit] ### Clinical features[edit] Neck stiffness, Texas meningitis epidemic of 1911–12 In adults, the most common symptom of meningitis is a severe headache, occurring in almost 90% of cases of bacterial meningitis, followed by neck stiffness (the inability to flex the neck forward passively due to increased neck muscle tone and stiffness).[16] The classic triad of diagnostic signs consists of neck stiffness, sudden high fever, and altered mental status; however, all three features are present in only 44–46% of bacterial meningitis cases.[16][17] If none of the three signs are present, acute meningitis is extremely unlikely.[17] Other signs commonly associated with meningitis include photophobia (intolerance to bright light) and phonophobia (intolerance to loud noises). Small children often do not exhibit the aforementioned symptoms, and may only be irritable and look unwell.[2] The fontanelle (the soft spot on the top of a baby's head) can bulge in infants aged up to 6 months. Other features that distinguish meningitis from less severe illnesses in young children are leg pain, cold extremities, and an abnormal skin color.[18][19] Nuchal rigidity occurs in 70% of bacterial meningitis in adults.[17] Other signs include the presence of positive Kernig's sign or Brudziński sign. Kernig's sign is assessed with the person lying supine, with the hip and knee flexed to 90 degrees. In a person with a positive Kernig's sign, pain limits passive extension of the knee. A positive Brudzinski's sign occurs when flexion of the neck causes involuntary flexion of the knee and hip. Although Kernig's sign and Brudzinski's sign are both commonly used to screen for meningitis, the sensitivity of these tests is limited.[17][20] They do, however, have very good specificity for meningitis: the signs rarely occur in other diseases.[17] Another test, known as the "jolt accentuation maneuver" helps determine whether meningitis is present in those reporting fever and headache. A person is asked to rapidly rotate the head horizontally; if this does not make the headache worse, meningitis is unlikely.[17] Other problems can produce symptoms similar to those above, but from non-meningitic causes. This is called meningism or pseudomeningitis. Meningitis caused by the bacterium Neisseria meningitidis (known as "meningococcal meningitis") can be differentiated from meningitis with other causes by a rapidly spreading petechial rash, which may precede other symptoms.[18] The rash consists of numerous small, irregular purple or red spots ("petechiae") on the trunk, lower extremities, mucous membranes, conjunctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typically non-blanching; the redness does not disappear when pressed with a finger or a glass tumbler. Although this rash is not necessarily present in meningococcal meningitis, it is relatively specific for the disease; it does, however, occasionally occur in meningitis due to other bacteria.[2] Other clues on the cause of meningitis may be the skin signs of hand, foot and mouth disease and genital herpes, both of which are associated with various forms of viral meningitis.[21] ### Early complications[edit] Charlotte Cleverley-Bisman developed severe meningococcal meningitis as a young child; in her case, the petechial rash progressed to gangrene and required amputation of all limbs. She survived the disease and became a poster child for a meningitis vaccination campaign in New Zealand. Additional problems may occur in the early stage of the illness. These may require specific treatment, and sometimes indicate severe illness or worse prognosis. The infection may trigger sepsis, a systemic inflammatory response syndrome of falling blood pressure, fast heart rate, high or abnormally low temperature, and rapid breathing. Very low blood pressure may occur at an early stage, especially but not exclusively in meningococcal meningitis; this may lead to insufficient blood supply to other organs.[2] Disseminated intravascular coagulation, the excessive activation of blood clotting, may obstruct blood flow to organs and paradoxically increase the bleeding risk. Gangrene of limbs can occur in meningococcal disease.[2] Severe meningococcal and pneumococcal infections may result in hemorrhaging of the adrenal glands, leading to Waterhouse-Friderichsen syndrome, which is often fatal.[22] The brain tissue may swell, pressure inside the skull may increase and the swollen brain may herniate through the skull base. This may be noticed by a decreasing level of consciousness, loss of the pupillary light reflex, and abnormal posturing.[3] The inflammation of the brain tissue may also obstruct the normal flow of CSF around the brain (hydrocephalus).[3] Seizures may occur for various reasons; in children, seizures are common in the early stages of meningitis (in 30% of cases) and do not necessarily indicate an underlying cause.[8] Seizures may result from increased pressure and from areas of inflammation in the brain tissue.[3] Focal seizures (seizures that involve one limb or part of the body), persistent seizures, late-onset seizures and those that are difficult to control with medication indicate a poorer long-term outcome.[2] Inflammation of the meninges may lead to abnormalities of the cranial nerves, a group of nerves arising from the brain stem that supply the head and neck area and which control, among other functions, eye movement, facial muscles, and hearing.[2][17] Visual symptoms and hearing loss may persist after an episode of meningitis.[2] Inflammation of the brain (encephalitis) or its blood vessels (cerebral vasculitis), as well as the formation of blood clots in the veins (cerebral venous thrombosis), may all lead to weakness, loss of sensation, or abnormal movement or function of the part of the body supplied by the affected area of the brain.[2][3] ## Causes[edit] Meningitis is typically caused by an infection with microorganisms. Most infections are due to viruses,[17] with bacteria, fungi, and protozoa being the next most common causes.[4] It may also result from various non-infectious causes.[4] The term aseptic meningitis refers to cases of meningitis in which no bacterial infection can be demonstrated. This type of meningitis is usually caused by viruses but it may be due to bacterial infection that has already been partially treated, when bacteria disappear from the meninges, or pathogens infect a space adjacent to the meninges (e.g. sinusitis). Endocarditis (an infection of the heart valves which spreads small clusters of bacteria through the bloodstream) may cause aseptic meningitis. Aseptic meningitis may also result from infection with spirochetes, a group of bacteria that includes Treponema pallidum (the cause of syphilis) and Borrelia burgdorferi (known for causing Lyme disease). Meningitis may be encountered in cerebral malaria (malaria infecting the brain) or amoebic meningitis, meningitis due to infection with amoebae such as Naegleria fowleri, contracted from freshwater sources.[4] ### Bacterial[edit] See also: Neonatal infection Streptococcus pneumoniae—a causative bacteria of meningitis (illustration). The types of bacteria that cause bacterial meningitis vary according to the infected individual's age group. * In premature babies and newborns up to three months old, common causes are group B streptococci (subtypes III which normally inhabit the vagina and are mainly a cause during the first week of life) and bacteria that normally inhabit the digestive tract such as Escherichia coli (carrying the K1 antigen). Listeria monocytogenes (serotype IVb) can be contracted when consuming improperly prepared food such as dairy products, produce and deli meats, [23] [24] and may cause meningitis in the newborn.[25] * Older children are more commonly affected by Neisseria meningitidis (meningococcus) and Streptococcus pneumoniae (serotypes 6, 9, 14, 18 and 23) and those under five by Haemophilus influenzae type B (in countries that do not offer vaccination).[2][8] * In adults, Neisseria meningitidis and Streptococcus pneumoniae together cause 80% of bacterial meningitis cases. Risk of infection with Listeria monocytogenes is increased in persons over 50 years old.[3][8] The introduction of pneumococcal vaccine has lowered rates of pneumococcal meningitis in both children and adults.[26] Recent skull trauma potentially allows nasal cavity bacteria to enter the meningeal space. Similarly, devices in the brain and meninges, such as cerebral shunts, extraventricular drains or Ommaya reservoirs, carry an increased risk of meningitis. In these cases, the persons are more likely to be infected with Staphylococci, Pseudomonas, and other Gram-negative bacteria.[8] These pathogens are also associated with meningitis in people with an impaired immune system.[2] An infection in the head and neck area, such as otitis media or mastoiditis, can lead to meningitis in a small proportion of people.[8] Recipients of cochlear implants for hearing loss are more at risk for pneumococcal meningitis.[27] Tuberculous meningitis, which is meningitis caused by Mycobacterium tuberculosis, is more common in people from countries in which tuberculosis is endemic, but is also encountered in persons with immune problems, such as AIDS.[28] Recurrent bacterial meningitis may be caused by persisting anatomical defects, either congenital or acquired, or by disorders of the immune system.[29] Anatomical defects allow continuity between the external environment and the nervous system. The most common cause of recurrent meningitis is a skull fracture,[29] particularly fractures that affect the base of the skull or extend towards the sinuses and petrous pyramids.[29] Approximately 59% of recurrent meningitis cases are due to such anatomical abnormalities, 36% are due to immune deficiencies (such as complement deficiency, which predisposes especially to recurrent meningococcal meningitis), and 5% are due to ongoing infections in areas adjacent to the meninges.[29] ### Viral[edit] Viruses that cause meningitis include enteroviruses, herpes simplex virus (generally type 2, which produces most genital sores; less commonly type 1), varicella zoster virus (known for causing chickenpox and shingles), mumps virus, HIV, LCMV,[21] Arboviruses (acquired from a mosquito or other insect), and the Influenza virus.[30] Mollaret's meningitis is a chronic recurrent form of herpes meningitis; it is thought to be caused by herpes simplex virus type 2.[31] ### Fungal[edit] There are a number of risk factors for fungal meningitis, including the use of immunosuppressants (such as after organ transplantation), HIV/AIDS,[32] and the loss of immunity associated with aging.[33] It is uncommon in those with a normal immune system[34] but has occurred with medication contamination.[35] Symptom onset is typically more gradual, with headaches and fever being present for at least a couple of weeks before diagnosis.[33] The most common fungal meningitis is cryptococcal meningitis due to Cryptococcus neoformans.[36] In Africa, cryptococcal meningitis is now the most common cause of meningitis in multiple studies,[37][38] and it accounts for 20–25% of AIDS-related deaths in Africa.[39] Other less common fungal pathogens which can cause meningitis include: Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, and Candida species.[33] ### Parasitic[edit] A parasitic cause is often assumed when there is a predominance of eosinophils (a type of white blood cell) in the CSF. The most common parasites implicated are Angiostrongylus cantonensis, Gnathostoma spinigerum, Schistosoma, as well as the conditions cysticercosis, toxocariasis, baylisascariasis, paragonimiasis, and a number of rarer infections and noninfective conditions.[40] ### Non-infectious[edit] Meningitis may occur as the result of several non-infectious causes: spread of cancer to the meninges (malignant or neoplastic meningitis)[41] and certain drugs (mainly non-steroidal anti-inflammatory drugs, antibiotics and intravenous immunoglobulins).[42] It may also be caused by several inflammatory conditions, such as sarcoidosis (which is then called neurosarcoidosis), connective tissue disorders such as systemic lupus erythematosus, and certain forms of vasculitis (inflammatory conditions of the blood vessel wall), such as Behçet's disease.[4] Epidermoid cysts and dermoid cysts may cause meningitis by releasing irritant matter into the subarachnoid space.[4][29] Rarely, migraine may cause meningitis, but this diagnosis is usually only made when other causes have been eliminated.[4] ## Mechanism[edit] The meninges comprise three membranes that, together with the cerebrospinal fluid, enclose and protect the brain and spinal cord (the central nervous system). The pia mater is a delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. The arachnoid mater (so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. The subarachnoid space separates the arachnoid and pia mater membranes and is filled with cerebrospinal fluid. The outermost membrane, the dura mater, is a thick durable membrane, which is attached to both the arachnoid membrane and the skull. In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream or through direct contact between the meninges and either the nasal cavity or the skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live upon mucous surfaces such as the nasal cavity. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucous surfaces. Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the blood–brain barrier is vulnerable – such as the choroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is less common in adults.[2] Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally, congenital defects of the dura mater can be identified.[2] The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but can rather largely be attributed to the response of the immune system to the entry of bacteria into the central nervous system. When components of the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and microglia), they respond by releasing large amounts of cytokines, hormone-like mediators that recruit other immune cells and stimulate other tissues to participate in an immune response. The blood–brain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing inflammation of the meninges and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to increased intracranial pressure; together with the lowered blood pressure often encountered in acute infection, this means that it is harder for blood to enter the brain, consequently brain cells are deprived of oxygen and undergo apoptosis (programmed cell death).[2] It is recognized that administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane products released through the destruction of bacteria. Particular treatments, such as the use of corticosteroids, are aimed at dampening the immune system's response to this phenomenon.[2][3] ## Diagnosis[edit] CSF findings in different forms of meningitis[43] Type of meningitis Glucose Protein Cells Acute bacterial low high PMNs, often > 300/mm³ Acute viral normal normal or high mononuclear, < 300/mm³ Tuberculous low high mononuclear and PMNs, < 300/mm³ Fungal low high < 300/mm³ Malignant low high usually mononuclear Diagnosing meningitis as promptly as possible can improve outcomes.[44] There is no specific sign or symptom that can diagnose meningitis and a lumbar puncture (spinal tap) to examine the cerebrospinal fluid is recommended for diagnosis.[44] Lumbar puncture is contraindicated if there is a mass in the brain (tumor or abscess) or the intracranial pressure (ICP) is elevated, as it may lead to brain herniation. If someone is at risk for either a mass or raised ICP (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), a CT or MRI scan is recommended prior to the lumbar puncture.[8][45][46] This applies in 45% of all adult cases.[3] There are no physical tests that can rule out or determine if a person has meningitis.[47] The jolt accentuation test is not specific or sensitive enough to completely rule out meningitis.[47] If someone is suspected of having meningitis, blood tests are performed for markers of inflammation (e.g. C-reactive protein, complete blood count), as well as blood cultures.[8][45] If a CT or MRI is required before LP, or if LP proves difficult, professional guidelines suggest that antibiotics should be administered first to prevent delay in treatment,[8] especially if this may be longer than 30 minutes.[45][46] Often, CT or MRI scans are performed at a later stage to assess for complications of meningitis.[2] In severe forms of meningitis, monitoring of blood electrolytes may be important; for example, hyponatremia is common in bacterial meningitis.[48] The cause of hyponatremia, however, is controversial and may include dehydration, the inappropriate secretion of the antidiuretic hormone (SIADH), or overly aggressive intravenous fluid administration.[3][48] ### Lumbar puncture[edit] Cloudy CSF from a person with meningitis due to Streptococcus Gram stain of meningococci from a culture showing Gram negative (pink) bacteria, often in pairs A lumbar puncture is done by positioning the person, usually lying on the side, applying local anesthetic, and inserting a needle into the dural sac (a sac around the spinal cord) to collect cerebrospinal fluid (CSF). When this has been achieved, the "opening pressure" of the CSF is measured using a manometer. The pressure is normally between 6 and 18 cm water (cmH2O);[49] in bacterial meningitis the pressure is usually elevated.[8][45] In cryptococcal meningitis, intracranial pressure is markedly elevated.[50] The initial appearance of the fluid may prove an indication of the nature of the infection: cloudy CSF indicates higher levels of protein, white and red blood cells and/or bacteria, and therefore may suggest bacterial meningitis.[8] The CSF sample is examined for presence and types of white blood cells, red blood cells, protein content and glucose level.[8] Gram staining of the sample may demonstrate bacteria in bacterial meningitis, but absence of bacteria does not exclude bacterial meningitis as they are only seen in 60% of cases; this figure is reduced by a further 20% if antibiotics were administered before the sample was taken. Gram staining is also less reliable in particular infections such as listeriosis. Microbiological culture of the sample is more sensitive (it identifies the organism in 70–85% of cases) but results can take up to 48 hours to become available.[8] The type of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or viral (usually lymphocyte-predominant),[8] although at the beginning of the disease this is not always a reliable indicator. Less commonly, eosinophils predominate, suggesting parasitic or fungal etiology, among others.[40] The concentration of glucose in CSF is normally above 40% of that in blood. In bacterial meningitis it is typically lower; the CSF glucose level is therefore divided by the blood glucose (CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial meningitis;[49] in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal.[8] High levels of lactate in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count.[49] If lactate levels are less than 35 mg/dl and the person has not previously received antibiotics then this may rule out bacterial meningitis.[51] Various other specialized tests may be used to distinguish between different types of meningitis. A latex agglutination test may be positive in meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli and group B streptococci; its routine use is not encouraged as it rarely leads to changes in treatment, but it may be used if other tests are not diagnostic. Similarly, the limulus lysate test may be positive in meningitis caused by Gram-negative bacteria, but it is of limited use unless other tests have been unhelpful.[8] Polymerase chain reaction (PCR) is a technique used to amplify small traces of bacterial DNA in order to detect the presence of bacterial or viral DNA in cerebrospinal fluid; it is a highly sensitive and specific test since only trace amounts of the infecting agent's DNA is required. It may identify bacteria in bacterial meningitis and may assist in distinguishing the various causes of viral meningitis (enterovirus, herpes simplex virus 2 and mumps in those not vaccinated for this).[21] Serology (identification of antibodies to viruses) may be useful in viral meningitis.[21] If tuberculous meningitis is suspected, the sample is processed for Ziehl-Neelsen stain, which has a low sensitivity, and tuberculosis culture, which takes a long time to process; PCR is being used increasingly.[28] Diagnosis of cryptococcal meningitis can be made at low cost using an India ink stain of the CSF; however, testing for cryptococcal antigen in blood or CSF is more sensitive.[52][53] A diagnostic and therapeutic difficulty is "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptive sinusitis). When this happens, CSF findings may resemble those of viral meningitis, but antibiotic treatment may need to be continued until there is definitive positive evidence of a viral cause (e.g. a positive enterovirus PCR).[21] ### Postmortem[edit] Histopathology of bacterial meningitis: autopsy case of a person with pneumococcal meningitis showing inflammatory infiltrates of the pia mater consisting of neutrophil granulocytes (inset, higher magnification). Meningitis can be diagnosed after death has occurred. The findings from a post mortem are usually a widespread inflammation of the pia mater and arachnoid layers of the meninges. Neutrophil granulocytes tend to have migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves and the spinal cord, may be surrounded with pus – as may the meningeal vessels.[54] ## Prevention[edit] For some causes of meningitis, protection can be provided in the long term through vaccination, or in the short term with antibiotics. Some behavioral measures may also be effective. ### Behavioral[edit] Bacterial and viral meningitis are contagious, but neither is as contagious as the common cold or flu.[55] Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone, but cannot be spread by only breathing the air where a person with meningitis has been.[55] Viral meningitis is typically caused by enteroviruses, and is most commonly spread through fecal contamination.[55] The risk of infection can be decreased by changing the behavior that led to transmission. ### Vaccination[edit] Since the 1980s, many countries have included immunization against Haemophilus influenzae type B in their routine childhood vaccination schemes. This has practically eliminated this pathogen as a cause of meningitis in young children in those countries. In the countries in which the disease burden is highest, however, the vaccine is still too expensive.[56][57] Similarly, immunization against mumps has led to a sharp fall in the number of cases of mumps meningitis, which prior to vaccination occurred in 15% of all cases of mumps.[21] Meningococcus vaccines exist against groups A, B, C, W135 and Y.[58][59][60] In countries where the vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially.[56] A quadrivalent vaccine now exists, which combines four vaccines with the exception of B; immunization with this ACW135Y vaccine is now a visa requirement for taking part in Hajj.[61] Development of a vaccine against group B meningococci has proved much more difficult, as its surface proteins (which would normally be used to make a vaccine) only elicit a weak response from the immune system, or cross-react with normal human proteins.[56][58] Still, some countries (New Zealand, Cuba, Norway and Chile) have developed vaccines against local strains of group B meningococci; some have shown good results and are used in local immunization schedules.[58] Two new vaccines, both approved in 2014, are effective against a wider range of group B meningococci strains.[59][60] In Africa, until recently, the approach for prevention and control of meningococcal epidemics was based on early detection of the disease and emergency reactive mass vaccination of the at-risk population with bivalent A/C or trivalent A/C/W135 polysaccharide vaccines,[62] though the introduction of MenAfriVac (meningococcus group A vaccine) has demonstrated effectiveness in young people and has been described as a model for product development partnerships in resource-limited settings.[63][64] Routine vaccination against Streptococcus pneumoniae with the pneumococcal conjugate vaccine (PCV), which is active against seven common serotypes of this pathogen, significantly reduces the incidence of pneumococcal meningitis.[56][65] The pneumococcal polysaccharide vaccine, which covers 23 strains, is only administered to certain groups (e.g. those who have had a splenectomy, the surgical removal of the spleen); it does not elicit a significant immune response in all recipients, e.g. small children.[65] Childhood vaccination with Bacillus Calmette-Guérin has been reported to significantly reduce the rate of tuberculous meningitis, but its waning effectiveness in adulthood has prompted a search for a better vaccine.[56] ### Antibiotics[edit] Short-term antibiotic prophylaxis is another method of prevention, particularly of meningococcal meningitis. In cases of meningococcal meningitis, preventative treatment in close contacts with antibiotics (e.g. rifampicin, ciprofloxacin or ceftriaxone) can reduce their risk of contracting the condition, but does not protect against future infections.[45][66] Resistance to rifampicin has been noted to increase after use, which has caused some to recommend considering other agents.[66] While antibiotics are frequently used in an attempt to prevent meningitis in those with a basilar skull fracture there is not enough evidence to determine whether this is beneficial or harmful.[67] This applies to those with or without a CSF leak.[67] ## Management[edit] Meningitis is potentially life-threatening and has a high mortality rate if untreated;[8] delay in treatment has been associated with a poorer outcome.[3] Thus, treatment with wide-spectrum antibiotics should not be delayed while confirmatory tests are being conducted.[46] If meningococcal disease is suspected in primary care, guidelines recommend that benzylpenicillin be administered before transfer to hospital.[18] Intravenous fluids should be administered if hypotension (low blood pressure) or shock are present.[46] It is not clear whether intravenous fluid should be given routinely or whether this should be restricted.[68] Given that meningitis can cause a number of early severe complications, regular medical review is recommended to identify these complications early[46] and to admit the person to an intensive care unit if deemed necessary.[3] Mechanical ventilation may be needed if the level of consciousness is very low, or if there is evidence of respiratory failure. If there are signs of raised intracranial pressure, measures to monitor the pressure may be taken; this would allow the optimization of the cerebral perfusion pressure and various treatments to decrease the intracranial pressure with medication (e.g. mannitol).[3] Seizures are treated with anticonvulsants.[3] Hydrocephalus (obstructed flow of CSF) may require insertion of a temporary or long-term drainage device, such as a cerebral shunt.[3] The osmotic therapy, glycerol, has an unclear effect on mortality but may decrease hearing problems.[69] ### Bacterial meningitis[edit] #### Antibiotics[edit] Structural formula of ceftriaxone, one of the third-generation cefalosporin antibiotics recommended for the initial treatment of bacterial meningitis. Empiric antibiotics (treatment without exact diagnosis) should be started immediately, even before the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment depends largely on the kind of bacteria that cause meningitis in a particular place and population. For instance, in the United Kingdom, empirical treatment consists of a third-generation cefalosporin such as cefotaxime or ceftriaxone.[45][46] In the US, where resistance to cefalosporins is increasingly found in streptococci, addition of vancomycin to the initial treatment is recommended.[3][8][45] Chloramphenicol, either alone or in combination with ampicillin, however, appears to work equally well.[70] Empirical therapy may be chosen on the basis of the person's age, whether the infection was preceded by a head injury, whether the person has undergone recent neurosurgery and whether or not a cerebral shunt is present.[8] In young children and those over 50 years of age, as well as those who are immunocompromised, the addition of ampicillin is recommended to cover Listeria monocytogenes.[8][45] Once the Gram stain results become available, and the broad type of bacterial cause is known, it may be possible to change the antibiotics to those likely to deal with the presumed group of pathogens.[8] The results of the CSF culture generally take longer to become available (24–48 hours). Once they do, empiric therapy may be switched to specific antibiotic therapy targeted to the specific causative organism and its sensitivities to antibiotics.[8] For an antibiotic to be effective in meningitis it must not only be active against the pathogenic bacterium but also reach the meninges in adequate quantities; some antibiotics have inadequate penetrance and therefore have little use in meningitis. Most of the antibiotics used in meningitis have not been tested directly on people with meningitis in clinical trials. Rather, the relevant knowledge has mostly derived from laboratory studies in rabbits.[8] Tuberculous meningitis requires prolonged treatment with antibiotics. While tuberculosis of the lungs is typically treated for six months, those with tuberculous meningitis are typically treated for a year or longer.[28] #### Steroids[edit] Additional treatment with corticosteroids (usually dexamethasone) has shown some benefits, such as a reduction of hearing loss, and better short term neurological outcomes[71] in adolescents and adults from high-income countries with low rates of HIV.[72] Some research has found reduced rates of death[72] while other research has not.[71] They also appear to be beneficial in those with tuberculosis meningitis, at least in those who are HIV negative.[73] Professional guidelines therefore recommend the commencement of dexamethasone or a similar corticosteroid just before the first dose of antibiotics is given, and continued for four days.[45][46] Given that most of the benefit of the treatment is confined to those with pneumococcal meningitis, some guidelines suggest that dexamethasone be discontinued if another cause for meningitis is identified.[8][45] The likely mechanism is suppression of overactive inflammation.[74] Additional treatment with corticosteroids have a different role in children than in adults. Though the benefit of corticosteroids has been demonstrated in adults as well as in children from high-income countries, their use in children from low-income countries is not supported by the evidence; the reason for this discrepancy is not clear.[71] Even in high-income countries, the benefit of corticosteroids is only seen when they are given prior to the first dose of antibiotics, and is greatest in cases of H. influenzae meningitis,[8][75] the incidence of which has decreased dramatically since the introduction of the Hib vaccine. Thus, corticosteroids are recommended in the treatment of pediatric meningitis if the cause is H. influenzae, and only if given prior to the first dose of antibiotics; other uses are controversial.[8] ### Viral meningitis[edit] Viral meningitis typically only requires supportive therapy; most viruses responsible for causing meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign course than bacterial meningitis. Herpes simplex virus and varicella zoster virus may respond to treatment with antiviral drugs such as aciclovir, but there are no clinical trials that have specifically addressed whether this treatment is effective.[21] Mild cases of viral meningitis can be treated at home with conservative measures such as fluid, bedrest, and analgesics.[76] ### Fungal meningitis[edit] Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of high dose antifungals, such as amphotericin B and flucytosine.[52][77] Raised intracranial pressure is common in fungal meningitis, and frequent (ideally daily) lumbar punctures to relieve the pressure are recommended,[52] or alternatively a lumbar drain.[50] ## Prognosis[edit] Disability-adjusted life year for meningitis per 100,000 inhabitants in 2004.[78] no data <10 10–25 25–50 50–75 75–100 100–200 200–300 300–400 400–500 500–750 750–1000 >1000 Untreated, bacterial meningitis is almost always fatal. Viral meningitis, in contrast, tends to resolve spontaneously and is rarely fatal. With treatment, mortality (risk of death) from bacterial meningitis depends on the age of the person and the underlying cause. Of newborns, 20–30% may die from an episode of bacterial meningitis. This risk is much lower in older children, whose mortality is about 2%, but rises again to about 19–37% in adults.[2][3] Risk of death is predicted by various factors apart from age, such as the pathogen and the time it takes for the pathogen to be cleared from the cerebrospinal fluid,[2] the severity of the generalized illness, a decreased level of consciousness or an abnormally low count of white blood cells in the CSF.[3] Meningitis caused by H. influenzae and meningococci has a better prognosis than cases caused by group B streptococci, coliforms and S. pneumoniae.[2] In adults, too, meningococcal meningitis has a lower mortality (3–7%) than pneumococcal disease.[3] In children there are several potential disabilities which may result from damage to the nervous system, including sensorineural hearing loss, epilepsy, learning and behavioral difficulties, as well as decreased intelligence.[2] These occur in about 15% of survivors.[2] Some of the hearing loss may be reversible.[79] In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive impairment (in 10%).[3] Tuberculous meningitis in children continues to be associated with a significant risk of death even with treatment (19%), and a significant proportion of the surviving children have ongoing neurological problems. Just over a third of all cases survives with no problems.[80] ## Epidemiology[edit] Demography of meningococcal meningitis. meningitis belt epidemic zones sporadic cases only Deaths from meningitis per million persons in 2012 0–2 3-3 4–6 7–9 10–20 21–31 32–61 62–153 154–308 309–734 Although meningitis is a notifiable disease in many countries, the exact incidence rate is unknown.[21] In 2013 meningitis resulted in 303,000 deaths – down from 464,000 deaths in 1990.[12] In 2010 it was estimated that meningitis resulted in 420,000 deaths,[81] excluding cryptococcal meningitis.[39] Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries. Population-wide studies have shown that viral meningitis is more common, at 10.9 per 100,000, and occurs more often in the summer. In Brazil, the rate of bacterial meningitis is higher, at 45.8 per 100,000 annually.[17] Sub-Saharan Africa has been plagued by large epidemics of meningococcal meningitis for over a century,[82] leading to it being labeled the "meningitis belt". Epidemics typically occur in the dry season (December to June), and an epidemic wave can last two to three years, dying out during the intervening rainy seasons.[83] Attack rates of 100–800 cases per 100,000 are encountered in this area,[84] which is poorly served by medical care. These cases are predominantly caused by meningococci.[17] The largest epidemic ever recorded in history swept across the entire region in 1996–1997, causing over 250,000 cases and 25,000 deaths.[85] Meningococcal disease occurs in epidemics in areas where many people live together for the first time, such as army barracks during mobilization, university and college campuses[2] and the annual Hajj pilgrimage.[61] Although the pattern of epidemic cycles in Africa is not well understood, several factors have been associated with the development of epidemics in the meningitis belt. They include: medical conditions (immunological susceptibility of the population), demographic conditions (travel and large population displacements), socioeconomic conditions (overcrowding and poor living conditions), climatic conditions (drought and dust storms), and concurrent infections (acute respiratory infections).[84] There are significant differences in the local distribution of causes for bacterial meningitis. For instance, while N. meningitides groups B and C cause most disease episodes in Europe, group A is found in Asia and continues to predominate in Africa, where it causes most of the major epidemics in the meningitis belt, accounting for about 80% to 85% of documented meningococcal meningitis cases.[84] ## History[edit] Some suggest that Hippocrates may have realized the existence of meningitis,[17] and it seems that meningism was known to pre-Renaissance physicians such as Avicenna.[86] The description of tuberculous meningitis, then called "dropsy in the brain", is often attributed to Edinburgh physician Sir Robert Whytt in a posthumous report that appeared in 1768, although the link with tuberculosis and its pathogen was not made until the next century.[86][87] It appears that epidemic meningitis is a relatively recent phenomenon.[88] The first recorded major outbreak occurred in Geneva in 1805.[88][89] Several other epidemics in Europe and the United States were described shortly afterward, and the first report of an epidemic in Africa appeared in 1840. African epidemics became much more common in the 20th century, starting with a major epidemic sweeping Nigeria and Ghana in 1905–1908.[88] The first report of bacterial infection underlying meningitis was by the Austrian bacteriologist Anton Weichselbaum, who in 1887 described the meningococcus.[90] Mortality from meningitis was very high (over 90%) in early reports. In 1906, antiserum was produced in horses; this was developed further by the American scientist Simon Flexner and markedly decreased mortality from meningococcal disease.[91][92] In 1944, penicillin was first reported to be effective in meningitis.[93] The introduction in the late 20th century of Haemophilus vaccines led to a marked fall in cases of meningitis associated with this pathogen,[57] and in 2002, evidence emerged that treatment with steroids could improve the prognosis of bacterial meningitis.[71][74][92] World Meningitis Day is observed on 24 April each year. ## References[edit] 1. ^ a b c d e f g h i j "Bacterial Meningitis". CDC. 1 April 2014. Archived from the original on 5 March 2016. Retrieved 5 March 2016. 2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab Sáez-Llorens X, McCracken GH (June 2003). "Bacterial meningitis in children". Lancet. 361 (9375): 2139–48. doi:10.1016/S0140-6736(03)13693-8. PMID 12826449. 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PMC 6698485. PMID 24163051. 67. ^ a b Ratilal BO, Costa J, Pappamikail L, Sampaio C (April 2015). "Antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures". The Cochrane Database of Systematic Reviews. 4 (4): CD004884. doi:10.1002/14651858.CD004884.pub4. PMID 25918919. 68. ^ Maconochie IK, Bhaumik S (November 2016). "Fluid therapy for acute bacterial meningitis" (PDF). The Cochrane Database of Systematic Reviews. 11: CD004786. doi:10.1002/14651858.CD004786.pub5. PMC 6464853. PMID 27813057. 69. ^ Wall EC, Ajdukiewicz KM, Bergman H, Heyderman RS, Garner P (February 2018). "Osmotic therapies added to antibiotics for acute bacterial meningitis". The Cochrane Database of Systematic Reviews. 2: CD008806. doi:10.1002/14651858.CD008806.pub3. PMC 5815491. PMID 29405037. 70. ^ Prasad K, Kumar A, Gupta PK, Singhal T (October 2007). Prasad K (ed.). "Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis". The Cochrane Database of Systematic Reviews (4): CD001832. doi:10.1002/14651858.CD001832.pub3. PMID 17943757. 71. ^ a b c d Brouwer MC, McIntyre P, Prasad K, van de Beek D (September 2015). "Corticosteroids for acute bacterial meningitis". The Cochrane Database of Systematic Reviews (9): CD004405. doi:10.1002/14651858.CD004405.pub5. PMC 6491272. PMID 26362566. 72. ^ a b Assiri AM, Alasmari FA, Zimmerman VA, Baddour LM, Erwin PJ, Tleyjeh IM (May 2009). "Corticosteroid administration and outcome of adolescents and adults with acute bacterial meningitis: a meta-analysis". Mayo Clinic Proceedings. 84 (5): 403–09. doi:10.4065/84.5.403. PMC 2676122. PMID 19411436. 73. ^ Prasad K, Singh MB, Ryan H (April 2016). "Corticosteroids for managing tuberculous meningitis". The Cochrane Database of Systematic Reviews. 4: CD002244. doi:10.1002/14651858.CD002244.pub4. PMC 4916936. PMID 27121755. 74. ^ a b de Gans J, van de Beek D (November 2002). "Dexamethasone in adults with bacterial meningitis". 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PMID 6366279. ## External links[edit] Classification D * ICD-10: G00–G03 * ICD-9-CM: 320–322 * MeSH: D008581 * DiseasesDB: 22543 External resources * MedlinePlus: 000680 * eMedicine: med/2613 emerg/309 emerg/390 * Patient UK: Meningitis Wikimedia Commons has media related to Meningitis. * Meningitis at Curlie * Meningitis Centers for Disease Control and Prevention (CDC) * Medicine portal * Viruses portal * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis * v * t * e Meningitis and other diseases of meninges Meningitis * Arachnoiditis * Bacterial * Tuberculous * Haemophilus * Pneumococcal * Viral * Herpesviral * Fungal * Cryptococcal * Aseptic * Drug-induced Other * Meningoencephalitis Authority control * NDL: 00568667 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Meningitis	c0025289	30,536	wikipedia	https://en.wikipedia.org/wiki/Meningitis	2021-01-18T19:02:30	{"mesh": ["D008581"], "umls": ["C0025289"], "wikidata": ["Q48143"]}
A rare genetic multiple congenital anomalies syndrome characterized by abnormal bone maturation with skeletal anomalies, airway obstructions, failure to thrive, developmental delay, moderate to severe intellectual disability and characteristic facial features with macrocephaly, prominent forehead, shallow orbits, proptosis and blue sclerae. ## Epidemiology Less than 60 cases have been reported in the literature to date. ## Clinical description Marshall-Smith syndrome was originally considered as an overgrowth condition based on advanced bone maturation. It is characterized by a dysostosis with skeletal anomalies including progressive kyphoscoliosis, postnatal failure to thrive in weight, short stature, and osteopenia with fractures. Wide bullet-shaped phalanges as well as large hands and feet are observed. Neonates and infants usually manifest with feeding difficulties and upper airway obstruction with respiratory distress due to glossoptosis, laryngomalacia and/or choanal stenosis. The majority of patients die in the neonatal period or early infancy from respiratory compromise. Respiratory infections are frequent. Patients surviving infancy also have developmental delay, moderate to severe intellectual disability and behavioral abnormalities such as anxiety and stereotyped movements. Brain MRI may show corpus callosum anomalies, macrogyria, pachygyria, delayed myelination, ventricular dilatation, hydrocephalus and periventricular leukomalacia. Characteristic facial features include high forehead, proptosis, blue sclerae, midface hypoplasia, short nose, depressed nasal bridge, anteverted nostrils and retrognathia. Vision impairment may occur as a result of optic nerve hypoplasia. Hypertrichosis, umbilical hernia, connective tissue, endocrine and cardiovascular anomalies may be associated. In a single case a concomitant Wilms tumor had developed, otherwise an increased risk of neoplasm development is not known. ## Etiology Marshall-Smith syndrome is cause by heterozygous de novo variants in the NFIX (Nuclear Factor I X; 19p13.13) gene. NFIX variants escape nonsense-mediated mRNA decay leading to abnormal proteins with an abnormal C-terminus (dominant-negative mechanism). The NFIX gene acts as the transcription factor in the nuclear factor one family, and is implicated in replication, signal transduction, and transcriptional processes, with, currently not fully elucidated mechanisms. ## Diagnostic methods The syndrome is clinically recognizable. The genetic diagnosis is established by identification of a heterozygous pathogenic variant in the NFIX gene. Most of the variants have been identified in exons 6-10 of the gene. ## Differential diagnosis The differential diagnoses for Marshall-Smith syndrome are Sotos syndrome, Malan overgrowth syndrome, Weaver syndrome, and bone fragility disorders. Radiological findings distinguish them based on skeletal findings. ## Antenatal diagnosis Prenatal diagnosis is possible if the disease-causing variant has been identified in the family. The recent implementation of prenatal whole exome sequencing could lead to molecular diagnostics during pregnancy. ## Genetic counseling Marshall-Smith syndrome is inherited in an autosomal dominant manner. All known pathogenic variants have occurred de novo, and in these cases the risk to sibs of the proband is very low due to a possible germinal mosaicism (<1%). ## Management and treatment Management of Marshall-Smith syndrome required a multidisciplinary approach with appropriate specialists. Patients need symptomatic treatment for airway obstruction, respiratory infections, and feeding difficulties, as well as specific management for bone fragility. ## Prognosis The prognosis is poor and most patients will die in the neonatal period or early infancy due to respiratory compromise. A few cases of prolonged survival have been reported in patients without respiratory complications. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Marshall-Smith syndrome	c0265211	30,537	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=561	2021-01-23T18:55:52	{"gard": ["6985"], "mesh": ["C536026"], "omim": ["602535"], "umls": ["C0265211"], "icd-10": ["Q87.3"], "synonyms": ["Accelerated skeletal maturation-facial dysmorphism-failure to thrive syndrome"]}
A rare, non-syndromic urogenital tract malformation characterized by the absence of a vagina or the presence of a vaginal dimple shorter than 5 cm. It is often associated with uterine agenesis, hematocolpos or primary amenorrhea and dyspareunia. Ovaries and fallopian tubes are normal. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Isolated partial vaginal agenesis	c1261251	30,538	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96269	2021-01-23T17:19:14	{"mesh": ["C536523"], "icd-10": ["Q52.0"], "synonyms": ["Congenital absence of vagina"]}
Crutchfield and Gutmann (1973) found that the accessory deep peroneal nerve, a branch of the superficial peroneal nerve, partially innervated the extensor digitorum brevis muscle of at least one foot in 22 of 100 healthy unrelated persons. Five families studied because of a member with anomalous innervation yielded results the authors interpreted as indicating dominant inheritance. Neuro \- Accessory deep peroneal nerve \- Partial innervation of extensor digitorum brevis muscle Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	PERONEAL NERVE, ACCESSORY DEEP	c1868426	30,539	omim	https://www.omim.org/entry/170980	2019-09-22T16:36:30	{"mesh": ["C536001"], "omim": ["170980"]}
Formication, a type of tactile hallucination, is the feeling of imaginary insects or spiders on the skin. Tactile hallucination is the false perception of tactile sensory input that creates a hallucinatory sensation of physical contact with an imaginary object.[1] It is caused by the faulty integration of the tactile sensory neural signals generated in the spinal cord and the thalamus and sent to the primary somatosensory cortex (SI) and secondary somatosensory cortex (SII).[2] Tactile hallucinations are recurrent symptoms of neurological diseases such as schizophrenia, Parkinson's disease, Ekbom's syndrome and delerium tremens. Patients who experience phantom limb pains also experience a type of tactile hallucination. Tactile hallucinations are also caused by drugs such as cocaine and alcohol.[1] ## Contents * 1 History and background * 2 Tactile hallucinations in schizophrenia * 3 Tactile hallucinations in Parkinson's disease * 4 Tactile hallucinations in restless legs syndrome * 5 Tactile hallucination in phantom limbs * 6 Drug-induced tactile hallucinations * 7 Cenesthopathic tactile hallucinations * 8 Pathophysiology * 9 See also * 10 References ## History and background[edit] In Ancient Greek times, touch was an unrefined perceptual system. During ancient Greek times, touch was considered to be an unrefined perceptual system because it differed from the other senses on the basis of the distance and timing of perception of the stimulus. Unlike vision and audition, one perceives touch simultaneously with the medium and the stimulus is always proximal and not distal.[1] By the 17th century, the British empiricist John Locke attributed the word "feeling" with two types of sensation.[1] Weber distinctly identified these two types of sensation as the sense of touch and common bodily sensibility.[1] This distinction further helped 19th century psychiatrists to distinguish between tactile hallucinations and cenesthopathy. During the 19th century, tactile hallucinations were classified as symptoms associated with insanity, organic and toxic syndromes and delusional parasitosis yet there was no identification on how such hallucinations were caused.[1] Currently, neuroscientists such as Dr. Oliver Sacks and Dr. V.S. Ramachandran have analyzed and attributed tactile hallucinations as a dysfunctional perception of the brain as opposed to just a symptom related to insanity. They have contributed significantly to propose tactile hallucinations as the false perception of tactile sensory input creating a sensation of touch with an imaginary object. ## Tactile hallucinations in schizophrenia[edit] Hallucinations of pain and touch are very rare in schizophrenic disorders but 20% of patients with schizophrenia experience some sort of tactile hallucinations along with visual and auditory hallucinations.[3] The most common tactile hallucination in patients with schizophrenia is a sensation in which a patch of their skin is stretched elastically across their head.[4] They vary in intensity, range and speed at which they feel this stretching painful sensation. They are usually triggered by emotional cues such as guilt, anger, fear and depression.[4] Other types of tactile hallucinations takes on a sexual form in patients with schizophrenia. Patients with schizophrenia may sometimes experience the feeling of being kissed or the feeling of someone lying by their side in response to their emotion of being lonely.[1] Additionally, they occasionally hallucinate the feeling of small animals such as snakes crawling over their body.[1] Such vivid tactile sensation of an object that is not present results from the unsuccessful attempt of the brain trying to perceive objects that are novel and that represent unreal situations usually triggered by guilt and fear.[4] Patients with schizophrenia also have a hard time portraying emotions as they divert most of their energy to control the pain from their tactile hallucinations.[4] Olfactory and tactile hallucinations correlate with one another in terms of prevalence in patients with schizophrenia.[3] One particular study was conducted by Langdon et al., in which the prevalence of olfactory hallucinations and tactile hallucinations was analyzed in two distinct clinical samples of patients with schizophrenia. One of the samples contained patients with schizophrenia with tactile hallucinations as reported by the World Health Organization while the other sample contained cases with negative and positive types of tactile hallucinations in patients with schizophrenia. It was concluded that about 13% to 17% of patients with schizophrenia experience olfactory and tactile hallucinations.[5] The study reported that socio-cultural factors influenced self-reporting of tactile hallucinations. Since hallucinations in general were feared as a symptoms of insanity, patients were reluctant to seek help for such symptoms.[5] Moreover, the study concluded that tactile hallucinations were usually accompanied by several other hallucinations associated with different modalities such as taste and sight.[5] However, the study failed to recognize the pathophysiology of tactile hallucinations in individuals with schizophrenia. ## Tactile hallucinations in Parkinson's disease[edit] Trihexyphenidyl: An antiparkinsonian agent that creates tactile hallucinations. About 7% of individuals with Parkinson's disease (PD) also experience mild or severe types of tactile hallucinations.[6] Most of these hallucinations are based on the sensation of a particular kind of animal.[6] Several case studies were conducted by Fénelon and his colleagues on patients with PD that had tactile hallucinations. One of his patients described that he sensed "spiders and cockroaches chewing on his lower limb" which was rather painful.[6] Several other patients felt that there was a parasitic infestation of their skin which caused lesions on their skins due to the obsessive need of itching.[6] Fénelon also analyzed the particular types of tactile hallucinations experienced, the timing of such experience and certain drugs that could eliminate such experience. It was concluded that patients with both PD and tactile hallucinations not only experienced sensations elicited by insects under their skin but also by vivid tactile sensations of people.[6] These hallucinations were aggravated during evening times due to altered arousal states and were alleviated by dopaminergic treatment such as the intake of clozapine.[6] The study also explains that the pathophysiology of tactile hallucinations is uncertain, however, such hallucinations can be attributed to narcoleptic rapid eye movement sleep disorders due to its concordance with visual hallucinations.[6] Moreover, it emphasizes that individuals who have had PD for a longer period of time have a more severe form of tactile hallucinations than with individuals who have succumbed to this disease for just a short period of time.[6] Clinical drugs used as an antiparkinsonian agent such as Trihexyphenidyl are known to create tactile hallucinations in patients with PD.[7][8] ## Tactile hallucinations in restless legs syndrome[edit] Hallucinatory itch due to sensation of insects under the skin leading to self-hurting behavior. Restless legs syndrome (RLS) causes unpleasant or uncomfortable sensations in the legs and an irresistible urge to move them.[9][10] Tactile hallucinations in RLS include feelings of itching, pulling, crawling or creeping mainly in the legs, with the accompanying overwhelming urge to move them.[9][10] These symptoms are more prominent in the late afternoon and at night, often causing insomnia.[9] The causes of RLS are generally unknown, though there are three major hypotheses: iron deficiency, dopamine insufficiency and genetic inheritance.[9][10] RLS can also occur due to nerve damage, or neuropathy.[9] Treatments for RLS typically focus on symptom relief through supplementing iron, blocking nerve receptors through the use of alpha-2 delta drugs such as gabapentin, or through the use of opioids or benzodiazepines.[10] ## Tactile hallucination in phantom limbs[edit] Main articles: Phantom limb and Mirror box Play media Treatments for phantom limb pains: Virtually Painless- Science Museum Painless Exhibition Series. Phantom limb pain is a type of tactile hallucination because it creates a sensation of excruciating pain in a limb that has been amputated.[11] In 1996, VS Ramachandran conducted a research on several amputees to pinpoint the neural reasons behind these illusionary pains. Most of these amputees that had an unbearable phantom limb pain are reported by patients whose limb was paralyzed before amputation. VS Ramachandran proposed the "learned paralysis" hypothesis. The hypothesis suggested that every time the patients tried to move their paralyzed limb, they received sensory feedback (through vision and proprioception) that the limb did not move. This feedback hardwired itself into the brain circuitry, so that, even when the limb was no longer present, the brain had learned that the phantom limb was paralyzed.[11] As a treatment for phantom limb pains, VS Ramachandran devised a mirror box that would superimpose the mirror image of the normal arm in place of the missing arm and the patient would immediately be relieved of the pain. This suggested that the brain had a plastic nature in the somatosensory system and the brain had reorganized its somatosensory region to accommodate for this new change.[11] Patients that experience this phantom limb pain are very important in research studies for their role in determining brain plasticity. The vivid tactile sensation of the arm that is no longer present suggest the highly complex nature of the brain to reorganize different functions which were once thought to be hardwired to specific regions (localization). ## Drug-induced tactile hallucinations[edit] Photo of cocaine Organic and toxic syndromes can also induce tactile hallucinations. The use of cocaine for recreational purposes has been reported to induce tactile hallucinations.[12] They usually have sensations of moving itches and crawling insects. Cocaine and alcohol can induce rapid firing of neuronal cells of the somatosensory region of the brain leading to vivid perception of illusionary bugs on the skin.[12] Additionally, as mentioned above, Trihexyphenidyl is an antiparkinsonian drug that creates tactile hallucination. The mechanism through which these drugs induce tactile hallucinations is still unknown. ## Cenesthopathic tactile hallucinations[edit] Cenesthopathy is a rare medical term used to refer to the feeling of being ill and this feeling is not localized to one region of the body.[1] Cenesthopathic hallucinatory experiences are caused by the hyperactive neuronal stimulation of the primary somatosensory cortex due to a disorder or a damage to this area. There are two theories that are established to portray sensation of unified bodily feeling. One of these theories is called associationism, which states that cenesthesia is an amalgamation of propioceptive and interoceptive sensations.[1] Faculty psychology is the other theory which states that there is a particular brain region where all of the sensory information converged and the integration of this information gives one cenesthetic sensation. The latter theory became more predominant and it established two types of cenestopathic hallucinations namely "painful" and "paraesthetic". Patients that experience "painful" type of cenesthopathic hallucination felt that their organs were stretched apart and twisted.[1] On the other hand, patients with "paraesthetic" cenesthopathic hallucination experience severe hallucinatory itching.[1] ## Pathophysiology[edit] Schematic and FMRI of cortical areas involved in pain processing which are similar to areas that are involved in tactile hallucinations. Tactile hallucinations are the result of a dysfunctional somatosensory and a dysfunctional awareness regions of the brain.[2] Tactile sensory input is produced and conducted through the spinal cord and thalamus and it is received at the primary somatosensory cortex. Once it has reached the primary somatosensory cortex, it is distributed across the brain and it will not be processed unless it is important and one pays close attention to the information based on a specific context. Consciousness to these specific tactile sensations is generated only through multiple feedback loops passing through higher cortical areas such as secondary somatosensory area, parietal, insular cortex and premotor areas.[2] The intensity of the tactile stimulus is directly proportional to the area of the primary somatosensory region activated.[13] A feedback mechanism from different cortical areas results in the awareness of touch. Even with complete sensory deprivation, discrete tactile memories can trigger spontaneous firing of impaired neurons.[2] Therefore, individuals with various psychiatric disorders are more prone to tactile hallucinations than normal individuals. Tactile hallucinations are especially possible due to faulty sensory integration of neuronal signals in the primary and secondary somatosensory system with neuronal signals in the parietal cortex, insular cortex and premotor cortex. Moreover, the posterior insula is responsible for mental body schema representation and can produce tactile hallucination if defected. Additionally, the regions of the brain involved in tactile hallucinations are similar to the regions of the brain involved in pain. ## See also[edit] * Closed-eye hallucination * Visual snow * Form constant * Scintillating scotoma * Phantosmia * Formication * Tactile illusion ## References[edit] 1. ^ a b c d e f g h i j k l Berrios, G.E. (1982). "Tactile hallucinations: conceptual and historical aspects". Journal of Neurology, Neurosurgery, and Psychiatry. 45 (4): 285–293. doi:10.1136/jnnp.45.4.285. PMC 491362. PMID 7042917. 2. ^ a b c d Gallace, A.; Spence, C. (2010). "Touch and the body: the role of the somatosensory cortex in tactile awareness". Psyche. 16 (1): 30–60. 3. ^ a b Lewandowski, Kathryn E. (2009). "Tactile, olfactory, and gustatory hallucinations in psychotic disorders: a descriptive study". Annals of the Academy of Medicine, Singapore. 38 (5): 383–385. PMID 19521636. 4. ^ a b c d Pfeifer, Louis (1970). "A subjective report of tactile hallucinations in schizophrenia". Journal of Clinical Psychology. 26 (1): 57–60. doi:10.1002/1097-4679(197001)26:1<57::aid-jclp2270260113>3.0.co;2-5. PMID 5411092. 5. ^ a b c Langdon, Robyn; Jonathan McGuire; Richard Stevenson; Stanley V. Catts (2011). "Clinical correlates of olfactory hallucinations in schizophrenia". British Journal of Clinical Psychology. 50 (2): 145–163. doi:10.1348/014466510X500837. PMID 21545448. 6. ^ a b c d e f g h Fénelon, Gilles; Stéphane Thobois; Anne-Marie Bonnet; Emmanuel Broussolle; François Tison (2002). "Tactile hallucinations in Parkinson's disease". Journal of Neurology. 249 (12): 1699–1703. doi:10.1007/s00415-002-0908-9. ISSN 1432-1459. PMID 12529792. 7. ^ "Trihexyphenidyl: MedlinePlus Drug Information". medlineplus.gov. Retrieved 2019-11-20. 8. ^ Funakawa, Itaru; Kenji Jinnai (2005). "Tactile hallucinations induced by trihexyphenidyl in a patient with Parkinson's disease". Rinsho Shinkeigaku. 45 (2): 125–127. PMID 15782612. 9. ^ a b c d e "Restless Legs Syndrome Fact Sheet \| National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 2019-11-20. 10. ^ a b c d Kieffer, Sara. "What is Restless Legs Syndrome (RLS)? \| The Johns Hopkins Center for Restless Legs Syndrome". www.hopkinsmedicine.org. Retrieved 2019-11-20. 11. ^ a b c Ramachandran, Vilayanur S; William Hirstein (1998). "The perception of phantom limbs. The DO Hebb lecture". Brain. 121 (9): 1603–1630. doi:10.1093/brain/121.9.1603. PMID 9762952. 12. ^ a b Morani, Aashish S.; Vikram Panwar; Kenneth Grasing (2013). "Tactile Hallucinations with Repetitive Movements Following Low‐Dose Cocaine: Implications for Cocaine Reinforcement and Sensitization". The American Journal on Addictions. 22 (2): 181–182. doi:10.1111/j.1521-0391.2013.00336.x. PMID 23414508. 13. ^ Blakemore, SJ; Bristow D; Bird G; Frith C; Ward J (2005). "Somatosensory activations during the observation of touch and a case of vision-touch synaesthesia". Brain. 128 (7): 1571–83. doi:10.1093/brain/awh500. PMID 15817510. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Tactile hallucination	c0233767	30,540	wikipedia	https://en.wikipedia.org/wiki/Tactile_hallucination	2021-01-18T19:09:33	{"mesh": ["D006212"], "umls": ["C0233767"], "wikidata": ["Q17162704"]}
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss. People with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision. People with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved. Between one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated. ## Frequency Microphthalmia occurs in approximately 1 in 10,000 individuals. ## Causes Microphthalmia may be caused by changes in many genes involved in the early development of the eye, most of which have not been identified. The condition may also result from a chromosomal abnormality affecting one or more genes. Most genetic changes associated with isolated microphthalmia have been identified only in very small numbers of affected individuals. Microphthalmia may also be caused by environmental factors that affect early development, such as a shortage of certain vitamins during pregnancy, radiation, infections such as rubella, or exposure to substances that cause birth defects (teratogens). ### Learn more about the genes associated with Microphthalmia * BCOR * GDF3 * GDF6 * OTX2 * PAX6 * SHH * SOX2 Additional Information from NCBI Gene: * BMP4 * MFRP * PRSS56 * RAX * SIX6 * STRA6 * VSX2 ## Inheritance Pattern Isolated microphthalmia is sometimes inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In some cases, parents of affected individuals have less severe eye abnormalities. When microphthalmia occurs as a feature of a genetic syndrome or chromosomal abnormality, it may cluster in families according to the inheritance pattern for that condition, which may be autosomal recessive or other patterns. Often microphthalmia is not inherited, and there is only one affected individual in a family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Microphthalmia	c1855052	30,541	medlineplus	https://medlineplus.gov/genetics/condition/microphthalmia/	2021-01-27T08:24:39	{"gard": ["12085"], "mesh": ["C565377"], "omim": ["251600", "610093", "611038", "613094", "611040", "613517", "613704", "615113", "156850", "300345", "605738", "610092", "251505", "611638", "613703", "615145", "156900", "212550"], "synonyms": []}
Ocular toxoplasmosis is an infection in the eye caused by the parasite, Toxoplasm a gondii. Toxoplasmosis is the most common cause of eye inflammation in the world. Toxoplamosis can be acquired or present at birth (congenital), having crossed the placenta from a newly infected mother to her fetus. Most humans acquire toxoplasmosis by eating raw or undercooked meat, vegetables or milk products, or by coming into contact with infected cat litterbox or sandboxes. In humans, the infection usually causes no symptoms, and resolves without treatment in a few months. In individuals with compromised immune systems, Toxoplasm a gondii can reactivate to cause disease. Reactivation of a congenital infection was traditionally thought to be the most common cause of ocular toxoplasmosis, but an acquired infection is now considered to be more common. A toxoplasmosis infection that affects the eye usually attacks the retina and initially resolves without symptoms. However, the inactive parasite may later reactivate causing eye pain, blurred vision, and possibly permanent damage, including blindness. Although most cases of toxoplasmosis resolve on their own, for some, inflammation can be treated with antibiotics and steroids. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Ocular toxoplasmosis	c0040561	30,542	gard	https://rarediseases.info.nih.gov/diseases/7238/ocular-toxoplasmosis	2021-01-18T17:58:38	{"mesh": ["D014126"], "umls": ["C0040561"], "synonyms": []}
## Summary ### Clinical characteristics. FREM1 autosomal recessive disorders include: Manitoba oculotrichoanal (MOTA) syndrome, bifid nose with or without anorectal and renal anomalies (BNAR syndrome), and isolated congenital anomalies of kidney and urinary tract (CAKUT). * MOTA syndrome is characterized by an aberrant hairline (unilateral or bilateral wedge-shaped extension of the anterior hairline from the temple region to the ipsilateral eye) and anomalies of the eyes (widely spaced eyes, anophthalmia/microphthalmia and/or cryptophthalmos, colobomas of the upper eyelid, and corneopalpebral synechiae), nose (bifid or broad nasal tip), abdominal wall (omphalocele or umbilical hernia), and anus (stenosis and/or anterior displacement of the anal opening). The manifestations and degree of severity vary even among affected members of the same family. Growth and psychomotor development are normal. * BNAR syndrome is characterized by a bifid or wide nasal tip, anorectal anomalies, and renal malformations (e.g., renal agenesis, renal dysplasia). Typically the eye manifestations of MOTA syndrome are absent. * FREM1-CAKUT was identified in one individual with bilateral vesicoureteral reflux (VUR) and a second individual with VUR and renal hypodysplasia. ### Diagnosis/testing. The diagnosis of a FREM1 autosomal recessive disorder is established in a proband by identification of biallelic pathogenic variants in FREM1 on molecular genetic testing. ### Management. Treatment of manifestations: * Intensive ocular lubrication to avoid exposure keratopathy before surgery is performed; release of synechiae between the eyelid and cornea; surgical intervention and/or prostheses for anophthalmia/microphthalmia and cryptophthalmos if warranted; supportive care for those with visual impairment * Rhinoplasty for notched ala nasi or bifid nose * Surgical closure of omphalocele; surgical or conservative management of umbilical hernia * Dilatation for anal stenosis * Supportive treatment to preserve renal functions and electrolyte balance; dialysis and transplant if indicated in individuals with renal failure * Psychosocial support ### Genetic counseling. MOTA, BNAR syndrome, and FREM1-CAKUT are inherited in an autosomal recessive manner. At conception, each full sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the FREM1 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis ## Clinical Characteristics ### Clinical Description #### Manitoba Oculotrichoanal (MOTA) Syndrome Ocular abnormalities include ipsilateral colobomas of the upper eyelid (sometimes referred to as a Tessier number 10 cleft by surgeons), corneopalpebral synechiae (i.e., adhesions between the eyelids and the cornea, also known as abortive cryptophthalmos), and microphthalmia/anophthalmia and/or cryptophthalmos. Anomalies may be unilateral or bilateral; the severity may differ between the two eyes. Visual impairment may result directly from the ocular malformations or indirectly from exposure keratopathy. The long-term visual outcome depends on the severity of the ocular malformations and is poor for individuals with bilateral complete cryptophthalmos. In those with milder ocular malformations, such as upper eyelid colobomas, vision is typically intact. Corneal clouding was described in one individual. Anal anomalies include anal stenosis and/or anteriorly placed anus. No associated anomalies of the sacrum, vertebrae, or tethered cord have been reported. No affected individuals have had refractory constipation, fecal incontinence, or procedure-related stenosis or fistula. Characteristic facial features include widely spaced eyes; an aberrant anterior hairline extending to the ipsilateral eye (unilateral or bilateral) that is often wedge-shaped but may also resemble a thin stripe or appear tongue-shaped; ipsilateral absent or interrupted eyebrow; and a broad nose or notched or bifid nasal tip. Omphalocele or umbilical hernia has been reported in approximately one third of affected individuals. Conservative management or surgical intervention for omphalocele or umbilical hernia is usually well tolerated and outcomes are excellent. Long-term intestinal complications have not been described. Other. Additional findings have been reported: renal pelviectasis, renal dysplasia, hydrometrocolpos and vaginal atresia, cutaneous syndactyly, and additional dysmorphic features (e.g., high forehead with a frontal upsweep of hair, dysplastic ears, maxillary hypoplasia, underdeveloped ala nasi, short philtrum, thin upper lip, and relative microstomia) [Slavotinek et al 2011, Mitter et al 2012, Nathanson et al 2013]. Growth and development. Individuals with MOTA syndrome assessed at various ages appear generally healthy with age-appropriate growth and cognition. Motor, social, and speech and language skills are typically normal, although development may be influenced by the presence of severe eye defects that lead to visual impairment. The manifestations and degree of severity vary even among affected members of the same family. #### Bifid Nose with or without Anorectal and Renal Anomalies (BNAR) Syndrome BNAR syndrome was described by Al-Gazali et al [2002] and Alazami et al [2009] in ten individuals from three consanguineous families of Egyptian, Afghani, and Pakistani origin. * Craniofacial features. Broad and/or bifid nose (100%), widely spaced eyes, short and thick oral frenula * Renal malformations (e.g., bilateral renal agenesis, unilateral renal agenesis) in 6/9 individuals evaluated * Anorectal malformations (e.g., anteriorly placed anus, anal stenosis) in 2/9 individuals evaluated * Airway malformations in 2/8 individuals evaluated #### FREM1 Congenital Anomalies of Kidney and Urinary Tract (CAKUT) FREM1-CAKUT phenotype has been reported in an individual with bilateral vesicoureteral reflux (VUR) grade III and in another individual with right-sided VUR grade V in conjunction with right-sided renal hypodysplasia [Kohl et al 2014]. #### Other Phenotypes The following other phenotypes have been reported in individuals with biallelic FREM1 pathogenic variants: * One individual with isolated congenital diaphragmatic hernia [Beck et al 2013] * One fetus with severe hydrocephalus and shortened limbs associated with novel FREM1 pathogenic variants [Yang et al 2017] ### Genotype-Phenotype Correlations Genotype-phenotype correlations have not been possible to date given the rarity of the condition and limited number of pathogenic variants described. ### Prevalence The prevalence of FREM1 autosomal recessive disorders are unknown. To date, the authors are aware of 27 published individuals with MOTA syndrome. Based on the number of individuals identified to date in the aboriginal Oji-Cree community of the Island Lake region of northern Manitoba, Canada, which had a population of 4,685 in 1996 and 2,020 in 2001 [First Nation Profiles 2004], the incidence of MOTA syndrome in that population is estimated at 2:1,000-6:1,000 births; however, this may be an underestimate in this population, as a few presumably affected individuals have also been identified through family histories of affected individuals, and some milder cases may not have come to medical attention. All affected individuals from the Island Lake region identified to date are presumed to be related. ## Differential Diagnosis The following disorders should be considered in the differential diagnosis of Manitoba oculotrichoanal (MOTA) syndrome and bifid nose with or without anorectal and renal anomalies (BNAR) syndrome (Table 2). ### Table 2. Disorders to Consider in the Differential Diagnosis of MOTA Syndrome and BNAR Syndrome View in own window DiffDx DisorderGene(s)MOIClinical Features of DiffDx Disorder Overlapping w/MOTA &/or BNAR syndromeDistinguishing from MOTA & BNAR syndromes Fraser syndrome (OMIM PS219000)FRAS1 REM2 GRIP1AR * Anophthalmia/microphthalmia, cryptophthalmos, eyelid colobomas, widely spaced eyes * Wedge-shaped lateral anterior hairline * Bifid nasal tip / notched ala nasi * Anal stenosis or imperforate anus 1 * Cognitive impairment * Often early mortality Frontonasal dysplasia (FND) (OMIM PS136760)ALX1 ALX3 ALX4AR * Widely spaced eyes * Broad forehead * Widow's peak * Range from notched ala nasi to bifid nose 2 * Cranium bifidum 3 * Absence of omphalocele & anorectal abnormalities Craniofrontonasal dysplasia (CFND) (OMIM 304110)EFNB1XLIn females w/CFND: 4 * Widely spaced eyes * Broad nasal bridge, bifid nasal tip * Craniosynostosis * Cranium bifidum * Absence of omphalocele & anorectal abnormalities Oculoauriculofrontonasal syndrome (OMIM 601452)UnknownUnknown * Upper eyelid colobomas, widely spaced eyes * Notched ala nasi or bifid nose * Normal intelligence * Hemifacial microsomia * Ear malformations, preauricular tags * Epibulbar dermoids * Abnormalities of the frontal bone FG syndrome type 1 (see MED12-Related Disorders)MED12XLIn a male infant: * Widely spaced eyes * Anteriorly placed anus, anal stenosis Often, additional findings such as: * Thumb anomalies * Vertebral abnormalities Townes-Brocks syndromeSALL1ADAnteriorly placed anus, anal stenosis VACTERL (OMIM 192350)UnknownUnknown Donnai-Barrow syndromeLRP2AR * Widely spaced eyes * Omphalocele * Agenesis of the corpus callosum * Sensorineural hearing loss * Diaphragmatic hernia AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; MOI = mode of inheritance; VACTERL = vertebral abnormalities, anal abnormalities, cardiac defects, tracheoesophageal fistula, renal and/or radial ray abnormalities, and limb anomalies; XL = X-linked 1\. Slavotinek & Tifft [2002], McGregor et al [2003], Vrontou et al [2003] 2\. Jones [2006] 3\. Cranium bifidum is a midline defect of the frontal bone detected on skull x-rays. 4\. CFND is inherited in a unique X-linked manner that paradoxically shows greater severity in heterozygous females than in hemizygous males. Typically, females have FND, craniofacial asymmetry, craniosynostosis, a bifid nasal tip, and grooved nails; they may also have skeletal abnormalities. In contrast, males typically show only widely spaced eyes [Twigg et al 2004, Wieland et al 2004]. FREM1 congenital anomalies of kidney and urinary tract (CAKUT). Isolated CAKUT has been associated with more than 20 genes to date and may be inherited in an autosomal dominant, autosomal recessive, or multifactorial manner [Nicolaou et al 2015]. The genetic etiology in most individuals with isolated CAKUT is unknown [Kohl et al 2014]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a FREM1 autosomal recessive disorder, the evaluations summarized in Table 3, Table 4, or Table 5 (depending on the phenotype) are recommended if they have not already been performed as part of the evaluation that led to the diagnosis: ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with MOTA Syndrome View in own window System/ConcernEvaluationComment OcularOphthalmologic evalFor coloboma &/or keratopathy GastrointestinalReferral to surgeonFor omphalocele, umbilical hernia, &/or anal anomalies if present ENTEval for bifid nose / notched ala nasiReferral to plastic surgeon as needed OtherConsultation w/clinical geneticist &/or genetic counselor ### Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with BNAR Syndrome View in own window System/ConcernEvaluationComment RenalRenal imaging & renal functional analysis GastrointestinalReferral to surgeonFor omphalocele, umbilical hernia, &/or anal anomalies if present Respiratory * ENT eval for bifid or notched nose * Eval of the airway Referral to plastic surgeon as needed OtherConsultation w/clinical geneticist &/or genetic counselor ### Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with FREM1-CAKUT View in own window System/ConcernEvaluation GenitourinaryClinical exam, imaging & surgical eval OtherConsultation w/clinical geneticist &/or genetic counselor ### Treatment of Manifestations Treatment of FREM1 autosomal recessive disorders consists primarily of surgical intervention with procedures tailored to the specific needs of the individual. A multidisciplinary team comprising a clinical geneticist, general surgeon, ophthalmologist, otolaryngologist, plastic surgeon, and social worker is preferred for optimal management. ### Table 6. Treatment of Manifestations in Individuals with FREM1 Autosomal Recessive Disorders View in own window Manifestation/ ConcernTreatmentConsiderations/Other Colobomas of the upper eyelids & synechiae * Managed conservatively w/intensive ocular lubrication * Surgical release of synechiae To avoid exposure keratopathy before surgery is performed Anophthalmia/microphthalmia & cryptophthalmosMay warrant surgical intervention & insertion of prosthesesTo facilitate development of ocular region 1 Visual impairment (e.g., refractive errors)Per ophthalmologistMay be assoc w/colobomas & corneopalpebral synechiae Notched ala nasi or bifid noseRhinoplastyMay be performed for cosmetic purposes Omphalocele & umbilical herniaMay be managed conservatively or surgicallyTo date, all persons w/a FREM1 AR disorder managed surgically have tolerated the procedure w/out complications. Anal stenosisSerial dilatations Anteriorly placed anusManaged conservatively or w/surgical interventionAs determined on an individual basis Renal malformations * Supportive treatment to preserve renal function & electrolyte balance * Surgical correction when indicated Dialysis & transplant may be indicated in persons w/renal failure. Psychosocial stressorsPsychosocial supportMay be indicated for parents & affected child AR = autosomal recessive 1\. Seah et al [2002] ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	FREM1 Autosomal Recessive Disorders	None	30,543	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1728/	2021-01-18T21:27:18	{"synonyms": []}
A group of interstitial lung diseases (ILD) induced by genetic mutations disrupting surfactant function and gas exchange in the lung. The disorders caused by these mutations affect full-term infants and older children and exhibit considerable overlap in their clinical and histologic presentation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies	None	30,544	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100049	2021-01-23T16:58:03	{"synonyms": ["Primary ILD specific to childhood due to pulmonary surfactant protein anomalies"]}
A rare variant of hepatocellular carcinoma (HCC) presenting in adolescents or young adults with no underlying liver disease. Clinical presentation is non specific, with abdominal mass, abdominal discomfort or pain, fatigue and weight loss. Patients can also be asymptomatic. HCC markers (alpha fetoprotein) are normal. Fibrolamellar HCC presents as a unique, well-delimited mass at imagery and a biopsy confirms the diagnosis, showing well-differentiated tumor cells surrounded by thick collagen bands. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Fibrolamellar hepatocellular carcinoma	c0334287	30,545	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=401920	2021-01-23T18:25:59	{"mesh": ["C537258"], "umls": ["C0334287"], "icd-10": ["C22.0"], "synonyms": ["FHCC", "Fibrolamellar hepatocarcinoma"]}
A number sign (#) is used with this entry because sideroblastic anemia-1 (SIDBA1) is caused by mutation in the gene encoding delta-aminolevulinate synthase-2 (ALAS2; 301300) on chromosome Xp11. Description The essential features of X-linked sideroblastic anemia include the following: (1) a hypochromic microcytic anemia and 2 discrete populations of red blood cells, one microcytic and the other normocytic; (2) marrow ringed sideroblasts, particularly prominent in the late erythroid precursors; (3) a variable hematologic response to pharmacologic doses of pyridoxine; and (4) systemic iron overload secondary to chronic ineffective erythropoiesis. The age of clinical onset of the disorder can vary from in utero to the ninth decade. Whereas males are preferentially affected, females may present with clinically severe anemia. More commonly, female carriers of the disease have an increased red blood cell distribution width and sometimes erythrocyte dimorphism (Fleming, 2002). ### Genetic Heterogeneity of Sideroblastic Anemia See also SIDBA2 (205950), caused by mutation in the SLC25A38 gene (610819) on chromosome 3p22; SIDBA3 (616860), caused by mutation in the GLRX5 gene (609588) on chromosome 14q32; and SIDBA4 (182170), caused by mutation in the HSPA9 gene (600548) on chromosome 5q31. Clinical Features X-linked sideroblastic anemia was first described by Cooley (1945), a Detroit pediatrician-hematologist who also first described thalassemia in a definitive way. He pointed out possible X-linkage in a family in which 19 males in 5 generations were affected, with transmission through unaffected females. Rundles and Falls (1946) reported 2 families, 1 of which was the same as that reported by Cooley. Somewhat enlarged spleens and minor red cell abnormalities without anemia were observed in female carriers. Pyridoxine responsiveness was demonstrated in at least 2 affected members of Rundles and Falls' family (Bishop and Bethel, 1959; Horrigan and Harris, 1964). Byrd and Cooper (1961) referred to the disorder as hereditary iron-loading anemia. Bickers et al. (1962) described the disorder in a man whose mother, sister, and 5 children had hematologic involvement in various degrees. Losowsky and Hall (1965) described a remarkably extensively affected family with a typical X-linked recessive inheritance pattern with clinical expression in some presumed heterozygous females. Associated hypolipidemia and hypocholesterolemia were pointed out by Spitzer et al. (1966). Prasad et al. (1968) studied a black family segregating both sideroblastic anemia and G6PD deficiency (300908). In females doubly heterozygous in coupling, there was a correlation between small red cells and low G6PD. Soslau and Brodsky (1989) described a 62-year-old male and his 30-year-old daughter with sideroblastic anemia. Both also had prolonged bleeding times with abnormalities of the platelets which appeared to represent a 'storage pool defect.' The sideroblastic anemia and the platelet abnormality may have been coincidentally associated. Pyridoxine deficiency is prevalent in patients undergoing dialysis (Kopple et al., 1981). Furuyama et al. (2003) reported an 81-year-old man who developed sideroblastic anemia while undergoing hemodialysis, The diagnosis of sideroblastic anemia was established by the presence of ringed sideroblasts in the bone marrow, which were completely eliminated by treatment with oral pyridoxine. The very late onset in this case of XLSA emphasized that nutritional deficiencies caused either by dietary irregularities in the elderly or, as in this case, by maintenance hemodialysis therapy, may uncover occult inherited enzymatic deficiencies in the heme biosynthetic pathway. Genetic analysis identified a mutation in the ALAS2 gene (D159N; 301300.0012). ### Heterozygous Females Peto et al. (1983) focused attention on iron overload in mild sideroblastic anemia after the death from cardiac iron loading of a middle-aged woman with a very mild form of familial sideroblastic anemia. Their studies demonstrated that iron overload can occur without severe anemia, most likely resulting from excessive absorption of dietary iron. Several additional patients had familial disease; mother and 2 sisters, mother and son, and 2 brothers were affected. None of the 5 patients tested showed linkage to the locus for hemochromatosis (235200). Peto et al. (1983) concluded that in heterozygous females 'even a minor population of hypochromic peripheral red cells may be important.' Cotter et al. (1995) described a previously unaffected 81-year-old woman in whom microcytic sideroblastic anemia developed. The initial diagnosis was myelodysplastic syndrome, but the recognition of the X-linked congenital sideroblastic anemia allowed successful treatment with pyridoxine. She was found to be heterozygous for a point mutation of the ALAS2 gene (301300.0005). There is evidence from other sources that skewed lyonization can be an acquired pattern. In the study of peripheral blood leukocytes by Busque et al. (1996), the incidence of skewing was 1.9% in neonates, 4.5% in women who were 28 to 32 years old, and 22.7% in women who were 60 years of age or older. Cazzola and Bergamaschi (1998) estimated that in 30 to 40% of elderly women, hematopoietic cells (erythroid cells, granulocytic cells, monocytes, and megakaryocytes) have more than 90% expression of 1 parental X chromosome. Puck and Willard (1998) reviewed mechanisms for a skewed pattern of X inactivation with a diagram of 3 different mechanisms. Aivado et al. (2006) reported a family in which a mother and her 2 daughters had pyridoxine-unresponsive sideroblastic anemia confirmed by genetic analysis. The disorder was variable in severity and X-chromosome inactivation studies were done. The mother developed progressive anemia in the fifth decade as she acquired an age-related nonrandom X-inactivation in hematopoietic cells. One daughter, with a mild phenotype at age 31, had moderate constitutive skewing of X-chromosome inactivation, and the other daughter, who was severely affected with clinical onset at age 16, had extreme constitutive skewing of X inactivation. There was also random X inactivation in reticulocytes of all 3 women that contrasted with a markedly skewed inactivation pattern in bone marrow erythroid cells. This discordance was attributed to apoptosis of erythroid precursors derived from progenitor cells with an active X-chromosome bearing the ALAS2 mutation. Biochemical Features Pinkerton (1967) observed 2 morphologically distinct populations of cells in heterozygotes. In a heterozygote, Lee et al. (1968) separated 2 populations of red cells by centrifugation in layered gum acacia solutions of different specific gravity. They found that the microcytes had a lower level of free protoporphyrin than did the normal cells, but unimpaired capacity to convert delta-aminolevulinic acid to protoporphyrin, suggesting a defect at or before the step in which delta-aminolevulinic acid is synthesized. Hines (1971) observed decreased levels of pyridoxal phosphokinase in red cells and livers of patients with pyridoxine-dependent refractory sideroblastic anemia. Aoki et al. (1973) found deficiency of delta-aminolevulinic acid synthetase in the red cells of patients with sideroblastic anemia, some of whom were males with congenital anemia which in some responded to treatment with B6. Aoki et al. (1979) found an apparent increase in proteolytic sensitivity of erythroblast ALAS in 2 patients with pyridoxine-responsive anemia. Clinical Management Paradoxically, phlebotomy is effective treatment for this form of anemia and can be done especially when there is a satisfactory response to pyridoxine. As in genetic hemochromatosis, the main objective is to prevent the development of diabetes, cirrhosis, and heart failure from iron overload. Phlebotomy must be done with more caution than in genetic hemochromatosis. Peto et al. (1983) noted that measures of erythroid expansion are useful in assessing risk of iron overload, and phlebotomy or iron-chelation therapy is indicated for prophylaxis. Gonzalez et al. (2000) reported a case of pyridoxine refractory hereditary sideroblastic anemia in a 19-year-old man who underwent peripheral blood stem cell transplantation from his HLA-identical brother. By using short tandem repeat polymorphism, 100% donor cells were observed in peripheral blood on day +21; bone marrow showed mixed chimerism from day +21 to day +221, when 100% cells of donor origin were observed. The patient developed extensive chronic graft-versus-host disease (GVHD; see 614395) with favorable response to treatment. When the hemoglobin range was normal, a program of phlebotomies reduced serum ferritin levels. Three years after transplantation, the patient had completely normal hemoglobin values. Molecular Genetics In a male with a pyridoxine-responsive form of X-linked sideroblastic anemia, Cotter et al. (1992) identified a causative mutation in the ALAS2 gene (301300.0001). In affected members of the original family with X-linked sideroblastic anemia described by Cooley (1945), Cotter et al. (1994) identified a missense mutation in the ALAS2 gene (301300.0003). In each of 4 unrelated males with X-linked sideroblastic anemia, Cotter et al. (1999) identified mutations in the ALAS2 gene (see, e.g., 301300.0008). All probands were clinically pyridoxine-responsive. One mutation was found to be the first de novo XLSA mutation, having occurred in a gamete of the proband's maternal grandfather. Genotype/Phenotype Correlations In 18 unrelated XLSA hemizygotes, Cotter et al. (1999) found a significantly higher frequency of coinheritance of the hereditary hemochromatosis HFE mutant allele C282Y (613609.0001) than found in the normal population. One proband with the Y199H mutation (301300.0017) with severe and early iron loading was homozygous for C282Y. The clinical and hematologic histories of 2 XLSA probands suggested that iron overload suppresses pyridoxine responsiveness. Reversal of the iron overload in the Y199H proband by phlebotomy resulted in higher hemoglobin concentrations during pyridoxine supplementation. The proband with the R452C mutation (301300.0018) was symptom-free on occasional phlebotomy and daily pyridoxine. These studies indicated the value of combined phlebotomy and pyridoxine supplementation in the management of XLSA probands in order to prevent a downward spiral of iron toxicity and refractory anemia. Animal Model The zebrafish mutant 'sauternes' (sau) has a microcytic, hypochromic anemia. During embryogenesis, sau mutants have delayed erythroid maturation and abnormal globin gene expression. Using positional cloning techniques, Brownlie et al. (1998) showed that sau encodes the erythroid-specific isoform of delta-aminolevulinate synthase, the enzyme required for the first step in heme biosynthesis. As mutations in ALAS2 cause congenital sideroblastic anemia in humans, History Weatherall et al. (1970) were unable to demonstrate lyonization of the Xg locus (314700) by observing 2 populations of cells in females heterozygous for familial sideroblastic anemia. Several reports (see Sessarego et al., 1983) suggested a connection between chromosomal rearrangement involving a breakpoint at Xp13 and the development of idiopathic acquired sideroblastic anemia progressing to acute nonlymphocytic leukemia. Holmes et al. (1990) found no consistent cytogenetic abnormalities in X-linked sideroblastic anemia. INHERITANCE \- X-linked recessive HEMATOLOGY \- Hypochromic, microcytic anemia \- Sideroblastic anemia \- Macrocytic anemia in manifesting females \- Pathologic perinuclear mitochondrial iron deposits in erythrocyte precursors LABORATORY ABNORMALITIES \- Low hemoglobin MISCELLANEOUS \- Variable age at onset, from birth to ninth decade \- Variable severity \- Female carriers may be affected \- May or may not be responsive to pyridoxine (vitamin B6) treatment \- Systemic iron overload due to ineffective erythropoiesis MOLECULAR BASIS \- Caused by mutation in the delta-aminolevulinate synthase 2 gene (ALAS2, 301300.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	ANEMIA, SIDEROBLASTIC, 1	c4551511	30,546	omim	https://www.omim.org/entry/300751	2019-09-22T16:19:44	{"doid": ["0060063"], "mesh": ["C536761"], "omim": ["300751"], "icd-10": ["D64.0"], "orphanet": ["75563"], "synonyms": ["ANEMIA, SIDEROBLASTIC, X-LINKED", "Alternative titles", "XLSA", "ANEMIA, HYPOCHROMIC", "HEREDITARY IRON-LOADING ANEMIA", "ANEMIA, HEREDITARY SIDEROBLASTIC"]}
Cartilage-hair hypoplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities; fine, sparse hair (hypotrichosis); and abnormal immune system function (immune deficiency) that can lead to recurrent infections. Signs and symptoms may vary among affected individuals. People with this condition are also at an increased risk of developing cancer, particularly blood, skin, and immune system cancers. Gastrointestinal problems are also common. Cartilage-hair hypoplasia is caused by mutations in the RMRP gene and is inherited in an autosomal recessive fashion. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Cartilage-hair hypoplasia	c0220748	30,547	gard	https://rarediseases.info.nih.gov/diseases/6996/cartilage-hair-hypoplasia	2021-01-18T18:01:36	{"mesh": ["C535916"], "omim": ["250250"], "orphanet": ["175"], "synonyms": ["Metaphyseal chondrodysplasia McKusick type", "CHH", "Cartilage hair hypoplasia like syndrome"]}
A number sign (#) is used with this entry because early infantile epileptic encephalopathy-6 (EIEE6) is caused by heterozygous mutation in the SCN1A gene (182389) on chromosome 2q24. About 95% of the mutations are de novo (Claes et al., 2001; Vadlamudi et al., 2010). Mutations in the SCN1A gene are also responsible for autosomal dominant generalized epilepsy with febrile seizures plus (GEFS+) (GEFSP2; 604403). Description Dravet syndrome, first described by Dravet (1978), is a clinical term for early-onset epileptic encephalopathy (EIEE) characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Seizures are usually refractory to treatment. Later, patients also manifest other seizure types, including absence, myoclonic, and partial seizures. The EEG is often normal at first, but later characteristically shows generalized spike-wave activity. Psychomotor development stagnates around the second year of life, and affected individuals show subsequent mental decline and other neurologic manifestations (summary by Harkin et al., 2007). Since mutation in the SCN1A gene can also cause the less severe disorder autosomal dominant generalized epilepsy with febrile seizures-plus, Dravet syndrome and migrating partial seizures of infancy (MPSI) are considered to be the most severe phenotypes within the spectrum of SCN1A-related epilepsies (Ohmori et al., 2002; Carranza Rojo et al., 2011). Deprez et al. (2009) provided a review of the genetics of epilepsy syndromes starting in the first year of life, and included a diagnostic algorithm. For a general phenotypic description and a discussion of genetic heterogeneity of early infantile epileptic encephalopathy, see EIEE1 (308350). Clinical Features Dravet syndrome, previously known as 'severe myoclonic epilepsy of infancy' (SMEI), is an epileptic syndrome characterized by normal development before onset, seizures beginning in the first year of life in the form of generalized or unilateral febrile clonic seizures, secondary appearance of myoclonic seizures, and occasionally partial seizures. It is associated with ataxia, slowed psychomotor development, and mental decline, and is often refractory to medication (Dravet et al., 1992; Sugawara et al., 2002). Renier and Renkawek (1990) reported that an autopsy of a 19-month-old boy with SMEI showed microdysgenesis of the cerebellum and cerebral cortex as well as malformation of the spinal cord. Doose et al. (1998) reported a large group of patients with severe intractable epilepsy of infancy or childhood with frequent generalized tonic-clonic seizures. At onset, the disorder was characterized by prolonged febrile and afebrile seizures as the only seizure type. With advancing age, the symptomatology became increasingly polymorphic due to additional seizure types, such as complex or focal. The most common triggering feature was fever or immersion in a hot bath, and most patients had severe impairment of mental development after seizure onset. Doose et al. (1998) noted the phenotypic overlap with SMEI. Fujiwara et al. (2003) reported 25 Japanese patients with SMEI and 10 Japanese patients with what they termed 'intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC),' which was only distinguished from SMEI by the absence of myoclonus. Twenty-two (62.8%) patients had a family history of seizures, including febrile convulsions and epilepsy consistent with GEFS+. The majority of patients had high voltage 4- to 7-Hz diffuse slow background activity on EEG. A total of 30 heterozygous mutations were identified in the SCN1A gene in this group of patients. Buoni et al. (2006) reported a 13-year-old boy with SMEI in whom the clinical phenotype evolved to GEFS+2 in adolescence. The patient had prolonged febrile seizures at ages 6, 10, and 13 months, afebrile complex partial seizures with secondary generalization beginning at age 18 months, and 2 episodes of status epilepticus at age 2 years. He also had abnormal EEG findings and myoclonic jerks. Antiepileptic medication was unsuccessful. At age 4 years, the seizure frequency decreased in response to medication, and by age 9, he had complex partial seizures with secondary generalization. By age 13, he was treated with valproate and had a febrile seizure. There was no mental retardation. Buoni et al. (2006) emphasized the relatively benign outcome in this patient despite having SMEI. Genetic analysis identified a de novo heterozygous 1-bp deletion in the SCN1A gene (182389.0017). Jansen et al. (2006) reported 14 adults with Dravet syndrome who ranged in age from 18 to 47 years. All had been referred for refractory epilepsy and intellectual disability without an etiologic diagnosis. Medical history revealed seizure onset between 3 to 11 months (mean 6 months), which was associated with fever in 9 patients. During childhood, all had generalized or unilateral tonic-clonic seizures, 12 had myoclonic seizures, 11 had absence seizures, 8 had complex partial seizures, and 6 had atonic seizures. Psychomotor development slowed in all after initial normal development. Eight patients had a family history of seizures. As adults, generalized tonic-clonic seizures were the dominant type, but all other types of seizures still occurred. Ten patients had motor abnormalities, including cerebellar signs in 4, pyramidal signs in 6, and extrapyramidal signs in 4. One patient had low-average intellect, 2 had mild intellectual disability, 5 were moderately retarded, and 6 had severe impairment. Two patients lived independently but were unemployed. Genetic analysis showed that 10 patients had mutations in the SCN1A gene and 1 had a mutation in the GABRG2 gene. Jansen et al. (2006) noted that the findings indicated a poor outcome for affected individuals and emphasized that correct diagnosis in adult patients requires a knowledge of early medical history. Riva et al. (2009) found that 2 unrelated children with genetically confirmed Dravet syndrome had progressive neurocognitive decline when longitudinally assessed from ages 11 and 23 months to 7 and 8 years, respectively. Importantly, delayed motor, intellectual, and rational development was already apparent at the time of seizure onset in both patients. One patient had a more severe seizure phenotype consistent with an epileptic encephalopathy, with numerous myoclonic seizures occurring almost daily and more frequent occurrence of tonic-clonic seizures compared to the second patient. However, both patients showed progressive deterioration in cognitive function over time, although there were differences in specific neuropsychologic functions affected. Riva et al. (2009) concluded that SCN1A mutations may play a role in early and progressive mental impairment in addition to their role in epilepsy. ### Clinical Variability Harkin et al. (2007) identified SCN1A mutations in a cohort of patients with a wide spectrum of infantile epileptic encephalopathies. Among a total of 188 patients, SCN1A mutations were found in 52 (79%) of 66 with SMEI (Dravet syndrome) and in 25 (69%) of 36 with 'severe myoclonic epilepsy of infancy-borderline (SMEB),' a phenotype lacking one or more features of SMEI, such as myoclonus or generalized spike-wave discharges on EEG. In addition, SCN1A mutations were less commonly found in patients with other forms of early-onset epilepsy, characterized as cryptogenic generalized or focal epilepsy, myoclonic-astatic epilepsy, and severe infantile multifocal epilepsy (SIMFE). Although the study indicated that a broader range of seizure phenotypes is associated with SCN1A mutations, Harkin et al. (2007) noted that the nosologic boundaries between these phenotypes is blurred. There were no apparent genotype/phenotype correlations. 'Malignant migrating partial seizures of infancy' (MPSI, MMPSI) is a clinical term for a severe form of infantile epileptic encephalopathy with seizure onset between 1 day and 6 months. EEG studies typically show migrating focal onset progressing to multifocal onset, and seizures are refractory to therapeutic intervention. Affected individuals have developmental regression after seizure onset, severe global developmental delay, and progressive microcephaly. Early death often occurs. The phenotype is considered to be more severe than that of typical Dravet syndrome (summary by Freilich et al., 2011 and Carranza Rojo et al., 2011). Freilich et al. (2011) reported a female infant with EIEE6 manifest clinically as MPSI associated with a heterozygous mutation in the SCN1A gene (A1669E; 182389.0023). She had a severe phenotype, with onset of seizures at age 10 weeks, progression to refractory recurrent seizures by age 5 months, status epilepticus, EEG evidence of migrating focal onset progressing to multifocal seizures, progressive microcephaly, and profound psychomotor delay. She died at age 9 months. Carranza Rojo et al. (2011) found that 2 of 15 unrelated infants with a clinical diagnosis of MPSI had defects in the SCN1A gene. One had a de novo missense mutation (R862G; 182389.0024) and the other had a de novo 11.06-Mb deletion of chromosome 2q24.2-q31.1 encompassing more than 40 genes that included SCN1A. The patient with the R862G mutation had onset of multifocal hemiclonic seizures at age 2 weeks with status epilepticus. She had acquired microcephaly, developmental regression, and severe intellectual disability. These reports expanded the severity of the epileptic phenotype associated with SCN1A mutations to include MPSI. Moreover, the lack of SCN1A mutations in 13 patients with a similar diagnosis by Carranza Rojo et al. (2011) indicated genetic heterogeneity for the MPSI entity. Inheritance Approximately 95% of patients with Dravet syndrome have de novo heterozygous mutations, which explains the unaffected status of many sibs and parents (Vadlamudi et al., 2010). Fujiwara et al. (1990) reported a pair of monozygotic male twins who both had SMEI and showed a similar phenotype with regard to seizure onset, seizure symptomatology, and EEG expression. Of 12 unrelated patients with Dravet syndrome, Singh et al. (2001) found that 11 had a family history of seizures and the twelfth was the offspring of a consanguineous marriage. A total of 39 related affected individuals were identified and the phenotypes included febrile seizures, partial seizures, and several unclassified seizures. Singh et al. (2001) suggested that Dravet syndrome is the most severe form of generalized epilepsy with febrile seizures plus (see 604233). Selmer et al. (2009) reported a family of Norwegian origin in which a mother with a history of migraine was somatic mosaic for a truncating SCN1A mutation that she transmitted, through 2 different husbands, to her 2 daughters who had Dravet syndrome. The mother had attacks of migraine without aura since age 12 to 14 years; the mutation was estimated to be present in approximately 5% of the mother's blood and inferred to be present in a proportion of her germ cells. Selmer et al. (2009) postulated that migraine in the mother may represent the mildest end of the phenotypic spectrum caused by SCN1A mutations. Of 44 SCN1A mutations that occurred de novo in patients with Dravet syndrome, Heron et al. (2010) found that 75% were of paternal origin and 25% were of maternal origin. The cohort included 1 set of affected sibs, whose originating parent was thought to have gonadal mosaicism. The average age of parents did not differ from that of the general population. The findings indicated that de novo SCN1A mutations originated most commonly, but not exclusively, from the paternal chromosome. Heron et al. (2010) suggested that the greater frequency of paternally derived SCN1A mutations was likely due to the greater chance of mutational events because of the increased number of mitoses during spermatogenesis compared to oogenesis, with a greater susceptibility to mutagenesis of methylated DNA characteristic of sperm cells. Depienne et al. (2010) studied 19 families in which at least 1 individual had Dravet syndrome due to an inherited SCN1A mutation. In 12 cases, the transmitting parent was mosaic for the mutation, and the proportion of each mutation in parental blood cells ranged from 0.4 to 85%. The mutation was inherited from the mother in 6 cases and from the father in 6 cases. Six of the parents who were mosaic had mild features, including febrile seizures and tonic-clonic seizures, and the seizure phenotype correlated partially with increasing mutation load in blood cells. In the 6 remaining families, an SCN1A missense mutation segregated with Dravet syndrome and with autosomal dominant GEFS+ (GEFSP2; 604403). The findings indicated that some families with SCN1A mutations show wide phenotypic variability, with Dravet syndrome at the severe end of the spectrum. Vadlamudi et al. (2010) reviewed the effect of timing of de novo mutagenesis in the SCN1A gene and described a discordant monozygotic twin pair, in which 1 SMEI-affected sib carried a heterozygous SCN1A truncation mutation. Detailed mutation analysis of various tissues from the affected twin identified a truncating SCN1A mutation (182389.0008) in lymphocytes, hair, buccal cells, skin fibroblasts, and cell lines derived from neuroepithelium, but not in tissues taken from the unaffected twin, the parents, or an unaffected sib. No evidence of somatic mosaicism was detected in the unaffected twin or the parents. Since the mutation was found in all tissues from the affected twin but not in tissues from the unaffected twin, Vadlamudi et al. (2010) concluded that the SCN1A mutation occurred in the premorula stage, most likely at the 2-cell stage. Cytogenetics Suls et al. (2010) reported a 4-generation Bulgarian family with epilepsy transmitting a heterozygous 400-kb deletion on chromosome 2q24 encompassing the SCN1A and TTC21B (612014) genes. The phenotype was variable, but all had onset of generalized tonic-clonic seizures around the first year of life (range, 8 to 14 months), and some had myoclonic or absence seizures. Three of 4 patients had febrile seizures in infancy. One patient had mild mental retardation, 1 had psychomotor slowing, and 1 had mental retardation from early infancy; all had reduced seizures on medication. The fourth patient died of status epilepticus at age 13 months. Thus, 2 patients had a phenotype reminiscent of Dravet syndrome, whereas the phenotype in the other 2 was more consistent with GEFS+2. The unaffected father in the first generation was found to be somatic mosaic for the deletion. Suls et al. (2010) noted that deletions involving SCN1A usually result in Dravet syndrome, in which affected individuals cannot raise a family and thus do not transmit the mutation. The report of this family with a deletion of SCN1A in which 2 affected individuals were able to raise a family suggested the presence of genetic modifiers and showed intrafamilial variability. Molecular Genetics ### Mutations in the SCN1A Gene In 7 patients with Dravet syndrome, Claes et al. (2001) found heterozygous mutations in the SCN1A gene, including 3 deletions and 1 insertion that resulted in premature stop codons, a nonsense, a splice donor site, and a missense mutation; see, e.g., 182389.0007-182389.0009. The mutations were absent in all parents, suggesting that de novo mutations are a major cause of SMEI. Claes et al. (2001) noted that most of the mutations resulted in early termination of translation, producing a truncated SCN1A protein. In 14 patients, including a pair of monozygotic twins, with classic symptoms of Dravet syndrome, Sugawara et al. (2002) identified 10 heterozygous mutations in the SCN1A gene. There were 3 frameshift mutations which resulted in intragenic stop codons and truncated channels, and 7 nonsense mutations which also resulted in truncated channels. In 4 patients, no mutations were detected in either the SCN1A or SCN1B (600235) genes. In 24 of 29 patients with Dravet syndrome, Ohmori et al. (2002) found heterozygous de novo mutations in SCN1A, mutations in which have been identified also in GEFS+. That mutations in the SCN1A gene can cause severe myoclonic epilepsy in infancy supports the suggestion of Singh et al. (2001) that Dravet is part of the GEFS+ spectrum. Indeed, Dravet syndrome and GEFS+ have been observed in the same family. Among 93 patients with Dravet syndrome, Nabbout et al. (2003) identified 29 different mutations in the SCN1A gene in 33 patients (35%). All cases were sporadic, but a history of febrile seizures and epilepsy was found in the families of 32% and 12% of the probands, respectively. Three of the mutations were inherited from a parent. The authors concluded that the disorder is genetically heterogeneous and may also exhibit complex inheritance. In 7 of 10 unrelated Japanese patients with intractable childhood epilepsy with generalized tonic-clonic seizures, Fujiwara et al (2003) identified mutations in the SCN1A gene (see, e.g., 182389.0013; 182389.0014). All of the mutations were missense. Two unrelated affected children had mothers with the mutation who had a phenotype consistent with GEFS+. Fujiwara et al. (2003) concluded that myoclonus is not a necessary feature of the disorder. Using multiplex ligation-dependent probe amplification (MLPA), Mulley et al. (2006) identified exon deletions in the SCN1A gene (182389.0018; 182389.0019) in 2 (15%) of 13 unrelated SMEI patients who did not have point or splice site mutations in the SCN1A gene. The findings provided a new molecular mechanism for the disorder. Depienne et al. (2009) identified pathogenic mutations or deletions, including 161 novel point mutations, in the SCN1A gene in 242 (73%) of 333 patients with Dravet syndrome. The most common mutations were missense (42%), and 14 patients had microrearrangements in or deletions of the gene. Thus, the disease mechanism appeared to be haploinsufficiency of the SCN1A gene. Mutations were scattered throughout the gene, and there were no apparent genotype/phenotype correlations. Orrico et al. (2009) identified 21 mutations, including 14 novel mutations, in the SCN1A gene in 22 (14.66%) of 150 Italian pediatric probands with epilepsy. SCN1A mutations were found in 21.2% of patients with GEFS+ (604233) and in 75% of patients with SMEI from the overall patient cohort. Only 1 potentially pathogenic mutation was identified in the SCN1B gene (600235), and no mutations were found in the GABRG2 gene (137164). Sun et al. (2010) identified pathogenic mutations in the SCN1A gene in 49 (77.8%) of 63 Chinese probands with Dravet syndrome. The majority of mutations were truncating (61.2%). The mutations included 19 missense, 14 frameshift, 6 nonsense, and 8 splice site alterations. MLPA analysis identified deletions or duplications of SCN1A in 2 (12.5%) of 16 patients who were negative by sequencing. Forty mutations were de novo, and 1 was inherited from a mother who was mosaic for the mutation and had a phenotype consistent with GEFS+. Ten of 12 de novo mutations studied were of paternal origin, and 2 were of maternal origin. Sun et al. (2010) emphasized that MLPA analysis is essential for correct diagnosis in sequencing-negative patients with Dravet syndrome. ### Potential Modifier Genes Harkin et al. (2002) reported a family with GEFS+ (604233) caused by a heterozygous mutation in the GABRG2 gene (Q351X; 137164.0003); 1 family member had a more severe phenotype, consistent with Dravet syndrome. However, Ohmori et al. (2002) found no mutations of the GABRG2 gene in 29 patients with Dravet syndrome. They also found no mutations in SCN1B (600235), the other gene that had been related to generalized epilepsy with febrile seizures. In 2 patients diagnosed with Dravet syndrome, Singh et al. (2009) identified a heterozygous mutation in the SCN9A gene (K655R; 603415.0019); one of the patients also had a mutation in the SCN1A gene (182389). The K655R mutation was also identified in a patient with GEFSP7 (see 604233). Singh et al. (2009) also presented evidence that the SCN9A gene on chromosome 2q24 may be a modifier of Dravet syndrome; 9 (8%) of 109 patients with Dravet syndrome were found to have an SCN9A mutation, including 6 patients who were double heterozygous for SCN9A and SCN1A mutations and 3 patients with only heterozygous SCN9A mutations, consistent with multifactorial inheritance. Population Genetics From an analysis of data on children with seizures from a national database, Hurst (1990) determined that the incidence of SMEI is 1 in 40,000. Nomenclature Dravet syndrome has also been referred to as 'severe myoclonic epilepsy of infancy' (SMEI), but the term 'Dravet syndrome' is preferred because not all affected individuals show myoclonus (Engel, 2001). Dravet syndrome is also referred to here as early infantile epileptic encephalopathy-6 (EIEE6). Animal Model Yu et al. (2006) found that Scn1a -/- mice developed severe ataxia and seizures and died on postnatal day 15. Scn1a +/- mice had spontaneous seizures and sporadic deaths beginning after postnatal day 21, with a notable dependence on genetic background. Loss of Scn1a did not change voltage-dependent activation or inactivation of sodium channels in hippocampal neurons. However, the sodium current density was substantially reduced in inhibitory interneurons of Scn1a -/- and +/- mice. The findings suggested that reduced sodium currents in GABAergic inhibitory interneurons resulting from heterozygous SCN1A mutations may cause the hyperexcitability that leads to epilepsy in patients with SMEI. Oakley et al. (2009) generated a mouse model of SMEI by targeted heterozygous deletion of the Scn1a gene. Mutant mice developed seizures induced by elevated core body temperature, whereas wildtype mice were unaffected. In 3 age groups studied, none of postnatal day (P) 17 to 18 mutant mice had temperature-induced seizures, but nearly all P20 to P22 and P30 to P46 mutant mice developed myoclonic seizures followed by generalized seizures caused by elevated core body temperature. There was an age-related susceptibility to seizures at lower temperatures as well as a general increase in severity of seizures with increasing age. Spontaneous seizures were only observed in mice older than P32, suggesting that mutant mice become susceptible to temperature-induced seizures before spontaneous seizures. Interictal EEG spike activity was seen at normal body temperature in most P30 to P46 mutant mice, but not in P20 to P22 or P17 to P18 mutant mice, indicating that interictal epileptic activity correlates with seizure susceptibility. Most P20 to P22 mutant mice had interictal spike activity with elevated body temperature. Oakley et al. (2009) concluded that their results defined a critical developmental transition for susceptibility to seizures in SMEI, demonstrated that body temperature elevation alone is sufficient to induce seizures in mutation carriers, and revealed a close correspondence between human and mouse SMEI in the temperature and age dependence of seizure frequency and severity. Martin et al. (2007) showed that the seizure severity of heterozygous Scn1a +/- mice (see Yu et al., 2006), which is a mouse model for SMEI, was ameliorated by a heterozygous point mutation (med-jo) in the Scn8a gene (600702). Double-heterozygous Scn1a +/- and Scn8a +/(med-jo) mice had seizure thresholds that were comparable to wildtype littermates, and the Scn8a(med-jo) allele was also able to rescue the premature lethality of Scn1a +/- mice and extended the life span of Scn1a -/- mice. The authors hypothesized that the opposing effects of Scn1a and Scn8a dysfunction on seizure thresholds result from differences in the cell types that are influenced by the respective sodium channel subtypes. Scn1a mutants result in reduced sodium currents in inhibitory GABAergic interneurons of the hippocampus and cortex, whereas Scn8a mutants affect excitatory pyramidal cells of the hippocampus and cortex, suggesting that reduced excitability of these cells may underlie the elevated seizure resistance of Scn8a-mutant mice. Martin et al. (2007) suggested that their results demonstrated that genetic interactions can alter seizure severity, and supported the hypothesis that genetic modifiers, including the SCN8A gene, contribute to the clinical variability observed in SMEI and GEFS+. Han et al. (2012) reported that mice with Scn1a haploinsufficiency exhibit hyperactivity, stereotyped behaviors, social interaction deficits, and impaired context-dependent spatial memory. Olfactory sensitivity is retained, but novel food odors and social odors are aversive to Scn1a +/- mice. GABAergic neurotransmission is specifically impaired by this mutation, and selective deletion of Na(v)1.1 channels in forebrain interneurons is sufficient to cause these behavioral and cognitive impairments. Remarkably, treatment with low-dose clonazepam, a positive allosteric modulator of GABA(A) receptors, completely rescued the abnormal social behaviors and deficits in fear memory in the mouse model of Dravet syndrome, demonstrating that they are caused by impaired GABAergic neurotransmission and not by neuronal damage from recurrent seizures. Han et al. (2012) concluded that their results demonstrated a critical role for Na(v)1.1 channels in neuropsychiatric functions and provided a potential therapeutic strategy for cognitive deficit and autism spectrum behaviors in Dravet syndrome. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Acquired microcephaly (in severe cases) Eyes \- Visual impairment, cortical (in severe cases) NEUROLOGIC Central Nervous System \- Generalized clonic or tonic-clonic seizures \- Unilateral clonic seizures \- Absence seizures \- Complex partial seizures \- Myoclonic seizures \- Delayed psychomotor development \- Psychomotor delay after second year \- Mental deterioration \- Ataxia \- Status epilepticus \- EEG may be normal at first \- EEG later shows generalized spike or polyspike waves and focal spikes \- EEG may show migrating focal or multifocal origin (in severe cases) \- Cerebral atrophy (in severe cases) MISCELLANEOUS \- Marked phenotypic variability \- Most mutations occur de novo \- Onset in first year of life \- Psychomotor delay may already be apparent at onset of seizures \- May be induced by fever or hot bath \- Often refractory to medical therapy \- May be extreme phenotype of generalized epilepsy with febrile seizures plus (GEFS+, 604233 ) MOLECULAR BASIS \- Caused by mutation in the alpha subunit of the voltage-gated sodium channel type I gene (SCN1A, 182389.0007 ) \- Caused by mutation in the alpha subunit of the voltage-gated sodium channel type IX gene (SCN9A, 603415.0019 ) \- Caused by mutation in the gamma-aminobutyric acid (GABA) A receptor, gamma-2 gene (GABRG2, 137164.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 6	c0751122	30,548	omim	https://www.omim.org/entry/607208	2019-09-22T16:09:32	{"doid": ["0080422"], "mesh": ["D004831"], "omim": ["607208"], "orphanet": ["33069"], "synonyms": ["Alternative titles", "DRAVET SYNDROME", "SEVERE MYOCLONIC EPILEPSY OF INFANCY"], "genereviews": ["NBK1318"]}
A rare osteonecrosis disease characterized by death of bone cellular components secondary to an interruption of the subchondral blood supply, typically manifesting with unilateral or bilateral, unifocal or multifocal lesions usually located on the epiphysis, metaphysis and/or diaphysis of the femoral heads, knees, shoulders, ankles and/or wrists, leading to gradual onset of pain and progressive joint degeneration resulting in loss of function. Association with corticosteroid usage, alcoholism, hyperbaric events, radiation or cytotoxic agent exposure, hemoglobinopathies, and/or underlying autoimmune or metabolic disease, amongst others, has been observed. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Secondary non-traumatic avascular necrosis	None	30,549	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=399180	2021-01-23T17:17:42	{"icd-10": ["M87.1", "M87.3"], "synonyms": ["Secondary non-traumatic AVN", "Secondary non-traumatic osteonecrosis"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Juvenile myelomonocytic leukemia" – news · newspapers · books · scholar · JSTOR (June 2014) (Learn how and when to remove this template message) Juvenile myelomonocytic leukemia SpecialtyOncology Juvenile myelomonocytic leukemia (JMML) is a serious chronic leukemia (cancer of the blood) that affects children mostly aged 4 and younger. The name JMML now encompasses all diagnoses formerly referred to as juvenile chronic myeloid leukemia (JCML), chronic myelomonocytic leukemia of infancy, and infantile monosomy 7 syndrome. The average age of patients at diagnosis is 2 years old. The World Health Organization has included JMML in the category of myelodysplastic and myeloproliferative disorders.[1] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 4.1 Splenectomy * 4.2 Chemotherapy * 4.3 Radiation * 4.4 Stem cell transplantation * 5 Prognosis * 6 Frequency * 7 History * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] The following symptoms are typical ones which lead to testing for JMML, though children with JMML may exhibit any combination of them: pallor, fever, infection, bleeding, cough, poor weight gain, a maculopapular rash (discolored but not raised, or small and raised but not containing pus), lymphadenopathy (enlarged lymph nodes), moderate hepatomegaly (enlarged liver), marked splenomegaly (enlarged spleen), leukocytosis (high white blood cell count in blood), absolute monocytosis (high monocyte count in blood), anemia (low red blood cell count in blood), and thrombocytopenia (low platelet count in blood).[2][3] Most of these conditions are common, nonspecific signs and symptoms. Children with JMML and neurofibromatosis 1 (NF1) (about 14% of children with JMML are also clinically diagnosed with NF1, though up to 30% carry the NF1 gene mutation) may also exhibit any of the following symptoms associated with NF1 (in general, only young children with NF1 are at an increased risk of developing JMML):[2] * 6 or more café-au-lait (flat, coffee-colored) spots on the skin * 2 or more neurofibromas (pea-size bumps that are noncancerous tumors) on or under the skin * Plexiform neurofibromas (larger areas on skin that appear swollen) * Optic glioma (a tumor on the optic nerve that affects vision) * Freckles under the arms or in the groin * 2 or more Lisch nodules (tiny tan or brown-colored spots on the iris of the eye) * Various bone deformations including bowing of the legs below the knee, scoliosis, or thinning of the shin bone Noonan syndrome (NS) may predispose to the development of JMML[4] or a myeloproliferative disorder (MPD) associated with NS (MPD/NS) which resembles JMML in the first weeks of life.[4] However, MPD/NS may resolve without treatment.[4] Children with JMML and Noonan's syndrome may also exhibit any of the following most-common symptoms associated with Noonan's syndrome:[2] * Congenital heart defects, in particular, pulmonic stenosis (a narrowing of the valve from the heart to the lungs) * Undescended testicles in males * Excess skin and low hair line on back of neck * Widely set eyes * Diamond-shaped eyebrows * Ears that are low-set, backward-rotated, thick outer rim * Deeply grooved philtrum (upper lip line) * Learning delays ## Genetics[edit] About 90% of JMML patients have some sort of genetic abnormality in their leukemia cells that can be identified with laboratory testing.[5] This includes:[6] * 15-20% of patients with neurofibromatosis 1 (NF1) * 25% of patients with mutations in one of the RAS family of oncogenes (only in their leukemia cells) * Another 35% of patients with a mutation in a gene called PTPN11 (again, only in their leukemia cells). ## Diagnosis[edit] The following criteria are required in order to diagnose JMML:[1] All 4 of the following: * No Philadelphia chromosome or BCR/ABL fusion gene.[7] * Peripheral blood monocytosis >1 x 109/L. * Less than 20% blasts (including promonocytes) in the blood and bone marrow (blast count is less than 2% on average) * Splenomegaly At least one of:[8] * Mutation in RAS or PTPN11 * Diagnosis of neurofibromatosis 1 * Chromosome 7 monosomy Or two or more of the following criteria: * Hemoglobin F increased for age. * Immature granulocytes and nucleated red cells in the peripheral blood. * White blood cell count >10 x 109/L. * Clonal chromosomal abnormality (e.g., monosomy 7). * Granulocyte macrophage colony-stimulating factor (GM-CSF) hypersensitivity of myeloid progenitors in vitro.[9] These criteria are identified through blood tests and bone marrow tests. The differential diagnosis list includes infectious diseases like Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, histoplasma, mycobacteria, and toxoplasma, which can produce similar symptoms. ## Treatment[edit] There are two internationally accepted treatment protocols, which are geographically based:[citation needed] * North America: the Children's Oncology Group (COG) JMML study * Europe: the European Working Group for Myelodysplastic Syndromes (EWOG-MDS) JMML study The following procedures are used in one or both of the current clinical approaches listed above: ### Splenectomy[edit] The theory behind splenectomy in JMML is that the spleen may trap leukemic cells, leading to the spleen's enlargement, by harboring dormant JMML cells that are not eradicated by radiation therapy or chemotherapy for the active leukemia cells, thus leading to later relapse if the spleen is not removed. However, the impact of splenectomy on post-transplant relapse, though, is unknown. The COG JMML study includes splenectomy as a standard component of treatment for all clinically stable patients. The EWOG-MDS JMML study allows each child's physician to determine whether or not a splenectomy should be done, and large spleens are commonly removed prior to bone marrow transplant. When a splenectomy is scheduled, JMML patients are advised to receive vaccines against Streptococcus pneumoniae and Haemophilus influenza at least 2 weeks prior to the procedure. Following splenectomy, penicillin may be administered daily in order to protect the patient against bacterial infections that the spleen would otherwise have protected against; this daily preventative regimen will often continue indefinitely.[citation needed] ### Chemotherapy[edit] The role of chemotherapy or other pharmacologic treatments against JMML before bone marrow transplant has not been studied completely and its importance is still unknown. Chemotherapy by itself has proven unable to bring about long-term survival in JMML. * Low-dose conventional chemotherapy: Studies have shown no influence from low-dose conventional chemotherapy on JMML patients’ length of survival. Some combinations of 6-mercaptopurine with other chemotherapy drugs have produced results such as decrease in organ size and increase or normalization of platelet and leukocyte count. * Intensive chemotherapy: Complete remission with ongoing durability from JMML has not been possible through use of intensive chemotherapy, but it is still used at times because it has improved the condition of a small but significant number of JMML patients who do not display an aggressive disease. The COG JMML study administers 2 cycles of fludarabine and cytarabine for 5 consecutive days along with 13-cis retinoic acid during and afterwards. The EWOG-MDS JMML study, however, does not recommend intensive chemotherapy before bone marrow transplant. * 13-cis retinoic acid (Isotretinoin): In the lab, 13-cis-retinoic acid has inhibited the growth of JMML cells. The COG JMML study therefore includes 13-cis-retinoic acid in its treatment protocol, though its therapeutic value for JMML remains controversial. ### Radiation[edit] Radiation to the spleen does not generally result in a decrease in spleen size or reduction of platelet transfusion requirement. ### Stem cell transplantation[edit] The only treatment that has resulted in cures for JMML is stem cell transplantation, also known as a bone marrow transplant, with about a 50% survival rate.[5][9] The risk of relapsing after transplant is high, and has been recorded as high as 50%. Generally, JMML clinical researchers recommend that a patient have a bone marrow transplant scheduled as soon as possible after diagnosis. A younger age at bone marrow transplant appears to predict a better outcome. * Donor: Transplants from a matched family donor (MFD), matched unrelated donor (MUD), and matched unrelated umbilical cord blood donors have all shown similar relapse rates, though transplant-related deaths are higher with MUDs and mostly due to infectious causes. Extra medicinal protection, therefore, is usually given to recipients of MUD transplants to protect the child from Graft Versus Host Disease (GVHD). JMML patients are justified for MUD transplants if no MFD is available due to the low rate of survival without a bone marrow transplant. * Conditioning regimen: The COG JMML study involves 8 rounds of total-body irradiation (TBI) and doses of cyclophosphamide to prepare the JMML child's body for bone marrow transplant. Use of TBI is controversial, though, because of the possibility of late side-effects such as slower growth, sterility, learning disabilities, and secondary cancers, and the fact that radiation can have devastating effects on very young children. It is used in this study, however, due to the concern that chemotherapy alone might not be enough to kill dormant JMML cells. The EWOG-MDS JMML Study includes busulfan in place of TBI due to its own research findings that appeared to show that busulfan was more effective against leukemia in JMML than TBI. The EWOG-MDS study also involves cyclophosphamide and melphalan in its conditioning regimen. * Post transplant management: patients can experience relapse, causing treatment failure. It can be prevented by starting the patient with withdrawal of immunosuppressants and/or begin donor lymphocyte infusion. [10] * Graft versus leukemia: Graft versus leukemia[clarification needed] has been shown many times to play an important role in curing JMML, and it is usually evidenced in a child after bone marrow transplant through some amount of acute or chronic Graft Versus Host Disease (GVHD). Evidence of either acute or chronic GVHD is linked to a lower relapse rate in JMML. Careful management of immunosuppressant drugs for control of GVHD is essential in JMML; importantly, children who receive less of this prophylaxis have a lower relapse rate. After bone marrow transplant, reducing ongoing immunosuppressive therapy has worked successfully to reverse the course of a bone marrow with a dropping donor percentage[clarification needed] and to prevent a relapse. Donor lymphocyte infusion (DLI), on the other hand, does not frequently work to bring children with JMML back into remission. ## Prognosis[edit] Prognosis refers to how well a patient is expected to respond to treatment based on their individual characteristics at time of diagnosis. In JMML, three characteristic areas have been identified as significant in the prognosis of patients:[11] Characteristic Values indicating a more favorable prognosis Sex Male Age at diagnosis < 2 years old Other existing conditions Diagnosis of Noonan syndrome Without treatment, the survival [5 years?][clarification needed] of children with JMML is approximately 5%.[citation needed] Only Hematopoietic Stem Cell Transplantation (HSCT), commonly referred to as a bone marrow or (umbilical) cord blood transplant, has been shown to be successful in curing a child of JMML. With HSCT, recent research studies have found the survival rate to be approximately 50%. Relapse is a significant risk after HSCT for children with JMML. It is the greatest cause of death in JMML children who have had stem cell transplants. Relapse rate has been recorded as high as 50%. Many children have been brought into remission after a second stem cell transplant.[citation needed] After bone marrow transplant, the relapse rate for children with JMML may be as high as 50%. Relapse often occurs within a few months after transplant and the risk of relapse drops considerably at the one-year point after transplant. A significant number of JMML patients do achieve complete remission and long-term cure after a second bone marrow transplant, so this additional therapy should always be considered for children who relapse. ## Frequency[edit] JMML accounts for 1-2% of childhood leukemias each year; in the United States, an estimated 25-50 new cases are diagnosed each year, which also equates to about 3 cases per million children. There is no known environmental cause for JMML. Since about 10% of patients are diagnosed before 3 months of age, it is thought that JMML is a congenital condition in these infants[citation needed] ## History[edit] Juvenile myelomonocytic leukemia (JMML) is a myelodysplastic and myeloproliferative disorder.[7][2][5] The diagnostic criteria were originally laid down by Neimeyer et al. in 1997[12] and 1998 and were incorporated in the WHO classification in 2008.[13] ## See also[edit] * List of cutaneous conditions * Hematologic diseases * List of cancer types ## References[edit] 1. ^ a b "Myelodysplastic/Myeloproliferative Diseases Treatment - National Cancer Institute". 2003-09-24. 2. ^ a b c d Loh M. L. (2010). "Childhood myelodysplastic syndrome: Focus on the approach to diagnosis and treatment of juvenile myelomonocytic leukemia". Hematology. 2010 (1): 357–62. doi:10.1182/asheducation-2010.1.357. PMID 21239819. 3. ^ Proytcheva, M. (Nov 2011). "Juvenile myelomonocytic leukemia". Semin Diagn Pathol. 28 (4): 298–303. doi:10.1053/j.semdp.2011.08.007. PMID 22195407. 4. ^ a b c Bastida P; García-Miñaúr S; Ezquieta B; Dapena J. L.; De Toledo Sanchez (2011). "Myeloproliferative disorder in Noonan syndrome". Journal of Pediatric Hematology/Oncology. 33 (1): e43–5. doi:10.1097/MPH.0b013e3181e7571e. PMID 20829714. S2CID 39815230. 5. ^ a b c Chang T. Y.; Dvorak C. C.; Loh M. L. (2014). "Bedside to bench in juvenile myelomonocytic leukemia: Insights into leukemogenesis from a rare pediatric leukemia". Blood. 124 (16): 2487–2497. doi:10.1182/blood-2014-03-300319. PMID 25163700. 6. ^ Niemeyer C. M. (2014). "RAS diseases in children". Haematologica. 99 (11): 1653–1662. doi:10.3324/haematol.2014.114595. PMC 4222471. PMID 25420281. 7. ^ a b Tiu R. V.; Sekeres M. A. (2014). "Making sense of the myelodysplastic/myeloproliferative neoplasms overlap syndromes". Current Opinion in Hematology. 21 (2): 131–40. doi:10.1097/MOH.0000000000000021. PMID 24378705. S2CID 28142057. 8. ^ Lee, Ming-Luen; Yen, Hsiu-Ju; Chen, Shu-Jen; Hung, Giun-Yi; Tsao, Pei-Chen; Soong, Wen-Jue (1 April 2016). "Juvenile Myelomonocytic Leukemia in a Premature Neonate Mimicking Neonatal Sepsis". Pediatrics & Neonatology. 57 (2): 149–152. doi:10.1016/j.pedneo.2013.06.009. ISSN 1875-9572. PMID 24269860. 9. ^ a b Yoshida N, Doisaki S, Kojima S (2012). "Current management of juvenile myelomonocytic leukemia and the impact of RAS mutations". Pediatric Drugs. 14 (3): 157–63. doi:10.2165/11631360-000000000-00000. PMID 22480363. S2CID 30523534. 10. ^ Yoshimi, Ayami; Niemeyer, Charlotte M.; Bohmer, Viktoria; Duffner, Ulrich; Strahm, Brigitte; Kreyenberg, Hermann; Dilloo, Dagmar; Zintl, Felix; Claviez, Alexander; Wössmann, Willi; Kremens, Bernhard (2005). "Chimaerism analyses and subsequent immunological intervention after stem cell transplantation in patients with juvenile myelomonocytic leukaemia". British Journal of Haematology. 129 (4): 542–549. doi:10.1111/j.1365-2141.2005.05489.x. ISSN 1365-2141. 11. ^ Satwani, Prakash; Kahn, Justine; Dvorak, Christopher C. (2015-02-01). "Juvenile Myelomonocytic Leukemia". Pediatric Clinics of North America. Childhood Leukemia and Cancer. 62 (1): 95–106. doi:10.1016/j.pcl.2014.09.003. ISSN 0031-3955. 12. ^ Niemeyer C. M.; Arico M; Basso G; Biondi A; Cantu Rajnoldi A; Creutzig U; Haas O; Harbott J; Hasle H; Kerndrup G; Locatelli F; Mann G; Stollmann-Gibbels B; Van't Veer-Korthof E. T.; Van Wering E; Zimmermann M (1997). "Chronic myelomonocytic leukemia in childhood: A retrospective analysis of 110 cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG-MDS)". Blood. 89 (10): 3534–43. PMID 9160658. 13. ^ Sethi N, Kushwaha S, Dhingra B, Pujani M, Chandra J, Shukla S (2013). "Juvenile myelomonocytic leukemia". Indian Journal of Hematology and Blood Transfusion. 29 (3): 164–6. doi:10.1007/s12288-012-0164-9. PMC 3710560. PMID 24426365. ## External links[edit] Classification D * ICD-10: C93.1 * ICD-10-CM: C93.3 * ICD-O: 9946 * OMIM: 607785 * MeSH: D054429 * SNOMED CT: 445227008 External resources * Orphanet: 86834 * v * t * e Myeloid-related hematological malignancy CFU-GM/ and other granulocytes CFU-GM Myelocyte AML: * Acute myeloblastic leukemia * M0 * M1 * M2 * APL/M3 MP * Chronic neutrophilic leukemia Monocyte AML * AMoL/M5 * Myeloid dendritic cell leukemia CML * Philadelphia chromosome * Accelerated phase chronic myelogenous leukemia Myelomonocyte AML * M4 MD-MP * Juvenile myelomonocytic leukemia * Chronic myelomonocytic leukemia Other * Histiocytosis CFU-Baso AML * Acute basophilic CFU-Eos AML * Acute eosinophilic MP * Chronic eosinophilic leukemia/Hypereosinophilic syndrome MEP CFU-Meg MP * Essential thrombocytosis * Acute megakaryoblastic leukemia CFU-E AML * Erythroleukemia/M6 MP * Polycythemia vera MD * Refractory anemia * Refractory anemia with excess of blasts * Chromosome 5q deletion syndrome * Sideroblastic anemia * Paroxysmal nocturnal hemoglobinuria * Refractory cytopenia with multilineage dysplasia CFU-Mast Mastocytoma * Mast cell leukemia * Mast cell sarcoma * Systemic mastocytosis Mastocytosis: * Diffuse cutaneous mastocytosis * Erythrodermic mastocytosis * Adult type of generalized eruption of cutaneous mastocytosis * Urticaria pigmentosa * Mast cell sarcoma * Solitary mastocytoma Systemic mastocytosis * Xanthelasmoidal mastocytosis Multiple/unknown AML * Acute panmyelosis with myelofibrosis * Myeloid sarcoma MP * Myelofibrosis * Acute biphenotypic leukaemia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Juvenile myelomonocytic leukemia	c0023480	30,550	wikipedia	https://en.wikipedia.org/wiki/Juvenile_myelomonocytic_leukemia	2021-01-18T18:55:55	{"gard": ["9884"], "mesh": ["D015477", "D054429"], "umls": ["C0023480"], "orphanet": ["86834"], "wikidata": ["Q2578247"]}
Sclerosing lymphangitis SpecialtyDermatology Sclerosing lymphangitis, also known as lymphangiosclerosis or sclerotic lymphangitis,[1] is a skin condition characterized by a cordlike structure encircling the coronal sulcus of the penis, or running the length of the shaft, that has been attributed to trauma during vigorous sexual play.[2]:43 Nonvenereal sclerosing lymphangitis is a rare penile lesion consisting of a minimally tender, indurated cord involving the coronal sulcus and occasionally adjacent distal penile skin. The condition involves the hardening of a lymph vessel connected to a vein in the penis. It can look like a thick cord and can feel like a hardened, almost calcified or fibrous, vein. It tends to not share the common blue tint with a vein however. It can be felt as a hardened lump or "Vein" even when the penis is flaccid, and is even more prominent during an erection.This disorder is fairly common and most often occurs after vigorous sexual activity and resolves spontaneously. ## Contents * 1 Cause * 2 Management * 3 See also * 4 References ## Cause[edit] Etiology of sclerosing lymphangitis is unknown but has been postulated to be secondary to thrombosis of lymphatic vessels.[citation needed] ## Management[edit] In most cases it tends to go away if given rest and more gentle care, for example by use of lubricants. Even without rest or gentle care, in some cases it will simply disappear after a few weeks on its own. Spontaneous recovery can occur anywhere within a couple weeks to several months.[citation needed] Although it is commonly recommended the patient abstain from sexual activity during recovery, there is no evidence that this expedites resolution or that engaging in sexual activity worsens the condition.[citation needed] ## See also[edit] * Skin lesion ## References[edit] 1. ^ "Lymphangiosclerosis". Healthline. Retrieved 4 August 2018. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. This article about a disease of the genitourinary system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Sclerosing lymphangitis	c0406626	30,551	wikipedia	https://en.wikipedia.org/wiki/Sclerosing_lymphangitis	2021-01-18T19:08:07	{"umls": ["C0406626"], "wikidata": ["Q6708235"]}
## Summary ### Clinical characteristics. FMR1 disorders include fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency (FXPOI). * Fragile X syndrome occurs in individuals with an FMR1 full mutation or other loss-of-function variant and is nearly always characterized in affected males by developmental delay and intellectual disability along with a variety of behavioral issues. Autism spectrum disorder is present in 50%-70% of individuals with FXS. Affected males may have characteristic craniofacial features (which become more obvious with age) and medical problems including hypotonia, gastroesophageal reflux, strabismus, seizures, sleep disorders, joint laxity, pes planus, scoliosis, and recurrent otitis media. Adults may have mitral valve prolapse or aortic root dilatation. The physical and behavioral features seen in males with FXS have been reported in females heterozygous for the FMR1 full mutation, but with lower frequency and milder involvement. * FXTAS occurs in individuals who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor followed by cognitive impairment. Psychiatric disorders are common. Age of onset is typically between 60 and 65 years and is more common among males who are hemizygous for the premutation (40%) than among females who are heterozygous for the premutation (16%-20%). * FXPOI, defined as hypergonadotropic hypogonadism before age 40 years, has been observed in 20% of women who carry a premutation allele compared to 1% in the general population. ### Diagnosis/testing. The diagnosis of an FMR1 disorder is established through the use of specialized molecular genetic testing to detect CGG trinucleotide repeat expansion in the 5' UTR of FMR1 with abnormal gene methylation for most alleles with >200 repeats. Typically, a definite diagnosis of FXS requires the presence of a full-mutation repeat size (>200 CGG repeats) while the diagnosis of FXTAS or FXPOI is associated with a premutation-sized repeat (55-200 CGG repeats). It should be noted that typical multigene panels and comprehensive genomic testing (exome or genome sequencing) are useful only when no CGG repeat expansion is detected but FXS is still suspected. ### Management. Treatment of manifestations: * Fragile X syndrome. Supportive and symptom-based therapy for children and adults typically consisting of a dual approach of psychopharmacologic treatment of symptoms as needed in conjunction with therapeutic services, such as behavioral intervention, speech and language therapy, occupational therapy, and individualized educational support; routine treatment of medical problems. * FXTAS. Symptomatic and supportive and should be tailored to the individual. * FXPOI. Gynecologic or reproductive endocrinologic evaluation can provide appropriate treatment and counseling for reproductive considerations and hormone replacement. Agents/circumstances to avoid: * FXTAS. Typical and atypical antipsychotics with significant anti-dopaminergic effects and metoclopramide, which can exacerbate parkinsonism; anticholinergic agents, which can exacerbate cognitive complaints; excessive alcohol, which can enhance cerebellar dysfunction and postural instability; agents with known cerebellar toxicity or side effects. * FXPOI. Tobacco use as this decreases ovarian reserve and the age of onset of FXPOI. ### Genetic counseling. FMR1 disorders are inherited in an X-linked manner: * All mothers of individuals with an FMR1 full mutation (expansion >200 CGG trinucleotide repeats and abnormal methylation) are heterozygous for an FMR1 pathogenic variant. Mothers and their female relatives who are heterozygous for a premutation are at increased risk for FXTAS, FXPOI, and fragile X-associated neuropsychiatric disorders (FXAND); those with a full mutation may have findings of fragile X syndrome. All are at increased risk of having offspring with fragile X syndrome, FXTAS, FXPOI, or FXAND. * Males with premutations are at increased risk for FXTAS. Males with FXTAS will transmit their FMR1 premutation expansion to all of their daughters, who will be heterozygous for a premutation and at increased risk for FXTAS, FXPOI, and FXAND. Males with FXTAS do not transmit their FMR1 premutation to sons. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible once an expanded (or altered) FMR1 allele has been identified in a family member. ## Diagnosis ### Suggestive Findings FMR1 disorders should be considered in individuals with the following clinical and associated findings. Fragile X syndrome (FXS) * Males and females with intellectual disability or developmental delay of unknown cause * Males with unexplained autism spectrum disorder and females with unexplained autism spectrum disorder and the presence of an additional indicator: phenotype compatible with FXS; family history of X-linked neurodevelopmental disorders; or premature ovarian failure, ataxia, or tremors in close relatives Fragile X-associated tremor/ataxia syndrome (FXTAS) * Males and females who are experiencing late-onset intention tremor and cerebellar ataxia of unknown cause. Men and women with dementia may also be considered, if ataxia, parkinsonism, or tremor are also present. * Males and females with multiple system atrophy, cerebellar subtype (especially if a prolonged course) Fragile X-associated primary ovarian insufficiency (FXPOI). Females with unexplained primary ovarian insufficiency or failure (hypergonadotropic hypogonadism) before age 40 years ### Establishing the Diagnosis The diagnosis of an FMR1 disorder is established through the use of specialized molecular genetic testing. It should be noted that typical multigene panels and comprehensive genomic testing (exome or genome sequencing) are useful only when no CGG repeat expansion is detected but FXS is still suspected. FMR1 related disorders are caused by CGG trinucleotide repeat expansion in the 5' UTR of FMR1 with abnormal gene methylation for most alleles with more than 200 repeats. Typically, a definite diagnosis of FXS requires the presence of a full-mutation repeat size (>200 CGG repeats) while the diagnosis of FXTAS or FXPOI is associated with a premutation-sized repeat (55-200 CGG repeats). #### Allele Size FMR1 alleles are categorized according to the number of 5' UTR CGG trinucleotide repeats and the methylation status of the repeat region. However, the distinction between allele categories is not absolute and must be made by considering both family history and repeat instability. The size boundary between intermediate and premutation categories listed below is not precise and caution is advised. See Table 3 for a summary of the types of FMR1 alleles and clinical status of individuals with expanded alleles. Stability of alleles of fewer than 90 repeats is heavily influenced by the number of AGG interspersions within the CGG repeat sequence, both with respect to risk for size change in intermediate alleles and small premutations and expansion to a full mutation in premutation alleles larger than about 60 repeats [Nolin et al 2013, Nolin et al 2019]. This information should be utilized when appropriate for counseling families about expansion risk. See Anticipation for detailed information on factors such as AGGs that influence FMR1 CGG repeat stability. Normal alleles. Approximately 5-44 repeats * Alleles of this size have little meiotic or mitotic instability and are typically transmitted without any increase or decrease in repeat number. However, some instability in normal repeats has been reported, with alleles that contain no AGG interspersions having a greater likelihood to be unstable [Nolin et al 2019]. * The population distribution of FMR1 repeat alleles shows the highest percentage of individuals with approximately 29-31 repeats; smaller but significant percentages cluster around 20 and 40 repeats. Intermediate alleles (also termed "gray zone" or "borderline"). Approximately 45-54 repeats * Intermediate alleles do not cause FXS. However, about 14% of intermediate alleles are unstable and may expand into the premutation range when transmitted by the mother [Nolin et al 2011]. They are not known to expand to full mutations; therefore, offspring are not at increased risk for FXS. * Historically, the largest repeat included in the intermediate range has been 54; the use of 54 as the upper limit for normal alleles is a conservative estimate reflecting observations that transmission of alleles with 54 or fewer repeats from mothers to their offspring has not resulted in an affected individual to date. The conservative nature of the estimate also reflects potential imprecision (usually stated as ±2-3 repeats) in laboratory measurement of repeat number during diagnostic testing; however, to date no transmission of alleles with 55 or fewer repeats is known to have resulted in an affected individual [Nolin et al 2015, Nolin et al 2019]. Note: Clinical laboratories performing FMR1 analysis typically state their estimated precision range when measuring intermediate alleles and usually report their estimates as ±2-3 repeats. Thus, it may be prudent to consider reported test results with 55 repeats as potential premutations. If the repeat precision estimate is not on the laboratory report, the laboratory should be contacted in order to determine if a result should be considered as a potential premutation. Premutation alleles. Approximately 55-200 repeats * Alleles of this size are not associated with FXS but do convey increased risk for FXTAS and FXPOI (Table 3). Because of potential repeat instability upon transmission of premutation alleles, women with alleles in this range are considered to be at risk of having children with FXS, although this risk is heavily dependent on the number of AGG interspersions for small premutation alleles [Nolin et al 2013, Nolin et al 2019]. Note: The upper limit of the premutation range is sometimes noted as approximately 230. Both numbers (200 and 230) are estimates derived from Southern blot analysis, in which repeat size can only be roughly estimated. Full-mutation alleles. More than 200 CGG repeats, with several hundred to several thousand repeats being typical and, in most cases, associated with aberrant hypermethylation of the FMR1 promoter. Almost always, extensive somatic variation of repeat number is observed in a peripheral blood specimen of an individual with a full mutation. As a result, clinical laboratories may report this somatic variation as a range of several hundred repeats. ### Clinical Criteria The clinical criteria for diagnosis of FXTAS or FXPOI in individuals with a premutation allele are as follows. #### FXTAS Three levels are used to indicate the confidence of a diagnosis of FXTAS in individuals with an FMR1 premutation based on symptom manifestation at the time of the evaluation [Jacquemont et al 2003, Berry-Kravis et al 2007, Hagerman & Hagerman 2016, National Fragile X Foundation FXTAS Guideline]. The three diagnostic categories: * Definite. Presence of one major radiologic sign plus one major clinical sign, or presence of FXTAS inclusions (characteristic ubiquitin-positive intranuclear inclusions within the nuclei of neurons and astrocytes) * Probable. Presence of either one major radiologic sign plus one minor clinical sign, or two major clinical signs * Possible. Presence of one minor radiologic sign plus one major clinical sign Radiologic signs * Major. MRI white matter lesions in middle cerebellar peduncles (MCP sign) * Minor * MRI white matter lesions in cerebral white matter * Moderate-to-severe generalized brain atrophy * MRI white matter lesions in the splenium of the corpus callosum Clinical signs * Major * Intention tremor * Cerebellar gait ataxia * Minor * Parkinsonism * Moderate-to-severe short-term memory deficiency * Executive function deficit * Neuropathy in lower extremities Neuropathologic signs. A major criterion is FXTAS intranuclear eosinophilic inclusions that are ubiquitin positive. #### FXPOI Diagnostic criteria are based on hypergonadotropic hypogonadism in women younger than age 40 who carry a premutation allele. POI is diagnosed when a woman has (1) experienced four to six months of amenorrhea (absent menses) and (2) has two serum menopausal level FSH values obtained at least one month apart [Nelson 2009, Fink et al 2018]. See Published Guidelines / Consensus Statements. ### Targeted Analysis for Pathogenic Variants Polymerase chain reaction (PCR) is used to size the CGG trinucleotide repeat region of FMR1 with high sensitivity. Although early PCR techniques for FMR1-specific PCR were less sensitive to larger premutations and failed to amplify full mutations, PCR techniques now exist to identify virtually all sizes of FMR1 expansion mutations. Repeat-primed PCR allows detection and location of AGG interspersions. Southern blot analysis detects all FMR1 alleles including normal, larger-sized premutations, and full mutations and in addition determines methylation status of the FMR1 promoter region. Southern blot may not resolve intermediate alleles well. Abnormal hypermethylation of FMR1 is the cause of transcriptional silencing and is critical to assess for full-mutation alleles. Note: PCR with newer and more sensitive assays is now adequate for diagnosis and size determination for the premutation, as well as for identification of the full mutation. Southern blot is currently only used to determine the methylation status for the full mutation and the X-inactivation ratio for females with a premutation or full mutation. As PCR methods for determining methylation gain acceptance in diagnostic testing, the need for Southern blot analysis for determination of methylation of the full mutation and activation ratios of women may decrease [Chen et al 2010, Chen et al 2011, Nahhas et al 2012, Orpana et al 2012, Hadd et al 2016, Hayward et al 2016, Hayward et al 2017]. Methylation status of a full mutation or activation ratio in female heterozygotes can be assessed by PCR-based methods independent of measuring the number of CGG repeats [Grasso et al 2014]. ### Additional Testing Fewer than 1% of individuals with FXS have a sequence variant, a partial deletion, or a full deletion of FMR1 (reviewed in Sitzmann et al [2018]). When no CGG repeat expansion is detected but FXS is still suspected, the options are either a multigene panel or comprehensive genomic testing: * A multigene panel that includes FMR1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * Comprehensive genomic testing involves either exome sequencing or genome sequencing. If exome sequencing is not diagnostic, exome array (when clinically available) needs be considered to detect (multi)exon deletions or duplications that cannot be detected by exome sequencing. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in FMR1 Disorders View in own window Gene 1MethodPathogenic Variants Detected 2Variant Detection Frequency by Method 3 FMR1Targeted analysis for pathogenic variantsPCR. CGG expansion in FMR1 4, 5>99% Southern blot. CGG expansion in FMR1 (all repeat ranges); methylation status for full-mutation alleles and to determine X-inactivation ratio in women 4, 6 Methylation analysisMethylation of FMR1 promoter region 7100% of alleles with this modification Deletion/duplication analysis 8Large (partial- or whole-gene) FMR1 deletions/duplications<1% Sequence analysis 9FMR1 sequence variants 4, 5<1% 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. The ability of the test method used to detect a variant that is present in the indicated gene 4\. Sequence analysis, targeted analysis for pathogenic variants using PCR, and in some instances Southern blot analysis cannot detect an exon or whole-gene deletion on the X chromosome in heterozygous females. 5\. Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis. 6\. As newer and more sensitive PCR methods gain acceptance in diagnostic testing, the need for Southern blot analysis may decrease [Chen et al 2010, Chen et al 2011, Orpana et al 2012, Nahhas et al 2012, Hayward et al 2016, Hayward et al 2017]. 7\. Methylation status can be determined by either Southern blot or methylation-specific PCR; the latter may offer a more rapid test turnaround time [Hayward et al 2017]. 8\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 9\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. Note: (1) If the clinical phenotype is strongly suggestive of FXS and molecular genetic testing of DNA extracted from leukocytes is normal, molecular genetic testing of a second tissue type (e.g., skin fibroblasts) should be considered as mosaicism has been reported [MacKenzie et al 2006]. (2) For intermediate and small premutation alleles in heterozygous females, AGG trinucleotide genotyping may be useful to assess risk of allele expansion upon transmission. See Anticipation. ## Clinical Characteristics ### Clinical Description #### Males with Fragile X Syndrome (Full-Mutation Alleles) The phenotypic features of males with fragile X syndrome (FXS) vary in relation to puberty [Kidd et al 2014]. Prepubertal features * Medical problems in infancy and childhood include hypotonia, gastroesophageal reflux, strabismus, seizures, sleep disorders, joint laxity, pes planus, scoliosis, and recurrent otitis media. Excessive softness and smoothness of the skin also have been noted. * Normal growth is typical but large occipitofrontal head circumference (>50th percentile) is often seen. * Delayed attainment of motor milestones and speech is apparent in the first several years of life. Developmental milestones (usual age of attainment in boys): * Sit alone (10 months) * Walk (20.6 months) * First clear words (20 months) * Intellectual disability. The mean IQ has been reported as 40-45 with a range from less than 10 to within the normal range [Sansone et al 2014]. * Behavior is a prominent issue in males and some females with FXS of all ages. Behavior issues can include attention-deficit/hyperactivity disorder (ADHD) symptoms: hyperactivity, problems with impulse control, distractibility stereotypies such as hand flapping, tactile defensiveness, anxiety, shyness, poor eye contact (gaze aversion), perseverative speech, temper tantrums, irritability, aggression, and self-injurious behavior such as hand biting. The behaviors tend to evolve over time, becoming more obvious, with reduced responsiveness and activity sometimes seen in children before age two years, and then progressively increasing hyperactivity and ADHD symptoms with anxiety and irritable behaviors emerging (to varying degrees) during childhood [Berry-Kravis et al 2012]. * Autism spectrum disorder (ASD) is present in 50%-70% of individuals with FXS and when present, tends to be associated with more severe behavioral issues and an increased rate of seizures [Kidd et al 2019]. * Physical features involving the craniofacies (long face, prominent forehead, large ears, and prominent jaw) not readily recognizable in the preschool-age child become more obvious with age. Only a subset of affected individuals have typical physical features of FXS and presence of these is not reliable for diagnosis. Postpubertal features * Medical problems including mitral valve prolapse and aortic root dilatation have been noted, most commonly in adults with FXS. * Anxiety and irritable/aggressive behavior may increase during or after puberty. Anxiety, including social phobia and specific phobias, anticipatory anxiety, performance anxiety, and separation anxiety, as well as generalized anxiety, is very common in FXS and often disabling, having been reported by caregivers as the most disabling problem for individuals with FXS [Weber et al 2019]. * Macroorchidism may be obvious earlier in childhood but is identified in essentially all males after completion of puberty. #### Females with FXS (Heterozygous for Full-Mutation Alleles) The physical and behavioral features seen in males with FXS have been reported in females heterozygous for the full mutation, but with lower frequency and milder involvement [Bartholomay et al 2019]. #### Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) FXTAS is characterized by late-onset progressive cerebellar ataxia and intention tremor in persons who have an FMR1 premutation [Hagerman & Hagerman 2016]. Onset is typically between ages 60 and 65 years. The age of onset and progression of symptoms of FXTAS vary significantly among individuals. Both age of onset and disease severity are related to repeat length, sex, and other features. The first sign of FXTAS is typically tremor followed by ataxia and cognitive impairment [Bourgeois 2016, Hall & Berry-Kravis 2018]. * Ataxia can lead to gait and postural instability with most individuals needing a walking aid within ten years of diagnosis. * Cognitive impairment typically starts with executive function impairment and expands to other domains such as working memory and information processing speed. Almost half of individuals with FXTAS meet criteria for dementia. Other findings include short-term memory loss, parkinsonism, peripheral neuropathy and neuropathic pain, lower-limb proximal muscle weakness, and autonomic dysfunction [Hagerman & Hagerman 2016, Hall et al 2016]. Psychiatric disorders are common and include anxiety, irritability, agitation, hostility, obsessive-compulsive disorder, apathy, and depression [Seritan et al 2013]. Both males and females with a premutation are at risk for FXTAS. Increasing premutation repeat lengths correlate with increasing likelihood of developing FXTAS [Tassone et al 2007, Leehey et al 2008]. The penetrance in individuals older than age 50 years is lower in females (16.5%) than in males (45.5%) [Rodriguez-Revenga et al 2009]. Males. The prevalence of FXTAS is estimated at approximately 40% overall for males with a premutation who are older than age 50 years [Hagerman & Hagerman 2016]. Penetrance in males is related to age (see Table 2) and repeat length. ### Table 2. Risk for FXTAS by Age in Males with an FMR1 Premutation View in own window Age in YearsRisk 50-5917% 60-6938% 70-7947% ≥8075% Adapted from Grigsby et al [2005] Females. While FXTAS is more difficult to ascertain in females because of milder clinical presentation, prevalence estimates range from approximately 16% to 20% of female premutation heterozygotes [Hagerman & Hagerman 2016]. #### Fragile X-Associated Primary Ovarian Insufficiency (FXPOI) FXPOI, defined as hypergonadotropic hypogonadism before age 40 years, has been observed in 20% of women who carry a premutation allele compared to 1% in the general population [Sherman 2000]. * Ovarian insufficiency has occurred as early as age 11 years and can present with primary amenorrhea and delayed puberty. * Women with FXPOI have high rates of infertility and menopausal-type symptoms, including vasomotor symptoms, mood changes, and vaginal dryness. * In contrast to menopause, ovarian function in women with POI is more erratic and unpredictable, so that some women continue to have irregular ovulation and menses for years after diagnosis. Some women are completely amenorrheic. * The diagnosis of POI does not eliminate the possibility of subsequent conception. It is estimated that up to 12.6% of women conceive after a diagnosis of FXPOI [Hipp et al 2016]. See Fink et al [2018] for a review. * Women with FXPOI are at risk of long-term health sequelae from a hypoestrogenic environment. These include osteoporosis and cardiovascular disease. * Women with POI (including those with FXPOI) are at increased risk of developing thyroid disease. The earlier findings that alleles in the high normal and intermediate range conferred an increased risk for FXPOI [Bretherick et al 2005, Bodega et al 2006] have not been supported by more recent robust studies [Voorhuis et al 2014, Schufreider et al 2015]. Women with full-mutation alleles are not at increased risk for FXPOI, nor do they have signs of diminished ovarian reserve [Avraham et al 2017]. #### Other Fragile X-Associated Phenotypes In addition to FXTAS and FXPOI, the following have been reported in the literature (see Wheeler et al [2017] for a review): * Cognitive and behavioral challenges. Preliminary studies of the correlation of FMR1 allele size variations in the normal and premutation range suggested a possible relationship to mild intellectual disability in females [Allen et al 2005] and males [Loat et al 2006, Hagerman et al 2009]. Evidence also suggested an increased risk for autism spectrum disorder [Farzin et al 2006, Hagerman et al 2009] and neurodevelopmental diagnoses in individuals with a premutation [Bailey et al 2008, Renda et al 2014]. However, findings across studies have been contradictory, with some studies biased by assessment of individuals who had been clinically referred. Thus, additional studies are needed. * Neuropsychiatric issues. Increased rates of anxiety, depression, and ADHD have been reported. Social phobia and social anxiety have also been reported. However, many studies on mental health outcomes are limited to women with a premutation who are mothers of children with FXS; thus, findings are likely confounded by the impact of elevated maternal stress on mental health [Wheeler et al 2017], though some studies have indicated that the premutation confers a heightened susceptibility to stress and dysregulation of the hypothalamic-pituitary axis [Hartley et al 2012, Seltzer et al 2012]. The term "fragile X-associated neuropsychiatric disorders" (FXAND) has been proposed to promote research into fully characterizing neuropsychiatric outcomes associated with the premutation allele [Hagerman et al 2018]. * Medical findings. Some studies have reported elevated rates of hypertension, hypothyroidism, fibromyalgia, migraines, insomnia, sleep apnea, restless leg syndrome, central pain sensitivity syndrome, and autoimmune disorders in individuals with a premutation compared to those without a premutation [Hagerman & Hagerman 2016]. However, these findings differ by investigator (reviewed in Wheeler et al [2014]). Unfortunately, most studies have been focused on women with a premutation and are based on questionnaires and chart reviews rather than objective medical examinations, which has created inconsistencies between research groups. Thus, the generalizability of these findings is unclear. Elevated rates of neurologic findings, such as tremor and ataxia, have been reported in individuals with premutations who do not meet diagnostic criteria of FXTAS. A study of 110 daughters of men with FXTAS demonstrated an increased incidence of neurologic and psychiatric symptoms compared to controls, providing more evidence for such an association [Chonchaiya et al 2010]. ### Genotype-Phenotype Correlations The phenotype of males with an FMR1 pathogenic variant depends almost entirely on the nature of the variant; the phenotype of females with an FMR1 pathogenic variant depends on both the nature of the FMR1 variant and random X-chromosome inactivation (see Table 3). ### Table 3. Types of FMR1 Repeat Expansion Pathogenic Variants View in own window Variant Type# of CGG Trinucleotide RepeatsMethylation Status of FMR1Clinical Status MaleFemale Premutation~55-200UnmethylatedAt risk for FXTAS 1 * At risk for FXPOI & FXTAS * Potential ↑ risk of other fragile X-assoc disorders 1 Full mutation>200Completely methylated100% have ID.~50% w/ID, ~50% normal intellect Repeat size mosaicismVaries between premutation & full mutation in different cell linesPartial: unmethylated in premutation cell line; methylated in full-mutation cell lineNearly 100% have ID; may be higher functioning 2 than males w/full mutation.Highly variable: ranges from normal intellect to affected Methylation mosaicism>200Partial: mixture of methylated & unmethylated cell lines Unmethylated full mutation>200Unmethylated * ID, if present, is typically high functioning. * May have anxiety &/or behavioral issues even w/out ID ID = intellectual disability 1\. Both males and females with premutations have been reported to have slightly elevated rates of some manifestations of fragile X syndrome, such as facial features, behavioral problems, learning disabilities, ADHD, and anxiety [Riddle et al 1998, Bourgeois et al 2009, Hunter et al 2009, Chonchaiya et al 2010]. Some studies also indicate an increased rate of additional outcomes, such as depression, pain disorders, autoimmune disorders, and other health outcomes [Wheeler et al 2017, Hagerman et al 2018]. 2\. FMR1 pathogenic variants are complex alterations involving nonclassic gene-inactivating variants (trinucleotide repeat expansion) and abnormal gene methylation. This complexity at the gene level affects production of the FMR1 protein (FMRP) and may result in an atypical presentation in which affected individuals occasionally have an IQ above 70, the traditional demarcation denoting intellectual disability (previously referred to as mental retardation). Premutation. Males and females who have an FMR1 premutation have normal intellect and appearance. As noted in Table 3, footnote 1, a subset of individuals with a premutation may have subtle intellectual or behavioral symptoms including learning difficulties or social anxiety. It is currently unclear whether these reported symptoms result from the premutation or are the product of an ascertainment bias toward identification of individuals with premutations who manifest intellectual or behavioral symptoms. The symptoms are usually not socially debilitating. * For FXTAS, repeat size is correlated with severity: higher repeat size is associated with greater motor impairment (tremor, ataxia, and parkinsonism), more severe peripheral neuropathy, higher number of intranuclear inclusions in the brain, MRI abnormalities (reduced cerebellar volume and increased ventricular volume and whole-brain white matter hyperintensity), and earlier age of onset [Hall & Berry-Kravis 2018]. * It is estimated that 21% of women who carry a premutation develop FXPOI [Sherman 2005]. The association between repeat size of the premutation allele and FXPOI is nonlinear; women with 80-99 repeats are at greatest risk for FXPOI [Sherman 2005] (see Table 4). * Additional studies indicate other vulnerabilities for the mid-repeat ranges of the premutation in women, such as an increased risk of psychological symptoms [Loesch et al 2015] and vulnerability to stress [Seltzer et al 2012]. It is unclear whether these relationships are due to the premutation itself or to the higher level of hormonal dysfunction in FXPOI seen in the mid-repeat ranges. ### Table 4. Odds Ratios for FXPOI by Premutation Size View in own window Premutation Size in CGG RepeatsOdds Ratio for FXPOI 59-796.9 80-9925.1 >10016.4 Sherman [2005] Full mutation. Males who have a full FMR1 mutation generally have moderate-to-severe intellectual disability and may or may not have a distinctive appearance. Approximately 50% of females who have a full FMR1 mutation are intellectually disabled; however, they are usually less severely affected than males with a full mutation. Conversely, approximately 50% of females who are heterozygous for the full mutation are intellectually normal. However, many of those with IQ in the normal range will have substantial issues with learning disability, ADHD, anxiety, and/or social-emotional dysfunction. The variability among females is believed to result from the ratio in the brain of active X chromosomes with the FMR1 full mutation to inactive X chromosomes with the normal FMR1 allele. Mosaicism. Mosaicism of FMR1 variants is common. Such mosaicism may be (1) "repeat size mosaicism," in which both full mutations and premutations are present (also termed "full-mutation/premutation mosaicism"), or (2) methylation mosaicism, in which full mutations have varying degrees of methylation. Although some data suggest that individuals with repeat size mosaicism or methylation mosaicism perform at a higher intellectual level than those with completely methylated full mutations, such individuals are usually intellectually disabled. Rarely, individuals with methylation mosaicism or completely unmethylated full mutations and normal intellect have been reported. The milder phenotype appears to be related to FMR1 protein (FMRP) production arising from transcription of unmethylated alleles [Tassone et al 1999]. Presumably, these individuals produce at least some FMRP because FMR1 is unmethylated. The existence of these exceptional individuals suggests that repeat expansion and methylation of the gene are not absolutely coupled. Han et al [2006] reported a male with complex FMR1 mosaicism (full mutation, premutation, and deletion) with only learning disability, which raises issues concerning gene and protein expression in FMR1-related phenotypes. ### Anticipation Fragile X syndrome (FXS) is a trinucleotide repeat disorder that may demonstrate anticipation in some families. Typically, anticipation occurs when less severely affected individuals with a premutation or mosaic mutation transmit unstable FMR1 alleles to their offspring (e.g., transmission from a grandfather who carries a premutation to his daughter, whose premutation expands into a full mutation when she transmits it to her son, who has intellectual disability as a result). However, the anticipation found in families with members affected with FXS is not classic, as is that found in, for example, myotonic dystrophy type 1, where the disease itself becomes worse and with earlier age at onset with advancing generations. Many families transmit premutation FMR1 alleles for generations with little or no presentation of clinical symptoms until a full mutation is produced, resulting in an individual with a diagnosis of FXS. The form of anticipation in FXS is increasing numbers of individuals with FXS with advancing generations. AGG trinucleotide repeat genotyping. In stable, normal alleles, the CGG region is interrupted by an AGG triplet at every nine to ten CGG repeats. AGG genotyping may be performed to determine the number and location of AGG trinucleotide interruptions within the CGG repeat. The number and position of AGG trinucleotide repeats are known to be important in the overall stability of the CGG repeat sequence. Recent results have linked the presence of an AGG interruption with a reduced risk of transmission to a full mutation in CGG repeat ranges below 100 [Yrigollen et al 2012, Yrigollen et al 2014, Nolin et al 2015]. Direct testing for the AGG triplets is available clinically, though it is not routinely performed, and its clinical usefulness is not yet fully understood. It may help predict risk of expansions from premutations of fewer than 100 repeats [Yrigollen et al 2012, Nolin et al 2015]. The impact of AGG interruptions on clinical outcomes in individuals with a premutation is unknown. Conflicting results regarding AGG interruptions and FXPOI have been published [Allen et al 2018, Lekovich et al 2018]. ### Nomenclature Fragile X syndrome has also been referred to as FXS, fragile X mental retardation, marker X syndrome, and Martin-Bell syndrome. FMR1 primary ovarian insufficiency has also been referred to as FMR1-related premature ovarian failure. ### Prevalence Fragile X syndrome. Prevalence estimates of males with fragile X syndrome (FXS) have been revised downward since the isolation of FMR1 in 1991. Original estimates of 80:100,000 males were based on detection of fragile sites on cytogenetic studies and resulted in an overestimate because fragile sites other than the one associated with FMR1 (FRAXA) were detected and included in the estimate. More recent studies using molecular genetic testing of FMR1 have estimated a prevalence of 16 to 25 per 100,000 males with FXS (using intellectual disability as the hallmark clinical finding) [de Vries et al 1997]. In an analysis of 36,124 newborn males, Coffee et al [2009] determined that the incidence of a full mutation (and hence, FXS) was approximately 19:100,000 males. A meta-analysis estimated prevalence of the full mutation as 14:100,000 [Hunter et al 2014]. The prevalence of females with FXS is presumed to be approximately one half the male prevalence due to reduced penetrance. FXS is the most common known single-gene cause of autism spectrum disorder (ASD) and accounts for about 2%-3% of all ASD cases [Kaufmann et al 2017]. FMR1 premutation. A meta-analysis estimated the prevalence of the premutation allele at 117:100,0000 males and 344:100,000 females [Hunter et al 2014]. However, a study of a population-based sample of 19,996 males and females resulted in higher prevalence estimates for the premutation: 345:100,000 males and 677:100,000 females [Maenner et al 2013]. FXTAS. After accounting for the prevalence of the premutation allele among males, the frequency of up to 70 repeat alleles, and penetrance of FXTAS in males with larger premutation alleles (33%), the prevalence of FXTAS in males in the US has been estimated at 1:4,848 [Hantash et al 2011]. The prevalence in women is more difficult to calculate given the variable presentation. An estimated 2%-4% of men with adult-onset cerebellar ataxia who represent simplex cases (i.e., a single occurrence in a family) have a premutation in FMR1 [Brussino et al 2005, Cellini et al 2006]. There have been no similar studies of women with adult-onset cerebellar ataxia. FXPOI. The prevalence of FXPOI in women in the US has been estimated at 1:3,560 based on the prevalence of the premutation allele and penetrance of FXPOI in women with the premutation (20%) [Hantash et al 2011]. The FMR1 premutation accounts for approximately 3.2% of isolated cases of POI and 11% of familial cases (reviewed in Fink et al [2018]). ## Differential Diagnosis Developmental delay / intellectual disability (DD/ID). The signs of fragile X syndrome (FXS) in early childhood are nonspecific, with DD being an almost universal manifestation among affected individuals. Any child (male or female) with delay of speech, language, or motor development of unknown etiology should be considered for fragile X testing, especially in the presence of a family history of ID and a consistent physical and behavioral phenotype, and the absence of structural abnormalities of the brain or other birth defects [Curry et al 1997, Moeschler & Shevell 2006]. When fragile X molecular genetic testing is used regularly in this large and loosely defined group of unselected males with ID, the yield of positive test results is relatively low (~3%-6%) [Curry et al 1997, Shevell et al 2003]. In a more recent study, Rauch et al [2006] found the yield to be 1.2%. Because chromosome abnormalities and copy number variants have been identified as frequently or more frequently than FMR1 pathogenic variants in individuals with DD or ID who are referred for fragile X testing, microarray testing should be performed as a part of the laboratory evaluation [Manning & Hudgins 2010, Miller et al 2010]. Conditions to be considered in the differential diagnosis of FXS include those summarized in Table 5. ### Table 5. Disorders to Consider in the Differential Diagnosis of Fragile X Syndrome View in own window DisorderGene / Genetic MechanismMOIClinical Features of Differential Diagnosis Disorder Overlapping w/FXSDistinguishing from FXS Sotos syndromeNSD1AD * Typical facial appearance * Mild-to-severe learning disability * Behavior problems * Seizures * Overgrowth * Congenital cardiac anomalies * Neonatal jaundice * Renal anomalies * Scoliosis Prader-Willi syndrome (PWS)See footnote 1See footnote 2 * A small subset of those w/FXS have the hyperphagia & obesity characteristic of PWS 3 * DD & cognitive impairment * Temper tantrums, stubbornness, manipulative behavior, & obsessive-compulsive traits * Hypogonadism (genital hypoplasia, incomplete puberty &, in most, infertility) * Characteristic PWS facial appearance * Short stature Autism spectrum disorderSee footnote 4AR AD XL MuAutistic-like behaviorAbsence of cognitive & physical features of FXS ADHDSee footnote 5AD MuHyperactivityAbsence of cognitive & physical features of FXS Fragile XE syndrome (FRAXE) (OMIM 309548)AFF2 6 (FMR2)XLMild ID (not as severe as is typically seen in FXS)Absence of physical features characteristic of FXS AD = autosomal dominant; ADHD = attention-deficit/hyperactivity disorder; AR = autosomal recessive; DD = developmental delay; FXS = fragile X syndrome; MOI = mode of inheritance; Mu = multifactorial; XL = X-linked 1\. PWS is caused by an absence of expression of imprinted genes in the paternally derived PWS/Angelman syndrome (AS) region (i.e., 15q11.2-q13) of chromosome 15 by one of several genetic mechanisms (paternal deletion, maternal uniparental disomy 15, and rarely an imprinting defect). 2\. The risk to the sibs of an affected child of having PWS depends on the genetic mechanism that resulted in the absence of expression of the paternally contributed 15q11.2-q13 region. 3\. PWS is characterized by severe infantile hypotonia and feeding difficulties, followed by early-childhood onset of excessive eating and development of morbid obesity unless controlled. 4\. See OMIM PS209850 for a list of genes associated with this phenotype in OMIM. 5\. See OMIM 143465 for discussion of multiple loci associated with susceptibility to ADHD. 6\. FRAXA and FRAXE are distinct fragile sites, albeit in close proximity on the X chromosome. The genes spanning the two fragile sites are designated FMR1 (FRAXA) and AFF2 (FRAXE). However, the genes do not have any detectable similarity at the DNA level and the associated clinical entities are discrete. Adult-onset neurologic disorders. The differential diagnosis for FXTAS is broad. One group of 56 individuals had 98 different diagnoses prior to the diagnosis of FXTAS. Most of these were in the following categories: parkinsonism, tremor, ataxia, dementia, autonomic dysfunction, and stroke [Biancalana et al 2005, Hall et al 2005]. Neuronal intranuclear inclusion disease is associated with a CGG repeat in NOTCH2NLC and is similar in morphology and clinical presentation to FXTAS [Sone et al 2016, Ishiura et al 2019, Sone et al 2019, Tian et al 2019]. See also Hereditary Ataxia Overview. Premature ovarian failure. Differential diagnosis for irregular menstrual cycles beyond primary ovarian insufficiency (POI) can include polycystic ovary syndrome, thyroid disorders, and high prolactin. Once POI is diagnosed, there are other causes beyond the FMR1 premutation to consider including Turner syndrome, autoimmune disorders, and past chemotherapy treatment. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with an FMR1 disorder, the evaluations summarized in phenotype-specific Tables 6, 7, and 8 (if not performed as part of the evaluation that led to diagnosis) are recommended. For all phenotypes, consultation with a clinical geneticist and/or genetic counselor is recommended. ### Table 6. Fragile X Syndrome: Recommended Evaluations Following Initial Diagnosis View in own window System/ConcernEvaluationComment DevelopmentComplete developmental & educational assessments for educational planning * Incl motor, adaptive, cognitive, & speech/language evaluation * Evaluation for early intervention / special education Occupational therapy evaluationEvaluate fine motor skills, motor planning, sensory issues, self-regulation skills, adaptive functioning, & daily life skills. Psychiatric/ BehavioralComprehensive behavioral & neuropsychiatric evaluationEvaluate for concentration/attention problems, anxiety, obsessive-compulsive disorder, aggression, depression, &/or traits suggestive of autism spectrum disorder. MusculoskeletalOrthopedics / physical medicine & rehabilitation / physical therapy evaluationEvaluate for joint hyperextensibility, pes planus, scoliosis, & hypotonia. NeurologicNeurology evaluation if history of spells that may represent seizuresEvaluate for seizures. Gastrointestinal/ FeedingGastroenterology / nutrition / feeding team evaluation if issues are presentEvaluate for infant feeding issues incl attention to possible gastroesophageal reflux. EyesOphthalmologic evaluationTo assess for strabismus Ears/HearingOtolaryngology/audiology evaluationAssess for evidence of recurrent otitis media & associated hearing loss. CardiacBaseline evaluation w/cardiologistIncl echocardiogram for mitral valve prolapse & aortic root dilatation SleepSleep study if sleep issues are presentEvaluate for sleep apnea. ### Table 7. Fragile X-Associated Tremor/Ataxia Syndrome(FXTAS): Recommended Evaluations Following Initial Diagnosis View in own window System/ConcernEvaluationComment NeurologicNeurologic evaluation w/movement disorder specialist MotorPhysical therapyPlan should be to maintain gait & assist w/optimal support equipment, if needed. Fine motorOccupational therapyManage tremor, work on assisted daily living, & obtain adaptive devices, if needed. Psychiatric/ BehavioralNeuropsychiatric evaluationIdentify & treat any comorbid psychiatric conditions. ### Table 8. FMR1 Primary Ovarian Insufficiency (FXPOI): Recommended Evaluations Following Initial Diagnosis View in own window System/ConcernEvaluationComment GenitourinaryGynecologic evaluationAssess ovarian reserve hormonal markers & perform transvaginal ultrasound. PsychiatricPsychological referralEvaluate for anxiety & depression. SkeletalDEXA scanEvaluate for low bone mineral density. EndocrineThyroid testingEvaluate for hypothyroidism. DEXA = dual x-ray absorptiometry ### Treatment of Manifestations – FXS No specific treatment is available. Supportive and symptom-based therapy for children and adults with fragile X syndrome (FXS) is currently provided by the Fragile X Clinical and Research Consortium (FXCRC). The National Fragile X Foundation has established and collaborates with the FXCRC, which currently consists of 32 clinics that specialize in FXS, performing evaluations and providing recommendations to local practitioners on management of a child or adult with FXS. The providers at the FXCRC clinics have generated and continue to update FXS treatment guidelines and recommendations (see fragilex.org). Treatment is typically a dual approach: psychopharmacologic treatment of symptoms as needed in conjunction with therapeutic services, such as behavioral intervention, speech and language therapy, occupational therapy, and individualized educational support. Medications used to treat symptoms in FXS are often the same medications used in the general population. However, individuals with FXS are more sensitive to the adverse effects of psychotropic medications. Thus, these medications should start at low doses and gradually increase to the optimal dosage to avoid adverse effects. Early educational intervention, special education, and vocational training should be aimed specifically at the known impediments to learning. Parents and teachers of children with FXS have recognized the need for individual attention, small class size, and the avoidance of sudden change. More specific guidelines are available through education resources (see Resources). See also Developmental Delay / Intellectual Disability Management Issues. Routine medical management of strabismus, otitis media, gastroesophageal reflux, cardiac issues, musculoskeletal concerns, and seizures is appropriate. #### Developmental Delay / Intellectual Disability (DD/ID) Management Issues The following information represents typical management recommendations for individuals with DD/ID in the United States; standard recommendations may vary from country to country. In terms of specific elements to consider in developmental and educational evaluations of individuals with FXS, expert consensus documents written by members of the FXCRC provide general guidelines as well as specific recommendations at each age level from preschool to high school and transition programs. These are posted on the National Fragile X Foundation website. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states and provides in-home services to target individual therapy needs. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life. Some issues to consider: * Individualized education plan (IEP) services: * An IEP provides specially designed instruction and related services for those who qualify. * IEP services will be reviewed annually to determine whether any changes are needed. * As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate. * Vision and hearing consultants should be a part of the child's IEP team to support access to academic material. * PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. * As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21. * A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text. * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. #### Motor Dysfunction Gross motor dysfunction * Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation). * Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers). * For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox®, anti-parkinsonian medications, or orthopedic procedures. Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing. Oral motor dysfunction should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the individual is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary. Feeding therapy can be helpful to improve coordination or sensory-related feeding issues. A nutritionist or dietician may be helpful in addressing issues such a picky eating and weight concerns. Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) if speech is very delayed. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech and in many cases, can improve it. #### Social/Behavioral Concerns Behavior challenges. Management of behavior can involve a multidisciplinary clinical team that includes a psychologist, a clinician to prescribe and manage medication treatment (psychiatrist, neurologist, or developmental pediatrician), occupational therapist, speech language therapist, and behavioral analyst. A functional behavioral assessment (FBA) may be helpful. Children with FXS should be evaluated for autism spectrum disorder (ASD). If they meet clinical criteria for ASD, children may qualify for and benefit from interventions used in treatment of ASD, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and is typically performed one on one with a board-certified behavior analyst. Hyperarousal. An occupational therapist can be helpful to guide the implementation of accommodations to avoid overstimulation as well as provide self-regulation skills to manage hyperarousal in individuals with FXS. Sensory issues. An occupational therapist can be helpful to identify interventions for sensory issues, which may include desensitization or accommodations. ADHD. Medications may include psychostimulants (such as methylphenidate- or dextroamphetamine-based medications), atomoxetine (a selective norepinephrine reuptake inhibitor), alpha-agonists, and alternative pharmacologic treatments (folic or folinic acid, L-acetylcarnitine). Medications can be used in conjunction with behavioral therapy and accommodations to avoid distractions. Aggression and/or self-injurious behavior. Medications can include selective serotonin reuptake inhibitors (SSRIs) if aggression and self-injury are due to anxiety, and antipsychotic medications (risperidone and aripiprazole) if behaviors are severe. Aripriprazole has also been shown to be effective in FXS [Erickson et al 2011, Berry-Kravis et al 2012]. Therapy could also include the recognition of triggers and accommodations to avoid them. In children, a crisis intervention plan can be part of an IEP. For adults, a plan could be applied in the home, work, or community setting. Irritability. Medication can include SSRIs (if irritability is due to anxiety or perseveration) or antipsychotics such as aripiprazole or risperidone. Anxiety. Medications can include SSRIs or other medications used to treat anxiety in the general population. Medication should be used in conjunction with behavioral therapy, such as recognition and avoidance of triggers, development of self-regulation and coping skills, accommodations, and cognitive behavioral therapy. Sleep problems. Management of sleep problems can include behavioral approaches such as the development of a sleep schedule, bedtime routine, and calming strategies. If needed, medication can include melatonin, clonidine, guanfacine, trazodone, and quetiapine. ### Treatment of Manifestations – FXTAS and FXPOI #### FXTAS No specific treatment is available. Treatment of FXTAS is currently symptomatic and supportive and should be tailored to the individual. Current recommendations are based on anecdotal evidence in individuals with FXTAS and evidence from disorders that are similar to FXTAS. Treatment should be multidisciplinary and include medications; specialty care in neurology and psychiatry; and therapy such as psychological counseling, speech therapy, occupational therapy, physical therapy, and gait training. ### Table 9. Treatment of Manifestations in Individuals with FXTAS View in own window Manifestation/ ConcernTreatmentConsiderations/Other TremorPrimidone, β-blockers, or levotriacetam Deep brain stimulation may be considered for individuals w/debilitating tremor w/little ataxia or white matter disease.Has been shown to improve tremor but worsen ataxia & speech Ataxia / Cerebellar dysfunctionMedications incl amantadine, buspirone, varenicline, riluzole, or ampyra can be considered.No evidence for efficacy in FXTAS Neuropathic painGabapentin, pregabalin, duloxetine, or topical lidocaine patchesAvoid opioids. Cognitive declineSupportive treatment onlyEvaluate & treat for clinical conditions assoc w/cognitive decline that may compound the cognitive decline in FXTAS: vitamin deficiencies (e.g., vitamin D, folate, B12 deficiencies), thyroid deficiency, hypertension, sleep apnea, & psychiatric problems. Depression/ AnxietyPsychiatric referral SSRIs or selective serotonin-noradrenaline reuptake inhibitorsIndividuals should be monitored for balance issues. #### FXPO No specific treatment is available. Gynecologic or reproductive endocrinologic evaluation can provide appropriate treatment and counseling for reproductive considerations and hormone replacement. ### Table 10. Treatment of Manifestations in Individuals with FXPOI View in own window Manifestation/ConcernTreatmentConsiderations/Other InfertilityReferral to gynecologist or reproductive endocrinologistDiscuss contraception & fertility treatment options incl spontaneous conception, donor oocyte, & donor embryo in vitro fertilization. Ovarian insufficiencyHormone replacementDue to risk of low bone mineral density & osteoporosis Depression/AnxietyReferral to psychologist Reproductive considerations. Some women can have sporadic ovulation, which carries an associated chance (or risk) of spontaneous conception. There is currently no fertility treatment available to increase these spontaneous conception rates. Preliminary studies, however, indicate that ethinyl estradiol may be helpful [Check et al 2004,Tartagni et al 2007]. * Women who are not preventing pregnancy should be referred for genetic counseling to discuss the risks of transmission of the premutation or full mutation to a child. * If women do not wish to conceive, reliable contraception is necessary. This includes long-acting contraceptives (e.g., intrauterine device or implant), tubal ligation, or vasectomy. Combined contraceptives (e.g., oral contraceptives, vaginal ring) may have a higher failure rate. * For women who desire fertility treatment to increase the chance of conception, both donor oocyte and donor embryo in vitro fertilization (IVF) are reasonable options. IVF in women with POI using autologous oocytes has very low success rates. Hormone replacement therapy (HRT). At the time of diagnosis, women with FXPOI are recommended to start HRT and continue until the median age of menopause to decrease development of low bone mineral density / osteoporosis, menopausal symptoms, and earlier cardiovascular disease [North American Menopause Society 2012]. * HRT can reverse the negative effects of a hypoestrogenic environment on bone mineral density. It can be administered through many routes, but transdermal estradiol with cyclic progesterone (or a progestin-releasing intrauterine device) mimics physiologic hormone levels. * There is evidence from smaller trials that this physiologic replacement is superior to combined contraception for bone mineral density [Crofton et al 2010, Cartwright et al 2016]. In addition, a transdermal route minimizes the associated risk for thromboembolism. Women should maintain adequate calcium and vitamin D intake, either through food or sunlight, respectively, or via supplements. Weight-bearing exercises are also recommended. Psychological concerns. The diagnosis of POI and its fertility implications in combination with its associated menopausal symptoms can be very difficult. In addition, women with FXPOI have higher rates of anxiety and depression. Referral for psychological support may be helpful. ### Surveillance ### Table 11. Recommended Surveillance for Individuals with Fragile X Syndrome View in own window System/ConcernEvaluationFrequency EyesComprehensive ophthalmologic exam by age 4 yrs to evaluate for strabismus & emergence of farsightedness2-yr follow up EarsVisualize tympanic membranes.Each visit DentalDental examAnnually CardiovascularChildren: assess for murmur or click; if present, refer to cardiologist.Each visit Adults: clinical exam, ECG, & echocardiogram; refer to cardiologist if needed (e.g., if murmur is heard).Annually RespiratoryAssess for signs of obstructive sleep apnea & perform sleep study if needed.Each visit GastrointestinalAssess for symptoms of gastroesophageal reflux disease; refer to GI specialist if needed.Each visit MusculoskeletalChildren: physical exam at birth; refer to orthopedics, physiotherapy, & orthotics if needed.Every 4 mos Adults: physical exam; refer to orthopedics, physiotherapy if needed.Each visit NeurologicChildren: assess history for signs of seizures; refer for EEG & neurology consult if needed.Each visit Adults: assess for atypical seizures if suspicious symptoms exist or intellectual function decreases; refer for EEG & neurology consult if needed.Each visit PsychiatricAdults: assess for anxiety, depression, & mood lability. Consider a serotonin agent for severe symptoms.Each visit ### Table 12. Recommended Surveillance for Individuals with FXTAS View in own window System/ConcernEvaluationFrequency CardiovascularAge-appropriate blood pressure & cholesterol monitoringOngoing aggressive management of CV risk factors recommended, given diffuse white matter injuries in FXTAS. CognitionMOCA survey 1Annual Psychiatric featuresBeck Depression Inventory or similarAnnual CV = cardiovascular 1\. Montreal Cognitive Assessment (MOCA) survey is a screening instrument for mild cognitive impairment. ### Table 13. Recommended Surveillance for Individuals with FXPOI View in own window System/ConcernEvaluationFrequency GenitourinaryReferral to gynecologist or reproductive endocrinologist for discussion of initiating/continuing HRT & fertility optionsAnnually SkeletalDEXA scan (only if history of low bone mineral density on initial evaluation &/or not taking adequate HRT)Every 2 yrs PsychiatricReferral to psychologist as needed DEXA = dual x-ray absorptiometry ### Agents/Circumstances to Avoid FXTAS. Affected individuals should avoid the following: * Typical and atypical antipsychotics with significant anti-dopaminergic effects, which can exacerbate parkinsonism * Metoclopramide, which can exacerbate parkinsonism * Anticholinergic agents, which can exacerbate cognitive complaints * Excessive alcohol, which can increase cerebellar dysfunction and postural instability * Agents with known cerebellar toxicity or side effects (use with caution) FXPOI. Affected individuals should avoid tobacco products. Tobacco use decreases ovarian reserve and the age of onset of FXPOI. Women who are smokers have, on average, POI onset five years earlier than nonsmokers [Allen et al 2007]. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Women with FXPOI who conceive have not been reported to have more pregnancy-related complications [Hipp et al 2016]. If donor oocyte in vitro fertilization is used, these pregnancies in general carry higher risks for hypertensive disorders of pregnancy (e.g., preeclampsia), prematurity, and small-for-gestational-age babies [Jeve et al 2016]. ### Therapies Under Investigation There are multiple ongoing trials of medication for behavior or drugs targeting the underlying neurobiological mechanism of fragile X syndrome (FXS) based on animal model studies. For example: * Metformin is a drug that is widely used to treat type 2 diabetes and has been shown to improve outcomes (including circadian rhythm and memory) in mouse and fly models of FXS [Gantois et al 2017, Monyak et al 2017]. Several trials are under way in children and adults with FXS to assess the efficacy of metformin on a variety of outcomes, including behavior problems, cognition, language deficits, and obesity/excessive appetite. * Mavoglurant targets neural plasticity through negatively regulating mGluR5 signaling that becomes enhanced in the absence of FMRP in FXS. Efficacy is being tested by assessing language outcomes following an intensive language intervention in young children with FXS [Gomez-Mancilla et al 2014]. Additional interventions under investigation for FXS include behavioral therapies, such as behavior analytic treatment to address disruptive behaviors and social gaze training to improve social gaze and shape social skills. Allopregnanolone is a naturally occurring neurosteroid that has shown promise in ameliorating the neuronal impairments of FXTAS in animal models [Cao et al 2012]. Studies in humans are in the early stages [Wang et al 2017, Napoli et al 2019]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	FMR1 Disorders	None	30,552	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1384/	2021-01-18T21:27:23	{"synonyms": []}
McGillivray syndrome Other namesFamilial scaphocephaly syndrome, McGillivray type, Scaphocephaly-macrocephaly-maxillary retrusion-intellectual disability syndrome This condition is inherited via an autosomal dominant manner SpecialtyCardiology McGillivray syndrome is a rare syndrome characterized mainly by heart defects, skull and facial abnormalities and ambiguous genitalia. The symptoms of this syndrome are ventricular septal defect, patent ductus arteriosus, small jaw, undescended testes, and webbed fingers. Beside to these symptoms there are more symptoms which is related with bone structure and misshape. McGillivray syndrome is a birth defect in which one or more of the joints between the bones of the baby's skull close prematurely, before the baby's brain is fully formed. When the baby has craniosynostosis, his or her brain cannot grow in its natural shape and the head is misshapen. It can affect one or more of the joints in the baby's skull. In some cases, craniosynostosis is associated with an underlying brain abnormality that prevents the brain from growing properly. Treating McGillivray usually involves surgery to separate the fused bones. If there is no underlying brain abnormality, the surgery allows the baby's brain to grow and develop in adequate space. ## Contents * 1 Symptoms * 2 Cause * 3 Diagnosis * 3.1 Rare types * 4 Treatments * 5 History * 6 References * 7 External links ## Symptoms[edit] The baby's skull has seven bones. Normally, these bones don't fuse until around age 2, giving the baby's brain time to grow. Joints called cranial sutures, made of strong, fibrous tissue, hold these bones together. In the front of the baby's skull, the sutures intersect in the large soft spot (fontanel) on the top of the baby's head. Normally, the sutures remain flexible until the bones fuse. The signs of craniosynostosis may not be noticeable at birth, but they become apparent during the first few months of the baby's life. The symptoms differs from types of synostosis. First of all there is Sagittal synostosis (scaphocephaly). Premature fusion of the suture at the top of the head (sagittal suture) forces the head to grow long and narrow, rather than wide. Scaphocephaly is the most common type of craniosynostosis. The other one is called Coronal synostosis (anterior plagiocephaly). Premature fusion of a coronal suture — one of the structures that run from each ear to the sagittal suture on top of the head — may force the baby's forehead to flatten on the affected side. It may also raise the eye socket and cause a deviated nose and slanted skull. The Bicoronal synostosis (brachycephaly). When both of the coronal sutures fuse prematurely, the baby may have a flat, elevated forehead and brow.[citation needed] ## Cause[edit] This section is empty. You can help by adding to it. (July 2017) ## Diagnosis[edit] First of all there is physical exam. Doctors examine the baby's head for abnormalities such as suture ridges and look the facial deformities. Also, they utilizes Computerized Tomography which scan of the baby's skull. Fused sutures are identifiable by their absences. X-rays also may be used to measure precise dimensions of the baby's skull, using a technique called cephalometry.[citation needed] Genetic testing. If the doctor suspects the baby's misshapen skull is caused by an underlying hereditary syndrome, genetic testing may help identify the syndrome. Genetic tests usually require a blood sample. Depending on what type of abnormality is suspected, the doctor may take a sample of the baby's hair, skin or other tissue, such as cells from the inside of the cheek. The sample is sent to a lab for analysis. ### Rare types[edit] There are two less common types of McGillivray syndromes are: Metopic synostosis (trigonocephaly). The metopic suture runs from the baby's nose to the sagittal suture. Premature fusion gives the scalp a triangular appearance. Another one is Lambdoid synostosis (posterior plagiocephaly). This rare form of craniosynostosis involves the lambdoid suture, which runs across the skull near the back of the head. It may cause flattening of the baby's head on the affected side. A misshapen head doesn't always indicate craniosynostosis. For example, if the back of the baby's head appears flattened, it could be the result of birth trauma or the baby's spending too much time on his or her back. This condition is sometimes treated with a custom-fit helmet that helps mold the baby's head back into a normal position.[citation needed] ## Treatments[edit] The major treatment is surgery for most babies. The type of surgery which they would undergo differs from age and strength they have. The main reason of doing the surgery is to alleviate pressure on the brain, and create a space for brain developing and growing. It would improve infant's appearance.[citation needed] The first one is Traditional surgery. During surgery, they make an incision in the baby's scalp and cranial bones, and reshape the portion of the skull. Sometimes plates and screws, often made of material that is absorbed over time, are used to hold the bones in place. Surgery, which is performed during general anesthesia, usually takes hours.[citation needed] After surgery, the baby remains in the hospital for at least three days. Some children may require a second surgery later because, the craniosynostosis reoccurs. Also, children with facial deformities often require future surgeries to reshape their faces.[citation needed] Another one is Endoscopic surgery. This less invasive form of surgery isn't an option for everyone. But in certain cases, the surgeon may use a lighted tube (endoscope) inserted through one or two small scalp incisions over the affected suture. The surgeon then opens the suture to enable the baby's brain to grow normally. Endoscopic surgery usually takes about an hour, causes less swelling and blood loss, and shortens the hospital stay, often to one day after surgery.[citation needed] ## History[edit] McGillivray Syndrome is referenced from the 1851 writings of Virchow. His understanding and descriptions of irregular calvarial growth patterns were the basis of the law of Virchow. According to his observations, the abnormal cranial growth observed in persons with craniosynostosis occurs perpendicular to the involved calvarial sutures. Therefore, if a suture line is prematurely ossified, no growth is present in the direction perpendicular to that suture. Surgical treatment for craniosynostosis was initially advocated by Odilon Lannelongue in 1890.[citation needed] His patients had microcephaly from craniosynostosis and were thought to be imbeciles. These patients accordingly underwent craniectomy to remove the involved suture line and to "release the brain". Soon after, in 1891, linear craniectomy was introduced. As with any new procedure, this one met with much resistance. However, the resistance to a surgical intervention was slowly put to rest with mounting evidence. Several studies indicated that craniosynostectomy was the treatment of choice for the release of fused suture lines in the skull. Studies showed that, over time, cranial suture areas excised during strip craniectomy still became fused and led to an abnormal cranial contour.[citation needed] Strip craniectomy was easier and involved less blood loss compared with the newer cranial vault reconstruction. Strip craniectomy also did not address the frontal bossing and associated abnormalities in calvarial shape and relied on the rapid growth of the brain to correct it. Strip craniectomy was optimal only in the first few months of infancy, while surgeons could use cranial vault reconstruction throughout infancy. Consequently, strip craniectomy lost favor, and the surgical treatment has been modified to include cranial vault remodeling. Recently, with the advent of endoscopy, attention has returned to endoscopic strip craniectomy. The endoscopic technique has only been tried over the last several years, but it offers the advantages of a shorter and safer operation, less cost, less in-hospital time, and less blood loss. The operation was shown to be a success in a study of 12 patients, all younger than 8 months. Critical to this success and a departure from the standard strip craniosynostectomy was the extensive use of a postoperative remodeling helmet. Although first introduced by Persing et al. in 1986, helmet therapy has not been used as extensively as a postoperative therapeutic intervention.[citation needed] ## References[edit] "Craniosynostosis." - Mayo Clinic. N.p., n.d. Web. 07 Mar. 2016. "Craniosynostosis Management." : Overview, History, Pathogenesis. N.p., n.d. Web. 17 Mar. 2016. Johns Hopkins Medicine. Johns Hopkins Hospital, n.d. Web. "Symptoms of McGillivray Syndrome." - RightDiagnosis.com. N.p., n.d. Web. 06 Mar. 2016. "The Craniosynostoses." Google Books. N.p., n.d. Web. 07 Mar. 2016. Research https://docs.google.com/document/d/1Z4L2UUyAlfR6_E9pCgdWjdv0Y0kp8GeOJpRASUmn46Y/edit# ## External links[edit] Classification D * ICD-10: Q87.0 * OMIM: 609579 * MeSH: C566511 External resources * Orphanet: 168624 * McGillivray syndrome \- NCBI * McGillivray syndrome \- Office of Rare Disease Research, NCBI * v * t * e Female congenital anomalies of the genitalia, including Intersex and DSD Internal Uterine malformation * Müllerian agenesis * Cervical agenesis * Unicornuate uterus * Uterus didelphys * Bicornuate uterus * Uterine septum * Arcuate uterus Vagina * Vaginal septum * Vaginal hypoplasia * Imperforate hymen * Vaginal adenosis * Cloacal exstrophy * Vaginal atresia External * Clitoromegaly * Progestin-induced virilization * Pseudohermaphroditism * True hermaphroditism * v * t * e Male congenital anomalies of the genitalia, including Intersex and DSD Internal Testicle * Cryptorchidism * Polyorchidism * Monorchism * Anorchia * Sertoli cell-only syndrome * True hermaphroditism * Mixed gonadal dysgenesis * Swyer syndrome Vas deferens * Congenital absence of the vas deferens Other * Persistent Müllerian duct syndrome External Penis * Hypospadias * Epispadias * Chordee * Micropenis * Penile agenesis * Diphallia * Penoscrotal transposition Other * Pseudohermaphroditism [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	McGillivray syndrome	c1865070	30,553	wikipedia	https://en.wikipedia.org/wiki/McGillivray_syndrome	2021-01-18T18:38:58	{"gard": ["3426"], "mesh": ["C566511"], "umls": ["C1865070"], "orphanet": ["168624"], "wikidata": ["Q16947790"]}
8p11 myeloproliferative syndrome is a blood cancer that involves different types of blood cells. Blood cells are divided into several groups (lineages) based on the type of early cell from which they are descended. Two of these lineages are myeloid cells and lymphoid cells. Individuals with 8p11 myeloproliferative syndrome can develop both myeloid cell cancer and lymphoid cell cancer. The condition can occur at any age. It usually begins as a myeloproliferative disorder, which is characterized by a high number of white blood cells (leukocytes). Most affected individuals also have an excess of myeloid cells known as eosinophils (eosinophilia). In addition to a myeloproliferative disorder, many people with 8p11 myeloproliferative syndrome develop lymphoma, which is a form of blood cancer that involves lymphoid cells. The cancerous lymphoid cells grow and divide in lymph nodes, forming a tumor that enlarges the lymph nodes. In most cases of 8p11 myeloproliferative syndrome, the cancerous cells are lymphoid cells called T cells. Lymphoma can develop at the same time as the myeloproliferative disorder or later. In most people with 8p11 myeloproliferative syndrome, the myeloproliferative disorder develops into a fast-growing blood cancer called acute myeloid leukemia. The rapid myeloid and lymphoid cell production caused by these cancers results in enlargement of the spleen and liver (splenomegaly and hepatomegaly, respectively). Most people with 8p11 myeloproliferative syndrome have symptoms such as fatigue or night sweats. Some affected individuals have no symptoms, and the condition is discovered through routine blood tests. ## Frequency The prevalence of 8p11 myeloproliferative syndrome is unknown. It is thought to be a rare condition. ## Causes 8p11 myeloproliferative syndrome is caused by rearrangements of genetic material (translocations) between two chromosomes. All of the translocations that cause this condition involve the FGFR1 gene, which is found on the short (p) arm of chromosome 8 at a position described as p11. The translocations lead to fusion of part of the FGFR1 gene with part of another gene; the most common partner gene is ZMYM2 on chromosome 13. These genetic changes are found only in cancer cells. The protein normally produced from the FGFR1 gene can trigger a cascade of chemical reactions that instruct the cell to undergo certain changes, such as growing and dividing. This signaling is turned on when the FGFR1 protein interacts with growth factors. In contrast, when the FGFR1 gene is fused with another gene, FGFR1 signaling is turned on without the need for stimulation by growth factors. The uncontrolled signaling promotes continuous cell growth and division, leading to cancer. Researchers believe the mutations that cause this condition occur in a very early blood cell called a stem cell that has the ability to mature into either a myeloid cell or a lymphoid cell. For this reason, this condition is sometimes referred to as stem cell leukemia/lymphoma. ### Learn more about the genes and chromosomes associated with 8p11 myeloproliferative syndrome * FGFR1 * ZMYM2 * chromosome 13 * chromosome 8 ## Inheritance Pattern This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	8p11 myeloproliferative syndrome	c3150773	30,554	medlineplus	https://medlineplus.gov/genetics/condition/8p11-myeloproliferative-syndrome/	2021-01-27T08:25:13	{"omim": ["613523"], "synonyms": []}
Abortion in Brunei is legal only when it is done to save a woman's life. In Brunei, a woman who induces her abortion is subject to up to seven years in prison. The penalty for someone who performs an abortion was 10–15 years.[1][2] In 2014, Brunei's government implemented Sharia criminal law to punish abortion with execution by stoning.[3][4] This part of the law was originally set to come into effect in 2016,[5] although now it is expected to come into effect in 2018.[citation needed] In 2016, a 22-year-old woman was sentenced to six months in prison for obtaining an abortion using the abortion pill.[6] She had faced a maximum sentence of seven years.[7] ## References[edit] 1. ^ "Brunei Darussalam". Abortion Policies: A Global Review (DOC). Country Profiles. United Nations Population Division. 2002. Retrieved 14 March 2017. 2. ^ "BRUNEI. Penal Code. Causing of Miscarriage; Injuries to Unborn Children; Exposure of Infants; and Concealment of Birth". www.hsph.harvard.edu. Archived from the original on 2016-03-25. Retrieved 2017-06-25. 3. ^ Cohen, Sandy (6 May 2014). "Beverly Hills Hotel Boycotted Over Brunei's Sharia Penal Code". The Huffington Post. Associated Press. Archived from the original on 8 May 2014. Retrieved 1 December 2014. 4. ^ "Sultan of Brunei introduces death by stoning under new Sharia laws". The National. Agence France-Presse. 22 October 2013. Retrieved 14 April 2018. 5. ^ Ozanick, Bill. "The Implications of Brunei's Sharia Law". The Diplomat. Retrieved 2017-06-25. 6. ^ "Local Woman Receive 6 Months Jail Sentenced for Aborting Baby". www.brudirect.com. 5 October 2016. Retrieved 2018-04-14. 7. ^ "Youth in Abortion Case Set for Time in Jail, fine". www.brudirect.com. 21 September 2016. Retrieved 2017-06-25. * v * t * e Abortion in Asia Sovereign states * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor (Timor-Leste) * Egypt * Georgia * India * Indonesia * Iran * Iraq * Israel * Japan * Jordan * Kazakhstan * North Korea * South Korea * Kuwait * Kyrgyzstan * Laos * Lebanon * Malaysia * Maldives * Mongolia * Myanmar * Nepal * Oman * Pakistan * Philippines * Qatar * Russia * Saudi Arabia * Singapore * Sri Lanka * Syria * Tajikistan * Thailand * Turkey * Turkmenistan * United Arab Emirates * Uzbekistan * Vietnam * Yemen States with limited recognition * Abkhazia * Artsakh * Northern Cyprus * Palestine * South Ossetia * Taiwan Dependencies and other territories * British Indian Ocean Territory * Christmas Island * Cocos (Keeling) Islands * Hong Kong * Macau * Book * Category * Asia portal * v * t * e Abortion Main topics * Definitions * History * Methods * Abortion debate * Philosophical aspects * Abortion law Movements * Abortion-rights movements * Anti-abortion movements Issues * Abortion and mental health * Beginning of human personhood * Beginning of pregnancy controversy * Abortion-breast cancer hypothesis * Anti-abortion violence * Abortion under communism * Birth control * Crisis pregnancy center * Ethical aspects of abortion * Eugenics * Fetal rights * Forced abortion * Genetics and abortion * Late-term abortion * Legalized abortion and crime effect * Libertarian perspectives on abortion * Limit of viability * Malthusianism * Men's rights * Minors and abortion * Natalism * One-child policy * Paternal rights and abortion * Prenatal development * Reproductive rights * Self-induced abortion * Sex-selective abortion * Sidewalk counseling * Societal attitudes towards abortion * Socialism * Toxic abortion * Unsafe abortion * Women's rights By country Africa * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde * Central African Republic * Chad * Egypt * Ghana * Kenya * Namibia * Nigeria * South Africa * Uganda * Zimbabwe Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor * Georgia * India * Iran * Israel * Japan * Kazakhstan * South Korea * Malaysia * Nepal * Northern Cyprus * Philippines * Qatar * Saudi Arabia * Singapore * Turkey * United Arab Emirates * Vietnam * Yemen Europe * Albania * Andorra * Austria * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Czech Republic * Denmark * Estonia * Finland * France * Germany * Greece * Hungary * Iceland * Ireland * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Ukraine * United Kingdom North America * Belize * Canada * Costa Rica * Cuba * Dominican Republic * El Salvador * Guatemala * Mexico * Nicaragua * Panama * Trinidad and Tobago * United States Oceania * Australia * Micronesia * Fiji * Kiribati * Marshall Islands * New Zealand * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu South America * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Law * Case law * Constitutional law * History of abortion law * Laws by country * Buffer zones * Conscientious objection * Fetal protection * Heartbeat bills * Informed consent * Late-term restrictions * Parental involvement * Spousal consent Methods * Vacuum aspiration * Dilation and evacuation * Dilation and curettage * Intact D&X * Hysterotomy * Instillation * Menstrual extraction * Abortifacient drugs * Methotrexate * Mifepristone * Misoprostol * Oxytocin * Self-induced abortion * Unsafe abortion Religion * Buddhism * Christianity * Catholicism * Hinduism * Islam * Judaism * Scientology * Category This abortion-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Abortion in Brunei	None	30,555	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Brunei	2021-01-18T18:39:57	{"wikidata": ["Q19568852"]}
Camptodactyly-arthropathy-coxa-vara-pericarditis (CACP) syndrome is a rare, genetic, rheumatologic disease characterized by congenital or early-onset camptodactyly and symmetrical, polyarticular, non-inflammatory, large joint arthropathy with synovial hyperplasia, as well as progressive coxa vara deformity and, occasionally, non-inflammatory pericarditis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Camptodactyly-arthropathy-coxa-vara-pericarditis syndrome	c1859690	30,556	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2848	2021-01-23T19:01:01	{"gard": ["306"], "mesh": ["C537560"], "omim": ["208250"], "umls": ["C1859690"], "synonyms": ["Arthropathy-camptodactyly syndrome", "CACP syndrome", "Jacobs syndrome", "Pericarditis-arthropathy-camptodactyly syndrome"]}
Majeed syndrome SpecialtyDermatology Majeed syndrome is an inherited skin disorder characterized by chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia and a neutrophilic dermatosis.[1] It is classified as an autoinflammatory bone disorder. The condition is found in people with two defective copies (autosomal recessive inheritance) of the LPIN2 gene. LPIN2 encodes lipin-2 which is involved in lipid metabolism. The pathogenesis of this mutation with the clinical manifestations has not been elucidated.[2] ## See also[edit] * TNF receptor associated periodic syndrome * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ "Majeed syndrome". Genetics Home Reference. Retrieved 17 April 2018. ## External links[edit] * Orphanet syndrome Majeed syndrome This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Majeed syndrome	c1864997	30,557	wikipedia	https://en.wikipedia.org/wiki/Majeed_syndrome	2021-01-18T18:38:15	{"gard": ["10088"], "mesh": ["C537839"], "umls": ["C1864997"], "orphanet": ["77297"], "wikidata": ["Q6737634"]}
Gonadal tissue neoplasm SpecialtyOncology A gonadal tissue neoplasm is a tumor having any histology characteristic of cells or tissues giving rise to the gonads. These tissues arise from the sex cord and stromal cells. The tumor may be derived from these tissues, or produce them. Although the tumor is composed of gonadal tissue, it is not necessarily located in an ovary or testicle. A gonadal tissue neoplasm should not be confused with a urogenital neoplasm, though the two topics are often studied together. The embryology of the gonads is only indirectly related to the embryology of the external genitals and urinary system. ## See also[edit] * Gonadoblastoma * Sex cord-gonadal stromal tumour ## References[edit] ## External links[edit] Classification D * MeSH: D018309 * v * t * e Tumors of the female urogenital system Adnexa Ovaries Glandular and epithelial/ surface epithelial- stromal tumor CMS: * Ovarian serous cystadenoma * Mucinous cystadenoma * Cystadenocarcinoma * Papillary serous cystadenocarcinoma * Krukenberg tumor * Endometrioid tumor * Clear-cell ovarian carcinoma * Brenner tumour Sex cord–gonadal stromal * Leydig cell tumour * Sertoli cell tumour * Sertoli–Leydig cell tumour * Thecoma * Granulosa cell tumour * Luteoma * Sex cord tumour with annular tubules Germ cell * Dysgerminoma * Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma/Struma ovarii * Choriocarcinoma Fibroma * Meigs' syndrome Fallopian tube * Adenomatoid tumor Uterus Myometrium * Uterine fibroids/leiomyoma * Leiomyosarcoma * Adenomyoma Endometrium * Endometrioid tumor * Uterine papillary serous carcinoma * Endometrial intraepithelial neoplasia * Uterine clear-cell carcinoma Cervix * Cervical intraepithelial neoplasia * Clear-cell carcinoma * SCC * Glassy cell carcinoma * Villoglandular adenocarcinoma Placenta * Choriocarcinoma * Gestational trophoblastic disease General * Uterine sarcoma * Mixed Müllerian tumor Vagina * Squamous-cell carcinoma of the vagina * Botryoid rhabdomyosarcoma * Clear-cell adenocarcinoma of the vagina * Vaginal intraepithelial neoplasia * Vaginal cysts Vulva * SCC * Melanoma * Papillary hidradenoma * Extramammary Paget's disease * Vulvar intraepithelial neoplasia * Bartholin gland carcinoma * v * t * e * Tumors of the male urogenital system Testicles Sex cord– gonadal stromal * Sertoli–Leydig cell tumour * Sertoli cell tumour * Leydig cell tumour Germ cell G * Seminoma * Spermatocytic tumor * Germ cell neoplasia in situ NG * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma * Choriocarcinoma * Embryoma Prostate * Adenocarcinoma * High-grade prostatic intraepithelial neoplasia * HGPIN * Small-cell carcinoma * Transitional cell carcinoma Penis * Carcinoma * Extramammary Paget's disease * Bowen's disease * Bowenoid papulosis * Erythroplasia of Queyrat * Hirsuties coronae glandis This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Gonadal tissue neoplasm	c0206722	30,558	wikipedia	https://en.wikipedia.org/wiki/Gonadal_tissue_neoplasm	2021-01-18T18:47:00	{"mesh": ["D018309"], "wikidata": ["Q5581314"]}
Jaw claudication Differential diagnosisgiant cell artiritis Jaw claudication is pain in the jaw associated with chewing. It is a classic symptom of giant-cell arteritis,[1][2] but can be confused with symptoms of temporomandibular joint disease, rheumatoid arthritis of the temporomandibular joint, myasthenia gravis, tumors of the parotid gland, or occlusion or stenosis of the external carotid artery.[3] The term is derived by analogy from claudication of the leg, where pain is caused by arterial insufficiency. ## References[edit] 1. ^ Jaw claudication is the only clinical predictor of giant-cell arteritis. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 29 (3): 264-269. Hitoshi Sato, Mariko Inoue, Wataru Muraoka, Takaaki Kamatani, Seiji Asoda, Hiromasa Kawana, Taneaki Nakagawa, Koichi Wajima. (May 2017) doi:10.1016/j.ajoms.2016.12.002 2. ^ Stone, John H. (2009). A Clinician's Pearls & Myths in Rheumatology. Springer Science & Business Media. p. 287. ISBN 9781848009349. Retrieved 11 November 2017. 3. ^ Goodman BW, Jr; Shepard, FA (February 1983). "Jaw claudication. Its value as a diagnostic clue". Postgraduate Medicine. 73 (2): 177–83. doi:10.1080/00325481.1983.11697764. PMID 6823455. * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension This medical symptom article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Jaw claudication	c0239064	30,559	wikipedia	https://en.wikipedia.org/wiki/Jaw_claudication	2021-01-18T18:41:37	{"umls": ["C0239064", "C0549415"], "wikidata": ["Q19597620"]}
Hürthle cell adenoma SpecialtyOncology Hürthle cell adenoma is a rare benign tumor, typically seen in women between the ages of 70 and 80 years old. This adenoma is characterized by a mass of benign Hürthle cells (Askanazy cells).[1] Typically such a mass is removed because it is not easy to predict whether it will transform into the malignant counterpart, a subtype of follicular thyroid cancer called a Hürthle cell carcinoma.[2][3] ## Contents * 1 Histology * 2 Diagnosis * 3 Treatment * 4 History * 5 References * 6 External links ## Histology[edit] Play media Hürthle Cell Adenoma nodule observed in 3D image of Thyroid Hürthle cells are characterized as enlarged epithelial cells. These cells, when stained with hematoxylin-eosin show as pink. This is due to the abundant mitochondria and granular eosinophilic matter within the cells' cytoplasm. These cells are often found in the thyroid. The thyroid is a butterfly-shaped organ, responsible for producing various hormones for metabolism. These cells are often benign, but they can be malignant and metastasize. Hürthle cells are resistant to radiation, but can be treated using radioactive iodine treatment.[4] ## Diagnosis[edit] This mass can be detected and removed before transformation and metastasis. The tumor is often detected by imaging such as ultrasound. The location and size of the tumor may cause pressure and pain to the patient. But often the tumor goes undetected. After detection, the mass is tested using an invasive fine-needle aspiration biopsy.[5] Hürthle cell adenoma is the benign analogue of Hürthle cell carcinoma. This adenoma is extremely rare; when it occurs, it usually occurs in women. Often the adenoma is harmless but is removed after detection because its future course cannot be trusted.[2][3] ## Treatment[edit] There are three main treatments for Hürthle cell adenomas. Once the adenoma is detected most often the nodules removed to prevent the cells from later metastisizing.[2][3] A total thyroidectomy is often performed, this results in a complete removal of the thyroid. Some patients may only have half of their thyroid removed, this is known as a thyroid lobectomy. Another treatment option includes pharmacological suppression of thyroid hormone. The thyroid gland is responsible for producing the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Patients with suppressed thyroid function often require oral thyroid replacement (e.g. levothyroxine) in order to maintain normal thyroid hormone levels. The final treatment option is RAI ablation (radioactive iodine ablation). This treatment option is used to destroy infected thyroid cells after total thyroidectomy. This treatment does not change prognosis of disease, but will diminish the recurrence rate. Also, Hürthle cells do not respond well to RAI. However, often doctors suggest this treatment to patients with Hürthle cell adenoma and Hürthle cell carcinoma because some Hürthle cells will respond and it will kill remaining tissue.[1] ## History[edit] The first Hürthle cell adenoma was discovered by Dr James Ewing in 1928. Hürthle cells were discovered in the 1890s and are named after Karl Hürthle and Max Askanazy. ## References[edit] 1. ^ a b "Thyroid Cancer: About Thyroid Cancer \| Memorial Sloan Kettering Cancer Center". www.mskcc.org. Retrieved 2015-11-23. 2. ^ a b c Ristevska, N; Stojanoski, S; Gjorceva, DP (2015), "Appearance of Hürthle cell carcinoma soon after surgical extirpation of Hürthle cell adenoma and follicular adenoma of the thyroid gland", Radiol Oncol, 49 (1): 26–31, doi:10.2478/raon-2014-0047, PMC 4362603, PMID 25810698. 3. ^ a b c Wasvary, H; et al. (1998), "Unilateral lobectomy for Hürthle cell adenoma", Am Surg, 64 (8): 729–732, PMID 9697901. 4. ^ "Hurthle Cell Adenoma". www.knowcancer.com. Retrieved 2015-11-23. 5. ^ "Follicular and Hurthle Cell Thyroid Cancer \| Columbia University Department of Surgery". columbiasurgery.org. Retrieved 2015-11-23. ## External links[edit] * http://www.knowcancer.com/oncology/hurthle-cell-adenoma/ * https://www.mskcc.org/cancer-care/types/thyroid/about-thyroid * http://columbiasurgery.org/conditions-and-treatments/follicular-and-hurthle-cell-thyroid-cancer [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Hürthle cell adenoma	c1336750	30,560	wikipedia	https://en.wikipedia.org/wiki/H%C3%BCrthle_cell_adenoma	2021-01-18T18:56:24	{"wikidata": ["Q16864144"]}
GACI - Pronounced "GACK-EE" Generalized arterial calcification of infancy Other namesIdiopathic infantile arterial calcification (IIAC), arterial calcification of infancy, idiopathic arterial calcification of infancy (IACI), occlusive infantile arterial calcification, occlusive infantile arteriopathy[1] SpecialtyMedical genetics Generalized arterial calcification of infancy (GACI) is an extremely rare,[2] genetic disorder. It is caused by mutations in the ENPP1 gene in 75% of the subjects[3] or in mutations in the ABCC6 genes in 10% of patients.[4] However, sometimes individuals affected with GACI do not have mutations in the ENPP1 or ABCC6 gene and in those cases the cause of the disorder is unknown.[4] The condition usually affects infants during the first 6 months of life. This condition is inherited as an autosomal recessive pattern. It is characterized by generalized calcification of the arterial internal elastic lamina, leading to rupture of the lamina and occlusive changes in the tunica intima with stenosis and decreased elasticity of the vessel wall.[5] Unfortunately, many infants die of vaso-occlusive disease, especially of the coronary arteries.[6] There are 2 forms of GACI that can be indicated on a genetic test: GACI Type 1 is caused by mutations in the ENPP1 gene. It is called ENPP1 Deficiency. Patients with the ENPP1 Deficiency are at risk of developing Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2). ARHR2 can cause weakening in the bones, pain in bones and joints bone deformities (knocked knees, bowed legs), dental problems, calcification of ligaments and short stature. With proper treatment the bones can be strengthened and side effects minimized.[7][8][9] GACI Type 2 is caused by mutations in the ABCC6 gene. It is called ABCC6 Deficiency. As children affected by GACI due to ABCC6 Deficiency get older, they can develop characteristics similar to pseudoxanthoma elasticum (PXE). This condition affects the elastic tissue of the skin, the eye, cardiovascular and gastrointestinal systems.[7][8][9] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Prognosis * 7 Research * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] Clinical presentation is variable. First symptoms usually occur at birth but can take place in the first 6 months of life or in utero.[2] Clinical Signs for GACI can include: * Decreased fetal activity * Gestation with an antenatal diagnosis of hydrops fetalis[10][11] * Polyhydramnios * Pericardial effusion[7] * Low biophysical profile * Marked cyanosis * Edema[12] * Severe hypertension[13] * Reduced or absent pulses * Refusal of feeds[14] * Tachypnea * Vomiting * Abdominal distension * General arterial rigidity[15] * Cardiac failure (most common clinical finding) * Strain pattern on electrocardiogram * Enlarged heart (cardiomegaly) [7] * Echogenicity of the arteries and/or heart on imaging [7] * High Blood Pressure (hypertension) [7] * Respiratory distress [7] * Blood vessel narrowing [7] * Joint calcifications [7] * Hearing loss [7] * Kidney failure [7] * Gastrointestinal complications [7] ## Cause[edit] GACI is inherited in an autosomal recessive pattern. The condition results from an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1 gene) or the ATP-binding C member 6 (ABBC6 gene), leading to decreased inorganic pyrophosphate (PPi).[7] This is a potent inhibitor of calcium deposition in the vessel wall. These mutations allow for unregulated calcium deposition within muscular arteries. The symptoms are caused by calcification of large and medium-sized arteries, including the aorta, coronary arteries, and renal arteries. Recently, homozygous or compound heterozygous mutations for ENPP1 gene were reported as causative for the disorder. ENPP1 regulates extracellular inorganic pyrophosphate (PPi), a major inhibitor of extracellular matrix calcification.[16] The critical period for babies affected by GACI is during the first 6 months after birth. This is due to calcium continuing to build up in the artery walls. If blood flow becomes restricted it can become life threatening.[7] GACI affects males and females equally and occurs in populations all across the world. It is estimated to occur in approximately 1 out of every 391,000 births with the carrier rate being 1:312. Survival statistics vary greatly.[7] ## Diagnosis[edit] Generalized arterial calcification of infancy should always be considered in infants and children presenting with hypertension, cardiac failure, or sudden death.[17] Plain radiography,[18] sonography[19] and MRI[20] can aid in the diagnosis. Postnatal gray-scale and color Doppler echocardiographic and sonographic examinations allowed noninvasive diagnosis, assessment of severity, and monitoring of progression.[21] Contrast-enhanced MR angiography with breath-hold and cardiac gating techniques can allow evaluation of the extent of the disease.[22] * Dilated and hypertrophied ventricles * Extramedullary hematopoiesis of liver [23] * Hypertrophy of myocardium * Bright and hyper-reflective myocardium[24] * Periarticular calcifications in the wrists, ears, shoulders, ankles and hip[25][26] * Heart usually looks structurally normal * Cardiomegaly and pulmonary plethora[24] * Diffuse arterial calcification involving aorta, carotid, cerebral, renal, mesenteric and cardiac arteries * Echo-dense aortic annulus, ascending aorta, transverse arch, descending aorta, main pulmonary artery, and coronary arteries unusually.[27] * Abdominal ultrasound can reveal hepatosplenomegaly, ascites, renal echogenicity and diffused arterial calcifications involving the aorta, common iliac, splenic, and renal arteries, as well as peritoneal calcifications involving the visceral peritoneum overlying the liver and intestine * Brain ultrasound can show dilated lateral ventricles, poorly developed corpus callosum, and leukomalacia * Echocardiogram can reveal a structurally normal heart, normal ventricular function, however mild concentric ventricular hypertrophy and multiple intracardiac as well as vascular calcifications[10] * Generalized arterial calcification of infancy should be suspected when there is hyperechogenicity of vessel walls, evidence of polyhydramnios or a past history of early neonatal deaths.[28] * DNA testing can identify one of the mutations responsible for the condition[29] ## Prevention[edit] * Potential role of genetic markers in the identification of persons at risk.[30] There is a 75% probability to identify the two ENPP1 mutations or 10% with ABCC6 mutations (one paternal, one maternal) that cause GACI.[4] Once the mutations are identified, preimplantation genetic diagnosis (PGD) or chorionic villus sampling (CVS) are possible options to identify the condition, either before or during pregnancy. * At week 20 of gestation, it is possible to detect an Echogenic intracardiac focus (EIF)[31] or intravascular calcifications, particularly in the iliac and [abdominal aorta]. EIF is a small bright spot seen in the baby’s heart on an ultrasound exam. This is thought to represent mineralization, or small deposits of calcium hydroxyapatite,[32] in the muscle of the heart. EIFs are found in about 3-5% of normal pregnancies and cause no health problems. * Ultrasound can show subtle intravascular calcifications, particularly in the abdominal aorta at week 23.[33] * Calcification has been detected at 33 weeks' gestation.[34] * The earliest detected manifestation (echogenic foci in the mitral valve Hepatic vascular) of the disease was prenatally at 14 weeks gestation.[7] ## Treatment[edit] * Currently, there is no curative treatment for GACI. However, in recent years, better medical treatment has led to increased survival rates.[7] * Use of bisphosphonates appears to significantly increase survival. Etidronate, a non-nitrogen-containing bisphosphonate, is the most commonly used based on its potent antimineralization effect.[7] * Prenatal[35] and postnatal treatment with low-dose, cyclical bisphosphonates, also called diphosphonate, resulted in a complete resolution of vascular calcifications in some cases using disodium pamidronate and risedronate.[36][37][38][39][40] * Sodium Thiosulfate (STS) is a calcium-chelating agent. It is typically used by patients who have excess calcium in their arteries due to kidney disease. In recent years, STS has also been used to treat patients with GACI.Proposed mechanism of STS action includes chelation or increased solubility of over mineralized calcium in arteries to be removed from the body. STS is typically administered intravenously through a central line in the chest. The dosage amount and length of time for STS treatment is determined by the patient’s medical team.[7] * PGE1 infusion is a possible therapeutic alternative for babies with idiopathic arterial calcification complicated by severe hypertension refractory to conventional treatment.[41] * Infants must reach a certain weight to allow for a transplant, commonly not reached.[42] There is minimal information available about heart transplants in patients with GACI. There is some clinical evidence that heart transplants can be successful, without recurrence of calcifications. Heart transplant for individuals with GACI has occurred in at least 3 known cases. In 2014, there was a follow up report about a 4 year old child with GACI who had a successful heart transplant.[43] ## Prognosis[edit] * Survival to adulthood has been reported,[44][45] sometimes with persistent hypertension and cardiovascular sequelae. * Spontaneous regression of arterial calcifications can occur, and antihypertensive treatment can be tapered off gradually. In some patients, the natural course of GACI may be more favourable than previously assumed.[46][47] * Despite the same genotype and similar sonographic and radiographic features in early infancy, the phenotype of GACI can vary to a great extent within one family.[48] ## Research[edit] In 2015, Demetrios Braddock, MD, PhD, a pathologist and professor from Yale University along with his team published an article in Nature Communications.[49] Their research revealed when mice with GACI were given a replacement version of the enzyme, it helped to reduce the calcifications and prevented the animals from dying.[49][50][51] This discovery has led to the development of Inozyme Pharma[51][9] a biotechnology company developing new medicines to treat rare disorders of calcification including GACI.[52] ## See also[edit] * ENPP1 * Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2) * ABCC6 * pseudoxanthoma elasticum (PXE) ## References[edit] 1. ^ Witzleben, C.L (1970). "Idiopathic infantile arterial calcification—A misnomer?". The American Journal of Cardiology. 26 (3): 305–9. doi:10.1016/0002-9149(70)90798-8. PMID 4196111. 2. ^ a b Chong, Curtis R.; Hutchins, Grover M. (2008). "Idiopathic Infantile Arterial Calcification: The Spectrum of Clinical Presentations". Pediatric and Developmental Pathology. 11 (5): 405–15. doi:10.2350/07-06-0297.1. PMID 17990935. 3. ^ Rutsch, Frank; Ruf, Nico; Vaingankar, Sucheta; Toliat, Mohammad R.; Suk, Anita; Höhne, Wolfgang; Schauer, Galen; Lehmann, Mandy; et al. (2003). "Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification". Nature Genetics. 34 (4): 379–81. doi:10.1038/ng1221. PMID 12881724. 4. ^ a b c "Generalized arterial calcification of infancy". Genetic Home Reference-US National Library of Medicine. 5. ^ Greenberg, S. Bruce; Gibson, James (2005). "New Findings in Idiopathic Arterial Calcification of Infancy Detected by MDCT". American Journal of Roentgenology. 185 (2): 530–2. doi:10.2214/ajr.185.2.01850530. PMID 16037532. 6. ^ Rutsch, Frank; Boyer, Petra; Nitschke, Yvonne; Ruf, Nico; Lorenz-Depierieux, Bettina; Wittkampf, Tanja; Weissen-Plenz, Gabriele; Fischer, Rudolf-Josef; et al. (2008). "Hypophosphatemia, Hyperphosphaturia, and Bisphosphonate Treatment Are Associated with Survival Beyond Infancy in Generalized Arterial Calcification of Infancy". Circulation: Cardiovascular Genetics. 1 (2): 133–40. doi:10.1161/CIRCGENETICS.108.797704. PMC 2794045. PMID 20016754. 7. ^ a b c d e f g h i j k l m n o p q r s Ferreira, Carlos; Ziegler, Shira; Gahl, William A. (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Generalized Arterial Calcification of Infancy", GeneReviews®, University of Washington, Seattle, PMID 25392903, retrieved 2019-10-17 8. ^ a b Ferreira, Carlos R.; van Karnebeek, Clara D. M.; Vockley, Jerry; Blau, Nenad (January 2019). "A proposed nosology of inborn errors of metabolism". Genetics in Medicine. 21 (1): 102–106. doi:10.1038/s41436-018-0022-8. ISSN 1530-0366. PMC 6286709. PMID 29884839. 9. ^ a b c "Company". Inozyme Pharma. Retrieved 2019-10-17. 10. ^ a b Abu-Asbeh, J; Khan, J; Shallal, A (2006). "Idiopathic infantile arterial calcification associated with leukomalacia". Journal of the Arab Neonatology Forum. 3 (1): 15–9. Archived from the original on 2013-06-16. Retrieved 2013-05-14. 11. ^ Nagar, Arpit M.; Hanchate, Vijay; Tandon, Ankit; Thakkar, Hemangini; Chaubal, Nitin G. (2003-06-01). "Antenatal Detection of Idiopathic Arterial Calcification With Hydrops Fetalis". Journal of Ultrasound in Medicine. 22 (6): 653–9. doi:10.7863/jum.2003.22.6.653. PMID 12795564. 12. ^ Maayan, Ch.; Peleg, O.; Eyal, F.; Mogle, P.; Rosenmann, E.; Ziv, J. Bar (1984). "Idiopathic infantile arterial calcification: A case report and review of the literature". European Journal of Pediatrics. 142 (3): 211–5. doi:10.1007/BF00442452. PMID 6468446. 13. ^ Milner, Laurence S.; Heitner, René; Thomson, Peter D.; Levin, Solomon E.; Rothberg, Alan D.; Beale, Peter; Ninin, Daniel T. (1984). "Hypertension as the major problem of idiopathic arterial calcification of infancy". The Journal of Pediatrics. 105 (6): 934–8. doi:10.1016/S0022-3476(84)80080-3. PMID 6502343. 14. ^ Hunt, A. C.; Leys, D. G. (1957). "Generalized Arterial Calcification of Infancy". BMJ. 1 (5015): 385–6. doi:10.1136/bmj.1.5015.385. PMC 1974337. PMID 13396267. 15. ^ Thiaville, A.; Smets, A.; Clercx, A.; Perlmutter, N. (1994). "Idiopathic infantile arterial calcification: A surviving patient with renal artery stenosis". Pediatric Radiology. 24 (7): 506–8. doi:10.1007/BF02015014. PMID 7885787. 16. ^ Rutsch, Frank; Vaingankar, Sucheta; Johnson, Kristen; Goldfine, Ira; Maddux, Betty; Schauerte, Petra; Kalhoff, Hermann; Sano, Kimihiko; et al. (2001). 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G.; Deangelis, G. A.; Lovell, Mark A.; Hagspiel, Klaus D.; Hagspiel, KD (1998). "Idiopathic arterial calcification of infancy: Sonographic and magnetic resonance findings with pathologic correlation". Pediatric Radiology. 28 (4): 256–9. doi:10.1007/s002470050344. PMID 9545482. 21. ^ Whitehall, John; Smith, Mark; Altamirano, Louis (2003). "Idiopathic infantile arterial calcification: Sonographic findings". Journal of Clinical Ultrasound. 31 (9): 497–501. doi:10.1002/jcu.10208. PMID 14595743. 22. ^ Tran, Kim H.; Boechat, M. Ines (2006). "Idiopathic infantile arterial calcification: Imaging evaluation and the usefulness of MR angiography". Pediatric Radiology. 36 (3): 247–53. doi:10.1007/s00247-005-0044-7. PMID 16429273. 23. ^ Sharmila, N.; Prashant, S. Joshi; Ravikumar, Vani (Jan–Mar 2010). "Idiopathic Infantile arterial calcification–A Very rare case". Online Journal of Health and Allied Sciences. 9 (1). 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PMID 11208697. 28. ^ Sundaram, S; Kuruvilla, S; Thirupuram, S (2004). "Idiopathic arterial calcification of infancy - a case report". Images in Paediatric Cardiology. 6 (1): 6–12. PMC 3232550. PMID 22368635. 29. ^ Dlamini, Nomazulu; Splitt, Miranda; Durkan, Anne; Siddiqui, Ata; Padayachee, Soundrie; Hobbins, Sue; Rutsch, Frank; Wraige, Elizabeth (2009). "Generalized arterial calcification of infancy: Phenotypic spectrum among three siblings including one case without obvious arterial calcifications". American Journal of Medical Genetics Part A. 149A (3): 456–60. doi:10.1002/ajmg.a.32646. PMID 19206175. 30. ^ Eller, Philipp; Hochegger, Kathrin; Feuchtner, Gudrun M.; Zitt, Emanuel; Tancevski, Ivan; Ritsch, Andreas; Kronenberg, Florian; Rosenkranz, Alexander R.; et al. (2007). "Impact of ENPP1 genotype on arterial calcification in patients with end-stage renal failure". Nephrology Dialysis Transplantation. 23 (1): 321–7. doi:10.1093/ndt/gfm566. PMID 17848394. 31. ^ Nasrallah, F. K.; Baho, H.; Sallout, A.; Qurashi, M. (2009). "Prenatal diagnosis of idiopathic infantile arterial calcification with hydrops fetalis". Ultrasound in Obstetrics and Gynecology. 34 (5): 601–4. doi:10.1002/uog.7438. PMID 19813208. 32. ^ Meradji, M.; De Villeneuve, V.H.; Huber, J.; De Bruijn, W.C.; Pearse, R.G. (1978). "Idiopathic infantile arterial calcification in siblings: Radiologic diagnosis and successful treatment". The Journal of Pediatrics. 92 (3): 401–5. doi:10.1016/S0022-3476(78)80427-2. PMID 416189. 33. ^ "SONOWORLD : Idiopathic infantile arterial calcification". 34. ^ Stuart, G; Wren, C; Bain, H (1990). "Idiopathic infantile arterial calcification in two siblings: Failure of treatment with diphosphonate". Heart. 64 (2): 156–9. doi:10.1136/hrt.64.2.156. PMC 1024357. PMID 2118367. 35. ^ Bellah, Richard D.; Zawodniak, Len; Librizzi, Ronald J.; Harris, Mary Catherine (1992). "Idiopathic arterial calcification of infancy: Prenatal and postnatal effects of therapy in an infant". 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"Idiopathic infantile arterial calcification: Clinical presentation, therapy and long-term follow-up". European Journal of Pediatrics. 165 (9): 590–3. doi:10.1007/s00431-006-0146-8. PMID 16649023. 40. ^ Culling, Bronwyn; Loughran-Fowlds, Alison; Munns, Craig; Sillence, David; Walsh, Corrina; Taylor, Peter; Buckley, Michael; Rutsch, Frank; Roscioli, Tony (August 6–10, 2006). Infantile Arterial Calcification: Successful Treatment with Bisphosphonate. 11th International Congress of Human Genetics. Brisbane, Australia. Archived from the original on May 12, 2006. 41. ^ Ciana, G.; Colonna, F.; Forleo, V.; Brizzi, F.; Benettoni, A.; de Vonderweid, U. (1997). "Idiopathic Arterial Calcification of Infancy: Effectiveness of Prostaglandin Infusion for Treatment of Secondary Hypertension Refractory to Conventional Therapy: Case Report". Pediatric Cardiology. 18 (1): 67–71. doi:10.1007/s002469900114. 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Retrieved 2019-10-17. ## External links[edit] Classification D * ICD-10: Q28.8 * OMIM: 208000 * MeSH: C537440 External resources * Orphanet: 51608 * OMIM 208000 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Generalized arterial calcification of infancy	c1859727	30,561	wikipedia	https://en.wikipedia.org/wiki/Generalized_arterial_calcification_of_infancy	2021-01-18T18:57:25	{"gard": ["8380"], "mesh": ["C537440"], "umls": ["C1859728", "C1859727"], "orphanet": ["51608"], "wikidata": ["Q9366868"]}
Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by generalized blistering with mottled or reticulate brown pigmentation. ## Epidemiology Prevalence is unknown but approximately 30 families have been reported to date. ## Clinical description Onset of the disease is usually at birth or in infancy. Blistering is often accompanied by mild nail dystrophy and focal palmoplantar keratoderma, and rarely by milia and mostly affects the limbs and trunk. ## Etiology Most EBS-MP cases are due to a missense mutation (p.P25L) within the KRT5 gene (12q13.13) encoding keratin 5, but rare cases resulting from other mutations in the KRT5 and KRT14 genes have also been reported. ## Genetic counseling Transmission is autosomal dominant and sporadic cases have been reported. ## Prognosis Although the disease can be severely disabling, life-expectancy is normal. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Epidermolysis bullosa simplex with mottled pigmentation	c0432316	30,562	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79397	2021-01-23T19:02:30	{"gard": ["9737"], "mesh": ["C535959"], "omim": ["131960"], "umls": ["C0432316"], "icd-10": ["Q81.0"], "synonyms": ["EBS-MP"]}
Camptodactyly of fingers is a rare, genetic, non-syndromic, congenital limb malformation disorder characterized by a painless, non-traumatic, non-neurogenic, often bilateral, permanent flexion contracture at the proximal interphalangeal joint of a postaxial finger, resulting in permanent volar inclination of the affected digit. The fifth finger is always involved, but additional digits might also be affected. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Camptodactyly of fingers	c1306668	30,563	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=295016	2021-01-23T18:56:31	{"omim": ["114200"], "icd-10": ["Q68.1"]}
A rare ophthalmic disorder characterized by generalized inflammation of all parts of the uveal tract (iris, ciliary body, and choroid), simultaneously involving adjacent vitreous and retina, without any predominant site of inflammation, due to viral, bacterial, fungal, or parasitic infections. Clinical symptoms include pain, photophobia, redness, blurring of vision, and floaters. Signs on examination are lid edema, ciliary injection, chemosis, keratic precipitates, cells in the anterior chamber, hypopyon, iris nodules and neovascularization, posterior synechiae, macular edema, vitreous and retinal hemorrhage, and retinal detachment, among others. Complications may result in visual loss. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Infectious panuveitis	None	30,564	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=279925	2021-01-23T17:46:10	{"icd-10": ["H44.1"]}
Tyrosinemia type 1 is a genetic disorder characterized by elevated blood levels of the amino acid tyrosine, a building block of most proteins. This condition is caused by a shortage of the enzyme fumarylacetoacetate hydrolase, one of the enzymes required for the multi-step process that breaks down tyrosine. This enzyme shortage is caused by mutations in the FAH gene. Symptoms usually appear in the first few months of life and include failure to thrive, diarrhea, vomiting, jaundice, cabbage-like odor, and increased tendency to bleed (particularly nosebleeds). Tyrosinemia type I can lead to liver and kidney failure, softening and weakening of the bones, problems affecting the nervous system, and an increased risk of liver cancer. This condition is inherited in an autosomal recessive manner. Treatment should be started as soon as the condition is diagnosed and includes a diet restricted in tyrosine and phenylalanine along with nitisinone, a medication that blocks the second step in the tyrosine degradation pathway. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Tyrosinemia type 1	c0268490	30,565	gard	https://rarediseases.info.nih.gov/diseases/2658/tyrosinemia-type-1	2021-01-18T17:57:15	{"mesh": ["D020176"], "omim": ["276700"], "orphanet": ["882"], "synonyms": ["Tyrosinemia type I", "Hepatorenal tyrosinemia", "Fumarylacetoacetase deficiency", "FAH deficiency"]}
A notifiable disease is any disease that is required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. In the case of livestock diseases, there may also be the legal requirement to kill the infected livestock upon notification. Many governments have enacted regulations for reporting of both human and animal (generally livestock) diseases. ## Contents * 1 Global * 1.1 Human * 1.2 Animal * 2 Australia * 2.1 Human * 2.2 Animal * 3 Brazil * 3.1 Human * 4 Canada * 4.1 Human * 5 France * 5.1 Human * 5.2 Animal * 6 New Zealand * 6.1 Human * 7 United Kingdom * 7.1 Human * 7.1.1 Children * 7.2 Animal * 8 United States * 9 See also * 10 References ## Global[edit] ### Human[edit] The World Health Organization's International Health Regulations 1969 require disease reporting to the organization in order to help with its global surveillance and advisory role. The current (1969) regulations are rather limited with a focus on reporting of three main diseases: cholera, yellow fever and plague.[1] Smallpox was a contagious disease during the 18th-20th century. It was endemic until mass vaccination, after which WHO certified Smallpox to be eradicated. This marked the first human disease to be successfully eradicated. The revised International Health Regulations 2005 broadens this scope and is no longer limited to the notification of specific diseases. Whilst it does identify a number of specific diseases, it also defines a limited set of criteria to assist in deciding whether an event is notifiable to WHO.[2][3] WHO states that "Notification is now based on the identification within a State Party’s territory of an "event that may constitute a public health emergency of international concern". This non-disease specific definition of notifiable events expands the scope of the IHR (2005) to include any novel or evolving risk to international public health, taking into account the context in which the event occurs. Such notifiable events can extend beyond communicable diseases and arise from any origin or source. This broad notification requirement aims at detecting, early on, all public health events that could have serious and international consequences, and preventing or containing them at source through an adapted response before they spread across borders."[4] ### Animal[edit] The OIE (World Organisation for Animal Health) monitors specific animal diseases on a global scale. * Diseases Notifiable to the OIE ## Australia[edit] ### Human[edit] The National Notifiable Diseases Surveillance System (NNDSS) was established in 1990. Notifications are made to the States or Territory health authority and computerised, de-identified records are then supplied to the Department of Health and Ageing for collation, analysis and publication.[5] The Australian national notifiable diseases list and case definitions are available online. For full list, see List of notifiable diseases. ### Animal[edit] Within Australia the Department of Agriculture, Fisheries and Forestry regulates the notification of infectious animal diseases. * National List of Notifiable Animal Diseases * State and Territory Notifiable Animal Diseases Lists ## Brazil[edit] ### Human[edit] Notification is regulated under Brazilian Ministry of Health Ordinance number 1.271 of June 6, 2014. * List of national notifiable diseases ## Canada[edit] ### Human[edit] * List of national notifiable diseases ## France[edit] ### Human[edit] The first policies of mandatory notifiable disease originated a long time ago in France, while exact times are unclear we know that at the end of the 18th century Plague was a highly enforced notifiable disease.[6] The current list of notifiable diseases is written in the Code de la santé publique Article D3113-6 and Article D3113-7 (last revision has been made in 2012), it contains 33 diseases : 31 infectious ones and 2 non-infectious disease directly linked to the environment (Lead poisoning and Mesothelioma). Notifications of both the disease and the distribution of specific medicine are made to a regional desk governmental agency called Agence régionale de santé by : * Physician and Biologists, both in public or in private workplaces, * Physician controllers (MISP) and Administratives civil-servant from Directions départementales des affaires sanitaires et sociales (DDASS), * Epidemiologists from the Institut de veille sanitaire (InVS), * Drugs sellers. Anonymous records are then used by the government health-insurance system. Ill people must cure them and in many case are put in quarantine. ### Animal[edit] Only infectious diseases are notifiable to the authorities. The complete list can be found in the Article L. 223-22 du code rural, it is updated with every new entry on World Organisation for Animal Health (OIE) lists A and B and with European Union mandatory lists. ## New Zealand[edit] ### Human[edit] Notification is regulated under the Health Act 1956, except for tuberculosis which is regulated under the Tuberculosis Act 1948. All diseases * List of national notifiable diseases ## United Kingdom[edit] Main article: Notifiable diseases in the United Kingdom ### Human[edit] Main article: UK statutory notification system Requirement for the notification of infectious diseases originated near the end of the 19th century. The list started with a few select diseases and has since grown to 31. Currently disease notification for humans in the UK is regulated under the Public Health (Control of Disease) Act 1984 and Public Health (Infectious Diseases) Regulations 1988. The governing body is Public Health England [7] [2] List of Notifiable Diseases can be found here [3]. #### Children[edit] There are also requirements for notification specific to children in the National standards for under 8s day care and childminding that state:[8] > "Office for Standards in Education should be notified of any food poisoning affecting two or more children looked after on the premises, any child having meningitis or the outbreak on the premises of any notifiable disease identified as such in the Public Health (Control of Disease) Act 1984 or because the notification requirement has been applied to them by regulations (the relevant regulations are the Public Health (Infectious Diseases) Regulations 1988). ### Animal[edit] In the UK notification of diseases in animals is regulated by the Animal Health Act 1981, as well as the Specified Diseases (Notification and Slaughter) Order 1992 (as amended) and Specified Diseases (Notification) Order 1996 (as amended). The act states that a police constable should be notified, however in practice a Defra divisional veterinary manager is notified and Defra will investigate.[9] * List of Notifiable Diseases ## United States[edit] In the past, notifiable diseases in the United States varied according to the laws of individual states. The Centers for Disease Control and Prevention (CDC) and the Council of State and Territorial Epidemiologists (CSTE) also produced a list of nationally notifiable diseases that health officials should report to the CDC's National Notifiable Diseases Surveillance System (NNDSS).[10] A uniform criterion for reporting diseases to the NNDSS was introduced in 1990.[11] See also: List of notifiable diseases and State health department ## See also[edit] * List of notifiable diseases * Public Health Emergency of International Concern * Disease surveillance ## References[edit] 1. ^ International Health Regulations Review - background 2. ^ WHO \| International Health Regulations 3. ^ WHO \| Frequently asked questions about the International Health Regulations 4. ^ \| Notification and other reporting requirements under the IHR (2005) IHR Brief No. 2 5. ^ Introduction to the National Notifiable Diseases Surveillance System 6. ^ Archives militaires de Vincennes,A 1 516 91 sc. 7. ^ [1] \| [General Information] 8. ^ HPA \| NOIDS \| Day Care and Child Minding (National Standards) 9. ^ Defra, UK - Disease surveillance and control - Notifiable diseases 10. ^ History and Background \| NNDSS 11. ^ "Centers for Disease Control and Prevention. Case definitions for public health surveillance" (PDF). 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Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Notifiable disease	None	30,566	wikipedia	https://en.wikipedia.org/wiki/Notifiable_disease	2021-01-18T18:49:03	{"wikidata": ["Q314676"]}
A number sign (#) is used with this entry because of evidence that susceptibility to IgA nephropathy-3 (IGAN3) is caused by heterozygous mutation in the SPRY2 gene (602466) on chromosome 13q31. One such family has been reported. For a phenotypic description and a discussion of genetic heterogeneity of IgA nephropathy, see IGAN1 (161950). Clinical Features Milillo et al. (2015) reported a 4-generation family of Sicilian descent with IgA nephropathy. Affected individuals had hypertension, proteinuria, and/or microhematuria. Renal biopsy, performed in 3 patients, showed IgA deposits. Two older patients had end-stage renal disease. Inheritance The transmission pattern of IGAN3 in the family reported by Milillo et al. (2015) was consistent with autosomal dominant inheritance. Molecular Genetics In affected members of a large Sicilian family with IGAN3, Milillo et al. (2015) identified a heterozygous missense mutation in the SPRY2 gene (R119W; 602466.0001). The mutation, which was found by exome sequencing, segregated with the disorder in family members over the age of 20 years; 3 family members under the age of 20 years did not have disease, although they were found to carry the mutation, suggesting age-dependent penetrance. Patient lymphoblastoid cells showed decreased amounts of SPRY2 mRNA, but normal protein levels resulting from increased stability of the mutant protein; there was no difference in the ratio between phosphorylated and nonphosphorylated forms compared to controls. Patient cells showed downregulation of the MAPK/ERK1/2 pathway. Cells from 2 unrelated patients with IgA nephropathy who did not have SPRY2 mutations also showed downregulation of the MAPK/ERK1/2 pathway, suggesting that it may be a common disease mechanism. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Hypertension GENITOURINARY Kidneys \- IgA nephropathy \- IgA deposition in the kidneys \- End-stage renal disease (in some patients) LABORATORY ABNORMALITIES \- Proteinuria \- Hematuria MISCELLANEOUS \- Onset after age 20 years \- Progressive disorder \- One family of Sicilian origin has been reported (last curated February 2016) MOLECULAR BASIS \- Caused by mutation in the sprouty RTK signaling antagonist 2 gene (SPRY2, 602466.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	IgA NEPHROPATHY, SUSCEPTIBILITY TO, 3	c4225194	30,567	omim	https://www.omim.org/entry/616818	2019-09-22T15:47:49	{"omim": ["616818"]}
Desmosterolosis is a condition that is characterized by neurological problems, such as brain abnormalities and developmental delay, and can also include other signs and symptoms. Children with desmosterolosis have delayed speech and motor skills (such as sitting and walking). Later in childhood, some affected individuals are able to walk with support; verbal communication is often limited to a few words or phrases. Common brain abnormalities in desmosterolosis include malformation of the tissue that connects the left and right halves of the brain (the corpus callosum) and loss of white matter, which consists of nerve fibers covered by a fatty substance called myelin. People with desmosterolosis commonly have muscle stiffness (spasticity) and stiff, rigid joints (arthrogryposis) affecting their hands and feet. Other features seen in some affected individuals include short stature, abnormal head size (either larger or smaller than normal), a small lower jaw (micrognathia), an opening in the roof of the mouth (cleft palate), involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus), heart defects, and seizures. ## Frequency The prevalence of desmosterolosis is unknown; at least 10 affected individuals have been described in the scientific literature. ## Causes Desmosterolosis is caused by mutations in the DHCR24 gene. This gene provides instructions for making an enzyme called 24-dehydrocholesterol reductase, which is involved in the production (synthesis) of cholesterol. Cholesterol is a waxy, fat-like substance that can be obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). It can also be produced in various tissues in the body. For example, the brain cannot access the cholesterol that comes from food, so brain cells must produce their own. Cholesterol is necessary for normal embryonic development and has important functions both before and after birth. DHCR24 gene mutations lead to the production of 24-dehydrocholesterol reductase with reduced activity. As a result, there is a decrease in cholesterol production. Because the brain relies solely on cellular production for cholesterol, it is most severely affected. Without adequate cholesterol, cell membranes are not formed properly and nerve cells are not protected by myelin, leading to the death of these cells. In addition, a decrease in cholesterol production has more severe effects before birth than during other periods of development because of the rapid increase in cell number that takes place. Disruption of normal cell formation before birth likely accounts for the additional developmental abnormalities of desmosterolosis. ### Learn more about the gene associated with Desmosterolosis * DHCR24 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Desmosterolosis	c1865596	30,568	medlineplus	https://medlineplus.gov/genetics/condition/desmosterolosis/	2021-01-27T08:25:28	{"gard": ["10283"], "mesh": ["C566555"], "omim": ["602398"], "synonyms": []}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (January 2021) Pneumothorax ex vacuo SpecialtyPulmonology Pneumothorax ex vacuo is a rare type of pneumothorax which forms adjacent to an atelectatic lobe.[1] It is seen preferentially with atelectasis of the right upper lobe and is the result of rapid atelectasis producing an abrupt decrease in the intrapleural pressure with subsequent release of nitrogen from pleural capillaries. ## Treatment[edit] Treatment consists of bronchoscopy rather than chest tube drainage. Radiographically, pneumothorax ex vacuo is suggested when an atelectatic lobe or lung, particularly right upper lobe atelectasis, is surrounded by a focal pneumothorax.[2] ## Related illness[edit] "Trapped lung" presents in the same way as pneumothorax ex vacuo and can occur in patients with visceral pleural thickening and following drainage of an effusion. ## References[edit] 1. ^ Ponrartana S, Laberge JM, Kerlan RK, Wilson MW, Gordon RL (2005). "Management of patients with "ex vacuo" pneumothorax after thoracentesis". Acad Radiol. 12 (8): 980–6. doi:10.1016/j.acra.2005.04.013. PMID 16087092. 2. ^ Staes W, Funaki B (2009). ""Ex vacuo" pneumothorax". Semin Intervent Radiol. 26 (1): 82–5. doi:10.1055/s-0029-1208386. PMC 3036450. PMID 21326535. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Pneumothorax ex vacuo	c1960446	30,569	wikipedia	https://en.wikipedia.org/wiki/Pneumothorax_ex_vacuo	2021-01-18T19:03:23	{"umls": ["C1960446"], "wikidata": ["Q7206014"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2017) Embryocardia SpecialtyNeonatology Embryocardia is a condition in which S1 and S2 (the two heart sounds that produce the typical "lubb-dubb" sound of the heart) become indistinguishable and equally spaced.[1] Thus the normal "lubb-dubb" rhythm of the heart becomes a "tic-toc" rhythm resembling the heart sounds of a fetus. This indicates a serious loss of natural fluctuation and often precedes a fatal collapse.[2][3] This condition is observed in myocarditis.[4] ## References[edit] 1. ^ Osler, Sir William; McCrae, Thomas (1908). Modern Medicine: Its Theory and Practice, in Original Contributions by American and Foreign Authors. Lea Brothers & Company. p. 275. Retrieved 7 March 2018. 2. ^ Pick, Alois (1911). Clinical Symptomatology. Appleton. p. 105. Retrieved 7 March 2018. "Embryocardia." 3. ^ "embryocardia". The Free Dictionary. Retrieved 22 November 2016. 4. ^ "Meaning of Embryocardia". Online Free Dictionary. Retrieved 18 March 2013. This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Embryocardia	c0232199	30,570	wikipedia	https://en.wikipedia.org/wiki/Embryocardia	2021-01-18T19:04:02	{"umls": ["C0232199"], "wikidata": ["Q16920320"]}
Nematode infection Deaths due to intestinal nematode infections per million persons in 2012 0-0 1-1 2-2 SpecialtyInfectious disease, helminthology A nematode infection is a type of helminthiasis caused by organisms in the nematode phylum.[1] An example is enterobiasis. Several antinematodal agents are available.[citation needed] ## References[edit] 1. ^ "Nematode Infections: Background, Pathophysiology, Epidemiology". 10 July 2019. Retrieved 22 July 2019. ## External links[edit] Classification D * ICD-10: B72-B80 * ICD-9-CM: 124-127 * MeSH: D009349 * v * t * e Parasitic disease caused by helminthiases Flatworm/ platyhelminth infection Fluke/trematode (Trematode infection) Blood fluke * Schistosoma mansoni / S. japonicum / S. mekongi / S. haematobium / S. intercalatum * Schistosomiasis * Trichobilharzia regenti * Swimmer's itch Liver fluke * Clonorchis sinensis * Clonorchiasis * Dicrocoelium dendriticum / D. hospes * Dicrocoeliasis * Fasciola hepatica / F. gigantica * Fasciolosis * Opisthorchis viverrini / O. felineus * Opisthorchiasis Lung fluke * Paragonimus westermani / P. kellicotti * Paragonimiasis Intestinal fluke * Fasciolopsis buski * Fasciolopsiasis * Metagonimus yokogawai * Metagonimiasis * Heterophyes heterophyes * Heterophyiasis Cestoda (Tapeworm infection) Cyclophyllidea * Echinococcus granulosus / E. multilocularis * Echinococcosis * Taenia saginata / T. asiatica / T. solium (pork) * Taeniasis / Cysticercosis * Hymenolepis nana / H. diminuta * Hymenolepiasis Pseudophyllidea * Diphyllobothrium latum * Diphyllobothriasis * Spirometra erinaceieuropaei * Sparganosis * Diphyllobothrium mansonoides * Sparganosis Roundworm/ Nematode infection Secernentea Spiruria Camallanida * Dracunculus medinensis * Dracunculiasis Spirurida Filarioidea (Filariasis) * Onchocerca volvulus * Onchocerciasis * Loa loa * Loa loa filariasis * Mansonella * Mansonelliasis * Dirofilaria repens * D. immitis * Dirofilariasis * Wuchereria bancrofti / Brugia malayi / \|B. timori * Lymphatic filariasis Thelazioidea * Gnathostoma spinigerum / G. hispidum * Gnathostomiasis * Thelazia * Thelaziasis Spiruroidea * Gongylonema Strongylida (hookworm) * Hookworm infection * Ancylostoma duodenale / A. braziliense * Ancylostomiasis / Cutaneous larva migrans * Necator americanus * Necatoriasis * Angiostrongylus cantonensis * Angiostrongyliasis * Metastrongylus * Metastrongylosis Ascaridida * Ascaris lumbricoides * Ascariasis * Anisakis * Anisakiasis * Toxocara canis / T. cati * Visceral larva migrans / Toxocariasis * Baylisascaris * Dioctophyme renale * Dioctophymosis * Parascaris equorum Rhabditida * Strongyloides stercoralis * Strongyloidiasis * Trichostrongylus spp. * Trichostrongyliasis * Halicephalobus gingivalis Oxyurida * Enterobius vermicularis * Enterobiasis Adenophorea * Trichinella spiralis * Trichinosis * Trichuris trichiura (Trichuriasis / Whipworm) * Capillaria philippinensis * Intestinal capillariasis * C. hepatica This parasitic animal\- related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Nematode infection	c0027583	30,571	wikipedia	https://en.wikipedia.org/wiki/Nematode_infection	2021-01-18T19:06:54	{"mesh": ["D009349"], "icd-9": ["124", "127"], "icd-10": ["B80", "B72"], "wikidata": ["Q2072680"]}
Urushiol-induced contact dermatitis SpecialtyDermatology Urushiol-induced contact dermatitis (also called Toxicodendron dermatitis or Rhus dermatitis) is a type of allergic contact dermatitis caused by the oil urushiol found in various plants, most notably species of the genus Toxicodendron: poison ivy, poison oak, poison sumac, and the Chinese lacquer tree. The name is derived from the Japanese word for the sap of the Chinese lacquer tree, urushi. Other plants in the sumac family (including mango, pistachio, the Burmese lacquer tree, the India marking nut tree, and the shell of the cashew) also contain urushiol,[1] as do unrelated plants such as Ginkgo biloba.[2] As is the case with all contact dermatitis, urushiol-induced allergic rashes are a Type IV hypersensitivity reaction, also known as delayed-type hypersensitivity. Symptoms include itching, inflammation, oozing, and, in severe cases, a burning sensation. The American Academy of Dermatology estimates that there are up to 50 million cases of urushiol-induced dermatitis annually in the United States alone, accounting for 10% of all lost-time injuries in the United States Forest Service. Poison oak is a significant problem in the rural Western and Southern United States, while poison ivy is most rampant in the Eastern United States. Dermatitis from poison sumac is less common. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Mechanism * 4 Treatments * 4.1 Further observations * 5 Prevention * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Urushiol causes an eczematous contact dermatitis characterized by redness, swelling, papules, vesicles, blisters, and streaking.[3] People vary greatly in their sensitivity to urushiol. In approximately 15%[4] to 30%[5] of people, urushiol does not trigger an immune system response, while at least 25% of people have a very strong immune response resulting in severe symptoms. Since the skin reaction is an allergic one, people may develop progressively stronger reactions after repeated exposures, or have no immune response on their first exposure but show sensitivity on subsequent exposures.[citation needed] Approximately 80% to 90% of adults will get a rash if they are exposed to 50 micrograms of purified urushiol. Some people are so sensitive that it only takes a trace of urushiol (two micrograms, or less than one ten-millionth of an ounce) on the skin to initiate an allergic reaction.[6] The rash takes one to two weeks to run its course and may cause scars, depending on the severity of the exposure. Severe cases involve small (1–2 mm), clear, fluid-filled blisters on the skin. Pus-filled vesicles containing a whitish fluid may indicate an infection. Most poison ivy rashes, without infections, will resolve within 14 days without treatment. Excessive scratching may result in infection, commonly by staphylococcal and streptococcal species; these may require antibiotics. * Severe allergic reaction to urushiol (poison oak) 4 days after exposure. * Blistering 48 hours after urushiol contact. * Poison ivy rash after 2 days. * Poison ivy rash with swelling about 3 days after direct contact. ## Cause[edit] Toxicodendron pubescens (Atlantic poison oak), one of a large number of species containing urushiol irritants. Urushiol-induced contact dermatitis is caused by contact with a plant or any other object containing urushiol oil. The oil adheres to almost anything with which it comes in contact, such as towels, blankets, clothing, and landscaping tools. Clothing or other materials that touch the plant and then, before being washed, touch the skin are common causes of exposure. For people who have never been exposed or are not yet allergic to urushiol, it may take 10 to 21 days for a reaction to occur the first time. Once allergic to urushiol, however, most people break out 48 to 72 hours after contact with the oil. Typically, individuals have been exposed at least once, if not several times, before they develop a rash.[7] The rash typically persists one to two weeks, but in some cases may last up to five weeks. Urushiol is primarily found in the spaces between cells beneath the outer skin of the plant, so the effects are less severe if the plant tissue remains undamaged on contact. Once the oil and resin are thoroughly washed from the skin, the rash is not contagious. Urushiol does not always spread once it has bonded with the skin, and cannot be transferred once the urushiol has been washed away. Although simple skin exposure is most common, ingestion of urushiol can lead to serious, systemic reactions. Burning plant material is commonly said to create urushiol-laden smoke that causes a systemic reaction, as well as a rash in the throat and eyes. Firefighters often get rashes and eye inflammation from smoke-related contact.[8] A high-temperature bonfire may incinerate urushiol before it can cause harm, while a smoldering fire may vaporize the volatile oil and spread it as white smoke. However, some sources dispute the danger of burning urushiol-containing plant material.[9] ## Mechanism[edit] Play media A video describing the mechanism of action for poison ivy and other plants containing urushiol. Urushiols are oxidized in-vivo, generating a quinone form of the molecules.[10][non-primary source needed] The toxic effect is indirect, mediated by an induced immune response. The oxidized urushiols act as haptens, chemically reacting with, binding to, and changing the shape of integral membrane proteins on exposed skin cells. Affected proteins interfere with the immune system's ability to recognize these cells as normal parts of the body, causing a T-cell-mediated immune response.[11] This response is directed at the complex of urushiol derivatives (namely, pentadecacatechol) bound in the skin proteins, attacking the cells as if they were foreign bodies. ## Treatments[edit] Treatment consists of two phases: stopping the urushiol contact that is causing the reaction (this must be done within minutes)[12] and, later, reducing the pain and/or itching.[6][13] Primary treatment involves washing exposed skin thoroughly with soap, cool water, and friction as soon as possible after exposure is discovered. Soap or detergent is necessary because urushiol is an oil; friction, with a washcloth or something similar, is necessary because urushiol adheres strongly to the skin.[14] Commercial removal preparations, which are available in areas where poison ivy grows, usually contain surfactants, such as the nonionic detergent Triton X-100, to solubilize urushiol; some products also contain abrasives. The U.S. Food and Drug Administration recommends applying a wet compress or soaking the affected area in cool water; topical corticosteroids (available over-the-counter) or oral corticosteroids (available by prescription); and topical skin protectants, such as zinc acetate, zinc carbonate, zinc oxide, and calamine. Baking soda or colloidal oatmeal can relieve minor irritation and itching. Aluminium acetate, sometimes known as Burow's solution, can also ease the rash.[15] Showers or compresses using hot (but not scalding) water can relieve itching for up to several hours, though this "also taxes the skin's integrity, opening pores and generally making it more vulnerable", and is only useful for secondary treatment (not for cleaning urushiol from the skin, which should be done with cold water).[16] People who have had a prior systemic reaction may be able to prevent subsequent exposure from turning systemic by avoiding heat and excitation of the circulatory system and applying moderate cold to any infected skin with biting pain. Antihistamine creams, or oral antihistamines, do not alleviate the itching of a developed urushiol-induced contact rash. This is because of the underlying histamine-independent physiology of a Type IV hypersensitivity reaction. The sleepiness that first generation oral antihistamines (i.e., diphenhydramine and other first generation H1 antagonists) produce may help people ignore the itch during the night, but do not stop nighttime scratching and may actually decrease overall sleep quality.[17] In cases of extreme symptoms, steroids such as prednisone, triamcinolone, or dexamethasone are sometimes administered to attenuate the immune response and prevent long-term skin damage, especially if the eyes are involved. Prednisone is the most commonly prescribed systemic treatment but can cause serious adrenal suppression, so it must be taken carefully and tapered off slowly.[18] If bacterial secondary infection of affected areas occurs, antibiotics may also be necessary. Scrubbing with plain soap and cold water will remove urushiol from skin if it is done within a few minutes of exposure.[12] Many home remedies and commercial products (e.g., Tecnu, Zanfel) also claim to prevent urushiol rashes after exposure. A study that compared Tecnu ($1.25/oz.) with Goop Hand Cleaner or Dial Ultra Dishwashing Soap ($0.07/oz.) found that differences among the three—in the range of 56–70% improvement over no treatment—were nonsignificant (P > 0.05), but that improvement over no treatment was significant at the same level of confidence.[19] ### Further observations[edit] * Ordinary laundering with laundry detergent will remove urushiol from most clothing[20] but not from leather or suede.[citation needed] * Urushiol oil left on clothing and surfaces can be deactivated using bleach.[21] * The fluid from the resulting blisters does not spread urushiol to others.[22][23] * Blisters should be left unbroken during healing.[24] * Poison ivy and poison oak are still harmful when the leaves have fallen off, as the toxic residue is persistent, and exposure to any parts of plants containing urushiol can cause a rash at any time of the year.[12] * Ice, cold water, cooling lotions, and cold air do not help cure poison ivy rashes, but cooling can reduce inflammation and soothe the itch.[20][dead link] * Results for jewelweed as a natural agent for treatment are conflicting. Some studies indicate that it "failed to decrease symptoms of poison ivy dermatitis" [1980] and had "no prophylactic effect" [1997].[25] The juice of the leaves and stems of Impatiens capensis is a traditional Native American remedy for skin rashes, including poison ivy.[26] A peer-reviewed study in 2012 suggests the mechanism of action may be saponins in the plant acting in a manner similar to soap. The study further indicates soap is more effective and should be preferred if available.[27] ## Prevention[edit] A rarely cited double-blind study in 1982 reported that a course of oral urushiol usually hyposensitized subjects.[28] ## See also[edit] Wikimedia Commons has media related to Urushiol-induced contact dermatitis. * Anti-itch drug * Toxin * List of cutaneous conditions ## References[edit] 1. ^ Gross, Michael; Baer, Harold; Fales, Henry M (1975). "Urushiols of poisonous anacardiaceae". Phytochemistry. 14 (10): 2263. doi:10.1016/S0031-9422(00)91113-0. 2. ^ Lepoittevin, J.-P., Benezra, C., Asakawa, Y. 1989. Allergic contact dermatitis to Ginkgo biloba L.: relationship with urushiol. Arch. Dermatol. Res., 281: 227-230. 3. ^ DermAtlas -1892628434 4. ^ Wilson, Stephanie (2005-09-23). "Howstuffworks "How Poison Ivy Works"". Science.howstuffworks.com. Retrieved 2010-06-04. 5. ^ Michael Rohde. "Contact-Poisonous Plants of the World". Mic-ro.com. Retrieved 2010-06-04. 6. ^ a b "Poison Oak". Waynesword.palomar.edu. 2011-01-16. Retrieved 2015-10-06. 7. ^ Ray, Thomas MD, Professor Emeritus of Dermatology. "Poison Ivy: The Most Common of Allergens". University of Iowa Health Care. Archived from the original on 12 January 2016. Retrieved 30 October 2015. 8. ^ "FIREFIGHTERS BATTLE HIDDEN DANGERS THIS WILDFIRE SEASON: POISON OAK, IVY AND SUMAC PLANTS TOP CAUSE OF DISABILITY, SICK TIME". Fireengineering.com. 26 July 2005. Retrieved 2015-10-06. 9. ^ Dietrich Frohne; Hans Jurgen Pfander (1984). A Colour Atlas of Poisonous Plants: A Handbook for Pharmacists, Doctors, Toxicologists, and Biologists. Wolfe Publishing Ltd. p. 291 pp. ISBN 978-0-7234-0839-0. 10. ^ Kalergis, Alexis M; López, Carolina B; Becker, Maria I; Diaz, Marisol I; Sein, Jorge; Garbarino, Juan A; De Ioannes, Alfredo E (Jan 1997). "Modulation of fatty acid oxidation alters contact hypersensitivity to urushiols: role of aliphatic chain beta-oxidation in processing and activation of urushiols". J Invest Dermatol. 108 (1): 57–61. doi:10.1111/1523-1747.ep12285632. PMID 8980288. 11. ^ C.Michael Hogan (2008) Western poison-oak: Toxicodendron diversilobum, GlobalTwitcher, ed. Nicklas Stromberg "Archived copy". Archived from the original on 2009-07-21. Retrieved 2010-04-21.CS1 maint: archived copy as title (link) 12. ^ a b c Bill Einsig, Bill (2002), Poison Ivy Myth: Science, Environment and Ecology Flash for Educators (No. 341), in Keystone Outdoors Magazine (May 11), excerpted by the Penn State Integrated Pest Management, accessed 7 October 2015. 13. ^ "Soothing Remedies for Poison Ivy and Poison Oak". Googobits.com. 2005-08-04. Retrieved 2010-06-04. 14. ^ "How to never have a serious poison ivy rash again" on YouTube 15. ^ [1] Archived July 16, 2010, at the Wayback Machine 16. ^ Hauser, Susan Carol; William L. Epstein (2008). A Field Guide to Poison Ivy, Poison Oak, and Poison Sumac. Globe Pequot. p. 60. ISBN 978-0-7627-4741-2. Retrieved 2010-11-21. 17. ^ Prok, Lori. "Poison Ivy: Beyond the Basics". UpToDate. Retrieved 22 July 2020. 18. ^ "Poison Ivy, Oak, and Sumac". Surviveoutdoors.com. Retrieved 2010-06-04. 19. ^ Stibich, A. S.; Yagan, M.; Sharma, V.; Herndon, B. & Montgomery, C. (2001). "Cost-effective post-exposure prevention of poison ivy dermatitis". International Journal of Dermatology. 39 (7): 515–518. doi:10.1046/j.1365-4362.2000.00003.x. PMID 10940115. S2CID 2958342. 20. ^ a b "Aetna InteliHealth: Featuring Harvard Medical School's Consumer Health Information". Intelihealth.com. Archived from the original on February 11, 2012. Retrieved 6 October 2015. 21. ^ Chastant, Lisa Renee; Davis, Thomas; Libow, Lester (2018-01-16). "Black-spot poison ivy, a report of 3 cases with clinicopathologic correlation". JAAD Case Reports. 4 (2): 140–142. doi:10.1016/j.jdcr.2017.09.035. ISSN 2352-5126. PMC 5789763. PMID 29387766. 22. ^ "Poison ivy, oak, and sumac". American Academy of Dermatology. 23. ^ "Outsmarting Poison Ivy and Other Poisonous Plants". U.S. Food and Drug Administration. 16 August 2019. 24. ^ "Poison Ivy, Oak and Sumac". OutDoorPlaces.com. Retrieved 22 September 2010. 25. ^ Shenefelt, Philip D. (2011). "Herbal Treatment for Dermatologic Disorders". Herbal Medicine. Herbal Medicine: Biomolecular and Clinical Aspects. Oxidative Stress and Disease. 20115386 (2nd ed.). Boca Raton, Florida, USA: CRC Press. pp. 383–403. doi:10.1201/b10787-19. ISBN 9781439807132. PMID 22593930. Retrieved October 5, 2015. 26. ^ Smith, Huron H., 1933, Ethnobotany of the Forest Potawatomi Indians, Bulletin of the Public Museum of the City of Milwaukee 7:1-230, page 42 27. ^ Motz; Bowers; Young; Kinder (2012). "The effectiveness of jewelweed, Impatiens capensis, the related cultivar I. balsamina and the component, lawsone in preventing post poison ivy exposure contact dermatitis". Journal of Ethnopharmacology. 143 (1): 314–318. doi:10.1016/j.jep.2012.06.038. PMID 22766473. 28. ^ Epstein, W. L.; Byers, V. S.; Frankart, W. (1982-09-01). "Induction of antigen specific hyposensitization to poison oak in sensitized adults". Archives of Dermatology. 118 (9): 630–633. doi:10.1001/archderm.1982.01650210010008. ISSN 0003-987X. PMID 06180687. ## External links[edit] Classification D * ICD-10: L23.7 * ICD-9-CM: 692.6 * MeSH: D011040 * DiseasesDB: 32755 External resources * eMedicine: emerg/452 * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Urushiol-induced contact dermatitis	c0032342	30,572	wikipedia	https://en.wikipedia.org/wiki/Urushiol-induced_contact_dermatitis	2021-01-18T18:52:48	{"mesh": ["D011040"], "umls": ["C0032342"], "icd-9": ["692.6"], "icd-10": ["L23.7"], "wikidata": ["Q7901561"]}
A number sign (#) is used with this entry because infantile parkinsonism-dystonia-1 (PKDYS1) is caused by homozygous or compound heterozygous mutation in the SLC6A3 gene (126455), which encodes a dopamine transporter (DAT1), on chromosome 5p15. Description Infantile parkinsonism-dystonia, also known as dopamine transporter deficiency syndrome (DTDS), is an autosomal recessive complex motor neurologic disorder with onset in infancy. Affected individuals show hyperkinesia with orolingual and limb dyskinesia, dystonia, and chorea, or hypokinesia with parkinsonian features, such as bradykinesia, rigidity, and tremor. Other features may include axial hypotonia, pyramidal tract signs, and eye movement abnormalities. Many patients are misdiagnosed as having cerebral palsy. Cognitive function appears to be less severely affected, but most patients die in the teenage years. There is no effective treatment. Laboratory studies show an increased ratio of homovanillic acid (HVA) to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), which represents an increased ratio of dopamine to serotonin metabolites (review by Kurian et al., 2011). ### Genetic Heterogeneity of Infantile Parkinsonism-Dystonia See also PKDYS2 (618049), caused by mutation in the SLC18A2 gene (193001) on chromosome 10q25. For an overlapping phenotype, see tyrosine hydroxylase deficiency (605407), also known as autosomal recessive Segawa syndrome. Clinical Features Kurian et al. (2009) reported 2 unrelated but consanguineous families in which 3 individuals had infantile onset of parkinsonism and dystonia. One family was of Pakistani origin and the other of European descent. Two patients were initially misdiagnosed with cerebral palsy. All had features of progressive parkinsonism, dystonia, pyramidal tract signs, and hypertonicity at examination between 6 and 12 months of age. There was evidence of global developmental delay, but later studies showed no psychiatric or behavioral abnormalities. CSF analysis showed markedly elevated concentrations of HVA, with normal 5-HIAA levels. All patients showed a poor clinical response to multiple therapeutic agents. All parents were unaffected. Kurian et al. (2011) reported 11 children with dopamine transporter deficiency confirmed by genetic analysis, including the 3 patients reported by Kurian et al. (2009). The patients were ascertained from 7 pediatric neurology centers. All children presented with a movement disorder with onset in early infancy (range 0.5 to 7 months). Before diagnosis, 7 children had been misdiagnosed with cerebral palsy. Symptoms were somewhat variable, but included neonatal irritability and early feeding difficulties, a hyperkinetic syndrome with dystonia and chorea, a predominantly hypokinetic syndrome with parkinsonism, or a mixed hyperkinetic and hypokinetic movement disorder. Other prominent features were axial hypotonia, orolingual dyskinesia, pyramidal tract symptoms, eye movement abnormalities, choreiform movements, dystonia, including status dystonicus with oculogyric crises, and gastrointestinal complications. Parkinsonian symptoms, such as bradykinesia, rigidity, hypomimia, and tremor, tended to occur later. All patients had cognitive impairment and lack of speech, but reception and understanding were good. CSF analysis showed an increased HVA:HIAA ratio in all patients. One patient who underwent testing showed complete loss of DAT activity in the basal ganglia on DaTSCAN imaging. There was no effective and sustained treatment for the symptoms. Four patients died between 9 and 16 years of age. Puffenberger et al. (2012) reported 2 Mennonite sisters with infantile parkinsonism-dystonia. The proband developed irritability and feeding difficulties soon after birth, followed by generalized rigidity and dystonia during early infancy. She had impaired motor development and severe rigid parkinsonism by late childhood. She could not speak or use her hands to communicate, and it was difficult to assess cognitive function or thought content. Brain structure was normal. Cerebrospinal fluid showed increased HVA. Treatment with L-DOPA was ineffective. A similarly affected sister had died. Inheritance The transmission pattern of PKDYS in the families reported by Kurian et al. (2009) and Puffenberger et al. (2012) was consistent with autosomal recessive inheritance. Molecular Genetics By linkage analysis followed by candidate gene sequencing of a consanguineous Pakistani family with infantile parkinsonism-dystonia, Kurian et al. (2009) identified a homozygous mutation (L368Q; 126455.0002) in the SLC6A3 gene. A similarly affected individual from a second family had a different homozygous mutation (P395L; 126455.0003). In vitro functional expression studies showed that both mutant proteins had no dopamine uptake activity. In 8 unrelated patients with dopamine transporter deficiency syndrome, Kurian et al. (2011) identified homozygous or compound heterozygous mutations in the SLC6A3 gene (see, e.g., 126455.0005-126455.0007). None of the patients shared a mutation, suggesting the absence of mutational hotspots. In vitro functional expression studies in HEK293 cells showed that the mutations caused a loss of transporter function and decreased expression of the normal protein. By homozygosity mapping followed by exome sequencing of a Mennonite family in which 2 sisters had infantile parkinsonism-dystonia, Puffenberger et al. (2012) identified a homozygous splice site mutation in the SLC6A3 gene (126455.0004). No carriers of this mutation were found among 201 Mennonite control samples. Pathogenesis This disorder is due to loss of function of the presynaptic dopamine transporter. Defective reuptake of dopamine is thought to lead to accumulation of dopamine in the synapse, which is catabolized and causes increased CSF levels of HVA. Poor dopamine reuptake leads to depletion of presynaptic stores of dopamine for extraneuronal release. Excess extraneuronal dopamine may also result in decreased production of dopamine and to downregulation or desensitization of dopamine receptors, thus mimicking dopamine deficiency (review by Kurian et al., 2011). INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Masked facies Eyes \- Ocular flutter \- Eye movement disorder \- Oculogyric crises Mouth \- Orolingual dyskinesia ABDOMEN Gastrointestinal \- Feeding difficulties \- Gastroesophageal reflux \- Constipation NEUROLOGIC Central Nervous System \- Gross motor delay \- Hypokinetic movements \- Hyperkinetic movements \- Lack of speech development \- Chorea \- Parkinsonism \- Dystonia \- Developmental delay, global \- Rigidity \- Tremor \- Bradykinesia \- Truncal hypotonia \- Limb dystonia \- Dyskinesia \- Hypertonicity \- Pyramidal tract signs LABORATORY ABNORMALITIES \- Increased CSF homovanillic acid (HVA) \- Normal CSF 5-hydroxyindoleacetic acid (5-HIAA) MISCELLANEOUS \- Onset in early infancy \- Progressive disorder \- Decreased life expectancy \- Death often in the teenage years \- Poor response to L-DOPA MOLECULAR BASIS \- Caused by mutation in the solute carrier family 6 (dopamine neurotransmitter transporter), member 3 gene (SLC6A3, 126455.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	PARKINSONISM-DYSTONIA, INFANTILE, 1	c2751067	30,573	omim	https://www.omim.org/entry/613135	2019-09-22T15:59:34	{"mesh": ["C567730"], "omim": ["613135"], "orphanet": ["238455"], "synonyms": ["Alternative titles", "PKDYS", "DOPAMINE TRANSPORTER DEFICIENCY SYNDROME"], "genereviews": ["NBK442323"]}
A form of lissencephaly with cerebellar hypoplasia characterized by subtle microcephaly, hypotonia and neurological and cognitive development delay. Hippocampal malformation is a characteristic imaging feature of this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Lissencephaly with cerebellar hypoplasia type B	c4274993	30,574	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100012	2021-01-23T17:36:52	{"icd-10": ["Q04.3"]}
Familial HDL deficiency is a rare genetic condition that causes low levels of "good" cholesterol (HDL) in the blood. HDL helps remove excess cholesterol and fats from your blood. People with familial HDL deficiency may develop cardiovascular disease at a relatively young age, often before age 50. This condition is caused by changes in the ABCA1 or the APOA1 genes. The deficiency is passed through families in an autosomal dominant pattern. More severely reduced levels of HDL in the blood is a characteristic feature of a related disorder called Tangier disease. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Familial HDL deficiency	c0342898	30,575	gard	https://rarediseases.info.nih.gov/diseases/2872/familial-hdl-deficiency	2021-01-18T18:00:34	{"omim": ["604091"], "orphanet": ["425"], "synonyms": ["Hypoalphalipoproteinemia, familial", "FHA", "High density lipoprotein deficiency", "HDLD", "Hypoalphalipoproteinemia, primary", "FHD"]}
A number sign (#) is used with this entry because of evidence that Axenfeld-Rieger syndrome type 1 (RIEG1) is caused by heterozygous mutation in the homeobox transcription factor gene PITX2 (601542) on chromosome 4q25. Description Axenfeld-Rieger syndrome is an autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals (Fitch and Kaback, 1978). Systemic anomalies are associated, including dental hypoplasia, failure of involution of periumbilical skin, and maxillary hypoplasia (Alkemade, 1969). ### Genetic Heterogeneity of Axenfeld-Rieger Syndrome Linkage studies indicate that a second type of Axenfeld-Rieger syndrome maps to chromosome 13q14 (RIEG2; 601499). A third form of Axenfeld-Rieger syndrome (RIEG3; 602482) is caused by mutation in the FOXC1 gene (601090) on chromosome 6p25. See 109120 for a form of Axenfeld-Rieger syndrome associated with partially absent eye muscles, hydrocephalus, and skeletal abnormalities. Nomenclature Alward (2000) reviewed the clinical features and molecular genetics of Axenfeld-Rieger syndrome and related disorders, noting that mutations in the 2 causative genes that had been identified, PITX2 and FOXC1, result in a wide variety of overlapping ocular phenotypes. Sowden (2007) reviewed the molecular and developmental mechanisms of anterior segment dysgenesis and stated that the umbrella term Axenfeld-Rieger syndrome is best applied to the range of conditions with overlapping clinical features most commonly associated with PITX2 and FOXC1 mutations. Clinical Features Hypodontia with malformation of the anterior chamber of the eye was recognized as a dominantly inherited disorder by Rieger (1935, 1941). The ocular features are microcornea with opacity, hypoplasia of the iris, and anterior synechiae. In 5 generations of a family, Busch et al. (1960) found myotonic dystrophy as a consistently associated feature. Others have not found myotonia. Pearce and Kerr (1965) studied a large kindred with many affected members and emphasized the variability in expression of the syndrome. A less well-known component of this syndrome is anal stenosis (Crawford, 1967; Brailey, 1890). Alkemade (1969) amply confirmed autosomal dominant inheritance. He pointed out characteristic facies consisting of broad nasal root with telecanthus and maxillary hypoplasia with protruding lower lip. A mother and 2 of her 3 children had severe developmental anomalies of the iris, associated with maldevelopment of the ear and maxilla, umbilical hernia and anal stenosis. Glaucoma occurred in all 3 patients. It is doubtful that Axenfeld anomaly (defects limited to the peripheral anterior segment of the eye) should be considered a separate entity. It is one feature of Rieger syndrome. Feingold et al. (1969) observed 6 cases in 3 generations with male-to-male transmission. De Hauwere et al. (1973) proposed that Rieger anomaly (peripheral abnormalities of the anterior segment with additional changes in the iris) with orbital hypertelorism and psychomotor retardation is a separate syndrome; see 109120. Jorgenson et al. (1978) pointed out that 'failure of involution of the periumbilical skin' is a cardinal feature. Surgery for umbilical hernia had been performed in several. Friedman (1985) described the distinctive umbilical changes of Aarskog syndrome, Rieger syndrome, and Robinow syndrome. He quoted the famous monograph on the umbilicus by Cullen (1916) which has illustrations by Max Broedel. Toppare et al. (1995) in Turkey measured the length of the periumbilical skin in 304 newborn babies. On the cranial side of the base of the umbilical cord the skin measured 12.36 (SD 3.23) mm and the caudal umbilical skin measured 8.76 (SD 3.10) mm on the average. Toppare et al. (1995) suggested that if the cranial skin measurement is greater than 2 standard deviations beyond the mean, i.e., greater than 18.82 mm, Rieger syndrome should be considered. Chisholm and Chudley (1983) reported a kindred with affected persons in 4 generations. Iridogoniodysgenesis was present in 10 persons, of whom 5 had established glaucoma. Somatic malformations were present in 5 persons in the third and fourth generations who did not have iridogoniodysgenesis. Nonocular features included characteristic facies (maxillary hypoplasia, short philtrum, and protruding lower lip of mild prognathism), dental anomalies (microdontia, hypodontia, and cone-shaped teeth), failure of involution of the umbilicus (often treated surgically in the neonatal period because of confusion with umbilical hernia), surgery for inguinal hernia in 8 persons, and hypospadias present in 4 males. Brooks et al. (1989) described Rieger anomaly together with other anomalies and suggested that it represented a previously unreported syndrome. The patient, a sporadic case born to nonconsanguineous, young parents, had bilateral microcondyles and bilateral choanal atresia as well as anal atresia, scoliosis, kyphosis, and short stature. Dental findings included severe enamel hypoplasia, conical and misshapen teeth, hypodontia, and impactions. The maxilla and mandible were underdeveloped. Chromosome studies were not reported. Brooks et al. (1989) suggested that this 'new' syndrome be called the short-FRAME syndrome for short stature, facial anomalies, Rieger anomaly, midline anomalies, and enamel defects. Mapping Shiang et al. (1987) studied DNA from a patient with a Rieger syndrome-like phenotype associated with a deletion at 4q23-q27. They found that probes for EGF (131530) and IL2 (147680) were deleted, whereas probes for ADH3 (ADH1C; 103710) were missing in a cell line that contained only the region of chromosome 4 from q25-qter. The patient had iris coloboma and delayed dentition in addition to other multiple anomalies. Since EGF and IL2 were deleted in the patient and FGFB (134920) may also be located in this region, they are possible candidate genes for Rieger syndrome. Vaux et al. (1992) described a baby with features of Rieger syndrome associated with a de novo interstitial deletion of 4q that included band 4q26 and an adjoining Giemsa light band, either q25 or q27. Vaux et al. (1992) concluded that the Rieger syndrome locus is located in either 4q25 or 4q27 inasmuch as Motegi et al. (1988) found no signs of Rieger syndrome in a patient with deletion of band 4q26. Fryns and van den Berghe (1992) likewise found a deletion of the G-dark band 4q26 and of part of the G-light band 4q25 in a 4.5-year-old patient with Rieger syndrome and mental retardation. Using a group of highly polymorphic short tandem repeat polymorphisms (STRP), including a tetranucleotide repeat for EGF, Murray et al. (1992) identified linkage of Rieger syndrome to 4q markers. Tight linkage to EGF supported its role as a candidate gene, although a recombinant in an unaffected individual had been identified. It is possible that this unaffected person in fact carried the gene, which in him was nonpenetrant. The possibility that autosomal dominant iris hypoplasia associated with early-onset glaucoma (137600) is allelic to Rieger syndrome was raised by the demonstration of Heon et al. (1995) of linkage to the same chromosomal region, 4q25. They studied a large family of Scandinavian descent who had a 5-generation history of iris hypoplasia. Iris hypoplasia was found in 15 individuals, 9 of whom had associated glaucoma. The highest observed lod score was 3.70 at theta = 0.0 for marker D4S1616. In a mother with Rieger syndrome and polycystic ovaries (see 184700) and a son manifesting SHORT syndrome (269880), Karadeniz et al. (2004) identified a t(1;4)(q31.2;q25) translocation. The authors suggested that these syndromes may represent a single condition reflecting variable expression of the PITX2 gene. Makita et al. (1995) described a boy with Rieger syndrome who had an apparently balanced reciprocal translocation between chromosomes 1 and 4. The clinical manifestations included irregular shaped pupils with a prominent Schwalbe line and an umbilical hernia. On cytogenetic studies, he was found to have a de novo reciprocal translocation 46,XY,t(1;4)(q23.1;q25), without visible deletion. Walter et al. (1996) performed linkage analysis in the family originally described by Chisholm and Chudley (1983), in which iridogoniodysgenesis was combined with somatic abnormalities, and obtained a peak lod score of 7.827 (theta = 0.00) at D4S407 on chromosome 4q25. Flomen et al. (1997) localized the proximal breakpoint of the constitutional deletion 4q in association with Rieger syndrome reported by Ligutic et al. (1981). They also described a new family with a de novo balanced reciprocal translocation t(4;12)(q25;q15) segregating with full Rieger syndrome in 2 generations. Using fluorescence in situ hybridization and P1 artificial chromosomes (PACs) as probes, Flomen et al. (1997) localized both the deletion and the translocation breakpoints between genetic markers that are known to be strongly linked to Rieger syndrome. They mapped both the proximal deletion breakpoint and the translocation breakpoint within a region between 2 groups of PACs bearing the markers for D4S2945 (on the centromeric side) and D4S193 and D4S2940 (on the telomeric side). ### Genetic Heterogeneity Nielsen and Tranebjaerg (1984) found partial monosomy of 21q22.2 in a case of Rieger syndrome. The patient had mental retardation, prominent occiput, enophthalmos, atresia of the right lacrimal duct, displaced anal opening, and supernumerary ribs. The mother had congenital stenosis of the lacrimal ducts. The proband had normal superoxide dismutase-1 (147450), confirming that the deletion was distal to 21q22.1. The malformation of the anterior chamber was manifest at birth by corneal clouding involving the stroma. The clouding gradually cleared over a few months except for a central opacity on the right associated with an anterior synechia. A sister of the maternal grandmother was said to have congenital corneal clouding. The authors reviewed the various chromosomal aberrations that have been found in association with an eye anomaly labeled Rieger syndrome; chromosomes 4, 6, 9, 13, and 18 have been implicated in addition to chromosome 21. Legius et al. (1994) described a family with Rieger syndrome in 3 successive generations. Linkage to EGF and D4S193, localized in 4q25, was excluded. Legius et al. (1994) concluded that the disorder in this family was genetically distinct from typical Rieger syndrome. Although the patients had the eye malformation of that disorder with maxillary hypoplasia and hypertelorism, they did not show the dental or umbilical anomalies found in typical Rieger syndrome. The eye anomalies involving the anterior chamber of the eye varied from iris hypoplasia, iris strands, and uncomplicated glaucoma arising at adult age to congenital buphthalmos. Legius et al. (1994) pointed out that the chromosome anomalies other than those involving 4q point to different candidate regions for other forms of dominantly inherited Rieger eye malformation, with or without hypodontia. Molecular Genetics Semina et al. (1996) isolated the novel homeobox gene PITX2 (601542), which they designated RIEG, and identified 6 mutations in this gene (601542.0001-601542.0006) in individuals with Rieger syndrome. PITX2 and DLX2 (126255) are transcription markers observed during early tooth development. Espinoza et al. (2002) demonstrated that PITX2 binds to bicoid and bicoid-like elements in the DLX2 promoter and activates this promoter 30-fold in Chinese hamster ovary cells. Mutations in PITX2 associated with Axenfeld-Rieger syndrome provided the first link of this homeodomain transcription factor to tooth development. One mutation produces Axenfeld-Rieger syndrome with iris hypoplasia but without tooth anomalies; this allele has a similar DNA binding specificity compared to wildtype PITX2 and transactivates the DLX2 promoter. In contrast, a different PITX2 mutation produces Rieger syndrome with the full spectrum of developmental anomalies, including tooth anomalies; this allele is unable to transactivate the DLX2 promoter. Since DLX2 expression is required for tooth and craniofacial development, the lack of tooth anomalies in the patient with iris hypoplasia may be due to the residual activity of this mutant in activating the DLX2 promoter. The authors proposed a molecular mechanism for tooth development involving DLX2 gene expression in Axenfeld-Rieger patients. Lines et al. (2002) reviewed the molecular genetics of Axenfeld-Rieger malformations, including the roles of PITX2 and FOXC1 (601090) in human disease and mouse models. History Schinzel (1987) gave an account of the life of Herwigh Rieger. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Maxillary hypoplasia \- Short philtrum \- Prominent supraorbital ridges Eyes \- Iris dysplasia (goniodysgenesis) \- Iris hypoplasia \- Prominent Schwalbe line (posterior embryotoxon) \- Glaucoma \- Displaced pupils \- Dyscoria \- Polycoria \- Aniridia \- Microcornea \- Megalocornea \- Strabismus Nose \- Broad nasal bridge Mouth \- Thin upper lip Teeth \- Hypodontia (maxillary incisors) ABDOMEN External Features \- Umbilical defect (redundant periumbilical skin) Gastrointestinal \- Imperforate anus \- Anal stenosis GENITOURINARY External Genitalia (Male) \- Hypospadias ENDOCRINE FEATURES \- Growth hormone deficiency MISCELLANEOUS \- Genetic heterogeneity (see RIEG2, 601499 ) \- Variable expressivity MOLECULAR BASIS \- Caused by mutations in the paired-like homeodomain transcription factor-2 gene (PITX2, 601542.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	AXENFELD-RIEGER SYNDROME, TYPE 1	c0265341	30,576	omim	https://www.omim.org/entry/180500	2019-09-22T16:35:09	{"doid": ["0110120"], "mesh": ["C535679"], "omim": ["180500"], "orphanet": ["782"], "synonyms": ["Alternative titles", "RIEGER SYNDROME, TYPE 1", "RIEG", "RGS"]}
A rare genetic neurological disorder characterized by infantile hypotonia, congenital ophthalmic anomalies (including strabismus, esotropia, nystagmus, and central visual impairment), global developmental delay and intellectual disability, behavioral abnormalities, and movement disorder (such as dystonia, chorea, hyperkinesia, stereotypies). Mild facial dysmorphism and skeletal deformities have also been reported. EEG testing shows marked abnormalities in the absence of overt epileptic seizures. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome	None	30,577	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=522077	2021-01-23T17:54:06	{"omim": ["618218"], "synonyms": ["SYT1-related neurodevelopmental disorder"]}
A number sign (#) is used with this entry because hyperbiliverdinemia (HBLVD) can be caused by heterozygous or homozygous mutation in the gene encoding bilirubin reductase-alpha (BLVRA; 109750) on chromosome 7p13. Description Hyperbiliverdinemia can manifest as green jaundice, which is a green discoloration of the skin, urine, serum, and other bodily fluids, due to increased biliverdin resulting from inefficient conversion to bilirubin. Although rarely reported, affected individuals appear to have symptoms only in the context of obstructive cholestasis and/or liver failure. In some cases, green jaundice can resolve after resolution of obstructive cholestasis. Green jaundice has also been associated with malnutrition, medication, and congenital biliary atresia (summary by Huffman et al., 2009). Clinical Features Gafvels et al. (2009) reported a 63-year-old Swedish man with alcoholic liver failure and hyperbiliverdinemia manifested as green jaundice. The patient first presented with fatigue, weight, loss, and nausea, and laboratory studies showed elevated liver enzymes with normal serum levels of bilirubin. He had a history of cholecystectomy and of heavy alcohol consumption. He developed bleeding esophageal varices, ascites, cirrhotic liver failure, and fatal encephalopathy. During the final months of his life, he had green-tainted skin, sclerae, urine, and ascitic fluid. Liquid chromatography and mass spectrometry identified the green plasma and urine component as unconjugated biliverdin, which was significantly increased compared to controls. Nytofte et al. (2011) reported 2 unrelated Inuit women from Greenland with episodic hyperbiliverdinemia and green jaundice. Both presented with obstructive cholestasis due to multiple gallstones; 1 was pregnant at the time. A green color developed in the skin, urine, serum, and bile, and in the milk from the pregnant woman. Laboratory studies showed increased liver enzymes and biliverdin in bodily fluids, but only 1 had increased serum bilirubin. The green discoloration resolved in both patients after surgical resolution of cholestasis. Nytofte et al. (2011) concluded that biliary obstruction was the primary event, and green jaundice appeared as a consequence. Molecular Genetics In a 63-year-old Swedish man with liver failure and hyperbiliverdinemia manifest as green jaundice, Gafvels et al. (2009) identified a heterozygous truncating mutation in the BLVRA gene (R18X; 109750.0001). His 2 children were also heterozygous for the mutation but had no clinical signs of liver disease and had normal levels of serum biliverdin. Gafvels et al. (2009) noted that the green jaundice in this patient was only apparent in the context of liver decompensation. In 2 unrelated Inuit women from Greenland with episodic hyperbiliverdinemia associated with obstructive cholestasis due to gallstones, Nytofte et al. (2011) identified a homozygous truncating mutation in the BLVRA gene (S44X; 109750.0002). Family study of 1 of the women showed that each unaffected parent was heterozygous for the mutation. The patient's sister, who was also homozygous for the mutation, did not have green jaundice or biliary obstruction but did have a solitary stone in the gallbladder and had biliverdin concentrations 3-fold higher than controls. The findings indicated that complete loss of BLVRA activity is a nonlethal condition. INHERITANCE \- Autosomal dominant \- Autosomal recessive ABDOMEN Liver \- Liver dysfunction Biliary Tract \- Cholestasis \- Cholelithiasis SKIN, NAILS, & HAIR Skin \- Jaundice, green LABORATORY ABNORMALITIES \- Green urine \- Green serum \- Increased biliverdin in bodily fluids \- Bilirubin may or may not be increased MISCELLANEOUS \- Three patients have been reported (as of August 2011) \- Green jaundice occurs only in the context of liver failure or obstructive cholestasis \- Green color resolves if cholestasis is treated \- Both heterozygous and homozygous mutations have been reported MOLECULAR BASIS \- Caused by mutation in the biliverdin reductase A gene (BLVRA, 109750.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	HYPERBILIVERDINEMIA	c3279964	30,578	omim	https://www.omim.org/entry/614156	2019-09-22T15:56:20	{"omim": ["614156"], "orphanet": ["276405"], "synonyms": ["GREEN JAUNDICE", "Alternative titles", "Green jaundice"]}
Autoimmune enteropathy SpecialtyImmunology Autoimmune enteropathy (AIE) is a rare disorder of the immune system condition that affects infants, young children and (rarely) adults causing severe diarrhea, vomiting, and other morbidities of the digestive tract. AIE causes malabsorption of food, vitamins, and minerals often necessitating replacement fluids and total parenteral nutrition. Some disorders, such as IPEX Syndrome, include autoimmune enteropathy as well as autoimmune "pathies" of the skin, thyroid, other glands, or kidneys. ## Contents * 1 Symptoms * 2 Diagnosis * 2.1 Types * 3 Treatment * 4 References * 5 External links ## Symptoms[edit] The main symptoms of AIE include: * Diarrhea (frequent loss of fluids) * Intestinal inflammation * Vomiting * Intestinal bleeding * Difficulty or inability to gain weight * Rapid weight loss * Decreased urine output from dehydration ## Diagnosis[edit] There is a diagnostic test for AIE that looks for an antibody against the enterocyte. The diagnostic test contains the Western Blot which can identify the antibody IgG or IgA and with the immunohistochemistry can localize these antibodies. Endoscopy with biopsies of the colon, small colon, stomach, and other locations may be helpful in diagnosing. This test is done to look at the stomach and small intestines and to see what cells are infiltrating the digestive tract. There are also documented cases of autoimmune enteropathy where the auto-antibodies were undetectable and the diagnosis was made on the basis of clinical presentation and response to treatment. ### Types[edit] There are 3 types of autoimmune enteropathy: Type 1: IPEX syndrome: Immune dysregulation, Polyendocrinopathy, Enteropathy, X – linked syndrome, which is caused by a mutation in the FOXP3 gene. This can only affect boys. Type 2: IPEX-like, which manifests similarly to IPEX syndrome but without recognizable mutations in the FOXP3 gene. This can affect both genders and includes a variety of manifestations of varying severity. Type 3: Autoimmune manifestations primarily limited to the GI tract. This can affect both genders and may also be considered IPEX-like. There is considerable overlap in these disorders, and it is often unclear how to properly distinguish between them as the responsible genes are generally poorly understood at this time. ## Treatment[edit] The first line of treatment are corticosteroids and other medicines used to suppress the immune system such as tacrolimus and sirolimus. An intravenous nutrition such as total parenteral nutrition and/or a special diet may be necessary. Hematopoietic stem cell transplantation may be curative. ## References[edit] ^ Montalto, M; D'Onofrio, F; Santoro, L; Gallo, A; Gasbarrini, A; Gasbarrini, G (2009). "Autoimmune enteropathy in children and adults". Scand. J. Gastroenterol. 44 (9): 1029–36. doi:10.1080/00365520902783691. PMID 19255930. S2CID 33004674. ^http://www.cincinnatichildrens.org/health/a/autoimmune-enteropathy/, Autoimmune Enteropathy. Cincinnati Children's, (1999 - 2013), Ohio. ^ http://www.rightdiagnosis.com/a/autoimmune_enteropathy/intro.htm, Autoimmune Enteropathy. Right Diagnosis, Last Update 7 May 2013. ^ http://www.naspghan.org/, Harland S. Winter (2010): Autoimmune Enteropathy: My Infant Patient Has Intractable Diarrhea. Boston, MA: Harvard Medical School. ## External links[edit] Classification D * ICD-10: E31.0 * OMIM: 304790 * MeSH: C538273 External resources * Orphanet: 37042 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Autoimmune enteropathy	c0341305	30,579	wikipedia	https://en.wikipedia.org/wiki/Autoimmune_enteropathy	2021-01-18T18:40:36	{"gard": ["8689"], "mesh": ["C538273"], "umls": ["C0341305"], "orphanet": ["94075"], "wikidata": ["Q17130915"]}
Henoch-Schonlein purpura (HSP), also called immunoglobulin A vasculitis (IgAV), is a vascular disease that primarily affects small blood vessels. The disease is characterized by abnormal deposits of immunoglobulin A (an antibody) in the blood vessels, leading to their inflammation (vasculitis). The small vessels of the skin, joints, kidneys, and digestive organs are particularly involved. Signs and symptoms usually begin suddenly (and progress over days) and may include purple-colored spots on the skin (purpura); joint pain; and gastrointestinal problems such as abdominal pain, nausea, bloody stools, and rarely, severe complications requiring surgery. People with HSP may also develop glomerulonephritis (injury to the kidneys caused by inflammation) and poor kidney function, which may result in swelling of parts of the body or face (edema), and blood and protein in the urine (hematuria and proteinuria). Most cases of HSP occur in children and go away without causing serious or long-term health problems. Less commonly, the disease affects adults and may be more severe, leading to chronic kidney disease and kidney failure. The cause of HSP is not completely understood, but research indicates that genes (especially those involved in regulating the immune system) may play a key role in predisposing a person to HSP, as well as its severity. However, while genes may increase the risk of developing the disease (and in some cases more than one family member has HSP), the disease itself is not inherited. Environmental “triggers” such as foods, infections, or medications may also play a role in the onset of the disease. The diagnosis of HSP may be made based on symptoms, blood and urine tests, imaging studies, and/or a biopsy of the skin or kidney. Most cases go away within several weeks without treatment. When needed, treatment aims to relieve symptoms and may include medications for pain and inflammation. People with chronic kidney involvement or advanced kidney disease may require immunosuppressive medications, hemodialysis, or kidney transplantation. The long-term outlook depends on the extent of kidney involvement. Rarely, HSP is fatal due to kidney complications. In some cases, the disease recurs, sometimes more than once. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Henoch-Schonlein purpura	c0034152	30,580	gard	https://rarediseases.info.nih.gov/diseases/8204/henoch-schonlein-purpura	2021-01-18T18:00:06	{"mesh": ["D011695"], "orphanet": ["761"], "synonyms": ["Purpura, Schonlein-Henoch", "Anaphylactoid purpura", "Vascular purpura", "Henoch Schonlein purpura", "Immunoglobulin A vasculitis", "Immunoglobulin-A vasculitis"]}
A number sign (#) is used with this entry because of evidence that congenital disorder of glycosylation type IIn (CDG2N) is caused by homozygous or compound heterozygous mutation in the SLC39A8 gene (608732) on chromosome 4q24. Description Congenital disorder of glycosylation type IIn (CDG2N) is an autosomal recessive severe multisystem developmental disorder characterized by delayed psychomotor development apparent from infancy, hypotonia, and variable additional features, such as short stature, seizures, visual impairment, and cerebellar atrophy. Serum transferrin analysis shows a CDG type II pattern (summary by Boycott et al., 2015 and Park et al., 2015). For a discussion of genetic heterogeneity of CDG type II, see CDG2A (212066). Clinical Features Boycott et al. (2015) reported 6 patients of Hutterite descent, including 2 patients from a large kindred from the Dariusleut group and 4 patients from 3 consanguineous families from the Schmiedeleut group, with a severe multisystem developmental disorder. The patients ranged in age from 6 to 23 years. They all had profound psychomotor retardation with delayed head control, severe hypotonia, inability to walk, variable ability to sit independently, and profound intellectual disability. Other features included strabismus, short stature, and recurrent infections; 2 patients had osteopenia, and 2 had seizures. Two sibs from a consanguineous Egyptian family had a similar phenotype, with severely delayed psychomotor development, hypotonia and hyperreflexia. Brain imaging in all patients showed cerebellar atrophy; 1 patient also had cortical atrophy. Laboratory studies showed decreased levels of manganese (Mn) and zinc (Zn) in blood, whereas urine levels tended to be high, indicating renal wasting. In addition, Park et al. (2015) found that 3 of the patients reported by Boycott et al. (2015) had abnormal transferrin glycosylation patterns, with decreased tetrasialo-transferrin and increased trisialo-, monosialo- and disialo-transferrin in a type II pattern. Park et al. (2015) reported 2 unrelated females with CDG2N. The first patient, born of unrelated German parents, was noted to have short stature, short limbs, and cutaneous syndactyly of the feet at birth. She presented at age 4 months with disproportionate dwarfism, craniosynostosis, absence of visual fixation, strabismus, and hearing impairment. She had a flat face and low-set ears, and brain imaging showed cerebral atrophy and enlarged ventricles with a normal cerebellum. Severe refractory seizures, associated with hypsarrhythmia on EEG, occurred up to 5 times a day. A few months later, she had episodic apnea/hypopnea and liver disease, both of which resolved. Serum and urinary manganese concentrations were undetectable, and serum transferrin analysis showed a pattern consistent with a type II congenital disorder of glycosylation, with increased amounts of asialo-, monosialo-, disialo-, and trisialo-transferrin compared to controls. The patient was treated with dietary galactose, which resulted in a dramatic improvement in the transferrin glycosylation defect, although the clinical benefits were unclear. The second patient was a 19-year-old who had short stature and severely delayed global development apparent in the first year of life. She was hypotonic, confined to a wheelchair without the ability to sit or walk without support, and had very poor speech. She had seizures as a child that remitted. Other features included hyperopia, astigmatism, strabismus, nystagmus, mild elbow and knee contractures, and cerebellar atrophy. Laboratory studies showed undetectable manganese and a type II CDG pattern of serum transferrin. Inheritance The transmission pattern of CDG2N in the families reported by Boycott et al. (2015) and Park et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 6 patients of Hutterite descent and in 2 sibs, born of consanguineous Egyptian parents, with CDG2N, Boycott et al. (2015) identified the same homozygous missense mutation in the SLC39A8 gene (G38R; 608732.0001). The mutations, which were found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the families. Haplotype analysis did not suggest a founder effect between the Hutterite and Egyptian patients. Patient cells showed normal localization of the mutant protein, but blood levels of Zn and Mn were low and urine levels of these cations were high, suggesting renal wasting and consistent with the mutation causing a loss of transporter function. Functional studies of the variant were not performed. In 2 unrelated patients with CDG2N, Park et al. (2015) identified compound heterozygous mutations in the SLC39A8 gene (608732.0001-608732.0004). The mutations in the first patient were found by whole-exome sequencing; mutations in the second patient were found by direct sequencing of the SLC39A8 gene in patients with unknown glycosylation defects. Functional studies of the variants were not performed, but the patients had no detectable serum or urinary manganese, consistent with a loss of transporter function. The findings linked a trace element deficiency to an inherited glycosylation disorder. Animal Model Galvez-Peralta et al. (2012) found that mice homozygous for a hypomorphic Slc39a8 allele had stunted growth, severe anemia, dysregulation of hematopoiesis, and failure of multiple organs, such as spleen, liver, kidney, and lung, to develop normally in utero, all of which ultimately resulted in neonatal lethality. Other features included malformed cranium, hypoplastic hind limbs, and underdeveloped eyes. The mutant mice had decreased zinc, iron, and manganese levels in multiple tissues. The findings indicated that Slc39a8 is indispensable for proper embryonic development, and highlighted the importance of zinc homeostasis during this period. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Ears \- Hearing loss (1 patient) Eyes \- Strabismus \- Astigmatism \- Nystagmus \- Poor visual fixation (in some patients) SKELETAL \- Osteopenia (in some patients) \- Joint hypermobility (in some patients) Skull \- Craniosynostosis (1 patient) MUSCLE, SOFT TISSUES \- Hypotonia, profound NEUROLOGIC Central Nervous System \- Delayed psychomotor development, profound \- Intellectual disability, profound \- Delayed head control \- Inability to walk \- Inability to sit (in some patients) \- Seizures (in some patients) \- Cerebellar atrophy \- Cerebral atrophy (in some patients) IMMUNOLOGY \- Recurrent infections (in some patients) LABORATORY ABNORMALITIES \- Serum transferrin glycosylation defect in a type II pattern \- Decreased plasma zinc and manganese \- Increased urinary zinc and manganese (in some patients) MISCELLANEOUS \- Onset at birth MOLECULAR BASIS \- Caused by mutation in the solute carrier family 39 (zinc transporter), member 8 gene (SLC39A8, 608732.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIn	c4225234	30,581	omim	https://www.omim.org/entry/616721	2019-09-22T15:48:06	{"doid": ["0070266"], "omim": ["616721"], "orphanet": ["468699"], "synonyms": ["CDG-IIn", "Congenital disorder of glycosylation type IIn", "Carbohydrate deficient glycoprotein syndrome type IIn", "CDG2N", "CDG IIn", "Alternative titles", "CDG syndrome type IIn", "SLC39A8 deficiency", "Congenital disorder of glycosylation type 2n"]}
Germinoma Micrograph of a germinoma, H&E stain SpecialtyOncology A germinoma is a type of germ-cell tumor,[1] which is not differentiated upon examination.[2] It may be benign or malignant. ## Contents * 1 Cause * 2 Histology * 3 Diagnosis * 3.1 Classification * 3.2 Locations * 3.2.1 Ovary (dysgerminoma) and testis (seminoma) * 3.2.2 Intracranial germinoma * 4 Treatment * 5 Prognosis * 6 See also * 7 References * 8 External links ## Cause[edit] Germinomas are thought to originate from an error of development, when certain primordial germ cells fail to migrate properly. Germinomas lack histologic differentiation, whereas nongerminomatous germ-cell tumors display a variety of differentiation. Like other germ-cell tumors, germinomas can undergo malignant transformation.[citation needed] ## Histology[edit] The tumor is uniform in appearance, consisting of large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic. On gross examination, the external surface is smooth and bosselated (knobby), and the interior is soft, fleshy, and either cream-coloured, gray, pink, or tan. Microscopic examination typically reveals uniform cells that resemble primordial germ cells. Typically, the stroma contains lymphocytes, and about 20% of patients have sarcoid-like granulomas.[citation needed] ## Diagnosis[edit] Metastasis has been noted in about 22% of cases at time of diagnosis. Males are roughly twice as commonly affected in developing germinomas. They are most commonly diagnosed between the ages of 10 and 21.[citation needed] Often, serum and spinal fluid tumor markers of alpha-fetoprotein and beta-HCG are tested. Pure germinomas are not associated with these markers. Nongerminomatous germ-cell tumors may be associated with increased markers such as alpha-fetoprotein with yolk sac tumors, as well as embryonic cell carcinomas and immature teratomas and beta-HCG, which occur in choriocarcinomas. In one to 15% of germinomas, a low level of beta-HCG may be produced. Although controversial, HCG-secreting germinomas may be more aggressive than nonsecreting ones.[citation needed] ### Classification[edit] The term "germinoma" most often refers to a tumor in the brain that has a histology identical to two other tumors, dysgerminoma in the ovary and seminoma in the testis.[3] Since 1994, MeSH has defined germinoma as "a malignant neoplasm of the germinal tissue of the gonads, mediastinum, or pineal region"[4] and within its scope included both dysgerminoma and seminoma. Collectively, these are the seminomatous or germinomatous tumors.[citation needed] ### Locations[edit] #### Ovary (dysgerminoma) and testis (seminoma)[edit] Dysgerminoma is the most common type of malignant germ-cell ovarian cancer. Dysgerminoma usually occurs in adolescence and early adult life; about 5% occur in prepubertal children. Dysgerminoma is extremely rare after age 50. It occurs in both ovaries in 10% of patients and, in a further 10%, a microscopic tumor is in the other ovary.[citation needed] A 7.4 x 5.5-cm seminoma in a radical orchiectomy specimen from a 27-year-old man Seminoma is the second-most common testicular cancer; the most common is mixed, which may contain seminoma.[citation needed] Abnormal gonads (due to gonadal dysgenesis and androgen insensitivity syndrome) have a high risk of developing a dysgerminoma.[5] Most dysgerminomas are associated with elevated serum lactic dehydrogenase, which is sometimes used as a tumor marker. Metastases are most often present in the lymph nodes.[citation needed] #### Intracranial germinoma[edit] Intracranial germinoma occurs in 0.7 per million children.[6] As with other germ-cell tumors (GCTs) occurring outside the gonads, the most common location of intracranial germinoma is on or near the midline, often in the pineal or suprasellar areas; in 5-10% of patients with germinoma in either area, the tumor is in both areas. Like other GCTs, germinomas can occur in other parts of the brain. Within the brain, this tumor is most common in the hypothalamic or hypophyseal regions. In the thalamus and basal ganglia, germinoma is the most common GCT.[citation needed] The diagnosis of an intracranial germinoma usually is based on biopsy, as the features on neuroimaging appear similar to other tumors.[citation needed] Cytology of the cerebrospinal fluid often is studied to detect metastasis into the spine. This is important for staging and radiotherapy planning. Intracranial germinomas have a reported 90% survival to five years after diagnosis.[7] Near total resection does not seem to influence the cure rate, so gross total resection is not necessary and can increase the risk of complications from surgery. The best results have been reported[citation needed] from craniospinal radiation with local tumor boost of greater than 4,000 centigray (cGy). ## Treatment[edit] Germinomas, like several other types of GCTs, are sensitive to both chemotherapy[8] and radiotherapy. For this reason, treatment with these methods can offer excellent chances of long-term survival, even cure.[citation needed] ## Prognosis[edit] Although chemotherapy can shrink germinomas, it is not generally recommended alone unless radiation has contraindications. In a study in the early 1990s, carboplatinum, etoposide, and bleomycin were given to 45 germinoma patients, and about half the patients relapsed. Most of these relapsed patients were then recovered with radiation or additional chemotherapy.[9] ## See also[edit] * Brown-Séquard syndrome (sections on cavernous malformation and germinoma) * Spermatocytic tumor ## References[edit] 1. ^ "Germinoma" at Dorland's Medical Dictionary 2. ^ Germinoma, Central Nervous System at eMedicine 3. ^ "Pathology". Retrieved 2007-11-03. 4. ^ Germinoma at the US National Library of Medicine Medical Subject Headings (MeSH) 5. ^ Sadler, T.W. 2006. Langman's Medical Embryology, 10th Edition, Chapter 15, pp. 251-252. Lippincott, Williams & Wilkins, Pub. 6. ^ Keene D, Johnston D, Strother D, et al. (2007). "Epidemiological survey of central nervous system germ cell tumors in Canadian children". J. Neurooncol. 82 (3): 289–95. doi:10.1007/s11060-006-9282-2. PMID 17120159. S2CID 5872972. 7. ^ Packer RJ, Cohen BH, Cooney K, Coney K (2000). "Intracranial germ cell tumors". Oncologist. 5 (4): 312–20. doi:10.1634/theoncologist.2000-0312. PMID 10964999. 8. ^ Ueba T, Yamashita K, Fujisawa I, et al. (2007). "Long-term follow-up of 5 patients with intracranial germinoma initially treated by chemotherapy alone". Acta Neurochirurgica. 149 (9): 897–902, discussion 902. doi:10.1007/s00701-007-1268-0. PMID 17690837. S2CID 24074801. 9. ^ Balmaceda C, Heller G, Rosenblum M, et al. (1996). "Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study". J. Clin. Oncol. 14 (11): 2908–15. doi:10.1200/JCO.1996.14.11.2908. PMID 8918487. ## External links[edit] Classification D * ICD-O: 9060-9061, M9064/3 * MeSH: D018237 * SNOMED CT: 28307001 * v * t * e Germ cell tumors Germinomatous * Germinoma * Seminoma * Dysgerminoma Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor/Yolk sac tumor * Teratoma: Fetus in fetu * Dermoid cyst * Struma ovarii * Strumal carcinoid * Trophoblastic neoplasm: Gestational trophoblastic disease * Hydatidiform mole * Choriocarcinoma * Placental site trophoblastic tumor * Polyembryoma * Gonadoblastoma * v * t * e Tumors of the female urogenital system Adnexa Ovaries Glandular and epithelial/ surface epithelial- stromal tumor CMS: * Ovarian serous cystadenoma * Mucinous cystadenoma * Cystadenocarcinoma * Papillary serous cystadenocarcinoma * Krukenberg tumor * Endometrioid tumor * Clear-cell ovarian carcinoma * Brenner tumour Sex cord–gonadal stromal * Leydig cell tumour * Sertoli cell tumour * Sertoli–Leydig cell tumour * Thecoma * Granulosa cell tumour * Luteoma * Sex cord tumour with annular tubules Germ cell * Dysgerminoma * Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma/Struma ovarii * Choriocarcinoma Fibroma * Meigs' syndrome Fallopian tube * Adenomatoid tumor Uterus Myometrium * Uterine fibroids/leiomyoma * Leiomyosarcoma * Adenomyoma Endometrium * Endometrioid tumor * Uterine papillary serous carcinoma * Endometrial intraepithelial neoplasia * Uterine clear-cell carcinoma Cervix * Cervical intraepithelial neoplasia * Clear-cell carcinoma * SCC * Glassy cell carcinoma * Villoglandular adenocarcinoma Placenta * Choriocarcinoma * Gestational trophoblastic disease General * Uterine sarcoma * Mixed Müllerian tumor Vagina * Squamous-cell carcinoma of the vagina * Botryoid rhabdomyosarcoma * Clear-cell adenocarcinoma of the vagina * Vaginal intraepithelial neoplasia * Vaginal cysts Vulva * SCC * Melanoma * Papillary hidradenoma * Extramammary Paget's disease * Vulvar intraepithelial neoplasia * Bartholin gland carcinoma * v * t * e Tumor markers Blood Lymphoma * Neprilysin Lymphosarcoma * CD3 * CD79a Endocrine Thyroid cancer * Thyroglobulin * Medullary thyroid cancer (Calcitonin * Carcinoembryonic antigen) Pheochromocytoma * Normetanephrine * Enolase 2 Neuroendocrine tumors * Synaptophysin * Chromogranin A Neuroblastoma * Homovanillic acid Nervous system Brain tumor * PCNA Astrocytoma * Glial fibrillary acidic protein NC/Melanoma * S100 protein * Melanoma inhibitory activity Cardiovascular/ respiratory Lung cancer * Carcinoembryonic antigen * Enolase 2 * Autocrine motility factor * hPG80 Hemangiosarcoma (endothelium) * Factor VIII Digestive Colorectal cancer * CA19-9 * Carcinoembryonic antigen * hPG80 Pancreatic cancer * CA19-9 * Carcinoembryonic antigen * CA 242 * Tumor-associated glycoprotein 72 * hPG80 Hepatocellular carcinoma * Alpha-fetoprotein/AFP-L3 Reproductive/ urinary/ breast Ovarian tumor * Surface epithelial-stromal tumor * CA-125 * EC * CD30 * hCG * EST * Alpha-fetoprotein * Choriocarcinoma * hCG * Dysgerminoma * LDH * Sertoli–Leydig cell tumour * Testosterone * GCT * Inhibin * hPG80 Testicular cancer * βhCG * Alpha-fetoprotein/AFP-L3 * CD30 * hPG80 Prostate cancer * Prostate-specific antigen * Prostatic acid phosphatase * Glutamate carboxypeptidase II * erbB-3 receptor * Early prostate cancer antigen-2 * SPINK1 * GOLM1 * PCA3 * TMPRSS2 * hPG80 Germ cell tumor * NANOG Bladder cancer * erbB-3 receptor * NMP22 Breast cancer * CA 15-3 * erbB-2 receptor * erbB-3 receptor * Cathepsin D * CA 27-29 * hPG80 General histology Sarcoma * Vimentin Carcinoma (epithelium) * Cytokeratin Musculoskeletal Rhabdomyosarcoma * Desmin [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Germinoma	c0206660	30,582	wikipedia	https://en.wikipedia.org/wiki/Germinoma	2021-01-18T18:54:14	{"mesh": ["D018237"], "umls": ["C0206660"], "orphanet": ["182127"], "wikidata": ["Q950838"]}
It has been suggested that this article be split into articles titled Asymptomatic hyperleukocytosis and symptomatic hyperleukocytosis. (Discuss) (September 2020) Leukostasis (also called symptomatic hyperleukocytosis) is a medical emergency most commonly seen in patients with acute myeloid leukemia. It is characterized by an extremely elevated blast cell count and symptoms of decreased tissue perfusion. The pathophysiology of leukostasis is not well understood, but inadequate delivery of oxygen to the body's cells is the result. Leukostasis is diagnosed when white cell plugs are seen in the microvasculature. The most common symptoms are dyspnea and hypoxia, usually accompanied by visual changes, headaches, dizziness, confusion, somnolence, and coma. Prompt treatment is required since, if left untreated, it has a very high mortality rate. Treatments aim to rapidly reduce white blood cell counts while also treating the underlying disorder. ## Contents * 1 Asymptomatic hyperleukocytosis and symptomatic hyperleukocytosis (leukostasis) * 2 Symptoms and signs * 3 Causes of asymptomatic/symptomatic hyperleukocytosis (leukostasis) * 4 Pathophysiology * 4.1 Theory 1 * 4.2 Theory 2 * 5 Diagnosis * 6 Prevention * 7 Treatment * 8 Prognosis * 9 Recent research * 10 Signs and symptoms * 11 Pathophysiology * 12 Diagnosis * 13 Management * 14 Prognosis * 15 Epidemiology * 16 References ## Asymptomatic hyperleukocytosis and symptomatic hyperleukocytosis (leukostasis)[edit] Leukocytes Symptomatic Hyperleukocytosis (Leukostasis) is defined by a tremendously high blast cell count along with symptoms of decreased tissue perfusion. Leukostasis is associated with people who suffer from bone and blood disorders and is very common among people suffering from acute myeloid leukemia or chronic myeloid leukemia. Leukostasis is a pathologic diagnosis that inhibits efficient flow to the microvasculature of the body. Continued and untreated leukostasis presents respiratory and neurological distress simultaneously and is a medical emergency, with untreated patient mortality rates reaching a minimum of 20 and a maximum of 40 percent. A leukemia blood cell count greater than 50 x 10^9/ L (50,000 / microL) or 100 x 10^9 L / (100,000/ microL) signifies hyperleukocytosis. Symptoms of leukostasis start when blood levels of leukocytes reach over 100 x 10^9 / L (100,000 / microL). As stated before, these counts are critical and associated with Leukemias.[1] ## Symptoms and signs[edit] When a patient is suffering from symptomatic leukocytosis, specifically caused by a form of leukemia, it is common to find leukostasis in all their organs. The majority of the time a patient dies from neurological complications (40% of patients die due to neurological conditions) as opposed to particular organ damage. The lungs alone account for approximately 30 percent of leukostasis fatalities. All other organs combined attribute to 30 percent of deaths, with the major outliers being neurological and respiratory failure equating to 70 percent of all death rates. Damage to the microvasculature of the body is the primary cause of death by leukostasis. Microvasculature damage to the lungs is only second to neurological damage because the body is already suffering from hypoxic conditions, which lead to lung tissue damage as the second leading cause of fatalities.[2] Pulmonary signs \- Dyspnea and hypoxia with or without diffuse interstitial or alveolar infiltrates on imaging studies. Neurological signs \- visual changes, headaches, dizziness, tinnitus, gait instability, confusion, somnolence, coma. The most common symptom is the patient is usually febrile, which is often linked with inflammation and possible infection. Less common signs include: myocardial ischemia / right ventricular overload, increased acute kidney injury, priapism, acute limb ischemia and bowel infarction. ## Causes of asymptomatic/symptomatic hyperleukocytosis (leukostasis)[edit] Causes of leukocytosis Neutrophilic leukocytosis (neutrophilia) * Acute bacterial infections, especially pyogenic infections[3] * Sterile inflammation * Tissue necrosis[3] * Myocardial infarction[3] * Burns[3] Eosinophilic leukocytosis (eosinophilia) * Allergic disorders * Asthma[3] * Hay fever[3] * Drug allergies[3] * Allergic skin diseases[3] * Pemphigus[3] * Dermatitis herpetiformis * Parasitic infections[3] * Some forms of malignancy * Hodgkin's lymphoma[3] * Some forms of Non-Hodgkin lymphoma[3] * Systemic autoimmune diseases[3] (e.g. SLE) * Some forms of vasculitis[3] * Cholesterol embolism (transiently)[3] Basophilic leukocytosis Basophilia (rare)[3] * Myeloproliferative disease, e.g. Chronic myelogenous leukemia[3] * Monocytosis * Chronic infections[3] * Tuberculosis[3] * Bacterial endocarditis[3] * Rickettsiosis[3] * Malaria[3] * Systemic autoimmune diseases, e.g. SLE[3] * Inflammatory bowel diseases, e.g. ulcerative colitis[3] Lymphocytosis * Chronic infections[3] * Tuberculosis[3] * Brucellosis[3] * Viral infections * Hepatitis[3] * Cytomegalovirus infection[3] * Infectious mononucleosis[3] * Pertussis[3] * some forms of malignancy, such as lymphocytic leukæmias Hyperleukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including viral, bacterial, fungal, or parasitic infection, cancer, hemorrhage, and exposure to certain medications. For lung diseases such as pneumonia and tuberculosis, white blood cell count is crucial for the diagnosis of the disease, as leukocytosis is usually present. Specific medications, including corticosteroids, lithium and beta-agonists can cause hyperleukocytosis.[4] ## Pathophysiology[edit] The mechanism in which hyperleukocytosis or leukostasis manifests and disrupts homeostasis is greatly associated with leukemia's but multiple other factors may cause leukocytosis. Major types of leukocytosis and their mechanisms depend on the types of leukemia that cause them. White blood cell levels either rise in distinct white blood levels or in unison with others, a patient may be suffering from neutrophilia, lymphocytosis, monocytosis, eosinophilia, basophilia or a rise in immature blast cells.[2] Acute myeloid leukemia \- 10 to 20 percent of patients newly diagnosed with this type leukemia have hyperleukocytosis. Acute lymphoblastic leukemia \- 20 to 30 percent of patients newly diagnosed with this type of leukemia have hyperleukocytosis. Chronic lymphocytic leukemia \- Exact percentage of people diagnosed with chronic lymphocytic leukemia is unknown but a significant number also suffer from hyperleukocytosis. Chronic myeloid leukemia \- The majority of patients suffering from chronic myeloid leukemia usually suffer from hyperleukocytosis. The primary pathophysiology of leukostasis is not completely understood, but there are two possible theories. ### Theory 1[edit] Increased blood viscosity due to large leukemic blast populations which are less deformable than mature leukocytes may lead to leukostasis. The accumulation of less malleable blast products in the bloodstream accumulate within the microcirculation causing an accumulation of blockages leading to leukostasis.[citation needed] ### Theory 2[edit] Hypoxic events in body regions may increase the high metabolic activity of dividing blast cells and lead to an increase in cytokine production. The increasing levels of cytokines within tissues may result in endothelial damage and subsequent hemorrhage. Therefore, hypoxia, in addition to various cytokine accumulations, act in unison to further damage tissue and attract leukemic blast cells to form a triad of damage.[citation needed] The combination of these theories, in addition to other events, may lead to hyperleukocytosis. ## Diagnosis[edit] White blood counts exceeding 100 x 10^9 / L (100,000 / microL) present symptoms of tissue hypoxia and may signal possible neurological and respiratory distress. Ongoing research has shown that patients have suffered from hypoxia at leukocyte levels below 100 x 10^9 / L (100,000 / microL), therefore patients with leukemia need regular neurological and respiratory monitoring when leukocyte counts are approaching 100 x 10^9 / L (100,000 / microL) to decrease chances of tissue hypoxia. Acquired biopsies are examined for damage to microvasculature, which serves as evidence of hypoxia through the identification of leukocyte blockage within the tissue. Due to the biopsy's invasive nature and the risks associated with the procedure, it is only used when deemed necessary.[2] Measurements for arterial pO2 have shown to be falsely decreased in patients with hyperleukocytosis because of white blood cells ability to utilize oxygen. Pulse oximetry should be used to more accurately assess pO2 levels of a patient suspected to be suffering from leukocytosis. Automated blood cell counters may be inaccurate due to fragments of blast cells being labeled on blood smears as platelets. The most accurate form of confirming platelet counts is by using a manual platelet count and a review of a peripheral smear. Serum potassium levels may also be artificially elevated by a release from leukemic blasts during in vitro clotting process, therefore serum potassium levels should be monitored by heparinized (the addition of heparin prevents coagulation) plasma samples in order to obtain accurate results of potassium levels. Disseminated intravascular coagulation may occur in a significant number of patients with presentation of various degrees of thrombin generation, followed by decreased fibrinogen and increased fibrinolysis.[citation needed] Spontaneous tumor lysis syndrome is present in approximately 10 percent of patients with leukostasis. Lab tests are used to measure the potential of elevated serum concentrations such as uric acid, potassium, phosphate, and hypocalcemia. Disseminated intravascular coagulation and spontaneous tumor lysis syndrome can develop before and after chemotherapy treatment. Patients undergoing this type of therapy need to be closely monitored before and after, in addition to undergoing prophylactic measures to prevent possible complications. ## Prevention[edit] Since leukostasis and hyperleukostasis are associated with leukemia, preventive treatments are taken upon diagnosis.[2] Patients with hyperleukocytosis associated with leukemia are always considered candidates for tumor lysis syndrome prophylaxis in addition to aggressive intravenous hydration with allopurinol or rasburicase to decrease serum uric acid levels. ## Treatment[edit] Treatment includes utilization of prophylactic methods if the patient has been diagnosed with hyperleukocytosis. This is usually in combination with other treatments, which are dependent on the type of leukemia. Specific treatments include lysis syndrome treatment in addition to aggressive intravenous hydration with allopurinol or rasburicase to decrease serum uric acid levels.[2] Hematopoietic cell transplants are critical to correct leukostasis and leukemia. Cytoreduction is also a critical course of treatment in order to rapidly decrease white blood cell counts. Twenty to forty percent of patients diagnosed with hyperleukocytosis die within the first week of symptom presentation. Patients with the best outcome have none or limited symptoms of respiratory or neurological distress. An accumulation of these symptoms lead to decreased levels of statistical survival compared to patients diagnosed with asymptomatic hyperleukocytosis alone. Cytoreduction methods include chemotherapy, utilizing the drug hydroxyurea (Hydroxyurea is usually used in asymptomatic hyperleukocytosis), and the less common leukapheresis procedure. This procedure is often utilized for asymptomatic hyperleukocytosis patients who have induction chemotherapy postponed for patient-specific factors.[citation needed] Variants of chemotherapy, including induction chemotherapy, are used to treat both elevated white blood cells counts while simultaneously targeting leukemia cells in the bone marrow.[citation needed] ## Prognosis[edit] Prognosis of patients suffering from hyperleukocytosis is dependent on the cause and type of leukemia the patient has. Patients diagnosed with asymptomatic hyperleukocytosis have significantly better survival rates than symptomatic hyperleukocytosis (leukostasis). Preventative measures and contentious monitoring of patients diagnosed with leukemia is critical in receiving treatment as early as possible to prevent and treat hyperleukocytosis.[citation needed] ## Recent research[edit] Recent and continuing research has shown that patients have suffered from hypoxia at leukocyte levels below 100 x 10^9 / L (100,000 / microL), therefore patients suffering from leukemia need regular neurological and respiratory monitoring when leukocyte counts are approaching 100 x 10^9 / L (100,000 / microL) to decrease chances of hypoxia.[2] Leukemia and population types are also believed to be associated with possible symptoms and may require a change in treatment.[2] Results of Tumor lysis/ consumption of coagulopathy in patients with acute leukemia is much more often than in patients with chronic malignant hematological diseases.[5] * Data retrieved for reference is 2017 Leukostasis, also known as symptomatic hyperleukocytosis, is a life-threatening complication of various leukemias characterized by an excess of white blood cells in the bloodstream. Hyperleukocytosis is arbitrarily defined as greater than 100,000 white blood cells per microliter of blood. The condition is characterized by abnormal aggregation and clumping of white blood cells in the blood vessels resulting in impaired blood flow and delivery of oxygen to the body's cells. The brain and lungs are the two most commonly affected organs.[6] Leukostasis most commonly occurs with acute myeloid leukemia. Hyperleukocytosis/leukostasis occurs more commonly, and at lower white blood cell (WBC) counts, in acute myeloid leukemia than in acute lymphocytic leukemia, because the cells of acute myeloid leukemia have a larger corpuscular (cell) volume than those of acute lymphocytic leukemia, and the cells of acute myeloid leukemia have more surface adhesion molecules than those of acute lymphocytic leukemia (i.e., the cancer cells in AML are "stickier"). ## Signs and symptoms[edit] Individuals affected by leukostasis may present with respiratory symptoms such as cough, difficulty breathing, breathing too quickly, or inadequate levels of oxygen in the blood requiring support with a mechanical ventilator.[6][7] Neurologic symptoms, such as temporary confusion, blurry vision, dizziness, ringing in the ears, ataxia, stupor, sleepiness, headaches, and coma, may be seen. Neurologic signs such as seizures, focal neurologic deficits (e.g., weakness in one arm or leg), swelling of the retina, retinal bleeding, and dilated blood vessels on inspection of the back of the eye.[7] Rare complications of leukostasis include renal vein thrombosis, priapism, and acute ischemia of the leg.[6] ## Pathophysiology[edit] The pathophysiology of leukostasis is not well understood. Inadequate delivery of oxygen to the body's cells is thought to be the main abnormal result of leukostasis.[7] Proposed mechanisms for this include increased blood viscosity due to the high number of white blood cells circulating in the blood and a higher proportion of cells with a greater mean corpuscular volume (larger cells) with decreased deformability occupying the blood vessels.[6] However, certain studies have demonstrated that the blood viscosity of affected individuals is not increased due to a compensatory decrease in the number of red blood cells sometimes resulting in anemia and a decreased hematocrit.[7] ## Diagnosis[edit] The clinical signs and symptoms of leukostasis are non-specific but should be suspected in susceptible individuals with leukemia, a high white blood cell count (e.g., over 100,000), and new-onset neurologic or respiratory signs or symptoms. Rales may be heard when listening to the lungs with a stethoscope.[6] A chest x-ray can be normal in those with leukostasis or may demonstrate an alveolar pattern of infiltrates.[7] Brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is useful and can demonstrate areas of bleeding, ischemic stroke, or masses.[7] Laboratory abnormalities seen in those with leukostasis include a markedly elevated white blood cell count (hyperleukocytosis) and electrolyte abnormalities seen with tumor lysis syndrome such as high concentrations of potassium, phosphorus, and uric acid in the blood and a low level of calcium in the blood (due to being bound by high amounts of circulating phosphorus).[7] ## Management[edit] It is an acute syndrome requiring aggressive cytoreductive modalities including chemotherapy and/or leukapheresis to both reduce the number of circulating leukocytes and to break apart any aggregates that have already formed. Such rapid and massive lysis of tissue poses a risk of complications (tumor lysis syndrome), but it is necessary to avoid a stroke. Leukostasis is different from leukemic infiltration, which is a neoplastic process where leukemic cells invade organs.[8] ## Prognosis[edit] Leukostasis is a high-risk condition and can lead to significant complications resulting from occlusion of blood vessels, including transient ischemic attacks and strokes. ## Epidemiology[edit] The incidence and prevalence of hyperleukocytosis and leukostasis vary depending on the form of leukemia.[7] Hyperleukocytosis is common in chronic myelogenous leukemia and chronic lymphocytic leukemia, but leukostasis rarely occurs.[7] Similarly, the incidence of hyperleukocytosis in people with acute lymphoblastic leukemia is between 10 and 30% but rarely does this progress to symptomatic leukostasis.[7] The incidence of hyperleukocytosis in acute myeloid leukemia (AML) ranges between 5-20% but leukostasis is less common than hyperleukocytosis in this population; leukostasis tends to occur more often in people with AML with monocytic features.[7] ## References[edit] 1. ^ Schiffer, Charles, MD. "Hyperleukocytosis and Leukostasis". UpToDate. Retrieved 11 November 2017. 2. ^ a b c d e f g "Hyperleukocytosis and leukostasis in hematologic malignancies". www.uptodate.com. Retrieved 2017-12-12. 3. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae Table 12-6 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007), Robbins Basic Pathology, Philadelphia: Saunders, ISBN 978-1-4160-2973-1 8th edition. 4. ^ Leukocytosis: Basics of Clinical Assessment, American Family Physician. November 2000. 5. ^ Schellongowski, P.; Staudinger, T. (September 2013). "[Leukostasis and tumor lysis: important complications of hyperleukocytosis]". Der Internist. 54 (9): 1051–1060. doi:10.1007/s00108-013-3260-5. ISSN 1432-1289. PMID 23943008. 6. ^ a b c d e Ganzel, C; Becker, J; Mintz, PD; Lazarus, HM; Rowe, JM (May 2012). "Hyperleukocytosis, leukostasis and leukapheresis: practice management". Blood Reviews. 26 (3): 117–22. doi:10.1016/j.blre.2012.01.003. PMID 22364832. 7. ^ a b c d e f g h i j k Ali, AM; Mirrakhimov, AE; Abboud, CN; Cashen, AF (June 2016). "Leukostasis in adult acute hyperleukocytic leukemia: a clinician's digest". Hematological Oncology. 34 (2): 69–78. doi:10.1002/hon.2292. PMID 27018197. 8. ^ "Leukostasis". Medical Subject Headings, 2009–2009-02-13. 1995-06-01. * v * t * e Diseases of monocytes and granulocytes Monocytes and macrophages ↑ -cytosis: * Monocytosis * Histiocytosis * Chronic granulomatous disease ↓ -penia: * Monocytopenia Granulocytes ↑ -cytosis: * granulocytosis * Neutrophilia * Eosinophilia/Hypereosinophilic syndrome * Basophilia * Bandemia ↓ -penia: * Granulocytopenia/agranulocytosis (Neutropenia/Severe congenital neutropenia/Cyclic neutropenia * Eosinopenia * Basopenia) Disorder of phagocytosis Chemotaxis and degranulation * Leukocyte adhesion deficiency * LAD1 * LAD2 * Chédiak–Higashi syndrome * Neutrophil-specific granule deficiency Respiratory burst * Chronic granulomatous disease * Neutrophil immunodeficiency syndrome * Myeloperoxidase deficiency * v * t * e Lymphatic disease: organ and vessel diseases Thymus * Abscess * Hyperplasia * Hypoplasia * DiGeorge syndrome * Ectopic thymus * Thymoma * Thymic carcinoma Spleen * Asplenia * Asplenia with cardiovascular anomalies * Accessory spleen * Polysplenia * Wandering spleen * Splenomegaly * Banti's syndrome * Splenic infarction * Splenic tumor Lymph node * Lymphadenopathy * Generalized lymphadenopathy * Castleman's disease * Intranodal palisaded myofibroblastoma * Kikuchi disease * Tonsils * see Template:Respiratory pathology Lymphatic vessels * Lymphangitis * Lymphangiectasia * Lymphedema * Primary lymphedema * Congenital lymphedema * Lymphedema praecox * Lymphedema tarda * Lymphedema–distichiasis syndrome * Milroy's disease * Secondary lymphedema * Bullous lymphedema * Factitial lymphedema * Postinflammatory lymphedema * Postmastectomy lymphangiosarcoma * Waldmann disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Leukostasis	c0282548	30,583	wikipedia	https://en.wikipedia.org/wiki/Leukostasis	2021-01-18T19:03:05	{"mesh": ["D018921"], "umls": ["C0282548"], "wikidata": ["Q3237103"]}
A number sign (#) is used with this entry because of evidence that familial hyperinsulinemic hypoglycemia-5 (HHF5) is caused by heterozygous mutation in the insulin receptor gene (INSR; 147670) on chromosome 19p13. For a phenotypic description and a discussion of genetic heterogeneity of familial hyperinsulinemic hypoglycemia, see HHF1 (256450). Clinical Features Hojlund et al. (2004) described a large 3-generation Danish family in which affected members had postprandial episodes of neuroglycopenia. The proband was a 21-year-old woman who since the age of 12 had experienced episodes of blurred vision, loss of consciousness, and seizures, occurring 2 to 5 hours after eating, often in conjunction with exercise and relieved by food ingestion. Her EEG was normal. At age 20, hyperinsulinemic hypoglycemia was documented; the patient was noted to be nonobese with no signs of insulin resistance such as skin pigmentation or hirsutism. Nine other family members in 3 generations also had episodes of hypoglycemia which ranged from moderate symptoms of hypoglycemia in 2 family members to episodes with loss of consciousness in 8 and seizures causing admission to emergency units in 5. The reported age of onset was between 3 and 30 years, and all affected family members were shown to have fasting hyperinsulinemia and an elevated serum insulin-to-C-peptide ratio. The proband's sister, who had moderate symptoms of hypoglycemia, showed mild skin pigmentation in the axillae, increased total and free serum levels of testosterone, and polycystic ovaries. Mapping By linkage analysis using DNA from 19 members of a 3-generation Danish family with hyperinsulinemic hypoglycemia, Hojlund et al. (2004) found complete cosegregation of the disease phenotype with a specific haplotype in the insulin receptor region on 19p13. A maximum lod score of 3.21 was achieved. Molecular Genetics In all affected members of a 3-generation Danish family with hyperinsulinemic hypoglycemia, Hojlund et al. (2004) identified heterozygosity for a point mutation in the insulin receptor gene (147670.0030). The mutation was not found in any unaffected family members. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Loss of consciousness due to hypoglycemia \- Seizures, hypoglycemic ENDOCRINE FEATURES \- Hyperinsulinemic hypoglycemia LABORATORY ABNORMALITIES \- Hypoglycemia, postprandial \- Hyperinsulinemia, fasting \- Elevated serum insulin-to-C-peptide ratio MISCELLANEOUS \- Genetic heterogeneity (see HHF1 256450 ) MOLECULAR BASIS \- Caused by mutation in the insulin receptor gene (INSR, 147670.0037 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 5	c1864952	30,584	omim	https://www.omim.org/entry/609968	2019-09-22T16:05:20	{"doid": ["0070220"], "mesh": ["C566494"], "omim": ["609968"], "orphanet": ["263458"], "synonyms": ["Hyperinsulinemic hypoglycemia due to INSR deficiency", "Hyperinsulinemic hypoglycemia due to insulin receptor deficiency"]}
## Mapping In a consanguineous Iranian family in which several members had an autosomal recessive form of prelingual profound sensorineural hearing loss, Delmaghani et al. (2003) found linkage of the disorder to a locus, designated DFNB40, on chromosome 22q11.21-q12.1. The approximately 9-Mb interval was bordered by markers D22S427 and D22S1144; a maximum lod score of 3.09 was obtained with D22S1174. The authors noted that the 'Bronx waltzer' (bv) mouse mutant, characterized by waltzing behavior, deafness, and degeneration of cochlear inner hair cells, had been mapped to mouse chromosome 5 in a region of syntenic homology to 22q. They suggested that DFNB40 and bv may result from orthologous gene defects. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Deafness, sensorineural, prelingual, profound \- Hearing threshold at or above 90 dB at all frequencies tested (0.25-8.0 kHz) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	DEAFNESS, AUTOSOMAL RECESSIVE 40	c1842345	30,585	omim	https://www.omim.org/entry/608264	2019-09-22T16:08:04	{"doid": ["0110499"], "mesh": ["C564266"], "omim": ["608264"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]}
Tetra-amelia syndrome is a very rare disorder characterized by the absence of all four limbs. ("Tetra" is the Greek word for "four," and "amelia" refers to the failure of an arm or leg to develop before birth.) This syndrome can also cause severe malformations of other parts of the body, including the face and head, heart, nervous system, skeleton, and genitalia. The lungs are underdeveloped in many cases, which makes breathing difficult or impossible. Because children with tetra-amelia syndrome have such serious medical problems, most are stillborn or die shortly after birth. ## Frequency Tetra-amelia syndrome has been reported in only a few families worldwide. ## Causes Researchers have found a mutation in the WNT3 gene in people with tetra-amelia syndrome from one large family. This gene is part of a family of WNT genes that play critical roles in development before birth. The protein produced from the WNT3 gene is involved in the formation of the limbs and other body systems during embryonic development. Mutations in the WNT3 gene prevent cells from producing functional WNT3 protein, which disrupts normal limb formation and leads to the other serious birth defects associated with tetra-amelia syndrome. In other affected families, the cause of tetra-amelia syndrome has not been determined. Researchers believe that unidentified mutations in WNT3 or other genes involved in limb development are probably responsible for the disorder in these cases. ### Learn more about the gene associated with Tetra-amelia syndrome * WNT3 ## Inheritance Pattern In most of the families reported so far, tetra-amelia syndrome appears to have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with tetra-amelia syndrome each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Tetra-amelia syndrome	c4012268	30,586	medlineplus	https://medlineplus.gov/genetics/condition/tetra-amelia-syndrome/	2021-01-27T08:24:38	{"gard": ["5148"], "omim": ["273395"], "synonyms": []}
Snyder-Robinson syndrome is a condition characterized by intellectual disability, muscle and bone abnormalities, and other problems with development. It occurs exclusively in males. Males with Snyder-Robinson syndrome have delayed development and intellectual disability beginning in early childhood. The intellectual disability can range from mild to profound. Speech often develops late, and speech difficulties are common. Some affected individuals never develop any speech. Most affected males are thin and have low muscle mass, a body type described as an asthenic habitus. Weakness or "floppiness" (hypotonia) typically becomes apparent in infancy, and the loss of muscle tissue continues with age. People with this condition often have difficulty walking; most have an unsteady gait. Snyder-Robinson syndrome causes skeletal problems, particularly thinning of the bones (osteoporosis) that starts in early childhood. Osteoporosis causes the bones to be brittle and to break easily, often during normal activities. In people with Snyder-Robinson syndrome, broken bones occur most often in the arms and legs. Most affected individuals also develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Affected individuals tend to be shorter than their peers and others in their family. Snyder-Robinson syndrome is associated with distinctive facial features, including a prominent lower lip; a high, narrow roof of the mouth or an opening in the roof of the mouth (a cleft palate); and differences in the size and shape of the right and left sides of the face (facial asymmetry). Other signs and symptoms that have been reported include seizures that begin in childhood and abnormalities of the genitalia and kidneys. ## Frequency Snyder-Robinson syndrome is a rare condition; its prevalence is unknown. About 10 affected families have been identified worldwide. ## Causes Snyder-Robinson syndrome results from mutations in the SMS gene. This gene provides instructions for making an enzyme called spermine synthase. This enzyme is involved in the production of spermine, which is a type of small molecule called a polyamine. Polyamines have many critical functions within cells. Studies suggest that these molecules play roles in cell growth and division, the production of new proteins, the repair of damaged tissues, the function of molecules called ion channels, and the controlled self-destruction of cells (apoptosis). Polyamines appear to be necessary for normal development and function of the brain and other parts of the body. Mutations in the SMS gene greatly reduce or eliminate the activity of spermine synthase, which decreases the amount of spermine in cells. A shortage of this polyamine clearly impacts normal development, including the development of the brain, muscles, and bones, but it is unknown how it leads to the specific signs and symptoms of Snyder-Robinson syndrome. ### Learn more about the gene associated with Snyder-Robinson syndrome * SMS ## Inheritance Pattern This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. No cases of Snyder-Robinson syndrome in females have been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Snyder-Robinson syndrome	c0796160	30,587	medlineplus	https://medlineplus.gov/genetics/condition/snyder-robinson-syndrome/	2021-01-27T08:24:43	{"gard": ["5615"], "mesh": ["C536678"], "omim": ["309583"], "synonyms": []}
Hepato-biliary diseases include liver diseases and biliary diseases. Their study is known as hepatology. ## Contents * 1 Liver diseases * 1.1 Viral hepatitis * 1.2 Other infectious diseases * 1.3 Other inflammatory diseases * 1.4 Alcohol * 1.5 Toxins * 1.6 Tumours * 1.7 End-stage liver disease * 1.8 Metabolic diseases * 1.9 Vascular disorders * 1.10 Cysts * 1.11 Others * 2 Gallbladder and biliary tract diseases * 2.1 References ## Liver diseases[edit] Further information: Chronic liver disease ### Viral hepatitis[edit] * Acute hepatitis A * Acute hepatitis B * Acute hepatitis C * Acute hepatitis D – this is a superinfection with the delta-agent in a patient already infected with hepatitis B * Acute hepatitis E * Chronic viral hepatitis * Other viral hepatitis viruses may exist but their relation to the disease is not firmly established like the previous ones (hepatitis F, GB virus C, hepatitis X) ### Other infectious diseases[edit] * Hepatitis: * cytomegalovirus infection * herpesviral: herpes simplex infection * Toxoplasmosis * Hepatosplenic schistosomiasis * Portal hypertension in schistosomiasis * Liver disease in syphilis * Epstein–Barr virus infection * yellow fever virus infection * rubella virus infection * leptospirosis * Echinococcosis * Amoebiasis ### Other inflammatory diseases[edit] * liver abscess * autoimmune hepatitis * primary biliary cholangitis (primary biliary cirrhosis) * phlebitis of the portal vein * granulomatous hepatitis * berylliosis * sarcoidosis * nonalcoholic steatohepatitis (NASH) ### Alcohol[edit] This may cause fatty liver, hepatitis, fibrosis and sclerosis leading to cirrhosis and finally liver failure. ### Toxins[edit] This includes mostly drug-induced hepatotoxicity, (DILI) which may generate many different patterns over liver disease, including * cholestasis * necrosis * acute hepatitis and chronic hepatitis of different forms, * cirrhosis * Effects of Acetaminophen (Tylenol) * other rare disorders like focal nodular hyperplasia, Hepatic fibrosis, peliosis hepatis and veno-occlusive disease. Liver damage is part of Reye syndrome. ### Tumours[edit] Malignant neoplasm of liver and intrahepatic bile ducts. The most frequent forms are metastatic malignant neoplasm of liver) * liver cell carcinoma * hepatocellular carcinoma * hepatoma * cholangiocarcinoma * hepatoblastoma * angiosarcoma of liver * Kupffer cell sarcoma * other sarcomas of liver Benign neoplasm of liver include hepatic hemangiomas, hepatic adenomas, and focal nodular hyperplasia (FNH). ### End-stage liver disease[edit] Chronic liver diseases like chronic hepatitis, chronic alcohol abuse or chronic toxic liver disease may cause * liver failure and hepatorenal syndrome * fibrosis and cirrhosis of liver Cirrhosis may also occur in primary biliary cirrhosis. Rarely, cirrhosis is congenital. ### Metabolic diseases[edit] * metabolic diseases (chapter E in ICD-10) * haemochromatosis * Wilson's disease * Gilbert's syndrome * Crigler–Najjar syndrome * Dubin–Johnson syndrome * Rotor syndrome ### Vascular disorders[edit] * chronic passive congestion of liver * central haemorrhagic necrosis of liver * infarction of liver * peliosis hepatis * veno-occlusive disease * portal hypertension * Budd–Chiari syndrome ### Cysts[edit] * Congenital cystic disease of the liver * Cysts caused by Echinococcus * Polycystic liver disease ### Others[edit] Amyloid degeneration of liver ## Gallbladder and biliary tract diseases[edit] * malignant neoplasm of the gallbladder * malignant neoplasm of other parts of biliary tract * extrahepatic bile duct * ampulla of Vater * cholelithiasis * cholecystitis * others (excluding postcholecystectomy syndrome), but including * other obstructions of the gallbladder (like strictures) * hydrops, perforation, fistula * cholesterolosis * biliary dyskinesia * ICD-10 code K83: other diseases of the biliary tract: * cholangitis (including ascending cholangitis and primary sclerosing cholangitis) * obstruction, perforation, fistula of biliary tract (bile duct) * spasm of sphincter of Oddi * biliary cyst * biliary atresia ### References[edit] ICD-10 codes K70-K77: Liver Diseases [1] * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * 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dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	List of hepato-biliary diseases	c0267792	30,588	wikipedia	https://en.wikipedia.org/wiki/List_of_hepato-biliary_diseases	2021-01-18T18:50:36	{"umls": ["C0267792"], "wikidata": ["Q2755530"]}
Scanning electron micrograph of Mycobacterium tuberculosis Tuberculosis is a serious public health problem in China.[1] China has the world's third largest cases of tuberculosis (after India and Indonesia), but progress in tuberculosis control was slow during the 1990s. Detection of tuberculosis had stagnated at around 30% of the estimated total of new cases, and multidrug-resistant tuberculosis[1] was a major problem. These signs of inadequate tuberculosis control can be linked to a malfunctioning health system. The spread of severe acute respiratory syndrome (SARS) in 2003, brought to light substantial weaknesses in the country's public health system. After the government realized the impact that the SARS outbreak had on the country, they increased leadership in their health department.[2] After the SARS epidemic was brought under control, the government increased its commitment and leadership to tackle public health problems and, among other efforts, increased public health funding, revised laws that concerned the control of infectious diseases, implemented the world's largest internet-based disease reporting system to improve transparency, reach and speed, and started a program to rebuild local public health facilities and national infrastructure. These measures contributed to acceleration in efforts to control tuberculosis. By 2005, the detection of cases of tuberculosis had increased to 80% of the estimated total new cases, permitting China to achieve the 2005 global tuberculosis control targets. At the same time, specific efforts to improve tuberculosis control also contributed to strengthening of the public health system. In this case, the strengthening of the disease control program and the public health system had worked together to achieve a desired health outcome. On February 23, 2007, the Chinese government undertook a review of the tuberculosis situation in China, which looked at the progress in tuberculosis control before the SARS epidemic, outlined the measures taken to improve the public health system after that epidemic, described how those measures contributed to the acceleration of tuberculosis control efforts, and discuss the challenges that China must address to halve the number of tuberculosis cases and deaths as part of the Millennium Development Goals (MDGs). ## Contents * 1 Epidemiology * 1.1 Focusing on vulnerable groups * 2 Control and prevention * 2.1 Tuberculosis control before SARS * 2.2 Efforts to control tuberculosis after SARS * 2.3 2009-2014 program * 3 Reviewing of strategy * 4 See also * 5 References * 6 Further reading * 7 External links ## Epidemiology[edit] In 2007, the prevalence of TB per 100,000 people was relatively high in Asia, and was highest in sub-Saharan Africa.[3][1] In China, tuberculosis has been the number 1 cause of death from infectious disease in adults. In 1990, 360,000 people in China died from tuberculosis. Tuberculosis is one of China's major public health problems. According to the 2015 WHO estimates, China has the world's third largest number of tuberculosis cases, behind only India and Indonesia, comprising around 10% of the world total.[4] Of the 37 notifiable communicable diseases in China, tuberculosis ranks first in terms of notified cases and deaths.[5] Despite the serious nature of this disease, the country's progress in tuberculosis control was slow during the 1990s and early part of the new millennium. The estimated proportion of new cases of sputum smear-positive tuberculosis that were diagnosed and treated by the public health program - a key indicator of efforts to control tuberculosis - had stagnated at around 30%, far below the 70% target set by the WHO. In 2003, an epidemic of severe acute respiratory syndrome (SARS) broke out in China. (See Progress of the SARS outbreak.) The spread of SARS brought to light substantial weaknesses in the country's public health system. After the SARS epidemic was brought under control, the Chinese government implemented a series of measures to strengthen its public health system. This effort coincided with acceleration in efforts to control tuberculosis. Within 3 years, implementation of the WHO-recommended DOTS (Directly Observed Therapy, Shortcourse) strategy to control tuberculosis increased from 68% to 100% of counties and the detection of cases of smear-positive tuberculosis by the public health system more than doubled, from 30% of new cases to 80%. Together with a tuberculosis treatment success rate of more than 90%, China achieved the 2005 global targets for tuberculosis control. Progress of tuberculosis control in China, 1991–2005 Year Proportion (%) of new smear-positive TB cases successfully treated Estimated proportion (%) of all new smear-positive TB cases detected Proportion (%) of counties implementing the WHO-recommended DOTS strategy 1991 69 4 5 1992 75 7 7 1993 79 10 19 1994 88 14 48 1995 92 21 58 1996 94 25 60 1997 94 26 61 1998 93 27 62 1999 92 28 63 2000 92 30 63 2001 91 29 65 2002 91 26 64 2003 92 44 77 2004 90 63 89 2005 90 80 100 ### Focusing on vulnerable groups[edit] One group of special concern are work migrants, most often poor men, who leave the countryside to join the wage economy in towns and cities all over China.[6][7][8][9] Some come from areas such as Henan Province where huge numbers of peasants were infected with HIV from scandalous plasma-donor practices in the 1990s. Many male migrants are at risk of unprotected sex when away from home. And men are also at higher risk of tuberculosis than women in China because the male-to-female ratio of adults with pulmonary tuberculosis is about 2:1 or more, reflecting a real risk excess rather than differential detection or notification.[10][11] So several factors converge in young male migrant workers to put them at risk of both HIV and tuberculosis, and this convergence has been of great concern. With this "floating" migrant population making up 10% of the total being poorer and having more tuberculosis than average, China has far more than its share of tuberculosis (disease burden) in the world. This problem is compounded because China's internal work migrants often live and work in circumstances that promote transmission of tuberculosis and impede its diagnosis and treatment.[6][7][9] They are usually so poor that the cost of adequate diagnosis and treatment is prohibitively expensive. Indeed, they may not be able to get treated at all unless they return to their home village in the poor interior, because subsidized management of tuberculosis (and other social welfare) is only available through facilities in the area where they were registered at birth.[8] Those born in rural zones are not allowed to switch registration to become urban residents. They have been allowed to leave their area (temporarily) or work since 1992 and now number more than 100 million. China's rapid economic growth depends on them, but if they get tuberculosis, they have to return home for treatment. Going home for rural healthcare in China is not ideal either. Over the past 30 years, that part of the health system has run down because government funding has fallen while everything else has become more expensive. Health facilities attempted to make up shortfalls by charging ever larger fees for diagnosis and treatment, especially for a difficult disease like tuberculosis. In China today, patients' payments keep the health services running and the medical staff have been encouraged to supply profitable health goods and services, especially drugs. Their own jobs depend on adequate operational funds, which are largely generated through user fees. Meanwhile, over the same 30 years, the socialist system of universal rural health-insurance collapsed and was not replaced apart from some pilot tests of an under-resourced community-based scheme in the 1990s.[12][13] Until recently, virtually all rural residents, 900 million in all, had no health insurance at all. This situation will change if the current experiments with community-based health-insurance succeed and are then adopted nationally, but in the meantime as many as 10% of rural households have catastrophic medical payments (exceeding 40% of their disposable income) every year.[13] ## Control and prevention[edit] ### Tuberculosis control before SARS[edit] Tuberculosis control has been a part of China's public health program since the 1950s. China developed and implemented two 5-year national plans in the 1980s and one 10-year plan in the 1990s to control tuberculosis. On the basis of national surveys in 1979 and 1990, the prevalence of tuberculosis fell by an average of 3.3% every year during the 1980s.[14] In the 1990s, the government implemented two major tuberculosis control projects as part of its 10-year plan to control tuberculosis. The first, funded in part by the World Bank loan of $58.2 million, covered half of China's population and implemented the DOTS strategy in 13 provinces between 1992 and 2001.[15] The second used limited funding from the Ministry of Health to subsidize treatment for patients in an extra 10-15% of the population. The project funded by the World Bank led to several important achievements. Nearly 1.5 million cases of smear-positive tuberculosis were diagnosed and cured.[15] A large cadre of healthcare workers was trained in the fundamental elements of DOTS, firmly establishing these methods as the national strategy for tuberculosis control. Most importantly, on the basis of results from the 2000 national tuberculosis survey, there was a 36% reduction in disease prevalence between 1990 and 2000 in the half of China that implemented the projects.[16] Despite these achievements, there were signs of difficulties elsewhere in the country's tuberculosis control program. In the half of China that did not implement the project funded by the World Bank, the prevalence of tuberculosis did not fall during the 1990s.[16] Thus, the fall in tuberculosis prevalence for the entire country slowed to 2.5% per year during the 1990s. The 2000 national tuberculosis survey revealed that one in ten patients with tuberculosis had multi-drug resistant (MDR) disease — i.e., resistant to both isoniazid and rifampicin.[16] Other studies confirmed a serious epidemic of MDR tuberculosis in several Chinese provinces, with rates of multidrug resistance in previously untreated cases that were five to ten times higher than the global mean.[17][18][1] The inadequate control of tuberculosis can be linked to a malfunctioning health system. From 1978 to 2002, the government's share of total health expenditure fell from 32% to 16%.[19] This reduction forced many Chinese health-care facilities and providers to focus on the generation of revenue, with little concern for public health. Hospitals and clinics essentially functioned (and continue to function) as for-profit entities.[20] In 2000, nearly 90% of patients with tuberculosis initiated their diagnostic and treatment process in hospitals and non-public health-care facilities, where they were given tests and drugs as long as they could pay.[16] Many patients who improved or ran out of money discontinued treatment. Thus, only 20% of patients with tuberculosis treated outside the public health system took their tuberculosis medications regularly in 2000.[16] Such irregular treatment breeds drug-resistant tuberculosis.[1] For those patients with tuberculosis who eventually ended up in the public health system, the problems did not end there. Governmental funding for public health had also declined over the years. In 2002, only about 41% of funding for the country's Center for Disease Control and Prevention (CDC) institutions came from the government.[19] To make ends meet, local CDCs concentrated on the generation of revenue. There was little incentive to undertake tuberculosis control activities, which are labor-intensive and create little income. Even in areas where government subsidies support free diagnosis and treatment of tuberculosis, many CDCs continue to charge patients for ancillary tests and drugs, some of which are of questionable benefit. Against this backdrop, the central government began efforts to revitalise its tuberculosis control program in 2000. Most important was the increased political commitment to tackle tuberculosis. In March 2000, the Minister of Health Zhang Wenkang and Vice-Minister of Finance Gao Qiang attended the Ministerial Conference on Tuberculosis and Sustainable Development in Amsterdam, where they committed to strengthen the country's efforts to control tuberculosis. In December 2000, the State Council of China held a nationwide video-teleconference on tuberculosis. Vice-Premier Li Lanqing gave explicit instructions to strengthen the tuberculosis control effort. In October 2001, the government issued the second 10-year plan (2001–10) to control tuberculosis.[21] In 2002, the central government increased its funding for tuberculosis from US$300 000 per year to $4·8 million per year. The government also organised a partnership with international agencies to support the country's efforts to control tuberculosis. Early in 2002, the government signed a 7-year, $104 million loan with the World Bank, which included blended grant funding from the UK's Department for International Development; also, the Japanese government began to provide free antituberculosis drugs in 12 provinces. In late 2002, China received a $48 million grant from the Global Fund to fight AIDS, Tuberculosis and Malaria to tackle tuberculosis. The Damien Foundation Belgium and the Canadian International Development Agency have supported efforts to control tuberculosis in several provinces. WHO served as the lead technical agency, providing policy and technical support to the national tuberculosis program. WHO sent an in-country adviser and many short-term consultants; the KNCV Tuberculosis Foundation also provided valuable technical support. By late 2002, with increased governmental and international support, DOTS began to expand to all provinces. ### Efforts to control tuberculosis after SARS[edit] Early in 2003, the SARS epidemic brought China to a virtual standstill. Most tuberculosis control activities came to a stop. However, after the SARS epidemic had been successfully controlled, tuberculosis control activities picked up rapidly in the second half of the year. By the end of 2003, 43% of the estimated total new cases of smear-positive tuberculosis had been diagnosed and treated in the country's DOTS program. With further acceleration of tuberculosis control efforts, 64% and 80% of these cases were diagnosed and treated in 2004 and 2005, respectively. The acceleration of efforts to control tuberculosis after the SARS epidemic would not have been possible if the government had not laid the foundation to revitalize the tuberculosis control program before 2003. However, the gains in tuberculosis control after SARS also resulted from measures to improve the public health system. The first of the key measures that have been implemented in the 3 years since the SARS crisis ended was greatly increased commitment and leadership from the government to tackle public health problems. During the SARS epidemic, governmental and communist party leaders at all levels—from Paramount leader Hu Jintao, Premier Wen Jiabo and members of the State Council down to village leaders—were involved in tackling a single public-health issue. The epidemic and its eventual control convinced Chinese leaders that the government should be much more involved in addressing public-health problems. After the SARS epidemic, the State Council developed a mechanism to oversee public-health emergencies directly.[22] The State Council has also involved itself with other pressing public-health challenges, including HIV/AIDS, avian influenza, occupational safety, and environmental health. The increased political commitment to public health has benefited tuberculosis control. In March 2004, Vice-Minister of Health Wang Longde attended the second Stop TB Partners' Forum in New Delhi, India,[23] and made a commitment on behalf of the government to achieve the 2005 global targets for tuberculosis control. In June 2004, the State Council held a video-teleconference with provincial Vice-Governors to discuss steps to accelerate efforts to control tuberculosis. The Ministry of Health identified 12 provinces with more than 85% of the "missing" cases needed to reach the 70% target for case detection in China and sent monitoring teams to these provinces to identify and solve existing problems. In December 2004, Vice-Minister Wang Longde and Shigeru Omi, WHO Regional Director of the Western Pacific, co-chaired a high-level tuberculosis meeting in China. Governmental leaders from the 12 provinces participated, including the Vice-Governors from eight provinces. In addition to increased involvement and commitment, the central government has increased funding for public health from $835 million in 2002 to $1·44 billion in 2004. Over this period, the proportion of total CDC funding provided by the government increased from 40·7% to 47·1%, reversing a downward trend.[19] The central government increased funding for four priority communicable diseases in particular—HIV/AIDS, tuberculosis, schistosomiasis, and hepatitis B. Tuberculosis funding increased by more than seven times during this period (reaching $36 million in 2005) and contributed to 26% of the total funding available for the national tuberculosis control program in 2005. The additional funding has been used to expand health promotion activities, to provide financial incentives to village workers to find and treat tuberculosis, and to provide free treatment for people with smear-negative pulmonary tuberculosis for the first time. Furthermore, the central government revised the law on the control of infectious diseases[24] in March 2004. The revision provides instructions to tackle infectious-disease outbreaks, improve the reporting of infectious diseases, implement interventions to control the spread of such diseases, provide clinical services, and fund the control of infectious diseases. This law directly benefited tuberculosis control by addressing the under-reporting of tuberculosis by health facilities. Tuberculosis now has to be reported to local public-health authorities within 24 hours. Because failure to report is now a crime, hospitals have begun to take the reporting of tuberculosis very seriously. In January 2004, the Ministry of Health implemented the world's largest internet-based communicable-disease reporting system.[25] This system addressed the delays and incomplete reporting of communicable diseases, which were most evident during the SARS epidemic, when governmental authorities could not quickly assess the extent of the epidemic. At the end of 2005, 93% of 19 716 health facilities at and above the county-level and 66% of 38 518 township-level health facilities were reporting the country's 37 notifiable diseases through this system. The mean length of time to report from a county-level health facility to the central level has been reduced from 29 days to 1 day.[25] With this new internet-based reporting system, individuals involved in tuberculosis control can rapidly identify cases of tuberculosis—both confirmed and suspected—in China's vast hospital system for the first time. This information is being used to trace patients with tuberculosis and ensure their proper diagnosis and treatment. In 2004, 447 777 suspected or confirmed cases of tuberculosis were reported from hospitals. This number increased to 686 742 in 2005 as more hospitals implemented this system; almost 64% of these patients were successfully followed up. On the basis of preliminary analysis by the China CDC, 25% of all cases of tuberculosis in 2005 were initially reported from hospitals via the internet. The government has also started a massive program to rebuild local public-health facilities. SARS revealed that public-health facilities were largely outdated and inadequate to tackle existing public-health problems, not to mention addressing new or emerging challenges. The government is currently investing $1·3 billion to rebuild 2448 CDC facilities in 27 provinces. When completed, more than 80% of the country's CDC facilities will be new. The central government will provide 28% of the needed funding, with the rest coming from governments at various levels. However, China's poorer western provinces will receive preferential support, with 65% of the needed funding coming from the central government. Tuberculosis control programs will directly benefit from this approach, since more than 80% of China's tuberculosis dispensaries are located in local CDC facilities. Although a strengthened public-health system has accelerated the national tuberculosis control effort, progress in tuberculosis control has also strengthened the public-health system. In terms of policy, the national tuberculosis control program has clear targets and well-defined technical policies based on the DOTS strategy. National and international partners work in a cohesive manner toward the same targets, with the same implementation framework. Other public-health programs are learning from this successful model. In financial terms, funding from different partners is harmonized under one financing plan with clear funding needs and gaps—another model for other programs. Furthermore, the failure to control tuberculosis in the past—when tuberculosis services were not free—and the success in tuberculosis control over the past few years—when tuberculosis services have been free—have provided policymakers with arguments to increase funding for public health from the government. With regard to management, several features of DOTS—e.g., directly observed therapy to manage treatment of patients and the management of logistics and drugs—are now used to tackle HIV/AIDS and in other public-health programs. Furthermore, although many public-health workers are being trained to implement DOTS, setbacks caused by inadequate numbers of trained workers have shown governmental leaders the importance of such resources in public health, and thus they have increased planning for them. In terms of information systems, the tuberculosis program's quarterly recording and reporting system has long been a model for other disease control programs. With the new internet-based reporting system for communicable diseases, the tuberculosis program leads the way in the use of information to improve public-health outcomes. Finally, the model of collaboration between hospitals and CDC facilities provided by the tuberculosis control program is one of the best examples to date of how hospitals should be involved in the prevention and control of infectious diseases, and has influenced the development of new policies that involve hospitals in the work of public health. Tuberculosis in China was most effectively prevented through spreading awareness. Information was widely spread throughout China, mainly throughout the form of government funded free pamphlets, handed out at children's sporting events. ### 2009-2014 program[edit] A new five-year initiative program, announced on 1 April 2009, aims to use innovative technologies to improve the detection and treatment of tuberculosis (TB) in China. Cutting edge diagnostic tests, drug regimens that reduce the number of pills a patient needs to take, and innovative ways of ensuring patients take their drugs — such as mobile phone text messaging — are to be rolled out under a program led by the Chinese Ministry of Health. It will be implemented in five designated provinces and one municipality — covering 20 million people at risk of TB. The proposed diagnostic tools will include the use of LED microscopes and DNA-based diagnosis. Using LEDs rather than standard phosphorescent lights in microscopes forms a clearer image and improves TB detection rates in patients' sputum from 50 to 65 per cent. And DNA testing, which can determine which strains of Mycobacterium tuberculosis are present in sputum[1] has 98 per cent accuracy and can be used to detect drug-resistant strains in as little as a day. DNA-based diagnosis is also cost-effective. As well as diagnosis, new management methods such as mobile phone text messaging and medicine kits with built-in reminder alarms will be used to enhance patients' drug compliance.[1] Drug combinations — where different drugs are combined in the same pill — will also be used to reduce the number of pills a patient has to take from around 13 to three or four a day. After two-and-a-half years effective interventions will be scaled up. Some 20 cities covering 100 million people should be included by the end of the fifth year of the program, funded by a US$33 million grant from the Bill & Melinda Gates Foundation. ## Reviewing of strategy[edit] Although China achieved the 2005 global targets for tuberculosis control, these are only targets for implementation and monitoring in the national and international efforts to control tuberculosis. More important are the targets of halving the prevalence of, and mortality from, tuberculosis. Countries in the Western Pacific region committed to these targets in 1999, as did the wider international community as part of the MDGs.[26][27] To achieve these targets, China needs to address existing challenges to its efforts to control tuberculosis. Foremost is the serious epidemic of MDR tuberculosis. WHO estimates that a third of the world's cases of MDR tuberculosis are in China, even though the country has only 15% of the global burden of tuberculosis.[28] The recent expansion of DOTS should help to limit the development of MDR tuberculosis. But reduction of the existing burden of multidrug resistance will take time, especially since poor-quality DOTS services in some areas and inappropriate treatment of tuberculosis in parts of the hospital system continue to generate new cases of MDR tuberculosis. The absence of a sound financing mechanism to fully fund tuberculosis services is a further problem. Although funding for tuberculosis services is at its highest level ever, the Ministry of Health estimates that the national tuberculosis control program still had a 23% funding gap in 2005. Additionally, more than a quarter of current funding comes from external grants and loans, making sustainable funding a major challenge. Another challenge is to make tuberculosis services accessible to the entire population. Although China has a policy of free tuberculosis services, in most places these are available only to permanent residents in a particular community. Urban migrants, who have relocated from poor rural areas to seek a better livelihood, are not eligible for such free services. These vulnerable, predominantly young migrants—now numbering more than 150 million—tend to live and work in crowded environments and are unlikely to seek medical care when they become ill. Such individuals contribute to the spread of tuberculosis, HIV infection, and other infectious diseases within urban centers. The growing epidemic of co-infection with tuberculosis and HIV if left unchecked will substantially increase the number of tuberculosis cases and deaths.[29] A further difficulty is presented by the shortage of trained health-care workers for tuberculosis control. CDC facilities are being rebuilt across the country but many are staffed inadequately or by poorly trained and unmotivated health-care workers. Finally, and perhaps most importantly, is the challenge of sustaining and further increasing long-term governmental commitment to the control of tuberculosis, which is essential to tackle the other challenges. China is developing tuberculosis-specific policies and interventions to address these challenges. The new 5-year implementation plan of the national tuberculosis control program (2006–10)[30] has incorporated key elements of the new Stop TB Strategy[31] and the second Global Plan to Stop TB.[32] These include a programmatic approach to diagnosis and treatment of MDR tuberculosis, tuberculosis control in migrants, and tuberculosis/HIV collaborative activities.[30] Additionally, the 5-year plan for implementation of the national HIV/AIDS program aims to stem the rise of the HIV/AIDS epidemic by expanding prevention, treatment, and care activities.[33] Implementation of these new policies and interventions will require a substantial increase in both domestic resources and international support, especially for poor areas in China's central-western provinces. Although disease-specific interventions are important, further strengthening of the public-health system will be needed if China is to halve the prevalence of tuberculosis and the number of deaths caused by the disease. To increase access, a package of essential public-health services for rural inhabitants and urban migrants should be provided with governmental subsidies. This package should include services for at least tuberculosis, immunisation, HIV/AIDS, sexually transmitted infections, and maternal and child health.[34][35] The government must also address the warped incentives in hospitals that encourage the generation of profits from drugs, tests, and state-of-the-art technologies.[36] This profit generation fuels the inappropriate diagnosis and treatment of many diseases, including tuberculosis. Finally, the government should provide operational costs for public-health services and full salaries for health-care workers, especially at and below the county level, where most of the rural population live.[36] The number of staff needed for essential public-health functions should be carefully calculated, and public-health workers must be given fair pay. Without this, the development and maintenance of a motivated and skilled public-health workforce to meet the challenges of the 21st century will be difficult. Ultimately, China's progress in the control of tuberculosis and public-health reform will depend on the degree of political commitment to address these challenges. In this regard, the indication by Premier Wen Jiabao, speaking at the National People's Congress in March 2006, that public health is a key component of the country's 11th 5-year development plan is very encouraging. He highlighted the need to improve rural and urban health services, making them affordable for all, and specifically mentioned the need to control HIV/AIDS, tuberculosis, and schistosomiasis.[37] With increased governmental commitment and funding to improve public health, China has reason to believe that the prevalence of tuberculosis and deaths caused by the disease can be halved within the next decade. In conclusion, the Chinese experience has shown that investment in both control programs and health systems—rather than investment in one or the other alone—was needed, and indeed essential, to achieve the 2005 global targets for tuberculosis, and provides an example for developing countries scaling-up efforts to achieve health-related MDGs. ## See also[edit] China-related * Public health in the People's Republic of China * Medicine in China * Pharmaceutical industry in China Tuberculosis-related * 2007 tuberculosis scare * Abreugraphy * ATC code J04 Drugs for treatment of TB * Buruli ulcer and leprosy: other diseases caused by mycobacteria * Latent tuberculosis * List of tuberculosis victims * Mycobacterium Tuberculosis Structural Genomics Consortium * National Center for HIV, STD, and TB Prevention * Nontuberculous mycobacteria * Overcrowding * Philip D'Arcy Hart * Tuberculosis in history and art * UNITAID * Nosocomial infection ## References[edit] 1. ^ a b c d e f g "Study shows movement, evolutionary history of TB in China". news.wisc.edu. Retrieved 2018-11-16. 2. ^ Wang L.; Liu J.; Chin D. P. (2007). "Progress in tuberculosis control and the evolving public-health system in china". The Lancet. 369 (9562): 691–6. doi:10.1016/S0140-6736(07)60316-X. PMC 7134616. PMID 17321314. 3. ^ "The Stop TB Strategy, case reports, treatment outcomes and estimates of TB burden". Global tuberculosis control: epidemiology, strategy, financing. World Health Organization. 2009. pp. 187–300. ISBN 978-92-4-156380-2. Archived from the original on 2009-11-19. Retrieved 2009-11-14. 4. ^ "Global tuberculosis Report 2015" (PDF). World Health Organization. 5. ^ "Ministry of Health report on status of national notifiable diseases in 2005". Ministry of Health Public Information Center. Retrieved 2007-01-05. 6. ^ a b Jackson S, Sleigh AC, Wang GJ, Liu XL (2006). "Household poverty, off-farm migration and pulmonary tuberculosis in rural Henan, China". In Sleigh AC, Chee HL, Yeoh BS, Phua KH, Safman R (eds.). Population dynamics and infectious diseases in Asia. Singapore: World Scientific. pp. 231–44. 7. ^ a b Jackson S, Sleigh AC, Wang GJ, Liu XL (2006). "Poverty and the economic effects of TB in rural China". Int. J. Tuberc. Lung Dis. 10 (10): 1104–10. PMID 17044202. 8. ^ a b Kelly D, Luo X (2006). "SARS and China's rural migrant labour: roots of a governance crisis". In Sleigh AC, Chee HL, Yeoh BS, Phua KH, Safman R (eds.). Population dynamics and infectious diseases in Asia. Singapore: World Scientific. pp. 389–408. 9. ^ a b Zhang LX, Tu DH, An YS, Enarson DA (2006). "The impact of migrants on the epidemiology of tuberculosis in Beijing, China". Int. J. Tuberc. Lung Dis. 10 (9): 959–62. PMID 16964784. 10. ^ China Tuberculosis Control Collaboration (2004). "The effect of tuberculosis control in China". Lancet. 364 (9432): 417–22. doi:10.1016/S0140-6736(04)16764-0. PMID 15288739. 11. ^ Borgdorff MW, Nagelkerke NJ, Dye C, Nunn P (2000). "Gender and tuberculosis: a comparison of prevalence surveys with notification data to explore sex differences in case detection". Int. J. Tuberc. Lung Dis. 4 (2): 123–32. PMID 10694090. 12. ^ Jackson S, Sleigh AC, Li P, Liu XL (2005). "Health finance in rural Henan: low premium insurance compared to the out-of-pocket system". China Q. 181: 137–57. doi:10.1017/S0305741005000081. 13. ^ a b Sun X, Jackson S, Carmichael G, Sleigh A (2007). "Catastrophic payment and health protection in rural China - impact of New Cooperative Medical Scheme in Shandong Province". Archived from the original on 2007-06-15. Retrieved 2007-02-15. 14. ^ Ministry of Public Health of the People's Republic of China. Nationwide random survey for the epidemiology of tuberculosis in 1990. Beijing: Ministry of Public Health of the People's Republic of China, 1992. 15. ^ a b Cai J, Chen X (eds) (2003). A model of tuberculosis control in China. Final evaluation report on tuberculosis control under the World Bank loaned China Infectious and Endemic Disease Control Project. Beijing: People's Medical Publishing House.CS1 maint: extra text: authors list (link) 16. ^ a b c d e Ministry of Health of the People's Republic of China. Report on nationwide random survey for the epidemiology of tuberculosis in 2000. Beijing: Ministry of Health of the People's Republic of China, 2002. 17. ^ WHO. Anti-tuberculosis drug resistance in the world: the WHO/IUATLD Global Project of Anti-tuberculosis Drug Resistance Surveillance. WHO/CDS/ TB/2000.278. Geneva: World Health Organization, 2000. 18. ^ WHO. Anti-tuberculosis drug resistance in the world: the WHO/IUATLD Global Project of Anti-tuberculosis Drug Resistance Surveillance. WHO/HTM/TB/2004.343. Geneva: World Health Organization, 2004. 19. ^ a b c China National Health Economics Institute. China national health accounts report. Beijing: China National Health Economics Institute, 2005. 20. ^ Blumenthal D, Hsiao W (2005). "Privatization and its discontents--the evolving Chinese health care system". N. Engl. J. Med. 353 (11): 1165–70. doi:10.1056/NEJMhpr051133. PMID 16162889. 21. ^ General Office of the State Council of the People's Republic of China. Announcement of the national tuberculosis prevention and control plan (2001–2010). Document number 2001: 75. Beijing, China. 22. ^ General Office of the State Council of the People's Republic of China. Regulation on the urgent handling of public health emergencies. Chin Prev Med 2003; 4 (suppl): 1-5. 23. ^ Stop TB Partnership. "Second Stop TB Partners' Forum". Archived from the original on 2006-10-25. Retrieved 2006-11-05. 24. ^ State Council of the People's Republic of China. Law of the People's Republic of China on the prevention and treatment of infectious diseases http://www.chinacdc.cn/n2722442/n272530/n272907/n272922[permanent dead link] (accessed Jan 5, 2007). 25. ^ a b Ma JQ, Yang GH, Shi XM (2006). "Information technology platform in China's disease surveillance system". Disease Surveillance. 21: 1–3. 26. ^ WHO Regional Committee for the Western Pacific. Tuberculosis prevention and control (WPR/RC51.R4) http://www.wpro.who.int/rcm/en/archives/rc51/rc_resolutions/wpr_rc51_r04.htm (accessed Nov 22, 2006). 27. ^ N Statistics Division. Millennium indicators database http://millenniumindicators.un.org/unsd/mdg/Host.aspx?Content=Indicators/OfficialList.htm (accessed June 14, 2006). 28. ^ Zigno M, Hosseini MS, Wright A, et al. (2006). "Global incidence of multidrug-resistant tuberculosis". J Infect Dis. 194 (4): 479–485. doi:10.1086/505877. PMID 16845631. 29. ^ Ministry of Health of ChinaUNAIDSWHO. 2005 update on the HIV/AIDS epidemic and response in China. Beijing: Ministry of Health, 2006. 30. ^ a b Anon. National tuberculosis prevention and control plan (2001–2010): 2006–2010 implementation plan. Beijing, China. General Office of the Ministry of Health. Publication number 2005–293. 31. ^ Raviglione MC, Uplekar MW (2006). "WHO's new Stop TB Strategy". Lancet. 367 (9514): 952–955. doi:10.1016/s0140-6736(06)68392-x. PMID 16546550. 32. ^ Stop TB PartnershipWHO. Global plan to Stop TB 2006–2015 (WHO/HTM/STB/2006.35). Geneva: World Health Organization, 2006:. 33. ^ General Office of the State Council of the People's Republic of China. China AIDS prevention and control implementation plan (2006–2010) "Archived copy". Archived from the original on 2007-08-07. Retrieved 2007-08-19.CS1 maint: archived copy as title (link) (accessed Nov 22, 2006). 34. ^ Lei H (2005). "A review and recommendations on building and remodeling China's public health system". China Development Review. 7: 81–108. 35. ^ United Nations Health Partners Group in China. A health situation assessment of the People's Republic of China. Beijing: World Health Organization, 2005. 36. ^ a b Project team of Development Research Center. An evaluation of and recommendations on the reforms of the health system in China (Executive summary). China Development Review 2005; 7: 1-24. 37. ^ Wen J. Report on work of the government. Fourth Session of the 10th National People's Congress and Chinese People's Political Consultative Conference http://china.org.cn/english/2006lh/161969.htm (accessed Nov 22, 2006). ## Further reading[edit] China * Sharma SK, Liu JJ (2006). "Progress of DOTS in global tuberculosis control". Lancet. 367 (9514): 951–2. doi:10.1016/S0140-6736(06)68391-8. PMID 16546549. * China Tuberculosis Control Collaboration (2004). "The effect of tuberculosis control in China". Lancet. 364 (9432): 417–22. doi:10.1016/S0140-6736(04)16764-0. PMID 15288739.. * Dye C, Fengzeng Z, Scheele S, Williams B (2000). "Evaluating the impact of tuberculosis control: number of deaths prevented by short-course chemotherapy in China" (PDF). International Journal of Epidemiology. 29 (3): 558–64. doi:10.1093/ije/29.3.558. PMID 10869331. * Squire SB, Tang S (2004). "How much of China's success in tuberculosis control is really due to DOTS?". Lancet. 364 (9432): 391–2. doi:10.1016/S0140-6736(04)16777-9. PMID 15288717. * Xianyi C, Fengzeng Z, Hongjin D, et al. (2002). "The DOTS strategy in China: results and lessons after 10 years". Bull. World Health Organ. 80 (6): 430–6. PMC 2567538. PMID 12131998. * World Health Organization. In: An expanded DOTS framework for effective tuberculosis control: stop TB communicable diseases. Geneva: WHO, 2002: 1-20WHO Document WHO/CDS/TB/2002·297. * China Tuberculosis Control Collaboration (1996). "Results of directly observed short-course chemotherapy in 112,842 Chinese patients with smear-positive tuberculosis. China Tuberculosis Control Collaboration". Lancet. 347 (8998): 358–62. doi:10.1016/S0140-6736(96)90537-1. PMID 8598701. * Tang S, Wang L, Wang X, Squire SB (2002). "Does rapid economic growth reduce TB prevalence in the absence of effective TB control". Int J TB Lung Dis. 6. (suppl 1): S149. * Tang S, Squire SB (2005). "What lessons can be drawn from tuberculosis (TB) control in China in the 1990s? An analysis from a health system perspective". Health Policy (Amsterdam, Netherlands). 72 (1): 93–104. doi:10.1016/j.healthpol.2004.06.009. PMID 15760702. General and applied * Zignol M, Hosseini MS, Wright A, et al. (2006). "Global incidence of multidrug-resistant tuberculosis". J. Infect. Dis. 194 (4): 479–85. doi:10.1086/505877. PMID 16845631. * Blumberg HM, Leonard MK, Jasmer RM (2005). "Update on the treatment of tuberculosis and latent tuberculosis infection". JAMA. 293 (22): 2776–84. doi:10.1001/jama.293.22.2776. PMID 15941808. * Dormandy, Thomas (2000). The White Death. New York: New York University Press. ISBN 978-0-8147-1927-5. * Joint Tuberculosis Committee of the British Thoracic Society (2000). "Control and prevention of tuberculosis in the United Kingdom: code of practice 2000". Thorax. 55 (11): 887–901. doi:10.1136/thorax.55.11.887. PMC 1745632. PMID 11050256. * Kidder, Tracy (2004). Mountains beyond Mountains. New York: Random House Trade Paperbacks. ISBN 978-0-8129-7301-3. A nonfiction account of treating TB in Haiti, Peru, and elsewhere. * Lawlor, Clark (2007). Consumption and Literature. Basingstoke: Palgrave Macmillan. ISBN 978-0-230-02003-0. * Nemery B, Yew WW, Albert R, et al. (2005). "Tuberculosis, nontuberculous lung infection, pleural disorders, pulmonary function, respiratory muscles, occupational lung disease, pulmonary infections, and social issues in AJRCCM in 2004". Am. J. Respir. Crit. Care Med. 171 (6): 554–62. doi:10.1164/rccm.2412009. PMID 15753485. * Walton D, Farmer P (2000). "MSJAMA: the new white plague". JAMA. 284 (21): 2789. doi:10.1001/jama.284.21.2789. PMID 11105192. ## External links[edit] Wikimedia Commons has media related to Tuberculosis. * Tuberculosis in China at Curlie * Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination. Core Curriculum on Tuberculosis: What the Clinician Should Know. 4th edition (2000). Updated Aug 2003. * (CDC) - Division of Tuberculosis Elimination News and updates. * (CDC) - Questions and Answers About TB, 2005. * BioHealthBase Bioinformatics Resource Center. Database of Mycobacterium tuberculosis genome sequences and related information. * Kaiser Family Foundation. Tuberculosis. Globalhealthfacts.org. * The Nobel Prize Website. Tuberculosis Educational Game * United States Agency for International Development (USAID). The Tuberculosis Coalition for Technical Assistance (TBCTA). * World Health Organization (WHO). 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N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: 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Avian Botulism is a strain of botulism that affects wild and captive bird populations, most notably waterfowl. This is a paralytic disease brought on by the Botulinum neurotoxin (BoNt) of the bacterium Clostridium botulinum.[1] C. botulinum can fall into one of 7 different types which are strains A through G.[2] Type C BoNt is most frequently associated with waterfowl mortality.[3] The Type E strain is also commonly associated with avian outbreaks and is frequently found in fish species which is why most outbreaks occur in piscivorous birds.[4] Avian Botulism occurs all over the world and its understanding is important for wildlife managers, hunters, bird watchers, and anyone who owns wetland property as this disease can account for over 1,000,000 waterbird deaths in a year.[3] ## Contents * 1 Prevalence and distribution * 2 Transmission * 3 Clinical signs * 4 Prevention and control * 5 References ## Prevalence and distribution[edit] Avian botulism occurs all over the world and is especially predominant in North American wetlands. The degree of avian botulism outbreaks in populations is largely determined by how favorable conditions are for C. botulinum.[5] Ideal conditions for the presence of the BoNt carrying bacterium consist of low-oxygen, high-protein available substrate.[1] This is common of shallow and stagnant waterways. Other factors such as pH and temperature, as well as a likely number of unknown factors contribute to the prevalence of outbreaks.[5] Geographic locations with great amounts of this habitat can be assumed to have a greater number of outbreaks. Notable locations include the Great Lakes, North Dakota, Japan, South Korea, and Saskatchewan. While this is frequently the trend there is also evidence of BoNt outbreaks in well-oxygenated lakes with low temperatures.[5] Furthermore, ideal habitats like those described do not all feature avian botulism in their waterfowl populations which supports there are still unknown factors at play.[5] ## Transmission[edit] Avian botulism is not contagious in that it is not spread from bird to bird. Instead it is spread to birds through their consumptions of maggots infected with the toxin.[6] Maggots become infected by feeding on substrates and organic material that host the Type C BoNt. Huge die offs caused by BoNt are the result of this maggot cycle. When an infected bird dies the maggots that feed off of it become infected themselves. These maggots are in turn consumed by additional birds. Thus with every infected carcass brings several infected maggots which increases the number of birds that can contract the disease.[6] In this way massive outbreaks can occur. ## Clinical signs[edit] The botulinum neurotoxin is lethal because it causes paralysis. Field identification involves locating birds showing flaccidity in the legs, wings and neck, as well as the presence of protuberant nictitating membrane.[7] The presence of several dozen, or even hundreds, of fresh waterbird carcasses is the stereotypical sign an outbreak has occurred. In this case the specimens need to be taken to disease laboratory to determine the cause of mortality. Most commonly, detection of C. botulinum in carcasses during lab work is accomplished through analysis of polymerase chain reactions (PCR) and is often the most successful method.[8] ## Prevention and control[edit] The presence of avian botulism is extremely hard to detect before an outbreak. Frequent surveillance of sites at risk is needed for early detection of the disease in order to take action and remove carcasses.[7] Vaccines are also developed, but they are expected to have limited effectiveness in stemming outbreaks in wild waterbird populations.[3] However may be effective in reducing mortality for endangered island waterfowl and small non-migratory wild populations. Field tests are needed. ## References[edit] 1. ^ a b Kadlec, John (2002). "Avian Botulism in Great Salt Lake Marshes: Perspectives and Possible Mechanisms". Wildlife Society Bulletin. 30 (3): 983–989. 2. ^ LaFrancois, Brenda; Stephen C. Riley; David S. Blehert; Anne E. Ballmann (2011). "Links between type E botulism outbreaks, lake levels, and surface water temperatures in Lake Michigan, 1963–2008". Journal of Great Lakes Research. 37: 86–91. doi:10.1016/j.jglr.2010.10.003. 3. ^ a b c Rocke, Tonie; Michael D. Samuel; Pamela K. Swift; Gregory S. Yarris (2000). "Efficacy of a Type C botulism vaccine in green-winged teal". Journal of Wildlife Diseases. 36 (3): 489–493. doi:10.7589/0090-3558-36.3.489. PMID 10941734. 4. ^ Yule, Adam; Ian K. Barker; John W. Austin; Richard D. Moccia (2006). "Toxicity of Clostridium Botulinum Type E Neurotoxin to Great Lakes Fish: Implications for Avian Botulism". Journal of Wildlife Diseases. 42 (3): 479–493. doi:10.7589/0090-3558-42.3.479. PMID 17092878. 5. ^ a b c d Soos, Catherine; Gary Wobeser (2006). "Identification of Primary Substrate in the Initiation of Avian Botulism Outbreaks". Journal of Wildlife Management. 70 (1): 43–53. doi:10.2193/0022-541x(2006)70[43:iopsit]2.0.co;2. 6. ^ a b Takeda, Masato; Kentaro Tsukamoto; Tomoko Kohda; Miki Matsui; Masafumi Mukamoto; Shunji Kozaki (2005). "Characterization of the Nerotoxin produced by isolates associated with avian botulism". Avian Diseases. 49 (3): 376–381. doi:10.1637/7347-022305r1.1. PMID 16252491. 7. ^ a b Work, Thierry; John L. Klavitter; Michelle H. Reynolds; David Blehert (2010). "AVIAN BOTULISM: A CASE STUDY IN TRANSLOCATED ENDANGERED LAYSAN DUCKS (ANAS LAYSANENSIS) ON MIDWAY ATOLL". Journal of Wildlife Diseases. 46 (2): 499–506. doi:10.7589/0090-3558-46.2.499. PMID 20688642. 8. ^ Franciosa, G; L. Fenicia; C. Caldiani; P. Aureli (1996). "PCR for detection of Clostridium botulinum type C in avian and environmental samples". Journal of Clinical Microbiology. 34 (4): 882–885. PMID 8815101. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Avian botulism	None	30,590	wikipedia	https://en.wikipedia.org/wiki/Avian_botulism	2021-01-18T18:38:30	{"wikidata": ["Q11236092"]}
Fungal growth that develops on wet materials This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Indoor mold" – news · newspapers · books · scholar · JSTOR (June 2014) (Learn how and when to remove this template message) The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. You may improve this article, discuss the issue on the talk page, or create a new article, as appropriate. (January 2014) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Indoor mold on the head jamb of the window in a multi-storey building. Mold (American English) or mould (British English), also sometimes referred to as mildew, is a fungal growth that develops on wet materials. Mold is a natural part of the environment and plays an important part in nature by breaking down dead organic matter such as fallen leaves and dead trees; indoors, mold growth should be avoided. Mold reproduce by means of tiny spores. The spores are like seeds, but invisible to the naked eye, that float through the air and deposit on surfaces. When the temperature, moisture, and available nutrient conditions are correct, the spores can form into new mold colonies where they are deposited.[1] There are many types of mold, but all require moisture and a food source for growth. ## Contents * 1 Health effects * 1.1 Mycotoxins * 1.2 Symptoms * 1.2.1 Asthma * 2 Causes and growing conditions * 2.1 Hidden mold * 3 Assessment * 3.1 Sampling * 3.1.1 Air sampling * 3.1.2 Swab and surface sampling * 3.1.3 Bulk and dust sampling * 4 Remediation * 4.1 Cleanup and removal methods * 4.2 Equipment * 5 Protection levels * 5.1 Residential mold prevention and control * 6 See also * 7 Notes * 8 External links ## Health effects[edit] Main article: Mold health issues Mold is ubiquitous, and mold spores are a common component of household and workplace dust. In large amounts they can be a health hazard to humans, potentially causing allergic reactions and respiratory problems. ### Mycotoxins[edit] Main article: Mycotoxin Some mold produce mycotoxins, chemical components of their cells walls, that can pose serious health risks to humans and animals. "Toxic mold" refers to mold which produce mycotoxins, such as Stachybotrys chartarum.[2] Exposure to high levels of mycotoxins can lead to neurological problems and death. Prolonged exposure (for example, daily exposure) can be particularly harmful. Mycotoxins can persist in the indoor environment even after death of the fungi. They can adhere to dust particles and can spread through the air attached to these dust particles or spores.[3] There must be very specific temperature and humidity conditions in order for fungi to produce mycotoxins.[3] ### Symptoms[edit] Symptoms of mold exposure may include nasal and sinus congestion; runny nose, eye irritation; itchy, red, watery eyes, respiratory problems, such as wheezing and difficulty breathing, chest tightness, cough, throat irritation, skin irritation (such as a rash), headache, and persistent sneezing.[4] Immune-compromised people and people with chronic lung illnesses, such as obstructive lung disease, may get serious infections in their lungs when they are exposed to mold. These people should stay away from areas that are likely to have mold, such as compost piles, cut grass, and wooded areas.[5] #### Asthma[edit] Infants may develop respiratory symptoms as a result of exposure to Penicillium, a fungal genus. Signs of mold-related respiratory problems in an infant include a persistent cough or wheeze. Increased exposure increases the probability of developing respiratory symptoms during the first year of life. Studies have indicated a correlation between the probability of developing asthma and exposure to Penicillium.[6] Mold exposure has a variety of health effects, and sensitivity to mold varies. Exposure to mold may cause throat irritation, nasal stuffiness, eye irritation, cough and wheezing and skin irritation in some cases. Exposure to mold may heighten sensitivity, depending on the time and nature of exposure. People with chronic lung diseases are at higher risk for mold allergies, and will experience more severe reactions when exposed to mold. Damp indoor environments correlate with upper-respiratory-tract symptoms, such as coughing and wheezing in people with asthma.[7] ## Causes and growing conditions[edit] Mold is found everywhere and can grow on almost any substance when moisture is present. They reproduce by spores, which are carried by air currents. When spores land on a moist surface suitable for life, they begin to grow. Mold is normally found indoors at levels which do not affect most healthy individuals. Because common building materials are capable of sustaining mold growth and mold spores are ubiquitous, mold growth in an indoor environment is typically related to water or moisture exposure and may be caused by incomplete drying of flooring materials (such as concrete). Flooding, leaky roofs, building-maintenance or indoor-plumbing problems can lead to interior mold growth. Water vapor commonly condenses on surfaces cooler than the moisture-laden air, enabling mold to flourish.[citation needed] This moisture vapor passes through walls and ceilings, typically condensing during the winter in climates with a long heating season. Floors over crawl spaces and basements, without vapor barriers or with dirt floors, are mold-prone. The "doormat test" detects moisture from concrete slabs without a sub-slab vapor barrier.[citation needed] Some materials, such as polished concrete, do not support mold growth. Significant mold growth requires moisture and food sources and a substrate capable of sustaining growth. Common cellulose-based building materials, such as plywood, drywall, furring strips, finish carpentry, cabinetry, wood framing, composite wood flooring, carpets, and carpet padding provide food for mold. In carpet, organic load such as invisible dust and cellulose are food sources. After water damage to a building, mold grows in walls and then becomes dormant until subsequent high humidity; suitable conditions reactivate mold. Mycotoxin levels are higher in buildings which have had a water incident. Although this home experienced minor exterior damage from Hurricane Katrina, small leaks and inadequate airflow permitted mold infestation. ### Hidden mold[edit] Mold is detectable by smell and signs of water damage on walls or ceiling and can grow in places invisible to the human eye. It may be found behind wallpaper or paneling, on the inside of ceiling tiles, the back of drywall, or the underside of carpets or carpet padding. Piping in walls may also be a source of mold, since they may leak (causing moisture and condensation).[8] Spores need three things to grow into mold: nutrients – cellulose (the cell wall of green plants) is a common food for indoor spores; moisture – to begin the decaying process caused by mold; and time – mold growth begins from 24 hours to 10 days after the provision of growing conditions. Mold colonies can grow inside buildings, and the chief hazard is the inhalation of mycotoxins. After a flood or major leak, mycotoxin levels are higher – even after a building has dried out.[citation needed] Food sources for mold in buildings include cellulose-based materials such as wood, cardboard and the paper facing on drywall and organic matter such as soap, fabrics, and dust containing skin cells. If a house has mold, the moisture may originate in the basement or crawl space, a leaking roof or a leak in plumbing pipes. Insufficient ventilation may accelerate moisture buildup. Visible mold colonies may form where ventilation is poorest and on perimeter walls (because they are nearest the dew point). If there are mold problems in a house only during certain times of the year, the house is probably too airtight or too drafty. Mold problems occur in airtight homes more frequently in the warmer months (when humidity is high inside the house, and moisture is trapped), and occur in drafty homes more frequently in the colder months (when warm air escapes from the living area and condenses). If a house is artificially humidified during the winter, this can create conditions favorable to mold. Moving air may prevent mold from growing, since it has the same desiccating effect as low humidity. Mold grows best in warm temperatures, 77 to 86 °F (25 to 30 °C), although growth may occur between 32 and 95 °F (0 and 35 °C).[citation needed] Removing one of the three requirements for mold reduces (or eliminates) new mold growth: moisture; food for the mold spores (for example, dust or dander); and warmth since mold generally does not grow in cold environments. HVAC systems can produce all three requirements for mold growth. The air conditioning system creates a difference in temperature, encouraging condensation. The high rate of dusty air movement through an HVAC system may furnish ample food for mold. Since the air-conditioning system is not always running, warm conditions are the final component for mold growth. ## Assessment[edit] An observation of the indoor environment should be conducted before any sampling is performed. The area should be surveyed for odors indicating mold or bacterial growth, moisture sources, such as stagnant water or leaking pipes, and water-damaged building materials.[9] This can include moving furniture, lifting (or removing) carpets, checking behind wallpaper or paneling, checking ventilation ductwork and exposing wall cavities. Efforts typically focus on areas where there are signs of liquid moisture or water vapor (humidity), or where moisture problems are suspected. Often, quick decisions about the immediate safety and health of the environment can be made by these observations before sampling is even needed.[9] The United States Environmental Protection Agency (EPA) does not generally recommend sampling unless an occupant of the space has symptoms. In most cases, if visible mold growth is present, sampling is unnecessary.[10] Sampling should be performed by a trained professional with specific experience in mold-sampling protocols, sampling methods and the interpretation of findings. It should be done only to make a particular determination, such as airborne spore concentration or identifying a particular species. ### Sampling[edit] Before sampling, a subsequent course of action should be determined. In the U.S., sampling and analysis should follow the recommendations of the Occupational Safety and Health Administration (OSHA), National Institute for Occupational Safety and Health (NIOSH), the EPA and the American Industrial Hygiene Association (AIHA). Types of samples include air, surface, bulk, dust, and swab.[3] Multiple types of sampling are recommended by the AIHA, since each has limitations.[11] #### Air sampling[edit] Further information: Bioaerosol Air is the most common form of sampling to assess mold levels. Although, the Environmental Protection Agency (EPA) does not have any current testing protocols. Air sampling is considered to be the most representative method for assessing respiratory exposure to mold.[12] Indoor and outdoor air are sampled, and their mold spore concentrations are compared. Indoor mold concentrations should be less than or equal to outdoor concentrations with similar distributions of species.[3] A predominant difference in species or higher indoor concentrations can indicate poor indoor air quality and a possible health hazard.[3] Air sampling can be used to identify hidden mold and is often used to assess the effectiveness of control measures after remediation.[12] An indoor mold air sampling campaign should be performed over the course of at least several days as the environmental conditions can lead to variations in the day-to-day mold concentration.[12] Stationary samplers assess a specific environment, such as a room or building, whereas personal samplers assess the mold exposure one person receives in all of the environments they enter over the course of sampling.[12] Personal samplers can be attached to workers to assess their respiratory exposures to molds on the job.[12] Personal samplers usually show higher levels of exposure than stationary samples due to the "personal cloud" effect, where the activities of the person re-suspend settled particles.[12] There are several methods that can be used for indoor mold air sampling. #### Swab and surface sampling[edit] Culture dish with A. fumigatus colonies, a species commonly found in indoor air. Surface sampling measures the number of mold spores deposited on indoor surfaces. With swab, a cotton swab is rubbed across the area being sampled, often a measured area, and subsequently sent to the mold testing laboratory. The swab can rubbed on an agar plate to grow the mold on a culture medium. Final results indicate mold levels and species located in the suspect area. Surface sampling can by used to identify the source of mold exposure. Molecular analyses, such as qPCR, may also be used for species identification and quantification. Swab and surface sampling can give detailed information about the mold, but cannot measure the actual mold exposure because it is not aerosolized.[12] #### Bulk and dust sampling[edit] Bulk removal of material from the contaminated area is used to identify and quantify the mold in the sample. This method is often used to verify contamination and identify the source of contamination.[12] Dust samples can be collected using a vacuum with a collection filter attached. Dust from surfaces such as floors, beds, or furniture is often collected to assess health effects from exposure in epidemiology studies.[12] Researchers of indoor mold also use a long-term settled dust collection method where a dust cloth or petri dish is left out in the environment for a set period of time, sometimes weeks.[12] Dust samples can be analyzed using culture-based or culture-independent methods. Quantitative PCR is a DNA-based molecular method that can identify and quantify fungal species. The Environmental Relative Moldiness Index (ERMI) is a numerical that can be used in epidemiological studies to assess mold burdens of houses in the United States. The ERMI consists of a list of 36 fungal species commonly associated with damp houses that can be measured using qPCR.[13][12] Like swab and surface sampling, bulk and dust sampling can give detailed information about the mold source, but cannot accurately determine the level of exposure to the source.[12] ## Remediation[edit] Mold remediation The first step in solving an indoor mold problem is to remove the moisture source;[14] new mold will begin to grow on moist, porous surfaces within 24 to 48 hours. There are a number of ways to prevent mold growth. Some cleaning companies specialize in fabric restoration, removing mold (and mold spores) from clothing to eliminate odor and prevent further damage to garments. The effective way to clean mold is to use detergent solutions which physically remove mold. Many commercially available detergents marketed for mold cleanup include an EPA-approved antifungal agent.[15][16] Significant mold growth may require professional mold remediation to remove the affected building materials and eradicate the source of excess moisture. In extreme cases of mold growth in buildings, it may be more cost-effective to condemn the building than to reduce mold to safe levels.[citation needed] The goals of remediation are to remove (or clean) contaminated materials, preventing fungi (and fungi-contaminated dust) from entering an occupied (or non-contaminated) area while protecting workers performing the abatement.[17] ### Cleanup and removal methods[edit] The purpose of cleanup is to eliminate mold and remove contaminated materials. Killing mold with a biocide is insufficient, since chemicals and proteins causing reactions in humans remain in dead mold. The following methods are used. * Evaluation: Before remediation, the area is assessed to ensure safety, clean up the entire moldy area, and properly approach the mold. The EPA provides the following instructions:[8] * HVAC cleaning: Should be done by a trained professional.[18] * Protective clothing: Includes a half- or full-face respirator mask. Goggles with a half-face respirator mask prevent mold spores from reaching the mucous membranes of the eyes. Disposable hazmat coveralls are available to keep out particles down to one micrometer, and protective suits keep mold spores from entering skin cuts. Gloves are made of rubber, nitrile, polyurethane, or neoprene.[8][17] * Dry brushing or agitation device: Wire brushing or sanding is used when microbial growth can be seen on solid wood surfaces such as framing or underlayment (the subfloor). * Dry-ice blasting: Removes mold from wood and cement; however, this process may spray mold and its byproducts into surrounding air. * Wet vacuum: Wet vacuuming is used on wet materials, and this method is one of those approved by the EPA.[citation needed] * Damp wipe: Removal of mold from non-porous surfaces by wiping or scrubbing with water and a detergent and drying quickly. * HEPA (high-efficiency particulate air) vacuum: Used in remediation areas after materials have been dried and contaminated materials removed; collected debris and dust is stored to prevent debris release. * Debris disposal: Sealed in the remediation area, debris is usually discarded with ordinary construction waste. ### Equipment[edit] Equipment used in mold remediation includes: moisture meter: measures drying of damaged materials; Humidity gauge: often paired with a thermometer; borescope: Camera at the end of a flexible snake, illuminating potential mold problems inside walls, ceilings and crawl spaces; digital camera: Documents findings during assessment; personal protective equipment (PPE): Respirators, gloves, impervious suit, and eye protection; thermographic camera: Infrared thermal-imaging cameras identify secondary moisture sources. ## Protection levels[edit] During mold remediation in the U.S., the level of contamination dictates the protection level for remediation workers.[19] Contamination levels have been enumerated as I, II, III, and IV:[citation needed] * Level I: Small, isolated areas (10 square feet (0.93 m2) or less); remediation may be conducted by trained building staff; * Level II: Mid-sized, isolated areas (10–30 square feet (0.93–2.79 m2)); may also be remediated by trained, protected building staff; * Level III: Large, isolated areas (30–100 square feet (2.8–9.3 m2)): Professionals experienced in microbial investigations or mold remediation should be consulted, and personnel should be trained in the handling of hazardous materials and equipped with respiratory protection, gloves and eye protection; * Level IV: Extensive contamination (more than 100 square feet (9.3 m2)); requires trained, equipped professionals After remediation, the premises should be reevaluated to ensure success. ### Residential mold prevention and control[edit] According to the EPA, residential mold may be prevented and controlled by cleaning and repairing roof gutters, to prevent moisture seepage into the home; keeping air-conditioning drip pans clean and drainage lines clear; monitoring indoor humidity; drying areas of moisture or condensation and removing their sources; ensuring that there is adequate ventilation by installing an exhaust fan in your bathroom; treating exposed structural wood or wood framing with an EPA-approved fungicidal encapsulation coating after pre-cleaning (particularly homes with a crawl space, unfinished basement or a poorly-ventilated; attic).[8] ## See also[edit] * Fungi portal * Environmental engineering * Environmental health * Greenguard Environmental Institute * High-ozone shock treatment * House dust mite * Hurricane response * Occupational asthma * Sick building syndrome ## Notes[edit] 1. ^ "Indoor Environmental Quality: Dampness and Mold in Buildings – NIOSH Workplace Safety and Health Topic". www.cdc.gov. Retrieved 2018-11-20. 2. ^ Indoor Environmental Quality Dampness and Mold in Buildings. National Institute for Occupational Safety and Health. August 1, 2008. 3. ^ a b c d e Clinical environmental health and toxic exposures. Sullivan, John B. (John Burke), Krieger, Gary R. (2nd ed.). Philadelphia: Lippincott Williams & Wilkins. 2001. ISBN 068308027X. OCLC 41606485.CS1 maint: others (link) 4. ^ Minnesota Department of Health. "Mold and Moisture in Homes". Minnesota North Star. Retrieved 22 November 2011. 5. ^ "Mold – General Information – Facts About Mold and Dampness". www.cdc.gov. 2018-04-13. Retrieved 2018-08-08. 6. ^ Gent, Janneane (2002). "Levels of Household Mold Associated with Respiratory Symptoms in the First Year of Life in a Cohort at Risk for Asthma". Environmental Health Perspectives. Department of Epidemiology and Public Health, Yale University. 110 (12): A781–A786. doi:10.1289/ehp.021100781. PMC 1241132. PMID 12460818. 7. ^ Cohen, Aaron. "WHO Guidelines for Indoor Air Quality: Dampness and Mould" (PDF). World Health Organization. Retrieved 18 November 2011. 8. ^ a b c d "A Brief Guide to Mold, Moisture, and Your Home. EPA 402-K-02-003". U. S. Environmental Protection Agency. September 2010. Retrieved 10 May 2013. 9. ^ a b Clinical environmental health and toxic exposures. Sullivan, John B. (John Burke), Krieger, Gary R. (2nd ed.). Philadelphia: Lippincott Williams & Wilkins. 2001. ISBN 068308027X. OCLC 41606485.CS1 maint: others (link) 10. ^ EPA, OAR, ORIA, IED, US. "Mold Testing or Sampling \| US EPA". US EPA. Retrieved 2018-08-07.CS1 maint: multiple names: authors list (link) 11. ^ Niemeier, R. Todd, Sivasubramani, Satheesh K., Reponen, Tiina and Grinshpun, Sergey A., (2006) "Assessment of Fungal Contamination in Moldy Homes: Comparison of Different Methods", Journal of Occupational and Environmental Hygiene, 3:5, 262–273 [1] 12. ^ a b c d e f g h i j k l Exposure to microbiological agents in indoor and occupational environments. Viegas, Carla Sofia Costa,, Viegas, Susana,, Gomes, Anita,, Täubel, Martin,, Sabino, Raquel. Cham, Switzerland. 2017. ISBN 978-3319616889. OCLC 1005921897.CS1 maint: others (link) 13. ^ Vesper, Stephen; McKinstry, Craig; Haugland, Richard; Wymer, Larry; Bradham, Karen; Ashley, Peter; Cox, David; Dewalt, Gary; Friedman, Warren (August 2007). "Development of an Environmental Relative Moldiness Index for US Homes". Journal of Occupational and Environmental Medicine. 49 (8): 829–833. doi:10.1097/JOM.0b013e3181255e98. ISSN 1076-2752. PMID 17693779. S2CID 43568045. 14. ^ "Mold Resources". United States Environmental Agency. Archived from the original on February 18, 2004. Retrieved July 12, 2015. 15. ^ https://www.epa.gov/pesticide-registration/selected-epa-registered-disinfectants EPA-approved antifungal agent 16. ^ "List A: Antimicrobial Products Registered with the EPA as Sterilizers" (PDF). US Environmental Protection Agency Office of Pesticide Programs. February 2014. Archived from the original (PDF) on March 5, 2014. Retrieved July 12, 2015. 17. ^ a b "Guidelines on Assessment and Remediation of Fungi in Indoor Environments" (PDF). New York City Department of Health and Mental Hygiene. November 2008. Archived from the original (PDF) on 21 May 2009. Retrieved 10 May 2013. 18. ^ NIOSH. "Recommendations for the cleaning and remediation of flood-contaminated HVAC system: A guide for building owners and managers". Center For Disease Control. Retrieved 18 November 2011. 19. ^ "Chapter 6 – Containment and Personal Protective Equipment (PPE)". EPA. Retrieved 29 June 2014. ## External links[edit] * Environmental Protection Agency Mold Homepage * Dunning, Brian (November 24, 2015). "Skeptoid #494: Black Mold: Peril or Prosaic?". 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nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Indoor mold	None	30,591	wikipedia	https://en.wikipedia.org/wiki/Indoor_mold	2021-01-18T18:45:30	{"wikidata": ["Q6895739"]}
Minkoff et al. (1980) described a case of congenital intrinsic deficiency of the platelet membrane phospholipid, platelet factor-3, which plays an important role in acceleration of coagulation. The proband, a 28-year-old woman, had had lifelong excessive bleeding, without a family history of same. Inheritance \- Autosomal dominant Lab \- Congenital deficiency of platelet membrane phospholipid Heme \- Bleeding tendency ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	PLATELET FACTOR 3 DEFICIENCY	c1868256	30,592	omim	https://www.omim.org/entry/173450	2019-09-22T16:36:09	{"mesh": ["C566798"], "omim": ["173450"]}
## Summary ### Clinical characteristics. Usher syndrome type II (USH2) is characterized by the following: * Congenital, bilateral sensorineural hearing loss that is mild to moderate in the low frequencies and severe to profound in the higher frequencies * Intact or variable vestibular responses * Retinitis pigmentosa (RP); progressive, bilateral, symmetric retinal degeneration that begins with night blindness and constricted visual fields (tunnel vision) and eventually includes decreased central visual acuity; the rate and degree of vision loss vary within and among families. ### Diagnosis/testing. The diagnosis of USH2 is established in a proband using electrophysiologic and subjective tests of hearing and retinal function. Identification of biallelic pathogenic variants in one of three genes – ADGRV1, USH2A, or WHRN – establishes the diagnosis if clinical features are inconclusive. ### Management. Treatment of manifestations: Early fitting of hearing aids and speech training. Children with incomplete speech and sentence rehabilitation with hearing aids and older individuals with severe-to-profound hearing loss should be considered for cochlear implantation. Standard treatments for retinitis pigmentosa; vestibular rehabilitation. Surveillance: Annual audiometry and tympanometry with hearing aids or cochlear implant to assure adequate auditory stimulation. Annual ophthalmologic evaluation from age 20 years to detect potentially treatable complications such as cataracts, refractive errors, and cystoid macular edema. Annual fundus photography, visual acuity, visual field, electroretinography, optical coherence tomography, and fundus autofluorescence from age ten years. Agents/circumstances to avoid: Tunnel vision and night blindness can increase the likelihood of accidental injury. Competition in sports requiring a full range of vision may be difficult and possibly dangerous. Progressive loss of peripheral vision impairs the ability to safely drive a car. Evaluation of relatives at risk: The hearing of at-risk sibs should be assessed as soon after birth as possible to allow early diagnosis and treatment of hearing loss. ### Genetic counseling. USH2 is inherited in an autosomal recessive manner. Each subsequent pregnancy of a couple who have had a child with Usher syndrome type II has a 25% chance of resulting in an affected child, a 50% chance of resulting in an unaffected child who is a carrier, and a 25% chance of resulting in an unaffected child who is not a carrier. Prenatal testing and preimplantation genetic testing are possible for pregnancies at increased risk if the pathogenic variants have been identified in the family. ## Diagnosis ### Suggestive Findings Usher syndrome type II (USH2) should be suspected in individuals with: * Congenital (i.e., prelingual) sensorineural hearing loss that is mild to moderate in the low frequencies and severe to profound in the higher frequencies (see Hereditary Hearing Loss and Deafness Overview); * Intact or variable vestibular responses; * Retinitis pigmentosa (RP); * Normal general health and intellect; otherwise normal physical examination; * A family history consistent with autosomal recessive inheritance. ### Establishing the Diagnosis The diagnosis of USH2 is established in a proband with the above clinical features and family history. Identification of biallelic pathogenic variants in one of the genes listed in Table 1 establishes the diagnosis if clinical features are inconclusive. The phenotype of USH2 is often indistinguishable from many other inherited disorders associated with hearing loss and/or RP, therefore the recommended molecular testing approaches can include use of a multigene panel or comprehensive genomic testing. Note: Single-gene testing is rarely useful and typically NOT recommended. * An Usher syndrome multigene panel or a more comprehensive multigene panel (e.g., inherited retinal dystrophy panel, hereditary hearing loss panel) that includes the genes listed in Table 1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * Comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Usher Syndrome Type II (USH2) View in own window Gene 1, 2USH2 SubtypeProportion of USH2 Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detected by Method Sequence analysis 4Gene-targeted deletion/duplication analysis 5 ADGRV1USH2C6.6%-19% 6>90% 73/49 individuals 8 USH2AUSH2A57%-79% 6>90% 7, 96%-9% 10, 11 WHRNUSH2D0%-9.5% 6>95% 7None reported 7 Unknown 12, 13NA 1\. Genes are listed in alphabetic order. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. See Molecular Genetics for information on allelic variants detected in this gene. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Bonnet et al [2011], Le Quesne Stabej et al [2012], García-García et al [2013] 7\. LOVD Usher Syndrome Database 8\. Hilgert et al [2009], Besnard et al [2012], Aparisi et al [2014] 9\. Several deep intronic variants outside of the exon and splice junction regions typically included in sequence analysis have been observed [Vaché et al 2012, Liquori et al 2016]. 10\. Bernal et al [2005], Dreyer et al [2008], Steele-Stallard et al [2013], Aparisi et al [2014], Baux et al [2014], Krawitz et al [2014], Sodi et al [2014], Dad et al [2015] 11\. By screening for duplications/deletions, Steele-Stallard et al [2013] found a second USH2A pathogenic variant in 26% (6/23) of individuals for whom only one disease-causing allele had been found by sequencing. 12\. A fourth locus associated with Usher syndrome type II has been provisionally mapped to 15q in a consanguineous Tunisian family [Ben Rebeh et al 2008]. 13\. To date, PDZD7 pathogenic variants have not been shown to cause Usher syndrome but may act as modifiers of the retinal phenotype in individuals with USH2A-related USH2 [Ebermann et al 2010]. Additionally, an individual with USH2 and compound heterozygous pathogenic variants in USH2A and PDZD7 and another affected individual with compound heterozygous variants in ADGRV1 and PDZD7 were reported, leading to the suggestion of digenic inheritance [Ebermann et al 2010]. ## Clinical Characteristics ### Clinical Description Usher syndrome type II (USH2) is characterized by moderate-to-severe sensorineural hearing loss at birth and retinitis pigmentosa (RP) that begins in late adolescence or early adulthood. Some individuals also have vestibular loss [Yang et al 2012, Blanco-Kelly et al 2015, Magliulo et al 2017]. ### Table 2. Select Features of Usher Syndrome Type II View in own window Feature% of Persons w/FeatureComment Hearing loss100%High-frequency loss which is usually stable RP100%Variable age of onset & rate of progression Vestibular loss40%-80%Usually asymptomatic but identifiable on specialized testing 1 RP = retinitis pigmentosa 1\. Magliulo et al [2017] #### Hearing Loss The hearing loss in USH2 is typically congenital and bilateral, occurring predominantly in the higher frequencies and ranging from moderate to severe. The degree of hearing loss varies within and among families; however, the "sloping" audiogram is characteristic of USH2. The hearing loss may be perceived by the affected individual as progressing over time because speech perception decreases, possibly as a result of diminished vision that interferes with subconscious lip reading. Hearing aids are usually adequate in individuals with USH2. Cochlear implants are highly effective if speech and sentence testing indicates inadequate response with hearing aids. Clinical variability of the hearing phenotype has been observed. In particular, a few individuals with USH2 have a mild but definite progression of hearing loss that is unrelated to presbycusis. A cross-sectional study of 27 persons with USH2A-USH2 confirmed by linkage analysis compared hearing threshold against age; significant progression of hearing impairment was observed but at a much slower rate than reported for Usher syndrome type III (USH3) [Pennings et al 2003]. In contrast, in a large study of 125 individuals with USH2, Reisser et al [2002] found no clinically relevant progression of hearing loss over a span of up to 17 years. #### Visual Loss Children with USH2 are often misdiagnosed as having nonsyndromic hearing impairment until tunnel vision and night blindness (early signs of RP) become severe enough to be noticeable, either by parents and teachers or by the individual. The onset of RP in individuals with USH2 is variable but typically starts in late adolescence or early adulthood and occasionally can start much earlier. RP is progressive, bilateral, symmetric photoreceptor degeneration of the retina that initiates in the mid-periphery; rods (photoreceptors active in the dark-adapted state) are mainly affected first, causing night blindness and constricted visual fields (tunnel vision). Cones (photoreceptors active in the light-adapted state) are affected second and eventually die and cause central blindness. Contrast sensitivities, color vision, and mobility may become severely affected as the retinal degeneration progresses. Visual fields become progressively constricted with time. The rate and degree of visual field loss show intra- and interfamilial variability. A visual field of 5-10 degrees ("severe tunnel") is common for a person with USH2 at age 30-40 years. Visual impairment worsens significantly each year [Iannaccone et al 2004, Pennings et al 2004]. Individuals with USH2 may become completely blind. Cataracts and/or cystoid macular edema sometimes reduce central vision. These two associated conditions are treatable. #### Vestibular Loss Vestibular loss has been identified in 40%-80% of individuals with USH2 in a small study of specialized vestibular testing [Magliulo et al 2017]. However, these individuals were found to be asymptomatic suggesting that they compensate for the loss of vestibular function. #### Heterozygotes Heterozygotes are asymptomatic; however, they may exhibit audiogram anomalies that are not sensitive or specific enough for carrier detection. ### Phenotype Correlations by Gene Sadeghi et al [2004] compared serial audiograms of individuals with USH2 who had pathogenic variants in USH2A (group 1) with those of individuals diagnosed with USH2 who did not have pathogenic variants in USH2A (group 2). They found significantly worse thresholds in group 1 than in group 2 after the second decade. These results suggested that the USH2A-USH2 auditory phenotype may be different from that of other subtypes of USH2. Abadie et al [2012], however, did not find any significant differences between the audiograms from 88 individuals with pathogenic variants in USH2A and ten individuals with pathogenic variants in ADGRV1. Schwartz et al [2005] did not observe any genotype-phenotype correlations between individuals with pathogenic variants in USH2A and those with variants in ADGRV1; however, only three sibs with pathogenic variants in ADGRV1 were evaluated. They found a wide spectrum of photoreceptor disease with more rod than cone dysfunction, and both intra- and interfamilial variation for USH2A-USH2. Frenzel et al [2012] performed two measures of touch sensation (tactile sensation and vibrational detection threshold) on two cohorts of individuals with USH2 from Germany and Spain. USH2A variants were associated with poor touch acuity as well as congenital hearing loss and adult-onset RP. ### Genotype-Phenotype Correlations USH2A. Deleterious null (e.g., nonsense, frameshift, splicing) variants are associated with USH2, whereas homozygous missense variants that generate partially functional proteins typically cause nonsyndromic RP [Lenassi et al 2015b, Hartel et al 2016, Jung 2020]. The visual phenotype in individuals with USH2A-USH2 pathogenic variants is associated with more severe RP compared with nonsyndromic USH2A-RP [Pierrache et al 2016, Sengillo et al 2017, Gao et al 2020]. The hearing phenotype in individuals with USH2A-USH2 is more severe and progressive in individuals with one or more deleterious USH2A variants [Hartel et al 2016, Jung 2020]. Lenassi et al [2015b] designated retinal disease-specific pathogenic variants in USH2A that cause RP with preservation of normal hearing. While these individuals did not report hearing loss, audiometric testing found variable hearing loss in a substantial number. A correlation between severity of hearing loss and severity of RP was not found. Individuals of Swedish or Dutch origin with biallelic USH2A truncating variants (including homozygous c.2299delG variants) developed significantly more severe and progressive hearing loss than individuals with one truncating USH2A variant combined with one nontruncating variant and individuals with two nontruncating variants. Similar findings were also reported in individuals of Korean ancestry [Hartel et al 2016, Jung 2020]. ### Penetrance Penetrance is 100% in USH2. ### Nomenclature The numbering system used in Usher syndrome classification (USH1, USH2, and USH3) corresponds with the associated severity of the clinical presentation (i.e., degree of hearing impairment, the presence or absence of vestibular areflexia, and the age of onset of retinitis pigmentosa). The letter following USH2 indicates the molecular subtype caused by biallelic variants in one of the related genes listed in Table 1. ### Prevalence The prevalence of Usher syndrome in the general US population has been conservatively estimated at 4.4:100,000. However, a study of children with hearing loss in Oregon found that 11% had pathogenic variants in genes associated with Usher syndrome and estimated that the prevalence may be as high as 1:6,000 [Kimberling et al 2010]. Usher syndrome has been estimated to be responsible for 3%-6% of all childhood deafness and approximately 50% of all deaf-blindness. These estimates were made prior to 1989, when Möller et al [1989] subdivided Usher syndrome into USH1 and USH2, and USH3 had not yet been recognized. The specialized educational requirements of the congenitally deaf have historically rendered the population with USH1 more accessible for study by researchers. Persons with USH2 or USH3 communicate orally and are mainstreamed into regular schools; thus, the prevalence of USH2 and USH3 in the general population cannot be estimated as accurately as that of USH1. Often, persons with USH2 are not diagnosed until early adulthood, when progressive RP becomes debilitating. The prevalence of Usher syndrome in Heidelberg, Germany and its suburbs has been calculated to be 6.2:100,000 [Spandau & Rohrschneider 2002]. In that study, the ratio of USH1 to USH2 was 1:3. ## Differential Diagnosis Often, a family with more than one affected sib is thought to have nonsyndromic hearing loss (NSHL) (see Hereditary Hearing Loss and Deafness Overview) until the oldest is diagnosed with retinitis pigmentosa (RP). Subsequent visual evaluation often reveals the presymptomatic early stages of RP in younger affected sibs. Pathogenic variants associated with NSHL and RP can be inherited independently by a single individual whose symptoms mimic those of Usher syndrome [Fakin et al 2012]. Larger families lessen the statistical probability of this occurrence because at least one sib is likely to inherit one pathogenic variant without the other. NSHL and RP are both relatively common, with frequencies of 1:1,000 and 1:4,000, respectively, and are characterized by extreme genetic heterogeneity (to date, >110 genes have been associated with NSHL and >80 genes have been associated with RP). Hereditary disorders characterized by both sensorineural hearing impairment and decreased visual acuity to consider in the differential diagnosis of Usher syndrome type II (USH2) are summarized in Table 4. ### Table 4. Genes of Interest in the Differential Diagnosis of Usher Syndrome Type II View in own window Gene(s)DisorderMOIClinical CharacteristicsComment CDH23 CIB2 MYO7A PCDH15 USH1C USH1GUSH1ARCongenital bilateral profound SNHL, vestibular areflexia, adolescent-onset RPChildren w/USH1 are usually do not walk until age 18 mos to 2 yrs due to vestibular involvement (those w/USH2 usually walk at age ~1 yr). CLRN1 HARS1USH3 (OMIM 276902, 614504)ARPostlingual progressive SNHL, late-onset RP, variable impairment of vestibular functionSome persons w/USH3 may have profound HL & vestibular disturbance & thus be clinically misdiagnosed w/USH1 or USH2. 1 PEX1 PEX6 PEX12 (13 genes) 2Zellweger spectrum disorder (ZSD) 3Intermediate/ milder ZSDAR (AD) 4Mainly sensory deficits &/or mild developmental delay; intellect may be normal.Milder ZSD & USH2 can both have SNHL & retinal pigmentary abnormalities, but visual impairment in milder ZSD is more variable. Also, those w/milder ZSD typically develop ameliogenesis imperfecta of secondary teeth. Severe ZSDARSevere neurologic dysfunction, craniofacial abnormalities, liver disfunction, absent peroxisomesInfants w/severe ZSD are significantly impaired & usually die during 1st yr of life, usually having made no developmental progress. PEX7 PHYHRefsum diseaseARRP, HL, anosmia, polyneuropathy, ataxiaRP is nearly always 1st noticeable feature; anosmia, polyneuropathy, & then mild-to-moderate HL follow. ABHD12Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, & cataract (PHARC) (OMIM 612674)ARPolyneuropathy, HL, ataxia, RP, cataractPersons w/PHARC typically develop polyneuropathy & ataxia in teens or early adulthood; & RP typically later in adulthood. TIMM8A 5Deafness-dystonia-optic neuronopathy syndrome (DDON)XLMales: pre- or postlingual SNHL in early childhood; optic atrophy → slowly progressive ↓ visual acuity from age ~20 yrs; dementia from age ~40 yrs; slowly progressive dystonia or ataxia in the teens 6 Females: mild hearing impairment & focal dystoniaIn DDON, appearance of the retina, night vision, & ERG are usually normal; in USH, impaired vision results from retinal dystrophy that first manifests as impaired dark adaptation. 7 AD = autosomal dominant; AR = autosomal recessive; HL = hearing loss; MOI = mode of inheritance; RP = retinitis pigmentosa; SNHL = sensorineural hearing loss; USH = Usher syndrome; XL = X-linked 1\. Pennings et al [2003] 2\. 60.5% of Zellweger spectrum disorder (ZSD) is associated with biallelic pathogenic variants in PEX1, 14.5% with pathogenic variant in PEX6, 7.6% with pathogenic variants in PEX12. In total, 13 genes are known to be associated with ZSD. 3\. The term "Zellweger spectrum disorder" refers to all individuals with a defect in one of the ZSD-PEX genes regardless of phenotype. 4\. One PEX6 variant, p.Arg860Trp, has been associated with ZSD in the heterozygous state due to allelic expression imbalance dependent on allelic background. 5\. DDON syndrome is caused by either (1) a hemizygous TIMM8A pathogenic variant in a male proband or a heterozygous TIMM8A pathogenic variant in a female proband or (2) a contiguous gene deletion of Xp22.1 involving TIMM8A. 6\. In DDON syndrome, hearing impairment appears to be constant in age of onset and progression, whereas the neurologic, visual, and neuropsychiatric signs (e.g., personality change and paranoia) vary in degree of severity and rate of progression. 7\. Sadeghi et al [2004] Other. Viral infections, diabetic neuropathy, and syndromes involving mitochondrial defects (see Mitochondrial Disorders Overview) can all produce concurrent symptoms of hearing loss and retinal pigmentary changes that suggest Usher syndrome. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Usher syndrome type II (USH2), the evaluations summarized in Table 5 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with Usher Syndrome Type II View in own window System/ConcernEvaluationComment AudiologyOtoscopy, puretone audiometry, assessment of speech perceptionConsider auditory brain stem response (ABR), electrocochleography (ECOG), and distortion product otoacoustic emission (DPOAE). Speech and sentence tests with hearing aids will determine if cochlear implantation offers better rehabilitation than hearing aids. Vestibular functionRotary chair, calorics, electronystagmography, ocular & cervical myogenic evoked potentials, video head impulse testing, computerized posturographyPatients describing imbalance or dizziness should undergo comprehensive vestibular testing to guide rehabilitation. OphthalmologyFundus photography, VA, VF (Goldmann perimetry, Humphrey perimetry, Dark adapted rod perimetry), ERG, OCT, FAFFundus photography documents extent of pigmentation & RPE atrophy; VA is often maintained until late in disease; VF maps extent of functional peripheral vision, retinal sensitivities, & functional rod & cone responses. ERG is often nondetectable at presentation; OCT allows determination of "live" photoreceptors (measuring the ellipsoid zone); FAF can measure the perifoveal hyperfluorescent ring lipofuscin disturbance. Genetic counselingBy genetics professionals 1To inform patients & families re nature, MOI, & implications of USH2 in order to facilitate medical & personal decision making Family support/ resourcesAssess: * Use of community or online resources such as Parent to Parent; * Need for social work involvement for parental support. ERG = electroretinography; FAF = fundus autofluorescence; OCT = optical coherence tomography; RPE = retinal pigment epithelium; VA = visual acuity; VF = visual field; MOI = mode of inheritance 1\. Medical geneticist, certified genetic counselor, certified advanced genetic nurse ### Treatment of Manifestations ### Table 6. Treatment of Manifestations in Individuals with Usher Syndrome Type II View in own window Manifestation/ ConcernTreatmentConsiderations/Other Hearing lossHearing aidsYoung children benefit from early fitting of hearing aids & speech training. Cochlear implantationChildren w/incomplete speech & sentence rehabilitation w/hearing aids & older persons w/severe-to-profound hearing loss: consider for cochlear implantation. Retinitis pigmentosa * See Retinitis Pigmentosa Overview, Management. * Argus II prosthesis 1 Tunnel vision & night blindness can ↑ likelihood of accidental injury. ImbalanceVestibular rehabilitationNeurologically active medications or sedatives can aggravate mild vestibular dysfunction. 1\. Nadal & Iglesias [2018] describe the visual outcomes and rehabilitation of a one individual with USH2 that underwent Argus II prosthesis surgery. ### Surveillance ### Table 7. Recommended Surveillance for Individuals with Usher Syndrome Type II View in own window System/ConcernEvaluationFrequency Hearing lossAudiometry & tympanometry w/hearing aids or cochlear implant to assure adequate auditory stimulationAnnually, incl testing w/hearing aids in place CataractsOphthalmologic evalAnnually from age 20 yrs or age of diagnosis Cystoid macular edemaOphthalmologic eval Retinitis pigmentosaFundus photography, VA, VF (Goldmann perimetry, Humphrey perimetry, dark adapted rod perimetry), ERG, OCT, FAFAnnually from age 10 yrs or age of diagnosis ERG = electroretinography; FAF = fundus autofluorescence; OCT = optical coherence tomography; VA = visual acuity; VF = visual field ### Agents/Circumstances to Avoid Competition in various sports requiring a full range of vision may be difficult and possibly dangerous. Progressive loss of peripheral vision impairs the ability to safely drive a car. An Esterman visual field test (automated Humphrey, static visual field analyzer) with both eyes open during testing is a helpful measure to assess degrees of peripheral vision along the midline. Night driving is impaired very early. ### Evaluation of Relatives at Risk It is appropriate to evaluate all sibs at risk for USH2 as soon after birth as possible to allow early support and management of the child and the family. Evaluations include: * Molecular genetic testing if the pathogenic variants in the family are known; * Auditory brain stem response (ABR) and distortion product otoacoustic emission (DPOAE) if the pathogenic variants in the family are not known. See Genetic Counseling for issues related to evaluation of at-risk relatives for genetic counseling purposes. ### Pregnancy Management High-dose vitamin A supplementation should not be used by affected pregnant women, as large doses of vitamin A (doses above the RDA for pregnant or lactating women) may be teratogenic to the developing fetus (see Other). ### Therapies Under Investigation QR-421 antisense treatment. Study to Evaluate Safety and Tolerability of QR-421a in Subjects with RP Due to Mutations in Exon 13 of the USH2A Gene (Stellar). This is an interventional, Phase I/II clinical trial to evaluate the safety of an antisense oligonucleotide (ASO) therapy to treat RP in individuals with USH2 due to specific USH2A pathogenic variants. This study is active and recruiting (see ClinicalTrials.gov). C-18-04 antioxidant treatment. Safety and Efficacy of NPI-001 Tablets for Retinitis Pigmentosa Associated with Usher Syndrome (SLO RP). This is an interventional, two-year, Phase I/II clinical trial to evaluate the safety and efficacy of NPI-001 tablets in individuals with RP associated with Usher syndrome. This trial is active and recruiting (see ClinicalTrials.gov). CL-17-01 antioxidant treatment. Phase I, Single- and Multiple-Ascending Dose Study of the Safety and Tolerability of NPI-001 Solution in Healthy Subjects. This clinical trial established that NPI-001 was generally well tolerated in all but the highest dose and determined key pharmacokinetic parameters of the NPI-001 solution (search on ACTRN12617000911392 at www.anzctr.org.au). Search ClinicalTrials.gov in the US, EU Clinical Trials Register in Europe, and ANZCTR Trial Search in Australia and New Zealand for access to information on clinical studies for a wide range of diseases and conditions. ### Other Vitamin A supplements. Vitamin A plays an essential role in the visual (retinoid) cycle as the photosensitive intermediate 11 cis retinal. Although treatment with vitamin A palmitate may limit the progression of RP in persons with isolated RP and USH2, no studies have evaluated the effectiveness of vitamin A palmitate in individuals with USH2. Vitamin A is fat soluble and not excreted in the urine. Therefore, high-dose vitamin A dietary supplements should be used only under the direction of a physician because of the need to monitor for harmful side effects such as hepatotoxicity [Sibulesky et al 1999]. Of note, the studies by Berson et al [1993] were performed on individuals older than age 18 years because of the unknown effects of high-dose vitamin A on children. High-dose vitamin A supplementation should not be used by affected pregnant women, as large doses of vitamin A (i.e., above the recommended daily allowance for pregnant or lactating women) may be teratogenic to the developing fetus. Lutein supplements may enhance retinal macular pigment. Lutein, zeaxanthin, meso-zeaxanthin, and their oxidative metabolites accumulate in the human fovea and macula as the macular pigment (MP). They are obtained through dietary sources (green leafy vegetables, yellow and/or orange fruits and vegetables). Inherited retinal dystrophies may cause or be associated with loss of MP [Aleman et al 2001]. Oral administration of lutein (20 mg/d) for seven months had no effect on central vision [Aleman et al 2001]. However, Berson et al [2010] showed that lutein supplementation of 12 mg/d slowed loss of midperipheral visual field among nonsmoking adults with RP taking vitamin A. Omega 3 supplements (e.g., docosahexaenoic acid [DHA]) may replenish membranes of the photoreceptor outer segments, which are largely composed of polyunsaturated fatty acids. Supplementation of DHA significantly elevated blood DHA levels and reduced the rate of progression in final dark-adapted thresholds and visual field sensitivity [Hoffman et al 2015]. N-acetyl-cysteine (NAC) supplements. NAC is a safe oral antioxidant used to treat liver toxicity due to acetaminophen overdose. NAC reduces oxidative damage and increases cone function and survival in animal models of RP [Lee et al 2011]. In a Phase l study, 600 mg, 1200 mg, or 1800 mg were safe in individuals with RP and significant improvements were found in cone function, including visual acuity [Campochiaro et al 2020]. Blueberry extract supplements. Blueberry fruits contain anthocyanins, members of the flavonoid group of phytochemicals, which are powerful antioxidants. No studies have been done on individuals with RP or USH2. Because of their natural occurrence, they are probably safe and may be efficacious. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Usher Syndrome Type II	None	30,593	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1341/	2021-01-18T20:51:04	{"synonyms": ["USH2"]}
A number sign (#) is used with this entry because of evidence that auriculocondylar syndrome-1 (ARCND1) is caused by heterozygous mutation in the GNAI3 gene (139370) on chromosome 1p13. Description Auriculocondylar syndrome (ARCND) is an autosomal dominant disorder of the first and second pharyngeal arches and is characterized by malformed ears (question mark ears), prominent cheeks, microstomia, abnormal temporomandibular joint, and mandibular condyle hypoplasia (summary by Masotti et al., 2008). ### Genetic Heterogeneity of Auriculocondylar Syndrome Auriculocondylar syndrome-2 (ARCND2; 614669) is caused by mutation in the PLCB4 gene (600810) on chromosome 20p12.3-p12.2. ARCND3 (615706) is caused by mutation in the EDN1 gene (131240) on chromosome 6p24. See also 612798 for isolated question mark ears. Clinical Features Uuspaa (1978) reported a mother and 2 sons with bilateral external ear malformations and hypoplastic mandible. Jampol et al. (1998) described a family in which several individuals in at least 5 generations had prominent, malformed ears, abnormality of the temporomandibular joint and condyle of the mandible, and microstomia, but normal hearing and normal ossicles of the middle ear. The ear deformity was referred to as 'prominent, constricted ears.' This may be the same as that called 'question mark ear,' by Brodovsky and Westreich (1997). The question mark ear had been noted in 2 sibs with unaffected parents by Takato et al. (1989). In the kindred reported by Jampol et al. (1998), the ear deformity was present in the father of the propositus and in a paternal aunt and her daughter, a paternal uncle, the paternal grandmother, and the paternal grandmother's father, as well as the paternal grandmother's paternal grandmother. None of these affected relatives was known to have had other birth defects. When the propositus was examined at the age of 8 years, the prominent ears were described as narrowing at the junction of the lower third and upper two-thirds and had no antihelix. The mandible was prognathic with type III malocclusion. This anomaly is presumably inherited as an autosomal dominant. Guion-Almeida et al. (1999) reported a patient with strikingly malformed ears, abnormalities of the condyle of the mandible, micrognathia, small mouth, and cleft uvula. The parents were nonconsanguineous, with normal phenotype and normal radiologic findings of the mandible and temporomandibular joint. The authors concluded that this patient may be affected with the condition reported by Jampol et al. (1998). They suggested that the absence of findings in the parents supports the possibility of a new mutation in this case. Guion-Almeida et al. (2002) described several members with auriculocondylar syndrome in 3 generations of a family. At 5 months of age the proband had microstomia with severely limited opening of her mouth, marked micrognathia, glossoptosis, and low-set ears with atretic external auditory canals and constriction at the junction of the upper two-thirds and lower third of the pinna. A CT scan excluded abnormalities of the bones of the middle ear. X-ray films showed condylar agenesis. The proband's father had similar facial features and ears but also had a history of cleft palate and sensorineural hearing loss. Guion-Almeida et al. (2002) compared the findings in reported patients with auriculocondylar syndrome with those in the mother and daughter reported by Erlich et al. (2000) as having the dysgnathia complex (202650). They concluded that the patients of Erlich et al. (2000) actually had auriculocondylar syndrome. In a literature review of 14 patients, Storm et al. (2005) reported the most common clinical signs of ARCND: abnormalities of the TMJ/condyle (100%), ear constriction (96.8%), micrognathia (71%), abnormal palate (62.5%), prominent cheeks (57.1%), microstomia (51.9%), glossoptosis (45.5%), respiratory distress (36.4%), stenotic ear canals (30%), and hearing loss (21%). Some patients may need orthodontic treatment, speech therapy, or orthognathic surgery. Storm et al. (2005) noted that the phenotype is highly variable, even within families. Nezarati and Aftimos (2007) reported a 26-year-old man, born of first-cousin parents, with severe micrognathia, absence of the upper portion of the helices, atresia of the external meatus and absence of the middle ear ossicles, mildly downslanting palpebral fissures, and a highly arched palate with a submucous cleft. The authors suggested that this constellation of findings might represent a more severe manifestation of the auriculocondylar syndrome or a previously undescribed syndrome. McGowan et al. (2011) reported 9 ARCND patients from 6 families. Micrognathia, microstomia, and prominent cheeks were present in all of the patients, but there was a significant degree of phenotypic variability. Six patients, who all had the typical auricular deformities of ARCND, underwent imaging, and all had either mandibular hypoplasia or abnormalities of the mandibular condyle. Facial asymmetry was a common feature, occurring in 7 of the 9 patients. In addition, patients in this series had other clinical signs not previously reported in ARCND, including facial cleft and preauricular and cheek pits. Citing the delay in diagnosis of ARCND as well as the phenotypic spectrum of abnormalities observed in their series, McGowan et al. (2011) suggested that ARCND is largely unrecognized and might be more common than would appear from published reports. Gordon et al. (2013) studied a father and daughter with ARCND. The daughter displayed asymmetric micrognathia, malocclusion, microstomia, and a notch between the lobe and helix of the right ear. She also displayed mildly hypoplastic first ribs on x-ray. Her father had normal ears but large cheeks and possible hypoplasia of the angle of the mandible. Mandibular x-rays were not available for the father. Pathogenesis Rieder et al. (2012) studied 8 probands with auriculocondylar syndrome and available affected relatives. In each case, mandibular ankylosis was progressive, of variable severity, and characterized by inconsistent fusion to the medial and lateral pterygoid plates. All cases demonstrated a similar phenotype, consisting of a lateral mandibular bony prominence with or without temporomandibular joint ankylosis, and had features consistent with classic ARCND. The anatomic features of these cases led Rieder et al. (2012) to hypothesize that the malformations observed in patients with ARCND are due to a homeotic transformation, with the mandible assuming a maxillary phenotype. Mapping After excluding 3 known loci associated with disorders of first and second branchial arches through segregation analysis, Masotti et al. (2008) conducted genomewide linkage analysis in 2 large families with auriculocondylar syndrome, 1 of which (family 'F2') was previously reported by Guion-Almeida et al. (2002). Masotti et al. (2008) obtained a maximum lod score of 3.01 on chromosome 1p21.1-q23.3 (at theta = 0.0) in family F2; haplotype reconstruction defined a 43-cM (60-Mb) critical region between D1S206 and D1S2878, which the authors stated contained at least 250 genes. This locus was not linked to the phenotype segregating in the other family, however, suggesting genetic heterogeneity for the disorder. Molecular Genetics By whole-exome sequencing followed by filtering of exome data, Rieder et al. (2012) identified a heterozygous missense mutation in the GNAI3 gene (139370.0001) on chromosome 1p13.3 in a mother and daughter with auriculocondylar syndrome, who were originally reported by Erlich et al. (2000), and in another unrelated ARCND proband. The unrelated proband inherited the mutation from her unaffected father, demonstrating incomplete penetrance. The mutation was not found in 10,758 control chromosomes. Gordon et al. (2013) analyzed the GNAI3 and PLCB4 genes in 27 patients, including 8 with clinical ARCND, 5 with 'atypical' ARCND who were previously described by McGowan et al. (2011), 3 with isolated question mark ears (612798), 6 diagnosed with either oculoauriculovertebral syndrome (OAVS) or Goldenhar syndrome (see 164210), and 4 with nonsyndromic auricular dysplasia with or without mandibular dysplasia. In a female proband with ARCND and her affected father, a missense mutation was identified in the GNAI3 gene (S47R; 139370.0002). In addition, 7 mutations were found in the PLCB4 gene. Gordon et al. (2013) noted that of 15 reported mutation-positive ARCND patients, 12 (80%) had a mutation in PLCB4 and 3 (20%) had a mutation in GNAI3. Among the mutation-negative patients were the 5 probands with 'atypical' ARCND originally reported by McGowan et al. (2011) (cases 1, 3, 4a, 5, and 6a). Gordon et al. (2013) stated that none of these 5 probands exhibited the indentation or cleft between the helix and lobe that is characteristic of PLCB4/GNAI3 mutation-positive ARCND cases. They concluded that despite intrafamilial variation in severity, the PLCB4/GNAI3-related auricular phenotype is highly specific and distinguishable from other human ear dysplasias. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Macrocephaly (25%) Face \- Micrognathia \- Round facial appearance \- Prominent cheeks Ears \- Malformed ears \- Auricular clefts \- Cleft at the junction of the lobule and helix \- Lobule may be separately from the rest of the external ear \- Cleft at the superior portion of the pinna \- Cupped pinna \- Overfolding of the superior helices \- Underdeveloped superior helices \- Pre- and post-auricular skin or cartilaginous tags \- Low-set ears \- Posteriorly rotated ears \- Stenotic ear canals (30%) \- Ear constriction (97%) Mouth \- Microstomia (52%) \- Glossoptosis (46%) \- Abnormal palate (63%) \- Cleft palate \- Mastication difficulties \- Speech articulation difficulties Teeth \- Crowded teeth \- Malocclusion \- Open anterior bite \- Posterior crossbite RESPIRATORY \- Respiratory difficulties due to orofacial malformations (36%) \- Apnea \- Snoring SKELETAL Skull \- Mandibular condyle hypoplasia \- Mandibular condyle aplasia \- Mandibular agenesis \- Asymmetric mandible \- Short mandibular rami \- Small mandibular coronoid processes \- Temporomandibular joint abnormalities \- Ankylosis of the temporomandibular joints MISCELLANEOUS \- Congenital disorder \- Variable phenotype within families ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	AURICULOCONDYLAR SYNDROME 1	c1865295	30,594	omim	https://www.omim.org/entry/602483	2019-09-22T16:13:40	{"mesh": ["C538270"], "omim": ["602483"], "orphanet": ["137888"], "synonyms": ["Alternative titles", "QUESTION MARK EARS SYNDROME"]}
Malignant acrospiroma Other namesHidradenocarcinoma, and Spiradenocarcinoma[1] SpecialtyOncology A malignant acrospiroma is a sweat gland carcinoma of the hand, which may recur locally in 50% of patients after excision, with distant metastases occurring in 60% of patients.[2] ## See also[edit] * Acrospiroma * Syringoma * Hidrocystoma * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ Wilson KM, Jubert AV, Joseph JI (May 1989). "Sweat gland carcinoma of the hand (malignant acrospiroma)". J Hand Surg Am. 14 (3): 531–5. doi:10.1016/S0363-5023(89)80018-8. PMID 2544641. ## External links[edit] Classification D * ICD-O: 8402/3 * MeSH: D018250 * v * t * e Cancers of skin and associated structures Glands Sweat gland Eccrine * Papillary eccrine adenoma * Eccrine carcinoma * Eccrine nevus * Syringofibroadenoma * Spiradenoma Apocrine * Cylindroma * Dermal cylindroma * Syringocystadenoma papilliferum * Papillary hidradenoma * Hidrocystoma * Apocrine gland carcinoma * Apocrine nevus Eccrine/apocrine * Syringoma * Hidradenoma or Acrospiroma/Hidradenocarcinoma * Ceruminous adenoma Sebaceous gland * Nevus sebaceous * Muir–Torre syndrome * Sebaceous carcinoma * Sebaceous adenoma * Sebaceoma * Sebaceous nevus syndrome * Sebaceous hyperplasia * Mantleoma Hair * Pilomatricoma/Malignant pilomatricoma * Trichoepithelioma * Multiple familial trichoepithelioma * Solitary trichoepithelioma * Desmoplastic trichoepithelioma * Generalized trichoepithelioma * Trichodiscoma * Trichoblastoma * Fibrofolliculoma * Trichilemmoma * Trichilemmal carcinoma * Proliferating trichilemmal cyst * Giant solitary trichoepithelioma * Trichoadenoma * Trichofolliculoma * Dilated pore * Isthmicoma * Fibrofolliculoma * Perifollicular fibroma * Birt–Hogg–Dubé syndrome Hamartoma * Basaloid follicular hamartoma * Folliculosebaceous cystic hamartoma * Folliculosebaceous-apocrine hamartoma Nails * Neoplasms of the nailbed This Epidermal nevi, neoplasms, cysts article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Malignant acrospiroma	c1260964	30,595	wikipedia	https://en.wikipedia.org/wiki/Malignant_acrospiroma	2021-01-18T18:48:06	{"umls": ["C1260964"], "wikidata": ["Q6743502"]}
Ichthyosis with confetti is a disorder of the skin. Individuals with this condition are born with red, scaly skin all over the body, which can be itchy in some people. In childhood or adolescence, hundreds to thousands of small patches of normal skin appear, usually on the torso. The numerous pale spots surrounded by red skin look like confetti, giving the condition its name. The patches of normal skin increase in number and size over time. In addition to red, scaly skin, people with ichthyosis with confetti typically have abnormally thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Many affected individuals have excess hair (hirsutism) on some parts of the body, particularly on the arms and legs. Because of their skin abnormalities, people with ichthyosis with confetti are at increased risk of developing skin infections. ## Frequency Ichthyosis with confetti is a rare disorder. Fewer than 20 affected individuals have been described in the medical literature. ## Causes Mutations in the KRT10 gene cause ichthyosis with confetti. This gene provides instructions for making a protein called keratin 10, which is found in cells called keratinocytes in the outer layer of the skin (the epidermis). In the fluid-filled space inside these cells (the cytoplasm), this tough, fibrous protein attaches to another keratin protein (produced from a different gene) to form fibers called intermediate filaments. These filaments assemble into strong networks that provide strength and resiliency to the skin. KRT10 gene mutations associated with ichthyosis with confetti alter the keratin 10 protein. The altered protein is abnormally transported to the nucleus of cells, where it cannot form networks of intermediate filaments. Loss of these networks disrupts the epidermis, contributing to the red, scaly skin. However, in some abnormal cells, the mutated gene corrects itself through a complex process by which genetic material is exchanged between chromosomes. As a result, normal keratin 10 protein is produced and remains in the cytoplasm. The cell becomes normal and, as it continues to grow and divide, forms small patches of normal skin that give ichthyosis with confetti its name. ### Learn more about the gene associated with Ichthyosis with confetti * KRT10 ## Inheritance Pattern Ichthyosis with confetti is considered to have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Usually, the condition is caused by a new mutation that occurs very early in embryonic development (called a de novo mutation). In these cases, the affected individuals have no history of the disorder in their family. In some cases, an affected person inherits the mutation from one affected parent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Ichthyosis with confetti	c3665704	30,596	medlineplus	https://medlineplus.gov/genetics/condition/ichthyosis-with-confetti/	2021-01-27T08:25:31	{"omim": ["609165"], "synonyms": []}
Oral-facial-digital syndrome, type 9 is characterized by highly arched palate with bifid tongue and bilateral supernumerary lower canines, hamartomatous tongue, multiple frenula, hypertelorism, telecanthus, strabismus, broad and/or bifid nasal tip, short stature, bifid halluces, forked metatarsal, poly- and syndactyly, mild intellectual deficit and specific retinal abnormalities (bilateral optic disc coloboma and retinal dysplasia with partial detachment). ## Epidemiology Less than ten cases have been described in the literature. ## Clinical description Recurrent aspiration pneumonia and severe microcephaly have been reported occasionally. ## Etiology The causative gene has not yet been identified. ## Genetic counseling Autosomal and X-linked recessive inheritance were initially suggested. Taking into consideration all reported cases so far, autosomal recessive inheritance seems most likely. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Orofaciodigital syndrome type 9	c0796102	30,597	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141007	2021-01-23T18:17:24	{"gard": ["10520"], "mesh": ["C557818"], "omim": ["258865"], "umls": ["C0796102"], "icd-10": ["Q87.0"], "synonyms": ["OFD9", "Oral-facial-digital syndrome type 9", "Oral-facial-digital syndrome with retinal abnormalities", "Orofaciodigital syndrome with retinal abnormalities"]}
A number sign (#) is used with this entry because of evidence that MEHMO syndrome (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) is caused by hemizygous mutation in the EIF2S3 gene (300161) on chromosome Xp22. Clinical Features Steinmuller et al. (1998) described a previously unrecognized X-chromosomal mental retardation syndrome and referred to it by the acronym MEHMO, which was derived from the clinical hallmarks: mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity. Life expectancy of the patients was less than 2 years. Leshinsky-Silver et al. (2002) provided evidence that MEHMO is an X-linked mitochondrial disorder. They described an Ethiopian Jewish boy with MEHMO and lactic acidosis, whose muscle biopsy revealed markedly reduced activities of respiratory chain enzymes of complex I (see 602694), III (see 516020), and IV (see 516030), whereas complex II (see 600857) (exclusively encoded by nuclear DNA) was not affected. The skeletal muscle histology showed abundant fatty infiltration and mitochondrial proliferation. Electron microscopy showed concentric arrangement of the cristae in huge mitochondria, irregular lamellar arrangement, and electron dense bodies. The family history of 2 male sibs of the mother who died in the first year of life suggested X-linked MEHMO syndrome. The multiple deficiencies of mtDNA encoded respiratory chain complexes with normal levels of nuclear encoded mitochondrial enzymes and the morphology of the mitochondria suggested that a nuclear defect located in the Xp22.13-p21.1 region leads to abnormal mitochondrial function. Borck et al. (2012) reported 3 males from a consanguineous family of Moroccan Jewish ancestry with X-linked syndromic intellectual disability with features of MEHMO. They had delayed psychomotor development since infancy, microcephaly (-3.8 to -4.8), short stature, ataxic gait, lower limb spasticity with hyperreflexia, and Achilles tendon shortening. Dysmorphic facial features included flat and broad nasal tip, temporal narrowing, long face with long chin, large ears, long philtrum, open mouth, and widely spaced teeth. Brain imaging showed thin corpus callosum and enlarged ventricles. Two brothers had growth hormone deficiency. Each patient had unique additional features, including cleft lip and palate in 1, seizures in a second, and hypogonadism and obesity in the third. One boy had behavioral abnormalities, including aggression, head banging, and attention deficit-hyperactivity disorder. Carrier females in the family were unaffected. Moortgat et al. (2016) reported 2 teenaged maternal half brothers, born of unrelated Belgian parents, with X-linked syndromic severe mental retardation. They showed global developmental delay, axial hypotonia, and spastic quadriparesis since birth. Each also had poor overall growth, progressive microcephaly (up to -8.5 SD), and poor or absent speech. They were either unable to walk or could only walk with aid. Dysmorphic features included strabismus and large ears. Other features included growth hormone deficiency, delayed puberty, hypogonadism, and evidence of pancreatic dysfunction, including hypoglycemia and pancreatitis. Brain imaging showed reduced white matter and thin corpus callosum. One patient developed seizures at age 9 months and had autistic features; the other patient did not have seizures or autism. One patient died at age 17 years from severe respiratory disease and multiorgan failure. A male infant in a second family of Spanish origin had poor growth, microcephaly, micrognathia, micropenis, and generalized hypertonia with no visual contact. He developed hypoglycemia soon after birth. He had severe global developmental delay and never achieved head control. He had onset of seizures at age 10 months and died at age 12 months. Three other male family members reportedly had a similar phenotype with early death. Skopkova et al. (2017) described 3 additional patients with MEHMO: 2 boys, aged 1.5 and 5 years, from nonconsanguineous Slovakian families, and a 5-year-old boy from a nonconsanguineous US family of northern European origin. Both Slovakian boys had severe intellectual disability, microcephaly, epileptic seizures resistant to treatment, hypogonadism, hypogenitalism, and central obesity. Both had onset of diabetes at 10 months of age. Neither achieved head control, had any social interactions, or was able to make any voluntary movements. Brain imaging showed myelination delay. The other child had microcephaly, hypospadias and cryptorchidism, developmental delay, and obesity. He did not have epileptic seizures, and an electroencephalogram was normal. ### Heterogeneity DeLozier-Blanchet et al. (1999) suggested that the disorder described by Steinmuller et al. (1998) was the same as the disorder reported by DeLozier-Blanchet et al. (1989). However, Skopkova et al. (2017) excluded mutation in the EIF2S3 gene in the family reported by DeLozier-Blanchet et al. (1989). Inheritance The transmission pattern of MEHMO in the family reported by Borck et al. (2012) was consistent with X-linked recessive inheritance. Mapping By haplotype and 2-point linkage analyses in the large 3-generation family with MEHMO, Steinmuller et al. (1998) assigned the disease locus to Xp22.13-p21.1, in a region flanked by CYBB (300481) and DXS365. Molecular Genetics In 3 males from a consanguineous family of Morocco Jewish ancestry with X-linked syndromic mental retardation with features of MEHMO, Borck et al. (2012) identified a hemizygous missense mutation in the EIF2S3 gene (I222T; 300161.0001). The mutation, which was found by a combination of linkage analysis and exome sequencing, segregated with the disorder in the family. Female carriers were unaffected. In vitro functional expression assays in yeast and in human cells showed that the mutation impaired binding to EIF2B (see, e.g., EIF2B1, 606686) and disrupted EIF2 complex formation, resulting in defects in translation initiation. In affected members of 2 unrelated families with an X-linked mental retardation syndrome, Moortgat et al. (2016) identified 2 different hemizygous mutations in the EIF2S3 gene: a missense mutation (I259M; 300161.0002), resulting in a slightly less severe phenotype, and a frameshift mutation (300161.0003), resulting in a more severe phenotype with death in infancy. Functional studies of the variant and studies of patient cells were not performed. In affected members of 4 families with MEHMO, including the original family reported by Steinmuller et al. (1998), Skopkova et al. (2017) identified mutations in the EIF2S3 gene: a frameshift mutation (300161.0004) in 3 families, and a missense mutation (S108R; 300161.0005) in 1 patient who had a milder form of the syndrome. Animal Model Moortgat et al. (2016) found that morpholino knockdown of eif2s3 in zebrafish resulted in morphologic defects, including morphants being shorter with a curved tail, smaller head, and small eyes compared to wildtype. Morphants also showed hypomotility. INHERITANCE \- X-linked recessive GROWTH Height \- Short stature Weight \- Obesity (1 patient) Other \- Poor overall growth HEAD & NECK Head \- Microcephaly (up to -8 SD) Face \- Long face \- Temporal narrowing \- Long chin \- Long philtrum Ears \- Large ears Eyes \- Strabismus \- Myopia Nose \- Broad nasal tip \- Flat nasal tip Mouth \- Open mouth \- Cleft lip \- Cleft palate \- Drooling Teeth \- Widely spaced teeth GENITOURINARY External Genitalia (Male) \- Hypogonadism \- Micropenis SKELETAL Feet \- Achilles tendon shortening MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Global developmental delay \- Intellectual disability \- Speech delay \- Poor speech \- Seizures (in some patients) \- Hypotonia \- Ataxic gait \- Spasticity \- Spastic quadriparesis \- Difficulty walking \- Inability to walk \- Hyperreflexia \- Extensor plantar responses \- Pyramidal syndrome \- Hypotonia \- Appendicular hypertonia \- Thin corpus callosum \- Enlarged ventricles \- Reduced white matter Behavioral Psychiatric Manifestations \- Behavioral abnormalities \- Autistic features \- Aggression ENDOCRINE FEATURES \- Hypogonadism \- Growth hormone deficiency \- Delayed puberty \- Hypoglycemia MISCELLANEOUS \- Variable severity \- Obligate female carriers are unaffected \- Three unrelated families have been reported (last curated October 2016) MOLECULAR BASIS \- Caused by mutation in the eukaryotic translation initiation factor 2, subunit 3 gene (EIF2S3, 300161.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	MEHMO SYNDROME	c1846278	30,598	omim	https://www.omim.org/entry/300148	2019-09-22T16:20:48	{"doid": ["0060801"], "mesh": ["C537451"], "omim": ["300148"], "orphanet": ["85282"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, EPILEPTIC SEIZURES, HYPOGONADISM AND HYPOGENITALISM, MICROCEPHALY, AND OBESITY", "MENTAL RETARDATION, X-LINKED, SYNDROMIC 20", "MENTAL RETARDATION, X-LINKED, SYNDROMIC 25", "MENTAL RETARDATION, X-LINKED, SYNDROMIC, BORCK TYPE"]}
Viliuisk encephalomyelitis SpecialtyNeurological Viliuisk Encephalomyelitis (VE) is a fatal progressive neurological disorder found only in the Sakha (Iakut/Yakut) population of central Siberia.[1][2] About 15 new cases are reported each year. VE is a very rare disease and little research has been conducted. The causative agents, origin of the disease, and involved candidate genes are currently unknown, but much research has been done in pursuit of the answers. Those inflicted with the disease survive for a period of only a few months to several years. VE follows three main courses of infection: an acute form, a sub-acute form subsiding into a progressive form, and a chronic form. Initially, the infected patients experience symptoms such as: severe headaches, delirium, lethargy, meningism, bradykinesia, and incoordination.[1] A small percentage of patients die during the acute phase as result of a severe coma. In all cases the disease is fatal. ## Contents * 1 Pathophysiology * 2 Disease transmission * 3 Diagnosis * 4 Treatment * 5 History * 6 References * 7 External links ## Pathophysiology[edit] As of 2007, fewer than 500 Yakut individuals have been infected with VE.[3] Viliuisk Encephalomyelitis is classified as a progressive neurological disorder that ultimately ends in the death of the infected individual. The disease has three distinguishable phases: The acute form, the progressive form, and the chronic form.[citation needed] The acute form is the most rapid and most violent of all the stages. It begins with the characteristic rigidity of the muscles, accompanied by slurred speech, severe headaches, and exaggeration of cold-like symptoms. Patients usually die within weeks of the initial symptoms. Routine post-mortem examinations yield: severe inflammation of the brain lining, clusters of dead cells and tissue, and largely increased amounts of macrophages and lymphocytes.[3][4] The progressive form is the most common case. Patients initially experience acute-like symptoms which are not as severe, and subside within a few weeks. Following the sub-acute phase, the patients experience a few mild symptoms including some behavioral changes, incoordination, and difficulty in speech. Eventually the disease developed fully and those infected were stricken with the characteristic symptoms of rigidity, slurred speech, and deterioration of cognitive functions.[3][4] Ultimately, brain function depreciates rapidly resulting in death.[citation needed] Many patients who undergo the chronic form claim never to have had an acute attack. These patients endure varying measures of impairment and suffer mental deterioration for the remainder of their lives. Usually they live to be very old and succumb to other diseases.[3][4] In almost all cases there are changes characteristic of VE. Early onset shows an increased number of lymphocytes and increased protein concentration — which reduces over many years. These factors help neurologists determine the form of VE based on progression. The trademark changes in the brain include: thickened inflamed meninges, necrotic cortical lesions, increased number of lymphocytes, and neuronal death.[3][5] ## Disease transmission[edit] Currently the mechanism of spread and infection is unknown despite the tedious epidemiological, clinical, and neurological studies that have been conducted.[6] Recent Studies show Horizontal Disease Transmission, or the transmission of a disease from one individual to another of the same generation. It appears that VE is an infectious disease; however, the incubation period would have to be very extensive[1] (in excess of 5 years). Many infected individuals attribute the initial symptoms as a result of a plunge in frigid waters. So far, no causative agent has been found in blood, spinal fluid, or brain tissue.[1][7] ## Diagnosis[edit] This section is empty. You can help by adding to it. (October 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (October 2017) ## History[edit] Research has concluded that VE has been present in the Viuli valley for many centuries among the Evenk populations of northern Siberia.[1][8] The disease had its debut through its first Yakut diagnosis a little over a century ago in villages of the Viuli region of Siberia. Not until after World War II did the Yakut people become aware of this mysterious killer. The locals and Northern Evenks referred to this illness as “Bokhoror” or “the stiffness” because of the typical rigidity of the limbs those infected individuals experienced. Viliuisk Encephalomyelitis is currently isolated in the Yakut (Sakha) populations of Siberia, Russia. However, extensive migration might allow the disease to become a continental epidemic as it has already spread the infection radius many miles since its induction in the early 1900s.[1] Fifty years ago it was believed that the Yakut people had extremely degraded immune systems as result of malnourishment and starvation from the World War. It was believed that this disease was docile and those with healthy immune systems could easily fight it off. This inclination appeared to be accurate until a case of a single Caucasian Russian woman. Supposedly, she infected herself as a means to end her own life. She injected herself with cerebrospinal fluid of a victim of VE, and died as a result of it. This is the first and only reported infection and death of a Caucasian.[citation needed] ## References[edit] 1. ^ a b c d e f Goldfarb, L.G.; Gajdusek, D.C. (1992). "Viliuisk Encephalomyelitis in the Iakut people of Siberia". Brain. 115 (4): 961–78. doi:10.1093/brain/115.4.961. PMID 1393513. 2. ^ Oleksyk, TK; Goldfarb, LG; Sivtseva, T; Danilova, AP; Osakovsky, VL; Shrestha, S; O'Brien, SJ; Smith, MW (2004). "Evaluating association and transmission of eight inflammatory genes with Viliuisk encephalomyelitis susceptibility". European Journal of Immunogenetics. 31 (3): 121–8. doi:10.1111/j.1365-2370.2004.00459.x. PMID 15182325. 3. ^ a b c d e Stone, R (2002). "Infectious disease. Siberia's deadly stalker emerges from the shadows". Science. 296 (5568): 642–5. doi:10.1126/science.296.5568.642. PMID 11976423. 4. ^ a b c McLean, CA; Masters, CL; Vladimirtsev, VA; Prokhorova, IA; Goldfarb, LG; Asher, DM; Vladimirtsev, AI; Alekseev, VP; Gajdusek, DC (1997). "Viliuisk encephalomyelitis--review of the spectrum of pathological changes". Neuropathology and Applied Neurobiology. 23 (3): 212–7. doi:10.1111/j.1365-2990.1997.tb01204.x. PMID 9223130. 5. ^ Garruto, R.M.; Little, M.A.; James, G.D.; Brown, B.D. (1999). "natural experimental models: the global search for biomedical paradigms among traditional, modernizing, and modern populations". Proceedings of the National Academy of Sciences USA. 96 (18): 10536–43. Bibcode:1999PNAS...9610536G. doi:10.1073/pnas.96.18.10536. PMC 17924. PMID 10468644. 6. ^ Gajdusek DC, Goldfarb LG. Bibliography of Viliuisk Encephalomyelitis in the Iakut (Sakha) People of Siberia. 3rd edn. Bethesda, Maryland, USA: Laboratory of Ventral Nervous System Studies, National Institute of Neurological Disorders and Stroke, national Institutes of Health, 1992. 7. ^ Green, AJ; Sivtseva, TM; Danilova, AP; et al. (August 2003). "Viliuisk encephalomyelitis: intrathecal synthesis of oligoclonal IgG". J. Neurol. Sci. 212: 69–73. doi:10.1016/s0022-510x(03)00107-2. PMID 12810001. 8. ^ World Health Organization. Program for Investigation of Viliuisk Encephalomyelitis in Collaboration with the Institute of Health, National Academy of Sciences, Sakha (Yakut) Republic, and a Group of International Experts. Geneva: W.H.O.; 1998. pp. 1 – 13. ## External links[edit] * Viliuisk Encephalomyelitis in the Iakut People of Siberia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone [HHAT]: hedgehog acyltransferase [Hh]: Hedgehog *[ABS]: amniotic band syndrome	Viliuisk encephalomyelitis	None	30,599	wikipedia	https://en.wikipedia.org/wiki/Viliuisk_encephalomyelitis	2021-01-18T18:36:19	{"wikidata": ["Q7930230"]}

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