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Neoplastic meningitis
Other namesCarcinomatous meningitis, leptomeningeal carcinoma, leptomeningeal carcinomatosis, leptomeningeal metastasis, meningeal carcinomatosis, meningeal metastasis, meningitis carcinomatosa
Meningeal carcinomatosis: tumor cell clusters in the subarachnoid space in a brain biopsy
SpecialtyOncology, neurology
Leptomeningeal cancer (also called leptomeningeal carcinomatosis, leptomeningeal disease (LMD), leptomeningeal metastasis, neoplastic meningitis, meningeal metastasis and meningeal carcinomatosis) is a rare complication of cancer in which the disease spreads from the original tumor site to the meninges surrounding the brain and spinal cord.[1] This leads to an inflammatory response, hence the alternative names neoplastic meningitis (NM), malignant meningitis, or carcinomatous meningitis.[2][3] The term leptomeningeal (from the Greek lepto, meaning 'fine' or 'slight') describes the thin meninges, the arachnoid and the pia mater, between which the cerebrospinal fluid is located.[4] The disorder was originally reported by Eberth in 1870.[5]
It occurs with cancers that are most likely to spread to the central nervous system.[6] The most common cancers to include the leptomeninges are breast cancer, lung cancer, and melanomas because they can metastasize to the subarachnoid space[7] in the brain which offers a hospitable environment for the growth of metastatic tumor cells.[7][8] Individuals whose cancer has spread to an area of the brain known as the posterior fossa have a greater risk of developing a leptomeningeal cancer.[9] The condition can also arise from primary brain tumor like medulloblastoma.
Leptomeningeal disease is becoming more evident because cancer patients are living longer and many chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells.[7]
## Contents
* 1 Epidemiology
* 2 Causes
* 3 Pathology
* 3.1 Spinal cord
* 3.2 From primary cancer to the meninges
* 3.3 Invasion routes
* 3.4 Infiltration to spinal cord
* 4 Signs and symptoms
* 5 Diagnosis
* 5.1 Difficulties in diagnosis
* 5.2 Techniques
* 5.3 Cerebral spinal fluid
* 5.3.1 Tumor markers
* 6 Treatment
* 6.1 Radiotherapy
* 6.2 Chemotherapy
* 6.3 Risks of treatments
* 7 Prognosis
* 7.1 Factors that lower survival
* 8 Current research
* 9 History
* 10 Related Diseases
* 11 Gallery
* 12 References
* 13 Further reading
* 14 External links
## Epidemiology[edit]
In the United States, 1–8% of cancer patients are diagnosed with leptomeningeal disease, with approximately 110,000 cases per year.[10] The exact incidence of leptomeningeal disease is difficult to determine, since gross examination at autopsy may overlook signs of leptomeningeal disease, and microscopic pathological inspection may be normal if the seeding is multifocal or if an unaffected area of the central nervous system (CNS) is examined.[citation needed]
## Causes[edit]
Leptomeningeal carcinomatosis occurs when the cancer cells invade the cerebrospinal fluid[5] and spread throughout the central nervous system.[6] The metastatic tumor cells grow either attached to the pia mater covering the brain and spinal cord or floating unattached to the subarachnoid space.[7] Tumors of diverse origins and hematologic cancers may spread to this space.[5]
Some patients can develop a leptomeningeal tumor while receiving chemotherapy for their primary tumor.
## Pathology[edit]
There are three anatomic patterns by which the tumor can spread in the subarachnoid space. More than one pattern may coexist in the same patient.
First, there may be plaque-like deposits of cells in the leptomeninges with invasion of Virchow-Robin spaces and, usually, the shedding of tumor cells into the cerebrospinal fluid.
Second, there may only be a thin coating of meninges, in some cases with only a single cell layer, but also with shedding of tumor cells into the cerebrospinal fluid. Third, there may be a pattern of nodular deposits of tumor on cranial and spinal nerve roots, frequently without tumor cells being shed into the cerebrospinal fluid.
The first and third patterns are common in solid tumors whereas the second occurs most frequently with leukemia and lymphoma.[7]
### Spinal cord[edit]
Neoplastic meningitis (NM) shows diffuse infiltration of tumor cells into the subarachnoid space which may be associated with increased intracranial pressure, signs of meningeal irritation, and damage to the cranial and spinal nerve roots. Pathological feature include:
* Circular necrosis of the white matter in the periphery of the spinal cord was also noted which probably resulted from circulatory disturbance secondary to tumor infiltration.
* Dorsal radiculopathy which is secondary ascending degeneration of the posterior funiculus may also occur due to malignant cells collecting or a presence of tumor which cause compression of the nerve.
* Tumor cell proliferation is observed around nerve roots as well as loss of myelinated nerve fibers and axonal swelling. In areas of tumor cells, infiltration of macrophages is observed. Nerve root infiltration has shown positive correlation with meningeal dissemination.
* Infiltration of the spinal cord parenchyma is found with destruction of the pia mater. Tumor cell infiltration is associated with spongy changes in the white matter of the spinal cord beneath the pia mater with demyelination, axonal swelling, and macrophage infiltration. Transverse necrosis of the spinal cord is usually marked with bleeding from tumor growth in the subarachnoid space and is the result of compression by the hematoma in the subarachnoid space.
### From primary cancer to the meninges[edit]
NM is a secondary cancer meaning that it is the result of neoplastic cells that have metastasized from a primary cancer site. These cancers develop an enzyme that is able to break down blood vessels at a microscopic level. These cells enter the blood vessels and travel across the body. Once the brain is reached, they break down the blood–brain barrier to enter the Cerebrospinal Fluid (CSF). There the cancerous cells seed and disseminate into the leptomeninges which are composed of the arachnoid and the pia. The CSF continues to carry neoplastic cells through the brain tracts and spreads the cancerous cells.
Lung cancer, breast cancer, and malignant melanoma comprise the majority of solid tumors spreading to the leptomeninges. Although rare, meningeal carcinomatosis can arise from cervical cancer.[11] Only eight cases of MC arising from squamous cell carcinoma of the uterine cervix are previously reported in the literature.[11]
Since NM is a result of primary cancer metastasis and can develop from primary brain tumors or parenchymal metastasis when tumor cells are lodged in small central nervous system (CNS) vasculature, causing local ischemia and vessel damage which result in tumor spillage into the Virchow-Robin spaces and providing access to the subarachnoid space.
### Invasion routes[edit]
* Hematogenous spread, or spread through blood vessels, occur either through the venous plexus of Batson or by arterial dissemination. This occurs with arterioles as a result of tumor cells being lodged in vessels that feed the meninges and later causing leakage into the meninges and CSF. This same situation also appear with spinal arteries where leakage of tumor cells is into the nerve roots. More regarding the effects of NM on spinal cord is discussed later. Tumor cells may also seed the choroid plexus, where CSF is produced, and ultimately gaining direct access to the CSF. Seeding of the choroid plexus is most common in patients with third and lateral ventricular hydrocephalus.
* Venous spread may occur when intra-abdominal or thoracic pressure increases and venous flow is retrograde which then allows tumor cells in the systemic venous system to enter the vertebral venous system.
* Centripetal migration from systemic tumors along perineural, invasion of nerve space, or perivascular spaces.[12] Malignant cells can migrate along spinal or cranial nerve epineurium-perineurium, invade the subpial space, and travel along blood vessels into the endoneurial space, or invade the nerve parenchyma.
Infiltration happens most often at the base of the brain, dorsal surface, and especially at the cauda equina (bundle of nerves occupying spinal column) which is largely due to the effect of gravity. Once in the CSF, malignant cells can extend along the membrane surfaces or spread freely in the CSF and attach to other locations. These cells have the ability to penetrate the pial membrane and invade the spinal cord and cranial nerves.[13]
### Infiltration to spinal cord[edit]
Infiltration from the subarachnoid space into the spinal cord occurs primarily along the perivascular tissues that surround blood vessels at the brain entrance. Infiltration from the anterior median fissure, a 3mm deep furrow on the anterior side of the spinal cord, to the anterior horn of the spinal cord, the ventral grey matter of the spinal cord, is found along the central artery. Direct infiltration of the nerve roots is also observed, mostly from the dorsal roots (the afferent sensory root of the spinal nerve) than the ventral roots (the efferent motor root of a spinal nerve).
With mild infiltration, tumor cells are found diffusely in the subarachnoid space from the cervical to sacral levels. In some cases however there are no differences between spine levels. Infiltration from the subarachnoid space into the spinal cord occurs mainly along the perivascular space of the white matter. However, in some cases, direct infiltration into the spinal cord parenchyma is found together with destruction of the pia mater.[14]
## Signs and symptoms[edit]
The most common symptoms of leptomeningeal cancer is pain and seizures. The other symptoms may include headaches (usually associated with nausea, vomiting, light-headedness), gait difficulties from weakness or ataxia, memory problems, incontinence, sensory abnormalities.[15][1] In some cases, symptoms may include double vision, numb chin,[6] back pain, leg weakness, sphincter-related problems, hydrocephalus,[16] loss of urine control, and difficulty walking. Depending on where the tumor cells settle, leptomeningeal cancer can cause almost any neurological problem.[17] Other symptoms that are less common cranial nerve abnormalities, spinal symptoms such as limb weakness and paresthesia, and bowel and bladder dysfunction. Diplopia is the most common symptom of cranial nerve dysfunction. Trigeminal sensory or motor loss, cochlear dysfunction, and optic neuropathy are also common findings. Spinal signs and symptoms include weakness, dermatomal or segmental sensory loss, and pain in the neck, back, or following radicular patterns.[citation needed]
3 affected domains of neurological function:
* Cerebral hemisphere (15%)
* Cranial Nerves (35%)
* Spinal cord and roots (60%)
Signs reported:
* headache
* mental status change
* confusion
* cognitive impairment
* seizures
* hemiparesis
* gait instability
## Diagnosis[edit]
Screening involves an MRI scan to identify and diagnose tumors in the subarachnoid region of the brain. MRI can make a diagnosis even without an analysis of the cerebrospinal fluid but it can sometimes be difficult to detect because MRI scans cannot always pick up the problem.[18]
Diagnosis is most commonly made by lumbar puncture to detect malignant cells in the CSF, although the tests may be negative in roughly 10% of patients.[5] Diagnosis often requires a high index of suspicion and is confirmed by neuroimaging and cerebrospinal fluid analysis.[19]
CSF examination is the most useful diagnostic tool for NM. Patients with suspected NM should undergo one or two lumbar punctures, cranial magnetic resonance imaging (MRI), spinal MRI, and a radioisotope CSF flow study to rule out sites of CSF block. If the cytology remains negative and radiological studies are not definitive, consideration may be given to ventricular or lateral cervical spine CSF analysis based on the suspected site of predominant disease. Consideration of signs, symptoms, and neuroimaging can help with the placement to where CSF is drawn. Median time of diagnosis from initial primary cancer diagnosis is between 76 days and 17 months.[20]
### Difficulties in diagnosis[edit]
NM is multifocal and CSF at a particular site may show no abnormalities if the pathological site is far away. Only 50% of those suspected with NM are actually diagnosed with NM and only the presence of malignant cells in the CSF is diagnosis conclusive.[citation needed]
### Techniques[edit]
* MRI: Meningeal findings are described with the following characteristics: Nodular meningeal tumor, meningeal thickening >3 mm and a subjectively strong contrast enhancement. A smooth contrast enhancement of the meninges was judged to be typical for inflammatory, nonneoplastic meningitis.[21]
* CSF cytology: is performed after drawing the CSF by lumbar puncture.
* Cytogenetic: measures chromosomal content of cells and fluorescence in situ hybridization which detects numerical and structural genetic aberrations as a sign of malignancy. This is especially useful for liquid tumors such as leukemia and lymphoma. Some of the techniques that achieve this are flow cytometry and DNA single-cell cytometry. However, cytogenetic only assist in diagnosis and is less preferred.
* Meningeal Biopsy: may be performed when all of the above criteria is inconclusive. Biopsy is only effective when performed at the region where there's enhancement on the MRI.[citation needed]
### Cerebral spinal fluid[edit]
Criteria for CSF abnormalities include:
* Increased opening pressure (> 200mm of H2O)
* Increased Leukocytes (>4/mm3)
* Elevated protein (>50 mg/dL)
* Decreased glucose (<60 mg/dL)
#### Tumor markers[edit]
These markers can be good indirect indicator of NM but most are not sensitive enough to improve cytogical diagnosis:
* Carcinoembryonic antigen (CEA)
* alpha-fetoprotein
* beta-human chorionic gonadotropin
* carbohydrate antigen19-9
* creatine-kinase BB
* isoenzyme
* tissue polypeptide antigen
* Beta-2 microglobulin
* beta-glucoronidase
* lactate dehydrogenase isoenzyme-5
* vascular endothelial growth factor
## Treatment[edit]
There is currently no cure for leptomeningeal disease as the tumor is hard to eradicate.[3] Current treatments for leptomeningeal tumors are palliative. The goals for treatment include prolonging survival and stabilizing neurological symptoms.
### Radiotherapy[edit]
Radiotherapy is used mostly for focal type of NM due to the nature of damage and success rate associated with the treatment. Radiotherapy targets the tumor and destroys the collective tissues of cancerous cells.
### Chemotherapy[edit]
Chemotherapy is injected directly into the cerebrospinal fluid, either by lumbar puncture (“spinal tap”) or through a surgically implanted device called an Ommaya reservoir.[17] Intrathecal Therapy is preferred since intravenous chemotherapy do not penetrate the BBB.[22] The most common chemicals used are liposomal cytarabine (DepoCyte) and intrathecal methotrexate (MTX).
The downside of a spinal tap diagnosis is that while it is highly accurate and reliable, it can also report false-negative results.[18] Chemotherapy is delivered intrathecally as it is hard for drugs to make it into the central nervous system. Intrathecal chemotherapy can only penetrate a few millimeters. If the tumor is any thicker, radiation is given to shrink it down.[6]
The treatment is done to reduce pressure on the brain caused by any cerebrospinal fluid buildup and to reduce the number of cancer cells causing the pressure. For the best care, patients should see a physician who regularly treats leptomeningeal cancer and is most up-to-date on medicines that penetrate the blood-brain barrier, how to treat the symptoms, and clinical trials that might include patients with leptomeningeal cancer.[23]
### Risks of treatments[edit]
Both Chemotherapy and Radiotherapy are harmful to the body and most definitely the brain. Caution must be utilized in treating patients with NM. Another factor that makes treatment difficult is that there is no suitable method to evaluate the disease progression.[24]
## Prognosis[edit]
The prognosis is generally poor with survival typically measured in months.[6] The median survival time of patients without treatment is four to six weeks. The best prognosis are seen from NM due to breast cancer with the median overall survival of no more than six months after diagnosis of NM.[25] Death is generally due to progressive neurological dysfunction. Treatment is meant to stabilize neurological function and prolong survival. Neurological dysfunction usually cannot be fixed but progressive dysfunction can be halted and survival may be increased to four to six months.
It occurs in approximately 3-5% of cancer patients.[8] The disease is usually terminal and if left untreated, the median survival is 4–6 weeks whereas if treated, the median survival can increase to 2–3 months.[1] Treatment will be more effective if it is done on the primary tumor before it metastasizes to the brain or spinal cord.
Patients with leukaemia achieve better results compared to patients with solid tumours who have undergone treatment. It was found that 75% of patients stabilize or improve over several months as opposed to 25% of patients who do not respond and have progressive disease. But despite initial improvement, most patients survive only a few months. Breast cancer and small cell lung cancer are the two solid tumors that respond best to treatment[26] Some patients do better than others, particularly those whose primary cancer is hematologic, bone marrow and lymph nodes.[27]
### Factors that lower survival[edit]
Much of prognosis can be determined from the damage due to primary cancer. Negative hormone receptor status, poor performance status, more than 3 chemotherapy regimes, and high Cyfra 21-1 level at diagnosis, all indicates lower survival period of patients with NM. Cyfra 21-1 is a fragment of the cytokeratin 19 and may reflect the tumor burden within the CSF.[citation needed]
## Current research[edit]
New treatments and clinical trial for breast cancer patients and non-small cell lung cancer patients with leptomeningeal disease are currently being explored.[6]
People with leptomeningeal metastasis are generally excluded from clinical trials, thereby limiting the systematic assessment of novel therapies in this subgroup of patients with poor prognosis. More patients with leptomeningeal metastasis should be enrolled into trials investigating novel agents with the potential to penetrate the blood–brain barrier.[28]
Novel approaches are being studied as currently available therapies are toxic and provide limited benefits.[8]
## History[edit]
Neoplastic Meningitis (NM) was first reported in the 1870s.[29]
## Related Diseases[edit]
* Parenchymal Disease occurs in 30-40% of those diagnosed with NM. The disease associated with the main functioning body of an organ, in this case the brain.
* acute cerebellar ataxia is a rare initial presenting feature of NM, particularly in gastric cancer. Paraneoplastic cerebellar degeneration (PCD) is a well-known cause of cerebellar ataxia associated with neoplastic disorders, and commonly, with positivity for various anti-neuronal antibodies.[30]
* Bilateral sensorineural hearing loss caused by complications with the vestibulocochlear nerves from onset of NM [31]
* Subacute Confusion: when functioning of the brain such as cognition deteriorates but at a less rapid rate than that of acute confusion [32]
## Gallery[edit]
* Meningeal carcinomatosis in a patient with breast cancer (contrast-enhanced axial T1-weighted MRI)
## References[edit]
1. ^ a b c "Leptomeningeal Carcinomatosis: Practice Essentials, Background, Pathophysiology". 2017-12-06. Cite journal requires `|journal=` (help)
2. ^ "Neoplastic meningitis". NCI Dictionary of Cancer Terms. National Cancer Institute. Retrieved 31 July 2018.
3. ^ a b "Leptomeningeal Tumor". Florida Hospital. Retrieved 2018-04-20.
4. ^ "Management of Leptomeningeal Disease From Solid Tumors | Cancer Network". www.cancernetwork.com. Retrieved 2018-04-20.
5. ^ a b c d "Leptomeningeal Carcinomatosis: Serious Cancer Complication". www.princetonbrainandspine.com. Retrieved 2018-04-20.
6. ^ a b c d e f staff, MD Anderson. "New hope for leptomeningeal disease care". www.mdanderson.org. Retrieved 2018-04-20.
7. ^ a b c d e "Carcinomatous Meningitis: It Does Not Have to Be a Death Sentence | Cancer Network". www.cancernetwork.com. Retrieved 2018-04-20.
8. ^ a b c Grossman, S. A.; Krabak, M. J. (April 1999). "Leptomeningeal carcinomatosis". Cancer Treatment Reviews. 25 (2): 103–119. doi:10.1053/ctrv.1999.0119. ISSN 0305-7372. PMID 10395835.
9. ^ "Causes of Leptomeningeal Tumor". Florida Hospital. Retrieved 2018-04-20.
10. ^ Groves, Morris D. (January 2011). "Leptomeningeal disease". Neurosurgery Clinics of North America. 22 (1): 67–78, vii. doi:10.1016/j.nec.2010.08.006. ISSN 1558-1349. PMID 21109151.
11. ^ a b Bishnu Devkota, MBBS, FRCS, FACP And Harnish Patel, MD (June 2010). "Meningeal Carcinomatosis From Cervical Cancer:A Case Report and Review of the Literature". Hospital Practice. 38 (3): 117–121. doi:10.3810/hp.2010.06.304.CS1 maint: multiple names: authors list (link)
12. ^ Chamberlain, Marc C. (2008). Neoplastic meningitis. The Oncologist, 13(9), 967-977.
13. ^ Mammoser, A., & Groves, M. (2010). Biology and therapy of neoplastic meningitis. Current Oncology Reports, 12(1), 41-49.
14. ^ Kizawa, M., Mori, N., Hashizume, Y., & Yoshida, M. (2008). Pathological examination of spinal lesions in meningeal carcinomatosis. Neuropathology, 28(3), 295-302.
15. ^ "Leptomeningeal Carcinomatosis: Practice Essentials, Background, Pathophysiology". 2017-12-06. Cite journal requires `|journal=` (help)
16. ^ "Symptoms and Signs of Leptomeningeal Tumor". Florida Hospital. Retrieved 2018-04-20.
17. ^ a b "Leptomeningeal Disease Treatment | Mount Sinai - New York". Mount Sinai Health System. Retrieved 2018-04-20.
18. ^ a b "Screening and Tests for Leptomeningeal Tumor". Florida Hospital. Retrieved 2018-04-20.
19. ^ "UpToDate". www.uptodate.com. Retrieved 2018-04-20.
20. ^ Park, K., Yang, S., Seo, K., Kim, Y., & Yoon, K. (2012). A case of metastatic leptomeningeal carcinomatosis from early gastric carcinoma. World Journal of Surgical Oncology, 1074. doi:10.1186/1477-7819-10-74
21. ^ Pauls, S., Fischer, A., Brambs, H., Fetscher, S., Höche, W., & Bommer, M. (2012). Use of magnetic resonance imaging to detect neoplastic meningitis: limited use in leukemia and lymphoma but convincing results in solid tumors. European Journal of Radiology, 81(5), 974-978.
22. ^ Gaviani, P., Silvani, A., Corsini, E., Erbetta, A., & Salmaggi, A. (2009). Neoplastic meningitis from breast carcinoma with complete response to liposomal cytarabine: case report. Neurological Sciences, 30(3), 251-254.
23. ^ Corbin, Zachary A.; Nagpal, Seema (2016-06-01). "Leptomeningeal Metastases". JAMA Oncology. 2 (6). doi:10.1001/jamaoncol.2015.3502. ISSN 2374-2437.
24. ^ Goto, Y., Katsumata, N., Nakai, S., Sasajima, Y., Yonemori, K., Kouno, T., & ... Fujiwara, Y. (2008). Leptomeningeal metastasis from ovarian carcinoma successfully treated by the intraventricular administration of methotrexate. International Journal of Clinical Oncology, 13(6), 555-558.
25. ^ Gauthier, H., Guilhaume, M., Bidard, F., Pierga, J., Girre, V., Cottu, P., & ... Diéras, V. (2010). Survival of breast cancer patients with meningeal carcinomatosis. Annals of Oncology, 21(11), 2183-2187.
26. ^ "Leptomeningeal metastasis". cancerforum.org.au. Retrieved 2018-04-20.
27. ^ "Survivability of Leptomeningeal Tumor". Florida Hospital. Retrieved 2018-04-20.
28. ^ Sahebjam, Solmaz; Forsyth, Peter A.; Smalley, Keiran S.; Tran, Nam D. (January 2017). "Experimental Treatments for Leptomeningeal Metastases From Solid Malignancies". Cancer Control. 24 (1): 42–46. doi:10.1177/107327481702400106. ISSN 1526-2359. PMID 28178711.
29. ^ Herrlinger (2004). Leptomeningeal metastasis: survival and prognostic factors in 155 patients. Journal of the Neurological Sciences, 223(2), 167-178. doi: 10.1016/j.jns.2004.05.008
30. ^ Seok, H., Eun, M., Yoo, J., & Jung, K. (2011). Neoplastic meningitis presenting with acute cerebellar ataxia. Journal of Clinical Neuroscience, 18(3), 441-442.
31. ^ Jeffs, G., Lee, G., & Wong, G. (2006). Leptomeningeal carcinomatosis: an unusual cause of sudden onset bilateral sensorineural hearing loss. Journal of Clinical Neuroscience, 13(1), 116-118.
32. ^ Kim, P., Ashton, D., & Pollard, J. (2005). Isolated hypoglycorrachia: leptomeningeal carcinomatosis causing subacute confusion. Journal of Clinical Neuroscience, 12(7), 841-843.
## Further reading[edit]
* Meningeal Carcinomatosis From Cervical Cancer:A Case Report and Review of the Literature
## External links[edit]
This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms".
Classification
D
* MeSH: D055756
External resources
* eMedicine: neuro/188
Wikimedia Commons has media related to Meningeal carcinomatosis.
*[v]: View this template
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*[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
| Leptomeningeal cancer | c0220654 | 1,600 | wikipedia | https://en.wikipedia.org/wiki/Leptomeningeal_cancer | 2021-01-18T18:35:53 | {"mesh": ["D055756"], "umls": ["C0220654"], "wikidata": ["Q1920586"]} |
For a discussion of genetic heterogeneity of quantitative trait loci for stature (STQTL), see STQTL1 (606255).
Mapping
Kimura et al. (2008) performed a genomewide association study with 23,465 microsatellite markers, applying selective genotyping to extremely tall and extremely short individuals from the Khalkh-Mongolian population, and found significant association at D15S988 on chromosome 15q22.33. Further analysis with 2 additional microsatellite markers and 64 SNPs revealed association involving an LD block at 15q22.32; the most strongly associated SNP (rs8038652; p = 0.0003), was located in intron 1 of the IQCH gene (612523). Association analysis under a recessive model for that SNP showed the lowest p value with the AA genotype (p = 0.000046), indicating that the AA genotype of rs8038652 has an adverse effect on adult height in Mongolians (odds ratio = 0.59).
*[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
| STATURE QUANTITATIVE TRAIT LOCUS 16 | c2675489 | 1,601 | omim | https://www.omim.org/entry/612579 | 2019-09-22T16:01:11 | {"omim": ["612579"]} |
A number sign (#) is used with this entry because hyperprolinemia type II (HYRPRO2) is caused by homozygous or compound heterozygous mutation in the pyrroline-5-carboxylate dehydrogenase gene (P5CDH; 606811) on chromosome 1p36.
For a discussion of genetic heterogeneity of hyperprolinemia, see HYRPRO1 (239500).
Clinical Features
Emery et al. (1968) described an affected mentally retarded 18-year-old girl whose retarded sister had died, presumably of the same disorder. Selkoe (1969) described a second type of hyperprolinemia with only mild mental retardation and without renal disease. Pavone et al. (1975) described 3 clinically normal sibs with type II hyperprolinemia. They lived in eastern Sicily and had first-cousin parents. All 3 also showed hyperglycinemia. The association is unexplained. No relation between proline and glycine metabolism is evident. Valle et al. (1979) found that both proline oxidase and hydroxyproline oxidase are deficient in hyperprolinemia type II.
Molecular Genetics
In 3 unrelated probands with type II hyperprolinemia, Geraghty et al. (1998) found 3 mutant alleles: 2 with frameshift mutations and 1 with a missense mutation (606811.0001-606811.0003).
Vasiliou et al. (1999) reviewed mutations in the ALDH4 gene that cause hyperprolinemia type II.
INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Recurrent seizures \- Mental retardation LABORATORY ABNORMALITIES \- Hyperprolinemia (10-15 times normal) \- Delta-1-pyrroline-5-carboxylate (P5C) levels increased in plasma \- P5C levels increased in urine \- Delta-1-pyrroline-3-hydroxy-5-carboxylate levels increased in urine \- Aminoaciduria \- Prolinuria \- Hydroxyprolinuria \- Glycinuria \- Delta-1-pyrroline-5-carboxylate dehydrogenase activity decreased in fibroblasts or leukocytes MOLECULAR BASIS \- Caused by mutations in the delta-1-pyrroline-5-carboxylate dehydrogenase gene (P5CDH, 606811.0001 ) ▲ Close
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*[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
| HYPERPROLINEMIA, TYPE II | c2931835 | 1,602 | omim | https://www.omim.org/entry/239510 | 2019-09-22T16:26:49 | {"doid": ["0080543"], "mesh": ["C538385"], "omim": ["239510"], "orphanet": ["79101"], "synonyms": ["Alternative titles", "HPII", "1-PYRROLINE-5-CARBOXYLATE DEHYDROGENASE DEFICIENCY"]} |
Ring chromosome 4 syndrome is an autosomal anomaly characterized by variable clinical features, most commonly including significant intrauterine and postnatal growth retardation, developmental delay, intellectual disability, microcephaly, and dysmorphic facial features. Some less frequent features are cleft lip and/or cleft palate, congenital cardiovascular, gastrointestinal and genitourinary system anomalies.
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*[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
| Ring chromosome 4 syndrome | c0265407 | 1,603 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1447 | 2021-01-23T18:00:17 | {"gard": ["1339"], "mesh": ["C537636"], "umls": ["C0265407", "C2931556"], "icd-10": ["Q93.2"], "synonyms": ["Ring 4", "Ring chromosome 4", "Syndrome r(4)", "r(4) syndrome"]} |
Satchmo's syndrome
Satchmo's syndrome is a disorder due to the rupture of Orbicularis oris muscle in trumpet players.[1] This syndrome is named after the nickname of Louis Armstrong, the trumpet player from New Orleans, because apparently it fits with the symptoms he experienced in 1935.
## Pathology[edit]
In order to produce the right music, the trumpet player has to exert strength and produce vibrations of the lip. This can sometimes lead to the rupture of the musculature of the lip. Due to the muscle rupture, there is possibly a lengthening of the circumference of the orbicularis oris, and it fails to exert normal strength. As a result, the trumpet player cannot produce high musical notes. This condition may be partly reversed by resting the lips for weeks to months. The muscle rupture can also be corrected surgically, in which case the trumpet player can perform as well as they did before the injury.[1]
## References[edit]
1. ^ a b "Rupture of the Orbicularis Oris in Trumpet Players (Satchmo's Syndrome)". www.clinicaplanas.com. Retrieved 19 January 2018.
*[v]: View this template
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*[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
| Satchmo's syndrome | None | 1,604 | wikipedia | https://en.wikipedia.org/wiki/Satchmo%27s_syndrome | 2021-01-18T18:48:54 | {"wikidata": ["Q48815240"]} |
## Description
Angioma serpiginosum is an uncommon benign skin disorder characterized by asymptomatic clusters of nonpurpuric punctate erythematous lesions. The rash is asymptomatic but may lead to cosmetic problems and can be treated by laser therapy. Women are most commonly affected, and the disorder is most often sporadic, although rare families suggestive of autosomal dominant inheritance have been reported (Sandhu and Gupta, 2005). No male-to-male transmission has been described, but father-to-daughter transmissions are known. It has been suggested that the pattern of skin involvement may be due to cutaneous somatic mosaicism (Chen et al., 2006; Blinkenberg et al., 2007).
An X-linked dominant form of angioma serpiginosum (300652) has been mapped. The few males described may actually represent somatic mosaicism of an X-linked gene.
Clinical Features
Angioma serpiginosum was first described by Jonathan Hutchinson (1889) in Plate IX of Vol. 1 of his Archives of Surgery. More common in females, the condition begins before puberty as pin-sized capillary puncta affecting any part of the body surface except the palms and soles and also sparing oral mucous membranes.
Marriott et al. (1975) reported 2 kindreds with several affected individuals, consistent with dominant inheritance and reduced penetrance; no male-to-male transmission was observed. Blinkenberg et al. (2007) commented that the large family reported by Marriott et al. (1975) did not exclude X-linked dominant inheritance.
Gerbig et al. (1995) reported a 34-year-old woman with angioma serpiginosum on the medial aspect of the left thigh extending to the groin and lower abdomen and on the volar aspect of the left forearm. Distribution was along the lines of Blaschko. Reexamination of earlier cases revealed that 6 of 7 had distribution of the lesions along the lines of Blaschko.
Al Hawsawi et al. (2003) reported an adolescent boy with angioma serpiginosum distributed in a linear pattern along the upper extremity. Skin biopsy showed the characteristic numerous thick-walled capillaries in the dermal papillae.
Sandhu and Gupta (2005) reported a father and daughter with angioma serpiginosum. Examination revealed irregular areas of multiple red puncta varying in size from 0.5 to 1 mm with minimal background erythema. The daughter had lesions covering the extensor aspect of the upper arm and lower abdomen; the father had bilateral distribution over the arms and buttocks. Skin biopsy showed dilated vessels in distended dermal papillae. A second unrelated woman had more extensive involvement with lesions over the lower legs, buttocks, trunk, and upper limbs.
Chen et al. (2006) described a 15-year-old Taiwanese girl with angioma serpiginosum arranged in a systematized segmental pattern with a midline separation. The spots first appeared at age 7 years on the anterior aspect of the right thigh and subsequently involved the right buttock, left upper quadrant of the abdomen and left back, posterolateral left leg and radial surface of the right arm. Physical examination revealed nonblanchable coppery to bright-red punctate lesions measuring up to 1 mm in diameter and grouped in patches. There was no family history of the disorder. Chen et al. (2006) suggested that the pattern of involvement may be due to cutaneous mosaicism, although it did not fit clearly into the accepted classification system of dermatologic mosaic patterns. The authors stated that sporadic cases may represent segmental manifestation of a disorder that can be transmitted as an autosomal dominant trait.
Pathogenesis
By electron microscopy, Kumakiri et al. (1980) found that the walls of the capillaries in angioma serpiginosum showed a heavy precipitation of fine fibrillar material admixed with collagen fibers. The endothelial cells formed accessory lumens or slit-like protrusions of lumen into the endothelial lining. The authors concluded that angioma serpiginosum is not a telangiectasia of preexisting vessels, but a type of capillary nevus with a tendency to manifest in the form of capillary dilation and proliferation.
INHERITANCE \- Autosomal dominant \- Isolated cases SKIN, NAILS, & HAIR Skin \- Non-purpuric punctate and linear erythematous rash \- Subepidermal capillary ectasia \- Lesions often follow Blaschko lines \- Lesions occur on the trunk, back, arms, legs, abdomen, buttocks \- Extensive cutaneous involvement rarely occurs \- Palms, soles, and oral mucosa are not involved Skin Histology \- Nests of dilated and thick-walled capillaries in the dermal papillae \- Hyperkeratosis \- Inflammation is usually absent Electron Microscopy \- Slit-like protrusion of capillary lumen into the endothelial lining MISCELLANEOUS \- Onset in childhood \- Slowly progressive \- More common in women (90%) \- Usually a sporadic disorder \- No male-to-male transmission \- Partially responsive to laser treatment \- See also X-linked dominant form ( 300652 ) ▲ Close
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*[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
| ANGIOMA SERPIGINOSUM, AUTOSOMAL DOMINANT | c1970130 | 1,605 | omim | https://www.omim.org/entry/106050 | 2019-09-22T16:45:04 | {"doid": ["4028"], "mesh": ["C536365"], "omim": ["106050"], "orphanet": ["95429"], "synonyms": []} |
Degos disease is a rare blood vessel disorder. It is characterized by blockages of small to medium sized blood vessels. This slows or stops the flow of blood through the affected vessels. Severity of symptoms depends on the extent and location of the affected blood vessels. Some individuals with Degos disease have isolated skin involvement and develop porcelain-white macules on their skin. Other individuals have more wide spread disease. Multiorgan disease can become life threatening. The cause of this condition is currently unknown.
*[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
| Malignant Atrophic Papulosis | c0221011 | 1,606 | gard | https://rarediseases.info.nih.gov/diseases/6249/malignant-atrophic-papulosis | 2021-01-18T17:59:15 | {"mesh": ["D054853"], "omim": ["602248"], "umls": ["C0221011"], "orphanet": ["679"], "synonyms": ["Degos's malignant atrophic papulosis", "Atrophic papulosis, malignant", "Kohlmeier-Degos disease", "Köhlmeier-Degos disease", "Papulosis atrophican maligna", "Degos disease", "Köhlmeier-Degos-Delort-Tricort syndrome"]} |
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Urethritis
SpecialtyUrology
Urethritis is the inflammation of the urethra. The most common symptoms include painful or difficult urination and urethral discharge.[1] It is a commonly treatable condition usually caused by infection with bacteria. This bacterial infection is often sexually transmitted, but not in every instance; it can be idiopathic, for example.[2] Some incidence of urethritis can appear asymptomatic as well.[3]
## Contents
* 1 Etiology/Causes
* 2 Symptoms
* 2.1 Complications
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 6 Epidemiology
* 7 References
* 8 External links
## Etiology/Causes[edit]
The disease is classified as either gonococcal urethritis, caused by Neisseria gonorrhoeae, or non-gonococcal urethritis (NGU), most commonly caused by Chlamydia trachomatis, which is accounted for 20-50% of routinely tested cases.[4] NGU, sometimes called nonspecific urethritis (NSU), has both infectious and noninfectious causes.
Other causes include:[1][5]
* Mycoplasma genitalium:[6] second most common cause accounting for 15-20% of non-gonococcal urethritis[7]
* Trichomonas vaginalis:[8] accounts for 2-13% of cases in the US; infection is mainly asymptomatic in most cases[9]
* Adenoviridae
* Uropathogenic Escherichia coli (UPEC)
* Herpes simplex virus
* Cytomegalovirus
* Reactive arthritis: urethritis is part of the triad of reactive arthritis,[10] also known as the Reiter Syndrome, which includes arthritis, urethritis, and conjunctivitis.
* Ureaplasma urealyticum
* Methicillin-resistant Staphylococcus aureus[11]
* Group B streptococcus[12]
* Irritation of the genital area:[13] for example catheter-induced, physical activity, tight clothing or soaps
* Fungal urethritis in immunosuppressed individual[9]
## Symptoms[edit]
Symptoms vary based on the cause of the diseases. For infectious causes of urethritis, symptoms may start a few weeks to several months after infection. Non-infectious causes of urethritis commonly show symptoms after a few days.[14] Common symptoms include painful urination, continuous urge to urinate, itching and, urethral discharge. Additional symptoms vary based on gender.[13] Men may experience blood in the urine or semen, itching, tenderness, or swelling of the penis, enlarged lymph nodes in the groin area, and/or pain with intercourse or ejaculation. Women may experience abdominal pain, pelvic pain, pain with intercourse, or vaginal discharge.[15] Non-gonococcal urethritis typically does not have noticeable symptoms in women, however, the infection can spread to parts of the female reproductive system.[14]
### Complications[edit]
Serious, yet rare complications associated with Neisseria gonorrhea, may include penile edema, abscessed tissue surrounding the urethra, urethral strictures such as scarring, and penile lymphangitis.[13] If left untreated, the bacteria that cause non-gonococcal urethritis can lead to various complications. In men, complications can lead to epididymitis, Reiter's syndrome, conjunctivitis, skin lesions, and discharge. In women, complications can lead to pelvic inflammatory disease, chronic pelvic pain, vaginitis, mucopurulent cervicitis, and miscarriages.[16]
## Diagnosis[edit]
Urethritis is usually diagnosed through collecting history on the individual and through a physical examination. In females, urethritis can be diagnosed with a number of tests including: urine test, blood test, vaginal culture, cytoscopy, or a nucleic acid test.[17] Women will also have abdominal and pelvic exams to check for urethral discharge, and tenderness of the lower abdomen or urethra.[15]
In men, urethritis is diagnosed by at least one of the following: mucopurlent or purulent urethral discharge on examination, ≥ 2 white blood cells per oil immersion field from a Gram stain of a urethral swab, or positive leukocyte esterase and/or ≥10 white blood cells per high power field of the first-void urine. Men who meet the criteria for urethritis commonly get Nucleic Acid Amplification Testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae to determine the type of urethritis.[13] Men will have an exam on the abdomen, bladder area, penis, and scrotom.[15] Additionally, a digital rectal examination of the prostate may be used if rectal pain is reported or if the individual is of older age.[18]
## Prevention[edit]
Primary prevention can be accomplished by the reduction of modifiable risk factors that increase the likelihood of developing urethritis. These factors include, but are not limited to, sexual intercourse (particularly unprotected intercourse) and genital irritation from contact with tight clothing, physical activity, and various irritants such as soap, lotion and spermicides.[13]
Bacterial infections leading to gonococcal and non-gonococcal urethritis can be prevented by:
* sexual abstinence
* use of barrier contraception, such as condoms
* pre-exposure vaccination: HPV and Hepatitis B vaccines
* reducing number of sexual partners[19]
Chlorhexidine is an antibacterial agent that covers a wide spectrum of gram-positive and gram-negative bacteria. Rinsing with 15 ml of a 0.12% or 10 ml of 0.2% chlorhexidine solution for 30 seconds produced large and prolonged reductions in salivary bacterial counts within 7 hours of its use. One hypothesis in 2010 posed the potential use of chlorhexidine rinsing before oral sex as a prevention strategy of recurrent non-gonococcal urethritis caused by bacteria entering the urethra from oral cavity following "insertive oral intercourse", particularly in men.[20] However, actual clinical studies are yet to be carried out in order to prove this hypothesis.
## Treatment[edit]
Antimicrobials are generally the drug of choice for gonococcal and non-gonococcal infections. The CDC in 2015 suggests using a dual therapy that consists of two antimicrobials that have different mechanisms of action would be an effective treatment strategy for urethritis and it could also potentially slow down antibiotic resistance.[21]
A variety of drugs may be prescribed based on the cause of urethritis:
* Gonococcal urethritis (caused by N. gonorrhoeae): The CDC recommends administering an injection dose of ceftriaxone 250 mg intramuscularly and oral dose of azithromycin 1g simultaneously.[21] Cefixime 400 mg oral single dose can be used as an alternative if ceftriaxone is not available.
* Non-gonococcal urethritis (caused by Chlamydia trachomatis): The CDC recommends administering an oral single dose of azithromycin 1g or a 7-day course of doxycycline 100 mg orally twice daily.'[6]
* Alternative treatments can also be used when the above options are not available:[6]
* Erythromycin base 500 mg orally four times daily for 7 days
* Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days
* Levofloxacin 500 mg orally once daily for 7 days
* Ofloxacin 300 mg orally twice daily for 7 days
Treatment for both gonococcal and non-gonococcal urethritis is suggested to be given under direct observation in a clinic or healthcare facility in order to maximize compliance and effectiveness.
For non-medication management, proper perineal hygiene should be stressed. This includes avoiding use of vaginal deodorant sprays and proper wiping after urination and bowel movements. Sexual intercourse should be avoided at least 7 days after completion of treatment (and until symptoms resolves, if present).[6] Past and current sexual partners should also be assessed and treated.[14]
Individuals displaying persistence or recurrence of symptoms should be instructed for possible re-evaluation. Although there is no standard definition, persistent urethritis is defined as urethritis that has failed to display improvement within the first week of initial therapy. Additionally, recurrent urethritis is defined as urethritis reappearing within 6 weeks after a previous episode of non-gonococcal urethritis.[22] If recurrent symptoms are supported by microscopic evidence of urethritis, then re-treatment is appropriate.[4] The following treatment recommendations are limited and based on clinical experience, expert opinions and guidelines for recurrent or persistent non-gonococcal urethritis:[4]
* If doxycycline was prescribed as initial therapy, give azithromycin 500 mg or 1 gram for the first day, then give azithromycin 250 mg once daily for 4 days plus metronidazole 400 – 500 mg twice daily for 5 days
* If azithromycin was prescribed as initial therapy, then give doxycycline 100 mg twice daily for 7 days plus metronidazole 400 – 500 mg twice daily for 5 – 7 days
* Moxifloxacin 400 mg orally once daily for 7 – 14 days can be given with use of caution, if macrolide-resistant M. genitalium infection is demonstrated [4]
Appropriate treatment for these individuals may require further referral to a urologist if symptoms persist after initial treatment.[6]
## Epidemiology[edit]
Urethritis is one of the most common sexually transmitted infections found in men. Gonorrhea and chlamydia are the main pathogens causing urethritis.[13] Health organizations break down the rate of urethritis based on its etiology. The estimated global prevalence of gonorrhoea is 0.9% in women and 0.7% in men. An estimated 87 million new infections of gonorrhoea occurred in 2016. Low-income countries have the highest prevalence of gonorrhoea.[23] Gonorrhea is more commonly seen in males than in females and infection rates are higher in adolescents and young adults.[13]
The estimated global prevalence of chlamydia, which is the most common cause of non-gonococcal urethritis, is 3.8% in women and 2.7% in men. An estimated 127 million new chlamydia cases occurred in 2016. Upper-middle income countries had the highest prevalence of chlamydia.[23] The rate of chlamydia is around two times higher in females than in males. Rates are also higher among adolescents and young adults.[13]
## References[edit]
1. ^ a b "Urethritis". PubMed Health. StatPearls Publishing LLC. 2020. Retrieved 4 August 2020.
2. ^ "Urethritis". Harvard Health Publishing. Retrieved 2020-07-27.
3. ^ Gillespie CW, Manhart LE, Lowens MS, Golden MR (March 2013). "Asymptomatic urethritis is common and is associated with characteristics that suggest sexually transmitted etiology". Sexually Transmitted Diseases. 40 (3): 271–4. doi:10.1097/OLQ.0b013e31827c9e42. PMID 23407472.
4. ^ a b c d Moi H, Blee K, Horner PJ (July 2015). "Management of non-gonococcal urethritis". BMC Infectious Diseases. 15 (1): 294. doi:10.1186/s12879-015-1043-4. PMC 4518518. PMID 26220178.
5. ^ "Disease characterized by urethritis and cervicitis". Centers for Disease Control and Prevention. 2015. Retrieved 4 August 2020.
6. ^ a b c d e "Diseases Characterized by Urethritis and Cervicitis - 2015 STD Treatment Guidelines". www.cdc.gov. Retrieved 2017-12-08.
7. ^ Territo H, Ashurst JV (2020). "Nongonococcal Urethritis (NGU)". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 30571032. Retrieved 2020-07-31.
8. ^ Caini S, Gandini S, Dudas M, Bremer V, Severi E, Gherasim A (August 2014). "Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis". Cancer Epidemiology. 38 (4): 329–38. doi:10.1016/j.canep.2014.06.002. PMID 24986642.
9. ^ a b Hakenberg OW, Harke N, Wagenlehner F (2017-04-01). "Urethritis in Men and Women". European Urology Supplements. Incorporating the EAU-EBU Update Series. 16 (4): 144–148. doi:10.1016/j.eursup.2017.01.002.
10. ^ Cheeti A, Chakraborty RK, Ramphul K (2020). "Reactive Arthritis (Reiter Syndrome)". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29763006. Retrieved 2020-07-31.
11. ^ Sharma P, Singal A (September 1999). "Methicillin-resistant Staphylococcus aureus non-gonococcal urethritis". Acta Dermato-Venereologica. 79 (5): 415. doi:10.1080/000155599750010599. PMID 10494743.
12. ^ Chowdhury MN, Pareek SS (February 1984). "Urethritis caused by group B streptococci: a case report". The British Journal of Venereal Diseases. 60 (1): 56–7. doi:10.1136/sti.60.1.56. PMC 1046272. PMID 6365237.
13. ^ a b c d e f g h Young A, Wray AA (2020). "Urethritis". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 30725967. Retrieved 2020-07-28.
14. ^ a b c "Non-gonococcal urethritis". nhs.uk. 2017-10-23. Retrieved 2020-08-02.
15. ^ a b c "Urethritis: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2020-07-30.
16. ^ "Non-Gonococcal Urethritis". www.idph.state.il.us. Retrieved 2020-08-02.
17. ^ "Urethritis in Women". Saint Luke's Health System. Retrieved 2020-07-30.
18. ^ Brill JR (April 2010). "Diagnosis and treatment of urethritis in men". American Family Physician. 81 (7): 873–8. PMID 20353145.
19. ^ "Clinical Prevention Guidance - 2015 STD Treatment Guidelines". www.cdc.gov. 2020-07-21. Retrieved 2020-07-31.
20. ^ Kolahi J, Abrishami M, Fazilati M, Soolari A (June 2010). "Chlorhexidine rinse for prevention of urethritis in men linked to oral sex". International Archives of Medicine. 3 (1): 9. doi:10.1186/1755-7682-3-9. PMC 2892434. PMID 20540731.
21. ^ a b "Gonococcal Infections - 2015 STD Treatment Guidelines". www.cdc.gov. 2019-03-15. Retrieved 2020-07-30.
22. ^ Grant PM, Hooton TM (2007). "Chapter 7. Persistent & Recurrent Urethritis". In Klausner JD, Hook EW (eds.). Current Diagnosis & Treatment of Sexually Transmitted Diseases. New York, NY: The McGraw-Hill Companies. Retrieved 2020-07-31.
23. ^ a b "WHO | Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016". WHO. Retrieved 2020-07-31.
## External links[edit]
Classification
D
* ICD-10: N34
* ICD-9-CM: 597 099.4
* MeSH: D014526
* DiseasesDB: 27902
External resources
* MedlinePlus: 000439
* eMedicine: med/2342
* v
* t
* e
Diseases of the urinary tract
Ureter
* Ureteritis
* Ureterocele
* Megaureter
Bladder
* Cystitis
* Interstitial cystitis
* Hunner's ulcer
* Trigonitis
* Hemorrhagic cystitis
* Neurogenic bladder dysfunction
* Bladder sphincter dyssynergia
* Vesicointestinal fistula
* Vesicoureteral reflux
Urethra
* Urethritis
* Non-gonococcal urethritis
* Urethral syndrome
* Urethral stricture
* Meatal stenosis
* Urethral caruncle
Any/all
* Obstructive uropathy
* Urinary tract infection
* Retroperitoneal fibrosis
* Urolithiasis
* Bladder stone
* Kidney stone
* Renal colic
* Malakoplakia
* Urinary incontinence
* Stress
* Urge
* Overflow
*[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
| Urethritis | c0311389 | 1,607 | wikipedia | https://en.wikipedia.org/wiki/Urethritis | 2021-01-18T18:31:51 | {"mesh": ["D014526"], "umls": ["C0311389", "C0041976"], "wikidata": ["Q1122485"]} |
Intradermal spindle cell lipoma is distinct in that it most commonly affects women, and has a wide distribution, occurring with relatively equal frequency on the head and neck, trunk, and upper and lower extremities.[1]:625[2]
## See also[edit]
* Spindle cell lipoma
* List of cutaneous conditions
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1838–9. ISBN 1-4160-2999-0.
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
| Intradermal spindle cell lipoma | None | 1,608 | wikipedia | https://en.wikipedia.org/wiki/Intradermal_spindle_cell_lipoma | 2021-01-18T18:48:54 | {"wikidata": ["Q16935264"]} |
A number sign (#) is used with this entry because evidence suggests that mutations in one or more genes can cause Gilles de la Tourette syndrome (GTS). See MOLECULAR GENETICS and MAPPING.
Description
Tourette syndrome is a neurobehavioral disorder manifest particularly by motor and vocal tics and associated with behavioral abnormalities. Tics are sudden, brief, intermittent, involuntary or semi-voluntary movements (motor tics) or sounds (phonic or vocal tics). They typically consist of simple, coordinated, repetitive movements, gestures, or utterances that mimic fragments of normal behavior. Motor tics may range from simple blinking, nose twitching, and head jerking to more complex throwing, hitting, or making rude gestures. Phonic tics include sniffling, throat clearing, blowing, coughing, echolalia, or coprolalia. Males are affected about 3 times more often than females, and onset usually occurs between 3 and 8 years of age. By age 18 years, more than half of affected individuals are free of tics, but they may persist into adulthood (review by Jankovic, 2001).
Clinical Features
Gilles de la Tourette (1885) first described this disorder as a nervous affliction characterized by motor incoordination accompanied by echolalia and coprolalia (see HISTORY).
Kurlan et al. (1986) reported on a large Mennonite kindred from Alberta with chronic motor tics and vocal tics inherited in a probable autosomal dominant pattern. Studies led them to conclude that 10 persons had definite and 15 probable Tourette syndrome, and that 3 had definite and 1 probable chronic motor tics. In this kindred, Kurlan et al. (1987) later found that 30% of 54 persons thought to be affected were unaware of tics noted by the examiners and only 18.5% of the affected members had sought medical care. From these findings, the authors concluded that most cases are mild and do not come to medical attention; therefore, the disorder may be more prevalent than is generally appreciated.
Although one of the most notorious symptoms of the Tourette syndrome, coprolalia is rather infrequent. Goldenberg et al. (1994) found only 8% of their 112 patients exhibited coprolalia.
Fabbrini et al. (2007) reported a large Italian family with Tourette syndrome. Fifteen individuals had tics or other behavioral abnormalities: 5 had definite GTS, 5 had chronic motor tics, 2 had nonspecific tic disorder, and 3 had obsessive-compulsive disorder without motor or phonic tics. The disorder spanned 5 generations and appeared to show autosomal dominant inheritance. The mean age at onset was 9.9 years. Motor tics involved mainly the head and neck, and included head turning, eye blinking, facial grimacing, and shoulder shrugging. One individual each had pathologic gambling (606349), panic disorder (167870), generalized anxiety disorder (607834), and major depression (MDD; 608516). No patients had coprolalia. The findings confirmed Tourette syndrome as a neuropsychiatric disorder with a strong genetic background.
Ercan-Sencicek et al. (2010) reported a 2-generation family in which a father and all 8 of his children had Tourette syndrome. The father and 3 of the children also had OCD; 1 of the children with OCD also had Asperger (see 209850) and trichotillomania (TTM; 613229). The features of Tourette syndrome included eye rolling and blinking, throat clearing, limb moving, snorting, humming, swearing, jaw tightening or jutting, and shoulder shrugging, to name a few. Most family members also had evidence of a possible connective tissue disorder, with hypermobile joints and pectus excavatum, but only 1 individual was diagnosed with a variant of Ehlers-Danlos syndrome (130000). The mother, who did not have Tourette syndrome, had a history of Chiari malformation type I (118420) with tethered spinal cord, which was present in 5 of the affected children. In addition to 8 living children, the mother had had 7 miscarriages.
Other Features
In a series of 114 patients with Tourette syndrome, Van Woert et al. (1977) found that 43% had self-mutilating behavior.
In a family study of 86 probands, Pauls et al. (1988) found an increased frequency of Tourette syndrome, chronic tics, and obsessive-compulsive disorder (OCD; 164230) among first-degree relatives, but did not find an increased frequency of attention deficit disorder, conduct disorder, major depressive disorder, manic-depressive disorder, panic disorder, phobic disorders, schizoid disorders, sleep disorders, specific reading disability, or stuttering, as had been suggested by Comings and Comings (1987). Comings and Comings (1988) gave a lengthy rebuttal.
In a controversial presidential address to the American Society of Human Genetics, Comings (1989) extended the phenotypic range of expression of the GTS gene to include male type II alcoholism and the female type of familial obesity. He suggested that 'the primary problem is an appetitive compulsion that takes the form of alcoholism in men and of overeating in women.'
In a full report of their study of 338 biologic relatives of 86 GTS probands, 21 biologically unrelated relatives of adopted GTS probands, and 22 relatives of normal subjects, Pauls et al. (1991) found that the rates of GTS, chronic tics, and OCD in the total sample of biologic relatives of GTS probands were significantly greater than in the relatives of controls. In addition, the morbid risks of GTS, OCD, and chronic tics were not significantly different in families of probands with OCD when compared to relatives of probands without OCD. These findings were presented as further evidence that OCD is etiologically related to GTS.
Sverd (1991) and Comings and Comings (1991) reported families in which autism (see 209850) or pervasive developmental disorder (PDD) and Tourette syndrome coexisted, sometimes in the same individual. Comings and Comings (1991) described a PDD-to-GTS transition.
In reviews of Tourette syndrome, Jankovic (2001) and O'Rourke et al. (2009) stated that GTS is highly associated with attention deficit-hyperactivity disorder (ADHD; 143465) and OCD. Other behavioral problems can include poor impulse and anger control.
Biochemical Features
Because self-mutilation is so conspicuous a feature of the Lesch-Nyhan syndrome (see 308000), attention was directed to purine metabolism in GTS. The activity of HGPRT and APRT of red cell lysates was normal, but red cell HGPRT was less stable than normal, and abnormal enzyme peaks were detected after isoelectric focusing (Van Woert et al., 1977).
Comings (1990) found significant decreases in the serotonin/platelet ratio and in blood tryptophan level in unmedicated patients with GTS. A comparable significant decrease was found in parents of GTS patients, and there was no difference between parents with and those without symptoms. From these findings, Comings (1990) suggested tryptophan oxygenase (TDO2; 191070) as a possible candidate gene.
Pathogenesis
Comings (1987) suggested that the spectrum of behavior in Tourette syndrome can be explained on the basis of a gene causing an imbalance of the mesencephalic-mesolimbic dopamine pathways, resulting in disinhibition of the limbic system. Comings (1987) pointed out that the limbic system has been characterized as controlling the 4 F's--fight, flight, feeding, and sexual activity. He concluded: 'It has not escaped my attention that the reason many of the disorders described in the present series of papers (Comings and Comings, 1987) are so common is that they are (1) genetic, (2) dominant, and (3) result in disinhibition, especially of sexual activity.' Pauls et al. (1988) criticized the methods and conclusions of the studies of Comings and Comings (1987).
Involvement of dopaminergic systems in the basal ganglia have long been suspected to be of etiologic importance in this disorder because of the efficacy of dopamine D2 receptor antagonists in ameliorating some symptoms and the exacerbation of symptoms by dopamimetic agents. Singer et al. (1991) provided additional evidence for involvement of the basal ganglia by demonstrating a significant difference in measures of symmetry in the putamen and lenticular nucleus between Tourette patients and normal controls.
Wolf et al. (1996) reported increased binding of iodobenzamide to D2 receptors (see, e.g., DRD1; 126449) in the caudate nucleus but not the putamen in all 5 identical twins who were more affected than their similarly diagnosed twin sibs. Additional studies demonstrated no difference in regional cerebral blood flow. Wolf et al. (1996) discounted confounding by treatment with neuroleptic drugs because they had kept their study subjects free of neuroleptics for an extended period of time before the study by single photon emission computed tomography (SPECT). However, no information was provided on possible earlier discrepancies in medication history between severely and less severely affected twins.
Tobe et al. (2010) observed an association between abnormal cerebellar morphology and Tourette syndrome. Using high-resolution MRI in 163 patients with GTS and 147 controls, Tobe et al. (2010) found that GTS patients had volume reduction of the lateral cerebellar hemispheres compared to controls. The affected regions were localized to the gray matter portions of crus I and lobules VI, VIIB, and VIIIA. In both cases and controls, these volumes showed a significantly progressive decline with age in males, but not in females. Volume contraction in these cerebellar regions was associated with more severe tic symptoms and motoric disinhibition. Comorbid OCD was associated with relative enlargement of these regions in proportion to increasing severity of OCD symptoms. There was no apparent effect for comorbid ADHD.
Inheritance
The familial nature of this syndrome was noted by de la Tourette (1885) when he observed that mild cases occurred in the families of patients with the classic clinical picture. Eisenberg et al. (1959) confirmed the familial aggregation.
Parent-offspring involvement is known (Sanders, 1973; Friel, 1973). In 2 of 6 patients studied by Johnson et al. (1977), other members of the family (a father and a maternal uncle) were also affected.
Golden (1978) supported dominant inheritance. In a study of the families of 40 cases, he found 12 with 17 additional cases: 3 fathers, 4 mothers, 4 sibs, and 6 other relatives. An overrepresentation of persons of Ashkenazi or Mediterranean origin was noted.
Wilson et al. (1978) questioned the existence of any significant genetic component.
Nee et al. (1980) evaluated 50 cases. In 16 patients there was a family history of Gilles de la Tourette syndrome and in another 16 a family history of tics. No preponderance of Jewish background was encountered. Obsessive-compulsive behavior was displayed by 34 patients.
Comings et al. (1984) analyzed the families of 250 consecutive, unselected patients with Tourette syndrome and evaluated the inheritance of the combined tic-Tourette trait. They concluded that the most likely mode of inheritance is a major semidominant gene, Ts, with low heritability of multifactorial background variation. They rejected a pure recessive major gene effect and rejected the hypothesis of no major gene effect for any estimate of lifetime risk less than 1.2%. They estimated the frequency of the semidominant autosomal allele to be 0.4 to 0.9%. Assuming a frequency of 0.5%, penetrance of about 94% was estimated for Ts/Ts homozygotes, 50% for Ts/ts heterozygotes, and less than 0.3% for ts/ts homozygotes. More than 2 of every 3 cases are heterozygotes and most other cases are phenocopies or new mutations. Devor (1984) arrived at a similar conclusion by analyzing 35 published pedigrees.
Comings and Comings (1985) presented the findings in a series of 250 consecutive patients seen in a 3-year period. The sex ratio was 4 males to 1 female. Again the disorder was not more frequent in Jews (10% of the cases).
Pauls and Leckman (1986) concluded that obsessive-compulsive disorder is etiologically related to Tourette syndrome and chronic tics and that the Tourette syndrome is inherited as a highly penetrant, sex-influenced, autosomal dominant. They based these conclusions on segregation analyses in 30 nuclear families identified through 27 index cases. In the analyses of subjects with Tourette syndrome, chronic tics, or obsessive-compulsive disorder, the estimates of penetrance for the genotypes AA, Aa, and aa (A denoting the abnormal allele) were 1.000, 1.000, and 0.002, respectively, for males and 0.709, 0.709, and 0.000 for females. They estimated that approximately 10% of all patients are phenocopies.
Zausmer and Dewey (1987) found 46 persons who were 'tiqueurs' among the first- and second-degree relatives of 91 proband child tiqueurs.
On the basis of detailed pedigree data on more than 1,200 GTS families, Comings et al. (1989) concluded that the inheritance is 'semidominant, semirecessive.'
Kurlan et al. (1994) assessed the frequency of bilineal (i.e., from both maternal and paternal sides) transmission of GTS in 39 families in which 5 or more relatives were reported to be affected and 39 consecutively ascertained probands referred for evaluation of the disorder. In the first group of pedigrees, bilineal transmission was evident in 33% (considering tics) and 41% (considering tics or obsessive-compulsive behavior) of families. For the consecutive pedigrees, bilineal transmission was seen in 15% (tics) and 26% (tics or obsessive-compulsive behavior) of families. Both parents of the proband were affected in 38% of the first group of pedigrees and 10% of the consecutive pedigrees. In the first group of pedigrees, the frequency of bilineal transmission appeared to be related to the severity of the disorder in the proband; for both pedigree groups, the frequency of both parents' being affected was higher in families in which the proband's symptoms were severe. Kurlan et al. (1994) concluded that bilineal transmission and homozygosity are common in Tourette syndrome and may play a role in severity of illness as well as account for difficulties in localizing the gene defect by linkage analysis.
In a single large pedigree containing 182 members, Hasstedt et al. (1995) tested for major locus inheritance using segregation analysis incorporating assortative mating. The analysis provided evidence of a major locus with an intermediate inheritance pattern for which the penetrance was estimated from the data as 28% in heterozygotes and 98 to 99% in homozygotes. A significant assortative mating correlation was estimated from the data as 70 to 79%. In contrast, when assortative mating was not included in the model, intermediate inheritance was not inferred. If, in addition, constancy of the allele frequencies across generations was not assumed, mendelian transmission was rejected. When each subject, affected or unaffected, was assigned a score reflecting the presence and severity of symptoms, higher mean scores in affected homozygotes than in affected heterozygotes suggested greater severity in homozygotes. (Genotype information was obtained from genotype probabilities computed assuming intermediate inheritance.)
Walkup et al. (1996) performed complex segregation analysis on the data obtained from 53 independently ascertained children and adolescents with GTS and their 154 first-degree relatives. The results suggested that the susceptibility to GTS is conveyed by a major locus in combination with a multifactorial background. Other models of inheritance were definitely rejected, including strictly polygenic models, all single major locus models, and mixed models with dominant and recessive major loci. The frequency of the GTS susceptibility allele was estimated to be 0.01. The major locus accounted for over half of the phenotypic variance for GTS, whereas a multifactorial background accounted for approximately 40% of phenotypic variance. Penetrance estimates suggested that all individuals homozygous for the susceptibility allele at the major locus are affected, whereas only 2.2% of males and 0.3% of females heterozygous at the major locus are affected. Of individuals affected with GTS, approximately 62% are heterozygous and approximately 38% are homozygous at the major locus. Walkup et al. (1996) noted that while none of the families had 2 parents affected with GTS, 19% of families had 2 parents affected with the broader GTS phenotype, which includes GTS, chronic tic disorder, or obsessive-compulsive disorder.
Patel (1996) reviewed the 'quest for the elusive genetic basis of Tourette syndrome.'
In a review of Tourette syndrome, Jankovic (2001) cited twin studies showing an 89 to 94% concordance for the disorder. One study involving 16 pairs of monozygotic twins showed that low birth weight was a strong predictor of more severe tics (Hyde et al., 1992). Transmission from both parents was found in 25 to 41% of families with Tourette syndrome (Hanna et al., 1999; Lichter et al., 1999).
Population Genetics
Kurlan et al. (1987) cited a prevalence of 28.7 per 100,000 in school children of Monroe County in New York. Kurlan (1994) estimated that 'developmental Tourette syndrome' occurred in at least 3% of all children and that up to 25% of children requiring special education may have mild to moderate Tourette syndrome. He proposed that these were the milder forms of the clinical spectrum that, at the extreme end, included the smallest group, patients with 'full-blown' Tourette syndrome.
Comings (1987) suggested that GTS is one of the most common genetic disorders affecting man, with a frequency of about 1 in 100, and that the complete range of behavioral problems is much broader than merely motor and vocal tics.
Mapping
### Linkage to Chromosome 2p
The Tourette Syndrome Association International Consortium for Genetics (2007) reported the results of the largest genetic linkage study that had been undertaken for Tourette syndrome. The sample analyzed included 238 nuclear families yielding 304 'independent' sib pairs and 18 separate multigenerational families, for a total of 2,040 individuals. A whole genome screen using 390 microsatellite markers was completed. Analyses were completed using 2 diagnostic classifications: (1) only individuals with TS were included as affected, and (2) individuals with either TS or chronic tic (CT) disorder were included as affected. Strong evidence of linkage was observed for a region on chromosome 2p (p = 3.8 x 10(-5)). Results from several of the regions also provided moderate evidence of additional susceptibility loci for TS. No support was provided in this study for SLITRK1 (609678) on chromosome 13 as a susceptibility gene for TS.
### Linkage to Chromosome 3
Brett et al. (1990) suggested possible linkage to markers located in the region 3p21-p14. Evidence of linkage was found to both THRB (190160) and RAF1 (164760), as well as to an anonymous marker, D3S11; a total maximum lod score of 2.998 was reported.
### Linkage to Chromosome 4q
The Tourette Syndrome Association International Consortium for Genetics (1999) reported the results of a systematic genome screen of Tourette syndrome, using 76 families with a total of 110 sib pairs. While no results reached acceptable statistical significance, the multipoint maximum-likelihood scores (MLSs) for 2 regions, 4q and 8p, were suggested (MLS more than 2.0). Four additional genomic regions also gave multipoint MLSs between 1.0 and 2.0. Zhang et al. (2002) found linkage of hoarding, a Tourette syndrome subphenotype, to 4q34-q35 (p = 0.0007); the 4q site is in proximity to D4S1625.
### Linkage to Chromosome 5
Zhang et al. (2002) found linkage of hoarding, a Tourette syndrome subphenotype, to 5q35.2-q35.3 (P = 0.000002).
### Linkage to Chromosome 6p21
Riviere et al. (2009) genotyped 14 SNPs spanning 3 genomic loci (chromosomes 2p, 6p, and 15q) that had been found to be associated with restless legs syndrome (see RLS6; 611185), which shares some common movement features and perhaps involvement of the frontostriatal circuits. In a case-control study of 322 French Canadian patients with GTS and and 290 controls, Riviere et al. (2009) found an association between GTS and SNPs in intron 7 of the BTBD9 gene (611237) on chromosome 6p21. The major T risk allele of rs9357271 showed the most significant association with GTS (p = 0.005). Phenotypic stratification of the patients showed that the BTBD9 variants were most strongly associated with GTS without obsessive-compulsive disorder (OCD; 164230), and that allelic frequency of rs9357271 inversely correlated with severity of OCD. The findings did not reach significance in a family study of 298 French Canadian family trios with GTS, which included the patients in the case-control study.
### Linkage to Chromosome 7
Because of cytogenetic studies implicating the 7q31 region in isolated cases of Tourette syndrome (Boghosian-Sell et al., 1996; Petek et al., 2001), Diaz-Anzaldua et al. (2004) undertook a family-based association study in a sample of French Canadian patients from Quebec using markers from that region. In the transmission disequilibrium test, they showed a biased transmission of alleles from heterozygote parents to their GTS offspring. When the analysis was restricted to patients without attention deficit hyperactivity disorder (ADHD; 143465) or OCD comorbidity, similar results were observed. A marker contained in the IMMP2L gene, which maps to the same region of 7q, also showed a tendency for association.
### Linkage to Chromosome 11
To detect the underlying susceptibility gene(s) for GTS, Merette et al. (2000) performed linkage analysis in a large French Canadian family from the Charlevoix region of Quebec, in which 20 family members were definitely affected by GTS and 20 others showed related tic disorders. Using model-based linkage analysis, they observed a lod score of 3.24 at chromosome 11q23. This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with GTS had been detected in an Afrikaner population by Simonic et al. (1998).
To replicate reports of association and linkage between Tourette syndrome and markers at 11q24, Diaz-Anzaldua et al. (2005) undertook a family-based association study in 199 French Canadian TS nuclear families. The transmission disequilibrium test (TDT) analysis failed to detect an association between TS and 6 markers from 11q24. No haplotype combining alleles from the region was associated with the disorder. Linkage disequilibrium analysis showed evidence of historical recombination between every contiguous pair of markers, indicating that these genetic variants are probably in equilibrium in the French Canadian population.
### Locus on Chromosome 13
See 'Variation in the SLITRK2 Gene' in Molecular Genetics Section.
### Locus on Chromosome 15
See 'Mutation in the HDC Gene' in Molecular Genetics Section.
### Linkage to Chromosome 17q25
Zhang et al. (2002) performed a genome scan of the hoarding phenotype (a component of OCD) on 77 sib pairs collected by the Tourette Syndrome Association International Consortium for Genetics. All sib pairs were concordant for a diagnosis of Gilles de la Tourette syndrome. Analyses reported by Zhang et al. (2002) were conducted for hoarding as both a dichotomous trait and a quantitative trait. Not all sib pairs in the sample were concordant for hoarding. Significant allele sharing was observed for both the dichotomous and the quantitative hoarding phenotypes for markers at 4q34-q35 (P = 0.0007), by use of GENEHUNTER, and at 5q35.2-q35.3 (P = 0.000002) and at 17q25 (P = 0.00002), by use of the Haseman-Elston method.
Because of the interest in a relationship between GTS and 17q25 raised by the study of Zhang et al. (2002) and others, Paschou et al. (2004) focused linkage studies on this area. An initial scan of chromosome 17 performed on 2 large pedigrees provided a nonparametric lod score of 2.41 near marker D17S928. Fine mapping with 17 additional microsatellite markers increased the peak to 2.61 (p = 0.002). The original families, as well as 2 additional pedigrees, were genotyped for 25 SNPs, with a focus on 3 genes in the 17q25 region which, based on their function and expression profile, could play a role in the development of GTS: NPTX1 (602367), IRSP53 (605475), and TBCD (604649). The background linkage disequilibrium (LD) of the region was studied in 8 populations of European origin. A complicated pattern was revealed, with the pairwise tests producing unexpectedly high LD values at the telomeric TBCD gene. Paschou et al. (2004) concluded that 17q25 was worthy of further investigation as a candidate susceptibility region for GTS.
### Genomewide Association Studies
Barr et al. (1999) tested for linkage to Tourette syndrome in multigenerational families segregating for this condition using a panel of 386 markers with the largest interval between any 2 markers being 28 cM and an average distance between markers of 10 cM. No significant evidence for linkage was found with parametric analysis. For the nonparametric analysis, 8 markers were observed with a p value less than 0.00005 for significant evidence of linkage in at least 1 family. Barr et al. (1999) urged caution, however, in the interpretation of the nonparametric analyses, as this statistic (the affected-pedigree-member method) is known to have a high false-positive rate.
### Exclusion Studies
On the basis of family linkage studies using DNA markers, Heutink et al. (1990) excluded all of chromosome 18 as well as the q21.3-qter region of chromosome 7 as the site for the GTS gene. By linkage studies, Pakstis et al. (1991) excluded more than 50% of the autosomal genome as the site of the Tourette syndrome (assuming that genetic heterogeneity is not an important factor).
The difficulties involved in linkage studies of GTS were reviewed by van de Wetering and Heutink (1993). They stated that an autosomal dominant pattern of inheritance with incomplete penetrance and variable expression was the most widely accepted model. Assuming that there is a single genetic vulnerability factor identical in all families, about 80% of the genome could be excluded as the site for the GTS gene by studies with over 600 DNA markers in an international collaborative effort.
Orth et al. (2007) reported a 3-generation family segregating both myoclonus dystonia (159900) and Gilles de la Tourette syndrome. There were 11 affected individuals: 3 had myoclonus dystonia, 2 had dystonia, 1 had GTS, 1 had tics, and 4 had various combinations of these with obsessive compulsive disorder. The phenotype of those with myoclonus dystonia was similar to that described for most families, with predominantly head, neck and arm myoclonus, mild cervical dystonia, and writer's cramp. Linkage analysis excluded association to the SGCE (604149), DYT15 (607488), DYT1 (128100), or DRD2 (126450) loci, and no pathogenic changes were identified in the SLITRK1 gene. Orth et al. (2007) suggested that there may be a novel susceptibility gene for both myoclonus dystonia and Tourette syndrome.
Cytogenetics
In linkage studies of 25 families, Comings et al. (1986) found no linkage but observed a family in which 6 members with various manifestations of Tourette syndrome carried a balanced translocation, t(7;18)(q22;q22.1). Linkage to COL1A2 (120160) on 7q22 was excluded, suggesting that the mutation is on chromosome 18. They noted with interest the assignment of the gene for gastrin-releasing peptide (bombesin; 137260) and pointed to this as a candidate for the site of the mutation in Tourette syndrome. They stated that injection of bombesin 'into the brains of mice reproduce many of the symptoms of Tourette syndrome.' Donnai (1987) presented further evidence for the location of the Tourette gene at 18q22.1; deletion at this site was found in a 23-year-old woman who 'had the behavioral characteristics described in members of Tourette families.' In the individual with the translocation between chromosomes 7 and 18 with Tourette syndrome reported by Comings et al. (1986), Boghosian-Sell et al. (1996) undertook physical mapping of the breakpoints on chromosomes 7 and 18 for identification of specific genes that might be involved in the Tourette syndrome phenotype. Using somatic cell hybrids retaining either the small der(7) or the der(18) chromosome, a more precise localization of the breakpoints was determined. Furthermore, physical mapping identified 2 YAC clones that span the translocation breakpoint on chromosome 18 as determined by fluorescence in situ hybridization.
Taylor et al. (1991) observed a de novo case of GTS in a boy who had deletion of the terminal portion of the short arm of chromosome 9, del(9)(qter-p2304:). The patient demonstrated only mild features of the 9p deletion syndrome, yet manifested all the features of GTS.
Petek et al. (2001) and Kroisel et al. (2001) identified a 13-year-old male with GTS and other anomalies who carried a de novo duplication of the long arm of chromosome 7 [46,XY,dup(7)(q22.1-q31.1)]. Further molecular analysis demonstrated that the duplication was inverted. The distal chromosomal breakpoint occurred between 2 genetic markers, D7S515 and D7S522, that define a region previously shown to be disrupted in a case of GTS (Boghosian-Sell et al., 1996). Additional anomalies in the patient reported by Petek et al. (2001) included reduced speech development, depression, strabismus convergens, a malformed left ear, stenosis of the meatus acusticus, slight microgenia, and gynecomastia. By further study, Petek et al. (2001) found that a novel gene, inner mitochondrial membrane peptidase-2-like (IMMP2L; 605977), was disrupted by both the breakpoint in the duplicated fragment and the insertion site in 7q31.
In a review of all published cases of chromosomal translocations or inversions identified in patients with GTS, State et al. (2003) found that 3 segments of the genome had been reported to be rearranged in more than 1 unrelated individual: chromosomes 18q (Donnai, 1987; Boghosian-Sell et al., 1996), 7q (Petek et al., 2001), and 8q (Matsumoto et al., 2000).
State et al. (2003) reported a 12-year-old boy of Korean descent with chronic tics and OCD who was found to carry a paracentric inversion involving 18q22. They mapped the telomeric end of the inversion to a genomic location within 1 Mb of a previously described translocation that cosegregated in a family with a range of clinical phenomena encompassing GTS, chronic tics, and OCD (Boghosian-Sell et al., 1996). A detailed characterization of the rearrangement breakpoint revealed a relatively gene-poor region with 2 nearby transcripts, neither of which was structurally altered by the chromosomal abnormality. Many reports confirmed that balanced chromosomal abnormalities many hundreds of kilobases from disease-related genes may lead to the expected disease phenotypes (Kleinjan and van Heyningen, 1998). To explore the possibility that long-range position effects might be playing a role in their patient, State et al. (2003) undertook experiments assessing replication synchrony versus asynchrony in the patient and controls to evaluate this hypothesis and characterize the epigenetic phenomena in this genomic interval. They found a significant increase in replication asynchrony in the patient compared to controls, with the inverted chromosome showing delayed replication timing across an interval of at least 500 kb. The findings were consistent with long-range functional dysregulation of 1 or more genes in the region. The data supported a link between chromosomal aberrations and epigenetic mechanisms in GTS and suggested that the study of the functional consequences of balanced chromosomal rearrangements is warranted in patients with phenotypes of interest, irrespective of the findings regarding structurally disrupted transcripts.
Crawford et al. (2003) described 2 unrelated families wherein balanced t(6;8) chromosomal translocations occurred in individuals diagnosed with Tourette syndrome. In 1 of these families, the transmission of the translocation was associated with learning and behavioral difficulties. In the other family, 1 parent was unaffected and the other could not be traced; thus, transmission could not be demonstrated and it is possible the translocation may have occurred de novo. The breakpoint on chromosome 8 occurred within the q13 band in both families, suggesting that a gene or genes in this region may contribute to the Tourette syndrome phenotype. Linkage studies had previously suggested involvement of 8q and previously balanced translocations t(3;8) and t(1;8) had been reported by Brett et al. (1996) and Devor and Magee (1999), respectively. In their case, Crawford et al. (2003) identified a 200-kb BAC, which, by FISH, they demonstrated encompasses the chromosome 8 breakpoint in both families. They suggested that the fact that the chromosomal breaks in the TS cases from both families occur within such a small region of chromosome 8 supports the hypothesis that disruption of a specific gene or genes on 8q contributes to the clinical phenotype.
Verkerk et al. (2003) reported a family in which the father had OCD and both of his children, a girl and a boy, had GTS, OCD, mental retardation, speech abnormalities, and growth retardation. All 3 individuals had a complex chromosomal insertion/translocation involving chromosomes 2 and 7. The father had inv(2)(p23q22),ins(7;2)(q35-q36;p21p23) and the 2 affected children inherited the abnormal chromosome 7, sharing the 2p21-p23 insertion on 7q35-q36. Both children had a normal chromosome 2; thus both children had 3 copies of this region on chromosome 2. Fine mapping of the involved regions using FISH and BAC clones showed that the insertion interrupted the contactin-associated protein-2 gene (CNTNAP2; 604569), which encodes a membrane protein located in axons at the nodes of Ranvier. Verkerk et al. (2003) hypothesized that disruption or decreased expression of CNTNAP2 could lead to a disturbed distribution of potassium channels in the nervous system, thereby influencing conduction and/or repolarization of action potentials, causing unwanted actions or movements in GTS.
Belloso et al. (2007) reported a familial balanced reciprocal translocation t(7;15)(q35;q26.1) in phenotypically normal individuals, in which the 7q35 breakpoint disrupted the CNTNAP2 gene (604569). The authors concluded that truncation of CNTNAP2 does not necessarily result in the Gilles de la Tourette syndrome.
Diagnosis
The diagnostic criteria for Tourette syndrome recommended by the American Psychiatric Association include both multiple motor and vocal tics over a period of more than 1 year, voluntary suppression of symptoms, a waxing and waning course, and onset between ages 2 and 15 years. An organic basis is supported by the finding of neuropsychologic dysfunction in many patients and the frequent therapeutic response to haloperidol.
Clinical Management
The self-mutilation and biochemical findings prompted trial of L-5-hydroxytryptophan, the precursor of serotonin, reported to relieve self-mutilation in the Lesch-Nyhan syndrome. Van Woert et al. (1977) described a 15-year-old boy who improved with this medication and who returned to aggressive behavior, tics, biting and facial punching when given a placebo.
Molecular Genetics
### Mutation in the HDC Gene
By genomewide linkage analysis followed by candidate gene sequencing in a large 2-generation family with Gilles de la Tourette syndrome, Ercan-Sencicek et al. (2010) identified a heterozygous nonsense mutation in the HDC gene (W317X; 142704.0001) in all 9 affected individuals. In vitro studies indicated that the mutation exerted a dominant-negative effect on the protein, resulting in lack of enzyme activity. Ercan-Sencicek et al. (2010) noted that animal studies had shown that lack of Hdc in mice results in increased locomotor and stereotypic behaviors, as well as increased anxiety. Overall, the findings suggested a role for histaminergic neurotransmission in neurobehavioral actions, such as tics.
### Variation in the SLITRK1 Gene
Abelson et al. (2005) studied SLITRK1 as a candidate gene for GTS on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with the syndrome and no family history. Although they found no mutation in the child, they identified 2 different mutations in the SLITRK1 gene among 174 unrelated probands with GTS. The proband in 1 family, who had GTS and ADHD, had a single-base deletion in the coding region, leading to a frameshift mutation (609678.0001). The mutation was also found in the patient's mother, who had trichotillomania (613229). In 2 other probands, who had GTS and symptoms of OCD, they identified a single-base change (designated var321) in the 3-prime UTR of the gene (609678.0002). The base change corresponds to a highly conserved nucleotide within the predicted binding site for a microRNA, hsa-miR-189. The var321 mutations occurred on different haplotypes in the patients, indicating that they arose independently. Abelson et al. (2005) demonstrated that SLITRK1 mRNA and hsa-miR-189 have an overlapping expression pattern in brain regions previously implicated in Tourette syndrome. Wildtype SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Abelson et al. (2005) concluded that their findings support the association of rare SLITRK1 sequence variants with Tourette syndrome.
There is controversial evidence about whether or not variation in the SLITRK1 gene plays a role in Tourette syndrome. Deng et al. (2006) and Chou et al. (2007) did not find the var321 change or any other potentially pathogenic changes in the SLITRK1 gene in 82 Caucasian and 160 Taiwanese patients with GTS, respectively. Fabbrini et al. (2007) also excluded the SLITRK1 as a basis for Tourette syndrome in a large Italian family. Although Fabbrini et al. (2007) did identify the var321 change in a few family members and 1 spouse, it did not segregate with the disorder. In addition, a genomewide linkage study by the Tourette Syndrome Association International Consortium for Genetics (2007) showed no support for a locus on chromosome 13 in Tourette syndrome.
### Exome Sequencing Studies
By whole-exome sequencing of a 3-generation family in which 7 individuals had Tourette syndrome/chronic tic disorder, Sundaram et al. (2011) identified 4 novel nonsynonymous variants that segregated perfectly with the phenotype in all 7 affected family members. These variants included a pro45-to-ser (P45S) substitution in the PVRL3 gene (607147); a ser75-to-asn (S75N) substitution in the MRPL3 gene (607118); an ala2057-to-ser (A2057S) substitution in the DNAJC13 gene (614334); and an arg129-to-gly (R129G) substitution in the OFCC1 gene (614287). Three of the variants (in the MRPL3, DNAJC13, and OFCC1 genes) could be validated by Sanger sequencing; the PVRL3 variant could not be reliably verified. None of the variants were present in 100 controls or in the 1000 Genomes project. Comorbid disorders in affected individuals included obsessive-compulsive disorder (OCD; 164230) and attention deficit-hyperactivity disorder (ADHD; 143465). Subsequent analysis of 94 patients with GTS/chronic tics found that 2 carried a variant in the 5-prime untranslated region of the OFCC1 gene. Functional studies were not performed, and Sundaram et al. (2011) could not provide any insight into a potential disease mechanism based on the known functions of these genes. However, the authors postulated that the disorder may be caused by multiple rare variants in different genes.
History
Critchley (1986) gave a charming interpretation of the name of this disorder and of naming in general.
Pearce (1993) suggested that the well-known tics, mannerisms, postures, and verbal repetitions displayed by Samuel Johnson (1709-1784), the great scholar-lexicographer, were indications that he was a victim of Gilles de la Tourette syndrome.
Much of Gilles de la Tourette's description of the disorder that bears his name, the classic typology, was based on 'the case of the cursing marquise' (Itard, 1825). According to Kushner (1995), Gilles de la Tourette never examined or even met her. Moreover, Kushner (1995) insisted that, contrary to all the indications in the literature thereafter, Charcot (see Charcot, 1987) never diagnosed, treated, or even talked with the marquise. The Marquise de Dampierre was 26 years old when Itard (1825) reported her case; Georges Gilles de la Tourette was a 28-year-old neurologist at l'Hopital de la Salpetriere when he selected the marquise's life history as the first and prototypic example of the syndrome he set out to describe in an article published in 1885. Tourette's mentor, Jean-Martin Charcot, the director of l'Hopital de la Salpetriere and the foremost neurologist of late 19th century France, almost immediately renamed convulsive tic syndrome in honor of Gilles de la Tourette. By constructing a nosology that clearly distinguished convulsive motor and vocal tics from Sydenham's and other choreas, Gilles de la Tourette had provided another disorder for Charcot's journal project of classifying groups of neurologic symptoms into syndromes. Kushner (1995) observed that 'lecturers, as most of us know from personal experience, often repeat the same story slightly differently over time, and Charcot's explication of his encounter with the Marquise de Dampierre was no exception. What is unambiguous in four of these [his] lectures, however, is the fact that Charcot never had any direct contact with the marquise, let alone any contact with her as her physician.' (It is noteworthy that in 1881, Gilles de la Tourette published a translation of the 1880 article on 'jumping Frenchman of Maine' (244100) by American neurologist George Beard (1878).)
Animal Model
Castellan Baldan et al. (2014) found that heterozygous Hdc-null (+/-) and homozygous Hdc-null (-/-) mice showed increased motor stereotypic behavior after amphetamine administration compared to wildtype. The stereotypy was more marked in homozygous mice compared to heterozygous mice. Haloperidol pretreament and intracerebroventricular infusion of histamine mitigated the stereotypies in both genotypes. Mutant mice had increased levels of striatal dopamine, which could be reduced by histamine infusion. Hdc+/- and Hdc-/- mice showed significant deficits in prepulse inhibition compared to wildtype, which recapitulated the human phenotype of Tourette syndrome. The results suggested that histamine regulates dopamine levels in the basal ganglia, that deficiency of histamine resulting from Hdc mutations causes dysregulation of the corticobasal ganglia circuits, and that this disruption may underlie Tourette syndrome.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Sleep disturbance \- Echolalia \- Coprolalia \- Self mutilation \- Aggressive behavior \- Obsessive-compulsive behavior \- Attention deficit hyperactivity disorder (ADHD) \- Motor and vocal tics MISCELLANEOUS \- Male:Female ratio 4:1 \- Onset ages 2 to 14 years ▲ 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
| GILLES DE LA TOURETTE SYNDROME | c0040517 | 1,609 | omim | https://www.omim.org/entry/137580 | 2019-09-22T16:40:44 | {"doid": ["11119"], "mesh": ["D005879"], "omim": ["137580"], "icd-9": ["307.23"], "icd-10": ["F95.2"], "synonyms": ["Alternative titles", "TOURETTE SYNDROME", "TOURETTE DISORDER"]} |
Achondroplasia is a disorder of bone growth that prevents the changing of cartilage (particularly in the long bones of the arms and legs) to bone. It is characterized by dwarfism, limited range of motion at the elbows, large head size (macrocephaly), small fingers, and normal intelligence. Achondroplasia can cause health complications such as interruption of breathing (apnea), obesity, recurrent ear infections, an exaggerated inward curve of the lumbar spine (lordosis). More serious problems include a narrowing of the spinal canal that can pinch (compress) the upper part of the spinal cord (spinal stenosis) and a buildup of fluid in the brain (hydrocephalus). Some people with achondroplasia may have delayed motor development early on, but cognition is normal. Achondroplasia is caused by mutations in the FGFR3 gene. Inheritance is autosomal dominant. Treatment may include medication with growth hormone, and surgery aimed to correct the spine, or bone problems, as well, as to reduce the pressure inside the brain in cases of hydrocephaly. Prognosis with achondroplasia is good except in cases of spinal compression at the neck.
*[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
| Achondroplasia | c0001080 | 1,610 | gard | https://rarediseases.info.nih.gov/diseases/8173/achondroplasia | 2021-01-18T18:02:22 | {"mesh": ["D000130"], "omim": ["100800"], "orphanet": ["15"], "synonyms": ["ACH", "Achondroplastic dwarfism"]} |
Alcelaphine gammaherpesvirus 1 (AlHV-1), Ovine gammaherpesvirus 2 (OHV-2)
Virus classification
(unranked): Virus
Realm: Duplodnaviria
Kingdom: Heunggongvirae
Phylum: Peploviricota
Class: Herviviricetes
Order: Herpesvirales
Family: Herpesviridae
Genus: Macavirus
Species:
Alcelaphine gammaherpesvirus 1 (AlHV-1), Ovine gammaherpesvirus 2 (OHV-2)
Eye Ring
Bovine malignant catarrhal fever (BMCF) is a fatal lymphoproliferative disease[1] caused by a group of ruminant gamma herpes viruses including Alcelaphine gammaherpesvirus 1 (AlHV-1)[2] and Ovine gammaherpesvirus 2 (OvHV-2)[1][3] These viruses cause unapparent infection in their reservoir hosts (sheep with OvHV-2 and wildebeest with AlHV-1), but are usually fatal in cattle and other ungulates such as deer, antelope, and buffalo.[2] In Southern Africa the disease is known as snotsiekte, from the Afrikaans.[4][5]
BMCF is an important disease where reservoir and susceptible animals mix. There is a particular problem with Bali cattle in Indonesia,[6] bison in the US[7] and in pastoralist herds in Eastern and Southern Africa.[8][9]
Disease outbreaks in cattle are usually sporadic although infection of up to 40% of a herd has been reported. The reasons for this are unknown. Some species appear to be particularly susceptible, for example Pére David's deer,[10] Bali cattle[6] and bison,[7] with many deer dying within 48 hours of the appearance of the first symptoms and bison within three days.[1][11] In contrast, post infection cattle will usually survive a week or more.[12]
## Contents
* 1 Epidemiology
* 2 Clinical signs
* 3 Factors
* 4 Diagnosis
* 5 Prognosis
* 6 Vaccine
* 7 References
* 8 External links
## Epidemiology[edit]
The term bovine malignant catarrhal fever has been applied to three different patterns of disease:
* In Africa, wildebeests carry a lifelong infection of AlHV-1 but are not affected by the disease.[2] The virus is passed from mother to offspring and shed mostly in the nasal secretions of wildebeest calves under one year old.[13][14] Wildebeest associated MCF is transmitted from wildebeest to cattle normally following the wildebeest calving period. Cattle of all ages are susceptible to the disease, with a higher infection rate in adults, particularly in peripartuent females.[15] Cattle are infected by contact with the secretions, but do not spread the disease to other cattle. Because no commercial treatment or vaccine is available for this disease, livestock management is the only method of control. This involves keeping cattle away from wildebeest during the critical calving period. This results in Massai pastoralists in Tanzania and Kenya being excluded from prime pasture grazing land during the wet season leading to a loss in productivity.[16] In Eastern and Southern Africa MCF is classed as one of the five most important problems affecting pastoralists along with East coast fever, contagious bovine pleuropneumonia, foot and mouth disease and anthrax.[17] Hartebeests and topi also may carry the disease.[18] However, hartebeests and other antelopes are infected by a variant, Alcelaphine herpesvirus 2.
* Throughout the rest of the world, cattle and deer contract BMCF by close contact with sheep or goats during lambing. The natural host reservoir for Ovine herpesvirus 2 is the subfamily Caprinae (sheep and goats) whilst MCF affected animals are from the families Bovidae, Cervidae and suidae.[19][20] Susceptibility to OHV-2 varies by species, with domestic cattle and zebus somewhat resistant, water buffalo and most deer somewhat susceptible, and bison, Bali cattle, and Père David's deer very susceptible.[21] OHV-2 viral DNA has been detected in the alimentary, respiratory and urino-genital tracts of sheep[22] all of which could be possible transmission routes. Antibody from sheep and from cattle with BMCF is cross reactive with AlHV-1.[18]
* AHV-1/OHV-2 can also cause problems in zoological collections, where inapparently infected hosts (wildebeest and sheep) and susceptible hosts are often kept in close proximity.[23]
* Feedlot bison in North America not in contact with sheep have also been diagnosed with a form of BMCF. OHV-2 has been recently documented to infect herds of up to 5 km away from the nearest lambs, with the levels of infected animals proportional to the distance away from the closest herds of sheep.[24]
The incubation period of BMCF is not known, however intranasal challenge with AHV-1 induced MCF in one hundred percent of challenged cattle between 2.5 and 6 weeks.[25] Shedding of the virus is greater from 6–9 month old lambs than from adults.[1] After experimental infection of sheep, there is limited viral replication in nasal cavity in the first 24 hours after infection, followed by later viral replication in other tissues.[1]
## Clinical signs[edit]
The most common form of the disease is the head and eye form. Typical symptoms of this form include fever, depression, discharge from the eyes and nose, lesions of the buccal cavity and muzzle, swelling of the lymph nodes, opacity of the corneas leading to blindness, inappetence and diarrhea. Some animals have neurologic signs, such as ataxia, nystagmus, and head pressing. Animals that become infected with the virus can become extremely sensitive to touch, especially around the head. It is also possible that become aggressive and charge at approaching animals and people. If the virus continues untreated, seizures could develop. Affected animal usually die five to ten days of the first signs of clinical signs. Once the cow shows clinical signs there is no chance of recovering.[26]
Peracute, alimentary and cutaneous clinical disease patterns have also been described.[27] Death usually occurs within ten days.[28] The mortality rate in symptomatic animals is 90 to 100 percent.[21] Treatment is supportive only.
## Factors[edit]
There are many factors that can increase the chances of infection or affect the severity of an outbreak. The amount of animals in the herd, population density and species of the susceptible hosts are huge factors. Other factors include closeness of contact and amount of virus available for transmission.[29]
## Diagnosis[edit]
Diagnosis of BMCF depends on a combination of history and symptoms, histopathology[27] and detection in the blood or tissues of viral antibodies by ELISA[30][31] or of viral DNA by PCR.[22][32][33] The characteristic histologic lesions of MCF are lymphocytic arteritis with necrosis of the blood vessel wall and the presence of large T lymphocytes mixed with other cells.[1] The similarity of MCF clinical signs to other enteric diseases, for example blue tongue, mucosal disease and foot and mouth make laboratory diagnosis of MCF important.[34] The world organisation for animal health[27] recognises histopathology as the definitive diagnostic test, but laboratories have adopted other approaches with recent developments in molecular virology. No vaccine has as yet been developed.
## Prognosis[edit]
Bovine malignant catarrhal fever usually is fatal in susceptible species like cattle and bison, and any animal that survives will remain infectious for the rest of its life even if it shows no subsequent signs of the disease. Such survivors may relapse and suffer attacks in later life, but what is of more practical importance is that animals with latent infections may be unrecognised carriers that cause unexplained cases. This possibility must be borne in mind when seeking the source of mysterious outbreaks.[29]
## Vaccine[edit]
Unfortunately a vaccine for malignant catarrhal fever (MCF) has not yet been developed.[1] Developing a vaccine has been difficult because the virus will not grow in cell culture and until recently it was not known why. Researchers at the Agricultural Research Service (ARS) found that the virus undergoes changes within the animal's body, a process known as "cell tropism switching". In cell tropism switching, the virus targets different cells at different points in its life cycle. This phenomenon explains why it has been impossible to grow the virus on any one particular cell culture.
Because the virus is transmitted from sheep to bison and cattle, researchers are first focusing on the viral life cycle in sheep. The viral life cycle is outlined in three stages: entry, maintenance, and shedding. Entry occurs through the sheep's nasal cavity and enters into the lungs where it replicates. The virus undergoes a tropic change and infects lymphocytes, also known as white blood cells, which play a role in the sheep's immune system. In the maintenance stage the virus remains on the sheep's lymphocytes and circulates the body. Finally, during the shedding stage, the virus undergoes another change and shifts its target cells from lymphocytes to nasal cavity cells, where it is then shed through nasal secretions.[35] This discovery undoubtedly puts scientists on the right track for developing a vaccine – starting with the correct cell culture for each stage of the virus lifecycle – but ARS researchers are also looking into alternative methods to develop a vaccine. Researchers are experimenting with the MCF virus that infects topi (an African antelope) because it will grow in cell culture and does not infect cattle. Researchers hope that inserting genes from the sheep MCF virus into the topi MCF virus will ultimately be an effective MCF vaccine for cattle and bison.[35] While there is much ground left to cover, scientists are getting closer and closer to developing a vaccine.
## References[edit]
1. ^ a b c d e f g o'Toole, D.; Li, H. (2014). "The Pathology of Malignant Catarrhal Fever, with an Emphasis on Ovine Herpesvirus 2". Veterinary Pathology. 51 (2): 437–452. doi:10.1177/0300985813520435. PMID 24503439.
2. ^ a b c Plowright, W.; Ferris, R. D.; Scott, G. R. (1960). "Blue Wildebeest and the Ætiological Agent of Bovine Malignant Catarrhal Fever". Nature. 188 (4757): 1167–1169. Bibcode:1960Natur.188.1167P. doi:10.1038/1881167a0. PMID 13736396. S2CID 37101022.
3. ^ Schultheiss, Patricia C.; Collins, James K.; Spraker, Terry R.; Demartini, James C. (2000). "Epizootic Malignant Catarrhal Fever in Three Bison Herds: Differences from Cattle and Association with Ovine Herpesvirus-2". Journal of Veterinary Diagnostic Investigation. 12 (6): 497–502. doi:10.1177/104063870001200602. PMID 11108448.
4. ^ Elizabeth S. Williams; Ian K. Barker (28 February 2008). Infectious Diseases of Wild Mammals. John Wiley & Sons. pp. 157–. ISBN 978-0-470-34481-1.
5. ^ Lee Merriam Talbot; Martha H. Talbot (1963). The Wildebeest in Western Masailand, East Africa. National Academies. pp. 52–. NAP:13180.
6. ^ a b Wiyono, A.; Baxter, S. I.; Saepulloh, M.; Damayanti, R.; Daniels, P.; Reid, H. W. (1994). "PCR detection of ovine herpesvirus-2 DNA in Indonesian ruminants--normal sheep and clinical cases of malignant catarrhal fever". Veterinary Microbiology. 42 (1): 45–52. doi:10.1016/0378-1135(94)90076-0. PMID 7839584.
7. ^ a b Berezowski, John Andrew; Appleyard, Greg D.; Crawford, Timothy B.; Haigh, Jerry; Li, Hong; Middleton, Dorothy M.; O'Connor, Brendan P.; West, Keith; Woodbury, Murray (2005). "An Outbreak of Sheep-Associated Malignant Catarrhal Fever in Bison (Bison Bison) after Exposure to Sheep at a Public Auction Sale". Journal of Veterinary Diagnostic Investigation. 17 (1): 55–58. doi:10.1177/104063870501700110. PMID 15690951.
8. ^ Cleaveland S; Kusiluka L; Ole Kuwai J; Bell C; Kazwala R. (2001). "Assessing the impact of Malignant Catarrhal Fever in Ngorongoro District, Tanzania" (PDF). Animal Health Programme, Department for International Development. pp. 57–72. Retrieved 9 September 2020.CS1 maint: uses authors parameter (link)
9. ^ Bedelian, Claire; Nkedianye, David; Herrero, Mario (2007). "Maasai perception of the impact and incidence of malignant catarrhal fever (MCF) in southern Kenya". Preventive Veterinary Medicine. 78 (3–4): 296–316. doi:10.1016/j.prevetmed.2006.10.012. PMID 17123651.
10. ^ Orr, M.B.; MacKintosh, C.G. (1988). "An outbreak of malignant catarrhal fever in Père David's deer (Elaphurus davidianus)". New Zealand Veterinary Journal. 36 (1): 19–21. doi:10.1080/00480169.1988.35466. PMID 16031426.
11. ^ O'Toole, D.; Li, H.; Sourk, C.; Montgomery, D. L.; Crawford, T. B. (2002). "Malignant Catarrhal Fever in a Bison (Bison Bison) Feedlot, 1993–2000". Journal of Veterinary Diagnostic Investigation. 14 (3): 183–193. doi:10.1177/104063870201400301. PMID 12033673.
12. ^ Holliman, A.; Daniel, R.; Twomey, D. F.; Barnett, J.; Scholes, S.; Willoughby, K.; Russell, G. (2007). "Malignant catarrhal fever in cattle in the UK". Veterinary Record. 161 (14): 494–495. doi:10.1136/vr.161.14.494-e. PMID 17921444. S2CID 26446432.
13. ^ Mushi, E. Z.; Rurangirwa, F. R. (1981). "Malignant catarrhal fever virus shedding by infected cattle". Bulletin of Animal Health and Production in Africa. 29 (1): 111–2. PMID 7296019.
14. ^ Baxter, S. I.; Wiyono, A.; Pow, I.; Reid, H. W. (1997). "Identification of Ovine Herpes Virus-2 infection in sheep". Archives of Virology. 142 (4): 823–831. doi:10.1007/s007050050121. PMID 9170507. S2CID 30143095.
15. ^ Barnard, B. J.; Van der Lugt, J. J.; Mushi, E. Z. (1994). "Malignant Catarrhal Fever". In Coetzer, J. A. W.; Thompson, G. R.; Tustin, R. C. (eds.). Infectious Diseases of Livestock. New York: Oxford University Press. ISBN 978-0-19-570506-5.
16. ^ Homewood, K. H.; Rodgers, W. A.; Arhem, K. (1987). "Ecology of pastoralism in Ngorongoro Conservation Area, Tanzania". The Journal of Agricultural Science. 108: 47–72. doi:10.1017/S0021859600064133.
17. ^ Boone, R. B.; Coughenour, M. B. (2001). A system for integrated management and assessment of east African pastoral lands. Balancing food security, wildlife conservation, and ecosystem integrity. Final report to the Global Livestock Collaborative Research Support Program (Report).
18. ^ a b Fenner, Frank J.; Gibbs, E.; Paul, J.; Murphy, Frederick A.; Rott, Rudolph; Studdert, Michael J.; White, David O. (1993). Veterinary Virology (2nd ed.). Academic Press. ISBN 978-0-12-253056-2.
19. ^ O'Toole, D.; Taus, N. S.; Montgomery, D. L.; Oaks, J. L.; Crawford, T. B.; Li, H. (2007). "Intra-nasal Inoculation of American Bison (Bison bison) with Ovine Herpesvirus-2 (OvHV-2) Reliably Reproduces Malignant Catarrhal Fever". Veterinary Pathology. 44 (5): 655–662. doi:10.1354/vp.44-5-655. PMID 17846237.
20. ^ Taus, N. S.; Herndon, D. R.; Traul, D. L.; Stewart, J. P.; Ackermann, M.; Li, H.; Knowles, D. P.; Lewis, G. S.; Brayton, K. A. (2007). "Comparison of ovine herpesvirus 2 genomes isolated from domestic sheep (Ovis aries) and a clinically affected cow (Bos bovis)". Journal of General Virology. 88 (Pt 1): 40–45. doi:10.1099/vir.0.82285-0. PMID 17170434.
21. ^ a b "Malignant Catarrhal fever" (PDF). The Center for Food Security and Public Health at Iowa State University. 2005. Retrieved 2006-05-13.
22. ^ a b Hussy, D.; Stauber, N.; Leutenegger, C. M.; Rieder, S.; Ackermann, M. (2001). "Quantitative Fluorogenic PCR Assay for Measuring Ovine Herpesvirus 2 Replication in Sheep". Clinical and Vaccine Immunology. 8 (1): 123–128. doi:10.1128/CDLI.8.1.123-128.2001. PMC 96020. PMID 11139205.
23. ^ Cooley, A. Jim; Taus, Naomi S.; Li, Hong (2008). "Development of a Management Program for a Mixed Species Wildlife Park Following an Occurrence of Malignant Catarrhal Fever". Journal of Zoo and Wildlife Medicine. 39 (3): 380–385. doi:10.1638/2007-0181.1. PMID 18817000. S2CID 24137474.
24. ^ Li, H.; Karney, G.; O'Toole, D.; Crawford, T. B. (2008). "Long distance spread of malignant catarrhal fever virus from feedlot lambs to ranch bison". The Canadian Veterinary Journal. 49 (2): 183–5. PMC 2216446. PMID 18309750.
25. ^ Haig, David M.; Grant, Dawn; Deane, David; Campbell, Iris; Thomson, Jackie; Jepson, Catherine; Buxton, David; Russell, George C. (2008). "An immunisation strategy for the protection of cattle against alcelaphine herpesvirus-1-induced malignant catarrhal fever". Vaccine. 26 (35): 4461–4468. doi:10.1016/j.vaccine.2008.06.056. PMID 18601965.
26. ^ "NADIS Animal Health Skills - Malignant Catarrhal Fever (MCF)". www.nadis.org.uk. Retrieved 2019-04-02.
27. ^ a b c OIE. OIE Manual of Diagnostic Tests and Vaccines for terrestrial Animal (5th ed.). France. pp. 570–579.
28. ^ Carter, G.R.; Flores, E.F.; Wise, D.J. (2006). "Herpesviridae". A Concise Review of Veterinary Virology. Retrieved 2006-06-10.
29. ^ a b "Overview of Malignant Catarrhal Fever - Generalized Conditions". Merck Veterinary Manual. Retrieved 2019-04-02.
30. ^ Fraser, S.J.; Nettleton, P.F.; Dutia, B.M; Haig, D.M.; Russell, G.C. (2006). "Development of an enzyme-linked immunosorbent assay for the detection of antibodies against malignant catarrhal fever viruses in cattle serum". Veterinary Microbiology. 116 (1–3): 21–28. doi:10.1016/j.vetmic.2006.03.002. PMID 16621342.
31. ^ Li, Hong; McGuire, Travis C.; Müller-Doblies, Uwe U.; Crawford, Timothy B. (2001). "A Simpler, More Sensitive Competitive Inhibition Enzyme-Linked Immunosorbent Assay for Detection of Antibody to Malignant Catarrhal Fever Viruses". Journal of Veterinary Diagnostic Investigation. 13 (4): 361–364. doi:10.1177/104063870101300417. PMID 11478614.
32. ^ Cunha, C. W.; Otto, L.; Taus, N. S.; Knowles, D. P.; Li, H. (2009). "Development of a Multiplex Real-Time PCR for Detection and Differentiation of Malignant Catarrhal Fever Viruses in Clinical Samples". Journal of Clinical Microbiology. 47 (8): 2586–2589. doi:10.1128/JCM.00997-09. PMC 2725674. PMID 19494077.
33. ^ Traul, Donald L.; Taus, Naomi S.; Oaks, J. Lindsay; Toole, Donal O'; Rurangirwa, Fred R.; Baszler, Timothy V.; Li, Hong (2007). "Validation of Nonnested and Real-Time PCR for Diagnosis of Sheep-Associated Malignant Catarrhal Fever in Clinical Samples". Journal of Veterinary Diagnostic Investigation. 19 (4): 405–408. doi:10.1177/104063870701900412. PMID 17609352.
34. ^ Bexiga, R.; Guyot, H.; Saegerman, C.; Mauroy, A.; Rollin, F.; Thiry, E.; Philbey, A. W.; Logue, D. N.; Mellor, D. J.; Barrett, D. C.; Ellis, K. (2007). "Clinical differentiation of malignant catarrhal fever, mucosal disease and bluetongue". The Veterinary Record. 161 (25): 858–9. PMID 18156595.
35. ^ a b "Figuring Out Puzzling Animal Diseases". USDA Agricultural Research Service. 2010-04-02. Archived from the original on 2010-04-05. Retrieved July 9, 2017.
## External links[edit]
Wikimedia Commons has media related to Bovine malignant catarrhal fever.
* Current status of Bovine malignant catarrhal fever worldwide at OIE. WAHID Interface - OIE World Animal Health Information Database
* Disease card
* v
* t
* e
Taxonomy of the Herpesvirales
Higher taxonomy: Duplodnaviria > Heunggongvirae > Peploviricota > Herviviricetes > Herpesvirales
Malacoherpesviridae
Aurivirus
* AbHV-1
Ostreavirus
* OsHV-1
Alloherpesviridae
Batrachovirus
* RaHV-1
* 2
* 3
Cyprinivirus
* AngHV-1
* CyHV-1
* 2
* 3
Ictalurivirus
* AciHV-2
* IcHV-1
* 2
Salmonivirus
* SalHV-1
* 2
* 3
Herpesviridae
IgHV-2
α
ChHV-6
Iltovirus
* GaHV-1
* PsHV-1
Mardivirus
* AnHV-1
* CoHV-1
* GaHV-2
* 3
* MeHV-1
* SpAHV-1
Scutavirus
* ChHV-5
* TeHV-3
Simplexvirus
* AtHV-1
* BoHV-2
* CeHV-2
* HHV-1
* 2
* LeHV-4
* McHV-1
* MaHV-1
* 2
* PnHV-3
* PaHV-2
* PtHV-1
* SaHV-1
Varicellovirus
* BoHV-1
* 5
* BuHV-1
* CaHV-1
* CpHV-1
* CeHV-9
* CvHV-1
* 2
* EHV-1
* 3
* 4
* 8
* 9
* FeHV-1
* HHV-3
* MoHV-1
* PhHV-1
* SuHV-1
β
CaHV-2
TuHV-1
Cytomegalovirus
* AoHV-1
* CbHV-1
* CeHV-5
* HHV-5
* McHV-3
* 8
* MnHV-1
* PnHV-2
* PaHV-3
* 4
* SaHV-4
Muromegalovirus
* MuHV-1
* 2
* 8
Proboscivirus
* ElHV-1
* 4
* 5
Roseolovirus
* HHV-6A
* 6B
* 7
* McHV-9
* MuHV-3
* SuHV-2
γ
EHV-7
PhHV-2
SgHV-1
Lymphocryptovirus
* CalHV-3
* CeHV-14
* GoHV-1
* HHV-4
* McHV-4
* 10
* PnHV-1
* PaHV-1
* PoHV-2
Macavirus
* AlHV-1
* 2
* BoHV-6
* CpHV-2
* HiHV-1
* OvHV-2
* SuHV-3
* 4
* 5
Percavirus
* EHV-2
* 5
* FeHV-1
* MusHV-1
* PhHV-3
* VeHV-1
Rhadinovirus
* AtHV-2
* 3
* BoHV-4
* CrHV-2
* HHV-8
* McHV-5
* 8
* 11
* 12
* MuHV-4
* 7
* SaHV-2
Unassigned species listed below parent taxon –– Source: ICTV –– Wikispecies
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*[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
| Bovine malignant catarrhal fever | c0276241 | 1,611 | wikipedia | https://en.wikipedia.org/wiki/Bovine_malignant_catarrhal_fever | 2021-01-18T18:55:59 | {"mesh": ["D008304"], "wikidata": ["Q552330"]} |
Fitzsimmons–Guilbert syndrome
Other namesParaplegia-brachydactyly-cone-shaped epiphysis syndrome
Fitzsimmons–Guilbert syndrome is an extremely rare genetic disease characterized by a slowly progressive spastic paraplegia, skeletal anomalies of the hands and feet with brachydactyly type E, cone-shaped epiphyses, abnormal metaphyseal–phalangeal pattern profile, sternal anomaly (pectus carinatum or excavatum), dysarthria, and mild intellectual deficit.[1]
## Contents
* 1 Pathophysiology
* 2 Diagnosis
* 3 Treatment
* 4 History
* 5 References
* 6 External links
## Pathophysiology[edit]
With so few described cases, establishing the basic pathophysiological mechanisms or genetic abnormalities has not been possible.[citation needed]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (July 2017)
## Treatment[edit]
This section is empty. You can help by adding to it. (July 2017)
## History[edit]
Fitzsimmons and Guilbert first described male uniovular twins, aged 20 years, who had had slowly progressive spastic paraplegia from early in life.[2] Both had skeletal abnormalities of the hands and feet: brachydactyly, cone-shaped epiphyses, and an abnormal metaphyseal-phalangeal pattern profile. In addition, they had nonspecific dysarthria and low-normal intellectual capacity.[2]
Since the original report, three more cases have been described, including two (Lacassie et al.) with a more severe mental retardation and a different metacarpal-phalangeal pattern profile, though these cases may represent a new disease entity.[3][4]
## References[edit]
1. ^ "Paraplegia – brachydactyly – cone-shaped epiphysis". ORPHANET. Retrieved 2007-03-17.
2. ^ a b Fitzsimmons J, Guilbert P (1987). "Spastic paraplegia associated with brachydactyly and cone shaped epiphyses". J Med Genet. 24 (11): 702–5. doi:10.1136/jmg.24.11.702. PMC 1050351. PMID 3430547.
3. ^ Hennekam R (1994). "Spastic paraplegia, dysarthria, brachydactyly, and cone shaped epiphyses: confirmation of the Fitzsimmons syndrome". J Med Genet. 31 (3): 251–2. doi:10.1136/jmg.31.3.251. PMC 1049754. PMID 8014978.
4. ^ Lacassie Y, Arriaza M, Duncan M, Dijamco C, McElveen C, Stahls P (1999). "Identical twins with mental retardation, dysarthria, progressive spastic paraplegia, and brachydactyly type E: a new syndrome or variant of Fitzsimmons-Guilbert syndrome?". Am J Med Genet. 84 (2): 90–3. doi:10.1002/(SICI)1096-8628(19990521)84:2<90::AID-AJMG2>3.0.CO;2-8. PMID 10323731.
## External links[edit]
Classification
D
* ICD-10: G82.1
* OMIM: 270710
* MeSH: C537938
External resources
* Orphanet: 2823
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*[AA]: Adrenergic agonist
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*[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
| Fitzsimmons–Guilbert syndrome | c0795942 | 1,612 | wikipedia | https://en.wikipedia.org/wiki/Fitzsimmons%E2%80%93Guilbert_syndrome | 2021-01-18T18:43:03 | {"gard": ["2343"], "mesh": ["C537938"], "umls": ["C0795942"], "orphanet": ["2823"], "wikidata": ["Q5455731"]} |
A number sign (#) is used with this entry because of evidence that combined lipase deficiency with severe hypertriglyceridemia is caused by homozygous mutation in the LMF1 gene (611761) on chromosome 16p13.
Clinical Features
Auwerx et al. (1990) described a large family with familial hepatic triglyceride lipase (HTGL; 151670) deficiency and a coexisting reduced lipoprotein lipase (LPL; 609708) similar to the heterozygous state of LPL deficiency. The proband was detected because of hypertriglyceridemia and chylomicronemia. Analysis of genomic DNA from these subjects by restriction enzyme digestion showed no major abnormalities in the structure of either the HTGL gene or the LPL gene. The authors incorrectly referred to 'compound heterozygotes for HTGL and LPL deficiency'; they should have referred to these individuals as 'double heterozygotes,' because the genes represent separate loci on separate chromosomes (chromosome 15 and chromosome 8, respectively).
The hypertriglyceridemia in the cld mouse (see Animal Model) is characterized by severe chylomicronemia that is caused by deficiency of lipoprotein lipase and exacerbated by partial deficiency of hepatic triglyceride lipase (HTGL; 151670). The mutation, however, affects neither the LPL nor the HTGL gene, but a transmembrane protein designated Lmf1 by Peterfy et al. (2007). To investigate the potential role of the LMF1 gene in human disease, Peterfy et al. (2007) screened 11 individuals with hypertriglyceridemia and decreased lipase activity for mutations. They identified a 48-year-old woman carrying an LMF1 mutation in homozygosity in whom severe hypertriglyceridemia was first noted at age 18 years. She had her first attack of pancreatitis at age 27, and had had at least 15 subsequent attacks. She began to develop lipodystrophy at age 44 that progressed to complete involvement of limbs and buttocks, sparing her face and abdomen. Also at age 44, type 2 diabetes was diagnosed, which was controlled with metformin. Bilateral large tuberous xanthomas on elbows, knees, and feet were present. Even in compliance with strict dietary fat restrictions, triglyceride concentration was 7 times the average of 31 control subjects at the lowest measurement, and increased markedly to over 70 times the control value when diet was not regulated. The severe hypertriglyceridemia was found to be due to LPL deficiency, as determined by a 93% decrease in LPL activity in the plasma of the affected individual. In addition, hepatic lipase activity was decreased by half, confirming the status of combined lipase deficiency.
Cefalu et al. (2009) screened 22 individuals with severe hypertriglyceridemia and identified 1 with a homozygous mutation in the LMF1 gene. The proband was a 42-year-old Tunisian man living in Sicily, Italy. His parents were apparently unrelated. His mother died at age 62 years of a respiratory disease; the 65-year-old father and his 7 sibs were all healthy. Severe hypertriglyceridemia was first noted at age 32 years when the patient had an episode of acute pancreatitis. A diet restriction to 15% of fat intake (less than 7% of saturated fat) and treatment with fibrates and omega-3 fatty acids were prescribed, but compliance was poor, and the patient had a second episode of pancreatitis at age 38 years. He was overweight, with a BMI of 29. Triglycerides were 2,400 mg/dL, total cholesterol was 374 mg/dL, and HDL cholesterol levels were 44 mg/dL. He had a third episode of acute pancreatitis at age 41 years and then developed type 2 diabetes.
Molecular Genetics
In a patient with combined deficiency of lipoprotein lipase and hepatic lipase, concomitant hypertriglyceridemia, and associated disorders, Peterfy et al. (2007) detected homozygosity for a premature termination mutation in the LMF1 gene (Y439X; 611761.0001). The authors considered LMF1 to be an important candidate gene in hypertriglyceridemia through its profound effect on lipase activity.
In a 42-year-old Tunisian man with severe hypertriglyceridemia in whom genetic analysis was negative for mutations in the LPL, APOC2 (608083), and APOA5 (606368) genes, Cefalu et al. (2009) identified a homozygous nonsense mutation in the LMF1 gene (W464X; 611761.0002).
Animal Model
Paterniti et al. (1983) described a mouse mutation, cld, that results in combined deficiency of LPL and HTGL. Homozygous mice develop lethal hyperchylomicronemia within 2 days postpartum as a consequence of nursing. The mutation is located on mouse chromosome 17 which carries the H2 locus homologous to HLA on human chromosome 6. Indeed, the cld mutation was discovered as a 'parasitic lethal gene' acting postnatally in the T/t complex of mice. Several possibilities to account for deficiency of 2 enzymes were discussed by the authors.
Davis et al. (1990) stated that in the mouse the Ldl and Hl (hepatic lipase) genes are on chromosomes 8 and 9, respectively. Since the cld mutation and lipase genes reside on separate chromosomes in the mouse, combined lipase deficiency cannot represent a contiguous gene syndrome. In cld mice, Davis et al. (1990) found Lpl synthetic rates to be 70% of control rates; values for Lpl in cld post-heparin plasma were markedly reduced to only 7% of control values, suggesting that most of the Lpl was not secreted. Davis et al. (1990) concluded that a selective impairment of intracellular transport and secretion of Lpl and Hl underlies the disorder in the mouse.
Peterfy et al. (2007) described the phenotype of the cld/cld mouse. Shortly after ingesting dietary milk, neonatal cld/cld mice develop severe hypertriglyceridemia owing to an accumulation of chylomicrons that gradually pack the lumina of capillaries and sinusoids. Mutant mice show a progressive increase in triglyceride, which measures 1,000 mg/dl several hours after birth and rises as high as 20,000 mg/dl 2 to 3 days later. The severe hypertriglyceridemia causes an increase in blood viscosity, ischemia, and cyanosis, and the inability of tissues to access circulating triglycerides results in starvation, poor thermoregulation, and death 2 to 3 days after birth. Mice heterozygous for the mutation have normal triglyceride concentrations and no known abnormalities.
Misc \- Lethal hyperchylomicronemia in mice \- No reports yet in man Lab \- Lipoprotein lipase (LPL) deficiency \- Hepatic triglyceride lipase (HTGL) deficiency Inheritance \- Autosomal recessive ▲ Close
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*[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
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*[BMI]: body mass index
| LIPASE DEFICIENCY, COMBINED | c1855498 | 1,613 | omim | https://www.omim.org/entry/246650 | 2019-09-22T16:25:48 | {"mesh": ["C535904"], "omim": ["246650"], "orphanet": ["535453"], "synonyms": ["LIPOPROTEIN LIPASE DEFICIENCY WITH HEPATIC TRIGLYCERIDE LIPASE DEFICIENCY", "Familial LMF1 deficiency", "Alternative titles", "LPL AND HTGL DEFICIENCY", "LPL AND HL DEFICIENCY"]} |
A number sign (#) is used with this entry because medulloblastoma can be caused by germline mutations in the SUFU gene (607035) on chromosome 10q and the BRCA2 gene (600185) on chromosome 3p.
Somatic mutations in several genes have been found in sporadic cases of medulloblastoma. These genes include PTCH2 (603673) on chromosome 1p32, CTNNB1 (116806) on chromosome 3p, and APC (611731) on chromosome 5q.
Germline mutation in the SUFU gene (607035.0007) has been reported in a Finnish family with familial meningioma (607174).
Description
Medulloblastoma is the most common brain tumor in children. It accounts for 16% of all pediatric brain tumors, and 40% of all cerebellar tumors in childhood are medulloblastoma. Medulloblastoma occurs bimodally, with peak incidences between 3 and 4 years and 8 and 9 years of age. Approximately 10 to 15% of medulloblastomas are diagnosed in infancy. Medulloblastoma accounts for less than 1% of central nervous system (CNS) tumors in adults, with highest incidence in adults 20 to 34 years of age. In 1 to 2% of patients, medulloblastoma is associated with Gorlin syndrome (109400), a nevoid basal carcinoma syndrome. Medulloblastoma also occurs in up to 40% of patients with Turcot syndrome (276300). Medulloblastoma is thought to arise from neural stem cell precursors in the granular cell layer of the cerebellum. Standard treatment includes surgery, chemotherapy, and, depending on the age of the patient, radiation therapy (Crawford et al., 2007).
Clinical Features
Crawford et al. (2007) reviewed medulloblastoma, with a focus on clinical presentation, diagnosis, and treatment.
Cerebellar medulloblastoma is a feature of basal cell nevus syndrome (109400), von Hippel-Lindau syndrome (193300), and familial adenomatous polyposis (175100). In a formal risk analysis for brain tumors in familial adenomatous polyposis, Hamilton et al. (1995) found that the relative risk of cerebellar medulloblastoma in patients with familial adenomatous polyposis was 92 times that for the general population (95% confidence interval, 29 to 269; P less than 0.001).
Pathogenesis
Studying the molecular basis for metastasis in medulloblastoma, MacDonald et al. (2001) obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or nonmetastatic (M0) and identified 85 genes whose expression differed significantly between classes. They found that platelet-derived growth factor receptor-alpha (PDGFRA; 173490) and members of the downstream Ras/mitogen-activated protein kinase (MAPK) signal transduction pathway are upregulated in M+ tumors. Immunohistochemical validation on an independent set of tumors showed significant overexpression of PDGFRA in M+ tumors compared to M0 tumors. Using in vitro assays, they showed that platelet-derived growth factor-alpha (PDGFA; 173430) enhances medulloblastoma migration and increases phosphorylation of downstream MAP2K1 (176872), MAP2K2 (601263), MAPK1 (176948), and MAPK3 (601795) in a dose-dependent manner. MacDonald et al. (2001) suggested that inhibitors of PDGFRA and RAS proteins should be considered as possible novel therapeutic strategies against medulloblastoma.
Gilbertson and Clifford (2003) stated that the oligonucleotide probe used by MacDonald et al. (2001) to determine PDGFRA expression actually identified PDGFRB (173410), and therefore called into question whether PDGFRA or PDGFRB is regulated in invasive forms of medulloblastoma. Gilbertson and Clifford (2003) presented data confirming that PDGFRB is preferentially expressed in metastatic medulloblastoma and suggested that it may prove useful as a prognostic marker and as a therapeutic target for the disease.
Pomeroy et al. (2002) approached the problems of CNS tumor classification by developing a system based on DNA microarray gene expression data derived from 99 patient samples. They demonstrated that medulloblastomas are molecularly distinct from other brain tumors including primitive neuroectodermal tumors (PNETs), atypical teratoid/rhabdoid tumors (609322), and malignant gliomas. They also found evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic hedgehog pathway (see 600725). Pomeroy et al. (2002) further showed that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumors at diagnosis. Malignant gliomas were clearly separable from medulloblastomas in that they express genes typical of the astrocytic and oligodendrocytic lineage. Medulloblastomas express ZIC (600470) and NSCL1 (162360), encoding transcription factors that are specific for cerebellar granule cells. Pomeroy et al. (2002) suggested that medulloblastomas, but not PNETs, arise from cerebellar granule cells, or alternatively, have activated the transcriptional program of cerebellar granule cells.
Hallahan et al. (2003) established that retinoids cause extensive apoptosis of medulloblastoma cells. In a xenograft model, retinoids largely abrogated tumor growth. Using receptor-specific retinoid agonists, Hallahan et al. (2003) defined a subset of mRNAs that were induced by all active retinoids in retinoid-sensitive cell lines. They also identified BMP2 (112261) as a candidate mediator of retinoid activity. BMP2 protein induced medulloblastoma cell apoptosis, whereas the BMP2 antagonist Noggin (602991) blocked both retinoid and BMP2-induced apoptosis. BMP2 also induced p38 MAPK (600289), which is necessary for BMP2- and retinoid-induced apoptosis. Retinoid-resistant medulloblastoma cells underwent apoptosis when treated with BMP2 or when cultured with retinoid-sensitive medulloblastoma cells. Retinoid-induced expression of BMP2 is thus necessary and sufficient for apoptosis of retinoid-responsive cells, and expression of BMP2 by retinoid-sensitive cells is sufficient to induce apoptosis in surrounding retinoid-resistant cells.
Leung et al. (2004) demonstrated that BMI1 (164831) is strongly expressed in proliferating cerebellar precursor cells in mice and humans. Using Bmi1-null mice, Leung et al. (2004) demonstrated a crucial role for BMI1 in clonal expansion of granule cell precursors both in vivo and in vitro. Deregulated proliferation of these progenitor cells, by activation of the Shh pathway, leads to medulloblastoma development. Leung et al. (2004) also demonstrated linked overexpression of BMI1 and PTCH1 (601309), suggestive of SHH pathway activation, in a substantial fraction of primary human medulloblastomas. Together with the rapid induction of Bmi1 expression on addition of Shh or on overexpression of the Shh target Gli1 in cerebellar granule cell cultures, Leung et al. (2004) concluded that their findings implicate BMI1 overexpression as an alternative or additive mechanism in the pathogenesis of medulloblastomas, and highlight a role for BMI1-containing polycomb complexes in proliferation of cerebellar precursor cells.
Because Drosophila Cic (612082) had been shown to mediate c-erbB (EGFR; see 131550) signaling via transcriptional repression, Lee et al. (2005) studied the expression of human CIC in medulloblastoma, where high levels of ERBB2 (164870) and ERBB4 (600543) correlate with poor prognosis. In silico SAGE analysis of human normal and malignant brain demonstrated that medulloblastoma exhibited the highest level of CIC expression and that expression was most common in tumors of the central nervous system in general. RT-PCR and in situ hybridization verified the expression of CIC in tumor cells, although the level of expression varied between different medulloblastoma subtypes. In mouse postnatally developing cerebellum, in silico analysis and in situ hybridization indicated a strong correlation between Cic expression and the maturation profile of cerebellar granule cell precursors.
Northcott et al. (2009) used high-resolution SNP genotyping to identify regions of genomic gain and loss in 212 medulloblastoma tumors. There were focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes, most not previously implicated in medulloblastoma. There were several amplifications and homozygous deletions, including highly focal genetic events, in genes targeting histone lysine methylation, particularly H3 histone (see 602810) lysine-9 (H3K9). In vitro studies showed that restoring expression of genes controlling H3K9 methylation greatly diminished proliferation of medulloblastoma cells. Northcott et al. (2009) postulated that defective control of the histone code may contribute to the pathogenesis of medulloblastoma.
Parsons et al. (2011) searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a set of 22 medulloblastomas. Parsons et al. (2011) found that, on average, each tumor had 11 gene alterations, fewer by a factor of 5 to 10 than in the adult solid tumors that had been sequenced to that time. In addition to alterations in the Hedgehog (see 600725) and Wnt pathways (see 164820), their analysis led to the discovery of genes not known to be altered in medulloblastomas. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 (602113) or MLL3 (606833) were identified in 16% of medulloblastoma patients. Parsons et al. (2011) concluded that their results demonstrated key differences between the genetic landscapes of adult and childhood cancers, highlighted dysregulation of developmental pathways as an important mechanism underlying medulloblastomas, and identified a role for a specific type of histone methylation in human tumorigenesis.
Gibson et al. (2010) provided evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (116806) arises outside the cerebellum from cells of the dorsal brainstem. They found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip and embryonic dorsal brainstem than in the upper rhombic lip and developing cerebellum. MRI and intraoperative reports showed that human WNT-subtype tumors infiltrate the dorsal brainstem, whereas SHH-subtype tumors are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1+ precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 (191170) was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. The data of Gibson et al. (2010) provided the first evidence that subtypes of medulloblastoma have distinct cellular origins, and provided an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas.
### Reviews
In their review, Crawford et al. (2007) provided an overview of the molecular biology of medulloblastoma.
Guessous et al. (2008) reviewed the involvement multiple signaling pathways in medulloblastoma malignancy, with a focus on their modes of deregulation, prognostic value, functional effects, cellular and molecular mechanisms of action, and implications for therapy.
Clinical Management
Berman et al. (2002) investigated therapeutic efficacy of the hedgehog pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. The compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, and thus established a specific role for hedgehog pathway activity in medulloblastoma growth.
Rudin et al. (2009) described a 26-year-old man with metastatic medulloblastoma that was refractory to multiple therapies. Molecular analysis of the tumor specimens demonstrated activation of the hedgehog pathway, with loss of heterozygosity and somatic mutation of the gene encoding patched-1 (PTCH1; 601309), a key negative regulator of hedgehog signaling. The patient was treated with a novel hedgehog pathway inhibitor, GDC-0449, and treatment resulted in a rapid, although transient, regression of the tumor and reduction of symptoms.
Mapping
### Medulloblastoma Locus on Chromosome 17
A locus for medulloblastoma may map to chromosome 17p. Isochromosome 17q has been observed in high frequency in cytogenetic studies of medulloblastoma. By studies using restriction fragment length polymorphisms, Cogen et al. (1990) showed loss of heterozygosity for 17p sequences in 45% of medulloblastomas. The finding was predictive of a poor clinical response to treatment. Furthermore, a deletion could be mapped to 17p13.1-p12, the same chromosomal region for which loss of alleles has been shown in tumor specimens from patients with colon cancer, and the same region to which the p53 gene (191170) has been mapped. However, using denaturing gradient gel electrophoresis and direct sequencing, Cogen et al. (1992) detected p53 mutations in only 2 of 20 medulloblastoma specimens. Moreover, additional RFLP studies of these 20 specimens showed loss of heterozygosity at a more distal and distinct site, 17p13.3.
Molecular Genetics
### BRCA2 Mutations in Medulloblastomas
In 2 brothers who developed Wilms tumor (194070) and brain tumors, Reid et al. (2005) identified 2 truncating BRCA2 mutations (600185.0027 and 600185.0031). One boy had recurrent medulloblastoma.
### SUFU Mutations in Desmoplastic Medulloblastomas and Medulloblastomas with Extensive Nodularity (MBEN)
Bayani et al. (2000) showed that loss of heterozygosity (LOH) on 10q24 is frequent in medulloblastomas, suggesting that this region contains 1 or more tumor suppressor genes. Taylor et al. (2002) reported children with medulloblastoma who carried germline and somatic mutations in the SUFU gene (607035) accompanied by LOH of the wildtype allele. Several of these mutations encoded truncated proteins that were unable to export the GLI transcription factor (165220) from nucleus to cytoplasm, resulting in activation of SHH signaling. Thus, SUFU is a tumor suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway. Taylor et al. (2002) noted that all 4 medulloblastomas with SUFU truncating mutations were of the desmoplastic subtype. Desmoplastic tumors make up about 20 to 30% of medulloblastomas, have a more nodular architecture than 'classical' medulloblastoma, and may have a better prognosis. Activation of the SHH pathway is particularly high in desmoplastic medulloblastomas, as shown by increased expression of the SHH target genes GLI, SMOH (601500), and PTCH.
Brugieres et al. (2010) identified germline truncating SUFU mutations in 2 unrelated families with several children under 3 years of age diagnosed with medulloblastoma (607035.0005 and 607035.0006, respectively). Among the 25 mutation carriers in the 2 families, 7 developed medulloblastomas; of the 5 tumors for which histology was reviewed, 3 were classified as medulloblastoma with extensive nodularity (MBEN) and 2 were typical desmoplastic/nodular medulloblastoma. No obvious physical stigmata of nevoid basal cell carcinoma syndrome was found among 21 mutation carriers from both families who were examined, including 11 patients who underwent brain MRI. SUFU sequence analysis of 1 tumor from each family confirmed that only the mutant allele was detected in the tumor DNA, thus demonstrating the loss of the wildtype allele and supporting a tumor-suppressor role for SUFU.
### Somatic Mutations in Medulloblastomas
Among 46 medulloblastomas derived from patients with sporadic disease, Huang et al. (2000) identified 2 with somatic mutations in the APC gene and 4 with somatic mutations in the beta-catenin gene. This study provided the first evidence that APC mutations are operative in a subset of sporadic medulloblastomas.
To identify mutations that drive medulloblastoma, Robinson et al. (2012) sequenced the entire genomes of 37 tumors and matched normal blood. One-hundred and thirty-six genes harboring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not theretofore implicated in medulloblastoma; several targeted distinct components of the epigenetic machinery in different disease subgroups, such as regulators of histone-3 lys27 (H3K27) and H3K4 trimethylation in subgroups 3 and 4 (e.g., KDM6A, 300128 and ZMYM3, 300061), and beta-catenin-1 (CTNNB1; 116806)-associated chromatin remodelers in WNT-subgroup tumors (e.g., SMARCA4, 603254 and CREBBP, 600140). Modeling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumors identified genes that maintain this cell lineage (DDX3X; 300160), as well as mutated genes that initiate (CDH1; 192090) or cooperate (PIK3CA; 171834) in tumorigenesis. Robinson et al. (2012) concluded that their data provided important new insights into the pathogenesis of medulloblastoma subgroups and highlighted targets for therapeutic development.
Northcott et al. (2012) reported somatic copy number aberrations in 1,087 unique medulloblastomas. These copy number variations are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP (603779), a gene associated with Parkinson disease (168600), which is exquisitely restricted to Group 4-alpha. Recurrent translocations of PVT1 (165140), including PVT1-MYC (190080) and PVT1-NDRG1 (605262), that arise through chromothripsis are restricted to Group 3. Numerous targetable somatic copy number aberrations, including recurrent events targeting TGF-beta (190180) signaling in Group 3, and NF-kappa-B (see 164011) signaling in Group 4, suggested future avenues for rational, targeted therapy.
Jones et al. (2012) described an integrative deep-sequencing analysis of 125 tumor-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 medulloblastomas, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1; PTCH1, 601309; MLL2, 602113; SMARCA4) and in genes not previously linked to this tumor (DDX3X; CTDNEP1, 610684; KDM6A, TBR1; 604616), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of, to their knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups.
Using whole-exome sequencing of 92 primary medulloblastoma/normal pairs, Pugh et al. (2012) observed that overall, medulloblastomas have low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. Pugh et al. (2012) identified 12 genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4, and TP53 (191170). Recurrent somatic mutations were newly identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2 (601935), BCOR (300485), and LDB1 (603451). Pugh et al. (2012) showed that mutant DDX3X potentiates transactivation of a transcription factor (TCF4; 602272) promoter and enhanced cell viability in combination with mutant, but not wildtype, beta-catenin. Pugh et al. (2012) concluded that their study revealed the alteration of WNT, hedgehog, histone methyltransferase, and N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominated the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma.
Northcott et al. (2017) analyzed the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analyzed cases, and identified subgroup-specific driver alterations that included novel actionable targets. Patients with Group 3 medulloblastomas were characterized by MYC (190080) amplifications. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 (617645) and 'enhancer hijacking' events that activate PRDM6 in patients with highly recurrent, stereotypical tandem duplications in the SNCAIP gene (603779), restricted to Group 4. Northcott et al. (2017) concluded that the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
### Deletions in DMBT1 in Medulloblastoma
Mollenhauer et al. (1997) identified the DMBT1 gene (601969) as the site of homozygous intragenic deletions at chromosome 10q25.3-q26.1 in medulloblastoma and glioblastoma multiforme tumor tissue, as well as in brain tumor cell lines.
Animal Model
Marino et al. (2000) generated a mouse model for medulloblastoma by Cre-LoxP-mediated inactivation of Rb (RB1; 614041) and p53 tumor suppressor genes in the cerebellar external granular layer (EGL) cells. Recombination mediated by Gfap (137780) promoter-driven Cre was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum. Gfap-Cre-mediated inactivation of Rb in a p53-null background produced mice that developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. Marino et al. (2000) concluded that loss of function of Rb is essential for medulloblastoma development in the mouse and stated that their results strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL.
INHERITANCE \- Somatic \- Autosomal dominant \- Autosomal recessive NEOPLASIA \- Medulloblastoma LABORATORY ABNORMALITIES \- Isochromosome 17q frequent in cytogenetic studies \- Loss of heterozygosity for 17p sequences in 45% of medulloblastomas MISCELLANEOUS \- Incomplete penetrance MOLECULAR BASIS \- Caused by mutation in the SUFU negative regulator of hedgehog signaling gene (SUFU, 607035.0005 ) \- Caused by mutation in the BRCA2 gene (BRCA2, 600185.0027 ) \- Caused by somatic mutation in the catenin beta 1 gene (CTNNB1, 116806.0007 ) \- Caused by somatic mutation in the patched 2 gene (PTCH2, 603673.0001 ) ▲ Close
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*[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
| MEDULLOBLASTOMA | c0025149 | 1,614 | omim | https://www.omim.org/entry/155255 | 2019-09-22T16:38:30 | {"doid": ["0050902"], "mesh": ["D008527"], "omim": ["155255"], "orphanet": ["616", "251858", "251863", "251867"]} |
A number sign (#) is used with this entry because of evidence that familial platelet disorder with associated myeloid malignancy (FPDMM) is caused by heterozygous mutation in the hematopoietic transcription factor CBFA2 (RUNX1; 151385) on chromosome 21q22.
Clinical Features
Dowton et al. (1985) described a large pedigree with an autosomal dominant familial 'aspirin-like' platelet disorder associated with the development of acute myelogenous leukemia (AML).
Arepally et al. (1998) reported a family of mixed Czechoslovakian and Hungarian background with a phenotype similar to the family of Dowton et al. (1985). The proband presented at the age of 4 years for hypospadias repair. He had easy bruising since infancy and was found preoperatively to have a platelet count of 106,000/microliter. The mother, maternal aunt, and maternal grandmother had low platelet counts and a bleeding diathesis. In addition to thrombocytopenia, both the index patient and his brother had hypospadias and umbilical hernia. At 41 years of age, the proband's mother developed progressive anemia and neutropenia and was shown to have refractory anemia. Within 6 months of diagnosis of myelodysplasia, increased marrow blast counts above 30% were noted. Cytogenetics yielded normal results, as did fluorescence in situ hybridization studies for monosomy 5 and 7. Immunohistochemical typing of her blasts confirmed acute myelogenous leukemia.
Beri-Dexheimer et al. (2008) reported a boy who presented at age 2 years with purpura without history of easy bruising or bleeding. Although platelet morphology was normal, he had thrombocytopenia, and the platelets showed impaired aggregation in response to ADP. A bone marrow aspirate showed a hypercellular bone marrow with blasts (20%) and myelodysplastic features. Blasts phenotype was immature with myeloid markers leading to a diagnosis of AML. He underwent successful bone marrow transplantation. His mother, who had no history of bleeding, was found to have mild isolated thrombocytopenia and similarly abnormal platelet behavior. Molecular analysis identified a heterozygous deletion in the RUNX1 gene (151385.0009) in the patient and his mother.
Preudhomme et al. (2009) reported 16 individuals with familial platelet disorder from 4 unrelated French families associated with heterozygous mutation in or deletion of the RUNX1 gene (see, e.g., 151385.0010). Among these patients, 7 developed AML, 1 had a T-acute lymphoblastic leukemia, 1 had T-ALL followed by AML, and 1 died of an uncharacterized leukemia. Of the 8 with AML, age at diagnosis of AML ranged from 12 to 60 years, and 6 were found to have a somatic RUNX1 mutation: 4 had acquired point mutations and 2 had acquired trisomy 21. The findings indicated that a second genetic event involving RUNX1 is often associated with progression to acute leukemia in patients with familial platelet disorder. In addition, heterozygous mutations in the RUNX1 gene may also predispose to the development of lymphoblastic leukemia.
Mapping
In the large family described by Dowton et al. (1985), Ho et al. (1996) found linkage of the platelet disorder to markers D21S263, D21S216, IFNAR (107450), and D21S65 on chromosome 21q, with lod scores of 6.19, 4.89, 9.40, and 10.48, respectively (theta = 0.001). They proposed a familial platelet disorder critical region of 15.2 cM in addition to approximate placement for markers D21S211 and UT7582/D21S1413. This critical region contains 5 candidate genes, including AML1 (151385), IFNAR, CRF2-4 (123889), GART (138440), and SON (182465). See also 176630.
By linkage analysis of a family with this disorder, Arepally et al. (1998) found evidence for linkage to chromosome 21 (maximum lod score of 1.682 at D21S65). Multipoint analyses placed the putative disease locus between D21S263 and D21S211. Maximum lod scores greater than 3 were obtained at each map interval. No evidence for allele sharing between this kindred and the French Canadian pedigree reported by Ho et al. (1996) was found.
### Genetic Heterogeneity
Minelli et al. (2004) stated that 12 families with familial platelet disorder with propensity to acute myelogenous leukemia (FPD/AML) had previously been reported. They described an Italian family with 3 members affected with FPD/AML, 2 sibs and their father, who developed myelodysplastic syndromes, which in one subsequently evolved into AML. Direct sequencing and polymorphism haplotype analysis of the region of chromosome 21 where the RUNX1 gene maps demonstrated that FPD/AML in this family was not caused by mutation in the RUNX1 gene, thus providing evidence for the genetic heterogeneity of the disorder. Cytogenetic studies showed monosomy 7 in the marrow of all 3 affected subjects, as well as an independent clone with trisomy 8 in the father.
Molecular Genetics
By mutation analysis of candidate genes in the region where this familial platelet disorder maps, Song et al. (1999) found a heterozygous mutation in the hematopoietic transcription factor CBFA2 (see, e.g., 151385.0001; 151385.0002) in affected members of 6 families. Analysis of bone marrow or peripheral blood cells from affected individuals showed a decrement in megakaryocyte colony formation, demonstrating that CBFA2 dosage affects megakaryopoiesis. The authors suggested a model for this familial platelet disorder in which haploinsufficiency of CBFA2 causes an autosomal dominant congenital platelet defect and predisposes to an acquisition of additional mutations that cause leukemia.
In affected members of 3 unrelated families with the autosomal dominant familial platelet disorder characterized by thrombocytopenia and a propensity to develop AML, Michaud et al. (2002) identified 3 heterozygous mutations in the RUNX1 gene (151385.0003-151385.0005).
INHERITANCE \- Autosomal dominant HEAD & NECK Nose \- Epistaxis SKIN, NAILS, & HAIR Skin \- Easy bruisability HEMATOLOGY \- Thrombocytopenia (birth) \- Abnormal platelet aggregation \- Prolonged bleeding time \- Normal platelet size \- Normal platelet morphology NEOPLASIA \- Acute monocytic leukemia \- Myelodysplasia \- Lymphosarcoma \- Lymphocytic lymphoma \- Acute myelocytic leukemia \- Neuroblastoma MOLECULAR BASIS \- Caused by mutation in the runt-related transcription factor 1 gene (RUNX1, 151385.0001 ) ▲ Close
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*[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
| PLATELET DISORDER, FAMILIAL, WITH ASSOCIATED MYELOID MALIGNANCY | c1832388 | 1,615 | omim | https://www.omim.org/entry/601399 | 2019-09-22T16:14:52 | {"mesh": ["C563324"], "omim": ["601399"], "orphanet": ["71290"], "synonyms": ["Alternative titles", "PLATELET DISORDER, ASPIRIN-LIKE", "THROMBOCYTOPENIA, FAMILIAL, WITH PROPENSITY TO ACUTE MYELOGENOUS LEUKEMIA"]} |
A very rare multiple congenital anomalies syndrome characterized by short stature, facial dysmorphism (elongated face, hypertelorism, broad and high nasal bridge, mild epicanthus, posteriorly angulated ears, narrow and high-arched palate), skeletal anomalies (mesomelic brachymelia, short broad hands, prominent finger pads, short stubby thumbs, hyperextensibility of small joints, small feet), hypernasality and normal intelligence. Delayed bone age has also been reported.
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*[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
| Velo-facial-skeletal syndrome | c1833380 | 1,616 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3424 | 2021-01-23T19:12:59 | {"gard": ["5469"], "mesh": ["C536536"], "omim": ["600736"], "umls": ["C1833380"], "icd-10": ["Q87.0"]} |
A number sign (#) is used with this entry because of evidence that short-rib thoracic dysplasia-19 with or without polydactyly (SRTD19) is caused by compound heterozygous mutation in the IFT81 gene (605489) on chromosome 12q24.
Description
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013).
There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330).
For a discussion of genetic heterogeneity of short-rib thoracic dysplasia with or without polydactyly, see SRTD1 (208500).
Clinical Features
Duran et al. (2016) studied 2 unrelated infants with short-rib thoracic dysplasia. The first patient (R98-443) was an African American boy who had dolichocephaly with prominent occiput, midface hypoplasia, handlebar clavicles, short ribs, and short curved appendicular bones, with the upper limbs particularly abnormally shaped. He developed respiratory distress soon after birth which worsened over time, and he died at 19 months of age. The second patient (R13-147A) was a male infant delivered at 35 weeks who died a few minutes after birth from respiratory failure due to severely hypoplastic lungs. Postnatal radiographs showed dolichocephaly with prominent occiput, midface hypoplasia, very small thorax with shortened horizontal ribs, markedly short long bones with rounded metaphyses, and marked hypoplasia of the radii, ulnae, tibiae, and fibulae. Other radiographic features included small iliac bones and postaxial polydactyly of all extremities. Although at birth the genitalia appeared phenotypically female, karyotype analysis showed 46,XY. The authors stated that the features of the first patient were consistent with asphyxiating thoracic dystrophy, whereas the clinical findings in the second patient supported short-rib polydactyly syndrome type II (Mohr-Majewski syndrome; see 263520).
Molecular Genetics
In 2 unrelated male patients with SRTD, Duran et al. (2016) performed exome sequencing and identified compound heterozygosity for mutations in the IFT81 gene (605489.0003-605489.0006). One of the patients (R98-443), an African American boy, was also heterozygous for a known variant (R867H; rs76726265) in the SRTD-associated gene TTC21B (612014), but RT-PCR and Western blot analysis showed no differences in mRNA or protein levels between patient and control chondrocytes, and the mutation appeared to be a polymorphism in the African American population, with an ethnicity-specific allele frequency of 0.006 in the ExAC database (February 2018).
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Dolichocephaly \- Relative macrocephaly \- Prominent occiput Face \- Prominent forehead \- Midface hypoplasia \- Long philtrum Ears \- Low-set ears Eyes \- Prominent eyes Nose \- Depressed nasal bridge CARDIOVASCULAR Heart \- Ventricular septal defect (in 1 patient) RESPIRATORY Lung \- Pulmonary hypoplasia CHEST Ribs Sternum Clavicles & Scapulae \- Handlebar clavicles \- Narrow chest \- Short ribs \- Horizontal ribs ABDOMEN External Features \- Omphalocele GENITOURINARY External Genitalia (Male) \- Ambiguous genitalia (in 1 patient) SKELETAL Skull \- Dolichocephaly \- Relative macrocephaly \- Prominent occiput Pelvis \- Small iliac bones (in 1 patient) Limbs \- Short long bones \- Curved long bones \- Hypoplasia of long bones \- Rounded metaphyses Hands \- Brachydactyly \- Postaxial polydactyly (in 1 patient) \- Syndactyly (in 1 patient) Feet \- Postaxial polydactyly (in 1 patient) \- Syndactyly (in 1 patient) NEUROLOGIC Central Nervous System \- Global hypotonia MISCELLANEOUS \- Death in infancy or early childhood \- Based on report of 2 unrelated male patients (last curated February 2018) MOLECULAR BASIS \- Caused by mutation in the intraflagellar transport 81 gene (IFT81, 605489.0003 ) ▲ Close
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*[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
| SHORT-RIB THORACIC DYSPLASIA 19 WITH OR WITHOUT POLYDACTYLY | c4693524 | 1,617 | omim | https://www.omim.org/entry/617895 | 2019-09-22T15:44:28 | {"omim": ["617895"]} |
A number sign (#) is used with this entry because pseudopseudohypoparathyroidism (PPHP) is caused by a mutation resulting in loss of function of the Gs-alpha isoform of the GNAS gene (139320) on the paternal allele. This results in expression of the Gs-alpha protein only from the maternal allele.
See also pseudohypoparathyroidism type Ia (PHP1A; 103580), which is caused by a mutation resulting in loss of function of the Gs-alpha isoform of the GNAS gene on the maternal allele and resultant expression of the Gs-alpha protein only from the paternal allele.
Description
Patients with pseudopseudohypoparathyroidism do not show resistance to parathyroid hormone (PTH; 168450) or other hormones, as is the case with PHP1A (103580), but do manifest the constellation of clinical features referred to as Albright hereditary osteodystrophy (AHO), which includes short stature, obesity, round facies, subcutaneous ossifications, brachydactyly, and other skeletal anomalies. Some patients have mental retardation (Kinard et al., 1979; Fitch, 1982; Mantovani and Spada, 2006).
PPHP occurs only after paternal inheritance of the molecular defect, whereas PHP1A occurs only after maternal inheritance of the molecular defect (see Inheritance and Pathogenesis below). This is an example of imprinting, with differential gene expression depending on the parent of origin of the allele (Davies and Hughes, 1993; Wilson et al., 1994).
For a general phenotypic description, classification, and a discussion of molecular genetics of pseudohypoparathyroidism, see PHP1A (103580).
Clinical Features
Albright et al. (1952) described a 29-year-old woman with physical features similar to those reported by Albright et al. (1942) as Albright hereditary osteodystrophy, but there were no serum calcium abnormalities suggestive of PTH resistance. Albright et al. (1952) termed this disorder 'pseudopseudohypoparathyroidism' (PPHP) to distinguish it from the disorder reported by Albright et al. (1942) as 'pseudohypoparathyroidism.'
Weinberg and Stone (1971) described a family in which a brother and sister had PHP1A (103580) and the son and daughter of the brother had PPHP. All had clinical features of AHO, which were more prominent in the patients with PHP1A. The patients were of normal intelligence but showed ectopic calcification and ossification, rounded facies, 'absent 4th knuckles,' and short feet and hands with particularly short fourth metacarpals.
Warner et al. (1998) reported a 24-year-old man with PPHP. Developmental delay, brachycephaly, and decreased muscle tone were noted by age 10 months. Throughout childhood he was small for his age and stocky in appearance. By 6 years, he developed learning disabilities as well as impulsive and aggressive behavior. Brachydactyly involved the distal phalanx of the thumb and the fourth metacarpals bilaterally. He also had intracranial calcifications in the globus pallidus. There was no evidence of resistance to parathyroid hormone or thyrotropin. Genetic analysis identified a de novo heterozygous mutation in the GNAS gene (139320.0016).
Fischer et al. (1998) reported a large kindred in which 2 mothers with PPHP had 6 offspring with PHP Ia. The PPHP patients had decreased erythrocyte Gs activity, but normal urinary cAMP responses to PTH, normal TSH levels and responses to TRH, and normal serum levels of calcium and PTH.
Biochemical Features
Chase et al. (1969) found that persons with PPHP showed abnormally high basal urinary excretion of cyclic AMP (cAMP) and a normal increase in urinary cAMP after PTH infusion. This finding was in contrast to persons with PHP1A (103580), who had blunted urinary cAMP excretion after PTH infusion.
Inheritance
Chase et al. (1969) reported a family in which 2 patients with PHP (103580) were the progeny of a mother with PPHP. Another family had 3 brothers with PHP; the mother had PPHP.
Weinberg and Stone (1971) described a family in which a brother and sister had PHP1 and the son and daughter of the brother had PPHP. All had clinical features of AHO, which were more prominent in the patients with PHP1. The patients were of normal intelligence but showed ectopic calcification and ossification, rounded facies, 'absent 4th knuckles,' and short feet and hands with particularly short fourth metacarpals.
In a review of the literature, Fitch (1982) favored autosomal dominant inheritance with sex modification.
Fitch (1982) and Kinard et al. (1979) also reported kindreds in which some individuals had AHO without hormone resistance (PPHP), while others had hormone resistance as well (PHP1A), suggesting that PHP and PPHP are genetically related.
Williams et al. (1977) described 4 females and 1 male in a family pedigree who showed wide clinical variability encompassing both PHP and PPHP. Farfel et al. (1981) reported a woman with PPHP whose daughter had classic PHP type Ia. The mother had AHO, no history of hypocalcemia or other endocrine abnormalities, and reduced N-protein activity.
Wilson et al. (1994) used an intragenic GNAS1 FokI polymorphism to determine the parental origin of the gene mutations in sporadic and familial AHO. A mutation identified in a sporadic case of PPHP was found to be paternally derived.
Pathogenesis
GNAS is a heavily imprinted locus, with different expression of its isoforms in different tissues dependent on the parental origin of the gene. Individuals with PHP1A (103580) and PPHP show about a 50% decrease in Gs expression in erythrocytes, which normally express both parental alleles. Renal tubule cells are unique in that they only express the maternal allele of Gs; the paternal allele is not expressed. Thus, renal cells of PPHP patients have normal Gs expression when a defect in the GNAS gene is inherited from the father because maternal expression remains normal. These patients have normal cAMP response to PTH infusion and lack features of hormone resistance. The features of AHO are believed to result from defective signaling in other cells due to Gs haploinsufficiency (Bastepe and Juppner, 2005; Mantovani and Spada, 2006).
Molecular Genetics
In a mother with PPHP and her 4 daughters with PHP Ia (103580) (Kinard et al., 1979), Weinstein et al. (1990) identified a heterozygous mutation in the GNAS gene (139320.0002). A son of 1 of the affected daughters also had PHP Ia and carried the mutation.
In affected members of a large kindred in which 2 mothers had PPHP and their 6 offspring had PHP Ia, Fischer et al. (1998) identified a heterozygous mutation in the GNAS gene (139320.0015).
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Weight \- Obesity HEAD & NECK Face \- Round face \- Full cheeks Eyes \- Cataract \- Nystagmus Nose \- Low nasal bridge Teeth \- Delayed tooth eruption \- Enamel hypoplasia Neck \- Short neck SKELETAL \- Osteoporosis Hands \- Brachydactyly \- Short metacarpals (especially 4th and 5th) Feet \- Brachydactyly \- Short metatarsals (especially 4th and 5th) SKIN, NAILS, & HAIR Skin \- Subcutaneous ossifications NEUROLOGIC Central Nervous System \- Cognitive deficits \- Mental retardation (less common) ENDOCRINE FEATURES \- No hormone resistance LABORATORY ABNORMALITIES \- Normal urinary cyclic AMP response to PTH administration \- Reduced erythrocyte Gs activity MISCELLANEOUS \- Variable phenotype \- Caused by inheritance of the mutation on the paternal allele (imprinting) \- See also pseudohypoparathyroidism type Ia ( 103580 ) MOLECULAR BASIS \- Caused by mutation in the guanine nucleotide-binding protein, alpha-stimulating activity polypeptide gene (GNAS, 139320.0002 ) ▲ Close
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*[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
| PSEUDOPSEUDOHYPOPARATHYROIDISM | c0033835 | 1,618 | omim | https://www.omim.org/entry/612463 | 2019-09-22T16:01:22 | {"doid": ["4183"], "mesh": ["D011556"], "omim": ["612463"], "orphanet": ["79445"], "synonyms": ["Alternative titles", "ALBRIGHT HEREDITARY OSTEODYSTROPHY WITHOUT MULTIPLE HORMONE RESISTANCE"], "genereviews": ["NBK459117"]} |
Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD)
Other namesCarnitine deficiency secondary to medium-chain acyl-CoA dehydrogenase deficiency,[1] MCAD deficiency or MCADD
This condition is inherited in an autosomal recessive manner.
SpecialtyEndocrinology
Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency or MCADD), is a disorder of fatty acid oxidation that impairs the body's ability to break down medium-chain fatty acids into acetyl-CoA. The disorder is characterized by hypoglycemia and sudden death without timely intervention, most often brought on by periods of fasting or vomiting.
Prior to expanded newborn screening, MCADD was an underdiagnosed cause of sudden death in infants. Individuals who have been identified prior to the onset of symptoms have an excellent prognosis.
MCADD is most prevalent in individuals of Northern European Caucasian descent, with an incidence of 1:4000 to 1:17,000 depending on the population. Treatment of MCADD is mainly preventive, by avoiding fasting and other situations where the body relies on fatty acid oxidation to supply energy.
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Incidence
* 7 References
* 8 External links
## Signs and symptoms[edit]
MCAD is one of the enzymes responsible for dehydrogenation of fatty acids as they cycle through the beta-oxidation spiral.
MCADD presents in early childhood with hypoketotic hypoglycemia and liver dysfunction, often preceded by extended periods of fasting or an infection with vomiting. Infants who are exclusively breast-fed may present in this manner shortly after birth, due to poor feeding. In some individuals the first manifestation of MCADD may be sudden death following a minor illness.[2] A number of individuals with MCADD may remain completely asymptomatic, provided they never encounter a situation that sufficiently stresses their metabolism.[2][3] With the advent of expanded newborn screening, some mothers have been identified with MCADD after their infants had positive newborn screens for low carnitine levels.[4]
The enzyme MCAD is responsible for the dehydrogenation step of fatty acids with chain lengths between 6 and 12 carbons as they undergo beta-oxidation in the mitochondria. Fatty acid beta-oxidation provides energy after the body has used up its stores of glucose and glycogen. This oxidation typically occurs during periods of extended fasting or illness when caloric intake is reduced, and energy needs are increased.
## Genetics[edit]
MCADD is inherited in an autosomal recessive manner, meaning an affected individual must inherit a mutated allele from both of their parents. ACADM is the gene involved, located at 1p31, with 12 exons and coding for a protein of 421 amino acids.[3] There is a common mutation among Northern European Caucasians, 985A>G, which results in a lysine being replaced by a glutamic acid at position 304 of the protein. Other mutations have been identified more commonly since newborn screening has expanded the mutation spectrum.[3] The 985A>G common mutation is present in the homozygous state in 80% of Caucasian individuals who presented clinically with MCADD and in 60% of the population identified by screening.[2]
An individual's genotype does not correlate well with their clinical phenotype for MCADD. The clinical presentation of an individual with MCADD depends not only on the presence of the mutations in the ACADM gene, but also on the presence of environmental or physiological stressors that require the body to depend on fatty acid oxidation for energy. Some mutations, identified through newborn screening programs and associated with higher residual enzyme activity have not been seen in individuals with clinical symptoms of MCADD. Despite this, treatment with fasting avoidance remains the norm for all those diagnosed with MCADD.[2]
## Diagnosis[edit]
Clinically, MCADD or another fatty acid oxidation disorder is suspected in individuals who present with lethargy, seizures, coma and hypoketotic hypoglycemia, particularly if triggered by a minor illness. MCADD can also present with acute liver disease and hepatomegaly, which can lead to a misdiagnosis of Reye syndrome. In some individuals, the only manifestation of MCADD is sudden, unexplained death often preceded by a minor illness that would not usually be fatal.[3]
Acylcarnitine profile of an individual with MCADD, showing characteristic elevation of octanoylcarnitine (C8).
In areas with expanded newborn screening using tandem mass spectrometry (MS/MS), MCADD is usually detected shortly after birth, by the analysis of blood spots collected on filter paper. Acylcarnitine profiles with MS/MS will show a very characteristic pattern of elevated hexanoylcarnitine (C6), octanoylcarnitine (C8), decanoylcarnitine (C10) or decenoylcarnitine (C10:1), with C8 being greater than C6 and C10. Secondary carnitine deficiency is sometimes seen with MCADD, and in these cases, acylcarnitine profiles may not be informative.[3] Urine organic acid analysis by gas chromatography-mass spectrometry (GC-MS) will show a pattern of dicarboxylic aciduria with low levels of ketones. Traces of acylglycine species may also be detected. Asymptomatic individuals may have normal biochemical lab results. For these individuals, targeted analysis of acylglycine species by GC-MS, specifically hexanoylglycine and suberylglycine can be diagnostic.[3][5] After biochemical suspicion of MCADD, molecular genetic analysis of ACADM can be used to confirm the diagnosis.[6] The analysis of MCAD activity in cultured fibroblasts can also be used for diagnosis.[3]
In cases of sudden death where the preceding illness would not usually have been fatal, MCADD is often suspected. The autopsy will often show fatty deposits in the liver. In cases where MCADD is suspected, acylcarnitine analysis of bile and blood can be undertaken postmortem for diagnosis. Where samples are not available, residual blood from newborn screening may be helpful. Biochemical testing of asymptomatic siblings and parents may also be informative.[7] MCADD and other fatty acid oxidation disorders have been recognized in recent years as undiagnosed causes of sudden infant death syndrome.[8][9]
## Treatment[edit]
As with most other fatty acid oxidation disorders, individuals with MCADD need to avoid fasting for prolonged periods of time. During illnesses, they require careful management to stave off metabolic decompensation, which can result in death.[2] Supplementation of simple carbohydrates or glucose during illness is key to prevent catabolism.[3] The duration of fasting for individuals with MCADD varies with age, infants typically require frequent feedings or a slow release source of carbohydrates, such as uncooked cornstarch. Illnesses and other stresses can significantly reduce the fasting tolerance of affected individuals.[10]
Individuals with MCADD should have an "emergency letter" that allows medical staff who are unfamiliar with the patient and the condition to administer correct treatment properly in the event of acute decompensation. This letter should outline the steps needed to intervene in a crisis and have contact information for specialists familiar with the individual's care.[3]
Misdiagnosis issues
* The MCADD disorder is commonly mistaken for Reye Syndrome by pediatricians. Reye Syndrome is a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu.
* Most cases of Reye Syndrome are associated with the use of Aspirin during these viral infections.
## Prognosis[edit]
A 1994 study of the entire population of New South Wales (Australia) found 20 patients. Of these, 5 (25%) had died at or before 30 months of age. Of the survivors, 1 (5%) was severely disabled and the remainder had either suffered mild disability or were making normal progress in school.[11] A 2006 Dutch study followed 155 cases and found that 27 individuals (17%) had died at an early age. Of the survivors, 24 (19%) suffered from some degree of disability, of which most were mild. All the 18 patients diagnosed neonatally were alive at the time of the follow-up.[12]
## Incidence[edit]
MCADD is most prevalent in individuals of Northern European Caucasian descent. The incidence in Northern Germany is 1:4000, currently the highest in the world. Northern Europe is also the origin of the common mutation in MCADD. For populations without origins in Northern Europe, the incidence is significantly lower, 1:51,000 in Japan and 1:700,000 in Taiwan. The common mutation has not been identified in MCADD cases identified in Asian populations.[3]
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Medium chain acyl CoA dehydrogenase deficiency". www.orpha.net. Retrieved 14 April 2019.
2. ^ a b c d e Morris, Andrew A.M.; Spiekerkoetter, Ute (2012). "Disorders of Mitochondrial Fatty Acid Oxidation and Related Metabolic Pathways". In Saudubray, Jean-Marie; van den Berghe, Georges; Walter, John H. (eds.). Inborn Metabolic Diseases: Diagnosis and Treatment (5th ed.). New York: Springer. pp. 201–216. ISBN 978-3-642-15719-6.
3. ^ a b c d e f g h i j Matern, D.; Rinaldo, P.; Pagon, R. A.; Bird, T. D.; Dolan, C. R.; Stephens, K.; Adam, M. P. (1993). "Medium-Chain Acyl-Coenzyme a Dehydrogenase Deficiency". PMID 20301597. Cite journal requires `|journal=` (help)
4. ^ Leydiker, K. B.; Neidich, J. A.; Lorey, F.; Barr, E. M.; Puckett, R. L.; Lobo, R. M.; Abdenur, J. E. (2011). "Maternal medium-chain acyl-CoA dehydrogenase deficiency identified by newborn screening". Molecular Genetics and Metabolism. 103 (1): 92–95. doi:10.1016/j.ymgme.2011.01.011. PMID 21354840.
5. ^ Rinaldo, P.; O'Shea, J. J.; Coates, P. M.; Hale, D. E.; Stanley, C. A.; Tanaka, K. (1988). "Medium-Chain Acyl-CoA Dehydrogenase Deficiency". New England Journal of Medicine. 319 (20): 1308–1313. doi:10.1056/NEJM198811173192003. PMID 3054550.
6. ^ "C8 Elevated + Lesser Elevations of C6 and C10" (PDF). American College of Medical Genetics. Retrieved 2012-06-09.
7. ^ Rinaldo, P.; Matern, D.; Bennett, M. J. (2002). "Fattyacidoxidationdisorders". Annual Review of Physiology. 64: 477–502. doi:10.1146/annurev.physiol.64.082201.154705. PMID 11826276.
8. ^ Hegyi, T.; Ostfeld, B.; Gardner, K. (1992). "Medium chain acyl-coenzyme a dehydrogenase deficiency and SIDS". New Jersey Medicine : The Journal of the Medical Society of New Jersey. 89 (5): 385–392. PMID 1635678.
9. ^ Keppen, L. D.; Randall, B. (1999). "Inborn defects of fatty acid oxidation: A preventable cause of SIDS". South Dakota Journal of Medicine. 52 (6): 187–188, discussion 188–9. PMID 10388343.
10. ^ Walter, J. H. (2009). "Tolerance to fast: Rational and practical evaluation in children with hypoketonaemia". Journal of Inherited Metabolic Disease. 32 (2): 214–217. doi:10.1007/s10545-009-1087-y. PMID 19255872.
11. ^ Wilcken, B.; Hammond, J.; Silink, M. (1994-05-01). "Morbidity and mortality in medium chain acyl coenzyme A dehydrogenase deficiency". Archives of Disease in Childhood. 70 (5): 410–412. doi:10.1136/adc.70.5.410. ISSN 1468-2044. PMC 1029830. PMID 8017963.
12. ^ Derks, Terry G.J.; Reijngoud, Dirk-Jan; Waterham, Hans R.; Gerver, Willem-Jan M.; Berg, Maarten P. van den; Sauer, Pieter J.J.; Smit, G. Peter A. (2006). "The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: Clinical presentation and outcome". The Journal of Pediatrics. 148 (5): 665–670.e3. doi:10.1016/j.jpeds.2005.12.028. PMID 16737882.
## External links[edit]
Classification
D
* ICD-10: E71.311
* ICD-9-CM: 277.85
* OMIM: 201450
* MeSH: C536038
* DiseasesDB: 7914
External resources
* eMedicine: ped/1392
* CDC MCADD
* NIH MCADD
* v
* t
* e
Inborn error of lipid metabolism: fatty-acid metabolism disorders
Synthesis
* Biotinidase deficiency (BTD)
Degradation
Acyl
transport
* Carnitine
* CPT1
* CPT2
* CDSP
* CACTD
* Adrenoleukodystrophy (ALD)
Beta
oxidation
General
* Acyl CoA dehydrogenase
* Short-chain SCADD
* Medium-chain MCADD
* Long-chain 3-hydroxy LCHAD
* Very long-chain VLCADD
* Mitochondrial trifunctional protein deficiency (MTPD): Acute fatty liver of pregnancy
Unsaturated
* 2,4 Dienoyl-CoA reductase deficiency (DECRD)
Odd chain
* Propionic acidemia (PCC deficiency)
Other
* 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADHD)
* Glutaric acidemia type 2 (MADD)
To
acetyl-CoA
* Malonic aciduria (MCD)
Aldehyde
* Sjögren–Larsson syndrome (SLS)
*[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
| Medium-chain acyl-coenzyme A dehydrogenase deficiency | c0220710 | 1,619 | wikipedia | https://en.wikipedia.org/wiki/Medium-chain_acyl-coenzyme_A_dehydrogenase_deficiency | 2021-01-18T19:03:59 | {"gard": ["540"], "mesh": ["C536038"], "umls": ["C0220710"], "icd-9": ["277.85"], "icd-10": ["E71.311"], "orphanet": ["42"], "wikidata": ["Q750826"]} |
Carcinosis, or carcinomatosis, is disseminated cancer, forms of metastasis, whether used generally or in specific patterns of spread.
## Contents
* 1 Usage
* 2 Lung
* 2.1 Lymphangitic carcinomatosis
* 2.2 Miliary carcinosis
* 3 Body cavities
* 3.1 Peritoneal carcinomatosis
* 3.2 Pleural carcinosis
* 3.3 Leptomeningeal carcinomatosis
* 4 Treatment
* 5 References
* 6 External links
## Usage[edit]
Carcinomatosis is often restricted to tumors of epithelial origin, adenocarcinomas, while sarcomatosis describes the dissemination of tumors of mesenchymal origin, sarcomas.[1]
## Lung[edit]
### Lymphangitic carcinomatosis[edit]
When most tumors metastasize to the lung, they form distinct nodules, but about 7% spread through the lymph vessels of the lung.[2] They may impair breathing in several ways; the lung becomes stiffer; blood vessels traveling alongside the distended lymph vessels become compressed.[3]
### Miliary carcinosis[edit]
A pattern of multiple small nodular metastases has been described as miliary carcinosis which has a radiographic appearance similar to miliary tuberculosis.[4]
## Body cavities[edit]
Any potential space may be seeded with tumor cells that grow along surfaces, but which may not invade below the surfaces. In rare cases, the joint spaces are affected.[5]
### Peritoneal carcinomatosis[edit]
Intestines with peritoneal carcinomatosis from gastric cancer, appearing as a grainy serosal surface.
Main article: Peritoneal carcinomatosis
The lining of the abdominal cavity is a common site for surface dissemination. Ovarian carcinomas are common. Fluid produced by the cells can produce ascites which is typical in carcinomatosis, but less common in peritoneal sarcomatosis.[1] Fluid can be serous as seen in primary peritoneal carcinoma or mucinous such as found in pseudomyxoma peritonei which is typically a tumor derived from the appendix.[6]
### Pleural carcinosis[edit]
Pleural carcinosis is associated with malignant pleural effusion and poor prognosis.[7]
### Leptomeningeal carcinomatosis[edit]
The meningeal covering of the central nervous system may be the site of tumor growth. Breast cancer, lung cancer and melanoma are the most common tumors.[8]
## Treatment[edit]
Colorectal cancer patients with peritoneal involvement can be treated with Oxaliplatin- or Irinotecan-based chemotherapy. Such treatment is not expected to be curative, but can extend the lives of patients.[9] Some patients may be cured through Hyperthermic intraperitoneal chemotherapy, but the procedure entails a high degree of risk for morbidity or death.
## References[edit]
1. ^ a b Oei, T. N.; Jagannathan, J. P.; Ramaiya, N.; Ros, P. R. (2010). "Peritoneal Sarcomatosis Versus Peritoneal Carcinomatosis: Imaging Findings at MDCT". American Journal of Roentgenology. 195 (3): W229–W235. doi:10.2214/AJR.09.3907. ISSN 0361-803X. PMID 20729420.
2. ^ Prakash, P.; Kalra, M. K.; Sharma, A.; Shepard, J.-A. O.; Digumarthy, S. R. (2009). "FDG PET/CT in Assessment of Pulmonary Lymphangitic Carcinomatosis". American Journal of Roentgenology. 194 (1): 231–236. doi:10.2214/AJR.09.3059. ISSN 0361-803X. PMID 20028927.
3. ^ Mark A. Marinella (7 May 2009). "12. Lymphangitic carcinomatosis". Handbook of Cancer Emergencies. Jones & Bartlett Learning. pp. 55–57. ISBN 978-0-7637-6989-5. Retrieved 29 February 2012.
4. ^ Marks, J. L. (1950). "Metastatic Tumors of the Lung". Chest. 17 (1): 63–73. doi:10.1378/chest.17.1.63. ISSN 0012-3692. PMID 15399335.
5. ^ Currall, Verity A.; Dixon, John H. (2008). "Synovial Metastasis". The Journal of Arthroplasty. 23 (4): 631–636. doi:10.1016/j.arth.2007.04.034. ISSN 0883-5403. PMID 18514889.
6. ^ Young, Robert H. (2004). "Pseudomyxoma peritonei and selected other aspects of the spread of appendiceal neoplasms". Seminars in Diagnostic Pathology. 21 (2): 134–150. doi:10.1053/j.semdp.2004.12.002. ISSN 0740-2570. PMID 15807473.
7. ^ Ruffini, E (2002). "The significance of intraoperative pleural effusion during surgery for bronchogenic carcinoma". European Journal of Cardio-Thoracic Surgery. 21 (3): 508–513. doi:10.1016/S1010-7940(01)01166-6. ISSN 1010-7940. PMID 11888772.
8. ^ Martins, Sandro José; Azevedo, Carla Rameri Alexandre Silva de; Chinen, Ludmilla Thomé Domingos; Cruz, Marcelo Rocha Sousa; Peterlevitz, Marcos Aurélio; Gimenes, Daniel Luiz (2011). "Meningeal carcinomatosis in solid tumors". Arquivos de Neuro-Psiquiatria. 69 (6): 973–980. doi:10.1590/S0004-282X2011000700024. ISSN 0004-282X. PMID 22297890.
9. ^ Joerg O W Pelz, Terence C. Chua, Jesus Esquivel, et al. BMC Cancer, Volume 10, Published - Dec 22 2010. https://jhu.pure.elsevier.com/en/publications/evaluation-of-best-supportive-care-and-systemic-chemotherapy-as-t-3
## External links[edit]
* Carcinosis entry in the public domain NCI Dictionary of Cancer Terms
*[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
| Carcinosis | c0205699 | 1,620 | wikipedia | https://en.wikipedia.org/wiki/Carcinosis | 2021-01-18T18:36:22 | {"mesh": ["D002277"], "umls": ["C0205699"], "wikidata": ["Q837583"]} |
Acute exacerbation of chronic obstructive pulmonary disease
Other namesAcute exacerbations of chronic bronchitis (AECB)
Chest X-ray in a case of COPD exacerbation where a nasopharyngeal swab detected Haemophilus influenzae, with right-sided opacities.
SpecialtyRespirology, emergency medicine
An acute exacerbation of chronic obstructive pulmonary disease or acute exacerbations of chronic bronchitis (AECB), is a sudden worsening of chronic obstructive pulmonary disease (COPD) symptoms including shortness of breath, quantity and color of phlegm that typically lasts for several days.
It may be triggered by an infection with bacteria or viruses or by environmental pollutants. Typically, infections cause 75% or more of the exacerbations; bacteria can roughly be found in 25% of cases, viruses in another 25%, and both viruses and bacteria in another 25%. Airway inflammation is increased during the exacerbation resulting in increased hyperinflation, reduced expiratory air flow and decreased gas exchange.[1][2]
Exacerbations can be classified as mild, moderate, and severe.[3] As COPD progresses, exacerbations tend to become more frequent, the average being about three episodes per year.[4]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 5.1 Oxygen
* 5.2 Medications
* 5.3 Mechanical ventilation
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and symptoms[edit]
An acute exacerbation of COPD is associated with increased frequency and severity of coughing.[5] It is often accompanied by worsened chest congestion and discomfort. Shortness of breath and wheezing are present in many cases.[5] Exacerbations may be accompanied by increased amount of cough and sputum productions, and a change in appearance of sputum.[citation needed] An abrupt worsening in COPD symptoms may cause rupture of the airways in the lungs, which in turn may cause a spontaneous pneumothorax.[4]
In infection, there is often weakness, fever and chills. If due to a bacterial infection, the sputum may be slightly streaked with blood and coloured yellow or green.[5]
## Causes[edit]
As the lungs tend to be vulnerable organs due to their exposure to harmful particles in the air, several things can cause an acute exacerbation of COPD:
* Respiratory infection, being responsible for approximately half of COPD exacerbations. Approximately half of these are due to viral infections and another half appears to be caused by bacterial infections.[6] Common bacterial pathogens of acute exacerbations include Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis.[7] Less common bacterial pathogens include Chlamydia pneumoniae and MRSA.[7] Pathogens seen more frequently in patients with impaired lung function (FEV<35% of predicted) include Haemophilus parainfluenzae (after repeated use of antibiotics), Mycoplasma pneumoniae and gram-negative, opportunistic pathogens like Pseudomonas aeruginosa and Klebsiella pneumoniae.[7]
* Allergens, e.g., pollens, wood or cigarette smoke, pollution[5]
* Toxins, including a variety of different chemicals[5]
* Air pollution[citation needed]
* Failing to follow a drug therapy program, e.g. improper use of an inhaler[citation needed]
In one-third of all COPD exacerbation cases, the cause cannot be identified.[citation needed]
## Diagnosis[edit]
See also: COPD § Diagnosis
The diagnostic criteria for acute exacerbation of COPD generally include a production of sputum that is purulent[7] and may be thicker[5] than usual, but without evidence of pneumonia (which involves mainly the alveoli rather than the bronchi).[5] Also, diagnostic criteria may include an increase in frequency and severity of coughing,[5] as well as increased shortness of breath.[7]
A chest X-ray is usually performed on people with fever and, especially, hemoptysis (blood in the sputum), to rule out pneumonia and get information on the severity of the exacerbation. Hemoptysis may also indicate other, potentially fatal, medical conditions.[5]
A history of exposure to potential causes and evaluation of symptoms may help in revealing the cause the exacerbation, which helps in choosing the best treatment. A sputum culture can specify which strain is causing a bacterial AECB.[5] An early morning sample is preferred.[7]
E-nose showed the ability to smell the cause of the exacerbation.[8]
The definition of a COPD exacerbation is commonly described as "lost in translation,"[9] meaning that there is no universally accepted standard with regard to defining an acute exacerbation of COPD. Many organizations consider it a priority to create such a standard, as it would be a major step forward in the diagnosis and quality of treatment of COPD.[citation needed]
## Prevention[edit]
Acute exacerbations can be partially prevented. Some infections can be prevented by vaccination against pathogens such as influenza and Streptococcus pneumoniae. Regular medication use can prevent some COPD exacerbations; long acting beta-adrenoceptor agonists (LABAs), long-acting anticholinergics, inhaled corticosteroids and low-dose theophylline have all been shown to reduce the frequency of COPD exacerbations.[10][11][12][13] Other methods of prevention include:
* Smoking cessation and avoiding dust, passive smoking, and other inhaled irritants[5]
* Yearly influenza and 5-year pneumococcal vaccinations[5]
* Regular exercise, appropriate rest, and healthy nutrition[5]
* Avoiding people currently infected with e.g. cold and influenza[5]
* Maintaining good fluid intake and humidifying the home, in order to help reduce the formation of thick sputum and chest congestion.[5]
## Treatment[edit]
Based on the severity different treatments may be used.[3] Mild exacerbations are treated with short acting bronchodilators (SABDs). Moderate exacerbations are treated with SABDs together with antibiotics or oral corticosteroids, or both. Severe exacerbations need hospital treatment, and the prognosis is poor.[3]
### Oxygen[edit]
Oxygen therapy should be initiated if there is significantly low blood oxygen. High flow oxygen may be harmful in those with an acute exacerbation of COPD. In the prehospital environment those given high flow O2 rather than titrating their O2 saturations to 88% to 92% had worse outcomes.[14] Antibiotics and steroids appear useful in mild to severe disease.[15]
### Medications[edit]
* Inhaled bronchodilators open up the airways in the lungs.[16] These include salbutamol and terbutaline (both β2-adrenergic agonists), and ipratropium (an anticholinergic).[5] Medication can be administered via inhaler or nebuliser. There is no evidence to prefer a nebuliser over an inhaler.[17]
* Antibiotics are used if a bacterial infection is the suspected cause.[5] However, antibiotics will not treat exacerbations caused by viruses. Viral infections will usually be cured with time with the aid of proper rest and care. Still, other medications may be needed to control symptoms.[5] Lipid-soluble antibiotics such as macrolides, tetracyclines, and fluoroquinolones penetrate the lung tissue well.[7] Macrolides are more active against Streptococcus pneumoniae than the tetracyclines and the older fluoroquinolones.[7] Within the macrolides, newer ones are more active against Haemophilus influenzae than the older erythromycin. Regimens should generally be given for five days.[7] Choice of antibiotics is also dependent on the severity of the symptoms:
* "Simple" COPD is generally where a person 65 years or less, has fewer than four exacerbations per year, has minimal or moderate impairment in respiratory function and no comorbid disease.[7] In patients with "simple" COPD, therapy should be targeted towards Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and possibly pathogens of atypical pneumonia.[7] The first-line treatment is a beta-lactam antibiotic such as amoxicillin. The choice will depend on resistance patterns.[7] In patients with penicillin allergy, doxycycline or trimethoprim are preferred.[7]
* More complicated bronchitis may be when the patient is more than 65 years old, has four or more exacerbations per year, has an FEV1/FVC ratio of less than 50% on spirometry, has failed to respond to previous antibiotic treatment, and/or has comorbidity.[7] In these cases, treatment should be aimed at Gram-negative bacteria and the possibility of high antibiotic resistance should be considered.[7] Sputum culture results are of great value in determining antibiotic resistance.[7] First-line treatment is cefuroxime or co-amoxiclav.[7] Third-line treatment, as well as treatment in penicillin-allergic patients, is a fluoroquinolone such as ciprofloxacin.[7] An agent active against Streptococcus pneumoniae may have to be added.[7]
* Corticosteroids such as prednisolone reduce inflammation in the airways.[16] According to a 2018 systematic review, a shorter, five-day course of systemic corticosteroids is likely comparable to longer (10–14 day) therapy for treatment of COPD exacerbation (Odds ratio (OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46).[18]
* Theophylline is generally not recommended.
There should also be a "care plan" in case of future exacerbations. Patients may watch for symptoms, such as shortness of breath, change in character or amount of mucus, and start self-treatment as discussed with a health care provider. This allows for treatment right away until a doctor can be seen.[5]
The symptoms of acute exacerbations are treated using short-acting bronchodilators. A course of corticosteroids, usually in tablet or intravenous rather than inhaled form, can speed up recovery.[1] The IV and oral forms of steroids have been found to be equivalent.[19] Antibiotics are often used but will only help if the exacerbation is due to an infection.[20] Antibiotics are indicated when a patient notes increased sputum production,[6] purulent sputum,[6] increased dyspnea,[6] has an elevated white count, or is febrile. Examples of first-line antibiotics are amoxicillin,[6] doxycycline,[6] and co-trimoxazole.[6]
### Mechanical ventilation[edit]
Severe exacerbations can require hospital care where treatments such as oxygen and mechanical ventilation may be required.[21] Mechanical ventilation can be invasive (endotracheal intubation) or non-invasive forms of ventilation such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP).[citation needed]
## Epidemiology[edit]
The incidence varies depending on which definition is used, but definitions by Anthonisen et al.[22] the typical COPD patient averages two to three AECB episodes per year.[23] With a COPD prevalence of more than 12 million (possibly 24 million including undiagnosed ones) in the United States,[24] there are at least 30 million incidences of AECB annually in the US.
## References[edit]
1. ^ a b Rabe KF, Hurd S, Anzueto A, et al. (2007). "Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary". Am. J. Respir. Crit. Care Med. 176 (6): 532–55. doi:10.1164/rccm.200703-456SO. hdl:2066/51740. PMID 17507545.
2. ^ van Geffen WH, Slebos DJ, Kerstjens HA (2015). "Hyperinflation in COPD exacerbations". The Lancet Respiratory Medicine. 3 (12): 43–44. doi:10.1016/S2213-2600(15)00459-2. PMID 26679031.
3. ^ a b c "Assessment of exacerbation risk" (PDF). pp. 32–33. Retrieved 22 September 2019.
4. ^ a b "Chronic Obstructive Pulmonary Disease (COPD)". Merck Sharp & Dohme Corp. Retrieved 19 May 2014.
5. ^ a b c d e f g h i j k l m n o p q r s > Acute Exacerbations of Chronic Bronchitis. Retrieved March 13, 2010
6. ^ a b c d e f g Uppsala Academic Hospital > Guidelines for treatment of acute lung diseases. August 2004. Authors: Christer Hanson, Carl-Axel Karlsson, Mary Kämpe, Kristina Lamberg, Eva Lindberg, Lavinia Machado Boman, Gunnemar Stålenheim
7. ^ a b c d e f g h i j k l m n o p q r s The British Society for Antimicrobial Chemotherapy > Acute exacerbations of chronic bronchitis (AECB) Archived 2006-04-06 at the Wayback Machine. Retrieved March 13, 2010
8. ^ Geffen, Wouter H. van; Bruins, Marcel; Kerstjens, Huib A. M. (2016-01-01). "Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study". Journal of Breath Research. 10 (3): 036001. Bibcode:2016JBR....10c6001V. doi:10.1088/1752-7155/10/3/036001. ISSN 1752-7163. PMID 27310311.
9. ^ Makris D, Bouros D (January 2009). "COPD Exacerbtion: Lost in Translation". BMC Pulm Med. 9 (6): 6. doi:10.1186/1471-2466-9-6. PMC 2640343. PMID 19178701.
10. ^ Calverley PM, Anderson JA, Celli B, et al. (2007). "Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease". N. Engl. J. Med. 356 (8): 775–89. doi:10.1056/NEJMoa063070. PMID 17314337.
11. ^ Tashkin DP, Celli B, Senn S, et al. (October 2008). "A 4-year trial of tiotropium in chronic obstructive pulmonary disease". The New England Journal of Medicine. 359 (15): 1543–54. doi:10.1056/NEJMoa0805800. hdl:2437/111564. PMID 18836213.
12. ^ Zhou Y, Wang X, Zeng X, et al. (2006). "Positive benefits of theophylline in a randomized, double-blind, parallel-group, placebo-controlled study of low-dose, slow-release theophylline in the treatment of COPD for 1 year". Respirology. 11 (5): 603–10. doi:10.1111/j.1440-1843.2006.00897.x. PMID 16916334. S2CID 28582690.
13. ^ Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK (2000). "Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial". BMJ. 320 (7245): 1297–303. doi:10.1136/bmj.320.7245.1297. PMC 27372. PMID 10807619.
14. ^ Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R (2010). "Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial". BMJ. 341: c5462. doi:10.1136/bmj.c5462. PMC 2957540. PMID 20959284.
15. ^ Dobler, CC; Morrow, AS; Beuschel, B; Farah, MH; Majzoub, AM; Wilson, ME; Hasan, B; Seisa, MO; Daraz, L; Prokop, LJ; Murad, MH; Wang, Z (17 March 2020). "Pharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-analysis". Annals of Internal Medicine. 172 (6): 413–422. doi:10.7326/M19-3007. PMID 32092762. S2CID 211476101.
16. ^ a b Bach PB, Brown C, Gelfand SE, McCrory DC (2001). "Management of acute exacerbations of chronic obstructive pulmonary disease: a summary and appraisal of published evidence". Ann. Intern. Med. 134 (7): 600–20. doi:10.7326/0003-4819-134-7-200104030-00016. PMID 11281745. S2CID 35537845.
17. ^ van Geffen WH, Douma WR, Slebos DJ, Kerstjens HA (August 2016). "Bronchodilators delivered by nebuliser versus pMDI with spacer or DPI for exacerbations of COPD". The Cochrane Database of Systematic Reviews (8): CD011826. doi:10.1002/14651858.CD011826.pub2. PMID 27569680.
18. ^ Walters, Julia Ae; Tan, Daniel J.; White, Clinton J.; Wood-Baker, Richard (19 March 2018). "Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 3: CD006897. doi:10.1002/14651858.CD006897.pub4. ISSN 1469-493X. PMC 6494402. PMID 29553157.
19. ^ Lindenauer PK, Pekow PS, Lahti MC, Lee Y, Benjamin EM, Rothberg MB (June 2010). "Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease". JAMA. 303 (23): 2359–67. doi:10.1001/jama.2010.796. PMID 20551406.
20. ^ Gibson, et al. Evidence-based Respiratory Medicine. Blackwell Publishing, 2005. ISBN 0-7279-1605-X. pp. 390–392.
21. ^ Quon BS, Gan WQ, Sin DD (March 2008). "Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis". Chest. 133 (3): 756–66. CiteSeerX 10.1.1.619.4554. doi:10.1378/chest.07-1207. PMID 18321904.
22. ^ Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA (February 1987). "Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease". Ann. Intern. Med. 106 (2): 196–204. doi:10.7326/0003-4819-106-2-196. PMID 3492164.
23. ^ Page 249 in: Balter MS, La Forge J, Low DE, Mandell L, Grossman RF (2003). "Canadian guidelines for the management of acute exacerbations of chronic bronchitis". Can. Respir. J. 10 Suppl B: 3B–32B. doi:10.1155/2003/486285. PMID 12944998. "Archived copy" (PDF). Archived from the original (PDF) on 2013-10-19. Retrieved 2013-10-18.CS1 maint: archived copy as title (link)
24. ^ MORBIDITY & MORTALITY: 2009 CHART BOOK ON CARDIOVASCULAR, LUNG, AND BLOOD DISEASES Archived October 19, 2013, at the Wayback Machine National Heart, Lung, and Blood Institute
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In psychology, false memory syndrome (FMS) describes a condition in which a person's identity and relationships are affected by false memories, recollections that are factually incorrect but yet are strongly believed.[1] Peter J. Freyd originated the term,[2] which his False Memory Syndrome Foundation (FMSF) subsequently popularized. The principle that individuals can hold false memories and the role that outside influence can play in their formation is widely accepted by scientists.[3][4][5][6] However FMS is not recognized as a psychiatric illness[7] in any medical manuals including the ICD-10[8] or the DSM-5.[9]
False memory syndrome may be the result of recovered memory therapy, a term also defined by the FMSF in the early 1990s,[10] which describes a range of therapy methods that are prone to creating confabulations. Some of the influential figures in the genesis of the theory are forensic psychologist Ralph Underwager, psychologist Elizabeth Loftus, and sociologist Richard Ofshe.
## Contents
* 1 Definition
* 2 Recovered memory therapy
* 2.1 Psychiatric controversy concerning recovered memories
* 3 Evidence for false memories
* 3.1 How memory works in the brain
* 3.2 How traumatic memories hide in the brain
* 4 Court cases
* 4.1 Sexual abuse cases
* 4.2 Malpractice cases
* 4.2.1 Injuries resulting from malpractice
* 5 Skepticism of the theory
* 6 In popular culture
* 7 See also
* 8 Footnotes
* 9 External links
## Definition[edit]
False memory syndrome is a condition in which a person's identity and interpersonal relationships center on a memory of a traumatic experience that is objectively false but that the person strongly believes occurred.[11]
The FMS concept is controversial,[12][13] and the Diagnostic and Statistical Manual of Mental Disorders does not include it. Paul R. McHugh, member of the FMSF, stated that the term was not adopted into the fourth version of the manual due to the pertinent committee being headed by believers in recovered memory.[2]
## Recovered memory therapy[edit]
Main article: Recovered memory therapy
Recovered memory therapy is used to describe the therapeutic processes and methods that are believed to create false memories and false memory syndrome. These methods include hypnosis, sedatives and probing questions where the therapist believes repressed memories of traumatic events are the cause of their client's problems.[14] The term is not listed in DSM-IV or used by any mainstream formal psychotherapy modality.[10]
Memory consolidation becomes a critical element of false memory and recovered memory syndromes. Once stored in the hippocampus, the memory may last for years or even for life, regardless that the memorized event never actually took place. Obsession to a particular false memory, planted memory, or indoctrinated memory can shape a person's actions or even result in delusional disorder.
Mainstream psychiatric and psychological professional associations now harbor strong skepticism towards the notion of recovered memories of trauma. The American Psychiatric Association and American Medical Association condemn practices fitting the description of "Recovered Memory Therapy".[medical citation needed] In 1998, the Royal College of Psychiatrists Working Group on Reported Recovered Memories of Sexual Abuse wrote:[15]
> No evidence exists for the repression and recovery of verified, severely traumatic events, and their role in symptom formation has yet to be proved. There is also striking absence in the literature of well-corroborated cases of such repressed memories recovered through psychotherapy. Given the prevalence of childhood sexual abuse, even if only a small proportion are repressed and only some of them are subsequently recovered, there should be a significant number of corroborated cases. In fact there are none.
That such techniques have been used in the past is undeniable. Their continued use is cause for malpractice litigation worldwide.[16] An Australian psychologist was de-registered for engaging in them.[17]
### Psychiatric controversy concerning recovered memories[edit]
In psychiatry, confabulation is a memory error defined as the production of fabricated, distorted, or misinterpreted memories about oneself or the world, without the conscious intention to deceive. Psychotherapists tried to reveal “repressed memories” in mental therapy patients through “hypnosis, guided imagery, dream interpretation and narco-analysis” in the 1980s. The reasoning was that if abuse couldn't be remembered, then it needed to be recovered by the therapist. This type of therapy became popular in the 1990s. Many victims don't remember their abuse, making the underlying phenomenon of trauma-induced amnesia nonetheless legitimate.
Therapists who subscribe to recovered memory theory point to a wide variety of common problems, ranging from eating disorders to sleeplessness, as evidence of repressed memories of sexual abuse.[18] The legal phenomena developed in the 1980s, with civil suits alleging child sexual abuse on the basis of “memories” recovered during psychotherapy. The term “repressed memory therapy” gained momentum and with it social stigma surrounded those accused of abuse. The “therapy” led to other psychological disorders in persons whose memories were recovered.
## Evidence for false memories[edit]
Human memory is created and highly suggestible, and can create a wide variety of innocuous, embarrassing, and frightening memories through different techniques—including guided imagery, hypnosis, and suggestion by others. Though not all individuals exposed to these techniques develop memories, experiments suggest a significant number of people do, and will actively defend the existence of the events, even if told they were false and deliberately implanted. Questions about the possibility of false memories created an explosion of interest in suggestibility of human memory and resulted in an enormous increase in the knowledge about how memories are encoded, stored and recalled, producing pioneering experiments such as the lost in the mall technique.[19] In Roediger and McDermott's (1995) experiment, subjects were presented with a list of related items (such as candy, sugar, honey) to study. When asked to recall the list, participants were just as, if not more, likely to recall semantically related words (such as sweet) than items that were actually studied, thus creating false memories.[20] This experiment, though widely replicated, remains controversial due to debate considering that people may store semantically related items from a word list conceptually rather than as language, which could account for errors in recollection of words without the creation of false memories. Susan Clancy discovered that people claiming to have been victims of alien abductions are more likely to recall semantically related words than a control group in such an experiment.[21]
The lost in the mall technique is a research method designed to implant a false memory of being lost in a shopping mall as a child to test whether discussing a false event could produce a "memory" of an event that did not happen. In her initial study, Elizabeth Loftus found that 25% of subjects came to develop a "memory" for the event which had never actually taken place.[22] Extensions and variations of the lost in the mall technique found that an average of one third of experimental subjects could become convinced that they experienced things in childhood that had never really occurred—even highly traumatic, and impossible events.[23]
Experimental researchers have demonstrated that memory cells in the hippocampus of mice can be modified to artificially create false memories.[24][25]
### How memory works in the brain[edit]
The cerebrum, or forebrain, makes up the largest part of the brain, and it is covered by a sheet of neural tissue known as the cerebral cortex, which envelops the part of our brain where memories are stored. Glutamate and GABA (two amino acids), act as the yin and yang of the brain, steering emotions by determining whether nerve cells are excited or inhibited (calm). Under normal conditions the system is balanced. But when individuals get hyper-aroused and vigilant, glutamate surges. Glutamate is also the primary chemical that helps to make it easy to remember memories stored in the brain. "Procedural memory, the unconscious memory of skills, for example, knowing how to ride a bike, is dependent upon repetition and practice and will operate automatically like muscle memory. Declarative memory, 'knowing what,' is memory of facts, experiences and events."[26]
### How traumatic memories hide in the brain[edit]
Memories of traumatic experiences hide deep in the brain, causing psychiatric problems. The memory of early childhood abuse can be forgotten and remembered with more or less accuracy. "It's difficult for therapists to help these patients," Jelena Radulovic, the Dunbar Professor in Bipolar Disease at Northwestern University Feinberg School of Medicine said, "because the patients themselves can't remember their traumatic experiences that are the root cause of their symptoms."[26] A special mechanism of the brain has been discovered to store stress related memories. If the brain registers an overwhelming trauma, then it can essentially block that memory in a process called dissociation or detachment from reality. "The brain will attempt to protect itself".[26] The same way the body can wall-off an abscess or foreign substance to protect the rest of the body, the brain can dissociate from an experience. In the midst of trauma, the brain may wander off and work to avoid the memory.[26]
## Court cases[edit]
### Sexual abuse cases[edit]
The question of the accuracy and dependability of a repressed memory that someone has later recalled has contributed to some investigations and court cases, including cases of alleged sexual abuse or child sexual abuse (CSA).[27][28][29] The research of Elizabeth Loftus has been used to counter claims of recovered memory in court[22] and it has resulted in stricter requirements for the use of recovered memories being used in trials, as well as a greater requirement for corroborating evidence. In addition, some U.S. states no longer allow prosecution based on recovered memory testimony. Insurance companies have become reluctant to insure therapists against malpractice suits relating to recovered memories.[22][30][31]
Supporters of recovered memories believe that there is "overwhelming evidence that the mind is capable of repressing traumatic memories of child sexual abuse."[32] Whitfield states that the "false memory" defense is "seemingly sophisticated, but mostly contrived and often erroneous." He states that this defense has been created by "accused, convicted and self-confessed child molesters and their advocates" to try to "negate their abusive, criminal behavior."[33] Brown states that when pro-false memory expert witnesses and attorneys state there is no causal connection between CSA and adult psychopathology, that CSA doesn't cause specific trauma-related problems like borderline and dissociative identity disorder, that other variables than CSA can explain the variance of adult psychopathology and that the long-term effects of CSA are non-specific and general, that this testimony is inaccurate and has the potential of misleading juries.[34]
### Malpractice cases[edit]
During the late 1990s, there were multiple lawsuits in the United States in which psychiatrists and psychologists were successfully sued, or settled out of court, on the charge of propagating iatrogenic memories of childhood sexual abuse, incest, and satanic ritual abuse.[35]
Some of these suits were brought by individuals who later declare that their recovered memories of incest or satanic ritual abuse had been false. The False Memory Syndrome Foundation uses the term retractors to describe these individuals, and have shared their stories publicly.[36] There is debate regarding the total number of retractions as compared to the total number of allegations,[37] and the reasons for retractions.[38]
#### Injuries resulting from malpractice[edit]
Sexual abuse of children and adolescents leads to severe negative consequences. Child sexual abuse is a risk factor for many classes of psychiatric disorders, including anxiety disorders, affective disorders, dissociative disorders and personality disorders.[39] Failure to meet recognized medical standards by psychiatrists causes injury to patients and the accused. Ramona v. Isabella was a prominent case of malpractice in 1994. A California Jury awarded $500,000 to Gary Ramona, whose daughter Holly had falsely accused him of sexual abuse as a child, based on false memories retrieved by therapists during treatment for bulimia. Los Angeles Superior Court Judge Burton Bach dismissed Holly Ramona's civil case against her father, holding that the outcome of her father's malpractice suit had resolved the issue of whether any abuse took place. The Washington Post titled the article Sex Abuse Suit Dismissed in False-Memory Case on December 14, 1994.[18] There were numerous cases brought to trial in the 1990s. Most included combinations of the misuse of hypnosis, guided imagery, sodium amytal, and anti-depressants.
The term "false memory syndrome" describes the phenomenon in which a mental therapy patient “remembers” an event such as childhood sexual abuse, that never occurred.[18] The link between certain therapy practices and the development of psychological disorders such as multiple personality disorder and dissociative identity disorder comes from malpractice suits and state licensure actions against therapists. These cases demonstrate the ease with which an individual can be led to exhibit dissociative symptoms, especially when hypnosis, sodium amytal, strong medications, or readings involving traumatic imagery magnify the effect of therapist suggestions or expectations.[medical citation needed] These cases also show that once the symptoms become established, the standard treatment modality often leads to a deterioration of the mental and emotional well being of the patient.[medical citation needed]
## Skepticism of the theory[edit]
[copyright violation]
False Memory Syndrome has been described as a widespread social phenomenon where misguided therapists cause patients to invent memories of sexual abuse (McCarty & Hough, 1992). The syndrome was described and named by the families and professionals who comprise the False Memory Syndrome Foundation (see Freyd, March 1993, p. 4), an organization formed by parents claiming to be falsely accused of child sexual abuse.
Since its establishment in 1992, the False Memory Syndrome Foundation has received 14,000 reports of sexual abuse accusations based on recovered memories.
Proponents of the syndrome claim that it is occurring at epidemic levels, and some have gone so far as to characterize it as the mental health crisis of the 1990s (e.g., Gardner, 1993, p. 370). Critics, on the other hand, have suggested that the syndrome is based on vague, unsubstantiated generalizations, which do not hold up to scientific scrutiny (e.g., Page, 1999), and that the syndrome's primary purpose is to discredit victims' testimony (e.g., Murphy, 1997). This article critically examines the assumptions underlying the concept to determine whether there is sufficient empirical evidence to support "False Memory Syndrome" as a valid diagnostic construct. Epidemiological evidence is then examined to determine whether there is data to support claims of either a public health crisis or epidemic.
Experts have described recovered memory theory as "either the most fascinating psychological discovery of the 20th century or the centerpiece of the most embarrassing mistake modern psychiatry and psychotherapy have ever made." Recovered memory theorists believe that individuals repress memories of traumatic events deep in the psyche.[medical citation needed]
The American Psychiatric Association (1993) in a statement on the issue of false memories, stated that repression did occur, but was unable to provide convincing references. On examination of a list of 31 references none adequately demonstrated that it took place. Meanwhile, studies in cognitive psychology have shown very clearly that memory is highly malleable and is a reconstructive process, not to be compared with the replaying of a disc or the review of an engraving or a videotape. The hypothesis that memory – so subject to attrition with time and so liable to revision by motive – can be recovered in a pristine form or even in a 50% accurate state after years of neglect, inattention or suppression becomes untenable.
## In popular culture[edit]
False Memory Syndrome has become so widely known that television shows and movies have been made about the phenomenon, such as the Netflix series The Sinner, which touches on the idea of recovering forgotten memories. The show focuses on a woman who kills a seemingly random man on the beach one day for playing a song that triggered a traumatic event from her past, which she has temporarily forgotten. Throughout the first season detectives try to trigger her memory and find a motive for her actions.[40]
## See also[edit]
* Alien abduction
* False allegation of child sexual abuse
* McMartin preschool trial
* Memory bias
* Memory conformity
* Memory implantation
## Footnotes[edit]
1. ^ McHugh, Paul Rodney (2008). Try to remember: Psychiatry's clash over meaning, memory and mind. Dana Press. pp. 66–67. ISBN 978-1-932594-39-3.
2. ^ a b McHugh 2008, p. 55.
3. ^ Paterson, H. M., Kemp, R. I., & Forgas, J. P. (2010). "Co-witnesses, confederates, and conformity: The effects of discussion and delay on eyewitness memory.," Psychiatry, Psychology and Law.
4. ^ Loftus, Elizabeth F. Memory: Surprising New Insights Into How We Remember and Why We Forget (Reading, Mass.: Addison-Wesley Pub. Co., 1980).
5. ^ Schacter, Daniel L. The Seven Sins of Memory : How the Mind Forgets and Remembers (Houghton Mifflin Co., 2001).
6. ^ Association for Psychological Science (2008, August 20). "False Memories Affect Behavior."
7. ^ Rix, Rebecca (2000). Sexual abuse litigation: a practical resource for attorneys, clinicians, and advocates. Routledge. p. 33. ISBN 978-0-7890-1174-9.
8. ^ "icd 10 codes: psychiatry". Priory Lodge Education Ltd. Retrieved October 21, 2013.
9. ^ American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. ISBN 978-0-89042-555-8.
10. ^ a b Whitfield, Charles L.; Joyanna L. Silberg; Paul Jay Fink (2001). Misinformation Concerning Child Sexual Abuse and Adult Survivors. Haworth Press. p. 56. ISBN 978-0-7890-1901-1.
11. ^ McHugh 2008, pp. 67–68.
12. ^ Dallam, S. (2002). "Crisis or Creation: A systematic examination of false memory claims". Journal of Child Sexual Abuse. 9 (3/4): 9–36. doi:10.1300/J070v09n03_02. PMID 17521989. S2CID 26047059. Retrieved June 27, 2008.
13. ^ Dalenberg, C (2006). "Recovered memory and the Daubert criteria: recovered memory as professionally tested, peer reviewed, and accepted in the relevant scientific community". Trauma Violence Abuse. 7 (4): 274–310. doi:10.1177/1524838006294572. PMID 17065548. S2CID 9964936.
14. ^ McHugh 2008, p. 63.
15. ^ Brandon S; Boakes J; Glaser D; Green R (1998). "Recovered memories of childhood sexual abuse: implications for clinical practice". British Journal of Psychiatry. 172 (4): 296–307. doi:10.1192/bjp.172.4.296. PMID 9722329.
16. ^ "Malpractice Suit Against Bennett Braun". Fortea.us. Archived from the original on March 10, 2010. Retrieved December 12, 2010.
17. ^ "Health Care Complaints Commission v. Tynan". Austlii.edu.au. February 10, 2010. Retrieved December 12, 2010.
18. ^ a b c Mertz, Elizabeth; Bowman, Cynthia (1998). "The Clinical Corner: Third-Party Liability in Repressed Memory Cases: Recent Legal Developments". doi:10.1037/e300392004-003. Cite journal requires `|journal=` (help)
19. ^ Schacter, DL (2002). The Seven Sins of Memory: How the Mind Forgets and Remembers. Houghton Mifflin Harcourt. pp. 123–30. ISBN 978-0-618-21919-3.
20. ^ Roediger, Henry L.; Kathleen B. McDermott (July 1995). "Creating False Memories: Remembering Words Not Presented in Lists". Journal of Experimental Psychology: Learning, Memory, and Cognition. 4. 21 (4): 803–14. CiteSeerX 10.1.1.495.353. doi:10.1037/0278-7393.21.4.803.
21. ^ "Starship memories". Harvard Gazette. October 31, 2002. Retrieved February 23, 2014.
22. ^ a b c Wilson, A (November 3, 2002). "War & remembrance: Controversy is a constant for memory researcher Elizabeth Loftus, newly installed at UCI". The Orange County Register. Retrieved January 19, 2009.
23. ^ Strange, D; Clifasefi S; Garry M (2007). "False memories". In Garry M; Hayne H (eds.). Do Justice and Let the Sky Fall: Elizabeth F. Loftus and Her Contributions to Science, Law, and Academic Freedom. Mahwah, NJ: Lawrence Erlbaum Associates. pp. 137–68. ISBN 978-0-8058-5232-5.
24. ^ Ramirez, S., et al., (2013). Creating a False Memory in the Hippocampus Science 26 July 2013: Vol. 341 no. 6144 pp. 387–91 doi:10.1126/science.1239073
25. ^ Jha, Alok (July 25, 2013). "False memory planted in mouse's brain". The Guardian.
26. ^ a b c d "Can you unconsciously forget an experience?". ScienceDaily. Retrieved November 20, 2018.
27. ^ "Are Recovered Memories Reliable?". Religioustolerance.org. Retrieved December 12, 2010.
28. ^ Colleen Born. "Elizabeth Loftus". Muskingum.edu. Archived from the original on January 8, 2011. Retrieved December 12, 2010.
29. ^ "The Recovered Memory Project". Brown.edu. May 3, 1993. Retrieved December 12, 2010.
30. ^ Neimark, J. (1996). The diva of disclosure, memory researcher Elizabeth Loftus. Psychology Today, 29, 48–53, 80.
31. ^ Saletan, William (June 4, 2010). "The memory doctor: the future of false memories". Slate. Retrieved May 8, 2012.
32. ^ Murphy, W. "Debunking 'false memory'myths in sexual abuse cases". Archived from the original on January 7, 2008. Retrieved January 10, 2008.
33. ^ Whitfield, C. (March 2002). "The "False Memory" Defense Using Disinformation and Junk Science In and Out of Court". Journal of Child Sexual Abuse. 9 (3/4): 53–78. doi:10.1300/J070v09n03_04. S2CID 24310658. Retrieved January 11, 2008.
34. ^ Brown, D. (2001). "(Mis)representation of the Long-Term Effects of Childhood Sexual Abuse in the Courts". Journal of Child Sexual Abuse. 9 (3/4): 79–107. doi:10.1300/J070v09n03_05. PMID 17521992. S2CID 20874393. Retrieved January 28, 2008.
35. ^ "Recovered Memory Lawsuit Sparks Litigation". Psychiatrictimes.com. Retrieved December 12, 2010.
36. ^ Macdonald, Gail (1999). "Women Against Women". Making of an Illness: My Experience With Multiple Personality Disorder. Sudbury, Ontario: Laurentian University Press. p. 111. ISBN 978-0-88667-045-0. Retrieved July 31, 2013.
37. ^ Whitfield M.D., Charles L. (1995). Memory and Abuse – Remembering and Healing the Effects of Trauma. Deerfield Beach, FL: Health Communications, Inc. p. 83. ISBN 978-1-55874-320-5.
38. ^ Summit, R. (1983). "The child sexual abuse accommodation syndrome". Child Abuse & Neglect. 7 (2): 177–93. doi:10.1016/0145-2134(83)90070-4. PMID 6605796.
39. ^ "False Memory Syndrome Foundation". www.fmsfonline.org. Retrieved November 20, 2018.
40. ^ Han, Karen (July 31, 2018). "The Sinner is the rare murder mystery that doesn't care whodunnit. Instead, it asks, "Why?"". Vox. Retrieved December 28, 2019.
## External links[edit]
* False memory syndrome at Curlie
* Memory controversies at Curlie
* Memory Wars is a website with information from all sides of the issue. Primary resources include an extensive bibliography / abstract database and pre-print archive. Also available are sections for criminal investigation, criminal defense and many other useful resources.
* False Memory Syndrome, Child & Woman Abuse Studies Unit of London Metropolitan University. Argues that "false memories" are real memories.
* False Memory Syndrome Foundation
* The false memory archive
* The false memory archive: did that really happen?
* v
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Human memory
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Satanic ritual abuse
List of satanic ritual abuse allegations
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* Cleveland child abuse scandal
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Publications and
media
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Related topics
* Believe the Children
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*[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
| False memory syndrome | c0376365 | 1,622 | wikipedia | https://en.wikipedia.org/wiki/False_memory_syndrome | 2021-01-18T18:43:12 | {"mesh": ["D012094"], "wikidata": ["Q195961"]} |
A number sign (#) is used with this entry because of evidence that congenital microcoria is caused by contiguous gene deletion at chromosome 13q32.
Description
Inherited congenital microcoria, also referred to as congenital miosis, is characterized by bilateral small pupils (diameter less than 2 mm) that result from an underdevelopment of the dilator pupillae muscle of the iris (Holth and Berner, 1923; Simpson and Parsons, 1989). Iris transillumination defects are a constant feature. The pupil dilates poorly or not at all in response to topically administered mydriatic drugs. The disorder is transmitted as an autosomal dominant trait with complete penetrance and is associated with goniodysgenesis and glaucoma (Tawara and Inomata, 1983; Mazzeo et al., 1986; Toulemont et al., 1995).
Clinical Features
Ardouin et al. (1964) described a family in which 25 persons had small pupils due apparently to hypoplasia of the dilator muscle of the iris. Myopia was present in all.
Tawara et al. (2005) restudied 6 affected members of a 3-generation Japanese family with congenital microcoria and goniodysgenetic glaucoma, originally reported by Tawara and Inomata (1983). Two brothers, who were followed for over 2 decades beginning at the ages of 8 and 10 years, had bilateral congenital microcoria. On examination, their irides had a featureless surface with poorly developed collarettes and crypts, and gonioscopy showed high insertion of the iris root into the scleral spur as well as a ciliary body band that was barely seen or invisible. Fundi were poorly visualized due to the patients' small pupils. Both patients developed high intraocular pressures associated with blurred vision and underwent trabeculectomies in their twenties and thirties. Histopathologic examination of iridocorneal angle tissue specimens showed thickened juxtacanalicular connective tissue (JCT) in the trabecular meshwork, with accumulations of extracellular matrix. On electron microscopy, the thickened JCT consisted of many layers of trabecular cells embedded in a basement membrane-like extracellular matrix of fibrous and amorphous material. The brothers' 32-year-old female cousin, followed since age 7 years, also exhibited bilateral congenital microcoria and goniodysgenesis, but had normal intraocular pressures and visual fields. There were no changes in the appearance of the irides, pupils, or iridocorneal angles in any of the 3 patients during follow-up. The brothers' father and the cousin's mother also had microcoria and goniodysgenetic glaucoma, and their deceased grandfather had been diagnosed with microcoria.
Ramirez-Miranda et al. (2011) reported a 3-generation Mexican Mestizo family with congenital microcoria. The proband was a 62-year-old woman who had blurred vision and nyctalopia since childhood and whose vision had gradually been deteriorating over the past 5 years. Examination showed bilateral pupillary diameters of less than 2 mm, with a hyperpigmented peripupillary area, transillumination defects of the peripheral iris, and no response to mydriatic drugs. She also had bilateral dense nuclear cataracts. Intraocular pressure was normal, but fundus could not be evaluated due to the small pupil. Her affected 41-year-old son and 9-year-old grandson had the same iris configuration with normal intraocular pressures, but no cataracts. Ultrabiomicroscopic examination in all 3 affected individuals showed a pupillary diameter of 1.8 mm and thinning of the iris (830 microns), with no angle findings. The proband underwent cataract surgery, at which time the pupillary margin was biopsied; histopathologic analysis confirmed that the iris was thinner as well richer in cells and ground substance, and that it had an incompletely developed dilator muscle. However, the innervation, vasculature, and cellular relationships were normal; in addition, there were no basement membrane alterations of the excised anterior lens capsule, confirming that the developmental anomaly was limited to the iris.
Mapping
Rouillac et al. (1998) described a linkage analysis in the French family reported by Ardouin et al. (1964), adding observations on another branch of the family. They found linkage between the disorder and markers located on 13q31-q32 (maximum lod = 9.79 at theta = 0.0). Haplotype analysis narrowed the linked region to an interval less than 8 cM between markers D13S1239 proximally and D13S1280 distally.
Molecular Genetics
Using comparative genomic hybridization (CGH), Fares-Taie et al. (2015) analyzed DNA from an affected member of the French family with microcoria originally reported by Ardouin et al. (1964) and identified a heterozygous deletion on chromosome 13 that extended from 95,227,374 to 95,277,864 (GRCh37). The centromeric and telomeric breakpoints were located within intron 11 and intron 8 of the tail-to-tail genes TGDS (616146) and GPR180 (607787), respectively. Array CGH confirmed the presence of heterozygous deletions at 13q32.1 in 5 other microcoria families, including those originally reported by Tawara et al. (2005) and Ramirez-Miranda et al. (2011). The deletions, which ranged in size from approximately 35 to 80 kb and invariably encompassed the TGDS and GPR180 genes, were not found in the Database of Genomic Variants or in a cohort of 96 individuals with other diseases analyzed by array CGH. Fares-Taie et al. (2015) noted that unlike TGDS, which has no known function in muscle cells, GPR180 is involved in the regulation of smooth muscle cell growth. In their in-house exome database, Fares-Taie et al. (2015) identified a GPR180 nonsense mutation (Q115X) that segregated with goniodysgenesis in a family with Leber congenital amaurosis (LCA; see 204000); however, none of the 5 individuals with both iridocorneal angle dysgenesis and the Q115X substitution had abnormal pupillary responses or iris transillumination. Fares-Taie et al. (2015) also examined heterozygous and homozygous Gpr180-null mouse eyes, and found that they were indistinguishable from adult age-matched controls. In addition, they screened the GPR180 gene in 21 individuals exhibiting goniodysgenesis, including 10 with Axenfeld-Rieger or Peters anomaly and 11 with congenital or juvenile glaucoma, all of whom were negative for mutations in known genes associated with those conditions, but found no GPR180 disease-causing variants. Fares-Taie et al. (2015) suggested that GPR180 ablation, alone or in combination with the loss of elements that regulate the expression of neighboring genes by position effect, may be the cause of microcoria.
### Exclusion Studies
In 2 brothers from a 3-generation Japanese family with congenital microcoria and goniodysgenetic glaucoma, originally reported by Tawara and Inomata (1983), Tawara et al. (2005) did not detect any mutations in the CYP1B1 (601771) or MYOC (601652) genes.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Small pupils \- Nonreactive or poorly reactive pupils \- Featureless surface of iris \- Poorly developed collarettes \- Poorly developed crypts \- Hypoplasia of the iris dilator muscle \- Myopia \- Goniodysgenesis (in some patients) \- Elevated intraocular pressure (in some patients) \- Glaucoma (in some patients) \- Thickened juxtacanalicular connective tissue \- Accumulation of basement membrane-like extracellular matrix MISCELLANEOUS \- Contiguous gene deletion syndrome MOLECULAR BASIS \- Contiguous gene syndrome caused by 35-80kb deletion of 13q21 encompassing at least TGDS ( 616146 ) and GPR180 ( 607787 ) ▲ Close
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*[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
| MICROCORIA, CONGENITAL | c1303009 | 1,623 | omim | https://www.omim.org/entry/156600 | 2019-09-22T16:38:15 | {"mesh": ["C537550"], "omim": ["156600"], "orphanet": ["566"], "synonyms": ["Alternative titles", "CHROMOSOME 13q32 DELETION SYNDROME", "MCOR", "MIOSIS, CONGENITAL"]} |
Epidermolytic acanthoma
Epidermolytic acanthoma
Epidermolytic acanthomas are a cutaneous condition characterized by discrete keratotic papules in adults.[1]
## See also[edit]
* Dermatosis papulosa nigra
* List of cutaneous conditions
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1674. ISBN 1-4160-2999-0.
* v
* t
* e
Skin cancer of the epidermis
Tumor
Carcinoma
BCC
* Forms
* Aberrant
* Cicatricial
* Cystic
* Fibroepithelioma of Pinkus
* Infltrative
* Micronodular
* Nodular
* Pigmented
* Polypoid
* Pore-like
* Rodent ulcer
* Superficial
* Nevoid basal cell carcinoma syndrome
SCC
* Forms
* Adenoid
* Basaloid
* Clear cell
* Signet-ring-cell
* Spindle-cell
* Marjolin's ulcer
* Bowen's disease
* Bowenoid papulosis
* Erythroplasia of Queyrat
* Actinic keratosis
Adenocarcinoma
* Aggressive digital papillary adenocarcinoma
* Extramammary Paget's disease
Ungrouped
* Merkel cell carcinoma
* Microcystic adnexal carcinoma
* Mucinous carcinoma
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* Malignant mixed tumor
Benign
tumors
Acanthoma
* Forms
* Large cell
* Fissuring
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* Epidermolytic
* Melanoacanthoma
* Pilar sheath acanthoma
* Seboacanthoma
* Seborrheic keratosis
* Warty dyskeratoma
Keratoacanthoma
* Generalized eruptive
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* Multiple
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Wart
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Other
Epidermal nevus
* Syndromes
* Epidermal nevus syndrome
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* Phakomatosis pigmentokeratotica
Other nevus
* Nevus unius lateris
* Patch blue nevus
* Unilateral palmoplantar verrucous nevus
* Zosteriform speckled lentiginous nevus
Ungrouped
* Cutaneous horn
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
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* 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
| Epidermolytic acanthoma | c1333414 | 1,624 | wikipedia | https://en.wikipedia.org/wiki/Epidermolytic_acanthoma | 2021-01-18T19:02:44 | {"umls": ["C1333414"], "wikidata": ["Q5382850"]} |
Glutaric acidemia type I (GA1) is a genetic metabolic disorder. People with GA1 don't make enough of one of the enzymes needed to break down certain amino acids found in the proteins we eat. Without enough of the enzyme, the breakdown products of these amino acids build up in tissues of the body. The buildup of these chemicals can damage the brain, especially the area of the brain called the basal ganglia. The basal ganglia helps control the body's movements.
Without treatment, newborns with GA1 may at first not have any symptoms other than possibly having a slightly large head. Some, however, may have weak muscles and early signs of developmental delay. For most children with GA1, if untreated, an infection or fever will trigger an episode that causes serious damage to the basal ganglia. In some children, the brain damage will happen without a triggering fever. Damage to the basal ganglia will make it hard for the child to control the movements of their body. The damage cannot be reversed. However if treatment is started in a newborn with GA1 before symptoms begin, 80-90% of people with GA1 will not develop symptoms. Treatment however must be followed strictly, especially for the first six years of life. Treatment includes a low-lysine diet, carnitine supplementaion, and emergency treatment during an fever or acute episode.
GA1 is caused by mutations in the GCDH gene and is inherited in an autosomal recessive manner. GA1 is included on the newborn screening panel in most countries.
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*[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
| Glutaric acidemia type I | c0268595 | 1,625 | gard | https://rarediseases.info.nih.gov/diseases/6522/glutaric-acidemia-type-i | 2021-01-18T18:00:17 | {"mesh": ["C536833"], "omim": ["231670"], "umls": ["C0268595"], "orphanet": ["25"], "synonyms": ["Glutaric acidemia type 1", "Glutaric acidemia 1", "Glutaric aciduria 1", "GA 1", "Glutaryl-CoA dehydrogenase deficiency"]} |
Salmon patch on the left upper eyelid of a neonate.
Midline nevus flammeus (also known as salmon patch and "angel's kiss") is a vascular birthmark which may be found on the glabellar region or on one upper eyelid, and presents in approximately 15% of newborns.[1][2]
## See also[edit]
* List of cutaneous conditions
* Mongolian spot
* Nevus flammeus
* Nevus flammeus nuchae
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. Page 582. ISBN 0-7216-2921-0.
2. ^ "salmon patch" at Dorland's Medical Dictionary
This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it.
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*[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
| Midline nevus flammeus | c1854409 | 1,626 | wikipedia | https://en.wikipedia.org/wiki/Midline_nevus_flammeus | 2021-01-18T18:36:53 | {"umls": ["C1854409"], "wikidata": ["Q6842569"]} |
Transfer of legally prescribed controlled pharmaceuticals to other individuals
Drug diversion is a medical and legal concept involving the transfer of any legally prescribed controlled substance from the individual for whom it was prescribed to another person for any illicit use.[1][2] The definition varies slightly among different jurisdictions, but the transfer of a controlled substance alone usually does not constitute a diversion, since certain controlled substances that are prescribed to a child are intended to be administered by an adult, as directed by a medical professional.[citation needed] The term comes from the "diverting" of the drugs from their original licit medical purpose. In some jurisdictions, drug diversion programs are available to first time offenders of diversion drug laws, which "divert" offenders from the criminal justice system to a program of education and rehabilitation.[citation needed]
## Contents
* 1 Commonly diverted drugs
* 2 Registration of drug suppliers
* 2.1 Examples
* 3 DEA investigation into oxycodone diversion
* 4 See also
* 5 References
* 6 External links
## Commonly diverted drugs[edit]
Z-drug example
Controlled prescription drug classes which are commonly diverted include:[3]
* Benzodiazepines – including diazepam, temazepam, clonazepam, and alprazolam – prescription anxiolytics and sedatives
* Opioids – including morphine, hydrocodone, oxycodone and codeine – prescription pain medications
* Stimulants – amphetamine, methylphenidate, and modafinil – prescribed to treat ADHD and narcolepsy
* Z-drugs – including zolpidem (Ambien), Eszopiclone (Lunesta) – prescription sleep medications
According to the United States Department of Justice, "Most pharmaceuticals abused in the United States are diverted by doctor shopping, forged prescriptions, theft and, increasingly, via the Internet."[4] To reduce the occurrence of pharmaceutical diversion by doctor shopping and prescription fraud, almost all states have established prescription monitoring programs (PMPs) that facilitate the collection, analysis, and reporting of information regarding pharmaceutical drug prescriptions.[5]
## Registration of drug suppliers[edit]
21 U.S.C. § 823 of the Controlled Substances Act provides for registration of manufacturers and distributors of controlled substances. The criteria for registering manufacturers of Schedule I and II drugs are particularly strict and call for "limiting the importation and bulk manufacture of such controlled substances to a number of establishments which can produce an adequate and uninterrupted supply of these substances under adequately competitive conditions for legitimate medical, scientific, research, and industrial purposes." The Attorney General must make a positive determination that the registration would be "consistent with the public interest."[citation needed]
For manufacturers of other drugs, and for drug distributors, the regulations are substantially less strict: "The Attorney General shall register an applicant… unless he determines that the issuance of such registration is inconsistent with the public interest." The criteria for both manufacture and distribution is somewhat biased in favor of established industries, favoring "past experience" and a record of compliance with drug laws[citation needed] The Controlled Substances Act also provides for the registration of medical practitioners (i.e., physicians, dentists, veterinarians, etc.), pharmacies and hospitals that prescribe, administer, or dispense controlled substances directly to patients, as well as individuals conducting approved research involving controlled substances. This category also includes narcotic treatment programs that administer and dispense primarily methadone for narcotic addiction treatment.[medical citation needed]
### Examples[edit]
This activity can occur in many venues:
The Cincinnati Post has reported on its frequency. John Burke, an expert on the issue, was quoted as saying, "Pharmaceutical diversion is kind of funny because it's going on in every community, but it appears not to exist unless you go after it purposely."[6]
## DEA investigation into oxycodone diversion[edit]
According to the US Justice Department, in 2011 CVS pharmacies in Sanford, Florida, ordered enough painkillers to supply a population eight times its size. Sanford has a population of 53,000 but the supply would support 400,000.[7] According to the Drug Enforcement Administration (DEA), in 2010 a single CVS pharmacy in Sanford ordered 1.8 million oxycodone pills, an average of 137,994 pills a month. Other pharmacy customers in Florida averaged 5,364 oxycodone pills a month. DEA investigators serving a warrant to a CVS pharmacy in Sanford on October 18, 2011 noted that "approximately every third car that came through the drive-thru lane had prescriptions for oxycodone or hydrocodone."
According to the DEA, a pharmacist at that location stated to investigators that "her customers often requested certain brands of oxycodone using street slang," an indicator that the drugs were being diverted and not used for legitimate pain management. In response, CVS in a statement issued February 17 in response to opioid trafficking questions from USA Today said the company is committed to working with the DEA and had taken "significant actions to ensure appropriate dispensing of painkillers in Florida."[8]
In February 2012, Joseph Rannazzisi, chief of the Drug Enforcement Administration’s Office of Diversion Control, issued immediate suspension orders against Cardinal Health's supply of oxycodone to suspected pill mills.[9] Deputy Attorney General James M. Cole then called Rannazzisi to a meeting at Justice Department headquarters where Cole warned him “it made good sense to listen to what Cardinal had to say”.[9] Rannazzisi was fired from the drug diversion office in August 2015.[9] Cardinal was never fined.[9]
Cardinal, alongside McKesson Corporation and AmerisourceBergen, spent $13 million lobbying Congress to pass Congressman Tom Marino's "Ensuring Patient Access and Effective Drug Enforcement Act".[9] The bill, which increases the burden of proof enforcers need to show against drug distributors, was signed into law by President Barack Obama in April 2016.[10]
## See also[edit]
* Diversion (disambiguation)
* Unused drug
* Oxycodone
* Pharmaceuticals in India
* Steroids
## References[edit]
1. ^ Berge KH, Dillon KR, Sikkink KM, Taylor TK, Lanier WL (2012). "Diversion of drugs within health care facilities, a multiple-victim crime: patterns of diversion, scope, consequences, detection, and prevention". Mayo Clin. Proc. 87 (7): 674–82. doi:10.1016/j.mayocp.2012.03.013. PMC 3538481. PMID 22766087.
2. ^ "Drug Diversion Defined: A Patient Safety Threat | Safe Healthcare | Blogs | CDC". blogs.cdc.gov. Archived from the original on 2015-07-16. Retrieved 2015-07-15.
3. ^ McCabe SE, Teter CJ, Boyd CJ (2006). "Medical use, illicit use, and diversion of abusable prescription drugs". J Am Coll Health. 54 (5): 269–78. doi:10.3200/JACH.54.5.269-278. PMC 1876754. PMID 16539219.
4. ^ US Department of Justice web site
5. ^ "Prescription Drug Monitoring Programs (PDMPs)". www.cdc.gov. Retrieved 2016-05-04.
6. ^ Whitehead, Shelly (2005-01-18). "Police target prescription abuse". The Cincinnati Post. E. W. Scripps Company. Archived from the original on 2005-03-12.
7. ^ Schoenberg, Tom (2012-02-29). "Cardinal Health Blocked From Shipping Painkiller in Florida". Bloomberg.
8. ^ "Most Popular E-mail Newsletter". USA Today. 2012-02-27.
9. ^ a b c d e Lenny Bernstein; Scott Higham (22 October 2016). "Investigation: The DEA slowed enforcement while the opioid epidemic grew out of control". The Washington Post. Retrieved 17 March 2017.
10. ^ S. 483, 114th Cong. (2015).
## External links[edit]
Look up diversion in Wiktionary, the free dictionary.
* Controlled Substances Act – U.S. Drug Enforcement Administration
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*[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
| Drug diversion | None | 1,627 | wikipedia | https://en.wikipedia.org/wiki/Drug_diversion | 2021-01-18T18:43:56 | {"mesh": ["D064226"], "wikidata": ["Q5308890"]} |
Greenberg dysplasia is a very severe disorder that that affects the bones. It is called a skeletal dysplasia because the bones do not develop properly. This condition is sometimes called HEM based on the main features of Hydrops fetalis, Ectopic calcifications, and "Moth-eaten" appearance of the skeleton. Greenberg dysplasia is an autosomal recessive condition caused by a mutation in the lamin B receptor (LBR) gene. Because of the very severe symptoms of Greenberg dysplasia, fetuses with this condition do not survive until birth.
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*[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
| Greenberg dysplasia | c2931048 | 1,628 | gard | https://rarediseases.info.nih.gov/diseases/8754/greenberg-dysplasia | 2021-01-18T18:00:12 | {"mesh": ["C535858"], "omim": ["215140"], "orphanet": ["1426"], "synonyms": ["Hydrops-ectopic calcification-motheaten syndrome", "Skeletal dysplasia, Greenberg type", "HEM", "Hydrops, Ectopic calcification, Moth-eaten skeletal dysplasia", "HEM dysplasia", "HEM/Greenberg dysplasia", "Greenberg skeletal dysplasia", "Autosomal recessive lethal chondrodystrophy with congenital hydrops"]} |
For a phenotypic description and a discussion of heterogeneity of keratoconus, see 148300.
Mapping
Hutchings et al. (2005) performed genomewide linkage analysis in 28 families with keratoconus recruited in France, Spain, and Guadeloupe (West Indies), representing a mixed, outbred population (Caucasian, Arab, and Caribbean African). They found evidence of linkage on chromosome 2p24 with a maximum lod score of 3.26 at D2S305; multipoint parametric analysis under a dominant model yielded a heterogeneity lod score of 5.13 (alpha = 0.52) at marker D2S320. Analysis of key recombination events placed the keratoconus locus in a 1.69-Mb region flanked by markers D2S305 and D2S2373.
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*[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
| KERATOCONUS 4 | c1836473 | 1,629 | omim | https://www.omim.org/entry/609271 | 2019-09-22T16:06:20 | {"mesh": ["C563752"], "omim": ["609271"]} |
Allopurinol hypersensitivity syndrome
Allopurinol
Allopurinol hypersensitivity syndrome typically occurs in persons with preexisting kidney failure.[1]:119 Weeks to months after allopurinol is begun, the patient develops a morbilliform eruption[1]:119 or, less commonly, develops one of the far more serious and potentially lethal severe cutaneous adverse reactions viz., the DRESS syndrome, Stevens Johnson syndrome, or toxic epidermal necrolysis.[2]
## See also[edit]
* Severe cutaneous adverse reactions (i.e. SCARs)
* Skin lesion
* List of cutaneous conditions
## References[edit]
1. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
2. ^ Wang CW, Dao RL, Chung WH (August 2016). "Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions". Current Opinion in Allergy and Clinical Immunology. 16 (4): 339–45. doi:10.1097/ACI.0000000000000286. PMID 27362322.
## External links[edit]
Classification
D
* ICD-10: Y54.8
* ICD-9-CM: E944.7
* v
* t
* e
Adverse drug reactions
Antibiotics
* Penicillin drug reaction
* Sulfonamide hypersensitivity syndrome
* Urticarial erythema multiforme
* Adverse effects of fluoroquinolones
* Red man syndrome
* Jarisch–Herxheimer reaction
Hormones
* Steroid acne
* Steroid folliculitis
Chemotherapy
* Chemotherapy-induced acral erythema
* Chemotherapy-induced hyperpigmentation
* Scleroderma-like reaction to taxanes
* Hydroxyurea dermopathy
* Exudative hyponychial dermatitis
Anticoagulants
* Anticoagulant-induced skin necrosis
* Warfarin necrosis
* Vitamin K reaction
* Texier's disease
Immunologics
* Adverse reaction to biologic agents
* Leukotriene receptor antagonist-associated Churg–Strauss syndrome
* Methotrexate-induced papular eruption
* Adverse reaction to cytokines
Other drugs
* Anticonvulsant hypersensitivity syndrome
* Allopurinol hypersensitivity syndrome
* Vaccine adverse event
* Eczema vaccinatum
* Bromoderma
* Halogenoderma
* Iododerma
General
Skin and body membranes
* Acute generalized exanthematous pustulosis
* Bullous drug reaction
* Drug-induced acne
* Drug-induced angioedema
* Drug-related gingival hyperplasia
* Drug-induced lichenoid reaction
* Drug-induced lupus erythematosus
* Drug-induced nail changes
* Drug-induced pigmentation
* Drug-induced urticaria
* Stevens–Johnson syndrome
* Injection site reaction
* Linear IgA bullous dermatosis
* Toxic epidermal necrolysis
* HIV disease-related drug reaction
* Photosensitive drug reaction
Other
* Drug-induced pseudolymphoma
* Fixed drug reaction
* Serum sickness-like reaction
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
| Allopurinol hypersensitivity syndrome | c3839950 | 1,630 | wikipedia | https://en.wikipedia.org/wiki/Allopurinol_hypersensitivity_syndrome | 2021-01-18T18:28:49 | {"icd-9": ["E944.7"], "icd-10": ["Y54.8"], "wikidata": ["Q4733137"]} |
Missouri Lyme disease
SpecialtyDermatology
Missouri Lyme disease is a cutaneous condition. The cause of ‘Missouri Lyme disease’ has been a source of controversy. True Lyme disease probably occurs in Missouri and other southern states, although Lyme disease-like illnesses not related to Borrelia burgdorferi also occur. Strains of B. burgdorferi have been isolated from A. americanum in Missouri, but the ticks are not efficient disease vectors.[1]
## See also[edit]
* Lyme disease
* 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 1-4160-2999-0.
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
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*[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
| Missouri Lyme disease | None | 1,631 | wikipedia | https://en.wikipedia.org/wiki/Missouri_Lyme_disease | 2021-01-18T18:43:35 | {"wikidata": ["Q6879590"]} |
Trevor disease
Other namesDysplasia epiphysealis hemimelica
Trevor disease in a 9 yr old girl: Talus
SpecialtyMedical genetics
Trevor disease, also known as dysplasia epiphysealis hemimelica and Trevor's disease, is a congenital bone developmental disorder. There is 1 case per million population. The condition is three times more common in males than in females.
## Contents
* 1 Presentation
* 2 Diagnosis
* 2.1 Differential diagnosis
* 3 Treatment
* 4 History
* 5 See also
* 6 References
* 7 External links
## Presentation[edit]
3D CT image of Trevor's disease of the ankle and talus.
This disorder is rare, and is characterised by an asymmetrical limb deformity due to localized overgrowth of cartilage, histologically resembling osteochondroma. It is believed to affect the limb bud in early fetal life. The condition occurs mostly in the ankle or knee region and it is always confined to a single limb. This usually involves only the lower extremities and on medial side of the epiphysis. It is named after researcher David Trevor.[1]
## Diagnosis[edit]
### Differential diagnosis[edit]
Trevor disease can often mimic posttraumatic osseous fragments,[2][3] synovial chondromatosis, ostechondroma, or anterior spur of ankle.[4][5][6][7] It is not possible to distinguish DEH from osteochondroma on the basis of histopathology alone.[8][6] Special molecular tests of the genes EXT1, EXT2 are used for the analysis of genetic expressions. These are within normal ranges in DEH, while they are lower in ostechondroma (owing to a mutation).[2][6][9][10] These tests are expensive and the diagnosis is often made on clinical and radiological findings. Synovial chondromatosis occurs in a much older age group and can be ruled out on this basis.[2]
## Treatment[edit]
Most reported cases of DEH in the literature have been treated surgically, usually with excision of the mass, as well as by the correction of any deformity, while preserving the integrity of the affected joint as much as possible.[2][11][12][13]
## History[edit]
Trevor disease was first described by the French surgeon Albert Mouchet and J. Belot in 1926. In 1956, the name "dysplasia epiphysealis hemimelica" was proposed by Fairbank.[1] The usual symptoms are the appearance of an osseous protuberance, on one side of the knee, ankle or foot joint which gradually increases Radiologically,[14] the condition shows a nonuniformity of growth and multiple unconnected ossification centers around the epiphyses.[8]
## See also[edit]
* Multiple epiphyseal dysplasia
## References[edit]
1. ^ a b www.whonamedit.com[full citation needed]
2. ^ a b c d Gökkus, K; Aydin, AT (2014). "Dysplasia epiphysealis hemimelica: a diagnostic dilemma for orthopedic surgeons and a nightmare for parents". Journal of Postgraduate Medicine. 60 (1): 1–2. doi:10.4103/0022-3859.128794. PMID 24625930.
3. ^ Yih-Huie, Lin; Yi-Jiun, Chou; Lee-Ren, Yeh; Clement, K. H.; Chen, Clement K. H.; Chen, Huay-Ban Pan; Chien-Fang, Yang (2001). "Dysplasia Epiphysealis Hemimelica or Trevor's Disease: A Case Report" (PDF). Journal of Radiological Science. 26 (5): 215–20.
4. ^ Glick, Rachel; Khaldi, Lubna; Ptaszynski, Konrad; Steiner, German C. (2007). "Dysplasia epiphysealis hemimelica (Trevor disease): a rare developmental disorder of bone mimicking osteochondroma of long bones". Human Pathology. 38 (8): 1265–72. doi:10.1016/j.humpath.2007.01.017. PMID 17490719.
5. ^ Murphey, Mark D.; Choi, James J.; Kransdorf, Mark J.; Flemming, Donald J.; Gannon, Frances H. (2000). "Imaging of osteochondroma: variants and complications with radiologic-pathologic correlation". Radiographics. 20 (5): 1407–34. doi:10.1148/radiographics.20.5.g00se171407. PMID 10992031.
6. ^ a b c Gokkus, Kemal; Aydin, Ahmet Turan; Uyan, Ayca; Cengiz, Menekse (2011). "Dysplasia epiphysealis hemimelica of the ankle joint: a case report" (PDF). Journal of Orthopaedic Surgery. 19 (2): 254–6. doi:10.1177/230949901101900227. PMID 21857058. S2CID 45805741.
7. ^ Gökkuş, Kemal; Aydın, Ahmet Turan; Sagtas, Ergin (2012). "Trevor's disease: mimicking anterior ankle impingement syndrome: case report". Knee Surgery, Sports Traumatology, Arthroscopy. 20 (9): 1875–8. doi:10.1007/s00167-011-1836-y. PMID 22198357. S2CID 23699201.
8. ^ a b Fairbank, TJ (1956). "Dysplasia epiphysialis hemimelica (tarso-ephiphysial aclasis)". The Journal of Bone and Joint Surgery. British Volume. 38-B (1): 237–57. doi:10.1302/0301-620X.38B1.237. PMID 13295331.
9. ^ Dorfman, H. D.; Vanel, D.; Czerniak, B.; Park, Y. K.; Kotz, R.; Unni, K. K. (2002). "WHO classification of tumours of bone: Introduction". In Fletcher, Christopher D. M.; Unni, K. Krishnan; Mertens, Fredrik (eds.). Pathology and Genetics of Tumours of Soft Tissue and Bone. IARC. pp. 227–30. ISBN 978-92-832-2413-6.
10. ^ Gökkuş, Kemal; Aydın, Ahmet Turan (2010). "Talus ostekondromu ve talus tutulumlu displazi epifiziyalis hemimelika ayırımı, zor bir ikilem" [Differential diagnosis of osteochondroma of talus and talus located dysplasia epiphysealis hemimelica, a diagnostic dilemma] (PDF). Eklem Hastalıkları Ve Cerrahisi (in Turkish). 21 (3): 182. PMID 21067502.
11. ^ Arkader, Alexandre; Friedman, Jared E; Moroz, Leslie; Dormans, John P (2007). "Acetabular dysplasia with hip subluxation in Trevor's disease of the hip". Clinical Orthopaedics and Related Research. 457: 247–52. doi:10.1097/BLO.0b013e31802ea479. PMID 17146363.
12. ^ Maylack, Fallon H.; Manske, Paul R.; Strecker, William B. (1988). "Dysplasia epiphysealis hemimelica at the metacarpophalangeal joint". The Journal of Hand Surgery. 13 (6): 916–20. doi:10.1016/0363-5023(88)90270-5. PMID 3225418.
13. ^ Dysplasia Epiphysealis Hemimelica at eMedicine
14. ^ Campanacci, Mario (1999). "Hemimelic Epiphyseal Dysplasia". Bone and Soft Tissue Tumors: Clinical Features, Imaging, Pathology and Treatment. pp. 207–211. doi:10.1007/978-3-7091-3846-5_11. ISBN 978-3-7091-3846-5.
## External links[edit]
Classification
D
* ICD-10: Q74.8
* OMIM: 127800
* MeSH: C537997
External resources
* Orphanet: 1822
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*[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
| Trevor disease | c0432282 | 1,632 | wikipedia | https://en.wikipedia.org/wiki/Trevor_disease | 2021-01-18T19:00:09 | {"gard": ["2019"], "mesh": ["C537997"], "umls": ["C0432282"], "icd-10": ["Q74.8"], "orphanet": ["1822"], "wikidata": ["Q7839508"]} |
Silverman et al. (1968) observed 2 children, brother and sister, who developed dyspnea, cyanosis and digital clubbing 11 and 18 months after episodes of hepatitis. Pulmonary arteriovenous fistulae too small to be demonstrated by angiography were postulated.
Skel \- Digital clubbing Respiratory \- Dyspnea Inheritance \- Autosomal recessive GI \- Hepatitis Skin \- Cyanosis ▲ Close
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*[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
| CYANOSIS AND HEPATIC DISEASE | c1857443 | 1,633 | omim | https://www.omim.org/entry/219400 | 2019-09-22T16:29:06 | {"mesh": ["C565660"], "omim": ["219400"]} |
Osgood-Schlatter disease is a traction apophysitis of the anterior tibial tubercle described in active adolescents and characterized by gradual onset of pain and swelling of the anterior knee causing limping that usually disappears at the end of growth.
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*[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
| Osgood-Schlatter disease | c0029376 | 1,634 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97335 | 2021-01-23T17:56:45 | {"mesh": ["D055034"], "umls": ["C0029376"], "icd-10": ["M93.2"], "synonyms": ["Aseptic necrosis of the tibial tubercle", "Osteochondrosis of the tibial tubercle"]} |
FG syndrome (FGS) is a genetic condition that affects many parts of the body and occurs almost exclusively in males. "FG" represents the surname initials of the first individuals diagnosed with the disorder. People with FG syndrome frequently have intellectual disability ranging from mild to severe, hypotonia, constipation and/or anal anomalies, a distinctive facial appearance, broad thumbs and great toes, a large head compared to body size (relative macrocephaly), and abnormalities of the corpus callosum. Medical problems including heart defects, seizures, undescended testicle, and an inguinal hernia have also been reported in some affected individuals. Researchers have identified five regions of the X chromosome that are linked to FG syndrome in affected families. Mutations in the MED12 gene appears to be the most common cause of this disorder, leading to FG syndrome 1. Other genes involved with FG syndrome include FLNA (FGS2), CASK (FGS4), UPF3B (FGS6), and BRWD3 (FGS7). FGS is inherited in an X-linked recessive pattern. Individualized early intervention and educational services are important so that each child can reach their fullest potential.
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*[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
| FG syndrome | c0220769 | 1,635 | gard | https://rarediseases.info.nih.gov/diseases/2317/fg-syndrome | 2021-01-18T18:00:29 | {"mesh": ["C537923"], "omim": ["305450", "300321", "300406", "300422", "300581"], "umls": ["C0220769"], "orphanet": ["323"], "synonyms": ["FGS", "Opitz-Kaveggia syndrome", "FGS1", "Mental retardation, large head, imperforate anus, congenital hypotonia, and partial agenesis of corpus callosum", "Keller syndrome"]} |
A rare syndromic cardiac disease characterized by communicating hydrocephalus, endocardial fibroelastosis, and congenital cataracts. A history of upper respiratory infection in the mother during the first trimester of pregnancy and polyhydramnios in the third trimester has been associated. No evience of toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and galactosemia is reported. There have been no further descriptions in the literature since 1995.
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*[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
| HEC syndrome | c1833607 | 1,636 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2119 | 2021-01-23T18:19:26 | {"gard": ["2620"], "mesh": ["C535855"], "omim": ["600559"], "umls": ["C1833607"], "icd-10": ["Q87.8"], "synonyms": ["Hydrocephalus-endocardial fibroelastosis-cataract syndrome"]} |
A number sign (#) is used with this entry because single-nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine receptor gene cluster on chromosome 15q25.1, represented by SNPs in the CHRNA3 (118503) and CHRNA5 (118505) genes, have been associated with susceptibility to smoking-related behavioral traits and lung cancer.
For a discussion of genetic influences on smoking behavior, see 188890. For a phenotypic description and a discussion of genetic heterogeneity of lung cancer, see 211980.
Pathogenesis
Lung cancer is caused predominantly by tobacco smoking. Hung et al. (2008) noted that independent biologic data suggested that nicotinic acetylcholine receptors could be involved in lung cancer through mechanisms other than smoking. It has been suggested that N-prime-nitrosonornicotine and nitrosamines may facilitate neoplastic transformation by stimulating angiogenesis and tumor growth mediated through their interaction with nicotinic acetylcholine receptors. The expression of these receptors can also be inhibited by nicotine receptor antagonists, which, if confirmed to be involved in disease etiology through such a mechanism, would suggest possible chemoprevention opportunities for lung cancer.
Mapping
Three genomewide association studies on smoking quantity were reported simultaneously and in partnership in 2010. Liu et al. (2010) performed a genomewide association study of smoking quantity, as measured by cigarettes per day (CPD) in a final database set of 41,150 individuals from 20 disease, population, and control cohorts. The single most significant locus was with the A allele of rs1051730 on chromosome 15q25 (p = 9.45 x 10(-19)). A repeat of the analysis using more SNPs in this region found a significant association with rs55853698 (p = 1.31 x 10(-16)); this SNP's location in the 5-prime untranslated region of the CHRNA5 gene makes it a candidate for affecting transcription. Another SNP in this region (rs16969968) also showed significance (p = 1.64 x 10(-18)).
Simultaneously, The Tobacco and Genetics Consortium (2010) reported their findings of genomewide association studies for number of cigarettes smoked per day among 38,181 individuals from multiple different cohorts. The most significant association was with rs12914385 in CHRNA3 (p = 4.2 x 10(-35)), followed by rs1051730 (p = 8.0 x 10(-33)), which was noted to be a synonymous SNP in the CHRNA3 gene. Significant association was also found with the G allele of rs16969968 (p = 4.48 x 10(-33)), also in the CHRNA3 gene. Thorgeirsson et al. (2010) found that the most significant association with number of cigarettes smoked per day in their study of 31,266 individuals was with the A allele of rs1051730 (p = 2.1 x 10(-33)). Each of the studies provided p value estimates for the combined effect of rs1051730 with smoking behavior from all 3 studies, including about 75,000 individuals: 1.71 x 10(-66) (Liu et al., 2010); 2.75 x 10(-73) (The Tobacco and Genetics Consortium, 2010), and 2.4 x 10(-69) (Thorgeirsson et al., 2010). Liu et al. (2010) and The Tobacco and Genetics Consortium (2010) also found significant association with the G allele of rs16969968 across all 3 studies (p = 4.29 x 10(-65) and 5.57 x 10(-72), respectively).
Molecular Genetics
To identify genetic factors that modify disease risk, Hung et al. (2008) conducted a genomewide association study by analyzing 317,139 SNPs in 1,989 lung cancer cases and 2,625 controls from 6 central European countries. Hung et al. (2008) identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in 5 separate lung cancer cases comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. In an examination of the association in different smoking categories, increased risks were seen for former smokers (P = 4 x 10(-7)) and current smokers (P = 3 x 10(-10)), as well as a potential increased risk for people who had never smoked (P = 0.013). The locus was not associated with smoking-related head and neck cancers. The association region contains several genes, including 3 that encode nicotinic acetylcholine receptor subunits (CHRNA5, 118505; CHRNA3, 118503; and CHRNB4, 118509). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells, and lung cancer cell lines, and they bind to N-prime-nitrosonornicotine and potential lung carcinogens. A nonsynonymous variant in CHRNA5, rs16969968, that induces an amino acid substitution (D398N; 118505.0001) at a highly conserved site in the second intracellular loop of the protein was among the markers with the strongest disease association. Hung et al. (2008) concluded that their results provided compelling evidence of a locus at chromosome 15q25 predisposing to lung cancer, and reinforced interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
Thorgeirsson et al. (2008) identified a common variant, rs1051730, in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, nicotine dependence, and the risk of 2 smoking-related diseases (lung cancer and peripheral artery disease) in populations of European descent. The SNP rs1051730, which resides in the CHRNA3 gene (118503.0001), was strongly associated with smoking quantity (P = 5 x 10(-16)). The same variant was associated with nicotine dependence in a previous genomewide association study that used low-quantity smokers as controls (Saccone et al., 2007; Bierut et al., 2007). With a similar approach, Thorgeirsson et al. (2008) observed a highly significant association with nicotine dependence. Thorgeirsson et al. (2008) studied the effect of the rs1051730 variant on lung cancer and peripheral artery disease risk directly, including indirect effects through smoking quantity and nicotine dependence. The lung cancer study included 1,024 cases and 32,244 controls from Iceland, Spain, and the Netherlands; the peripheral artery disease study was based on 2,738 cases and 29,964 controls from 5 Caucasian populations (Iceland, New Zealand, Austria, Sweden, and Italy). Significant association was found with both diseases. Combining the results from all 3 groups in the lung cancer study gave an odds ratio (OR) of 1.31 (P = 10(-8)). Combining results from all 5 peripheral artery disease study groups yielded an OR of 1.19 (P = 1.4 x 10(-7)). Thorgeirsson et al. (2008) concluded that their findings provided a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.
Both Hung et al. (2008) and Thorgeirsson et al. (2008) noted that rs1051730 and rs16969968 are in strong linkage disequilibrium; Hung et al. (2008) gave the squared correlation coefficient (r(2)) between the 2 variants as 0.99, while Thorgeirsson et al. (2008) cited r(2) = 0.90 for the 2 in the HapMap project.
To identify risk variants for nonsmall cell lung cancer, Amos et al. (2008) conducted a multistage genomewide association study. In the discovery phase, the authors analyzed 315,450 tagging SNPS in 1,154 current and former (ever) smoking cases of European ancestry with nonsmall cell lung cancer versus 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, Amos et al. (2008) evaluated 10 SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 (118503.0001) and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing the PSMA4 (176846) and the nicotinic acetylcholine receptor unit genes CHRNA3 (118503.0001) and CHRNA5 (118505), were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P less than 1 x 10(-17)) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. Amos et al. (2008) concluded that variation in a region of 15q25.1 containing nicotinic acetylcholine receptor genes contributes to lung cancer risk. The SNP rs8034191 lies within the LOC123688 gene. The SNPs rs1051730 and rs8034191 are separated by 88 kb, and the genotypes are highly correlated (r(2) = 0.88 in the discovery set and 0.81 in HapMap for the population of European ancestry).
In a genomewide association study pooling data from 3 studies including 5,095 patients with lung cancer and 5,200 controls, Wang et al. (2008) found a significant association between susceptibility to lung cancer and rs8042374 on chromosome 15q25.1 (p = 7.75 x 10(-12)), confirming previous reports.
Keskitalo et al. (2009) measured the number of cigarettes smoked per day (CPD) and immune-reactive serum cotinine level (a nicotine metabolite) in 516 daily smokers (aged 30-75 years; 303 males and 213 females) from an adult Finnish population. Association of 21 SNPs from a 100-kb region of chromosome 15q25.1 with cotinine and CPD were examined. The SNP rs1051730 showed the strongest association to both measures. However, this SNP accounted for nearly a 5-fold larger proportion of variance in cotinine levels than in CPD (r(2) 4.3% vs 0.9%). The effect size of the SNP was 0.30 for cotinine level, whereas it was 0.13 for CPD. Keskitalo et al. (2009) concluded that variation at the CHRNA5/CHRNA3/CHRNB4 cluster influences nicotine level, measured as cotinine, more strongly than smoking quantity, measured by CPD, and appears thus to be involved in regulation of nicotine levels among smokers.
*[v]: View this template
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*[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
| SMOKING AS A QUANTITATIVE TRAIT LOCUS 3 | c2677571 | 1,637 | omim | https://www.omim.org/entry/612052 | 2019-09-22T16:02:28 | {"omim": ["612052"], "synonyms": ["Alternative titles", "NICOTINE DEPENDENCE, SUSCEPTIBILITY TO"]} |
Complex regional pain syndrome (CRPS) is a rare neurologic disease painful progressive condition that corresponds to a group of disorders characterized by a disproportionate spontaneous or stimulus-induced pain, accompanied by a variably mixed myriad of autonomic and motor disorders including symptoms such as swelling, allodynia, skin blood supply and trophic disturbances. CRPS most often affects one of the arms, legs, hands, or feet and usually occurs after an injury or trauma to that limb.
*[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
| Complex regional pain syndrome | c0458219 | 1,638 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83452 | 2021-01-23T17:12:31 | {"gard": ["4647"], "mesh": ["D020918"], "omim": ["604335"], "umls": ["C0458219"], "icd-10": ["G56.4", "M89.0"]} |
Restrictive lung disease
Other namesRestrictive ventilatory defect[1]
SpecialtyPulmonology
Restrictive lung diseases are a category of extrapulmonary, pleural, or parenchymal respiratory diseases that restrict lung expansion,[2] resulting in a decreased lung volume, an increased work of breathing, and inadequate ventilation and/or oxygenation. Pulmonary function test demonstrates a decrease in the forced vital capacity.
## Contents
* 1 Presentation
* 2 Causes
* 2.1 Intrinsic
* 2.2 Extrinsic
* 3 Pathophysiology
* 4 Diagnosis
* 5 Management
* 6 See also
* 7 References
* 8 External links
## Presentation[edit]
Due to the chronic nature of this disease, the leading symptom of restrictive lung disease is progressive exertional dyspnea.[3] For acute on chronic cases, shortness of breath, cough, and respiratory failure are some of the more common signs.[3]
## Causes[edit]
Restrictive lung diseases may be due to specific causes which can be intrinsic to the parenchyma of the lung, or extrinsic to it.[3]
### Intrinsic[edit]
* Pneumoconiosis caused by long-term exposure to dusts, especially in mining. For example, Asbestosis.
* Radiation fibrosis, usually from the radiation given for cancer treatment.
* Certain drugs such as amiodarone, bleomycin and methotrexate.
* As a consequence of another disease such as rheumatoid arthritis.
* Hypersensitivity pneumonitis due to an allergic reaction to inhaled particles.
* Acute respiratory distress syndrome (ARDS), a severe lung condition occurring in response to a critical illness or injury.
* Infant respiratory distress syndrome due to a deficiency of surfactant in the lungs of a baby born prematurely.
* Tuberculosis[4]
Many cases of restrictive lung disease are idiopathic (have no known cause). Still, there is generally pulmonary fibrosis.[5] Examples are:
* Idiopathic pulmonary fibrosis
* Idiopathic interstitial pneumonia, of which there are several types
* Sarcoidosis
* Eosinophilic pneumonia
* Lymphangioleiomyomatosis
* Pulmonary Langerhans' cell histiocytosis
* Pulmonary alveolar proteinosis
Conditions specifically affecting the interstitium are called interstitial lung diseases.
### Extrinsic[edit]
* Nonmuscular diseases of the upper thorax such as kyphosis, pectus carinatum and pectus excavatum.[6]
* Diseases restricting lower thoracic/abdominal volume (e.g. obesity, diaphragmatic hernia, or the presence of ascites).[6]
* Pleural thickening.
## Pathophysiology[edit]
In normal respiratory function, the air flows in through the upper airway, down through the bronchi and into the lung parenchyma (the bronchioles down to the alveoli) where gas exchange of carbon dioxide and oxygen occurs.[7] During inspiration, the lungs expand to allow airflow into the lungs and thereby increasing total volume. After inspiration follows expiration during which the lungs recoil and push air back out of the pulmonary pathway. Lung compliance is the difference of volume during inspiration and expiration.[7]
Restrictive lung disease is characterized by reduced lung volumes, and therefore reduced lung compliance, either due to an intrinsic reason, for example a change in the lung parenchyma, or due to an extrinsic reason, for example diseases of the chest wall, pleura, or respiratory muscles.[3] Generally, intrinsic causes are from lung parenchyma diseases that cause inflammation of scarring of the lung tissue, such as interstitial lung disease or pulmonary fibrosis, or from having the alveoli air spaces filled with external material such as debris or exudate in pneumonitis.[3] As some diseases of the lung parenchyma progress, the normal lung tissue can be gradually replaced with scar tissue that is interspersed with pockets of air.[5] This can lead to parts of the lung having a honeycomb-like appearance. The extrinsic causes result in lung restriction, impaired ventilatory function, and even respiratory failure due to the diseases that effect the lungs ability to create a change in lung volumes during respiration due to the diseases of the systems stated above.[3]
## Diagnosis[edit]
In restrictive lung disease, both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) are reduced, however, the decline in FVC is more than that of FEV1, resulting in a higher than 80% FEV1/FVC ratio. In obstructive lung disease however, the FEV1/FVC is less than 0.7, indicating that FEV1 is significantly reduced when compared to the total expired volume. This indicates that the FVC is also reduced, but not by the same ratio as FEV1.[8]
One definition requires a total lung capacity which is 80% or less of the expected value.[9]
## Management[edit]
Medical treatment for restrictive lung disease is normally limited to supportive care since both the intrinsic and extrinsic causes can have irreversible effects on lung compliance.[10] The supportive therapies focus on maximizing pulmonary function and preserving activity tolerance through oxygen therapy, bronchodilators, inhaled beta-adrenergic agonists, and diuretics.[10] Because there is no effective treatment for restrictive lung disease, prevention is key.[10]
## See also[edit]
* Chronic obstructive pulmonary disease
* Extrapulmonary restriction
* Obstructive lung disease
## References[edit]
1. ^ Johns Hopkins School of Medicine's Interactive Respiratory Physiology > Restrictive Ventilatory Defect Retrieved on February 25, 2010
2. ^ Sharma, Sat. "Restrictive Lung Disease". Retrieved 2008-04-19.
3. ^ a b c d e f "eMedicine - Restrictive Lung Disease : Article by Sat Sharma". Retrieved 2008-11-21.
4. ^ Amaral, André F.S.; Coton, Sonia; Kato, Bernet; Tan, Wan C.; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D.; Buist, Sonia; Burney, Peter G.J. (October 2015). "Tuberculosis associates with both airflow obstruction and low lung function: BOLD results". European Respiratory Journal. 46 (4): 1104–1112. doi:10.1183/13993003.02325-2014. PMC 4594762. PMID 26113680.
5. ^ a b PULMONARY FUNCTION TESTS A Workshop on Simple Spirometry & Flow Volume Loops. Dr. S. Osborne, Dept. Cellular & Physiological Sciences. Mars 2009
6. ^ a b eMedicine Specialties > Pulmonology > Interstitial Lung Diseases > Restrictive Lung Disease Author: Lalit K Kanaparthi, MD, Klaus-Dieter Lessnau, MD, Sat Sharma, MD. Updated: Jul 27, 2009
7. ^ a b Capriotti, Theresa (2016). Pathophysiology : introductory concepts and clinical perspectives. Frizzell, Joan Parker. Philadelphia. ISBN 978-0-8036-1571-7. OCLC 900626405.
8. ^ Lee, H., Lim, S., Kim, J., Ha, H., & Park, H. (2015). Comparison Of Various Pulmonary Function Parameters In The Diagnosis Of Obstructive Lung Disease In Patients With Normal Fev1/FVC And Low FVC. American Journal of Respiratory and Critical Care Medicine, 191, American Journal of Respiratory and Critical Care Medicine, 2015, Vol.191.
9. ^ Brack T, Jubran A, Tobin MJ (May 2002). "Dyspnea and decreased variability of breathing in patients with restrictive lung disease". Am. J. Respir. Crit. Care Med. 165 (9): 1260–4. doi:10.1164/rccm.2201018. PMID 11991875.
10. ^ a b c Focus on adult health : medical-surgical nursing. Honan, Linda, 1955- (1st ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. 2013. ISBN 978-1-58255-877-6. OCLC 756895022.CS1 maint: others (link)
## External links[edit]
Classification
D
* ICD-9-CM: 518.89
External resources
* eMedicine: article/301760
* v
* t
* e
Diseases of the respiratory system
Upper RT
(including URTIs,
common cold)
Head
sinuses
Sinusitis
nose
Rhinitis
Vasomotor rhinitis
Atrophic rhinitis
Hay fever
Nasal polyp
Rhinorrhea
nasal septum
Nasal septum deviation
Nasal septum perforation
Nasal septal hematoma
tonsil
Tonsillitis
Adenoid hypertrophy
Peritonsillar abscess
Neck
pharynx
Pharyngitis
Strep throat
Laryngopharyngeal reflux (LPR)
Retropharyngeal abscess
larynx
Croup
Laryngomalacia
Laryngeal cyst
Laryngitis
Laryngopharyngeal reflux (LPR)
Laryngospasm
vocal cords
Laryngopharyngeal reflux (LPR)
Vocal fold nodule
Vocal fold paresis
Vocal cord dysfunction
epiglottis
Epiglottitis
trachea
Tracheitis
Laryngotracheal stenosis
Lower RT/lung disease
(including LRTIs)
Bronchial/
obstructive
acute
Acute bronchitis
chronic
COPD
Chronic bronchitis
Acute exacerbation of COPD)
Asthma (Status asthmaticus
Aspirin-induced
Exercise-induced
Bronchiectasis
Cystic fibrosis
unspecified
Bronchitis
Bronchiolitis
Bronchiolitis obliterans
Diffuse panbronchiolitis
Interstitial/
restrictive
(fibrosis)
External agents/
occupational
lung disease
Pneumoconiosis
Aluminosis
Asbestosis
Baritosis
Bauxite fibrosis
Berylliosis
Caplan's syndrome
Chalicosis
Coalworker's pneumoconiosis
Siderosis
Silicosis
Talcosis
Byssinosis
Hypersensitivity pneumonitis
Bagassosis
Bird fancier's lung
Farmer's lung
Lycoperdonosis
Other
* ARDS
* Combined pulmonary fibrosis and emphysema
* Pulmonary edema
* Löffler's syndrome/Eosinophilic pneumonia
* Respiratory hypersensitivity
* Allergic bronchopulmonary aspergillosis
* Hamman-Rich syndrome
* Idiopathic pulmonary fibrosis
* Sarcoidosis
* Vaping-associated pulmonary injury
Obstructive / Restrictive
Pneumonia/
pneumonitis
By pathogen
* Viral
* Bacterial
* Pneumococcal
* Klebsiella
* Atypical bacterial
* Mycoplasma
* Legionnaires' disease
* Chlamydiae
* Fungal
* Pneumocystis
* Parasitic
* noninfectious
* Chemical/Mendelson's syndrome
* Aspiration/Lipid
By vector/route
* Community-acquired
* Healthcare-associated
* Hospital-acquired
By distribution
* Broncho-
* Lobar
IIP
* UIP
* DIP
* BOOP-COP
* NSIP
* RB
Other
* Atelectasis
* circulatory
* Pulmonary hypertension
* Pulmonary embolism
* Lung abscess
Pleural cavity/
mediastinum
Pleural disease
* Pleuritis/pleurisy
* Pneumothorax/Hemopneumothorax
Pleural effusion
Hemothorax
Hydrothorax
Chylothorax
Empyema/pyothorax
Malignant
Fibrothorax
Mediastinal disease
* Mediastinitis
* Mediastinal emphysema
Other/general
* Respiratory failure
* Influenza
* Common cold
* SARS
* Coronavirus disease 2019
* Idiopathic pulmonary haemosiderosis
* Pulmonary alveolar proteinosis
*[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
| Restrictive lung disease | c0085581 | 1,639 | wikipedia | https://en.wikipedia.org/wiki/Restrictive_lung_disease | 2021-01-18T19:02:01 | {"umls": ["C0085581"], "icd-9": ["518.89"], "wikidata": ["Q7316336"]} |
A rare genetic disease characterized by lethal non-spherocytic, non-immune hemolytic anemia, in association with abnormalities of the external genitalia (such as micropenis and hypospadias). Reported dysmorphic features include flat occiput, dimpled earlobes, deep plantar creases, and increased space between the first and second toes. There have been no further descriptions in the literature since 1995.
*[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
| Lethal hemolytic anemia-genital anomalies syndrome | c1838120 | 1,640 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1046 | 2021-01-23T18:02:52 | {"mesh": ["C563935"], "omim": ["600461"], "umls": ["C1838120"], "icd-10": ["D58.8"], "synonyms": ["Water-West syndrome"]} |
A number sign (#) is used with this entry because of evidence that Char syndrome (CHAR) is caused by heterozygous mutation in the TFAP2B (601601) gene on chromosome 6p12.
Clinical Features
Davidson (1993) described a large family in which 9 members in 6 sibships in 3 generations had patent ductus arteriosus (PDA; see 607411) in association with unusual facial features, namely, broad, high forehead, flat profile, and short nose with a broad, flattened tip. The facial features appeared to follow an autosomal dominant pedigree pattern with at least 1 instance of male-to-male transmission; PDA showed incomplete penetrance. PDA was reported by the family to be present in 2 other members, one of whom was said to have the facial features and one not.
Pierpoint and Sletten (1994) used the eponym Char syndrome for familial PDA with unusual facial features, including long philtrum, downslanting palpebral fissures, and thick lips. They reported a new family in which 7 members had PDA. Premature birth was not a factor in any of these individuals. PDA had been the only form of congenital heart anomaly present in family members except for one 8-year-old boy who had a small muscular ventricular septal defect. Three generations were affected in an autosomal dominant pedigree pattern.
Sletten and Pierpont (1995) observed 7 relatives in 5 sibships in 3 generations of a family with patent ductus arteriosus and a slightly unusual facial appearance with prominent midface with nose elongation and flattening of the nasal bridge, wide-set eyes, downturned palpebral fissures, mild ptosis, thick lips, and apparently slightly low-set ears. The pattern was consistent with autosomal dominant inheritance although no male-to-male transmission was observed. Sletten and Pierpont (1995) gave an extensive tabulation of reports of familial PDA. They pointed to the syndrome reported by Char (1978) in which patent ductus arteriosus was associated with a much more unusual facies with short philtrum, 'duck-bill' lips, ptosis, and low-set ears. Temple (1992) also described this syndrome, referring to it as Char syndrome.
Slavotinek et al. (1997) described a family with PDA, a distinctive facial appearance (eyebrow flare, short nose, and 'duck-bill' lips), polydactyly, and fifth finger clinodactyly. The facial features were considered consistent with CHAR syndrome. Seven members of 3 generations were affected, with 2 instances of male-to-male transmission. This was the first report of associated polydactyly that was interstitial in type. The foot of 1 patient with 2 toes attached to the fourth metatarsal was illustrated. Evolution of the phenotype with age was noted; the facial findings in older relatives were less pronounced and the 'duck-bill' lips less prominent.
Satoda et al. (1999) pictured characteristic facial features, including short philtrum, prominent lips, flat nasal bridge with upturned nares, and ptosis. They also illustrated the changes in the hand: absent fifth middle phalanges with hypoplasia of the fifth proximal and distal phalanges.
Zannolli et al. (2000) reported a father and daughter with Char syndrome. Both had the typical facial features as well as strabismus and foot anomalies. The daughter also had patent ductus arteriosus. Both patients had supernumerary nipples (163700), a finding not described before in Char syndrome.
Sweeney et al. (2000) reported a mother, son, and daughter with the typical facial features of Char syndrome. The son had symphalangism of the distal interphalangeal joints of the fifth fingers with loss of overlying skin creases and clinodactyly. The mother had similar digital features, and the daughter was said to have had them but was not personally examined by the authors.
Mani et al. (2005) studied a large 3-generation family with Char syndrome (family K144) in which there were 22 affected individuals, including 9 with PDA, facial dysmorphism, and clinodactyly, and 13 who showed dysmorphology and clinodactyly without PDA. In addition, there was 1 obligate carrier who was nonpenetrant for all features, and 1 infant died in the neonatal period from heart failure, with coarctation of the aorta, bicuspid aortic valve, and a large PDA. All 9 PDA patients, including the deceased infant, were born at term from a normal gestation, and were diagnosed between the neonatal period and age 30 years. Thus, in this family, PDA showed incomplete penetrance, whereas dysmorphic facies and clinodactyly showed evidence of high penetrance. Further evaluation of family members revealed additional features segregating with the disorder, including hypodontia in 14 affected individuals, who retained their primary teeth and either partially or completely lacked secondary teeth, and parasomnia in 13, involving sleepwalking associated with food-seeking behavior. There were also 10 affected family members who exhibited protuberant occipital bone with overlying coarse hair; in each case, the border of the occiput had a sharp ridge, suggestive of craniosynostosis. None of these additional features was observed in any unaffected family member. Mani et al. (2005) also studied an affected father and 2 daughters from an unrelated family with Char syndrome (family K145). All exhibited PDA, dysmorphic facies, and clinodactyly; the father's sister was also reported to be affected. Mani et al. (2005) noted that in addition to finger clinodactyly, affected members of both kindreds had varying degrees of clinodactyly of the fourth and fifth toes, and syndactyly of the fourth and fifth toes was seen in 4 affected individuals.
Mapping
Satoda et al. (1999) performed linkage analysis in 2 previously reported multigenerational kindreds with Char syndrome (Char, 1978; Sletten and Pierpont, 1995). Linkage was found with several polymorphic DNA markers mapping to 6p21-p12. A maximum 2-point lod score of 8.39 was observed with D6S1638 at theta = 0.00. Haplotype analysis identified recombinant events that defined the Char syndrome locus with high probability to a 3.1-cM region.
Molecular Genetics
Satoda et al. (2000) used a positional candidate gene strategy and mapped TFAP2B (601601), encoding a transcription factor expressing neural crest cells, to the Char syndrome critical region and identified heterozygous missense mutations altering conserved residues in 2 affected families (601601.0001-601601.0002). Mutant TFAP2B proteins dimerized properly in vitro but showed abnormal binding to TFAP2 target sequence. Dimerization of both mutants with normal TFAP2B adversely affected transactivation, demonstrating a dominant-negative mechanism. Satoda et al. (2000) concluded that their work shows that TFAP2B has a role in ductal, facial, and limb development and suggests that Char syndrome results from derangement of neural crest cell derivatives.
Zhao et al. (2001) studied 8 patients with Char syndrome and identified 4 novel mutations in the TFAP2B gene; 3 occurred in the basic domain (601601.0003-601601.0005) and the other affected a conserved PY motif in the transactivation domain (601601.0006). Zhao et al. (2001) found that all 4 mutations, as well as 2 previously identified mutations in the basic domain, had dominant-negative effects when expressed in eukaryotic cells. Affected individuals with the PY motif mutation had a high prevalence of patent ductus arteriosus, but only mild facial and hand abnormalities as compared to individuals with basic domain (DNA-binding) mutations. The authors concluded that this correlation supports the existence of TFAP2 coactivators that have tissue specificity and are important for ductal development but less critical for craniofacial and limb development.
In a large 3-generation family segregating autosomal dominant Char syndrome, Mani et al. (2005) identified heterozygosity for a splice site mutation (601601.0007) in the TFAP2B gene that segregated with disease in the family and was not found in 200 unrelated control chromosomes. In addition, heterozygosity for a different splice site mutation in TFAP2B was identified in an unrelated family with Char syndrome. The authors noted that in contrast to previously reported dominant-negative TFAP2B mutations in Char syndrome, the mechanism of disease in these 2 kindreds was likely to be haploinsufficiency.
INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Broad forehead \- Short philtrum Ears \- Prominent ears \- Low-set ears Eyes \- Ptosis \- Hypertelorism \- Thick, flared eyebrows \- Strabismus Nose \- Broad nasal tip Mouth \- Prominent 'duckbill' lips \- Triangular mouth Teeth \- Retention of primary teeth (in some patients) \- Partial or complete absence of secondary teeth (in some patients) CARDIOVASCULAR Vascular \- Patent ductus arteriosus SKELETAL Skull \- Protuberant occipital bone \- Sharp elevated ridge at border of occipital bone Hands \- Fifth finger clinodactyly \- Fifth finger distal interphalangeal joint symphalangism Feet \- Clinodactyly of fourth and fifth toes (in some patients) \- Syndactyly of fourth and fifth toes (rare) NEUROLOGIC Central Nervous System \- Developmental delay, mild Behavioral Psychiatric Manifestations \- Parasomnia \- Sleepwalking associated with food-seeking behavior MISCELLANEOUS \- Intrafamilial variability, with some family members exhibiting only facial dysmorphism and clinodactyly MOLECULAR BASIS \- Caused by mutations in the transcription factor AP-2 beta gene (TFAP2B, 601601.0001 ) ▲ 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
| CHAR SYNDROME | c1868570 | 1,641 | omim | https://www.omim.org/entry/169100 | 2019-09-22T16:36:31 | {"doid": ["0060563"], "mesh": ["C566815"], "omim": ["169100"], "orphanet": ["46627"], "synonyms": ["Alternative titles", "PATENT DUCTUS ARTERIOSUS WITH FACIAL DYSMORPHISM AND ABNORMAL FIFTH DIGITS"], "genereviews": ["NBK1106"]} |
Despite decreasing HIV prevalence nationwide, Haiti still remains one of the most HIV infected nations in the Caribbean.[1]
With an estimated 150,000 people living with HIV/AIDS in 2016 (or an approximately 2.1 percent prevalence rate among adults aged 15–49), Haiti has the most overall cases of HIV/AIDS in the Caribbean and its HIV prevalence rates among the highest percentage-wise in the region.[2] There are many risk factors groups for HIV infection in Haiti, with the most common ones including lower socioeconomic status, lower educational levels, risky behavior, and lower levels of awareness regarding HIV and its transmission.[3][4] However, HIV prevalence in Haiti is largely dropping as a result of a strong AIDS/HIV educational program, support from non-governmental organizations and private donors, as well as a strong healthcare system supported by UNAIDS. Part of the success of Haiti's HIV healthcare system lies in the governmental commitment to the issue, which alongside the support of donations from the Global Fund and President's Emergency Plan For AIDS Relief (PEPFAR), allows the nation to prioritize the issue.[1] Despite the extreme poverty afflicting a large Haitian population, the severe economic impact HIV has on the nation, and the controversy surrounding how the virus spread to Haiti and the United States, Haiti is on the path to provide universal treatment, with other developing nations emulating its AIDS treatment system.[1]
## Contents
* 1 History
* 2 Prevalence
* 3 Risk factors
* 4 Economic impact
* 5 HIV treatment and prevention
* 5.1 Elimination of mother to child transmission
* 5.2 HIV Equity Initiative
* 5.3 HIV prevention
* 5.4 Challenges
* 6 The Haitian connection controversy
* 7 See also
* 8 References
## History[edit]
AIDS in Haitians was first recognized in 34 Haitians living in the United States in 1982, and in the same year eleven individuals in Haiti were suspected to be HIV infected.[1] Since the majority of these individuals did not fall into the classic risk factor groups, Haitians were classified as a separate risk factor group, causing damage to Haiti's image and economy and affecting tourism. In the same year, the Haitian Study Group on Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) was formed to study the new epidemic. GHESKIO used retrospective diagnosis to conclude that from 1979 to 1982, there were 61 cases of AIDS in Haiti. Through various studies and analyses, GHESKIO concluded that the risk factors identified in the 61 individuals were no different from those in other countries, with the primary risk factor being the fact that most of the patients lived in the suburb of Carrefour where prostitution was prevalent. The stigmatization of Haiti, however, continued, and during the presidency of Jean-Claude Duvalier, it was illegal to mention AIDS/HIV in Haiti.[5] From 1983 to 1987, the virus spread quickly through the population mostly through heterosexual sex, as HIV infected cases attributed to homosexuals or bisexuals went down from 50% to less than 1%.[1] In a 1985 to 2000 study, the virus spread twice as fast in developed nations prior to the use of antiretrovirals, as malnutrition, infectious communities, and active tuberculosis were all prevalent in Haiti.[1] Jean-Bertrand Aristide, the first democratically elected President of Haiti, was the first Haitian president to include HIV/AIDS into his platform for his 2001–2004 presidency and initiated governmental policies to ensure the blood supply remains uncontaminated and to prevent and treat the virus amongst the population.[6]
## Prevalence[edit]
In Haiti, the three groups where HIV/AIDS is most prevalent are men who have sex with men, sex workers, and prisoners, with prevalence rates of 18.2, 8.4, and 4.3 respectively.[2] As opposed to the United States, intravenous drug use in Haiti was more rare and the blood supply was not initially affected by HIV infected individuals. As such, intravenous drug users and hemophiliacs were never major risk factor groups in Haiti since the start of the epidemic.[1]
As of 2017, UNAIDS, the Joint United Nations Programme on HIV/AIDS, reports that HIV in Haiti is most prevalent among adults aged 15 to 49 and is primarily transmitted through heterosexual contact and mother-to-infant transmission.[7]
The recent declines in HIV infection rates are most notable in urban areas, and have been attributed to significant behavioral changes, including decreased number of partners, decreased sexual debut, and increased condom use. Other explanations for the recent trends include AIDS-related mortality and improvements made in blood safety early in the epidemic. However, continued political instability, high internal migration rates, high prevalence of sexually transmitted infections, and weakened health and social services persist as factors with potential negative impacts on the epidemic.[2]
## Risk factors[edit]
According to a 2010 study, one major risk factor for HIV infection in Haiti, especially in women, is lower socioeconomic status.[3] In rural Haitian populations where education levels for women are low and many women are economically dependent on their husbands, a correlation between the stability of the occupation of the husband and HIV prevalence in the wives is observed.[3] Women whose husbands are market vendors or mechanics are at a higher risk of HIV infection. On the contrary, the wives of farmers, a more stable occupation, have a 60% lower risk of HIV infection.[3] Other indicators of low socioeconomic status, like the use of charcoal for cooking and food insecurity also show correlation with higher HIV infection rates in women.[3] The study stipulates that low socioeconomic status and high rates of HIV infection may be connected to the use of transactional sex as an economic survival strategy, a behavior shown in a related South African study to increase HIV infection rates by 1.5 times.[8] Similar trends from related studies have also been seen in other developing nations with gender disparities, such as Malawi, Rwanda, Kenya, Ghana, Democratic Republic of Congo, Zambia, and Uganda.[3]
Another vulnerable group is adolescents and young adults. For females, risk factor groups include those who have low levels of education, live away from their parents, have been married, or have had a child.[4] For males, factors indicative of HIV infection are intravenous drug use and sexual debut with an unknown individual.[4] For both genders, young adults who are less aware of HIV and its transmission through risky behavior are more likely to be infected, and amongst females, those who talked more openly about HIV infection and testing were less likely to be infected.[4] Finally, having sexual contact with unfaithful partners, having an STI, especially syphilis, and not using condoms are all additional risk factors that affect both genders.[4]
## Economic impact[edit]
On the national level, HIV causes damage to the Haitian economy because the individuals most affected by the epidemic are the young adults that contribute the most to the country's economy.[9] At the start of the epidemic, Haiti's tourism and export industries suffered when Haitians were classified as an HIV risk group.[10] According to Jean Pape, the head of the largest Haitian HIV research center, Haitian products could no longer be sold in the US and tourism, which was the basis of the Haitian economy, declined drastically.[10] With 54% of the Haiti economy based on the service and tourism sector, HIV further weakened Haiti's already struggling economy.[5]
On a household level, HIV causes significant economic strain to the family of infected individuals.[11] HIV infection in a parent can lead to the loss of one source of income which in turn leads to malnutrition, lack of access to education for the children, and increased risk of child labor.[9] The cost of healthcare is another burden on the family.[11] From a 1997 study involving 600 households from Côte d'Ivoire, Burundi, and Haiti, households with at least one HIV infected family member spent nearly twice the amount on healthcare (around 10.6%) compared to families without HIV infected individuals, decreasing household consumption in other areas.[11] The HIV treatment also on average took up 80% of the entire family's healthcare budget. Even after the death of the HIV infected individual, the household never completely returned to its original level of consumption.[11]
## HIV treatment and prevention[edit]
Nearly 75% of HIV treatment in Haiti is sponsored and overseen by the NGOs Partners In Health and Haitian Study Group on Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) in collaboration with the Haitian Ministry of Health.[1] Alongside them, the Joint United Nations Team on AIDS (Joint Team) in Haiti also helps provide the resources to tackle HIV through prevention, treatment, and testing, accelerating the nationwide HIV response.[2] As of 2016, around 55% of HIV positive Haitians received antiretroviral therapy.[2]
### Elimination of mother to child transmission[edit]
Prior to the efforts to eliminate vertical transmission of HIV, around 27% of babies born to HIV infected mothers in Haiti contracted the virus from their mothers through breast milk.[1] As a preventative measure, GHESKIO and the Ministry of Health set up national guidelines for HIV infected mothers and newborn babies to receive doses of zidovudine. Since 2003, Haiti has altered its guidelines to allow triple drug ART for pregnant HIV infected women, treatments for existing opportunistic infections, and counseling on the use of formula feed instead of breast milk to lower transmission rates.[1] Since the use of triple therapy, HIV transmission rates from mother to child for those on triple drug ART has decreased to around 1.9%, while the transmission rates among all pregnant women treated for HIV in any form has dropped to 9.2%, both of which are significant decreases from the initial 27% vertical transmission.[1] The Joint Team and UNICEF also provides manuals on preventing mother to child transmission of HIV and offers prenatal and postpartum counseling services to HIV infected mothers to stem vertical transmission in Haiti.[2] However, further educational efforts are necessary as only around 40% of Haitian HIV infected mothers attend these counseling services, and an even smaller amount get tested for HIV prior to childbirth.[1] Around 80% of Haitians recognize that the virus can be transmitted vertically, however, the majority of Haitians do not know that treatment of both the mother and child in the weeks before and after childbirth can greatly decrease the risk of infection in the baby.[1] This coupled with the fact that around 80% of childbirth in Haiti takes place at home instead of in a hospital necessitates that further connection of HIV infected individuals with the health networks in Haiti is essential to stem vertical transmission.[1]
### HIV Equity Initiative[edit]
In 1985, Paul Farmer and his colleagues created a clinic in the Central Plateau of Haiti to serve those displaced by the creation of a hydroelectric dam. The first case of HIV recorded at this clinic was in 1986. In 1987, Farmer spearheaded the effort that lead to the founding of Partners in Health. After a 1994 paper detailing the effects of AZT on lowering the rates of transmission from mother to child, the HIV clinic began offering HIV testing and antiretroviral therapy to pregnant mothers, leading to a sharp decline of cases of mother to child transmission.[12] Starting in 1997, the clinic made post-exposure prophylaxis (PEP) available to women who suffered from rape and HIV health workers who had occupation injuries. In late 1998, individuals with long term severe opportunistic infections were offered antiretroviral therapy as opposed to only being allowed to treat their symptoms for free. For those infected with the more life-threatening tuberculosis, anti-tuberculous therapy was prioritized over ART.[12] Partners in Health's success largely comes from the directly observed therapy that is given to the patients, through health care workers known as accompagnateurs.[12] Accompagnateurs help the therapy process by making sure the pills are taken on time, answering questions and concerns, and offering moral support to patients and their families. The clinic also assists the family by offering social services such as payment of tuition and highly attended meetings for patients to stay involved in the treatment process.[12] The success of the program in Haiti served as a model to other developing nations that, despite high unemployment, low GDP per capita, and high HIV prevalence, a nation can have a successful HIV treatment program, regardless of urbanization and wealth.[12]
### HIV prevention[edit]
HIV prevention has been brought about, especially in the younger generation, through education and the spreading of awareness of safe sex practices and condom use.[1] The Joint Team, in 2016, has collaborated with the Ministry of Education to create health clubs and programs in 100 schools as well as trained 566 educators, supplied over a million condoms, hosted more than 7000 HIV tests, and referred more than 80% of infected individuals from those tests to seek treatment.[2] UNICEF also sponsored efforts to create a video series and a Facebook page targeted towards the 15–35 age group to spread awareness about the risks of HIV and measures to prevent transmission.[2]
### Challenges[edit]
After the devastation caused by the 2010 Haitian Earthquake, Haiti's HIV treatment system was affected greatly. Estimates by the Haitian government indicate that around 40% of the initial 24,000 Haitians lost access to antiretrovirals after the earthquake.[13] HIV positive individuals displaced due to the earthquake often live in substandard conditions in tent cities, decreasing their immunity and increasing their susceptibility to infection or progressing to AIDS. The large concentration of HIV positive individuals in confined tent cities also increases the risk of HIV transmission within the smaller community of individuals.[13] However, the overall structure of the HIV treatment system has largely remained intact and the majority of HIV infected patients continue to receive access to antiviral therapy while the nation rebuilds the rest of its healthcare system.[1]
Other challenges to the HIV treatment and prevention efforts in Haiti include more recent events, such as Hurricane Matthew, the cholera outbreak, and additional refugees arriving from the Dominican Republic, the limitations on the human and financial resources the NGOs can provide, and the fluctuating level of cooperation from the Haitian government.[2]
## The Haitian connection controversy[edit]
The Haitian connection controversy refers to the debate regarding the origins of the HIV virus in Haiti and the United States and whether or not HIV was spread into the US by Haitians or into Haiti by Americans. The controversy began in the 1982, when the CDC noted that 34 cases of immunodeficient patients were Haitian.[1] This "connection" noted by physicians caused the erroneous labeling of Haitians as a risk factor group for HIV, leading to the rise of the term "the 4-H's" referring to Homosexuals, Hemophiliacs, Heroin addicts, and Haitians as the major groups prone to HIV infection.[14]
Dr. Jacques Pépin, a Quebecer author of The Origins of AIDS, stipulated that Haiti was one of HIV's entry points to the United States. In July 1960, when Belgian Congo gained independence, the United Nations recruited Francophone experts and technicians from all over the world to assist in filling administrative gaps left by Belgium.[15] By 1962, Haitians made up the second largest group of well-educated experts in the country totaling around 4500. One of them may have carried HIV back across the Atlantic in the 1960s. Pépin argues that its spread in Haiti was sped by poor Haitians in need of money selling their blood plasma at centers such as Hemo-Caribbean, which was known to have poor hygienic practices.[15] Plasma centers separated plasma from blood cells and failed to change needles and tubing between patients, a practice that rapidly spreads blood-borne diseases. Luckner Cambronne, co-owner of Hemo-Caribbean and known as the "Vampire of the Caribbean", was notorious for selling Haitian blood and cadavers abroad for medical uses. Plasma from Hemo-Caribbean was exported to the United States at a maximum rate of 5,000 to 6,000 litres per month in the early 1970s.[15]
In his 1990 book "AIDS and Accusation," Paul Farmer refutes the idea that Haiti was an HIV entry point to the USA. Referencing an epidemiological study on the prevalence of sarcomas associated with HIV/AIDS contraction, Farmer suggests that Cambronne's plasma business occurred before identifiers of HIV infection were recorded in Haiti, indicating that the disease did not arrive in Haiti until at least the late-1970s.[16] Farmer instead argues that HIV/AIDS in Haiti was introduced by visitors from the US.[16]
In a 2007 study, 5 HIV isolates from different regions were compared on the molecular level. By comparing the number of mutations present in different strands of HIV found from patients from Central Africa, the United States, and Haiti, the results predict that the Haitian strain of the virus is the genetic midpoint between the strains found in Central Africa and the United States, and that the virus traveled from Haiti to the United States about 3 years after it reached Haiti.[17] However, this study is refuted by Jean Pape as a continuation of decades old prejudice against Haiti in regards to the AIDS epidemic, as the study does not provide conclusive evidence that the virus traveled from Haiti to the US.[17]
Regardless of origin, the consequences of HIV/AIDS in Haiti were severe. The disease spread rapidly throughout Haiti, infecting thousands.[1] Haiti's burgeoning tourist industry suffered greatly from the association with HIV/AIDS, and Haitians living in the USA were placed on the banned list for blood donations, alongside homosexuals and intravenous drug users, until 1990.[18]
## See also[edit]
* HIV/AIDS in North America
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r Koenig, Serena; Ivers, Lc; Pace, S; Destine, R; Leandre, F; Grandpierre, R; Mukherjee, J; Farmer, Pe; Pape, Jw (2010-03-01). "Successes and challenges of HIV treatment programs in Haiti: aftermath of the earthquake". HIV Therapy. 4 (2): 145–160. doi:10.2217/hiv.10.6. ISSN 1758-4310. PMC 3011860. PMID 21197385.
2. ^ a b c d e f g h i "Haiti". www.unaids.org. Retrieved 2017-10-25.
3. ^ a b c d e f Fawzi, M.C. Smith; Lambert, W.; Boehm, F.; Finkelstein, J.l.; Singler, J.m.; Léandre, F.; Nevil, P.; Bertrand, D.; Claude, M.s. (2010-04-10). "Economic Risk Factors for HIV Infection Among Women in Rural Haiti: Implications for HIV Prevention Policies and Programs in Resource-Poor Settings". Journal of Women's Health. 19 (5): 885–892. doi:10.1089/jwh.2008.1334. ISSN 1540-9996. PMC 2875958. PMID 20380576.
4. ^ a b c d e Dorjgochoo, Tsogzolmaa; Noel, Francine; Deschamps, Marie Marcelle; Theodore, Harry; Dupont, William; Wright, Peter F; Fitzgerald, Dan W; Vermund, Sten H; Pape, Jean W (2009). "Risk Factors for HIV Infection Among Haitian Adolescents and Young Adults Seeking Counseling and Testing in Port-au-Prince". Journal of Acquired Immune Deficiency Syndromes. 52 (4): 498–508. doi:10.1097/qai.0b013e3181ac12a8. PMC 3196358. PMID 19738486.
5. ^ a b "The Sleeping Catastrophe: HIV/AIDS in an Already Devastated Haiti". Retrieved 2018-01-04.
6. ^ Hempstone, Hope (2004). "HIV/AIDS in Haiti: A Literature Review" (PDF).
7. ^ "Caribbean HIV & AIDS Statistics".
8. ^ Dunkle, Kristin L.; Jewkes, Rachel K.; Brown, Heather C.; Gray, Glenda E.; McIntryre, James A.; Harlow, Sioḃán D. (2004). "Transactional sex among women in Soweto, South Africa: prevalence, risk factors and association with HIV infection". Social Science & Medicine. 59 (8): 1581–1592. doi:10.1016/j.socscimed.2004.02.003. PMID 15279917.
9. ^ a b Georges, Yves Marie Dominique (2011). HIV/AIDS in Haiti. An Analysis of Demographics, Lifestyle, STD Awareness, HIV Knowledge and Perception that Influence HIV Infection among Haitians (Thesis). Georgia State University.
10. ^ a b "HIV/AIDS in Haiti and Latin America – The Globalist". The Globalist. 2009-05-02. Retrieved 2017-12-13.
11. ^ a b c d "The Impact of AIDS". www.un.org. Retrieved 2017-12-12.
12. ^ a b c d e Farmer, P.; Léandre, F.; Mukherjee, J. S.; Claude, M.; Nevil, P.; Smith-Fawzi, M. C.; Koenig, S. P.; Castro, A.; Becerra, M. C. (2001-08-04). "Community-based approaches to HIV treatment in resource-poor settings". Lancet. 358 (9279): 404–409. doi:10.1016/s0140-6736(01)05550-7. ISSN 0140-6736. PMID 11502340. S2CID 4650642.
13. ^ a b "After the Quake: HIV/AIDS in Haiti". Pulitzer Center. 2010-08-19. Retrieved 2017-11-22.
14. ^ "Origin of HIV & AIDS". AVERT. 2015-07-20. Retrieved 2017-11-07.
15. ^ a b c Pépin, Jacques, ed. (2011-09-01). The Origin of Aids. Cambridge University Press. p. 188; 201. ISBN 9781139501415. Retrieved 13 March 2016.
16. ^ a b 1959–, Farmer, Paul (2006). AIDS and accusation : Haiti and the geography of blame (Updated with a new preface ed.). Berkeley: University of California Press. ISBN 9780520248397. OCLC 62738653.CS1 maint: numeric names: authors list (link)
17. ^ a b Cohen, Jon (2007-11-02). "Reconstructing the Origins of the AIDS Epidemic From Archived HIV Isolates". Science. 318 (5851): 731. doi:10.1126/science.318.5851.731a. ISSN 0036-8075. PMID 17975041. S2CID 27535587.
18. ^ Hilts, Philip J.; Times, Special to The New York (1990-04-24). "F.D.A. Set To Reverse Blood Ban". The New York Times. ISSN 0362-4331. Retrieved 2017-12-01.
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*[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
| HIV/AIDS in Haiti | None | 1,642 | wikipedia | https://en.wikipedia.org/wiki/HIV/AIDS_in_Haiti | 2021-01-18T18:38:02 | {"wikidata": ["Q5629848"]} |
Pendred syndrome is a condition usually characterized by sensorineural hearing loss in both ears (bilateral) and euthyroid goiter (enlargement of the thyroid gland with normal thyroid gland function). The amount of hearing loss varies among affected people. In many cases, significant hearing loss is present at birth. In other cases, hearing loss does not develop until later in infancy or childhood. Some people have problems with balance caused by dysfunction of the part of the inner ear that helps with balance and orientation (the vestibular system). Pendred syndrome is inherited in an autosomal recessive manner. Mutations in 3 genes are currently known to cause the condition (SLC26A4, FOXI1, and KCNJ10) and are found in about half of affected people. Other genes responsible for the condition have not yet been identified.
*[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
| Pendred syndrome | c0271829 | 1,643 | gard | https://rarediseases.info.nih.gov/diseases/4271/pendred-syndrome | 2021-01-18T17:58:23 | {"mesh": ["C536648"], "omim": ["274600"], "umls": ["C0271829"], "orphanet": ["705"], "synonyms": ["PDS", "Deafness with goiter", "Goiter-deafness syndrome", "Autosomal recessive sensorineural hearing impairment and goiter"]} |
A number sign (#) is used with this entry because split-hand/foot malformation-4 (SHFM4) is caused by heterozygous mutation in the tumor protein p63 gene (TP63; 603273) on chromosome 3q28.
Description
Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients with SHFM4 have been found to have mental retardation, ectodermal findings, and orofacial clefting (Elliott and Evans, 2006).
For additional phenotypic information and a discussion of genetic heterogeneity in this disorder, see SHFM1 (183600).
Clinical Features
Spranger and Schapera (1988) described an instructive South African family in which 3 unaffected sibs with normal parents had each produced affected offspring. An offspring of 1 of the unaffected sibs, himself unaffected, produced affected children. Once originated in the family, the disorder was transmitted, in 2 branches of the family, through 3 generations as a regular dominant. Premutation of an autosomal dominant gene or cosegregation of an epistatic gene linked to the gene for split-hand was suggested. The spectrum of clinical manifestations in this family was broad, ranging from the presence of a split hand in 1 individual to bilateral monodactyly and unilateral aplasia of the right lower extremity with a split left foot in another individual. No family members had any significant abnormalities other than those of the extremities.
Ianakiev et al. (2000) described a family with SHFM that also came from Cape Province, South Africa. The phenotype in this family ranged from severe 'lobster claw' malformations of the feet in 1 individual, to minor 3/4 syndactyly of the left foot appearing as the only manifestation in another individual. The daughter of the latter individual had distal duplications of her thumbs bilaterally with absence of the second and third phalanges of the right hand and an absent second phalanx with 3/4 syndactyly of the left hand. No members of the family had significant abnormality of the face, palate, skin, teeth, hair, or nails. No abnormalities of the mammary glands or nipples were noted.
In a literature review including 48 SHFM1 patients, 40 SHFM3 (246560) patients, 45 SHFM4 patients, and 20 SHFM5 (606708) patients, Elliott et al. (2005) found that preaxial involvement of the upper extremities was a significant locus discriminator, most commonly seen in patients with SHFM3 (60% of patients). Preaxial involvement occurred in approximately 40% of SHFM5, 4% of SHFM4, and 2% of SHFM1 patients. In further analysis of the previously studied SHFM patients, Elliott and Evans (2006) identified phenotypic patterns involving mental retardation, ectodermal and craniofacial findings, and orofacial clefting associated with the mapped genetic SHFM loci.
In a cohort of 56 families with SHFM, Klopocki et al. (2012) identified 17p13.3 duplications (SHFLD3; 612576) in 17 (30%) of the families, 10q24 duplications (SHFM3; 246560) in 11 (20%), and TP63 mutations in 5 (9%).
Molecular Genetics
In 2 multigenerational families with SHFM in which segregation analysis had excluded linkage to all previously identified autosomal regions, Ianakiev et al. (2000) identified heterozygous missense mutations in the TP63 gene (603273.0005 and 603273.0006, respectively). One of the families had previously been reported by Spranger and Schapera (1988).
INHERITANCE \- Autosomal dominant SKELETAL Hands \- Split hand, unilateral or bilateral \- 'Lobster-claw anomaly \- Monodactyly \- Missing phalanges \- Missing metacarpals \- Syndactyly \- Webbing \- Duplication of thumbs \- Triphalangeal thumb Feet \- Split foot, unilateral or bilateral \- 'Lobster-claw anomaly \- Missing metatarsals \- Syndactyly \- Webbing MISCELLANEOUS \- Variable phenotype \- Reduced penetrance has been reported MOLECULAR BASIS \- Caused by mutation in the tumor protein p63 gene (TP63, 603273.0005 ) ▲ Close
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*[t]: Discuss this template
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*[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
| SPLIT-HAND/FOOT MALFORMATION 4 | c0265554 | 1,644 | omim | https://www.omim.org/entry/605289 | 2019-09-22T16:11:25 | {"doid": ["0090023"], "mesh": ["C574275"], "omim": ["605289"], "orphanet": ["2440"], "genereviews": ["NBK43797"]} |
Abnormal number or structure of chromosomes
A chromosomal disorder, chromosomal anomaly, chromosomal aberration, or chromosomal mutation is a missing, extra, or irregular portion of chromosomal DNA.[1] These can occur in the form of numerical abnormalities, where there is an atypical number of chromosomes, or as structural abnormalities, where one or more individual chromosomes are altered. Chromosome mutation was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one gene.[2] Chromosome anomalies usually occur when there is an error in cell division following meiosis or mitosis. Chromosome abnormalities may be detected or confirmed by comparing an individual's karyotype, or full set of chromosomes, to a typical karyotype for the species via genetic testing.
## Contents
* 1 Numerical abnormality
* 1.1 Sperm aneuploidy
* 2 Structural abnormalities
* 3 Inheritance
* 4 Acquired chromosome abnormalities
* 5 DNA damage during spermatogenesis
* 6 Detection
* 7 See also
* 8 References
* 9 External links
## Numerical abnormality[edit]
A karyotype of an individual with trisomy 21, showing three copies of chromosome 21.
An abnormal number of chromosomes is called aneuploidy, and occurs when an individual is either missing a chromosome from a pair (resulting in monosomy) or has more than two chromosomes of a pair (trisomy, tetrasomy, etc.).[3][4] Aneuploidy can be full, involving a whole chromosome missing or added, or partial, where only part of a chromosome is missing or added.[3] Aneuploidy can occur with sex chromosomes or autosomes.
An example of trisomy in humans is Down syndrome, which is a developmental disorder caused by an extra copy of chromosome 21; the disorder is therefore also called trisomy 21.[5]
An example of monosomy in humans is Turner syndrome, where the individual is born with only one sex chromosome, an X.[6]
### Sperm aneuploidy[edit]
Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa.[7] In particular, risk of aneuploidy is increased by tobacco smoking,[8][9] and occupational exposure to benzene,[10] insecticides,[11][12] and perfluorinated compounds.[13] Increased aneuploidy is often associated with increased DNA damage in spermatozoa.
## Structural abnormalities[edit]
The three major single-chromosome mutations: deletion (1), duplication (2) and inversion (3).
The two major two-chromosome mutations: insertion (1) and translocation (2).
When the chromosome's structure is altered, this can take several forms:[14]
* Deletions: A portion of the chromosome is missing or has been deleted. Known disorders in humans include Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4; and Jacobsen syndrome, also called the terminal 11q deletion disorder.
* Duplications: A portion of the chromosome has been duplicated, resulting in extra genetic material. Known human disorders include Charcot-Marie-Tooth disease type 1A, which may be caused by duplication of the gene encoding peripheral myelin protein 22 (PMP22) on chromosome 17.
* Inversions: A portion of the chromosome has broken off, turned upside down, and reattached, therefore the genetic material is inverted.
* Insertions: A portion of one chromosome has been deleted from its normal place and inserted into another chromosome.
* Translocations: A portion of one chromosome has been transferred to another chromosome. There are two main types of translocations:
* Reciprocal translocation: Segments from two different chromosomes have been exchanged.
* Robertsonian translocation: An entire chromosome has attached to another at the centromere \- in humans these only occur with chromosomes 13, 14, 15, 21, and 22.
* Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without loss of genetic material.
* Isochromosome: Formed by the mirror image copy of a chromosome segment including the centromere.
Chromosome instability syndromes are a group of disorders characterized by chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies.
## Inheritance[edit]
Most chromosome abnormalities occur as an accident in the egg cell or sperm, and therefore the anomaly is present in every cell of the body. Some anomalies, however, can happen after conception, resulting in Mosaicism (where some cells have the anomaly and some do not). Chromosome anomalies can be inherited from a parent or be "de novo". This is why chromosome studies are often performed on parents when a child is found to have an anomaly. If the parents do not possess the abnormality it was not initially inherited; however it may be transmitted to subsequent generations.
## Acquired chromosome abnormalities[edit]
Most cancers, if not all, could cause chromosome abnormalities,[15] with either the formation of hybrid genes and fusion proteins, deregulation of genes and overexpression of proteins, or loss of tumor suppressor genes (see the "Mitelman Database" [16] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[17]). Furthermore, certain consistent chromosomal abnormalities can turn normal cells into a leukemic cell such as the translocation of a gene, resulting in its inappropriate expression.[18]
## DNA damage during spermatogenesis[edit]
During the mitotic and meiotic cell divisions of mammalian gametogenesis, DNA repair is effective at removing DNA damages.[19] However, in spermatogenesis the ability to repair DNA damages decreases substantially in the latter part of the process as haploid spermatids undergo major nuclear chromatin remodeling into highly compacted sperm nuclei. As reviewed by Marchetti et al.,[20] the last few weeks of sperm development before fertilization are highly susceptible to the accumulation of sperm DNA damage. Such sperm DNA damage can be transmitted unrepaired into the egg where it is subject to removal by the maternal repair machinery. However, errors in maternal DNA repair of sperm DNA damage can result in zygotes with chromosomal structural aberrations.
Melphalan is a bifunctional alkylating agent frequently used in chemotherapy. Meiotic inter-strand DNA damages caused by melphalan can escape paternal repair and cause chromosomal aberrations in the zygote by maternal misrepair.[20] Thus both pre- and post-fertilization DNA repair appear to be important in avoiding chromosome abnormalities and assuring the genome integrity of the conceptus.
## Detection[edit]
Depending on the information one wants to obtain, different techniques and samples are needed.
* For the prenatal diagnosis of a foetus, amniocentesis, chorionic villus sampling or circulating foetal cells would be collected and analysed in order to detect possible chromosomal abnormalities.
* For the preimplantational diagnosis of an embryo, a blastocyst biopsy would be performed.
* For a lymphoma or leukemia screening the technique used would be a bone marrow biopsy.
## See also[edit]
* Aneuploidy
* Chromosome segregation
* Genetic disorder
* List of genetic disorders
* Gene therapy
* Nondisjunction
* Obstetrical complications
## References[edit]
1. ^ NHGRI. 2006. Chromosome Abnormalities Archived 2006-09-25 at the Wayback Machine
2. ^ Rieger, R.; Michaelis, A.; Green, M.M. (1968). "Mutation". A glossary of genetics and cytogenetics: Classical and molecular. New York: Springer-Verlag. ISBN 9780387076683.
3. ^ a b Gardner, R. J. M. (2012). Chromosome abnormalities and genetic counseling. Sutherland, Grant R., Shaffer, Lisa G. (4th ed.). Oxford: Oxford University Press. ISBN 978-0-19-974915-7. OCLC 769344040.
4. ^ "Numerical Abnormalities: Overview of Trisomies and Monosomies - Health Encyclopedia - University of Rochester Medical Center". www.urmc.rochester.edu. Retrieved 2020-11-17.
5. ^ Patterson, David (2009-07-01). "Molecular genetic analysis of Down syndrome". Human Genetics. 126 (1): 195–214. doi:10.1007/s00439-009-0696-8. ISSN 1432-1203.
6. ^ "Turner Syndrome". National Institute of Child Health and Human Development. Retrieved 2020-11-17.
7. ^ Templado C, Uroz L, Estop A (2013). "New insights on the origin and relevance of aneuploidy in human spermatozoa". Mol. Hum. Reprod. 19 (10): 634–43. doi:10.1093/molehr/gat039. PMID 23720770.
8. ^ Shi Q, Ko E, Barclay L, Hoang T, Rademaker A, Martin R (2001). "Cigarette smoking and aneuploidy in human sperm". Mol. Reprod. Dev. 59 (4): 417–21. doi:10.1002/mrd.1048. PMID 11468778.
9. ^ Rubes J, Lowe X, Moore D, Perreault S, Slott V, Evenson D, Selevan SG, Wyrobek AJ (1998). "Smoking cigarettes is associated with increased sperm disomy in teenage men". Fertil. Steril. 70 (4): 715–23. doi:10.1016/S0015-0282(98)00261-1. PMID 9797104.
10. ^ Xing C, Marchetti F, Li G, Weldon RH, Kurtovich E, Young S, Schmid TE, Zhang L, Rappaport S, Waidyanatha S, Wyrobek AJ, Eskenazi B (2010). "Benzene exposure near the U.S. permissible limit is associated with sperm aneuploidy". Environ. Health Perspect. 118 (6): 833–9. doi:10.1289/ehp.0901531. PMC 2898861. PMID 20418200.
11. ^ Xia Y, Bian Q, Xu L, Cheng S, Song L, Liu J, Wu W, Wang S, Wang X (2004). "Genotoxic effects on human spermatozoa among pesticide factory workers exposed to fenvalerate". Toxicology. 203 (1–3): 49–60. doi:10.1016/j.tox.2004.05.018. PMID 15363581.
12. ^ Xia Y, Cheng S, Bian Q, Xu L, Collins MD, Chang HC, Song L, Liu J, Wang S, Wang X (2005). "Genotoxic effects on spermatozoa of carbaryl-exposed workers". Toxicol. Sci. 85 (1): 615–23. doi:10.1093/toxsci/kfi066. PMID 15615886.
13. ^ Governini L, Guerranti C, De Leo V, Boschi L, Luddi A, Gori M, Orvieto R, Piomboni P (2014). "Chromosomal aneuploidies and DNA fragmentation of human spermatozoa from patients exposed to perfluorinated compounds". Andrologia. 47 (9): 1012–9. doi:10.1111/and.12371. PMID 25382683.
14. ^ "Chromosome Abnormalities". atlasgeneticsoncology.org. Archived from the original on 14 August 2006. Retrieved 9 May 2018.
15. ^ "Chromosomes, Leukemias, Solid Tumors, Hereditary Cancers". atlasgeneticsoncology.org. Archived from the original on 28 January 2015. Retrieved 9 May 2018.
16. ^ "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer". Archived from the original on 2016-05-29.
17. ^ "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org. Archived from the original on 2011-02-23.
18. ^ Chaganti, R. S.; Nanjangud, G.; Schmidt, H.; Teruya-Feldstein, J. (October 2000). "Recurring chromosomal abnormalities in non-Hodgkin's lymphoma: biologic and clinical significance". Seminars in Hematology. 37 (4): 396–411. doi:10.1016/s0037-1963(00)90019-2. ISSN 0037-1963. PMID 11071361.
19. ^ Baarends WM, van der Laan R, Grootegoed JA (2001). "DNA repair mechanisms and gametogenesis". Reproduction. 121 (1): 31–9. doi:10.1530/reprod/121.1.31. PMID 11226027.
20. ^ a b Marchetti F, Bishop J, Gingerich J, Wyrobek AJ (2015). "Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair". Sci Rep. 5: 7689. doi:10.1038/srep07689. PMC 4286742. PMID 25567288.
## External links[edit]
* Chromosome+disorders at the US National Library of Medicine Medical Subject Headings (MeSH)
* v
* t
* e
Chromosome abnormalities
Autosomal
Trisomies/Tetrasomies
* Down syndrome
* 21
* Edwards syndrome
* 18
* Patau syndrome
* 13
* Trisomy 9
* Tetrasomy 9p
* Warkany syndrome 2
* 8
* Cat eye syndrome/Trisomy 22
* 22
* Trisomy 16
Monosomies/deletions
* (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome)
* 1
* Wolf–Hirschhorn syndrome
* 4
* Cri du chat syndrome/Chromosome 5q deletion syndrome
* 5
* Williams syndrome
* 7
* Jacobsen syndrome
* 11
* Miller–Dieker syndrome/Smith–Magenis syndrome
* 17
* DiGeorge syndrome
* 22
* 22q11.2 distal deletion syndrome
* 22
* 22q13 deletion syndrome
* 22
* genomic imprinting
* Angelman syndrome/Prader–Willi syndrome (15)
* Distal 18q-/Proximal 18q-
X/Y linked
Monosomy
* Turner syndrome (45,X)
Trisomy/tetrasomy,
other karyotypes/mosaics
* Klinefelter syndrome (47,XXY)
* XXYY syndrome (48,XXYY)
* XXXY syndrome (48,XXXY)
* 49,XXXYY
* 49,XXXXY
* Triple X syndrome (47,XXX)
* Tetrasomy X (48,XXXX)
* 49,XXXXX
* Jacobs syndrome (47,XYY)
* 48,XYYY
* 49,XYYYY
* 45,X/46,XY
* 46,XX/46,XY
Translocations
Leukemia/lymphoma
Lymphoid
* Burkitt's lymphoma t(8 MYC;14 IGH)
* Follicular lymphoma t(14 IGH;18 BCL2)
* Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH)
* Anaplastic large-cell lymphoma t(2 ALK;5 NPM1)
* Acute lymphoblastic leukemia
Myeloid
* Philadelphia chromosome t(9 ABL; 22 BCR)
* Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1)
* Acute promyelocytic leukemia t(15 PML,17 RARA)
* Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1)
Other
* Ewing's sarcoma t(11 FLI1; 22 EWS)
* Synovial sarcoma t(x SYT;18 SSX)
* Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB)
* Myxoid liposarcoma t(12 DDIT3; 16 FUS)
* Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS)
* Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1)
Other
* Fragile X syndrome
* Uniparental disomy
* XX male syndrome/46,XX testicular disorders of sex development
* Marker chromosome
* Ring chromosome
* 6; 9; 14; 15; 18; 20; 21, 22
* v
* t
* e
Mutation
Mechanisms of mutation
* Insertion
* Deletion
* Substitution
* Transversion
* Transition
Mutation with respect to structure
Point mutation
* Nonsense mutation
* Missense mutation
* Conservative mutation
* Silent mutation
* Frameshift mutation
* Dynamic mutation
Large-scale mutation
* Chromosomal translocations
* Chromosomal inversions
Mutation with respect to overall fitness
* Deleterious mutation
* Advantageous mutation
* Neutral mutation
* Nearly neutral mutation
* Synonymous mutation
* Nonsynonymous mutation
Authority control
* GND: 4010163-0
* LCCN: sh85025385
* NDL: 00570781
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*[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
| Chromosome abnormality | c0948447 | 1,645 | wikipedia | https://en.wikipedia.org/wiki/Chromosome_abnormality | 2021-01-18T18:37:35 | {"mesh": ["D002869"], "umls": ["C0948447"], "orphanet": ["68335"], "wikidata": ["Q744962"]} |
Limb-girdle muscular dystrophy is a group of disorders which affect the voluntary muscles around the hips and shoulders. The conditions are progressive, leading to a loss of muscle strength and bulk over a number of years. Onset may occur in childhood, adolescence, young adulthood, or even later. Males and females are affected in equal numbers. Most forms of limb girdle muscular dystrophy are inherited in an autosomal recessive manner. Several rare forms are inherited in an autosomal dominant pattern. While there are no treatments which directly reverse the muscle weakness associated with this condition, supportive treatment can decrease the complications. There are at least 20 different types of limb-girdle muscular dystrophy.
*[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
| Limb-girdle muscular dystrophy | c0686353 | 1,646 | gard | https://rarediseases.info.nih.gov/diseases/6907/limb-girdle-muscular-dystrophy | 2021-01-18T17:59:24 | {"mesh": ["D049288"], "orphanet": ["263"], "synonyms": ["Limb girdle muscular dystrophy", "LGMD"]} |
Small-cell carcinoma
Other namesSmall-cell lung cancer, or Oat-cell carcinoma
Micrograph of a small-cell carcinoma of the lung showing cells with nuclear moulding, minimal amount of cytoplasm and stippled chromatin. FNA specimen. Field stain.
SpecialtyOncology
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung,[1] although it can occasionally arise in other body sites, such as the cervix,[2] prostate,[3] and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma has a shorter doubling time, higher growth fraction, and earlier development of metastases.
Extensive stage small cell lung cancer is classified as a rare disorder.[4] Ten-year relative survival rate is 3.5%; however, women have higher survival rate, 4.3%, and men lower, 2.8%.[5] Survival can be higher or lower based on a combination of factors including stage, age, gender and race.[6]
## Contents
* 1 Types of SCLC
* 1.1 LS-SCLC
* 1.2 ES-SCLC
* 2 Signs and symptoms
* 2.1 Small cell lung cancer
* 2.2 Combined small-cell lung carcinoma (c-SCLC)
* 2.3 Extrapulmonary small-cell carcinoma
* 2.4 Extrapulmonary small-cell carcinoma localized in the lymph nodes
* 2.5 Small-cell carcinoma of the prostate
* 3 Genetics
* 4 Diagnosis
* 5 Treatment
* 5.1 Chemotherapy
* 5.1.1 Cisplatin-resistance
* 5.2 Immunotherapy
* 5.2.1 Funding controversy
* 5.3 Radiation therapy
* 5.4 In case of relapse
* 5.4.1 Novel agents
* 6 Prognosis
* 6.1 5-year survival rates
* 6.1.1 Survival rates by sex
* 6.1.2 Survival Rates by race, sex, age
* 7 Epidemiology
* 8 Recalcitrant Cancer Research Act
* 9 Additional images
* 10 See also
* 11 References
## Types of SCLC[edit]
Small-cell lung carcinoma has long been divided into two clinicopathological stages, including limited stage (LS) and extensive stage (ES).[7] The stage is generally determined by the presence or absence of metastases, whether or not the tumor appears limited to the thorax, and whether or not the entire tumor burden within the chest can feasibly be encompassed within a single radiotherapy portal.[8] In general, if the tumor is confined to one lung and the lymph nodes close to that lung, the cancer is said to be LS. If the cancer has spread beyond that, it is said to be ES.
### LS-SCLC[edit]
Main article: Limited-stage small cell lung carcinoma
In cases of LS-SCLC, combination chemotherapy (often including cyclophosphamide, cisplatin, doxorubicin, etoposide, vincristine and/or paclitaxel) is administered together with concurrent chest radiotherapy (RT).[citation needed]
Chest RT has been shown to improve survival in LS-SCLC.[9]
Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. However, relapse rate remains high, and median survival is only 18 to 24 months.[citation needed]
Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s.[10] However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy ("adjuvant chemotherapy").[11]
### ES-SCLC[edit]
In ES-SCLC, platinum-based combination chemotherapy is the standard of care,[12] with radiotherapy added only to palliate symptoms such as dyspnea, pain from liver or bone metastases, or for treatment of brain metastases, which, in small-cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.
Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, and the evidence surrounding the risk of treatment compared to the potential benefit of chemotherapy for people who have extensive SCLC is not clear.[12]
If complete response to chemotherapy occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.[citation needed]
In August 2018, the FDA approved nivolumab to treat patients with metastatic small cell lung cancer (SCLC) who failed to respond to platinum-based chemotherapy and at least one other line of treatment. Nivolumab is approved in more than 60 countries. According to LUNGevity Foundation, “This approval marks a major milestone for the patients touched by this unrelenting disease and may motivate them to pursue further treatment where there previously were no other approved options.”[13]
In September 2018, the results from the global, randomized phase I/III IMpower 133 trial were announced at the World Congress on Lung Cancer in Toronto, ON. In this study, patients with ES-SCLC were treated with standard carboplatin plus etoposide and were randomized to receive atezolizumab or placebo. Atezolizumab was associated with a significant improvement in overall survival (HR for death = 0.70)[14]
## Signs and symptoms[edit]
right side lung, side S2-S3 small cell carcinoma
Small-cell carcinoma of the lung usually presents in the central airways and infiltrates the submucosa leading to narrowing of bronchial airways. Common symptoms include cough, dyspnea, weight loss, and debility. Over 70% of patients with small-cell carcinoma present with metastatic disease; common sites include liver, adrenals, bone, and brain.[citation needed]
Due to its high grade neuroendocrine nature, small-cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone (ACTH) and anti-diuretic hormone (ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).[citation needed]
Lambert-Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small-cell carcinoma.[15]
### Small cell lung cancer[edit]
Histopathologic image of small-cell carcinoma of the lung. CT-guided core needle biopsy. H&E stain.
When associated with the lung, it is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm. Caution is required when diagnosing SCLC, because small cell mesothelioma — an extremely rare subtype of lung cancer — can be mistaken for small cell lung cancer.[16]
It is thought to originate from neuroendocrine cells (APUD cells) in the bronchus called Feyrter cells (named for Friedrich Feyrter).[17] Hence, they express a variety of neuroendocrine markers, and may lead to ectopic production of hormones like ADH and ACTH that may result in paraneoplastic syndromes and Cushing's syndrome.[18] Approximately half of all individuals diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) will eventually be found to have a small-cell carcinoma of the lung.[15]
Small-cell carcinoma is most often more rapidly and widely metastatic than non-small-cell lung carcinoma[19] (and hence staged differently). There is usually early involvement of the hilar and mediastinal lymph nodes. [18] The mechanisms of its metastatic progression are not well-understood.[20]
### Combined small-cell lung carcinoma (c-SCLC)[edit]
Main article: Combined small-cell lung carcinoma
Small-cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancer,[21] including extremely complex malignant tissue admixtures.[22] [23] When it is found with one or more differentiated forms of lung cancer, such as squamous cell carcinoma or adenocarcinoma, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma (c-SCLC).[21] C-SCLC is the only currently recognized subtype of SCLC.[21]
Although combined small-cell lung carcinoma is currently staged and treated similarly to "pure" small-cell carcinoma of the lung, recent research suggests surgery might improve outcomes in very early stages of this tumor type.[citation needed]
Smoking is a significant risk factor.Symptoms and signs are as for other lung cancers. In addition, because of their neuroendocrine cell origin, small-cell carcinomas will often secrete substances that result in paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome.
### Extrapulmonary small-cell carcinoma[edit]
Very rarely, the primary site for small-cell carcinoma is outside of the lungs and pleural space; in these cases, it is referred to as extrapulmonary small-cell carcinoma (EPSCC). Outside of the respiratory tract, small-cell carcinoma can appear in the cervix, prostate, liver, pancreas, gastrointestinal tract, or bladder.[24] It is estimated to account for 1,000 new cases a year in the U.S. Histologically similar to small-cell lung cancer, therapies for small-cell lung cancer are usually used to treat EPSCC.[25] First-line treatment is usually with cisplatin and etoposide. In Japan, first-line treatment is shifting to irinotecan and cisplatin.When the primary site is in the skin, it is referred to as a Merkel-cell carcinoma.[citation needed]
### Extrapulmonary small-cell carcinoma localized in the lymph nodes[edit]
This is an extremely rare type of small cell, and there has been little information in the scientific community. It appears to occur in only one or more lymph nodes, and nowhere else in the body. Treatment is similar to small cell lung cancer, but survival rates are much higher than other small-cell carcinomas.[26]
### Small-cell carcinoma of the prostate[edit]
In the prostate, small-cell carcinoma (SCCP) is a rare form of cancer (approx 1% of PC).[27] Due to the fact that there is little variation in prostate specific antigen levels, this form of cancer is normally diagnosed at an advanced stage, after metastasis.
It can metastasize to the brain.[28]
## Genetics[edit]
TP53 is mutated in 70 to 90% of SCLCs. RB1 and the retinoblastoma pathway are inactivated in most SCLCs. PTEN is mutated in 2 to 10%. MYC amplifications and amplification of MYC family members are found in 30% of SCLCs. Loss of heterozygocity on chromosome arm 3p is found in more than 80% of SCLCs, including the loss of FHIT.[29] One hundred translocations have so far been reported in SCLCs (see the "Mitelman Database"[30] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[31]).
## Diagnosis[edit]
When
* Localized: the cancer is confined to the lung (aka: limited stage SCLC).
* Regional: the cancer has spread to lymph nodes (or glands) within the chest (between limited and extensive stage SCLC). Lymph nodes act as a filtering system outside the lung, collecting cancer cells that are beginning to migrate out of the lung.
* Distant: the cancer has spread (or metastasized) to other parts of the body (aka: extensive stage SCLC).[32]
At the time of diagnosis, 60 – 70% of people already have metastases.[20]
Small-cell carcinoma is an undifferentiated neoplasm composed of primitive-appearing cells. As the name implies, the cells in small-cell carcinomas are smaller than normal cells, and barely have room for any cytoplasm. Some researchers identify this as a failure in the mechanism that controls the size of the cells.[33]
## Treatment[edit]
Small Cell Lung Cancer is most commonly treated with a combination of 2 drugs, which is more effective than one drug alone.
### Chemotherapy[edit]
1. Cisplatin and Etoposide,
2. Carboplatin and Etoposide.
#### Cisplatin-resistance[edit]
The drug paclitaxel may be useful in the treatment of cisplatin-resistant cancer. About 68.1% of cisplatin-resistant cells appear to be sensitive to paclitaxel and 66.7% of paclitaxel-resistant cells to cisplatin. The mechanism for this activity is unknown.[34] Paclitaxel-based chemotherapy showed modest activity in SCLC patients refractory to both etoposide- and camptothecin-based chemotherapy.[35] New agent Lurbinectedin is active in relapsed SCLC and is awaiting FDA approval.
### Immunotherapy[edit]
Recently, the FDA approved two immunotherapies for small cell lung cancer:
1\. Opdivo (Nivolumab),[36][37] and
2\. Tecentriq (Atezolizumab) [38][39]
#### Funding controversy[edit]
Tecentriq treatment costs on average $13,200 per month, depending on the dosage schedule.[40] Despite updated data showing 30% more people with extensive stage small cell lung cancer are alive at 24 months compared to those who received chemotherapy alone,[41] Canadian regulator had rejected to fund Tecentriq for extensive stage small-cell lung cancer "as too costly" followed by United Kingdom also citing "drug’s cost-effectiveness."[42][43]
### Radiation therapy[edit]
Chest radiation helps SCLC patients live longer by killing cancer cells and helping prevention of cancer recurrence.[44] Another type of radiation, prophylactic cranial radiation, prevents central nervous system recurrence and can improve survival in patients with good performance status who have had a complete response or a very good partial response to chemoradiation in LD or chemotherapy in ED.[45]
### In case of relapse[edit]
If small cell lung cancer comes back after treatment, the following combination of drugs may be used as a salvage therapy:[46]
1. Cyclophosphamide (Cytoxan, Procytox),
2. Doxorubicin (Adriamycin) and
3. Vincristine (Oncovin)
4. Paclitaxel (Taxol)
5. Irinotecan (Camptosar) [47]
Current guidelines recommend that patients who relapse > 6 months from initial therapy should be retreated with the original chemotherapy regimen. For patients who relapse in < 6 months, single-agent chemotherapy either topotecan second-line therapy, or paclitaxel can be used.[48]
#### Novel agents[edit]
Several newer agents, including temozolomide and bendamustine, have activity in relapsed SCLC. Of note, temozolomide yielded a response rate of 38% for brain metastases due to SCLC.[48]
In a clinical trial of 50 patients, combination of Olaparib and Temozolomide in relapsed small-cell lung cancer yielded overall response rate of 41.7%, median progression-free survival 4.2 months, and overall survival was 8.5 months.[49]
Lurbinectedin is the most promising new agent that substantially increased overall survival rate in relapsed small cell lung cancer among sensitive disease patients. As a single agent, lurbinectedin demonstrated following clinical results in refractory small cell lung cancer trial:
* Overall survival rate of 15.2 months for sensitive disease (chemotherapy-free interval of ≥ 90 days) with a disease control rate of 79.3% and overall response rate of 46.6%, and
* Overall survival rate of 5.1 months for resistant (chemotherapy-free interval of < 90 days) with a disease control rate of 46.8% and overall response rate 21.3%.[50]
Lurbinectedin is also being investigated in combination with doxorubicin as second-line therapy in a randomized phase 3 trial. While overall survival in this trial is not yet known, response rates at second line were
* 91.7% in sensitive disease with median progression-free survival of 5.8 months , and
* 33.3% in resistant disease with median progression-free of 3.5 months.[51]
Lurbinectedin is currently available in the U.S. under Expanded Access Program (EAP).[52][51][53]
Trilaciclib, a CKD4/6 inhibitor, reduces chemotheraphy-associated toxicity in patients being treated for SCLC.[54][55][56] Trilaciclib’s developer, G1 Therapeutics, makes the drug available in the U.S. under Expanded access while the FDA considers its New Drug Application (NDA). An approval decision on the NDA is expected by February 15, 2021.[57]
## Prognosis[edit]
5-year survival rates for small cell lung cancer (extensive and limited) range between 3.6% and 32.2% for women, and between 2.2% and 24.5% for men.[58] Relative 5-year survival rate for both sexes has increased from 3.6% in 1975 to 6.7% in 2014.[59]
Small-cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse and median survival remains low. The overall incidence and mortality rates of SCLC in the United States have decreased during the past few decades.[60]
Pie chart showing incidence of small-cell lung cancer (shown in red at right), as compared to other lung cancer types, with fractions of smokers versus non-smokers shown for each type.[61]
In limited-stage disease, relative 5-year survival rate (both sexes, all races, all ages) is 21.3%; however, women have higher 5-year survival rates, 26.9%, and men have lower survival rates, 21.3%.[62]
The prognosis is far more grim in extensive-stage small-cell lung carcinoma where 5-year relative survival rate (both sexes, all races, all ages) is 2.8%; however, women have higher 5-year survival rates, 3.4%, and men have lower 5-year survival rates, 2.2%.[62]
Long term survival of more than 5 years can be achieved with proper treatment. According to the 17th World Conference on Lung Cancer (WCLC), "patients who received chest radiation and prophylactic cranial irradiation along with a mean of five chemotherapy cycles could achieve a median survival of more than 5 years."[63][58]
In some cases, long term survival of 10+ years is achieved with chemotherapy and radiation alone.[64][65]
### 5-year survival rates[edit]
The SEER database tracks 5-year relative survival rates based on age, sex, and race and is considered the most accurate source of survival information.[66] This database uses terms "Localized," "Regional," and "Distant" to describe various stages of small cell lung cancer.
5-year relative survival rate for "both sexes" and "all races" affected by
* "Localized" small cell lung cancer is 28.5%;
* "Regional" small cell lung cancer 14.9%; and for
* "Distant" small cell lung cancer 2.9%.[58]
#### Survival rates by sex[edit]
Women affected by small-cell lung cancer tend to have higher 5-year survival rates than men.[67]
* Localized: Women — 32.20% | Men — 24.50%
* Regional: Women — 17.0% | Men — 12.30%
* Distant: Women — 3.60% | Men — 2.20%
#### Survival Rates by race, sex, age[edit]
5-year relative survival statistics are more accurate and, in some cases, higher when specific race and age range are combined with sex and stage at diagnosis. For example,
* Black / Female | Ages < 50 (at diagnosis) | Distant (ES SCLC) | = 7.00%.[68]
* White / Female | Ages < 50 (at diagnosis) | Distant (ES SCLC) | = 6.10% [69]
National Cancer Institute's SEER maintains publicly accessible database for specific survival rates.[70]
## Epidemiology[edit]
15% of lung cancers in the US are of this type.[71] Small cell lung cancer occurs almost exclusively in smokers; most commonly in heavy smokers and rarely in non-smokers.[72][73] According to available data, slightly more than half of the lung cancers caused by factors other than active smoking occur in never smokers (who can still be subject to second-hand tobacco smoke).[74] About half of patients who are diagnosed with lung cancer have either never smoked (15%) or are former smokers (35%) who quit long time ago.[75] Second-hand smoke causes lung cancer in adults who have never smoked.[76]
## Recalcitrant Cancer Research Act[edit]
In 2013, the US Congress passed the Recalcitrant Cancer Research Act, which mandated increased attention to certain recalcitrant cancers, including small cell lung cancer. That led to the National Cancer Institute supporting small cell–specific research through a consortium.
As a result, new experimental drugs for small cell lung cancer are currently being tested, including Iadademstat (ORY-1001) and Keytruda (pembrolizumab).[77][78][79][80]
## Additional images[edit]
* Anaplastic (microcellular, oat cell) carcinoma from the lung (histopathology)
* Histopathologic image of small-cell carcinoma of the lung. CT-guided core needle biopsy.
## See also[edit]
* Brown-Séquard syndrome
* Cervical cancer
* Combined small-cell lung carcinoma
* Lung cancer
* Prostate cancer
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69. ^ [SEER Database, Cancer Survival Rates | https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=5&compareBy=age_range&series=sex&chk_sex_3=3&chk_race_8=8&chk_age_range_9=9&chk_stage_106=106&advopt_precision=1&advopt_show_se=on&advopt_show_ci=on&showDataFor=race_8_and_stage_106]
70. ^ [SEER Small Cell Lung Cancer Survival Rates | https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=6&compareBy=stage&chk_sex_3=3&chk_race_1=1&chk_age_range_1=1&chk_stage_101=101&advopt_precision=1&showDataFor=sex_3_and_race_1_and_age_range_1]
71. ^ World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 5.1. ISBN 978-9283204299.
72. ^ Ettinger, DS; Aisner, J (1 October 2006). "Changing face of small-cell lung cancer: real and artifact". Journal of Clinical Oncology. 24 (28): 4526–7. doi:10.1200/jco.2006.07.3841. PMID 17008688.
73. ^ Muscat, JE; Wynder, EL (6 January 1995). "Lung cancer pathology in smokers, ex-smokers and never smokers". Cancer Letters. 88 (1): 1–5. doi:10.1016/0304-3835(94)03608-l. PMID 7850764.
74. ^ Samet, J. M.; Avila-Tang, E.; Boffetta, P.; Hannan, L. M.; Olivo-Marston, S.; Thun, M. J.; Rudin, C. M. (14 September 2009). "Lung Cancer in Never Smokers: Clinical Epidemiology and Environmental Risk Factors". Clinical Cancer Research. 15 (18): 5626–5645. doi:10.1158/1078-0432.CCR-09-0376. PMC 3170525. PMID 19755391.
75. ^ Lung Cancer Canada | http://www.lungcancercanada.ca/Lung-Cancer.aspx
76. ^ "The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General" (PDF). U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2014. Retrieved August 22, 2020.
77. ^ Fred Hutch "A new focus on small cell lung cancer" | https://www.fredhutch.org/en/news/center-news/2019/02/q-a-with-david-macpherson-lung-cancer.html
78. ^ Augert, Arnaud; Eastwood, Emily; Ibrahim, Ali H.; Wu, Nan; Grunblatt, Eli; Basom, Ryan; Liggitt, Denny; Eaton, Keith D.; Martins, Renato; Poirier, John T.; Rudin, Charles M.; Milletti, Francesca; Cheng, Wei-Yi; Mack, Fiona; MacPherson, David (5 February 2019). "Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition". Science Signaling. 12 (567): eaau2922. doi:10.1126/scisignal.aau2922. PMC 6530478. PMID 30723171.
79. ^ Oryzon Genomics "ORY-1001 - Patient Info" | https://www.oryzon.com/en/patient/patient-information
80. ^ Cure Magazine "Keytruda Shows Benefit in Small Cell Lung Cancer" | https://www.curetoday.com/articles/keytruda-shows-benefit-in-small-cell-lung-cancer
Classification
D
* ICD-O: M8041/3
* MeSH: D018288
* SNOMED CT: 11010461000119101
External resources
* MedlinePlus: 000122
* eMedicine: med/1336
* v
* t
* e
Glandular and epithelial cancer
Epithelium
Papilloma/carcinoma
* Small-cell carcinoma
* Combined small-cell carcinoma
* Verrucous carcinoma
* Squamous cell carcinoma
* Basal-cell carcinoma
* Transitional cell carcinoma
* Inverted papilloma
Complex epithelial
* Warthin's tumor
* Thymoma
* Bartholin gland carcinoma
Glands
Adenomas/
adenocarcinomas
Gastrointestinal
* tract: Linitis plastica
* Familial adenomatous polyposis
* pancreas
* Insulinoma
* Glucagonoma
* Gastrinoma
* VIPoma
* Somatostatinoma
* Cholangiocarcinoma
* Klatskin tumor
* Hepatocellular adenoma/Hepatocellular carcinoma
Urogenital
* Renal cell carcinoma
* Endometrioid tumor
* Renal oncocytoma
Endocrine
* Prolactinoma
* Multiple endocrine neoplasia
* Adrenocortical adenoma/Adrenocortical carcinoma
* Hürthle cell
Other/multiple
* Neuroendocrine tumor
* Carcinoid
* Adenoid cystic carcinoma
* Oncocytoma
* Clear-cell adenocarcinoma
* Apudoma
* Cylindroma
* Papillary hidradenoma
Adnexal and
skin appendage
* sweat gland
* Hidrocystoma
* Syringoma
* Syringocystadenoma papilliferum
Cystic, mucinous,
and serous
Cystic general
* Cystadenoma/Cystadenocarcinoma
Mucinous
* Signet ring cell carcinoma
* Krukenberg tumor
* Mucinous cystadenoma / Mucinous cystadenocarcinoma
* Pseudomyxoma peritonei
* Mucoepidermoid carcinoma
Serous
* Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma
Ductal, lobular,
and medullary
Ductal carcinoma
* Mammary ductal carcinoma
* Pancreatic ductal carcinoma
* Comedocarcinoma
* Paget's disease of the breast / Extramammary Paget's disease
Lobular carcinoma
* Lobular carcinoma in situ
* Invasive lobular carcinoma
Medullary carcinoma
* Medullary carcinoma of the breast
* Medullary thyroid cancer
Acinar cell
* Acinic cell carcinoma
* v
* t
* e
Cancer involving the respiratory tract
Upper RT
Nasal cavity
Esthesioneuroblastoma
Nasopharynx
Nasopharyngeal carcinoma
Nasopharyngeal angiofibroma
Larynx
Laryngeal cancer
Laryngeal papillomatosis
Lower RT
Trachea
* Tracheal tumor
Lung
Non-small-cell lung carcinoma
* Squamous-cell carcinoma
* Adenocarcinoma (Mucinous cystadenocarcinoma)
* Large-cell lung carcinoma
* Rhabdoid carcinoma
* Sarcomatoid carcinoma
* Carcinoid
* Salivary gland–like carcinoma
* Adenosquamous carcinoma
* Papillary adenocarcinoma
* Giant-cell carcinoma
Small-cell carcinoma
* Combined small-cell carcinoma
Non-carcinoma
* Sarcoma
* Lymphoma
* Immature teratoma
* Melanoma
By location
* Pancoast tumor
* Solitary pulmonary nodule
* Central lung
* Peripheral lung
* Bronchial leiomyoma
Pleura
* Mesothelioma
* Malignant solitary fibrous tumor
* 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
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*[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
| Small-cell carcinoma | c0262584 | 1,647 | wikipedia | https://en.wikipedia.org/wiki/Small-cell_carcinoma | 2021-01-18T19:08:39 | {"mesh": ["D018288"], "umls": ["C0334239", "C0262584"], "wikidata": ["Q738170"]} |
ADNP syndrome is a condition that causes a wide variety of signs and symptoms. Its hallmark features are intellectual disability and autism spectrum disorder, which is characterized by impaired communication and social interaction. Affected individuals also have distinctive facial features and abnormalities of multiple body systems.
Individuals with ADNP syndrome have mild to severe intellectual disability and delayed development of speech and motor skills such as sitting and walking. Some affected individuals are never able to speak. People with this disorder exhibit features typical of autism spectrum disorder, including repetitive behaviors and difficulty with social interactions. ADNP syndrome is also associated with mood disorders or behavioral problems, such as anxiety, temper tantrums, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder, or sleep problems.
Many people with ADNP syndrome have distinctive facial features, which most commonly include a prominent forehead, a high hairline, outside corners of the eyes that point upward or downward (upslanting or downslanting palpebral fissures), droopy eyelids (ptosis), a broad nasal bridge, and a thin upper lip. These individuals may also have unusually shaped ears or hand and finger abnormalities. Eye and vision abnormalities, such as eyes that do not point in the same direction (strabismus) and farsightedness (hyperopia), also occur in ADNP syndrome. Some people with this condition have early appearance (eruption) of primary (baby) teeth.
Some people with ADNP syndrome have weak muscle tone (hypotonia) and feeding difficulties in infancy. They may also have digestive system problems, such as backflow of stomach acids into the esophagus (gastroesophageal reflux), vomiting, and constipation. Other features that occur in ADNP syndrome include obesity, seizures, and heart abnormalities.
## Frequency
The prevalence of ADNP syndrome is unknown. It is estimated to account for 0.17 percent of all cases of autism spectrum disorder, making it one of the most common genetic causes of this condition.
## Causes
ADNP syndrome is caused by mutations in the ADNP gene. The protein produced from this gene helps control the activity (expression) of other genes through a process called chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed.
By regulating gene expression, the ADNP protein is involved in many aspects of growth and development. It is particularly important for regulation of genes involved in normal brain development, and it likely controls the activity of genes that direct the development and function of other body systems.
Although it is unclear how mutations in the ADNP gene affect ADNP protein function, researchers suggest that the mutations result in abnormal chromatin remodeling. Disturbance of this process alters the activity of many genes and disrupts development or function of several of the body's tissues and organs, including the brain. These changes likely explain the intellectual disability, autism spectrum disorder, and other diverse signs and symptoms of ADNP syndrome.
### Learn more about the gene associated with ADNP syndrome
* ADNP
## Inheritance Pattern
ADNP syndrome is not inherited. It results from new (de novo) mutations in the ADNP gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. The condition occurs in people with no history of the disorder in their family.
*[v]: View this template
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*[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
| ADNP syndrome | c4014538 | 1,648 | medlineplus | https://medlineplus.gov/genetics/condition/adnp-syndrome/ | 2021-01-27T08:25:11 | {"gard": ["12931"], "omim": ["615873"], "synonyms": []} |
Familial multiple lipomatosis is a rare, benign, genetic skin disease characterized by numerous, painless, encapsulated lipomas located in the subcutaneous adipose tissue of the trunk and extremities, with relative sparing of the neck and shoulders. Association with gastroduodenal lipomatosis, brain anomalies or lipomatosis, and refractory epilepsy has been reported.
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*[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
| Familial multiple lipomatosis | c3489413 | 1,649 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199276 | 2021-01-23T18:48:29 | {"gard": ["12925"], "mesh": ["D008067"], "omim": ["151900"], "umls": ["C3489413"], "icd-10": ["E88.2"]} |
For broader coverage of this topic, see Photosensitivity.
Light sensitivity or photosensitivity refers to a notable or increased reactivity to light. Apart from vision, human beings have many physiological and psychological responses to light. In rare individuals an atypical response may result in serious discomfort, disease, or injury. Some drugs have a photosensitizing effect. Properties of natural or artificial light that may abnormally affect people include:
* Timing of light (upset of normal circadian rhythms, seasonal affective disorder, sleep disorders)
* Intensity of light (photophobia, sunburn, skin cancer)[1][2]
* Wavelength of light (in lupus, urticaria)
* Rapid flickers in intensity of light may trigger or aggravate photosensitive epilepsy, epileptic seizure, or migraine headaches.[3]
Conditions that may include sensitivity to light include vertigo and chronic fatigue syndrome.
Controlled application of artificial light can be used in a program of light therapy to treat some disorders.
## Contents
* 1 Sunlight
* 2 Fluorescent lamps
* 3 See also
* 4 References
## Sunlight[edit]
Main article: Health effects of sun exposure
Sunlight, especially its ultraviolet radiation component, can cause increased or additional types of damage in predisposed individuals, such as those taking certain phototoxic drugs, or those with certain conditions associated with photosensitivity, including:
* Psoriasis[4]
* Atopic eczema[4]
* Mastocytosis
* Mast cell activation syndrome
* Histamine intolerance
* Erythema multiforme[4]
* Seborrhoeic dermatitis[4]
* Autoimmune bullous diseases (immunobullous diseases)[4]
* Mycosis fungoides[4]
* Smith–Lemli–Opitz syndrome[4]
* Porphyria cutanea tarda
Also, many conditions are aggravated by strong light, including:
* Systemic lupus erythematosus[4]
* Sjögren’s syndrome[4]
* Sinear Usher syndrome[4]
* Rosacea[4]
* Dermatomyositis[4]
* Darier’s disease[4]
* Kindler-Weary syndrome[4]
## Fluorescent lamps[edit]
This section called "Fluorescent lamps" possibly contains inappropriate or misinterpreted citations that do not verify the text. Please help improve this article by checking for citation inaccuracies. (October 2013) (Learn how and when to remove this template message)
Further information: Fluorescent lamps and health
The Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) in 2008 reviewed[5] the connections between light from fluorescent lamps, especially from compact fluorescent lamp, and numerous human diseases, with results including:
* The inner-ear condition Ménière's disease can be aggravated by flicker. Sufferers of vertigo are recommended to not use fluorescent lights.
* Polymorphous light eruption is a condition affecting the skin thought to be caused by an adverse reaction to ultraviolet light. Its prevalence across Europe is 10-20% of the population. Artificial light sources may provoke the condition, and compact fluorescent light have been shown to produce an eruption.
* Chronic actinic dermatitis is a condition where a subject's skin becomes inflamed due to a reaction to sunlight or artificial light. Its prevalence in Scotland is 16.5 per 100,000 population. There is evidence that compact fluorescent light worsen the condition.
* With the autoimmune disease lupus, chronic exposure to compact fluorescent lamps could possibly be a problem.
* There is evidence that actinic prurigo is worsened by compact fluorescent light. This disease affects 3.3% of the general population.
* 3.1% of the population[citation needed] suffer from solar urticaria, a skin disorder affected by ultraviolet light. Some patients are directly affected by compact fluorescent light.
* Phytophotodermatitis may be aggravated by the additional levels of ultraviolet light emitted by compact fluorescent light.
* Patients undergoing photodynamic therapy are at additional risk of adverse photosensitive reactions caused by compact fluorescent light.
* One cause of cataracts is exposure to ultraviolet light. Provided the level of UV emission from lamps is within safe limits, and the lamp a sufficient distance away from the individual, there should be no increased risk of developing cataracts.
* Photophobia is a symptom of excessive sensitivity to light which affects 5 to 20% of the population. No studies have been conducted into the effect of compact fluorescent light on sufferers of photophobia but there is the possibility for compact fluorescent light to affect sufferers.
* There is evidence that flicker can cause seizures in patients with photosensitive epilepsy, but there has yet to be any evidence to date attributing seizures to compact fluorescent lamps.
* Self-reporting suggests fluorescent lamps aggravate dyslexia.
## See also[edit]
* Asthenopia (eye strain)
* Photophobia
* Phototoxicity
* Photosensitivity
* Photosensitivity in animals
* Photodermatitis
* Phytophotodermatitis
## References[edit]
1. ^ Guide to Photophobia/Light Sensitivity, axonoptics.com. Retrieved 11 January 2019.
2. ^ Lightmare, lightmare.org. Retrieved 11 January 2019.
3. ^ Light and Sensitivity, headaches.org. Retrieved 11 January 2019.
4. ^ a b c d e f g h i j k l m n European Guidelines for Photodermatoses > 2 Photoaggravated Disorders[permanent dead link] at European Dermatology Forum
5. ^ "Light Sensitivity, Scientific Committee on Emerging and Newly Identified Health Risks" (PDF). Director-General for Health and Consumers, European Commission. 2008. pp. 26–27. Retrieved 2009-08-31.
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*[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
| Photosensitivity in humans | c0031762 | 1,650 | wikipedia | https://en.wikipedia.org/wiki/Photosensitivity_in_humans | 2021-01-18T19:06:09 | {"mesh": ["D010787"], "wikidata": ["Q2944236"]} |
Solid pseudopapillary carcinoma of the pancreas is a rare carcinoma of the pancreas characterized by a variable combination of nonspecific signs and symptoms, such as abdominal pain, jaundice, abdominal fullness, anorexia, nausea, vomiting, and weight loss. One-third of the patients are asymptomatic. The tumor has low malignant potential, but can invade locally.
*[v]: View this template
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*[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
| Solid pseudopapillary carcinoma of pancreas | c1336029 | 1,651 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=424065 | 2021-01-23T18:04:08 | {"icd-10": ["C25.0", "C25.1", "C25.2", "C25.7", "C25.8"], "synonyms": ["Pancreatic solid pseudopapillary carcinoma", "Solid pseudopapillary neoplasm of the pancreas"]} |
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: "Malgaigne's fracture" – news · newspapers · books · scholar · JSTOR (November 2018)
A Malgaigne fracture is vertical pelvic fracture with bilateral sacroiliac dislocation and fracture of the pubic rami.
It is named for Joseph-François Malgaigne.
## Classification[edit]
* Tile classification \- C3
* Young-Burgess classification \- VS
* OTA/AO \- 61-C3.1
## References[edit]
## External links[edit]
Classification
D
* ICD-10: S32
External resources
* Radiopedia: malgaigne-fracture
* AO Foundation: 61-C3.1
* Wheeless textbook: malgaigne_fracture_vertical_shear
* Orthobullets: trauma/1030/pelvic-ring-fractures
This article about Orthopedic surgery is a stub. You can help Wikipedia by expanding it.
* v
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*[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
| Malgaigne's fracture | c1397723 | 1,652 | wikipedia | https://en.wikipedia.org/wiki/Malgaigne%27s_fracture | 2021-01-18T18:39:38 | {"umls": ["C1397723"], "wikidata": ["Q20707195"]} |
Atypical polypoid adenomyoma
Micrograph of an atypical polypoid adenomyoma. H&E stain.
SpecialtyPathology
Atypical polypoid adenomyoma (APA) is a rare uncommon benign tumour of the uterus.[1]
## Contents
* 1 Pathology
* 2 See also
* 3 References
## Pathology[edit]
APAs are characterized by glands with abnormal shapes that: (1) often have squamous metaplasia, and (2) are surrounded by benign smooth muscle.[1] Nuclear atypia, if present, is mild.
The microscopic differential diagnosis includes endometrial carcinoma and endocervical adenocarcinoma.
* Intermed. mag.
* Very high mag.
## See also[edit]
* Adenomyoma
* Cervical cancer
## References[edit]
1. ^ a b Jakus, S.; Edmonds, P.; Dunton, C.; Holland, G. (Jan 2002). "Atypical polypoid adenomyoma mimicking cervical adenocarcinoma". J Low Genit Tract Dis. 6 (1): 33–8. doi:10.1046/j.1526-0976.2002.61007.x. PMID 17050990.
This oncology article is a stub. You can help Wikipedia by expanding it.
* v
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*[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
| Atypical polypoid adenomyoma | c1300347 | 1,653 | wikipedia | https://en.wikipedia.org/wiki/Atypical_polypoid_adenomyoma | 2021-01-18T18:33:24 | {"umls": ["C1300347"], "wikidata": ["Q4818893"]} |
## Summary
### Clinical characteristics.
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (includes fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The exact cancer risks differ slightly depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant.
### Diagnosis/testing.
The diagnosis of BRCA1 and BRCA2 HBOC is established in a proband by identification of a heterozygous germline pathogenic variant in BRCA1 or BRCA2 on molecular genetic testing.
### Management.
Treatment of manifestations: National Comprehensive Cancer Network guidelines suggest that women with a BRCA1/2 pathogenic variant could consider bilateral mastectomy as a primary surgical treatment of breast cancer because of their elevated rate of ipsilateral and contralateral breast cancer. Treatment of ovarian and other cancers in individuals with a BRCA1/2 pathogenic variant is similar to that for sporadic cancers.
Prevention of primary manifestations: Prophylactic bilateral mastectomy, prophylactic oophorectomy, and chemoprevention (e.g., tamoxifen) have been used for breast cancer prevention, but have not been assessed by randomized trials in high-risk women. Prophylactic oophorectomy for ovarian cancer prevention.
Surveillance: Breast cancer screening in women relies on a combination of monthly breast self-examination, annual or semiannual clinical breast examination, annual mammography, and breast MRI. Annual transvaginal ultrasound and CA-125 concentration beginning at age 35 years may be considered for ovarian cancer screening. However, this screening has not been effective in detecting early-stage ovarian cancer, either in high-risk or average-risk women. For men, breast cancer screening includes breast self-examination education and training and annual clinical breast examination beginning at age 35. Annual prostate cancer screening should begin at age 45. Screening for melanoma should be individualized based on the family history. Screening of asymptomatic individuals for pancreatic cancer is not generally recommended.
Evaluation of relatives at risk: Once a cancer-predisposing BRCA1 or BRCA2 germline pathogenic variant has been identified in a family, testing of at-risk relatives can identify those family members who also have the familial pathogenic variant and thus need increased surveillance and early intervention when a cancer is identified.
### Genetic counseling.
Germline pathogenic variants in BRCA1 and BRCA2 are inherited in an autosomal dominant manner. The vast majority of individuals with a BRCA1 or BRCA2 pathogenic variant have inherited it from a parent. However, because of incomplete penetrance, variable age of cancer development, cancer risk reduction resulting from prophylactic surgery, or early death, not all individuals with a BRCA1 or BRCA2 pathogenic variant have a parent affected with cancer.
Offspring of an individual with a BRCA1 or BRCA2 germline pathogenic variant have a 50% chance of inheriting the variant. Prenatal testing is possible for pregnancies at increased risk if the cancer-predisposing variant in the family is known; however, requests for prenatal diagnosis of adult-onset diseases are uncommon and require careful genetic counseling.
## Diagnosis
### Suggestive Findings
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) should be suspected in individuals with a personal or family history (1st-, 2nd-, or 3rd-degree relative in either lineage) of any of the following characteristics [NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian]:
* Breast cancer diagnosed at or before age 50 years
* Ovarian cancer
* Multiple primary breast cancers either in one or both breasts
* Male breast cancer
* Triple-negative (estrogen receptor-negative, progesterone receptor-negative, and HER2/neu [human epidermal growth factor receptor 2]-negative) breast cancer, particularly when diagnosed before age 60 years
* The combination of pancreatic cancer and/or prostate cancer (Gleason score ≥7) with breast cancer, and/or ovarian cancer
* Breast cancer diagnosed at any age in an individual of Ashkenazi Jewish ancestry
* Two or more relatives with breast cancer, one under age 50
* Three or more relatives with breast cancer at any age
* A previously identified BRCA1 or BRCA2 pathogenic variant in the family
Notes: (1) "Breast cancer" includes both invasive cancer and ductal carcinoma in situ (DCIS). (2) "Ovarian cancer" includes epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.
#### Probability Models for BRCA1/2 Pathogenic Variants
Several models have been developed to estimate the likelihood that an individual or family has a germline pathogenic variant in BRCA1 or BRCA2 [Parmigiani et al 1998, Frank et al 2002, Antoniou et al 2004, Evans et al 2004, Tyrer et al 2004]. According to the American Society of Clinical Oncology (ASCO) policy statement on genetic testing for cancer susceptibility [American Society of Clinical Oncology 2003], there is no numeric threshold generated from these models that should be used in determining the appropriateness of genetic testing. The use of probability models, however, has been shown to help further discriminate which individuals are more likely to have a BRCA1 or BRCA2 pathogenic variant, even among experienced providers [Euhus et al 2002, de la Hoya et al 2003]. For more information about probability models for BRCA1/2 pathogenic variants, click here.
### Establishing the Diagnosis
The diagnosis of BRCA1\- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) is established in a proband by identification of a heterozygous germline pathogenic variant in BRCA1 or BRCA2 on molecular genetic testing (see Table 1).
Note: (1) Molecular testing is most likely to be informative in an individual with a BRCA1/2-associated cancer (e.g., breast cancer at age <50 years, ovarian cancer) and is often referred to as the "best test candidate." Thus, molecular genetic testing ideally should be performed initially on the "best test candidate" as opposed to a family member who may have an unrelated cancer or who may not have a personal history of cancer. (2) If the "best test candidate" is not available, molecular testing may be performed on another individual, without a cancer history, with the understanding that failure to detect a pathogenic variant does not eliminate the possibility of a BRCA1 or BRCA2 pathogenic variant being present in the family.
Molecular testing approaches can include a BRCA1 and BRCA2 gene panel and use of a multigene panel:
* BRCA1 and BRCA2 gene panel. Sequence analysis of BRCA1 and BRCA2 is performed concurrently with deletion/duplication analysis.
Targeted analysis can be considered in individuals of Ashkenazi Jewish ancestry by starting with targeted testing for three BRCA1 and BRCA2 pathogenic founder variants: BRCA1 c.68_69delAG (BIC: 185delAG) BRCA1 c.5266dupC (BIC: 5382insC), and BRCA2 c.5946delT (BIC: 6174delT), which together account for up to 99% of pathogenic variants identified in individuals of Ashkenazi Jewish ancestry. If no pathogenic variant is identified by targeted analysis, it may be appropriate to proceed with sequence and deletion/duplication analyses of BRCA1 and BRCA2 or a multigene panel.
Note: In a family known to have a BRCA1 or BRCA2 germline pathogenic variant, at-risk adults may be tested for the family-specific germline pathogenic variant. In most cases, relatives at risk need only be tested for the family-specific germline pathogenic variant, except in the following situations:
* Individuals of Ashkenazi Jewish heritage should consider testing for all three founder germline pathogenic variants because of the high population frequency of these founder pathogenic variants as well as reports of the coexistence of more than one founder germline pathogenic variant in some families.
* Individuals with a familial BRCA1 or BRACA2 pathogenic variant on one side of the family and characteristics of HBOC on the other side of the family may consider sequence analysis and deletion/duplication analysis of BRCA1 and BRCA2, which would (1) detect the familial germline pathogenic variant if present and also (2) address whether a germline pathogenic variant is present on the other side of the family.
* A multigene panel that includes BRCA1 and BRCA2 and other genes of interest (see Differential Diagnosis) may also be considered. 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; thus, clinicians need to determine which multigene panel 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. (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.
### Table 1.
Molecular Genetic Testing Used in BRCA1 and BRCA2 Associated Hereditary Breast/Ovarian Cancer (HBOC)
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Gene 1Proportion of BRCA1/BRCA2 Associated HBOC Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 2 Detected by Method
Sequence analysis 3Gene-targeted deletion/duplication analysis 4
BRCA166%>80% 5~10% 5
BRCA234%>80% 5~10% 5
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\.
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.
4\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used 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.
5\.
The majority of pathogenic variants (≥80%) in BRCA1 and BRCA2 are detected through whole-gene sequencing, with an additional 10% detected through deletion/duplication analysis, which may vary across different populations [Palma et al 2008, Ewald et al 2009, Kang et al 2010, Judkins et al 2012].
## Clinical Characteristics
### Clinical Description
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk for male and female breast cancer, ovarian cancer (includes fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. Estimates of malignancy risk vary considerably depending on the context in which they were derived. The following is a summary of the risk for malignancy in an individual with a germline BRCA1 or BRCA2 pathogenic variant.
### Table 2.
Risk of Malignancy in Individuals with a Germline BRCA1 or BRCA2-Pathogenic Variant.
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Cancer TypeGeneral Population RiskRisk for Malignancy 1
BRCA1BRCA2
Breast12%46%-87%38%-84%
Second primary breast2% within 5 years21.1% within 10 yrs
83% by age 7010.8% within 10 yrs
62% by age 70
Ovarian1%-2%39%-63%16.5%-27%
Male breast0.1%1.2%Up to 8.9%
Prostate6% through age 698.6% by age 6515% by age 65
20% lifetime
Pancreatic0.50%1%-3%2%-7%
Melanoma (cutaneous & ocular)1.6%Elevated Risk
1\.
Ford et al [1994], Easton et al [1995], Ford et al [1998], Robson et al [1998], Breast Cancer Linkage Consortium [1999], Verhoog et al [2000], Satagopan et al [2002], Thompson & Easton [2002], Hearle et al [2003], Kirova et al [2005], Robson et al [2005], van Asperen et al [2005], Chen et al [2006], Risch et al [2006], Tai et al [2007], Graeser et al [2009], Evans et al [2010], van der Kolk et al [2010], Kote-Jarai et al [2011], Iqbal et al [2012], Leongamornlert et al [2012], Moran et al [2012], Mavaddat et al [2013], van den Broek et al [2015]
Breast cancer. Breast cancer is the most common malignancy in individuals with a germline BRCA1 or BRCA2 pathogenic variant with a lifetime risk ranging from 46% to 87%.
The first estimates of breast cancer risk associated with BRCA1 pathogenic variants was based on 33 families with evidence of linkage to BRCA1 with an estimated cumulative risk of 87% by age 70 years [Ford et al 1994]. For BRCA2, early cumulative breast cancer risk estimates reached 84% by age 70 years [Ford et al 1998]. Subsequent studies have revealed lower risk estimates. In a US study that included 676 Ashkenazi families and 1272 families of other ethnicities, Chen et al [2006] estimated the cumulative breast cancer risk in women with a germline BRCA1 pathogenic variant to age 70 years at 46%. Satagopan et al [2001] studied incident breast cancer cases among Ashkenazi Jewish women and found the penetrance of breast cancer at age 80 years among BRCA1 heterozygotes to be 59% (95% CI = 40%-93%) and among BRCA2 heterozygotes to be 38% (95% CI = 20%-68%). More recently, in a cohort of 978 individuals with a BRCA1 pathogenic variant and 909 individuals with a BRCA2 pathogenic variant from the United Kingdom, Mavaddat et al [2013] estimated the average cumulative breast cancer risks by age 70 in BRCA1 heterozygotes to be 60% and 55% for BRCA2 heterozygotes (see Table 2).
A total of 16 studies comprising 10,180 individuals were recently analyzed to determine overall survival among those with BRCA1/2 pathogenic variants [Templeton et al 2016]. The pooled analysis showed no association between the presence of germline BRCA1/2 pathogenic variants and overall survival (HR 1.06, 95% CI 0.84-1.34, p=0.61). The findings were similar when the influence of BRCA1 and BRCA2 pathogenic variants were evaluated on overall survival independently (BRCA1: HR 1.20, 95% CI 0.89-1.61, p=0.24; BRCA2: HR 1.01, 95% CI 0.80-1.27, p = 0.95). There, however, appears to be a strong and statistically significant association between estrogen receptor (ER) expression and overall survival in individuals with germline BRCA1 pathogenic variants but not with age or progesterone receptor (PR) expression.
BRCA1-related tumors show an excess of medullary histopathology, are of higher histologic grade, are more likely than sporadic tumors to be estrogen receptor-negative and progesterone receptor-negative, and are less likely to demonstrate HER2/neu overexpression; thus, BRCA1-related tumors fall within the category of "triple-negative" breast cancer [Rakha et al 2008, Lee et al 2011] and overlap with basal-like breast cancers. Several reports have also suggested a link between germline BRCA2 pathogenic variants and triple-negative breast cancer. In studies of persons with triple-negative breast cancer, the incidence of germline BRCA2 pathogenic variants ranges from 3% to 17% [Evans et al 2011, Meyer et al 2012, Couch et al 2015]. The evidence that a germline BRCA1/2 pathogenic variant is associated with poor survival outcomes for breast cancer has been inconsistent [Verhoog et al 2000, Bordeleau et al 2010, van den Broek et al 2015, Zhong et al 2015].
Contralateral breast cancer (CBC). Several studies have reported higher rates of CBC [Graeser et al 2009, Malone et al 2010, Pierce et al 2010, van der Kolk et al 2010, Metcalfe et al 2011a, Vichapat et al 2012, van den Broek et al 2015] in women treated conservatively. Predictors of CBC include age at first breast cancer, family history of early-onset breast cancer, and the affected BRCA gene [Graeser et al 2009, Malone et al 2010, Metcalfe et al 2011a, van den Broek et al 2015]. The risk for CBC was decreased among women who had undergone prophylactic oophorectomy [Metcalfe et al 2011a]. In an unselected cohort of individuals with breast cancer, ten-year cumulative contralateral breast cancer risks of 21.1% for those with BRCA1 pathogenic variants and 10.8% for those with BRCA2 pathogenic variants were found.
Using a cohort of 978 BRCA1 and 909 BRCA2 heterozygotes from the United Kingdom, Mavaddat et al estimated the cumulative risk of contralateral breast cancer to be 83% in BRCA1 heterozygotes and 62% for BRCA2 heterozygotes by age 70 [Mavaddat et al 2013].
Ipsilateral breast cancer. Two case-control studies reported significantly higher rates of ipsilateral breast cancer in individuals with a germline BRCA1/2 pathogenic variant compared with sporadic controls [Haffty et al 2002, Seynaeve et al 2004], however, other studies have not found an increased risk for ipsilateral breast cancer in those with germline BRCA1/2 pathogenic variants when compared with women who had sporadic breast cancer [Robson et al 2004, Graeser et al 2009] and also demonstrated a significant ipsilateral breast cancer risk reduction in individuals receiving radiation therapy compared with those who were not receiving radiation therapy [Metcalfe et al 2011b].
Ovarian cancer (including fallopian tube and primary peritoneal cancers). BRCA germline pathogenic variants confer an excessive risk for ovarian cancer ranging from 16.5% to 63%. The first estimates of ovarian cancer risk associated with BRCA1 pathogenic variants were as high as 63% by age 70 [Easton et al 1995] and for BRCA2 pathogenic variants were as high as 27% by age 70 [Ford et al 1998]. Subsequent studies have revealed lower risk estimates. In the US population study that included 676 Ashkenazi families and 1272 families of other ethnicities, Chen et al [2006] estimated ovarian cancer risk to age 70 years in individuals with a germline BRCA1 pathogenic variant at 39% (95% CI = 0.30%-0.50%). Satagopan et al [2002] found the estimated penetrance of ovarian cancer at age 70 years among BRCA1 heterozygotes to be 37% (95% CI = 25%-71%) and among BRCA2 heterozygotes to be 21% (95% CI = 13%-41%). More recently, in a cohort of 978 BRCA1 and 909 BRCA2 heterozygotes from the United Kingdom, Mavaddat et al [2013] estimated the average cumulative risks by age 70 in BRCA1 heterozygotes to be 59% for ovarian cancer and 16.5% for BRCA2 heterozygotes (see Table 2).
An excess of serous adenocarcinomas have been observed in women with germline BRCA1 or BRCA2 pathogenic variants [McLaughlin et al 2013]. Serous adenocarcinomas are generally of higher grade and exhibit prominent intraepithelial lymphocytes, marked nuclear atypia, and abundant mitoses [Fujiwara et al 2012]. Given recent advances in the understanding of the molecular pathways of ovarian cancer, it has been concluded that most cases of high-grade serous cancers arise from the fallopian tubes rather than the ovaries [Daly et al 2015].
Studies on ovarian cancer survival in women with a germline BRCA1/2 pathogenic variant have yielded conflicting results. A pooled analysis of 26 observational studies found a more favorable survival rate among individuals with a detectable BRCA1 or BRCA2 pathogenic variant compared to individuals without a BRCA1/2 pathogenic variant, (BRCA1 HR 0.78, 95% CI 0.68-0.89; BRCA2 HR 0.61, 95% CI 0.50-0.76). These results persisted when controlling for stage, grade, histology, and age at diagnosis [Bolton et al 2012]. A large population-based case-control study found a higher response to platinum-based therapy, longer progression-free survival, and improved overall survival among individuals with a germline BRCA1/2 pathogenic variant [Alsop et al 2012]. Similarly, individuals with platinum-sensitive epithelial ovarian tumors were more likely to have germline BRCA1/2 pathogenic variants than individuals with platinum-resistant tumors [Dann et al 2012]. More recently, in a large series of unselected individuals with ovarian cancer, the short-term survival of individuals with ovarian cancer with germline BRCA1/2 pathogenic variants was better than that of individuals without an identified BRCA1/2 pathogenic variant, however, the survival advantage was short lived and did not lead to a long-term survival benefit [McLaughlin et al 2013].
Male breast cancer. Based on data from 1939 families with 97 male subjects with breast cancer, the risk of developing breast cancer in males with a BRCA1 or BRCA2 pathogenic variant were evaluated. The cumulative risk of breast cancer was higher in both BRCA1 and BRCA2 male heterozygotes than in males without a BRCA1/2 pathogenic variant at all ages. With respect to the relative risks of developing breast cancer, the risk was higher for men in their 30s and 40s and decreased with increasing age. When compared to BRCA1, males with BRCA2 pathogenic variants had higher relative and cumulative risks. The estimated cumulative risk of breast cancer for males with BRCA1 pathogenic variants at age 70 years was 1.2% (95% CI 0.22%-2.8%) and for males with a BRCA2 pathogenic variant was 6.8% (95% CI 3.2%-12%) [Tai et al 2007].
In the largest study of families with BRCA2 to date, using both retrospective and prospective analyses of 321 families, three breast cancers occurred in male first-degree relatives, suggesting a risk for male breast cancer to 80 years of 8.9% [Evans et al 2010] (see Table 2).
Prostate cancer. A series of 913 males with prostate cancer, ranging in age from 36 to 86 years, were screened for germline BRCA1 pathogenic variants; four pathogenic variants were identified; three of which were identified in individuals diagnosed at or before age 65 years. Based on previously estimated population frequencies of BRCA1 pathogenic variants, it was estimated that BRCA1 pathogenic variants confer a relative risk of prostate cancer of approximately 3.7-fold (95% CI 1.02-9.6), which translates to an 8.6% cumulative risk by age 65 years [Leongamornlert et al 2012].
The lifetime risk for prostate cancer in males with BRCA2 pathogenic variants has been estimated at 20% [Breast Cancer Linkage Consortium 1999]. In 2011, Kote-Jarai et al screened 1864 males with prostate cancer diagnosed between age 36 and 88 years for BRCA2 pathogenic variants. Nineteen protein-truncating variants were identified, all of which occurred in individuals who were diagnosed with prostate cancer at or before age 65 years. Based on previously estimated frequencies of BRCA2 pathogenic variants, it was estimated that BRCA2 pathogenic variants confer an increased relative risk of prostate cancer of approximately 8.6-fold (95% CI 5.1-12.6) by age 65 years corresponding to an absolute risk of approximately 15% by age 65 years [Kote-Jarai et al 2011]. In addition, BRCA2-related prostate cancer has been associated with a higher histologic grade [Gallagher et al 2010] and results in a poorer overall survival [Thorne et al 2011] (see Table 2).
Pancreatic cancer. An increased risk for pancreatic (adenocarcinoma) cancer has been associated with pathogenic variants in BRCA1 and BRCA2. In the cross-sectional study of the Breast Cancer Linkage Consortium [1999], Thompson & Easton [2002] reported a significant increase in the risk for pancreatic cancer in those with germline BRCA1 pathogenic variants (RR=2.26, 95% CI=1.26-4.06, P=0.004) and in those with BRCA2 pathogenic variants (RR=3.51, 95% CI=1.87-6.58, P=0.0012). Risch et al [2006] estimated the risk of pancreatic cancer among relatives of females with invasive ovarian cancer in 1171 unselected females with ovarian cancer in Ontario. The relative risk for pancreatic cancer was 3.1 (95% CI=0.45-21) in relatives of those with BRCA1 pathogenic variants and 6.6% (95% CI=1.9-23) in relatives of those with BRCA2 pathogenic variants, compared to relatives of those without pathogenic variants. More recently, a prospective study of 5149 females with BRCA1 or BRCA2 pathogenic variants showed a statistically significant 2.4-fold increase in the incidence of pancreatic cancer and – unlike in previous studies – the increase in the incidence of pancreatic cancer was similar for BRCA1 (SIR=2.55) and BRCA2 (SIR=2.13) [Iqbal et al 2012] (see Table 2).
Melanoma. Although it is less well studied, the literature suggests that melanoma risk, both cutaneous and ocular, may be elevated in some but not all families with a BRCA2 pathogenic variant [Breast Cancer Linkage Consortium 1999, Hearle et al 2003, van Asperen et al 2005]. An analysis of 490 families with BRCA1/2 pathogenic variants showed an increased risk for ocular melanoma in individuals with germline BRCA2 pathogenic variants (RR=99.4, 95%CI=11.1-359.8) [Moran et al 2012] (see Table 2).
Other cancers. In addition to the above-mentioned cancers, individuals with BRCA1 and BRCA2 pathogenic variants may be at a higher risk for additional malignancies based on family-based studies as well as case-control studies [Breast Cancer Linkage Consortium 1999, Thompson et al 2001, van Asperen et al 2005], although the absolute risks for these other cancers are small. The Breast Cancer Linkage Consortium reported an increased relative risk for cancers of the uterine body and cervix, with relative risks of 2.6 and 3.7, in women younger than age 65 years with a germline BRCA1 pathogenic variant [Thompson & Easton 2002]. The Netherlands Collaborative Group on Hereditary Breast Cancer reported statistically increased relative risks for cancers of the gallbladder and bile duct, with relative risks of 3.5 and 5.0, respectively [van Asperen et al 2005]. It is important to note, however, that in some of these studies, diagnoses were not consistently confirmed by pathology and therefore, excess risk of cervix and uterus as well as gallbladder and bile duct cancers may represent misclassifications of ovarian and pancreatic cancers, respectively. Furthermore, data suggesting a causative link between endometrial cancer and pathogenic variants of BRCA1/2 may be related to tamoxifen exposure [Beiner et al 2007] rather than the presence of a pathogenic variant, as previous studies have found that uterine papillary serous cancer does not appear to be a manifestation of HBOC [Goshen et al 2000]. Finally, initial reports of increased colorectal cancer risk have generally not been replicated [Gruber & Petersen 2002, Niell et al 2004].
No associated benign tumors or physical abnormalities are presently known to be associated with pathogenic variants in BRCA1 or BRCA2.
### Phenotype Correlations by Gene
Ovarian cancer and primary papillary serous carcinoma of the peritoneum are considerably more common and tend to develop at an earlier age in women with a germline BRCA1 pathogenic variant as compared to women with a germline BRCA2 pathogenic variant [Casey et al 2005, Yates et al 2011]. However, those with BRCA2 pathogenic variants tend to be at greater risk for male breast cancer, prostate cancer, pancreatic cancer, and melanoma.
### Genotype-Phenotype Correlations
Some genotype-phenotype correlations have been identified in families with BRCA1 and BRCA2 pathogenic variants. Such correlations are not currently used in individual risk assessment and management, but may be in future with appropriate validation.
Families with protein-truncating BRCA1 pathogenic variants from the Breast Cancer Linkage Consortium reported breast cancer risk to be lower with pathogenic variants in the central region of the gene (nucleotides 2,401-4,190) compared with surrounding regions. Furthermore, ovarian cancer risk was associated with a lower risk with pathogenic variants 3’ to nucleotide 4,191 [Thompson et al 2001].
Studies in the Ashkenazi Jewish population have also found higher rates of ovarian cancer in individuals with the c.68_69delAG (BIC: 185delAG) pathogenic variant, in the 5' end of BRCA1, as compared to individuals with the c.5266dupC (BIC: 5382insC) pathogenic variant, which is in the 3' end of the gene [Lubinski et al 2004]. However, c.5266dupC pathogenic variants appear to confer a higher risk for breast cancer, including bilateral breast cancer, and both breast and ovarian cancer in the same individual when compared to both c.68_69delAG (BIC: 185delAG) in BRCA1 and c.5946delT (BIC: 6174delT) in BRCA2 [Satagopan et al 2002, Lubinski et al 2004].
An ovarian cancer cluster region (OCCR) in or near exon 11 in both BRCA1 and BRCA2 has been identified [Rebbeck et al 2015]. Pathogenic variants within the OCCR have been associated with a higher ratio of ovarian to breast cancer than is seen in families with a pathogenic variant elsewhere in the genes.
In BRCA1 and BRCA2, multiple breast cancer cluster regions (BCCR) have been observed and are associated with relatively elevated breast cancer risk and lower ovarian cancer risk [Rebbeck et al 2015].
### Penetrance (Cancer Risk)
Female breast and ovarian cancers remain the most common cancers associated with BRCA1/2 pathogenic variants. Females with BRCA1/2 pathogenic variants have up to an 87% risk of developing an associated cancer, while males have up to a 20% risk.
### Prevalence
BRCA1\- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) is the most common form of hereditary breast and ovarian cancer and occurs in all ethnic and racial populations. The prevalence of BRCA1/2 pathogenic variants in the general population (excluding Ashkenazim) is estimated at 1:400 to 1:500 [Anglian Breast Cancer Study Group 2000, Whittemore et al 2004b].
Ashkenazi Jewish. The combined frequency of the following three pathogenic variants in the Ashkenazi Jewish population is 1:40 [King et al 2003]:
* BRCA1 c.68_69delAG (BIC: 185delAG) occurs with a frequency of 1%;
* BRCA1 c.5266dupC (BIC: 5382insC) has an estimated prevalence of 0.1%-0.15%;
* BRCA2 c.5946delT (BIC: 6174delT) occurs with a frequency of about 1.52%.
[Ferla et al 2007]
## Differential Diagnosis
Syndromic breast cancer. Individuals with the following cancer susceptibility syndromes and/or genes have an elevated breast cancer risk. In many instances, BRCA1 and BRCA2 HBOC can be distinguished from these other disorders based on the constellation of tumors present in the family; however, in some cases, molecular genetic testing may be necessary to differentiate.
### Table 3.
Disorders to Consider in the Differential Diagnosis of BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer
View in own window
Cancer Susceptibility Syndrome / GeneGene(s)MOILifetime Breast Cancer Risk & Other Associated CancersOther Distinguishing Features
Li-Fraumeni syndromeTP53ADBreast cancer ≤79% 1
(often pre-menopausal)
Soft tissue sarcoma
Osteosarcoma
Brain tumors
Adrenocortical carcinoma
LeukemiasCancers often occur in childhood or young adulthood.
Survivors are at increased risk for multiple primary cancers.
Cowden syndrome
(see PTEN Hamartoma Tumor Syndrome)PTENADBreast cancer 25%-50%, may be ≤85% 2
Thyroid cancer
Renal cell carcinoma
Endometrial carcinoma
Colorectal cancerMultiple hamartomas, macrocephaly, trichilemmomas, papillomatous papules
Affected individuals usually present by late 20s
Hereditary diffuse gastric cancerCDH1ADBreast cancer 39%-52% 3
(lobular breast cancer)
Diffuse gastric cancerMajority of cancers occur before age 40 years
CHEK2
(OMIM 604373)CHEK2ADBreast cancer 25%-39% 4
Prostate cancer 5
Stomach cancer 5
Sarcoma 5
Kidney cancer 5
ATM heterozygotes
(see Ataxia-Telangiectasia)ATMADBreast cancer 17%-52% 6
Other cancers
PALB2
(OMIM 610355)PALB2ADBreast cancer ≤58% 7
Male breast cancer 8
Pancreatic cancer 9
Peutz-Jeghers syndromeSTK11 1ADBreast cancer 32%-54%
Gastrointestinal malignancies
Ovarian (mostly SCTAT)
Cervical cancer (adenoma malignum)
Uterine cancer
Pancreatic cancer
Sertoli cell testicular cancer
Lung cancerGastrointestinal polyposis, mucocutaneous pigmentation, hyperpigmented macules on the fingers
Bloom's syndromeBLMARBreast cancer risk increased 10
Epithelial carcinoma
Lymphoma
Leukemia
Other cancersSevere pre- & postnatal growth deficiency, sparse subcutaneous fat tissue, short stature, sun-sensitive, erythematous skin lesion of the face
Werner syndromeWRNARBreast cancer risk increased 11
Sarcomas
Melanoma
Thyroid cancer
Hematologic malignanciesCharacterized by the appearance, usually in the 20s, of features associated w/normal aging
RAD51C
(OMIM 602774)RAD51COvarian cancerBreast cancer risk unknown
Lynch syndromeMLH1
MSH2
MSH6
PMS2
EPCAMADOvarian cancer 12
Nonpolyposis colorectal cancer
Endometrial cancer
Other cancersIt is currently unknown whether Lynch syndrome is associated w/increased risk for breast cancer. 13
RR = relative risk
MOI = mode of inheritance
AD = autosomal dominant
AR = autosomal recessive
SCTAT = sex cord tumor with annular tubules
XL = X-linked
1\.
Ruijs et al [2010]
2\.
Lifetime breast cancer risk is estimated at between 25% and 50% among women with Cowden syndrome [Hobert & Eng 2009]. Other studies have reported risks as high as 85% [Tan et al 2012, Bubien et al 2013, Ngeow et al 2014, Nieuwenhuis et al 2014]; however, there are concerns regarding selection bias in these studies.
3\.
Brooks-Wilson et al [2004], Kaurah et al [2007]
4\.
CHEK2 variant c.1100delC (NM_007194.3) associated with estimated two- to threefold increase in breast cancer risk in women and a tenfold increase of risk in men [CHEK2 Breast Cancer Case-Control Consortium 2004, Bernstein et al 2006, Weischer et al 2007]
5\.
Associated with CHEK2 founder alleles: c.1100delC, c.319+1G>A(IVS2+1G>A), p.Ile157Thr (NM_007194.3) [Näslund-Koch et al 2016]
6\.
The cancer risk to individuals heterozygous for ATM disease-causing variants is approximately four times that of the general population, primarily because of an increased risk for breast cancer [Renwick et al 2006, Tavtigian et al 2009, Goldgar et al 2011, Roberts et al 2012]. Some specific pathogenic ATM variants may cause an even higher female breast cancer risk (≤52%-69%).
7\.
Antoniou et al [2014]
8\.
Male breast cancer has also been observed in families with molecularly confirmed PALB2-associated breast cancer [Casadei et al 2011, Ding et al 2011].
9\.
Germline pathogenic variants in PALB2 have been identified in families with multiple cases of pancreatic cancer, but the exact risk for pancreatic cancer conferred by germline variants in PALB2 has not yet been established [Jones et al 2009, Slater et al 2010].
10\.
Sixteen individuals with breast cancer, of 207 individuals with Bloom's syndrome reported in Bloom's Syndrome Registry
11\.
Seven of 248 neoplasms reported in individuals with Werner syndrome [Lauper et al 2013]
12\.
Lifetime risks of ovarian cancer in Lynch syndrome range from 4% to 12%. Unlike ovarian cancer associated with germline pathogenic variants in BRCA1/2, those associated with Lynch syndrome are more likely to be endometrioid or clear cell [Ketabi et al 2011].
13\.
Breast cancer has been reported in families with Lynch syndrome, but consistent associations have not been demonstrated [Gruber & Petersen 2002, Müller et al 2002, Walsh et al 2010].
## Management
### Evaluations Following Initial Diagnosis
Individuals who have a germline pathogenic variant in BRCA1 or BRCA2 are counseled at the time of disclosure of molecular genetic test results about their options for Surveillance and Prevention of Primary Manifestations.
### Treatment of Manifestations
National Comprehensive Cancer Network (NCCN) guidelines suggest that women with a BRCA1/2 pathogenic variant could consider bilateral mastectomy as a primary surgical treatment of breast cancer because of their elevated rate of ipsilateral and contralateral breast cancer [NCCN Guidelines].
### Prevention of Primary Manifestations
Breast cancer
* Consider prophylactic bilateral mastectomy
* Given the conflicting data on the degree of risk reduction of breast cancer associated with prophylactic oophorectomy, consider discussing the risks and benefits of this approach with a genetics specialist.
* Chemoprevention. In a retrospective study tamoxifen reduced the risk for breast cancer by 62% among healthy women with a BRCA2 germline variant [King et al 2001]. The sample size, however, was extremely small. In a nested case-control study, tamoxifen use was associated with a 41%-50% reduction in the risk of developing contralateral breast cancer [Narod et al 2000, Metcalfe et al 2005]. There have been no prospective randomized trials of tamoxifen as a chemoprevention agent in women with BRCA1/2 pathogenic variants.
* Breast feeding for a cumulative total of more than one year reduced the risk for breast cancer [Jernström et al 2004].
Ovarian cancer/fallopian tube cancer
* Consider prophylactic oophorectomy, recognizing that completion of childbearing may factor into this decision. Several studies have documented a significant (80%-96%) risk reduction in ovarian cancer following risk-reducing oophorectomy [Kauff et al 2002, Rebbeck et al 2002, Rutter et al 2003].
* Salpingectomy. Recent advances in understanding the molecular events preceding ovarian cancer have established the fallopian tube as the origin of the majority of high-grade serous ovarian cancers, leading to the consideration of salpingectomy with ovarian retention until the age of natural menopause as the first step in primary prevention. This approach is likely to reduce the health hazards of premature menopause, but its adoption will require prospective data to establish its safety and efficacy [Daly et al 2015].
* Tubal ligation. A meta-analysis of 13 studies showed a reduction in risk for ovarian cancer of 34% in the general population after tubal ligation [Cibula et al 2011]. A meta-analysis of modifiers of risk of cancer in individuals with pathogenic variants in BRCA1/2 found a reduction in the risk of ovarian cancer in females with a BRCA1 pathogenic variant, although study design issues limit the impact of these findings [Friebel et al 2014].
* Oral contraceptive use has been associated with a reduction in ovarian cancer risk of 14% among women who had ever used oral contraceptives and 38% among long-term users [Whittemore et al 2004a].
Note: There is no evidence that use of current (after 1975) oral contraceptive formulations increases the risk for early-onset breast cancer for women with a germline BRCA1 or BRCA2 pathogenic variant.
### Prevention of Secondary Complications
Significant adverse consequences of tamoxifen treatment included higher rates of endometrial cancer and thromboembolic episodes (including pulmonary embolism) in those individuals who took the medication than in those who did not. Women with a history of thromboembolic disease or with a coagulation disorder should avoid taking tamoxifen. Women on tamoxifen should be counseled to report any abnormal vaginal bleeding immediately to their gynecologist.
### Surveillance
Women
* Monthly breast self-examination
* Clinical breast examination every 6-12 months beginning at age 25
* Annual breast MRI beginning at age 25, or individualized based on family history if a breast cancer diagnosis before age 30 is present
* Annual mammogram beginning at age 30
* Annual transvaginal ultrasound and serum CA-125 concentration beginning at age 35 years (or individualized based on the earliest age of onset in the family) may be considered for those women who have not elected to undergo prophylactic oophorectomy.
Note: Annual pelvic ultrasound and/or CA-125 concentration has not been effective in detecting early-stage ovarian cancer, either in high-risk or average-risk women.
Men
* Breast self-examination training and regular monthly breast self-examination beginning at age 35
* Annual clinical breast examination beginning at age 35
* Annual prostate cancer screening beginning at age 45
Women and men
* Screening for melanoma should be individualized based on the family history.
* Screening of asymptomatic individuals for pancreatic cancer is not generally recommended, but is possible in research settings.
### Agents/Circumstances to Avoid
No data specific to individuals with BRCA1/2 pathogenic variants are available.
### Evaluation of Relatives at Risk
Once a cancer-predisposing BRCA1 or BRCA2 germline variant has been identified in a family, testing of at-risk relatives can identify those family members who also have the familial variant and thus need increased surveillance and early intervention when a cancer is identified.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Several studies currently underway are looking at novel approaches to the treatment of BRCA-associated breast and ovarian cancer. The majority of the studies involve PARP inhibitors, and have led to FDA approval for one of these agents in treatment of recurrent ovarian cancer. Newer studies are exploring the use of PARP inhibitors in other BRCA-associated cancers (e.g., pancreatic cancer). Given the experimental data showing increased sensitivity of BRCA cell lines to platinum-based agents, there is interest in platinum-based regimens for breast cancer in the neoadjuvant, adjuvant, and metastatic setting.
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.
### Other
Hormone replacement therapy (HRT). General population studies suggest that long-term estrogen replacement therapy in postmenopausal women may increase breast cancer risk, but that short-term use to treat menopausal symptoms does not. However, even relatively short-term combined estrogen plus progestin use was shown to increase the incidence of breast cancers in a randomized, placebo control trial of HRT [Chlebowski et al 2003].
Three observational studies on the impact of HRT on breast cancer risk in BRCA 1/2 heterozygotes have been published. Rebbeck et al [2005] evaluated breast cancer risk associated with HRT after bilateral prophylactic oophorectomy in a cohort of 462 women with a BRCA1 or BRCA2 germline pathogenic variant and found that HRT of any type after bilateral prophylactic oophorectomy did not significantly alter the reduction in breast cancer risk associated with the surgery. The postoperative follow up was 3.6 years. It was concluded that short-term HRT does not substantially increase the risk for breast cancer in women with a BRCA1 or BRCA2 germline pathogenic variant. A subsequent study of expanded data from this cohort included 1299 women with a mean follow-up of 5.4 years. There was no increase in breast cancer risk, and a significant decrease in breast cancer risk was found among BRCA1 heterozygotes [Domchek et al 2011]. In another matched case-control study of 472 postmenopausal women with a BRCA1 pathogenic variant, the use of HRT was associated with a reduction in breast cancer risk [Eisen et al 2008]. Finally, a case-control study of 432 matched pairs with a mean follow up of 4.3 years also found a decrease in the risk for breast cancer in BRCA1 heterozygotes [Kotsopoulos et al 2016]. Taken together, these studies support the short-term use of HRT among BRCA1/2 heterozygotes who have undergone surgical menopause.
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*[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
| BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer | None | 1,654 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1247/ | 2021-01-18T21:40:26 | {"synonyms": ["HBOC"]} |
Myotonic dystrophy type 2, one of the two types of myotonic dystrophy, is an inherited muscular dystrophy that affects the muscles and other body systems (e.g., heart, eyes, and pancreas). It is characterized by prolonged muscle tensing (myotonia) as well as muscle weakness, pain, and stiffness. Signs and symptoms usually develop during a person's twenties or thirties. Muscles in the neck, fingers, elbows, and hips are typically affected; facial and ankle muscles are less commonly involved. The severity of myotonic dystrophy type 2 varies widely among affected people, even among family members. It is inherited in an autosomal dominant pattern and is caused by mutations in the CNBP gene. Treatment is based on each person's specific signs and symptoms.
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*[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
| Myotonic dystrophy type 2 | c2931689 | 1,655 | gard | https://rarediseases.info.nih.gov/diseases/9728/myotonic-dystrophy-type-2 | 2021-01-18T17:58:49 | {"mesh": ["D009223"], "omim": ["602668"], "orphanet": ["606"], "synonyms": ["Dystrophia myotonica type 2", "DM2", "Proximal myotonic myopathy", "PROMM", "Myotonic myopathy, proximal", "Ricker syndrome"]} |
Somatostatinoma (SSoma) is an extremely rare pancreatic neuroendocrine tumor or duodenal endocrine tumor (see these terms) that originates either in the pancreas (50%) or the gastrointestinal tract (50%) and mainly presents with non-specific symptoms of abdominal pain, weight loss, jaundice and diarrhea but, in approximately 20% of pancreatic cases, leads to a somatostatin hypersecretion syndrome (somatostatinoma syndrome) characterized by diabetes mellitus, cholelithiasis, steatorrhea and hypochlorhydria.
## Epidemiology
The estimated incidence is of 1/40,000,000. Approximately 80 cases of pancreatic SSoma have been reported to date but this is probably an underestimate.
## Clinical description
SSomas usually range in size from 3-11cm. Most SSomas present with non-specific symptoms of abdominal pain, weight loss, painless obstructive jaundice and diarrhea. Somatostatinoma syndrome occurs in those with a functioning pancreatic SSoma with manifestations including diabetes mellitus, cholelithiasis, diarrhea, weight loss, steatorrhea and hypochlorhydria. More than half of all SSomas are malignant and they have often metastasized at the time of diagnosis. Duodenal somatostatinoma is often associated with neurofibromatosis type 1 (NF1; see this term).
## Etiology
Some SSomas are components of familial endocrine tumor syndromes. The cause of sporadic SSomas is not clear. SSoma hypersecretes stomatostatin, which inhibits the secretion of numerous gastrointestinal hormones (such as gastrin, secretin, insulin, glucagon, and cholecystokinin), resulting in somatostatinoma syndrome
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*[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
| Somatostatinoma | c0037661 | 1,656 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97283 | 2021-01-23T17:03:55 | {"gard": ["4900"], "mesh": ["D013005"], "umls": ["C0037661"], "icd-10": ["E16.8"]} |
A number sign (#) is used with this entry because of evidence that platelet-type bleeding disorder-22 (BDPLT22) is caused by homozygous mutation in the EPHB2 gene (600997) on chromosome 1p36. One such family has been reported.
Description
Platelet-type bleeding disorder-22 (BDPLT22) is an autosomal recessive bleeding disorder resulting from impaired platelet aggregation due to intracellular signaling defects. Patients present in the first decade with spontaneous subcutaneous bleeding and excessive bleeding after minor injuries. Platelet counts are usually normal, although platelets show abnormal morphology (summary by Berrou et al., 2018).
Clinical Features
Berrou et al. (2018) reported 2 sibs, born of consanguineous parents, who were noted to have excessive spontaneous subcutaneous bleeding and heavy bleeding after minor wounds between 12 and 15 years of age. One of the patients had chronic gastrointestinal bleeding during childhood that necessitated iron treatment. Platelet count was essentially normal, although 1 patient had mildly decreased platelet counts as a young adult. Other hematopoietic lineages were normal in both patients and in the unaffected parents. Electron microscopic examination of platelets showed some abnormalities in the patients, including abnormal shape, large platelets, and fragmentation defects with large fragments of megakaryocytes.
Molecular Genetics
In 2 sibs, born of consanguineous parents, with BDPLT22, Berrou et al. (2018) identified a homozygous missense mutation in the EPHB2 gene (R745C; 600997.0005). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional analysis of patient platelets showed strongly impaired platelet aggregation in response to ADP and thrombin, with decreased thrombus formation, as well as partially impaired granule secretion. There was an absence of activation of the platelet integrin IIb (607759)/IIIa (173470) receptor. Response to ristocetin was normal, and the platelets had normal levels of alpha and dense granules. Overexpression of wildtype and the R745C EPHB2 variant in rat basophilic leukemia cells stably expressing human glycoprotein VI (GPVI; 605546) confirmed that the EPHB2 R745C mutation impaired EPHB2 autophosphorylation. However, it had no effect on ephrin ligand-induced EPHB2 clustering, suggesting it did not interfere with EPHB2-ephrin-mediated cell-to-cell contact. Overall, the findings indicated that the EPHB2 variant impaired activation of the GP VI receptor and downstream signaling of the IIb/IIIa receptor.
Animal Model
Vaiyapuri et al. (2015) found expression of the Ephb2 gene in mouse platelets and demonstrated that Ephb2 has a complex role in platelet activation involving both contact-dependent and contact-independent signaling. Functional studies of platelets from mice with Ephb2 lacking the intracellular region (LacZ mutants) showed that interruption of the intracellular region abrogated platelet activation, granule secretion, calcium mobilization, fibrinogen (see 134820) binding, and thrombus formation. These functional defects were associated with reduced inside-out signaling through PI3K and platelet integrin ITGA2B/ITGB3. Defective spreading and clot retraction in mutant platelets suggested that Ephb2 may also be involved in outside-in signaling when fibrinogen binds to ITGA2B/ITGB3. These changes occurred even though ligand binding of Ephb2 at the platelet surface was unaffected. Mutant mice showed increased bleeding.
INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Skin \- Subcutaneous bleeding HEMATOLOGY \- Increased bleeding after minor wounds \- Normal platelet count \- Functional platelet aggregation and activation defect MISCELLANEOUS \- Onset in the first decade \- Two sibs have been reported (last curated June 2019) MOLECULAR BASIS \- Caused by mutation in the ephrin receptor EphB2 gene (EPHB2, 600997.0005 ) ▲ Close
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*[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
| BLEEDING DISORDER, PLATELET-TYPE, 22 | None | 1,657 | omim | https://www.omim.org/entry/618462 | 2019-09-22T15:41:47 | {"omim": ["618462"]} |
Progression of a Histocytoma on a French Bulldog Ear -2 months time
A histiocytoma on the ear of a dog
Canine Cutaneous Histiocytoma on a young boxer dog
A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes (histiocytosis), a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis.[1] Dog breeds that may be more at risk for this tumor include Bulldogs, American Pit Bull Terriers, American Staffordshire Terriers, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers. They also rarely occur in goats and cattle.[2]
## Contents
* 1 Histiocytic disorders
* 2 Tumor biology
* 3 Symptoms
* 4 Treatment
* 5 References
* 6 External links
## Histiocytic disorders[edit]
A histiocyte is a differentiated tissue cell that has its origin in the bone marrow. The source for histiocytes is the monocyte/macrophage line. Monocytes (found in the blood) and macrophages (found in tissue) are responsible for phagocytosis (ingestion) of foreign material in the body. Langerhans cells are dendritic cells found in the skin and function by internalizing antigens (foreign particles) and presenting them to T cells. They arise from monocytes.[3] Histiocytic disorders refer to diseases that are caused by abnormal behavior of these cells. They include the following:
* Reactive diseases of Langerhans cells
* Histiocytomas
* Cutaneous histiocytosis
* Systemic histiocytosis
* Reactive diseases of macrophages
* Hemophagocytic syndrome \- a condition where macrophages phagocytose myeloid and erythroid precursors (similar to hemophagocytic lymphohistiocytosis in humans)
* Malignant diseases of Langerhans cells
* Malignant histiocytosis \- a condition found in Bernese Mountain Dogs
* Diffuse histiocytic sarcoma
* Localized histiocytic sarcoma
* Malignant diseases of macrophages
* Histiocytic lymphoma
## Tumor biology[edit]
Canine histiocytoma cytology
A histiocytoma originates from epidermal Langerhans cells of antigen-presenting cell lineage.[4] Spontaneous regression is common in these tumors, and it is mediated by infiltration of CD8-expressing T cells followed by expression of Type 1 T helper cell cytokines (such as Interferon-gamma) and recruitment of antitumour effector cells.[5]
## Symptoms[edit]
Most commonly histiocytomas are found in young dogs and appear as a small, solitary, hairless lump,[6] although Shar Peis may be predisposed to multiple histiocytomas.[7] They are most commonly found on the head, neck, ears, and limbs, and are usually less than 2.5 cm in diameter.[8] Ulceration of the mass is common. Diagnosis is made through cytology of the mass. Cytology reveals cells with clear to lightly basophilic cytoplasm and round or indented nuclei with fine chromatin and indistinct nucleoli.[9]
## Treatment[edit]
Most histiocytomas will regress within two or three months.[6] Surgical removal may be necessary if the tumor does not regress or if it is growing rapidly to a large size. Histiocytomas should never be treated with an intralesional injection of a corticosteroid, as remission relies on recognition of the tumour by the body's immune system which is suppressed by steroids.
## References[edit]
1. ^ Marchal T, Saint-André I, Magnol J, Dezutter-Dambuyant C, Schmitt D (1995). "[Dendritic cells in dogs and cats: models of study in human pathology]". Pathol. Biol. 43 (10): 910–20. PMID 8786898.
2. ^ "Tumors with Histiocytic Differentiation". The Merck Veterinary Manual. 2006. Retrieved 2007-04-29.
3. ^ Ginhoux F, Tacke F, Angeli V, Bogunovic M, Loubeau M, Dai XM, Stanley ER, Randolph GJ, Merad M (2006). "Langerhans cells arise from monocytes in vivo". Nat. Immunol. 7 (3): 265–73. doi:10.1038/ni1307. PMC 4727824. PMID 16444257.
4. ^ Moore P, Schrenzel M, Affolter V, Olivry T, Naydan D (1996). "Canine cutaneous histiocytoma is an epidermotropic Langerhans cell histiocytosis that expresses CD1 and specific beta 2-integrin molecules". Am. J. Pathol. 148 (5): 1699–708. PMC 1861573. PMID 8623937.
5. ^ Kaim U, Moritz A, Failing K, Baumgärtner W (2006). "The regression of a canine Langerhans cell tumour is associated with increased expression of IL-2, TNF-alpha, IFN-gamma and iNOS mRNA". Immunology. 118 (4): 472–82. doi:10.1111/j.1365-2567.2006.02394.x. PMC 1782326. PMID 16764690.
6. ^ a b Morrison, Wallace B. (1998). Cancer in Dogs and Cats (1st ed.). Williams and Wilkins. ISBN 0-683-06105-4.
7. ^ Cronin, Kim (Dec 2006). "Deciphering the histiocytic code". DVM. Advanstar Communications: 1S–8S.
8. ^ Affolter, Verena K. (2004). "Histiocytic Proliferative Diseases in Dogs and Cats". Proceedings of the 29th World Congress of the World Small Animal Veterinary Association. Retrieved 2007-04-29.
9. ^ Raskin, R.E.; DeNicola, D. (2006). "Cytology of Neoplasia". Proceedings of the North American Veterinary Conference. Retrieved 2007-04-29.
## External links[edit]
* Histiocytoma from The Pet Health Library
* Histiocytoma and Histiocytic Sarcoma in Cats and Dogs from Pet Cancer Center
* Photos of histiocytoma in a Shetland Sheepdog (Sheltie)
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*[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
| Histiocytoma (dog) | None | 1,658 | wikipedia | https://en.wikipedia.org/wiki/Histiocytoma_(dog) | 2021-01-18T18:30:01 | {"wikidata": ["Q5773037"]} |
Klippel-Trenaunay syndrome (KTS) is a syndrome that affects the development of blood vessels, soft tissues, and bones. This syndrome has three characteristic features: a red birthmark called a port-wine stain, overgrowth of soft tissues and bones, and vein malformations such as varicose veins or malformations of deep veins in the limbs. The overgrowth of bones and soft tissues usually begins in infancy and is most often only affects one leg. However, it can also affect the arms or sometimes the upper body area (torso). The overgrowth can cause pain, a feeling of heaviness, and make the affected leg (or arm) hard to move.
Most, if not all, cases of KTS are caused by somatic mutations in the PIK3CA gene. Medical researchers believe KTS is part of a group of disorders known as PIK3CA-related overgrowth spectrum (PROS) which also includes MCAP and CLOVES syndromes, hemimegalencephaly, fibroadipose hyperplasia, and epidermal nevus. Treatment is symptomatic and supportive.
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*[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
| Klippel-Trenaunay syndrome | c0022739 | 1,659 | gard | https://rarediseases.info.nih.gov/diseases/3122/klippel-trenaunay-syndrome | 2021-01-18T17:59:35 | {"mesh": ["D007715"], "omim": ["149000"], "orphanet": ["2346"], "synonyms": ["Klippel Trenaunay syndrome", "Klippel-Trenaunay-Weber syndrome", "KTW syndrome", "Weber-Klippel-Trenaunay", "Angio-osteohypertrophy syndrome", "KTS", "Klippel-Trénaunay-Weber syndrome"]} |
Mandibulofacial dysostosis with microcephaly (MFDM) is a disorder characterized by developmental delay and abnormalities of the head and face. Affected people are usually born with a small head that does not grow at the same rate as the body (progressive microcephaly). Developmental delay and intellectual disability can range from mild to severe. Facial abnormalities may include underdevelopment of the midface and cheekbones; a small lower jaw; small and abnormally-shaped ears; and other distinctive facial features. Other features of MFDM may include hearing loss, cleft palate, heart problems, abnormalities of the thumbs, abnormalities of the trachea and/or esophagus, and short stature. MFDM is caused by mutations in the EFTUD2 gene and is inherited in an autosomal dominant manner.
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*[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
| Mandibulofacial dysostosis with microcephaly | c1864652 | 1,660 | gard | https://rarediseases.info.nih.gov/diseases/10056/mandibulofacial-dysostosis-with-microcephaly | 2021-01-18T17:59:15 | {"mesh": ["C537405"], "omim": ["610536"], "umls": ["C1864652"], "orphanet": ["79113"], "synonyms": ["Mandibulofacial dysostosis, Guion-Almeida type", "MFDGA", "MFDM", "Mandibulofacial dysostosis-microcephaly syndrome", "Growth delay - intellectual disability - mandibulofacial dysostosis - microcephaly - cleft palate", "MFDM syndrome", "Growth delay-intellectual disability-mandibulofacial dysostosis-microcephaly-cleft palate syndrome"]} |
This article may be confusing or unclear to readers. Please help us clarify the article. There might be a discussion about this on the talk page. (December 2011) (Learn how and when to remove this template message)
TAN syndrome
SpecialtyDermatology
Tegumental angiomyxoma-neurothekeoma (TAN syndrome)[1] is a syndrome, an acronym, and eponym[citation needed] proposed by Malaysian ophthalmologist of Chinese Descent, Tan Aik Kah (b. June 1975).[1] Angiomyxomas are associated with LAMB (lentigines, atrial myxomas, muco-cutaneous myxomas, and blue naevi) syndrome,[2] NAME (nevi, atrial myxoma, myxoid neurofibromas, and ephelides)[3] syndrome and Carney syndrome (atrial, cutaneous and mammary myxomas, lentigines, blue naevi, endocrine disorders and testicular tumours).[4]
TAN syndrome is characterized by multiple superficial angiomyxoma and neurothekeoma confined only to the skin (tegument).[1] TAN syndrome may be used to describe myxomas confined to the skin without visceral involvement.[citation needed]
## Case[edit]
Tan et al. reported a 10-year-old girl with multiple superficial angiomyxoma associated with neurothekeoma palpebrae.[1] There was no evidence of visceral involvement. The lesions were excised with no recurrence during follow up.[1]
## References[edit]
1. ^ a b c d e Aik Kah, Tan; Chui Yong, Ku; Annuar, Faridah Hanom (2011). "Neurothekeoma palpebrae in association with multiple superficial angiomyxomas: Tegumental Angiomyxoma- Neurothekeoma syndrome (TAN syndrome)". Clinics and Practice. 1 (3): e67. doi:10.4081/cp.2011.e67. PMC 3981382. PMID 24765328.
2. ^ Rhodes, Arthur R.; Silverman, Robert A.; Harrist, Terence J.; Perez-Atayde, Antonio R. (1984). "Mucocutaneous lentigines, cardiomucocutaneous myxomas, and multiple blue nevi: The 'LAMB' syndrome". Journal of the American Academy of Dermatology. 10 (1): 72–82. doi:10.1016/S0190-9622(84)80047-X. PMID 6693605.
3. ^ Kamath, Sreenivas (2006). "Cardiac Neoplasms". In Griffin, Brian P.; Rimmerman, Curtis M.; Topol, Eric J. (eds.). The Cleveland Clinic Cardiology Board Review. Lippincott Williams & Wilkins. pp. 50–6. ISBN 978-0-7817-5942-7.
4. ^ Carney Complex at eMedicine
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*[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
| TAN syndrome | None | 1,661 | wikipedia | https://en.wikipedia.org/wiki/TAN_syndrome | 2021-01-18T18:35:38 | {"wikidata": ["Q7669314"]} |
Miller-Dieker syndrome is a condition characterized by a pattern of abnormal brain development known as lissencephaly. Normally the exterior of the brain (cerebral cortex) is multi-layered with folds and grooves. People with lissencephaly have an abnormally smooth brain with fewer folds and grooves. These brain malformations cause severe intellectual disability, developmental delay, seizures, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. Seizures usually begin before six months of age, and some occur from birth. Typically, the smoother the surface of the brain is, the more severe the associated symptoms are.
In addition to lissencephaly, people with Miller-Dieker syndrome tend to have distinctive facial features that include a prominent forehead; a sunken appearance in the middle of the face (midface hypoplasia); a small, upturned nose; low-set and abnormally shaped ears; a small jaw; and a thick upper lip. Some individuals with this condition also grow more slowly than other children. Rarely, affected individuals will have heart or kidney malformations or an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. People with Miller-Dieker syndrome may also have life-threatening breathing problems. Most individuals with this condition do not survive beyond childhood.
## Frequency
Miller-Dieker syndrome appears to be a rare disorder, although its prevalence is unknown.
## Causes
Miller-Dieker syndrome is caused by a deletion of genetic material near the end of the short (p) arm of chromosome 17. The signs and symptoms of Miller-Dieker syndrome are probably related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals.
Researchers are working to identify all of the genes that contribute to the features of Miller-Dieker syndrome. They have determined that the loss of a particular gene on chromosome 17, PAFAH1B1, is responsible for the syndrome's characteristic sign of lissencephaly. The loss of another gene, YWHAE, in the same region of chromosome 17 increases the severity of the lissencephaly in people with Miller-Dieker syndrome. Additional genes in the deleted region probably contribute to the varied features of Miller-Dieker syndrome.
### Learn more about the genes and chromosome associated with Miller-Dieker syndrome
* PAFAH1B1
* YWHAE
* chromosome 17
## Inheritance Pattern
Most cases of Miller-Dieker syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.
When Miller-Dieker syndrome is inherited, its inheritance pattern is considered autosomal dominant because a deletion in one copy of chromosome 17 in each cell is sufficient to cause the condition. About 12 percent of people with Miller-Dieker syndrome inherit a chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with Miller-Dieker syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 17, which results in the health problems characteristic of this disorder.
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*[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
| Miller-Dieker syndrome | c0265219 | 1,662 | medlineplus | https://medlineplus.gov/genetics/condition/miller-dieker-syndrome/ | 2021-01-27T08:24:51 | {"gard": ["3669"], "mesh": ["D054221"], "omim": ["247200"], "synonyms": []} |
X-linked intellectual disability-cubitus valgus-dysmorphism syndrome is characterised by moderate intellectual deficit, marked cubitus valgus, mild microcephaly, a short philtrum, deep-set eyes, downslanting palpebral fissures and multiple nevi. Less than ten individuals have been described so far. Transmission is thought to be X-linked recessive.
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*[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
| X-linked intellectual disability-cubitus valgus-dysmorphism syndrome | c1845450 | 1,663 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85280 | 2021-01-23T19:11:38 | {"mesh": ["C564510"], "omim": ["300471"], "umls": ["C1845450"], "icd-10": ["Q87.8"]} |
Subclavian steal syndrome
Other namesSubclavian steal phenomenon or Subclavian steal steno-occlusive disease
The proximal part of left subclavian is blocked on left side so no flow in vertebral and to left arm. Blood from right vertebral enters left vertebral and flows back to supply left arm
SpecialtyNeurology
Subclavian steal syndrome (SSS), also called subclavian steal steno-occlusive disease, is a constellation of signs and symptoms that arise from retrograde (reversed) blood flow in the vertebral artery or the internal thoracic artery, due to a proximal stenosis (narrowing) and/or occlusion of the subclavian artery. This flow reversal is called the subclavian steal or subclavian steal phenomenon, regardless of signs/symptoms being present.[1] The arm may be supplied by blood flowing in a retrograde direction down the vertebral artery at the expense of the vertebrobasilar circulation. It is more severe than typical vertebrobasilar insufficiency.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Pathophysiology
* 3.1 Hemodynamics
* 3.2 Vascular anatomy
* 3.3 Blood flow
* 4 Diagnostic tests
* 4.1 Differential diagnosis
* 5 Treatment
* 6 Additional images
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
* Presyncope (sensation that one is about to faint)
* Syncope (fainting)
* Neurologic deficits
* Blood pressure differential between the arms
* severe memory problems
* hands showing circulation problems (hands can have blotchy patches of red and white) (associated with other stigmata of vascular disease (e.g. vascular insufficiency ulcers of the fingers).
## Causes[edit]
There are multiple processes that can cause obstruction of the subclavian artery before the vertebral artery, giving opportunity for SSS.
Atherosclerosis is the most common cause of SSS;[2] all atherosclerotic risk factors are risk factors for SSS.
Thoracic outlet syndrome (TOS) increases the risk for SSS.[2] TOS doesn't directly cause SSS, because the site of subclavian artery compression is over the first rib, which is distal to the vertebral artery. TOS has been reported to cause stroke through theorized clot propagation towards the vertebral artery;[3] a similar mechanism could explain how TOS causes SSS. Presence of a cervical rib is a risk factor for both TOS and SSS.
Takayasu's arteritis is a disease causing inflammation of arteries, including the subclavian artery. Inflammation leaves behind dense scar tissue, which can become stenotic and restrict blood flow.[4]
SSS can be iatrogenic, meaning a complication or side effect of medical treatment, one example being the obstructive fibrosis or thrombosis resulting from repair of aortic coarctation.[5] Another example is Blalock–Taussig anastomosis for treatment of tetralogy of Fallot. The procedure involves dividing the subclavian artery and reconnecting the proximal portion to the pulmonary arteries, leaving the vertebral artery as the primary supply to the distal subclavian artery.[6]
Various congenital vascular malformations cause SSS, examples including aortic coarctation and interrupted aortic arch.[7]
## Pathophysiology[edit]
Classically, SSS is a consequence of a redundancy in the circulation of the brain[8][9] and the flow of blood.
SSS results when the short low resistance path (along the subclavian artery) becomes a high resistance path (due to narrowing) and blood flows around the narrowing via the arteries that supply the brain (left and right vertebral artery, left and right internal carotid artery). The blood flow from the brain to the upper limb in SSS is considered to be stolen as it is blood flow the brain must do without. This is because of collateral vessels.
As in vertebral-subclavian steal, coronary-subclavian steal may occur in patients who have received a coronary artery bypass graft using the internal thoracic artery (ITA), also known as internal mammary artery.[10] As a result of this procedure, the distal end of the ITA is diverted to one of the coronary arteries (typically the LAD), facilitating blood supply to the heart. In the setting of increased resistance in the proximal subclavian artery, blood may flow backward away from the heart along the ITA, causing myocardial ischemia due to coronary steal. Vertebral-subclavian and coronary-subclavian steal can occur concurrently in patients with an ITA CABG.[11]
### Hemodynamics[edit]
Blood, like electric current, flows along the path of least resistance. Resistance is affected by the length and width of a vessel (i.e. a long, narrow vessel has the greatest resistance and a short, wide one the least), but crucially in the human body width is generally more limiting than length because of Poiseuille's Law. Thus, if blood is presented with two paths, a short one that is narrow (with a high overall resistance) and a long one that is wide (with a low overall resistance), it will take the long and wide path (the one with the lower resistance).
### Vascular anatomy[edit]
The blood vessels supplying the brain arise from the vertebral arteries and internal carotid arteries and are connected to one another by communicating vessels that form a circle (known as the circle of Willis).
### Blood flow[edit]
Normally, blood flows from the aorta into the subclavian artery, and then some of that blood leaves via the vertebral artery to supply the brain.
In SSS a reduced quantity of blood flows through the proximal subclavian artery. As a result, blood travels up one of the other blood vessels to the brain (the other vertebral or the carotids), reaches the basilar artery or goes around the cerebral arterial circle and descends via the (contralateral) vertebral artery to the subclavian (with the proximal blockage) and feeds blood to the distal subclavian artery (which supplies the upper limb and shoulder).
## Diagnostic tests[edit]
Doppler ultrasound of subclavian steal phenomenon
* Doppler ultrasound
* CT angiography
### Differential diagnosis[edit]
* Stroke
## Treatment[edit]
* Carotid subclavian bypass
* Stent and balloon angioplasty
* Endarterectomy
## Additional images[edit]
Angiogram of subclavian steal phenomenon before and after stent placement
CT angiography of subclavian steal phenomenon
## See also[edit]
* Vascular access steal syndrome
* Peripheral artery disease
## References[edit]
1. ^ Labropoulos, N; Nandivada, P; Bekelis, K (July 2010). "Prevalence and impact of the subclavian steal syndrome". Annals of Surgery. 252 (1): 166–70. doi:10.1097/SLA.0b013e3181e3375a. PMID 20531004. S2CID 2165442.
2. ^ a b Potter, BJ; Pinto, DS (3 June 2014). "Subclavian steal syndrome". Circulation. 129 (22): 2320–3. doi:10.1161/CIRCULATIONAHA.113.006653. PMID 24891625.
3. ^ Meumann, EM; Chuen, J; Fitt, G; Perchyonok, Y; Pond, F; Dewey, HM (May 2014). "Thromboembolic stroke associated with thoracic outlet syndrome". Journal of Clinical Neuroscience. 21 (5): 886–9. doi:10.1016/j.jocn.2013.07.030. hdl:11343/123833. PMID 24321459. S2CID 41769069.
4. ^ Roldán-Valadéz, E; Hernández-Martínez, P; Osorio-Peralta, S; Elizalde-Acosta, I; Espinoza-Cruz, V; Casián-Castellanos, G (September 2003). "Imaging diagnosis of subclavian steal syndrome secondary to Takayasu arteritis affecting a left-side subclavian artery". Archives of Medical Research. 34 (5): 433–8. doi:10.1016/j.arcmed.2003.06.002. PMID 14602512.
5. ^ Saalouke, MG; Perry, LW; Breckbill, DL; Shapiro, SR; Scott LP, 3rd (July 1978). "Cerebrovascular abnormalities in postoperative coarctation of aorta. Four cases demonstrating left subclavian steal on aortography". The American Journal of Cardiology. 42 (1): 97–101. doi:10.1016/0002-9149(78)90991-8. PMID 677042.
6. ^ Kurlan, R; Krall, RL; Deweese, JA (March 1984). "Vertebrobasilar ischemia after total repair of tetralogy of Fallot: significance of subclavian steal created by Blalock-Taussig anastomosis. Vertebrobasilar ischemia after correction of tetralogy of Fallot". Stroke. 15 (2): 359–62. doi:10.1161/01.str.15.2.359. PMID 6701943.
7. ^ Deeg, KH; Hofbeck, M; Singer, H (December 1993). "Diagnosis of subclavian steal in infants with coarctation of the aorta and interruption of the aortic arch by color-coded Doppler sonography". Journal of Ultrasound in Medicine. 12 (12): 713–8. doi:10.7863/jum.1993.12.12.713. PMID 8301709. S2CID 42139662.
8. ^ Klingelhöfer J, Conrad B, Benecke R, Frank B (1988). "Transcranial Doppler ultrasonography of carotid-basilar collateral circulation in subclavian steal". Stroke. 19 (8): 1036–42. doi:10.1161/01.STR.19.8.1036. PMID 3041649.
9. ^ Lord R, Adar R, Stein R (1969). "Contribution of the circle of Willis to the subclavian steal syndrome". Circulation. 40 (6): 871–8. doi:10.1161/01.CIR.40.6.871. PMID 5377222.
10. ^ Takach T, Reul G, Cooley D, Duncan J, Livesay J, Ott D, Gregoric I (2006). "Myocardial thievery: the coronary-subclavian steal syndrome". Ann Thorac Surg. 81 (1): 386–92. doi:10.1016/j.athoracsur.2005.05.071. PMID 16368420.
11. ^ Lee S, Jeong M, Rhew J, Ahn Y, Na K, Song H, Bom H, Cho J, Ahn B, Park J, Kim S, Kang J (2003). "Simultaneous coronary - subclavian and vertebral - subclavian steal syndrome". Circ J. 67 (5): 464–6. doi:10.1253/circj.67.464. PMID 12736489.
## External links[edit]
Classification
D
* ICD-10: G45.8
* ICD-9-CM: 435.2
* MeSH: D013349
* DiseasesDB: 31525
* SNOMED CT: 15258001
External resources
* eMedicine: article/418203 article/462036
* Subclavian Steal Syndrome \- emedicine.com
* v
* t
* e
Cerebrovascular diseases including stroke
Ischaemic stroke
Brain
* Anterior cerebral artery syndrome
* Middle cerebral artery syndrome
* Posterior cerebral artery syndrome
* Amaurosis fugax
* Moyamoya disease
* Dejerine–Roussy syndrome
* Watershed stroke
* Lacunar stroke
Brain stem
* Brainstem stroke syndrome
* Medulla
* Medial medullary syndrome
* Lateral medullary syndrome
* Pons
* Medial pontine syndrome / Foville's
* Lateral pontine syndrome / Millard-Gubler
* Midbrain
* Weber's syndrome
* Benedikt syndrome
* Claude's syndrome
Cerebellum
* Cerebellar stroke syndrome
Extracranial arteries
* Carotid artery stenosis
* precerebral
* Anterior spinal artery syndrome
* Vertebrobasilar insufficiency
* Subclavian steal syndrome
Classification
* Brain ischemia
* Cerebral infarction
* Classification
* Transient ischemic attack
* Total anterior circulation infarct
* Partial anterior circulation infarct
Other
* CADASIL
* Binswanger's disease
* Transient global amnesia
Haemorrhagic stroke
Extra-axial
* Epidural
* Subdural
* Subarachnoid
Cerebral/Intra-axial
* Intraventricular
Brainstem
* Duret haemorrhages
General
* Intracranial hemorrhage
Aneurysm
* Intracranial aneurysm
* Charcot–Bouchard aneurysm
Other
* Cerebral vasculitis
* Cerebral venous sinus thrombosis
*[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
| Subclavian steal syndrome | c0038531 | 1,664 | wikipedia | https://en.wikipedia.org/wiki/Subclavian_steal_syndrome | 2021-01-18T19:04:11 | {"mesh": ["D013349"], "umls": ["C0038531"], "icd-10": ["G45.8"], "wikidata": ["Q742099"]} |
Branch retinal vein occlusion
Branch retinal vein occlusion
SpecialtyNeurology
Branch retinal vein occlusion is a common retinal vascular disease of the elderly. It is caused by the occlusion of one of the branches of central retinal vein.[1]
## Contents
* 1 Signs and symptoms
* 2 Risk factors
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
Patients with branch retinal vein occlusion usually have a sudden onset of blurred vision or a central visual field defect. The eye examination findings of acute branch retinal vein occlusion include superficial hemorrhages, retinal edema, and often cotton-wool spots in a sector of retina drained by the affected vein. The obstructed vein is dilated and tortuous.
The quadrant most commonly affected is the superotemporal (63%).
Retinal neovascularization occurs in 20% of cases within the first 6–12 months of occlusion and depends on the area of retinal nonperfusion. Neovascularization is more likely to occur if more than five disc diameters of nonperfusion are present and vitreous hemorrhage can ensue.[2]
## Risk factors[edit]
Studies have identified the following abnormalities as risk factors for the development of branch retinal vein occlusion:
* hypertension
* cardiovascular disease
* obesity
* glaucoma
Diabetes mellitus was not a major independent risk factor.
## Diagnosis[edit]
Branch retinal vein occlusion revealed by laser Doppler imaging through flow alteration in the upper right branch artery.
The diagnosis of branch retinal vein occlusion is made clinically by finding retinal hemorrhages in the distribution of an obstructed retinal vein.
* Fluorescein angiography is a helpful adjunct. Findings include delayed venous filling, hypofluorescence caused by hemorrhage and capillary nonperfusion, dilation and tortuosity of veins, leakage due to neovascularization and macular edema.
* Optical coherence tomography is an adjunctive test in branch retinal vein occlusion. Macular edema is commonly seen on optical coherence tomography exams. Serial optical coherence tomograph is used as a rapid and noninvasive way of monitoring the macular edema.
* Laser Doppler imaging[3] reveals dynamic hemodynamics discrepancies between branch arteries and veins, from local vascular resistance increase by the venous occlusion.
## Treatment[edit]
Several options exist for the treatment of branch retinal vein occlusion. These treatments aim for the two of the most significant complications, namely macular edema and neovascularization.[1]
* Systemic treatment with oral aspirin, subcutaneous Heparin, or intravenous thrombolysis have not been shown to be effective treatments for central retinal vein occlusion and for branch retinal vein occlusion no reliable clinical trial has been published.
* Laser treatment of the macular area to reduce macular edema is indicated in patients who have 20/40 or worse vision and did not spontaneously improve for at least 3 months (to permit the maximum spontaneous resolution) after the development of the vein occlusion. It is typically administered with the argon laser and is focused on edematous retina within the arcades drained by the obstructed vein and avoiding the foveal avascular zone. Leaking microvascular abnormalities may be treated directly, but prominent collateral vessels should be avoided. In a Cochrane Review comparing laser treatment to other treatments, grid laser was found to be preferable to no laser. [4] Due to quality of evidence it is uncertain whether bevacizumab injections or subthreshold diode were preferable to grid laser treatments.
* The second indication of laser treatment is in case of neovascularization. Retinal photocoagulation is applied to the involved retina to cover the entire involved segment, extending from the arcade out to the periphery. Ischemia alone is not an indication for treatment provided that follow-up could be maintained.
* Preservative-free, nondispersive Triamcinolone acetonide in 1 or 4 mg dosage may be injected into the vitreous to treat macular edema but has complications including elevated intraocular pressure and development of cataract. Triamcinolone injection is shown to have similar effect on visual acuity when compared with standard care (Laser therapy), However, the rates of elevated intraocular pressure and cataract formation is much higher with the triamcinolone injection, especially the higher dosage.[5] Intravitreal injection of Dexamethasone implant (Ozurdex; 700,350 μg) is being studied, its effect may last for 180 days. The injection may be repeated however with less pronounced effect. Although the implant was designed to cause less complications, pressure rise and cataract formation is noted with this treatment too.[6]
* Anti-vascular endothelial growth factor (VEGF) drugs such as bevacizumab (Avastin; 1.25 -2.5 mg in 0.05ml) and ranibizumab (Lucentis) injections are widely used and there is good evidence of improved visual and anatomic outcomes with these agents.[7] Intravitreal anti-VEGF drugs have a low incidence of adverse side effects compared with intravitreal steroids, but are often requiring repeated injections. They are the treatment of choice for macular edema or neovascularization. The mechanism of action and duration of anti-VEGF effect on macular edema is currently unknown. The intraocular levels of VEGF are increased in eyes with macular edema secondary to branch retinal vein occlusion and the elevated VEGF levels are correlated to the degree and severity of the areas of capillary nonperfusion and macular edema.[8]
* Surgery is employed occasionally for longstanding vitreous hemorrhage and other serious complications such as epiretinal membrane and retinal detachment.
* Arteriovenous sheathotomy has been reported in small, uncontrolled series of patients with branch retinal vein occlusion. Branch retinal vein occlusiontypically occurs at arteriovenous crossings, where the artery and vein share a common adventitial sheath. In arteriovenous sheathotomy an incision is made in the adventitial sheath adjacent to the arteriovenous crossing and is extended along the membrane that holds the blood vessels in position to the point where they cross, the overlying artery is then separated from the vein.
## Prognosis[edit]
In general, branch retinal vein occlusion has a good prognosis: after 1 year 50–60% of eyes have been reported to have a final visual acuity of 20/40 or better even without any treatment. With time the dramatic picture of an acute branch retinal vein occlusion becomes more subtle, hemorrhages fade so that the retina can look almost normal. Collateral vessels develop to help drain the affected area.
## Epidemiology[edit]
* branch retinal vein occlusion is four times more common than central retinal vein occlusion.
* Usual age of onset is 60–70 years.
* An analysis of population from several countries estimates that approximately 16 million people worldwide may have retinal vein occlusion.[9]
## See also[edit]
* Central retinal vein occlusion
* Central retinal artery occlusion
* Branch retinal artery occlusion
## References[edit]
1. ^ a b "Retina and vitreous". Basic and clinical science course. American Academy of Ophthalmology. 2011–2012. pp. 150–154. ISBN 978-1615251193.
2. ^ Yanoff M, Duker JS (2009). Ophthalmology (3rd ed.). Mosby Elsevier. ISBN 9780323043328.
3. ^ Puyo, L., M. Paques, M. Fink, J-A. Sahel, and M. Atlan. "In vivo laser Doppler holography of the human retina." Biomedical optics express 9, no. 9 (2018): 4113-4129.
4. ^ Lam FC, Chia SN, Lee RM (May 2015). "Macular grid laser photocoagulation for branch retinal vein occlusion". The Cochrane Database of Systematic Reviews (5): CD008732. doi:10.1002/14651858.cd008732.pub2. PMID 25961835.
5. ^ Scott IU, Ip MS, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M, et al. (September 2009). "A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular Edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6". Archives of Ophthalmology. 127 (9): 1115–28. doi:10.1001/archophthalmol.2009.233. PMC 2806600. PMID 19752420.
6. ^ Haller JA, Bandello F, Belfort R, Blumenkranz MS, Gillies M, Heier J, et al. (December 2011). "Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results". Ophthalmology. 118 (12): 2453–60. doi:10.1016/j.ophtha.2011.05.014. PMID 21764136.
7. ^ Shalchi Z, Mahroo O, Bunce C, Mitry D (July 2020). "Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion". The Cochrane Database of Systematic Reviews. 7: CD009510. doi:10.1002/14651858.cd009510.pub3. PMC 7388176. PMID 32633861.
8. ^ Karia N (July 2010). "Retinal vein occlusion: pathophysiology and treatment options". Clinical Ophthalmology. 4: 809–16. doi:10.2147/opth.s7631. PMC 2915868. PMID 20689798.
9. ^ Rogers S, McIntosh RL, Cheung N, Lim L, Wang JJ, Mitchell P, et al. (February 2010). "The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia". Ophthalmology. 117 (2): 313–9.e1. doi:10.1016/j.ophtha.2009.07.017. PMC 2945292. PMID 20022117.
## External links[edit]
Classification
D
External resources
* eMedicine: article/1223498
*[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
| Branch retinal vein occlusion | c0154842 | 1,665 | wikipedia | https://en.wikipedia.org/wiki/Branch_retinal_vein_occlusion | 2021-01-18T18:52:44 | {"umls": ["C0154842"], "wikidata": ["Q4956400"]} |
A number sign (#) is used with this entry because of evidence that various conotruncal heart malformations can be caused by mutation in one of several genes. A mutation in the TBX1 gene (602054) has been found in individuals with conotruncal anomaly face syndrome (CAFS). Mutation in the NKX2-6 gene (611770) has been identified in 2 consanguineous families with conotruncal heart malformations, including persistent truncus arteriosus (PTA). Mutation in the NKX2-5 gene (600584) has been found in a patient with interrupted aortic arch and in a patient with PTA. Mutation in the GATA6 gene (601656) has been found in patients with PTA. Mutation in the ZFPM2 gene (603693) has been identified in patients with DORV.
Clinical Features
In a study of the families of children with cardiac malformations, Pierpont et al. (1988) found that conotruncal malformations carry a higher recurrence risk than other cardiac defects and proposed a monogenic mode of inheritance. Rein et al. (1990) described a large kindred in which 2 sibs had truncus arteriosus communis, a first cousin once removed had transposition of the great arteries (TGA; see 608808), and a second cousin had double-outlet right ventricle. Rein and Sheffer (1994) reported 2 additional sibs with conotruncal malformations born into the consanguineous kindred they had previously reported. Le Marec et al. (1989) had raised the question of autosomal recessive inheritance of truncus arteriosus.
Typical facial features of conotruncal anomaly face syndrome (CAFS) are ocular hypertelorism (with increased interpupillary distance due to increased separation of the inner canthi), short palpebral fissures, 'bloated' eyelids, a low nasal bridge, a small mouth, and minor ear lobe anomalies. These features are almost always associated with nasal voice (often associated with cleft palate/submucosal cleft palate/bifid uvula) and mild mental retardation (frequently associated with developmental retardation and, occasionally, dwarfism), and often associated with cardiovascular anomalies. The cardiovascular anomalies in patients with the conotruncal anomaly face syndrome mainly consist of cardiac outflow tract defects, such as tetralogy of Fallot (TOF; 187500), pulmonary atresia, double-outlet right ventricle, truncus arteriosus communis, and aortic arch anomalies. Some patients also have hypocalcemia, especially in the neonatal period (sometimes associated with hypoparathyroidism), and thymic aplasia or hypoplasia (Matsuoka et al., 1998).
Cytogenetics
Conotruncal heart malformations may be components of certain syndromes, e.g., DiGeorge syndrome (188400), the velocardiofacial syndrome (192430), and genitopalatocardiac syndrome (231060). Using DNA markers, Emanuel et al. (1992) found loss of heterozygosity indicating microdeletions of chromosome 22q11.2 in 30% of isolated conotruncal anomalies. These results were confirmed by fluorescence in situ hybridization (FISH).
Matsuoka et al. (1994) performed FISH analysis using the D22S75 DiGeorge critical region probe (DCGR) in 50 CAFS patients, 11 parent couples, and 10 mothers of CAFS patients. Monosomy for the region 22q11.2 was found in 42 CAFS patients and in 4 mothers and 1 father who had CAFS without congenital heart disease. No deletion of 22q11.2 was found in 60 patients who had congenital heart disease without CAFS.
Conotruncal defects (CTD) account for a fourth to a third of all nonsyndromic congenital heart defects. Debrus et al. (1996) searched for a 22q11 microdeletion in familial cases of nonsyndromic CTD. The study involved 36 cases of various isolated conotruncal defects, that is, without history of hypocalcemia, immune deficiency, absent thymus, or dysmorphic appearance. With 48F8, a cosmid probe localized in the smallest deleted region of the DiGeorge critical region, they found no deletions by FISH in these 36 affected individuals from 16 families. The second marker, D22S264, a microsatellite localized at the distal part of the largest deleted region, showed heterozygosity in 32 of 37 patients and hence was not related at this locus, whereas 5 markers were uninformative.
To investigate molecular and clinical aspects of CAFS, Matsuoka et al. (1998) studied the correlation between deletion size and phenotype and the mode of inheritance in 183 CAFS patients. Hemizygosity for a region of 22q11.2 was found in 180 (98%) of the patients by FISH analysis using the D22S75 (N25) DGCR probe. No hemizygosity was found in 3 (2%) of the patients with CAFS by FISH using 9 DCGR probes and another probe from a related region. None of these 3 patients had mental retardation and only 1 had nasal speech, which was observed in almost all of the 180 CAFS patients who carried identified deletions (mental retardation in 92%; nasal voice in 88%). Familial CAFS was found in 19 (13%) of 143 families and 16 affected parents (84%) were mothers. Although only 2 of the affected parents had cardiovascular anomalies, the deletion size in the 16 affected parents and their affected family members, who were studied by FISH analysis, was the same. This indicated that extragenic factors may play a role in the genesis of phenotypic variability, especially in relation to cardiovascular anomalies. No familial cases were found among CAFS patients with absent thymus/DiGeorge anomaly (DGA). Also, in all 18 CAFS patients with completely absent thymus/DGA and in all 6 CAFS patients with schizophrenia, the deletion was found to be longer distally. In a study of the origin of the deletion using microsatellite analyses in 48 de novo patients, the mother was shown to be the source in 65% of CAFS patients, while the father was the source in 64% of DGA patients. In addition to the major features of CAFS, other notable extracardiac anomalies were susceptibility to infection, schizophrenia, atrophy or dysmorphism of the brain, thrombocytopenia, short stature, facial palsy, anal atresia, and mild limb abnormalities.
Takahashi et al. (1995) found a submicroscopic deletion in 22q11 in 5 of 64 patients with a conotruncal heart malformation. Devriendt et al. (1996) prospectively analyzed 150 patients with a conotruncal heart disease for the presence of a del22q11 by means of FISH, using the probe DO832. Patients with a transposition of the great arteries were not included in this study. The main diagnoses were tetralogy of Fallot (105 patients), tetralogy of Fallot with additional cardiopathies (18 patients), and truncus arteriosus (6 patients). Among the 140 patients in whom blood culture was successful, 18 had a deletion (12.8%). All patients with the deletion showed additional clinical features of the velocardiofacial syndrome. In 7 of the 150 patients (4.6%), the family history was positive for the presence of a conotruncal heart defect.
Saitta et al. (1999) identified a patient with CAFS who had a novel deletion of 22q11.2. His deletion was distal to the usual 3-Mb deletion found in most patients with velocardiofacial syndrome. The deletion did not overlap with any of the previously described 'minimal critical regions' for velocardiofacial syndrome/DiGeorge syndrome. The patient showed hypertelorism, posteriorly rotated ears, micrognathia, a loud cardiac murmur, hypospadias, descended testes, single palmar creases, and bilateral fifth-finger clinodactyly. The cardiac defect was truncus arteriosus type II and a ventricular septal defect. Borderline hypocalcemia was found. The deletion was found to exclude UFD1L (601754), raising questions about the role of this gene in the CATCH22 syndrome. The CDC45L gene (603465) was also excluded from the deletion.
Molecular Genetics
Yagi et al. (2003) identified mutations in the TBX1 gene (602054.0001 and 602054.0003) in heterozygous state in 3 patients with phenotypes related to the 22q11.2 deletion syndrome (see 188400), including CAFS.
In 1 (4%) of 23 patients with interrupted aortic arch and 1 (4%) of 22 patients with truncus arteriosus, McElhinney et al. (2003) identified heterozygosity for a missense mutation in the NKX2-5 gene (R25C; 600584.0004).
Heathcote et al. (2005) used autozygosity mapping of a large consanguineous Kuwaiti family segregating PTA to map the causative locus to chromosome 8p21. They subsequently identified homozygosity for a missense mutation in the NKX2-6 gene (611770.0001) in all affected individuals.
In 3 sibs, born of consanguineous Palestinian parents, with conotruncal heart malformations, Ta-Shma et al. (2014) identified a homozygous truncating mutation in the NKX2-6 gene (611770.0002). The mutation was found by exome sequencing. Two patients had truncus arteriosus and 1 had a complex conotruncal defect with malalignment ventricular septal defect and aortic arch hypoplasia, as well as asymptomatic athymia.
Kodo et al. (2009) screened the genomes of 21 unrelated Japanese patients with nonsyndromic persistent truncus arteriosus and identified heterozygosity for a 2-bp deletion (601656.0001) and a missense mutation (601656.0002) in the GATA6 gene, respectively, in 2 probands. The 2-bp deletion was also present in the first proband's father and sister, both of whom had pulmonary stenosis. The sister also had patent ductus arteriosus and atrial septal defect. Atrial septal defect was also present in the first proband. The second proband's mutation occurred de novo, and neither was found in 182 Japanese controls.
In 2 (15.4%) of 13 Italian patients with DORV, De Luca et al. (2011) identified heterozygosity for 2 different missense mutations in the ZFPM2 gene, E30G (603693.0002) and I227V (603693.0006).
In a 10-year-old Chinese boy with Langer-Giedion syndrome (150230) and DORV, Tan et al. (2012) identified a de novo balanced chromosomal translocation t(8; 18)(q22;q21) that appeared to disrupt the ZFPM2 gene on chromosome 8q23. Analysis of the ZFPM2 gene in 145 Chinese patients with conotruncal defects, including 95 with tetralogy of Fallot, 38 with sporadic DORV, and 12 with transposition of the great arteries, revealed 5 heterozygous missense mutations in patients with DORV (see, e.g., 603693.0004 and 603693.0008) that were not found in 250 Chinese controls in whom conotruncal heart disease had been excluded by echocardiography. No mutations were identified in the patients with TOF or TGA. Tan et al. (2012) suggested that ZFPM2 variants might be a common cause of DORV.
### Associations Pending Confirmation
For discussion of a possible relationship between variation in the NRP1 gene and truncus arteriosus, see 602069.0001.
For discussion of a possible relationship between variation in the PRKD1 gene and truncus arteriosus, see 605435.0001.
Ta-Shma et al. (2013) studied the consanguineous Iranian Jewish family in which 4 sisters had isolated truncus arteriosus, previously reported by Rein et al. (1990) and Rein and Sheffer (1994). Exome sequencing in the 1 surviving sister revealed homozygosity for a missense mutation in the PLXND1 gene (R1299C). The mutation was not detected in a first-cousin once-removed male with transposition of the great arteries; DNA was not available from a second cousin with double-outlet right ventricle and an unbalanced atrioventricular septal defect, or from her parents. The mutation was not found in 60 Iranian Jewish controls or in the Exome Variant Server or dbSNP (build 137) databases.
Animal Model
Patterson et al. (1993) studied the inheritance and embryology of conotruncal defects in the Keeshond breed of dogs. Defects in related Keeshonds included the same variety of conotruncal malformations found in man: conal ventricular septal defects, tetralogy of Fallot, and persistent truncus arteriosus type 1. In addition, some closely related dogs that were clinically normal had minor defects of the right ventricular outlet septum on postmortem examination. In initial breeding experiments inheritance of conotruncal defects was nonmendelian, but after selective inbreeding, results were consistent with a single gene defect. Penetrance was complete in homozygotes (conotruncal malformation of some degree present). Subclinical defects were present in 8% of heterozygotes. Embryologic studies showed that in affected embryos myocardial growth in the conotruncal region was retarded during the critical window when the conotruncal cushions fuse to form the conotruncal septum.
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*[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
| CONOTRUNCAL HEART MALFORMATIONS | c1857586 | 1,666 | omim | https://www.omim.org/entry/217095 | 2019-09-22T16:29:27 | {"doid": ["6406"], "mesh": ["C535464"], "omim": ["217095"], "icd-9": ["745.0", "747.11", "745.11"], "icd-10": ["Q25.21", "Q20.0", "Q20.1"], "orphanet": ["2445", "3426", "3384"]} |
A rare demyelinating hereditary motor and sensory neuropathy characterized by prominent gait ataxia, pes cavus, tendon areflexia, distal limb weakness, tremor in the upper limbs, distal sensory loss, kyphoscoliosis, and progressive muscle atrophy. The disease becomes symptomatic in infancy or childhood, mode of inheritance is autosomal dominant.
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*[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
| Roussy-Lévy syndrome | c0205713 | 1,667 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3115 | 2021-01-23T18:08:37 | {"gard": ["4741"], "mesh": ["D002607"], "omim": ["180800"], "umls": ["C0205713"], "icd-10": ["G60.0"], "synonyms": ["Hereditary areflexic dystasia, Roussy-Lévy type"]} |
A number sign (#) is used with this entry because of evidence that hypomyelinating leukodystrophy-13 (HLD13) is caused by homozygous mutation in the HIKESHI gene (614908) on chromosome 11q14.
Description
Hypomyelinating leukodystrophy-13 is an autosomal recessive neurodegenerative disorder characterized by infantile onset of delayed psychomotor development, axial hypotonia, and spasticity associated with delayed myelination and periventricular white matter abnormalities on brain imaging. More variable neurologic deficits, such as visual impairment, may also occur. Some patients may experience cardiac failure during acute illness (summary by Edvardson et al., 2016).
For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080.
Clinical Features
Edvardson et al. (2016) reported 6 children from 3 unrelated families of Ashkenazi Jewish descent with a severe neurodevelopmental and neurodegenerative disorder apparent since infancy. The patients presented with feeding difficulties, axial hypotonia, and failure to thrive, followed by significantly delayed psychomotor development with poor or absent language, progressively decreasing head circumference percentile (up to -2 SD), spasticity, increased muscle tone, hyperreflexia, and clonus, more prominent in the lower limbs. Three sibs in 1 family had optic atrophy, visual impairment, and nystagmus; 1 also had central conduction delay on brainstem auditory evoked response. All 3 sibs died suddenly after short febrile illnesses before 15 years of age; 1 of these sibs had heart failure, but autopsy was not performed. In a second family, 1 patient, hospitalized for a febrile illness, had transient left ventricular hypertrophy associated with acute perimyocarditis which resolved after the acute illness. One patient from the third family had ataxia. Brain imaging in all patients showed periventricular white matter abnormalities and delayed myelination, consistent with a leukodystrophy.
Inheritance
The transmission pattern of HLD13 in the family reported by Edvardson et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 6 children from 3 unrelated families of Ashkenazi Jewish descent with HLD13, Edvardson et al. (2016) identified a homozygous missense mutation in the HIKESHI gene (V54L; 614908.0001). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. Mutant protein was undetectable in patient fibroblasts, suggesting that it is readily degraded. Patient cells also showed poor nuclear expression of HSP70 (see, e.g., HSPA1A, 140550) during heat shock stress, suggesting that cells are unprotected. Abnormal cytoplasmic accumulation of HSP70 may also be detrimental to the cell. The cellular defect was rescued by expression of wildtype C11ORF73.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Head \- Small head circumference, progressive, postnatal (up to -2 SD) Eyes \- Optic atrophy (in some patients) \- Visual impairment (in some patients) \- Nystagmus CARDIOVASCULAR Heart \- Heart failure, associated with febrile illness ABDOMEN Gastrointestinal \- Feeding difficulties SKELETAL \- Joint contractures MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Poor or absent speech \- Spasticity \- Hypertonia \- Hyperreflexia \- Clonus \- Ataxia (in some patients) \- Periventricular white matter abnormalities \- Hypomyelinating leukodystrophy \- Delayed myelination MISCELLANEOUS \- Onset in infancy \- Sudden death may occur \- Three families of Ashkenazi Jewish descent have been reported (last curated March 2016) MOLECULAR BASIS \- Caused by mutation in the chromosome 11 open reading frame 73 gene (C11orf73, 614908.0001 ) ▲ Close
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*[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
| LEUKODYSTROPHY, HYPOMYELINATING, 13 | c4225170 | 1,668 | omim | https://www.omim.org/entry/616881 | 2019-09-22T15:47:33 | {"doid": ["0060795"], "omim": ["616881"], "orphanet": ["495844"], "synonyms": ["C11ORF73-related autosomal recessive hypomyelinating leukoencephalopathy", "Hypomyelinating leukodystrophy due to hikeshi deficiency"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive Robinow syndrome-2 (RRS2) is caused by homozygous or compound heterozygous mutation in the NXN gene (612895) on chromosome 17p13.
Description
Autosomal recessive Robinow syndrome-2 is a skeletal dysplasia characterized by postnatal mesomelic short stature and relative macrocephaly as well as dysmorphic facial features, including frontal bossing, hypertelorism, prominent eyes, wide short nose with anteverted nares, and triangular mouth. Variable other congenital anomalies may be present, including omphalocele, ventral hernia, and cardiac anomalies (White et al., 2018).
For a discussion of genetic heterogeneity of autosomal recessive Robinow syndrome, see RRS1 (268310).
Clinical Features
White et al. (2018) studied 2 sisters (BAB9844 and BAB9847, from family HOU3634), ages 3 years and 6 months, respectively, and an unrelated 5-year-old Turkish girl (BAB8841, from family HOU3189), who exhibited features of autosomal recessive Robinow syndrome. All 3 had short stature and relative macrocephaly, and shared dysmorphic features including high forehead, hypertelorism, low-set posteriorly rotated ears with dysmorphic helices, prominent eyes, broad and low nasal bridge, broad nasal tip with anteverted nares, and micrognathia. Skeletal anomalies included mesomelia and brachydactyly, as well as broad thumbs and first toes. The Turkish girl exhibited other congenital anomalies including omphalocele and ventral hernia, bicuspid aortic valve with dilation of the ascending aorta, and aberrant right coronary artery. She also had developmental delay, not walking until 36 months of age and only putting words into phrases at age 5 years. Development appeared to be normal in the sisters.
Molecular Genetics
In a 5-year-old Turkish girl with autosomal recessive Robinow syndrome, who was negative for mutation in the ROR2 gene (602337), White et al. (2018) performed exome sequencing and identified homozygosity for a nonsense mutation in the NXN gene (R209X; 612895.0001) that segregated with disease in the family. Using GeneMatcher, the authors identified a second family in which 2 similarly affected sisters were compound heterozygous for mutations in NXN, a 3-bp deletion (612895.0002) and an intragenic 84-bp deletion (612895.0003). Their unaffected parents were each heterozygous for 1 of the mutations.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (postnatal onset) HEAD & NECK Head \- Relative macrocephaly Face \- High forehead \- Frontal bossing \- Midface hypoplasia \- Long philtrum \- Micrognathia Ears \- Low-set ears \- Posteriorly rotated ears \- Dysmorphic helices Eyes \- Hypertelorism \- Prominent eyes \- Long eyelashes Nose \- Short nose \- Wide nasal bridge \- Broad nasal tip \- Anteverted nares Mouth \- Triangular mouth \- Gingival hyperplasia \- Absent uvula \- Notched upper lip \- Cleft lip and palate Teeth \- Dental anomalies CARDIOVASCULAR Heart \- Bicuspid aortic valve (patient A) Vascular \- Dilation of the ascending aorta (patient A) \- Aberrant right coronary artery (patient A) ABDOMEN External Features \- Omphalocele (patient A) \- Ventral hernia (patient A) SKELETAL Skull \- Relative macrocephaly Limbs \- Mesomelia Hands \- Brachydactyly \- Clinodactyly \- Camptodactyly \- Broad thumbs \- Fetal finger pads Feet \- Broad first toe \- Fetal toe pads NEUROLOGIC Central Nervous System \- Developmental delay (patient A) \- Speech delay (patient A) MISCELLANEOUS \- Based on 3 affected girls from 2 unrelated families (last curated August 2019) MOLECULAR BASIS \- Caused by mutation in the nucleoredoxin gene (NXN, 612895.0001 ) ▲ Close
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*[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
| ROBINOW SYNDROME, AUTOSOMAL RECESSIVE 2 | None | 1,669 | omim | https://www.omim.org/entry/618529 | 2019-09-22T15:41:33 | {"omim": ["618529"]} |
Acyanotic heart defect
Other namesNon-cyanotic heart defect
Ventricular septum
SpecialtyCardiology
An acyanotic heart defect, is a class of congenital heart defects. In these, blood is shunted (flows) from the left side of the heart to the right side of the heart, most often due to a structural defect (hole) in the interventricular septum.[1] People often retain normal levels of oxyhemoglobin saturation in systemic circulation.
This term is outdated, because a person with an acyanotic heart defect may show cyanosis (turn blue due to insufficient oxygen in the blood).[1]
## Contents
* 1 Signs and symptoms
* 1.1 Complications
* 1.2 Types
* 2 Management
* 3 See also
* 4 References
## Signs and symptoms[edit]
* Shortness of breath
* Congested cough
* Diaphoresis
* Fatigue
* Frequent respiratory infections
* Machine-like heart murmur
* Tachycardia
* Tachypnea
* Respiratory distress
* Mild cyanosis (in right sided heart failure)
* Poor growth and development (from increased energy spent on breathing)
### Complications[edit]
This condition can cause congestive heart failure.[1]
### Types[edit]
Left to right shunting heart defects include:
* Ventricular septal defect (VSD) (30% of all congenital heart defects)
* Atrial septal defect (ASD)
* Atrioventricular septal defect (AVSD)
* Patent ductus arteriosus (PDA)
Others:
* levo-Transposition of the great arteries (l-TGA),
Acyanotic heart defects without shunting include:
* Pulmonary stenosis (a narrowing of the pulmonary valve)
* Aortic stenosis
* Coarctation of the aorta
## Management[edit]
* Medications: Digoxin/Lanoxin
* Diuretics: Furosemide/Lasix
* Surgery
## See also[edit]
* Cyanotic heart defect
## References[edit]
1. ^ a b c Pillitteri, Adele (2013-11-25). Maternal and Child Health Nursing: Care of the Childbearing and Childrearing Family. Lippincott Williams & Wilkins. p. 1201. ISBN 9781469833224.
^NCLEX-PN Review 2nd Ed. (2006). Lippincott Williams & Wilkins. ISBN 1-58255-915-5.
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This article about a medical condition affecting the circulatory system is a stub. You can help Wikipedia by expanding it.
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*[AA]: Adrenergic agonist
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*[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
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| Acyanotic heart defect | c0265807 | 1,670 | wikipedia | https://en.wikipedia.org/wiki/Acyanotic_heart_defect | 2021-01-18T18:31:54 | {"umls": ["C0265807"], "wikidata": ["Q4677976"]} |
Extravasation of urine
SpecialtyUrology
Extravasation of urine refers to the condition where an interruption of the urethra leads to a collection of urine in other cavities, such as the scrotum or the penis in males. It can be associated with a calculus.[citation needed]
## Contents
* 1 Mechanism
* 2 Urinoma
* 3 References
* 4 External links
## Mechanism[edit]
An injury to the urethra leaving Buck's fascia intact results in a collection of urine (extravasation) limited to the penis, deep to Buck's fascia. However, if the injury to the bulb of the penis results in urethral injury accompanying a tear of the Buck's fascia, then extravasated blood and urine would accumulate in the superficial perineal space, passing into the penis (outer to Buck's fascia) as well as the scrotum and lower anterior abdominal wall. Extravasation of urine involving a compromised Buck's fascia can be appreciated clinically by blood collecting in the superficial pouch, resulting in a 'butterfly'-shaped region around the penis.[citation needed]
## Urinoma[edit]
Long term complications of renal trauma, ureteral obstruction, or kidney transplant can lead to the formation of an urinoma encapsulating extravasated urine.[1]
## References[edit]
1. ^ Gild, Philipp; Kluth, Luis A.; Vetterlein, Malte W.; Engel, Oliver; Chun, Felix K.H.; Fisch, Margit (2018). "Adult iatrogenic ureteral injury and stricture–incidence and treatment strategies". Asian Journal of Urology. pp. 101–106. doi:10.1016/j.ajur.2018.02.003. Retrieved 1 November 2020.
## External links[edit]
Classification
D
* ICD-10: R39.0
* ICD-9-CM: 788.8
* v
* t
* e
Symptoms and signs relating to the urinary system
Pain
* Dysuria
* Renal colic
* Costovertebral angle tenderness
* Vesical tenesmus
Control
* Urinary incontinence
* Enuresis
* Diurnal enuresis
* Giggling
* Nocturnal enuresis
* Post-void dribbling
* Stress
* Urge
* Overflow
* Urinary retention
Volume
* Oliguria
* Anuria
* Polyuria
Other
* Lower urinary tract symptoms
* Nocturia
* urgency
* frequency
* Extravasation of urine
* Uremia
Eponymous
* Addis count
* Brewer infarcts
* Lloyd's sign
* Mathe's sign
This medical sign article is a stub. You can help Wikipedia by expanding it.
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*[DOR]: δ-opioid receptor
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| Extravasation of urine | c0152245 | 1,671 | wikipedia | https://en.wikipedia.org/wiki/Extravasation_of_urine | 2021-01-18T18:53:54 | {"umls": ["C0152245"], "icd-10": ["R39.0"], "wikidata": ["Q5422284"]} |
Coffin–Lowry syndrome
X-linked dominant inheritence
SpecialtyMedical genetics
Coffin–Lowry syndrome is a genetic disorder that is X-linked dominant and which causes severe mental problems sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis, as well as auditory and visual abnormalities.
## Contents
* 1 Presentation
* 2 Causes
* 2.1 Genetics
* 3 Cell physiology
* 4 Diagnosis
* 4.1 Imaging studies
* 5 Treatment
* 6 Prognosis
* 7 Epidemiology
* 8 History
* 9 Culture
* 10 References
* 11 Sources
* 12 External links
## Presentation[edit]
Symptoms of disease are more severe in males, who are generally diagnosed in early childhood. Children afflicted by CLS display cognitive disabilities of varying severity. Additional neuromuscular features include sleep apnea, muscular spasticity, progressive loss of muscle strength and tone leading to paraplegia or partial paralysis. Affected individuals are at elevated risk of stroke. Some patients experience stimulus-induced drop attacks (SIDAs, temporary paralytic episodes without loss of consciousness), triggered by unpredictable environmental stimuli (touch, scents, sounds, etc.). SIDA episodes become more frequent as the disease progresses, and become frequent around adolescence in males. Additional clinical physical features include small, soft hands with tapered fingers. Distinct facial architecture such as a flattened nose, widely separated and downward sloping eyes, a prominent forehead, and a wide mouth with large lips are reported as coincident facial features in patients with the disorder. Some individuals experience hearing loss. Others display kyphoscoliosis (multidirectional curvature of the spine) which can lead to difficulty with breathing and/or pulmonary hypertension. Cardiorespiratory complications may arise, which is why it is recommended that CLS patients undergo regular monitoring for spinal irregularities. Physical exams, CT imaging and X-ray imaging are standard methods of assessment.[citation needed]
## Causes[edit]
The syndrome is caused by mutations in the RPS6KA3 gene.[1] This gene is located on the short arm of the X chromosome (Xp22.2). The RPS6KA3 gene makes a protein that is involved with signaling within cells. Researchers believe that this protein helps control the activity of other genes and plays an important role in the brain. The protein is involved in cell signaling pathways that are required for learning, the formation of long-term memories, and the survival of nerve cells. The protein RSK2 which is encoded by the RPS6KA3 gene is a kinase which phosphorylates some substrates like CREB and histone H3. RSK2 is involved at the distal end of the Ras/MAPK signaling pathway. Mutations in the RPS6KA3 disturb the function of the protein, but it is unclear how a lack of this protein causes the signs and symptoms of Coffin–Lowry syndrome. At this time more than 120 mutations have been found.[2] Some people with the features of Coffin–Lowry syndrome do not have identified mutations in the RPS6KA3 gene. In these cases, the cause of the condition is unknown.[citation needed]
This condition is inherited in an X-linked dominant pattern. A condition is considered X-linked if the gene that causes the disorder is located on the X chromosome (one of the two sex chromosomes). The inheritance is dominant if one copy of the altered gene is sufficient to cause the condition.[citation needed]
A majority of boys with Coffin–Lowry syndrome have no history of the condition in their families. These cases are caused by new mutations in the RPS6KA3 gene (de novo mutations). A new mutation means that neither parent has the altered gene, but the affected individual could pass it on to his children.[citation needed]
### Genetics[edit]
Coffin–Lowry syndrome is an X-linked disorder resulting from loss-of-function mutations in the RPS6KA3 gene, which encodes RSK2 (ribosomal S6 kinase 2). Multiple mutations have been identified in RPS6KA3 that can give rise to the disorder, including missense mutations, nonsense mutations, insertions and deletions. Individuals with CLS rarely have affected parents, suggesting that most incidents arise from de novo mutations in the germline. The lack of an inheritance pattern may be due to the fact that affected individuals are unlikely to parent children. In 20–30% of cases, however, there is a family history of disease. In these cases, the disorder is typically inherited from the maternal parent. Because RPS6KA3 is located on the X chromosome, males (who possess only one copy of the X chromosome) display more severe symptoms than females. Affected females usually possess one mutated copy of the RPS6KA3 gene and one wild type copy. Random inactivation of one copy of the X chromosome in females mitigates the impact of possessing a mutant allele. Occasionally females are born with two mutated alleles. In these cases the symptoms are as severe as in males with the disease.[3]
## Cell physiology[edit]
RSK2 controls the activity of proteins crucial for normal cellular function.
Mutations in the RPS6KA3 gene can result in expression of an RSK2 protein (ribosomal S6 kinase 2) with reduced or absent kinase function. RSK2 is a downstream component of the MAPK (mitogen-activated protein kinase) cascade that is itself a kinase. RSK2 phosphorylates cellular proteins (including histone H3, and CREB), which regulate eukaryotic gene expression. In individuals with Coffin–Lowry syndrome, phosphorylation of transcriptional regulators is reduced due to the weakened activity of RSK2 kinase activity. RSK2 is normally activated by the ERK MAP kinase. Mutated RSK2 may be deficient for activation by ERK, or its kinase activity may be reduced despite activation by ERK. The most common mutation in RPS6KA3 is an early stop codon that fails to produce a functional protein, indicating that disease etiology most likely arises from loss-of-function effects. Substitution mutations (which alter a single amino acid) have also been shown to give rise to the disease. RSK2 is highly expressed in the brain, specifically in the neocortex, hippocampus, and Purkinje cells, all of which are involved in cognitive function and behavior. There is some experimental evidence that RSK2 regulates synaptic transmission and plasticity in neuronal cell types.[3]
## Diagnosis[edit]
Affected individuals are often short in stature. Behavioral symptoms include aggression and depression, but these may be secondary to the emotional consequences of significant physical disabilities associated with the disorder.[4]
Coffin–Lowry patients may be affected by chewing and swallowing difficulties, for which there are diagnostic assessments. Among these are the Videofluoroscopic Swallowing Evaluation (VFSE), the Karaduman Chewing Performance Scale, and the Penetration Aspiration Scale (PAS) which is used to evaluate accidental aspiration of food particles.[5] The Pediatric Assessment Tool (PEDI-EAT-10) also includes measurement of severity of dysphagia (difficulty in swallowing). Molecular genetic testing can be used to confirm the genetic diagnosis of Coffin–Lowry syndrome or to assess pregnancy risk in affected families.[citation needed]
Symptoms table:
* Generally symptoms listed as "rare" are common in more severe cases.
Symptom Description Frequency (male) Frequency (female) When first observed Prognosis Treatment
Cognitive disabilities Mental retardation Most severe Ranges from severe to relatively normal intellect Variable
Sleep apnea Sleep disorder where breathing starts/stops, a lot of times the person will snore More common Less common Progressive CPAP machine
Muscular spasticity Stiff muscles Most common Less common Muscle relaxers
Loss of muscle strength Paraplegia or partial paralysis Physical therapy
Delayed speech Limited vocabulary Most common Least common Speech therapy
Cardiovascular complications Mitral valve dysfunction, congestive heart failure Most severe Common Premature death
Stroke Interrupted blood flow to the brain
Convulsions Sudden, irregular body movements that can be violent Common Common 1 year of age and onwards Depending on severity can lead to death Medications, such as valproate
Stimulus-induced drop attacks (SIDAs) Instantaneous loss of muscle tone as a result of sudden unexpected tactile of auditory stimuli but without loss of consciousness Rare but observed Rare but observed Adolescence Progressive Prescribed benzodiazepines
Small/soft/fleshy hands More common Less common At birth
Tapered fingers More common Less common At birth
Flattened nose Most common Least common but variable Childhood
Widely separated/ downward sloping eyes Most common Least common but variable At birth
Prominent forehead Protruding forehead Most common Least common but variable Early infancy
Wide mouth / large lips Most severe Least common but variable 2 years of age Progressive
Sensorineural deafness Hearing Loss Most common Least common No cure; can utilize cochlear implants or hearing aids
Kyphoscoliosis Abnormal curvature of the spine in 2 planes, outward rounding of the spine Most severe Least common Progressive Severe cardiorespiratory compromise and ultimately death Physical therapy
Short stature Range of height is 115–158cm Most common Least common Early childhood
Aggression Violent behavior Risperidone prescription
Depression Feelings of sadness Very rare Most severe 20 years of age Psychiatric therapy, selective serotonin reuptake inhibitors
Difficulty swallowing Difficult time swallowing Common Common 3 years of age Rehabilitation
Difficulty chewing Difficult time chewing Common Common 3 years of age Rehabilitation
Coughing while eating Coughing while eating Common Common 3 years of age Rehabilitation
Long-lasting wheezing Coughs accompanied with a whistling sound from the chest that lasts long term Common Common 3 years of age Rehabilitation
Sputum Coughing up saliva and mucus Common Common 3 years of age Rehabilitation
Inability to ingest food Inability to eat food easily Common Common 3 years of age Rehabilitation
### Imaging studies[edit]
X-ray and neuroimaging studies may be helpful in confirming a diagnosis of Coffin–Lowry syndrome. Decreased ribosomal S6 kinase activity in cultured fibroblast or transformed lymphoblast cells from a male indicates Coffin–Lowry syndrome. Studies of enzyme activity can not be used to diagnose an affected female.[citation needed]
Molecular genetic testing on a blood specimen or cells from a cheek swab is available to identify mutations in the RSK2 gene. This testing can be used to confirm but not rule out the diagnosis of Coffin–Lowry syndrome because not all affected individuals have a detectable mutation.[6]
## Treatment[edit]
There is no cure for Coffin–Lowry syndrome. Clinical objectives are centered on symptom management. Because stimulus-induced drop attacks (SIDAs) can result in physical harm to patients with the disorder, the use of medication to prevent or reduce the number of SIDA episodes is a safety priority. Physical precautionary measures have also been used to protect patients from injury, including the use of a helmet or a wheelchair. Because sudden excitement or fright can trigger a SIDA episode it is important to minimize exposure to startling stimuli. Medications prescribed include benzodiazepines (tranquilizers used to treat anxiety), valproate (used to manage epilepsy and bipolar disorder), and selective serotonin reuptake inhibitors (SSRIs) (used to treat major depression). When affected individuals display aggressive or destructive behavior that could harm themselves or others, the antipsychotic medication risperidone may eventually be prescribed. It is recommended that spinal development be monitored regularly by X-ray and physical exams. Echocardiograms are recommended every 5-10 years to assess cardiac function and development. Families are encouraged to receive genetic counseling in order to understand and prepare to provide care for children affected by Coffin–Lowry syndrome.[4]
## Prognosis[edit]
Lifespan may be significantly shortened in males with Coffin-Lowry syndrome. Patients may survive into their late twenties, but generally suffer from early mortality due to cardiac, respiratory, and post-operative complications. The progression of reduced cardiac functioning over time may necessitate surgical procedures to counteract mitral valve dysfunction, congenital heart disease, patent ductus arteriosus, and ventricular hypertrophy. Kyphoscoliosis may worsen over time and contribute to these pathologies.[3]
## Epidemiology[edit]
The prevalence of CLS is uncertain due to the rarity of the disease, but CLS is estimated to affect between 1 in 50,000 and 1 in 100,000 people. Prenatal testing is available to test for CLS of an offspring if a family member has been diagnosed with CLS. [3]
## History[edit]
Coffin–Lowry was first described by Grange S. Coffin (b. 1923) in 1966 and independently by Robert Brian Lowry (b. 1932) in 1971.[2][7][8] Dr. Temtamy showed that the cases represented a single syndrome in 1975.[citation needed]
In 1972, Peter G. Procopis and B. Turner published a case study on a family of four brothers with Coffin-Lowry Syndrome, with female relatives, specifically sisters, only possessing some mild deformities and abnormalities.[9] In 1975, Samia Temtamy reported eight patients from three different families displaying symptoms of Coffin-Lowry Syndrome, suggesting that the disorder is more common than believed and often goes underdiagnosed. On the basis of these reports, AG Hunter, Simone Gilgenkrantz, and ID Young established Coffin-Lowry Syndrome as an novel medical diagnosis and named it for the two doctors to originally describe its clinical symptoms. Additional case studies have since expanded the original list of clinical signs and symptoms. In 2002, Helen Fryssira and RJ Simensen identified a 3 base pair deletion in the gene encoding RSK2, which was the first report of the gene responsible for Coffin-Lowry.[citation needed]
## Culture[edit]
The Coffin–Lowry Syndrome Foundation[10] acts as a clearinghouse for information on Coffin–Lowry syndrome and hosts a forum for affected families. The family matching program facilitates community building and resource sharing for recent diagnoses.[11]
The Coffin-Lowry Syndrome Foundation was created in 1991. The mission of the Foundation is to provide informational links, resources, and databases to families and patients dealing with the disease and enables them to communicate with one another. Families and patients can share their experiences and retrieve advice on the foundation’s online site as well as locate helpful services, telephone support, and day-to-day news on medical progress into understanding and treating those affected by Coffin-Lowry Syndrome. The symbol of the foundation is an apple, chosen for its representation of knowledge, feminine beauty, immortality, rebirth, and peace. The foundation provides a support network and source of hope for the families of patients with Coffin-Lowry Syndrome.[citation needed]
## References[edit]
1. ^ Delaunoy JP, Dubos A, Marques Pereira P, Hanauer A (August 2006). "Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin–Lowry syndrome". Clin. Genet. 70 (2): 161–6. doi:10.1111/j.1399-0004.2006.00660.x. PMID 16879200. S2CID 31521326.
2. ^ a b synd/3425 at Who Named It?
3. ^ a b c d Marques Pereira, P., Schneider, A., Pannetier, S. et al. "Coffin–Lowry syndrome". European Journal of Human Genetics 18, 627–633 (2010). doi:10.1038/ejhg.2009.189
4. ^ a b Rogers RC, Abidi FE. Coffin–Lowry Syndrome. 16 July 2002 [Updated 1 February 2018. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews [Internet]. Seattle, Washington: University of Washington, Seattle.
5. ^ Kübra Şahan, A. (2019, December 23). "Chewing and Swallowing Training Program in Coffin-Lowry Syndrome".
6. ^ "Coffin Lowry Syndrome - NORD (National Organization for Rare Disorders)". RareDiseases.org. Retrieved February 2, 2017.
7. ^ Coffin GS, Siris E, Wegienka LC (1966). "Mental retardation with osteocartilaginous anomalies". Am. J. Dis. Child. 112 (3): 205–213. doi:10.1001/archpedi.1966.02090120073006.
8. ^ Lowry B, Miller JR, Fraser FC (June 1971). "A new dominant gene mental retardation syndrome. Association with small stature, tapering fingers, characteristic facies, and possible hydrocephalus". Am. J. Dis. Child. 121 (6): 496–500. doi:10.1001/archpedi.1971.02100170078009. PMID 5581017.
9. ^ McKusick, V. A., & Kniffin, C. L. (2019, November 11). COFFIN-LOWRY SYNDROME; CLS. Retrieved from https://www.omim.org/entry/303600
10. ^ "Home". www.clsf.info.
11. ^ "Coffin–Lowry Syndrome Foundation". National Institute of Neurological Disorders and Stroke. Retrieved 29 February 2016.
## Sources[edit]
This article incorporates public domain text from The U.S. National Library of Medicine and the National Institute of Neurological Disorders and Stroke.
## External links[edit]
Classification
D
* ICD-10: Q87.8
* ICD-9-CM: 759.89
* OMIM: 303600
* MeSH: D038921
* DiseasesDB: 2934
* GeneReviews/UW/NIH entry on Coffin–Lowry syndrome
* http://ghr.nlm.nih.gov/condition/coffin-lowry-syndrome
* 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
* t
* e
Deficiencies of intracellular signaling peptides and proteins
GTP-binding protein regulators
GTPase-activating protein
* Neurofibromatosis type I
* Watson syndrome
* Tuberous sclerosis
Guanine nucleotide exchange factor
* Marinesco–Sjögren syndrome
* Aarskog–Scott syndrome
* Juvenile primary lateral sclerosis
* X-Linked mental retardation 1
G protein
Heterotrimeic
* cAMP/GNAS1: Pseudopseudohypoparathyroidism
* Progressive osseous heteroplasia
* Pseudohypoparathyroidism
* Albright's hereditary osteodystrophy
* McCune–Albright syndrome
* CGL 2
Monomeric
* RAS: HRAS
* Costello syndrome
* KRAS
* Noonan syndrome 3
* KRAS Cardiofaciocutaneous syndrome
* RAB: RAB7
* Charcot–Marie–Tooth disease
* RAB23
* Carpenter syndrome
* RAB27
* Griscelli syndrome type 2
* RHO: RAC2
* Neutrophil immunodeficiency syndrome
* ARF: SAR1B
* Chylomicron retention disease
* ARL13B
* Joubert syndrome 8
* ARL6
* Bardet–Biedl syndrome 3
MAP kinase
* Cardiofaciocutaneous syndrome
Other kinase/phosphatase
Tyrosine kinase
* BTK
* X-linked agammaglobulinemia
* ZAP70
* ZAP70 deficiency
Serine/threonine kinase
* RPS6KA3
* Coffin-Lowry syndrome
* CHEK2
* Li-Fraumeni syndrome 2
* IKBKG
* Incontinentia pigmenti
* STK11
* Peutz–Jeghers syndrome
* DMPK
* Myotonic dystrophy 1
* ATR
* Seckel syndrome 1
* GRK1
* Oguchi disease 2
* WNK4/WNK1
* Pseudohypoaldosteronism 2
Tyrosine phosphatase
* PTEN
* Bannayan–Riley–Ruvalcaba syndrome
* Lhermitte–Duclos disease
* Cowden syndrome
* Proteus-like syndrome
* MTM1
* X-linked myotubular myopathy
* PTPN11
* Noonan syndrome 1
* LEOPARD syndrome
* Metachondromatosis
Signal transducing adaptor proteins
* EDARADD
* EDARADD Hypohidrotic ectodermal dysplasia
* SH3BP2
* Cherubism
* LDB3
* Zaspopathy
Other
* NF2
* Neurofibromatosis type II
* NOTCH3
* CADASIL
* PRKAR1A
* Carney complex
* PRKAG2
* Wolff–Parkinson–White syndrome
* PRKCSH
* PRKCSH Polycystic liver disease
* XIAP
* XIAP2
See also intracellular signaling peptides and proteins
*[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
| Coffin–Lowry syndrome | c0795900 | 1,672 | wikipedia | https://en.wikipedia.org/wiki/Coffin%E2%80%93Lowry_syndrome | 2021-01-18T18:35:22 | {"gard": ["8589", "6123"], "mesh": ["C536435", "D038921"], "umls": ["C0795900"], "icd-9": ["759.89"], "icd-10": ["Q87.8"], "orphanet": ["192"], "wikidata": ["Q1106881"]} |
See 163800 for a discussion of disturbance of the sinoatrial node, including the so-called sick sinus syndrome (SSS). Onat (1986) described SSS in father, daughter and son. The 2 elder affected persons had severe degenerative myopia. It was suggested that the youngest affected person, still under age 7 years, might develop this feature.
Cardiac \- Sinoatrial node disease \- Sick sinus syndrome Eyes \- Severe degenerative myopia 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
| SINUS NODE DISEASE AND MYOPIA | c0037052 | 1,673 | omim | https://www.omim.org/entry/182190 | 2019-09-22T16:34:52 | {"mesh": ["D012804"], "omim": ["182190"], "orphanet": ["166282"], "synonyms": ["Alternative titles", "SICK SINUS SYNDROME AND MYOPIA", "SSS-MYOPIA SYNDROME"]} |
Feline odontoclastic resorptive lesions on a molar.
Feline Tooth Resorption (TR) is a syndrome in cats characterized by resorption of the tooth by odontoclasts, cells similar to osteoclasts. TR has also been called "feline odontoclastic resorption lesion" (FORL), neck lesion, cervical neck lesion, cervical line erosion, feline subgingival resorptive lesion, feline caries, or feline cavity. It is one of the most common diseases of domestic cats, affecting up to two-thirds.[1] TRs have been seen more recently in the history of feline medicine due to the advancing ages of cats,[2] but 800-year-old cat skeletons have shown evidence of this disease.[3] Purebred cats, especially Siamese and Persians, may be more susceptible.[4]
Dental anatomy
TRs clinically appear as erosions of the surface of the tooth at the gingival border. They are often covered with calculus or gingival tissue. It is a progressive disease, usually starting with loss of cementum and dentin and leading to penetration of the pulp cavity. Resorption continues up the dentinal tubules into the tooth crown. The enamel is also resorbed or undermined to the point of tooth fracture. Resorbed cementum and dentin is replaced with bone-like tissue.
## Contents
* 1 Clinical signs
* 2 Cause
* 3 Treatment
* 4 Differential diagnosis: dental caries
* 5 References
* 6 External links
## Clinical signs[edit]
FORL of the lower third premolar
Clinical signs of TRs are often minimal since the discomfort can be minor. However, there may be subtle signs of discomfort while chewing, as well as anorexia, dehydration, weight loss, and tooth fracture. The lower third premolar is the most commonly affected tooth.[2]
## Cause[edit]
There are two types of TR. "Type 1" lesions are focal defects often caused by local inflammation. "Type 2" lesions are characterized by a generalized loss of root radiopacity on a dental radiograph. The definitive cause of type 2 TRs is unknown, but histologically destruction of the cementum and other mineralized tissue of the tooth root by odontoclasts is seen. It occurs secondary to the loss of the protective covering of the root (the periodontal ligaments) and possibly to a stimulus such as periodontal disease and the release of cytokines, leading to odontoclast migration.[5] However, FORLs can develop in the absence of inflammation.[2] The natural inhibition to root resorption provided by the lining of the root may be altered by increased amounts of Vitamin D, in cats supplied by their diet.[3]
## Treatment[edit]
Treatment for TRs is limited to tooth extraction because the lesion is progressive. Amputation of the tooth crown without root removal has also been advocated in cases demonstrated on a radiograph to be type 2 resorption without associated periodontal or endodontic disease because the roots are being replaced by bone.[6] However, X-rays are recommended prior to this treatment to document root resorption and lack of the periodontal ligament.[7]
Tooth restoration is not recommended because resorption of the tooth will continue underneath the restoration. Use of alendronate has been studied to prevent TRs and decrease progression of existing lesions.
## Differential diagnosis: dental caries[edit]
True dental caries are uncommon among companion animals.[8] Although it has not been accurately documented in cats, the incidence of caries in dogs has been estimated at approximately 5%.[9] The term feline cavities is commonly used to refer to TRs; however, sacchrolytic acid-producing bacteria are not involved in this condition.
## References[edit]
1. ^ van Wessum, R; Harvey, CE; Hennet, P (Nov 1992). "Feline dental resorptive lesions. Prevalence patterns". Vet Clin North Am Small Anim Pract. 22 (6): 1405–16. doi:10.1016/s0195-5616(92)50134-6. PMID 1455579.
2. ^ a b c Gorrel, Cecilia (2003). "Feline Odontoclastic Resorptive Lesions". Proceedings of the 28th World Congress of the World Small Animal Veterinary Association. Retrieved 2006-10-22.
3. ^ a b Lyon, Kenneth F. (2005). "Odontoclastic Resorptive Lesions". In August, John R. (ed.). Consultations in Feline Internal Medicine Vol. 5. Elsevier Saunders. ISBN 0-7216-0423-4.
4. ^ Dodd, Johnathon R. "Feline Odontoclastic Resorptive Lesions". Small Animal Dental Service. Texas A&M University Veterinary Medical Teaching Hospital. Archived from the original on 2006-09-03. Retrieved 2006-10-22.
5. ^ Bar-am, Yoav. "Ethiopathogenesis of feline odontoclastic resorption lesions". Koret School of Veterinary Medicine. Retrieved 2006-10-22.
6. ^ Carmichael, Daniel T. (February 2005). "Dental Corner: How to detect and treat feline odontoclastic resorptive lesions". Veterinary Medicine. Archived from the original on 2006-05-05. Retrieved 2006-10-22.
7. ^ Beckman, Brett (March 2007). "Off with the crown?". DVM. Advanstar Communications: 34.
8. ^ "Cavities". American Veterinary Dental Society. Archived from the original on 2006-10-13. Retrieved 2006-10-23.
9. ^ Hale, FA (Jun 1998). "Dental caries in the dog". J Vet Dent. 15 (2): 79–83. doi:10.1177/089875649801500203. PMID 10597155.
## External links[edit]
* Feline odontoclastic resorption lesions \- American Veterinary Dental College position statement.
* Feline Oral Resorptive Lesions (FORL) from Veterinary Partner
*[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
| Feline odontoclastic resorptive lesion | None | 1,674 | wikipedia | https://en.wikipedia.org/wiki/Feline_odontoclastic_resorptive_lesion | 2021-01-18T18:54:37 | {"wikidata": ["Q1389389"]} |
Benign familial infantile epilepsy (BFIE) is a genetic epileptic syndrome characterized by the occurrence of afebrile repeated seizures in healthy infants, between the third and eighth month of life.
## Epidemiology
Although BFIE cases have been reported worldwide, prevalence and incidence remain unknown. In an Argentinian case series, BFIE have been listed as the third most common type of epilepsy in the first two years of life.
## Clinical description
Seizures usually occur between 3 to 8 months of life, with clusters (8-10 a day) of repeated and brief episodes (2-5 minutes) over a few days. They are usually focal but can sometimes become generalized. Patients present with motor arrest, unresponsiveness, head and/or eye deviation to one side, staring, fluttering of eyelids, grunting, cyanosis, diffuse hypertonia and unilateral or bilateral clonic jerks of the limbs. During the interictal period, patients regain full consciousness and activity. Psychomotor development is normal. A family history of the same epilepsy is a constant finding. A syndrome called familial infantile convulsions and choreoathetosis (ICCA; see this term) has been observed in which BFIE patients present in childhood and/or adolescence with choreoathetotic dyskinetic attacks occurring spontaneously or following diverse stimuli (e.g. exercise, stress). In some rare cases, BFIE has been associated with familial or sporadic hemiplegic migraine.
## Etiology
BFIE is a genetically heterogeneous disease. In the majority of cases, mutations in the proline-rich transmembrane protein 2 (PRRT2) gene located at 16p11.2 have been found. This gene encodes a membrane protein that interacts with the presynaptic protein SNAP-25. Mutations have also been found in the SCN2A gene (2q24.3) encoding the brain sodium channel NaV1.2 and rarely in the KCNQ2 (20q13.33) and KCNQ3 (8q24) genes both encoding potassium channels. Additionally, three other chromosomal loci have been identified that are mapped to chromosome 19q, 16p and 1p.
## Diagnostic methods
Family history can orient the diagnosis which is based on electroencephalography (EEG) and video recordings. Ictal EEG shows that partial seizures originate from the parietal-occipital region and that the side of the hemisphere involved can vary between episodes. Seizures can sometimes spread and involve the entire brain. During a cluster of seizures, postictal EEG shows lateralized occipito-parietal delta waves and spikes. Outside the cluster, waking and sleeping interictal EEG is normal. Interictal neurological examination and brain imaging (brain CT and/or MRI) are normal. Genetic testing confirms the diagnosis.
## Differential diagnosis
Differential diagnosis includes benign familial neonatal-infantile seizures (see this term), an epileptic syndrome with an intermediate onset between the neonatal and infantile age that shares overlapping clinical characteristics with BFIE and that is mainly due to mutations in the SCN2A gene. Other differential diagnoses are benign non-familial infantile seizures, benign infantile seizures associated with mild gastroenteritis and benign infantile focal epilepsy with midline spikes and waves during sleep (BIMSE) (see these terms).
## Genetic counseling
BFIE is transmitted as an autosomal dominant trait with incomplete penetrance.
## Management and treatment
With anti-epileptic treatment (e.g. carbamazepine, valproate, phenobarbital), symptoms quickly disappear and no other type of epilepsy has been reported to reappear. In patients with a clear familial history the treatment can be interrupted within a few months.
## Prognosis
Prognosis is good. Seizures normally disappear after the first year of life and patients do not display any neurological sequelae.
*[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
| Benign familial infantile epilepsy | c0220669 | 1,675 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=306 | 2021-01-23T19:02:20 | {"gard": ["856", "857"], "mesh": ["D020936"], "omim": ["601764", "605751", "607745", "612627", "617080"], "umls": ["C0220669"], "icd-10": ["G40.3"], "synonyms": ["BFIE", "BFIS", "Benign familial infantile convulsions", "Benign familial infantile seizures"]} |
Sideroblastic anemia
A ring sideroblast visualized by Prussian blue stain
SpecialtyHematology
Sideroblastic anemia, or sideroachrestic anemia, is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes).[1] In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need in order to transport oxygen efficiently. The disorder may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome,[2] which can develop into hematological malignancies (especially acute myeloid leukemia).
Sideroblasts (sidero- \+ -blast) are nucleated erythroblasts (precursors to mature red blood cells) with granules of iron accumulated in the mitochondria surrounding the nucleus.[3] Normally, sideroblasts are present in the bone marrow, and enter the circulation after maturing into a normal erythrocyte. The presence of sideroblasts per se does not define sideroblastic anemia. Only the finding of ring (or ringed) sideroblasts characterizes sideroblastic anemia.
Ring sideroblasts are named so because iron-laden mitochondria form a ring around the nucleus. It is a subtype of basophilic granules of the erythrocyte, but which can only be seen in bone marrow. To count a cell as a ring sideroblast, the ring must encircle a third or more of the nucleus and contain five or more iron granules, according to the 2008 WHO classification of the tumors of the hematopoietic and lymphoid tissues.[4]
## Contents
* 1 Types
* 2 Symptoms and signs
* 3 Causes
* 4 Diagnosis
* 4.1 Classification
* 4.2 Laboratory findings
* 5 Treatment
* 6 Prognosis
* 7 See also
* 8 References
* 9 External links
## Types[edit]
The WHO International Working Group on Morphology of MDS (IWGM-MDS) defined three types of sideroblasts:
1. Type 1 sideroblasts: fewer than 5 siderotic granules in the cytoplasm
2. Type 2 sideroblasts: 5 or more siderotic granules, but not in a perinuclear distribution
3. Type 3 or ring sideroblasts: 5 or more granules in a perinuclear position, surrounding the nucleus or encompassing at least one third of the nuclear circumference.
Type 1 and type 2 are found in non-sideroblastic anemias. Type 3 is found only in sideroblastic anemia.
## Symptoms and signs[edit]
Symptoms of sideroblastic anemia include skin paleness, fatigue, dizziness, and enlarged spleen and liver. Heart disease, liver damage, and kidney failure can result from iron buildup in these organs.[5]
## Causes[edit]
Causes of sideroblastic anemia can be categorized into three groups: congenital sideroblastic anemia, acquired clonal sideroblastic anemia, and acquired reversible sideroblastic anemia. All cases involve dysfunctional heme synthesis or processing. This leads to granular deposition of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell. Congenital forms often present with normocytic or microcytic anemia while acquired forms of sideroblastic anemia are often normocytic or macrocytic.
* Congenital sideroblastic anemia
* X-linked sideroblastic anemia: This is the most common congenital cause of sideroblastic anemia and involves a defect in ALAS2,[6] which is involved in the first step of heme synthesis. Although X-linked, approximately one third of patients are women due to skewed X-inactivation (lyonizations).
* Autosomal recessive sideroblastic anemia involves mutations in the SLC25A38 gene. The function of this protein is not fully understood, but it is involved in mitochondrial transport of glycine. Glycine is a substrate for ALAS2 and necessary for heme synthesis. The autosomal recessive form is typically severe in presentation.
* Genetic syndromes: Rarely, sideroblastic anemia may be part of a congenital syndrome and present with associated findings, such as ataxia, myopathy, and pancreatic insufficiency.
* Acquired clonal sideroblastic anemia
* Clonal sideroblastic anemias fall under the broader category of myelodysplastic syndromes (MDS). Three forms exist and include refractory anemia with ringed sideroblasts (RARS), refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T), and refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS). These anemias are associated with increased risk for leukemic evolution.
* Acquired reversible sideroblastic anemia
* Causes include excessive alcohol use (the most common cause of sideroblastic anemia), pyridoxine deficiency (vitamin B6 is the cofactor in the first step of heme synthesis[7]), lead poisoning[8] and copper deficiency.[9] Excess zinc[10] can indirectly cause sideroblastic anemia by decreasing absorption and increasing excretion of copper. Antimicrobials that may lead to sideroblastic anemia include isoniazid (which interferes with pyridoxine metabolism), chloramphenicol (which, by inhibiting the synthesis of mitochondrial membrane protein, impairs mitochondrial respiration[11]), cycloserine, and linezolid.[12]
## Diagnosis[edit]
Bone marrow aspirate: ring sideroblasts
Ringed sideroblasts are seen in the bone marrow.
On the peripheral blood smear can be found erythrocytes with basophilic stippling (cytoplasmic granules of RNA precipitates) and Pappenheimer bodies (cytoplasmic granules of iron).[13]
The anemia is moderate to severe and dimorphic. Microscopic viewing of the red blood cells will reveal marked unequal cell size and abnormal cell shape. Basophilic stippling is marked and target cells are common. The mean cell volume is commonly decreased (i.e., a microcytic anemia), but it may also be normal or even high. The RDW is increased with the red blood cell histogram shifted to the left. Leukocytes and platelets are normal. Bone marrow shows erythroid hyperplasia with a maturation arrest.
In excess of 40% of the developing erythrocytes are ringed sideroblasts. Serum iron, percentage saturation and ferritin are increased. The total iron-binding capacity of the cells is normal to decreased. Stainable marrow hemosiderin is increased.
### Classification[edit]
Sideroblastic anemia is typically divided into subtypes based on its cause.
* Hereditary or congenital sideroblastic anemia may be X-linked[14] or autosomal.
OMIM Name Gene
300751 X-linked sideroblastic anemia (XLSA) ALAS2
301310 sideroblastic anemia with spinocerebellar ataxia (ASAT) ABCB7
205950 pyridoxine-refractory autosomal recessive sideroblastic anemia SLC25A38
206000 pyridoxine-responsive sideroblastic anemia (vitamin B6 deficiency; pyridoxal phosphate required for heme synthesis)
GLRX5 has also been implicated.[15]
* Acquired, or secondary, sideroblastic anemia develops after birth and is divided according to its cause.
### Laboratory findings[edit]
* Serum Iron: high
* increased ferritin levels
* decreased total iron-binding capacity
* high transferrin saturation
* Hematocrit of about 20-30%
* The mean corpuscular volume or MCV is usually normal or low for congenital causes of sideroblastic anemia but normal or high for acquired forms.
* With lead poisoning, see coarse basophilic stippling of red blood cells on peripheral blood smear
* Specific test: Prussian blue stain of RBC in marrow shows ringed sideroblasts. Prussian blue staining involves a non-enzymatic reaction of ferrous iron with ferrocyanide forming ferric-ferrocyanide, which is blue in color. A counterstain may be used to provide better visualization.
## Treatment[edit]
Occasionally, the anemia is so severe that support with transfusion is required. These patients usually do not respond to erythropoietin therapy.[16] Some cases have been reported that the anemia is reversed or heme level is improved through use of moderate to high doses of pyridoxine (vitamin B6). In severe cases of SBA, bone marrow transplant is also an option with limited information about the success rate. Some cases are listed on MedLine and various other medical sites. In the case of isoniazid-induced sideroblastic anemia, the addition of B6 is sufficient to correct the anemia. Deferoxamine, a chelating agent, is used to treat iron overload from transfusions. Therapeutic phlebotomy can be used to manage iron overload.[17]
## Prognosis[edit]
Sideroblastic anemias are often described as responsive or non-responsive in terms of increased hemoglobin levels to pharmacological doses of vitamin B6.[citation needed]
1- Congenital: 80% are responsive, though the anemia does not completely resolve.
2- Acquired clonal: 40% are responsive, but the response may be minimal.
3- Acquired reversible: 60% are responsive, but course depends on treatment of the underlying cause.
Severe refractory sideroblastic anemias requiring regular transfusions and/or that undergo leukemic transformation (5-10%) significantly reduce life expectancy.
## See also[edit]
* Anemia
* Siderosis
* List of hematologic conditions
* Hematopoietic stem cell transplantation
## References[edit]
1. ^ Caudill JS, Imran H, Porcher JC, Steensma DP (October 2008). "Congenital sideroblastic anemia associated with germline polymorphisms reducing expression of FECH". Haematologica. 93 (10): 1582–4. doi:10.3324/haematol.12597. PMID 18698088.
2. ^ Sideroblastic Anemias: Anemias Caused by Deficient Erythropoiesis at Merck Manual of Diagnosis and Therapy Professional Edition
3. ^ "Sideroblast" at Dorland's Medical Dictionary[dead link]
4. ^ Mufti, GJ; Bennett, JM; Goasguen, J; Bain, BJ; Baumann, I; Brunning, R; Cazzola, M; Fenaux, P; Germing, U; Hellström-Lindberg, E; Jinnai, I; Manabe, A; Matsuda, A; Niemeyer, CM; Sanz, G; Tomonaga, M; Vallespi, T; Yoshimi, A; International Working Group on Morphology of Myelodysplastic, Syndrome (Nov 2008). "Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts". Haematologica. 93 (11): 1712–7. doi:10.3324/haematol.13405. PMID 18838480.
5. ^ Genetics Home Reference: Genetic Conditions > X-linked sideroblastic anemia Reviewed October 2006. Retrieved on 5 Mars, 2009
6. ^ Aivado M, Gattermann N, Rong A, et al. (2006). "X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns". Blood Cells Mol. Dis. 37 (1): 40–5. doi:10.1016/j.bcmd.2006.04.003. PMID 16735131.
7. ^ Shander, Petra Seeber, Aryeh (2013). Basics of blood management (2nd ed.). Chichester, West Sussex: Wiley-Blackwell. p. 46. ISBN 978-0-470-67070-5.
8. ^ Lubran, MM (1980). "Lead toxicity and heme biosynthesis". Annals of Clinical and Laboratory Science. 10 (5): 402–13. PMID 6999974.
9. ^ Canada, editors, John P. Greer, MD, Professor, Departments of Medicine and Pediatrics, Divisions of Hermatology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee; Daniel A. Arber, MD, Professor and Vice Chair, Department of Pathology, Stanford University, Director of Anatomic and Clinical Pathology Services, Stanford University Medical Center, Stanford, California; Bertil Glader, MD, Professor, Departments of Pediatrics and Pathology, Stanford University Medical Center, Stanford, California, Lucile Packard Children's Hospital, Palo Alto, California; Alan F. List, MD, Senior Member, Department of Malignant Hematology, President and CEO, Moffit Cancer Center, Tampa Florida; Robert T. Means Jr., MD, PhD, Professor of Internal Medicine, Executive Dean, University of Kentucky College of Medicine, Lexington, Kentucky; Frixos Paraskevas, MD, Professor of Internal Medicine and Immunology (Retired), University of Manitoba Medical School, Associate Member, Institute of Cell Biology-Cancer Care, Manitoba, Winnipeg, Manitoba, Canada; George M. Rodgers, MD, Professor of Medicine and Pathology, University of Utah School of Medicine, Health Sciences Center, Medical Director, Coagulation Laboratory, ARUB Laboratories, Salt Lake City, Utah; Editor Emeritus, John Foerster, MD, FRCPC, Professor and Physician Emertius, Winnipeg (2014). Wintrobe's clinical hematology (Thirteenth ed.). p. 656. ISBN 978-1451172683.CS1 maint: extra text: authors list (link)
10. ^ Forman, W.B. (1990). "Zinc abuse: an unsuspected cause of sideroblastic anemia". West J Med. 152 (2): 190–2. PMC 1002314. PMID 2400417.
11. ^ Canada, editors, John P. Greer, MD, Professor, Departments of Medicine and Pediatrics, Divisions of Hermatology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee; Daniel A. Arber, MD, Professor and Vice Chair, Department of Pathology, Stanford University, Director of Anatomic and Clinical Pathology Services, Stanford University Medical Center, Stanford, California; Bertil Glader, MD, Professor, Departments of Pediatrics and Pathology, Stanford University Medical Center, Stanford, California, Lucile Packard Children's Hospital, Palo Alto, California; Alan F. List, MD, Senior Member, Department of Malignant Hematology, President and CEO, Moffit Cancer Center, Tampa Florida; Robert T. Means Jr., MD, PhD, Professor of Internal Medicine, Executive Dean, University of Kentucky College of Medicine, Lexington, Kentucky; Frixos Paraskevas, MD, Professor of Internal Medicine and Immunology (Retired), University of Manitoba Medical School, Associate Member, Institute of Cell Biology-Cancer Care, Manitoba, Winnipeg, Manitoba, Canada; George M. Rodgers, MD, Professor of Medicine and Pathology, University of Utah School of Medicine, Health Sciences Center, Medical Director, Coagulation Laboratory, ARUB Laboratories, Salt Lake City, Utah; Editor Emeritus, John Foerster, MD, FRCPC, Professor and Physician Emertius, Winnipeg (2014). Wintrobe's clinical hematology (Thirteenth ed.). p. 656. ISBN 978-1451172683.CS1 maint: extra text: authors list (link)
12. ^ Saini, N; Jacobson, JO; Jha, S; Saini, V; Weinger, R (April 2012). "The perils of not digging deep enough--uncovering a rare cause of acquired anemia". American Journal of Hematology. 87 (4): 413–6. doi:10.1002/ajh.22235. PMID 22120958.
13. ^ Rodak, Bernadette F. (2007). Hematology : clinical principles and applications (3rd ed.). Philadelphia: Saunders. p. 535. ISBN 978-1416030065.
14. ^ X-linked sideroblastic anemia at NLM Genetics Home Reference
15. ^ Camaschella C (September 2008). "Recent advances in the understanding of inherited sideroblastic anaemia". Br. J. Haematol. 143 (1): 27–38. doi:10.1111/j.1365-2141.2008.07290.x. PMID 18637800.
16. ^ Papadakis, Maxine A.; Tierney, Lawrence M.; McPhee, Stephen J. (2005). "Sideroblastic Anemia". Current Medical Diagnosis & Treatment, 2006. McGraw-Hill Medical. ISBN 978-0-07-145410-0.
17. ^ Peto, T. E. A., Pippard, M. J., Weatherall, D. J. Iron overload in mild sideroblastic anaemias" Lancet 321: 375-378, 1983. Note: Originally Volume I.
## External links[edit]
Classification
D
* ICD-10: D64.0-D64.3
* ICD-9-CM: 285.0
* OMIM: 301310 206000 300751
* MeSH: D000756
* DiseasesDB: 12110
* GeneReviews/NCBI/NIH/UW entry on X-Linked Sideroblastic Anemia and Ataxia
* v
* t
* e
Diseases of red blood cells
↑
Polycythemia
* Polycythemia vera
↓
Anemia
Nutritional
* Micro-: Iron-deficiency anemia
* Plummer–Vinson syndrome
* Macro-: Megaloblastic anemia
* Pernicious anemia
Hemolytic
(mostly normo-)
Hereditary
* enzymopathy: Glucose-6-phosphate dehydrogenase deficiency
* glycolysis
* pyruvate kinase deficiency
* triosephosphate isomerase deficiency
* hexokinase deficiency
* hemoglobinopathy: Thalassemia
* alpha
* beta
* delta
* Sickle cell disease/trait
* Hereditary persistence of fetal hemoglobin
* membrane: Hereditary spherocytosis
* Minkowski–Chauffard syndrome
* Hereditary elliptocytosis
* Southeast Asian ovalocytosis
* Hereditary stomatocytosis
Acquired
AIHA
* Warm antibody autoimmune hemolytic anemia
* Cold agglutinin disease
* Donath–Landsteiner hemolytic anemia
* Paroxysmal cold hemoglobinuria
* Mixed autoimmune hemolytic anemia
* membrane
* paroxysmal nocturnal hemoglobinuria
* Microangiopathic hemolytic anemia
* Thrombotic microangiopathy
* Hemolytic–uremic syndrome
* Drug-induced autoimmune
* Drug-induced nonautoimmune
* Hemolytic disease of the newborn
Aplastic
(mostly normo-)
* Hereditary: Fanconi anemia
* Diamond–Blackfan anemia
* Acquired: Pure red cell aplasia
* Sideroblastic anemia
* Myelophthisic
Blood tests
* Mean corpuscular volume
* normocytic
* microcytic
* macrocytic
* Mean corpuscular hemoglobin concentration
* normochromic
* hypochromic
Other
* Methemoglobinemia
* Sulfhemoglobinemia
* Reticulocytopenia
* 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
* 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
* t
* e
Genetic disorder, membrane: ABC-transporter disorders
ABCA
* ABCA1 (Tangier disease)
* ABCA3 (Surfactant metabolism dysfunction 3)
* ABCA4 (Stargardt disease 1, Retinitis pigmentosa 19)
* ABCA12 (Harlequin-type ichthyosis, Lamellar ichthyosis 2)
ABCB
* ABCB4 (Progressive familial intrahepatic cholestasis 3)
* ABCB7 (ASAT)
* ABCB11 (Progressive familial intrahepatic cholestasis 2)
ABCC
* ABCC2 (Dubin–Johnson syndrome)
* ABCC6 (Pseudoxanthoma elasticum)
* ABCC7 (Cystic fibrosis)
* ABCC8 (HHF1, TNDM2)
* ABCC9 (Dilated cardiomyopathy 1O)
ABCD
* ABCD1 (Adrenoleukodystrophy, Adrenomyeloneuropathy)
ABCG
* ABCG5 (Sitosterolemia)
* ABCG8 (Gallbladder disease 4, Sitosterolemia)
see also ABC transporters
*[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
| Sideroblastic anemia | c0002896 | 1,676 | wikipedia | https://en.wikipedia.org/wiki/Sideroblastic_anemia | 2021-01-18T18:49:35 | {"gard": ["667"], "mesh": ["D000756"], "umls": ["C0002896"], "orphanet": ["1047"], "wikidata": ["Q2610084"]} |
Blomstrand lethal chondrodysplasia (BLC) is a neonatal osteosclerotic dysplasia (see this term) characterized by advanced endochondral bone maturation, very short limbs, dwarfism and prenatal lethality.
## Epidemiology
To date, less than 10 cases have been described in the literature.
## Clinical description
BLC is a congenital disorder characterized by a low birth weight, facial dysmorphism (widely spaced and protruding eyes (which typically show cataract), depressed nasal bridge, short columella, long philtrum, macroglossia, protruding tongue, severe micrognathia), short trunk, narrow thorax and severe rhizo-meso-acromelic shortness of the limbs. Other anomalies also observed include tooth and mammary gland development defects, hypoplastic lungs, aorta coarctation (see this term), and bowel malrotation. Two forms of BCL, have been described: type I which is the severe, classical form and type II which has less severe features (such as absence of short trunk or, severely shortened arms but moderately shortened legs).
## Etiology
BLC is caused by inactivating homozygous or compound heterozygous mutations in PTH1R (3p22-p21.1) which encodes the parathyroid hormone (PTH)/parathyroid-hormone-related peptide (PTHrP) receptor (PTH1R). These mutations result in the decrease in binding or response to PTH and PTHrP.
## Diagnostic methods
Diagnosis is based on the clinical and radiological characteristics which show generalized increase in bone density with advanced ossification, severe shortness of the long bones with wide metaphyses and club-shaped distal ends, long narrow thorax, calcified hyoid bone and laryngeal cartilage and underdeveloped viscerocranium. Histopathological examination shows an important acceleration of the endochondral ossification in tubular bones, narrow cartilages of the epiphyses and large epiphyseal ossification centers. Diagnosis is confirmed by the genetic screening of PTH1R.
## Differential diagnosis
Differential diagnosis includes primary failure of tooth eruption (see this term) and other lethal short limbed dwarfisms.
## Antenatal diagnosis
Prenatal diagnosis is achieved by sonographic examination showing polyhydramnios, hydrops fetalis (see this term) and a fetus with very short limbs, nuchale dema, macroglossia, a protuberant abdomen, internal anomalies and markedly advanced endochondral bone formation.
## 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.
## Prognosis
Both forms of BLC are lethal either prenatally or shortly after birth.
*[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
| Blomstrand lethal chondrodysplasia | c1859148 | 1,677 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=50945 | 2021-01-23T18:50:21 | {"gard": ["914"], "mesh": ["C537914"], "omim": ["215045"], "umls": ["C1859148"], "icd-10": ["Q78.8"], "synonyms": ["BLC", "BOCD", "Blomstrand chondrodysplasia", "Blomstrand osteochondrodysplasia", "Chondrodysplasia, Blomstrand type"]} |
Bodily responses to the functional effects of ethanol in alcoholic beverages
Beer Street and Gin Lane by William Hogarth, 1751, detailing the Gin Craze in UK cities during the early Industrial Revolution.
Alcohol tolerance refers to the bodily responses to the functional effects of ethanol in alcoholic beverages. This includes direct tolerance, speed of recovery from insobriety and resistance to the development of alcoholism.
## Contents
* 1 Consumption-induced tolerance
* 2 Physiology of alcohol tolerance
* 3 Alcohol tolerance in different ethnic groups
* 4 Footnotes
* 5 References
* 6 Further reading
## Consumption-induced tolerance[edit]
Alcohol tolerance is increased by regular drinking.[1] This reduced sensitivity requires that higher quantities of alcohol be consumed in order to achieve the same effects as before tolerance was established. Alcohol tolerance may lead to (or be a sign of) alcohol dependency.[1]
Heavy alcohol consumption over a period of years can lead to "reverse tolerance". A liver can be damaged by chronic alcohol use, leading to a buildup of fat and scar tissue.[2] The reduced ability of such a liver to metabolize or break down alcohol means that small amounts can lead to a high blood alcohol concentration (BAC) and more rapid intoxication.[citation needed]
## Physiology of alcohol tolerance[edit]
Alcohol dehydrogenase is a dimeric zinc metalloenzyme that catalyzes the reversible oxidation of alcohols to aldehydes
Direct alcohol tolerance is largely dependent on body size. Large-bodied people will require more alcohol to reach insobriety than lightly built people.[3] Thus men, being larger than women on average, will typically have a higher alcohol tolerance. The alcohol tolerance is also connected with activity of alcohol dehydrogenases (a group of enzymes responsible for the breakdown of alcohol) in the liver, and in the bloodstream.
High level of alcohol dehydrogenase activity results in fast transformation of ethanol to more toxic acetaldehyde. Such atypical alcohol dehydrogenase levels are less frequent in alcoholics than in nonalcoholics.[4] Furthermore, among alcoholics, the carriers of this atypical enzyme consume lower ethanol doses, compared to the individuals without the allele.
An estimated one out of twenty people have an alcohol flush reaction. It is not in any way an indicator for the drunkenness of an individual.[5][6] A mild flushing reaction occurs when the body metabolizes alcohol more quickly into acetaldehyde, a toxic metabolite.[4][7] A more severe flushing reaction occurs when the body metabolizes the acetaldehyde more slowly, generally due to an inactive aldehyde dehydrogenase enzyme. Both of those conditions—faster conversion of alcohol to acetaldehyde and slower removal of acetaldehyde—reduce the risk for excessive drinking and alcohol dependence.[4]
## Alcohol tolerance in different ethnic groups[edit]
See also: Race and health and Genetic epidemiology
To engage in alcohol consumption and development of alcoholism appear to be common to primates, and is not a specific human phenomenon.[8] Humans have access to alcohol on far greater quantity than non-human primates, and the availability increased particularly with the development of agriculture.[9] The tolerance to alcohol is not equally distributed throughout the world's population.[10] Genetics of alcohol dehydrogenase indicate resistance has arisen independently in different cultures.[11] In North America, Native Americans have the highest probability of developing alcoholism compared to Europeans and Asians.[12][13][14][15] Different alcohol tolerance also exists within Asian groups, such as between Chinese and Koreans.[16] The health benefits of a modest alcohol consumption reported in people of European descent appear not to exist among people of African descent.[17]
Higher body masses and the prevalence of high levels of alcohol dehydrogenase in an individual increase alcohol tolerance, and both adult weight and enzymes vary with ethnicity.[18][19] Not all differences in tolerance can be traced to biochemistry however.[20] Differences in tolerance levels are also influenced by socio-economic and cultural difference including diet, average body weight and patterns of consumption.[21][22]
## Footnotes[edit]
1. ^ a b "Alcohol and Tolerance". National Institute on Alcohol Abuse and Alcoholism (NIAAA), Alcohol Alert (28). April 1995. Retrieved 2009-08-13.
2. ^ "Alcohol-Induced Liver Disease". UC San Diego Health. Retrieved 4 October 2020.
3. ^ "Factors That Affect How Alcohol is Absorbed & Metabolized". Student affairs - Office of Alcohol Policy and Education. Stanford University. Retrieved 26 May 2018.
4. ^ a b c Hurley TD, Edenberg HJ (2012). "Genes encoding enzymes involved in ethanol metabolism". Alcohol Res. 34 (3): 339–344. PMC 3756590. PMID 23134050.
5. ^ "Myth or reality? The Asian alcohol 'gene' explained". Difford's Guide. September 10, 2013. Archived from the original on 2013-10-22. Retrieved 2013-10-22.
6. ^ "Identifying the Signs of Intoxication" (PDF). Government of Western Australia. December 2010. Archived from the original (PDF) on March 27, 2011.
7. ^ Eng, MY; Luczak, SE; Wall, TL (2007). "ALDH2, ADH1B, and ADH1C genotypes: A literature review". Alcohol Research & Health. 30 (1): 22–7. PMC 3860439. PMID 17718397.
8. ^ Juarez, J; Guzman-Flores, C; Ervin, FR; Palmour, RM (December 1993). "Voluntary alcohol consumption in vervet monkeys: individual, sex, and age differences". Pharmacology Biochemistry and Behavior. 46 (4): 985–8. doi:10.1016/0091-3057(93)90232-I. PMID 8309979. S2CID 33697201.
9. ^ Curry, A. (2017-01-17). "Our 9,000-Year Love Affair With Booze". National Geographic. Retrieved 26 May 2018.
10. ^ Chan, AW (1986). "Racial differences in alcohol sensitivity". Alcohol and Alcoholism (Oxford, Oxfordshire). 21 (1): 93–104. PMID 2937417.
11. ^ Osier, Michael V.; Pakstis, Andrew J.; Soodyall, Himla; Comas, David; Goldman, David; Odunsi, Adekunle; Okonofua, Friday; Parnas, Josef; et al. (2002). "A Global Perspective on Genetic Variation at the ADH Genes Reveals Unusual Patterns of Linkage Disequilibrium and Diversity". American Journal of Human Genetics. 71 (1): 84–99. doi:10.1086/341290. PMC 384995. PMID 12050823.
12. ^ "Alcohol Use Disorder". NY Times. 2013. Retrieved July 21, 2016.
13. ^ Mail & al. (eds., 2002): Alcohol Use Among American Indians and Alaska Natives: Multiple Perspectives on a Complex Problem. NIAAA Research Monograph No. 37. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism[page needed]
14. ^ Caetano, Raul; Clark, Catherine L (1998). "Trends in Alcohol-Related Problems among Whites, Blacks, and Hispanics: 1984-1995". Alcoholism: Clinical and Experimental Research. 22 (2): 534–538. doi:10.1111/j.1530-0277.1998.tb03685.x.
15. ^ Karen Chartier; Raul Caetano. "Ethnicity and Health Disparities in Alcohol Research".
16. ^ Duranceaux & al. (2008). "Ethnic differences in level of response to alcohol between Chinese Americans and Korean Americans". J Stud Alcohol Drugs. 69 (2): 227–234. doi:10.15288/jsad.2008.69.227. PMC 2739570. PMID 18299763.
17. ^ Jackson, Chandra L.; Hu, Frank B.; Kawachi, Ichiro; Williams, David R.; Mukamal, Kenneth J.; Rimm, Eric B. (July 2015). "Black–White Differences in the Relationship Between Alcohol Drinking Patterns and Mortality Among US Men and Women". American Journal of Public Health. 105 (S3): S534–S543. doi:10.2105/AJPH.2015.302615. PMC 4455501. PMID 25905819.
18. ^ Yin, S. -J.; Cheng, T. -C.; Chang, C. -P.; Chen, Y. -J.; Chao, Y. -C.; Tang, H. -S.; Chang, T. -M.; Wu, C. -W. (1988). "Human stomach alcohol and aldehyde dehydrogenases (ALDH): A genetic model proposed for ALDH III isozymes". Biochemical Genetics. 26 (5–6): 343–60. doi:10.1007/BF00554070. PMID 3214414. S2CID 9315241.
19. ^ Fenna, D; Schaefer, O; Mix, L; Gilbert, JA (1971). "Ethanol metabolism in various racial groups". Canadian Medical Association Journal. 105 (5): 472–5. PMC 1931291. PMID 5112118.
20. ^ Bennion L.; Li T. K. (1976). "Alcohol metabolism in American Indians and whites". New England Journal of Medicine. 294 (1): 9–13. doi:10.1056/nejm197601012940103. PMID 1244489.
21. ^ Waldram, J. B.; Herring, A. & Young, K. (1995). Aboriginal Health in Canada: Historical, Cultural, and Epidemiological Perspectives. Toronto: University of Toronto Press. ISBN 9780802085795.
22. ^ Saggers, S. & Gray, D. (1998b). Dealing with Alcohol: Indigenous Usage in Australia, New Zealand and Canada. Cambridge: Cambridge University Press[page needed]
## References[edit]
* Carroll, Charles R. Drugs in Modern Society . NY: McGraw-Hill, 2000 (fifth ed.).
* Chesher, G.; Greeley, J. (1992). "Tolerance to the effects of alcohol". Alcohol, Drugs and Driving. 8 (2): 93–106.
* Osier, M; Pakstis, AJ; Kidd, JR; Lee, JF; Yin, SJ; Ko, HC; Edenberg, HJ; Lu, RB; Kidd, KK (1999). "Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism". American Journal of Human Genetics. 64 (4): 1147–57. doi:10.1086/302317. PMC 1377839. PMID 10090900.
* Muramatsu, T; Wang, ZC; Fang, YR; Hu, KB; Yan, H; Yamada, K; Higuchi, S; Harada, S; Kono, H (1995). "Alcohol and aldehyde dehydrogenase genotypes and drinking behavior of Chinese living in Shanghai". Human Genetics. 96 (2): 151–4. doi:10.1007/BF00207371. PMID 7635462. S2CID 1624596.
* Neumark, YD; Friedlander, Y; Thomasson, HR; Li, TK (1998). "Association of the ADH2*2 allele with reduced ethanol consumption in Jewish men in Israel: A pilot study". Journal of Studies on Alcohol. 59 (2): 133–9. doi:10.15288/jsa.1998.59.133. PMID 9500299.
* Borinskaya, S. A.; Gasemianrodsari, F.; Kalyina, N. R.; Sokolova, M. V.; Yankovsky, N. K. (2005). "Polymorphism of Alcohol Dehydrogenase Gene ADH1B in Eastern Slavic and Iranian-Speaking Populations". Russian Journal of Genetics. 41 (11): 1291–4. doi:10.1007/s11177-005-0231-5. S2CID 4686166. Translated from "Polymorphism of alcohol dehydrogenase gene ADH1B in eastern Slavic and Iranian-speaking populations". Genetika. 41 (11): 1563–6. 2005. PMID 16358724.
* Borinskaya, Svetlana; Kal'Ina, Nina; Marusin, Andrey; Faskhutdinova, Gulnaz; Morozova, Irina; Kutuev, Ildus; Koshechkin, Vladimir; Khusnutdinova, Elza; et al. (2009). "Distribution of the Alcohol Dehydrogenase ADH1B∗47His Allele in Eurasia". American Journal of Human Genetics. 84 (1): 89–92, author reply 92–4. doi:10.1016/j.ajhg.2008.12.007. PMC 2668054. PMID 19124091.
* Li, Hui; Borinskaya, Svetlana; Yoshimura, Kimio; Kal’Ina, Nina; Marusin, Andrey; Stepanov, Vadim A.; Qin, Zhendong; Khaliq, Shagufta; et al. (2009). "Refined Geographic Distribution of the Oriental ALDH2*504Lys (nee 487Lys) Variant". Annals of Human Genetics. 73 (3): 335–45. doi:10.1111/j.1469-1809.2009.00517.x. PMC 2846302. PMID 19456322.
## Further reading[edit]
* Caetano R, Clark CL, Tam T (1998). "Alcohol consumption among racial/ethnic minorities: theory and research" (PDF). Alcohol Health Res World. 22 (4): 233–41. PMC 6761890. PMID 15706749. Archived from the original (PDF) on June 16, 2015.
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*[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
| Alcohol tolerance | c0556369 | 1,678 | wikipedia | https://en.wikipedia.org/wiki/Alcohol_tolerance | 2021-01-18T18:56:50 | {"umls": ["C0556369"], "wikidata": ["Q4713312"]} |
B-cell growth factor is released by T lymphocytes after either lectin or antigen stimulation as a protein of Mr 12,000-14,000. Sahasrabuddhe et al. (1984) demonstrated that this relatively small molecule is derived from a precursor molecule of Mr 60,000-80,000 which exists in an intracytoplasmic pool in the T cells.
*[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
| B-CELL GROWTH FACTOR | None | 1,679 | omim | https://www.omim.org/entry/109540 | 2019-09-22T16:44:28 | {"omim": ["109540"], "synonyms": ["Alternative titles", "B-CELL GROWTH FACTOR 1"]} |
Restrictive dermopathy
Other namesHyperkeratosis-contracture syndrome, Lethal restrictive dermopathy
Restrictive dermopathy is inherited in an autosomal recessive manner[1]
SpecialtyMedical genetics
Restrictive dermopathy (RD) is a rare, lethal autosomal recessive skin condition characterized by syndromic facies, tight skin, sparse or absent eyelashes, and secondary joint changes.[2]:563
## Contents
* 1 Mechanism
* 2 Diagnosis
* 3 Treatment
* 4 See also
* 5 References
* 6 External links
## Mechanism[edit]
Restrictive dermopathy (RD) is caused either by the loss of the gene ZMPSTE24, which encodes a protein responsible for the cleavage of farnesylated prelamin A into mature non-farnesylated lamin, or by a mutation in the LMNA gene. This results in the accumulation of farnesyl-prelamin A at the nuclear membrane.[3] Mechanistically, restrictive dermopathy is somewhat similar to Hutchinson–Gilford progeria syndrome (HGPS), a disease where the last step in lamin processing is hindered by a mutation that causes the loss of the ZMPSTE24 cleavage site in the lamin A gene.[citation needed]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (August 2017)
## Treatment[edit]
This section is empty. You can help by adding to it. (August 2017)
## See also[edit]
* Relapsing linear acantholytic dermatosis
* List of cutaneous conditions
* Lamellar ichthyosis – Possible differential diagnosis
## References[edit]
1. ^ "OMIM Entry - # 275210 - RESTRICTIVE DERMOPATHY, LETHAL". omim.org. Retrieved 7 August 2017.
2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
3. ^ Young SG, Meta M, Yang SH, Fong LG (December 2006). "Prelamin A farnesylation and progeroid syndromes". J. Biol. Chem. 281 (52): 39741–39745. doi:10.1074/jbc.R600033200. PMID 17090536.
## External links[edit]
Classification
D
* ICD-10: Q82.8
* OMIM: 275210
* MeSH: C536920 C536920, C536920
* DiseasesDB: 32974
External resources
* Orphanet: 1662
* v
* t
* e
Progeroid syndromes
DNA repair
RecQ-associated
* Werner syndrome
* Bloom syndrome
* Rothmund–Thomson syndrome
NER protein-associated
* Cockayne syndrome
* Xeroderma pigmentosum
* Trichothiodystrophy
Lamin A/C
* Hutchinson–Gilford progeria syndrome
* Restrictive dermopathy
Other/related disorders
* Li–Fraumeni syndrome
* Rapadilino syndrome
* Baller–Gerold syndrome
* DeSanctis–Cacchione syndrome
* Nijmegen breakage syndrome
* Fanconi anemia
* Dyskeratosis congenita
* Ataxia telangiectasia
* De Barsy syndrome
* PIBI(D)S syndrome
* BIDS syndrome
* Marfanoid–progeroid–lipodystrophy syndrome
See also: DNA replication and repair-deficiency 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
| Restrictive dermopathy | c0406585 | 1,680 | wikipedia | https://en.wikipedia.org/wiki/Restrictive_dermopathy | 2021-01-18T18:37:59 | {"gard": ["1516"], "mesh": ["C536920"], "umls": ["C0406585"], "orphanet": ["1662"], "wikidata": ["Q7316329"]} |
Ord's disease
SpecialtyEndocrinology
Ord's thyroiditis is a common form of thyroiditis, an autoimmune disease where the body's own antibodies fight the cells of the thyroid.
It is named after the physician, William Miller Ord, who first described it in 1877 and again in 1888. It is more common among women than men.
## Contents
* 1 Signs and symptoms
* 2 Pathophysiology
* 3 Diagnosis
* 4 Treatment
* 5 Epidemiology
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
Symptoms of Ord's thyroiditis include symptoms of hypothyroidism and atrophy of the thyroid gland.[citation needed]
## Pathophysiology[edit]
Physiologically, antibodies to thyroid peroxidase and/or thyroglobulin cause gradual destruction of follicles in the thyroid gland. Accordingly, the disease can be detected clinically by looking for these antibodies in the blood. It is also characterised by invasion of the thyroid tissue by leukocytes, chiefly T-lymphocytes.[citation needed]
Ord's thyroiditis usually results in hypothyroidism. Transient hyperthyroid states in the acute phase, (a common observation in Hashimoto's thyroiditis), are rare in Ord's disease.[citation needed]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (October 2017)
## Treatment[edit]
Treatment is as with hypothyroidism, daily thyroxine(T4) and/or triiodothyronine(T3).[citation needed]
## Epidemiology[edit]
Outside Europe a goitrous form of autoimmune thyroiditis (Hashimoto's Thyroiditis) is more common than Ord's disease.[citation needed]
## See also[edit]
* Thyroiditis
* Hypothyroidism
* Hashimoto's thyroiditis
## References[edit]
* Davies, T. F. (2003), Ord-Hashimoto's Disease: Renaming a Common Disorder - Again. Thyroid 13 (4) 317. PMID 12820593.
* Williams D. (2003), Hashimoto's and Ord's diseases. Thyroid. 13(12): 1189. PMID 14751044
## External links[edit]
Classification
D
* ICD-10: E06.5
* ICD-9-CM: 245.8
* MeSH: D013967
* DiseasesDB: 34307
*[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
| Ord's thyroiditis | None | 1,681 | wikipedia | https://en.wikipedia.org/wiki/Ord%27s_thyroiditis | 2021-01-18T18:58:28 | {"icd-9": ["245.8"], "icd-10": ["E06.5"], "wikidata": ["Q7100346"]} |
Nasolacrimal duct cyst describes a unilateral or bilateral congenital cyst of the nasolacrimal duct, which is almost always associated with dacryocystocele, presenting most commonly at birth or a few weeks of age (but rarely presenting in adulthood) as a benign, grayish blue mass in the inferomedial canthus or in the nasal cavity, that can cause epiphora, dacryocystitis (inflammation of the lacrimal sac) and nasal obstruction. It is more commonly reported in females.
*[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
| Nasolacrimal duct cyst | c0155241 | 1,682 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141083 | 2021-01-23T19:03:42 | {"umls": ["C0155241"], "icd-10": ["H04.6"], "synonyms": ["Dacryocele", "Dacryocystocele", "Nasolacrimal mucocele"]} |
Charcot-Marie-Tooth disease type 4B3 (CMT4B3) is a subtype of Charcot-Marie-Tooth type 4 characterized by a childhood onset of slowly progressing, demyelinating sensorimotor neuropathy, focally folded myelin sheaths in nerve biopsy, reduced nerve conduction velocities (less than 38 m/s), and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, and sensory 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
| Charcot-Marie-Tooth disease type 4B3 | c3695063 | 1,683 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363981 | 2021-01-23T18:07:33 | {"omim": ["615284"], "icd-10": ["G60.0"], "synonyms": ["CMT4B3", "Charcot-Marie-Tooth disease with focally folded myelin"]} |
## Clinical Features
Beutler et al. (1985) found a family segregating for partial deficiency of 6-phosphogluconolactonase (PGLS; 604951) as an autosomal dominant trait. Hemolytic anemia occurred in a 14-month-old girl who was heterozygous for G6PD deficiency of nonhemolytic type and for 6PGL deficiency. The authors concluded that the child inherited the 6PGL deficiency from the mother and the G6PD variant from the father. Although he was not available for study, it was thought that he also gave the daughter alpha-thalassemia trait. The interaction of 6PGL deficiency with the G6PD polymorphic variant was thought to be responsible for the hemolytic anemia.
Inheritance \- Autosomal dominant Misc \- Interaction of 6PGL deficiency with G6PD variant Lab \- 6-Phosphogluconolactonase deficiency Heme \- Hemolytic anemia ▲ Close
*[v]: View this template
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*[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
| 6-PHOSPHOGLUCONOLACTONASE DEFICIENCY | c1868355 | 1,684 | omim | https://www.omim.org/entry/172150 | 2019-09-22T16:36:17 | {"mesh": ["C566803"], "omim": ["172150"], "synonyms": ["Alternative titles", "PGLS DEFICIENCY", "6PGL DEFICIENCY"]} |
MECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Most people with this condition also have weak muscle tone in infancy, feeding difficulties, poor or absent speech, or muscle stiffness (rigidity). Individuals with MECP2 duplication syndrome have delayed development of motor skills such as sitting and walking. About half of individuals have seizures, often of the tonic-clonic type. This type of seizure involves a loss of consciousness, muscle rigidity, and convulsions and may not respond to medication. Some affected individuals experience the loss of previously acquired skills (developmental regression). Approximately half of individuals learn to walk, and about one-third of people with this condition require assistance when walking. Many individuals with MECP2 duplication syndrome have recurrent respiratory tract infections. These respiratory infections are a major cause of death in affected individuals, with only half surviving past age 25.
## Frequency
The prevalence of MECP2 duplication syndrome is unknown; more than 200 affected individuals have been described in the scientific literature. It is estimated that this condition is responsible for 1 to 2 percent of all cases of intellectual disability caused by changes in the X chromosome.
## Causes
MECP2 duplication syndrome is caused by a genetic change in which there is an extra copy of the MECP2 gene in each cell. This extra copy of the MECP2 gene is caused by a duplication of genetic material on the long (q) arm of the X chromosome. The size of the duplication varies from 100,000 to a few million DNA building blocks (base pairs). The MECP2 gene is always included in this duplication, and other genes may also be involved, depending on the size of the duplicated segment. It is unclear whether extra copies of these other genes affect the severity of the condition.
The MECP2 gene provides instructions for making a protein called MeCP2 that is critical for normal brain function. Researchers believe that this protein has several functions, including regulating other genes in the brain by controlling when they are able to participate in protein production. An extra copy of the MECP2 gene leads to the production of excess MeCP2 protein and an increase in protein function. The resulting changes in gene regulation and protein production in the brain lead to abnormal nerve cell (neuronal) function. These neuronal changes disrupt normal brain activity, causing the signs and symptoms of MECP2 duplication syndrome.
### Learn more about the gene associated with MECP2 duplication syndrome
* MECP2
## Inheritance Pattern
MECP2 duplication syndrome is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes in each cell. In males (who have only one X chromosome), a duplication of the only copy of the MECP2 gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a duplication of one of the two copies of the gene typically does not cause the disorder, but can be associated with behavioral and psychiatric symptoms such as depression, anxiety, and features of autism spectrum disorder that affect communication and social interaction.
Females with a MECP2 gene duplication tend to be unaffected or less severely affected than males because the X chromosome that contains the duplication may be turned off (inactive) in many of their cells due to a process called X-inactivation. Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, such that each X chromosome is active in about half of the body's cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation.
Females with a MECP2 gene duplication often have skewed X-inactivation, which results in the inactivation of the X chromosome containing the duplication in most cells of the body. Although this skewed X-inactivation ensures that the chromosome with the normal MECP2 gene is active most often, some of these females develop behavioral and psychiatric symptoms thought to be related to the additional genetic material. It is unclear why these features develop in a small number of females with skewed X-inactivation. Researchers speculate that in these females some cells in the brain may have a different pattern of X-inactivation than the cells in the rest of the body so that the X chromosome with the duplicated MECP2 gene is active, resulting in behavioral and psychiatric symptoms.
*[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
| MECP2 duplication syndrome | c1846058 | 1,685 | medlineplus | https://medlineplus.gov/genetics/condition/mecp2-duplication-syndrome/ | 2021-01-27T08:24:51 | {"gard": ["9781"], "mesh": ["C537723"], "omim": ["300260"], "synonyms": []} |
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¡Aborto legal ya!, 'Legal abortion now!'—Pro-abortion banner at the Argentine Congress, 10 December 2020
Abortion in Argentina is legal up to the 14th week of pregnancy since January 2021, when the corresponding bill was signed into law by President Alberto Fernández, after being passed by the National Congress in December 2020.[1][2][3] After the 14th week, abortion is legal only in cases of rape or if the mother's health is in danger.[4] According to this law, any woman can request the procedure at any public or private health facility. Doctors are legally binded to either perform it or, if they are conscientious objectors, refer the patient to another physician or health facility.[5] The law will enter into force and be effective across Argentina 8 days after the signature and official publication, on the 24th January 2021. Only three other Latin American countries had previously legalised abortion on request: Cuba in 1965, Guyana in 1995 and Uruguay in 2012.[6] The latest polls showed 50-60% of Argentinians opposed the bill.[7]
The voluntary termination of pregnancy (IVE, by its Spanish acronym) was demanded by the feminist movement since the 1970s.[8] In 2005, the National Campaign for Legal, Safe and Free Abortion, an organisation that leads the cause for abortion legalisation, was founded.[9] Since 2007, the Campaign has anually submitted an abortion legalisation bill to the National Congress, but it was added to the legislative agenda for the first time in 2018,[10] when then President Mauricio Macri sponsored the debate. The bill was passed by the Chamber of Deputies, but rejected by the Senate.[11][12][13][14] In 2020, Alberto Fernandez fulfilled his campaign promise and sent a new, government-sponsored bill (slightly different to the one written by the Campaign) for legalising abortion on request up to the 14th week of pregnancy. [15] It was passed again by the Chamber of Deputies, and this time, by the Senate, in December 2020.[2]
Prior to 2020, a 1921 law regulated access to and penalties for abortions.[16] Induced abortion was considered a crime against a life and a person. Any woman that intentionally caused her own abortion or consented to another person performing one on her, was faced with one to four years of prison. In addition, any participant in the procedure could face up to fifteen years of prison, depending on the consent given by the woman, her eventual death and the intent of the participant. The same penalty applied to doctors, surgeons, midwives and pharmacists that induced or cooperated in the induction of an abortion, with the addition of a special license withdrawal for two times the length of their sentence. However, abortion could be performed legally by a certified doctor if:
1. It had been made to avoid a threat to the life or health of the woman and this danger could not be avoided by other means;
2. The pregnancy was a result of rape, or an indecent assault against a feeble-minded or demented woman.
The last and only official report on the number of abortions was published in 2005, and according to this report, there are around 370,000 to 520,000 both legal and illegal abortions per year in Argentina.[17][18] Many failed abortion attempts and deaths due to them are not recorded as such and/or are not notified to the authorities.[19][20][21] Enforcement of anti-abortion legislation is variable and complex; there are multiple NGOs providing women with help to access drugs that can interrupt pregnancies, as well as doctors who openly perform the procedure. The pro-life movement, along with the Catholic Church, have lobbied against any bill or protocol that makes abortion legal, and have even threatened to take the new abortion law to court.[22]
## Contents
* 1 Legal and political debate
* 1.1 2018 bill
* 1.2 2020 bill
* 2 Abortion protocols
* 3 Social debate
* 4 Recent cases
* 4.1 The 2006 cases
* 5 References
* 6 External links
## Legal and political debate[edit]
The Constitution of Argentina does not establish specific provisions for abortion, but the 1994 reform added constitutional status for a number of international pacts, such as the Pact of San José, which declares the right to life "in general, from the moment of conception". The interpretation of the expression "in general" in certain cases of abortion is still subject to debate.
In 1998, after a visit to the Vatican and an interview with Pope John Paul II, President Carlos Menem passed a decree declaring 25 March the Day of the Unborn Child. The date was due to the Catholic Holy Day of the Annunciation (that is, the conception, by the Blessed Virgin Mary, of Jesus Christ, the Son of God, in her womb). The Menem administration had already aligned with the Holy See in its complete rejection of abortion and contraception. During the first celebration of the new holiday, in 1999, the President stated that "the defense of life" was "a priority of [Argentina's] foreign policy".[23]
President Fernando de la Rúa (1999–2001) was not outspoken about its Catholic belief and its influence in government policies, but effectively kept them unchanged.
President Néstor Kirchner (elected in 2003) professed the Catholic faith but was considered more progressive than his predecessors. In 2005, Health Minister Ginés González García publicly stated his support for the legalization of abortion. Kirchner did neither support nor criticize González García's opinion in public. In a private interview, later, he assured that the law regarding abortion would not be changed during his term. In any case, harsh criticism from the Catholic Church soon shifted the focus to a "war of words" between the religious hierarchy and the national government.[24][25][26]
Carmen Argibay, the first woman ever to be appointed to the Supreme Court of Argentina by a democratic government, also caused great controversy as she admitted her support for abortion rights. Pro-life organizations, led by the Catholic Church, expressed their opposition to the appointment for this cause.[27][28]
In May 2006 the government made public a project to reform the Penal Code, which includes the de-criminalization of abortion. A commission studied the issue and produced a draft, intended to be presented to Congress. The project was signed by the Secretary of Criminal Policy and Penitentiary Affairs, Alejandro Slokar. On 28 May 2007, a group of 250 NGOs forming the National Campaign for Legal, Safe and Free Abortion presented a draft legislative bill to the Argentine Chamber of Deputies that would provide unrestricted access to abortion on demand up to the 12th week of pregnancy, and allow women to abort after that time in cases of rape, grave fetal malformations and mental or physical risk to the woman.[29] [30]
In March 2012 the Supreme Court ruled that abortion in case of rape or threat to women's life is legal and that an affidavit of being raped is enough to allow a legal abortion. It also ruled that provincial governments should write protocols for the request and treatment of legal abortions in case of rape or life threat.[31][32]
### 2018 bill[edit]
Main article: Voluntary Termination of Pregnancy Bill (Argentina)
In early 2018, after years of lobbying by different groups, then President Mauricio Macri encouraged the discussion of an abortion law during the 2018 opening of regular sessions of the National Congress of Argentina.[33] He stated that, despite identifying as anti-abortion on this issue, he would not ban a decision by Congress on the matter.[34][35] Therefore, Congress began debating a bill written by the National Campaign for Legal, Safe and Free Abortion, that would effectively legalize abortion on request in Argentina and make it available in all hospitals and clinics. The bill was debated alongside other measures to address gender inequality, such as extension of parental leave. On June 14, 2018, the Chamber of Deputies passed the bill with 129 votes for, 125 against and 1 abstention.[11][12][13] The proposal divided both the legislators of Cambiemos and the Justicialist Party.[36] However, on 9 August 2018 the bill was rejected by the Senate with 31 votes for, 38 against and 2 abstentions.[37]
### 2020 bill[edit]
Alberto Fernández, elected President of Argentina in 2019, made legal abortion a central point of his campaign.[38] Days after his inauguration, the Ministry of Health issued a protocol that stated how hospitals and clinics should handle abortion in case of rape.[39] Due to the COVID-19 pandemic, the introduction of the bill was postponed until November 2020.[40] In that month, the Argentinian government sent a bill that would legalise abortion on demand up to the 14th week, along with a second bill which aimed to protect women that chose to continue with their pregnancy.[41] After the 14th week, abortion would only be legal in cases of rape or if the mother's health is in danger.[42] This bill was first passed by the Chamber of Deputies 131 to 117 (with 6 abstentions) after a 20-hour debate[43] and later by the Senate 38 to 29 (with 1 abstention).[2] The bill's passing resulted in large-scale celebrations by pro-abortion activists who had long campaigned for the right to abortion.[44] Alberto Fernández signed the bill into law the 14th January 2021.[45]
## Abortion protocols[edit]
Provinces under the Nation Protocol
Sentenced by the court protocol (10)
Partially sentenced by the court protocol (6)
Without regulation protocols (8)
It is often the case that women who may have sought an abortion under the legal provisions of the Penal Code are not appropriately (or at all) informed of this possibility by the attending physicians, or are subject to long delays when they request a legal abortion. Physicians, due to lack of knowledge of the law and fearing legal punishment, often demand that the patient or her family request judicial authorization before terminating a pregnancy, which sometimes can extend the wait beyond the time when it is advisable to abort.
In March 2007, Buenos Aires Province health authorities released a protocol addressing the provision of legal abortion procedures without delays or need for judicial authorization. The main change regarding previous treatments of abortion was the explicit recognition that any case of rape can be a threat to the psychic health of the victim and thus justify an abortion request.[46]
An abortion protocol drafted by the National Institute Against Discrimination, Xenophobia and Racism (INADI) was presented, starting in May 2007, to provincial health ministers and legislatures for consideration. This protocol includes a series of procedures to be conducted in order to assess an abortion and the maximum permissible time spans for them. It also features a proposal to create a national registry of conscientious objectors.[47][48]
In June 2007, the legislative body of Rosario, Santa Fe Province, adopted a protocol similar to that of Buenos Aires. Physicians assisting a woman covered by Article 86 of the Penal Code are obligated to explain her condition to the patient, offering the choice of terminating the pregnancy, as well as counseling before and after the abortion. The protocol explicitly forbids the judicialization of the procedure and warns that physicians who delay a legal abortion are liable to administrative sanctions and civil or penal prosecution. [49] [50]
In November 2007, the legislature of La Pampa Province passed an abortion protocol law which included provisions for conscientious objectors and dictated that public hospitals would have to comply with an abortion request in any case. This would have made La Pampa the first district in Argentina to have an abortion protocol with the status of provincial law. [51] [52] The law, however, was vetoed by governor Oscar Mario Jorge as one of his first acts of government, less than three weeks later, with the argument that its new interpretation of previous legislation could be deemed unconstitutional. The protocol was attacked with the same argument by the bishop of Santa Rosa, Rinaldo Fidel Bredice, on the day it was first passed.[53]
On December 12, 2019, the Argentina Ministry of Health issued a protocol expanding hospital abortion access to pregnancies which resulted from rape.[39] In addition, the protocol provided that girls as young as 13 years of age can have abortions in such cases without the consent of either of their parents.[39] The protocol also weakened a doctor's ability to refuse to perform such abortions due to personal objection as well.[39]
Stages during pregnancy. Embryogenesis is marked in green. Weeks and months are numbered by gestation.
## Social debate[edit]
Argentina has a robust network of women's organizations whose demands include public access to abortion and contraception, such as the Women's Informative Network of Argentina (RIMA) and Catholic Women for the Right to Choose (Católicas por el Derecho a Decidir).[54] The National Women's Meeting [es], held annually in different cities, gathers these and other feminist and pro-abortion groups. The 34th Women's Meeting, held in October 2019 in La Plata, included a 200,000-people demonstration for, among other women's rights, legalization of abortion.[55]
The opposition to abortion is centered on two fronts: the religious one, led by the Catholic Church, and voiced by the ecclesiastical hierarchy[56] and a number of civil organizations, which consider abortion a murder; and the legal one, represented by those who claim that abortion is forbidden by the Constitution (which must override the Penal Code).[citation needed]
A December 2003 Graciela Romer y Asociados survey found that 30% of Argentines thought that abortion should be allowed "regardless of situation", 47% that it should be allowed "under some circumstances", and 23% that it should not be allowed "regardless of situation".[57]
A survey conducted in early 2005, commissioned by the Argentine branch of the Friedrich-Ebert Foundation, showed that 76% respondents were in favour of legalizing abortion for cases of rape (that is, regardless of the mental capacity of the woman), and that many (69%) also wanted abortion legalized when the fetus suffers from a deformity that will make it impossible for it to survive outside the womb.[58]
In a survey conducted in September 2011, nonprofit organization Catholics for Choice found that 45% of Argentineans were in favor of abortion for any reason in the first twelve weeks. This same poll conducted in September 2011 also suggested that most Argentineans favoured abortion being legal when a woman's health or life is at risk (81%), when the pregnancy is a result of rape (80%) or the fetus has severe abnormalities (68%).[59]
A March 2020 survey by the Universidad de San Andrés, found that 43% favor abortion "regardless of situation". In case of rape, an average of 75% agreed with abortion (with a 95% of non-believers agreed, while in the most religious segment fell to 69%).[60]
It is a common belief in Argentina that, the higher the economic status of the pregnant woman, the easier it is for her to get a safe abortion, while poorer women often cannot afford a clandestine procedure under sanitary conditions or post-abortion care.[61][62]
## Recent cases[edit]
Several cases of pregnancy resulting from rape and one involving a nonviable fetus have sparked debate about abortion in Argentina since the beginning of the 21st century. In 2001, 25-year-old Luciana Monzón, from Rosario, Santa Fe, discovered that the fetus in her womb, at 16 weeks of gestation, was anencephalic. There was virtually no chance of survival for the baby once it left the womb. Four weeks later she asked for judicial authorization to terminate the pregnancy. First one judge and then another excused themselves from dealing with the request, and the case went to the Supreme Court of Santa Fe, which dictated that the first judge should decide. By that time, however, Monzón had decided to take it to term, because of the delay. The baby was born spontaneously, weighing only 558 grams, and died 45 minutes after birth.[63][64][65]
In 2003, a 19-year-old rape victim from Jujuy Province, Romina Tejerina, had a baby in secret and killed her, according to tests, in a psychotic episode. In 2005 she was sentenced to 14 years in prison. She had not accused the rapist, and had managed to conceal her state. Townspeople, public figures and some politicians expressed her support for Tejerina as a victim, and many pointed out that she should have had the chance to resort to abortion. Most notably, the sentence prompted Health Minister Ginés González García to state his support for legal abortion for rape victims.[66][67][68]
### The 2006 cases[edit]
In 2006, two cases of rape of mentally disabled women became subject of extensive media coverage and debate. One of them involved 19-year-old L.M.R., from Guernica, Buenos Aires Province. Her mother noticed the pregnancy, guessed what had taken place, and went to the public San Martín Hospital in La Plata to request the abortion, allowed under the provisions of the Penal Code. The Ethics Committee of the hospital studied the case, as usual, but the prosecutor of the rape case alerted judge Inés Siro about the upcoming abortion, and Siro blocked it, based on "personal convictions". The block was appealed, and the Supreme Court of Buenos Aires overruled Siro, but the physicians at the hospital excused themselves saying that the pregnancy was now too advanced. The family of the victim was approached by a non-governmental organization that collected money and paid for the mentally disabled woman to have the abortion performed in a private context, by an undisclosed physician.
The other case, which came into the public light at about the same time, was that of a 25-year-old rape victim in Mendoza Province with an acute mental and physical disability. The mother of the victim requested and was granted judicial authorization, but as the pre-surgical tests were being performed at the Luis Lagomaggiore Hospital, the abortion was blocked by a judicial request (a kind of injunction) interposed by a Catholic organization. On appeal, the injunction was rejected by the Supreme Court of Mendoza, and the abortion was performed as originally planned.[69]
As a result of both cases, all but two of the provincial Health Ministers issued a joint statement supporting the medical teams and health authorities responsible for the abortions, and expressing their commitment to the law. Minister González García further stated that "there are fanatics that intimidate and threaten" and that "tolerance to fanatical groups must be ended".[70][71]
On 23 August 2006 the Argentine Episcopal Conference issued a document titled "A Question of Life or Death", stating the Church tries to protect life "moved by the deep love of God... [and] the desire of giving value to each of the lives that are conceived", and pleading not to "seed the culture of death in our society."[72]
## References[edit]
1. ^ Goñi, Uki; Phillips, Tom (30 December 2020). "Argentina legalises abortion in landmark moment for women's rights: Country becomes only the third in South America to permit elective abortions". Abortion. The Guardian. Archived from the original on 30 December 2020. Retrieved 30 December 2020.
2. ^ a b c Politi, Daniel; Londoño, Ernesto (30 December 2020). "Argentina Legalizes Abortion, a Milestone in a Conservative Region:The Senate vote on Wednesday was a major victory for Latin America's growing feminist movement, and its ripple effects are likely to be widespread". Americas. The New York Times. Archived from the original on 30 December 2020. Retrieved 30 December 2020.
3. ^ "Buenos Aires Times | Abortion becomes legal in Argentina as Chile starts a debate". batimes.com.ar. Retrieved 2021-01-15.
4. ^ "InfoLEG - Código Penal de la Nación Argentina". servicios.infoleg.gob.ar (in Spanish). 2021. Retrieved 2021-01-15.
5. ^ "BOLETÍN OFICIAL REPUBLICA ARGENTINA - Ley 27610 - ACCESO A LA INTERRUPCIÓN VOLUNTARIA DEL EMBARAZO -". www.boletinoficial.gob.ar (in Spanish). Retrieved 2021-01-16.
6. ^ Politi, Daniel; Londoño, Ernesto (2020-12-30). "Argentina Legalizes Abortion, a Milestone in a Conservative Region". The New York Times. ISSN 0362-4331. Retrieved 2021-01-15.
7. ^ San Martín, Inés (30 December 2020). "Argentine senate legalizes abortion in Pope Francis's homeland". Crux.
8. ^ Tarducci, Monica; Daich, Debora (2018). «Antropólogas feministas por el derecho a decidir. Aportes para una historia de la lucha por la despenalización y legalización del aborto en Argentina» (in Spanish). Publicar en Antropología y Ciencias Sociales (Argentina: Colegio de Graduados en Antropología de la República Argentina) (24). ISSN 0327-6627. Retrieved 2021-01-04.
9. ^ "Quiénes somos – Campaña Nacional por el Derecho al Aborto Legal Seguro y Gratuito" (in Spanish). Retrieved 2021-01-15.
10. ^ "Aborto: finalmente Macri pidió que se abra el debate". www.lanacion.com.ar (in Spanish). Retrieved 2021-01-15.
11. ^ a b "Aborto: ahora la discusión se traslada al Senado, donde hay más resistencias" (in Spanish). Retrieved 14 June 2018.
12. ^ a b "Uno por uno, cómo votó cada diputado el proyecto de legalización del aborto" (in Spanish). Retrieved 14 June 2018.
13. ^ a b Abrevaya, Sebastian (15 June 2018). "La ola verde llega al Senado | Cómo recibirá la Cámara alta el proyecto de despenalización del aborto". PAGINA12 (in Spanish). Retrieved 14 June 2018.
14. ^ "Argentina senate rejects bill to legalise abortion". the Guardian. 2018-08-09. Retrieved 2021-01-15.
15. ^ "Buenos Aires Times | Fernández sends Congress bill to legalise abortion in Argentina". www.batimes.com.ar. Retrieved 2021-01-15.
16. ^ "InfoLEG - Código Penal de la Nación Argentina". servicios.infoleg.gob.ar (in Spanish). 1921. Retrieved 2021-01-15.
17. ^ Mario, Silvia; Pantelides, Edith Alejandra (2009). "Estimación de la magnitud del aborto inducido en la Argentina" (in Spanish). Cite journal requires `|journal=` (help)
18. ^ "Legalización del aborto: ¿qué datos existen en la Argentina?". Chequeado (in Spanish). Retrieved 2021-01-15.
19. ^ "Argentina: Limits on Birth Control Threaten Human Rights". Human Rights Watch. Archived from the original on 2006-09-10. Retrieved 2006-08-28.
20. ^ "The International Encyclopedia of Sexuality: Argentina". Humboldt-Universität zu Berlin. Archived from the original on 31 August 2006. Retrieved 2006-08-28.
21. ^ Nadia Berenstein. "Abortion in Argentina". Planned Parenthood. Archived from the original on October 12, 2006. Retrieved 2006-08-28.
22. ^ mdzol.com. "Los celestes irán por la inconstitucionalidad del aborto y denunciarán al Gobierno por "genocidio"". MdzOnline (in Spanish). Retrieved 2021-01-15.
23. ^ "Speech by President Menem during the commemoration of the Day of the Unborn Child" (in Spanish). 25 March 1999. Archived from the original on 22 September 2008. Retrieved 31 August 2006.
24. ^ "'Me ofrecieron millones para frenar los genéricos'" (in Spanish). Página/12. 2005-02-14. Retrieved 2006-08-29.
25. ^ "Argentinean Health Minister declares legalization of abortion part of his agenda". Catholic News Agency. 2005-02-15. Retrieved 2006-08-29.
26. ^ "Argentina: Row Over Church & State". About.com. 2005-02-19. Retrieved 2006-08-29.
27. ^ "Atheist Heads to High Court Seat". Institute for Humanist Studies. 2004-01-28. Archived from the original on October 28, 2007. Retrieved 2006-08-29.
28. ^ "Impugnaciones a la doctora Argibay" (in Spanish). Argentine Catholic News Agency. Archived from the original on 23 August 2006. Retrieved 2006-08-29.
29. ^ "Para que la maternidad sea una elección" (in Spanish). Página/12. 28 May 2007. Archived from the original on 22 June 2007. Retrieved 2007-06-02.
30. ^ Marcela Valente. "ARGENTINA: Abortion - No Longer a Taboo Subject". Inter Press Service. Archived from the original on 2007-06-12.
31. ^ "El fallo que pone en vereda a jueces y médicos". Página/12 (in Spanish). Retrieved 2020-12-31.
32. ^ "La Corte Suprema precisó el alcance del aborto no punible y dijo que estos casos no deben ser judicializados". CIJ (Centro de información judicial). Retrieved 2020-12-31.
33. ^ "Mauricio Macri en el Congreso: reviví el minuto a minuto de la Asamblea Legislativa" [Mauricio Macri in the Congress, relive the minute by minute of the Legislative assembly] (in Spanish). La Nación. March 1, 2018. Retrieved February 28, 2018.
34. ^ "Macri asegura que no vetará la ley del aborto en Argentina si es aprobada por el Senado". abc (in Spanish). 2018-07-12. Retrieved 2020-12-31.
35. ^ "Radiografia del Aborto en Argentina" (in Spanish). Telam. Retrieved 2018-03-09.
36. ^ "Argentina lower house passes legal abortion bill in tight vote". Reuters. June 14, 2018. Retrieved July 10, 2018.
37. ^ "Legal abortion bill rejected in Argentina". BBC News. 2018-08-09. Retrieved 2018-08-10.
38. ^ Clarín.com (2019-08-13). "Alberto Fernández, sobre el aborto: 'Tengo la decisión política de legalizarlo'". www.clarin.com (in Spanish). Retrieved 2021-01-15.
39. ^ a b c d Reuters (2019-12-12). "Argentina Moves to Guarantee Abortion Access in Rape Cases (Published 2019)". The New York Times. ISSN 0362-4331. Retrieved 2021-01-15.
40. ^ "Alberto Fernández aseguró que postergó el envío de la ley de aborto al Congreso por la pandemia de coronavirus". infobae (in Spanish). 19 June 2020. Retrieved 2021-01-15.
41. ^ "Alberto Fernández envió al Congreso el proyecto de legalización del aborto y el plan de los 1000 días". www.telam.com.ar (in Spanish). Retrieved 2021-01-15.
42. ^ Página12 (30 December 2020). "Aborto legal: qué dice la ley | Los principales puntos texto que sancionó el Senado". PAGINA12 (in Spanish). Retrieved 2021-01-15.
43. ^ "La Cámara de Diputados de Argentina aprueba el proyecto para legalizar el aborto, que deberá recibir el visto bueno del Senado". BBC News Mundo (in Spanish). Retrieved 2021-01-15.
44. ^ Uki Goñi & Tom Phillips (11 December 2020). "Argentina's lower house passes bill to allow abortion". The Guardian. Retrieved 12 December 2020.
45. ^ "Alberto Fernández promulgó la ley del aborto: "Estoy muy feliz de estar poniéndole fin al patriarcado"". infobae (in Spanish). Retrieved 2021-01-15.
46. ^ "Guía pública para los abortos no punibles" (in Spanish). Página/12. 18 March 2007. Retrieved 2007-03-18.
47. ^ "Pasos y plazos ante un caso" (in Spanish). Página/12. 23 May 2007. Retrieved 2007-06-15.
48. ^ "General Recommendation No. 002/07: Discrimination in the provision of healthcare for cases of legal abortion and post-abortion treatment" (PDF) (in Spanish). INADI. 23 May 2007. Archived from the original (PDF) on 2007-09-28. Retrieved 2007-06-15.
49. ^ "Para que no haya ninguna duda" (in Spanish). Rosario/12. 15 June 2007. Retrieved 2007-06-15.
50. ^ Pablo Colono (March 2007). "Project of bill for the creation of a "Protocol for the Integral Attention of the Woman in Cases of Non-punishable Abortion"" (in Spanish). Deliberative Council of Rosario. Archived from the original on 2007-10-09.
51. ^ "Un derecho garantizado por ley" (in Spanish). Página/12. 28 November 2007. Archived from the original on 30 November 2007. Retrieved 2007-11-28.
52. ^ "Abortos no punibles garantizados" (in Spanish). Página/12. 29 November 2007. Archived from the original on 2 December 2007. Retrieved 2007-11-29.
53. ^ "Un veto de la hostia" (in Spanish). Página/12. 18 December 2007. Archived from the original on 20 December 2007. Retrieved 2007-12-18.
54. ^ Tessa, Sonia (2020-12-30). "Estoy llorando" [I'm crying]. PAGINA12 (in Spanish). Retrieved 2021-01-03.
55. ^ Iglesias, Mariana (2019-10-16). "Video: lo que dejó el Encuentro Nacional de Mujeres en La Plata". www.clarin.com (in Spanish). Archived from the original on 2020-11-26. Retrieved 2021-01-03.
56. ^ Sastre, Ángel (2020-12-30). "Argentina legaliza el aborto hasta las 14 semanas de embarazo". La Razón (in Spanish). Retrieved 2021-01-03.
57. ^ "Argentines Assess Abortion Changes." (Mar. 4, 2004). Angus Reid Global Monitor. Retrieved January 10, 2006.
58. ^ Carbajal, Mariana (2005-04-19). "El aborto, una práctica naturalizada" [Abortion, a naturalized practice]. Página/12 (in Spanish). Retrieved 2020-12-31.
59. ^ "Views on Changing the Law on Abortion in Argentina" (PDF). Belden Russonello Strategists LLC. October 2011. Archived from the original (PDF) on 2012-05-24. Retrieved 2011-11-22.
60. ^ "Según una encuesta realizada en el país, el 43% de los argentinos aprueba el aborto "en cualquier caso"" [According to a survey carried out in the country, 43% of Argentines approve of abortion "in any case"]. Infobae (in Spanish). 2020-03-08. Retrieved 2020-12-31.
61. ^ ""El aborto se practica en todas las clases sociales, pero solamente mueren las mujeres pobres"" [Abortion is practiced in all social classes, but only poor women die]. DiarioJornada. Retrieved 2020-12-31.
62. ^ Fernández, Ana M. (2004-12-16). "Psicología :: Pobres abortos de niñas ricas" [Poor rich girl abortions]. Pagina/12 (in Spanish). Retrieved 2020-12-31.
63. ^ "Una mujer aún espera que la Justicia responda a su pedido de aborto terapéutico" (in Spanish). La Capital. 2001-10-23. Retrieved 2006-08-28.
64. ^ "Anencefalia: sigue con su embarazo por una demora de la Justicia" (in Spanish). Clarín. 2001-11-03. Retrieved 2006-08-28.
65. ^ "Muere bebé de mujer que había solicitado a la justicia abortar" (in Spanish). CIMAC Noticias. 2001-11-14. Archived from the original on 2006-08-23. Retrieved 2006-08-28.
66. ^ "Romina Tejerina: "Si hubiera quedado embarazada de quien quería, no lo habría hecho"" (in Spanish). Clarín. 2005-06-12. Retrieved 2006-08-28.
67. ^ Popper, Helen (2005-06-05). "Jailed baby killer fuels debate on abortion after rape". London: Guardian Unlimited. Retrieved 2006-08-28.
68. ^ "Promising Signs in Argentine Struggle for Safe, Legal Abortion". OneWorld.net. 2005-05-28. Archived from the original on 2006-01-14. Retrieved 2006-08-28.
69. ^ "Otro pedido de aborto para una discapacitada" (in Spanish). La Nación. 2006-08-18. Retrieved 2006-08-28.
70. ^ "Ministros de salud de todo el país apoyaron la práctica del aborto" (in Spanish). La Nación. 2006-08-24. Retrieved 2006-08-28.
71. ^ "Church defends abortion stance". Buenos Aires Herald. 2006-08-27. Archived from the original on September 28, 2007. Retrieved 2006-08-28.
72. ^ "Una cuestión de vida o muerte" (in Spanish). Argentine Episcopal Conference. 2006-08-23.
## External links[edit]
* (in Spanish) Red Informativa de Mujeres de Argentina (Women's Informative Network of Argentina, RIMA).
* (in Spanish) Católicas por el Derecho a Decidir (Catholic Women for the Right to Decide).
* (in Spanish) Derecho al Aborto (Right to Abortion)
* (in Spanish) Vida Humana Internacional (Latin American chapter of Human Life International)
* (in Spanish) Pro Vida
* (in Spanish) Fundación 25 de Marzo (25 March Foundation).
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*[v]: View this template
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*[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
| Abortion in Argentina | None | 1,686 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_Argentina | 2021-01-18T18:51:22 | {"wikidata": ["Q8184130"]} |
A Dolichodouglas (word derived from ancient Greek Δόλιχος (dolichos), the long distance in running and the Douglas' pouch) is the medical term describing an abnormally profound Douglas' pouch (recto-uterine pouch). It may be congenital or acquired. The increased depth of the Douglas' pouch brings it in close anatomical contact with the posterior vaginal wall. Therefore, intestinal loops may apply pressure to this wall, causing a condition known as enterocele, which presents as an outpouching on the posterior vaginal wall. This can be felt and seen during pelvic exam.
[1]JTA 2001 : Elytrocele
This anatomy article is a stub. You can help Wikipedia by expanding it.
* v
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* e
*[v]: View this template
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*[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
| Dolichodouglas | None | 1,687 | wikipedia | https://en.wikipedia.org/wiki/Dolichodouglas | 2021-01-18T18:35:55 | {"wikidata": ["Q5289044"]} |
Sialuria is a rare disorder that has variable effects on development. Affected infants are often born with a yellow tint to the skin and the whites of the eyes (neonatal jaundice), an enlarged liver and spleen (hepatosplenomegaly), and unusually small red blood cells (microcytic anemia). They may develop a somewhat flat face and distinctive-looking facial features that are described as "coarse." Temporarily delayed development and weak muscle tone (hypotonia) have also been reported.
Young children with sialuria tend to have frequent upper respiratory infections and episodes of dehydration and stomach upset (gastroenteritis). Older children may have seizures and learning difficulties. In some affected children, intellectual development is nearly normal.
The features of sialuria vary widely among affected people. Many of the problems associated with this disorder appear to improve with age, although little is known about the long-term effects of the disease. It is likely that some adults with sialuria never come to medical attention because they have very mild signs and symptoms or no health problems related to the condition.
## Frequency
Fewer than 10 people worldwide have been diagnosed with sialuria. There are probably more people with the disorder who have not been diagnosed, as sialuria can be difficult to detect because of its variable features.
## Causes
Mutations in the GNE gene cause sialuria. The GNE gene provides instructions for making an enzyme found in cells and tissues throughout the body. This enzyme is involved in a chemical pathway that produces sialic acid, which is a simple sugar that attaches to the ends of more complex molecules on the surface of cells. By modifying these molecules, sialic acid influences a wide variety of cellular functions including cell movement (migration), attachment of cells to one another (adhesion), signaling between cells, and inflammation.
The enzyme produced from the GNE gene is carefully controlled to ensure that cells produce an appropriate amount of sialic acid. A feedback system shuts off the enzyme when no more sialic acid is needed. The mutations responsible for sialuria disrupt this feedback mechanism, resulting in an overproduction of sialic acid. This simple sugar builds up within cells and is excreted in urine. Researchers are working to determine how an accumulation of sialic acid in the body interferes with normal development in people with sialuria.
### Learn more about the gene associated with Sialuria
* GNE
## Inheritance Pattern
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most reported cases have occurred in people with no known history of the disorder in their family and may result from new mutations in the gene.
*[v]: View this template
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*[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
| Sialuria | c0342853 | 1,688 | medlineplus | https://medlineplus.gov/genetics/condition/sialuria/ | 2021-01-27T08:24:43 | {"gard": ["4865"], "mesh": ["D029461"], "omim": ["269921"], "synonyms": []} |
Multiple sulfatase deficiency (MSD) is a very rare and fatal lysosomal storage disease characterized by a clinical phenotype that combines the features of different sulfatase deficiencies (whether lysosomal or not) that can have neonatal (most severe), infantile (most common) and juvenile (rare) presentations with manifestations including hypotonia, coarse facial features, mild deafness, skeletal anomalies, ichthyosis, hepatomegaly, developmental delay, progressive neurologic deterioration and hydrocephalus.
*[v]: View this template
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*[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
| Multiple sulfatase deficiency | c0268263 | 1,689 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=585 | 2021-01-23T18:14:20 | {"gard": ["5061"], "mesh": ["D052517"], "omim": ["272200"], "umls": ["C0268263", "C1720864"], "icd-10": ["E75.2"], "synonyms": ["Juvenile sulfatidosis, Austin type", "MSD", "Mucosulfatidosis"]} |
Weaver syndrome is a rare condition that is characterized primarily by tall stature. Other signs and symptoms of the condition may include macrocephaly (unusually large head size); intellectual disability; distinctive facial features; camptodactyly (permanently bent digits) of the fingers and/or toes; poor coordination; soft and doughy skin; umbilical hernia; abnormal muscle tone; and a hoarse, low-pitched cry during infancy. Some studies also suggest that people affected by Weaver syndrome may have an increased risk of developing neuroblastoma. Weaver syndrome is usually caused by changes (mutations) in the EZH2 gene. Although the condition is considered autosomal dominant, most cases occur as de novo mutations in people with no family history of the condition. Treatment is based on the signs and symptoms present in each person.
*[v]: View this template
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*[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
| Weaver syndrome | c0265210 | 1,690 | gard | https://rarediseases.info.nih.gov/diseases/7878/weaver-syndrome | 2021-01-18T17:57:07 | {"mesh": ["C536687"], "omim": ["277590"], "orphanet": ["3447"], "synonyms": ["Weaver Smith syndrome", "WSS", "Overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly", "Camptodactyly - overgrowth - unusual facies", "Camptodactyly-overgrowth-unusual facies syndrome", "EZH2 Related Overgrowth", "Weaver like syndrome"]} |
A rare association syndrome, reported in several members of two families to date, characterized by arterial dissection, occurring at an early age and presenting with a range of manifestations depending on the vascular territory involved (ex. headache, dysphasia, hemiparesis), in association with cystic medial necrosis and multiple lentigines (brown and black in color and mainly affecting the skin of the trunk and extremities).
*[v]: View this template
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*[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
| Arterial dissection-lentiginosis syndrome | c1838122 | 1,691 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1682 | 2021-01-23T17:18:09 | {"mesh": ["C563937"], "omim": ["600459"], "umls": ["C1838122"], "icd-10": ["Q87.8"]} |
A number sign (#) is used with this entry because of evidence that variation in the TPCN2 gene (612163), located on chromosome 11q13, influences skin, hair, and eye pigmentation.
For a general phenotypic description and a discussion of genetic heterogeneity of variation in skin, hair, and eye pigmentation, see 227220.
Molecular Genetics
Sulem et al. (2008) presented results from a genomewide association study for variants associated with human pigmentation characteristics among 5,130 Icelanders, with follow-up analyses in 2,116 Icelanders and 1,214 Dutch individuals. The authors found 4 single-nucleotide polymorphisms (SNPs) on chromosome 11q13.2 that showed association with blond versus brown hair color in the Icelandic discovery sample that reached genomewide significance. These SNPs were located within a single linkage disequilibrium block that overlaps with only one gene, TPCN2. Sulem et al. (2008) identified 3 common nonsynonymous variants in exons of TPCN2 that, on the basis of HapMap data, correlated with the 4 SNPs originally showing significant association. All of the observed association with blond versus brown hair could be explained by 2 of the coding SNPs: rs35264875 (612163.0001) and rs3829241 (612163.0002).
*[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
| SKIN/HAIR/EYE PIGMENTATION, VARIATION IN, 10 | c2677088 | 1,692 | omim | https://www.omim.org/entry/612267 | 2019-09-22T16:02:00 | {"mesh": ["C567376"], "omim": ["612267"], "synonyms": ["Alternative titles", "SKIN/HAIR/EYE PIGMENTATION 10, BLOND/BROWN HAIR"]} |
For other uses, see Evil Eye (disambiguation).
Curse believed to be cast by a malevolent glare, causing many cultures to create measures against it
Part of a series on the
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* v
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Nazars, charms used to ward off the evil eye.
The evil eye (Greek:[1] Mάτι, meaning "eye")(Hebrew: עין הרע) is a superstitious curse or legend originating [2] in Ancient Greece and Rome, believed to be cast by a malevolent glare, usually given to a person when one is unaware. It is a type of apotropaic magic. Many cultures believe that receiving the evil eye will cause misfortune or injury,[3] while others believe it to be a kind of supernatural force that casts or reflects a malevolent gaze back-upon those who wish harm upon others (especially innocents). Talismans or amulets created to protect against the evil eye are also frequently called "evil eyes".[4][5] Older iterations of the symbol were often made by ceramic or clay, however, proceeding the production of glass beads in the Mediterranean in approximately 1500 B.C., evil eye beads popularised with the Phonecians, Greeks, Romans and Ottomans.[6] Blue was likely used as it was relatively easy to create, however, modern evil eyes can be a range of colors.
The idea expressed by the term causes many different cultures to pursue protective measures against it, with around 40% of the world's population believing in the evil eye.[7] The concept and its significance vary widely among different cultures, but it is especially prominent in the Mediterranean and West Asia. The idea appears multiple times in Jewish rabbinic literature.[8] It was a widely extended belief among many Mediterranean and Asian tribes and cultures. Charms and decorations with eye-like symbols known as nazars, which are used to repel the evil eye, are a common sight across Cyprus, Greece, Portugal, Brazil, Israel, Ethiopia, Georgia, Armenia, Azerbaijan, Albania, Algeria, Tunisia, Lebanon, Turkey, Palestine, Egypt, Jordan, Saudi Arabia, Bangladesh, Iran, Iraq, Italy, Nepal, Pakistan, parts of India, Utah, Morocco, southern Spain, parts of Mexico, Malta, Montenegro, Romania, North Macedonia, Bulgaria, the Balkans, the Levant, Afghanistan, Syria, and Bahrain, and have become a popular choice of souvenir with tourists. Other popular amulets and talismans used to ward off the evil eye include the hamsa, while Italy (especially Southern Italy) employs a variety of other unique charms and gestures to defend against the evil eye, including the cornicello, the cimaruta, and the sign of the horns. While the Egyptian Eye of Horus is a similar symbol of protection and good health, the Greek evil eye talisman specifically protects against malevolent gazes.
## Contents
* 1 History
* 1.1 Classical antiquity
* 1.1.1 Protection from the eye
* 2 Around the world
* 3 Protective talismans and cures
* 3.1 Caribbean/West Indies
* 3.2 Greece
* 3.3 In Islam
* 3.4 Assyrians
* 3.5 In Judaism
* 3.6 Turkey
* 3.7 Ethiopia
* 3.8 Senegal
* 3.9 Pakistan
* 3.10 Italy
* 3.11 Malta
* 3.12 Brazil
* 3.13 Spain and Latin America
* 3.13.1 Mexico
* 3.13.2 Puerto Rico
* 3.14 India
* 3.15 United States
* 4 Media and press coverage
* 5 Names in various languages
* 6 See also
* 6.1 Amulets and other protections
* 6.2 Creatures
* 6.3 Concepts
* 7 Notes
* 8 References
* 9 Further reading
* 10 External links
## History[edit]
Belief in the evil eye dates back to Greek Classical antiquity. It is referenced by Hesiod, Callimachus, Plato, Diodorus Siculus, Theocritus, Plutarch, Heliodorus, Pliny the Elder, and Aulus Gellius. Peter Walcot's Envy and the Greeks (1978) listed more than one hundred works by these and other authors mentioning the evil eye. Noting, that Greeks as an ethnic group are indigenous to South-East Europe and Asia Minor this makes the evil eye native to those regions.
### Classical antiquity[edit]
Roman-era mosaic from Antioch depicting a plethora of devices against the evil eye
Classical authors attempted both to describe and to explain the function of the evil eye. Plutarch's scientific explanation stated that the eyes were the chief, if not sole, source of the deadly rays that were supposed to spring up like poisoned darts from the inner recesses of a person possessing the evil eye. Plutarch treated the phenomenon of the evil eye as something seemingly inexplicable that is a source of wonder and cause of incredulity.[a] Pliny the Elder described the ability of certain African enchanters to have the "power of fascination with the eyes and can even kill those on whom they fix their gaze".[b]
The idea of the evil eye appears in the poetry of Virgil in a conversation between the shepherds Menalcas and Damoetas.[c] In the passage, Menalcas is lamenting the poor health of his stock: "What eye is it that has fascinated my tender lambs?".
#### Protection from the eye[edit]
The belief in the evil eye during antiquity varied across different regions and periods. The evil eye was not feared with equal intensity in every corner of the Roman Empire. There were places in which people felt more conscious of the danger of the evil eye. In Roman times, not only were individuals considered to possess the power of the evil eye but whole tribes, especially those of Pontus and Scythia, were believed to be transmitters of the evil eye.[citation needed]
The phallic charm called fascinum in Latin, from the verb fascinare, "to cast a spell" (the origin of the English word "fascinate") is one example of an apotropaic object used against the evil eye. They have been found throughout Europe and into the Middle East from contexts dating from the first century BC to the fourth century AD.[9] The phallic charms were often objects of personal adornment (such as pendants and finger rings), but also appeared as stone carvings on buildings,[10] mosaics, and wind-chimes (tintinnabula).[11][12] Examples of stone phallic carvings, such as from Leptis Magna, depict a disembodied phallus attacking an evil eye by ejaculating towards it.[10]
In describing their ability to deflect the Evil Eye, Ralph Merrifield described the Roman phallic charm as a "kind of lightning conductor for good luck".[13]
## Around the world[edit]
Tree with nazars in Cappadocia, Turkey.
John Phillip, The Evil Eye (1859), a self-portrait depicting the artist sketching a Spanish gypsy who thinks she is being given the evil eye.
Belief in the evil eye is strongest in West Asia, Latin America, East and West Africa, Central America, South Asia, Central Asia, and Europe, especially the Mediterranean region; it has also spread to areas, including northern Europe, particularly in the Celtic regions, and the Americas, where it was brought by European colonists and West Asian immigrants.[citation needed]
Belief in the evil eye is found in the Islamic doctrine, based upon the statement of Prophet Muhammad, "The influence of an evil eye is a fact..." [Sahih Muslim, Book 26, Number 5427].[14] Authentic practices of warding off the evil eye are also commonly practiced by Muslims: rather than directly expressing appreciation of, for example, a child's beauty, it is customary to say Masha'Allah, that is, "God has willed it", or invoking God's blessings upon the object or person that is being admired.[15] A number of beliefs about the evil eye are also found in folk religion, typically revolving around the use of amulets or talismans as a means of protection.
In the Aegean Region and other areas where light-colored eyes are relatively rare, people with green eyes, and especially blue eyes, are thought to bestow the curse, intentionally or unintentionally.[16] Thus, in Greece and Turkey amulets against the evil eye take the form of blue eyes, and in the painting by John Phillip, below, we witness the culture-clash experienced by a woman who suspects that the artist's gaze implies that he is looking at her with the evil eye.
Among those who do not take the evil eye literally, either by reason of the culture in which they were raised or because they simply do not believe it, the phrase, "to give someone the evil eye" usually means simply to glare at the person in anger or disgust. The term has entered into common usage within the English language. Within the broadcasting industry it refers to when a presenter signals to the interviewee or co-presenter to stop talking due to a shortage of time.[citation needed]
## Protective talismans and cures[edit]
The Hamsa, a charm made to ward off the evil eye.
Attempts to ward off the curse of the evil eye have resulted in a number of talismans in many cultures. As a class, they are called "apotropaic" (Greek for "prophylactic" / προφυλακτικός or "protective", literally: "turns away") talismans, meaning that they turn away or turn back harm.
Disks or balls, consisting of concentric blue and white circles (usually, from inside to outside, dark blue, light blue, white, and dark blue) representing an evil eye are common apotropaic talismans in West Asia, found on the prows of Mediterranean boats and elsewhere; in some forms of the folklore, the staring eyes are supposed to bend the malicious gaze back to the sorcerer.
Known as nazar (Turkish: nazar boncuğu or nazarlık), this talisman is most frequently seen in Turkey, found in or on houses and vehicles or worn as beads
Detail of a 19th-century Anatolian kilim, with rows of crosses (Turkish: Haç) and scattered S-shaped hooks (Turkish: Çengel), both to ward off the evil eye[17]
A blue or green eye can also be found on some forms of the hamsa hand, an apotropaic hand-shaped talisman against the evil eye found in West Asia. The word hamsa, also spelled khamsa and hamesh, means "five" referring to the fingers of the hand. In Jewish culture, the hamsa is called the Hand of Miriam; in some Muslim cultures, the Hand of Fatima. Though condemned as superstition by doctrinaire Muslims, it is almost exclusively among Muslims in the Near East and Mediterranean that the belief in envious looks containing destructive power or the talismanic power of a nazar to defend against them. To adherents of other faiths in the region, the nazar is an attractive decoration
A variety of motifs to ward off the evil eye are commonly woven into tribal kilim rugs. Such motifs include a cross (Turkish: Haç) to divide the evil eye into four, a hook (Turkish: Çengel) to destroy the evil eye, or a human eye (Turkish: Göz) to avert the evil gaze. The shape of a lucky amulet (Turkish: Muska; often, a triangular package containing a sacred verse) is often woven into kilims for the same reason.[17]
### Caribbean/West Indies[edit]
In Trinidad and Tobago, the evil eye is called maljo (from French mal yeux, meaning 'bad eye'). The term is used in the infinitive (to maljo) and as a noun (to have/get maljo) referring to persons who have been afflicted. Maljo may be passed on inadvertently, but is believed to be more severe when coming from an envious person or one with bad intentions. It is thought to happen more readily when a person is stared at- especially while eating food. A person who has been taken by the ‘bad eye’ may experience unexplained illness or misfortune. In traditional rural legends, ‘The general belief is that doctors cannot cure maljo----only people who know prayers can "cut" the maljo and thus cure the victim.’
[18]
There are several secular approaches to combatting maljo, but more extreme cases are usually referred to spiritual rituals, with a particularly strong influence from the Hindu religion.
In non-religious respects, there is a strong cultural association that between the evil eye and the colour blue. It is believed to ward off maljo when worn as clothing or accessories, so much so that some striking shades are referred to as ‘maljo blue’. Blue ornaments may be used to protect a household, and blue Milk of Magnesia bottles are sometimes hung on bearing fruit trees or in placed in the yard surrounding the property.
Blue soap and Albion Blue (an indigo dye referred to Trinbagonians simply as ‘blue’) are traditionally used for domestic washing, but are also considered to prevent maljo if used in bath water, or to anoint the soles of the feet.
Jumbie beads are the poisonous seeds of the Rosary Pea tree which are used to make jewelry that also wards off maljo and evil spirits.
One superstition is that a pinch can reverse maljo following interpersonal interactions, especially if one is stared at or given a compliment. Some also believe that rubbing one's own saliva in their hair will counteract maljo in general, but particularly from envy of the hair texture and length.
A bath in the sea is also thought to relieve an afflicted person.
Maljo believers are particularly concerned with safeguarding babies and children, who are considered to be most vulnerable to its effects. It may be ‘caused by someone born with a "blight" in the eye, when such a person looks admiringly at a child. It can also occur with a pat on the head, or with just a glance. Whether it is intended or not, compliments (…) can cause maljo. It can be caused by a stranger, a member of the child's immediate family or by another relative.’[18] It may even be passed on by a parent who is obsessed with their own child. A baby with maljo ‘refuses to eat or drink, cries continually and “pines away.”. It may have an “attack of fever”.’[19]
Bracelets made of jet beads are traditionally given to newborns to wear as a preventative measure, while elders also recommend securing a bag of blue (dye) to the baby's clothes.
Following East Indian influence, a tikka is a black dot that is placed on a baby’s forehead- thought to distract the attention of the evil eye and protect the child as such.
The most common maljo remedy comes in the form of a Hindu ritual called a jharay. It may be practised at home (usually by parents or elders) or by a pundit or spiritual practitioner. There are many variations to the ritual, and non-Hindu persons readily participate if they are considered to have been affected by maljo.
The main implement in a jharay is either a peacock feather or a cocoyea broom\- a traditional broom made using the midrib of the coconut palm leaf. Some also report a knife or machete being used. In some instances, the cocoyea broom is measured against a particular part of the body at the beginning of the ceremony, and it is believed to be confirmation of maljo if the recorded length has changed by the end of the session. The officiant will say a prayer while using the tool of choice to brush the person from head to toe. The prayer is conventionally said in Hindi, but may also be said in English.
A jharay may focus on a specific point of affliction or pain (head, hair, back, feet and so on).
It is not unusual for a jharay ceremony to be carried out on children and babies. ‘People believe that maljo can cause death. Two types were reported: the "'dragging" kind, where the baby gets smaller and smaller and goes through all of the symptoms mentioned above, before withering and dying; the "Twenty-four hour" maljo, said to kill in just twenty-four hours if effective help is not obtained.’[18]
Another Hindu ritual called the oucchay is also employed to heal maljo- though this might also be interchangeably called a jharay. Ingredients such as onion skin, salt, cobweb, hot pepper or mustard seeds, piece of a cocoyea broom, a lock of the victim’s hair (in the case of children, it is a lock of the mother’s hair) are wrapped in a tissue or newspaper. The officiant will circle the wrapped objects around the victim’s body before burning them all. It is believed that if the items create a large, crackling flame and a foul stench, it is an indication that the victim had a severe case of maljo. At the end of the ritual, the victim may be asked to walk away without looking back while the objects burn.
In Afro-Caribbean Spiritual Baptist and Orisha tradition, a special piece of jewelry called a 'guard' will be blessed by an elder, who invokes its protection on the wearer. It may be a waist bead, anklet, bracelet, or necklace. For babies, a large safety pin might be used as a guard.
### Greece[edit]
The evil eye, known as μάτι (mati), "eye", as an apotropaic visual device, is known to have been a fixture in Greece dating back to at least the 6th century BC, when it commonly appeared on drinking vessels.[20] In Greece, the evil eye is cast away through the process of xematiasma (ξεμάτιασμα), whereby the "healer" silently recites a secret prayer passed over from an older relative of the opposite sex, usually a grandparent. Such prayers are revealed only under specific circumstances, as according to their customs those who reveal them indiscriminately lose their ability to cast off the evil eye. There are several regional versions of the prayer in question, a common one being: "Holy Virgin, Our Lady, if [insert name of the victim] is suffering of the evil eye, release him/her of it." Evil repeated three times. According to custom, if one is indeed afflicted with the evil eye, both victim and "healer" then start yawning profusely. The "healer" then performs the sign of the cross three times, and emits spitting-like sounds in the air three times.
Another "test" used to check if the evil eye was cast is that of the oil: under normal conditions, olive oil floats in water, as it is less dense than water. The test of the oil is performed by placing one drop of olive oil in a glass of water, typically holy water.[21] If the drop floats, the test concludes there is no evil eye involved. If the drop sinks, then it is asserted that the evil eye is cast indeed. Another form of the test is to place two drops of olive oil into a glass of water. If the drops remain separated, the test concludes there is no evil eye, but if they merge, there is. There is also a third form where in a plate full of water the "healer" places three or nine drops of oil. If the oil drops become larger and eventually dissolve in the water there is evil eye. If the drops remain separated from water in a form of a small circle there isn't. The first drops are the most important and the number of drops that dissolve in water indicate the strength of the evil eye. Note that a secret chant is spoken when these tests are conducted. The words of the chant are closed practised and can only be passed from man to woman, or woman to man.
There is another form of the "test" where the "healer" prepares a few cloves by piercing each one with a pin. Then she lights a candle and grabs a pinned clove with a pair of scissors. She then uses it to do the sign of the cross over the afflicted whilst the afflicted is asked to think of a person who may have given him the evil eye. Then the healer holds the clove over the flame. If the clove burns silently, there is no evil eye present; however, if the clove explodes or burns noisily, that means the person in the thoughts of the afflicted is the one who has cast the evil eye.[citation needed] As the clove explodes, the evil eye is released from the afflicted. Cloves that burn with some noise are considered to be λόγια - words - someone foul-mouthing you that you ought to be wary of. The burned cloves are extinguished into a glass of water and are later buried in the garden along with the pins as they are considered to be contaminated. Greek people will also ward off the evil eye by saying φτου να μη σε ματιάξω! which translates to "I spit so that I won't give you the evil eye." Contrary to popular belief, the evil eye is not necessarily given by someone wishing you ill, but it stems from admiration - if one considers admiration to be a compelled emotion of astonishment at a rival's success over one's evil plan. Since it is technically possible to give yourself the evil eye, it is advised to be humble.
The Greek Fathers accepted the traditional belief in the evil eye, but attributed it to the Devil and envy. In Greek theology, the evil eye or vaskania (βασκανία) is considered harmful for the one whose envy inflicts it on others as well as for the sufferer. The Greek Church has an ancient prayer against vaskania from the Megan Hieron Synekdemon (Μέγαν Ιερόν Συνέκδημον) book of prayers.[citation needed]
### In Islam[edit]
This section needs expansion with: Possible additional sayings exist. Please remember to cite reliable sources. You can help by adding to it. (August 2018)
The evil eye, or al-’ayn العين, is a common belief that individuals have the power to look at people, animals or objects to cause them harm.[22] It is tradition among many Muslims that if a compliment is to be made one should say "TabarakAllah" (تبارك الله) ("Blessings of God")[citation needed] or "Masha'Allah" (ما شاء الله) ("God has willed it")[23] to ward off the evil eye. Reciting Sura Ikhlas, Sura Al-Falaq and Sura Al-Nas from the Qur'an, three times after Fajr and after Maghrib is also used as a means of personal protection against the evil eye.[24][better source needed][failed verification]
Salafi scholars have pointed some conditions from the Quran and Hadith, which includes performing exorcism using the words of God or his names, reciting in Arabic or in a language which can be understood by the people, not using any talismans or amulets or fortune-tellers or any magic, nor asking jinns to help.[25][26][27][28] Scholars have difference of opinion whether talismans using the Quran is permissible or not.[25]
### Assyrians[edit]
A Ruby Eye Pendant from an ancient civilization in Mesopotamia was possibly used as an amulet to protect against the evil eyes. Adilnor Collection.
Assyrians are also strong believers in the evil eye. They will usually wear a blue/turquoise bead around a necklace to be protected from the evil eye. Also, they might pinch the buttocks, comparable to Armenians. It is said that people with green or blue eyes are more prone to the evil eye effect.[citation needed][clarification needed] A simple and instant way of protection in European Christian countries is to make the sign of the cross with your hand and point two fingers, the index finger and the middle finger, towards the supposed source of influence or supposed victim as described in the first chapter of Bram Stoker's novel Dracula published in 1897:
> When we started, the crowd round the inn door, which had by this time swelled to a considerable size, all made the sign of the cross and pointed two fingers towards me. With some difficulty, I got a fellow passenger to tell me what they meant. He would not answer at first, but on learning that I was English, he explained that it was a charm or guard against the evil eye.[29]
### In Judaism[edit]
Clay hamsa with an inscription in Hebrew (translates to "good luck")
The evil eye is mentioned several times in the classic Pirkei Avot (Ethics of Our Fathers). In Chapter II, five disciples of Rabbi Yochanan ben Zakai give advice on how to follow the good path in life and avoid the bad. Rabbi Eliezer says an evil eye is worse than a bad friend, a bad neighbor, or an evil heart.
Talmudic exegete, Rashi, says in the wake of the words of Israel's Sages that when the ten sons of Jacob went down into Egypt to buy provisions, they made themselves inconspicuous by each entering into a separate gate, so that they would not be gazed upon by the local Egyptians and, thereby, trigger a malevolent response (the Evil eye) by their onlookers, seeing that they were all handsome and of brave and manly dispositions.[30]
Some Jews believe that a "good eye" designates an attitude of good will and kindness towards others. Someone who has this attitude in life will rejoice when his fellow man prospers; he will wish everyone well.[31] An "evil eye" denotes the opposite attitude. A man with "an evil eye" will not only feel no joy but experience actual distress when others prosper, and will rejoice when others suffer. A person of this character represents a great danger to our moral purity, according to some Jews.[32]
Rabbi Abraham Isaac Kook explained that the evil eye is "an example of how one soul may affect another through unseen connections between them. We are all influenced by our environment.... The evil eye is the venomous impact from malignant feelings of jealousy and envy of those around us."[33]
Many observant Jews avoid talking about valuable items they own, good luck that has come to them and, in particular, their children. If any of these are mentioned, the speaker and/or listener will say b'li ayin hara (Hebrew), meaning "without an evil eye", or kein eina hara (Yiddish; often shortened to kennahara), "no evil eye". Another way to ward off the evil eye is to spit three times (or pretend to). Romans call this custom "despuere malum," to spit at evil.[34] It has also been suggested[by whom?] the 10th Commandment: "Do not covet anything that belongs to your neighbor" is a law against bestowing the evil eye on another person.
### Turkey[edit]
Main article: Nazar (amulet)
Traditionally shaped nazar ornaments
A typical nazar is made of handmade glass featuring concentric circles or teardrop shapes in dark blue, white, light blue and black, occasionally with a yellow/gold edge.[35]
Cultures that have nazars or some variation include, Turkey, Romania, Albania, North Macedonia,Bosnia and Herzegovina, Greece, Cyprus, Syria, Lebanon, Palestine, Egypt, Armenia, Iran, India, Pakistan, Uzbekistan, Afghanistan, Iraq and Azerbaijan,[36] where the nazar is often hung in homes, offices, cars, children's clothing, or incorporated in jewellery and ornaments.[35] They are a popular choice of souvenir with tourists.[37]
### Ethiopia[edit]
Main article: Buda (folk religion)
Belief in the evil eye, or buda (var. bouda), is widespread in Ethiopia.[38] Buda is generally believed to be a power held and wielded by those in a different social group, for example among the metalworkers. Some Ethiopian Christians carry an amulet or talisman, known as a kitab, or will invoke God's name, to ward off the ill effects of buda.[39] A debtera, who is either an unordained priest or educated layperson, will create these protective amulets or talismans.[40][41]
### Senegal[edit]
The equivaent of the evil eye in Wolof would be the "thiat". It is believed that beautiful objects may break if enviously stared at by others. To repel the effect of the evil eye senegalese people may wear cowrie shell bracelets. The sea shells are said to absorb the negative energy of the thiat and gradually darken untill the bracelet breaks. It is also common for superstitious people to wear "gris-gris" made by a marabouts to avoid misfortune.[citation needed]
### Pakistan[edit]
In Pakistan, the evil eye is called Nazar (نظر). People usually may resort to reading the last three chapters of the Quran, namely Sura Ikhlas, Sura Al-Falaq and Sura Al-Nas. "Masha'Allah" (ما شاء الله) ("God has willed it") is commonly said to ward off the evil eye. Understanding of the evil eye varies by the level of education. Some perceive the use of black color to be useful in protecting from the evil eye. Others use "taawiz" to ward off the evil eye. Truck owners and other public transport vehicles may commonly be seen using a small black cloth on the bumpers to prevent the evil eye.[42]
### Italy[edit]
Various evil eye amulets from Italy such as the cornicello, cimaruta, and lunula (1895).
The cornicello, "little horn", also called the cornetto ("little horn", plural cornetti), is a long, gently twisted horn-shaped amulet. Cornicelli are usually carved out of red coral or made from gold or silver. The type of horn they are intended to copy is not a curled-over sheep horn or goat horn but rather like the twisted horn of an African eland or a chili pepper.[43]
One idea that the ribald suggestions made by sexual symbols distract the witch from the mental effort needed to successfully bestow the curse. Another is that since the effect of the eye was to dry up liquids, the drying of the phallus (resulting in male impotence) would be averted by seeking refuge in the moist female genitals. Among the ancient Romans and their cultural descendants in the Mediterranean nations, those who were not fortified with phallic charms had to make use of sexual gestures to avoid the eye. Such gestures include scratching one's testicles (for men), as well as the mano cornuta gesture and the fig sign; a fist with the thumb pressed between the index and middle fingers, representing the phallus within the vagina. In addition to the phallic talismans, statues of hands in these gestures, or covered with magical symbols, were carried by the Romans as talismans. In Latin America, carvings of the fist with the thumb pressed between the index and middle fingers continue to be carried as good luck charms.
Two handsigns (fig sign and horned sign) used in Italy against the evil eye (1914).
The wielder of the evil eye, the jettatore, is described as having a striking facial appearance, high arching brows with a stark stare that leaps from his black eyes. He often has a reputation for clandestine involvement with dark powers and is the object of gossip about dealings in magic and other forbidden practices. Successful men having tremendous personal magnetism quickly gain notoriety as jettatori. Pope Pius IX was dreaded for his evil eye, and a whole cycle of stories about the disasters that happened in his wake were current in Rome during the latter decades of the 19th century. Public figures of every type, from poets to gangsters, have had their specialized abilities attributed to the power of their eyes.[44]
### Malta[edit]
The symbol of the eye, known as "l-għajn", is common on traditional fishing boats which are known as luzzu. They are said to protect fishermen from storms and malicious intentions.[45]
### Brazil[edit]
Brazilians generally will associate mal-olhado, mau-olhado ("act of giving a bad look") or olho gordo ("fat eye" i.e. "gluttonous eye") with envy or jealousy on domestic and garden plants (that, after months or years of health and beauty, will suddenly weaken, wither and die, with no apparent signs of pest, after the visitation of a certain friend or relative), attractive hair and less often economic or romantic success and family harmony.
Unlike in most cultures mal-olhado is not seen to be something that risks young babies. "Pagans" or non-baptized children are instead assumed to be at risk from bruxas (witches), that have malignant intention themselves rather than just mal-olhado. It probably reflects the Galician folktales about the meigas or Portuguese magas, (witches), as Colonial Brazil was primarily settled by Portuguese people, in numbers greater than all Europeans to settle pre-independence United States. Those bruxas are interpreted to have taken the form of moths, often very dark, that disturb children at night and take away their energy. For that reason, Christian Brazilians often have amulets in the form of crucifixes around, beside or inside beds where children sleep.
Nevertheless, older children, especially boys, that fulfill the cultural ideals of behaving extremely well (for example, having no problems whatsoever in eating well a great variety of foods, being obedient and respectful toward adults, kind, polite, studious, and demonstrating no bad blood with other children or their siblings) who unexpectedly turn into problematic adolescents or adults (for example lacking good health habits, extreme laziness or lacking motivation towards their life goals, having eating disorders, or being prone to delinquency), are said to have been victims of mal-olhado coming from parents of children whose behavior was not as admirable.
Amulets that protect against mal-olhado tend to be generally resistant, mildly to strongly toxic and dark plants in specific and strategic places of a garden or the entry to a house. Those include comigo-ninguém-pode ("against-me-nobody-cans"), Dieffenbachia (the dumbcane), espada-de-são-jorge ("St. George's sword"), Sansevieria trifasciata (the snake plant or mother-in-law's tongue) and guiné ("Guinea"), among various other names, Petiveria alliacea (the guinea henweed). For those lacking in space or wanting to "sanitize" specific places, they may all be planted together in a single sete ervas ("seven [lucky] herbs") pot, that will also include arruda (common rue), pimenteira (Capsicum annuum), manjericão (basil) and alecrim (rosemary).[46] (Though the last four ones should not be used for their common culinary purposes by humans.) Other popular amulets against evil eye include: the use of mirrors, on the outside of your home's front door, or also inside your home facing your front door; an elephant figurine with its back to the front door; and coarse salt, placed in specific places at home.[47]
### Spain and Latin America[edit]
The evil eye or 'Mal de Ojo' has been deeply embedded in Spanish popular culture throughout its history and Spain is the origin of this superstition in Latin America.
In Mexico and Central America, infants are considered at special risk for the evil eye (see mal de ojo, above) and are often given an amulet bracelet as protection, typically with an eye-like spot painted on the amulet. Another preventive measure is allowing admirers to touch the infant or child; in a similar manner, a person wearing an item of clothing that might induce envy may suggest to others that they touch it or some other way dispel envy.
One traditional cure in rural Mexico involves a curandero (folk healer) sweeping a raw chicken egg over the body of a victim to absorb the power of the person with the evil eye. The egg is later broken into a glass with water and placed under the bed of the patient near the head. Sometimes it is checked immediately because the egg appears as if it has been cooked. When this happens it means that the patient did have Mal De Ojo. Somehow the Mal De Ojo has transferred to the egg and the patient immediately gets well. (Fever, pain and diarrhea, nausea/vomiting goes away instantly) In the traditional Hispanic culture of the Southwestern United States and some parts of Mexico, the egg may be passed over the patient in a cross-shaped pattern all over the body, while reciting The Lord's Prayer. The egg is also placed in a glass with water, under the bed and near the head, sometimes it is examined right away or in the morning and if the egg looks like it has been cooked then it means that they did have Mal de Ojo and the patient will start feeling better. Sometimes if the patient starts getting ill and someone knows that they had stared at the patient, usually a child, if the person who stared goes to the child and touches them, the child's illness goes away immediately so the Mal De Ojo energy is released.[48]
In some parts of South America the act of ojear, which could be translated as to give someone the evil eye, is an involuntary act. Someone may ojear babies, animals and inanimate objects just by staring and admiring them. This may produce illness, discomfort or possibly death on babies or animals and failures on inanimate objects like cars or houses. It's a common belief that since this is an involuntary act made by people with the heavy look, the proper way of protection is by attaching a red ribbon to the animal, baby or object, in order to attract the gaze to the ribbon rather than to the object intended to be protected.[49]
#### Mexico[edit]
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Mal de ojo (Mal: Illness - de ojo: Of eye. "To be made ill by an eye's gaze") often occurs without the dimension of envy, but insofar as envy is a part of ojo, it is a variant of this underlying sense of insecurity and relative vulnerability to powerful, hostile forces in the environment. In her study of medical attitudes in the Santa Clara Valley of California, Margaret Clark arrives at essentially the same conclusion: "Among the Spanish-speaking folk of Sal si Puedes, the patient is regarded as a passive and innocent victim of malevolent forces in his environment. These forces may be witches, evil spirits, the consequences of poverty, or virulent bacteria that invade his body. The scapegoat may be a visiting social worker who unwittingly 'cast the evil eye' ... Mexican folk concepts of disease are based in part on the notion that people can be victimized by the careless or malicious behavior of others".[citation needed]
Another aspect of the mal ojo syndrome in Ixtepeji is a disturbance of the hot-cold equilibrium in the victim. According to folk belief, the bad effects of an attack result from the "hot" force of the aggressor entering the child's body and throwing it out of balance. Currier has shown how the Mexican hot-cold system is an unconscious folk model of social relations upon which social anxieties are projected. According to Currier, "the nature of Mexican peasant society is such that each individual must continuously attempt to achieve a balance between two opposing social forces: the tendency toward intimacy and that toward withdrawal. [It is therefore proposed] that the individual's continuous preoccupation with achieving a balance between 'heat' and 'cold' is a way of reenacting, in symbolic terms, a fundamental activity in social relations."[50]
#### Puerto Rico[edit]
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In Puerto Rico, Mal de Ojo or “Evil Eye” is believed to be caused when someone gives a wicked glare of jealousy to someone, usually when the person receiving the glare is unaware. The jealousy can be disguised into a positive aspect such as compliments or admiration. Mal de Ojo is considered a curse and illness. It is believed that without proper protection, bad luck, injury, and illness are expected to follow. Mal de Ojo impact is believed to affect speech, relationships, work, family and most notably, health. Since Mal de Ojo centers around envy and compliments, it creates fear of interacting with people that are outside of their culture. Indirect harm could be brought to them or their family. When it comes to children, they are considered to be more susceptible to Mal de Ojo and it is believed that it can weaken them, leading to illness. As a child grows every effort is taken to protect them. When diagnosing Mal de Ojo, it is important to notice the symptoms. Physical symptoms can include: loss of appetite, body weakness, stomach ache, insomnia, fever, nausea, eye infections, lack of energy, and temperament.
Environmental symptoms can include financial, family, and personal problems as simple as a car breaking down. It is important for those who believe to be aware of anything that has gone wrong because it may be linked to Mal de Ojo. Puerto Ricans are protected through the use of Azabache bracelets. Mal de Ojo can also be avoided by touching an infant when giving admiration. The most common practice of protection in Puerto Rico is the use of Azabache bracelets. These bracelets traditionally have a black or red coral amulet attached. The amulet is in the shape of a fist with a protruding index finger knuckle.
Azabache bracelet charm with a first and protruding index finger knuckle
Eggs are the most common method to cure Mal De Ojo. The red string and oils also used are more common in other cultures but still used in Puerto Rico depending on the Healer, or the person who is believed to have the ability to cure those who have been targeted. Ultimately, the act of giving someone the "Evil Eye" is a rather simple process and is practiced throughout the world.
### India[edit]
Main article: Nazar Battu
In the northern states of India, like the Punjab, Uttar Pradesh, Rajasthan, Haryana, Uttarakhand and Himachal Pradesh, the evil eye is called "nazar" (meaning gaze or vision) or more commonly as Buri Nazar. A charm bracelet, tattoo or other object (Nazar battu), or a slogan (Chashme Baddoor (slogan)), may be used to ward-off the evil eye. Some truck owners write the slogan to ward off the evil eye: "buri nazar wale tera muh kala" ("O evil-eyed one, may your face turn black").
In Andhra Pradesh and Telangana, people call it as 'Disti' or 'Drusti', while people of Tamil Nadu call it 'drishti' or 'kannu' (translated, means evil eye). To remove Drishti, people follow several methods based on their culture/area. Items often used are either rock salt, red chilies, white pumpkins, oiled cloth, or lemons coated with kumkuma. People remove Drishti by rotating any one of these items and around the affected person. The person who removes it will then burn the item, or discard it in a place where others are not likely to stamp on these items. People hang pictures of fierce and scary ogres in their homes or vehicles, to ward off the evil eye.[51]
In India, babies and newborn infants will usually have their eye adorned with kajal, or eyeliner. This would be black, as it is believed in India that black wards off the evil eye or any evil auras. The umbilical cord of babies is often preserved and cast into a metal pendant, and tied to a black string — babies can wear this as a chain, bracelet or belt — the belief, once more, is that this protects the infant from drishti. This is a practice that has been followed right from historical times. People usually remove drishti on full-moon or new-moon days, since these days are considered to be auspicious in India.
Indians often leave small patches of rock salt outside their homes, and hang arrangements of green chilies, neem leaves, and lemons on their stoop. The belief is that this will ward away the evil eye cast on families by detractors.[52]
### United States[edit]
In 1946, the American magician Henri Gamache published a text called Terrors of the Evil Eye Exposed! (later reprinted as Protection against Evil), which offers directions to defend oneself against the evil eye.[53]
## Media and press coverage[edit]
In some cultures over-complimenting is said to cast a curse. So does envy. Since ancient times such maledictions have been collectively called the evil eye. According to the book The Evil Eye by folklorist Alan Dundes,[54] the belief's premise is that an individual can cause harm simply by looking at another's person or property. However, protection is easy to come by with talismans that can be worn, carried, or hung in homes, most often incorporating the contours of a human eye. In Aegean countries, people with light-colored eyes are thought to be particularly powerful, and amulets in Greece and Turkey are usually blue orbs. Indians and Jews use charms with palm-forward hands with an eye in the center; Italians employ horns, phallic shapes meant to distract spell casters.[55]
## Names in various languages[edit]
In most languages, the name translates literally into English as "bad eye", "evil eye", "evil look", or just "the Eye". Some variants on this general pattern from around the world are:
* In Albanian it is known as "syri i keq" (Standard and Tosk), or as "syni keq" (Gheg) meaning "bad eye". Also "mësysh" is used commonly, meaning "cast an evil eye".
* In Arabic, ʿayn al-ḥasūd, عين الحسود, "the eye of envy". ʿAyn ḥārrah (عين حارّة) is also used, literally translating to "hot eye".
* In Armenian, char atchk (չար աչքն) "evil eye" or "bad eye". Regarding the act of giving an evil gaze, it is said (directly translated), "to give with the eye" or in Armenian, "atchkov tal".
* In Azerbaijani, "Göz dəyməsi" – translating as being struck by an eye
* In Chinese it is called 邪惡之眼 (Traditional Chinese characters) / 邪恶之眼 (Simplified Chinese characters) (xié è zhī yǎn, literally "evil eye") or simply 邪眼 (xié yǎn).
* In Corsican it is called "l'Ochju" (The Eye).
* In Dutch it is called "het boze oog", literally "the malicious eye" or "the angry eye".
* In Esperanto, it is called "malica okulo" (malicious eye).
* In Finnish, it's called "paha silmä" (evil/bad eye)
* In French, it is named "le mauvais Œil" (The bad eye)
* In Galician, it is called "meigallo", from meiga, "witch" (and maybe -allo, diminutive or aumentative suffix; or contracted with either ollo, "eye"; or allo, "garlic").
* In German, it is called "böser Blick", literally "evil gaze".
* In Greek, to matiasma (μάτιασμα) or mati (μάτι) someone refers to the act of casting the evil eye (mati being the Greek word for eye); also: vaskania (βασκανία, the Greek word for jinx)[56]
* In Hebrew, ʿáyin hā-ráʿ (עַיִן הָרַע, "eye of evil")
* In Hindi and other languages of South Asia, (Hindi: nazar (नज़र); nazar lagna (नज़र लगना)) means to be afflicted by the evil eye. (However, it generally has no evil connotations because a doting mother's eye can supposedly also cause harm.) In Urdu, another variant of Hindustani, nazar (نظر)"Chashm-é bad"( چشمِ بد); nazar lagna means to be afflicted by the evil eye.
* In Hungarian, gonosz szem means "evil eye", but more widespread is the expression szemmelverés (lit. "beating with eye"), which refers to the supposed/alleged act of harming one by an evil look
* In Irish, the term drochshúil is used for the 'evil eye', being a compound of 'droch' (bad, poor, evil, ill) and 'súil (eye). This can also be used to refer to someone with weak eyesight.
* In Italian, the word malocchio (pronounced [maˈlɔkkjo]) refers to the evil eye.
* In Japanese it is known as "邪視" ("jashi").
* In Ke/Tz Luo, it is called "Sihoho/Juog wang'".
* In Kurdish, it is called "Çav pîs/Chaw pis/ چاو پیس"
* In Lithuanian evil eye is known as "pikta akis", while act of evil watching is called "nužiūrėjimas" (noun), "nužiūrėti" (verb).
* In Malayalam it is known as kannu veykkuka – to cast an evil eye while "kannu peduka" means to be on the receiving end of the malefic influence. "kannu dosham" refers to a bad effect caused by an evil eye.
* In Maltese it is known as "l-għajn". It is a common symbol for warding off evil intentions.
* In Neapolitan it is known as "'o mma'uocchje" which translates literally into "the evil/bad/maleficent eye", which afflicts people, especially women and children who are supposedly the most vulnerable, with multiple issues and problems, stemming from pre-natal issues, miscarriages, early childhood death or sickness or death of a mother during birth, as well as afflicting women with infertility, sexual problems, early widowhood, etc., while afflicted men suffer from cancer, laziness, greed, gluttony, and other diseases, disabilities and ailments.
* In Persian it is known as "چشم زخم" (injurious look/eyes causing injury) or "چشم شور" (omen eye)[57] "Cheshmeh Hasood", meaning Jealous eye, or "Cheshme Nazar" meaning evil eye.
* In Polish it is known as "złe oko" or "złe spojrzenie".
* In Portuguese, it is called "mau olhado", ou "olho gordo" (literally "fat eye"). The first expression is used in Portugal and the second one is more common in Brazil.
* In Romanian, it is known as "deochi", meaning literally "un-eye".
* In Russian, "дурной глаз" (durnoy glaz) means "bad/evil eye"; "сглаз" (sglaz) literally means "from eye".
* In Sanskrit, an ancient Indo-Aryan language, it is called "drishti dosha" (दृष्टि दोष) meaning malice caused by evil eye. (But cf. "drishti (yoga)".)
* In Serbo-Croatian (Serbian, Croatian, Bosnian and Montenegrin), it is called Urokljivo oko (Cyr. Урокљиво око).[58] The first word is an adjective of the word urok/урок, which means spell or curse, and the second word means eye.
* In Slovak, it is known as "z očí", meaning "(coming) from eyes".
* In Somali, it is called "il", or "ilaaco" or "sihir" (the first two words literally meaning "eye" and the other word meaning 'black magic')
* In Sinhala it is known as "ඇස්වහ" (æsvaha).
* In Spanish, mal de ojo literally means "evil from the Eye" as the name does not refer to the actual eye but to the evil that supposedly comes from it. Casting the evil eye is then echar mal de ojo, i.e. "to cast evil from the Eye".[59]
* In Tamil, "கண் படுதல்" (kan padudhal) literally means "casting an eye" (with an intention to cause harm). "கண்ணூறு" (kannooru) "harm from the eye"
* In Trinidadian Creole it is called 'maljo', derived from the French 'mal yeux' meaning "bad eye"
* In Turkish kem göz means evil eye and the cure is having a "nazar boncuğu", the nazar amulet.
* In Welsh y llygad drwg, y llygad mall, drwglygad [60]
* In Yiddish עין הרע (ayin hora אַייִן האָראַ)
## See also[edit]
### Amulets and other protections[edit]
* Azabache - Spanish and Latin American amulet used to ward off the evil eye, especially in the form of a pin placed on infants
* Cornicello \- Italian amulet used to ward off the evil eye
* Eye of Horus \- an Ancient Egyptian symbol of protection and power against evil.
* Eyespot (mimicry) \- as found in living organisms
* Hamsa \- middle eastern protection amulet
* Harmal \- plant used as protection against the evil eye
* Mirror armour \- believed to protect not from only cold steel and arrows, but also from the evil eye
* Nazar
* Red string (Kabbalah)
* Sign of the horns \- horned hand gesture used for warding off the Evil Eye and other purposes
* Jumbie beads\- poisonous seeds of the Rosary Pea tree which are used to make jewelry that wards off maljo (bad eye) and evil spirits in Trinbagonian tradition
* The color blue\- in Trinidad and Tobago is believed to ward off the evil eye, particularly when worn as garments or accessories, as well as in indigo dye
### Creatures[edit]
* Balor \- a character in Irish legend
* Basilisk \- Death glance/petrifying glance
* Beholder (Dungeons & Dragons) \- modern invention
* Cockatrice \- Death glance/petrifying glance
* Medusa and Gorgon \- Petrification glance, picture also used on as protection from the evil eye.
* Petrifaction in mythology and fiction.
### Concepts[edit]
* Eye of Providence \- a symbol showing an eye surrounded by rays of light or a glory, and usually enclosed by a triangle.
* Lashon hara \- Jewish concept of the "evil tongue"
* Matthew 6:23 "If thine eye be evil" - The evil eye as ungenerosity of spirit, hence darkness / blindness / evil itself.
* Rule of Three
* Scopophobia \- fear of being stared at
* Usog \- a Filipino version.
## Notes[edit]
1. ^ Plutarch, Moralia, Book VII
2. ^ Pliny the Elderh, Natural History (Pliny), VII.2
3. ^ Virgil, Eclogues, III.1.103
## References[edit]
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8. ^ Ulmer, Rivka (1994). KTAV Publishing House, Inc. (ed.). The evil eye in the Bible and in rabbinic literature. p. 176. ISBN 978-0-88125-463-1.
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11. ^ Parker, A. (2018). "The Bells! The Bells! Approaching tintinnabula in Roman Britain and Beyond". In Parker, A.; Mckie, S. (eds.). Material Approaches to Roman Magic: Occult Objects and Supernatural Substances. TRAC Themes in Roman Archaeology 2. Oxford: Oxbow. pp. 57–68.
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25. ^ a b https://www.kalamullah.com/Books/Selected%20Fatwas%20on%20Faith%20Healing%20and%20Witchcraft.pdf
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28. ^ http://www.islamtomorrow.com/books/major_sins/majorSins.pdf
29. ^ Dracula Archived 2009-05-05 at the Wayback Machine, Bram Stoker's novel 1897 edition online. p. ?
30. ^ Rashi's commentary on Genesis 42:5; cf. Midrash Rabba (Genesis Rabba, section 91:6); Midrash Tanhuma (Warsaw edition), P. Miketz, section 6; Targum Pseudo-Jonathan on Genesis 42:5
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32. ^ Chapters of the Fathers, Translation & Commentary by Samson Raphael Hirsch, Feldheim Publishers, ISBN 0-87306-182-9 pg. 32
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34. ^ Joyce Eisenberg and Ellen Scolnic. "The Whole Spiel: Funny essays about digital nudniks, seder selfies and chicken soup memories," Incompra Press, ISBN 978-0-692-72625-9 pg. 153
35. ^ a b Lonely Planet Middle East.Lonely Planet; 6 edition, 2009, p. 559.
36. ^ Stoltz, Dustin (May 26, 2012). "The Evil Eye and Mountain Karma in Azerbaijan". www.dustinstoltz.com.
37. ^ "The History and the meaning of the Turkish Evil Eye".
38. ^ Turner, John W. "Ethiopian Orthodox Christianity: Faith and practices". A Country Study: Ethiopia. Thomas P. Ofcansky and LaVerle Berry, eds. Washington: Library of Congress Federal Research Division, 1991.
39. ^ Kemp, Charles. "Ethiopians & Eritreans. Archived 2012-12-10 at Archive.today" Refugee Health – Immigrant Health. Waco, TX: Baylor University.
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41. ^ Geleta, Amsalu Tadesse. "Case Study: Demonization and the Practice of Exorcism in Ethiopian Churches Archived 2010-01-01 at the Wayback Machine". Lausanne Committee for World Evangelization, Nairobi, August 2000.
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43. ^ Lucky Mojo. "The Corno (Italian Horn Amulet)". Retrieved 9 February 2015.
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45. ^ "A traditional seacraft gradually on the decline".
46. ^ Guizetti, Franco. "Conheça o poder e a proteção das sete ervas" (in Portuguese). Retrieved Jan 19, 2012.
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54. ^ Dundes, Alan (ed.) (1992) The Evil Eye: A Casebook University of Wisconsin Press, Madison, Wisconsin, ISBN 0-299-13334-6; originally published in 1981 by Garland Publishing, New York
55. ^ Rizzo, Johnna (April 2013) National Geographic Magazine
56. ^ Vaskania (Βασκανία) in Εγκυκλοπαιδικό Λεξικό Ελευθερουδάκη, (Encyclopedic Lexicon Eleftheroudakis) ed. 1928
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## Further reading[edit]
* Dundes, Alan (1992). The Evil Eye: A Casebook. Madison, WI: The University of Wisconsin Press. ISBN 0-299-13334-6.
* Borthwick, E. Kerr (2001) "Socrates, Socratics, and the Word ΒΛΕΠΕΔΑΙΜΩΝ" The Classical Quarterly New Series, 51(1): pp. 297–301
* Dickie, Mathew W. (January 1991) "Heliodorus and Plutarch on the Evil Eye" Classical Philology 86(1): pp. 17–29
* Elliott, John H. (2015) Beware the Evil Eye: The Evil Eye in the Bible and the Ancient World: Volume 1: Introduction, Mesopotamia, and Egypt. Eugene, OR: Cascade.
* Elliott, John H. (2016) Beware the Evil Eye: The Evil Eye in the Bible and the Ancient World: Volume 2: Greece and Rome. Eugene, OR: Cascade.
* Elworthy, Frederick Thomas (1895) The Evil Eye. An Account of this Ancient & Widespread Superstition John Murray, London, OCLC 2079005; reprinted in 2004 as: The Evil Eye: The Classic Account of an Ancient Superstition Dover Publications, Mineola, New York, ISBN 0-486-43437-0 (online text)
* Gifford, Edward S. (1958) The Evil Eye: Studies in the Folklore of Vision Macmillan, New York, OCLC 527256
* Jones, Louis C. (1951) "The Evil Eye among European-Americans" Western Folklore 10(1): pp. 11–25
* Limberis, Vasiliki (April 1991) "The Eyes Infected by Evil: Basil of Caesarea's Homily" The Harvard Theological Review 84(2): pp. 163–184
* Lykiardopoulos, Amica (1981) "The Evil Eye: Towards an Exhaustive Study" Folklore 92(2): pp. 221–230
* Meerloo, Joost Abraham Maurits (1971) Intuition and the Evil Eye: The Natural History of a Superstition Servire, Wassenaar, Netherlands, OCLC 415660
* Shamash, Jack (2020) 'The Evil Eye - The Magic of Envy and Destruction' Foxy Books, London ISBN 978-1-5272-5860-0
* Slone, Kathleen Warner and Dickie, M.W. (1993) "A Knidian Phallic Vase from Corinth" Hesperia 62(4): pp. 483–505
* Mal de ojo
## External links[edit]
Look up evil eye in Wiktionary, the free dictionary.
Wikisource has the text of the 1911 Encyclopædia Britannica article Evil Eye.
Media related to Evil eye at Wikimedia Commons
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| Evil eye | None | 1,693 | wikipedia | https://en.wikipedia.org/wiki/Evil_eye | 2021-01-18T18:29:58 | {"wikidata": ["Q1020115"]} |
A number sign (#) is used with this entry because glucose/galactose malabsorption (GGM) is caused by homozygous mutation in the gene encoding the intestinal sodium/glucose transporter (SLC5A1; 182380) on chromosome 22q12.
Description
Glucose/galactose malabsorption (GGM) is a rare autosomal recessive disorder caused by a defect in glucose and galactose transport across the intestinal brush border. Patients with GGM present with neonatal onset of severe life-threatening watery diarrhea and dehydration. If diagnosed and treated properly, patients can fully recover and show normal growth and development (summary by Xin and Wang, 2011).
Clinical Features
The intestinal monosaccharide transporter deficiency known as glucose/galactose malabsorption (GGM) produces a clinical picture indistinguishable from that of intestinal disaccharidase deficiency (222900). In GGM, fructose and xylose are absorbed normally. The disorder manifests itself within the first weeks of life, and the consequent severe diarrhea and dehydration are usually fatal unless glucose and galactose are eliminated from the diet. Meeuwisse (1970) pointed out that almost all patients with glucose/galactose malabsorption show a slight, intermittent glucosuria. Elsas et al. (1970) concluded that heterozygotes are detectable and demonstrate a reduced capacity for glucose transport, and that absent intestinal glucose transport is accompanied by partial impairment of renal glucose transport. Lebenthal et al. (1971) observed improvement in the tolerance of glucose and sucrose as an affected child grew older. Elsas and Lambe (1973) likewise found clinical remission with increased age in severe glucose/galactose malabsorption even though active jejunal glucose transport remained absent.
Abdullah et al. (1996) reported 8 children with diarrhea which started immediately after breast- or bottle-feeding. All showed wasting at the time of presentation. The diagnosis was confirmed in each case by blood glucose and galactose levels after loading with glucose or galactose. All improved dramatically on a fructose-based formula.
Xin and Wang (2011) reported GGM in 33 individuals in an extended Old Order Amish pedigree with multiple lines of common descent. After a normal birth, patients presented with watery diarrhea on day 2 or 3 of life soon after breast or formula feeding. The diarrhea was continuous despite normal nursing, and affected infants became dehydrated and lost weight. Other features included distended abdomen, increased bowel sounds, acidic stool, metabolic acidosis, and hypernatremia. There were 3 main clinical courses: a dramatic improvement and normal development if correctly diagnosed and managed; prolonged disease course until correct diagnosis and management, followed by normal development; and lack of correct diagnosis due to less severe symptoms, with chronic diarrhea until correct diagnosis and treatment. All patients slowly developed tolerance to carbohydrates over time, although the speed and degree of improvement varied.
Diagnosis
### Prenatal Diagnosis
Martin et al. (1996) performed prenatal diagnosis in 2 subsequent pregnancies in a large consanguineous affected family, using EcoRV restriction digestion. One showed that the fetus was heterozygous and the other showed that the fetus was not a carrier of the D28N mutation (182380.0001). Both children at 2 years of age remained healthy with no diarrhea.
Pathogenesis
Mutation in the SLC5A1 gene (182380) results in a dysfunctional sodium/glucose cotransporter protein. Normally, the cotransporter actively absorbs glucose and galactose into the cells lining the villi of the gastrointestinal tract. Mutations such as nonsense or frameshift that result in a premature stop codon lead to a truncated protein (cotransporter) that does not function properly (Turk et al., 1993). Many of the missense mutations, by contrast, lead to translation of a full protein, but cause a defect in trafficking of the protein to the plasma membrane. Martin et al. (1996) showed that sugar uptake by oocytes was severely impaired in the case of 15 missense mutants, even though Western blot analysis indicated that the amount of mutant protein in oocytes was comparable to wildtype. Both types of defect in the cotransporter gene ultimately lead to unabsorbed carbohydrate in the intestinal lumen, which further causes an osmotic diarrhea, hyperosmolar dehydration, and metabolic acidosis (Wright et al., 2001).
Inheritance
Occurrence in both sexes, familial incidence (Lindquist et al., 1963; Anderson et al., 1965; Elsas et al., 1970), and instances of parental consanguinity (Lebenthal et al., 1971) support autosomal recessive inheritance of glucose/galactose malabsorption.
Lebenthal et al. (1971) described 3 affected offspring from consanguineous marriages in an Iraqi-Babylonian Jewish family. The parents were first cousins in 4 of the 6 affected Arab families reported by Abdullah et al. (1996).
Molecular Genetics
Turk et al. (1991) identified a missense mutation (182380.0001) in 2 related patients with glucose/galactose malabsorption. Martin et al. (1996) screened 30 patients for mutations in the SGLT1 gene (182380) and used a heterologous expression system to link the mutations to the phenotype. Thirty-one novel mutations of SLC5A1 were identified in 25 families with glucose/galactose malabsorption. Martin et al. (1996) performed prenatal diagnosis in 2 pregnancies in affected families using EcoRV restriction digestion. One showed that the fetus was heterozygous and the other showed that the fetus was not a carrier of the D28N mutation. Both children at 2 years of age remained healthy with no diarrhea.
In 33 patients from an extended Old Order Amish pedigree with GGM, Xin and Wang (2011) identified a homozygous mutation in the SLC5A1 gene (R558H; 182380.0003). The mutation, which segregated with the disorder in the families, was not found in a large control database. All patients were also homozygous for 3 additional nonsynonymous variants in the SLC5A1 gene that were found in a large control database (N51S, rs17683011; A411T, rs17683430; and H615Q, rs33954001). All 4 mutations segregated with the disorder in the families. Heterozygosity for the 4 mutations, which were present on a common haplotype, was found in 5% of Amish control alleles, indicating a founder effect. Xin and Wang (2011) noted that N51S occurred at a conserved residue and may also affect the protein. No functional studies were performed, and it was unclear how each individual mutation affected SLC5A1 protein function.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive ABDOMEN \- Distended abdomen Gastrointestinal \- Diarrhea, severe, chronic \- Increased bowel sounds METABOLIC FEATURES \- Hyperosmolar dehydration \- Metabolic acidosis LABORATORY ABNORMALITIES \- Glucosuria, mild, intermittent \- Abnormal glucose oral tolerance test \- Glucose breath hydrogen test shows malabsorption of glucose and galactose MISCELLANEOUS \- Onset in first days of life \- Diarrhea persists even with vigorous nursing \- May be lethal if untreated \- Patients gradually develop tolerance to carbohydrates over time \- Dramatic improvement with proper treatment \- High incidence among Old Order Amish MOLECULAR BASIS \- Caused by mutation in the intestinal sodium/glucose transporter gene (SLC5A1, 182380.0001 ) ▲ 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
| GLUCOSE/GALACTOSE MALABSORPTION | c0268186 | 1,694 | omim | https://www.omim.org/entry/606824 | 2019-09-22T16:09:58 | {"mesh": ["C562602"], "omim": ["606824"], "icd-10": ["E74.39"], "orphanet": ["35710"], "synonyms": ["Alternative titles", "MONOSACCHARIDE MALABSORPTION"]} |
Inflammatory demyelinating disease
MOG antibody disease, MOGAD[1] or Anti-MOG associated encephalomyelitis is an inflammatory demyelinating disease of the central nervous system. Serum anti-myelin oligodendrocyte glycoprotein antibodies are present in up to half of patients with an acquired demyelinating syndrome and have been described in association with a range of phenotypic presentations, including acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, and neuromyelitis optica.[2]
## Contents
* 1 Presentation
* 1.1 Seronegative neuromyelitis optica
* 1.2 ADEM
* 1.3 Tumefactive demyelination
* 2 Causes
* 3 Histopathology
* 4 Diagnosis
* 5 Clinical course
* 6 Prognosis
* 7 Treatment
* 8 Research
* 9 History
* 10 References
## Presentation[edit]
The clinical presentation is variable and largely dependent upon the overall clinical manifestation.
The presence of anti-MOG autoantibodies has been described in association with the following conditions:[3]
* Seronegative neuromyelitis optica.[4]
* Acute disseminated encephalomyelitis, especially in recurrent and fulminant cases.[5]
* Multiple sclerosis.[3][6][7][8]
* Optic neuritis[3] (including cases of CRION (chronic relapsing inflammatory optic neuropathy[9])
* Transverse myelitis[3]
* Aseptic meningitis and meningoencephalitis (typically post-infectious).[10]
The most common presenting phenotypes are acute disseminated encephalomyelitis (ADEM) in children and optic neuritis (ON) in adults.[11] Some of these phenotypes have been studied in detail:
### Seronegative neuromyelitis optica[edit]
Anti-MOG antibodies have been described in some patients with NMOSD[12][13] who were negative for the aquaporin 4 (AQP-4) antibody. However, NMOSD is an astrocytopathy, whereas MOG antibody-associated disease is an oligodendrocytopathy, suggesting that these are two separate pathologic entities.[14] Rare cases have been described of patients with antibodies against both AQP4 and MOG. These patients typically have MS-like brain lesions, multifocal spine lesions and optic nerve atrophy.[15] However, the coexistence of both antibodies is still a matter of ongoing debate.[16]
### ADEM[edit]
The presence of anti-MOG antibodies is more common in children with ADEM.[17][18]
### Tumefactive demyelination[edit]
Rare cases of anti-MOG antibodies in association with tumefactive multiple sclerosis have been described.[19]
## Causes[edit]
The reason why anti-MOG auto-antibodies appear remains unknown.
A post-infectious autoimmune process has been proposed as a possible pathophysiologic mechanism.[20] Other reports point to molecular mimicry between MOG and some viruses as a possible etiology.[21]
## Histopathology[edit]
Demyelinating lesions of MOG-associated encephalomyelitis resemble more those observed in multiple sclerosis[22] than NMO. They are similar to pattern-II multiple sclerosis[23] with T-cells and macrophages surrounding blood vessels, preservation of oligodendrocytes and signs of complement system activation.
## Diagnosis[edit]
MOG-IgG is detected by means of so-called cell-based assays (CBA). CBA using live cells transfected with full-length human MOG and employing Fc-specific detection antibodies are the gold standard for anti-MOG antibody testing.[24] Serum is the specimen of choice; cerebrospinal fluid (CSF) analysis is less sensitive compared to serum testing.[24][25][26]
Cerebrospinal fluid oligoclonal bands, the diagnostic mainstay in multiple sclerosis (MS), are rare in MOG-EM, both in adults[27] and in children.[28] If present at all, intrathecal IgG synthesis is low in most patients, often transient, and mainly restricted to acute attacks.[27][28] CSF findings are significantly more pronounced in acute myelitis than in acute ON, which is frequently associated with normal CSF findings, and depends significantly on disease activity (more pronounced during acute attacks), attack severity, and spinal cord lesion extension.[27][28] CSF white cell numbers in MOG-EM may be higher than in MS, especially in acute myelitis, but normal cell numbers do not rule out the disease.[27][28] CSF often contains neutrophil granulocytes and CSF L-lactate levels may be elevated, thus mimicking bacterial meningitis in some cases.[27][28] The intrathecal, polyclonal antiviral immune response (so-called MRZ reaction), which is present in around 63% of MS patients, is absent in MOG-EM.[27][28]
Proposed diagnostic criteria require serum positivity for MOG antibody as detected by CBA, a clinicoradiological presentation consistent with an acquired demyelinating syndrome (VEP can replace radiological evidence only in patients with acute ON), and exclusion of alternative diagnoses;[24] in addition, so-called 'red flags' have been defined, which, if present, should prompt physicians to challenge the diagnosis and to prompt re-testing for MOG-IgG, ideally using a second, methodologically different assay.[24]
In the young, MRI typically shows ADEM–like lesions and longitudinally extensive transverse myelitis (LETM), whereas optic neuritis and short transverse myelitis are more commonly seen in older patients.[29] However, rare cases of symptomatic MRI-negative MOG-related disease have been described.[30]
## Clinical course[edit]
Two clinical courses have been described:[31]
* Monophasic (most common)
* Relapsing
## Prognosis[edit]
Residual disability develops in 50–80% of patients, with transverse myelitis at onset being the most significant predictor of long-term outcome.
## Treatment[edit]
Acute therapy consists of high-dose corticosteroids, IVIG, or plasma exchange, and long-term immunosuppression may be necessary in recurrent cases.[32][33] Anti-MOG positive patients should not be treated with interferons as these may worsen the disease course similar to those with NMOSD.[26]
There are also anecdotal reports against using fingolimod [34] or Alemtuzumab.[35]
## Research[edit]
Animal models in experimental autoimmune encephalomyelitis, EAE, have shown that “MOG-specific EAE models (of different animal strains) display/mirror human multiple sclerosis" but EAE pathology is closer to NMO and ADEM than to the confluent demyelination observed in MS.[36]
## History[edit]
Reports describing the possible involvement of anti-MOG antibodies in multiple sclerosis and other demyelinating conditions first appeared in the literature in the late 1980s, but evidence to support their role in demyelinating disease was always weak and inconsistent.[37] The possibility of an anti-MOG MS-subtype was considered around 2000.[38]
The turning point was in 2011, when Mader et al. developed a cell-based assay using HEK 293 cells which increased the detection rate of these antibodies in the serum.[39]
Reports about prevalence of anti-MOG in selected Multiple Sclerosis cases began to appear in 2016[40]
## References[edit]
1. ^ Tajfirouz, Deena A.; Bhatti, M. Tariq; Chen, John J. (26 November 2019). "Clinical Characteristics and Treatment of MOG-IgG–Associated Optic Neuritis". Current Neurology and Neuroscience Reports. 19 (12): 100. doi:10.1007/s11910-019-1014-z. PMID 31773369. S2CID 208278781.
2. ^ Ramanathan, Sudarshini; Dale, Russell C.; Brilot, Fabienne (2016). "Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination". Autoimmunity Reviews. 15 (4): 307–324. doi:10.1016/j.autrev.2015.12.004. PMID 26708342.
3. ^ a b c d Reindl, M; Di Pauli, F; Rostásy, K; Berger, T (Aug 2013). "The spectrum of MOG autoantibody-associated demyelinating diseases". Nat Rev Neurol. 9 (8): 455–61. doi:10.1038/nrneurol.2013.118. PMID 23797245. S2CID 7219279.
4. ^ Hyun, Jae-Won; Woodhall, Mark R; Kim, Su-Hyun; Hye Jeong, In; Kong, Byungsoo; Kim, Gayoung; Kim, Yeseul; Su Park, Min; Irani, Sarosh R; Waters, Patrick; Jin Kim, Ho (2017). "Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases". Journal of Neurology, Neurosurgery & Psychiatry. 88 (10): 811–817. doi:10.1136/jnnp-2017-315998. PMID 28684532. S2CID 22732252.
5. ^ Baumann, M.; Hennes, E.M.; Schanda, K.; Karenfort, M.; Bajer-Kornek, B.; Diepold, K.; Fiedler, B.; Marquardt, I.; Strautmanis, J.; Vieker, S.; Reindl, M.; Rostásy, K. (2015). "Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies". European Journal of Paediatric Neurology. 19 (Supplement 1): S21. doi:10.1016/S1090-3798(15)30066-0.
6. ^ Jarius S, Metz I, König FB, Ruprecht K, Reindl M, Paul F, Brück W, Wildemann B. "Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in 'pattern II multiple sclerosis' and brain biopsy findings in a MOG-IgG-positive case Mult Scler. 2016 Feb;
7. ^ Di Pauli, F. (2015). "Fulminant demyelinating encephalomyelitis: Insights from antibody studies and neuropathology". Neurology: Neuroimmunology. 2 (6): e175. doi:10.1212/NXI.0000000000000175. PMC 4635550. PMID 26587556.
8. ^ Spadaro, Melania (2016). "Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis". Neurology - Neuroimmunology Neuroinflammation. 3 (5): e257. doi:10.1212/NXI.0000000000000257. PMC 4949775. PMID 27458601.
9. ^ Chalmoukou, Konstantina; et al. (2015). "Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis". Neurol Neuroimmunol Neuroinflamm. 2 (4): e131. doi:10.1212/NXI.0000000000000131. PMC 4496630. PMID 26185777.
10. ^ Narayan, Ram N; Wang, Cynthia; Sguigna, Peter; Husari, Khalil; Greenberg, Benjamin (2019). "Atypical Anti-MOG syndrome with aseptic meningoencephalitis and pseudotumor cerebri-like presentations". Multiple Sclerosis and Related Disorders. 27: 30–33. doi:10.1016/j.msard.2018.10.003. PMID 30300850.
11. ^ de Mol, CL; Wong, YYM; van Pelt, ED; Wokke, BHA; Siepman, TAM; Neuteboom, RF; Hamann, D; Hintzen, RQ (16 May 2019). "The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults". Multiple Sclerosis Journal. 26 (7): 806–814. doi:10.1177/1352458519845112. PMC 7294530. PMID 31094288.
12. ^ Pröbstel, Anne-Katrin; et al. (2015). "Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype". Journal of Neuroinflammation. 12 (1): 46. doi:10.1186/s12974-015-0256-1. PMC 4359547. PMID 25889963.
13. ^ CYNTHIA MCKELVEY, Press Report, What’s the Role of Myelin Oligodendrocyte Glycoprotein in NMO? [1]
14. ^ Ramanathan, Sudarshini; Dale, Russell C.; Brilot, Fabienne (2016). "Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination". Autoimmunity Reviews. 15 (4): 307–324. doi:10.1016/j.autrev.2015.12.004. PMID 26708342.
15. ^ Ya, Yaping; et al. (2015). "Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD". Science China Life Sciences. 59 (12): 1270–1281. doi:10.1007/s11427-015-4997-y. PMC 5101174. PMID 26920678.
16. ^ Weber, Martin S.; Derfuss, Tobias; Brück, Wolfgang (2018). "Anti–Myelin Oligodendrocyte Glycoprotein Antibody–Associated Central Nervous System Demyelination—A Novel Disease Entity?". JAMA Neurol. 75 (8): 909–910. doi:10.1001/jamaneurol.2018.1055. PMID 29913011.
17. ^ Knapp-Tężycka, Justyna; Zawadzka, Marta; Knurowska, Agata; Anuszkiewicz, Karolina; Stogowski, Piotr; Wiśniewska, Sylwia; Lemka, Małgorzata; Mazurkiewicz-Bełdzińska, Maria (2020). "Zapalenie nerwów wzrokowych, mózgu i rdzenia związane z MOG-IgG (MONEM)". Polski Przeglad Neurologiczny. 16: 46–50. doi:10.5603/PPN.2020.0005.
18. ^ Silvia Tenembaum et al. Spectrum of MOG Autoantibody-Associated Inflammatory Diseases in Pediatric Patients, Neurology April 6, 2015 vol. 84 no. 14 Supplement I4-3A
19. ^ Yaqing Shu Youming Long Shisi Wang Wanming Hu Jian Zhou Huiming Xu Chen Chen Yangmei Ou Zhengqi Lu Alexander Y. Lau Xinhua Yu Allan G. Kermode Wei Qiu, Brain histopathological study and prognosis in MOG antibody‐associated demyelinating pseudotumor, 08 January 2019, https://doi.org/10.1002/acn3.712
20. ^ Kakalacheva, Kristina; et al. (2016). "Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein". Viruses. 8 (2): 51. doi:10.3390/v8020051. PMC 4776206. PMID 26907324.
21. ^ De Luca et al. Cross-reactivity between myelin oligodendrocyte glycoprotein and human endogenous retrovirus W protein: nanotechnological evidence for the potential trigger of multiple sclerosis, Micron Volume 120, May 2019, Pages 66-73, doi: https://doi.org/10.1016/j.micron.2019.02.005
22. ^ Spadaro Melania; et al. (2015). "Histopathology and clinical course of MOG-antibody-associated encephalomyelitis". Annals of Clinical and Translational Neurology. 2 (3): 295–301. doi:10.1002/acn3.164. PMC 4369279. PMID 25815356.
23. ^ Deena A. Tajfirouz, M. Tariq Bhatti, John J. Chen, Clinical Characteristics and Treatment of MOG-IgG–Associated Optic Neuritis Current Neurology and Neuroscience Reports, December 2019
24. ^ a b c d Jarius S, Paul F, Aktas O, Asgari N, Dale RC, de Seze J, et al. (May 2018). "MOG encephalomyelitis: international recommendations on diagnosis and antibody testing". J Neuroinflammation. 15 (1): 134. doi:10.1186/s12974-018-1144-2. PMC 5932838. PMID 29724224.
25. ^ Jarius, Sven (2016). "MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin". Journal of Neuroinflammation. 13: 279. doi:10.1186/s12974-016-0717-1. PMID 27788675.
26. ^ a b Nakashima, Ichiro (2015). "Anti-myelin oligodendrocyte glycoprotein antibody in demyelinating diseases". Clinical and Experimental Neuroimmunology. 6: 59–63. doi:10.1111/cen3.12262. S2CID 74183244.
27. ^ a b c d e f Jarius, Sven (2020). "Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1: Results from 163 lumbar punctures in 100 adult patients". Journal of Neuroinflammation. 17 (1): 261. doi:10.1186/s12974-020-01824-2. PMC 7470615. PMID 32883348.
28. ^ a b c d e f Jarius, Sven (2020). "Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 2: Results from 108 lumbar punctures in 80 pediatric patients". Journal of Neuroinflammation. 17: 261. doi:10.1186/s12974-020-01825-1.
29. ^ Maciej Jurynczyk Ruth Geraldes Fay Probert Mark R. Woodhall Patrick Waters George Tackley Gabriele DeLuca Saleel Chandratre Maria I. Leite Angela Vincent, Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis, Brain, Volume 140, Issue 3, 1 March 2017, Pages 617–627, https://doi.org/10.1093/brain/aww350, 24 February 2017
30. ^ Pérez CA, Garcia-Tarodo S, Troxell R. MRI-Negative Myelitis Associated With Myelin Oligodendrocyte Glycoprotein Antibody Spectrum Demyelinating Disease. Child Neurol Open. 2019;6:2329048X19830475. Published 2019 Feb 17. https://doi.org/10.1177/2329048X19830475
31. ^ Pandit, Lekha; Mustafa, Sharik; Nakashima, Ichiro; Takahashi, Toshyuki; Kaneko, Kimhiko (2018). "MOG-IgG-associated disease has a stereotypical clinical course, asymptomatic visual impairment and good treatment response". Multiple Sclerosis Journal - Experimental, Translational and Clinical. 4 (3): 205521731878782. doi:10.1177/2055217318787829. PMC 6050870. PMID 30038790.
32. ^ Oshiro A, Nakamura S, Tamashiro K, Fujihara K. Anti-MOG + neuromyelitis optica spectrum disorders treated with plasmapheresis, No To Hattatsu. 2016 May;48(3):199-203
33. ^ Rocio Vazquez do Campo, Ramon Yarza, Sebastian Lopez Chiriboga and Kevin Barrett, Myelin Oligodendrocyte Glycoprotein (MOG) Autoimmunity. A Case Report, Neurology April 5, 2016 vol. 86 no. 16 Supplement P5.346
34. ^ Miyazaki, T; Nakajima, H; Motomura, M; Tanaka, K; Maeda, Y; Shiraishi, H; Tsujino, A (2016). "A case of recurrent optic neuritis associated with cerebral and spinal cord lesions and autoantibodies against myelin oligodendrocyte glycoprotein relapsed after fingolimod therapy". Rinsho Shinkeigaku. 56 (4): 265–9. doi:10.5692/clinicalneurol.cn-000756. PMID 27010093.
35. ^ Seneviratne, Sinali; Marriott, Mark; Monif, Mastura (2019). "065 Presence of anti-myelin oligodendrocyte glycoprotein antibodies in the serum of two patients following alemtuzumab therapy for suspected multiple sclerosis". Journal of Neurology, Neurosurgery & Psychiatry. 90: A21.2–A21. doi:10.1136/jnnp-2019-anzan.57.
36. ^ Kezuka; et al. (2012). "Relationship Between NMO-Antibody and Anti–MOG Antibody in Optic Neuritis". Journal of Neuro-Ophthalmology. 32 (2): 107–110. doi:10.1097/WNO.0b013e31823c9b6c. PMID 22157536. S2CID 46667141.
37. ^ Fujihara K, et al. (8 March 2018). "Myelin oligodendrocyte glycoprotein immunoglobulin G-associated disease: An overview". Clin. And Exp. Neuroinmunology. 9: 48–55. doi:10.1111/cen3.12434.
38. ^ Egg, R; Reindl, M; Deisenhammer, F; Linington, C; Berger, T (October 2001). "Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis". Multiple Sclerosis Journal. 7 (5): 285–289. doi:10.1177/135245850100700503. PMID 11724443. S2CID 23520476.
39. ^ Mader, S; Gredler, V; Schanda, K; et al. (2011). "Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders". J Neuroinflammation. 8: 184. doi:10.1186/1742-2094-8-184. PMC 3278385. PMID 22204662.
40. ^ Spadaro, M; Gerdes, LA; Krumbholz, M; Ertl-Wagner, B; Thaler, FS; Schuh, E; Metz, I; Blaschek, A; Dick, A; Brück, W; Hohlfeld, R; Meinl, E; Kümpfel, T (2016). "Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis". Neurol Neuroimmunol Neuroinflamm. 3 (5): e257. doi:10.1212/NXI.0000000000000257. PMC 4949775. PMID 27458601.
* v
* t
* e
Multiple sclerosis and other demyelinating diseases of the central nervous system
Signs and symptoms
* Ataxia
* Depression
* Diplopia
* Dysarthria
* Dysphagia
* Fatigue
* Incontinence
* Nystagmus
* Optic neuritis
* Pain
* Uhthoff's phenomenon
Investigations and diagnosis
* Multiple sclerosis diagnosis
* McDonald criteria
* Poser criteria
* Clinical
* Clinically isolated syndrome
* Expanded Disability Status Scale
* Serological and CSF
* Oligoclonal bands
* Radiological
* Radiologically isolated syndrome
* Lesional demyelinations of the central nervous system
* Dawson's fingers
Approved[by whom?] treatment
* Management of multiple sclerosis
* Alemtuzumab
* Cladribine
* Dimethyl fumarate
* Fingolimod
* Glatiramer acetate
* Interferon beta-1a
* Interferon beta-1b
* Mitoxantrone
* Natalizumab
* Ocrelizumab
* Ozanimod
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* Teriflunomide
Other treatments
* Former
* Daclizumab
* Multiple sclerosis research
Demyleinating diseases
Autoimmune
* Multiple sclerosis
* Neuromyelitis optica
* Diffuse myelinoclastic sclerosis
Inflammatory
* Acute disseminated encephalomyelitis
* MOG antibody disease
* Balo concentric sclerosis
* Marburg acute multiple sclerosis
* Neuromyelitis optica
* Diffuse myelinoclastic sclerosis
* Tumefactive multiple sclerosis
* Experimental autoimmune encephalomyelitis
Hereditary
* Adrenoleukodystrophy
* Alexander disease
* Canavan disease
* Krabbe disease
* Metachromatic leukodystrophy
* Pelizaeus–Merzbacher disease
* Leukoencephalopathy with vanishing white matter
* Megalencephalic leukoencephalopathy with subcortical cysts
* CAMFAK syndrome
Other
* Central pontine myelinolysis
* Marchiafava–Bignami disease
* Mitochondrial DNA depletion syndrome
Other
* List of multiple sclerosis organizations
* List of people with multiple sclerosis
* Multiple sclerosis drug pipeline
* Pathophysiology
* v
* t
* e
Hypersensitivity and autoimmune diseases
Type I/allergy/atopy
(IgE)
Foreign
* Atopic eczema
* Allergic urticaria
* Allergic rhinitis (Hay fever)
* Allergic asthma
* Anaphylaxis
* Food allergy
* common allergies include: Milk
* Egg
* Peanut
* Tree nut
* Seafood
* Soy
* Wheat
* Penicillin allergy
Autoimmune
* Eosinophilic esophagitis
Type II/ADCC
* * IgM
* IgG
Foreign
* Hemolytic disease of the newborn
Autoimmune
Cytotoxic
* Autoimmune hemolytic anemia
* Immune thrombocytopenic purpura
* Bullous pemphigoid
* Pemphigus vulgaris
* Rheumatic fever
* Goodpasture syndrome
* Guillain–Barré syndrome
"Type V"/receptor
* Graves' disease
* Myasthenia gravis
* Pernicious anemia
Type III
(Immune complex)
Foreign
* Henoch–Schönlein purpura
* Hypersensitivity vasculitis
* Reactive arthritis
* Farmer's lung
* Post-streptococcal glomerulonephritis
* Serum sickness
* Arthus reaction
Autoimmune
* Systemic lupus erythematosus
* Subacute bacterial endocarditis
* Rheumatoid arthritis
Type IV/cell-mediated
(T cells)
Foreign
* Allergic contact dermatitis
* Mantoux test
Autoimmune
* Diabetes mellitus type 1
* Hashimoto's thyroiditis
* Multiple sclerosis
* Coeliac disease
* Giant-cell arteritis
* Postorgasmic illness syndrome
* Reactive arthritis
GVHD
* Transfusion-associated graft versus host disease
Unknown/
multiple
Foreign
* Hypersensitivity pneumonitis
* Allergic bronchopulmonary aspergillosis
* Transplant rejection
* Latex allergy (I+IV)
Autoimmune
* Sjögren syndrome
* Autoimmune hepatitis
* Autoimmune polyendocrine syndrome
* APS1
* APS2
* Autoimmune adrenalitis
* Systemic autoimmune 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
| MOG antibody disease | None | 1,695 | wikipedia | https://en.wikipedia.org/wiki/MOG_antibody_disease | 2021-01-18T19:10:55 | {"wikidata": ["Q25339739"]} |
Porocephaliasis
SpecialtyInfectious disease
Porocephaliasis is a condition associated with species in the closely related genera Porocephalus and Armillifer. (The term "pentastomiasis" encompasses all diseases of Pentastomida, which includes porocephaliasis and linguatulosis.)
Porocephaliasis is associated with contact with snakes. (This is in contrast with linguatulosis, which is associated with contact with dogs or wolves.)
It has been reported from Africa, Malaysia and the Middle East. Its occurrence has been rare in Europe and North America where it has been found in immigrants and travelers.[1]
## Contents
* 1 Transmission and presentation
* 2 Diagnosis
* 3 Treatment and prevention
* 4 References
* 5 External links
## Transmission and presentation[edit]
It is prevalent in parts of Africa[2] and Asia[3] where eating snake meat is common. In Africa it has also been associated with groups who use the snake as a totem.[4] Unlike linguatuliasis, humans are only ever an accidental intermediate host for Armillifer, i.e. the larvae establish themselves in the visceral organs causing human visceral pentastomiasis, but adults do not occur in the human respiratory system. After a while the larvae die within the host and sometimes calcify, leaving characteristic crescent-shaped structures seen in X-ray.[5] In extreme cases a heavy parasite burden can have serious medical consequences[6] and can even be fatal.[7]
## Diagnosis[edit]
Diagnosis is by histopathology.[1]
## Treatment and prevention[edit]
No treatment is necessary in asymptomatic patients, but there is no antiparasitic chemotherapy or medical treatment available for pentastomiasis. Surgery may be needed for infection by many parasites.[1] Infection can be prevented by washing the hands after touching snake secretions or meat and cooking snake meat thoroughly prior to consumption.[1]
## References[edit]
1. ^ a b c d Dennis Tappe & Dietrich W. Büttner (2009). Bethony, Jeffrey M. (ed.). "Diagnosis of Human Visceral Pentastomiasis". PLoS Neglected Tropical Diseases. 3 (2): 1–7. doi:10.1371/journal.pntd.0000320. PMC 2643528. PMID 19238218.
2. ^ V. du Plessis; A. J. Birnie; I. Eloff; H. Reuter; S. Andronikou (2007). "Pentastomiasis (Armillifer armillatus infestation)" (PDF). South African Medical Journal. 97: 928–930.[permanent dead link]
3. ^ M. H. Yao; F. Wu; L. F. Tang (2008). "Human pentastomiasis in China: case report and literature review". Journal of Parasitology. 94 (6): 1295–1298. doi:10.1645/GE-1597.1. PMID 18576869.
4. ^ J. C. B. Dakubo; S. B. Naaeder; R. Kumodji (2008). "Totemism and the Transmission of Human Pentastomiasis". Ghana Medical Journal. 42 (4): 165–168. PMC 2673832. PMID 19452026.
5. ^ E. M. Mapp; M. D. Pollack; L. H. Goldman (1976). "Roentgen diagnosis of Armillifer armillatus infestation (porocephalosis) in man". Journal of the National Medical Association. 68 (3): 198–200. PMC 2609651. PMID 933188.
6. ^ C.-M. Pan; H.-F. Tang; M.-H. Qui; Q.-X. Xiong (2005). "Heavy infection with Armillifer moniliformis: a case report". Chinese Medical Journal. 118: 262–264. Archived from the original on 2011-07-18.
7. ^ H. Yapo Ette; L. Fanton; K. D. Adou Bryn; K. Botti; K. Koffi; D. Malicier (2003). "Human pentastomiasis discovered post-mortem". Forensic Science International. 137 (1): 52–54. doi:10.1016/S0379-0738(03)00281-0. PMID 14550614.
## External links[edit]
Classification
D
* ICD-10: B88.8
* DiseasesDB: 33345
* v
* t
* e
Arthropods and ectoparasite-borne diseases and infestations
Insecta
Louse
* Body louse (pediculosis corporis) / Head louse (head lice infestation)
* Crab louse (phthiriasis)
Hemiptera
* Bed bug (cimicosis)
Fly
* Dermatobia hominis / Cordylobia anthropophaga / Cochliomyia hominivorax (myiasis)
* Mosquito (mosquito-borne disease)
Flea
* Tunga penetrans (tungiasis)
Crustacea
Pentastomida
* Linguatula serrata (linguatulosis)
* Porocephalus crotali / Armillifer armillatus (porocephaliasis)
* For ticks and mites, see Template:Tick and mite-borne diseases and infestations
*[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
| Porocephaliasis | c0277483 | 1,696 | wikipedia | https://en.wikipedia.org/wiki/Porocephaliasis | 2021-01-18T18:32:03 | {"umls": ["C0277483"], "icd-10": ["B88.8"], "wikidata": ["Q4373155"]} |
A number sign (#) is used with this entry because of evidence that trichotillomania is caused by heterozygous mutation in the SLITRK1 gene (609678) on chromosome 13q31. One such patient has been reported.
Description
Trichotillomania (TTM) is a neuropsychiatric disorder characterized by chronic, repetitive, or compulsive hair pulling resulting in noticeable hair loss. The activity causes distress to the individual and often interferes with functioning. Affected individuals may develop physical complications and often have overlapping psychologic disorders, such as Tourette syndrome (GTS; 137580) or obsessive-compulsive disorder (OCD; 164230) (review by Novak et al., 2009).
Clinical Features
Kerbeshian and Burd (1991) reported a 37-year-old woman with trichotillomania manifest as chronic pulling out of her eyebrows and eyelashes. She reported compulsive behavior, such as avoiding sidewalk cracks and counting the number of drips from a faucet, from age 6 years. She had experienced repeated sexual and physical abuse throughout her life. The episodes of trichotillomania were described as an irresistible impulse followed by a sense of tension release. She also had depression (608516). Treatment with clomipramine resulted in symptom improvement. Her sister and brother also had trichotillomania, but detailed history was not available.
Inheritance
Kerbeshian and Burd (1991) reported 3 affected sibs.
Novak et al. (2009) evaluated 33 female twin pairs and 1 male twin pair in which either 1 or both twins had trichotillomania. Significant differences in monozygotic and dizygotic concordance rates were observed for 3 of 5 diagnostic schemes: DSM-IV criteria (0.381 vs 0.00; p = 0.047), modified DSM criteria (0.391 vs 0.00; p = 0.021), and noncosmetic hair pulling (0.583 vs 0.200; p = 0.046), yielding heritability estimates between 0.76 to 0.78. The findings suggested that a significant proportion of trichotillomanic behavior can be accounted for by genetic factors. Analysis of concordance rates for possible similar phenotypes, including skin picking and hair manipulation, were not significantly different, suggesting that these are not alternate phenotypes of TTM.
Molecular Genetics
Abelson et al. (2005) identified a 1-bp deletion in the SLITRK1 gene (609678.0001) in a boy with Tourette syndrome and ADHD (143465). The mother, who had severe trichotillomania, also had the mutation, which was not found in 3,600 control chromosomes.
Animal Model
Greer and Capecchi (2002) noted that the behavior of Hoxb8 (142963)-null mice is not unlike that of humans suffering from the obsessive-compulsive spectrum disorder (OCD) trichotillomania. Consistent with this, they detected expression of Hoxb8 in regions of the CNS known as the 'OCD-circuit,' where OCD patients are thought to have abnormal metabolic activity. They hypothesized that trichotillomania may arise from a misregulation of an innate autogrooming behavior and presented Hoxb8-mutant mice as a model of OCD-like phenotypes.
Welch et al. (2007) generated Sapap3 (DLGAP3;611413)-deficient mice and found that they had increased anxiety and compulsive grooming behavior leading to facial hair loss (e.g., trichotillomania) and skin lesions. Both behaviors were alleviated by a selective serotonin reuptake inhibitor. Electrophysiologic, structural, and biochemical studies of Sapap3-mutant mice revealed defects in corticostriatal synapses.
INHERITANCE \- Autosomal dominant \- Multifactorial SKIN, NAILS, & HAIR Hair \- Alopecia resulting from compulsive hair pulling NEUROLOGIC Behavioral Psychiatric Manifestations \- Hair pulling, chronic, compulsive, repetitive \- Distress and functional impairment resulting from hair pulling behavior MISCELLANEOUS \- Affected individuals can pull hair from any part of the body, including eyelashes and eyebrows \- Overlap with obsessive-compulsive disorder (OCD, 164230 ) \- Overlap with Tourette syndrome ( 137580 ) \- Affects 1 to 3% of the population \- One patient reported with SLITRK1 mutation (as of January 2010) MOLECULAR BASIS \- Caused by mutation in the slit- and ntrk-like family, member 1 gene (SLITRK1, 609678.0001 ) ▲ 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
| TRICHOTILLOMANIA | c0040953 | 1,697 | omim | https://www.omim.org/entry/613229 | 2019-09-22T15:59:15 | {"doid": ["0050587"], "mesh": ["D014256"], "omim": ["613229"], "icd-10": ["F63.3"]} |
MUTYH-associated polyposis
Other namesMYH-associated polyposis
SpecialtyMedical genetics, gastroenterology
ComplicationsColorectal cancer
CausesDNA repair gene mutation
Diagnostic methodColonoscopy
Differential diagnosisFamilial adenomatous polyposis, Lynch syndrome
TreatmentColonoscopy
Polypectomy
Frequency<1%
MUTYH-associated polyposis (also known as MYH-associated polyposis) is an autosomal recessive polyposis syndrome.[1] The disorder is caused by mutations in both alleles (genetic copies) of the DNA repair gene, MUTYH. The MUTYH gene encodes a base excision repair protein, which corrects oxidative damage to DNA. Affected individuals have an increased risk of colorectal cancer, precancerous colon polyps (adenomas) and an increased risk of several additional cancers. About 1–2 percent of the population possess a mutated copy of the MUTYH gene, and less than 1 percent of people have the MUTYH associated polyposis syndrome. The presence of 10 or more colon adenomas should prompt consideration of MUTYH-associated polyposis, familial adenomatous polyposis and similar syndromes.[2]
## Epidemiology[edit]
Without surveillance or screening, between 43% and 100% of individuals with MUTYH-associated polyposis develop colorectal cancer.[3]
## References[edit]
1. ^ Tomlinson, Ian (April 2015). "An update on the molecular pathology of the intestinal polyposis syndromes". Diagnostic Histopathology. 21 (4): 147–151. doi:10.1016/j.mpdhp.2015.04.006.
2. ^ Gupta, S; Provenzale, D; Llor, X; Halverson, AL; Grady, W; Chung, DC; Haraldsdottir, S; Markowitz, AJ; Slavin TP, Jr; Hampel, H; CGC.; Ness, RM; Weiss, JM; Ahnen, DJ; Chen, LM; Cooper, G; Early, DS; Giardiello, FM; Hall, MJ; Hamilton, SR; Kanth, P; Klapman, JB; Lazenby, AJ; Lynch, PM; Mayer, RJ; Mikkelson, J; CGC.; Peter, S; Regenbogen, SE; Dwyer, MA; CGC.; Ogba, N (1 September 2019). "NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019". Journal of the National Comprehensive Cancer Network : JNCCN. 17 (9): 1032–1041. doi:10.6004/jnccn.2019.0044. PMID 31487681.
3. ^ Nielsen, Maartje; Lynch, Henry; Infante, Elena; Brand, Randall. "MUTYH-Associated Polyposis". NCBI. GeneReviews.
* v
* t
* e
Digestive system neoplasia
GI tract
Upper
Esophagus
* Squamous cell carcinoma
* Adenocarcinoma
Stomach
* Gastric carcinoma
* Signet ring cell carcinoma
* Gastric lymphoma
* MALT lymphoma
* Linitis plastica
Lower
Small intestine
* Duodenal cancer
* Adenocarcinoma
Appendix
* Carcinoid
* Pseudomyxoma peritonei
Colon/rectum
* Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers
Cronkhite–Canada
* Polyposis syndromes: Juvenile
* MUTYH-associated
* Familial adenomatous/Gardner's
* Polymerase proofreading-associated
* Serrated polyposis
* Neoplasm: Adenocarcinoma
* Familial adenomatous polyposis
* Hereditary nonpolyposis colorectal cancer
Anus
* Squamous cell carcinoma
Upper and/or lower
* Gastrointestinal stromal tumor
* Krukenberg tumor (metastatic)
Accessory
Liver
* malignant: Hepatocellular carcinoma
* Fibrolamellar
* Hepatoblastoma
* benign: Hepatocellular adenoma
* Cavernous hemangioma
* hyperplasia: Focal nodular hyperplasia
* Nodular regenerative hyperplasia
Biliary tract
* bile duct: Cholangiocarcinoma
* Klatskin tumor
* gallbladder: Gallbladder cancer
Pancreas
* exocrine pancreas: Adenocarcinoma
* Pancreatic ductal carcinoma
* cystic neoplasms: Serous microcystic adenoma
* Intraductal papillary mucinous neoplasm
* Mucinous cystic neoplasm
* Solid pseudopapillary neoplasm
* Pancreatoblastoma
Peritoneum
* Primary peritoneal carcinoma
* Peritoneal mesothelioma
* Desmoplastic small round cell tumor
*[v]: View this template
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*[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
| MUTYH-associated polyposis | c3272841 | 1,698 | wikipedia | https://en.wikipedia.org/wiki/MUTYH-associated_polyposis | 2021-01-18T18:40:03 | {"gard": ["10805"], "umls": ["C1828108"], "wikidata": ["Q1266575"]} |
Malalignment of the nail plate
SpecialtyDermatology
Malalignment of the nail plate is a congenital malalignment of the nail of the great toe, and is often misdiagnosed although it is a common condition.[1]:659–60
## See also[edit]
* Skin lesion
## References[edit]
1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
This condition of the skin appendages 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
| Malalignment of the nail plate | None | 1,699 | wikipedia | https://en.wikipedia.org/wiki/Malalignment_of_the_nail_plate | 2021-01-18T19:05:01 | {"wikidata": ["Q6741211"]} |
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