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A rare neurologic disease characterized by bilateral cataract, Dandy-Walker malformation, and childhood onset of distal spinal muscular atrophy. Patients present with progressively deteriorating symmetrical distal muscle weakness and atrophy of the lower limbs (and, to a much lesser degree, also the upper limbs) and decreased tendon reflexes in the lower and upper limbs.
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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
| Spinal muscular atrophy-Dandy-Walker malformation-cataracts syndrome | None | 1,000 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=73245 | 2021-01-23T17:00:42 | {"icd-10": ["G12.8"]} |
Erythromelalgia is a condition characterized by episodes of pain, redness, and swelling in various parts of the body, particularly the hands and feet. These episodes are usually triggered by increased body temperature, which may be caused by exercise or entering a warm room. Ingesting alcohol or spicy foods may also trigger an episode. Wearing warm socks, tight shoes, or gloves can cause a pain episode so debilitating that it can impede everyday activities such as wearing shoes and walking. Pain episodes can prevent an affected person from going to school or work regularly.
The signs and symptoms of erythromelalgia typically begin in childhood, although mildly affected individuals may have their first pain episode later in life. As individuals with erythromelalgia get older and the disease progresses, the hands and feet may be constantly red, and the affected areas can extend from the hands to the arms, shoulders, and face, and from the feet to the entire legs.
Erythromelalgia is often considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.
## Frequency
The prevalence of erythromelalgia is unknown.
## Causes
Mutations in the SCN9A gene can cause erythromelalgia. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.
The SCN9A gene mutations that cause erythromelalgia result in NaV1.7 sodium channels that open more easily than usual and stays open longer than normal, increasing the flow of sodium ions into nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the signs and symptoms of erythromelalgia. It is unknown why the pain episodes associated with erythromelalgia mainly occur in the hands and feet.
An estimated 15 percent of cases of erythromelalgia are caused by mutations in the SCN9A gene. Other cases are thought to have a nongenetic cause or may be caused by mutations in one or more as-yet unidentified genes.
### Learn more about the gene associated with Erythromelalgia
* SCN9A
## Inheritance Pattern
Some cases of erythromelalgia occur in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some of these instances, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
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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
| Erythromelalgia | c0014805 | 1,001 | medlineplus | https://medlineplus.gov/genetics/condition/erythromelalgia/ | 2021-01-27T08:25:46 | {"gard": ["6377"], "mesh": ["D004916"], "omim": ["133020"], "synonyms": []} |
Mucopolysaccharidosis type IV (MPS IV), also known as Morquio syndrome, is a rare metabolic condition in which the body is unable to break down long chains of sugar molecules called glycosaminoglycans. As a result, toxic levels of these sugars accumulate in cell structures called lysosomes, leading to the various signs and symptoms associated with the condition. Affected people generally develop features of MPS IV between the ages of 1 and 3. These signs and symptoms may include abnormalities of the skeleton, eyes, heart and respiratory system. There are two forms of MPS IV:
* MPS IVA is caused by changes (mutations) in the GALNS gene.
* MPS IVB is caused by mutations in the GLB1 gene.
Both forms are inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person.
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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
| Mucopolysaccharidosis type IV | c0026707 | 1,002 | gard | https://rarediseases.info.nih.gov/diseases/12562/mucopolysaccharidosis-type-iv | 2021-01-18T17:58:56 | {"mesh": ["D009085"], "orphanet": ["582"], "synonyms": ["MPS4", "MPSIV", "Mucopolysaccharidosis type 4", "Morquio disease"]} |
Chudley et al. (1985) described a family in which an adult brother and sister had congenital, nonprogressive myopathy due to multicore disease, severe mental retardation, short stature, and small pituitary fossa with sexual infantilism due to hypogonadotropic hypogonadism. Both had generalized mild weakness, bilateral ptosis and facial weakness, and exaggerated lumbar lordosis. Muscle biopsies showed variation in fibrodiameter, internal nuclei, atrophy of type I fibers, focal loss of cross-striations, and cores of myofibrillar disruption with associated absence of mitochondria. The parents were first cousins. Arginine, L-DOPA, and propranolol stimulation resulted in normal growth hormone responses.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Face \- Facial weakness Eyes \- Ptosis GENITOURINARY External Genitalia (Male) \- Hypogonadotropic hypogonadism Internal Genitalia (Female) \- Hypogonadotropic hypogonadism SKELETAL Spine \- Lumbar lordosis, exaggerated MUSCLE, SOFT TISSUES \- Congenital, nonprogressive myopathy \- Mild muscle weakness \- Variation in fibrodiameter seen on muscle biopsy \- Internal nuclei \- Atrophy of type I fibers \- Focal loss of cross- striations \- Cores of myofibrillar disruption with associated absence of mitochondria NEUROLOGIC Central Nervous System \- Small sella \- Mental retardation, severe ENDOCRINE FEATURES \- Hypogonadotropic hypogonadism LABORATORY ABNORMALITIES \- Normal growth hormone responses to arginine, L-dopa, and propranolol stimulation MISCELLANEOUS \- Sexual infantilism ▲ 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
| MULTICORE MYOPATHY WITH MENTAL RETARDATION, SHORT STATURE, AND HYPOGONADOTROPIC HYPOGONADISM | c1854663 | 1,003 | omim | https://www.omim.org/entry/253320 | 2019-09-22T16:24:55 | {"mesh": ["C535458"], "omim": ["253320"], "orphanet": ["3068"], "synonyms": ["Alternative titles", "CHUDLEY SYNDROME"]} |
A rare primary immunodeficiency due to a defect in innate immunity characterized by a marked decrease or absence of myeloperoxidase activity in neutrophils and monocytes. Clinically, most patients are asymptomatic. Occasionally, severe infectious complications may occur, particularly recurrent candida infections, being especially severe in the setting of comorbid diabetes mellitus.
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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
| Myeloperoxidase deficiency | c0398595 | 1,004 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2587 | 2021-01-23T17:07:03 | {"gard": ["3868"], "mesh": ["C562864"], "omim": ["254600"], "umls": ["C0398595"], "icd-10": ["E80.3"], "synonyms": ["MPO deficiency"]} |
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Secondary poisoning" – news · newspapers · books · scholar · JSTOR (April 2017) (Learn how and when to remove this template message)
Secondary poisoning, or relay toxicity, is the poisoning that results when one organism comes into contact with or ingests another organism that has poison in its system. It typically occurs when a predator eats an animal, such as a mouse, rat, or insect, that has previously been poisoned by a commercial pesticide. If the level of toxicity in the prey animal is sufficiently high, it will harm the predator.
Mammals susceptible to secondary poisoning include humans, with infants and small children being the most susceptible. Pets such as cats and dogs, as well as wild birds, also face significant risk of secondary poisoning.
## Pesticides[edit]
Various pesticides such as rodenticides may cause secondary poisoning.[1] Some pesticides require multiple feedings spanning several days; this increases the time a target organism continues to move after ingestion, raising the risk of secondary poisoning of a predator.
Pesticide Type Classification Target Oral Toxicity Feedings Secondary Risk to Mammals Secondary Risk to Birds
Warfarin Anticoagulant Hydroxycoumarin Rodenticide Moderate Multiple Low Minimal
Bromadiolone Anticoagulant Hydroxycoumarin Rodenticide High Single Moderate Moderate
Difethialone Anticoagulant Hydroxycoumarin Rodenticide High Single Moderate Highest
Brodifacoum Anticoagulant Hydroxycoumarin Rodenticide Highest Single Highest Highest
Chlorophacinone Anticoagulant Indandione Rodenticide High Multiple Highest Minimal
Diphacinone Anticoagulant Indandione Rodenticide High Multiple Highest Moderate
Bromethalin CNS other Rodenticide High Single Low Low
Fluoroacetate Metabolism other Rodenticide Highest Single High Highest
Zinc phosphide other other Rodenticide High Single Minimal Low
## References[edit]
1. ^ Rodenticides: Topic Fact Sheet, National Pesticide Information Center
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*[c.]: circa
*[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
| Secondary poisoning | None | 1,005 | wikipedia | https://en.wikipedia.org/wiki/Secondary_poisoning | 2021-01-18T18:40:29 | {"wikidata": ["Q7443865"]} |
A number sign (#) is used with this entry because of evidence that susceptibility to multiple types of pituitary adenoma (PITA5) is conferred by heterozygous mutation in the CDH23 gene (605516) on chromosome 10q21.
Description
Both familial and sporadic pituitary adenomas have been found to be caused by germline mutation in the CDH23 gene. Familial pituitary adenoma types include growth hormone (GH)-secreting and nonfunctional tumors. Sporadic pituitary adenoma types include GH-secreting, nonfunctional, prolactin (PRL)-secreting, adrenocorticotropin (ACTH)-secreting, thyroid-stimulating hormone (TSH)-secreting, and plurihormonal (GH and TSH) tumors.
For a general description and a discussion of genetic heterogeneity of pituitary adenomas, see PITA1 (102200).
Clinical Features
Zhang et al. (2017) reported a family in which 4 individuals developed pituitary adenomas. Two patients had GH-secreting tumors and underwent surgical resection, whereas the other 2 patients had nonfunctional tumors with occasional headaches and did not undergo surgery. Subsequently, 3 additional families in which more than 2 individuals had either GH-secreting or nonfunctional pituitary tumors were identified. Finally, 15 patients with apparently sporadic pituitary tumors associated with CDH23 mutations were identified. The tumor types among these patients varied, and included 1 nonfunctional, 3 PRL-secreting, 2 GH-secreting, 4 ACTH-secreting, 1 glomus tumor, 3 TSH-secreting, and 1 plurihormonal (GH and TSH).
Inheritance
The transmission pattern of pituitary adenomas in the families reported by Zhang et al. (2017) was consistent with autosomal dominant inheritance with incomplete penetrance.
Molecular Genetics
In affected members of 4 unrelated families with both functional growth hormone-secreting and nonfunctional pituitary adenomas, Zhang et al. (2017) identified germline heterozygous missense mutations in the CDH23 gene (605516.0016-605516.0019). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. There was evidence of age-dependent or incomplete penetrance. Whole-exome sequencing of 125 individuals with sporadic pituitary adenoma identified CDH23 mutations in 15 individuals (12.0%); 13 had heterozygous mutations and 2 had homozygous mutations. The tumor types in these patients varied. All mutations identified occurred at highly conserved residues in the EC domains of CDH23, and were predicted to adversely affect calcium binding or protein folding. Functional studies of the variants were not performed. Compared to pituitary adenomas with wildtype CDH23, those associated with CDH23 mutations were smaller in diameter and less invasive. Heterozygous, putatively functional variants in the CDH23 gene were found in 2 (0.8%) of 260 control individuals.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Pituitary adenoma ENDOCRINE FEATURES \- Pituitary adenoma MISCELLANEOUS \- Adult onset \- Adenomas may be functioning or nonfunctioning \- Incomplete penetrance MOLECULAR BASIS \- Susceptibility conferred by mutation in the cadherin 23 gene (CDH23, 605516.0016 ) ▲ 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
| PITUITARY ADENOMA 5, MULTIPLE TYPES | c4539685 | 1,006 | omim | https://www.omim.org/entry/617540 | 2019-09-22T15:45:36 | {"omim": ["617540"]} |
An acute arboviral infection caused by the La Crosse bunyavirus transmitted by an infected mosquito, usually observed in infants, children or adolescents (6 months to 16 years), and characterized by the onset of flulike symptoms such as fever, chills, nausea, vomiting, headache, and abdominal pain, followed by the onset of encephalitis characterized by somnolence, obtundation, and even seizures, focal neurologic signs (asymmetrical reflexes or Babinski signs), paralysis or even coma. CE can leave sequelae such as residual epilepsy and neurocognitive deficits.
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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
| La Crosse encephalitis | c0014053 | 1,007 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83483 | 2021-01-23T19:00:37 | {"gard": ["10820", "10925"], "mesh": ["D004670"], "umls": ["C0014053"], "icd-10": ["A83.5"], "synonyms": ["Californian encephalitis"]} |
Ectopic thymus is a condition where thymus tissue is found in an abnormal location. It is thought to be the result of either a failure of descent or a failure of involution of normal thymus tissue.
## Contents
* 1 Signs and Symptoms
* 2 Cause
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 References
## Signs and Symptoms[edit]
Ectopic thymus most often does not cause symptoms. It is most frequently discovered as a mass or swelling in the neck of infants and children.[1] However, when symptoms do occur they are most commonly due to compression of nearby structures such as the trachea and esophagus. This can lead to hoarseness, stridor, difficulty breathing and/or difficulty swallowing.[2][3]
## Cause[edit]
During embryological development, the thymus is formed from the third and fourth pharyngeal pouches. It descends along a pathway from the mandible to its final resting place of the mediastinum.[1] When the thymus tissue fails to descend appropriately or fails to involute, thymus tissue remains in various locations along this pathway. Locations that solid thymus tissue has been reported include near the thyroid (most common), within the thyroid, the base of the skull, and within the pharynx or trachea.[4][1]
## Diagnosis[edit]
Ultrasound is the recommended diagnostic modality used to diagnose cervical ectopic thymus.[4] The thymus has a unique appearance on ultrasound which allows for specific diagnosis.[5][6] Upon ultrasound, ectopic thymus appears hypoechoic with characteristic linear echogenic foci.[2] However, MRI can and has been utilized as well to better characterize and identify the location of the ectopic thymus.[1] On MRI, ectopic cervical thymus appears as a homogeneous mass which is isointense to muscle on T1-weighted scans and hyperintense on T2-weighted scans.[2] Biopsy or histological examination upon resection can also be used to make a definitive diagnosis.[citation needed]
An appropriate differential diagnosis depends upon location of the ectopic thymus. For cervical ectopic thymus the differential diagnosis should include additional causes of neck masses. This includes common causes of neck masses in children such as thyroglossal duct cyst, branchial cleft cyst, dermoid cyst, inflammatory lymphadenitis, sternocleidomastoid (SCM) tumor of infancy, a salivary gland infection or benign tumor.[7][4] Rare causes of neck masses in children include lymphoma, rhabdomyosarcoma, thyroid nodules and thyroid cancer.[7][4]
## Treatment[edit]
If the patient is asymptomatic and the mass is identified based upon radiologic findings, biopsy and/or resection may be avoided.[4] Surgical removal of the mass is the definitive treatment for ectopic thymus tissue that is causing symptoms.[3] It has been reported that the ectopic thymus tissue can transform into cancerous tissue.[3] However, due to most diagnosed ectopic thymus tissue being resected due to this concern, the natural progression is not well explored. The data supporting malignant transformation is limited and ectopic thymus tissue that is not causing problems can likely be left to involute.[8] Given the thymus's role in the body's adaptive immune system, it should be confirmed that the patient has a mediastinal thymus prior to surgery in order to prevent the potential for future immune deficiencies.[3]
## Prognosis[edit]
Following surgical removal of the ectopic thymus, there have been no reported recurrences.[3]
## Epidemiology[edit]
Ectopic thymus is rarely reported in the literature.[1] The prevalence of ectopic thymus reportedly ranges from 1 to 90%. This variation in prevalence is largely dependent upon the method of investigation used and how extensive the workup is.[9] With most ectopic thymus tissue being asymptomatic, it is likely the prevalence is higher than typically reported.[2]
## References[edit]
1. ^ a b c d e Lavini, Corrado; Moran, Cesar A.; Morandi, Uliano; Schoenhuber, Rudolf (2009-05-08). Thymus Gland Pathology: Clinical, Diagnostic and Therapeutic Features. Springer Science & Business Media. ISBN 978-88-470-0828-1.
2. ^ a b c d Herman, T. E.; Siegel, M. J. (February 2009). "Cervical ectopic thymus". Journal of Perinatology. 29 (2): 173–174. doi:10.1038/jp.2008.89. ISSN 1476-5543. PMID 19177048.
3. ^ a b c d e Anastasiadis, Kyriakos; Ratnatunga, Chandi (2007-06-07). The Thymus Gland: Diagnosis and Surgical Management. Springer Science & Business Media. ISBN 978-3-540-33426-2.
4. ^ a b c d e Bang, Myung Hoon; Shin, JinShik; Lee, Kwan Seop; Kang, Min Jae (2018-04-06). "Intrathyroidal ectopic thymus in children". Medicine. 97 (14): e0282. doi:10.1097/MD.0000000000010282. ISSN 0025-7974. PMC 5902273. PMID 29620644.
5. ^ Han, Bokyung K.; Yoon, H.-K.; Suh, Yeon-Lim (2001-07-01). "Thymic ultrasound". Pediatric Radiology. 31 (7): 480–487. doi:10.1007/s002470100468. ISSN 1432-1998. PMID 11486800. S2CID 2797344.
6. ^ Yildiz, Adalet Elcin; Ceyhan, Koray; Sıklar, Zeynep; Bilir, Pelin; Yağmurlu, Emin Aydın; Berberoğlu, Merih; Fitoz, Suat (September 2015). "Intrathyroidal Ectopic Thymus in Children: Retrospective Analysis of Grayscale and Doppler Sonographic Features". Journal of Ultrasound in Medicine. 34 (9): 1651–1656. doi:10.7863/ultra.15.14.10041. ISSN 1550-9613. PMID 26269296.
7. ^ a b Philadelphia, The Children's Hospital of (2016-04-11). "Neck Masses". www.chop.edu. Retrieved 2020-04-11.
8. ^ Schloegel, Luke J.; Gottschall, Joshua A. (2009-03-01). "Ectopic cervical thymus: Is empiric surgical excision necessary?". International Journal of Pediatric Otorhinolaryngology. 73 (3): 475–479. doi:10.1016/j.ijporl.2008.10.031. ISSN 0165-5876. PMID 19117616.
9. ^ Marx, A.; Rüdiger, T.; Rößner, E.; Tzankov, A.; de Montpréville, V. T.; Rieker, R. R.; Ströbel, P.; Weis, C.‑A. (2018-09-01). "Ektopien des Thymus und ektope Thymustumoren". Der Pathologe (in German). 39 (5): 390–397. doi:10.1007/s00292-018-0485-z. ISSN 1432-1963. PMID 30159601. S2CID 52123197.
Classification
D
* ICD-10: Q89.2
* ICD-9-CM: 759.2
* v
* t
* e
Lymphatic disease: organ and vessel diseases
Thymus
* Abscess
* Hyperplasia
* Hypoplasia
* DiGeorge syndrome
* Ectopic thymus
* Thymoma
* Thymic carcinoma
Spleen
* Asplenia
* Asplenia with cardiovascular anomalies
* Accessory spleen
* Polysplenia
* Wandering spleen
* Splenomegaly
* Banti's syndrome
* Splenic infarction
* Splenic tumor
Lymph node
* Lymphadenopathy
* Generalized lymphadenopathy
* Castleman's disease
* Intranodal palisaded myofibroblastoma
* Kikuchi disease
* Tonsils
* see Template:Respiratory pathology
Lymphatic vessels
* Lymphangitis
* Lymphangiectasia
* Lymphedema
* Primary lymphedema
* Congenital lymphedema
* Lymphedema praecox
* Lymphedema tarda
* Lymphedema–distichiasis syndrome
* Milroy's disease
* Secondary lymphedema
* Bullous lymphedema
* Factitial lymphedema
* Postinflammatory lymphedema
* Postmastectomy lymphangiosarcoma
* Waldmann disease
*[v]: View this template
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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
| Ectopic thymus | c1333375 | 1,008 | wikipedia | https://en.wikipedia.org/wiki/Ectopic_thymus | 2021-01-18T18:41:36 | {"umls": ["C1333375"], "icd-9": ["759.2"], "icd-10": ["Q89.2"], "wikidata": ["Q5334295"]} |
For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia (SPG), see SPG5A (270800).
Clinical Features
Zortea et al. (2002) reported a consanguineous Italian family in which 4 of 8 sibs were affected with adult-onset (range 30 to 46 years) pyramidal symptoms in the lower limbs. In all 4 affected sibs, the paresis was accompanied or preceded by spinal pain radiating to the upper or lower limbs, and all of them had spinal disc herniation with minor spondylosis detected by neuroimaging.
Mapping
By genomewide linkage analysis of a consanguineous Italian family with spastic paraplegia, Zortea et al. (2002) found linkage to chromosome 6q23.3-q24.1 (maximum multipoint lod score of 3.28 between markers D6S1699 and D6S314).
INHERITANCE \- Autosomal recessive HEAD & NECK Neck \- Neck pain SKELETAL Spine \- Spinal disc herniation, various regions of the spine \- Spondylosis \- Back pain NEUROLOGIC Central Nervous System \- Spastic paraplegia \- Pain in the upper and lower limbs \- Pyramidal signs secondary to spinal cord compression Peripheral Nervous System \- Sensory or motor neuropathy, mild (in some patients) MISCELLANEOUS \- Adult onset of neurologic symptoms (range 30 to 46 years) \- One consanguineous Italian family has been reported (last curated August 2015) ▲ 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
| SPASTIC PARAPLEGIA 25, AUTOSOMAL RECESSIVE | c2936860 | 1,009 | omim | https://www.omim.org/entry/608220 | 2019-09-22T16:08:10 | {"doid": ["0110776"], "mesh": ["C536861"], "omim": ["608220"], "orphanet": ["101005"], "synonyms": ["Alternative titles", "DISC HERNIATION WITH SPASTIC PARAPLEGIA, AUTOSOMAL RECESSIVE"]} |
Abortion in Estonia has been legal since 23 November 1955, when Estonia was part of the Soviet Union. Estonia fine-tuned their legislation after the restoration of independence.[1]
Estonia allows abortion on-demand for any purpose,[1] before the end the 11th week of pregnancy.[2] Later abortions are permitted up to the 21st week (included) if the woman is younger than 15 years old or older than 45 years old, if the pregnancy endangers the woman's health, if the child may have a serious physical or mental defect, or if the woman's illness or other medical problem hinders the child's development.[2]
Women who want to have an abortion for personal reasons not specified in the abortion legislation will be expected to pay a fee according to the abortion provider's price list.[1] Abortion performed for medical reasons is covered for insured persons by the Estonian Health Insurance Fund.[3]
38.7% of pregnancies ended in abortion in Estonia in 2006, a decline from 49.4% just six years before.[4]
In 2010, there were 9087 abortions in Estonia, which meant 57.4 abortions for every hundred live births.[5] As of 2010[update], the abortion rate was 25.5 abortions per 1000 women aged 15–44 years.[6]
Mifepristone (medical abortion) was registered in 2003.[7]
## References[edit]
1. ^ a b c Estonia - ABORTION POLICY - United Nations
2. ^ a b "Raseduse katkestamise ja steriliseerimise seadus" (in Estonian). Elektrooniline Riigi Teataja. 25 November 1998.
3. ^ "abort - haigekassa.ee" (in Estonian). Estonian Health Insurance Fund. 28 February 2011. Archived from the original on 27 July 2011.
4. ^ Estonia: abortion rates by county, 2000-2006
5. ^ "Abortide arv langeb jätkuvalt". ERR.
6. ^ "World Abortion Policies 2013". United Nations. 2013. Retrieved 3 March 2014.
7. ^ "Archived copy". Archived from the original on 2017-09-26. Retrieved 2017-09-29.CS1 maint: archived copy as title (link)
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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 Estonia | None | 1,010 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_Estonia | 2021-01-18T18:41:11 | {"wikidata": ["Q1425609"]} |
A rare ophthalmic disorder characterized by intraocular inflammation primarily localized to the vitreous and peripheral retina. It incorporates pars planitis, posterior cyclitis, and hyalitis. Patients present with painless floaters, decreased or blurred vision, less frequently with pain, redness, and photophobia. On examination, snow banking, vitreous snowballs, peripheral retinal vascular sheathing, vitreous cells, and vitreous haze can be seen. Complications include epiretinal membrane formation, cataract formation, cystoid macular edema, or band keratopathy, among others. The condition may be idiopathic or occur in the context of infectious or systemic diseases.
*[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
| Intermediate uveitis | c0042166 | 1,011 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=279914 | 2021-01-23T17:37:29 | {"mesh": ["D015867"], "umls": ["C0042166"], "icd-10": ["H30.2"], "synonyms": ["IU"]} |
A number sign (#) is used with this entry because of evidence that proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as encephaloclastic proliferative vasculopathy, is caused by homozygous or compound heterozygous mutation in the FLVCR2 gene (610865) on chromosome 14q24.
Description
The proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome is a rare, autosomal recessive, usually prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. It is usually diagnosed by ultrasound between 26 and 33 weeks' gestation (summary by Meyer et al., 2010). Rarely, affected individuals may survive, but are severely impaired with almost no neurologic development (Kvarnung et al., 2016).
Clinical Features
In identical male twins, Moeschler and Marin-Padilla (1989) described a disorder that had been reported in 5 sibs by Fowler et al. (1972) and in 2 sibs by Harper and Hockey (1983). Of the sibs reported by Harper and Hockey (1983), one had hydranencephaly at birth; the other had a normal ultrasound examination at 22 weeks, but later developed hydranencephaly which was evident on ultrasound at 26 weeks. The twins reported by Moeschler and Marin-Padilla (1989) were born at 25 weeks' gestation and survived only 12 minutes. Ultrasound at 16 weeks was normal. Although the brain in each was normal on gross examination, CNS proliferative vasculopathy was noted on microscopic examination. Identical anomalies were found in the dorsolateral posterior region of the right frontal lobe. Distinctive 'glomeruloid' lesions representing abnormal focal vascularization of the cortical mantle by tufts of blood vessels had resulted from focal proliferation of endothelial cells. This proliferative vasculopathy damaged the developing CNS by disruption and disorganization of the developing organ, rupture of the pial/glial surface, and hemorrhagic necrosis. Moeschler and Marin-Padilla (1989) suggested that the twins would have eventually developed typical hydranencephaly but were born before the full evolution of this abnormality.
Witters et al. (2002) described a 13-week-old female fetus with early-onset fetal akinesia deformation sequence (FADS; 208150) and hydranencephaly. In a previous pregnancy, the same ultrasonographic findings were noted in the fetus at 13 weeks' gestation. Fetopathologic examination of both female fetuses confirmed FADS with severe arthrogryposis, multiple pterygia, and muscular hypoplasia. Neuropathologic examination showed massive cystic dilatation of the cerebral ventricles (hydranencephaly) with calcification of the basal ganglion and brainstem and a proliferative vasculopathy throughout the central nervous system. This represented the earliest echographic diagnosis of Fowler-type hydranencephaly and supported autosomal recessive inheritance of this distinct form of hydranencephaly.
Bessieres-Grattagliano et al. (2009) reported 16 fetuses from 8 unrelated families with Fowler syndrome, including 4 families that were consanguineous. Common ultrasound findings beginning as early as 12 weeks' gestational age showed showed hydrocephalus with macrocrania, decreased fetal movements, severe arthrogryposis with fetal akinesia sequence, and cystic hygroma. Cleft palate and/or microretrognathia were common. Neuropathologic examinations showed encephaloclastic proliferative vasculopathy (EPV), intracranial calcifications, thin-walled cerebral hemispheres, and hypoplastic brainstem, cerebellum, and spinal cord. Immunohistochemical studies of the proliferating cells showed endothelial cell CD34 staining but decreased staining for smooth muscle actin, which stains pericytes. Fourteen fetuses showed EPV changes in both the brain and spinal cord, whereas 2 sibs had more focal involvement only of the brain. Analysis of the cerebral vasculature showed that the normal thin-walled leptomeningeal superficial vascular channels were followed by a deeper sheet of thickened perforating vessels, with some endothelial cells containing PAS-positive bodies. In the brain parenchyma, the wall of abnormal vessels contained enlarged CD34-positive endothelial cells. The most striking abnormality, best seen in the glomeruloids, was the lack of a single vascular lumina, replaced by multiple small microcavities, containing few red blood cells. Bessieres-Grattagliano et al. (2009) suggested that the disorder may result from a defect in vascular remodeling during angiogenesis.
Williams et al. (2010) reported 14 fetuses from 10 families with Fowler syndrome. Sibs were affected in 4 families, and 6 families were consanguineous, indicating autosomal recessive inheritance. The gestational age at diagnosis ranged from 13 to 27 weeks. All had the characteristic finding of glomeruloid cerebral vascular proliferation involving various brain regions, such as brainstem, cerebellum, germinal matrix, deep cerebral gray matter, white matter, cortex, and spinal cord. Within the vascular proliferation, endothelial cells contained diastase-resistant intracytoplasmic globular inclusions. Other brain features were variable but included ventriculomegaly, agenesis of the corpus callosum, hypoplastic cerebellum, and dystrophic calcification. Although ultrasound indicated hydranencephaly, histologic studies showed a hemispheric mantle in all cases, more consistent with severe hydrocephalus. Extraneurologic manifestations included intrauterine growth retardation, limb contractures, reduced muscle bulk, pterygia, low-set ears, and micrognathia.
Lalonde et al. (2010) reported a fetus, born of unrelated French Canadian parents, with Fowler syndrome ascertained at 23 weeks' gestation by the finding of ventriculomegaly and limb deformities. Postmortem examination showed fetal akinesia deformation sequence, muscular atrophy, and cutaneous webbing. Neuropathologic examination showed bag-like cerebral hemispheres with no internal structures, such as basal ganglia or thalami. The brain parenchyma showed microcalcifications and hyperplastic microvessels forming glomeruloid structures. Residual brain parenchyma was highly disorganized. Another fetus from this family had been similarly affected.
Kvarnung et al. (2016) reported 2 sibs, born of consanguineous parents from Somalia, with a severe neurologic disorder. One child had unremarkable ultrasound findings at 18 weeks' gestation, whereas the other child showed microcephaly, profound ventriculomegaly, and lissencephaly at 32 weeks' gestation. After birth, the first child was noted to have similar brain abnormalities; both also had intracranial calcifications in the cortex, cerebellum, and brainstem. Both had basically normal development until about 2 months, when they showed hypotonia, severely delayed or even absent development, and onset of seizures associated with hypsarrhythmia on EEG. Neither patient developed functional movements or communication, and both had central visual impairment. The older sib died at age 3 years, whereas the younger sib was still alive at age 6, but had refractory seizures and needed a feeding tube. Kvarnung et al. (2016) emphasized that the findings indicated that PVHH may be compatible with life.
Inheritance
The transmission pattern of PVHH in the family reported by Kvarnung et al. (2016) was consistent with autosomal recessive inheritance.
Mapping
By genomewide linkage analysis of 2 consanguineous Pakistani families with PVHH, Meyer et al. (2010) identified a locus on chromosome 14q24 (maximum combined lod score of 3.69 at D14S61).
Molecular Genetics
By candidate gene sequencing, Meyer et al. (2010) identified a homozygous mutation in the FLVCR2 gene (T430R; 610865.0001) in 5 fetuses with PVHH from 3 consanguineous Pakistani families. Two additional fetuses of northern European origin with the disorder were each found to be compound heterozygous for 2 mutations in the FLVCR2 gene (610865.0002-610865.0005).
Using exome sequencing, Lalonde et al. (2010) identified compound heterozygosity for 2 mutations in the FLVCR2 gene (610865.0006 and 610865.0007) in a fetus with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome.
By genomewide linkage analysis followed by high-throughput sequencing of 7 families with Fowler syndrome, Thomas et al. (2010) identified homozygous or compound heterozygous mutations affecting the FLVCR2 gene (see, e.g., Y134X, 610865.0008). Two of the families, of Turkish origin, carried a large deletion. The patients and families had previously been reported by Bessieres-Grattagliano et al. (2009).
In 2 sibs, born of consanguineous Somalian parents, with Fowler syndrome, Kvarnung et al. (2016) identified a homozygous missense mutation in the FLVCR2 gene (T430M; 610865.0009). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Kvarnung et al. (2016) noted that both of these affected children survived beyond birth, although they had essentially no neurologic development. Functional studies of the variant and studies of patient cells were not performed.
INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation (IUGR) HEAD & NECK Head \- Microcephaly Face \- Micrognathia Eyes \- Glomeruloid vascular proliferation in the retina Central visual impairment SKELETAL \- Joint contractures \- Fetal akinesia deformation sequence \- Limb deformities MUSCLE, SOFT TISSUES \- Muscular atrophy, neurogenic NEUROLOGIC Central Nervous System \- Hydrocephaly \- Hydranencephaly \- Hydrocephalus, severe \- Ventriculomegaly \- Glomeruloid vascular proliferation in brain and spinal cord \- Endothelial intracytoplasmic globular inclusions \- Cortical thinning \- Agenesis of the corpus callosum \- Cerebellar hypoplasia \- Hypoplastic brainstem \- Dandy-Walker malformation \- Ischemic necrotic lesions \- Calcifications in white matter, basal ganglia, brainstem, cerebellum, and spinal cord \- Lack of psychomotor development \- Seizures PRENATAL MANIFESTATIONS \- Prenatal diagnosis by ultrasound Amniotic Fluid \- Polyhydramnios Delivery \- Premature delivery MISCELLANEOUS \- Stillborn or neonatal death \- Diagnosis occurs between 23 and 33 weeks' gestation \- Variable clinical presentation \- Affected individuals may rarely survive MOLECULAR BASIS \- Caused by mutation in the feline leukemia virus subgroup C receptor 2 gene (FLVCR2, 610865.0001 ) ▲ 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
| PROLIFERATIVE VASCULOPATHY AND HYDRANENCEPHALY-HYDROCEPHALY SYNDROME | c1856972 | 1,012 | omim | https://www.omim.org/entry/225790 | 2019-09-22T16:28:19 | {"mesh": ["C565593"], "omim": ["225790"], "orphanet": ["221126"], "synonyms": ["Alternative titles", "HYDRANENCEPHALY, FOWLER TYPE", "FOWLER SYNDROME", "HYDROCEPHALY/HYDRANENCEPHALY DUE TO CEREBRAL VASCULOPATHY", "ENCEPHALOCLASTIC PROLIFERATIVE VASCULOPATHY"]} |
Bart syndrome
SpecialtyDermatology
Bart syndrome is a genetic disorder characterized by the association of congenital localized absence of skin, epidermolysis bullosa, lesions of the mouth mucosa, and dystrophic nails.[1][2]
## Contents
* 1 Genetics
* 2 Diagnosis
* 3 See also
* 4 References
* 5 External links
## Genetics[edit]
The disease is inherited by autosomal dominant transmission with complete penetrance but variable expression. This means that children of an affected parent that carries the gene have a 50% chance of developing the disorder, although the extent to which they are affected is variable.[citation needed]
Bart syndrome is caused by ultrastructural abnormalities in the anchoring fibrils. Genetic linkage of the inheritance of the disease points to the region of chromosome 3 near the collagen, type VII, alpha 1 gene (COL7A1).[3]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (June 2018)
## See also[edit]
* List of cutaneous conditions
* Bart-Pumphrey syndrome
## References[edit]
1. ^ Butler DF, Berger TG, James WD, Smith TL, Stanely JR, Rodman OG (1986). "Bart's syndrome: microscopic, ultrastructural, and immunofluorescent mapping features". American Family Physician. 3 (2): 113–118. doi:10.1111/j.1525-1470.1986.tb00500.x. PMID 3513144. S2CID 22247333.
2. ^ James W, Berger T, Elston D (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 558. ISBN 978-0-7216-2921-6.
3. ^ Christiano AM, Bart BJ, Epstein EH Jr, Uitto J (1996). "Genetic basis of Bart's syndrome: a glycine substitution mutation in the type VII collagen gene". American Family Physician. 106 (6): 1340–2. doi:10.1111/1523-1747.ep12349293. PMID 8752681.
## External links[edit]
Classification
D
* OMIM: 132000
* MeSH: C562638
* v
* t
* e
Diseases of collagen, laminin and other scleroproteins
Collagen disease
COL1:
* Osteogenesis imperfecta
* Ehlers–Danlos syndrome, types 1, 2, 7
COL2:
* Hypochondrogenesis
* Achondrogenesis type 2
* Stickler syndrome
* Marshall syndrome
* Spondyloepiphyseal dysplasia congenita
* Spondyloepimetaphyseal dysplasia, Strudwick type
* Kniest dysplasia (see also C2/11)
COL3:
* Ehlers–Danlos syndrome, types 3 & 4
* Sack–Barabas syndrome
COL4:
* Alport syndrome
COL5:
* Ehlers–Danlos syndrome, types 1 & 2
COL6:
* Bethlem myopathy
* Ullrich congenital muscular dystrophy
COL7:
* Epidermolysis bullosa dystrophica
* Recessive dystrophic epidermolysis bullosa
* Bart syndrome
* Transient bullous dermolysis of the newborn
COL8:
* Fuchs' dystrophy 1
COL9:
* Multiple epiphyseal dysplasia 2, 3, 6
COL10:
* Schmid metaphyseal chondrodysplasia
COL11:
* Weissenbacher–Zweymüller syndrome
* Otospondylomegaepiphyseal dysplasia (see also C2/11)
COL17:
* Bullous pemphigoid
COL18:
* Knobloch syndrome
Laminin
* Junctional epidermolysis bullosa
* Laryngoonychocutaneous syndrome
Other
* Congenital stromal corneal dystrophy
* Raine syndrome
* Urbach–Wiethe disease
* TECTA
* DFNA8/12, DFNB21
see also fibrous proteins
*[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
| Bart syndrome | c0268371 | 1,013 | wikipedia | https://en.wikipedia.org/wiki/Bart_syndrome | 2021-01-18T19:04:08 | {"mesh": ["C562638"], "umls": ["C0268371"], "wikidata": ["Q4865135"]} |
A number sign (#) is used with this entry because of evidence that autosomal dominant mental retardation-47 (MRD47) is caused by heterozygous mutation in the STAG1 gene (604358) on chromosome 3q22.
Clinical Features
Lehalle et al. (2017) described 13 patients from 12 unrelated families with delayed psychomotor development and intellectual disability, mostly mild to moderate, usually with delayed speech. Three patients had severe intellectual disability, including 1 born of consanguineous parents. Most of the patients were children, but 1 was aged 15 years and another 29 years. Many patients had feeding difficulties and/or gastroesophageal reflux early in life; some had mild growth retardation. The patients shared some dysmorphic features, including deep-set eyes, a wide mouth, and a high nasal bridge; these features tended to become more apparent with age. Five patients had seizures, ranging from recurrent febrile seizures to epileptic encephalopathy (1 patient). Other more variable features included hypotonia, joint hyperlaxity, autistic features, and nonspecific brain anomalies, such as cerebral atrophy. The patients were identified from several large patient pools and data sharing from worldwide research cohorts.
Cytogenetics
Lehalle et al. (2017) reported 4 unrelated patients with de novo heterozygous deletions of chromosome 3q22 including the STAG1 and PCCB (232050) genes. The deletions were found by array-CGH. The patients had intellectual disability and features similar to those observed in patients with point mutations in the STAG1 gene; however, those with larger deletions had a higher prevalence of microcephaly, which reached statistical significance.
Inheritance
The transmission pattern of MRD47 in the family reported by Lehalle et al. (2017) was consistent with autosomal dominant inheritance.
Molecular Genetics
In 6 members of a family (family 5) with MRD47, Lehalle et al. (2017) identified a heterozygous intragenic deletion within the STAG1 gene (604358.0001). The deletion, which was found by array-CGH, segregated with the disorder in the family. Whole-exome sequencing of several large patient cohorts identified 11 additional nonrecurrent de novo heterozygous missense or frameshift mutations in the STAG1 gene (see, e.g., 604358.0002-604358.0006) in 11 unrelated patients with a similar phenotype. Functional studies of the variants and studies of patient cells were not performed, but Lehalle et al. (2017) postulated that the neurodevelopmental phenotype is caused by STAG1 haploinsufficiency with a putative disruptive effect on transcriptional regulation.
INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Microcephaly, mild (in some patients) Face \- Variable dysmorphic features Eyes \- Deep-set eyes \- Thin eyebrows Nose \- High nasal bridge Mouth \- Wide mouth Teeth \- Widely-spaced incisors ABDOMEN \- Feeding difficulties \- Gastroesophageal reflux GENITOURINARY External Genitalia (Male) \- Cryptorchidism SKELETAL \- Joint hyperlaxity MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability, mild to severe \- Speech delay \- Seizures (in some patients) \- Cerebral atrophy (in some patients) Behavioral Psychiatric Manifestations \- Autistic features MISCELLANEOUS \- De novo mutation (in most patients) \- One family with autosomal dominant transmission has been reported (last curated August 2017) MOLECULAR BASIS \- Caused by mutation in the stromal antigen 1 gene (STAG1, 604358.0001 ) ▲ Close
*[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
| MENTAL RETARDATION, AUTOSOMAL DOMINANT 47 | c4539951 | 1,014 | omim | https://www.omim.org/entry/617635 | 2019-09-22T15:45:18 | {"doid": ["0080238"], "omim": ["617635"], "orphanet": ["502434"], "synonyms": []} |
Extreme or irrational fear of heights
For the online game, see Acrophobia (game). For the amusement park ride, see Acrophobia (ride). For the fear of open spaces, see Agoraphobia.
Not to be confused with Fear of falling.
Acrophobia
Some jobs require working at heights.
SpecialtyPsychiatry
Acrophobia is an extreme or irrational fear or phobia of heights, especially when one is not particularly high up. It belongs to a category of specific phobias, called space and motion discomfort, that share both similar causes and options for treatment.
Most people experience a degree of natural fear when exposed to heights, known as the fear of falling. On the other hand, those who have little fear of such exposure are said to have a head for heights. A head for heights is advantageous for those hiking or climbing in mountainous terrain and also in certain jobs such as steeplejacks or wind turbine mechanics.
People with acrophobia can experience a panic attack in high places and become too agitated to get themselves down safely. Approximately 2–5% of the general population has acrophobia, with twice as many women affected as men.[1] The term is from the Greek: ἄκρον, ákron, meaning "peak, summit, edge" and φόβος, phóbos, "fear".
## Contents
* 1 Confusion with vertigo
* 2 Causes
* 3 Assessment
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 Society and culture
* 8 See also
* 9 References
* 10 External links
## Confusion with vertigo[edit]
"Vertigo" is often used (incorrectly) to describe a fear of heights, but it is more accurately a spinning sensation that occurs when one is not actually spinning. It can be triggered by looking down from a high place, by looking straight up at a high place or tall object, or even by watching something (i.e. a car or a bird) go past at high speed, but this alone does not describe vertigo. True vertigo can be triggered by almost any type of movement (e.g. standing up, sitting down, walking) or change in visual perspective (e.g. squatting down, walking up or downstairs, looking out of the window of a moving car or train). Vertigo is called height vertigo when the sensation of vertigo is triggered by heights.
Height vertigo is caused by a conflict between vision, vestibular and somatosensory senses.[2] This occurs when vestibular and somatosensory systems sense a body movement that is not detected by the eyes. More research indicate that this conflict lead to both motion sickness and anxiety.[3][4][5]
## Causes[edit]
Traditionally, acrophobia has been attributed, like other phobias, to conditioning or a traumatic experience. Recent studies have cast doubt on this explanation.[6][5] Individuals with acrophobia are found to be lacking in traumatic experiences. Nevertheless, this may be due to the failure to recall the experiences, as memory fades as time passes.[7] To address the problems of self report and memory, a large cohort study with 1000 participants was conducted from birth; the results showed that participants with less fear of heights had more injuries because of falling.[8][5] More studies have suggested a possible explanation for acrophobia is that it emerges through accumulation of non-traumatic experiences of falling that are not memorable but can influence behaviours in the future. Also, fear of heights may be acquired when infants learn to crawl. If they fell, they would learn the concepts about surfaces, posture, balance, and movement.[5] Cognitive factors may also contribute to the development of acrophobia. People tend to wrongly interpret visuo-vestibular discrepancies as dizziness and nausea and associate them with a forthcoming fall.[9] A traumatic conditional event of falling may not be necessary at this point.
A fear of falling, along with a fear of loud noises, is one of the most commonly suggested inborn or "non-associative" fears. The newer non-association theory is that a fear of heights is an evolved adaptation to a world where falls posed a significant danger. If this fear is inherited, it is possible that people can get rid of it by frequent exposure of heights in habituation. In other words, acrophobia could be attributed to the lack of exposure in early times.[10] The degree of fear varies and the term phobia is reserved for those at the extreme end of the spectrum. Researchers have argued that a fear of heights is an instinct found in many mammals, including domestic animals and humans. Experiments using visual cliffs have shown human infants and toddlers, as well as other animals of various ages, to be reluctant in venturing onto a glass floor with a view of a few meters of apparent fall-space below it.[11] Although human infants initially experienced fear when crawling on the visual cliff, most of them overcame the fear through practice, exposure and mastery and retained a level of healthy cautiousness.[12] While an innate cautiousness around heights is helpful for survival, an extreme fear can interfere with the activities of everyday life, such as standing on a ladder or chair, or even walking up a flight of stairs. Still, it is uncertain if acrophobia is related to the failure to reach a certain developmental stage. Besides associative accounts, a diathetic-stress model is also very appealing for considering both vicarious learning and hereditary factors such as personality traits (i.e., neuroticism).
Another possible contributing factor is a dysfunction in maintaining balance. In this case the anxiety is both well founded and secondary. The human balance system integrates proprioceptive, vestibular and nearby visual cues to reckon position and motion.[13][14] As height increases, visual cues recede and balance becomes poorer even in normal people.[15] However, most people respond by shifting to more reliance on the proprioceptive and vestibular branches of the equilibrium system.
Some people are known to be more dependent on visual signals than others.[16] People who rely more on visual cues to control body movements are less physically stable.[17][5] An acrophobic, however, continues to over-rely on visual signals whether because of inadequate vestibular function or incorrect strategy. Locomotion at a high elevation requires more than normal visual processing. The visual cortex becomes overloaded, resulting in confusion. Some proponents of the alternative view of acrophobia warn that it may be ill-advised to encourage acrophobics to expose themselves to height without first resolving the vestibular issues. Research is underway at several clinics.[18] Recent studies found that participants experienced increased anxiety not only during elevation in height, but also when they were required to move sideways in a fixed height.[19]
A recombinant model of the development of acrophobia is very possible, in which learning factors, cognitive factors (e.g. interpretations), perceptual factors(e.g. visual dependence), and biological factors (e.g. heredity) interact to provoke fear or habituation.[5]
## Assessment[edit]
ICD-10 and DSM-V are used to diagnose acrophobia.[20] Acrophobia Questionnaire (AQ) is a self report that contains 40 items, assessing anxiety level on a 0-6 point scale and degree of avoidance on a 0-2 point scale.[21][22] The Attitude Towards Heights Questionnaires (ATHQ)[23] and Behavioural Avoidance Tests (BAT) are also used.[5]
However, acrophobic individuals tend to have biases in self report. They often overestimate the danger and question their abilities of addressing height relevant issues.[24] A Height Interpretation Questionnaire (HIQ) is a self-report to measure these height relevant judgements and interpretations.[22] The Depression Scale of the Depression Anxiety Stress Scales short form (DASS21-DS) is a self report used to examine validity of the HIQ.[22]
## Treatment[edit]
Traditional treatment of phobias is still in use today. Its underlying theory states that phobic anxiety is conditioned and triggered by a conditional stimulus. By avoiding phobic situation, anxiety is reduced. However, avoidance behaviour is reinforced through negative reinforcement.[5][25] Wolpe developed a technique called systematic desensitization to help participants avoid "avoidance".[26] Research results have suggested that even with a decrease in therapeutic contact densensitization is still very effective.[27] However, other studies have shown that therapists play an essential role in acrophobia treatment.[28] Treatments like reinforced practice and self-efficacy treatments also emerged.[5]
There have been a number of studies into using virtual reality therapy for acrophobia.[29][30] Botella and colleagues[31] and Schneider[31] were the first to use VR in treatment.[5] Specifically, Schneider utilised inverted lenses in binoculars to "alter" the reality. Later in mid 1990s, VR became computer based and was widely available for therapists. A cheap VR equipment uses a normal PC with head-mounted display (HMD). In contrast, VRET uses an advanced computer automatic virtual environment (CAVE).[32] VR has several advantages over in vivo treatment:[5] (1) therapist can control the situation better by manipulating the stimuli,[33] in terms of their quality, intensity, duration and frequency;[34] (2) VR can help participants avoid public embarrassment and protect their confidentiality; (3) therapist's office can be well maintained; (4) VR encourages more people to seek treatment; (5) VR saves time and money as participants do not need to leave the consulting room.[32]
Many different types of medications are used in the treatment of phobias like fear of heights, including traditional anti-anxiety drugs such as benzodiazepines, and newer options like antidepressants and beta-blockers.[citation needed]
## Prognosis[edit]
Some desensitization treatments produce short-term improvements in symptoms.[35] Long-term treatment success has been elusive.[35]
## Epidemiology[edit]
True acrophobia is uncommon.
A related, milder form of visually triggered fear or anxiety is called visual height intolerance(vHI).[36] Up to one-third of people may have some level of visual height intolerance.[36] Pure vHI usually has smaller impact on individuals compared to acrophobia, in terms of intensity of syptoms load, social life, and overall life quality. However, only few people with visual height intolerance seek for professional help.[37]
## Society and culture[edit]
In the Alfred Hitchcock film Vertigo, John "Scottie" Ferguson, played by James Stewart, has to resign from the police force after an incident which causes him to develop both acrophobia and vertigo. The word "vertigo" is only mentioned once, while "acrophobia" is mentioned several times. Early on in the film, Ferguson faints while climbing a stepladder. There are numerous references throughout the film to fear of heights and falling.
## See also[edit]
* Fear of falling
* Acclimatization
* Head for heights
* List of phobias
## References[edit]
1. ^ Juan, M. C.; et al. (2005). "An Augmented Reality system for the treatment of acrophobia" (PDF). Presence. 15 (4): 315–318. doi:10.1162/pres.15.4.393. S2CID 797073. Retrieved 2015-09-12.
2. ^ Bles, Willem; Kapteyn, Theo S.; Brandt, Thomas; Arnold, Friedrich (1980-01-01). "The Mechanism of Physiological Height Vertigo: II. Posturography". Acta Oto-Laryngologica. 89 (3–6): 534–540. doi:10.3109/00016488009127171. ISSN 0001-6489. PMID 6969517.
3. ^ Whitney, Susan L.; Jacob, Rolf G.; Sparto, Patrick J.; Olshansky, Ellen F.; Detweiler-Shostak, Gail; Brown, Emily L.; Furman, Joseph M. (May 2005). "Acrophobia and pathological height vertigo: indications for vestibular physical therapy?". Physical Therapy. 85 (5): 443–458. doi:10.1093/ptj/85.5.443. ISSN 0031-9023. PMID 15842192.
4. ^ Redfern, M. S.; Yardley, L.; Bronstein, A. M. (January 2001). "Visual influences on balance". Journal of Anxiety Disorders. 15 (1–2): 81–94. doi:10.1016/s0887-6185(00)00043-8. ISSN 0887-6185. PMID 11388359.
5. ^ a b c d e f g h i j k Coelho, Carlos M.; Waters, Allison M.; Hine, Trevor J.; Wallis, Guy (2009). "The use of virtual reality in acrophobia research and treatment". Journal of Anxiety Disorders. 23 (5): 563–574. doi:10.1016/j.janxdis.2009.01.014. ISSN 0887-6185. PMID 19282142.
6. ^ Menzies, RG; Clarke, JC (1995). "The etiology of acrophobia and its relationship to severity and individual response patterns". Behaviour Research and Therapy. 33 (31): 499–501. doi:10.1016/0005-7967(95)00023-Q. PMID 7677717. 7677717.
7. ^ Loftus, Elizabeth F. (2016). "Memories of Things Unseen". Current Directions in Psychological Science. 13 (4): 145–147. doi:10.1111/j.0963-7214.2004.00294.x. ISSN 0963-7214. S2CID 37717355.
8. ^ Poulton, Richie; Davies, Simon; Menzies, Ross G.; Langley, John D.; Silva, Phil A. (1998). "Evidence for a non-associative model of the acquisition of a fear of heights". Behaviour Research and Therapy. 36 (5): 537–544. doi:10.1016/S0005-7967(97)10037-7. ISSN 0005-7967. PMID 9648329.
9. ^ Davey, Graham C.L.; Menzies, Ross; Gallardo, Barbara (1997). "Height phobia and biases in the interpretation of bodily sensations: Some links between acrophobia and agoraphobia". Behaviour Research and Therapy. Elsevier BV. 35 (11): 997–1001. doi:10.1016/s0005-7967(97)10004-3. ISSN 0005-7967. PMID 9431729.
10. ^ Poulton, Richie; Waldie, Karen E; Menzies, Ross G; Craske, Michelle G; Silva, Phil A (2001-01-01). "Failure to overcome 'innate' fear: a developmental test of the non-associative model of fear acquisition". Behaviour Research and Therapy. 39 (1): 29–43. doi:10.1016/S0005-7967(99)00156-4. ISSN 0005-7967. PMID 11125722.
11. ^ Eleanor J. Gibson; Richard D. Walk. "The "Visual Cliff"". Retrieved 2013-05-13. Cite journal requires `|journal=` (help)
12. ^ Campos, Joseph J.; Anderson, David I.; Barbu-Roth, Marianne A.; Hubbard, Edward M.; Hertenstein, Matthew J.; Witherington, David (2000-04-01). "Travel Broadens the Mind". Infancy. 1 (2): 149–219. doi:10.1207/S15327078IN0102_1. PMID 32680291. S2CID 704084.
13. ^ Furman, Joseph M (May 2005). "Acrophobia and pathological height vertigo: indications for vestibular physical therapy?". Physical Therapy. 85 (5): 443–58. doi:10.1093/ptj/85.5.443. PMID 15842192. Archived from the original on 2007-09-26. Retrieved 2007-09-10.
14. ^ Jacob, Rolf G; Woody, Shelia R; Clark, Duncan B; et al. (December 1993). "Discomfort with space and motion: A possible marker of vestibular dysfunction assessed by the situational characteristics questionnaire". Journal of Psychopathology and Behavioral Assessment. 15 (4): 299–324. doi:10.1007/BF00965035. ISSN 0882-2689. S2CID 144661241.
15. ^ Brandt, T; F Arnold; W Bles; T S Kapteyn (1980). "The mechanism of physiological height vertigo. I. Theoretical approach and psychophysics". Acta Otolaryngol. 89 (5–6): 513–523. doi:10.3109/00016488009127169. PMID 6969515.
16. ^ Kitamura, Fumiaki; Matsunaga, Katsuya (December 1990). "Field Dependence and Body Balance". Perceptual and Motor Skills. 71 (3): 723–734. doi:10.2466/pms.1990.71.3.723. ISSN 0031-5125. PMID 2293175. S2CID 46272261.
17. ^ Isableu, Brice; Ohlmann, Théophile; Crémieux, Jacques; Amblard, Bernard (May 2003). "Differential approach to strategies of segmental stabilisation in postural control". Experimental Brain Research. 150 (2): 208–221. doi:10.1007/s00221-003-1446-0. ISSN 0014-4819. PMID 12677318. S2CID 32279602.
18. ^ Whitney, SL; Jacob, Rolf G; Sparto, BG (May 2005). "Acrophobia and pathological height vertigo: indications for vestibular physical therapy?". Physical Therapy. 85 (5): 443–458. doi:10.1093/ptj/85.5.443. ISSN 0031-9023. PMID 15842192.
19. ^ Coelho, Carlos M.; Santos, Jorge A.; Silva, Carlos; Wallis, Guy; Tichon, Jennifer; Hine, Trevor J. (2008-11-09). "The Role of Self-Motion in Acrophobia Treatment". CyberPsychology & Behavior. 11 (6): 723–725. doi:10.1089/cpb.2008.0023. hdl:10072/23304. ISSN 1094-9313. PMID 18991529.
20. ^ Huppert, Doreen; Grill, Eva; Brandt, Thomas (2017). "A New Questionnaire for Estimating the Severity of Visual Height Intolerance and Acrophobia by a Metric Interval Scale". Frontiers in Neurology. 8: 211. doi:10.3389/fneur.2017.00211. ISSN 1664-2295. PMC 5451500. PMID 28620340.
21. ^ Cohen, David Chestney (1977-01-01). "Comparison of self-report and overt-behavioral procedures for assessing acrophobia". Behavior Therapy. 8 (1): 17–23. doi:10.1016/S0005-7894(77)80116-0. ISSN 0005-7894.
22. ^ a b c Steinman, Shari A.; Teachman, Bethany A. (2011-10-01). "Cognitive processing and acrophobia: Validating the Heights Interpretation Questionnaire". Journal of Anxiety Disorders. 25 (7): 896–902. doi:10.1016/j.janxdis.2011.05.001. ISSN 0887-6185. PMC 3152668. PMID 21641766.
23. ^ Abelson, James L.; Curtis, George C. (1989-01-01). "Cardiac and neuroendocrine responses to exposure therapy in height phobics: Desynchrony within the 'physiological response system'". Behaviour Research and Therapy. 27 (5): 561–567. doi:10.1016/0005-7967(89)90091-0. hdl:2027.42/28207. ISSN 0005-7967. PMID 2573337.
24. ^ Menzies, Ross G.; Clarke, J. Christopher (1995-02-01). "Danger expectancies and insight in acrophobia". Behaviour Research and Therapy. 33 (2): 215–221. doi:10.1016/0005-7967(94)P4443-X. ISSN 0005-7967. PMID 7887882.
25. ^ "APA PsycNet". psycnet.apa.org. Retrieved 2020-04-15.
26. ^ Wolpe, Joseph (1968-10-01). "Psychotherapy by reciprocal inhibition". Conditional Reflex. 3 (4): 234–240. doi:10.1007/BF03000093 (inactive 2021-01-17). ISSN 1936-3567. PMID 5712667.CS1 maint: DOI inactive as of January 2021 (link)
27. ^ Baker, Bruce L.; Cohen, David C.; Saunders, Jon Terry (February 1973). "Self-directed desensitization for acrophobia". Behaviour Research and Therapy. 11 (1): 79–89. doi:10.1016/0005-7967(73)90071-5. PMID 4781961.
28. ^ Williams, S. Lloyd; Dooseman, Grace; Kleifield, Erin (1984). "Comparative effectiveness of guided mastery and exposure treatments for intractable phobias". Journal of Consulting and Clinical Psychology. 52 (4): 505–518. doi:10.1037/0022-006X.52.4.505. ISSN 1939-2117. PMID 6147365.
29. ^ Coelho, Carlos; Alison Waters; Trevor Hine; Guy Wallis (2009). "The use of virtual reality in acrophobia research and treatment". Journal of Anxiety Disorders. 23 (5): 563–574. doi:10.1016/j.janxdis.2009.01.014. PMID 19282142.
30. ^ Emmelkamp, Paul; Mary Bruynzeel; Leonie Drost; Charles A. P. G. van der Mast (1 June 2001). "Virtual Reality Treatment in Acrophobia: A Comparison with Exposure in Vivo". CyberPsychology & Behavior. 4 (3): 335–339. doi:10.1089/109493101300210222. PMID 11710257.
31. ^ a b Botella, C.; Baños, R. M.; Perpiñá, C.; Villa, H.; Alcañiz, M.; Rey, A. (1998-02-01). "Virtual reality treatment of claustrophobia: a case report". Behaviour Research and Therapy. 36 (2): 239–246. doi:10.1016/S0005-7967(97)10006-7. ISSN 0005-7967. PMID 9613029.
32. ^ a b Krijn, Merel; Emmelkamp, Paul M. G.; Biemond, Roeline; de Wilde de Ligny, Claudius; Schuemie, Martijn J.; van der Mast, Charles A. P. G. (2004-02-01). "Treatment of acrophobia in virtual reality: The role of immersion and presence". Behaviour Research and Therapy. 42 (2): 229–239. doi:10.1016/S0005-7967(03)00139-6. ISSN 0005-7967. PMID 14975783.
33. ^ Choi, Young H.; Jang, Dong P.; Ku, Jeong H.; Shin, Min B.; Kim, Sun I. (2001-06-01). "Short-Term Treatment of Acrophobia with Virtual Reality Therapy (VRT): A Case Report". CyberPsychology & Behavior. 4 (3): 349–354. doi:10.1089/109493101300210240. ISSN 1094-9313. PMID 11710259.
34. ^ Morina, Nexhmedin; Ijntema, Hiske; Meyerbröker, Katharina; Emmelkamp, Paul M. G. (2015-11-01). "Can virtual reality exposure therapy gains be generalized to real-life? A meta-analysis of studies applying behavioral assessments". Behaviour Research and Therapy. 74: 18–24. doi:10.1016/j.brat.2015.08.010. ISSN 0005-7967. PMID 26355646.
35. ^ a b Arroll, Bruce; Wallace, Henry B.; Mount, Vicki; Humm, Stephen P.; Kingsford, Douglas W. (2017-04-03). "A systematic review and meta-analysis of treatments for acrophobia". The Medical Journal of Australia. 206 (6): 263–267. doi:10.5694/mja16.00540. ISSN 1326-5377. PMID 28359010. S2CID 9559825.
36. ^ a b Huppert, Doreen; Grill, Eva; Brandt, Thomas (2013-02-01). "Down on heights? One in three has visual height intolerance". Journal of Neurology. 260 (2): 597–604. doi:10.1007/s00415-012-6685-1. ISSN 1432-1459. PMID 23070463. S2CID 21302997.
37. ^ Kapfhammer, Hans-Peter; Fitz, Werner; Huppert, Doreen; Grill, Eva; Brandt, Thomas (2016). "Visual height intolerance and acrophobia: distressing partners for life". Journal of Neurology. 263 (10): 1946–1953. doi:10.1007/s00415-016-8218-9. ISSN 0340-5354. PMC 5037147. PMID 27383642.
## External links[edit]
Classification
D
* ICD-10: F40.2
* ICD-10-CM: F40.241
* ICD-9-CM: 300.29
* "The scariest path in the world?", a direct test, video shot on El Camino del Rey, approaching Makinodromo
* "Fear of Heights" A comprehensive guide with useful resources on Acrophobia known as Fear of Heights.
*[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
| Acrophobia | c0233701 | 1,015 | wikipedia | https://en.wikipedia.org/wiki/Acrophobia | 2021-01-18T18:54:59 | {"wikidata": ["Q207783"]} |
Wiersma et al. (1976) reported mother and daughter with this combination. The uterus is double with two cervices. A partial vaginal septum obstructs one cervix which empties into a blind sac.
GU \- Double uterus \- Two cervices \- Partial vaginal septum \- Unilateral hematocolpos \- Renal agenesis 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
| UTERUS BICORNIS BICOLLIS WITH PARTIAL VAGINAL SEPTUM AND UNILATERAL HEMATOCOLPOS WITH IPSILATERAL RENAL AGENESIS | c1860549 | 1,016 | omim | https://www.omim.org/entry/192050 | 2019-09-22T16:32:09 | {"mesh": ["C566010"], "omim": ["192050"], "orphanet": ["3411"]} |
Human spinal cord disorder
Brown-Séquard syndrome
Other namesBrown-Séquard's paralysis
SpecialtyNeurology
Brown-Séquard syndrome (also known as Brown-Séquard's hemiplegia, Brown-Séquard's paralysis, hemiparaplegic syndrome, hemiplegia et hemiparaplegia spinalis, or spinal hemiparaplegia) is caused by damage to one half of the spinal cord, i.e. hemisection of the spinal cord resulting in paralysis and loss of proprioception on the same (or ipsilateral) side as the injury or lesion, and loss of pain and temperature sensation on the opposite (or contralateral) side as the lesion. It is named after physiologist Charles-Édouard Brown-Séquard, who first described the condition in 1850.[1]
## Contents
* 1 Causes
* 2 Pathophysiology
* 3 Diagnosis
* 3.1 Classification
* 4 Treatment
* 5 Epidemiology
* 6 History
* 7 Notes
* 8 Sources
* 9 External links
## Causes[edit]
Brown-Séquard syndrome may be caused by injury to the spinal cord resulting from a spinal cord tumor, trauma [such as a fall or injury from gunshot or puncture to the cervical or thoracic spine], ischemia (obstruction of a blood vessel), or infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. In its pure form, it is rarely seen. The most common cause is penetrating trauma such as a gunshot wound or stab wound to the spinal cord.[citation needed] Decompression sickness may also be a cause of Brown-Séquard syndrome.[2]
The presentation can be progressive and incomplete. It can advance from a typical Brown-Séquard syndrome to complete paralysis. It is not always permanent and progression or resolution depends on the severity of the original spinal cord injury and the underlying pathology that caused it in the first place.[citation needed]
## Pathophysiology[edit]
Lesion on the patient's right
1. loss of all sensation, hypotonic paralysis
2. spastic paralysis and loss of vibration and proprioception (position sense) and fine touch
3. loss of pain and temperature sensation
The hemisection of the cord results in a lesion of each of the three main neural systems:[citation needed]
* the principal upper motor neuron pathway of the corticospinal tract
* one or both dorsal columns
* the spinothalamic tract
As a result of the injury to these three main brain pathways the patient will present with three lesions:
* The corticospinal lesion produces spastic paralysis on the same side of the body below the level of the lesion (due to loss of moderation by the UMN). At the level of the lesion, there will be flaccid paralysis of the muscles supplied by the nerve of that level (since lower motor neurons are affected at the level of the lesion).
* The lesion to fasciculus gracilis or fasciculus cuneatus (dorsal column) results in ipsilateral loss of vibration and proprioception (position sense) as well as loss of all sensation of fine touch.
* The loss of the spinothalamic tract leads to pain and temperature sensation being lost from the contralateral side beginning one or two segments below the lesion.
In addition, if the lesion occurs above T1 of the spinal cord it will produce ipsilateral horner's syndrome with involvement of the oculosympathetic pathway.
## Diagnosis[edit]
Magnetic resonance imaging (MRI) is the imaging of choice in spinal cord lesions.[citation needed]
Brown-Séquard syndrome is an incomplete spinal cord lesion characterized by findings on clinical examination which reflect hemisection of the spinal cord (cutting the spinal cord in half on one or the other side). It is diagnosed by finding motor (muscle) paralysis on the same (ipsilateral) side as the lesion and deficits in pain and temperature sensation on the opposite (contralateral) side. This is called ipsilateral hemiplegia and contralateral pain and temperature sensation deficits. The loss of sensation on the opposite side of the lesion is because the nerve fibers of the spinothalamic tract (which carry information about pain and temperature) crossover once they meet the spinal cord from the peripheries.[citation needed]
### Classification[edit]
Any presentation of spinal injury that is an incomplete lesion (hemisection) can be called a partial Brown-Séquard or incomplete Brown-Séquard syndrome.[citation needed]
Brown-Séquard syndrome is characterized by loss of motor function (i.e. hemiparaplegia), loss of vibration sense and fine touch, loss of proprioception (position sense), loss of two-point discrimination, and signs of weakness on the ipsilateral (same side) of the spinal injury. This is a result of a lesion affecting the dorsal column-medial lemniscus tract, well localized (deep) touch, conscious proprioception, vibration, pressure and 2-point discrimination, and the corticospinal tract, which carries motor fibers. On the contralateral (opposite side) of the lesion, there will be a loss of pain and temperature sensation and crude touch 1 or 2 segments below the level of the lesion via the Spinothalamic Tract of the Anterolateral System. Bilateral (both sides) ataxia may also occur if the ventral spinocerebellar tract and dorsal spinocerebellar tract are affected.[citation needed]
Crude touch, pain and temperature fibers are carried in the spinothalamic tract. These fibers decussate at the level of the spinal cord. Therefore, a hemi-section lesion to the spinal cord will demonstrate loss of these modalities on the contralateral side of the lesion, while preserving them on the ipsilateral side. Upon touching this side, the patient will not be able to localize where they were touched, only that they were touched. This is because fine touch fibers are carried in the dorsal column-medial lemniscus pathway. The fibers in this pathway decussate at the level of the medulla. Therefore, a hemi-section lesion of the spinal cord will demonstrate loss of fine touch on ipsilateral side (preserved on the contralateral side) and crude touch (destruction of the decussated spinothalamic fibers from the contralateral side) on the contralateral side.[citation needed]
Pure Brown-Séquard syndrome is associated with the following:
* Interruption of the lateral corticospinal tracts:
* Ipsilateral spastic paralysis below the level of the lesion
* Babinski sign ipsilateral to lesion
* Abnormal reflexes and Babinski sign may not be present in acute injury
* Interruption of posterior white column:
* Ipsilateral loss of tactile discrimination, vibratory, and position sensation below the level of the lesion
* Interruption of lateral spinothalamic tracts:
* Contralateral loss of pain and temperature sensation. This usually occurs 2–3 segments below the level of the lesion.
## Treatment[edit]
Treatment is directed at the pathology causing the paralysis. If the syndrome is caused by a spinal fracture, this should be identified and treated appropriately. Although steroids may be used to decrease cord swelling and inflammation, the usual therapy for spinal cord injury is expectant.[citation needed]
## Epidemiology[edit]
Brown-Séquard syndrome is rare as the trauma would have to be something that damaged the nerve fibres on just one half of the spinal cord.[3]
## History[edit]
Charles-Édouard Brown-Séquard studied the anatomy and physiology of the spinal cord. He described this injury after observing spinal cord trauma which happened to farmers while cutting sugar cane in Mauritius. French physician, Paul Loye, attempted to confirm Brown-Séquard's observations on the nervous system by experimentation with decapitation of dogs and other animals and recording the extent of each animal's movement after decapitation.[4]
## Notes[edit]
1. ^ C.-É. Brown-Séquard: De la transmission croisée des impressions sensitives par la moelle épinière. Comptes rendus de la Société de biologie, (1850) 1851, 2: 33–44.
2. ^ Kimbro, T; Tom, T; Neuman, T (May 1997). "A case of spinal cord decompression sickness presenting as partial Brown-Sequard syndrome". Neurology. 48 (5): 1454–56. doi:10.1212/wnl.48.5.1454. PMID 9153492. S2CID 26978471.
3. ^ "Brown-Sequard Syndrome: Overview – eMedicine Emergency Medicine". 2018-09-21. Cite journal requires `|journal=` (help)
4. ^ Loye, Paul (1889). "Death by Decapitation". The American Journal of the Medical Sciences. 97 (4): 387. doi:10.1097/00000441-188904000-00008. ISSN 0002-9629.
## Sources[edit]
* Egido Herrero JA, Saldanã C, Jiménez A, Vázquez A, Varela de Seijas E, Mata P (1992). "Spontaneous cervical epidural hematoma with Brown-Séquard syndrome and spontaneous resolution. Case report". J Neurosurg Sci. 36 (2): 117–19. PMID 1469473.
* Ellger T, Schul C, Heindel W, Evers S, Ringelstein EB (June 2006). "Idiopathic spinal cord herniation causing progressive Brown-Séquard syndrome". Clin Neurol Neurosurg. 108 (4): 388–91. doi:10.1016/j.clineuro.2004.07.005. PMID 16483712. S2CID 35644328.
* Finelli PF, Leopold N, Tarras S (May 1992). "Brown-Sequard syndrome and herniated cervical disc". Spine. 17 (5): 598–600. doi:10.1097/00007632-199205000-00022. PMID 1621163. S2CID 37493662.
* Hancock JB, Field EM, Gadam R (1997). "Spinal epidural hematoma progressing to Brown-Sequard syndrome: report of a case". J Emerg Med. 15 (3): 309–12. doi:10.1016/S0736-4679(97)00010-3. PMID 9258779.
* Harris P (November 2005). "Stab wound of the back causing an acute subdural haematoma and a Brown-Sequard neurological syndrome". Spinal Cord. 43 (11): 678–9. doi:10.1038/sj.sc.3101765. PMID 15852056.
* Henderson SO, Hoffner RJ (1998). "Brown-Sequard syndrome due to isolated blunt trauma". J Emerg Med. 16 (6): 847–50. doi:10.1016/S0736-4679(98)00096-1. PMID 9848698.
* Hwang W, Ralph J, Marco E, Hemphill JC (June 2003). "Incomplete Brown-Séquard syndrome after methamphetamine injection into the neck". Neurology. 60 (12): 2015–16. doi:10.1212/01.wnl.0000068014.89207.99. PMID 12821761. S2CID 13491137.
* Kraus JA, Stüper BK, Berlit P (1998). "Multiple sclerosis presenting with a Brown-Séquard syndrome". J. Neurol. Sci. 156 (1): 112–13. doi:10.1016/S0022-510X(98)00016-1. PMID 9559998. S2CID 44403915.
* Lim E, Wong YS, Lo YL, Lim SH (April 2003). "Traumatic atypical Brown-Sequard syndrome: case report and literature review". Clin Neurol Neurosurg. 105 (2): 143–45. doi:10.1016/S0303-8467(03)00009-X. PMID 12691810. S2CID 37419566.
* Lipper MH, Goldstein JH, Do HM (August 1998). "Brown-Séquard syndrome of the cervical spinal cord after chiropractic manipulation". AJNR Am J Neuroradiol. 19 (7): 1349–52. PMID 9726481.
* Mastronardi L, Ruggeri A (January 2004). "Cervical disc herniation producing Brown-Sequard syndrome: case report". Spine. 29 (2): E28–31. doi:10.1097/01.BRS.0000105984.62308.F6. PMID 14722422. S2CID 36231998.
* Miyake S, Tamaki N, Nagashima T, Kurata H, Eguchi T, Kimura H (February 1998). "Idiopathic spinal cord herniation. Report of two cases and review of the literature". J. Neurosurg. 88 (2): 331–35. doi:10.3171/jns.1998.88.2.0331. PMID 9452246.
* Rumana CS, Baskin DS (April 1996). "Brown-Sequard syndrome produced by cervical disc herniation: case report and literature review". Surg Neurol. 45 (4): 359–61. doi:10.1016/0090-3019(95)00412-2. PMID 8607086.
* Stephen AB, Stevens K, Craigen MA, Kerslake RW (October 1997). "Brown-Séquard syndrome due to traumatic brachial plexus root avulsion". Injury. 28 (8): 557–58. doi:10.1016/S0020-1383(97)83474-2. PMID 9616398.
## External links[edit]
Wikimedia Commons has media related to Brown-Séquard syndrome.
* Case studies of Brown-Séquard syndrome
Classification
D
* ICD-10: G83.8
* ICD-9-CM: 344.89
* MeSH: D018437
* DiseasesDB: 31117
External resources
* eMedicine: emerg/70 pmr/17
* v
* t
* e
Focal lesions of the spinal cord
General
* Myelopathy
* Myelitis
* Spinal cord compression
By location
* Brown-Séquard syndrome
* Posterior cord syndrome
* Anterior cord syndrome
* Central cord syndrome
* Cauda equina syndrome
Other
* Polio
* Demyelinating disease
* Transverse myelitis
* Tropical spastic paraparesis
* Epidural abscess
* Syringomyelia
* Syringobulbia
* Morvan's syndrome
* Sensory ataxia
* Tabes dorsalis
* Abadie's sign
* Subacute combined degeneration of spinal cord
* Vascular myelopathy
* Anterior spinal artery syndrome
* Foix–Alajouanine syndrome
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Brown-Séquard syndrome | c0242644 | 1,017 | wikipedia | https://en.wikipedia.org/wiki/Brown-S%C3%A9quard_syndrome | 2021-01-18T18:59:40 | {"gard": ["5964"], "mesh": ["D018437"], "umls": ["C0242644"], "icd-9": ["344.89"], "wikidata": ["Q991037"]} |
A rare, genetic, acrokeratoderma disease characterized by multiple, symmetrical, asymptomatic, skin-colored (rarely, brownish), flat-topped, wart-like papules located on the dorsal aspects of the hands and feet (occasionally found on other parts of the body, such as knees, elbows and forearms), typically associated with palmoplantar punctate keratosis and variable nail involvement (including leukonychia, thickening, ridging, longitudinal striations and splitting). Histology reveals undulating hyperkeratosis, papillomatosis, hypergranulosis, and acanthosis, creating a characteristic 'church spire' appearance, with no acantholysis nor dyskeratosis associated.
*[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
| Acrokeratosis verruciformis of Hopf | c0265971 | 1,018 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79151 | 2021-01-23T18:45:47 | {"mesh": ["D007644"], "omim": ["101900"], "umls": ["C0265971"], "icd-10": ["Q82.8"], "synonyms": ["AKV of Hopf"]} |
Mucolipidosis III gamma is a slowly progressive disorder that affects many parts of the body. Signs and symptoms of this condition typically appear around age 3.
Individuals with mucolipidosis III gamma grow slowly and have short stature. They also have stiff joints and dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Many affected individuals develop low bone mineral density (osteoporosis), which weakens the bones and makes them prone to fracture. Osteoporosis and progressive joint problems in people with mucolipidosis III gamma also cause pain, which becomes more severe over time.
People with mucolipidosis III gamma often have heart valve abnormalities and mild clouding of the clear covering of the eye (cornea). Their facial features become slightly thickened or "coarse" as they get older. A small percentage of people with this condition have mild intellectual disability or learning problems. Individuals with mucolipidosis III gamma generally survive into adulthood, but they may have a shortened lifespan.
## Frequency
Mucolipidosis III gamma is a rare disorder, although its exact prevalence is unknown. It is estimated to occur in about 1 in 100,000 to 400,000 individuals worldwide.
## Causes
Mutations in the GNPTG gene cause mucolipidosis III gamma. This gene provides instructions for making one part (subunit) of an enzyme called GlcNAc-1-phosphotransferase. This enzyme helps prepare certain newly made enzymes for transport to lysosomes. Lysosomes are compartments within the cell that use digestive enzymes to break down large molecules into smaller ones that can be reused by cells. GlcNAc-1-phosphotransferase is involved in the process of attaching a molecule called mannose-6-phosphate (M6P) to specific digestive enzymes. Just as luggage is tagged at the airport to direct it to the correct destination, enzymes are often "tagged" after they are made so they get to where they are needed in the cell. M6P acts as a tag that indicates a digestive enzyme should be transported to the lysosome.
Mutations in the GNPTG gene that cause mucolipidosis III gamma result in reduced activity of GlcNAc-1-phosphotransferase. These mutations disrupt the tagging of digestive enzymes with M6P, which prevents many enzymes from reaching the lysosomes. Digestive enzymes that do not receive the M6P tag end up outside the cell, where they have increased activity. The shortage of digestive enzymes within lysosomes causes large molecules to accumulate there. Conditions that cause molecules to build up inside lysosomes, including mucolipidosis III gamma, are called lysosomal storage disorders. The signs and symptoms of mucolipidosis III gamma are most likely due to the shortage of digestive enzymes inside lysosomes and the effects these enzymes have outside the cell.
### Learn more about the gene associated with Mucolipidosis III gamma
* GNPTG
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Mucolipidosis III gamma | c1854896 | 1,019 | medlineplus | https://medlineplus.gov/genetics/condition/mucolipidosis-iii-gamma/ | 2021-01-27T08:24:38 | {"mesh": ["C565367"], "omim": ["252605"], "synonyms": []} |
PANDAS is an acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with a group A beta-hemolytic Streptococcal infection and applied to a subgroup of children with obsessive-compulsive disorder (OCD) and/or tic disorders.
## Epidemiology
The prevalence is unknown but the boy-to-girl ratio is 2.6:1.
## Clinical description
The current diagnostic criteria for the PANDAS are: presence of OCD and/or a tic disorder, very young age at onset (prepubertal), sudden and dramatic onset of symptoms, association between streptococcal infections and episodic relapsing-remitting exacerbations manifesting as neuropsychiatric symptoms (motor hyperactivity or adventitious movements including choreiform movements or tics). The increased severity of symptoms usually persists for at least several weeks, but may last for several months or longer, followed by a slow, gradual improvement. The major distinctive feature of PANDAS is the temporal association between neuropsychiatric symptom exacerbations and streptococcal infections. Additional neuropsychiatric symptoms occur frequently: emotional lability, separation anxiety, anorexia, impulsivity, distractibility and motor hyperactivity characteristic of attention deficit hyperactivity disorder (ADHD). Comorbid disorders include major depression (36%), major dysthymia (6%) and separation anxiety disorder (20%).
## Etiology
The etiology is uncertain. One theory is that streptococcal infections trigger an antibody response in some children that causes changes in the basal ganglia. No specific genetic factors have been identified.
## Diagnostic methods
Diagnosis of PANDAS is clinical. Neuroimaging studies may reveal increased basal ganglia volumes.
## Management and treatment
Management includes standard interventions for obsessive-compulsive and tic disorders: cognitive-behavioural therapy, reversal therapy in the case of tic disorders and pharmacologic therapy (neuropsychiatric drugs, antibiotics to prevent infections and intravenous immunoglobulin therapy).
*[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
| PANDAS | c2931429 | 1,020 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=66624 | 2021-01-23T17:59:27 | {"gard": ["7312"], "mesh": ["C537163"], "synonyms": ["Pediatric autoimmune disorders associated with Streptococcus infections", "Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections"]} |
Pleomorphic adenoma
Pleomorphic adenoma consists of mixed epithelial (left) and mesenchymal cell components (right). The latter often exhibits myxofibrous appearance and in some instances shows chondromatous differentiation.
SpecialtyOncology
Pleomorphic adenoma is a common benign salivary gland neoplasm characterised by neoplastic proliferation of parenchymatous glandular cells along with myoepithelial components, having a malignant potentiality. It is the most common type of salivary gland tumor and the most common tumor of the parotid gland. It derives its name from the architectural Pleomorphism (variable appearance) seen by light microscopy. It is also known as "Mixed tumor, salivary gland type", which refers to its dual origin from epithelial and myoepithelial elements as opposed to its pleomorphic appearance.
## Contents
* 1 Clinical presentation
* 2 Histology
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Clinical presentation[edit]
The tumor is usually solitary and presents as a slow growing, painless, firm single nodular mass. Isolated nodules are generally outgrowths of the main nodule rather than a multinodular presentation. It is usually mobile unless found in the palate and can cause atrophy of the mandibular ramus when located in the parotid gland. When found in the parotid tail, it may present as an eversion of the ear lobe. Though it is classified as a benign tumor, pleomorphic adenomas have the capacity to grow to large proportions and may undergo malignant transformation, to form carcinoma ex-pleomorphic adenoma, a risk that increases with time (9.5% chance to convert into malignancy in 15 years). Although it is "benign", the tumor is aneuploid, it can recur after resection, it invades normal adjacent tissue, and distant metastases have been reported after long (+10 years) time intervals. This tumour most often presents in the lower pole of the superficial lobe of the gland, about 10% of the tumours arise in the deeper portions of the gland. It occurs more frequently in females than in males, the ratio approximating 6:4. The majority of the lesion are found in patients in the fourth to sixth decades with an average age of occurrences of about 43 years, but these are relatively common in young adults and have been known to occur in children.
## Histology[edit]
Sialadenectomy specimen showing a well outlined solid neoplasm with cartilaginous areas.
Morphological diversity is the most characteristic feature of this neoplasm. Histologically, it is highly variable in appearance, even within individual tumors. Classically it is biphasic and is characterized by an admixture of polygonal epithelial and spindle-shaped myoepithelial elements in a variable background stroma that may be mucoid, myxoid, cartilaginous or hyaline. Epithelial elements may be arranged in duct-like structures, sheets, clumps and/or interlacing strands and consist of polygonal, spindle or stellate-shaped cells (hence pleiomorphism). Areas of squamous metaplasia and epithelial pearls may be present. The tumor is not enveloped, but it is surrounded by a fibrous pseudocapsule of varying thickness. The tumor extends through normal glandular parenchyma in the form of finger-like pseudopodia, but this is not a sign of malignant transformation.
The tumor often displays characteristic chromosomal translocations between chromosomes #3 and #8. This causes the PLAG gene to be juxtaposed to the gene for beta catenin. This activates the catenin pathway and leads to inappropriate cell division.
## Diagnosis[edit]
Pleomorphic adenoma in ultrasound
The diagnosis of salivary gland tumors utilize both tissue sampling and radiographic studies. Tissue sampling procedures include fine needle aspiration (FNA) and core needle biopsy (bigger needle comparing to FNA). Both of these procedures can be done in an outpatient setting. Diagnostic imaging techniques for salivary gland tumors include ultrasound, computer tomography (CT) and magnetic resonance imaging (MRI).
Fine needle aspiration biopsy (FNA), operated in experienced hands, can determine whether the tumor is malignant in nature with sensitivity around 90%.[1][2] FNA can also distinguish primary salivary tumor from metastatic disease.
Core needle biopsy can also be done in outpatient setting. It is more invasive but is more accurate compared to FNA with diagnostic accuracy greater than 97%.[3] Furthermore, core needle biopsy allows more accurate histological typing of the tumor.
In terms of imaging studies, ultrasound can determine and characterize superficial parotid tumors. Certain types of salivary gland tumors have certain sonographic characteristics on ultrasound.[4] Ultrasound is also frequently used to guide FNA or core needle biopsy.
CT allows direct, bilateral visualization of the salivary gland tumor and provides information about overall dimension and tissue invasion. CT is excellent for demonstrating bony invasion. MRI provides superior soft tissue delineation such as perineural invasion when compared to CT only.[5]
## Treatment[edit]
Overall, the mainstay of the treatment for salivary gland tumor is surgical resection. Needle biopsy is highly recommended prior to surgery to confirm the diagnosis. More detailed surgical technique and the support for additional adjuvant radiotherapy depends on whether the tumor is malignant or benign.
Surgical treatment of parotid gland tumors is sometimes difficult, partly because of the anatomical relationship of the facial nerve and the parotid lodge, but also through the increased potential for postoperative relapse. Thus, detection of early stages of a tumor of the parotid gland is extremely important in terms of prognosis after surgery.[6]
Generally, benign tumors of the parotid gland are treated with superficial or total parotidectomy; local dissection of the tumor is not recommended due to high incidence of recurrence.[7] The facial nerve should be preserved whenever possible. The benign tumors of the submandibular gland is treated by simple excision with preservation of mandibular branch of the facial nerve, the hypoglossal nerve, and the lingual nerve.[8] Other benign tumors of minor salivary glands are treated similarly.
Malignant salivary tumors usually require wide local resection of the primary tumor. However, if complete resection cannot be achieved, adjuvant radiotherapy should be added to improve local control.[9][10] This surgical treatment has many sequellae such as cranial nerve damage, Frey's syndrome, cosmetic problems, etc.
Usually about 44% of the patients have a complete histologic removal of the tumor and this refers to the most significant survival rate.
## See also[edit]
* Warthin's tumor \- monomorphic adenoma
* Carcinoma
* Sialadenitis
## References[edit]
1. ^ Cohen EG, Patel SG, Lin O, et al. (Jun 2004). "Fine-needle aspiration biopsy of salivary gland lesions in a selected patient population". Arch Otolaryngol Head Neck Surg. 130 (6): 773–8. doi:10.1001/archotol.130.6.773. PMID 15210562.
2. ^ Batsakis JG, Sneige N, el-Naggar AK (Feb 1992). "Fine-needle aspiration of salivary glands: its utility and tissue effects". Ann Otol Rhinol Laryngol. 101 (2 Pt 1): 185–8. doi:10.1177/000348949210100215. PMID 1739267.
3. ^ Wan YL, Chan SC, Chen YL, et al. (Oct 2004). "Ultrasonography-guided core-needle biopsy of parotid gland masses". AJNR Am J Neuroradiol. 25 (9): 1608–12. PMID 15502149.
4. ^ Białek EJ, Jakubowski W, Karpińska G (Sep 2003). "Role of ultrasonography in diagnosis and differentiation of pleomorphic adenomas: work in progress". Arch Otolaryngol Head Neck Surg. 129 (9): 929–33. doi:10.1001/archotol.129.9.929. PMID 12975263.
5. ^ Koyuncu M, Seşen T, Akan H, et al. (Dec 2003). "Comparison of computed tomography and magnetic resonance imaging in the diagnosis of parotid tumors". Otolaryngol Head Neck Surg. 129 (6): 726–32. doi:10.1016/j.otohns.2003.07.009. PMID 14663442.
6. ^ Alexandru Bucur; Octavian Dincă; Tiberiu Niță; Cosmin Totan; Cristian Vlădan (Mar 2011). "Parotid tumors: our experience". Rev. chir. oro-maxilo-fac. implantol. (in Romanian). 2 (1): 7–9. ISSN 2069-3850. 18. Archived from the original on 2013-01-13. Retrieved 2012-06-06.(webpage has a translation button)
7. ^ Stennert E, Guntinas-Lichius O, Klussmann JP, Arnold G (Dec 2001). "Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases". Laryngoscope. 111 (12): 2195–200. doi:10.1097/00005537-200112000-00024. PMID 11802025.
8. ^ Leonetti JP, Marzo SJ, Petruzzelli GJ, Herr B (Sep 2005). "Recurrent pleomorphic adenoma of the parotid gland". Otolaryngol Head Neck Surg. 133 (3): 319–22. doi:10.1016/j.otohns.2005.04.008. PMID 16143173.
9. ^ Ganly I, Patel SG, Coleman M, Ghossein R, Carlson D, Shah JP (Jul 2006). "Malignant minor salivary gland tumors of the larynx". Arch Otolaryngol Head Neck Surg. 132 (7): 767–70. doi:10.1001/archotol.132.7.767. PMID 16847187.
10. ^ Terhaard CH, Lubsen H, Rasch CR, et al. (Jan 2005). "The role of radiotherapy in the treatment of malignant salivary gland tumors". Int J Radiat Oncol Biol Phys. 61 (1): 103–11. doi:10.1016/j.ijrobp.2004.03.018. PMID 15629600.
## External links[edit]
Classification
D
* ICD-10: D11
* ICD-9-CM: 210.2
* ICD-O: 8940/0
* OMIM: 181030
* MeSH: D008949
External resources
* eMedicine: radio/531
* v
* t
* e
Connective/soft tissue tumors and sarcomas
Not otherwise specified
* Soft-tissue sarcoma
* Desmoplastic small-round-cell tumor
Connective tissue neoplasm
Fibromatous
Fibroma/fibrosarcoma:
* Dermatofibrosarcoma protuberans
* Desmoplastic fibroma
Fibroma/fibromatosis:
* Aggressive infantile fibromatosis
* Aponeurotic fibroma
* Collagenous fibroma
* Diffuse infantile fibromatosis
* Familial myxovascular fibromas
* Fibroma of tendon sheath
* Fibromatosis colli
* Infantile digital fibromatosis
* Juvenile hyaline fibromatosis
* Plantar fibromatosis
* Pleomorphic fibroma
* Oral submucous fibrosis
Histiocytoma/histiocytic sarcoma:
* Benign fibrous histiocytoma
* Malignant fibrous histiocytoma
* Atypical fibroxanthoma
* Solitary fibrous tumor
Myxomatous
* Myxoma/myxosarcoma
* Cutaneous myxoma
* Superficial acral fibromyxoma
* Angiomyxoma
* Ossifying fibromyxoid tumour
Fibroepithelial
* Brenner tumour
* Fibroadenoma
* Phyllodes tumor
Synovial-like
* Synovial sarcoma
* Clear-cell sarcoma
Lipomatous
* Lipoma/liposarcoma
* Myelolipoma
* Myxoid liposarcoma
* PEComa
* Angiomyolipoma
* Chondroid lipoma
* Intradermal spindle cell lipoma
* Pleomorphic lipoma
* Lipoblastomatosis
* Spindle cell lipoma
* Hibernoma
Myomatous
general:
* Myoma/myosarcoma
smooth muscle:
* Leiomyoma/leiomyosarcoma
skeletal muscle:
* Rhabdomyoma/rhabdomyosarcoma: Embryonal rhabdomyosarcoma
* Sarcoma botryoides
* Alveolar rhabdomyosarcoma
* Leiomyoma
* Angioleiomyoma
* Angiolipoleiomyoma
* Genital leiomyoma
* Leiomyosarcoma
* Multiple cutaneous and uterine leiomyomatosis syndrome
* Multiple cutaneous leiomyoma
* Neural fibrolipoma
* Solitary cutaneous leiomyoma
* STUMP
Complex mixed and stromal
* Adenomyoma
* Pleomorphic adenoma
* Mixed Müllerian tumor
* Mesoblastic nephroma
* Wilms' tumor
* Malignant rhabdoid tumour
* Clear-cell sarcoma of the kidney
* Hepatoblastoma
* Pancreatoblastoma
* Carcinosarcoma
Mesothelial
* Mesothelioma
* Adenomatoid tumor
* v
* t
* e
Tumors of lip, oral cavity and pharynx / head and neck cancer
Oral cancer
Salivary gland
malignant epithelial tumors
* Acinic cell carcinoma
* Mucoepidermoid carcinoma
* Adenoid cystic carcinoma
* Salivary duct carcinoma
* Epithelial-myoepithelial carcinoma
* Polymorphous low-grade adenocarcinoma
* Hyalinizing clear cell carcinoma
benign epithelial tumors
* Pleomorphic adenoma
* Warthin's tumor
ungrouped:
* Oncocytoma
Tongue
* Leukoplakia
* Rhabdomyoma
* Oropharynx
*[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
| Pleomorphic adenoma | c0026277 | 1,021 | wikipedia | https://en.wikipedia.org/wiki/Pleomorphic_adenoma | 2021-01-18T18:28:37 | {"mesh": ["D008949"], "umls": ["C0026277"], "icd-9": ["210.2"], "icd-10": ["D11"], "orphanet": ["454821"], "wikidata": ["Q2064603"]} |
MYH9-related thrombocytopenia (MYH9RD) is a genetic condition caused by mutations in the MYH9 gene and is characterized by large platelets and thrombocytopenia (low number of platelets) which increases the risk for mild to serious bleeding in the body or in the skin. Young-adult onset high frequency sensorineural hearing loss, presenile (early) cataract, and kidney disease also variably occurs in people with this condition. This condition is inherited in an autosomal dominant fashion.
The following conditions, once thought to be separate, are now known to be part of MYH9RD.
Epstein syndrome
Fechtner syndrome
May-Hegglin anomaly
Sebastian 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
| MYH9 related thrombocytopenia | c1854520 | 1,022 | gard | https://rarediseases.info.nih.gov/diseases/180/myh9-related-thrombocytopenia | 2021-01-18T17:58:51 | {"mesh": ["C535507"], "omim": ["155100"], "orphanet": ["182050"], "synonyms": ["MYH9 related disorders", "Sebastian syndrome (subtype)", "May-Hegglin anomaly (subtype)", "Fechtner syndrome (subtype)", "Epstein syndrome (subtype)", "MYH9-RD", "MYH9-related disease", "MYH9-related disorder", "MYH9-related syndrome", "MYH9-related syndromic thrombocytopenia", "Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss"]} |
A number sign (#) is used with this entry because of evidence that multiple types of congenital heart defects (CHTD2) are caused by heterozygous mutation in the TAB2 gene (605101) on chromosome 6q25.
For a discussion of genetic heterogeneity of multiple types of congenital heart defects, see 306955.
Clinical Features
Thienpont et al. (2010) described 2 patients with multiple types of congenital heart defects who were found to have a mutation in the TAB2 gene. One patient was a woman with left ventricular outflow tract obstruction, subaortic stenosis due to a fibromuscular shelf, residual aortic regurgitation, and atrial fibrillation; she died from heart failure at 61 years of age. The other patient was a man with a bicuspid aortic valve and aortic dilation.
Weiss et al. (2015) reported a 3-generation family in which 4 individuals had congenital heart defects. The proband was a female infant who was noted at birth to have tetralogy of Fallot, short-segment pulmonary atresia, large malalignment ventricular septal defect, and small atrial septal defect. The mitral and tricuspid valves were both prolapsed, with thickened and myxomatous leaflets. The proband's 32-year-old mother was diagnosed at age 2 years with bicuspid aortic valve and ventricular septal defect. Echocardiogram in adulthood also showed mild aortic valve stenosis and mildly prolapsing myxomatous mitral and tricuspid valves. The 66-year-old maternal grandmother was diagnosed at age 13 years with mitral regurgitation due to a myxomatous and prolapsed valve, for which she underwent valve replacement at age 22. Echocardiography later showed a myxomatous and prolapsed tricuspid valve, and she also had atrial fibrillation. Family history revealed that the grandmother's first pregnancy resulted in a male stillbirth; autopsy showed bicuspid aortic valve and aortic stenosis, as well as hydrops fetalis.
Mapping
Thienpont et al. (2010) reviewed the genotype and phenotype data from 12 patients with a chromosomal deletion on 6q (see 612863) and delineated an 850-kb critical region for congenital heart disease on chromosome 6q25.1.
Molecular Genetics
Thienpont et al. (2010) analyzed the TAB2 gene in 402 patients with cardiac outflow tract defects and identified heterozygosity for missense mutations in 2 patients with multiple types of congenital heart defects (605101.0001 and 605101.0002); neither mutation was found in 658 ethnically matched control chromosomes.
In the proband from a 3-generation family with congenital heart defects, Weiss et al. (2015) performed SNP microarray and identified a 281-kb deletion at chromosome 6q25.1. The minimum deleted segment was mapped at genomic location chr6:149,580,983-149,861,981 (GRCh37) and included 4 genes: TAB2, SUMO4 (608829), ZC3H12D (611106), and PPIL4 (607609). FISH analysis confirmed deletion at 6q25.1 in the affected mother and maternal grandmother, whereas the unaffected father and maternal aunt had normal hybridization signals. Weiss et al. (2015) stated that this was the smallest reported deletion involving TAB2 that segregated with congenital heart defects.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Bicuspid aortic valve \- Myxomatous mitral valve \- Myxomatous tricuspid valve \- Ventricular septal defect \- Aortic valve stenosis \- Subaortic stenosis \- Aortic regurgitation \- Atrial fibrillation \- Tetralogy of Fallot \- Left ventricular outflow tract obstruction Vascular \- Aortic dilation MISCELLANEOUS \- Variable cardiac phenotype MOLECULAR BASIS \- Caused by mutation in the TGF-beta activated kinase 1 binding protein 2 gene (TAB2, 605101.0001 ) ▲ 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
| CONGENITAL HEART DEFECTS, MULTIPLE TYPES, 2 | c3554279 | 1,023 | omim | https://www.omim.org/entry/614980 | 2019-09-22T15:53:30 | {"omim": ["614980"]} |
Secondary lymphedema is a condition characterized by swelling of the soft tissues in which an excessive amount of lymph has accumulated, and is caused by certain malignant diseases such as Hodgkin's disease and Kaposi sarcoma.[1]:849
Secondary lymphedema also can be caused by several non-malignant diseases, such as lipedema, and can result from the removal of lymph nodes during various cancer surgeries, especially for breast and prostate cancers.
## See also[edit]
* Lymphedema
* Skin lesion
## References[edit]
1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
This 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
| Secondary lymphedema | c0265191 | 1,024 | wikipedia | https://en.wikipedia.org/wiki/Secondary_lymphedema | 2021-01-18T18:31:59 | {"umls": ["C0265191"], "wikidata": ["Q7443853"]} |
A number sign (#) is used with this entry because of evidence that Bardet-Biedl syndrome-20 (BBS20) is caused by compound heterozygous mutation in the IFT74 gene (608040) on chromosome 9p21. One such patient has been reported.
Description
BBS20 is an autosomal recessive ciliopathy described in a single patient and characterized by retinitis pigmentosa, obesity, polydactyly, hypogonadism, and intellectual disability (Lindstrand et al., 2016).
For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Clinical Features
Lindstrand et al. (2016) reported a 36-year-old man (AR672-04) with BBS. The patient had obesity, polydactyly, hypogonadism, intellectual disability, microcephaly, and retinitis pigmentosa.
Inheritance
The transmission pattern of BBS20 in the family reported by Lindstrand et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In a patient with BBS20, Lindstrand et al. (2016) identified compound heterozygous mutations in the IFT74 gene (608040.0001-608040.0002). One mutation was a splice site mutation and the other was an intragenic deletion, and the mutations segregated with the disorder in the family. Analysis of the position of the splice site mutation and the deletion predicted that the patient would have ablated function of only the long isoform of IFT74. Short IFT74 isoforms could partially rescue the phenotype of morpholino knockdown of the ift74 gene in zebrafish, suggesting that the patient was hypomorphic for IFT74 function. The patient was 1 of 92 probands with BBS who were screened for copy number variants in candidate genes. Another BBS patient (AR634-03) with biallelic mutations in the BBS7 gene (607590) carried a heterozygous missense variant in the IFT74 gene (V579M) suggesting oligogenic inheritance. The V579M variant was found in 682 of 120,714 alleles in the ExAC database; functional studies of this variant were not performed.
Animal Model
Lindstrand et al. (2016) found that morpholino knockdown of the ift74 gene and CRISPR/CASP9 genome editing of the ift74 locus in zebrafish resulted in significant gastrulation defects and renal abnormalities consistent with a ciliopathy. The phenotype could be rescued by wildtype IFT74.
INHERITANCE \- Autosomal recessive GROWTH Weight \- Obesity HEAD & NECK Head \- Microcephaly Eyes \- Retinitis pigmentosa GENITOURINARY External Genitalia (Male) \- Hypogonadism SKELETAL Hands \- Polydactyly NEUROLOGIC Central Nervous System \- Intellectual disability MISCELLANEOUS \- One patient has been reported (last curated September 2016) MOLECULAR BASIS \- Caused by mutation in the intraflagellar transport 74 gene (IFT74, 608040.0001 ) ▲ 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
| BARDET-BIEDL SYNDROME 20 | c0752166 | 1,025 | omim | https://www.omim.org/entry/617119 | 2019-09-22T15:46:54 | {"mesh": ["D020788"], "omim": ["617119"], "orphanet": ["110"]} |
Beta-ketothiolase deficiency
Other names3-oxothiolase deficiency, Mitochondrial acetoacetyl-coenzyme A thiolase deficiency, Alpha-methyl-acetoacetyl-CoA thiolase deficiency
Isoleucine
Beta-ketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or the products of lipid breakdown.[1][2]
The typical age of onset for this disorder is between 6 months and 24 months.
## Contents
* 1 Symptoms and signs
* 2 Genetic
* 3 Diagnosis
* 4 Treatment
* 5 References
* 6 External links
## Symptoms and signs[edit]
The signs and symptoms of beta-ketothiolase deficiency include vomiting, dehydration, trouble breathing, extreme tiredness, and occasionally convulsions. These episodes are called ketoacidotic attacks and can sometimes lead to coma. Attacks occur when compounds called organic acids (which are formed as products of amino acid and fat breakdown) build up to toxic levels in the blood. These attacks are often triggered by an infection, fasting (not eating), or in some cases, other types of stress.[citation needed]
## Genetic[edit]
Beta-ketothiolase deficiency is autosomal recessive
This condition is inherited in an autosomal recessive pattern and is extremely rare having only been reported in 50 to 60 individuals throughout the world.[citation needed]
Mutations in the ACAT1 gene cause beta-ketothiolase deficiency. The enzyme made by the ACAT1 gene plays an essential role in breaking down proteins and fats in the diet. Specifically, the enzyme is responsible for processing isoleucine, an amino acid that is part of many proteins. This enzyme also processes ketones, which are produced during the breakdown of fats. If a mutation in the ACAT1 gene reduces or eliminates the activity of this enzyme, the body is unable to process isoleucine and ketones properly. As a result, harmful compounds can build up and cause the blood to become too acidic (ketoacidosis), which impairs tissue function, especially in the central nervous system.[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)
## References[edit]
1. ^ RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Beta ketothiolase deficiency". www.orpha.net. Retrieved 2017-07-02.
2. ^ "OMIM Entry - # 203750 - ALPHA-METHYLACETOACETIC ACIDURIA". omim.org. Retrieved 2017-07-02.
This article incorporates public domain text from The U.S. National Library of Medicine
## External links[edit]
Classification
D
* ICD-10: E71.1
* OMIM: 203750
* MeSH: C535434, C535818 C535818, C535434, C535818
* DiseasesDB: 29824
External resources
* Orphanet: 134
* v
* t
* e
Inborn error of amino acid metabolism
K→acetyl-CoA
Lysine/straight chain
* Glutaric acidemia type 1
* type 2
* Hyperlysinemia
* Pipecolic acidemia
* Saccharopinuria
Leucine
* 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
* 3-Methylglutaconic aciduria 1
* Isovaleric acidemia
* Maple syrup urine disease
Tryptophan
* Hypertryptophanemia
G
G→pyruvate→citrate
Glycine
* D-Glyceric acidemia
* Glutathione synthetase deficiency
* Sarcosinemia
* Glycine→Creatine: GAMT deficiency
* Glycine encephalopathy
G→glutamate→
α-ketoglutarate
Histidine
* Carnosinemia
* Histidinemia
* Urocanic aciduria
Proline
* Hyperprolinemia
* Prolidase deficiency
Glutamate/glutamine
* SSADHD
G→propionyl-CoA→
succinyl-CoA
Valine
* Hypervalinemia
* Isobutyryl-CoA dehydrogenase deficiency
* Maple syrup urine disease
Isoleucine
* 2-Methylbutyryl-CoA dehydrogenase deficiency
* Beta-ketothiolase deficiency
* Maple syrup urine disease
Methionine
* Cystathioninuria
* Homocystinuria
* Hypermethioninemia
General BC/OA
* Methylmalonic acidemia
* Methylmalonyl-CoA mutase deficiency
* Propionic acidemia
G→fumarate
Phenylalanine/tyrosine
Phenylketonuria
* 6-Pyruvoyltetrahydropterin synthase deficiency
* Tetrahydrobiopterin deficiency
Tyrosinemia
* Alkaptonuria/Ochronosis
* Tyrosinemia type I
* Tyrosinemia type II
* Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin
* Albinism: Ocular albinism (1)
* Oculocutaneous albinism (Hermansky–Pudlak syndrome)
* Waardenburg syndrome
Tyrosine→Norepinephrine
* Dopamine beta hydroxylase deficiency
* reverse: Brunner syndrome
G→oxaloacetate
Urea cycle/Hyperammonemia
(arginine
* aspartate)
* Argininemia
* Argininosuccinic aciduria
* Carbamoyl phosphate synthetase I deficiency
* Citrullinemia
* N-Acetylglutamate synthase deficiency
* Ornithine transcarbamylase deficiency/translocase deficiency
Transport/
IE of RTT
* Solute carrier family: Cystinuria
* Hartnup disease
* Iminoglycinuria
* Lysinuric protein intolerance
* Fanconi syndrome: Oculocerebrorenal syndrome
* Cystinosis
Other
* 2-Hydroxyglutaric aciduria
* Aminoacylase 1 deficiency
* Ethylmalonic encephalopathy
* Fumarase deficiency
* Trimethylaminuria
*[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
| Beta-ketothiolase deficiency | c1536500 | 1,026 | wikipedia | https://en.wikipedia.org/wiki/Beta-ketothiolase_deficiency | 2021-01-18T18:37:43 | {"gard": ["872"], "mesh": ["C535434", "C535818"], "umls": ["C1536500"], "orphanet": ["134"], "wikidata": ["Q4897218"]} |
Salivary gland disease
Blockage of the submandibular gland by a stone with subsequent infection. Arrow marks pus coming out of the opening of the submandibular gland
SpecialtyGastroenterology, oral and maxillofacial surgery
Salivary gland diseases (SGD) are multiple and varied in cause.[1]
There are three paired major salivary glands in humans – (the parotid glands, the submandibular glands, and the sublingual glands), and about 800-1000 minor salivary glands in the mucosa of the mouth. The parotid gland is located in front of the ear, and it secretes its mostly serous saliva via the parotid duct (Stenson duct) into the mouth, usually opening roughly opposite the maxillary second molar. The submandibular gland is located medial to the angle of the mandible, and it drains its mixture of serous and mucous saliva via the submandibular duct (Wharton duct) into the mouth, usually opening in a punctum located in the floor of mouth. The sublingual gland is located below the tongue, in the floor of the mouth. It drains its mostly mucous saliva into the mouth via about 8-20 ducts which open along the plica sublingualis (a fold of tissue under the tongue).[2]
The function of the salivary glands is to secrete saliva, which has a lubricating function, which protects the oral mucosa of the mouth during eating and speaking.[2] Saliva also contains digestive enzymes (e.g. salivary amylase) and has antimicrobial action and acts as a buffer.[citation needed] Salivary gland dysfunction occurs when salivary rates are reduced and this can result in xerostomia (dry mouth).[citation needed]
Various examples of disorders affecting the salivary glands are listed below. Some are more common than others, and they are considered according to a surgical sieve, but this list is not exhaustive. Sialadenitis is inflammation of a salivary gland, usually caused by infections, although there are other less common causes of inflammation such as irradiation, allergic reactions or trauma.[3]
## Contents
* 1 Congenital
* 2 Acquired
* 2.1 Dysfunction
* 2.2 Vascular
* 2.3 Infective
* 2.4 Traumatic
* 2.5 Autoimmune
* 2.6 Inflammatory
* 2.7 Neurological
* 2.8 Neoplastic
* 2.9 Diverticulum
* 2.10 Unknown
* 3 References
* 4 External links
## Congenital[edit]
Stafne defect
Congenital disorders of the salivary glands are rare,[3] but may include:
* Aplasia
* Atresia
* Ectopic salivary gland tissue
* Stafne defect \- an uncommon condition which some consider to be an anatomic variant rather than a true disease. It is thought to be created by an ectopic portion of salivary gland tissue which causes the bone of the mandible to remodel around the tissue, creating an apparent cyst like radiolucent area on radiographs. Classically, this lesion is discovered as a chance finding,[4] since it causes no symptoms. It appears below the inferior alveolar nerve canal in the posterior region of the mandible.
## Acquired[edit]
### Dysfunction[edit]
Salivary gland dysfunction affects the flow, amount, or quality of saliva produced. A reduced salivation is termed hyposalivation. Hyposalivation often results in a dry mouth condition called xerostomia, and this can cause tooth decay due to the loss of the protective properties of saliva. In addition, The results of a study [5] have suggested that hyposalivation could lead to acute respiratory infection. There are two potential reasons for increasing the incidence rate of this infection. First, reduced saliva secretion may impair the oral and airway mucosal surface as a physical barrier, which consequently enhances the adhesion and colonization of viruses. Second, this reduction may also impair the secretion of antimicrobial proteins and peptides.[5] Considering presence of many proteins and peptides with established antiviral properties in saliva, some of which can potentially inhibit virus replication especially coronavirus, it gives the impression that the protective effect of these salivary proteins against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be the same.[6] Therefore, hyposalivation could be a potential risk factor for acute respiratory infection. It may expose patients at high risk of getting coronavirus disease (COVID-19). However, further investigations are crucial to prove this hypothesis.[6]
Hypersalivation is the overproduction of saliva and has many causes.[7][8]
### Vascular[edit]
* Necrotizing sialometaplasia—a lesion that usually arises from a minor salivary gland on the palate. It is thought to be due to vascular infarction of the salivary gland lobules. It is often mistaken for oral cancer, but the lesion is not neoplastic.[2]
### Infective[edit]
Infections involving the salivary glands can be viral or bacterial (or rarely fungal).
* Mumps is the most common viral sialadenitis. It usually occurs in children, and there is preauricular pain (pain felt in front of the ear), swelling of the parotid, fever, chills, and headaches.[2]
* Bacterial sialadentitis is usually caused by ascending organisms from the oral cavity. Risk factors include reduced salivary flow rate.
* Human immunodeficiency virus-associated salivary gland disease (HIV-SGD).[1]
### Traumatic[edit]
Mucocele
* Mucocele — these are common and are caused by rupture of a salivary gland duct and mucin spillage into the surrounding tissues. Usually they are caused by trauma. Classically, a mucocele is blusish and fluctuant, and most commonly occurs on the lower lip.[9]
* Ranula — the name used when a mucocele occurs in the floor of the mouth (underneath the tongue). Ranulas may grow to a larger size than mucoceles at other sites, and they are usually associated with the sublingual gland, although less commonly they may also arise from the submandibular gland or a minor salivary gland.[9] Uncommonly, a ranula may descend into the neck rather than the mouth (plunging ranula). If small, the ranula may be left alone, but if larger and causing symptoms, excision of the sublingual gland may be indicated.
* Nicotinic stomatitis — the hard palate is whitened by hyperkeratosis caused by the heat from tobacco use or hot liquid consumption. This irritation also causes inflammation of the duct openings of the minor salivary glands of the palate, and they become dilated. This manifests as red patches or spots on a white background.[10]
### Autoimmune[edit]
* Sjögren's syndrome
* Graft-versus-host disease
### Inflammatory[edit]
* Post-irradiation sialadenitis
* Sarcoidosis—there may be parotitis alone or uveoparotitis (inflammation of both the parotid and the uvea of the eyes), which occurs in Heerfordt's syndrome.
* Cheilitis glandularis—This is inflammation of the minor salivary glands, usually in the lower lip, eversion and swelling of the lip.[9]
* Chronic sclerosing sialadenitis is a salivary gland manifestation of IgG4-related disease.[11][12]
### Neurological[edit]
* Frey's syndrome
### Neoplastic[edit]
* Salivary gland neoplasm
### Diverticulum[edit]
A salivary diverticulum (plural diverticuli) is a small pouch or out-pocketing of the duct system of a major salivary gland.[13] Such diverticuli typically cause pooling of saliva and recurrent sialadenitis,[14] especially parotitis.[15] A diverticulum may also cause a sialolith to form.[16][17] The condition can be diagnosed by sialography.[14] Affected individuals may "milk" the salivary gland to encourage flow of saliva through the duct.[14]
### Unknown[edit]
* Sialolithiasis \- although several possibly coexisting factors have been suggested to be involved in the formation of salivary stones, including altered acidity of saliva, reduced salivary flow rate, abnormal calcium metabolism and abnormalities in the sphincter mechanism of the duct opening, the exact cause in many cases is unknown.
* Sialadenosis (sialosis) is an uncommon, non-inflammatory, non-neoplastic, recurrent swelling of the salivary glands. The cause is hypothesized to be abnormalities of neurosecretory control. It may be associated with alcoholism.[3][18][19]
## References[edit]
1. ^ a b Jeffers, L; Webster-Cyriaque, JY (April 2011). "Viruses and salivary gland disease (SGD): lessons from HIV SGD". Advances in Dental Research. 23 (1): 79–83. doi:10.1177/0022034510396882. PMC 3144046. PMID 21441486.
2. ^ a b c d Hupp JR, Ellis E, Tucker MR (2008). Contemporary oral and maxillofacial surgery (5th ed.). St. Louis, Mo.: Mosby Elsevier. pp. 397–419. ISBN 9780323049030.
3. ^ a b c Soames JV, Southam JC, JV (1999). Oral pathology (3rd ed.). Oxford: Oxford Univ. Press. pp. 247–265. ISBN 978-0192628947.
4. ^ Wray D, Stenhouse D, Lee D, Clark AJ (2003). Textbook of general and oral surgery. Edinburgh [etc.]: Churchill Livingstone. pp. 236–237. ISBN 978-0443070839.
5. ^ a b Iwabuchi, Hiroshi; Fujibayashi, Takashi; Yamane, Gen-yuki; Imai, Hirohisa; Nakao, Hiroyuki (2012). "Relationship between Hyposalivation and Acute Respiratory Infection in Dental Outpatients". Gerontology. 58 (3): 205–211. doi:10.1159/000333147. ISSN 1423-0003. PMID 22104982.
6. ^ a b Farshidfar, Nima; Hamedani, Shahram (2020-04-29). "Hyposalivation as a potential risk for SARS‐CoV‐2 infection: Inhibitory role of saliva". Oral Diseases: odi.13375. doi:10.1111/odi.13375. ISSN 1354-523X. PMID 32348636.
7. ^ McGeachan AJ, Mcdermott CJ (10 February 2017). "Management of oral secretions in neurological disease". Practical Neurology (Review). Association of British Neurologists. 17 (2): 96–103. doi:10.1136/practneurol-2016-001515. PMID 28188210 – via BMJ Journals.
8. ^ Miranda-Rius J, Brunet-Llobet L, Lahor-Soler E, Farré M (22 September 2015). "Salivary Secretory Disorders, Inducing Drugs, and Clinical Management". International Journal of Medical Sciences (Review). Ivyspring. 12 (10): 811–824. doi:10.7150/ijms.12912. PMC 4615242. PMID 26516310.
9. ^ a b c Neville BW, Damm DD, Allen CA, Bouquot JE (2002). Oral & maxillofacial pathology (2nd ed.). Philadelphia: W.B. Saunders. pp. 389–430. ISBN 978-0721690032.
10. ^ Illustrated Dental Embryology, Histology, and Anatomy, Bath-Balogh and Fehrenbach, Elsevier, 2011, page 137
11. ^ John H. Stone; Arezou Khosroshahi; Vikram Deshpande; et al. (October 2012). "Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations". Arthritis & Rheumatism. 64 (10): 3061–3067. doi:10.1002/art.34593. PMC 5963880. PMID 22736240.
12. ^ Aly, Fatima (2011-10-07). "Salivary glands: Inflammation: Sialadenitis". Pathology Outlines. Retrieved 2013-12-05.
13. ^ Ghom AG; Ghom SA (1 July 2014). Textbook of Oral Medicine. JP Medical Ltd. p. 606. ISBN 978-93-5152-303-1.
14. ^ a b c Glick M (1 September 2014). Burket's oral medicine (12th ed.). coco. p. 233. ISBN 978-1-60795-188-9.
15. ^ Chaudhary M; Chaudhary SD (1 April 2012). Essentials of Pediatric Oral Pathology. JP Medical Ltd. p. 304. ISBN 978-93-5025-374-8.
16. ^ Afanas'ev, VV; Abdusalamov, MR (2004). "[Diverticulum of the submandibular salivary gland ducts]". Stomatologiia. 83 (5): 31–3. PMID 15477837.
17. ^ Ligtenberg A; Veerman E (31 May 2014). Saliva: Secretion and Functions. Karger Medical and Scientific Publishers. p. 141. ISBN 978-3-318-02596-5.
18. ^ Pape, SA; MacLeod, RI; McLean, NR; Soames, JV (September 1995). "Sialadenosis of the salivary glands". British Journal of Plastic Surgery. 48 (6): 419–22. doi:10.1016/s0007-1226(95)90233-3. PMID 7551515.
19. ^ Mandel, L; Hamele-Bena, D (October 1997). "Alcoholic parotid sialadenosis". Journal of the American Dental Association. 128 (10): 1411–5. doi:10.14219/jada.archive.1997.0060. PMID 9332142.
## External links[edit]
Classification
D
* MeSH: D012466
Wikimedia Commons has media related to Diseases and disorders of salivary glands.
* v
* t
* e
Oral and maxillofacial pathology
Lips
* Cheilitis
* Actinic
* Angular
* Plasma cell
* Cleft lip
* Congenital lip pit
* Eclabium
* Herpes labialis
* Macrocheilia
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*[AA]: Adrenergic agonist
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*[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
| Salivary gland disease | c0036093 | 1,027 | wikipedia | https://en.wikipedia.org/wiki/Salivary_gland_disease | 2021-01-18T19:10:18 | {"mesh": ["D012466"], "umls": ["C0036093"], "icd-10": ["K11"], "wikidata": ["Q17152566"]} |
A number sign (#) is used with this entry because of evidence that familial focal epilepsy with variable foci-2 (FFEVF2) is caused by heterozygous mutation in the NPRL2 gene (607072) on chromosome 3p21.
Description
Familial focal epilepsy with variable foci (FFEVF) is an autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and nocturnal frontal lobe epilepsy (NFLE). A subset of patients have structural brain abnormalities, particularly focal cortical dysplasia (FCD). There is significant incomplete penetrance, with many unaffected mutation carriers within a family (summary by Ricos et al., 2016).
For a discussion of genetic heterogeneity of FFEVF, see FFEVF1 (604364).
Clinical Features
Ricos et al. (2016) reported 10 patients from 5 unrelated families with FFEVF2. Seizure types included NFLE, TLE, and FLE. One patient had intellectual disability and perisylvian polymicrogyria, and another had a frontal tumor-like brain lesion on imaging. Additional clinical details were limited.
Weckhuysen et al. (2016) reported 2 sisters from a nonconsanguineous family (family E) of French descent with FFEVF2. The 27-year-old proband had onset of refractory NFLE at age 3 years. EEG showed abnormal activity in the frontal regions. Although brain MRI was normal, PET scanning showed hypometabolism in the right frontal region which was associated with an area with increased cortical thickness and blurring of the gray-white matter. She underwent a right frontoorbital brain resection at age 18 years, which resulted in a 50% decrease in seizure frequency. Histopathology showed focal cortical dysplasia. Her 20-year-old sister had onset of TLE at age 13 years. EEG showed left temporal epileptic activity; MRI was normal. Family history was limited, but there were 3 additional family members on the paternal side of the family who had nonspecific seizures, including 1 individual who died suddenly of seizures at age 22 years, with a diagnosis of possible SUDEP (sudden death in epilepsy).
Inheritance
The transmission pattern of FFEVF2 in the families reported by Ricos et al. (2016) and Weckhuysen et al. (2016) was consistent with autosomal dominant inheritance with incomplete penetrance.
Molecular Genetics
In 10 patients from 5 unrelated families with FFEVF2, Ricos et al. (2016) identified 5 different heterozygous mutations in the NPRL2 gene (see, e.g., 607072.0001-607072.0003), including 2 truncating mutations and 3 missense mutations. There was evidence of incomplete penetrance. The mutation in 1 large family was found by exome sequencing; the remaining 4 probands were ascertained from a cohort of 404 individuals with focal epilepsy who underwent targeted sequencing for genes in the GATOR1 complex. Functional studies of the variants and studies of patient cells were not performed. The NPRL2 gene is part of the GATOR1 complex, which negatively regulates mTOR (601231), a regulator of cell growth and metabolism. The findings suggested that loss of function of the GATOR1 complex due to NPRL2 mutations can cause deregulated cellular growth and may play an important role in cortical dysplasia and focal epilepsy.
In 2 French sisters with FFEVF2, Weckhuysen et al. (2016) identified a heterozygous frameshift mutation in the NPRL2 gene (607072.0004). The mutation, which was found by sequencing a targeted epilepsy gene panel, was confirmed by Sanger sequencing. The unaffected father and an unaffected sib also carried the mutation, consistent with incomplete penetrance. A distant relative on the paternal side of the family with an unspecified epilepsy also carried the mutation. Analysis of patient cells showed that the mutant transcript was not subject to nonsense-mediated mRNA decay, but was predicted to result in a very shortened protein. Brain sample from 1 of the patients, who had focal cortical dysplasia, showed hyperactivation of the mTOR pathway in neurons of normal appearance. These findings suggested the NPRL2 mutation resulted in a loss of function of the GATOR1 complex. The family was from a larger cohort of 93 probands with focal epilepsy with or without FCD who underwent screening; NPRL3 mutations thus occurred in 1.1% of probands studied.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Seizures, focal \- Frontal lobe epilepsy \- Nocturnal frontal lobe epilepsy \- Temporal lobe epilepsy \- Focal cortical dysplasia (in some patients) MISCELLANEOUS \- Onset in early childhood \- Incomplete penetrance MOLECULAR BASIS \- Caused by mutation in the NPR2-like protein, GATOR1 complex subunit gene (NPRL2, 607072.0001 ) ▲ Close
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*[AA]: Adrenergic agonist
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*[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
| EPILEPSY, FAMILIAL FOCAL, WITH VARIABLE FOCI 2 | c4310709 | 1,028 | omim | https://www.omim.org/entry/617116 | 2019-09-22T15:46:47 | {"omim": ["617116"], "orphanet": ["98820"], "synonyms": ["FFEVF", "Familial partial epilepsy with variable foci"]} |
Snowflake vitreoretinal degeneration (SVD) is characterised by the presence of small granular-like deposits resembling snowflakes in the retina, fibrillary vitreous degeneration and cataract. The prevalence is unknown but the disorder has been described in several families. Transmission is autosomal dominant and the causative gene has been localised to a small region on chromosome 2q36.
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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
| Snowflake vitreoretinal degeneration | c1860405 | 1,029 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91496 | 2021-01-23T17:04:04 | {"gard": ["9706"], "mesh": ["C536677"], "omim": ["193230"], "umls": ["C1860405"], "icd-10": ["H35.5"]} |
Left tension pneumothorax seen as a large, well-demarcated area devoid of lung markings with tracheal deviation and movement of the heart away from the affected side (mediastinal shift). There is also small pleural effusion on the left side.
Mediastinal shift is the deviation of the mediastinal structures towards one side of the chest cavity, usually seen on chest radiograph. It indicates a severe asymmetry of intrathoracic pressures.[1] Mediastinal shift may be caused by volume expansion on one side of the thorax, volume loss on one side of the thorax, mediastinal masses and vertebral or chest wall abnormalities. An emergent condition classically presenting with mediastinal shift is tension pneumothorax.
Mediastinal shift may be detected on antenatal ultrasound in certain fetal conditions.[2]
## References[edit]
1. ^ Reed, James C. (2018). Chest radiology : patterns and differential diagnoses (Seventh ed.). Philadelphia, PA: Elsevier. ISBN 9780323510219. OCLC 1012134513.
2. ^ Colombani, M.; Rubesova, E.; Potier, A.; Quarello, E.; Barth, R.A.; Devred, P.; Petit, P.; Gorincour, G. (February 2011). "Conduite à tenir devant une déviation médiastinale fœtale : une approche pratique". Journal de Radiologie. 92 (2): 118–124. doi:10.1016/j.jradio.2010.12.002. PMID 21352743.
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*[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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| Mediastinal shift | c0264576 | 1,030 | wikipedia | https://en.wikipedia.org/wiki/Mediastinal_shift | 2021-01-18T18:56:10 | {"umls": ["C0264576"], "wikidata": ["Q1324598"]} |
Eye disease characterized by leakage of fluid under the retina
Central serous retinopathy
An occurrence of central serous retinopathy of the fovea centralis imaged using optical coherence tomography.
SpecialtyOphthalmology
Central serous retinopathy (CSR), also known as central serous chorioretinopathy (CSC or CSCR), is an eye disease that causes visual impairment, often temporary, usually in one eye.[1][2] When the disorder is active it is characterized by leakage of fluid under the retina that has a propensity to accumulate under the central macula. This results in blurred or distorted vision (metamorphopsia). A blurred or gray spot in the central visual field is common when the retina is detached. Reduced visual acuity may persist after the fluid has disappeared.[1]
The disease is considered of unknown cause. It mostly affects white males in the age group 20 to 50 (male:female ratio 6:1)[3] and occasionally other groups. The condition is believed to be exacerbated by stress or corticosteroid use.[4]
## Contents
* 1 Pathophysiology
* 2 Risk factors
* 3 Diagnosis
* 4 Treatment
* 4.1 Laser treatments
* 4.2 Oral medications
* 4.3 Topical treatment
* 4.4 Lifestyle changes
* 5 Prognosis
* 6 See also
* 7 References
* 8 External links
## Pathophysiology[edit]
Recently, central serous chorioretinopathy has been understood to be part of the pachychoroid spectrum.[5][6] In pachychoroid spectrum disorders, of which CSR represents stage II, the choroid, the highly vascularized layer below the retina, is thickened and congested with increased blood vessel diameter, especially in the deep choroid (the so-called Haller's layer). This results in increased pressure from the deep choroid against the superficial choroid close to the retina, damaging the fine blood vessels (capillaries) needed to supply oxygen and nutrients to the retinal pigment epithelium and retina. Additionally, fluid can leak from these damaged vessels and accumulate under the retina.
Different stages of the pachychoroid are defined depending on the amount of cumulative damage.[5][6] If there are defects in the retinal pigment epithelium without accumulation of fluid below the retina, a pachychoroid pigmentepitheliopathy (PPE) is present. Accumulation of fluid results in central serous chorioretinopathy (CSR). The development of secondary blood vessels, so-called choroidal neovascularization (CNV) leads to pachychoroid neovasculopathy (PNV). If parts of these new vessels bulge outward, so-called aneurysms develop within this CNV, defining pachychoroid aneurysmal type 1 CNV (or, still widely used, polypoidal choroidal vasculopathy (PCV)).
Since the individual stages develop one after the other from the respective preliminary stage, pachychoroidal diseases of the macula are divided into 4 stages according to Siedlecki, Schworm and Priglinger:[7]
Pachychoroid spectrum disorders of the macula (after Siedlecki et al.[7])
0 Uncomplicated pachychoroid (UCP)
I Pachychoroid pigmentepitheliopathy (PPE)
II Central serous chorioretinopathy (CCS)
III Pachychoroid neovasculopathy (PNV)
a) with neurosensory detachment (=subretinal fluid)
b) without neurosensory detachment (no subretinal fluid)
IV Pachychoroid aneurysmal type 1 choroidal neovascularization (PAT1)
(also polypoidal choroidal vasculopathy, PCV)
## Risk factors[edit]
CSR is sometimes called idiopathic CSR which means that its cause is unknown. Nevertheless, stress appears to play an important role. An oft-cited but potentially inaccurate conclusion is that persons in stressful occupations, such as airplane pilots, have a higher incidence of CSR.
CSR has also been associated with cortisol and corticosteroids. Persons with CSR have higher levels of cortisol.[8] Cortisol is a hormone secreted by the adrenal cortex which allows the body to deal with stress, which may explain the CSR-stress association. There is extensive evidence to the effect that corticosteroids (e.g. cortisone), commonly used to treat inflammations, allergies, skin conditions and even certain eye conditions, can trigger CSR, aggravate it and cause relapses.[9][10][11] In a study documented by Indian Journal of Pharmacology, a young male was using Prednisolone and began to display subretinal fluid indicative of CSR. With the discontinuation of the steroid drop the subretinal fluid resolved and did not show any sign of recurrence. Thus indicating the steroid was the probable cause of the CSR.[12] A study of 60 persons with Cushing's syndrome found CSR in 3 (5%).[13] Cushing's syndrome is characterized by very high cortisol levels. Certain sympathomimetic drugs have also been associated with causing the disease.[14]
Evidence has also implicated helicobacter pylori (see gastritis) as playing a role.[15][16] It would appear that the presence of the bacteria is well correlated with visual acuity and other retinal findings following an attack.
Evidence also shows that sufferers of MPGN type II kidney disease can develop retinal abnormalities including CSR caused by deposits of the same material that originally damaged the glomerular basement membrane in the kidneys.[17]
## Diagnosis[edit]
Optical coherence tomography imaging of central serous retinopathy
Indocyanine green angiography (left) and laser Doppler imaging (right) of the macula in central serous retinopathy, revealing choroidal vessels. Blue and red correspond ot low and high blood flow respecively.[18]
The diagnosis usually starts with a dilated examination of the retina, followed with confirmation by optical coherence tomography and fluorescein angiography. The angiography test will usually show one or more fluorescent spots with fluid leakage. In 10%-15% of the cases these will appear in a "classic" smokestack shape.[citation needed] Differential diagnosis should be immediately performed to rule out retinal detachment, which is a medical emergency. A clinical record should be taken to keep a timeline of the detachment. An Amsler grid can be useful in documenting the precise area of the visual field involved. The affected eye will sometimes exhibit a refractive spectacle prescription that is more far-sighted than the fellow eye due to the decreased focal length caused by the raising of the retina.
Indocyanine green angiography or laser Doppler imaging can be used to reveal the underlying swollen choroidal vessels under the retinal pigment epithelium and assess the health of the retina in the affected area which can be useful in making a treatment decision.
## Treatment[edit]
Any ongoing corticosteroid treatment should be tapered and stopped, where possible. It is important to check current medication, including nasal sprays and creams, for ingredients of corticosteroids, if found seek advice from a medical practitioner for an alternative.
Most eyes with CSR undergo spontaneous resorption of subretinal fluid within 3–4 months. Recovery of visual acuity usually follows. Treatment should be considered if resorption does not occur within 3–4 months,[19] spontaneously or as the result of counselling.[1] The available evidence suggests that half-dose (or half-fluence) photodynamic therapy is the treatment of choice for CSR with subretinalfluid for longer than 3–4 months.[20]
Due to the natural disease course of CSR - in which spontaneous resolution of subretinal fluid may occur - retrospective studies may erroneously report positive treatment outcomes and should, therefore, be evaluated with caution.
### Laser treatments[edit]
Full-dose photodynamic therapy (PDT) with verteporfin was first described in CSR back in 2003.[21] Later, reduced-settings PDT (half-dose, half-fluence, and half-time) was found to have the same efficacy and a lower chance of complications. Follow-up studies have confirmed the treatment's long-term effectiveness[22] including its effectiveness for the chronic variant of the disease.[23] In the PLACE trial, half-dose photodynamic therapy was found to be superior compared to high-density subthreshold micropulse laser, both with regard to anatomical and functional outcomes.[24] Indocyanine green angiography can be used to predict how the patient will respond to PDT.[19][25]
Laser photocoagulation, which effectively burns the leak area shut, may be considered in cases where there is little improvement in a 3- to 4-month duration, and the leakage is confined to a single or a few sources of leakage at a safe distance from the fovea. Laser photocoagulation is not indicated for cases where the leak is very near the central macula or for cases where the leakage is widespread and its source is difficult to identify. Laser photocoagulation can permanently damage vision where applied. Carefully tuned lasers can limit this damage.[26] Even so, laser photocoagulation is not a preferred treatment for leaks in the central vision and is considered an outdated treatment by some doctors.[19] Foveal attenuation has been associated with more than 4 months' duration of symptoms, however a better long-term outcome has not been demonstrated with laser photocoagulation than without photocoagulation.[1]
In chronic cases, transpupillary thermotherapy has been suggested as an alternative to laser photocoagulation where the leak is in the central macula.[27]
Yellow micropulse laser has shown promise in very limited retrospective trials.[4]
### Oral medications[edit]
Spironolactone is a mineralocorticoid receptor antagonist that may help reduce the fluid associated with CSR. In a retrospective study noted by Acta Ophthalmologica, spironolactone improved visual acuity in CSR patients over the course of 8 weeks.[28]
Epleronone is another mineralocorticoid receptor antagonist that has been thought to reduce the subretinal fluid that is present with CSR. In a study noted in International Journal of Ophthalmology, results showed Epleronone decreased the subretinal fluid both horizontally and vertically over time.[29] However, the most recent randomized controlled trial showed that eplerenone had no significant effect on chronic CSR.[30][31]
Low dosage ibuprofen has been shown to quicken recovery in some cases.[32]
### Topical treatment[edit]
Though no topical treatment has been proven to be effective in the treatment of CSR. Some doctors have attempted to use nonsteroidal topical medications to reduce the subretinal fluid associated with CSR. The nonsteroidal topical medications that are sometimes used to treat CSR are, Ketorolac, Diclofenac, or Bromfenac.[33]
### Lifestyle changes[edit]
People who have irregular sleep patterns, type A personalities, sleep apnea, or systemic hypertension are more susceptible to CSR, as stated in Medscape. “The pathogenesis here is thought to be elevated circulating cortisol and epinephrine, which affect the autoregulation of the choroidal circulation.” [34] With management of these lifestyle patterns and associated cortisol and epinephrine levels, it has been shown that the fluid associated with CSR can spontaneously resolve. Melatonin has been shown to help regulate sleep in people who have irregular sleep patterns (such as 3rd shift workers, or overnight employees), in turn, better regulating cortisol and epinephrine levels to manage CSR.
A Cochrane review seeking to compare the effectiveness of various treatment for CSR found low quality evidence that half-dose PDT treatment resulted in improved visual acuity and less recurrence of CSR in patients with acute CSR, compared to patients in the control group.[35] The review also found benefits in micropulse laser treatments, where patients with acute and chronic CSR had improved visual acuity compared to control patients.[35]
## Prognosis[edit]
The prognosis for CSR is generally excellent. While immediate vision loss may be as poor as 20/200 in the affected eye, clinically, over 90% of patients regain 20/25 vision or better within 45 days.[1] Once the fluid has resolved, either spontaneously or through treatment, distortion is reduced and visual acuity improves as the eye heals. However, some visual abnormalities can remain even where visual acuity is measured at 20/20. Lasting problems include decreased night vision, reduced color discrimination, and localized distortion caused by scarring of the sub-retinal layers.[36]
Complications include subretinal neovascularization and pigment epithelial detachment.[37]
The disease can re-occur causing progressive vision loss. There is also a chronic form, titled as type II central serous retinopathy, which occurs in approximately 5% of cases. This exhibits diffuse rather than focalized abnormality of the pigment epithelium, producing a persistent subretinal fluid. The serous fluid in these cases tends to be shallow rather than dome shaped. The prognosis for this condition is less favorable and continued clinical consultation is advised.[citation needed]
## See also[edit]
* Diabetic retinopathy
* Hypertensive retinopathy
* Macular degeneration
* Posterior vitreous detachment
## References[edit]
1. ^ a b c d e Wang M, Munch IC, Hasler PW, Prünte C, Larsen M (March 2008). "Central serous chorioretinopathy". Acta Ophthalmologica. 86 (2): 126–45. doi:10.1111/j.1600-0420.2007.00889.x. PMID 17662099. S2CID 42537355.
2. ^ Quillen DA, Gass DM, Brod RD, Gardner TW, Blankenship GW, Gottlieb JL (January 1996). "Central serous chorioretinopathy in women". Ophthalmology. 103 (1): 72–9. doi:10.1016/s0161-6420(96)30730-6. PMID 8628563.
3. ^ Sartini F, Figus M, Nardi M, Casini G, Posarelli C (July 2019). "Non-resolving, recurrent and chronic central serous chorioretinopathy: available treatment options". Eye. 33 (7): 1035–1043. doi:10.1038/s41433-019-0381-7. PMC 6707196. PMID 30824822.
4. ^ a b André Maia (February 2010). "A New Treatment for Chronic Central Serous Retinopathy". Retina Today. Archived from the original on 2012-08-09. Retrieved 2013-08-11. Cite journal requires `|journal=` (help)
5. ^ a b Cheung CM, Lee WK, Koizumi H, Dansingani K, Lai TY, Freund KB (January 2019). "Pachychoroid disease". Eye. 33 (1): 14–33. doi:10.1038/s41433-018-0158-4. PMC 6328576. PMID 29995841.
6. ^ a b Akkaya S (October 2018). "Spectrum of pachychoroid diseases". International Ophthalmology. 38 (5): 2239–2246. doi:10.1007/s10792-017-0666-4. PMID 28766279. S2CID 4022900.
7. ^ a b Siedlecki J, Schworm B, Priglinger SG (December 2019). "The Pachychoroid Disease Spectrum-and the Need for a Uniform Classification System". Ophthalmology. Retina. 3 (12): 1013–1015. doi:10.1016/j.oret.2019.08.002. PMID 31810570.
8. ^ Garg SP, Dada T, Talwar D, Biswas NR (November 1997). "Endogenous cortisol profile in patients with central serous chorioretinopathy". The British Journal of Ophthalmology. 81 (11): 962–4. doi:10.1136/bjo.81.11.962. PMC 1722041. PMID 9505819.
9. ^ Pizzimenti JJ, Daniel KP (August 2005). "Central serous chorioretinopathy after epidural steroid injection". Pharmacotherapy. 25 (8): 1141–6. doi:10.1592/phco.2005.25.8.1141. PMID 16207106.
10. ^ Bevis T, Ratnakaram R, Smith MF, Bhatti MT (August 2005). "Visual loss due to central serous chorioretinopathy during corticosteroid treatment for giant cell arteritis". Clinical & Experimental Ophthalmology. 33 (4): 437–9. doi:10.1111/j.1442-9071.2005.01017.x. PMID 16033370.
11. ^ Fernández Hortelano A, Sádaba LM, Heras Mulero H, García Layana A (April 2005). "[Central serous chorioretinopathy as a complication of epitheliopathy under treatment with glucocorticoids]" [Central serous chorioretinopathy as a complication of epitheliopathy under treatment with glucocorticoids]. Archivos de la Sociedad Espanola de Oftalmologia (in Spanish). 80 (4): 255–8. doi:10.4321/S0365-66912005000400010. PMID 15852168.
12. ^ Shah SP, Desai CK, Desai MK, Dikshit RK (September 2011). "Steroid-induced central serous retinopathy". Indian Journal of Pharmacology. 43 (5): 607–8. doi:10.4103/0253-7613.84985. PMC 3195140. PMID 22022013.
13. ^ Bouzas EA, Scott MH, Mastorakos G, Chrousos GP, Kaiser-Kupfer MI (September 1993). "Central serous chorioretinopathy in endogenous hypercortisolism". Archives of Ophthalmology. 111 (9): 1229–33. doi:10.1001/archopht.1993.01090090081024. PMID 8363466.
14. ^ Michael JC, Pak J, Pulido J, de Venecia G (July 2003). "Central serous chorioretinopathy associated with administration of sympathomimetic agents". American Journal of Ophthalmology. 136 (1): 182–5. doi:10.1016/S0002-9394(03)00076-X. PMID 12834690.
15. ^ Ahnoux-Zabsonre A, Quaranta M, Mauget-Faÿsse M (December 2004). "[Prevalence of Helicobacter pylori in central serous chorioretinopathy and diffuse retinal epitheliopathy: a complementary study]" [Prevalence of Helicobacter pylori in central serous chorioretinopathy and diffuse retinal epitheliopathy: a complementary study]. Journal Français d'Ophtalmologie (in French). 27 (10): 1129–33. doi:10.1016/S0181-5512(04)96281-X. PMID 15687922.
16. ^ Cotticelli L, Borrelli M, D'Alessio AC, Menzione M, Villani A, Piccolo G, et al. (2006). "Central serous chorioretinopathy and Helicobacter pylori". European Journal of Ophthalmology. 16 (2): 274–8. doi:10.1177/112067210601600213. PMID 16703546. S2CID 37258065.
17. ^ Colville D, Guymer R, Sinclair RA, Savige J (August 2003). "Visual impairment caused by retinal abnormalities in mesangiocapillary (membranoproliferative) glomerulonephritis type II ("dense deposit disease")". American Journal of Kidney Diseases. 42 (2): E2-5. doi:10.1016/S0272-6386(03)00665-6. PMID 12900843.
18. ^ Puyo, Léo, Michel Paques, Mathias Fink, José-Alain Sahel, and Michael Atlan. "Choroidal vasculature imaging with laser Doppler holography." Biomedical optics express 10, no. 2 (2019): 995-1012.
19. ^ a b c Boscia F (April 2010). "When to Treat and Not to Treat Patients With Central Serous Retinopathy". Retina Today. Archived from the original on 2012-10-17.
20. ^ van Rijssen, TJ (2019). "Central serous chorioretinopathy: Towards an evidence-based treatment guideline". Prog Retin Eye Res. 73: 100770. doi:10.1016/j.preteyeres.2019.07.003. PMID 31319157.
21. ^ Yannuzzi, L. A. (2003). "Indocyanine green angiography-guided photodynamic therapy for treatment of chronic central serous chorioretinopathy: a pilot study". Retina. 23 (3): 288–98. doi:10.1097/00006982-200306000-00002. PMID 12824827.
22. ^ Chan WM, Lai TY, Lai RY, Liu DT, Lam DS (October 2008). "Half-dose verteporfin photodynamic therapy for acute central serous chorioretinopathy: one-year results of a randomized controlled trial". Ophthalmology. 115 (10): 1756–65. doi:10.1016/j.ophtha.2008.04.014. PMID 18538401.
23. ^ Karakus SH, Basarir B, Pinarci EY, Kirandi EU, Demirok A (May 2013). "Long-term results of half-dose photodynamic therapy for chronic central serous chorioretinopathy with contrast sensitivity changes". Eye. 27 (5): 612–20. doi:10.1038/eye.2013.24. PMC 3650272. PMID 23519277.
24. ^ van Dijk, Elon (2018-05-20). "Half-Dose Photodynamic Therapy versus High-Density Subthreshold Micropulse Laser Treatment in Patients with Chronic Central Serous Chorioretinopathy: The PLACE Trial". Ophthalmology. 125 (10): 1547–1555. doi:10.1016/j.ophtha.2018.04.021. PMID 29776672.
25. ^ Inoue R, Sawa M, Tsujikawa M, Gomi F (March 2010). "Association between the efficacy of photodynamic therapy and indocyanine green angiography findings for central serous chorioretinopathy". American Journal of Ophthalmology. 149 (3): 441–6.e1–2. doi:10.1016/j.ajo.2009.10.011. PMID 20172070.
26. ^ Roider J, Brinkmann R, Wirbelauer C, Laqua H, Birngruber R (August 1999). "Retinal sparing by selective retinal pigment epithelial photocoagulation". Archives of Ophthalmology. 117 (8): 1028–34. doi:10.1001/archopht.117.8.1028. PMID 10448745.
27. ^ Wei SY, Yang CM (2005). "Transpupillary thermotherapy in the treatment of central serous chorioretinopathy". Ophthalmic Surgery, Lasers & Imaging. 36 (5): 412–5. doi:10.3928/1542-8877-20050901-11. PMID 16238041.
28. ^ Lee J.Y. (2016). "Spironolactone in the treatment of non-resolving central serous chorioretinopathy: a comparative analysis". Acta Ophthalmologica. 94. doi:10.1111/j.1755-3768.2016.0285.
29. ^ Singh RP, Sears JE, Bedi R, Schachat AP, Ehlers JP, Kaiser PK (2015). "Oral eplerenone for the management of chronic central serous chorioretinopathy". International Journal of Ophthalmology. 8 (2): 310–4. doi:10.3980/j.issn.2222-3959.2015.02.17. PMC 4413566. PMID 25938046.
30. ^ Lotery A, Sivaprasad S, O'Connell A, Harris RA, Culliford L, Ellis L, et al. (January 2020). "Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease for more than 4 months (VICI): a randomised, double-blind, placebo-controlled trial". Lancet. 395 (10220): 294–303. doi:10.1016/S0140-6736(19)32981-2. PMID 31982075.
31. ^ Trials Centre, Bristol. "VICI Trial YouTube video". Twitter.
32. ^ Pecora JL (November 1978). "Ibuprofen in the treatment of central serous chorioretinopathy". Annals of Ophthalmology. 10 (11): 1481–3. PMID 727624.
33. ^ "Retinal Physician - Central Serous Chorioretinopathy and Topical NSAIDs". Retinal Physician. Archived from the original on 30 August 2017. Retrieved 15 October 2017.
34. ^ "Central Serous Chorioretinopathy: Background, Pathophysiology, Epidemiology". 16 March 2017. Archived from the original on 16 October 2017. Retrieved 15 October 2017 – via eMedicine. Cite journal requires `|journal=` (help)
35. ^ a b Salehi M, Wenick AS, Law HA, Evans JR, Gehlbach P (December 2015). "Interventions for central serous chorioretinopathy: a network meta-analysis". The Cochrane Database of Systematic Reviews. 12 (12): CD011841. doi:10.1002/14651858.CD011841.pub2. PMC 5030073. PMID 26691378.
36. ^ Baran NV, Gürlü VP, Esgin H (August 2005). "Long-term macular function in eyes with central serous chorioretinopathy". Clinical & Experimental Ophthalmology. 33 (4): 369–72. doi:10.1111/j.1442-9071.2005.01027.x. PMID 16033348.
37. ^ Kanyange ML, De Laey JJ (2002). "Long-term follow-up of central serous chorioretinopathy (CSCR)". Bulletin de la Société Belge d'Ophtalmologie (284): 39–44. PMID 12161989.
## External links[edit]
Classification
D
* ICD-10: H35.7
* ICD-9-CM: 362.41
* MeSH: D056833
* DiseasesDB: 31277
External resources
* MedlinePlus: 001612
* eMedicine: oph/689
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Infections
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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
| Central serous retinopathy | c0730328 | 1,031 | wikipedia | https://en.wikipedia.org/wiki/Central_serous_retinopathy | 2021-01-18T18:56:33 | {"gard": ["200"], "mesh": ["D056833"], "umls": ["C0730328"], "icd-9": ["362.41"], "icd-10": ["H35.7"], "orphanet": ["443079"], "wikidata": ["Q1431217"]} |
Vitamin D deficiency has become a worldwide health epidemic with clinical rates on the rise. In the years of 2011–12, it was estimated that around 4 million adults were considered deficient in Vitamin D throughout Australia.[1] The Australian Bureau of Statistics (ABS) found 23%, or one in four Australian adults suffer from some form of Vitamin D deficiency.[1] Outlined throughout the article are the causes of increase through subgroups populations, influencing factors and strategies in place to control deficiency rates throughout Australia.
## Contents
* 1 Background
* 1.1 Importance of vitamin D
* 1.2 Vitamin D deficiency
* 2 Health effects
* 2.1 Rickets
* 2.2 Osteoporosis
* 3 High risk groups
* 3.1 Age
* 3.2 Skin colour
* 3.3 Sun exposure
* 3.4 Obesity
* 3.5 Pregnancy
* 4 Contributing factors
* 5 Government strategies
* 5.1 Mandatory fortification
* 6 Treatment
* 7 See also
* 8 References
## Background[edit]
### Importance of vitamin D[edit]
Synthesis of Vitamin D
Vitamin D plays an important role in which it supports calcium absorption in the body, sustaining good bone health as well as muscle function. When calcium in the body becomes under provided for normal bodily functions, calcitriol, an active form of Vitamin D, pairs with parathyroid hormone. Together they act to assemble cells in order to increase the calcium stores taken from bone.[2]
The popular term Sunshine vitamin, as it's often called, is one of the one main sources of achieving sufficient Vitamin D through sunlight on the skin known as D3. The second form is commonly known as D2, which is found in foods such as fatty fish and fortified products like margarine and milk.[1]
Additionally, if you consume vitamin D through your diet, or make vitamin D in your skin from UVB exposure, it is processed through two organs before it becomes activated. Vitamin D is first processed in the liver, before heading to the kidneys where it becomes activated to the form 1-25 dihydroxy vitamin D or alternatively named chemical calcitriol.[3]
### Vitamin D deficiency[edit]
Vitamin D deficiency historically used to be identified through counting cases of rickets. The old theory was that if someone had enough vitamin D to prevent rickets and osteomalacia, two skeletal disorders, they were considered safe from a deficiency. Nowadays through technological advancements Vitamin D deficiencies are now identified and thus calculated through the measurement of the serum 25-OH. According to the Australian Bureau of Statistics National Health Measures Survey (NHMS), the recommend Vitamin D levels to determine deficiency are categorised as follows:
•Adequate levels: > 50 nmol/L
•Mild deficiency: 30-49 nmol/L
•Moderate deficiency: 13 – 29nmol/L
•Severe deficiency: < 13 nmol/L [4]
In 1997, the prevalence of deficiency, defined as <17.5 nmol/L, was 2.8%, and the prevalence of insufficiency, defined as <37.5 nmol/L, was 27.6% among Australians over the age of 15.[5] In 2011-2012 23% of Adults had a deficiency defined as below 49 nmol/L.[6]
## Health effects[edit]
This fundamental fat-soluble vitamin has been long known for its important role in calcium absorption in the body, especially in musculoskeletal health. The health impacts commonly caused by deficiency of Vitamin D are rickets in children and osteoporosis in the elderly populations. Low levels of Vitamin D have also been associated with other conditions such as heart disease, cancer and kidney disease but further research is required.[1] Recent evidence suggests Vitamin D is also linked to many other health diseases such as cardiovascular disease, chronic kidney disease, diabetes mellitus, multiple sclerosis and some form of cancer.[7]
### Rickets[edit]
Photograph of children with rickets
Rickets can be traced back to the 1600s, where a pandemic arose with children around the globe from Vitamin D deficiency.[8] The inadequate intake of UV exposure consequently lead children to numerous health problems such as, growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany and seizures.[8] During the late 19th century autopsies conducted in the Netherlands concluded that 80-90% of children were suffering from Rickets.[8] The incidents of rickets observed within Sydney hospitals during the years of 2003 – 2004 have doubled. This major spike can be attributed to the growing population of migrants in Australia, many of whom are considered high risk of vitamin D deficiency.[2]
As shown in the image the skeletal deformities such as knock knees and bow legs in these young children as a result of rickets.
### Osteoporosis[edit]
Because of the high prevalence of vitamin D deficiency, conditions such as osteoporosis alongside Australia's aging population have now seen many Australians over 60 suffering this now wide spread condition among the elderly. Osteoporosis can be defined as very fragile and brittle bones, in which serious fractures can occur with just the slightest bump or fall.[9] Osteoporosis Australia have predicted that half of all women and one third of men all men over the age of 60 years will suffer the debilitating effects of osteoporosis.[9]
Osteoporosis also commonly known as the silent disease as in most cases individuals don't know they are affected until they fracture a bone as a result from a fall.[9]
## High risk groups[edit]
### Age[edit]
Several studies conducted in Australia have revealed deficiency ranging from 15-52% amongst the senior populations. These deficiencies have been found to be higher amongst those who are homebound or living within institutions with less access sun exposure.[10] Vitamin D concentration levels below 28 nmol/L are common amongst the studies conducted. Throughout Sydney nursing home studies, it has revealed that 86% of woman and 68% of men are falling into moderate deficiency ranges.[2]
In a study based in Western Australia, 63% of patients admitted with hip fractures were observed to have serum levels less than 50 nmol/L in comparison to the 25% to the controlled.[2]
### Skin colour[edit]
In Australia, vitamin D deficiency has been recognised within particular subgroups such as age, dark skinned and veiled women.[11] There is deficiencies in around 80%, particularly in dark skinned and or veiled populations.[12] The prevalence of vitamin D deficiency amongst dark skinner or who cover their skin for religious reasons can be directly attributed to the extremely low of sun exposure to which is the main source of vitamin D in Australia.
Veiled women or individuals with dark skin pigmentation are easily vulnerable to fall into levels considered deficient in Australia. This is most likely because of the clothing worn acts as a direct barrier as well as absorbing the UVB irradiation.[13] Dark Skin also has high levels of melanin pigmentation which decreases the cutaneous production of vitamin D. African-Americans require six times more UVB dosages to stimulate the production of vitamin D in the skin, compared with those of European descendants.[13]
### Sun exposure[edit]
Despite Australia having a sunlit climate, Australians are remarkably falling short of adequate levels ultraviolet B (UVB) light from the sun. Associated factors contributing to the low vitamin D levels are seasonal variations such as winter, where there is minimal sun exposure, less time spent outdoors and people covering up due to the cold weather.[2] Environmental influences that impact the vitamin D production are the angle of the sun, distance from the equator, latitudes and amount of cloud cover.
To ensure adequate vitamin D levels are reached, an average daily amount, roughly 10% of the sunburn threshold is required on a sensible amount of skin, not just the backs of hands. A burn time for a fair-skinned person could be limited to just 8 minutes in the middle of the day, during summer without sunscreens. A dark skinned or covered individual might need hours to achieve that same desired amount. The strength of the UVB changes throughout the day so time will be change accordingly.[3]
### Obesity[edit]
There is conflicting evidence to suggest whether obesity contributes to vitamin D deficiency. Obese individuals have an increased risk of being vitamin D deficient likely caused by lack of sun exposure from reduced mobility and or low levels of physical activity.[11] The serum levels of obese Australian were 8.3- 9.5 nmol/L lower in both genders comparable to those of healthy weight ranges.[11] During the AusDiab study conducted throughout Australia serum levels within obese people were shown to be 57% lower than with normal weight after receiving the same amount of UV exposure.[11]
Inconsistent to the findings of AusDiab Study, The Australian Bureau of Statistics (ABS) found there to be no correlation between weight levels and vitamin D serum level.[4] According to ABS the Vitamin D supplementation was said to not be a contributing factor as supplement use was similar across all weight ranges.[4]
### Pregnancy[edit]
Pregnancy also poses as another high risk factor for vitamin D deficiency. The status levels of vitamin D during the last stages of pregnancy directly impact the newborns first initial months of life.[10] Babies who are exclusively breastfed with minimal exposure to sunlight or supplementation can be at greater risk of vitamin D deficiency, as human milk often has minimal vitamin D present. Recommendations for infants of the age 0–12 months are set at 5 ug/day, to assist in preventing rickets in young babies.[10] 80% of dark skinned and or veiled women in Melbourne were found to have serum levels lower than 22.5 nmol/L considering them to be within moderate ranges of vitamin D deficiency.[2]
## Contributing factors[edit]
Australia's vitamin D deficiency levels in recent years[when?] have been on the increase, due to factors such as the long-term success of SunSmart government campaigns like Slip, Slop, Slap as well as Cancer Council Australia that have increased the general public's awareness of the risks associated with excessive sun exposure and skin cancers.[3] The 'sun smart' campaign created in 1988 had a significant impact on the public approach and behaviours towards sun exposure.[14] The success of this campaign reduced the sunburn rate by 50%, which researchers believe to have contributed to the rise in vitamin D deficiencies across Australia.[14]
In addition to the reduced sun exposure amongst the Australia populations, there have been decreases in the form of dietary intake as many people are no longer taking fatty fish oil tablets as a method of regulating vitamin D.[3]
Other factors previously mentioned are sun exposure, geographical longitude as well as season change. Greater latitudes receive sunlight that is of lesser ultra radiation strength in contrast to regions close to the equator, who receive lower variation to hours of daylight during the summer periods.[7]
## Government strategies[edit]
### Mandatory fortification[edit]
Vitamin D fortification in table spreads
In light of the increase of vitamin D deficiency throughout Australia the federal government introduced mandatory fortification of vitamins and minerals such as vitamin D in certain foods like edible oil spreads as indicated in the: Australian Standard 2.4.2.[15] It is mandatory for all food manufacturing companies producing table spreads like butter and margarine to have no less than 55 mg/kg of vitamin D, as a response to a growing public health requirements.[15]
In response to recent advances, public policies are being reconsidered to ensure vitamin D is evidently being measured.[2] With the vitamin D deficiency resurfacing the nutrient reference value guidelines were established, in turn creating the dietary vitamin D recommendations.[2]
The dietary vitamin D guidelines are assuming limited exposure to UVB sunlight are:
Infants, Children and Adults < 50 years: 5 μg/day (200 IU/day)
Adults > 50 - < 70 years: 10 μg/day (400 IU/day)
Adults > 70 years: 15 μg/day (600 IU/day)[2]
## Treatment[edit]
Day to day requirements of vitamin D are set around 800-1000IU to maintain healthy levels which in most cases can be provided by sun exposure. Increased amounts are required for individuals who are previously diagnosed as deficient. For those of moderate deficiencies, oral supplementation can be implemented into the diet at levels of 3000-5000 IU per day for a 6- to 12-week period continued by an ongoing reduced dose of 1000- 2000 IU per day to maintain stores in the body.
Severe deficiency is treated through megadose therapy where patients are given doses around 100 000 IU to assist in raising stores faster to ensure physical health in restored to prevent further illness or disease.[16]
## See also[edit]
* Vitamin D deficiency
* Vitamin D
* Sun exposure
## References[edit]
1. ^ a b c d "Australian Health Survey: Biomedical Results for Nutrients, 2011-12" (PDF).
2. ^ a b c d e f g h i Shrapnel, William; Truswell, Stewart (2006-12-01). "Vitamin D deficiency in Australia and New Zealand: What are the dietary options?". Nutrition & Dietetics. 63 (4): 206–212. doi:10.1111/j.1747-0080.2006.00080.x. ISSN 1747-0080.
3. ^ a b c d "Vitamin D". Radio National. Retrieved 2015-09-02.
4. ^ a b c "Australian Health Survey: Biomedical Results for Nutrients,2011-12" (PDF).
5. ^ https://www.nrv.gov.au/nutrients/vitamin-d
6. ^ https://www.abs.gov.au/ausstats/abs@.nsf/Lookup/4364.0.55.006Chapter2002011-12
7. ^ a b Quaggiotto, P; Tran, H; Bhanugopan, M (2014-01-01). "Vitamin D deficiency remains prevalent despite increased laboratory testing in New South Wales, Australia". Singapore Medical Journal. 55 (5): 271–280. doi:10.11622/smedj.2014071. PMC 4291993. PMID 24862752.
8. ^ a b c Holick, M. F. (2006-01-01). "Resurrection of vitamin D deficiency and rickets". Journal of Clinical Investigation. 116 (8): 2062–2072. doi:10.1172/jci29449. PMC 1523417. PMID 16886050.
9. ^ a b c "Calcium, Vitamin D and Osteoporosis" (PDF).
10. ^ a b c "Vitamin D | Nutrient Reference Values". www.nrv.gov.au. 2014-03-17. Retrieved 2015-09-02.
11. ^ a b c d Daly, Robin M.; Gagnon, Claudia; Lu, Zhong X.; Magliano, Dianna J.; Dunstan, David W.; Sikaris, Ken A.; Zimmet, Paul Z.; Ebeling, Peter R.; Shaw, Jonathan E. (2012-07-01). "Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study". Clinical Endocrinology. 77 (1): 26–35. doi:10.1111/j.1365-2265.2011.04320.x. ISSN 1365-2265. PMID 22168576.
12. ^ "VItamin D in Australia" (PDF).
13. ^ a b "Vitamin D deficiency and multicultural Australia". The Medical Journal of Australia. 2001.
14. ^ a b Timms, Brad (2002). ""Slip, Slop, Slap" campaign may need rethink". Oncology. 3 (10): 588. doi:10.1016/S1470-2045(02)00892-6.
15. ^ a b "Vitamins and minerals added to food". www.foodstandards.gov.au. Retrieved 2015-09-03.
16. ^ "Vitamin D deficiency in adults". 2010.
*[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
| Vitamin D deficiency in Australia | None | 1,032 | wikipedia | https://en.wikipedia.org/wiki/Vitamin_D_deficiency_in_Australia | 2021-01-18T18:45:59 | {"wikidata": ["Q22091804"]} |
Skeletal dysplasia with wormian bone-multiple fractures-dentinogenesis imperfecta is a skeletal disorder, reported in three patients to date, characterized clinically by multiple fractures, wormian bones of the skull, dentinogenesis imperfecta and facial dysmorphism (hypertelorism, periorbital fullness). Although the signs are very similar to osteogenesis imperfecta, characteristic cortical defects in the absence of osteopenia and collagen abnormalities are considered to be distinctive. There have been no further descriptions in the literature since 1999.
*[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
| Wormian bone-multiple fractures-dentinogenesis imperfecta-skeletal dysplasia | c1858032 | 1,033 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166277 | 2021-01-23T16:55:49 | {"gard": ["10290"], "mesh": ["C565734"], "omim": ["604922"], "umls": ["C1858032"], "icd-10": ["Q78.8"], "synonyms": ["Suarez-Stickler syndrome"]} |
Cowden syndrome
Other namesCowden's disease, multiple hamartoma syndrome
Cumulative risk for the development of cancer in males and females with Cowden syndrome from birth to age 70.
SpecialtyOncology, Dermatology, Gastroenterology, Neurology
Frequency1 in 200,000 individuals
Cowden syndrome (also known as Cowden's disease and multiple hamartoma syndrome) is an autosomal dominant inherited condition characterized by benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, and other cancers.[1] It is often underdiagnosed due to variability in disease presentation, but 99% of patients report mucocutaneous symptoms by age 20-29.[2] Despite some considering it a primarily dermatologic condition, Cowden's syndrome is a multi-system disorder that also includes neurodevelopmental disorders such as macrocephaly.[3]
The incidence of Cowden's disease is about 1 in 200,000, making it quite rare.[4] Furthermore, early and continuous screening is essential in the management of this disorder to prevent malignancies.[4] It is associated with mutations in PTEN on 10q23.3, a tumor suppressor gene otherwise known as phosphatase and tensin homolog, that results in dysregulation of the mTOR pathway leading to errors in cell proliferation, cell cycling, and apoptosis.[5] The most common malignancies associated with the syndrome are adenocarcinoma of the breast (20%), followed by adenocarcinoma of the thyroid (7%), squamous cell carcinomas of the skin (4%), and the remaining from the colon, uterus, or others (1%).[6]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Screening
* 5 Treatment
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Signs and symptoms[edit]
See also: List of cutaneous neoplasms associated with systemic syndromes
Cowden's disease displaying typical trichilemmomas on the bilateral dorsal hands
As Cowden's disease is a multi-system disorder, the physical manifestations are broken down by organ system:
Skin
Adolescent patients affected with Cowden syndrome develop characteristic lesions called trichilemmomas, which typically develop on the face, and verrucous papules around the mouth and on the ears.[7] Oral papillomas are also common.[7] Furthermore, shiny palmar keratoses with central dells are also present.[7] At birth or in childhood, classic features of Cowden's include pigmented genital lesions, lipomas, epidermal nevi, and cafe-au-lait spots.[7] Squamous cell carcinomas of the skin may also occur.[6]
Thyroid
Two thirds of patients suffer from thyroid disorders, and these typically include benign follicular adenomas or multinodular goiter of the thyroid.[8] Additionally, Cowden's patients are more susceptible to developing thyroid cancer than the general population.[9] It is estimated that less than 10 percent of individuals with Cowden syndrome may develop follicular thyroid cancer.[8] Cases of papillary thyroid cancer have been reported as well.[3]
Female and Male Genitourinary
Females have an elevated risk of developing endometrial cancers, which is highest for those under the age of 50.[3] Currently, it is not clear whether uterine leiomyomata (fibroids) or congenital genitourinary abnormalities occur at an increased rate in Cowden syndrome patients as compared to the general population.[3] The occurrence of multiple testicular lipomas, or testicular lipomatosis, is a characteristic finding in male patients with Cowden syndrome.[3]
Gastrointestinal
Polyps are extremely common as they are found in about 95% of Cowden syndrome patients undergoing a colonoscopy.[3] They are numerous ranging from a few to hundreds, usually of the hamartomatous subtype, and distributed across the colon as well as other areas within the gastrointestinal tract.[3][10] Other types of polyps that may be encountered less frequently include ganglioneuromatous, adenomatous, and lymphoid polyps.[10] Diffuse glycogenic acanthosis of the esophagus is another gastrointestinal manifestation associated with Cowden syndrome.[3]
Breast
Females are at an increased risk of developing breast cancer, which is the most common malignancy observed in Cowden's patients.[3] Although some cases have been reported, there is not enough evidence to indicate an association between Cowden syndrome and the development of male breast cancer.[3] Up to 75% demonstrate benign breast conditions such as intraductal papillomatosis, fibroadenomas, and fibrocystic changes.[3] However, there is currently not enough evidence to determine if benign breast disease occurs more frequently in Cowden's patients as compared to individuals without a hereditary cancer syndrome.[3]
Central Nervous System
Macrocephaly is observed in 84% of patients with Cowden syndrome.[11] It typically occurs due to an abnormally enlarged brain, or megalencepahly.[12] Patients may also exhibit dolichocephaly.[12] Varying degrees of autism spectrum disorder and intellectual disability have been reported as well.[11] Lhermitte-Duclos disease is a benign cerebellar tumor that typically does not manifest until adulthood in patients with Cowden syndrome.[13]
## Genetics[edit]
Cowden syndrome is inherited in an autosomal dominant fashion.[14] Germline mutations in PTEN (phosphatase and tensin homolog), a tumor suppressor gene, are found in up to 80% of Cowden's patients.[10] Several other hereditary cancer syndromes, such as Bannayan-Riley-Ruvalcaba syndrome, have been associated with mutations in the PTEN gene as well.[15] PTEN negatively regulates the cytoplasmic receptor tyrosine kinase pathway, which is responsible for cell growth and survival, and also functions to repair errors in DNA.[14][10] Thus, in the absence of this protein, cancerous cells are more likely to develop, survive, and proliferate.[10]
Recently, it was discovered that germline heterozygous mutations in SEC23B, a component of coat protein complex II vesicles secreted from the endoplasmic reticulum, are associated with Cowden syndrome.[16] A possible interplay between PTEN and SEC23B has recently been suggested, given emerging evidence of each having a role in ribosome biogenesis, but this has not been conclusively determined.[17]
## Diagnosis[edit]
The revised clinical criteria for the diagnosis of Cowden's syndrome for an individual is dependent on either one of the following: 1.) 3 major criteria are met or more that must include macrocephaly, Lhermitte-Duclos, or GI hamartomas 2.) two major and three minor criteria.[3] The major and minor criteria are listed below:
Cowden Syndrome Diagnostic Criteria (Suggested by Pilarski et al)[3] Major criteria
Breast cancer
Endometrial cancer (epithelial)
Thyroid cancer (follicular)
Gastrointestinal hamartomas (including ganglioneuromas, but excluding hyperplastic polyps; ≥3)
Lhermitte-Duclos disease (adult)
Macrocephaly (≥97 percentile: 58 cm for females, 60 cm for males)
Macular pigmentation of the glans penis
Multiple mucocutaneous lesions (any of the following):
Multiple trichilemmomas (≥3, at least one biopsy proven)
Acral keratoses (≥3 palmoplantar keratotic pits and/or acral hyperkeratotic papules)
Mucocutaneous neuromas (≥3)
Oral papillomas (particularly on tongue and gingiva), multiple (≥3) OR biopsy proven OR dermatologist diagnosed
Minor criteria
Autism spectrum disorder
Colon cancer
Esophageal glycogenic acanthosis (≥3)
Lipomas (≥ 3)
Mental retardation (ie, IQ ≤ 75)
Renal cell carcinoma
Testicular lipomatosis
Thyroid cancer (papillary or follicular variant of papillary)
Thyroid structural lesions (eg, adenoma, multinodular goiter)
Vascular anomalies (including multiple intracranial developmental venous anomalies)
## Screening[edit]
The management of Cowden syndrome centers on the early detection and prevention of cancer types that are known to occur as part of this syndrome.[1] Specific screening guidelines for Cowden syndrome patients have been published by the National Comprehensive Cancer Network (NCCN).[11] Surveillance focuses on the early detection of breast, endometrial, thyroid, colorectal, renal, and skin cancer.[11] See below for a complete list of recommendations from the NCCN:
Screening guidelines for patients with Cowden syndrome (adapted from the NCCN)[11] Women Men and Women
Breast awareness starting at age 18 years of age Annual comprehensive physical exam starting at 18 years of age or 5 years before the youngest age of diagnosis of a component cancer in the family (whichever comes first), with particular attention to breast and thyroid exam
Clinical breast exam, every 6–12 month, starting at age 25 y or 5–10 y before the earliest known breast cancer in the family Annual thyroid starting at age 18 y or 5-10 y before the earliest known thyroid cancer in the family, whichever is earlier
Annual mammography and breast MRI screening starting at age 30–35 y or individualized based on earliest age of onset in family Colonoscopy, starting at age 35 y, then every 5 y or more frequently if patient is symptomatic or polyps found
For endometrial cancer screening, encourage patient education and prompt response to symptoms and participation in a clinical trial to determine the effectiveness or necessity of screening modalities Consider renal ultrasound starting at age 40 y, then every 1-2 y
Discuss risk-reducing mastectomy and hysterectomy and counsel regarding degree of protection, extent of cancer risk and reconstruction options Dermatological management may be indicated for some patients
Address psychosocial, social, and quality-of-life aspects of undergoing risk-reducing mastectomy and/or hysterectomy Consider psychomotor assessment in children at diagnosis and brain MRI if there are symptoms
Education regarding the signs and symptoms of cancer
## Treatment[edit]
Malignancies that occur in Cowden syndrome are usually treated in the same fashion as those that occur sporadically in patients without a hereditary cancer syndrome.[12] Two notable exceptions are breast and thyroid cancer.[12] In Cowden syndrome patients with a first-time diagnosis of breast cancer, treatment with mastectomy of the involved breast as well as prophylactic mastectomy of the uninvolved contralateral breast should be considered.[1] In the setting of thyroid cancer or a follicular adenoma, a total thyroidectomy is recommended even in cases where it appears that only one lobe of the thyroid is affected.[12] This is due to the high likelihood of recurrence as well as the difficulty in distinguishing a benign from malignant growth with a hemithyroidectomy alone.[12]
The benign mucocutaneous lesions observed in Cowden syndrome are typically not treated unless they become symptomatic or disfiguring.[12] If this occurs, numerous treatment options, including topical agents, cryosurgery, curettage, laser ablation, and excision, may be utilized.[12]
## See also[edit]
* List of cutaneous neoplasms associated with systemic syndromes
## References[edit]
1. ^ a b c Mester J, Eng C (January 2015). "Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome". Journal of Surgical Oncology. 111 (1): 125–30. doi:10.1002/jso.23735. PMID 25132236.
2. ^ Gosein MA, Narinesingh D, Nixon CA, Goli SR, Maharaj P, Sinanan A (August 2016). "Multi-organ benign and malignant tumors: recognizing Cowden syndrome: a case report and review of the literature". BMC Research Notes. 9: 388. doi:10.1186/s13104-016-2195-z. PMC 4973052. PMID 27488391.
3. ^ a b c d e f g h i j k l m n Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E (November 2013). "Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria". Journal of the National Cancer Institute. 105 (21): 1607–16. doi:10.1093/jnci/djt277. PMID 24136893.
4. ^ a b Habif TP (2016). Clinical dermatology : a color guide to diagnosis and therapy (Sixth ed.). [St. Louis, Mo.] ISBN 978-0-323-26183-8. OCLC 911266496.
5. ^ Porto AC, Roider E, Ruzicka T (2013). "Cowden Syndrome: report of a case and brief review of literature". Anais Brasileiros de Dermatologia. 88 (6 Suppl 1): 52–5. doi:10.1590/abd1806-4841.20132578. PMC 3876002. PMID 24346879.
6. ^ a b Callen JP. Dermatological signs of systemic disease (Fifth ed.). Edinburgh. ISBN 978-0-323-35829-3. OCLC 947111367.
7. ^ a b c d Bolognia J, Schaffer JV, Duncan KO, Ko CJ (2014). Dermatology essentials. Oxford. ISBN 9781455708413. OCLC 877821912.
8. ^ a b Kasper D, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J (2015-04-08). Harrison's Principles of Internal Medicine 19/E (Vol.1 & Vol.2) (19th ed.). McGraw Hill. p. 2344. ISBN 978-0-07-180215-4.
9. ^ Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, Abeloff MD. Abeloff's clinical oncology (Fifth ed.). Philadelphia, PA. ISBN 9781455728657. OCLC 857585932.
10. ^ a b c d e Ma, Huiying; Brosens, Lodewijk A. A.; Offerhaus, G. Johan A.; Giardiello, Francis M.; de Leng, Wendy W. J.; Montgomery, Elizabeth A. (January 2018). "Pathology and genetics of hereditary colorectal cancer". Pathology. 50 (1): 49–59. doi:10.1016/j.pathol.2017.09.004. ISSN 1465-3931. PMID 29169633.
11. ^ a b c d e Jelsig AM, Qvist N, Brusgaard K, Nielsen CB, Hansen TP, Ousager LB (July 2014). "Hamartomatous polyposis syndromes: a review". Orphanet Journal of Rare Diseases. 9: 101. doi:10.1186/1750-1172-9-101. PMC 4112971. PMID 25022750.
12. ^ a b c d e f g h Gustafson S, Zbuk KM, Scacheri C, Eng C (October 2007). "Cowden syndrome". Seminars in Oncology. 34 (5): 428–34. doi:10.1053/j.seminoncol.2007.07.009. PMID 17920899.
13. ^ Pilarski R (February 2009). "Cowden syndrome: a critical review of the clinical literature". Journal of Genetic Counseling. 18 (1): 13–27. doi:10.1007/s10897-008-9187-7. PMID 18972196.
14. ^ a b Kumar V, Abbas AK, Aster JC, Perkins JA (2014). Robbins and Cotran pathologic basis of disease (Ninth ed.). Philadelphia, PA. ISBN 9781455726134. OCLC 879416939.
15. ^ Turnpenny, Peter D.; Ellard, Sian (2012). Emery's elements of medical genetics (14th ed.). Philadelphia, PA: Elsevier/Churchill Livingstone. ISBN 9780702040436. OCLC 759158627.
16. ^ Yehia, Lamis; Niazi, Farshad; Ni, Ying; Ngeow, Joanne; Sankunny, Madhav; Liu, Zhigang; Wei, Wei; Mester, Jessica; Keri, Ruth; Zhang, Bin; Eng, Charis (5 November 2015). "Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer". Am J Hum Genet. 97 (5): 661–676. doi:10.1016/j.ajhg.2015.10.001. PMC 4667132. PMID 26522472.
17. ^ Yehia, Lamis; Jindal, Supriya; Komar, Anton; Eng, Charis (15 September 2018). "Non-canonical role of cancer-associated mutant SEC23B in the ribosome biogenesis pathway". Hum Mol Genet. 27 (18): 3154–3164. doi:10.1093/hmg/ddy226. PMC 6121187. PMID 29893852.
## Further reading[edit]
* de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WT, Oosterwijk JC, Kleibeuker JH, Schaapveld M, de Vries EG (April 2002). "Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility". Journal of Medical Genetics. 39 (4): 225–42. doi:10.1136/jmg.39.4.225. PMC 1735082. PMID 11950848.
* Eng C (November 2000). "Will the real Cowden syndrome please stand up: revised diagnostic criteria". Journal of Medical Genetics. 37 (11): 828–30. doi:10.1136/jmg.37.11.828. PMC 1734465. PMID 11073535.
* Kelly P (October 2003). "Hereditary breast cancer considering Cowden syndrome: a case study". Cancer Nursing. 26 (5): 370–5. doi:10.1097/00002820-200310000-00005. PMID 14710798.
* Pilarski R, Eng C (May 2004). "Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome". Journal of Medical Genetics. 41 (5): 323–6. doi:10.1136/jmg.2004.018036. PMC 1735782. PMID 15121767.
* Waite KA, Eng C (April 2002). "Protean PTEN: form and function". American Journal of Human Genetics. 70 (4): 829–44. doi:10.1086/340026. PMC 379112. PMID 11875759.
* Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg LA, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C (August 2003). "Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway". American Journal of Human Genetics. 73 (2): 404–11. doi:10.1086/377109. PMC 1180378. PMID 12844284.
## External links[edit]
Classification
D
* ICD-10: Q85.8
* ICD-9-CM: 759.6
* OMIM: 158350 612359 615106 615107 615108 615109 616858
* MeSH: D006223
* DiseasesDB: 31336
External resources
* eMedicine: derm/86
* Orphanet: 201
Wikimedia Commons has media related to Cowden syndrome.
* GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS)
* v
* t
* e
Phakomatosis
Angiomatosis
* Sturge–Weber syndrome
* Von Hippel–Lindau disease
Hamartoma
* Tuberous sclerosis
* Hypothalamic hamartoma (Pallister–Hall syndrome)
* Multiple hamartoma syndrome
* Proteus syndrome
* Cowden syndrome
* Bannayan–Riley–Ruvalcaba syndrome
* Lhermitte–Duclos disease
Neurofibromatosis
* Type I
* Type II
Other
* Abdallat–Davis–Farrage syndrome
* Ataxia telangiectasia
* Incontinentia pigmenti
* Peutz–Jeghers syndrome
* Encephalocraniocutaneous lipomatosis
* 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
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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
| Cowden syndrome | c0018553 | 1,034 | wikipedia | https://en.wikipedia.org/wiki/Cowden_syndrome | 2021-01-18T18:47:42 | {"gard": ["6202"], "mesh": ["D006223"], "umls": ["C0018553", "C0391826"], "orphanet": ["201"], "wikidata": ["Q1138188"]} |
Intellectual disability, Buenos-Aires type is a rare intellectual disability syndrome characterized by growth retardation, microcephaly, characteristic facial features (including narrow forehead, bushy eyebrows, hypertelorism, small, downward-slanting palpebral fissures with blepharoptosis, malformed and low-set ears, broad straight nose, thin upper lip, and a wide, tented mouth), developmental delay, intellectual disability, speech disorder, and multiple organ malformations (e.g. ventricular septal defect, megaloureter, dilated renal pelvis). Additional manifestations reported include neurocutaneous lesions (including palmoplantar hyperkeratosis), internal hydrocephalus, and bilateral partial soft-tissue syndactyly of second and third toe.
*[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
| Intellectual disability, Buenos-Aires type | c0796080 | 1,035 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3079 | 2021-01-23T17:41:38 | {"gard": ["3485"], "mesh": ["C563095"], "omim": ["249630"], "umls": ["C0796080"], "icd-10": ["Q87.8"], "synonyms": ["Mutchinick syndrome"]} |
A special form of intestinal atresia with absence of mesentery, which is most likely due to an intrauterine intestinal vascular accident. Newborns are usually preterm infants with low birth-weights, that encounter feeding difficulties (including vomiting with initial feeds, which may later worsened and the abdomen becomes progressively distended) as well as failure to thrive. Affected children present disrupted bowel loops assuming a spiral configuration resembling an 'apple peel' and may have less than half of the normal length of the small bowel and a physiologically short bowel. This disorder is characterized by jejunal atresia near the ligament of Treitz, foreshortened bowel, and a large mesenteric gap. The bowel distal to the atresia is precariously supplied. It may be a manifestation of cystic fibrosis and the most important cause of mortality is short bowel syndrome, encountered in 65% of cases.
*[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
| Atresia of small intestine | c0266175 | 1,036 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1201 | 2021-01-23T18:29:24 | {"gard": ["140"], "mesh": ["C538260", "D007409"], "omim": ["243600"], "umls": ["C0021828", "C0266172", "C0266175"], "icd-10": ["Q41.0", "Q41.1", "Q41.2", "Q41.8", "Q41.9"], "synonyms": ["Apple peel syndrome", "Intestinal atresia type IIIb", "Jejunal atresia", "Jejunoileal atresia", "Small intestinal atresia"]} |
For a general phenotypic description and a discussion of genetic heterogeneity of preeclampsia, see PEE1 (189800).
Mapping
Hypothesizing that the genetic background of preeclampsia might show reduced heterogeneity in a founder population such as that of the Kainuu province in central eastern Finland, Laivuori et al. (2003) performed a genomewide scan in 15 multiplex families in that area. They found 2 loci that exceeded the threshold for significant linkage: 2p25 (PEE2), at 21.70 cM, and 9p13 (PEE3; 609403), at 38.90 cM. They concluded that the susceptibility locus on 2p25 was clearly different from the locus (PEE1) at 2p13 found in the Icelandic study of Arngrimsson et al. (1999).
*[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
| PREECLAMPSIA/ECLAMPSIA 2 | c0032914 | 1,037 | omim | https://www.omim.org/entry/609402 | 2019-09-22T16:06:09 | {"doid": ["10591"], "mesh": ["D011225"], "omim": ["609402"], "orphanet": ["275555"]} |
A rare ciliopathy characterized by congenital or childhood onset sensorineural hearing loss (HL) and retinitis pigmentosa (RP) that occurs in a second step with a night blindness and a progressive vision loss and, in some cases, vestibular dysfunction.
## Epidemiology
Prevalence of Usher syndrome (US) is estimated at 1/30,000. It is by far the most common cause of hereditary, combined deafness-blindness.
## Clinical description
Sensorineural hearing loss is typically congenital and three clinical entities have been defined according to severity of hearing loss severity. Type 1 (around 40% of cases) is characterized by profound, nonprogressive congenital deafness, typically associated with vestibular areflexia that leads to delayed acquisitions (delayed head control, unassisted sitting and walking). Type 2 (around 60% of cases) is characterized by moderate or severe, congenital hearing loss that is slowly progressive and not associated with vestibular disorders. Type 3 (< 3% of cases, but more frequent in the Finnish and Ashkenazi Jewish populations) is characterized by rapidly progressive hearing loss that is often diagnosed during the first decade; vestibular disorders are associated with half of the cases. Retinitis pigmentosa appears later, mainly in the second or third decades, with characteristic night vision and progressive peripheral visual field impairment. Night blindness can be noted in early childhood. The only reported retinal phenotype is rod cone dystrophy. A central visual impairment can be caused by a macular edema. A cataract is frequently observed before the age of 50 years.
## Etiology
So far, mutations in five genes (MYO7A, USH1C, CDH23, PCDH15, USH1G) have been implicated in USH type 1. Mutations in three genes (USH2A, ADGRV1 and WHRN) have been implicated in USH type 2. Mutations in a predominant gene (CLRN1) have been identified for USH type 3. Some genes are called into question: CIB2 and PDZD7 seem eventually to be involved in non syndromic HL.
## Diagnostic methods
Clinical diagnosis is based on findings of a bilateral sensorineural hearing loss associated with a retinitis pigmentosa defined by a night blindness and a peripheral visual field impairment. Multimodal imaging with color, fundus autofluorescence frames (FAF), spectral domain-optical coherence tomography and full-field electroretinogram are required to confirm the diagnosis of rod cone dystrophy. Genetic testing is feasible now based on massively parallel sequencing (gene panels or exomes).
## Differential diagnosis
Differential diagnoses include oculo-acoustic syndromes associated with peroxysomal gene alterations (Heimler syndrome with enamel dysplasia), metabolic genetic inherited diseases (Refsum disease), moderate forms of Alstrom syndrome, or mitochondrial DNA mutations (MIDD, Kearns-Sayre syndrome). Mutations in TUBB4B gene can cause a dominant inherited oculo-acoustic phenotype, Leber congenital amaurosis and early-onset HL. In some patients, HL can coexist independently of RP.
## Antenatal diagnosis
Prenatal diagnosis is feasible for families in which the disease-causing mutations have already been identified.
## Genetic counseling
Transmission is autosomal recessive. Genetic counseling is straightforward but patients should be informed that heterozygous USH2A mutations are relatively frequent in the general population.
## Management and treatment
Management requires a multidisciplinary team with experience in the management of combined deafness and blindness (ENT specialist, ophthalmologist, speech therapist, psychologist, hearing aid specialist, occupational therapist, and all professionals implicated in adapted learning programs for patients with both hearing and visual deficits). Conventional hearing aids may be indicated for patients wit h moderate or severe hearing loss. Cochlear implants, (in most cases bilateral), are now more frequently used for patients with profound congenital hearing loss. Both cochlear implants and hearing aids are more effective when implemented early. Lenses with specialized filters may be recommended for the management of the rod cone dystrophy. A specific treatment with anhydrase carbonic inhibitor can be indicated in case of macular edema. Cataract surgery can be required. Current research is directed towards gene therapy, antisense oligonucleotide therapy (USH2A), neuroprotection and artificial vision systems.
## Prognosis
The prognosis mainly depends on the progression of rod cone dystrophy: a severe visual impairment occurs between 50 and 70 years of age in most cases.
*[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
| Usher syndrome | c0271097 | 1,038 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=886 | 2021-01-23T17:38:00 | {"gard": ["7843"], "mesh": ["D052245"], "omim": ["276900", "276901", "276902", "276904", "500004", "601067", "602083", "602097", "605472", "606943", "611383", "612632", "614504", "614869", "614990"], "umls": ["C0271097"], "icd-10": ["H35.5"], "synonyms": ["Retinitis pigmentosa-deafness syndrome", "Retinitis pigmentosa-hearing loss syndrome", "USH"]} |
Nipple adenoma
Micrograph of a nipple adenoma. H&E stain.
SpecialtyOncology
A nipple adenoma is a rare benign tumour of the breast.
The condition may also be known as :
* Florid papillomatosis of the nipple
* Florid adenomatosis
* Subareolar duct papillomatosis
* Erosive adenomatosis[1]
## Contents
* 1 Signs and symptoms
* 2 Diagnosis
* 2.1 Definition
* 2.2 Differential diagnosis
* 2.3 Imaging
* 2.4 Biopsy
* 3 Treatment
* 4 Prognosis
* 5 Epidemiology
* 6 References
* 7 External links
## Signs and symptoms[edit]
Nipple adenomas may be felt as a lump under the nipple or areola. They may come to attention because of nipple pain, ulceration, swelling or discharge.[1]
## Diagnosis[edit]
### Definition[edit]
A nipple adenoma is a type of intraductal papilloma that arises within the lactiferous ducts that are located within the nipple.[2]
### Differential diagnosis[edit]
The microscopic appearance of a nipple adenoma can be mistaken for carcinoma.[1] Other conditions that have similar symptoms and signs as nipple adenoma include Paget's disease of the breast, other intraductal papillomas, ductal carcinoma in situ (DCIS), syringomatous adenoma of the nipple and subareolar sclerosing duct hyperplasia.[1]
### Imaging[edit]
Lesions of the nipple and areola, such as nipple adenoma, may be difficult to image clearly on routine mammogram or ultrasonography. Nipple adenomas can be imaged using magnetic resonance imaging (MRI) and conventional or MR ductogram.[3]
### Biopsy[edit]
Once excised, the macroscopic appearance of nipple adenomas is of a poorly defined nodular mass. The microscopic appearance can be quite bizarre, and may be misinterpreted as a carcinoma. Nipple adenomas usually have a rounded outline at low magnification, and at higher magnification can be seen to consist of a haphazardly arranged mass of proliferating tubular structures composed of epithelial and myoepithelial cells within varying amounts of fibrous stroma. The epithelial cells are usually columnar, but the columnar epithelial cells can undergo apocrine or squamous metaplasia. Mitotic figures and necrosis are not commonly seen.[1]
## Treatment[edit]
The appropriate treatment in contemporary western medicine is complete surgical excision of the abnormal growth with a small amount of normal surrounding breast tissue.[1]
## Prognosis[edit]
Nipple adenomas are non-cancerous growths, which can recur if not completely surgically removed.[1] There are reported cases of cancers arising within nipple adenomas, and following excision of nipple adenomas, but these are rare occurrences.[4]
## Epidemiology[edit]
Nipple adenomas most commonly occur in 30- to 40-year-old women,[1] but can also occur in men.[5] They can also occur at any age, including in the elderly, in adolescence,[6] and in infants.[7]
## References[edit]
1. ^ a b c d e f g h Stoler, Mark A.; Mills, Stacey E.; Carter, Darryl; Joel K Greenson; Reuter, Victor E. (2009). Sternberg's Diagnostic Surgical Pathology. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7942-1.
2. ^ Pfeifer, John D.; Humphrey, Peter A.; Dehner, Louis P. (2008). The Washington Manual of surgical pathology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 0-7817-6527-7.
3. ^ Sarica O, Zeybek E, Ozturk E (July 2010). "Evaluation of nipple-areola complex with ultrasonography and magnetic resonance imaging". J Comput Assist Tomogr. 34 (4): 575–86. doi:10.1097/RCT.0b013e3181d74a88. PMID 20657228.
4. ^ Rao P, Shousha S (2010). "Male nipple adenoma with DCIS followed 9 years later by invasive carcinoma". Breast J. 16 (3): 317–8. doi:10.1111/j.1524-4741.2010.00900.x. PMID 20408826.
5. ^ Tuveri M, Calò PG, Mocci C, Nicolosi A (September 2010). "Florid papillomatosis of the male nipple". Am. J. Surg. 200 (3): e39–40. doi:10.1016/j.amjsurg.2009.10.026. PMID 20409515.
6. ^ Tao W, Kai F, Yue Hua L (2010). "Nipple adenoma in an adolescent". Pediatr Dermatol. 27 (4): 399–401. doi:10.1111/j.1525-1470.2010.01176.x. PMID 20653865.
7. ^ Clune JE, Kozakewich HP, VanBeek CA, Labow BI, Greene AK (November 2009). "Nipple adenoma in infancy". J. Pediatr. Surg. 44 (11): 2219–22. doi:10.1016/j.jpedsurg.2009.08.020. PMID 19944237.
## External links[edit]
Classification
D
* ICD-10: D24
* ICD-9-CM: 217
* ICD-O: M8506/0
* v
* t
* e
Breast cancer
Types
Ductal
* Ductal carcinoma in situ (DCIS): Paget's disease of the breast
* Comedocarcinoma
* Invasive ductal carcinoma (IDC)
* Intraductal papilloma
Lobular
* Lobular carcinoma in situ (LCIS)
* Invasive lobular carcinoma (ILC)
Fibroepithelial/stromal
* Fibroadenoma
* Phyllodes tumor
Other
* Medullary carcinoma
* Male breast cancer
* Inflammatory breast cancer
* Precursor lesions
* Atypical ductal hyperplasia
* Nipple adenoma
General
* Breast cancer
* Classification
* Risk factors
* Alcohol
* Hereditary breast—ovarian cancer syndrome
* BRCA mutation
* Screening
* Treatment
Other
* Breast cancer awareness
* Pink ribbon
* National Breast Cancer Awareness Month
* List of people with breast cancer
* 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]: 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
| Nipple adenoma | c0334378 | 1,039 | wikipedia | https://en.wikipedia.org/wiki/Nipple_adenoma | 2021-01-18T18:29:20 | {"umls": ["C0334378"], "icd-9": ["217"], "icd-10": ["D24"], "wikidata": ["Q7039586"]} |
Foot rot, or infectious pododermatitis, is a hoof infection commonly found in sheep, goats, and cattle. As the name suggests, it rots away the foot of the animal, more specifically the area between the two toes of the affected animal. It is extremely painful and contagious. It can be treated with a series of medications, but if not treated, the whole herd can become infected. The cause of the infection in cattle is two species of anaerobic bacteria, Fusobacterium necrophorum and Bacteroides melaninogenicus.[1] Both bacteria are common to the environment in which cattle live, and Fusobacterium is present in the rumen and fecal matter of the cattle. In sheep, F. necrophorum first invades the interdigital skin following damage to the skin, and causes interdigital lesions and slight inflammation. The second stage of the disease is marked by the invasion of the foot by the foot rot bacterium Dichelobacter nodosus, a Gram-negative anaerobe. Usually, an injury to the skin between the hooves allows the bacteria to infect the animal. Another cause of foot rot may be high temperatures or humidity, causing the skin between the hooves to crack and let the bacteria infect the foot. This is one of the reasons foot rot is such a major problem in the summer. Foot rot is easily identifiable by its appearance and foul odor. Treatment is usually with an antibiotic medication, and preventing injury to the feet is the best way to prevent foot rot.
The disease is different in cattle and sheep and cross-infection is not thought to occur.[2]
## Contents
* 1 Signs of infection
* 2 See also
* 3 References
* 4 Further reading
* 5 External links
## Signs of infection[edit]
The first sign of a foot-rot infection is when the skin between the claws of the hoof begins to swell (cellulitis). Swelling usually appears 24 hours after infection. The skin between the toes may be very red and tender and the toes may separate because of all the swelling. This is very painful to the animal and can cause lameness. The animal may also have a raised body temperature. A crack can develop along the infected part and is yellow in color. The foot will have a foul odor. Tendons and joints in the area can become infected, which is much harder to treat. A condition known as "super foot rot" is seen in some animals. Super foot rot infection occurs much faster and is usually much more severe. Most normal foot rot treatments will not cure this foot rot and a veterinarian should be contacted immediately.
Vaccines have been developed, but their efficacy is questionable and the immunity they provide is of short duration.[2]
## See also[edit]
* Trench foot
* Thrush (horse)
## References[edit]
1. ^ "Foot Rot & Hoof Rot in Sheep". RaisingSheep.net. Retrieved 4 July 2015.
2. ^ a b Footrot - Cattle reviewed and published by WikiVet, accessed 11 October 2011.
## Further reading[edit]
* W.G. Kvasnica, DVM, Ben Bruce, Ph.D., Ron Torell, MS. Foot Rot of Cattle
## External links[edit]
* Image of a foot with foot rot
* Foot rot information
* [1]
* Information on foot rot in sheep
* Foot rot in Estonian
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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
| Foot rot | c0016513 | 1,040 | wikipedia | https://en.wikipedia.org/wiki/Foot_rot | 2021-01-18T18:50:49 | {"mesh": ["D005535"], "wikidata": ["Q1942000"]} |
Tyrosinemia type 2 is a genetic disorder in which individuals have elevated blood levels of the amino acid tyrosine, a building block of most proteins. This condition can affect the eyes, skin, and intellectual development. Symptoms of tyrosinemia type 2 often begin in early childhood and include excessive tearing, abnormal sensitivity to light (photophobia), eye pain and redness, and painful skin lesions on the palms and soles (palmoplantar hyperkeratosis). About 50 percent of individuals with this condition have an intellectual disability. Tyrosinemia type 2 is caused by a deficiency of the enzyme tyrosine aminotransferase, one of the enzymes required for the multi-step process that breaks down tyrosine. This enzyme shortage is caused by mutations in the TAT gene. This condition is inherited in an autosomal recessive manner. There is no cure for this condition; however, some of the symptoms may be managed with a diet that limits certain amino acids, such as phenylalanine and tyrosine. A medication called NTBC may also be used to help control the amount of tyrosine in the body.
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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
| Tyrosinemia type 2 | c0268487 | 1,041 | gard | https://rarediseases.info.nih.gov/diseases/3105/tyrosinemia-type-2 | 2021-01-18T17:57:15 | {"mesh": ["D020176"], "omim": ["276600"], "umls": ["C0268487"], "orphanet": ["28378"], "synonyms": ["Tyrosinemia type II", "Richner Hanhart syndrome", "TAT deficiency", "Tyrosine transaminase deficiency", "Keratosis palmoplantaris with corneal dystrophy", "Oregon type tyrosinemia", "Tyrosinosis oculocutaneous type", "Tyrosine aminotransferase deficiency", "Oculocutaneous tyrosinemia"]} |
In a brother and sister and a paternal first cousin of theirs, Bryan and Coskey (1967) described an asymptomatic, papular and plaquelike erythema appearing in infancy and involving the external ears and limbs. In the sibship of the affected sibs, 4 had clubfoot and dental anomalies.
Limbs \- Clubfoot Teeth \- Dental anomalies Inheritance \- Autosomal recessive Skin \- Infantile papular plaquelike erythema of external ears and limbs ▲ 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
| ERYTHEMA OF ACRAL REGIONS | c1856900 | 1,042 | omim | https://www.omim.org/entry/227000 | 2019-09-22T16:28:07 | {"omim": ["227000"]} |
Temple-Baraitser syndrome is a rare developmental anomalies syndrome characterized by severe intellectual disability and distal hypoplasia of digits, particularly of thumbs and halluces, with nail aplasia or hypoplasia. Facial dysmorphism with a pseudo-myopathic appearance has been reported, which may include high anterior hairline or low frontal hairline with central cowlick, flat forehead, ptosis, hypertelorism, downslanting palpebral fissures, epicanthal folds, ears with thick helices, broad depressed nasal bridge with anteverted nares, short columella, long philtrum, high-arched palate, broad mouth with thick vermilion border of the upper or the lower lip and downturned corners. Marked hypotonia, seizures and global developmental delay have been reported, associated with autistic spectrum disorder manifestations in some patients.
*[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
| Temple-Baraitser syndrome | c2678486 | 1,043 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=420561 | 2021-01-23T17:46:41 | {"mesh": ["C567516"], "omim": ["611816"], "umls": ["C2678486"], "icd-10": ["Q87.2"], "synonyms": ["Severe intellectual disability-aplasia/hypoplasia of thumb and hallux syndrome", "TMBTS"]} |
Gibberd and Gavrilescu (1966) described a family in which 4 persons in 3 generations had a progressive hypertrophic polyneuritis associated with an abnormal protein in serum, cerebrospinal fluid and urine. Motor and sensory changes began at about age 50 years. Nerve conduction velocity was delayed. Sural nerve on biopsy showed marked demyelination with Schwann cell proliferation. The total spinal fluid protein was only slightly increased.
Misc \- Onset about age 50 Neuro \- Progressive hypertrophic polyneuritis Lab \- Paraprotein in serum, CSF, and urine \- Nerve demyelination with Schwann cell proliferation \- Delayed nerve conduction velocity Inheritance \- Autosomal dominant ▲ 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
| NEUROPATHY, WITH PARAPROTEIN IN SERUM, CEREBROSPINAL FLUID AND URINE | c1834180 | 1,044 | omim | https://www.omim.org/entry/162600 | 2019-09-22T16:37:25 | {"mesh": ["C563516"], "omim": ["162600"]} |
Juberg and Hayward (1969) described a syndrome with oral, cranial and digital manifestations in 5 of 6 children of normal, unrelated parents. Two brothers had cleft lip and palate, microcephaly, hypoplasia and distal placement of the thumbs, and elbow deformities limiting extension. One of the brothers had toe anomalies, as did 3 of the 4 sisters. Among the sisters microcephaly, stiff thumbs and forme fruste cleft lip were observed. Kingston et al. (1982) described a single case. In addition to unilateral cleft lip and palate, the 17-year-old boy had bilateral absent thumbs, anomalous carpal bones, deformity of the radial heads, and short stature (143.3 cm). He was found to have growth hormone deficiency. The sella turcica was normal by x-ray. Nevin et al. (1981) reported a case in a female who had absence of the pituitary fossa but no evident endocrine dysfunction to account for short stature. Verloes et al. (1992) described 3 nonfamilial cases of orocraniodigital syndrome. The main features were cleft lip/palate, hypertelorism, bowed and upward slanting eyebrows, thumb hypo/aplasia or proximal/distal thumb displacement, luxation of the radial head, elbow restriction, minor vertebral and rib anomalies and horseshoe kidneys. New features observed by Verloes et al. (1992) were mental retardation (not correlated with the severity of malformations), anterior anal displacement, and ptosis. Verloes et al. (1992) thought that recessive inheritance was likely but that autosomal dominant inheritance could not be totally excluded, making it wise to exercise caution in the genetic counseling of the parents of an affected child and of affected patients themselves.
Silengo and Tornetta (2000) reported a 10-year-old male with Juberg-Hayward syndrome. He had a cleft palate, distally placed thumbs, and multiple cervical hemivertebrae, but did not have a cleft lip. The parents were unrelated, and there was advanced parental age of 42. The mode of inheritance was unclear.
Reardon et al. (2001) reported a 9-year-old boy whose clinical presentation resembled Malpuech syndrome (248340), but who had radiologic features similar to those seen in patients with Juberg-Hayward syndrome. Clinical features in this patient consistent with both syndromes included short stature, hypertelorism, and cleft lip/palate; but he also had renal agenesis, umbilical hernia, and shawl scrotum, which had not been reported in Juberg-Hayward syndrome but had been seen in Malpuech syndrome. Radiologic features consistent with Juberg-Hayward syndrome included mesomelic shortening, elbow dislocation, carpal bone abnormalities, mild scoliosis, and vertebral endplate irregularity. Reardon et al. (2001) suggested that the Malpuech and Juberg-Hayward syndromes may be allelic.
Hedera and Innis (2003) reported a 14-year-old male with absent thumbs, bilateral cleft lip/palate, and microcephaly, severe mental retardation, severe skeletal abnormalities, as well as a facial appearance supporting the diagnosis of Juberg-Hayward syndrome. New findings in this patient included Dandy-Walker abnormality, hypospadias, and oral abnormalities, expanding the clinical spectrum of this syndrome. Hedera and Innis (2003) suggested possible overlap with orofaciodigital (see 258850) and Malpuech (248340) syndromes.
Skel \- Thumbs hypo/aplastic \- Thumbs proximal/distally placed \- Elbow limited extension \- Toe anomalies \- Stiff thumbs \- Anomalous carpal bones \- Deformity of radial heads \- Minor vertebral and rib anomalies GU \- Horseshoe kidneys Growth \- Short stature Neuro \- Mental retardation Inheritance \- Autosomal recessive, dominance not excluded Endocrine \- Growth hormone deficiency HEENT \- Cleft lip/palate \- Microcephaly \- Hypertelorism \- Bowed and upward slanting eyebrows \- Ptosis GI \- Anterior anal displacement ▲ 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
| CLEFT LIP/PALATE WITH ABNORMAL THUMBS AND MICROCEPHALY | c0796099 | 1,045 | omim | https://www.omim.org/entry/216100 | 2019-09-22T16:29:32 | {"mesh": ["C537690"], "omim": ["216100"], "orphanet": ["2319"], "synonyms": ["Alternative titles", "OROCRANIODIGITAL SYNDROME", "JUBERG-HAYWARD SYNDROME"]} |
L-arginine:glycine amidinotransferase (AGAT) deficiency is a rare condition that primarily affects the brain. People with AGAT deficiency generally have mild to moderate intellectual disability. Other signs and symptoms may include seizures, delayed language development, muscle weakness, failure to thrive, autistic behaviors, and delayed motor milestones (i.e. walking, sitting). AGAT deficiency is caused by changes (mutations) in the GATM gene and is inherited in an autosomal recessive manner. Treatment of AGAT deficiency is focused on increasing cerebral creatine levels and generally consists of supplementation with creatine monohydrate.
*[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
| L-arginine:glycine amidinotransferase deficiency | c2675179 | 1,046 | gard | https://rarediseases.info.nih.gov/diseases/10323/l-arginineglycine-amidinotransferase-deficiency | 2021-01-18T17:59:33 | {"mesh": ["C567192"], "omim": ["612718 "], "umls": ["C2675179"], "orphanet": ["35704"], "synonyms": ["AGAT deficiency", "Arginine:glycine amidinotransferase deficiency", "Creatine deficiency syndrome due to AGAT deficiency", "GATM deficiency"]} |
Neurosarcoidosis
Other namesBesnier-Boeck-Schaumann disease
This condition affects the cranial nerves
SpecialtyNeurology
Diagnostic methodBiopsy
Treatmentimmunosuppression
Neurosarcoidosis (sometimes shortened to neurosarcoid) refers to a type of sarcoidosis, a condition of unknown cause featuring granulomas in various tissues, in this type involving the central nervous system (brain and spinal cord). Neurosarcoidosis can have many manifestations, but abnormalities of the cranial nerves (a group of twelve nerves supplying the head and neck area) are the most common. It may develop acutely, subacutely, and chronically. Approximately 5–10 percent of people with sarcoidosis of other organs (e.g. lung) develop central nervous system involvement. Only 1 percent of people with sarcoidosis will have neurosarcoidosis alone without involvement of any other organs. Diagnosis can be difficult, with no test apart from biopsy achieving a high accuracy rate. Treatment is with immunosuppression.[1] The first case of sarcoidosis involving the nervous system was reported in 1905.[2][3]
## Contents
* 1 Signs and symptoms
* 1.1 Neurological
* 1.2 Endocrine
* 1.3 Mental and other
* 2 Pathophysiology
* 3 Diagnosis
* 3.1 Criteria
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 Notable cases
* 8 References
* 9 External links
## Signs and symptoms[edit]
### Neurological[edit]
Abnormalities of the cranial nerves are present in 50–70 percent of cases. The most common abnormality is involvement of the facial nerve, which may lead to reduced power on one or both sides of the face (65 percent resp 35 percent of all cranial nerve cases), followed by reduction in visual perception due to optic nerve involvement. Rarer symptoms are double vision (oculomotor nerve, trochlear nerve or abducens nerve), decreased sensation of the face (trigeminal nerve), hearing loss or vertigo (vestibulocochlear nerve), swallowing problems (glossopharyngeal nerve) and weakness of the shoulder muscles (accessory nerve) or the tongue (hypoglossal nerve). Visual problems may also be the result of papilledema (swelling of the optic disc) due to obstruction by granulomas of the normal cerebrospinal fluid (CSF) circulation.[1]
Seizures (mostly of the tonic-clonic/"grand mal" type) are present in about 15 percent and may be the presenting phenomenon in 10 percent.[1]
Meningitis (inflammation of the lining of the brain) occurs in 3–26 percent of cases. Symptoms may include headache and nuchal rigidity (being unable to bend the head forward). It may be acute or chronic.[1]
Accumulation of granulomas in particular areas of the brain can lead to abnormalities in the function of that area. For instance, involvement of the internal capsule would lead to weakness in one or two limbs on one side of the body. If the granulomas are large, they can exert a mass effect and cause headache and increase the risk of seizures. Obstruction of the flow of cerebrospinal fluid, too, can cause headaches, visual symptoms (as mentioned above) and other features of raised intracranial pressure and hydrocephalus.[1]
Involvement of the spinal cord is rare, but can lead to abnormal sensation or weakness in one or more limbs, or cauda equina symptoms (incontinence to urine or stool, decreased sensation in the buttocks).[1]
### Endocrine[edit]
Granulomas in the pituitary gland, which produces numerous hormones, is rare but leads to any of the symptoms of hypopituitarism: amenorrhoea (cessation of the menstrual cycle), diabetes insipidus (dehydration due to inability to concentrate the urine), hypothyroidism (decreased activity of the thyroid) or hypocortisolism (deficiency of cortisol).[1]
### Mental and other[edit]
Psychiatric problems occur in 20 percent of cases; many different disorders have been reported, e.g. depression and psychosis. Peripheral neuropathy has been reported in up to 15 percent of cases of neurosarcoidosis.[1]
Other symptoms due to sarcoidosis of other organs may be uveitis (inflammation of the uveal layer in the eye), dyspnoea (shortness of breath), arthralgia (joint pains), lupus pernio (a red skin rash, usually of the face), erythema nodosum (red skin lumps, usually on the shins), and symptoms of liver involvement (jaundice) or heart involvement (heart failure).[1]
## Pathophysiology[edit]
Main article: Causes and pathophysiology of sarcoidosis
Sarcoidosis is a disease of unknown cause that leads to the development of granulomas in various organs. While the lungs are typically involved, other organs may equally be affected. Some subforms of sarcoidosis, such as Löfgren syndrome, may have a particular precipitant and have a specific course. It is unknown which characteristics predispose sarcoidosis patients to brain or spinal cord involvement.[1]
## Diagnosis[edit]
Left image: MRI findings (T1-weighted images) in a patient with neurosacoidosis showing thickening of infundibulum and both optic nerves (white signal marked with yellow arrows; width 6 mm).
Right image: MRI brain with contrast showing near resolution of enhancement after treatment.
The diagnosis of neurosarcoidosis often is difficult. Definitive diagnosis can only be made by biopsy (surgically removing a tissue sample). Because of the risks associated with brain biopsies, they are avoided as much as possible. Other investigations that may be performed in any of the symptoms mentioned above are computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, lumbar puncture, electroencephalography (EEG) and evoked potential (EP) studies. If the diagnosis of sarcoidosis is suspected, typical X-ray or CT appearances of the chest may make the diagnosis more likely; elevations in angiotensin-converting enzyme and calcium in the blood, too, make sarcoidosis more likely. In the past, the Kveim test was used to diagnose sarcoidosis. This now obsolete test had a high (85 percent) sensitivity, but required spleen tissue of a known sarcoidosis patient, an extract of which was injected into the skin of a suspected case.[1]
Only biopsy of suspicious lesions in the brain or elsewhere is considered useful for a definitive diagnosis of neurosarcoid. This would demonstrate granulomas (collections of inflammatory cells) rich in epithelioid cells and surrounded by other immune system cells (e.g. plasma cells, mast cells). Biopsy may be performed to distinguish mass lesions from tumours (e.g. gliomas).[1]
MRI with gadolinium enhancement is the most useful neuroimaging test. This may show enhancement of the pia mater or white matter lesions that may resemble the lesions seen in multiple sclerosis.[1]
Lumbar puncture may demonstrate raised protein level, pleiocytosis (i.e. increased presence of both lymphocytes and neutrophil granulocytes) and oligoclonal bands. Various other tests (e.g. ACE level in CSF) have little added value.[1]
### Criteria[edit]
Some recent papers propose to classify neurosarcoidosis by likelihood:[1]
* Definite neurosarcoidosis can only be diagnosed by plausible symptoms, a positive biopsy and no other possible causes for the symptoms
* Probable neurosarcoidosis can be diagnosed if the symptoms are suggestive, there is evidence of central nervous system inflammation (e.g. CSF and MRI), and other diagnoses have been excluded. A diagnosis of systemic sarcoidosis is not essential.
* Possible neurosarcoidosis may be diagnosed if there are symptoms not due to other conditions but other criteria are not fulfilled.
## Treatment[edit]
Neurosarcoidosis, once confirmed, is generally treated with glucocorticoids such as prednisolone. If this is effective, the dose may gradually be reduced (although many patients need to remain on steroids long-term, frequently leading to side-effects such as diabetes or osteoporosis). Methotrexate, hydroxychloroquine, cyclophosphamide, pentoxifylline, thalidomide and infliximab have been reported to be effective in small studies. In patients unresponsive to medical treatment, radiotherapy may be required. If the granulomatous tissue causes obstruction or mass effect, neurosurgical intervention is sometimes necessary. Seizures can be prevented with anticonvulsants, and psychiatric phenomena may be treated with medication usually employed in these situations.[1]
## Prognosis[edit]
Of the phenomena occurring in neurosarcoid, only facial nerve involvement is known to have a good prognosis and good response to treatment. Long-term treatment is usually necessary for all other phenomena.[1] The mortality rate is estimated at 10 percent[4]
## Epidemiology[edit]
Sarcoidosis has a prevalence of 40 per 100,000 in the general population. However, though those with the GG genotype at rs1049550 in the ANXA11 gene were found to have 1.5–2.5 times higher odds of sarcoidosis compared to those with the AG genotype, while those with the AA genotype had about 1.6 times lower odds.[5][6] Furthermore, those with Common Variable Immunodeficiency (CVID) may be at even higher risk. One study of 80 CVID patients found eight of these had sarcoidosis, suggesting as high a prevalence in CVID populations as one in 10.[7] Given that less than 10 percent of those with sarcoidosis will have neurological involvement, and possibly later on in their disease course, neurosarcoidosis has a prevalence of less than four per 100,000.[1]
Sarcoidosis most commonly affects young adults of both sexes, although studies have reported more cases in females. Incidence is highest for individuals younger than 40 and peaks in the age-group from 20 to 29 years; a second peak is observed for women over 50.[8][9]
Sarcoidosis occurs throughout the world in all races with an average incidence of 16.5/100,000 in men and 19/100,000 in women. The disease is most prevalent in Northern European countries and the highest annual incidence of 60/100,000 is found in Sweden and Iceland. In the United States sarcoidosis is more common in people of African descent than Caucasians, with annual incidence reported as 35.5 and 10.9/100,000, respectively.[10] Sarcoidosis is less commonly reported in South America, Spain, India, Canada, and the Philippines. There may be a higher susceptibility to sarcoidosis in those with coeliac disease. An association between the two disorders has been suggested.[11]
The differing incidence across the world may be at least partially attributable to the lack of screening programs in certain regions of the world and the overshadowing presence of other granulomatous diseases, such as tuberculosis, that may interfere with the diagnosis of sarcoidosis where they are prevalent.[9] There may also be differences in the severity of the disease between people of different ethnicities. Several studies suggest that the presentation in people of African origin may be more severe and disseminated than for Caucasians, who are more likely to have asymptomatic disease.[12]
Manifestation appears to be slightly different according to race and sex. Erythema nodosum is far more common in men than in women and in Caucasians than in other races. In Japanese patients, ophthalmologic and cardiac involvement are more common than in other races.[8]
Sarcoidosis is one of the few pulmonary diseases with a higher prevalence in non-smokers.[13]
## Notable cases[edit]
The American television personality and actress Karen Duffy wrote "Model Patient: My Life As an Incurable Wise-Ass" on her experiences with neurosarcoidosis.[14]
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r Joseph FG, Scolding NJ (2007). "Sarcoidosis of the nervous system". Practical Neurology. 7 (4): 234–44. doi:10.1136/jnnp.2007.124263. PMID 17636138. S2CID 9658767.
2. ^ Colover J (1948). "Sarcoidosis with involvement of the nervous system". Brain. 71 (Pt. 4): 451–75. doi:10.1093/brain/71.4.451. PMID 18124739.
3. ^ Burns TM (August 2003). "Neurosarcoidosis". Archives of Neurology. 60 (8): 1166–8. doi:10.1001/archneur.60.8.1166. PMID 12925378.
4. ^ Hoitsma E, Sharma OP (2005). "Neurosarcoidosis". In Drent M, Costabel U (eds.). Sarcoidosis (Monograph). UK: European Respiratory Society. pp. 164–187. ISBN 1-90409-737-5.
5. ^ Li, Y.; Pabst, S.; Kubisch, C.; Grohé, C.; Wollnik, B. (2010). "First independent replication study confirms the strong genetic association of ANXA11 with sarcoidosis". Thorax. 65 (10): 939–940. doi:10.1136/thx.2010.138743. PMID 20805159.
6. ^ Hofmann, S.; Franke, A.; Fischer, A.; Jacobs, G.; Nothnagel, M.; Gaede, K. I.; Schürmann, M.; Müller-Quernheim, J.; Krawczak, M.; Rosenstiel, P.; Schreiber, S. (2008). "Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis". Nature Genetics. 40 (9): 1103–1106. doi:10.1038/ng.198. PMID 19165924. S2CID 205344714.
7. ^ Fasano, M. B.; Sullivan, K. E.; Sarpong, S. B.; Wood, R. A.; Jones, S. M.; Johns, C. J.; Lederman, H. M.; Bykowsky, M. J.; Greene, J. M.; Winkelstein, J. A. (1996). "Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature". Medicine. 75 (5): 251–261. doi:10.1097/00005792-199609000-00002. PMID 8862347.
8. ^ a b Nunes H, Bouvry D, Soler P, Valeyre D (2007). "Sarcoidosis". Orphanet J Rare Dis. 2: 46. doi:10.1186/1750-1172-2-46. PMC 2169207. PMID 18021432.
9. ^ a b Syed J, Myers R (January 2004). "Sarcoid heart disease". Can J Cardiol. 20 (1): 89–93. PMID 14968147.
10. ^ Henke, CE.; Henke, G.; Elveback, LR.; Beard, CM.; Ballard, DJ.; Kurland, LT. (May 1986). "The epidemiology of sarcoidosis in Rochester, Minnesota: a population-based study of incidence and survival". Am J Epidemiol. 123 (5): 840–5. doi:10.1093/oxfordjournals.aje.a114313. PMID 3962966.
11. ^ Rutherford RM, Brutsche MH, Kearns M, Bourke M, Stevens F, Gilmartin JJ (September 2004). "Prevalence of coeliac disease in patients with sarcoidosis". Eur J Gastroenterol Hepatol. 16 (9): 911–5. doi:10.1097/00042737-200409000-00016. PMID 15316417. S2CID 24306517.
12. ^ "Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999". American Journal of Respiratory and Critical Care Medicine. 160 (2): 736–755. 1999. doi:10.1164/ajrccm.160.2.ats4-99. PMID 10430755.
13. ^ Warren, C. P. (1977). "Extrinsic allergic alveolitis: a disease commoner in non-smokers" (PDF). Thorax. 32 (5): 567–569. doi:10.1136/thx.32.5.567. PMC 470791. PMID 594937.
14. ^ Duffy, Karen Grover (2001). Model Patient : My Life As an Incurable Wise-Ass. New York, NY: Perennial. ISBN 0-06-095727-1.
## External links[edit]
Classification
D
* ICD-10: D86.0 D86.1 D86.2 D86.3 D86.8 D86.9
* OMIM: 181000
* MeSH: D012507
* SNOMED CT: 230193008
External resources
* MedlinePlus: 000720
* eMedicine: neuro/649
* Orphanet: 797
* v
* t
* e
Sarcoidosis
* Skin
* Lupus pernio
* Neurosarcoidosis
* Löfgren syndrome
* Heerfordt's syndrome
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Neurosarcoidosis | c0393485 | 1,047 | wikipedia | https://en.wikipedia.org/wiki/Neurosarcoidosis | 2021-01-18T19:00:58 | {"mesh": ["C535814"], "umls": ["C0393485"], "wikidata": ["Q12859178"]} |
Benign paroxysmal positional vertigo
Exterior of labyrinth of the inner ear.
SpecialtyOtorhinolaryngology
SymptomsRepeated periods of a spinning sensation with movement[1]
Usual onsetAge from 50s to 70s[2]
DurationEpisodes less than a minute[3]
Risk factorsOlder age, minor head injury[3]
Diagnostic methodPositive Dix–Hallpike test after other possible causes have been ruled out[1]
Differential diagnosisLabyrinthitis, Ménière's disease, stroke, vestibular migraine[3][4]
TreatmentEpley maneuver or Brandt–Daroff exercises[3][5]
PrognosisResolves in days to months[6]
Frequency2.4% affected at some point[1]
Benign paroxysmal positional vertigo (BPPV) is a disorder arising from a problem in the inner ear.[3] Symptoms are repeated, brief periods of vertigo with movement, characterized by a spinning sensation upon changes in the position of the head.[1] This can occur with turning in bed or changing position.[3] Each episode of vertigo typically lasts less than one minute.[3] Nausea is commonly associated.[7] BPPV is one of the most common causes of vertigo.[1][2]
BPPV is a type of balance disorder along with labyrinthitis and Ménière's disease.[3] It can result from a head injury or simply occur among those who are older.[3] Often, a specific cause is not identified.[3] When found, the underlying mechanism typically involves a small calcified otolith moving around loose in the inner ear.[3] Diagnosis is typically made when the Dix–Hallpike test results in nystagmus (a specific movement pattern of the eyes) and other possible causes have been ruled out.[1] In typical cases, medical imaging is not needed.[1]
BPPV is often treated with a number of simple movements such as the Epley maneuver or Brandt–Daroff exercises.[3][5] Medications, including antihistamines such as meclizine,[8] may be used to help with nausea.[7] There is tentative evidence that betahistine may help with vertigo, but its use is not generally needed.[1][9] BPPV is not a serious medical condition,[7] but may present serious risks of injury through falling or other spatial disorientation-induced accidents.
Typically, it resolves in days to months.[6] It, however, may recur in some people.[7]
The first medical description of the condition occurred in 1921 by Róbert Bárány.[10] Approximately 2.4% of people are affected at some point in time.[1] Among those who live until their 80s, 10% have been affected.[2] BPPV affects females twice as often as males.[7] Onset is typically in people between the ages of 50 and 70.[2]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Mechanism
* 4 Diagnosis
* 4.1 Differential diagnosis
* 5 Treatment
* 5.1 Repositioning maneuvers
* 5.1.1 Epley maneuver
* 5.1.2 Semont maneuver
* 5.1.3 Brandt–Daroff exercises
* 5.1.4 Roll maneuver
* 5.2 Medications
* 5.3 Surgery
* 6 References
* 7 Further reading
* 8 External links
## Signs and symptoms[edit]
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Symptoms:
* Paroxysmal—appears suddenly, and in episodes of short duration: lasts only seconds to minutes
* Positional—is induced by a change in position, even slight
* Vertigo—a spinning dizziness, which must have a rotational component
* Torsional nystagmus—a diagnostic symptom where the top of the eye rotates toward the affected ear in a beating or twitching fashion, which has a latency and can be fatigued (vertigo should lessen with deliberate repetition of the provoking maneuver): nystagmus should only last for 30 seconds to one minute
* Pre-syncope—(feeling faint) or syncope (fainting) is unusual, but possible
* Visual disturbance—due to associated nystagmus, making it difficult to read or see during an attack
* Nausea—is often associated
* Vomiting—is common, depending on the strength of vertigo itself and the causes for this illness
Many people will report a history of vertigo as a result of fast head movements. Many are also capable of describing the exact head movements that provoke their vertigo. Purely horizontal nystagmus and symptoms of vertigo lasting more than one minute can also indicate BPPV occurring in the horizontal semicircular canal.
The spinning sensation experienced from BPPV is usually triggered by movement of the head, will have a sudden onset, and can last anywhere from a few seconds to several minutes. The most common movements people report triggering a spinning sensation are tilting their heads upward in order to look at something and when rolling over in bed.[11]
People with BPPV do not experience other neurological deficits such as numbness or weakness. If those symptoms are present, a more serious etiology, such as posterior circulation stroke or ischemia, must be considered.
## Cause[edit]
Within the labyrinth of the inner ear lie collections of calcium crystals known as otoconia or otoliths. In people with BPPV, the otoconia are dislodged from their usual position within the utricle, and over time, migrate into one of the semicircular canals (the posterior canal is most commonly affected due to its anatomical position). When the head is reoriented relative to gravity, the gravity-dependent movement of the heavier otoconial debris (colloquially "ear rocks") within the affected semicircular canal causes abnormal (pathological) endolymph fluid displacement and a resultant sensation of vertigo. This more common condition is known as canalithiasis.
In rare cases, the crystals themselves can adhere to a semicircular canal cupula, rendering it heavier than the surrounding endolymph. Upon reorientation of the head relative to gravity, the cupula is weighted down by the dense particles, thereby inducing an immediate and sustained excitation of semicircular canal afferent nerves. This condition is termed cupulolithiasis.
There is evidence in the dental literature that malleting of an osteotome during closed sinus floor elevation, otherwise known as osteotome sinus elevation or lift, transmits percussive and vibratory forces capable of detaching otoliths from their normal location and thereby leading to the symptoms of BPPV.[12][13]
BPPV can be triggered by any action that stimulates the posterior semi-circular canal including:
* Looking up or down
* Following head injury
* Sudden head movement
* Rolling over in bed
* Tilting the head
BPPV may be made worse by any number of modifiers which may vary among individuals:
* Changes in barometric pressure – people may feel increased symptoms up to two days before rain or snow
* Lack of sleep (required amounts of sleep may vary widely)
* Stress
An episode of BPPV may be triggered by dehydration, such as that caused by diarrhea. For this reason, it commonly occurs in people with post-operative diarrhea induced by post-operative antibiotics.
BPPV is one of the most common vestibular disorders in people presenting with dizziness; a migraine is implicated in idiopathic cases. Proposed mechanisms linking the two are genetic factors and vascular damage to the labyrinth.[14]
Although BPPV can occur at any age, it is most often seen in people older than the age of 60.[15] Besides aging, there are no major risk factors known for BPPV, although previous episodes of head trauma, or the inner ear infection labyrinthitis, may predispose to the future development of BPPV.[11]
## Mechanism[edit]
The inside of the ear is composed of an organ called the vestibular labyrinth. The vestibular labyrinth includes semicircular canals, which contain fluids and fine hairlike sensors that act as a monitor to the rotations of the head. An important structure in the inner ear includes the otolith organs that contain crystals that are sensitive to gravity. These crystals are responsible for sensitivity to head positions, and can also be dislocated, causing them to lodge inside one of the semicircular canals, which causes dizziness.[citation needed]
## Diagnosis[edit]
The condition is diagnosed by the person's history, and by performing the Dix–Hallpike test or the roll test, or both.[16][17]
The Dix–Hallpike test is a common test performed by examiners to determine whether the posterior semicircular canal is involved.[17] It involves a reorientation of the head to align the posterior semicircular canal (at its entrance to the ampulla) with the direction of gravity. This test will reproduce vertigo and nystagmus characteristic of posterior canal BPPV.[16]
When performing the Dix–Hallpike test, people are lowered quickly to a supine position, with the neck extended by the person performing the maneuver. For some people, this maneuver may not be indicated, and a modification may be needed that also targets the posterior semicircular canal. Such people include those who are too anxious about eliciting the uncomfortable symptoms of vertigo, and those who may not have the range of motion necessary to comfortably be in a supine position. The modification involves the person moving from a seated position to side-lying without their head extending off the examination table, such as with Dix–Hallpike. The head is rotated 45 degrees away from the side being tested, and the eyes are examined for nystagmus. A positive test is indicated by the patient report of a reproduction of vertigo and clinician observation of nystagmus. Both the Dix–Hallpike and the side-lying testing position have yielded similar results, and as such the side-lying position can be used if the Dix–Hallpike cannot be performed easily.[18]
The roll test can determine whether the horizontal semicircular canal is involved.[16] The roll test requires the person to be in a supine position with their head in 30° of cervical flexion. Then the examiner quickly rotates the head 90° to the left side, and checks for vertigo and nystagmus. This is followed by gently bringing the head back to the starting position. The examiner then quickly rotates the head 90° to the right side and checks again for vertigo and nystagmus.[16] In this roll test, the person may experience vertigo and nystagmus on both sides, but rotating toward the affected side will trigger a more intense vertigo. Similarly, when the head is rotated toward the affected side, the nystagmus will beat toward the ground and be more intense.[17]
As mentioned above, both the Dix–Hallpike and roll test provoke the signs and symptoms in subjects suffering from archetypal BPPV. The signs and symptoms people with BPPV experience are typically a short-lived vertigo and observed nystagmus. In some people, although rarely, vertigo can persist for years. Assessment of BPPV is best done by a medical health professional skilled in the management of dizziness disorders, commonly a physiotherapist, audiologist, or other physician.
The nystagmus associated with BPPV has several important characteristics that differentiate it from other types of nystagmus.
* Latency of onset: there is a 5–10 second delay prior to onset of nystagmus
* Nystagmus lasts for 5–60 seconds
* Positional: the nystagmus occurs only in certain positions
* Repeated stimulation, including via Dix–Hallpike maneuvers, cause the nystagmus to fatigue or disappear temporarily
* Rotatory/Torsional component is present, or (in the case of lateral canal involvement) the nystagmus beats in either a geotropic (toward the ground) or ageotropic (away from the ground) fashion
* Visual fixation suppresses nystagmus due to BPPV
Although rare, CNS disorders can sometimes present as BPPV. A practitioner should be aware that if a person whose symptoms are consistent with BPPV, but does not show improvement or resolution after undergoing different particle repositioning maneuvers — detailed in the Treatment section below — need to have a detailed neurological assessment and imaging performed to help identify the pathological condition.[1]
### Differential diagnosis[edit]
Vertigo, a distinct process sometimes confused with the broader term, dizziness, accounts for about six million clinic visits in the United States every year; between 17 and 42% of these people are eventually diagnosed with BPPV.[1] Other causes of vertigo include:
* Motion sickness/motion intolerance: a disjunction between visual stimulation, vestibular stimulation, and/or proprioception
* Visual exposure to nearby moving objects (examples of optokinetic stimuli include passing cars and falling snow)
* Other diseases: (labyrinthitis, Ménière's disease, and migraine,[19] etc.)
## Treatment[edit]
### Repositioning maneuvers[edit]
A number of maneuvers have been found to be effective including: the Epley maneuver, the Semont maneuver, and to a lesser degree Brandt–Daroff exercises.[5] Both the Epley and the Semont maneuvers are equally effective.[5][20]
#### Epley maneuver[edit]
Main article: Epley maneuver
The Epley maneuver employs gravity to move the calcium crystal build-up that causes the condition.[21] This maneuver can be performed during a clinic visit by health professionals, or taught to people to perform at home, or both.[22] Postural restriction after the Epley maneuver increases its effect somewhat.[23]
When practiced at home, the Epley maneuver is more effective than the Semont maneuver. The most effective repositioning treatment for posterior canal BPPV is the therapist-performed Epley combined with home-practiced Epley maneuvers.[24] Devices such as the DizzyFIX can help users conduct the Epley maneuver at home, and are available for the treatment of BPPV.[25]
The Epley maneuver does not address the presence of the particles (otoconia); rather it changes their location. The maneuver aims to move these particles from some locations in the inner ear that cause symptoms such as vertigo, and reposition them to where they do not cause these problems.
#### Semont maneuver[edit]
Main article: Semont maneuver
The Semont maneuver has a cure rate of 90.3%.[26] It is performed as follows:
1. The person is seated on a treatment table with their legs hanging off the side of the table. The therapist then turns the person's head 45 degrees toward the unaffected side.
2. The therapist then quickly tilts the person so they are lying on the affected side. The head position is maintained, so their head is turned up 45 degrees. This position is maintained for 3 minutes. The purpose is to allow the debris to move to the apex of the ear canal.
3. The person is then quickly moved so they are lying on the unaffected side with their head in the same position (now facing downward 45 degrees). This position is also held for 3 minutes. The purpose of this position is to allow the debris to move toward the exit of the ear canal.
4. Finally, the person is slowly brought back to an upright seated position. The debris should then fall into the utricle of the canal and the symptoms of vertigo should decrease or end completely.
Some people will only need one treatment, but others may need multiple treatments, depending on the severity of their BPPV. In the Semont maneuver, as with the Epley maneuver, people are able to achieve canalith repositioning by themselves.[22]
#### Brandt–Daroff exercises[edit]
The Brandt–Daroff exercises may be prescribed by the clinician as a home treatment method, usually in conjunction with particle-repositioning maneuvers or in lieu of the particle-repositioning maneuver. The exercise is a form of habituation exercise, designed to allow the person to become accustomed to the position that causes the vertigo symptoms. The Brandt–Daroff exercises are performed in a similar fashion to the Semont maneuver; however, as the person rolls onto the unaffected side, the head is rotated toward the affected side.[27] The exercise is typically performed 3 times a day with 5–10 repetitions each time, until symptoms of vertigo have resolved for at least 2 days.[16]
#### Roll maneuver[edit]
For the lateral (horizontal) canal, a separate maneuver has been used for productive results. It is unusual for the lateral canal to respond to the canalith repositioning procedure used for the posterior canal BPPV. Treatment is therefore geared toward moving the canalith from the lateral canal into the vestibule.[28]
The roll maneuver or its variations are used, and involve rolling the person 360 degrees in a series of steps to reposition the particles.[1][29] This maneuver is generally performed by a trained clinician who begins seated at the head of the examination table with the person supine[30] There are four stages, each a minute apart, and at the third position the horizontal canal is oriented in a vertical position with the person's neck flexed and on forearm and elbows.[30] When all four stages are completed, the head roll test is repeated, and if negative, treatment ceases.[30]
### Medications[edit]
Medical treatment with anti-vertigo medications may be considered in acute, severe exacerbation of BPPV, but in most cases are not indicated. These primarily include drugs of the antihistamine and anticholinergic class, such as meclizine[8] and hyoscine butylbromide (scopolamine), respectively. The medical management of vestibular syndromes has become increasingly popular over the last decade, and numerous novel drug therapies (including existing drugs with new indications) have emerged for the treatment of vertigo/dizziness syndromes. These drugs vary considerably in their mechanisms of action, with many of them being receptor- or ion channel-specific. Among them are betahistine or dexamethasone/gentamicin for the treatment of Ménière's disease, carbamazepine/oxcarbazepine for the treatment of paroxysmal dysarthria and ataxia in multiple sclerosis, metoprolol/topiramate or valproic acid/tricyclic antidepressant for the treatment of vestibular migraine, and 4-aminopyridine for the treatment of episodic ataxia type 2 and both downbeat and upbeat nystagmus.[31] These drug therapies offer symptomatic treatment, and do not affect the disease process or resolution rate. Medications may be used to suppress symptoms during the positioning maneuvers if the person's symptoms are severe and intolerable. More dose-specific studies are required, however, in order to determine the most effective drug(s) for both acute symptom relief and long-term remission of the condition.[31]
### Surgery[edit]
Surgical treatments, such as a semi-circular canal occlusion, exist for severe and persistent cases that fail vestibular rehabilitation (including particle repositioning and habituation therapy). As they carry the same risks as any neurosurgical procedure, they are reserved as last resorts.
## References[edit]
1. ^ a b c d e f g h i j k l Bhattacharyya N, Baugh RF, Orvidas L, Barrs D, Bronston LJ, Cass S, Chalian AA, Desmond AL, Earll JM, Fife TD, Fuller DC, Judge JO, Mann NR, Rosenfeld RM, Schuring LT, Steiner RW, Whitney SL, Haidari J (November 2008). "Clinical practice guideline: benign paroxysmal positional vertigo". Otolaryngology–Head and Neck Surgery. 139 (5 Suppl 4): S47-81. doi:10.1016/j.otohns.2008.08.022. PMID 18973840. S2CID 16175316. Lay summary – AAO-HNS (2008-11-01).
2. ^ a b c d Dickson, Gretchen (2014). Primary Care ENT, An Issue of Primary Care: Clinics in Office Practice, Volume 41, Issue 1 of The Clinics: Internal Medicine. Elsevier Health Sciences. p. 115. ISBN 9780323287173. Archived from the original on 15 August 2016. Retrieved 25 July 2016.
3. ^ a b c d e f g h i j k l "Balance Disorders". National Institute for Deafness and Other Communication Disorders (NIDCD). August 10, 2015. Archived from the original on 27 July 2016. Retrieved 25 July 2016.
4. ^ Ferri, Fred F. (2016). Ferri's Clinical Advisor 2017 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 170. ISBN 9780323448383. Archived from the original on 2017-09-08.
5. ^ a b c d Hilton MP, Pinder DK (December 2014). "The Epley (canalith repositioning) manoeuvre for benign paroxysmal positional vertigo". The Cochrane Database of Systematic Reviews (12): CD003162. doi:10.1002/14651858.CD003162.pub3. PMID 25485940.
6. ^ a b "Benign Paroxysmal Positional Vertigo". NORD (National Organization for Rare Disorders). Retrieved 19 January 2020.
7. ^ a b c d e "Positional vertigo: Overview". PubMed Health. 30 January 2014. Retrieved 25 July 2016.
8. ^ a b "Meclizine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 22 March 2019.
9. ^ Murdin L, Hussain K, Schilder AG (June 2016). "Betahistine for symptoms of vertigo" (PDF). The Cochrane Database of Systematic Reviews (6): CD010696. doi:10.1002/14651858.CD010696.pub2. PMC 7388750. PMID 27327415.
10. ^ Daroff, Robert B. (2012). "Chapter 37". Bradley's neurology in clinical practice (6th ed.). Philadelphia, PA: Elsevier Saunders. ISBN 9781455728077. Archived from the original on 2016-12-21.
11. ^ a b "Benign positional vertigo". A.D.A.M. Medical Encyclopedia. Archived from the original on 26 October 2013. Retrieved 16 April 2014.
12. ^ Sammartino G, Mariniello M, Scaravilli MS (June 2011). "Benign paroxysmal positional vertigo following closed sinus floor elevation procedure: mallet osteotomes vs. screwable osteotomes. A triple blind randomized controlled trial". Clinical Oral Implants Research. 22 (6): 669–672. doi:10.1111/j.1600-0501.2010.01998.x. PMID 21054553.
13. ^ Kim MS, Lee JK, Chang BS, Um HS (April 2010). "Benign paroxysmal positional vertigo as a complication of sinus floor elevation". Journal of Periodontal & Implant Science. 40 (2): 86–89. doi:10.5051/jpis.2010.40.2.86. PMC 2872812. PMID 20498765.
14. ^ Lempert T, Neuhauser H (March 2009). "Epidemiology of vertigo, migraine and vestibular migraine". Journal of Neurology. 256 (3): 333–338. doi:10.1007/s00415-009-0149-2. PMID 19225823. S2CID 27402289.
15. ^ Mayo Clinic Staff (July 10, 2012). "Benign paroxysmal positional vertigo (BPPV)". Archived from the original on 16 April 2014. Retrieved 16 April 2014.
16. ^ a b c d e Schubert, Michael C. (2019-01-25). "Vestibular Disorders". In O'Sullivan, Susan B.; Schmitz, Thomas J.; Fulk, George D. (eds.). Physical Rehabilitation (7th ed.). pp. 918–49. ISBN 978-0-8036-9464-4.
17. ^ a b c Korres SG, Balatsouras DG (October 2004). "Diagnostic, pathophysiologic, and therapeutic aspects of benign paroxysmal positional vertigo". Otolaryngology–Head and Neck Surgery. 131 (4): 438–44. doi:10.1016/j.otohns.2004.02.046. PMID 15467614. S2CID 28018301.
18. ^ Cohen HS (March 2004). "Side-lying as an alternative to the Dix-Hallpike test of the posterior canal". Otology & Neurotology. 25 (2): 130–4. doi:10.1097/00129492-200403000-00008. PMID 15021771. S2CID 12649245.
19. ^ Buchholz, D. Heal Your Headache. New York:Workman Publishing;2002:74-75
20. ^ Gold, Daniel. "Posterior Canal - BPPV: Epley and Semont maneuvers". Neuro-Ophthalmology Virtual Education Library (NOVEL): Daniel Gold Collection. Spencer S. Eccles Health Sciences Library. Retrieved 9 September 2019.
21. ^ von Brevern M, Seelig T, Radtke A, Tiel-Wilck K, Neuhauser H, Lempert T (August 2006). "Short-term efficacy of Epley's manoeuvre: a double-blind randomised trial". Journal of Neurology, Neurosurgery, and Psychiatry. 77 (8): 980–2. doi:10.1136/jnnp.2005.085894. PMC 2077628. PMID 16549410.
22. ^ a b Radtke A, von Brevern M, Tiel-Wilck K, Mainz-Perchalla A, Neuhauser H, Lempert T (July 2004). "Self-treatment of benign paroxysmal positional vertigo: Semont maneuver vs Epley procedure". Neurology. 63 (1): 150–2. doi:10.1212/01.WNL.0000130250.62842.C9. PMID 15249626.
23. ^ Hunt WT, Zimmermann EF, Hilton MP (April 2012). "Modifications of the Epley (canalith repositioning) manoeuvre for posterior canal benign paroxysmal positional vertigo (BPPV)". The Cochrane Database of Systematic Reviews (4): CD008675. doi:10.1002/14651858.CD008675.pub2. PMC 6885068. PMID 22513962.
24. ^ Helminski JO, Zee DS, Janssen I, Hain TC (May 2010). "Effectiveness of particle repositioning maneuvers in the treatment of benign paroxysmal positional vertigo: a systematic review". Physical Therapy. 90 (5): 663–78. doi:10.2522/ptj.20090071. PMID 20338918.
25. ^ Beyea JA, Wong E, Bromwich M, Weston WW, Fung K (January 2008). "Evaluation of a particle repositioning maneuver Web-based teaching module". The Laryngoscope. 118 (1): 175–80. doi:10.1097/MLG.0b013e31814b290d. PMID 18251035.
26. ^ Chen Y, Zhuang J, Zhang L, Li Y, Jin Z, Zhao Z, Zhao Y, Zhou H (September 2012). "Short-term efficacy of Semont maneuver for benign paroxysmal positional vertigo: a double-blind randomized trial". Otology & Neurotology. 33 (7): 1127–30. doi:10.1097/mao.0b013e31826352ca. PMID 22892804. S2CID 32993812.
27. ^ Vesely DL, Chiou S, Douglass MA, McCormick MT, Rodriguez-Paz G, Schocken DD (March 1996). "Atrial natriuretic peptides negatively and positively modulate circulating endothelin in humans". Metabolism. 45 (3): 315–9. doi:10.1016/S0026-0495(96)90284-X. PMID 8606637.
28. ^ Hegemann SC, Palla A (August 2010). "New methods for diagnosis and treatment of vestibular diseases". F1000 Medicine Reports. 2: 60. doi:10.3410/M2-60. PMC 2990630. PMID 21173877.
29. ^ Gold, Daniel. "Horizontal Canal - BPPV: BBQ Roll to treat the right side". Neuro-Ophthalmology Virtual Education Library (NOVEL): Daniel Gold Collection. Spencer S. Eccles Health Sciences Library. Retrieved 20 November 2019.
30. ^ a b c Hornibrook J (2011). "Benign Paroxysmal Positional Vertigo (BPPV): History, Pathophysiology, Office Treatment and Future Directions". International Journal of Otolaryngology. 2011: 1–13. doi:10.1155/2011/835671. PMC 3144715. PMID 21808648.
31. ^ a b Huppert D, Strupp M, Mückter H, Brandt T (March 2011). "Which medication do I need to manage dizzy patients?". Acta Oto-Laryngologica. 131 (3): 228–41. doi:10.3109/00016489.2010.531052. PMID 21142898. S2CID 32591311.
## Further reading[edit]
* Parnes LS, Agrawal SK, Atlas J (September 2003). "Diagnosis and management of benign paroxysmal positional vertigo (BPPV)". CMAJ. 169 (7): 681–93. PMC 202288. PMID 14517129.
* Huppert D, Strupp M, Mückter H, Brandt T (March 2011). "Which medication do I need to manage dizzy patients?". Acta Oto-Laryngologica. 131 (3): 228–41. doi:10.3109/00016489.2010.531052. PMID 21142898. S2CID 32591311.
* Solomon D (September 2000). "Benign Paroxysmal Positional Vertigo" (PDF). Current Treatment Options in Neurology. 2 (5): 417–428. doi:10.1007/s11940-000-0040-z. PMID 11096767. S2CID 45763227.
* "Videos". Neurology. 2018-12-30. in Radtke A, von Brevern M, Tiel-Wilck K, Mainz-Perchalla A, Neuhauser H, Lempert T (July 2004). "Self-treatment of benign paroxysmal positional vertigo: Semont maneuver vs Epley procedure". Neurology. 63 (1): 150–2. doi:10.1212/01.WNL.0000130250.62842.C9. PMID 15249626.
## External links[edit]
Classification
D
* ICD-10: H81.1
* ICD-9-CM: 386.11
* OMIM: 193007
* MeSH: D014717
* DiseasesDB: 1344
External resources
* MedlinePlus: 001420
* eMedicine: ent/761 emerg/57 neuro/411
* Patient UK: Benign paroxysmal positional vertigo
* v
* t
* e
Disorders of hearing and balance
Hearing
Symptoms
* Hearing loss
* Excessive response
* Tinnitus
* Hyperacusis
* Phonophobia
Disease
Loss
* Conductive hearing loss
* Otosclerosis
* Superior canal dehiscence
* Sensorineural hearing loss
* Presbycusis
* Cortical deafness
* Nonsyndromic deafness
Other
* Deafblindness
* Wolfram syndrome
* Usher syndrome
* Auditory processing disorder
* Spatial hearing loss
Tests
* Hearing test
* Rinne test
* Tone decay test
* Weber test
* Audiometry
* pure tone
* visual reinforcement
Balance
Symptoms
* Vertigo
* nystagmus
Disease
* Balance disorder
* Peripheral
* Ménière's disease
* Benign paroxysmal positional vertigo
* Labyrinthitis
* Labyrinthine fistula
Tests
* Dix–Hallpike test
* Unterberger test
* Romberg's test
* Vestibulo–ocular reflex
*[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 paroxysmal positional vertigo | c0155502 | 1,048 | wikipedia | https://en.wikipedia.org/wiki/Benign_paroxysmal_positional_vertigo | 2021-01-18T18:36:45 | {"gard": ["5915"], "mesh": ["D065635"], "umls": ["C0155502"], "icd-10": ["H81.1"], "wikidata": ["Q817310"]} |
Intestinal neuronal dysplasia
Other namesNeuronal intestinal dysplasia
SpecialtyGastroenterology
Intestinal neuronal dysplasia (IND) is an inherited disease of the intestine that affects one in 3000 children and adults. The intestine uses peristalsis to push its contents toward the anus; IND sufferers have a problem with the motor neurons that lead to the intestine, inhibiting this process and thus preventing digestion.
It can often be confused for Hirschsprung's disease, as both have similar symptoms.[1]
## Contents
* 1 Presentation
* 2 Diagnosis
* 3 Treatment
* 4 Society
* 5 References
* 6 External links
## Presentation[edit]
IND can be grouped into NID A and NID B, with the "A" form affecting the sympathetic innervation, and the "B" version affecting the parasympathetic innervation.[2][3] In 2002 Martucciello and colleagues published the first analysis of associated anomalies in IND population is an important clinical approach to investigate possible pathogenetic correlations. Two recessive syndromes were identified (3 families). The first was characterized by NID B, intestinal malrotation, and congenital short bowel, the second by NID B, short stature, mental retardation, and facial dysmorphism. In this study, gastrointestinal anomalies accounted for 67.4% of all associated disorders. These data suggest a strong correlation between IND and intestinal development.[4]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (November 2017)
## Treatment[edit]
Conservative treatment involves the long term use of laxatives and enemas, and has limited success. Dietary changes in order to control the disease are ineffective and high fiber diets often worsen the symptoms in children. As a last resort, surgical treatment (internal sphincter myectomy or colon resection) is used.[5] In extreme cases, the only effective cure is a complete transplant of the affected parts.[citation needed]
## Society[edit]
A famous case of IND is that of Adele Chapman, who had a triple transplant of the small intestine, pancreas and liver, the first of its kind in the UK; therefore the official charity of IND is the Adele Chapman Foundation.[citation needed]
## References[edit]
1. ^ Mahesha V, Saikia UN, Shubha AV, Rao KL (February 2008). "Intestinal neuronal dysplasia of the myenteric plexus—new entity in humans?". European Journal of Pediatric Surgery. 18 (1): 59–60. doi:10.1055/s-2008-1038324. PMID 18302074.
2. ^ Fadda B, Maier WA, Meier-Ruge W, Schärli A, Daum R (October 1983). "Neuronale intestinale Dysplasie. Eine kritische 10-Jahres-Analyse klinischer und bioptischer Diagnostik" [Neuronal intestinal dysplasia. Critical 10-years' analysis of clinical and biopsy diagnosis]. Zeitschrift für Kinderchirurgie (in German). 38 (5): 305–11. doi:10.1055/s-2008-1059994. PMID 6649903.
3. ^ Barone V, Weber D, Luo Y, Brancolini V, Devoto M, Romeo G (March 1996). "Exclusion of linkage between RET and neuronal intestinal dysplasia type B". American Journal of Medical Genetics. 62 (2): 195–8. doi:10.1002/(SICI)1096-8628(19960315)62:2<195::AID-AJMG15>3.0.CO;2-J. PMID 8882403.
4. ^ Martucciello, G; Torre, M; Pini Prato, A; Lerone, M; Campus, R; Leggio, S; Jasonni, V (2002). "Associated anomalies in intestinal neuronal dysplasia". Journal of Pediatric Surgery. 37 (2): 219–223. doi:10.1053/jpsu.2002.30258. PMID 11819202.
5. ^ Gillick J, Tazawa H, Puri P (May 2001). "Intestinal neuronal dysplasia: results of treatment in 33 patients". Journal of Pediatric Surgery. 36 (5): 777–9. doi:10.1053/jpsu.2001.22959. PMID 11329588.
## External links[edit]
Classification
D
* OMIM: 243180 601223
* MeSH: C537394
*[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
| Intestinal neuronal dysplasia | c1855733 | 1,049 | wikipedia | https://en.wikipedia.org/wiki/Intestinal_neuronal_dysplasia | 2021-01-18T19:05:51 | {"mesh": ["C537394"], "orphanet": ["99811"], "wikidata": ["Q6057481"]} |
A number sign (#) is used with this entry because of evidence that variation in the serotonin transmitter (SLC6A4; 182138) confers susceptibility to anxiety-related traits.
Description
Human personality is shaped by genetic and environmental factors, and evidence suggests that the genetic component is highly complex, polygenic, and epistatic. Genetic factors are thought to contribute to 40 to 60% of trait variance. Molecular genetics has tried to identify specific genes for quantitative traits, called quantitative trait loci (QTLs). The QTL concept suggests that complex personality traits or dimensions are not attributable to single genes, but to multiple interacting genes (Reif and Lesch, 2003).
Fullerton et al. (2003) stated that psychologists were in agreement that the wide variation in human personalities can be explained by a small number of personality factors, including neuroticism (a measure of emotional stability), which manifests at one extreme as anxiety, depression, moodiness, low self-esteem, and diffidence. They cited a number of studies that had described a relationship between high scores on measures of neuroticism and major depressive disorder. They also noted that theoretical studies had suggested that large samples of randomly ascertained sibs could be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits.
See also panic disorder (PAND1; 167870), which is a subtype of anxiety disorder.
Mapping
Fullerton et al. (2003) reported a genetic linkage scan using 182 extremely discordant and 379 extremely concordant sib pairs selected from 34,580 sib pairs in the southwest of England who completed a personality questionnaire. They performed a genomewide scan for QTLs influencing variation in neuroticism and found 5 loci that met or exceeded the 5% genomewide significance threshold of 3.8 (negative logarithm of the P value) on chromosomes 1q, 4q, 7p, 12q, and 13q. QTLs on chromosomes 1, 12, and 13 were thought to be female-specific. The locus on chromosome 1 was syntenic with a rat QTL influencing emotionality, a model of neuroticism, suggesting that some animal and human QTLs influencing emotional stability may be homologous.
Cloninger et al. (1998) performed a genomewide scan in 758 sib pairs in 177 nuclear families of alcoholics. Personality traits were assessed using the Tridimensional Personality Questionnaire (TPQ). Significant linkage between a measure of anxiety proneness called harm avoidance and a locus on chromosome 8p23-p21 explained 38% of the trait variance. There was also significant evidence of epistasis between the locus on 8p and others on chromosomes 18p, 20p, and 21q, and these interactions explained most of the variance in harm avoidance.
In 384 sib pairs recruited from the general population, Zohar et al. (2003) found linkage between harm avoidance, as assessed by the TPQ, and a locus on 8p23-p21, with a maximum multipoint lod score of 2.34. The lod score increased to 2.9 when female gender was considered.
Nash et al. (2004) explored genetic variants for the liability to depression (608516) and anxiety in a large community-based sample of 34,371 individuals. A composite index of liability (G) was constructed and used to select a smaller but statistically powerful sample for DNA collection (757 individuals, 297 sibships). These individuals were genotyped with more than 400 microsatellite markers. Linkage analysis revealed 2 potential quantitative trait loci (QTL): 1 on chromosome 1p (lod = 2.2) around 64 cM near D1S2892 and another on chromosome 6p (lod = 2.7) around 47 cM near D6S1610. The authors further noted that these QTLs might have sex-limited effects.
Neale et al. (2005) analyzed a genome scan for neuroticism on a sample of 129 sib-pair families (113 with a single sib pair, 18 with multiple sib pairs) containing a total of 201 possible sib pairs, ascertained for concordance on nicotine dependence. The study replicated peaks for neuroticism described by prior studies on chromosomes 1q (137 cM) and 11 (132 cM) with lod scores of 2.52 and 1.97 (p = 0.003 and 0.0108), respectively, as well as evidence for a novel finding on chromosome 12 (45.5 cM) with a lod of 2.85 (p = 0.0014).
Inheritance
In a study of 2,287 Australian and 1,185 Dutch twins and sibs, Middeldorp et al. (2005) found a correlation of 0.20 for generalized anxiety disorder, yielding an upper heritability estimate of 40%.
To characterize the neural circuitry associated with anxious temperament and the extent to which the function of this circuit is heritable, Oler et al. (2010) studied a large sample of rhesus monkeys phenotyped for anxious temperament. Using 238 young monkeys from a multigenerational single-family pedigree, Oler et al. (2010) simultaneously assessed brain metabolic activity and anxious temperament while monkeys were exposed to the relevant ethologic condition that elicits the phenotype. High-resolution (18)F-labeled deoxyglucose positron-emission tomography (FDG-PET) was selected as the imaging modality because it provides semiquantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behavior and brain activity, and has a time course suited for assessing temperament-associated sustained brain responses. Oler et al. (2010) demonstrated that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of anxious temperament. They also showed significant heritability of the anxious temperament phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, Oler et al. (2010) revealed significant heritability of metabolic activity in anxious temperament-associated hippocampal regions. However, activity in the amygdala region predictive of anxious temperament was not observed to be significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differed from each other. Oler et al. (2010) concluded that even though these structures are closely linked, the results suggested differential influences of genes and environment on how these brain regions mediate anxious temperament and the ongoing risk of developing anxiety and depression.
Molecular Genetics
### Serotonin Transporter
Transporter-facilitated uptake of serotonin has been implicated in anxiety in humans and in animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Lesch et al. (1996) found that transcription of the gene for serotonin transporter (SERT, or SLC6A4; 182138) is modulated by a common polymorphism in its upstream regulatory region. They found that the short variant of the polymorphism (182138.0001), designated 5-HTTLPR, reduces the transcriptional efficiency of the SLC6A4 gene promoter, resulting in decreased serotonin transporter expression and serotonin uptake in lymphoblasts. In family studies of 2 independently collected groups (505 total subjects), Lesch et al. (1996) found that neuroticism, the NEO personality inventory factor which is composed of anxiety and depression-related subfactors, was significantly associated with the SLC6A4 promoter polymorphism. The polymorphism was also associated with anxiety-related traits including 'tension,' 'suspiciousness,' and 'harm avoidance,' in 2 other personality assessment models. Lesch et al. (1996) determined that the polymorphism accounted for 3 to 4% of total variation and 7 to 9% of inherited variance of anxiety-related personality traits. The authors noted that if other genes were hypothesized to contribute similar gene dosage effects to anxiety, 10 to 15 genes might be predicted to be involved.
Mazzanti et al. (1998) found a relationship between the SLC6A4 promoter polymorphism and 2 anxiety-related subdimensions of harm avoidance in sib pairs, but found no association between the polymorphism and harm avoidance in others. Among 759 individuals, Jorm et al. (1998) found no association between the polymorphism and personality traits, including neuroticism, anxiety, depression, and alcoholism. In 74 same-sex sib pairs, Osher et al. (2000) found an association between 5-HTTLPR and harm avoidance and neuroticism. Sib-pair linkage analysis further supported a role of the polymorphism in anxiety-related personality traits.
To provide statistical measures of the strength of the relationship between long/short promoter polymorphisms of the serotonin transporter gene and trait anxiety, Schinka et al. (2004) conducted a metaanalysis of 26 studies of various ethnic groups. The results provided no support for a relationship between anxiety and the presence of the short form of the promoter polymorphism; however, there was strong evidence for the presence of moderating variables, and subsequent analysis revealed that choice of the measure of trait anxiety was significant. Studies using a neuroticism scale based on the 5-factor model of personality were found to produce a small positive effect.
Savitz and Ramesar (2004) reviewed the evidence that alleles of the serotonin transporter and the DRD4 (126452) genes impact variations in personality. They argued for the existence of a genuine effect: a gene-personality relationship rendered periodically latent through genetic epistasis, gene-environment interactions, variation in genetic background, and the presence of other variables.
Sen et al. (2004) noted that at least 26 studies had investigated a putative association between the functional serotonin transporter promoter polymorphism 5-HTTLPR and anxiety-related personality traits, with inconsistent results. They conducted a metaanalysis of these studies, which included 5,629 individuals, and found suggestive evidence for an association between the short allele (S) and increased anxiety-related personality trait scores (p = 0.087). Analysis of heterogeneity revealed that substantial variation was introduced by the inventories used; when analyses were stratified by inventory type, there was a significant association between 5-HTTLPR and neuroticism as measured by the NEO personality inventory (p = 0.000016) but not by other rating scales. Sen et al. (2004) concluded that there is a strong association between the serotonin transporter promoter variant and neuroticism, and that nonreplications are largely due to small sample size and use of different inventories.
### Tryptophan Hydroxylase
Nash et al. (2005) noted that genetic susceptibility to depression and anxiety is both overlapping and dimensional. To index this common genetic susceptibility, they created a quantitative phenotype from several depression and anxiety-related measures. They studied 119 sibships comprising 312 individuals from a community-based sample of 34,371 individuals, selected for extreme scores on this measure. A pathway-based candidate gene study examined 5 microsatellite markers located within or close to 5 serotonin system genes, i.e., HTR2C (312861), HTR1D (182133), HTR1B (182131), TPH1 (191060), and MAOB (309860). Statistical analysis using the quantitative TDT gave significant association with a microsatellite downstream of TPH1. When further analysis included a life-events composite as a covariable, a stronger association with TPH1 was observed.
### Association Studies
For a possible association between variation in expression of the NTRK3 gene and panic disorder related to agoraphobia, see 191316.
For a possible association between variation in the SIRT1 gene and anxiety disorders, see 604479.
In a study of 67 college-aged students, Roe et al. (2009) found a significant association between harm avoidance and the rs4603829 and rs4522666 SNPs in the CHRNA4 gene (118504) on chromosome 20q13 (p = 0.029 and p = 0.042, respectively, after false discovery rate (FDR) correction). Both SNPs are located in the 3-prime region of the CHRNA4 gene and showed partial linkage disequilibrium. Harm avoidance was assessed as a psychologic risk attitude measurement. Roe et al. (2009) postulated that the association may be related to dopamine modulation in the mesolimbic region, and may reflect changes in inhibitory responses.
Pituitary adenylate cyclase-activating polypeptide (PACAP), encoded by the ADCYAP1 gene (102980), and its receptor PAC1 (ADCYAP1R1; 102981) play an integral role in the regulation of cellular and behavioral stress responses. Ressler et al. (2011) hypothesized that PACAPergic systems may be important mediators of abnormal stress responses following psychological trauma contributing to posttraumatic stress disorder (PTSD), an extreme maladaptive and debilitating psychiatric disorder affecting up to 40% of individuals over lifetime exposure to traumatic events. To investigate this hypothesis, Ressler et al. (2011) analyzed blood levels of PACAP and genetic variation and methylation of PACAP and PAC1 genes in more than 1,200 heavily traumatized subjects with and without PTSD. They found a sex-specific association of PACAP blood levels with fear physiology, PTSD, and symptoms in females. Ressler et al. (2011) examined 44 SNPs spanning the PACAP and PAC1 genes, demonstrating a sex-specific association with PTSD. A single SNP in a putative estrogen response element with ADCYAP1R1, rs2267735, predicted PTSD diagnosis and symptoms in females only. This SNP also associated with fear discrimination and with ADCYAP1R1 mRNA expression in human brain. Methylation of ADCYAP1R1 in peripheral blood was also associated with PTSD. Complementing these human data, ADCYAP1R1 mRNA was induced with fear conditioning or estrogen replacement in rodent models. The data of Ressler et al. (2011) suggested that perturbations in the PACAP-PAC1 pathway are involved in abnormal stress responses underlying PTSD. These sex-specific effects may occur via estrogen regulation of ADCYAP1R1. Ressler et al. (2011) suggested that PACAP levels and ADCYAP1RA SNPs may serve as useful biomarkers to further the mechanistic understanding of PTSD.
Animal Model
Using a combination of behavioral analysis of 6 inbred mouse strains with quantitative gene expression profiling of several brain regions, Hovatta et al. (2005) identified 17 genes with expression patterns that correlated with anxiety-like behavioral phenotypes. Using lentivirus-mediated gene transfer, they found that local overexpression of glyoxalase-1 (138750) and glutathione reductase-1 (138300) in the mouse brain resulted in increased anxiety-like behavior, while local inhibition of glyoxalase-1 expression by RNA interference decreased the anxiety-like behavior. Hovatta et al. (2005) concluded that both of these genes are involved in oxidative stress metabolism, linking this pathway with anxiety-related behavior.
Johnson et al. (2010) showed that orexin (HCRT; 602358) may be involved in panic disorder and anxiety, both of which are disorders associated with increased arousal, hypervigilance, and stimulation of the autonomic nervous system. A rat model of panic disorder showed increased activation of Hcrt-positive cells in the dorsomedial-perifornical hypothalamus after sodium lactate administration that correlated with anxious behavior compared to nonpanic rats. This response was attenuated with siRNA against the Hcrt gene, as well as by antagonists to the Hcrt receptor (HCRTR1; 602392) injected directly into the stria terminalis. These attenuating effects mimicked treatment with benzodiazepines, which result in increased GABAergic activity. Finally, cerebrospinal fluid levels of orexin were increased among 53 individuals with panic anxiety compared to controls, suggesting that the orexin system may be involved in the pathophysiology of panic anxiety.
Mervis et al. (2012) found that transgenic mice with 3 or 4 copies of the Gtf2i gene (601679) on chromosome 7q11 showed significantly increased maternal separation-induced anxiety compared to mice with 1 or 2 copies of the Gtf2i gene, as measured by ultrasonic vocalizations. The authors studied this gene specifically after observing that patients with Williams-Beuren (WBS) duplication syndrome (609757) had significantly higher levels of separation anxiety compared to patients with WBS (194050) and to the general population. The GTF2I gene lies within the WBS critical region.
*[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
| ANXIETY | c0003467 | 1,050 | omim | https://www.omim.org/entry/607834 | 2019-09-22T16:08:41 | {"doid": ["2030"], "mesh": ["D001007"], "omim": ["607834"], "icd-10": ["F41.1"]} |
A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-30 (COXPD30) is caused by homozygous or compound heterozygous mutation in the TRMT10C gene (615423) on chromosome 3q12.
For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Clinical Features
Metodiev et al. (2016) reported 2 unrelated infants with a fatal systemic mitochondrial disease. One patient was of Caucasian descent and the other was of Kurdish descent. The patients presented at birth with hypotonia, feeding difficulties, and deafness. One also had cardiac left ventricular hypertrophy and brain imaging suggestive of frontal polymicrogyria. Laboratory studies in both patients showed lactic acidosis, increased cerebrospinal fluid lactate levels, increased serum alanine, and abnormal liver function tests. Both infants died of respiratory failure at age 5 months. Patient skeletal muscle cells showed decreased activities of mitochondrial complexes I and IV in both patients, and decreased complex III activity in only 1 patient. Muscle biopsy, performed in 1 patient, showed COX-deficient ragged-red fibers.
Inheritance
The transmission pattern of COXPD30 in the families reported by Metodiev et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 2 unrelated infants with fatal COXPD30, Metodiev et al. (2016) identified homozygous or compound heterozygous missense mutations in the TRMT10C gene (R181L, 615423.0001 and T272A, 615423.0002). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Patient fibroblasts showed decreased assembly of complexes I and IV, with mildly decreased complex III. This was associated with impaired mitochondrial protein synthesis as well as impaired mt-RNA processing efficiency with a mild accumulation of mitochondrial precursor RNA, but without severe effects on mature mt-mRNA or mt-tRNA steady-state levels. There was no effect on m(1)R9 methyltransferase activity. Transfection of patient cells with wildtype TRMT10C rescued the respiratory chain complex deficiencies and the defects in mitochondrial translation.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Ears \- Deafness, sensorineural CARDIOVASCULAR Heart \- Left ventricular hypertrophy (1 patient) ABDOMEN Liver \- Liver dysfunction Gastrointestinal \- Poor feeding \- Gastroesophageal reflux MUSCLE, SOFT TISSUES \- Hypotonia \- Decreased levels of mitochondrial respiratory complexes I, III, and IV \- Ragged red fibers \- COX-deficient fibers METABOLIC FEATURES \- Lactic acidosis LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased serum alanine \- Increased CSF lactate \- Abnormal liver enzymes MISCELLANEOUS \- Onset at birth \- Death in infancy may occur \- Two unrelated patients have been reported (last curated June 2016) MOLECULAR BASIS \- Caused by mutation in the tRNA methyltransferase 10C, mitochondrial RNase P subunit gene (TRMT10C, 615423.0001 ) ▲ 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
| COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 30 | c4310773 | 1,051 | omim | https://www.omim.org/entry/616974 | 2019-09-22T15:47:16 | {"omim": ["616974"], "orphanet": ["478042"], "synonyms": ["COXPD30"]} |
Telogen effluvium
An Afghan child displaying hair loss due to severe malnutrition
SpecialtyDermatology
Telogen effluvium is a scalp disorder characterized by the thinning or shedding of hair resulting from the early entry of hair in the telogen phase (the resting phase of the hair follicle).[1][2] It is in this phase that telogen hairs begin to shed at an increased rate, where normally the approximate rate of hair loss (having no effect on one's appearance) is 125 hairs per day.[3]
There are 5 potential alterations in the hair cycle that could lead to this shedding; immediate anagen release, delayed anagen release, short anagen syndrome, immediate telogen release, and delayed telogen release.[3][4]
* Immediate anagen release occurs when follicles leave anagen and are stimulated to enter telogen prematurely. The effects become visible 2–3 months later with increased telogen effluvium.
* Delayed anagen release, most commonly associated with pregnancy, involves the prolongation of anagen under the effect of pregnancy hormones, resulting in delayed but synchronous and heavy postpartum hair shedding.
* Short anagen syndrome is characterized by an idiopathic and persistent telogen hair shedding, as well as the inability to grow hair long. This is a result of the shortening of the duration of anagen, meaning a greater number of telogen hairs at any given time, and is responsible for the majority of chronic TE cases.
* Immediate telogen release generally occurs with drug-induced shortening of telogen leading to the premature reentrance of follicles to anagen, which causes a massive release of club (telogen) hairs. Drugs such as minoxidil can precipitate immediate telogen release.
* Delayed telogen release involves a prolonged telogen phase followed by a delayed transition to anagen. This occurs in animals with synchronous hair cycles that shed their hair or winter coats seasonally. This is also sometimes responsible for seasonal hair loss in humans.[3][4][5]
Emotional or physiological stress may result in an alteration of the normal hair cycle and cause the disorder, with potential causes including eating disorders, crash diets, pregnancy and childbirth, chronic illness, major surgery, anemia, severe emotional disorders, hypothyroidism, and drugs.[1][6]
Diagnostic tests, which may be performed to verify the diagnosis, include a trichogram, trichoscopy[7] and biopsy.[6] Effluvium can present with similar appearance to alopecia totalis, with further distinction by clinical course, microscopic examination of plucked follicles, or biopsy of the scalp.[8] Histology would show telogen hair follicles in the dermis with minimal inflammation in effluvium, and dense peribulbar lymphocytic infiltrate in alopecia totalis.[9]
Vitamin D levels may also play a role in the normal hair cycle.[10]
Many new cosmetic treatments have been reported, including stemoxydine, nioxin, minoxidil, and a leave-on technology combination: caffeine, niacinamide, panthenol, dimethicone, and an acrylate polymer (CNPDA). This treatment has shown to increase the diameter of existing, individual scalp hair fibres by 2–5 μm, yielding a significant increase of approximately 10% in the cross-sectional area of each hair. Additionally, CNPDA-thickened hairs also demonstrate altered mechanical properties of thicker fibres; increased suppleness/pliability, and increased ability to withstand force without breaking.[11]
## See also[edit]
* Anagen effluvium
* Noncicatricial alopecia
## References[edit]
1. ^ a b Marks, James G; Miller, Jeffery (2006). Lookingbill and Marks' Principles of Dermatology (4th ed.). Elsevier Inc. Page 263. ISBN 1-4160-3185-5.
2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
3. ^ a b c Khan Mohammad Beigi, Pooya (2018). "Introduction". In Khan Mohammad Beigi, Pooya (ed.). Alopecia Areata: A Clinician's Guide. Springer International Publishing. pp. 3–5. doi:10.1007/978-3-319-72134-7_1. ISBN 9783319721347.
4. ^ a b Liyanage, Deepa; Sinclair, Rodney (2016-03-25). "Telogen Effluvium". Cosmetics. 3 (2): 13. doi:10.3390/cosmetics3020013. ISSN 2079-9284.
5. ^ Grover, Chander; Khurana, Ananta (2013). "Telogen effluvium". Indian Journal of Dermatology, Venereology and Leprology. 79 (5): 591–603. doi:10.4103/0378-6323.116731. ISSN 0378-6323. PMID 23974577.
6. ^ a b Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
7. ^ Rudnicka L, Olszewska M, Rakowska A, Kowalska-Oledzka E, Slowinska M (2008). "Trichoscopy: a new method for diagnosing hair loss". J Drugs Dermatol. 7 (7): 651–654. PMID 18664157.
8. ^ Werner, B.; Mulinari-Brenner, F. (2012). "Clinical and histological challenge in the differential diagnosis of diffuse alopecia: Female androgenetic alopecia, telogen effluvium and alopecia areata – part II". Anais Brasileiros de Dermatologia. 87 (6): 884–890. doi:10.1590/S0365-05962012000600010. PMC 3699921. PMID 23197208.
9. ^ Alkhalifah, A. (2012). "Alopecia Areata Update". Dermatologic Clinics. 31 (1): 93–108. doi:10.1016/j.det.2012.08.010. PMID 23159179.
10. ^ Amor KT, Rashid RM, Mirmirani P (2010). "Does D matter? The role of vitamin D in hair disorders and hair follicle cycling". Dermatol. Online J. 16: 3. PMID 20178699.CS1 maint: multiple names: authors list (link)
11. ^ Davis, M.G.; Thomas, J.H.; van de Velde, S.; Boissy, Y.; Dawson, T.L.; Iveson, R.; Sutton, K. (December 2011). "A novel cosmetic approach to treat thinning hair". British Journal of Dermatology. 165: 24–30. doi:10.1111/j.1365-2133.2011.10633.x. ISSN 0007-0963. PMID 22171682.
## External links[edit]
Classification
D
* ICD-10: L65.0 (ILDS L65.000)
* ICD-9-CM: 704.02
* DiseasesDB: 12926
* v
* t
* e
Diseases of the skin and appendages by morphology
Growths
Epidermal
* Wart
* Callus
* Seborrheic keratosis
* Acrochordon
* Molluscum contagiosum
* Actinic keratosis
* Squamous-cell carcinoma
* Basal-cell carcinoma
* Merkel-cell carcinoma
* Nevus sebaceous
* Trichoepithelioma
Pigmented
* Freckles
* Lentigo
* Melasma
* Nevus
* Melanoma
Dermal and
subcutaneous
* Epidermal inclusion cyst
* Hemangioma
* Dermatofibroma (benign fibrous histiocytoma)
* Keloid
* Lipoma
* Neurofibroma
* Xanthoma
* Kaposi's sarcoma
* Infantile digital fibromatosis
* Granular cell tumor
* Leiomyoma
* Lymphangioma circumscriptum
* Myxoid cyst
Rashes
With
epidermal
involvement
Eczematous
* Contact dermatitis
* Atopic dermatitis
* Seborrheic dermatitis
* Stasis dermatitis
* Lichen simplex chronicus
* Darier's disease
* Glucagonoma syndrome
* Langerhans cell histiocytosis
* Lichen sclerosus
* Pemphigus foliaceus
* Wiskott–Aldrich syndrome
* Zinc deficiency
Scaling
* Psoriasis
* Tinea (Corporis
* Cruris
* Pedis
* Manuum
* Faciei)
* Pityriasis rosea
* Secondary syphilis
* Mycosis fungoides
* Systemic lupus erythematosus
* Pityriasis rubra pilaris
* Parapsoriasis
* Ichthyosis
Blistering
* Herpes simplex
* Herpes zoster
* Varicella
* Bullous impetigo
* Acute contact dermatitis
* Pemphigus vulgaris
* Bullous pemphigoid
* Dermatitis herpetiformis
* Porphyria cutanea tarda
* Epidermolysis bullosa simplex
Papular
* Scabies
* Insect bite reactions
* Lichen planus
* Miliaria
* Keratosis pilaris
* Lichen spinulosus
* Transient acantholytic dermatosis
* Lichen nitidus
* Pityriasis lichenoides et varioliformis acuta
Pustular
* Acne vulgaris
* Acne rosacea
* Folliculitis
* Impetigo
* Candidiasis
* Gonococcemia
* Dermatophyte
* Coccidioidomycosis
* Subcorneal pustular dermatosis
Hypopigmented
* Tinea versicolor
* Vitiligo
* Pityriasis alba
* Postinflammatory hyperpigmentation
* Tuberous sclerosis
* Idiopathic guttate hypomelanosis
* Leprosy
* Hypopigmented mycosis fungoides
Without
epidermal
involvement
Red
Blanchable
Erythema
Generalized
* Drug eruptions
* Viral exanthems
* Toxic erythema
* Systemic lupus erythematosus
Localized
* Cellulitis
* Abscess
* Boil
* Erythema nodosum
* Carcinoid syndrome
* Fixed drug eruption
Specialized
* Urticaria
* Erythema (Multiforme
* Migrans
* Gyratum repens
* Annulare centrifugum
* Ab igne)
Nonblanchable
Purpura
Macular
* Thrombocytopenic purpura
* Actinic/solar purpura
Papular
* Disseminated intravascular coagulation
* Vasculitis
Indurated
* Scleroderma/morphea
* Granuloma annulare
* Lichen sclerosis et atrophicus
* Necrobiosis lipoidica
Miscellaneous
disorders
Ulcers
*
Hair
* Telogen effluvium
* Androgenic alopecia
* Alopecia areata
* Systemic lupus erythematosus
* Tinea capitis
* Loose anagen syndrome
* Lichen planopilaris
* Folliculitis decalvans
* Acne keloidalis nuchae
Nail
* Onychomycosis
* Psoriasis
* Paronychia
* Ingrown nail
Mucous
membrane
* Aphthous stomatitis
* Oral candidiasis
* Lichen planus
* Leukoplakia
* Pemphigus vulgaris
* Mucous membrane pemphigoid
* Cicatricial pemphigoid
* Herpesvirus
* Coxsackievirus
* Syphilis
* Systemic histoplasmosis
* Squamous-cell carcinoma
* v
* t
* e
Disorders of skin appendages
Nail
* thickness: Onychogryphosis
* Onychauxis
* color: Beau's lines
* Yellow nail syndrome
* Leukonychia
* Azure lunula
* shape: Koilonychia
* Nail clubbing
* behavior: Onychotillomania
* Onychophagia
* other: Ingrown nail
* Anonychia
* ungrouped: Paronychia
* Acute
* Chronic
* Chevron nail
* Congenital onychodysplasia of the index fingers
* Green nails
* Half and half nails
* Hangnail
* Hapalonychia
* Hook nail
* Ingrown nail
* Lichen planus of the nails
* Longitudinal erythronychia
* Malalignment of the nail plate
* Median nail dystrophy
* Mees' lines
* Melanonychia
* Muehrcke's lines
* Nail–patella syndrome
* Onychoatrophy
* Onycholysis
* Onychomadesis
* Onychomatricoma
* Onychomycosis
* Onychophosis
* Onychoptosis defluvium
* Onychorrhexis
* Onychoschizia
* Platonychia
* Pincer nails
* Plummer's nail
* Psoriatic nails
* Pterygium inversum unguis
* Pterygium unguis
* Purpura of the nail bed
* Racquet nail
* Red lunulae
* Shell nail syndrome
* Splinter hemorrhage
* Spotted lunulae
* Staining of the nail plate
* Stippled nails
* Subungual hematoma
* Terry's nails
* Twenty-nail dystrophy
Hair
Hair loss/
Baldness
* noncicatricial alopecia: Alopecia
* areata
* totalis
* universalis
* Ophiasis
* Androgenic alopecia (male-pattern baldness)
* Hypotrichosis
* Telogen effluvium
* Traction alopecia
* Lichen planopilaris
* Trichorrhexis nodosa
* Alopecia neoplastica
* Anagen effluvium
* Alopecia mucinosa
* cicatricial alopecia: Pseudopelade of Brocq
* Central centrifugal cicatricial alopecia
* Pressure alopecia
* Traumatic alopecia
* Tumor alopecia
* Hot comb alopecia
* Perifolliculitis capitis abscedens et suffodiens
* Graham-Little syndrome
* Folliculitis decalvans
* ungrouped: Triangular alopecia
* Frontal fibrosing alopecia
* Marie Unna hereditary hypotrichosis
Hypertrichosis
* Hirsutism
* Acquired
* localised
* generalised
* patterned
* Congenital
* generalised
* localised
* X-linked
* Prepubertal
Acneiform
eruption
Acne
* Acne vulgaris
* Acne conglobata
* Acne miliaris necrotica
* Tropical acne
* Infantile acne/Neonatal acne
* Excoriated acne
* Acne fulminans
* Acne medicamentosa (e.g., steroid acne)
* Halogen acne
* Iododerma
* Bromoderma
* Chloracne
* Oil acne
* Tar acne
* Acne cosmetica
* Occupational acne
* Acne aestivalis
* Acne keloidalis nuchae
* Acne mechanica
* Acne with facial edema
* Pomade acne
* Acne necrotica
* Blackhead
* Lupus miliaris disseminatus faciei
Rosacea
* Perioral dermatitis
* Granulomatous perioral dermatitis
* Phymatous rosacea
* Rhinophyma
* Blepharophyma
* Gnathophyma
* Metophyma
* Otophyma
* Papulopustular rosacea
* Lupoid rosacea
* Erythrotelangiectatic rosacea
* Glandular rosacea
* Gram-negative rosacea
* Steroid rosacea
* Ocular rosacea
* Persistent edema of rosacea
* Rosacea conglobata
* variants
* Periorificial dermatitis
* Pyoderma faciale
Ungrouped
* Granulomatous facial dermatitis
* Idiopathic facial aseptic granuloma
* Periorbital dermatitis
* SAPHO syndrome
Follicular cysts
* "Sebaceous cyst"
* Epidermoid cyst
* Trichilemmal cyst
* Steatocystoma
* simplex
* multiplex
* Milia
Inflammation
* Folliculitis
* Folliculitis nares perforans
* Tufted folliculitis
* Pseudofolliculitis barbae
* Hidradenitis
* Hidradenitis suppurativa
* Recurrent palmoplantar hidradenitis
* Neutrophilic eccrine hidradenitis
Ungrouped
* Acrokeratosis paraneoplastica of Bazex
* Acroosteolysis
* Bubble hair deformity
* Disseminate and recurrent infundibulofolliculitis
* Erosive pustular dermatitis of the scalp
* Erythromelanosis follicularis faciei et colli
* Hair casts
* Hair follicle nevus
* Intermittent hair–follicle dystrophy
* Keratosis pilaris atropicans
* Kinking hair
* Koenen's tumor
* Lichen planopilaris
* Lichen spinulosus
* Loose anagen syndrome
* Menkes kinky hair syndrome
* Monilethrix
* Parakeratosis pustulosa
* Pili (Pili annulati
* Pili bifurcati
* Pili multigemini
* Pili pseudoannulati
* Pili torti)
* Pityriasis amiantacea
* Plica neuropathica
* Poliosis
* Rubinstein–Taybi syndrome
* Setleis syndrome
* Traumatic anserine folliculosis
* Trichomegaly
* Trichomycosis axillaris
* Trichorrhexis (Trichorrhexis invaginata
* Trichorrhexis nodosa)
* Trichostasis spinulosa
* Uncombable hair syndrome
* Wooly hair nevus
Sweat
glands
Eccrine
* Miliaria
* Colloid milium
* Miliaria crystalline
* Miliaria profunda
* Miliaria pustulosa
* Miliaria rubra
* Occlusion miliaria
* Postmiliarial hypohidrosis
* Granulosis rubra nasi
* Ross’ syndrome
* Anhidrosis
* Hyperhidrosis
* Generalized
* Gustatory
* Palmoplantar
Apocrine
* Body odor
* Chromhidrosis
* Fox–Fordyce disease
Sebaceous
* Sebaceous hyperplasia
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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
| Telogen effluvium | c0263518 | 1,052 | wikipedia | https://en.wikipedia.org/wiki/Telogen_effluvium | 2021-01-18T19:01:44 | {"umls": ["C0263518"], "wikidata": ["Q26967"]} |
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Adiadochokinesia" – news · newspapers · books · scholar · JSTOR (September 2018) (Learn how and when to remove this template message)
Adiadochokinesia is a dyskinesia consisting of inability to perform the rapid alternating movements of diadochokinesia. Called also adiadochocinesia, adiadochokinesis, and adiadokokinesia.[1]
Compare with dysdiadochokinesia, which is an impairment of the ability to perform rapidly alternating movements.
## References[edit]
1. ^ "Adiadochokinesia - Oxford Reference". Retrieved 2018-07-31.
* Taber's Cyclopedic Medical Dictionary, 21ed. 2009
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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
| Adiadochokinesia | c0234357 | 1,053 | wikipedia | https://en.wikipedia.org/wiki/Adiadochokinesia | 2021-01-18T18:34:19 | {"mesh": ["D002524"], "umls": ["C0234357"], "wikidata": ["Q8272913"]} |
A number sign (#) is used with this entry because autosomal recessive cutis laxa type IA (ARCL1A) is caused by homozygous or compound heterozygous mutation in the FBLN5 gene (604580) on chromosome 14q32.
Heterozygous mutation in the FBLN5 gene can cause an autosomal dominant form of cutis laxa (ADCL2; 614434).
Description
Cutis laxa is a collection of disorders that are typified by loose and/or wrinkled skin that imparts a prematurely aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The skin lacks elastic recoil, in marked contrast to the hyperelasticity apparent in classical Ehlers-Danlos syndrome (see 130000). These properties are nearly always attributable to loss, fragmentation, or severe disorganization of dermal elastic fibers (summary by Davidson and Giro, 2002).
The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. Type I autosomal recessive cutis laxa (ARCL1) is a specific, life-threatening disorder with organ involvement, lung atelectasis and emphysema, diverticula of the gastrointestinal and genitourinary systems, and vascular anomalies. Associated cranial anomalies, late closure of the fontanel, joint laxity, hip dislocation, and inguinal hernia have been observed but are uncommon. Diminution of elastic fibers throughout the dermis and abnormal elastin components by electron microscopy are pathognomonic (summary by Morava et al., 2009).
Classification of autosomal recessive cutis laxa is further divided into type II (ARCL2), associated with bone dystrophy, joint laxity, and developmental delay; and type III (ARCL3), or de Barsy syndrome, which presents very severe symptoms, with ocular involvement and mental retardation (summary by Davidson and Giro, 2002).
For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant cutis laxa, see 123700.
### Genetic Heterogeneity of Autosomal Recessive Cutis Laxa
Also see ARCL1B (614437), caused by mutation in the FBLN4 gene (EFEMP2; 604633), and ARCL1C (613177), caused by mutation in the LTBP4 gene (FAM72A; 614710).
ARCL2A (219200) is caused by mutation in the ATP6V0A2 gene (611716). ARCL2B (612940) is caused by mutation in the PYCR1 gene (179035). ARCL2C (617402) is caused by mutation in the ATP6V1E1 gene (108746). ARCL2D (617403) is caused by mutation in the ATP6V1A gene (607027).
ARCL3A (219150) is caused by mutation in the ALDH18A1 gene (138250). ARCL3B (614438) is caused by mutation in the PYCR1 gene (179035).
Clinical Features
Goltz et al. (1965) described affected brothers and suggested recessive inheritance because of other reported instances of affected sibs as well as parental consanguinity. One child had multiple diverticula (esophagus, duodenum, ileum, bladder). The other had pulmonary emphysema and died at 18 months from cor pulmonale. The authors suggested 'generalized elastolysis' as a more satisfactory designation. Death from pulmonary emphysema was also described by Christiaens et al. (1954).
Hayden et al. (1968) described a 4-year-old patient with cutis laxa and congenital pulmonary artery stenosis. A deficiency of elastic fibers in the skin was reported.
Hajjar and Joyner (1968) described a 6-month-old Puerto Rican child with advanced pulmonary emphysema. Serum copper level was low and urinary excretion high, consistent with the theory that deficiency of serum copper produces a low elastase inhibitor substance with increased destruction of elastic fibers (Goltz et al., 1965). The patient of Maxwell and Esterly (1969) had pulmonary emphysema. Hernias have been an important feature of many cases (Schreiber and Tilley, 1961; Cashman, 1957; Goltz et al., 1965).
Welch et al. (1971) described 3 sons of a consanguineous mating who had features suggesting cutis laxa of the malignant form. Unusual features were tortuous arteries and arterial aneurysms. The father and many of his relatives had the benign hypermobile form of Ehlers-Danlos syndrome. Beighton (1972) reported a case with first-cousin parents and a case resulting from a father-daughter mating. Sestak (1962) reported affected brother and sister whose parents were first cousins once removed and who had a common ancestor of the 2 parents reported affected. One of these sibs was pictured by Cashman (1957). Dallaire et al. (1976) reported a leprechaunoid disorder in 3 male infants from 2 related and consanguineous pairs of parents of Italian origin. Many of the features suggested cutis laxa. All 3 boys died in the first year of life of severe cardiopulmonary complications.
Fitzsimmons et al. (1985) reported 3 affected brothers, 2 of whom had significant involvement of other organs. They emphasized that the skin changes may be rather inconspicuous.
One patient with cutis laxa diagnosed in the early years of life had by age 36 developed mild emphysema, despite the fact that she was a nonsmoker, and had hypertension for more than a decade due to fibromuscular dysplasia in both renal arteries. Fibromuscular dysplasia was demonstrated also in the right carotid artery (17:McKusick, 1972). In a 1-year-old child with cutis laxa, McKusick (1972) found evidence of multiple pulmonary artery stenoses, possibly due to fibromuscular dysplasia.
In 3 of 4 sibs (2 boys, 1 girl) from a consanguineous Irish-American mating, Anderson et al. (1984) described severe congenital hemolytic anemia of unknown cause and early-onset pulmonary emphysema. Two of the 3 affected sibs died of septic shock after splenectomy, at ages 7 and 3.5 years. The third sib, 20 years old at the time of report, demonstrated severe pulmonary emphysema and cutis laxa by age 15. Autopsy of the 2 deceased sibs showed bilateral hemorrhagic necrosis of the adrenals and pulmonary changes of emphysema. In the 7-year-old, extensive, diffuse giant cell infiltration was found in the lungs, bone marrow, lymph nodes and epicardium; the lungs of the 3.5-year-old showed scattered multinucleated giant cells.
In 3 sibs born of second-cousin Turkish parents, Van Maldergem et al. (1988) described severe congenital cutis laxa with pulmonary emphysema.
In 2 boys from separate families, Khakoo et al. (1997) described autosomal recessive cutis laxa and deficiency of lysyl oxidase (153455). Neither boy had the occipital osseous projections or abnormality of copper metabolism that are characteristic of the X-linked form (304150). Both showed wormian bones of the lambdoid sutures and osteoporosis of the lumbar vertebrae in addition to the characteristic feature of congenital cutis laxa. In 1 family, the mother showed partial deficiency of lysyl oxidase; in the other, the parents were first cousins.
Armstrong et al. (2003) described a form of cutis laxa in a 7.5-year-old boy with loose translucent skin, aortic dilatation, hyperextensible veins, recurrent respiratory problems, pectus excavatum, arthralgias, lax joints, mild epiphyseal dysplasia, and umbilical and inguinal hernias. He also had developmental delay, progressive bilateral sensorineural hearing loss, an unusual facial appearance, unusual radiographic changes in some of the phalanges, glanular hypospadias, shawl scrotum, and undescended testes. Electrophoresis of types I and III procollagens and collagens, and quantification of serum copper and ceruloplasmin, were normal. Armstrong et al. (2003) concluded that the patient had a previously unrecognized form of cutis laxa.
Biochemical Features
Olsen et al. (1988) found no qualitative difference between control and cutis laxa elastin mRNAs. However, quantitation of the elastin mRNA by slot blot hybridization showed markedly reduced levels in all 6 patients studied. This may account for the diminished elastin production in these patients. The patients varied from newborn to 36 months of age. The reduced elastin mRNA levels could result either from an alteration in the rate of transcription of the elastin gene (130160) or from instability of the cutis laxa elastin mRNAs, causing enhanced degradation. In some cases, enhanced degradation of elastin has been demonstrated (Uitto, 1985; Anderson et al., 1985), attesting to the molecular heterogeneity of cutis laxa.
In the case of a 27-month-old boy with this disorder, Kitano et al. (1989) found diminution of elastic fibers throughout the dermis and, by electron microscopy, globular and unstained elastin and relatively large amounts of the microfibrillar components of elastic fibers.
Molecular Genetics
Loeys et al. (2002) studied a large consanguineous Turkish family, originally described by Van Maldergem et al. (1988), in which 4 patients were affected by autosomal recessive cutis laxa type I. An affected infant from this family manifested loose skin, poorly developed elastic fibers in skin (seen microscopically), supravalvular aortic stenosis, and flaccid trachea. She developed emphysema of the anterior segments of both lungs by age 6 months. Hemizygosity for an elastin deletion was excluded by FISH, and the locus was further excluded by linkage analysis. The authors demonstrated the presence of a homozygous missense mutation in the FBLN5 gene, resulting in a ser227-to-pro substitution (S227P; 604580.0001) in the fourth cbEGF-like domain of the FBLN5 protein.
Because missense mutations in the FBLN5 gene cause either autosomal recessive cutis laxa type I or ARMD3 (608895), Lotery et al. (2006) raised the possibility that patients with autosomal recessive cutis laxa caused by FBLN5 mutation may have early-onset ARMD, and that their parents (heterozygous for these mutations) may themselves be at higher risk of ARMD than the general population.
Hu et al. (2006) analyzed 2 disease-causing missense substitutions in fibulin-5, C217R (604580.0010) and S227P, and found evidence for misfolding, decreased secretion, and reduced interaction with elastin and fibrillin-1, resulting in impaired elastic fiber development. These findings supported the hypothesis that fibulin-5 is necessary for elastic fiber formation by facilitating the deposition of elastin onto a microfibrillar scaffold via direct molecular interactions.
Callewaert et al. (2013) analyzed the FBLN4 (604633), FBLN5, and LTBP4 (604710) genes in 12 families with type 1 ARCL, and identified homozygous mutations in the FLBN5 gene in 2 families (604580.0010 and 604580.0011). Homozygous or compound heterozygous mutations in LTBP4 were identified in 9 families (see, e.g., 604710.0005-604710.0008). No mutations were found in the FBLN4 gene, and no mutations were detected in 1 family in which the proband had cutis laxa and bladder diverticula without obvious emphysema. Callewaert et al. (2013) noted that the FBLN5 and LTBP4 mutations caused a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seemed to be more severe in patients with LTBP4 mutations.
History
Agha et al. (1978) suggested that there are 2 forms of recessive cutis laxa. In one type, congenital cutis laxa is associated with a generalized disorder of elastic tissue leading to diaphragmatic and other hernias, diverticula of the gastrointestinal and urinary tract, and infantile emphysema. Death usually occurs in the first year of life. Beighton (1972), Cashman (1957), Christiaens et al. (1954), Goltz et al. (1965), Hajjar and Joyner (1968), Maxwell and Esterly (1969) and Sestak (1962) reported cases. The second form is accompanied by prenatal and postnatal growth deficiency, large fontanels with delayed closure, congenital hip dislocation, and lax joints; see 219200.
INHERITANCE \- Autosomal recessive GROWTH Height \- Fetal overgrowth HEAD & NECK Head \- Microcephaly Face \- Sagging cheeks CARDIOVASCULAR Heart \- Supravalvular aortic stenosis Vascular \- Vascular tortuosity \- Ascending aortic aneurysm RESPIRATORY \- Recurrent respiratory infections Lung \- Emphysema CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum Diaphragm \- Diaphragmatic hernia ABDOMEN External Features \- Umbilical hernias GENITOURINARY External Genitalia (Male) \- Inguinal hernia External Genitalia (Female) \- Inguinal hernia Bladder \- Bladder diverticula SKELETAL \- Congenital fractures \- Joint laxity Hands \- Arachnodactyly SKIN, NAILS, & HAIR Skin \- Cutis laxa \- Loose redundant skin \- Excessive skin folds \- Normal wound healing \- No skin hyperelasticity Skin Histology \- Increased vascularization, reduced collagen bundle size \- Underdeveloped elastic fibers in dermis PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios MISCELLANEOUS \- Genetic heterogeneity MOLECULAR BASIS \- Caused by mutation in the fibulin 5 gene (FBLN5, 604580.0001 ) ▲ Close
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*[Ki]: Inhibitor constant
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*[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
| CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IA | c0432336 | 1,054 | omim | https://www.omim.org/entry/219100 | 2019-09-22T16:29:13 | {"doid": ["0070135"], "omim": ["219100"], "orphanet": ["90349"], "synonyms": ["Alternative titles", "ARCL1", "CUTIS LAXA, AUTOSOMAL RECESSIVE"], "genereviews": ["NBK5201"]} |
Yagi et al. (1994) presented the cases of 3 brothers with congenital hypopituitarism (see 613038) and central diabetes insipidus (see 125700). All 3 showed clinical features typical of congenital hypopituitarism: neonatal hypoglycemia, short stature, protruding forehead, and microgenitalia. All had hypoplastic genitalia indicating in utero gonadotropin deficiency, and all had complete growth hormone deficiency. One had low levels of thyroid hormones and TSH, indicating central hypothyroidism. Two water deprivation tests showed complete arginine vasopressin deficiency in two and partial deficiency in the third. Magnetic resonance imaging indicated absence of the pituitary stalk and severe hypoplasia of the anterior pituitary in all 3 brothers. The posterior pituitary was absent in 2 of the 3; the other sib had an ectopic posterior pituitary.
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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
| HYPOPITUITARISM, CONGENITAL, WITH CENTRAL DIABETES INSIPIDUS | c1855800 | 1,055 | omim | https://www.omim.org/entry/241540 | 2019-09-22T16:26:35 | {"mesh": ["C565477"], "omim": ["241540"]} |
Paget disease of bone is a disorder that causes bones to grow larger and weaker than normal. Affected bones may be misshapen and easily broken (fractured).
The classic form of Paget disease of bone typically appears in middle age or later. It usually occurs in one or a few bones and does not spread from one bone to another. Any bones can be affected, although the disease most commonly affects bones in the spine, pelvis, skull, or legs.
Many people with classic Paget disease of bone do not experience any symptoms associated with their bone abnormalities. The disease is often diagnosed unexpectedly by x-rays or laboratory tests done for other reasons. People who develop symptoms are most likely to experience pain. The affected bones may themselves be painful, or pain may be caused by arthritis in nearby joints. Arthritis results when the distortion of bones, particularly weight-bearing bones in the legs, causes extra wear and tear on the joints. Arthritis most frequently affects the knees and hips in people with this disease.
Other complications of Paget disease of bone depend on which bones are affected. If the disease occurs in bones of the skull, it can cause an enlarged head, hearing loss, headaches, and dizziness. If the disease affects bones in the spine, it can lead to numbness and tingling (due to pinched nerves) and abnormal spinal curvature. In the leg bones, the disease can cause bowed legs and difficulty walking.
A rare type of bone cancer called osteosarcoma has been associated with Paget disease of bone. This type of cancer probably occurs in less than 1 in 1,000 people with this disease.
Early-onset Paget disease of bone is a less common form of the disease that appears in a person's teens or twenties. Its features are similar to those of the classic form of the disease, although it is more likely to affect the skull, spine, and ribs (the axial skeleton) and the small bones of the hands. The early-onset form of the disorder is also associated with hearing loss early in life.
## Frequency
Classic Paget disease of bone occurs in approximately 1 percent of people older than 40 in the United States. Scientists estimate that about 1 million people in this country have the disease. It is most common in people of western European heritage.
Early-onset Paget disease of bone is much rarer. This form of the disorder has been reported in only a few families.
## Causes
A combination of genetic and environmental factors likely play a role in causing Paget disease of bone. Researchers have identified changes in several genes that increase the risk of the disorder. Other factors, including infections with certain viruses, may be involved in triggering the disease in people who are at risk. However, the influence of genetic and environmental factors on the development of Paget disease of bone remains unclear.
Researchers have identified variations in three genes that are associated with Paget disease of bone: SQSTM1, TNFRSF11A, and TNFRSF11B. Mutations in the SQSTM1 gene are the most common genetic cause of classic Paget disease of bone, accounting for 10 to 50 percent of cases that run in families and 5 to 30 percent of cases in which there is no family history of the disease. Variations in the TNFRSF11B gene also appear to increase the risk of the classic form of the disorder, particularly in women. TNFRSF11A mutations cause the early-onset form of Paget disease of bone.
The SQSTM1, TNFRSF11A, and TNFRSF11B genes are involved in bone remodeling, a normal process in which old bone is broken down and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy. Paget disease of bone disrupts the bone remodeling process. Affected bone is broken down abnormally and then replaced much faster than usual. When the new bone tissue grows, it is larger, weaker, and less organized than normal bone. It is unclear why these problems with bone remodeling affect some bones but not others in people with this disease.
Researchers are looking for additional genes that may influence a person's chances of developing Paget disease of bone. Studies suggest that genetic variations in certain regions of chromosome 2, chromosome 5, and chromosome 10 appear to contribute to disease risk. However, the associated genes on these chromosomes have not been identified.
### Learn more about the genes associated with Paget disease of bone
* SQSTM1
* TNFRSF11A
* TNFRSF11B
## Inheritance Pattern
In 15 to 40 percent of all cases of classic Paget disease of bone, the disorder has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that having one copy of an altered gene in each cell is sufficient to cause the disorder.
In the remaining cases, the inheritance pattern of classic Paget disease of bone is unclear. Many affected people have no family history of the disease, although it sometimes clusters in families. Studies suggest that close relatives of people with classic Paget disease of bone are 7 to 10 times more likely to develop the disease than people without an affected relative.
Early-onset Paget disease of bone is inherited in an autosomal dominant pattern. In people with this form of the disorder, having one altered copy of the TNFRSF11A gene in each cell is sufficient to cause the disease.
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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
| Paget disease of bone | c4085251 | 1,056 | medlineplus | https://medlineplus.gov/genetics/condition/paget-disease-of-bone/ | 2021-01-27T08:25:02 | {"gard": ["8615", "4191"], "omim": ["602080", "167250", "606263", "239000"], "synonyms": []} |
Becker muscular dystrophy (BMD) is an inherited condition that causes progressive weakness and wasting of the skeletal and cardiac (heart) muscles. It primarily affects males. The age of onset and rate of progression can vary. Muscle weakness usually becomes apparent between the ages of 5 and 15. In some cases, heart involvement (cardiomyopathy) is the first sign. BMD is caused by a mutation in the DMD gene and is inherited in an X-linked recessive manner. BMD is very similar to Duchenne muscular dystrophy, except that in BMD, symptoms begin later and progress at a slower rate. There is no cure for this condition, but there is ongoing research that shows significant promise in treating the disease. Current treatment aims to relieve symptoms and improve quality of life. People with BMD may survive into their 40s or beyond.
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*[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
| Becker muscular dystrophy | c0917713 | 1,057 | gard | https://rarediseases.info.nih.gov/diseases/5900/becker-muscular-dystrophy | 2021-01-18T18:01:52 | {"mesh": ["D020388"], "omim": ["300376"], "umls": ["C0917713"], "orphanet": ["98895"], "synonyms": ["Benign pseudohypertrophic muscular dystrophy", "Becker's muscular dystrophy", "Muscular dystrophy, Becker type", "Muscular dystrophy pseudohypertrophic progressive, Becker type", "Becker dystrophinopathy"]} |
## Clinical Features
Barnes et al. (1969) reported 2 unrelated infants with thoracic dystrophy. The second child showed classic features of Jeune syndrome (see 208500); the first, however, was unusual in that the rib shortening was less severe, there was laryngeal stenosis, and similar but less severe clinical features were present in the mother. Subsequently the mother gave birth to a second child with the same syndrome. In view of the early death of the first sib, surgery to increase thoracic volume was performed. This intervention, a qualified success, was reported by Barnes et al. (1971). Burn et al. (1986) gave a follow-up of this family with the conclusion that it represents a distinct disorder which they called thoracolaryngopelvic dysplasia or Barnes syndrome. The mother had 'chest infections' in early childhood, grew to an adult height of 170.2 cm, required cesarean section because of small pelvis, and had complications of anesthesia because of laryngeal stenosis and reduced lung volume. Her first child, reported by Barnes et al. (1969), died at 7 weeks of age. Necropsy showed small lungs, abnormal laryngeal cartilages, and widely expanded costochondral junctions with 'dystrophic' changes histologically. Her second child was the subject of the report by Barnes et al. (1971). At 6.5 months the sternum was split and bone grafts inserted as struts to hold the halves apart. She remained on ventilatory support at home until age 4 years and had a tracheostomy in place until age 9 years. At the age of 14 years she developed respiratory failure following a chest infection and again required tracheostomy. Her height was at the 50th centile. Death due to severe respiratory failure and cor pulmonale occurred soon thereafter. Burn et al. (1986) suggested that the family reported by Bankier and Danks (1983) as thoracopelvic dysostosis (187770) may have had this disorder.
INHERITANCE \- Autosomal dominant GROWTH Height \- Normal height Other \- Asthenic habitus RESPIRATORY Larynx \- Laryngeal stenosis CHEST External Features \- Small, rigid chest \- Bell-shaped chest Ribs Sternum Clavicles & Scapulae \- Short, horizontal ribs \- Widened metaphyses \- Irregular chondrocostal junctions SKELETAL Spine \- Scoliosis \- Irregular endplates Pelvis \- Narrow pelvis \- Flared iliac crest \- Small iliac wings \- Shallow sacroiliac notch PRENATAL MANIFESTATIONS Maternal \- Small pelvis necessitates caesarean section ▲ 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
| THORACOLARYNGOPELVIC DYSPLASIA | c1861197 | 1,058 | omim | https://www.omim.org/entry/187760 | 2019-09-22T16:32:42 | {"mesh": ["C536517"], "omim": ["187760"], "orphanet": ["3317"], "synonyms": ["Alternative titles", "BARNES SYNDROME"]} |
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Find sources: "Ocular tilt reaction" – news · newspapers · books · scholar · JSTOR (June 2017) (Learn how and when to remove this template message)
The Ocular tilt reaction (OTR), comprises skew deviation, head tilt and ocular torsion involving structures of the inner ear responsible for maintenance of balance of the body i.e. the semi-circular canals (SCC), utricle and saccule.
Each anterior semi-circular canals has excitatory projections to the ipsilateral superior rectus muscle and its yoke i.e., the contralateral inferior oblique while simultaneously inhibiting the ipsilateral inferior rectus muscle and its yoke i.e. the contralateral superior oblique. Also, each posterior semi-circular canals has excitatory projections to the ipsilateral superior oblique and its yoke i.e. the contralateral inferior rectus, while simultaneously inhibiting the ipsilateral inferior oblique and its yoke i.e. the contralateral superior rectus. A head tilt causes stimulation of both anterior semi-circular canals and the posterior semi-circular canals resulting in excitation of ipsilateral intorters (superior oblique and superior rectus) and contralateral extorters (inferior oblique and inferior rectus) while their antagonists are simultaneously inhibited. The otoliths (utricle and saccule) probably follow a similar pathway.
Normally, a body tilt (along with the initial head tilt) to the right causes a shift of the subjective visual vertical (SVV) to the left resulting in reflex, compensatory orientation of the head to left to realign the SVV to the true vertical.
The initial head tilt to right will cause stimulation of the right utricle resulting in excitory signals to pass to the SR and SO (right eye), and IO and IR (left eye). Simultaneously, inhibitory signals pass to their antagonists. The stimulated two intorters (right eye) and the two extorters (left eye) have opposite vertical actions i.e., one is an elevator and the other is a depressor. The opposite vertical actions nearly cancel each other and therefore only a small vertical deviation occurs, whereas their identical torsional actions are additive. In case of any lesion from the utricle to the brainstem, diminished input from the affected vestibular pathway, for example the left vestibular is the same as stimulation of right vestibular pathway, resulting in the erroneous interpretation by the brain that the head is tilted to the right and consequently that the SVV is tilted to the left. This causes reflex rotation of the head to the left, thus realigning the eyes and head to a position that is actually tilted but which the brain interprets as vertical.
Published literature on ocular torsion in physiologic ocular counter-roll are usually not very clear on the type of head tilt inducing the torsion, i.e., initial head tilt causing a tilt in the SVV or the compensatory head tilt to realign SVV with the true vertical. It has been stated that the ocular torsion in physiologic ocular counter-roll appears in the opposite direction as that of the head tilt in contrast to the same direction of ocular torsion as the head tilt in pathologic ocular tilt reaction.
If instead of the actual head tilt (as compared to true vertical), the direction of the head tilt as interpreted by the brain (subjective head tilt) is given importance, then it is seen that the head tilt and ocular torsion are actually in the same direction in both the physiologic ocular counter-roll and the pathologic ocular tilt reaction. The subjective head tilt as interpreted by the brain in the presence of asymmetric signals from the inner ear neural afferents is the principal factor in determining the direction of ocular torsion in ocular tilt reaction.
## References[edit]
*[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
| Ocular tilt reaction | c4518721 | 1,059 | wikipedia | https://en.wikipedia.org/wiki/Ocular_tilt_reaction | 2021-01-18T18:39:02 | {"umls": ["CL537114"], "wikidata": ["Q25313161"]} |
Humerus trochlea aplasia is an extremely rare familial bone deformity described only in Japanese patients to date. The deformity is bilateral in nearly half of patients (with bilateral involvement, the condition is symmetrical) and sometimes causes ulnar nerve palsy or cubitus varus.
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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
| Humerus trochlea aplasia | c1860773 | 1,060 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3383 | 2021-01-23T17:26:43 | {"gard": ["2750"], "mesh": ["C566022"], "omim": ["191000"], "umls": ["C1860773"], "icd-10": ["Q74.0"]} |
A rare central nervous system malformation characterized by an abnormally large brain, accompanied by abnormal head circumference measurements evident at birth or developing over the first years of life. The condition can be unilateral or bilateral and affects males more often than females. There is no typical pattern of symptoms, but mental retardation, seizures, and other neurologic abnormalities have been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Megalencephaly | c0221355 | 1,061 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2477 | 2021-01-23T18:28:24 | {"mesh": ["D058627"], "omim": ["155350", "248000"], "umls": ["C0221355", "C2720434"], "icd-10": ["Q04.5"], "synonyms": ["Macroencephaly"]} |
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Find sources: "Ethmocephaly" – news · newspapers · books · scholar · JSTOR (October 2019)
Ethmocephaly is a type of cephalic disorder caused by holoprosencephaly. Ethmocephaly is the least common facial anomaly. It consists of a proboscis separating narrow-set eyes with an absent nose and microphthalmia (abnormal smallness of one or both eyes). Cebocephaly, another facial anomaly, is characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely set eyes.
The least severe in the spectrum of facial anomalies is the median cleft lip, also called premaxillary agenesis.
Although the causes of most cases of holoprosencephaly remain unknown, some may be due to dominant or chromosome causes. Such chromosomal anomalies as trisomy 13 and trisomy 18 have been found in association with holoprosencephaly, or other neural tube defects. Genetic counseling and genetic testing, such as amniocentesis, is usually offered during a pregnancy if holoprosencephaly is detected. The recurrence risk depends on the underlying cause. If no cause is identified and the fetal chromosomes are normal, the chance to have another pregnancy affected with holoprosencephaly is about 6%.
There is no treatment for holoprosencephaly and the prognosis for individuals with the disorder is poor. Most of those who survive show no significant developmental gains. For children who survive, treatment is symptomatic. It is possible that improved management of diabetic pregnancies may help prevent holoprosencephaly, however there is no means of primary prevention.
## See also[edit]
* Holoprosencephaly
* Cephalic disorder
* Cyclopia
## References[edit]
*[v]: View this template
*[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
| Ethmocephaly | c0266680 | 1,062 | wikipedia | https://en.wikipedia.org/wiki/Ethmocephaly | 2021-01-18T18:41:40 | {"wikidata": ["Q5404130"]} |
A number sign (#) is used with this entry because of evidence that transient neonatal zinc deficiency (TNZD), which results from reduced zinc in maternal breast milk, is caused by maternal heterozygous mutation in the SLC30A2 gene (609617) on chromosome 1p36.
Description
Transient neonatal zinc deficiency occurs in breast-fed infants as a consequence of low milk zinc concentration in their nursing mothers, which cannot be corrected by maternal zinc supplementation. A large amount of zinc, an essential trace mineral, is required for normal growth particularly in infants, and breast milk normally contains adequate zinc to meet the requirement for infants up to 4 to 6 months of age. Zinc deficiency can lead to dermatitis, alopecia, decreased growth, and impaired immune function. The disorder shows autosomal dominant inheritance with incomplete penetrance (summary by Chowanadisai et al., 2006).
Some aspects of TNZD resemble the more severe disorder acrodermatitis enteropathica (AEZ; 201100), an autosomal recessive disorder caused by mutation in the zinc transporter SLC39A4 (607059). However, infants with transient neonatal zinc deficiency do not require zinc supplementation following weaning and have normal zinc absorption, whereas those with AEZ require lifelong zinc supplementation (summary by Chowanadisai et al., 2006).
Clinical Features
Sharma et al. (1988) showed that the condition in humans predisposing mothers to produce zinc-deficient breast milk is inherited. They described an Indian pedigree in which 10 children in 3 interrelated families were affected with a variant of acrodermatitis enteropathica (201100) that had its onset before weaning and disappeared when the child started a normal solid diet. The pedigree pattern and consanguinity suggested autosomal recessive inheritance. Sharma et al. (1988) suggested the designation 'self-limiting acrodermatitis enteropathica.'
Glover and Atherton (1988) described transient zinc deficiency in 2 full-term breast-fed sibs that could be related to low maternal breast milk zinc concentration.
Chowanadisai et al. (2006) reported a large family in which 2 women had infants affected with transient neonatal zinc deficiency. Both infants were exclusively breast-fed for 5 months and developed severe zinc deficiency manifest as severe dermatitis and alopecia. The mothers had low zinc concentration in breast milk, but normal zinc levels in serum. Dermatitis improved significantly in both infants after 1 week of zinc supplementation and did not recur with cessation of zinc treatment after weaning.
Lasry et al. (2012) reported 2 unrelated women of Ashkenazi Jewish descent, each of whom had an infant with transient neonatal zinc deficiency. The 2 infants were exclusively breast-fed, and both showed severe dermatitis particularly affecting the face and perineal regions. One developed partial alopecia of the eyebrows, eyelashes, and temple area. Both responded rapidly and well to oral zinc supplementation. Analysis of the mothers' breast milk showed low zinc content. Family history of 1 infant revealed that her brother had been exclusively breast-fed and had mild dermatitis that responded to zinc supplementation. The second infant had 2 sisters that were exclusively breast-fed but showed no symptoms of zinc deficiency.
Clinical Management
Aggett et al. (1980) and Aggett (1983) noted that acrodermatitis enteropathica is characterized by decreased mucosal zinc uptake in the small intestine, and that patient-derived fibroblasts show decreased uptake of zinc. In AEZ, maternal milk is protective and the symptoms of zinc deficiency develop after weaning. In contrast, zinc deficiency in breastfed babies (TNZD) is caused by low levels of zinc in the maternal milk, and there is no impairment in zinc uptake in the gut in affected babies.
In contrast to the ability to rescue the 'lethal milk' (lm) phenotype in mice by maternal zinc administration, oral supplementation of zinc to human mothers with low zinc content of their milk does not lead to an increased zinc content (Kuramoto et al., 1991)
Infants with TNZD do not require zinc supplementation following weaning. Correct diagnosis of TNZD is important because misdiagnosis of the disorder as AEZ may result in zinc oversupplementation, which can induce copper deficiency and immune dysregulation (summary by Chowanadisai et al., 2006).
Inheritance
The transmission pattern of TNZD in the families reported by Lasry et al. (2012) was consistent with autosomal dominant inheritance with incomplete penetrance.
Molecular Genetics
In 2 female relatives, each of whom had an infant with transient neonatal zinc deficiency, Chowanadisai et al. (2006) identified a heterozygous mutation in the SLC30A2 gene (H54R; 609617.0001). In vitro cellular expression studies indicated that the mutant protein formed insoluble perinuclear intracellular aggregates, resulting in decreased abundance of functional SLC30A2 and decreased zinc excretion by the maternal mammary epithelial cells into breast milk.
Lasry et al. (2012) identified a heterozygous mutation in the SLC30A2 gene (G87R; 609617.0002) in 2 unrelated women of Ashkenazi Jewish descent, each of whom had an infant with transient neonatal zinc deficiency. In vitro functional expression studies in various cell lines showed that the mutant protein caused impaired zinc secretion and mislocalization of the protein. Coexpression of the mutant protein and the wildtype protein indicated a dominant-negative effect for the G87R mutation.
### Exclusion Studies
The mouse lm phenotype is caused by mutation in the Znt4 gene (602095). To investigate whether changes in the ZNT4 gene are responsible for reduced zinc in breast milk in humans, Michalczyk et al. (2003) studied 2 unrelated mothers with low zinc milk levels whose babies had developed zinc deficiency. Their findings suggested that the lm mouse is not the corresponding model for the human zinc deficiency condition.
INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Dermatitis \- Acrodermatitis enteropathica, transient, seen in breastfed offspring of affected mothers Hair \- Alopecia, partial LABORATORY ABNORMALITIES \- Affected mother has reduced zinc levels in breast milk (may be up to 40% less than normal breast milk) \- Affected mother has normal plasma zinc levels and is not zinc-deficient \- Breastfed offspring have transient decrease of plasma zinc levels MISCELLANEOUS \- Reduced zinc in affected mother's breast milk is unresponsive to oral zinc supplementation \- Symptoms of zinc deficiency occur only in exclusively breastfed infants \- Dermatitis resolves in offspring after zinc supplementation and/or weaning \- Zinc deficiency in breastfed offspring resolves after weaning \- Mother who carries the mutation is clinically unaffected MOLECULAR BASIS \- Caused by mutation in the solute carrier family 30 (zinc transporter), member 2 gene (SLC30A2, 609617.0001 ) ▲ 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
| ZINC DEFICIENCY, TRANSIENT NEONATAL | c1842486 | 1,063 | omim | https://www.omim.org/entry/608118 | 2019-09-22T16:08:14 | {"mesh": ["C564286"], "omim": ["608118"], "synonyms": ["Alternative titles", "ZINC DEFICIENCY, NEONATAL, DUE TO LOW BREAST MILK ZINC"]} |
Craniofrontonasal syndrome is a rare condition characterized by the premature closure of certain bones of the skull (craniosynostosis) during development, which affects the shape of the head and face. The condition is named for the areas of the body that are typically affected: the skull (cranio-), face (fronto-), and nose (nasal).
In people with craniofrontonasal syndrome, the skull bones along the coronal suture, which is the growth line that goes over the head from ear to ear, closes early. These changes can result in an abnormally shaped head and distinctive facial features. The size and shape of facial structures may differ between the right and left sides of the face (facial asymmetry) in individuals with craniofrontonasal syndrome. Affected individuals may also have wide-set eyes (ocular hypertelorism), eyes that do not point in the same direction (strabismus), involuntary eye movements (nystagmus), a slit (cleft) in the tip of the nose, a wide nasal bridge, an upper lip that points outward (called a tented lip), or a cleft in the upper lip with or without a cleft in roof of the mouth (palate). Some affected individuals have brain abnormalities, such as absent or underdeveloped tissue connecting the left and right halves of the brain (agenesis or dysgenesis of the corpus callosum). However, intelligence is usually unaffected in people with this condition. Females with craniofrontonasal syndrome typically have more severe signs and symptoms than affected males, who often have hypertelorism and rarely, cleft lip.
Other common features of craniofrontonasal syndrome include extra folds of skin on the neck (webbed neck), ridged nails, unusual curving of the fingers or toes (clinodactyly), extra fingers (polydactyly) or fingers that are fused together (syndactyly), low-set breasts, a sunken chest (pectus excavatum), a spine that curves to the side (scoliosis), or narrow and sloped shoulders with reduced range of motion. People with this condition may also have eyebrows that grow together in the middle (synophrys), a widow's peak hairline with a low hairline in the back, or wiry hair.
## Frequency
Craniofrontonasal syndrome is a very rare condition, although its prevalence is unknown. More than 115 cases have been described in the scientific literature.
## Causes
Craniofrontonasal syndrome is caused by mutations in a gene known as EFNB1. This gene provides instructions for making a protein called ephrin B1. This protein spans the cell membrane where it can attach (bind) to other proteins on the surface of neighboring cells. Protein binding between nearby cells helps cells stick to one another (cell adhesion) and communicate, which are important for the normal shaping (patterning) of many tissues and organs before birth.
Mutations in the EFNB1 gene result in a shortage (deficiency) of ephrin B1 protein. Most of these mutations lead to an abnormally short version of the molecule that acts as the genetic blueprint for the ephrin B1 protein. The shortened molecules are quickly broken down before protein can be made. A deficiency of ephrin B1 protein prevents cell adhesion, which disrupts normal patterning in tissues before birth, leading to the signs and symptoms of craniofrontonasal syndrome.
### Learn more about the gene associated with Craniofrontonasal syndrome
* EFNB1
## Inheritance Pattern
Craniofrontonasal syndrome is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. Males have only one X chromosome and females have two copies of the X chromosome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
Researchers suspect that the signs and symptoms of craniofrontonasal syndrome vary in severity between males and females in part because of a normal process called X-inactivation. Early in embryonic development in females, one of the two X chromosomes is permanently turned off (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, so that each X chromosome is active in about half the body's cells. This means that in affected females with craniofrontonasal syndrome, the X chromosome with an EFNB1 gene mutation is active in about half of cells, and the X chromosome with the normal EFNB1 gene is active in about half. Because X-inactivation leads to some cells that produce functional ephrin B1 protein and some cells that do not, patterning of tissues becomes patchy, which can alter development of the head and face.
In affected males, all cells have a single X chromosome with an EFNB1 gene mutation. Because ephrin B1 activity is completely missing in all cells, normal tissue patterning cannot occur and it is thought that other proteins perform similar functions to compensate.
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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
| Craniofrontonasal syndrome | c0220767 | 1,064 | medlineplus | https://medlineplus.gov/genetics/condition/craniofrontonasal-syndrome/ | 2021-01-27T08:24:49 | {"gard": ["1578"], "mesh": ["C536456"], "omim": ["304110"], "synonyms": []} |
Adopted child syndrome is a controversial term that has been used to explain behaviors in adopted children that are claimed to be related to their adoptive status. Specifically, these include problems in bonding, attachment disorders, lying, stealing, defiance of authority, and acts of violence. The term has never achieved acceptance in the professional community. The term is not found in the American Psychiatric Association's Diagnostic and Statistical Manual, 4th edition, TR.
## Contents
* 1 History of the term
* 2 See also
* 3 References
* 4 External links
## History of the term[edit]
David Kirschner, who coined the term, says that most adoptees are not disturbed and that the syndrome only applies to "a small clinical subgroup".[1]
Researchers Brodizinsky, Schechter, and Henig[2] find that in a review of the literature, generally children adopted before the age of six-months fare no differently than children raised with their biological parents. Later problems that develop among children adopted from the child welfare system at an older age are usually associated with the effects of chronic early maltreatment in the caregiving relationship; abuse and neglect.
Psychologist Betty Jean Lifton, herself an adopted person, has written extensively on psychopathology in adopted people, primarily in Lost and Found: The Adoption Experience, and Journey of the Adopted Self: A Quest for Wholeness and briefly discusses Adopted child syndrome.[1][3][4]
## See also[edit]
* Child abuse
* Child welfare
* Attachment disorder
* Relative outcomes of parenting by biological and adoptive parents
## References[edit]
1. ^ a b Lifton, Betty Jean (1975). Lost and Found: The Adoption Experience. Dial Press. pp. 274–275. ISBN 0-06-097132-0.
2. ^ Brodzinsky, David M.; Marshall D. Schecter; Robin Marantz Henig (1993). Being Adopted: The Lifelong Search for Self. Anchor Books. ISBN 0-385-41426-9.
3. ^ Lifton, Betty Jean (1994). Journey of the Adopted Self: A Quest for Wholeness. Basic Books. ISBN 0-465-03675-9. Archived from the original on 2007-03-05. Retrieved 2007-02-02. "Adopted Child Syndrome page, including bibliography"
4. ^ Smith, Jerome. "The Adopted Child Syndrome: A Methodological Perspective" Families in Society 82 no5 491-7 S/O 2001
## External links[edit]
* Adopted Child Syndrome page, including bibliography
* Adoption History: Psychopathology Studies
* Adoption: Uncharted Waters Official Book Web Site
* v
* t
* e
Adoption and foster care
Adoption by country
* Australia
* France
* Guatemala
* Italy
* Philippines
* United States
* South Korea
Foster care by country
* Australia
* Canada
* United Kingdom
* United States
Issues
* Adopted child syndrome
* Adoption disclosure
* Adoption home study
* Adoption reunion registry
* Adoption tax credit
* Aging out
* Child abuse
* Trafficking of children § Adoption
* Child laundering
* Political abuse of psychiatry
* Closed adoption
* Cultural variations in adoption
* Disruption
* Genealogical bewilderment
* International adoption
* Interracial adoption
* Language of adoption
* LGBT adoption
* Open adoption
* Sealed birth records
* History of children in the military
Laws
* Access to Adoption Records Act (Ontario)
* Adoption Information Disclosure Act (Ontario)
* Adoption and Safe Families Act (US)
* Christian law of adoption (India)
* Dima Yakovlev Law (Russia)
* Foster Care Independence Act (US)
* Hague Adoption Convention
* Hindu Adoptions and Maintenance Act (India)
* Islamic adoptional jurisprudence
* Putative father registry (US)
* Uniform Adoption Act (US)
History
* Adoption in ancient Rome
* Fosterage
Controversial violations of rights
in adoption or child custody
* List of international adoption scandals
* Present-day United States
* Pre-1978 United States
* Tennessee Children's Home Society
* Cambodia
* Russia
* Baby Scoop Era
* Sixties Scoop
* Home Children
* Romania
* Missionaries of Charity, Jharkhand
* Michael A. Hess
* Vincent Nichols § Acknowledgement of adoption controversy
* Forced adoption in Australia
* Forced adoption in the United Kingdom
* Operation Condor in Argentina
* Dirty War era Argentina
* Devshirme
* Kidnapping of children by Nazi Germany
* Tianjin Massacre
* Mortara case
* Postremo mense
* Salzburg Protestants § Defereggen Valley expulsion
Historical criticism of orphanages
* Orphanage § Criticism
* Duplessis Orphans
* St. Thomas–St. Vincent Orphanage § Sexual and physical abuse
* Abuse scandal in the Sisters of Mercy § Other abuse allegations
* Mount Cashel Orphanage
* Clontarf Aboriginal College § Allegations of abuse
* Mary Norris
* St. John's Orphanage
* Roman Catholic Diocese of Burlington § History
* Sisters of Nazareth § Child abuse
* Daughters of Charity of Saint Vincent de Paul § Allegations of child abuse in Scotland
*[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
| Adopted child syndrome | None | 1,065 | wikipedia | https://en.wikipedia.org/wiki/Adopted_child_syndrome | 2021-01-18T18:56:33 | {"wikidata": ["Q366225"]} |
Infectious disease caused by the monkeypox virus that can occur in certain animals including humans
Monkeypox
The rash of monkeypox
SpecialtyInfectious disease
SymptomsFever, headache, muscle pains, blistering rash, swollen lymph nodes[1]
Usual onset5-21 days post exposure[1]
Duration2 to 5 weeks[1]
CausesMonkeypox virus[2]
Diagnostic methodTesting for viral DNA[3]
Differential diagnosisChickenpox, smallpox[4]
PreventionSmallpox vaccine[3]
MedicationCidofovir[4]
FrequencyRare[2]
DeathsUp to 10%[1]
Monkeypox is an infectious disease caused by the monkeypox virus that can occur in certain animals including humans.[2] Symptoms begin with fever, headache, muscle pains, swollen lymph nodes, and feeling tired.[1] This is followed by a rash that forms blisters and crusts over.[1] The time from exposure to onset of symptoms is around 10 days.[1] The duration of symptoms is typically 2 to 5 weeks.[1]
Monkeypox may be spread from handling bushmeat, an animal bite or scratch, body fluids, contaminated objects, or close contact with an infected person.[5] The virus is believed to normally circulate among certain rodents in Africa.[5] Diagnosis can be confirmed by testing a lesion for the virus's DNA.[3] The disease can appear similar to chickenpox.[4]
The smallpox vaccine is believed to prevent infection.[3] In 2019 a vaccine was approved for the disorder in the United States.[6] There is no known cure.[7] Cidofovir or brincidofovir may be useful.[4][7] The risk of death in those infected is up to 10%.[1][8]
The disease mostly occurs in Central and West Africa.[9] It was first identified in 1958 among laboratory monkeys.[9] The first cases in humans were found in 1970 in the Democratic Republic of the Congo.[9] An outbreak that occurred in the United States in 2003 was traced to a pet store where imported Gambian rodents were sold.[3]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Monkeypox virus
* 2.2 Reservoir
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 6 Epidemiology
* 6.1 2003 U.S. outbreak
* 6.2 2017–19 Nigeria outbreak
* 6.3 2018 United Kingdom cases
* 6.4 2019 Singapore case
* 7 History
* 8 In popular culture
* 9 References
* 10 External links
## Signs and symptoms[edit]
An image of the rash of monkeypox
Monkeypox is similar to smallpox, although it is often milder.[10]
Limited person-to-person spread of infection has been reported in disease-endemic areas in Africa.[8]
## Cause[edit]
### Monkeypox virus[edit]
Main article: Monkeypox virus
Monkeypox virus causes the disease in both humans and animals. It was first identified in 1958 as a pathogen of crab-eating macaque monkeys (Macaca fascicularis) being used as laboratory animals. The crab-eating macaque is often used for neurological experiments. Monkeypox virus is an Orthopoxvirus, a genus of the family Poxviridae that contains other viral species that target mammals. The virus is found mainly in tropical rainforest regions of Central and West Africa.[2]
The virus was first discovered in monkeys (hence the name) in 1958, and in humans in 1970. Between 1970 and 1986, over 400 cases in humans were reported. Small viral outbreaks with a death rate in the range of 10% and a secondary human-to-human infection rate of about the same amount occur routinely in equatorial Central and West Africa.[11] The primary route of infection is thought to be contact with the infected animals or their bodily fluids.[11] The first reported outbreak outside of the African continent occurred in the United States in 2003 in the Midwestern states of Illinois, Indiana, and Wisconsin, with one occurrence in New Jersey. The outbreak was traced to a prairie dog infected from an imported Gambian pouch rat.[3] No deaths occurred.[12]
Humans can be infected by an animal via a bite, or by direct contact with an infected animal’s bodily fluids. The virus can also spread from human to human, by respiratory (airborne) contact or by contact with an infected person's bodily fluids. Risk factors for transmission include sharing a bed or room, or using the same utensils as an infected person. An increased transmission risk is associated with factors involving introduction of virus to the oral mucosa.[13] The incubation period is 10–14 days. Prodromal symptoms include swelling of lymph nodes, muscle pain, headache, and fever prior to the emergence of the rash. The rash is usually only present on the trunk, but may spread to the palms and soles of the feet in a centrifugal distribution. The initial macular lesions exhibit a papular, then vesicular and pustular appearance.[13]
### Reservoir[edit]
In addition to monkeys, reservoirs for the virus are found in Gambian pouched rats (Cricetomys gambianus), dormice (Graphiurus spp.) and African squirrels (Heliosciurus, and Funisciurus). The use of these animals as food may be an important source of transmission to humans.[14]
## Diagnosis[edit]
Diagnosis can be verified by testing for the virus. The virus does not remain very long in the blood, and hence blood testing may not detect the disease. Test results interpreted together with clinical features.[10]
## Prevention[edit]
Vaccination against smallpox is assumed to provide protection against human monkeypox infection, because they are closely related viruses and the vaccine protects animals from experimental lethal monkeypox challenge.[15] This has not been conclusively demonstrated in humans, because routine smallpox vaccination was discontinued following the apparent eradication of smallpox and owing to safety concerns with the vaccine.
Smallpox vaccine has been reported to reduce the risk of monkeypox among previously vaccinated persons in Africa. The decrease in immunity to poxviruses in exposed populations is a factor in the prevalence of monkeypox. It is attributed both to waning cross-protective immunity among those vaccinated before 1980 when mass smallpox vaccinations were discontinued, and to the gradually increasing proportion of unvaccinated individuals.[13] The United States Centers for Disease Control and Prevention (CDC) recommends that persons investigating monkeypox outbreaks and involved in caring for infected individuals or animals should receive a smallpox vaccination to protect against monkeypox. Persons who have had close or intimate contact with individuals or animals confirmed to have monkeypox should also be vaccinated.
The CDC does not recommend pre-exposure vaccination for unexposed veterinarians, veterinary staff, or animal control officers, unless such persons are involved in field investigations.
## Treatment[edit]
Currently, no treatment for monkeypox has been shown to be effective or safe.[7] A number of measures may be used to try to decrease spread of the disease including the smallpox vaccine, cidofovir, and vaccinia immune globulin (VIG).[7]
## Epidemiology[edit]
Monkeypox as a disease in humans was first associated with an illness in the Democratic Republic of the Congo (formerly Zaire), in the town of Basankusu, Équateur Province, in 1970.[16] A second outbreak of human illness was identified in DRC/Zaire in 1996–1997. In 2003, a small outbreak of human monkeypox in the United States occurred among owners of pet prairie dogs.[17] The outbreak originated from Villa Park, Illinois, outside of Chicago, when an exotic animal dealer kept young prairie dogs in close proximity to an infected Gambian pouched rat (Cricetomys gambianus) recently imported from Accra, Ghana. Seventy-one people were reportedly infected, in which no fatalities occurred. In 2005, 49 cases were reported Sudan for the first time. No one who was infected died.[18] The genetic analysis suggests that the virus did not originate in Sudan but was imported, most likely from DRC.[19]
Many more monkeypox cases have been reported in Central and West Africa, and in the Democratic Republic of Congo in particular. The collected data is often incomplete and unconfirmed which hinders realistic estimations of the people affected and the number of cases of monkeypox over time. Nevertheless, it was suggested that the number of reported monkeypox cases has increased and that the geographical occurrence broadened in recent years.[20]
### 2003 U.S. outbreak[edit]
Gambian pouched rat
Main article: 2003 Midwest monkeypox outbreak
In May 2003, a young child became ill with fever and rash after being bitten by a prairie dog purchased at a local swap meet near Milwaukee, Wisconsin.[21] In total, 71 cases of monkeypox were reported through June 20, 2003. All cases were traced to Gambian pouched rats imported by a Texas exotic animal distributor, from Accra, Ghana, in April, 2003. No deaths resulted.[22] Electron microscopy and serologic studies were used to confirm that the disease was human monkeypox.
People with monkeypox typically experienced prodromal symptoms of fever, headaches, muscle aches, chills, and drenching sweats. Roughly one-third of infected people had nonproductive coughs. This prodromal phase was followed 1–10 days later by the development of a papular rash that typically progressed through stages of vesiculation, pustulation, umbilication, and crusting. In some people, early lesions had become ulcerated. Rash distribution and lesions occurred on head, trunk, and extremities; many of the people had initial and satellite lesions on palms, soles, and extremities. Rashes were generalized in some people. After onset of the rash, people generally manifested rash lesions in different stages. Everyone affected reported direct or close contact with prairie dogs, later found to be infected with the monkeypox virus.[23]
### 2017–19 Nigeria outbreak[edit]
Monkeypox has been reportedly spread around southeast and south Nigeria. Some states and the federal government of Nigeria are currently seeking a way to contain it, as well as find a cure for the infected ones. It has spread to Akwa Ibom, Abia, Bayelsa, Benue, Cross River, Delta, Edo, Ekiti, Enugu, Imo, Lagos, Nasarawa, Oyo, Plateau, Rivers and Federal Capital Territory.[24][25] The outbreak started in September 2017 and remains ongoing across multiple states as of May 2019.[26]
### 2018 United Kingdom cases[edit]
In September 2018, the United Kingdom's first case of monkeypox was recorded. The person, a Nigerian national, is believed to have contracted monkeypox in Nigeria before travelling to the United Kingdom.[27] According to Public Health England, the person was staying in a naval base in Cornwall before being moved to the Royal Free Hospital's specialised infectious disease unit. People who had been in contact with the person since he contracted the disease were contacted.[28] A second case was confirmed in the town of Blackpool,[29][30] with a further case that of a medical worker who cared for the case from Blackpool.[31] A fourth case occurred on 3 December 2019, when monkeypox was diagnosed in a person in south west England. They were travelling to the UK from Nigeria.[32]
### 2019 Singapore case[edit]
On 8 May 2019, a 38-year-old man who travelled from Nigeria was hospitalised in an isolation ward at the National Centre for Infectious Diseases in Singapore, after being confirmed as the country's first case of monkeypox. As a result, 22 people were quarantined.[33] The case may be linked to the ongoing outbreak in Nigeria.[26]
## History[edit]
A Cynomolgus monkey, or crab-eating macaque
Monkeypox was first reported by Preben von Magnus in 1958 in laboratory cynomolgus monkeys, when two outbreaks of a smallpox-like disease occurred in colonies of monkeys kept for research.[2] The first report of monkeypox in humans was discovered more than a decade later, in a person with a suspected smallpox infection in the Democratic Republic of Congo during efforts to eradicate smallpox.[2][4] It was subsequently reported in humans in other central and western African countries.[2] Almost 50 cases were reported between 1970 and 1979, with more than two thirds of these being from Zaire. The other cases originated from Liberia, Nigeria, Ivory Coast and Sierra Leone.[34]
## In popular culture[edit]
In the season 8 finale of the NBC medical drama ER, two children are brought in with monkeypox, which the doctors initially fear to be smallpox.
## References[edit]
1. ^ a b c d e f g h i "Signs and Symptoms Monkeypox". CDC. 11 May 2015. Archived from the original on 15 October 2017. Retrieved 15 October 2017.
2. ^ a b c d e f g "About Monkeypox". CDC. 11 May 2015. Archived from the original on 15 October 2017. Retrieved 15 October 2017.
3. ^ a b c d e f "2003 U.S. Outbreak Monkeypox". CDC. 11 May 2015. Archived from the original on 15 October 2017. Retrieved 15 October 2017.
4. ^ a b c d e McCollum AM, Damon IK (January 2014). "Human monkeypox". Clinical Infectious Diseases. 58 (2): 260–7. doi:10.1093/cid/cit703. PMID 24158414.
5. ^ a b "Transmission Monkeypox". CDC. 11 May 2015. Archived from the original on 15 October 2017. Retrieved 15 October 2017.
6. ^ "FDA approves first live, non-replicating vaccine to prevent smallpox and monkeypox". FDA. 24 September 2019. Retrieved 27 September 2019.
7. ^ a b c d "Treatment | Monkeypox | Poxvirus | CDC". www.cdc.gov. 28 December 2018. Retrieved 11 October 2019.
8. ^ a b Hutin YJ, Williams RJ, Malfait P, Pebody R, Loparev VN, Ropp SL, et al. (2001). "Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997". Emerging Infectious Diseases. 7 (3): 434–8. doi:10.3201/eid0703.010311. PMC 2631782. PMID 11384521.
9. ^ a b c "Monkeypox". CDC. 11 May 2015. Archived from the original on 15 October 2017. Retrieved 15 October 2017.
10. ^ a b "Monkeypox". World Health Organization. Retrieved 30 September 2018.
11. ^ a b Meyer H, Perrichot M, Stemmler M, Emmerich P, Schmitz H, Varaine F, et al. (August 2002). "Outbreaks of disease suspected of being due to human monkeypox virus infection in the Democratic Republic of Congo in 2001". Journal of Clinical Microbiology. 40 (8): 2919–21. doi:10.1128/JCM.40.8.2919-2921.2002. PMC 120683. PMID 12149352.
12. ^ "2003 United States Outbreak of Monkeypox | Monkeypox | Poxvirus | CDC". www.cdc.gov. 2018-12-19. Retrieved 2020-01-22.
13. ^ a b c Kantele A, Chickering K, Vapalahti O, Rimoin AW (August 2016). "Emerging diseases-the monkeypox epidemic in the Democratic Republic of the Congo". Clinical Microbiology and Infection. 22 (8): 658–9. doi:10.1016/j.cmi.2016.07.004. PMID 27404372.
14. ^ Falendysz EA, Lopera JG, Lorenzsonn F, Salzer JS, Hutson CL, Doty J, et al. (2015-10-30). "Further Assessment of Monkeypox Virus Infection in Gambian Pouched Rats (Cricetomys gambianus) Using In Vivo Bioluminescent Imaging". PLOS Neglected Tropical Diseases. 9 (10): e0004130. doi:10.1371/journal.pntd.0004130. PMC 4627722. PMID 26517839.
15. ^ Marriott KA, Parkinson CV, Morefield SI, Davenport R, Nichols R, Monath TP (January 2008). "Clonal vaccinia virus grown in cell culture fully protects monkeys from lethal monkeypox challenge". Vaccine. 26 (4): 581–8. doi:10.1016/j.vaccine.2007.10.063. PMID 18077063.
16. ^ Ladnyj ID, Ziegler P, Kima E (1972). "A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo". Bulletin of the World Health Organization. 46 (5): 593–7. PMC 2480792. PMID 4340218.
17. ^ "What You Should Know About Monkeypox" (PDF). Fact Sheet. Centers for disease control and prevention. 2003-06-12. Archived (PDF) from the original on 2008-06-25. Retrieved 2008-03-21.
18. ^ Damon IK, Roth CE, Chowdhary V (August 2006). "Discovery of monkeypox in Sudan". The New England Journal of Medicine. 355 (9): 962–3. doi:10.1056/NEJMc060792. PMID 16943415.
19. ^ Nakazawa Y, Emerson GL, Carroll DS, Zhao H, Li Y, Reynolds MG, et al. (February 2013). "Phylogenetic and ecologic perspectives of a monkeypox outbreak, southern Sudan, 2005". Emerging Infectious Diseases. 19 (2): 237–45. doi:10.3201/eid1902.121220. PMC 3559062. PMID 23347770.
20. ^ Sklenovská N, Van Ranst M (September 2018). "Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans". Frontiers in Public Health. 6: 241. doi:10.3389/fpubh.2018.00241. PMC 6131633. PMID 30234087.
21. ^ Anderson MG, Frenkel LD, Homann S, and Guffey J. (2003), "A case of severe monkeypox virus disease in an American child: emerging infections and changing professional values"; Pediatr Infect Dis J;22(12): 1093–1096; discussion 1096–1098.
22. ^ "Medscape Monkeypox Review". Bcbsma.medscape.com. Retrieved 2013-03-22.
23. ^ CDC, Morbidity and Mortality Weekly Report. Atlanta, Georgia. (MMWR) July 11, 2003. (52) 27; 642-646.
24. ^ "Monkeypox – Nigeria". WHO. 21 December 2017. Retrieved 26 July 2020.
25. ^ "Monkeypox – Nigeria". WHO. 5 October 2018. Retrieved 26 July 2020.
26. ^ a b "Monkeypox – Singapore". WHO. 16 May 2019. Retrieved 17 May 2019.
27. ^ "First ever case of monkeypox recorded in the UK". the Guardian. 8 September 2018. Retrieved 8 September 2018.
28. ^ "Monkeypox case in England". gov.uk. 8 September 2018. Retrieved 8 September 2018.
29. ^ "Blackpool monkeypox case confirmed as second in UK". BBC News. 11 September 2018. Retrieved 11 September 2018.
30. ^ Vaughan A, Aarons E, Astbury J, Balasegaram S, Beadsworth M, Beck CR, et al. (September 2018). "Two cases of monkeypox imported to the United Kingdom, September 2018". Euro Surveillance. 23 (38). doi:10.2807/1560-7917.es.2018.23.38.1800509. PMC 6157091. PMID 30255836.
31. ^ Gayle D (26 September 2018). "Medic becomes third person infected with monkeypox in England". The Guardian.
32. ^ "Monkeypox case confirmed in England". GOV.UK. Public Health England. 4 December 2019. Retrieved 12 December 2019.
33. ^ "News Scan for May 09, 2019, Singapore sees first monkeypox case — in Nigerian national". CIDRAP. Center for Infectious Disease Research and Policy, University of Minnesota. Retrieved 10 May 2019.
34. ^ Breman JG, Steniowski MV, Zanotto E, Gromyko AI, Arita I (1980). "Human monkeypox, 1970-79". Bulletin of the World Health Organization. 58 (2): 165–82. PMC 2395797. PMID 6249508.
## External links[edit]
Classification
D
* ICD-10: B04
* ICD-9-CM: 059.01
* MeSH: D045908
* SNOMED CT: 359811007
* CDC - Monkeypox Fact Sheet
* WHO - Monkeypox Fact Sheet
* Virology.net Picturebook: Monkeypox
* Could Monkeypox Take Over Where Smallpox Left Off? Smallpox may be gone, but its viral cousins—monkeypox and cowpox—are staging a comeback March 4, 2013 Scientific American
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| Monkeypox | c0276180 | 1,066 | wikipedia | https://en.wikipedia.org/wiki/Monkeypox | 2021-01-18T18:32:17 | {"gard": ["10722"], "mesh": ["D045908"], "umls": ["C0276180"], "wikidata": ["Q382370"]} |
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Find sources: "Visual hallucinations in psychosis" – news · newspapers · books · scholar · JSTOR (April 2018)
Visual hallucinations in psychosis are hallucinations accompanied by delusions, which are abnormal beliefs that are endorsed by patients as real, that persist in spite of evidence to the contrary, and that are not part of a patient's culture or subculture.[1]
## Contents
* 1 Presentation
* 1.1 Simple vs. complex
* 1.2 Content
* 2 Causes
* 3 Prevalence
* 4 References
## Presentation[edit]
Visual hallucinations in psychoses are reported to have physical properties similar to real perceptions. They are often life-sized, detailed, and solid, and are projected into the external world. They typically appear anchored in external space, just beyond the reach of individuals, or further away. They can have three-dimensional shapes, with depth and shadows, and distinct edges. They can be colorful or in black and white and can be static or have movement.[2][3][4][5][6][7][8]
### Simple vs. complex[edit]
Visual hallucinations may be simple, or non-formed visual hallucinations, or complex, or formed visual hallucinations.
Simple visual hallucinations are also referred to as non-formed or elementary visual hallucinations. They can take the form of multicolored lights, colors, geometric shapes, indiscrete objects. Simple visual hallucinations without structure are known as phosphenes and those with geometric structure are known as photopsias.[9][10][11] These hallucinations are caused by irritation to the primary visual cortex (Brodmann's area 17).[12]
Complex visual hallucinations are also referred to as formed visual hallucinations. They tend to be clear, lifelike images or scenes, such as faces of animals or people. Sometimes, hallucinations are 'Lilliputian', i.e., patients experience visual hallucinations where there are miniature people, often undertaking unusual actions. Lilliputian hallucinations may be accompanied by wonder, rather than terror.[13][14]
### Content[edit]
The frequency of hallucinations varies widely from rare to frequent, as does duration (seconds to minutes). The content of hallucinations varies as well. Complex (formed) visual hallucinations are more common than Simple (non-formed) visual hallucinations.[5][7] In contrast to hallucinations experienced in organic conditions, hallucinations experienced as symptoms of psychoses tend to be more frightening. An example of this would be hallucinations that have imagery of bugs, dogs, snakes, distorted faces. Visual hallucinations may also be present in those with Parkinson's, where visions of dead individuals can be present. In psychoses, this is relatively rare, although visions of God, angels, the devil, saints, and fairies are common.[6][7] Individuals often report being surprised when hallucinations occur and are generally helpless to change or stop them.[4] In general, individuals believe that visions are experienced only by themselves.[4][5]
## Causes[edit]
Two neurotransmitters are particularly important in visual hallucinations – serotonin and acetylcholine. They are concentrated in the visual thalamic nuclei and visual cortex.[13]
The similarity of visual hallucinations that stem from diverse conditions suggest a common pathway for visual hallucinations. Three pathophysiologic mechanisms are thought to explain this.
The first mechanism has to do with cortical centers responsible for visual processing. Irritation of visual association cortices (Brodmann's areas 18 and 19) cause complex visual hallucinations.[12][15]
The second mechanism is deafferentation, the interruption or destruction of the afferent connections of nerve cells, of the visual system, caused by lesions, leading to the removal of normal inhibitory processes on cortical input to visual association areas, leading to complex hallucinations as a release phenomenon.[14][15]
The third mechanism has to do with the reticular activating system, which plays a role in the maintenance of arousal. Lesions in the brain stem can cause visual hallucinations. Visual hallucinations are frequent in those with certain sleep disorders, occurring more often when drowsy. This suggests that the reticular activating system plays a part in visual hallucinations, although the precise mechanism has still not fully been established.[13][15]
## Prevalence[edit]
Hallucinations in those with psychoses are often experienced in color, and most often are multi-modal, consisting of visual and auditory components. They frequently accompany paranoia or other thought disorders, and tend to occur during the daytime and are associated with episodes of excess excitability.[9] The DSM-V lists visual hallucinations as a primary diagnostic criterion for several psychotic disorders, including schizophrenia and schizoaffective disorder.[1] The lifetime prevalence of all psychotic disorders is 3.48% and that of the different diagnostic groups are as follows: 0.87%[10] for schizophrenia, 0.32% for schizoaffective disorder, 0.07% for schizophreniform disorder, 0.18% for delusional disorder, 0.24% for bipolar I disorder, 0.35% for major depressive disorder with psychotic features, 0.42% for substance-induced psychotic disorders, and 0.21% for psychotic disorders due to a general medical condition.[16] Visual hallucinations can occur as a symptom of the above psychotic disorders in 24% to 72% of patients at some point in the course of their illness.[2][17] Not all individuals who experience hallucinations have a psychotic disorder. Many physical and psychiatric disorders can manifest with hallucinations, and some individuals may have more than one disorder that could cause different types of hallucinations.[11]
## References[edit]
1. ^ a b American Psychiatric Association (2013). The Diagnostic and Statistical Manual Revision V (DSM-V).
2. ^ a b Goodwin, Donald W.; Rosenthal, Randall (January 1971). "Clinical Significance of Hallucinations in Psychiatric Disorders: A study of 116 hallucinatory patients". Archives of General Psychiatry. 24 (1): 76–80. doi:10.1001/archpsyc.1971.01750070078011. PMID 5538855.
3. ^ Gauntlett-Gilbert, Jeremy; Kuipers, Elizabeth (March 2003). "Phenomenology of Visual Hallucinations in Psychiatric Conditions". The Journal of Nervous and Mental Disease. 191 (3): 203–205. doi:10.1097/01.nmd.0000055084.01402.02. PMID 12637850.
4. ^ a b c Dudley, Robert; Wood, Markku; Spencer, Helen; Brabban, Alison; Mosimann, Urs P.; Collerton, Daniel (May 2012). "Identifying Specific Interpretations and Use of Safety Behaviours in People with Distressing Visual Hallucinations: An Exploratory Study" (PDF). Behavioural and Cognitive Psychotherapy. 40 (3): 367–375. doi:10.1017/S1352465811000750. PMID 22321567.
5. ^ a b c Bracha, H. Stefan; Wolkowitz, Owen M.; Lohr, James B.; Karson, Craig N.; Bigelow, Llewellyn B. (April 1989). "High prevalence of visual hallucinations in research subjects with chronic schizophrenia". American Journal of Psychiatry. 146 (4): 526–528. doi:10.1176/ajp.146.4.526. PMID 2929755.
6. ^ a b Lowe, Gordon R. (December 1973). "The phenomenology of hallucinations as an aid to differential diagnosis". The British Journal of Psychiatry. 123 (577): 621–633. doi:10.1192/bjp.123.6.621. PMID 4772302.
7. ^ a b c Frieske, David A.; Wilson, William P. (December 1966). "Formal qualities of hallucinations: a comparative study of the visual hallucinations in patients with schizophrenic, organic, and affective psychoses". Proceedings of the Annual Meeting of the American Psychopathological Association. 54: 49–62. PMID 5951932.
8. ^ Assad, Ghazi; Shapiro, Bruce (September 1986). "Hallucinations: theoretical and clinical overview". The American Journal of Psychiatry. 143 (9): 1088–1097. doi:10.1176/ajp.143.9.1088. PMID 2875662.
9. ^ a b Block, Michael N. (March 2012). "An overview of visual hallucinations: patients who experience hallucinations secondary to a host of underlying conditions often will look to you for guidance, reassurance and treatment". Review of Optometry. 149 (3): 82–90.
10. ^ a b Cummings, Jeffrey L.; Miller, Bruce L. (January 1987). "Visual hallucinations: Clinical Occurrence and Use in Differential Diagnosis". The Western Journal of Medicine. 146 (1): 46–61. PMC 1307180. PMID 3825109.
11. ^ a b Ali, Shahid; Patel, Milapkumar; Avenido, Jaymie; Bailey, Rahn K.; Jabeen, Shagufta; Riley, Wayne J. (November 2011). "Hallucinations: Common features and causes". Current Psychiatry. 10 (11): 22–29.
12. ^ a b Price, John; Whitlock, Frances A.; Hall, R.T. (1983). "The psychiatry of vertebro-basilar insufficiency with the report of a case". Psychopathology. 16 (1): 26–44. doi:10.1159/000283948. PMID 6844659.
13. ^ a b c Manford, Mark; Andermann, Frederick (October 1998). "Complex visual hallucinations. Clinical and neurobiological insights". Brain. 121 (10): 1819–1840. doi:10.1093/brain/121.10.1819. PMID 9798740.
14. ^ a b Menon, G. Jayakrishna; Rahman, Imran; Menon, Sharmila J.; Dutton, Gordon N (January 2003). "Complex Visual Hallucinations in the Visually Impaired: The Charles Bonnet Syndrome". Survey of Ophthalmology. 48 (1): 58–72. doi:10.1016/S0039-6257(02)00414-9. PMID 12559327.
15. ^ a b c Teeple, Ryan C.; Caplan, Jason P.; Stern, Theodore A. (2009). "Visual Hallucinations: Differential Diagnosis and Treatment". Prim Care Companion J Clin Psychiatry. 11 (1): 26–32. doi:10.4088/pcc.08r00673. PMC 2660156. PMID 19333408.
16. ^ Perala, Jonna; Suvisaari, Jaana; Saarni, Samuli I.; Kuoppasalmi, Kimmo; Isometsa, Erkki; Pirkola, Sami; Partonen, Timo; Tuulio-Henriksson, Annamari; Hintikka, Jukka; Kieseppa, Tuula; Harkanen, Tommi; Koskinen, Seppo; Lonnqvist, Jouko (January 2007). "Lifetime Prevalence of Psychotic and Bipolar I Disorders in a General Population". Archives of General Psychiatry. 64 (1): 19–28. doi:10.1001/archpsyc.64.1.19. PMID 17199051.
17. ^ Mott, Richard H; Small, Iver F; Anderson, John M (June 1965). "Comparative Study Of Hallucinations". Archives of General Psychiatry. 12 (6): 595–601. doi:10.1001/archpsyc.1965.01720360067011. PMID 14286889.
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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
| Visual hallucinations in psychosis | None | 1,067 | wikipedia | https://en.wikipedia.org/wiki/Visual_hallucinations_in_psychosis | 2021-01-18T18:42:23 | {"wikidata": ["Q30302405"]} |
Although there are many syndromes of renal and/or genitorenal anomalies with radial ray dysostoses (Evans et al., 1992), the association of renal anomalies with ulnar ray dysgenesis has been found to occur mainly in 2 entities, the ulnar-mammary syndrome (181450) and Weyers ulnar ray/oligodactyly syndrome (602418). Kaplan and Bellah (1999) described brothers with variable expression of a possibly unique syndrome: an acrorenal syndrome with ulnar dysgenesis, oligodactyly, polydactyly, and dysplastic kidneys.
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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
| ULNAR RAY DYSGENESIS WITH POSTAXIAL POLYDACTYLY AND RENAL CYSTIC DYSPLASIA | c1858422 | 1,068 | omim | https://www.omim.org/entry/604380 | 2019-09-22T16:12:00 | {"mesh": ["C565783"], "omim": ["604380"]} |
A number sign (#) is used with this entry because of evidence that retinal arterial macroaneurysm associated with supravalvular pulmonic stenosis (RAMSVPS) can be caused by homozygous mutation in the IGFBP7 gene (602867) on chromosome 4q12.
Description
Retinal arterial macroaneurysm is an autosomal recessive condition characterized by the bilateral appearance of 'beading' along the major retinal arterial trunks, with the subsequent formation of macroaneurysms. Affected individuals also have supravalvular pulmonic stenosis, often requiring surgical correction (summary by Abu-Safieh et al., 2011).
Clinical Features
Dhindsa and Abboud (2002) reported 3 unrelated Saudi Arabian families in which 2 or more sibs displayed multiple retinal arterial macroaneurysms. Age at onset ranged from 3 months to 19 years; some cases were originally diagnosed as 'atypical bilateral Coats' (see 300216). All 7 patients had beading and macroaneurysms along the major retinal arterial trunks bilaterally. In 5 patients, recurrent bleeding and leakage from the macroaneurysyms occurred, resulting in loss of vision. The clinical course was unpredictable, with leakage developing after periods of seeming stabilization. The blood was mainly located under the internal limiting membrane and resorbed spontaneously with improved visual acuity. Argon laser photocoagulation of leaking macroaneurysms resulted in clinical improvement in 3 patients. Vascular sheathing was seen in some patients, but no signs of active vasculitis appeared, despite many years of follow-up (average, 7.8 years). Thorough examination of all patients, specifically of cardiovascular, neurologic, and musculoskeletal systems, revealed no associated systemic disease. One patient underwent brain MRI with magnetic resonance angiography that showed no vascular anomalies of the central nervous system. Dhindsa and Abboud (2002) stated that the retinal disease in these patients represented a new condition, which they designated 'familial retinal arterial macroaneurysms.'
Abu-Safieh et al. (2011) performed thorough dysmorphologic, ophthalmologic, and cardiologic evaluation in 22 patients with retinal arterial macroaneurysm from 8 consanguineous Saudi Arabian families, including 2 families reported by Dhindsa and Abboud (2002). In addition to typical ophthalmologic findings, the 12 patients who underwent echocardiography were found to have supravalvular pulmonic stenosis, which in some patients required surgical correction. There were no obvious dysmorphic features, and no evidence of other systemic involvement was noted.
Mapping
In 8 consanguineous Saudi Arabian families segregating autosomal recessive retinal arterial macroaneurysm and supravalvular pulmonic stenosis, including 2 families reported by Dhindsa and Abboud (2002), Abu-Safieh et al. (2011) performed homozygosity and linkage analysis. Each of the 8 families showed a run of homozygosity on chromosome 4, and a collective lod score of 11.4 was obtained for an approximately 5.1-Mb locus delimited by the SNPs rs6833480 and rs10017149. Analysis of microsatellites and additional SNPs refined the region to an approximately 4.7-Mb interval flanked by rs76451666 and D4S398.
Molecular Genetics
In 8 consanguineous Saudi Arabian families with retinal arterial macroaneurysm and supravalvular pulmonic stenosis mapping to chromosome 4q, including 2 families reported by Dhindsa and Abboud (2002), Abu-Safieh et al. (2011) analyzed 6 candidate genes and identified homozygosity for a splice variant in the IGFBP7 gene (602867.0001) that segregated with disease in each family. Although they had different tribal and geographic backgrounds, the 8 families were found to share a common haplotype, and screening of 300 Saudi controls revealed the presence of 1 heterozygous carrier, whose genotypic analysis confirmed carriage of the mutation on the same disease haplotype. Abu-Safieh et al. (2011) concluded that the mutation was of common ancestral origin, and noted that the very small shared haplotype made it likely that it was also ancient in origin.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Retinal arterial beading along all 4 retinal arterial trunks \- Retinal arterial macroaneurysms, multiple, developing at sites of beading \- Exudative maculopathy \- Exudative retinal detachment \- Hemorrhage beneath internal limiting membrane due to leaking macroaneurysms \- Pigmentary changes, retinal and/or subretinal (in some patients) \- Vascular sheathing (in some patients) CARDIOVASCULAR Vascular \- Pulmonic stenosis, supravalvular MOLECULAR BASIS \- Caused by mutation in the insulin-like growth factor-binding protein-7 gene (IGFBP7, 602867.0001 ) ▲ 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
| RETINAL ARTERIAL MACROANEURYSM WITH SUPRAVALVULAR PULMONIC STENOSIS | c3280205 | 1,069 | omim | https://www.omim.org/entry/614224 | 2019-09-22T15:55:59 | {"omim": ["614224"], "orphanet": ["284247"], "synonyms": ["FRAM", "Retinal arterial macroaneurysm and supravalvular pulmonic stenosis"]} |
An extremely rare penile epithelial neoplasm, histologically composed of nests of epithelilal cells floating in lakes of extracellular, PAS-positive mucin, clinically characterized by a nonhealing ulcer or soft mass in the preputium or glans area, with itching and burning often preceding appearance of the lesion. Lymphadenopathy may indicate dissemination. Mucinous metaplasia of the penis may be a risk factor.
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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
| Adenocarcinoma of the penis | c0221286 | 1,070 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=398053 | 2021-01-23T18:26:17 | {"icd-10": ["C60.0", "C60.1", "C60.2", "C60.8", "C60.9"], "synonyms": ["Penile adenocarcinoma"]} |
Dhumeaux and Berthelot (1975) described a third form of conjugated hyperbilirubinemia presumably distinct from either the Rotor form (237450) or the Dubin-Johnson form (237500). The plasma disappearance rate and hepatic transport maximum for sulfobromophthalein, dibromosulfophthalein, rose bengal, and indocyanin green were decreased, but the most striking feature was marked reduction in dye storage by the liver. Bilirubin UDP-glucuronyltransferase activity, plasma bile acid concentration and conventional liver function tests were all normal. A primary defect in hepatic uptake or storage of bilirubin was postulated. The proband was a 19-year-old Portuguese woman living in France. A brother was studied and found normal, but no other family studies were possible.
Inheritance \- Autosomal recessive Lab \- Conjugated hyperbilirubinemia Skin \- Jaundice ▲ 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
| HYPERBILIRUBINEMIA, CONJUGATED, TYPE III | c0400964 | 1,071 | omim | https://www.omim.org/entry/237550 | 2019-09-22T16:26:52 | {"mesh": ["C562885"], "omim": ["237550"]} |
Epizootic ulcerative syndrome (EUS), also known as mycotic granulomatosis (MG) or red spot disease (RSD), is a disease caused by the water mould Aphanomyces invadans. It infects many freshwater and brackish fish species in the Asia-Pacific region and Australia. The disease is most commonly seen when there are low temperature and heavy rainfall in tropical and sub-tropical waters.
## Clinical signs and diagnosis[edit]
At first, fish develop red spots on the skin. These lesions expand to form ulcers and extensive erosions filled with necrotic tissue and mycelium. This is followed by the development of granulomas on the internal organs and death.
A provisional diagnosis can be made by using squash preparations of the skeletal muscle from beneath an ulcer to identify the septate hyphae of the water mould. Definitive diagnosis can be made based on histopathogical findings and isolation of the pathogen.
## Treatment and control[edit]
Infected fish should be moved into high quality water, where they may recover if their clinical signs are mild.
If disease occurs eradication is required. Once the disease is eradicated good husbandry, surveillance and biosecurity measures are necessary to prevent recurrence. In countries free of epizootic ulcerative syndrome, quarantine and health certificates are necessary for the movement of all live fish to prevent the introduction of the disease.
## References[edit]
* Epizootic Ulcerative Syndrome, reviewed and published by Wikivet at http://en.wikivet.net/Epizootic_Ulcerative_Syndrome, accessed 08/09/2011.
* v
* t
* e
Fish diseases and parasites
Pathogens
* Aeromonas salmonicida
* Nervous necrosis virus
* Columnaris
* Enteric redmouth
* Fin rot
* Fish dropsy
* Flavobacterium
* Hematopoietic necrosis
* Heterosigma akashiwo
* Hole in the head
* Hypodermal and hematopoietic necrosis
* Infectious pancreatic necrosis
* Koi herpes virus
* Mycobacterium marinum
* Novirhabdovirus
* Pfiesteria piscicida
* Photobacterium damselae ssp piscicida
* Salmon anemia
* Streptococcus iniae
* Spring viraemia of carp
* Taura syndrome
* UDN
* VHS
* White spot
* Yellowhead
Parasites
* Abergasilus
* Amoebic gill disease
* Anisakis
* Carp lice
* Ceratomyxa shasta
* Clinostomum marginatum
* Dactylogyrus vastator
* Diphyllobothrium
* Cymothoa exigua
* Eustrongylidosis
* Epizootic ulcerative syndrome
* Flukes
* Glugea
* Gyrodactylus salaris
* Henneguya zschokkei
* Ich (freshwater)
* Ich (marine)
* Kudoa thyrsites
* Lernaeocera branchialis
* Microsporidia
* Monogenea
* Myxobolus cerebralis
* Myxosporea
* Nanophyetus salmincola
* Pseudorhabdosynochus spp.
* Salmon lice
* Saprolegnia
* Schistocephalus solidus
* Sea louse
* Sphaerothecum destruens
* Swim bladder disease
* Tetracapsuloides bryosalmonae
* Velvet
* Xenoma
Fish groups
* Diseases and parasites in cod
* Diseases and parasites in salmon
* Disease in ornamental fish
* List of aquarium diseases
Related topics
* Amnesic shellfish poisoning
* Brevetoxin
* Ciguatera
* Diarrheal shellfish poisoning
* Fish kill
* Marine viruses
* Neurotoxic shellfish poisoning
* Paralytic shellfish poisoning
* Saxitoxin
*[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
| Epizootic ulcerative syndrome | None | 1,072 | wikipedia | https://en.wikipedia.org/wiki/Epizootic_ulcerative_syndrome | 2021-01-18T18:38:32 | {"wikidata": ["Q2691562"]} |
Multiple epiphyseal dysplasia is a disorder of cartilage and bone development primarily affecting the ends of the long bones in the arms and legs (epiphyses). There are two types of multiple epiphyseal dysplasia, which can be distinguished by their pattern of inheritance. Both the dominant and recessive types have relatively mild signs and symptoms, including joint pain that most commonly affects the hips and knees, early-onset arthritis, and a waddling walk. Although some people with multiple epiphyseal dysplasia have mild short stature as adults, most are of normal height. The majority of individuals are diagnosed during childhood; however, some mild cases may not be diagnosed until adulthood.
Recessive multiple epiphyseal dysplasia is distinguished from the dominant type by malformations of the hands, feet, and knees and abnormal curvature of the spine (scoliosis). About 50 percent of individuals with recessive multiple epiphyseal dysplasia are born with at least one abnormal feature, including an inward- and upward-turning foot (clubfoot), an opening in the roof of the mouth (cleft palate), an unusual curving of the fingers or toes (clinodactyly), or ear swelling. An abnormality of the kneecap called a double-layered patella is also relatively common.
## Frequency
The incidence of dominant multiple epiphyseal dysplasia is estimated to be at least 1 in 10,000 newborns. The incidence of recessive multiple epiphyseal dysplasia is unknown. Both forms of this disorder may actually be more common because some people with mild symptoms are never diagnosed.
## Causes
Mutations in the COMP, COL9A1, COL9A2, COL9A3, or MATN3 gene can cause dominant multiple epiphyseal dysplasia. These genes provide instructions for making proteins that are found in the spaces between cartilage-forming cells (chondrocytes). These proteins interact with each other and play an important role in cartilage and bone formation. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.
The majority of individuals with dominant multiple epiphyseal dysplasia have mutations in the COMP gene. About 10 percent of affected individuals have mutations in the MATN3 gene. Mutations in the COMP or MATN3 gene prevent the release of the proteins produced from these genes into the spaces between the chondrocytes. The absence of these proteins leads to the formation of abnormal cartilage, which can cause the skeletal problems characteristic of dominant multiple epiphyseal dysplasia.
The COL9A1, COL9A2, and COL9A3 genes provide instructions for making a protein called type IX collagen. Collagens are a family of proteins that strengthen and support connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Mutations in the COL9A1, COL9A2, or COL9A3 gene are found in less than five percent of individuals with dominant multiple epiphyseal dysplasia. It is not known how mutations in these genes cause the signs and symptoms of this disorder. Research suggests that mutations in these genes may cause type IX collagen to accumulate inside the cell or interact abnormally with other cartilage components.
Some people with dominant multiple epiphyseal dysplasia do not have a mutation in the COMP, COL9A1, COL9A2, COL9A3, or MATN3 gene. In these cases, the cause of the condition is unknown.
Mutations in the SLC26A2 gene cause recessive multiple epiphyseal dysplasia. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of recessive multiple epiphyseal dysplasia.
### Learn more about the genes associated with Multiple epiphyseal dysplasia
* COL9A1
* COL9A2
* COL9A3
* COMP
* MATN3
* SLC26A2
## Inheritance Pattern
Multiple epiphyseal dysplasia can have different inheritance patterns.
This condition can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.
Multiple epiphyseal dysplasia can also be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.
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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
| Multiple epiphyseal dysplasia | c3279941 | 1,073 | medlineplus | https://medlineplus.gov/genetics/condition/multiple-epiphyseal-dysplasia/ | 2021-01-27T08:24:32 | {"gard": ["10756"], "omim": ["120210", "132400", "600204", "600969", "226900", "607078"], "synonyms": []} |
A rare autosomal recessive congenital myopathy characterized by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy including facial weakness, ocular abnormalities (ptosis and external ophthalmoplegia) and predominant proximal muscle weakness of variable severity with possible distal involvement.
## Epidemiology
The exact prevalence remains unknown.
## Clinical description
The age of onset varies from birth to childhood. AR-CNM is characterized by facial weakness including severe involvement of the masticatory muscles, and ocular abnormalities such as ptosis and external ophthalmoplegia. Muscle weakness is observed with variable severity. It is usually prominently proximal, but there may be additional distal weakness and wasting in the lower limbs. Foot abnormalities are frequent and other skeletal deformities (including high arched palate and scoliosis) are common. Respiratory involvement may be severe. An associated cardiomyopathy has been documented in a few, genetically unresolved cases. Urinary incontinence may be an associated feature.
## Etiology
The disease is associated with mutations in BIN1 (2q14), encoding Myc box-dependent-interacting protein 1. AR- CNMs can be also related to biallelic mutation in RYR1 (19q13.2) , SPEG (2q35) and TTN (2q31.2) genes.
## Diagnostic methods
Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features. Genetic testing is required to confirm the diagnosis. Muscle MRI may be helpful to distinguish AR-CNM from other forms of CNM.
## Differential diagnosis
The main differential diagnoses include other congenital myopathies, myotonic dystrophy and, if facial involvement is prominent, facioscapulohumeral dystrophy.
## Antenatal diagnosis
Prenatal diagnosis is possible where the mutation has previously been identified in a family member.
## Genetic counseling
The pattern of inheritance is autosomal recessive. The risk to siblings of inheriting the disease is 25%. Offspring of affected individuals are obligate carriers. Genetic counseling should be offered to all patients and their families.
## Management and treatment
There is no curative treatment currently available. Management is supportive and based on a multidisciplinary approach.
## Prognosis
In the absence of severe cardiorespiratory involvement, the prognosis appears favorable, with mild progressive proximal weakness.
*[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
| Autosomal recessive centronuclear myopathy | c0410204 | 1,074 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=169186 | 2021-01-23T17:20:27 | {"gard": ["12718"], "mesh": ["C562934"], "omim": ["255200", "615959"], "umls": ["C0410204", "C3645536"], "icd-10": ["G71.2"], "synonyms": ["AR-CNM"]} |
Pseudoinflammatory fundus dystrophy was described by Sorsby et al. (1949) as a dominant disorder (see 136900). The existence of a recessive form was suggested by several reports. From Finland, Forsius et al. (1982) reported a family in which both parents (who were related) were affected and all of their 8 children were also affected. Among collateral relatives, 3 other cases were found. All affected individuals over age 30 years had an 'exudative' process in the central part of the retina, often complicated at some stage by hemorrhages. The age of onset varied from the second to the fourth decade. Myopia increased rapidly in the active stages. The recessive form may have somewhat earlier age of onset on the average. An apparently recessive form was reported in 1 family by Sorsby (1940). Francois (1961) reported 2 brothers who were thought to have the recessive form. Eriksson et al. (1990) provided follow-up on the family reported by Forsius et al. (1982). They presented a pedigree documenting that the grandparents and parents of all 8 affected children were related in many ways. One of the 8 children had an affected daughter and an unaffected son. Eriksson et al. (1990) gave a comparison of the autosomal dominant and autosomal recessive forms of pseudoinflammatory fundus dystrophy, called by them the Sorsby type and the Lavia (Finnish) type, respectively. The Finnish type, thought to be inherited as an autosomal recessive, had earlier onset than the Sorsby type, with relatively rapid loss of visual acuity and striking peripheral retinal degeneration and secondary dyschromatopsia. Dark adaptation was normal in the Sorsby type and disturbed in the Lavia type.
However, after heterozygous mutations in the gene encoding tissue inhibitor of metalloproteinases-3 (TIMP3; 188826) were found as the cause of Sorsby fundus dystrophy, Felbor et al. (1997) restudied the Lavia kindred and showed that all affected members were heterozygous for a gly166-to-cys mutation in the TIMP3 gene (188826.0004) and provided strong evidence for an autosomal dominant inheritance of the Sorsby fundus dystrophy phenotype in this kindred. They concluded from all available data that SFD is a genetically homogeneous, although clinically heterogeneous, autosomal dominant disorder.
Eyes \- Pseudoinflammatory fundus dystrophy \- Central retinal exudate \- Retinal hemorrhages \- Myopia \- Relatively rapid loss of visual acuity \- Striking peripheral retinal degeneration \- Secondary dyschromatopsia \- Disturbed dark adaptation Misc \- Onset from second to fourth decade Inheritance \- Autosomal recessive ▲ 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
| FUNDUS DYSTROPHY, PSEUDOINFLAMMATORY, RECESSIVE FORM | c1850938 | 1,075 | omim | https://www.omim.org/entry/264420 | 2019-09-22T16:23:04 | {"mesh": ["C564992"], "omim": ["136900", "264420"], "orphanet": ["59181"], "synonyms": ["Alternative titles", "PFD, LAVIA TYPE", "PFD, FINNISH TYPE"]} |
A number sign (#) is used with this entry because of evidence that Joubert syndrome-6 (JBTS6) is caused by homozygous or compound heterozygous mutation in the TMEM67 (609884) on chromosome 8q22.
Description
Joubert syndrome is an autosomal recessive disorder presenting with psychomotor delay, hypotonia, ataxia, oculomotor apraxia, and neonatal breathing abnormalities. Neuroradiologically, Joubert syndrome is characterized by peculiar malformation of the midbrain-hindbrain junction known as the 'molar tooth sign' (MTS) consisting of cerebellar vermis hypoplasia or aplasia, thick and maloriented superior cerebellar peduncles, and abnormally deep interpeduncular fossa (Romano et al., 2006).
For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
Clinical Features
Baala et al. (2007) identified a genetically distinct form of Joubert syndrome designated JBTS6. Two of the patients had been described by Romano et al. (2006). One, a 14-year-old girl, was severely handicapped and presented with hypotonia, severe mental retardation, stereotypic movements, and no independent walking. She had breathing abnormalities but no oculomotor apraxia or abnormal eye movements, and no renal or hepatic involvement. The other, a mildly affected 7-year-old girl, presented with hypotonia, ataxia, oculomotor apraxia, and abnormal eye movements. She had no breathing abnormalities or retinal, renal, or hepatic involvement. She had mild motor delay and moderate mental retardation. The third patient was a 7-year-old boy presenting developmental delay, cerebellar ataxia, abnormal breathing, and vermis agenesis. No MRI was performed; the association of hyperechogenic kidneys with cysts and severe hepatic involvement with vermis agenesis led to the diagnosis of Joubert syndrome.
In a comprehensive study of 279 patients from 232 unrelated families with Joubert syndrome in whom a genetic basis was determined by molecular analysis of 27 candidate genes, Bachmann-Gagescu et al. (2015) found a significant association between mutations in the TMEM67 gene and liver fibrosis (odds ratio (OR) of 17.3) and coloboma (OR of 22.9). In addition, there was a negative correlation between TMEM67 mutations and retinal disease (OR of 0.1).
Molecular Genetics
Baala et al. (2007) found mutation in the TMEM67 gene (609884) in compound heterozygosity or homozygosity in patients with Joubert syndrome (609884.0006-609884.0010).
Otto et al. (2009) identified TMEM67 mutations (609884.0011; 609884.0013; 609884.0019; 609884.0021-609884.0023) in 4 (3.3%) of 120 unrelated probands with Joubert syndrome. All patients had ataxia, hypotonia or psychomotor retardation or showed cerebellar vermis hypo- or aplasia. All developed end-stage renal disease between 8 and 15 years, and 4 had hepatic fibrosis. Four also had ocular involvement, including blindness, retinal degeneration or retinal coloboma.
In a German girl with Joubert syndrome, Dafinger et al. (2011) identified 2 pathogenic missense mutations in the TMEM67 gene (I833T, 609884.0013 and P358L, 609884.0024), consistent with JBTS6, as well as a heterozygous 12-bp deletion in the KIF7 gene (611254.0008). The patient had mental retardation, molar tooth sign on brain MRI, ataxia, hypertelorism, low-set ears, coloboma, and elevated liver enzymes.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Abnormal eye movements \- Oculomotor apraxia \- Retinal degeneration \- Chorioretinal coloboma \- Blindness RESPIRATORY \- Breathing dysregulation ABDOMEN Liver \- Hepatic fibrosis \- Bile duct proliferation GENITOURINARY Kidneys \- Nephronophthisis \- End-stage renal failure \- Microcysts NEUROLOGIC Central Nervous System \- Cerebellar vermis hypoplasia \- Hypotonia \- Developmental delay \- Mental retardation \- Molar tooth sign on MRI \- Deep posterior interpeduncular fossa \- Thick, elongated superior cerebellar peduncles \- Ataxia MISCELLANEOUS \- Genetic heterogeneity (see 213300 ) MOLECULAR BASIS \- Caused by mutation in the transmembrane protein 67 gene (TMEM67, 609884.0006 ) ▲ 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
| JOUBERT SYNDROME 6 | c4551568 | 1,076 | omim | https://www.omim.org/entry/610688 | 2019-09-22T16:04:12 | {"doid": ["0111001"], "mesh": ["C536293"], "omim": ["213300", "610688"], "orphanet": ["475"], "synonyms": ["CPD IV", "Cerebelloparenchymal disorder IV", "Classic Joubert syndrome", "Joubert syndrome type A", "Joubert-Boltshauser syndrome", "Pure Joubert syndrome"], "genereviews": ["NBK1325"]} |
Hypotonia
Other namesFloppy baby syndrome
An infant with botulism; despite not being asleep or sedated, he cannot open his eyes or move; he also has a weak cry.
SpecialtyPediatrics
SymptomsMuscle weakness
Hypotonia is a state of low muscle tone[1] (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength. Hypotonia is a lack of resistance to passive movement, whereas muscle weakness results in impaired active movement. Central hypotonia originates from the central nervous system, while peripheral hypotonia is related to problems within the spinal cord, peripheral nerves and/or skeletal muscles.[2] Severe hypotonia in infancy commonly known as floppy baby syndrome. Recognizing hypotonia, even in early infancy, is usually relatively straightforward, but diagnosing the underlying cause can be difficult and often unsuccessful. The long-term effects of hypotonia on a child's development and later life depend primarily on the severity of the muscle weakness and the nature of the cause. Some disorders have a specific treatment but the principal treatment for most hypotonia of idiopathic or neurologic cause is physical therapy and/or occupational therapy for remediation.
Hypotonia is thought to be associated with the disruption of afferent input from stretch receptors and/or lack of the cerebellum’s facilitatory efferent influence on the fusimotor system, the system that innervates intrafusal muscle fibers thereby controlling muscle spindle sensitivity.[3] On examination a diminished resistance to passive movement will be noted and muscles may feel abnormally soft and limp on palpation.[3] Diminished deep tendon reflexes also may be noted. Hypotonia is a condition that can be helped with early intervention.[citation needed]
## Contents
* 1 Signs and symptoms
* 1.1 Floppy baby syndrome
* 1.2 Developmental delay
* 1.3 Muscle tone vs. muscle strength
* 2 Cause
* 2.1 Acquired
* 3 Diagnosis
* 3.1 Terminology
* 4 Prognosis and treatment
* 5 See also
* 6 References
* 7 Further reading
* 8 External links
## Signs and symptoms[edit]
Hypotonic patients may display a variety of objective manifestations that indicate decreased muscle tone. Motor skills delay is often observed, along with hypermobile or hyperflexible joints, drooling and speech difficulties, poor reflexes, decreased strength, decreased activity tolerance, rounded shoulder posture, with leaning onto supports, and poor attention. The extent and occurrence of specific objective manifestations depends upon the age of the patient, the severity of the hypotonia, the specific muscles affected, and sometimes the underlying cause. For instance, some people with hypotonia may experience constipation, while others have no bowel problems.[citation needed]
### Floppy baby syndrome[edit]
The term "floppy infant syndrome" is used to describe abnormal limpness when an infant is born. Infants who suffer from hypotonia are often described as feeling and appearing as though they are "rag dolls". They are unable to maintain flexed ligaments, and are able to extend them beyond normal lengths. Often, the movement of the head is uncontrollable, not in the sense of spasmatic movement, but chronic ataxia. Hypotonic infants often have difficulty feeding, as their mouth muscles cannot maintain a proper suck-swallow pattern, or a good breastfeeding latch.[citation needed]
### Developmental delay[edit]
Children with normal muscle tone are expected to achieve certain physical abilities within an average timeframe after birth. Most low-tone infants have delayed developmental milestones, but the length of delay can vary widely. Motor skills are particularly susceptible to the low-tone disability. They can be divided into two areas, gross motor skills, and fine motor skills, both of which are affected. Hypotonic infants are late in lifting their heads while lying on their stomachs, rolling over, lifting themselves into a sitting position, remaining seated without falling over, balancing, crawling, and sometimes walking. Fine motor skills delays occur in grasping a toy or finger, transferring a small object from hand to hand, pointing out objects, following movement with the eyes, and self-feeding.[citation needed]
Speech difficulties can result from hypotonia. Low-tone children learn to speak later than their peers, even if they appear to understand a large vocabulary, or can obey simple commands. Difficulties with muscles in the mouth and jaw can inhibit proper pronunciation, and discourage experimentation with word combination and sentence-forming. Since the hypotonic condition is actually an objective manifestation of some underlying disorder, it can be difficult to determine whether speech delays are a result of poor muscle tone, or some other neurological condition, such as intellectual disability, that may be associated with the cause of hypotonia. Additionally, lower muscle tone can be caused by Mikhail-Mikhail syndrome, which is characterized by muscular atrophy and cerebellar ataxia which is due to abnormalities in the ATXN1 gene.[citation needed]
### Muscle tone vs. muscle strength[edit]
The low muscle tone associated with hypotonia must not be confused with low muscle strength or the definition commonly used in bodybuilding. Neurologic muscle tone is a manifestation of periodic action potentials from motor neurons. As it is an intrinsic property of the nervous system, it cannot be changed through voluntary control, exercise, or diet.[citation needed]
"True muscle tone is the inherent ability of the muscle to respond to a stretch. For example, quickly straightening the flexed elbow of an unsuspecting child with normal tone, will cause their biceps to contract in response (automatic protection against possible injury). When the perceived danger has passed, (which the brain figures out once the stimulus is removed), the muscle relaxes and returns to its normal resting state."
"...The child with low tone has muscles that are slow to initiate a muscle contraction, contract very slowly in response to a stimulus, and cannot maintain a contraction for as long as his 'normal' peers. Because these low-toned muscles do not fully contract before they again relax (muscle accommodates to the stimulus and so shuts down again), they remain loose and very stretchy, never realizing their full potential of maintaining a muscle contraction over time. "
## Cause[edit]
Some conditions known to cause hypotonia include:
Congenital – i.e. disease a person is born with (including genetic disorders presenting within 6 months)
* Genetic disorders are the most common cause
* 22q13 deletion syndrome a.k.a. Phelan–McDermid syndrome
* 3-Methylcrotonyl-CoA carboxylase deficiency[4]
* Achondroplasia
* Aicardi syndrome
* Autism spectrum disorders[5]
* Canavan disease
* Centronuclear myopathy (including myotubular myopathy)
* Central core disease
* CHARGE syndrome
* Cohen syndrome
* Costello syndrome
* Dejerine–Sottas disease (HMSN Type III)
* Down syndrome a.k.a. trisomy 21 — most common
* Ehlers–Danlos syndrome
* Familial dysautonomia (Riley–Day syndrome)
* FG syndrome
* Fragile X syndrome
* Griscelli syndrome Type 1 (Elejalde syndrome)
* Disorder Growth Hormone Disorder Pituitary Dwarfism
* Holocarboxylase synthetase deficiency / Multiple carboxylase deficiency[6]
* Krabbe disease
* Leigh's disease
* Lesch–Nyhan syndrome[7]
* Marfan's syndrome
* Menkes syndrome
* Methylmalonic acidemia
* Myotonic dystrophy
* Niemann–Pick disease
* Nonketotic hyperglycinemia (NKH) or Glycine encephalopathy (GCE)
* Noonan syndrome
* Neurofibromatosis
* Patau syndrome a.k.a. trisomy 13
* Prader–Willi syndrome
* Rett syndrome
* Septo-optic dysplasia (de Morsier syndrome)
* Snyder–Robinson syndrome (SRS)
* Spinal muscular atrophy (SMA)
* Succinic semialdehyde dehydrogenase deficiency (SSADH)
* Tay–Sachs disease
* Werdnig–Hoffmann syndrome – Spinal muscular atrophy with congenital degeneration of anterior horns of spinal cord. Autosomal recessive [8]
* Wiedemann–Steiner syndrome
* Williams syndrome
* Zellweger syndrome a.k.a. cerebrohepatorenal syndrome
* Developmental disability
* Cerebellar ataxia (congenital)
* Sensory processing disorder
* Developmental coordination disorder
* Hypothyroidism (congenital)
* Hypotonic cerebral palsy
* Teratogenesis from in utero exposure to Benzodiazepines
### Acquired[edit]
Acquired – i.e. onset occurs after birth
* Genetic
* Muscular dystrophy (including Myotonic dystrophy) – most common
* Metachromatic leukodystrophy
* Rett syndrome
* Spinal muscular atrophy
* Infections
* Encephalitis
* Guillain–Barré syndrome
* Infant botulism
* Meningitis
* Poliomyelitis
* Sepsis
* Toxins
* Infantile acrodynia (childhood mercury poisoning)
* Autoimmunity disorders
* Myasthenia gravis – most common
* Abnormal vaccine reaction
* Celiac disease[9]
* Metabolic disorder
* Hypervitaminosis
* Kernicterus
* Rickets
* Neurological
* Traumatic brain injury, such as the damage that is caused by shaken baby syndrome
* Lower motor neuron lesions
* Upper motor neuron lesions
* Miscellaneous
* Central nervous system dysfunction, including cerebellar lesions and cerebral palsy
* Hypothyroidism
* Sandifer syndrome
* Neonatal benzodiazepine withdrawal syndrome in children born to mothers treated in late pregnancy with benzodiazepine medications[10]
## Diagnosis[edit]
The approach to diagnosing the cause of hypotonia (as with all syndromes in neurology) is first localization. The physician must first determine if the hypotonia is due to muscle, neuromuscular junction, nerve, or central cause. This will narrow the possible causes. If the cause of the hypotonia is found to lie in the brain, then it can be classified as a cerebral palsy. If the cause is localized to the muscles, it can be classified as a muscular dystrophy. If the cause is thought to be in the nerves, it is called hypotonia due to polyneuropathy. Many cases cannot be definitively diagnosed.[11]
Diagnosing a patient includes obtaining family medical history and a physical examination, and may include such additional tests as computerized tomography (CT) scans, magnetic resonance imaging (MRI) scans, electroencephalogram (EEG), blood tests, genetic testing (such as chromosome karyotyping and tests for specific gene abnormalities), spinal taps, electromyography muscle tests, or muscle and nerve biopsy.[citation needed]
Mild or benign hypotonia is often diagnosed by physical and occupational therapists through a series of exercises designed to assess developmental progress, or observation of physical interactions. Since a hypotonic child has difficulty deciphering his spatial location, he may have some recognizable coping mechanisms, such as locking the knees while attempting to walk. A common sign of low-tone infants is a tendency to observe the physical activity of those around them for a long time before attempting to imitate, due to frustration over early failures. Developmental delay can indicate hypotonia.[citation needed]
### Terminology[edit]
The term hypotonia comes from the Ancient Greek ὑπο- (hypo-), "under" and τόνος (tónos), from τείνω (teinō), "to stretch". Other terms for the condition include:[citation needed]
* Low Muscle Tone
* Benign Congenital Hypotonia
* Congenital Hypotonia
* Congenital Muscle Hypotonia
* Congenital Muscle Weakness
* Amyotonia Congenita
* Floppy Baby Syndrome
* Infantile Hypotonia
## Prognosis and treatment[edit]
This section needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Hypotonia" – news · newspapers · books · scholar · JSTOR (April 2016)
There is currently no known treatment or cure for most (or perhaps all) causes of hypotonia, and objective manifestations can be lifelong. The outcome in any particular case of hypotonia depends largely on the nature of the underlying disease. In some cases, muscle tone improves over time, or the patient may learn or devise coping mechanisms that enable them to overcome the most disabling aspects of the disorder. However, hypotonia caused by cerebellar dysfunction or motor neuron diseases can be progressive and life-threatening.
Along with normal pediatric care, specialists who may be involved in the care of a child with hypotonia include developmental pediatricians (specialize in child development), neurologists, neonatologists (specialize in the care of newborns), geneticists, occupational therapists, physical therapists, speech therapists, orthopedists, pathologists (conduct and interpret biochemical tests and tissue analysis), and specialized nursing care.
If the underlying cause is known, treatment is tailored to the specific disease, followed by symptomatic and supportive therapy for the hypotonia. In very severe cases, treatment may be primarily supportive, such as mechanical assistance with basic life functions like breathing and feeding, physical therapy to prevent muscle atrophy and maintain joint mobility, and measures to try to prevent opportunistic infections such as pneumonia. Treatments to improve neurological status might involve such things as medication for a seizure disorder, medicines or supplements to stabilize a metabolic disorder, or surgery to help relieve the pressure from hydrocephalus (increased fluid in the brain).
The National Institute of Neurological Disorders and Stroke states that physical therapy can improve motor control and overall body strength in individuals with hypotonia. This is crucial to maintaining both static and dynamic postural stability, which is important since postural instability is a common problem in people with hypotonia.[3] A physiotherapist can develop patient specific training programs to optimize postural control, in order to increase balance and safety.[3] To protect against postural asymmetries the use of supportive and protective devices may be necessary.[3] Physical therapists might use neuromuscular/sensory stimulation techniques such as quick stretch, resistance, joint approximation, and tapping to increase tone by facilitating or enhancing muscle contraction in patients with hypotonia.[3] For patients who demonstrate muscle weakness in addition to hypotonia strengthening exercises that do not overload the muscles are indicated.[3] Electrical Muscle Stimulation, also known as Neuromuscular Electrical Stimulation (NMES) can also be used to “activate hypotonic muscles, improve strength, and generate movement in paralyzed limbs while preventing disuse atrophy (p.498).”[3] When using NMES it is important to have the patient focus on attempting to contract the muscle(s) being stimulated. Without such concentration on movement attempts, carryover to volitional movement is not feasible.[3] NMES should ideally be combined with functional training activities to improve outcomes.
Occupational therapy can assist the patient with increasing independence with daily tasks through improvement of motor skills, strength, and functional endurance. Speech-language therapy can help with any breathing, speech, and/or swallowing difficulties the patient may be having. Therapy for infants and young children may also include sensory stimulation programs. A physical therapist may recommend an ankle/foot orthosis to help the patient compensate for weak lower leg muscles. Toddlers and children with speech difficulties may benefit greatly by using sign language.
## See also[edit]
* Hypertonia
## References[edit]
1. ^ "Hypotonia". MedlinePlus Medical Encyclopedia.
2. ^ Sarah Bager (2009). "Central Hyptonia" (PDF). Retrieved 22 April 2017.
3. ^ a b c d e f g h i O'Sullivan S. B. (2007). Strategies to Improve Motor Function. In S. B. O’Sullivan, & T. J. Schmitz (Eds.), Physical Rehabilitation (5th Ed.) Philadelphia: F.A. Davis Company.
4. ^ "3-methylcrotonyl-CoA carboxylase deficiency (3-MCC deficiency)". Genetics Home Reference. Retrieved 28 November 2013.
5. ^ Xue Ming, et al. Prevalence of motor impairment in autism spectrum disorders. Brain and Development. Volume 29, Issue 9, October 2007, Pages 565–570.
6. ^ "Holocarboxylase Synthetase Deficiency / Multiple Carboxylase Deficiency". HLCS Gene Sequencing. GeneDx. Retrieved 28 November 2013.
7. ^ Kliegman, Robert. Nelson Textbook of Pediatrics (20 ed.). p. 747. ISBN 978-1455775668.
8. ^ http://www.webmd.com/children/werdnig-hoffman-disease
9. ^ Zelnik N, Pacht A, Obeid R, Lerner A (June 2004). "Range of neurologic disorders in patients with celiac disease". Pediatrics. 113 (6): 1672–6. CiteSeerX 10.1.1.545.9692. doi:10.1542/peds.113.6.1672. PMID 15173490.
10. ^ McElhatton PR. (November–December 1994). "The effects of benzodiazepine use during pregnancy and lactation". Reprod Toxicol. 8 (6): 461–75. doi:10.1016/0890-6238(94)90029-9. PMID 7881198.
11. ^ "The Benign Congenital Hypotonia Site". Retrieved 2007-06-07.
## Further reading[edit]
* Martin K, Inman J, Kirschner A, Deming K, Gumbel R, Voelker L (2005). "Characteristics of hypotonia in children: a consensus opinion of pediatric occupational and physical therapists". Pediatric Physical Therapy. 17 (4): 275–82. doi:10.1097/01.pep.0000186506.48500.7c. PMID 16357683. S2CID 24077081.
## External links[edit]
* hypotonia at NINDS
* Hypotonia – Medline Plus
Classification
D
* ICD-10: P94.2
* ICD-9-CM: 358,781.3
* MeSH: D009123
* DiseasesDB: 21417
External resources
* MedlinePlus: 003298
* v
* t
* e
Diseases of muscle, neuromuscular junction, and neuromuscular disease
Neuromuscular-
junction disease
* autoimmune
* Myasthenia gravis
* Lambert–Eaton myasthenic syndrome
* Neuromyotonia
Myopathy
Muscular dystrophy
(DAPC)
AD
* Limb-girdle muscular dystrophy 1
* Oculopharyngeal
* Facioscapulohumeral
* Myotonic
* Distal (most)
AR
* Calpainopathy
* Limb-girdle muscular dystrophy 2
* Congenital
* Fukuyama
* Ullrich
* Walker–Warburg
XR
* dystrophin
* Becker's
* Duchenne
* Emery–Dreifuss
Other structural
* collagen disease
* Bethlem myopathy
* PTP disease
* X-linked MTM
* adaptor protein disease
* BIN1-linked centronuclear myopathy
* cytoskeleton disease
* Nemaline myopathy
* Zaspopathy
Channelopathy
Myotonia
* Myotonia congenita
* Thomsen disease
* Neuromyotonia/Isaacs syndrome
* Paramyotonia congenita
Periodic paralysis
* Hypokalemic
* Thyrotoxic
* Hyperkalemic
Other
* Central core disease
Mitochondrial myopathy
* MELAS
* MERRF
* KSS
* PEO
General
* Inflammatory myopathy
* Congenital myopathy
* v
* t
* e
Conditions originating in the perinatal period / fetal disease
Maternal factors
complicating pregnancy,
labour or delivery
placenta
* Placenta praevia
* Placental insufficiency
* Twin-to-twin transfusion syndrome
chorion/amnion
* Chorioamnionitis
umbilical cord
* Umbilical cord prolapse
* Nuchal cord
* Single umbilical artery
presentation
* Breech birth
* Asynclitism
* Shoulder presentation
Growth
* Small for gestational age / Large for gestational age
* Preterm birth / Postterm pregnancy
* Intrauterine growth restriction
Birth trauma
* scalp
* Cephalohematoma
* Chignon
* Caput succedaneum
* Subgaleal hemorrhage
* Brachial plexus injury
* Erb's palsy
* Klumpke paralysis
Affected systems
Respiratory
* Intrauterine hypoxia
* Infant respiratory distress syndrome
* Transient tachypnea of the newborn
* Meconium aspiration syndrome
* Pleural disease
* Pneumothorax
* Pneumomediastinum
* Wilson–Mikity syndrome
* Bronchopulmonary dysplasia
Cardiovascular
* Pneumopericardium
* Persistent fetal circulation
Bleeding and
hematologic disease
* Vitamin K deficiency bleeding
* HDN
* ABO
* Anti-Kell
* Rh c
* Rh D
* Rh E
* Hydrops fetalis
* Hyperbilirubinemia
* Kernicterus
* Neonatal jaundice
* Velamentous cord insertion
* Intraventricular hemorrhage
* Germinal matrix hemorrhage
* Anemia of prematurity
Gastrointestinal
* Ileus
* Necrotizing enterocolitis
* Meconium peritonitis
Integument and
thermoregulation
* Erythema toxicum
* Sclerema neonatorum
Nervous system
* Perinatal asphyxia
* Periventricular leukomalacia
Musculoskeletal
* Gray baby syndrome
* muscle tone
* Congenital hypertonia
* Congenital hypotonia
Infections
* Vertically transmitted infection
* Neonatal infection
* rubella
* herpes simplex
* mycoplasma hominis
* ureaplasma urealyticum
* Omphalitis
* Neonatal sepsis
* Group B streptococcal infection
* Neonatal conjunctivitis
Other
* Miscarriage
* Perinatal mortality
* Stillbirth
* Infant mortality
* Neonatal withdrawal
*[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
| Hypotonia | c0026827 | 1,077 | wikipedia | https://en.wikipedia.org/wiki/Hypotonia | 2021-01-18T18:52:22 | {"mesh": ["D009123"], "umls": ["C0026827"], "icd-9": ["781.3", "358"], "icd-10": ["P94.2"], "wikidata": ["Q1753547"]} |
Far East scarlet-like fever
Other namesScarlatinoid fever
SpecialtyInfectious disease
Far East scarlet-like fever is an infectious disease caused by the gram negative bacillus Yersinia pseudotuberculosis. In Japan it is called Izumi fever.[1]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Differential diagnosis
* 5 History
* 6 References
## Signs and symptoms[edit]
These include[2][3]
* red skin rash usually of the face, elbows, and knees
* skin desquamation
* exanthema
* red tongue
* toxic shock syndrome
Other features include mesenteric lymphadenitis and arthritis. Kidney failure rarely occurs.
Relapses occur in up to 50% of patients.
## Cause[edit]
The cause of this disease is Yersinia pseudotuberculosis serotype O1. 95% are subtype O1b.
Yersinia pseudotuberculosis has been divided into 6 genetic groups: group 1 has only been isolated from the Far East.[4]
## Pathophysiology[edit]
The clinical features of this disease appear to be due—at least in part—to the production of a superantigen—YpM (Yersinia pseudotuberculosis-derived mitogen). This is present in almost all strains from the Far East but only 20% of European isolates.[5] The antigen was discovered in 1993 and is encoded by a 456-base gene. The protein has 151 amino acids, with a signal sequence of 20 amino acids. The mitogenic antigens are scattered across the protein but two cysteine residues (residues 32 and 129) which form a disulfide bridge are critical.
The G+C content of this gene is 35%—lower than the genomic average (47%) suggesting that this gene has been acquired from some other organism.[5] The organism from which this gene originated has not yet been identified. This gene seems likely to have been introduced into the genome by a bacteriophage, given the nearby presence of a phage integration site, but the mechanism of entry into the genome is not currently known.
## Diagnosis[edit]
### Differential diagnosis[edit]
The main differential diagnosis is scarlet fever.[6]
## History[edit]
The first outbreak of this disease was reported from the Pacific coastal areas (Primorsky Krai) of Russia in the 1950s.
## References[edit]
1. ^ Sato K, Ouchi K, Taki M (1983) Yersinia pseudotuberculosis infection in children, resembling Izumi fever and Kawasaki syndrome. Pediatr Infect Dis 2: 123–126
2. ^ Zalmover IIu, Znamenskiĭ VA, Ignatovich VO, Vishniakov AK, Serov GD (1969) Clinical aspects of Far Eastern scarlatina-like fever. Voen Med Zh 1:47–51
3. ^ Solozhenkin VG (1978) Scarlet fever-like disease in children. Pediatriia (1):27–28
4. ^ Fukushima H Matsuda Y, Seki R, Tsubokura M, Takeda N, Shubin FN, Paik IK, Zheng XB (2001) Geographical heterogeneity between Far Eastern and Western countries in prevalence of the virulence plasmid, the superantigen Yersinia pseudotuberculosis-derived mitogen, and the high-pathogenicity island among Yersinia pseudotuberculosis strains. J Clin Microbiol 39:3541–3547
5. ^ a b Yoshino K, Ramamurthy T, Nair GB, Fukushima H, Ohtomo Y, Takeda N, Kaneko S, Takeda T (1995) Geographical heterogeneity between Far East and Europe in prevalence of the ypm gene encoding the novel superantigen among Yersinia pseudotuberculosis strains. J Clin Microbiol 33(12) 3356–3358
6. ^ Antonov VS (1978) Differential diagnosis of scarlet fever-like forms of pseudotuberculosis and scarlet fever in children. Pediatriia 52(1):6–9
*[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
| Far East scarlet-like fever | c0043410 | 1,078 | wikipedia | https://en.wikipedia.org/wiki/Far_East_scarlet-like_fever | 2021-01-18T19:07:04 | {"mesh": ["D015012"], "icd-10": ["A04.8,A28.2"], "wikidata": ["Q18371582"]} |
Distal trisomy 9q is a rare chromosomal anomaly, resulting from the partial trisomy of the long arm of chromosome 9, with a variable phenotype mostly characterized by psychomotor and speech delay, intellectual disability, hypotonia, long narrow habitus, craniofacial dysmorphism (incl. micro/dolichocephaly, facial asymmetry, narrow palpebral fissures, deep-set eyes, strabismus, microphthalmia, abnormally shaped ears, microstomia, micro/retrognathia) and hand and feet anomalies (incl. arachnodactyly, camptodactyly, abnormal implantation of digits). Congenital flexion contractures and limited joint movements have also been observed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Distal trisomy 9q | c4706939 | 1,079 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96101 | 2021-01-23T18:09:28 | {"icd-10": ["Q92.3"], "synonyms": ["Distal duplication 9q", "Telomeric duplication 9q", "Trisomy 9qter"]} |
## Summary
### Clinical characteristics.
Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including familial hemiplegic migraine) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech); FHM must include motor involvement, i.e., hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with FHM1 have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia. Cerebral infarction and death have rarely been associated with hemiplegic migraine.
### Diagnosis/testing.
Diagnostic criteria for FHM: (1) fulfills criteria for migraine with aura; (2) aura includes some degree of hemiparesis and may be prolonged; (3) at least one first-degree relative (i.e., parent, sib, offspring) has identical attacks. Three genes are known to be associated with FHM: CACNA1A (FHM1), ATP1A2 (FHM2), and SCN1A (FHM3).
### Management.
Treatment of manifestations: A trial of acetazolamide for individuals with FHM1 or a trial of standard migraine prophylactic drugs (tricyclic antidepressants, beta blockers, calcium channel blockers) for all FHM types may be warranted for frequent attacks. Antiepileptic treatment may be necessary for seizures, which are prevalent in FHM2.
Agents/circumstances to avoid: Vasoconstricting agents because of the risk of stroke; cerebral angiography as it may precipitate a severe attack.
### Genetic counseling.
FHM is inherited in an autosomal dominant manner. Because the diagnosis of FHM requires at least one affected first-degree relative, most individuals diagnosed with familial hemiplegic migraine have an affected parent. The proportion of cases caused by a de novo pathogenic variant is unknown. Each child of an individual with familial hemiplegic migraine has a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in the family has been identified.
## Diagnosis
### Diagnostic Criteria
The diagnosis of familial hemiplegic migraine (FHM) relies on clinical diagnostic criteria. Two sets of criteria have been proposed.
Criteria adapted from the Headache Classification Subcommittee of the International Headache Society [2004] (full text)
Familial hemiplegic migraine (HM) is a category of migraine with aura (MA). Diagnostic criteria for HM are as follows:
* Headaches fulfill criteria for MA (see Note).
* Aura includes some degree of hemiparesis and may be prolonged but fully reversible.
* HM is categorized as familial if at least one first-degree relative (i.e., parent, sib, and/or offspring) or second-degree relative has identical attacks.
* HM is sporadic if no first- or second-degree relative meets criteria for hemiplegic migraine.
Note: Migraine with aura (MA) is an idiopathic, recurring disorder of neurologic symptoms unequivocally localizable to the cerebral cortex or brain stem. The aura usually develops over a period of five to 20 minutes and lasts less than 60 minutes. Headache, nausea and/or photophobia usually follow neurologic aura symptoms, either immediately or after a symptom-free interval of less than an hour. The headache usually lasts four to 72 hours but may be completely absent (acephalagia). Diagnostic criteria for MA:
* At least two episodes characterized by three or more of the following:
* One or more aura symptoms are fully reversible, indicating focal cerebral cortical and/or brain stem dysfunction.
* At least one aura symptom develops gradually over more than four minutes, or two or more symptoms occur in succession.
* No aura symptom lasts more than 60 minutes. If more than one aura symptom is present, duration of symptoms is proportionally increased.
* Headache follows aura with a symptom-free interval of less than 60 minutes (headache may also begin before or simultaneously with the aura).
* Ruling out of other classes of headache (i.e., head trauma, vascular disorders, nonvascular intracranial disorders, substance use or their withdrawal, non-cephalic infection, metabolic disorder, pain associated with other facial or cranial disorders)
Criteria proposed by Thomsen et al [2002]*
At least two attacks that meet all of the following criteria:
* Fully reversible symptoms including motor weakness and at least one of the following: visual, sensory, or speech disturbance
* At least two of the following:
* At least one aura symptom develops gradually over at least five minutes, or symptoms occur in succession.
* Each aura symptom lasts less than 24 hours.
* Some degree of headache is associated with the aura.
* Not attributed to another disorder
* At least one first- or second-degree relative with migraine with aura including motor weakness and fulfilling all of the criteria above
*Based on findings in 147 affected individuals from 44 families
### Establishing the Genetic Cause
The genetic basis of FHM is established in a proband who meets diagnostic criteria when a heterozygous pathogenic variant is identified in one of the three genes known to be associated with FHM (CACNA1A, ATP1A2, and SCN1A) (see Table 1).
Note: (1) In the majority of persons with adult-onset hemiplegic migraine without nystagmus, seizures, or other unusual associated neurologic features, the yield for genetic testing is low. (2) Multiple studies have shown that pathogenic variants in the three known FHM-related genes are not a major cause of simplex hemiplegic migraine (i.e., hemiplegic migraine in a single person in a family).
One genetic testing strategy is serial single-gene molecular genetic testing based on the individual’s clinical findings (see Clinical Characteristics) and/or the order in which pathogenic variants most commonly occur (i.e., CACNA1A, ATP1A2, and SCN1A). Note that those with pathogenic variants in CACNA1A commonly present with nystagmus and other cerebellar signs [Ophoff et al 1996], and those with pathogenic variants in ATP1A2 frequently have epilepsy [De Fusco et al 2003].
An alternative genetic testing strategy is use of a multigene panel that includes CACNA1A, ATP1A2, and SCN1A and other genes of interest (see Differential Diagnosis). 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 Familial Hemiplegic Migraine
View in own window
Gene 1
(Locus Name)Proportion of FHM Attributed to Pathogenic Variants in GeneMethod
CACNA1A (FHM1)3/42 (7%) 2Sequence analysis 3
Gene-targeted deletion/duplication analysis 4, 5
ATP1A2 (FHM2)3/42 (7%) 2Sequence analysis 3
SCN1A (FHM3)Unknown 6Sequence analysis 3
Gene-targeted deletion/duplication analysis 4, 7
Unknown 8UnknownNA
1\.
See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.
2\.
Thomsen et al [2007]
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single exon deletions or duplications.
6\.
Dichgans et al [2005a]
5\.
A 39.5-kb CACNA1A deletion of the last 16 coding exons was reported in three affected members of one family with episodic ataxia [Riant et al 2008].
7\.
To date, no SCN1A deletions or duplications as causative of FHM have been reported.
8\.
Possible locus heterogeneity: Gardner et al [1997] identified an FHM susceptibility locus on 1q31, designated FHM4/MGR6, which is telomeric to FHM2 (OMIM 607516). Cuenca-León et al [2009] mapped an FHM locus to 14q32 in a large Spanish kindred.
## Clinical Characteristics
### Clinical Description
In migraine with aura, including familial hemiplegic migraine, the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech), and for FHM must include motor involvement (e.g., hemiparesis [weakness of an extremity]) [Thomsen et al 2002]:
* Visual disturbances can include scotoma (blind spots), photopsia (flashing lights), fortification spectra (zigzag pattern), and diplopia (double vision).
* Dysphasia usually occurs when hemiplegia is right-sided.
* Hemiparesis occurs with at least one other symptom during FHM aura [Ducros et al 2000].
Note: Recent family studies found that approximately 10% of family members with a CACNA1A pathogenic variant do not have hemiplegic attacks but often have migraine with or without aura [Ducros et al 2001].
Some confusion and/or drowsiness may be present even without dysphasia. Impaired consciousness ranging from drowsiness to coma is well described in FHM [Terwindt et al 1998, Chabriat et al 2000, Vahedi et al 2000]. Intermittent confusion and psychosis have been reported [Feely et al 1982] including one probable family with FHM1 and ataxia [Spranger et al 1999].
Neurologic deficits with HM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. Persistent attention and memory loss can last weeks to months [Kors et al 2003]. Permanent motor, sensory, language, or visual symptoms are extremely rare [Ducros et al 2001].
Cerebral infarction and death have rarely been associated with hemiplegic migraine and should instead raise the possibility of other disorders associated with migraine and stroke (see Differential Diagnosis).
Familial hemiplegic migraine is often earlier in onset than typical migraine, frequently beginning in the first or second decade. In the report of Ducros et al [2001], the attacks started at a young age in the majority of subjects (mean: 11.7 ±8 years; range: 1-51 years). The natural history was variable. The frequency of attacks ranged from one per day to fewer than five in a lifetime (mean: 2-3/year). Long attack-free intervals were often reported (range: 2-37 years). The frequency of FHM attacks tends to decrease with age. The eventual neurologic outcome is often benign in the pure FHM group, although FHM1 can have progressive cerebellar deficit.
FHM attacks may be provoked by typical migraine triggers (e.g., foods, odors, exertion, stress), minor head trauma, and cerebral angiography.
Among families with hemiplegic migraine, the major significant clinical differences are presence or absence of cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia, which occurs in up to 40%-50% of families with FHM1 [Ducros et al 2000]; within such families, up to 60% of affected individuals have permanent cerebellar signs [Ducros et al 2001].
Seizures during severe attacks have been reported in some families with FHM2 along with recurrent coma in one individual [Echenne et al 1999]. Focal seizures during severe attacks have been described in two individuals with FHM1 who have no family history of FHM1 [Chabriat et al 2000], including one with severe intellectual disability, congenital ataxia, and early cerebellar atrophy [Vahedi et al 2000].
Imaging studies. The only abnormalities observed on traditional imaging studies are vermian cerebellar atrophy in some families with FHM1 [Battistini et al 1999]. Rare exceptions include transient diffusion-weighted signal changes on brain MRI suggesting cytotoxic edema during severe prolonged attacks in individuals with FHM1 [Chabriat et al 2000, Vahedi et al 2000] with hemispheric cerebral atrophy usually contralateral to the hemiparesis [Hayashi et al 1998, Chabriat et al 2000, Vahedi et al 2000].
Abnormalities in the cerebellum on magnetic resonance spectroscopy (MRS) have been reported [Dichgans et al 2005b].
### Genotype-Phenotype Correlations
CACNA1A. Although further correlation is needed, some suggestive genotype-phenotype correlations exist based on limited data regarding CACNA1A pathogenic variants commonly presenting with nystagmus and other cerebellar signs [Ophoff et al 1996, Ducros et al 2001].
* p.Arg192Gln and p.Val1457Leu [Carrera et al 1999] are associated with hemiplegic attacks only, whereas unconsciousness occurs commonly during attacks with the p.Val714Ala pathogenic variant [Terwindt et al 1998].
* p.Thr666Met, p.Ile1811Leu, p.Arg583Gln [Alonso et al 2003], and p.Asp715Glu [Ducros et al 1999] have been associated with hemiplegic attacks plus ataxia. In the Ducros et al [2001] study, p.Thr666Met was associated with the highest frequency of hemiplegic migraine, severe attacks of coma, and nystagmus. During attacks, unconsciousness sometimes occurs in individuals with the p.Thr666Met and p.Ile1811Leu pathogenic variants [Terwindt et al 1998]. Kors et al [2003] reported a family with the p.Thr666Met pathogenic variant and progressive cognitive dysfunction.
* p.Arg583Gln can be associated with stupor, fever, and progressive ataxia [Battistini et al 1999, Ducros et al 2001]. Affected individuals were thought to have fewer attacks after treatment with acetazolamide.
* p.Asp715Glu has the lowest frequency (64%) of attacks of hemiplegic migraine [Ducros et al 2001].
* A de novo variant, p.Tyr1385Cys, identified in a single individual with no known family history of FHM, has been associated with prolonged severe attacks including focal seizures, coma, fever, and CSF neutrophilic pleocytosis [Chabriat et al 2000, Vahedi et al 2000]. Cerebral hemispheric and cerebellar atrophy are seen on imaging studies [Vahedi et al 2000] with reversible MRI signal changes suggestive of cytotoxic edema during attacks [Chabriat et al 2000]. Additionally, the single individual with the p.Thr1384Cys pathogenic variant had otherwise unexplained severe intellectual disability, developmental delay, and congenital or early-onset ataxia.
* p.Ser218Leu has been associated with delayed cerebral edema and fatal coma after minor head trauma [Kors et al 2001].
See Table 2.
ATP1A2
* In the first two families in which FHM2 was genetically defined, De Fusco et al [2003] noted the history of seizures in several affected individuals. Subsequent reports of FHM2 further suggest seizures as an associated clinical feature.
* A severe phenotype with seizures, coma, and elevated temperature has been reported with a p.Gly301Arg pathogenic variant in ATP1A2 [Spadaro et al 2004].
* A severe phenotype with seizures and intellectual disability has been reported with the pathogenic variants p.Asp718Asn and p.Pro979Leu [Jurkat-Rott et al 2004].
See Table 3.
### Penetrance
Penetrance for FHM1, 2, and 3 appears to be high and is estimated to be approximately 80% [Jurkat-Rott et al 2004, Riant et al 2005].
### Nomenclature
Although families with FHM in which attacks are strikingly identical do exist, the term familial hemiplegic migraine is often used inconsistently to describe families in which different forms of migraine occur, as most individuals with hemiplegic attacks have these attacks intermingled with more frequent attacks of migraine without hemiparesis.
### Prevalence
In Denmark, Thomsen et al [2002] found the prevalence of hemiplegic migraine to be 0.01% with a M:F sex ratio of 1:3 and equal prevalence of familial and sporadic cases.
## Differential Diagnosis
Migraine without aura (OMIM 157300). Migraine without aura (MO or MOA) (common migraine) is an idiopathic, recurring headache disorder manifesting in attacks lasting four to 72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea, photophobia, and phonophobia. This headache occurs without neurologic aura symptoms and specifically without hemiparesis.
Typical migraine is thought to be genetically complex and to have undefined environmental components. A clinical distinction between familial and nonfamilial cases has long been entertained, beginning with the first report of FHM by Clarke [1910]. Wieser et al [2003] found no pathogenic variants in CACNA1A in individuals with common migraine. Some families having migraine without aura have shown linkage to 4q21 [Björnsson et al 2003] and 14q21.2-q22.3 [Soragna et al 2003]. One family having migraine with or without aura showed linkage to 6p12.2-p21.1 [Carlsson et al 2002].
Migraine with aura (OMIM 157300). Brugnoni et al [2002] found no CACNA1A pathogenic variants in individuals with familial migraine with aura. Some families having migraine with aura show linkage to 4q24 [Wessman et al 2002].
"Sporadic" hemiplegic migraine (SHM). "Sporadic" hemiplegic migraine refers to simplex cases (i.e., affected individuals with no relatives with hemiplegic migraine). Such individuals may or may not have other family members with typical migraine. To investigate the genetic basis of hemiplegic migraine in simplex cases:
* Terwindt et al [2002] evaluated 27 individuals who had no family history of hemiplegic migraine and found a pathogenic variant in CACNA1A in two, one of whom had ataxia, nystagmus, and cerebellar atrophy on cranial CT; the other did not.
* de Vries et al [2007] sequenced all three FHM-related genes in 39 individuals with SHM and found one CACNA1A pathogenic variant (FHM1), five ATP1A2 pathogenic variants (FHM2), and one SCN1A benign variant (FHM3).
* Thomsen et al [2008] examined 100 individuals with SHM and found only a handful of novel, not clearly pathogenic nucleotide variants in CACNA1A and ATP1A2, suggesting that FHM-related genes are not major genes in SHM.
Other inherited disorders associated with migrainous headache that may include hemiplegic aura:
* MELAS, MERRF, and other mitochondrial disorders. MELAS is a multisystem disorder with onset typically between ages two and ten years. The most common initial symptoms are generalized tonic-clonic seizures, recurrent headaches, anorexia, and recurrent vomiting. Seizures are often associated with stroke-like episodes of transient hemiparesis or cortical blindness, which may be associated with altered consciousness and may be recurrent. The cumulative residual effects of the stroke-like episodes gradually impair motor abilities, vision, and cognition, often by adolescence or young adulthood. Sensorineural hearing loss is common. The most common mitochondrial DNA (mtDNA) pathogenic variant, present in more than 80% of individuals with typical clinical findings of MELAS, is an A-to-G transition at nucleotide 3243 in the tRNALeu(UUR) of mtDNA.
* CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is characterized by history of migraine with aura, mid-adult (30s-60s) onset of cerebrovascular, mood disturbance, apathy, cognitive disturbance progressing to dementia, and diffuse white matter lesions and subcortical infarcts on neuroimaging. One family with CADASIL was reported to have hemiparetic aura [Hutchinson et al 1995]. The pathologic hallmark of CADASIL is electron-dense granules in the media of arterioles that can often be identified by electron microscopic (EM) evaluation of skin biopsies. More than 90% of individuals have pathogenic variants in NOTCH3. Inheritance is autosomal dominant.
* RVCL (retinal vasculopathy with cerebral leukodystrophy) is characterized by systemic microvasculopathy with adult onset (30s-40s) of retinal vasculopathy and cerebrovascular disease variably associated with migraine. The pathologic hallmark of RVCL is multi-laminated subendothelial basement membrane by EM evaluation of multiple organs including skin. Affected individuals have pathogenic variants in TREX1. Inheritance is autosomal dominant.
* Hereditary hemorrhagic telangiectasia (HHT) is characterized by the presence of multiple arteriovenous malformations (AVMs) that lack intervening capillaries and result in direct connections between arteries and veins. Small AVMs, or telangiectases, close to the surface of skin and mucous membranes often rupture and bleed after slight trauma. The most common clinical manifestation is spontaneous and recurrent nosebleeds beginning at approximately age 12 years. Large AVMs often cause symptoms when they occur in brain, lung, or the gastrointestinal tract; complications from bleeding or shunting may be sudden and catastrophic. Migraine with aura has been reported in 50% of affected individuals. HHT is caused by pathogenic variants in ENG, ACVRL1, SMAD4, and at least two other as-yet unidentified genes. Inheritance is autosomal dominant.
* Familial cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord consisting of closely clustered enlarged capillary channels (caverns) with a single layer of endothelium without normal intervening brain parenchyma or mature vessel wall elements. CCMs have been reported in infants and children, but the majority of individuals present with symptoms between the second and fifth decades. Approximately 50%-75% of persons with CCM have symptoms, including seizures, focal neurologic deficits, nonspecific headaches, and cerebral hemorrhage. Up to 50% of individuals with CCM remain symptom free throughout their lives. The three genes associated with familial CCM are KRIT1, CCM2, and CCM3. Inheritance is autosomal dominant.
* Dutch form of hereditary cerebral amyloid angiopathy (OMIM 605714). Migraines often precede the onset of cerebral and cerebellar hemorrhage in the fourth or fifth decade. Senile plaques and vascular wall amyloid are found in the brain in association with amino acid changes in the APP beta-amyloid precursor protein, a protease inhibitor. Inheritance is autosomal dominant.
Alternating hemiplegia of childhood (AHC) is a rare condition with clinical features that overlap with FHM. AHC is characterized by recurrent hemiplegia with onset before age 18 months, variable other transient neurological findings, and progressive cognitive decline. Some individuals with AHC have a heterozygous pathogenic variant in ATP1A2 (the gene that is mutated in FHM2) [Bassi et al 2004, Swoboda et al 2004]; however, the majority are heterozygous for a pathogenic variant in ATP1A3 [Heinzen et al 2012] and are allelic with rapid-onset dystonia parkinsonism and CAPOS. Inheritance is autosomal dominant.
Hemiplegia. The differential diagnosis of hemiplegia includes post-ictal weakness following seizure, transient ischemic attack (TIA), stroke, and other non-genetic causes of transient hemiparesis.
Stroke. When family history is positive for hemiparetic attacks with migraine, the presence of infarct on imaging studies raises the possibility of other inherited disorders such as MELAS, CADASIL, or thrombophilia, such as factor V Leiden [Gaustadnes et al 1999]. Additional stroke risk factors may also be present.
Caution: Even with normal imaging studies and description of spreading aura, an age-appropriate stroke evaluation should be considered at presentation. Overlap in clinical features, inaccuracies of historical family information, rarity of true FHM, and the seriousness of stroke-related disorders warrant this cautious approach. Stroke or other CNS-related disorders should be even more strongly considered if family history is negative for hemiplegic migraine.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with familial or sporadic hemiplegic migraine, the following evaluations are recommended:
* Quantitative eye movement examination in individuals with nystagmus or complaints of incoordination or imbalance to look for additional clues of cerebellar involvement
* EEG and neuroimaging studies if seizures are present in order to further characterize the seizure disorder.
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Symptomatic support during an episode of hemiplegic migraine is the only therapy available.
A trial of acetazolamide for individuals with FHM1 or a trial of standard migraine prophylactic drugs (tricyclic antidepressants, beta blockers, calcium channel blockers, anti-epileptic medications) for all FHM types may be warranted for frequent attacks. Limited correlation exists between drug response and hemiplegic migraine type.
There are anecdotal reports of therapeutic response to antiepileptic medications including topiramate, lacosamide, levetiracetam, and valproate, along with other medications commonly used for migraine prophylaxis.
Antiepileptic treatment may be necessary for seizures that are prevalent in FHM2 (caused by pathogenic variants in ATP1A2).
### Agents/Circumstances to Avoid
In general, vasoconstricting agents should be avoided because of the risk of stroke.
Cerebral angiography is hazardous as it may precipitate a severe attack [Chabriat et al 2000].
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Familial Hemiplegic Migraine | c0338484 | 1,080 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1388/ | 2021-01-18T21:27:03 | {"mesh": ["D020325"], "synonyms": []} |
Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance.
## Epidemiology
To date, CCFDN has been found to occur exclusively in patients of Roma (Gypsy) ethnicity; over 100 patients have been diagnosed.
## Clinical description
Developmental abnormalities include congenital cataracts and microcorneae, primary hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, mild facial dysmorphism and hypogonadism. Para-infectious rhabdomyolysis is a serious complication reported in an increasing number of patients. During general anaesthesia, patients with CCFDN require careful monitoring as they have an elevated risk of complications.
## Etiology
CCFDN is a genetically homogeneous condition in which all patients are homozygous for the same ancestral mutation in the CTDP1 gene. CTDP1 maps to 18qter and encodes a protein phosphatase whose only known substrate is the phosphorylated serine residues of the carboxy-terminal domain of the largest subunit of RNA polymerase II, indicating that CCFDN affects basic cellular processes of gene expression and developmental regulation.
## Diagnostic methods
Diagnosis is clinical and is supported by electrophysiological and brain imaging studies. The definitive diagnosis is molecular, based on homozygosity for the CTDP1 mutation.
## Differential diagnosis
The major differential diagnosis is Marinesco-Sjogren syndrome.
## Genetic counseling
Families benefit from genetic counselling and predictive testing.
## Management and treatment
Management includes surgical treatment of the cataracts, and rehabilitation and corrective orthopaedic surgery for the peripheral neuropathy.
## Prognosis
Thus, the most disabling manifestations, though not curable, are manageable, and allow an acceptable quality of life and everyday living. Current data indicate that patients survive well into adulthood.
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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
| Congenital cataracts-facial dysmorphism-neuropathy syndrome | c1858726 | 1,081 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=48431 | 2021-01-23T18:40:15 | {"mesh": ["C565822"], "omim": ["604168"], "umls": ["C1858726"], "icd-10": ["Q87.8"], "synonyms": ["CCFDN"]} |
Deacon et al. (1974) described brother and sister with a form of infantile cardiomyopathy characterized by accumulation of lipid in the sarcoplasm of myocardial fibers. Only sporadic cases had been reported previously (Reid et al., 1968). In Deacon's cases onset was at birth and 4 weeks of age and death at 19 days and 4 months from congestive heart failure. Both had microcephaly. Severe mitochondrial changes were found in the myocardial fibrils in addition to the accumulation of neutral fat. The parents were thought to be nonconsanguineous. McKusick (2002) noted that these may be cases of infantile histiocytoid cardiomyopathy (500000).
Cardiac \- Infantile cardiomyopathy \- Congestive heart failure Growth \- Death in infancy Lab \- Cardiac sarcoplasmic lipidosis \- Cardiac mitochondrial changes Cranium \- Microcephaly Inheritance \- Autosomal recessive ▲ 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
| CARDIAC LIPIDOSIS, FAMILIAL | c1708371 | 1,082 | omim | https://www.omim.org/entry/212080 | 2019-09-22T16:30:07 | {"mesh": ["C535584"], "omim": ["212080"], "orphanet": ["137675"]} |
## Clinical Features
Medlej-Hashim et al. (2002) described 4 members of a consanguineous Jordanian family with severe hearing loss. Age at onset was in early childhood.
Mapping
By genomewide linkage analysis, followed by homozygosity mapping, in a consanguineous Jordanian family segregating nonsyndromic deafness, Medlej-Hashim et al. (2002) mapped the deafness locus, designated DFNB33, to a 6.3-cM region between markers D9S1826 and D9S1838. Sequence analysis excluded mutations in 23 candidate genes in this interval on chromosome 9q34 (Belguith et al., 2009). In a reanalysis of the genomewide screening results from the Jordanian family reported by Medlej-Hashim et al. (2002), Belguith et al. (2009) identified a second candidate peak on chromosome 10. Using additional markers to analyze this family, the authors identified linkage to a 13.8-cM region on chromosome 10p11.23-q21.1 (maximum lod score of 3.99 at D10S199 and D10S220). Belguith et al. (2009) stated that they reassigned the DFNB33 locus to chromosome 10p11.23-q21.1 and concluded that the previous assignment to 9q34.3 was not identity by descent but rather homozygosity by chance. Sequence analysis excluded mutations in the CX40.1 (611922) and FXYD4 (616926) genes on chromosome 10.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, bilateral (severe) MISCELLANEOUS \- Onset in early childhood \- Based on one Jordanian family (last curated August 2015) ▲ 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
| DEAFNESS, AUTOSOMAL RECESSIVE 33 | c1846576 | 1,083 | omim | https://www.omim.org/entry/607239 | 2019-09-22T16:09:30 | {"doid": ["0110492"], "mesh": ["C564602"], "omim": ["607239"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]} |
A number sign (#) is used with this entry because of evidence that Crisponi/cold-induced sweating syndrome-1 (CISS1) is caused by homozygous or compound heterozygous mutation in the CRLF1 gene (604237) on chromosome 19p13.
Description
Crisponi/cold-induced sweating syndrome is an autosomal recessive disorder characterized in the neonatal period by orofacial weakness with impaired sucking and swallowing resulting in poor feeding necessitating medical intervention. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. During the first year, most infants have spiking fevers. These features, referred to as 'Crisponi syndrome' in infancy, can result in early death without advanced care. After the first 2 years, the abnormal muscle contractions and fevers abate, and most patients show normal psychomotor development. From childhood onward, the most disabling symptoms stem from impaired thermoregulation and disabling abnormal sweating, which can be treated with clonidine. Patients have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Other features include characteristic facial anomalies, such as round face, chubby cheeks, micrognathia, high-arched palate, low-set ears, and depressed nasal bridge, dental decay, camptodactyly, and progressive kyphoscoliosis (summary by Hahn et al., 2010).
### Genetic Heterogeneity of Crisponi/Cold-Induced Sweating Syndrome
Crisponi/cold-induced sweating syndrome-2 (CISS2; 610313), which is clinically indistinguishable from CISS1, is caused by mutation in the CLCF1 gene (607672) on chromosome 11q13. CISS3 (617055) is caused by mutation in the KLHL7 gene (611119) on chromosome 7p15.
Nomenclature
Sohar et al. (1978) first described cold-induced sweating syndrome, and Crisponi (1996) first described a disorder in infancy that was characterized by muscular contraction of the facial muscles, poor feeding, and episodic fever, often resulting in early death. Both conditions were found to be due to mutation in the same gene. Moreover, it became apparent that most older patients with CISS have a history of features consistent with Crisponi syndrome early in life, indicating that these 2 disorders represent a single entity with variable severity and/or different manifestations according to age. Herholz et al. (2011) suggested the term 'Sohar-Crisponi syndrome' to refer to the disorder.
Clinical Features
Sohar et al. (1978) observed 2 Israeli sisters who, since childhood, sweated profusely from the back and chest when exposed to temperatures of 7 to 18 degrees C. They also showed high palate, inability to extend the elbows fully, and slight kyphoscoliosis--features demonstrated by neither the parents nor the sibs. The parents shared a grandfather, i.e., were half first cousins.
Knappskog et al. (2003) observed 2 Norwegian brothers with a clinical phenotype similar to that in the Israeli sisters. The disorder in the brothers was more severe than that in the Israeli sisters, with earlier age of onset, feeding difficulties, serious kyphoscoliosis, and reduced pain and temperature sensitivity. The older brother would not suckle in the neonatal period, leading to dehydration. He was fed first by a nasogastric tube and subsequently by a special sucking device intended for newborn lambs. These feeding problems, complicated by bronchopulmonary and urinary tract infections, led to hospitalization for his first 3 months of life. His younger brother was admitted at 1 day of age, primarily because of respiratory problems. He too did not suckle spontaneously and had to be fed in the same manner as his older brother. Both had difficulty fully opening their mouths. While playing in the snow, the older brother repeatedly experienced frostbite in his hands. Furthermore, he could hold his palms in a flame or put his hands in boiling water without any sensory pain. Both brothers had severe progressive kyphoscoliosis requiring extensive surgery, following which the boys had an unusually low requirement for pain-relieving medication. Both brothers had short hands with pronounced clinodactyly and tapering of fingers. They could not fully extend their elbows. Their sweating problem was noted at the age of approximately 7 years. The patchwise distribution in affected areas closely resembled those described in the Israeli sisters. These areas did not sweat at warm temperatures, during fever episodes, or during exercise. The mother sometimes had to cool her overheated children by putting their feet in cold water. Subtropical environment did not bother these patients. They could stay in bright sunlight without feeling the heat and had no desire to take their clothes off for cooling.
Crisponi (1996) described an autosomal recessive syndrome observed in 17 newborns (8 males, 9 females) from 12 different families in southern Sardinia. The disorder was evident at birth and was characterized by marked muscular contraction of the facial muscles in response to tactile stimuli or during crying, with trismus and abundant salivation simulating a tetanic spasm. The contractions slowly disappear as the infant calms. There is also neck muscle hypertonia with a tendency to opisthotonos. All patients presented facial anomalies such as large face, chubby cheeks, broad nose with anteverted nostrils, and long philtrum, and showed bilateral camptodactyly. The clinical course in all patients had been characterized by marked feeding difficulties and appearance of variable fever at about 38 degrees centigrade, with peaks of irregular hyperthermia of over 42 degrees centigrade, with onset ranging from birth to a few weeks. In some patients generalized seizures occurred. Death occurred after a period of a few weeks to some months and coincided with fever about 42 degrees centigrade. Crisponi (1996) stated that no useful pathogenetic features were revealed by laboratory investigations. Only 2 patients were alive at the time of report. One patient (aged 14 years) presented slow regression of the dystonic features, while dysthermia and mild psychomotor delay persisted.
Accorsi et al. (2003) reported a patient with features consistent with Crisponi syndrome. The patient was born of unrelated parents, but both parents came from a small village in a geographically isolated area in northern Italy with a high rate of inbreeding. The pregnancy was complicated by polyhydramnios, and unspecified fetal hand abnormalities were noted by ultrasound. Dysmorphic features were noted at birth, including hypomimic, rounded face, puffy cheeks, broad nose with anteverted nostrils, small mouth with thin and contracted lips, micrognathia, low-set ears, low anterior and posterior hairlines, and a short neck. The hands showed bilateral camptodactyly with ulnar deviation of the fingers and adducted thumbs. The patient exhibited episodes of marked contraction of both facial and neck muscles associated with flexion of the upper limbs, clenching of the hands, and hyperextension of the lower limbs. During these episodes, there was abundant salivation with inability to swallow. Respiratory muscle contractions caused dyspnea, cyanosis, and short apneic spells. The episodes were elicited by crying and by tactile or painful sensation; they did not occur during rest or sleep. At 2 months of age, the patient developed intermittent hyperthermia with fever peaks and rapid falls unassociated with infection. These hyperthermic episodes were followed by hypernatremic dehydration and acute renal failure. The child died at age 4 months of cardiorespiratory failure following a hyperthermic crisis. Skeletal radiography showed mild anomalies and scoliosis. Karyotype analysis identified a pericentric inversion of the heterochromatic region of chromosome 9 of paternal origin. Accorsi et al. (2003) noted the phenotypic similarities to Freeman-Sheldon syndrome (193700) and Stuve-Wiedemann syndrome (601559).
Nannenberg et al. (2005) reported a 4-year-old boy of Portuguese descent with Crisponi syndrome. Four days after birth, the infant was noted to have bouts of generalized muscle contractions occurring 6 to 10 times per day. The attacks were triggered by external stimuli and involved contraction of the facial muscles, clenching of the hands, jerky movements of the legs, and respiratory abnormalities. The attacks also occurred during sleep. Facial features included round face, broad nose with anteverted nostrils, small mouth, high-arched palate, micrognathia, and retroversion of the ears. He had bilateral camptodactyly and clubfeet. Polysomnography during a paroxysmal event showed a severe obstructive breathing pattern. The overall breathing pattern outside the attacks showed a mix of disorders of control of breathing, including central apnea, hypopnea, obstructive apnea, and long periods of expiratory apneas while the boy was awake. The hyperexcitability disappeared in the course of the first year of life. As he grew older, he developed scoliosis and showed severely delayed psychomotor development. Hyperthermia was never recorded. Nannenberg et al. (2005) noted the similarities to Stuve-Wiedemann syndrome, but concluded that Crisponi syndrome is a unique entity.
Following up on one of the surviving patients of Crisponi (1996), Dagoneau et al. (2007) noted that she developed scoliosis, which required surgery at age 12 years, and mild developmental delay with attention deficit disorder, requiring special schooling. At age 13 years, growth parameters were at less than -2 SD. See 604237.0003. Dagoneau et al. (2007) also described 2 cousins from a Gypsy family with Crisponi syndrome. One of the patients presented at birth with camptodactyly, overlapping toes, joint contractures of elbows, contractions of facial muscles with trismus, major feeding difficulties, and dysmorphic features (small nose with anteverted nostrils, small mouth, short neck, and low-set ears). He had repeated episodes of hyperthermia (body temperature greater than 42 degrees centigrade) until age 3 years and then profuse sweating of the back. Kyphoscoliosis appeared at age 1 year. At the time of the report, he was 6 years old; growth parameters were at -2 SD, and he had some speech delay. His first cousin also presented with facial muscle contractions, camptodactyly, elbow contractures, and feeding difficulties, and he developed seizures and temperature instability with access of hyperthermia and kyphoscoliosis.
Thomas et al. (2008) reported an Indian boy, born of consanguineous parents, with Crisponi syndrome. He presented with respiratory distress soon after birth and was noted to have sparse light hair, upslanting eyes, blepharophimosis, broad nose with anteverted nares, long philtrum, retrognathia, and bilateral camptodactyly. He developed tetanus-like spasms on the second day of life characterized by marked contraction of all the muscles, particularly the facial muscles, with trismus, excess salivation, and opisthotonus. Cyanosis and apnea requiring oxygen were present during some of these episodes. He also had episodes of hyperthermia. At 10 months of age, he was still having feeding problems, remained hypertonic with intermittent spasms, and was developmentally delayed. Genetic analysis identified a homozygous 5-kb deletion surrounding exon 1 of the CRLF1 gene. Thomas et al. (2008) emphasized that the dysmorphic features aided in the correct diagnosis, which would otherwise have been considered to be neonatal tetanus. The authors also noted that since the CRLF1 gene is involved in motor neuron survival and in the function of the autonomic nervous system, Crisponi syndrome is characterized by dysautonomic symptoms including disturbances in temperature regulation and neonatal feeding/swallowing, as well as respiratory trismus, facial spasms, and paradoxical sweating.
Okur et al. (2008) reported a 9-month-old boy of Turkish descent with typical features of Crisponi syndrome who also had velopharyngeal insufficiency, incomplete cleft palate, and thin corpus callosum.
Yamazaki et al. (2010) reported a 30-year-old Japanese woman, born of consanguineous parents, with CISS1 confirmed by molecular studies. After birth, she showed poor feeding, flexion contractures of the fingers, scoliosis, and recurrent episodes of fever. Notable facial features included large face with thick and arched eyebrows, short nose with anteverted nostrils, full cheeks, and small mouth. Later in childhood, she developed profuse cold-induced sweating as well as decreased sensitivity to pain. She also had severe dental caries requiring complete tooth extraction. Examination at age 30 showed a marfanoid habitus, dolichocephaly, slender face with poor expression, narrow nose, malar hypoplasia, prognathism, and small mouth. Neurologic examination showed hyporeflexia of the upper extremities, and brain MRI showed multiple high-intensity spots on the subcortical white matter of the frontal lobes. She also had camptodactyly with finger joint malalignment and kyphoscoliosis. The longitudinal data from this patient suggested that CISS and Crisponi syndrome are one clinical entity with variable clinical expression or different phenotypic stages according to age.
Hahn et al. (2010) reported 2 unrelated patients with CISS1. A 24-year-old woman had features of Crisponi syndrome in infancy, including poor feeding, facial muscle contractions, opisthotonus posturing when handled, tight jaw and inability to open the mouth fully, high-arched palate, micrognathia, elbow contractures, and camptodactyly. She could not tolerate summer heat and showed profuse cold-induced sweating of the upper body. She had normal psychomotor development. Later, she developed progressive scoliosis and severe dental decay. Treatment with clonidine alleviated the hyperhidrosis. A 19-year-old Norwegian man had similar features, but was also noted to have decreased pain perception and chronic exposure keratitis due to an inability to close his eyes fully during sleep.
Herholz et al. (2011) reviewed the clinical features of 19 patients with CRLF1 mutations, including 14 classified as having Crisponi syndrome and 5 as having CISS1. Fourteen of the patients had previously been reported. There was some phenotypic overlap between the 2 groups. In particular, a pair of Norwegian brothers reported by Knappskog et al. (2003) as having CISS1 showed feeding difficulties in infancy, and 1 had facial muscle contractions, chubby cheeks, and episodes of hyperthermia early in life, consistent with Crisponi syndrome. In addition, those with a diagnosis of Crisponi syndrome early in life who survived past age 2 years developed scoliosis, and those older than 6 years developed cold-induced sweating. Most of the initial symptoms resolved in the first 2 years of life. Physical measurements did not reveal a significant difference in facial features compared to controls, suggesting that earlier attributes of a long and large face, long philtrum, and broad nose should not be included as obligatory features. Herholz et al. (2011) concluded that both groups of patients show a clinical course of varying severity, often depending on the age at examination. Molecular analysis showed no clear genotype/phenotype correlation, but the severity of the disorder was associated with altered secretion of the mutant CRLF1 protein; weak secretion was associated with a more severe phenotype compared to strong secretion.
Tuysuz et al. (2013) reported 2 Turkish brothers, born of consanguineous parents, with CISS1 confirmed by molecular studies. They were 22 and 13 years of age at the time of the report. The older brother showed normal psychomotor development, but had a history of poor feeding and unexplained fevers in the postnatal period. He had a round face, chubby cheeks, broad nasal bridge, anteverted nostrils, short and smooth tongue, adducted thumbs, camptodactyly, progressive kyphoscoliosis, and cryptorchidism. He also had weakness of the lower jaw and a hypernasal voice. Around age 11 to 12 years, he developed cold-induced sweating of the upper body, as well as decreased pain sensitivity. Brain MRI showed multiple small hyperintensities in the subcortical white matter. His younger brother showed delayed psychomotor development and severe mental retardation. He was an irritable baby and had feeding difficulties. Other features, including cold-induced sweating, were similar to those observed in his brother, including the subcortical brain lesions on MRI.
Inheritance
The transmission pattern of CISS1 in the family reported by Sohar et al. (1978) was consistent with autosomal recessive inheritance.
Mapping
Although no parental consanguinity was known in the Norwegian family studied by Knappskog et al. (2003), genealogic studies revealed several shared ancestors, the closest of which was 9 generations back. Exploiting the possibility in this family of homozygosity for a mutant gene inherited from a common ancestor, Knappskog et al. (2003) employed a combination of coarse-scale homozygosity mapping, based on the Israeli inbred kindred with a common great-grandfather, and finer-scale localization, based on the Norwegian sibship with distant common ancestors. Thus, on the basis of only 4 patients, they identified the candidate chromosomal segment, candidate gene, and likely causative mutations. A maximum multipoint lod score of 4.22 was obtained for a 1.4-Mb homozygous region on chromosome 19p12.
Using high-density single-nucleotide polymorphism arrays, Crisponi et al. (2007) performed homozygosity mapping in 5 Sardinian and 3 Turkish families with Crisponi syndrome and identified a critical region on 19p13.1-p12.
Molecular Genetics
By DNA sequencing of 25 genes within the candidate region that they identified for cold-induced sweating syndrome, Knappskog et al. (2003) identified potentially deleterious CRLF1 sequence variants (604237.0001-604237.0003) in both the Israeli and Norwegian families with the disorder. The variants were not found in unaffected control individuals.
Dagoneau et al. (2007) identified homozygous or compound heterozygous mutations in the CRLF1 gene (604237.0003-604237.0006) in 4 children with Crisponi syndrome from 3 unrelated families. The 4 mutations were located in the immunoglobulin-like and type III fibronectin domains, and 3 of them predicted premature termination of translation.
In 5 Sardinian and 3 Turkish families with Crisponi syndrome, Crisponi et al. (2007) detected 4 different CRLF1 mutations in the CRLF1 gene, identified as the most prominent candidate gene in the critical region mapped by them to chromosome 19p13.1-p12. Crisponi et al. (2007) noted that CRLF1 is involved in the pathogenesis of cold-induced sweating syndrome-1, which belongs to a group of conditions with overlapping phenotypes, including cold-induced sweating syndrome-2 (610313) and Stuve-Wiedemann syndrome (601559). All of these syndromes are caused by mutations of genes in the ciliary neurotrophic factor receptor pathway (see 118946). Comparison of the mutation spectra of Crisponi syndrome and CISS1 suggested that neither the type nor the location of the CRLF1 mutations pointed to a phenotype/genotype correlation that would account for the most severe phenotype in Crisponi syndrome. Crisponi et al. (2007) suggested that the syndromes mentioned comprise a family of 'CNTF receptor-related disorders.'
In the 2 patients of Crisponi (1996) to survive infancy, Crisponi et al. (2007) found compound heterozygosity for the same mutations, a 1-bp insertion (604237.0003) and a missense mutation (604237.0004). Dagoneau et al. (2007) studied 1 of these families as well, and reported the same mutations.
In a Turkish patient with Crisponi syndrome, Okur et al. (2008) identified homozygosity for a mutation in the CRLF1 gene (R277X; 604237.0009). Both parents were heterozygous for the mutation.
Pathogenesis
Hahn et al. (2010) reviewed and summarized recent findings in the pathogenesis of abnormal sweating in CISS. Sweating is controlled by the sympathetic nervous system, and mature eccrine sweat glands are normally innervated by cholinergic postsynaptic sympathetic neurons. However, during development, the innervating postganglionic sympathetic neurons express a noradrenergic transmitter phenotype. Thus, these sweat gland-innervating neurons normally undergo a process of neurokine-dependent transdifferentiation in response to a retrogradely acting signal secreted from the sweat glands as they become active and mature after birth. This sweat gland-derived signal has been shown to be a member of the IL-6 cytokine family. Both CLCF1 and CRLF1 have been shown to be expressed in sweat glands, and the CLCF1/CRLF1 complex has been shown to induced cholinergic differentiation of sympathetic neurons in culture (Stanke et al., 2006). Thus, mutations in either of these genes is predicted to result in loss of severely reduced function of the cytokine complex, causing a defect in cholinergic differentiation in sweat glands during development. The distribution of abnormal sweating in affected individuals reflects a complex pattern of function connections between pre- and post-ganglionic sympathetic neurons along the rostrocaudal axis.
INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth in infancy HEAD & NECK Face \- Severe contractions of the facial muscles \- Facial trismus \- Large face \- Chubby cheeks \- Micrognathia \- Retrognathia \- Facial weakness Ears \- Low-set ears Eyes \- Chronic keratitis \- Inability to fully close eyes during sleep Nose \- Depressed nasal bridge \- Broad nose \- Anteverted nostrils \- Long philtrum Mouth \- High-arched palate \- Abundant salivation \- Small mouth \- Dental caries, severe Neck \- Neck muscle hypertonia \- Short neck RESPIRATORY \- Dyspnea \- Apneic spells ABDOMEN Gastrointestinal \- Feeding difficulties SKELETAL Spine \- Scoliosis \- Kyphosis Limbs \- Elbow contractures Hands \- Camptodactyly \- Tapered fingers \- Ulnar deviation of the fingers \- Adducted thumbs Feet \- Club feet SKIN, NAILS, & HAIR Skin \- Profuse sweating of the upper body induced by cold exposure \- Poor sweating in response to heat MUSCLE, SOFT TISSUES \- Generalized muscle contractions, episodic \- Tetanus-like muscle contractions NEUROLOGIC Central Nervous System \- Seizures (less common) \- Opisthotonus \- Mental retardation (rare) \- Subcortical white matter abnormalities seen on MRI Peripheral Nervous System \- Decreased pain sensitivity VOICE \- Nasal voice METABOLIC FEATURES \- Variable fever \- Hyperthermia, episodic MISCELLANEOUS \- Onset in early infancy \- High early mortality rate if untreated \- Muscle contractions in infancy occur in response to tactile stimulation or crying \- Fever, muscle cramping, and poor feeding remit by age 2 years \- Cold-induced sweating develops late in the first decade \- Clonidine can alleviate hyperhidrosis MOLECULAR BASIS \- Caused by mutation in the cytokine-like factor 1 gene (CRLF1, 604237.0001 ) ▲ Close
*[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
| CRISPONI/COLD-INDUCED SWEATING SYNDROME 1 | c1848947 | 1,084 | omim | https://www.omim.org/entry/272430 | 2019-09-22T16:21:58 | {"doid": ["0080329"], "mesh": ["C536214"], "omim": ["272430"], "orphanet": ["157820"], "synonyms": ["MUSCLE CONTRACTIONS, TETANOFORM, WITH CHARACTERISTIC FACE, CAMPTODACTYLY, HYPERTHERMIA, AND SUDDEN DEATH", "SOHAR-CRISPONI SYNDROME", "Alternative titles", "CRISPONI SYNDROME", "CISS"], "genereviews": ["NBK52917"]} |
## Clinical Features
The designation ophthalmomandibulomelic dysplasia was given by Pillay (1964) to a syndrome he observed in a father, son and daughter. Changes were found in the eye (corneal clouding), in the mandible (temporomandibular fusion, absent coronoid process, obtuse mandibular angle) and limbs (radiohumeral and radioulnar dislocations, aplasia of the lateral humeral condyle, radial head and distal ulna, etc.). Chromosome studies were negative.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Blindness \- Corneal opacities \- Megalocornea CHEST Ribs Sternum Clavicles & Scapulae \- Shallow glenoid fossa SKELETAL Skull \- Temporomandibular joint fusion \- Obtuse mandibular angle \- Absent coronoid process Pelvis \- Coxa valga Limbs \- Mesomelia (upper limbs) \- Lateral humeral condyle aplasia \- Radiohumeral dislocation \- Proximal radioulnar dislocation \- Bowed radii \- Absent radial heads \- Short fibula Hands \- Ulnar deviated club hands \- Decreased mobility 3rd-5th fingers ▲ 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
| OPHTHALMOMANDIBULOMELIC DYSPLASIA | c1833872 | 1,085 | omim | https://www.omim.org/entry/164900 | 2019-09-22T16:37:07 | {"mesh": ["C563501"], "omim": ["164900"], "orphanet": ["2741"], "synonyms": ["Alternative titles", "OMM SYNDROME"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive spinocerebellar ataxia-12 (SCAR12) is caused by homozygous mutation in the WWOX gene (605131) on chromosome 16q23.
Biallelic mutation in the WWOX gene can also cause early infantile epileptic encephalopathy-28 (EIEE28; 616211), a more severe disorder with some overlapping features.
Description
Autosomal recessive spinocerebellar ataxia-12 is a neurologic disorder characterized by onset of generalized seizures in infancy, delayed psychomotor development with mental retardation, and cerebellar ataxia. Some patients may also show spasticity (summary by Mallaret et al., 2014).
Clinical Features
Gribaa et al. (2007) reported 4 sibs, born of consanguineous Saudi Arabian parents, with early-childhood onset of cerebellar ataxia associated with generalized seizures and delayed psychomotor development. Seizure onset occurred between 9 and 12 months. All showed gait ataxia when they achieved walking, which was delayed until 2 to 3 years of age. Other features included upper and lower limb ataxia, dysarthria, gaze-evoked nystagmus, and learning difficulties. Brain MRI of 2 patients showed mild cerebellar atrophy.
Mallaret et al. (2014) reported 2 sibs, born of consanguineous Israeli Palestinian parents, with onset of generalized tonic-clonic seizures in the first 2 years of life. They also had mental retardation, ataxia, and prominent upper motor neuron signs with leg spasticity and extensor plantar responses.
Inheritance
The transmission pattern of spinocerebellar ataxia in the family reported by Gribaa et al. (2007) was consistent with autosomal recessive inheritance.
Mapping
By genomewide linkage analysis of a Saudi Arabian family with complicated autosomal recessive spinocerebellar ataxia, Gribaa et al. (2007) found linkage to a 19-Mb interval on chromosome 16q21-q23 between markers D16S3091 and D16S3050 (lod score of 3.3). Molecular studies excluded mutations in the GAN gene (605379).
Molecular Genetics
In affected members of 2 consanguineous families of Saudi Arabian and Israeli Palestinian descent, respectively, with autosomal recessive spinocerebellar ataxia-12, Mallaret et al. (2014) identified 2 different homozygous missense mutations in the WWOX gene (P47T, 605131.0002 and G372R, 605131.0003). One of the families had previously been reported by Gribaa et al. (2007). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Western blot analysis of patient fibroblasts showed normal amounts of the mutant P47T protein, but in vitro functional studies showed that the mutant protein was unable to bind a PPPY-containing oligopeptide, suggesting that the mutation causes a conformational change that alters its ability to interact with normal protein motifs. None of the patients or heterozygous carriers developed cancer. No WWOX mutations were found in 189 additional unrelated ataxic patients.
Animal Model
Mallaret et al. (2014) observed that Wwox-null mice developed spontaneous seizures and noise-induced seizures at around 2 weeks of age. Knockout mice also developed balance disturbances. The progression of these symptoms suggested a neurodegenerative process. These mice died from failure to thrive before age 4 weeks.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Gaze-evoked nystagmus NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Seizures \- Mental retardation \- Cerebellar ataxia \- Limb ataxia \- Gait ataxia \- Dysarthria \- Spasticity (1 family) \- Extensor plantar responses (1 family) \- Cerebellar atrophy, mild Peripheral Nervous System \- Hyporeflexia MISCELLANEOUS \- Onset of seizures between 9 and 12 months of age \- Two unrelated consanguineous families (Saudi Arabian and Israeli Palestinian) have been reported (last curated February 2014) MOLECULAR BASIS \- Caused by mutation in the WW domain-containing oxidoreductase gene (WWOX, 605131.0002 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 12 | c3280452 | 1,086 | omim | https://www.omim.org/entry/614322 | 2019-09-22T15:55:42 | {"doid": ["0080060"], "omim": ["614322"], "orphanet": ["284282"], "synonyms": ["Autosomal recessive spinocerebellar ataxia type 12", "Alternative titles", "SCAR12", "SPINOCEREBELLAR ATAXIA WITH MENTAL RETARDATION AND EPILEPSY"]} |
Although Senegal is a relatively underdeveloped country, HIV prevalence in the general population is low at around 0.08 per 1000 people, under 1% of the population.[1] This relatively low prevalence rate is aided by the fact that few people are infected every year– in 2016, 1100 new cases were reported vs 48,000 new cases in Brazil. Senegal's death due to HIV rate, particularly when compared it to its HIV prevalence rate, is relatively high with 1600 deaths in 2016.[2] Almost two times as many women were infected with HIV as men in 2016, and while almost three times as many women were receiving antiretroviral therapy (ARV) as men, only 52% of HIV positive people in Senegal received ARV treatment in 2016.[2]
One way that Senegal maintains a low HIV prevalence is through conservative cultural norms that discourage sex outside of marriage[citation needed], limiting the number of sexual partners an average Senegalese person will have and thus limiting their chance of coming into contact with the virus. The government also passed legislation to make working closely with sex workers to ensure they get regular STI and HIV tests and treatment possible.[3] Senegal also has had huge public health campaigns to promote condom usage. Senegalese hospitals have also had their blood supplies screened for syphilis and hepatitis since 1970, leading to the removal of some blood contaminated with HIV before an HIV antibody test was created. Currently, hospitals are well equipped with sterile equipment in order to prevent transmission of HIV by hospital procedure.[3]
## Contents
* 1 New infection statistics
* 1.1 At risk populations
* 2 National response
* 3 See also
* 4 References
## New infection statistics[edit]
In the general population, 80% of new infections occur in people in monogamous relationships. According to Senegal's AIDS authority, among the newly infected, three-quarters of people engage in some high risk behavior. About one quarter of the newly infected engage in high risk behaviors themselves and about half of the newly infected have a partner who engages in high risk activities.[4] Because homosexuality is illegal in Senegal, many MSMs have long term female partners as well as male partners, so many women unknowingly have a partner who is in a high risk group.[4]
### At risk populations[edit]
While the overall HIV prevalence rate in Senegal is low, the prevalence rate is significantly higher in certain populations. Among men who have sex with men (MSM), the prevalence rate is around 19% and among sex workers, the prevalence rate is close to 22%. As a result, the Senegalese government has put emphasis on preventing transmission of the virus from these groups.[5] The HIV transmission rate in MSM communities has not decreased, partially because Senegal maintains laws against homosexuality.[6] As a result, MSMs fear seeking testing and treatment for HIV for fear of being arrested.[7] Despite promising to work to reduce the HIV prevalence rate in communities of people having non-heterosexual sex, the Senegalese government arrested 9 men working in HIV prevention for violating anti-homosexuality laws. Despite the later overturning of their convictions, the arrests created fear and suspicion in the MSM community.[7]
The Senegalese government provides medical services to registered sex workers, but in recent years, the number of covert sex workers has been increasing. These unregistered sex workers cannot access sex worker-specific government health services.[8] As many as 80% of all Senegalese sex workers may be unregistered. As a result, most sex workers do not have access to government sponsored STI and HIV testing and education about HIV prevention.[9]
## National response[edit]
Unlike many African countries which denied the existence of the HIV epidemic, Senegal responded quickly when its first AIDS case was diagnosed in 1986. The Programme National de Lutte contre le SIDA (PNLS) was established to coordinate the government's anti-AIDS activity in 1986 and was later renamed the Conseil National de Lutte contre le SIDA (CNLS).[3] The Senegalese government worked in cooperation with religious leaders and health professionals in order to maximize the reach of HIV/AIDS prevention education.[9] In addition to working with religious figures to enhance public cooperation, the Senegalese government ran a condom marketing campaign and distributed more than 10 million free condoms in partnership with USAID in order to try to limit HIV transmission.[3] Many HIV positive people make efforts to hide their status because there is much discrimination against them, which complicates the government's attempts to provide services to the HIV positive population.[3] The Senegalese government is still working to stop the spread of AIDS. CNLS's goals for 2030 include zero new infections, zero deaths tied to AIDS, and zero discrimination against HIV-positive Senegalese citizens.[4]
## See also[edit]
* Health in Senegal
* HIV
* Senegal
## References[edit]
1. ^ "Senegal". www.unaids.org. Retrieved 2017-10-31.
2. ^ a b "AIDSinfo | UNAIDS". aidsinfo.unaids.org. Retrieved 2017-10-31.
3. ^ a b c d e "HIV/AIDS in Senegal: A USAID Brief" (PDF). US AID. July 2002.
4. ^ a b c yacine. "Conseil National de Lutte contre le Sida - Plan Stratégique 2014-2017". www.cnls-senegal.org (in French). Retrieved 2017-11-09.
5. ^ Drame, Fatou Maria; Foley, Ellen E. (2015-05-01). "HIV/AIDS in mid-sized cities in Senegal: From individual to place-based vulnerability". Social Science & Medicine. 133 (Supplement C): 296–303. doi:10.1016/j.socscimed.2014.11.038. PMID 25433973.
6. ^ Wade, Abdoulaye S.; Larmarange, Joseph; Diop, Abdou K.; Diop, Oulimata; Gueye, Khady; Marra, Adama; Sene, Amsata; Enel, Catherine; Diallo, Pape Niang (2010-04-01). "Reduction in risk-taking behaviors among MSM in Senegal between 2004 and 2007 and prevalence of HIV and other STIs. ELIHoS Project, ANRS 12139". AIDS Care. 22 (4): 409–414. doi:10.1080/09540120903253973. ISSN 0954-0121. PMID 20131126.
7. ^ a b Poteat, Tonia; Diouf, Daouda; Drame, Fatou Maria; Ndaw, Marieme; Traore, Cheikh; Dhaliwal, Mandeep; Beyrer, Chris; Baral, Stefan (2011-12-14). "HIV Risk among MSM in Senegal: A Qualitative Rapid Assessment of the Impact of Enforcing Laws That Criminalize Same Sex Practices". PLOS ONE. 6 (12): e28760. doi:10.1371/journal.pone.0028760. ISSN 1932-6203. PMC 3237497. PMID 22194906.
8. ^ Foley, Ellen E.; Nguer, Rokhaya (2010-12-01). "Courting success in HIV/AIDS prevention: the challenges of addressing aconcentrated epidemic in Senegal". African Journal of AIDS Research. 9 (4): 325–336. doi:10.2989/16085906.2010.545628. ISSN 1608-5906. PMID 25875881.
9. ^ a b Diouf, D. (2007) HIV/AIDS Policy in Senegal: A Civil Society Perspective. New York, Open Society Institute.
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| HIV/AIDS in Senegal | None | 1,087 | wikipedia | https://en.wikipedia.org/wiki/HIV/AIDS_in_Senegal | 2021-01-18T18:34:58 | {"wikidata": ["Q5629883"]} |
## Summary
### Clinical characteristics.
The spectrum of GRN frontotemporal dementia (GRN-FTD) includes the behavioral variant (bvFTD), primary progressive aphasia (PPA; further subcategorized as progressive non-fluent aphasia [PNFA] and semantic dementia [SD]), and movement disorders with extrapyramidal features such as parkinsonism and corticobasal syndrome (CBS). A broad range of clinical features both within and between families is observed. The age of onset ranges from 35 to 87 years. Behavioral disturbances are the most common early feature, followed by progressive aphasia. Impairment in executive function manifests as loss of judgment and insight. In early stages, PPA often manifests as deficits in naming, word finding, or word comprehension. In late stages, affected individuals often become mute and lose their ability to communicate. Early findings of parkinsonism include rigidity, bradykinesia or akinesia (slowing or absence of movements), limb dystonia, apraxia (loss of ability to carry out learned purposeful movements), and disequilibrium. Late motor findings may include myoclonus, dysarthria, and dysphagia. Most affected individuals eventually lose the ability to walk. Disease duration is three to 12 years.
### Diagnosis/testing.
The diagnosis of GRN-FTD is established in a proband with suggestive findings and a heterozygous pathogenic variant in GRN identified by molecular genetic testing.
### Management.
Treatment of manifestations: Behavioral manifestations such as apathy, impulsivity, and compulsiveness may respond to selective serotonin reuptake inhibitors. Roaming, delusions, and hallucinations may respond to antipsychotic medications. Reports have suggested potential benefits with certain pharmacotherapy on management of FTD; however, evidence from randomized controlled trials is limited. Small-scale studies have suggested that trazodone may be helpful for treating irritability, agitation, depression, and eating disorders; methylphenidate and dextro-amphetamine may help minimize risk-taking behavior. Cholinesterase inhibitors examined in clinical trials were generally well tolerated: galantamine was used to treat PPA with stabilization of symptoms; rivastigmine was used to treat behavioral manifestations and appeared to decrease caregiver burden. Two open-label studies of memantine, an NMDA partial agonist-antagonist, demonstrated some efficacy on frontal behavior in those with bvFTD and improvement in cognitive performance in those with PPA-PNFA.
### Genetic counseling.
GRN-FTD is inherited in an autosomal dominant manner. About 95% of individuals diagnosed with GRN-FTD have an affected parent. The proportion of affected individuals with a de novo GRN pathogenic variant is unknown but is estimated to be 5% or fewer. Each child of an individual with GRN-FTD has a 50% chance of inheriting the pathogenic variant. Once a GRN pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.
## Diagnosis
### Suggestive Findings
GRN frontotemporal dementia (GRN-FTD) should be suspected in individuals with the following clinical presentations and neuroimaging findings.
#### Clinical Presentations
Clinical presentations of GRN-FTD vary widely both among and within families and may resemble behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), atypical parkinsonism, or corticobasal syndrome.
Behavioral variant FTD [Rascovsky et al 2011]
* Early behavioral disinhibition (including one of the following):
* Socially inappropriate behavior
* Loss of manners or decorum
* Impulsive, rash, or careless actions
* Early apathy or inertia (one of the following):
* Apathy
* Inertia
* Early loss of sympathy or empathy (one of the following):
* Diminished response to other people's needs and feelings
* Diminished social interest, interrelatedness, or personal warmth
* Early perseverative, stereotyped, or compulsive/ritualistic behavior (one of the following):
* Simple repetitive movements
* Complex, compulsive, or ritualistic behaviors
* Stereotypy of speech
* Hyperorality and dietary changes (one of the following):
* Altered food preferences
* Binge eating, increased consumption of alcohol or cigarettes
* Oral exploration or consumption of inedible objects
* Neuropsychological profile: executive/generation deficits with relative sparing of memory and visuospatial functions (all of the following):
* Deficits in executive tasks
* Relative sparing of episodic memory
* Relative sparing of visuospatial skills
Primary progressive aphasia (PPA). PPA has been further classified into three subtypes [Gorno-Tempini et al 2011]:
* Progressive nonfluent aphasia (PNFA, also known as nonfluent or agrammatic subtype of PPA)
* Semantic dementia (SD)
* Logopenic variant (logopenic PPA)
Note: To date, the logopenic variant has not been associated with GRN-FTD.
The majority of the literature describes PNFA to be the predominant form of PPA in GRN-FTD, although there are a few reports of the SD phenotype as well.
The currently proposed diagnostic algorithm for PNFA requires a two-step process. First, individuals must meet the criteria for PPA, and after the diagnosis of PPA is established, the main features of the speech and language abnormalities may be considered to subcategorize into each of the PPA variants.
The diagnostic criteria of PPA [Mesulam 2001]:
* The most prominent clinical feature is difficulty with language.
* Language deficits are the principal cause of impaired daily living activities.
* Aphasia is the most prominent deficit at symptom onset and for the initial phases of the disease.
Note: The pattern of deficits cannot be accounted for by other nondegenerative diseases of the nervous system, medical disorders, or psychiatric diagnoses.
PPA subtypes
* Nonfluent variant of PPA (PPA-PNFA). The diagnostic criteria of PPA-PNFA include clinical presentation of aphasia with [Gorno-Tempini et al 2011]:
* At least one of the following core features:
* Agrammatism in language production
* Effortful, halting speech with inconsistent speech sound errors and distortions (apraxia of speech)
* At least two of the three following supportive features:
* Impaired comprehension of syntactically complex sentences
* Spared single-word comprehension
* Spared object knowledge
* Semantic variant of PPA (PPA-SD). The diagnostic criteria of PPA-SD require the presence of both of the following core features:
* Impaired confrontation naming
* Impaired single-word comprehension
AND at least three of the following four additional diagnostic features:
* Impaired object knowledge, particularly for low frequency or low-familiarity items
* Surface dyslexia or dysgraphia
* Spared repetition
* Spared speech production (grammar and motor speech)
Atypical parkinsonism. Clinical features include the following:
* Bradykinesia
* Rigidity
* Gait instability
* Resting tremor
Corticobasal syndrome. Clinical features include the following [Armstrong et al 2013]:
* Progressive asymmetric rigidity
* Apraxia
* Alien-limb phenomenon
* Cortical sensory loss
* Focal dystonia
* Myoclonus
* Dementia
#### Neuroimaging
Computed tomography (CT) or magnetic resonance imaging (MRI) may show focal, often asymmetric atrophy in the frontal, temporal, and/or parietal lobes [Rohrer & Warren 2011]. Volumetric studies comparing the rate of brain atrophy between GRN-FTD and MAPT-FTD showed that individuals with GRN-FTD have a higher rate of whole-brain atrophy (3.5% per year) than those with MAPT-related FTD [Whitwell et al 2011].
Single photon emission computed tomography (SPECT) may reveal decreased perfusion in the frontal and temporal lobes [Pasquier et al 2003]. There is also evidence of poor cerebral perfusion in both anterior parietal lobes, predominantly on the left hemisphere and on the right inferior parietal cortex [Le Ber et al 2008].
Positron emission tomography (PET) may demonstrate decreased glucose metabolism in the frontal and temporal regions in the presymptomatic stage prior to structural changes [Jacova et al 2013, Caroppo et al 2015].
### Establishing the Diagnosis
The diagnosis of GRN frontotemporal dementia (GRN-FTD) is established in a proband with a heterozygous pathogenic variant in GRN by molecular genetic testing (see Table 1).
Gene-targeted testing (multigene panel) requires that the clinician determine which gene(s) are likely involved, whereas comprehensive genomic testing does not. Because the phenotype of GRN-FTD is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of GRN-FTD has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
A frontotemporal dementia multigene panel that includes GRN and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For GRN-FTD a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1).
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
Comprehensive genomic testing. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic – and particularly when evidence supports autosomal dominant inheritance – exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in GRN Frontotemporal Dementia
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
GRNSequence analysis 3~98.5% 4
Gene-targeted deletion/duplication analysis 5~1.5% 4, 6
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\.
Cruts et al [2006], Chen-Plotkin et al [2011], Van Langenhove et al [2013], Pottier et al [2018]. Note: Pottier et al [2018] identified 449 affected individuals with GRN disease-associated variants detected by sequence and deletion/duplication analysis in the ascertainment step of a genome-wide association study (see Pottier et al [2018], Supplementary Table 2).
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described by Milan et al [2017]) may not be detected by these methods.
6\.
Gijselinck et al [2008], Pickering-Brown et al [2008], Rovelet-Lecrux et al [2008], Finch et al [2009], Chen-Plotkin et al [2011], Rohrer et al [2013], Van Langenhove et al [2013], Clot et al [2014]
## Clinical Characteristics
### Clinical Description
GRN frontotemporal dementia (GRN-FTD) generally affects the frontal and temporal cortex leading to behavioral changes, executive dysfunction, and language disturbances. In GRN-FTD, the parietal cortex and basal ganglia may be affected as well, resulting in parkinsonism, cortical basal syndrome, and memory impairment [Baker et al 2006, Masellis et al 2006, Mukherjee et al 2006, Behrens et al 2007, Josephs et al 2007, Mesulam et al 2007, Spina et al 2007].
Age of onset. The age of onset of GRN-FTD ranges from 35 to 87 years with a mean of 64.9 ± 11.3 years [Bruni et al 2007, Le Ber et al 2007, Rademakers et al 2007, Chen-Plotkin et al 2011].
Comparison studies demonstrate that onset age in individuals with GRN-FTD does not differ significantly from that in individuals without an identified GRN pathogenic variant [Beck et al 2008, Pickering-Brown et al 2008], while some studies suggested a younger onset age in those with GRN-FTD [Huey et al 2006, Davion et al 2007].
Neurocognitive symptoms. Neuropsychological testing may demonstrate early impairment on frontal lobe tasks or specific language dysfunction prior to the onset of frank dementia.
Behavioral disturbances are the most common early feature, followed by progressive aphasia [Gass et al 2006, Josephs et al 2007]. This is usually an insidious but profound change in personality and conduct, characterized by distractibility, loss of initiative, apathy, and loss of interest in their environment, often accompanied by neglect in personal hygiene and social disinhibition. Some affected individuals demonstrate impulsiveness or compulsiveness and may alter their eating habits with food fads and food craving.
With impairment in executive function, there is loss of judgment and insight, which may manifest early in the disease course as, for example, making poor financial decisions, quitting jobs abruptly, or becoming unduly forward or rude to strangers. Alternatively, persons with predominant apathy may lose all interest and initiative with usual activities, appear socially withdrawn, give up all previous hobbies and interests, and be unable to complete tasks due to lack of persistence. Early in the course of the illness, affected individuals may be misdiagnosed as having psychiatric conditions such as depression, mania, or psychosis because of the unusual and bizarre nature of their behavior. Psychometric testing may demonstrate impairment on frontal executive tasks including the Trail-Making Test, proverb interpretation, descriptions of similarities, categorical naming, and abstract pattern recognition (e.g., Wisconsin Card Sort Test).
Language deficits. Primary progressive aphasia (PPA), particularly the progressive non-fluent aphasia (PNFA) variant, can be another presentation of GRN-FTD [Mesulam et al 2007]. In early stages, PPA-PNFA often manifests as deficits in naming, word finding, or word comprehension. Although behavioral manifestations tend to be more common than language deficits as the initial presentation of GRN-FTD, in one series 82% of affected individuals eventually developed language problems [Josephs et al 2007, Caso et al 2012].
In contrast with PPA-PNFA, semantic dementia is characterized by impaired naming and comprehension, semantic paraphasias, and impaired recognition of familiar faces or objects. Although rare in GRN-FTD, pure semantic dementia (PPA-SD) has been described in a few studies [Whitwell et al 2007, Beck et al 2008]. In late stages, individuals with PPA-SD may develop impaired face recognition and behavioral changes including disinhibition and compulsion [Seeley et al 2005].
A number of studies have reported individuals with GRN-FTD who have presented with amnestic mild cognitive impairment, which may be mistaken for Alzheimer disease [Carecchio et al 2009, Kelley et al 2010].
Movement disorders. In several families with GRN-FTD, parkinsonism is prominent, and in some the initial clinical diagnosis was corticobasal syndrome [Gass et al 2006, Masellis et al 2006, Benussi et al 2009, Moreno et al 2009]. Early findings include rigidity, bradykinesia or akinesia (slowing or absence of movements), limb dystonia, apraxia (loss of ability to carry out learned purposeful movements), and disequilibrium. Late motor findings may include myoclonus, dysarthria, and dysphagia. Most affected individuals eventually lose the ability to walk.
Motor neuron disease. Although the histopathologic findings of ubiquitin-positive inclusions were initially associated with motor neuron disease, it appears to occur only rarely (if at all) in GRN-FTD [Schymick et al 2007].
Disease course. The mean age at death is 65±8 years. Disease duration ranges from three to 12 years [Gass et al 2006].
Neuropathology. The neuropathology of GRN-FTD is characterized by the following [Mackenzie et al 2006, Mackenzie et al 2011]:
* Tau-negative alpha-synuclein-negative ubiquitin-positive "cat-eye" or lentiform-shaped neuronal intranuclear inclusions (NII), often found in the neocortex and striatum
* Superficial laminar spongiosis with ubiquitin-positive neurites and neuronal cytoplasmic inclusions (NCI) in the neocortex
* Granular appearance of the ubiquitin-immunoreactive (ub-ir) neurites in the striatum and the NCI in the hippocampus
* Phosphorylation of S409/410 of TDP-43 in pathologic inclusions [Neumann et al 2009]
The major protein component of these ubiquitin inclusions is a TAR DNA-binding protein of 43 kd (TDP-43). TDP-43 is a nuclear factor involved in regulating transcription and alternative splicing [Arai et al 2006, Neumann et al 2006]. It is mostly a nuclear protein, although recent studies have shown that it shuttles between the nucleus and cytoplasm in normal conditions [Ayala et al 2008]. While its physiologic function remains unclear, it has been demonstrated to bind to a large number of RNA targets with a preference for UG-rich intronic regions and is important in many vital cellular processes [Sendtner 2011].
It is now recognized that pathologically, GRN-FTD is a major subtype of frontotemporal lobar degeneration (FTLD). The neuropathologic diagnostic criteria for FTLD have been updated based on current molecular understanding of the disease [Mackenzie et al 2011].
### Genotype-Phenotype Correlations
No obvious correlations between age of onset, disease duration, or clinical phenotype and specific GRN pathogenic variants have been identified. Clinical variability is high among individuals with the same GRN pathogenic variant.
### Penetrance
Penetrance of GRN-FTD is about 90% by age 75 years, but apparent reduced penetrance has also been observed on occasion [Cruts et al 2006, Gass et al 2006].
A study of the common p.Arg493Ter pathogenic variant showed that 60% of individuals with this variant were affected by age 60 years, and more than 95% were affected by age 70 years [Rademakers et al 2007]. Age at onset of frontotemporal lobar degeneration (FTLD) was younger in individuals with a GRN pathogenic variant vs those without one (median: 58.0 vs 61.0 years), as was age at death (median: 65.5 vs 69.0 years) [Chen-Plotkin et al 2011].
In a large series in France, 3.2% of simplex cases (i.e., only one affected individual in a family) with FTD were found to have a GRN pathogenic variant, suggesting possible de novo variant or incomplete penetrance [Le Ber et al 2007].
### Nomenclature
The term frontotemporal dementia (FTD) is used in this GeneReview to designate the clinical presentation of the dementing illness, while the term frontotemporal lobar degeneration (FTLD) is used to denote the pathologic diagnosis of the disease.
Note that PGRN, the earlier designation for the gene GRN, may be used in the literature as well (e.g., PGRN-FTD).
Prior to the identification of GRN as the gene in which a pathogenic variant is responsible for this form of FTD, a number of terms were used to describe this disorder.
* FTDU-17. Analogous to FTDP-17, the term "FTDU-17" has been used because the pathologic characteristics of this condition are associated with ubiquitinated inclusions and the genetic locus was also located on chromosome 17.
* HDDD1 and HDDD2. Familial dementia in other kindreds with similar clinical presentations was descriptively named hereditary dysphasic disinhibition dementia (HDDD1 and HDDD2). It has now been shown that GRN pathogenic variants are also responsible for the phenotype in these families, and therefore these are now considered GRN-FTD [Mukherjee et al 2006, Behrens et al 2007].
### Prevalence
Frontotemporal dementia (FTD) accounts for 5%-10% of all individuals with dementia and 10%-20% of individuals with dementia with onset before age 65 years [Bird et al 2003].
GRN-FTD represents about 5% of all FTD, and 20% of FTD in which the family history is positive.
### Genetically Related (Allelic) Disorders
Individuals with biallelic GRN pathogenic variants and the phenotype of neuronal ceroid lipofuscinosis, a lysosomal storage disease that is strikingly different from FTD, have been reported [Smith et al 2012, Kamate et al 2019]. This finding further highlights the role of GRN in lysosomal function and regulation (see Molecular Genetics).
## Differential Diagnosis
Neuroimaging can evaluate for other conditions that mimic frontotemporal dementia (FTD) (e.g., white matter diseases, frontotemporal focal lesions, frontal lobe tumors, and cerebrovascular disease).
The clinical manifestations of GRN-FTD significantly overlap with those of other conditions including FTD with or without parkinsonism associated with pathogenic variants in MAPT (OMIM 600274), Parkinson disease, Alzheimer disease, Pick disease (OMIM 172700), other inherited FTD disorders, corticobasal degeneration, progressive supranuclear palsy, and Creutzfeldt-Jacob disease (OMIM 123400). This clinical overlap makes it difficult to predict which family has a GRN pathogenic variant by clinical presentation alone.
Up to 50% of individuals with FTD have a positive family history of dementia, usually with autosomal dominant inheritance. Table 2 below lists the most common genes associated with familial FTD.
### Table 2.
Genes in the Differential Diagnosis of GRN Frontotemporal Dementia
View in own window
Gene(s)Differential
Diagnosis
DisorderClinical Features of Differential Diagnosis Disorder
OnsetDisease
DurationPathologyComment
Most commonly involved genes
C9orf72ALS & FTDMean: 54.3 yrs; range: 34-74 yrsMean: 5.3 yrs; range: 1-16 yrsTDP-43 pathology is found in a wide neuroanatomic distribution, w/particular involvement in extramotor neocortex & hippocampus & in lower motor neuronsMay be misdiagnosed as bvFTD, PPA-PNFA, or ALS. 1 Heterogeneity in clinical presentation is common w/in families. Phenotypes tend to converge w/disease progression.
MAPTFTDP-17
(OMIM 600274)Usually age 40-60 yrs; may occur earlier or laterUsually 5-10 yrs; may be up to 20-30 yrsAt autopsy, all persons w/FTDP-17 show tau-positive inclusion pathology, whereas all persons w/GRN-FTD show ub-ir neuronal intranuclear inclusions. 2Presenile dementia affecting frontal & temporal cortex & some subcortical nuclei. Variable presentation; may present w/slowly progressive behavioral changes, language disturbances, &/or extrapyramidal signs; progresses over a few yrs to profound dementia w/mutism. 25%-40% of families w/AD FTD have mutation of MAPT.
Less commonly involved genes
CHMP2BFTD-3Typically in late 50sNeuropathology assoc w/ubiquitin-positive but TDP-43- & FUS-negative inclusionsUsually presents w/a frontal lobe syndrome, parkinsonism, dystonia, pyramidal signs. Myoclonus may occur later in disease course.
TARDBPALS or ALS w/FTD (see TARDBP-ALS)41-60 yrs2-4 yrsTDP-43 inclusions in upper & lower motor neurons & cortexAssoc w/~3% of familial ALS & occasionally FTD w/ALS
VCPInclusion body myopathy w/Paget disease of bone & FTD (IBMPFD)Muscle disease & PDB: age 42 yrs; FTD: age 55 yrsNumerous intranuclear & infrequent # of neuronal cytoplasmatic inclusions & dystrophic neuritis seen in neuropathologyAdult-onset proximal & distal muscle weakness (clinically LGMD 3), early-onset PDB 4, & FTD. Early-stage FTD: dysnomia, dyscalculia, comprehension deficits, paraphasic errors, & relative preservation of memory. Later stages: inability to speak, auditory comprehension deficits for even 1-step commands, alexia, & agraphia
AD= autosomal dominant; ALS = amyotrophic lateral sclerosis; FTD = frontotemporal dementia; bvFTD = behavioral variant FTD; FTDP = frontotemporal dementia with parkinsonism; FUS = fused in sarcoma; LGMD = limb-girdle muscular dystrophy; PNFA = progressive nonfluent aphasia; PDB = Paget disease of bone; PPA = primary progressive aphasia
1\.
See Amyotrophic Lateral Sclerosis Overview.
2\.
Ghetti et al [2003], Mackenzie [2007]
3\.
Muscle weakness progresses to involve other limb & respiratory muscles; cardiac failure & cardiomyopathy have been observed in later stages of IBMPFD.
4\.
Paget disease of bone (PDB) involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with GRN frontotemporal dementia (GRN-FTD), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:
* Detailed general, neurologic, and family history
* Physical examination
* Neurologic examination
* Cognitive examination. When clinical cognitive assessments are not informative enough, a neuropsychological assessment may be performed to provide a more comprehensive and objective view of a patient's cognitive function. Formal neuropsychological assessment requires comparison of the patient's raw score on a specific test to a large general population normative sample which is usually drawn from a population comparable to that of the person being examined. This allows for the patient's performance to be compared to a suitable control group, adjusted for age, gender, level of education, and/or ethnicity. While much more sensitive than bedside clinical cognitive examination, such assessment is resource intensive and time consuming.
* Discussion of capabilities for job and for driving
* Discussion of advanced care planning
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
There is currently no known treatment for GRN-FTD or FTD in general. Psychosocial support is essential in the management of FTD and should include occupational therapy and environmental and physical interventions.
However, some behavioral manifestations such as apathy, impulsivity, and compulsiveness may respond to selective serotonin reuptake inhibitors. Behavioral changes and the loss of insight and judgment in individuals with GRN-FTD often present a considerable burden for caregivers. Information about the disease and psychological support for partners or other caregivers is essential. Caregiver support groups are valuable.
The behavioral and psychological manifestations should be treated as in other types of FTD. There is no consensus treatment guideline for GRN-FTD. In clinical practice those affected individuals who have very aggressive behavior have proven quite difficult to treat and have in some instances been treated with high doses of antipsychotics and/or antidepressants in order to relieve the physical aggressiveness. Administered antipsychotics should be reevaluated at short intervals with the purpose of discontinuation as soon as feasible.
Roaming, delusions, and hallucinations may respond to antipsychotic medications.
Although reports have suggested potential benefits with certain pharmacotherapy on management of FTD in general, evidence from randomized controlled trials is limited [Freedman 2007]. All of the following findings require confirmation with larger clinical trials:
* One double-blind placebo-controlled crossover trial suggests that trazodone, a serotonergic agent, may be beneficial in treating the symptoms of irritability, agitation, depression, and eating disorders in FTD [Lebert et al 2004].
* While an open-label study suggested some benefits on behavioral symptoms with paroxetine, a double-blind placebo-controlled trial of ten subjects found worsening of performance on paired associates learning, reversal learning, and delayed pattern recognition [Moretti et al 2003, Deakin et al 2004].
* A study of galantamine in bvFTD and primary progressive aphasia (PPA) found significant benefits in subjects with PPA but not in those with bvFTD [Kertesz et al 2005]. A follow-up study of 36 individuals who were on galantamine therapy for 18 weeks revealed stabilization but not improvement on language scores in the PPA group [Kertesz et al 2008].
* A 12-month open-label rivastigmine trial showed improvement of behavioral symptoms and decreased caregiver burden in individuals with FTD; however, the treatment did not prevent cognitive decline [Moretti et al 2004].
* A double-blind placebo-controlled crossover study of methylphenidate found attenuation of risk-taking behavior but worsening of spatial span [Rahman et al 2006].
* A small clinical trial of dextroamphetamine treatment on eight individuals with bvFTD revealed improvement of behavioral symptoms [Huey et al 2008].
* A few open-label studies of memantine, a partial NMDA agonist, demonstrated an improvement on the frontal battery inventory in individuals with bvFTD after a six-month trial, but a decline in other cognitive performance [Diehl-Schmid et al 2008]. Among the three subtypes of FTD, PPA-PNFA remained stable on cognitive and functional measurements when treated with memantine [Boxer et al 2009]. A study using [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) as a surrogate outcome in individuals with semantic dementia found that cortical metabolic activity in salience network hubs was sustained when treated with memantine over a six-month period [Chow et al 2013]. While a meta-analysis suggest some benefit with memantine, the sample sizes were small and further studies with larger samples sizes are needed [Kishi et al 2015].
Note: Donepezil treatment has been associated with exacerbation of disinhibition and compulsion symptoms [Mendez et al 2007].
### Surveillance
Patients are often followed in a memory disorder clinic or a similar multidisciplinary clinic involving neurologic and psychiatric services and follow-up medical care.
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| GRN Frontotemporal Dementia | c0338451 | 1,088 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1371/ | 2021-01-18T21:23:43 | {"mesh": ["D057180"], "synonyms": ["FTD-GRN"]} |
This article is about haemochromatosis associated with the HFE gene. For other causes of haemochromatosis, see iron overload.
Haemochromatosis type 1
Other namesHFE hereditary haemochromatosis[1] HFE-related hereditary haemochromatosis[2]
Iron accumulation demonstrated by Prussian blue staining in a patient with homozygous genetic haemochromatosis (microscopy, 10x magnified): Parts of normal pink tissue are scarcely present.
SpecialtyEndocrinology, hepatology
Differential diagnosisHemochromatosis type 4
Hereditary haemochromatosis (or hemochromatosis)[3] is a genetic disorder characterized by excessive intestinal absorption of dietary iron, resulting in a pathological increase in total body iron stores.[4] Humans, like most animals, have no means to excrete excess iron.[5]
Excess iron accumulates in tissues and organs, disrupting their normal function. The most susceptible organs include the liver, adrenal glands, heart, skin, gonads, joints, and the pancreas; patients can present with cirrhosis, polyarthropathy, adrenal insufficiency, heart failure, or diabetes.[6]
The hereditary form of the disease is most common among those of Northern European ancestry, in particular those of Celtic descent.[7] The disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.[8] Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.[8]
## Contents
* 1 Signs and symptoms
* 1.1 End-organ damage
* 2 Genetics
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Blood tests
* 4.2 Liver biopsy
* 4.3 MRI
* 4.4 Other imaging
* 4.5 Functional testing
* 4.6 Stages
* 4.7 Differential diagnosis
* 5 Screening
* 6 Treatment
* 6.1 Phlebotomy
* 6.2 Desferrioxamine mesilate
* 6.3 Organ damage
* 6.4 Diet
* 6.5 Chelating polymers
* 7 Prognosis
* 8 Epidemiology
* 9 Terminology
* 10 History
* 11 References
* 12 External links
## Signs and symptoms[edit]
Haemochromatosis is protean in its manifestations, i.e., often presenting with signs or symptoms suggestive of other diagnoses that affect specific organ systems. Many of the signs and symptoms below are uncommon, and most patients with the hereditary form of haemochromatosis do not show any overt signs of disease nor do they suffer premature morbidity, if they are diagnosed early, but, more often than not, the condition is diagnosed only at autopsy.[9]
Presently, the classic triad of cirrhosis, bronze skin, and diabetes is less common because of earlier diagnosis.[10]
The more common clinical manifestations include:[6][10][11][12]
* Fatigue
* Malaise
* Joint and bone pain
* Liver cirrhosis (with an increased risk of hepatocellular carcinoma): Liver disease is always preceded by evidence of liver dysfunction, including elevated serum enzymes specific to the liver, clubbing of the fingers, leuconychia, asterixis, hepatomegaly, palmar erythema, and spider naevi. Cirrhosis can also present with jaundice (yellowing of the skin) and ascites.
* Insulin resistance (often, patients have already been diagnosed with diabetes mellitus type 2) due to pancreatic damage from iron deposition.)
* Erectile dysfunction and hypogonadism, resulting in decreased libido
* Congestive heart failure, abnormal heart rhythms, or pericarditis
* Arthritis of the hands (especially the second and third metacarpophalangeal joints), but also the knee and shoulder joints
* Damage to the adrenal gland, leading to adrenal insufficiency
Less common findings including:
* Deafness[13]
* Dyskinesias, including Parkinsonian symptoms[13][14][15]
* Dysfunction of certain endocrine organs:
* Parathyroid gland (leading to hypocalcaemia)
* Pituitary gland
* More commonly, a slate-grey or less commonly darkish colour to the skin (see pigmentation, hence its name "bronze diabetes" when it was first described by Armand Trousseau in 1865)
* An increased susceptibility to certain infectious diseases caused by siderophilic microorganisms:
* Vibrio vulnificus infections from eating seafood or wound infection[16]
* Listeria monocytogenes
* Yersinia enterocolica
* Salmonella enterica (serotype Typhymurium)[17]
* Klebsiella pneumoniae
* Escherichia coli
* Rhizopus arrhizus
* Mucor species
* Aspergillus fumigatus
* Cytomegalovirus
* Hepatitis B virus
* Hepatitis C virus
Males are usually diagnosed after their forties and fifties, and women several decades later, owing to the fact that symptoms mimic those of menopause. Most people display symptoms in their 30s but due to the lack of knowledge surrounding haemochromatosis, they are diagnosed years later. The severity of clinical disease in the hereditary form varies considerably. Some evidence suggests that hereditary haemochromatosis patients affected with other liver ailments such as hepatitis or alcoholic liver disease suffer worse liver disease than those with either condition alone. Also, juvenile forms of hereditary haemochromatosis present in childhood with the same consequences of iron overload.
### End-organ damage[edit]
Iron is stored in the liver, pancreas, and heart. Long-term effects of haemochromatosis on these organs can be very serious, even fatal when untreated.[18] For example, similar to alcoholism, haemochromatosis can cause cirrhosis of the liver. The liver is a primary storage area for iron and naturally accumulates excess iron. Over time, the liver is likely to be damaged by iron overload. Cirrhosis itself may lead to additional and more serious complications, including bleeding from dilated veins in the esophagus (esophageal varices) and stomach (gastric varices) and severe fluid retention in the abdomen (ascites). Toxins may accumulate in the blood and eventually affect mental functioning. This can lead to confusion or even coma (hepatic encephalopathy).Cirrhosis and haemochromatosis together can increase the risk of liver cancer. (Nearly one-third of people with haemochromatosis and cirrhosis eventually develop liver cancer.)The pancreas, which also stores iron, is very important in the body's mechanisms for sugar metabolism. Diabetes affects the way the body uses blood sugar (glucose). Diabetes is, in turn, the leading cause of new blindness in adults and may be involved in kidney failure and cardiovascular disease. If excess iron in the heart interferes with its ability to circulate enough blood, a number of problems can occur, such as congestive heart failure and death. The condition may be reversible when haemochromatosis is treated and excess iron stores are reduced. Arrhythmia or abnormal heart rhythms can cause heart palpitations, chest pain, and light-headedness, and are occasionally life-threatening. This condition can often be reversed with treatment for haemochromatosis.[citation needed]
Bronze or grey coloration of the skin pigmentation is caused primarily by increased melanin deposition, with iron deposition playing a lesser role.[19]
Severity of periodontal disease is associated with high transferrin saturation in haemochromatosis patients.[20][21]
## Genetics[edit]
The regulation of dietary iron absorption is complex and understanding is incomplete. One of the better-characterized genes responsible for hereditary haemochromatosis is HFE[22] on chromosome 6, which codes for a protein that participates in the regulation of iron absorption. The HFE gene has three often observed genetic variants:[23][24]
* rs1799945, c.187C>G, p.His63Asp (H63D);
* rs1800562, c.845G>A, p.Cys282Tyr (C282Y);
* rs1800730, c.193A>T, p.Ser65Cys (S65C).
The worldwide prevalence rates for H63D, C282Y and S65C (minor allele frequencies) are 10%, 3% and 1% respectively.[25][26][27]
The C282Y allele is a transition point mutation from guanine to adenine at nucleotide 845 in HFE, resulting in a missense mutation that replaces the cysteine residue at position 282 with a tyrosine amino acid.[28] Heterozygotes for either allele can manifest clinical iron overload, if they have two of any alleles. This makes them compound heterozygous for haemochromatosis and puts them greatly at risk of storing excess iron in the body.[medical citation needed] Homozygosity for the C282Y genetic variant is the most common genotype responsible for clinical iron accumulation, though heterozygosity for C282Y/H63D variants, so-called compound heterozygotes, results in clinically evident iron overload. Considerable debate exists regarding the penetrance—the probability of clinical expression of the trait given the genotype— for clinical disease in homozygotes.[medical citation needed] Most males homozygous for HFE C282Y show at least one manifestation of iron-storage disease by middle age.[29] Individuals with the relevant genetic variants may never develop iron overload. Phenotypic expression is present in 70% of C282Y homozygotes with less than 10% going on to experience severe iron overload and organ damage.[30]
The H63D variant is just a gene polymorphism, and if there are no other changes, it may not have clinical significance.[31][32][33] In a 2014 study, H63D homozygosity was associated with an elevated mean ferritin level, but only 6.7% had documented iron overload at follow-up.[34] As about the people with one copy of the H63D alteration (heterozygous carriers), this genotype is very unlikely to cause a clinical presentation, there is no predictable risk of iron overload.[35] Besides that, a 2020 study revealed that the frequency of homozygous or heterozygous H63D variant is significantly higher in elite endurance athletes comparing to ethnically-matched controls, and is associated with high V̇O2max in male athletes.[36]
See also: HFE H63D gene mutation
Each patient with the susceptible genotype accumulates iron at different rates depending on iron intake, the exact nature of the genetic variant, and the presence of other insults to the liver, such as alcohol and viral disease. As such, the degree to which the liver and other organs are affected is highly variable and is dependent on these factors and co-morbidities, as well as age at which they are studied for manifestations of disease.[37] Penetrance differs between populations.
Disease-causing genetic variants of the HFE gene account for 90% of the cases of non-transfusion iron overload.[medical citation needed]
This gene is closely linked to the HLA-A3 locus.[citation needed]
See also: HFE (gene) § Clinical significance
## Pathophysiology[edit]
The normal distribution of body iron stores
Since the regulation of iron metabolism is still poorly understood, a clear model of how haemochromatosis operates is still not available. A working model describes the defect in the HFE gene, where a mutation puts the intestinal absorption of iron into overdrive. Normally, HFE facilitates the binding of transferrin, which is iron's carrier protein in the blood. Transferrin levels are typically elevated at times of iron depletion (low ferritin stimulates the release of transferrin from the liver). When transferrin is high, HFE works to increase the intestinal release of iron into the blood. When HFE is mutated, the intestines perpetually interpret a strong transferrin signal as if the body were deficient in iron. This leads to maximal iron absorption from ingested foods and iron overload in the tissues. However, HFE is only part of the story, since many patients with mutated HFE do not manifest clinical iron overload, and some patients with iron overload have a normal HFE genotype. A possible explanation is the fact that HFE normally plays a role in the production of hepcidin in the liver, a function that is impaired in HFE mutations.[38]
People with abnormal iron regulatory genes do not reduce their absorption of iron in response to increased iron levels in the body. Thus, the iron stores of the body increase. As they increase, the iron which is initially stored as ferritin is deposited in organs as haemosiderin and this is toxic to tissue, probably at least partially by inducing oxidative stress.[39] Iron is a pro-oxidant. Thus, haemochromatosis shares common symptomology (e.g., cirrhosis and dyskinetic symptoms) with other "pro-oxidant" diseases such as Wilson's disease, chronic manganese poisoning, and hyperuricaemic syndrome in Dalmatian dogs. The latter also experience "bronzing".
## Diagnosis[edit]
The diagnosis of haemochromatosis is often made following the incidental finding on routine blood screening of elevated serum liver enzymes or elevation of the transferrin saturation. Arthropathy with stiff joints, diabetes, or fatigue, may be the presenting complaint.[40]
### Blood tests[edit]
Serum transferrin and transferrin saturation are commonly used as screening for haemochromatosis. Transferrin binds iron and is responsible for iron transport in the blood.[41] Measuring transferrin provides a crude measure of iron stores in the body. Fasting transferrin saturation values in excess of 45% for males or 35% in premenopausal women (i.e. 300 ng/l in males and 200 ng/l in females) are recognized as a threshold for further evaluation of haemochromatosis.[10][42] Transferrin saturation greater than 62% is suggestive of homozygosity for mutations in the HFE gene.[43]
Ferritin, a protein synthesized by the liver, is the primary form of iron storage within cells and tissues. Measuring ferritin provides another crude estimate of whole-body iron stores, though many conditions, particularly inflammation (but also chronic alcohol consumption, nonalcoholic fatty liver disease, and others), can elevate serum ferritin, which can account for up to 90% of cases where elevated levels are observed.[4] Normal values for males are 12–300 ng/ml and for female, 12–150 ng/ml.[40][44] Serum ferritin in excess of 1000 ng/ml of blood is almost always attributable to haemochromatosis.
Other blood tests routinely performed include blood count, renal function, liver enzymes, electrolytes, and glucose (and/or an oral glucose tolerance test).
### Liver biopsy[edit]
Liver biopsies involve taking a sample of tissue from the liver, using a thin needle. The amount of iron in the sample is then quantified and compared to normal, and evidence of liver damage, especially cirrhosis, is measured microscopically. Formerly, this was the only way to confirm a diagnosis of haemochromatosis, but measures of transferrin and ferritin along with a history are considered adequate in determining the presence of the malady. Risks of biopsy include bruising, bleeding, and infection. Now, when a history and measures of transferrin or ferritin point to haemochromatosis, whether a liver biopsy is still necessary to quantify the amount of accumulated iron is debatable.[40]
### MRI[edit]
MRI-based testing is a noninvasive and accurate alternative to measure liver iron concentrations.[45]
### Other imaging[edit]
Clinically, the disease may be silent, but characteristic radiological features may point to the diagnosis. The increased iron stores in the organs involved, especially in the liver and pancreas, result in characteristic findings on unenhanced CT and a decreased signal intensity in MRI scans. Haemochromatosis arthropathy includes degenerative osteoarthritis and chondrocalcinosis. The distribution of the arthropathy is distinctive, but not unique, frequently affecting the second and third metacarpophalangeal joints of the hand.[citation needed] The arthropathy can, therefore, be an early clue as to the diagnosis of haemochromatosis.
### Functional testing[edit]
Based on the history, the doctor might consider specific tests to monitor organ dysfunction, such as an echocardiogram for heart failure, or blood glucose monitoring for patients with haemochromatosis diabetes.
### Stages[edit]
The American Association for the Study of Liver Diseases suggests the following three stages for the condition (identified by the European Association for the Study of Liver Diseases):[30]
1. Genetic susceptibility but no iron overload. Individuals who have the genetic disorder only.
2. Iron overload but no organ or tissue damage.
3. Organ or tissue damage as a result of iron deposition.
Individuals at each stage do not necessarily progress on to the next stage, and end stage disease is more common in males.
### Differential diagnosis[edit]
Other causes of excess iron accumulation exist, which have to be considered before haemochromatosis is diagnosed.
* African iron overload, formerly known as Bantu siderosis, was first observed among people of African descent in Southern Africa. Originally, this was blamed on ungalvanised barrels used to store home-made beer, which led to increased oxidation and increased iron levels in the beer. Further investigation has shown that only some people drinking this sort of beer get an iron overload syndrome, and that a similar syndrome occurred in people of African descent who have had no contact with this kind of beer (e.g., African Americans). This led investigators to the discovery of a gene polymorphism in the gene for ferroportin, which predisposes some people of African descent to iron overload.[46]
* Transfusion haemosiderosis is the accumulation of iron, mainly in the liver, in patients who receive frequent blood transfusions (such as those with thalassaemia).
* Dyserythropoeisis, also known as myelodysplastic syndrome, is a disorder in the production of red blood cells. This leads to increased iron recycling from the bone marrow and accumulation in the liver.
## Screening[edit]
Standard diagnostic measures for haemochromatosis, transferrin saturation and ferritin tests, are not a part of routine medical testing. Screening for haemochromatosis is recommended if the patient has a parent, child, or sibling with the disease.[47]
Routine screening of the general population for hereditary haemochromatosis is generally not done. Mass genetic screening has been evaluated by the U.S. Preventive Services Task Force, among other groups, which recommended against genetic screening of the general population for hereditary haemochromatosis because the likelihood of discovering an undiagnosed patient with clinically relevant iron overload is less than one in 1,000. Although strong evidence shows that treatment of iron overload can save lives in patients with transfusional iron overload, no clinical study has shown that for asymptomatic carriers of hereditary haemochromatosis treatment with venesection (phlebotomy) provides any clinical benefit.[48][49] Recently, patients are suggested to be screened for iron overload using serum ferritin as a marker. If serum ferritin exceeds 1000 ng/ml, iron overload is very likely the cause.
## Treatment[edit]
### Phlebotomy[edit]
Early diagnosis is vital, as the late effects of iron accumulation can be wholly prevented by periodic phlebotomies (by venesection) comparable in volume to blood donations.[50] Initiation of treatment is recommended when ferritin levels reach 500 μg/l.[51]
Phlebotomy (or bloodletting) is usually done at a weekly interval until ferritin levels are less than 50 μg/l. To prevent iron reaccumulation, subsequent phlebotomies are normally carried out about once every three to four months for males, and twice a year for females.[52]
### Desferrioxamine mesilate[edit]
Where venesection is not possible, long-term administration of desferrioxamine mesylate is useful. Desferrioxamine is an iron-chelating compound, and excretion induced by desferrioxamine is enhanced by administration of vitamin C. It cannot be used during pregnancy or breast-feeding due to risk of defects in the child.[citation needed]
### Organ damage[edit]
* Treatment of organ damage (heart failure with diuretics and ACE inhibitor therapy)[citation needed]
### Diet[edit]
* Limiting intake of alcoholic beverages, vitamin C (increases iron absorption in the gut), red meat (high in iron), and potential causes of food poisoning (shellfish, seafood)[53]
* Increasing intake of substances that inhibit iron absorption, such as high-tannin tea, calcium, and foods containing oxalic and phytic acids (such as collard greens, which must be consumed at the same time as the iron-containing foods to be effective)[54]
### Chelating polymers[edit]
A novel experimental approach to the hereditary haemochromatosis treatment is the maintenance therapy with polymeric chelators.[55][56][57] These polymers or particles have a negligible or null systemic biological availability and they are designed to form stable complexes with Fe2+ and Fe3+ in the GIT and thus limiting the uptake of these ions and their long-term accumulation. Although this method has only a limited efficacy, unlike small-molecular chelators, such an approach has virtually no side effects in sub-chronic studies.[57] Interestingly, the simultaneous chelation of Fe2+ and Fe3+ increases the treatment efficacy.[57]
## Prognosis[edit]
Persons with symptomatic haemochromatosis have somewhat reduced life expectancy compared to the general population, mainly due to excess mortality from cirrhosis and liver cancer. Patients who were treated with phlebotomy lived longer than those who were not.[58][59] Patients without liver disease or diabetes had similar survival rate to the general population.
## Epidemiology[edit]
Haemochromatosis is one of the most common heritable genetic conditions in people of Northern European extraction, with a prevalence of one in 200. The disease has a variable penetration, and about one in 10 people of this demographic carry a mutation in one of the genes regulating iron metabolism, the most common allele being the C282Y allele in the HFE gene.[60] The prevalence of mutations in iron-metabolism genes varies in different populations. A study of 3,011 unrelated white Australians found that 14% were heterozygous carriers of an HFE mutation, 0.5% were homozygous for an HFE mutation, and only 0.25% of the study population had clinically relevant iron overload. Most patients who are homozygous for HFE mutations do not manifest clinically relevant haemochromatosis (see Genetics above).[37] Other populations have a lower prevalence of both the genetic mutation and the clinical disease.
Genetics studies suggest the original haemochromatosis mutation arose in a single person, possibly of Celtic ethnicity, who lived 60–70 generations ago.[61] At that time, when dietary iron may have been scarcer than today, the presence of the mutant allele may have provided an evolutionary or natural selection reproductive advantage by maintaining higher iron levels in the blood.
## Terminology[edit]
The term "haemochromatosis" is used by different sources in many different ways.
It is often used to imply an association with the HFE gene. For many years, HFE was the only known gene associated with haemochromatosis, and the term "hereditary haemochromatosis" was used to describe haemochromatosis type 1. However, many different genetic associations with this condition are now known. The older the text, or the more general the audience, the more likely that HFE is implied."Haemochromatosis" has also been used in contexts where a genetic cause for iron accumulation had not been known. In some cases, however, a condition that was thought to be due to diet or environment was later linked to a genetic polymorphism, as in African iron overload.[citation needed]
## History[edit]
The disease was first described in 1865 by Armand Trousseau in a report on diabetes in patients presenting with a bronze pigmentation of their skin.[62] Trousseau did not associate diabetes with iron accumulation; the recognition that infiltration of the pancreas with iron might disrupt endocrine function resulting in diabetes was made by Friedrich Daniel von Recklinghausen in 1890.[63][64]
## References[edit]
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35. ^ "Heterozygous for p.H63D".
36. ^ Semenova EA, Miyamoto-Mikami E, Akimov EB, Al-Khelaifi F, Murakami H, Zempo H, Kostryukova ES, Kulemin NA, Larin AK, Borisov OV, Miyachi M, Popov DV, Boulygina EA, Takaragawa M, Kumagai H, Naito H, Pushkarev VP, Dyatlov DA, Lekontsev EV, Pushkareva YE, Andryushchenko LB, Elrayess MA, Generozov EV, Fuku N, Ahmetov II (March 2020). "The association of HFE gene H63D polymorphism with endurance athlete status and aerobic capacity: novel findings and a meta-analysis". European Journal of Applied Physiology. 120 (3): 665–673. doi:10.1007/s00421-020-04306-8. PMC 7042188. PMID 31970519.
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39. ^ Shizukuda Y, Bolan C, Nguyen T, Botello G, Tripodi D, Yau Y, Waclawiw M, Leitman S, Rosing D (2007). "Oxidative stress in asymptomatic subjects with hereditary hemochromatosis". Am J Hematol. 82 (3): 249–50. doi:10.1002/ajh.20743. PMID 16955456. S2CID 12068224.
40. ^ a b c "Hemochromatosis: Tests and diagnosis". Mayo Foundation for Medical Education and Research (MFMER). Retrieved 2009-04-20.
41. ^ "Transerrin and Iron Transport Physiology". sickle.bwh.harvard.edu. Archived from the original on 2007-03-07. Retrieved 2007-03-17.
42. ^ Adams, PC; Reboussin, DM; Barton, JC; McLaren, CE; Eckfeldt, JH; McLaren, GD; Dawkins, FW; Acton, RT; Harris, EL; Gordeuk, VR; Leiendecker-Foster, C; Speechley, M; Snively, BM; Holup, JL; Thomson, E; Sholinsky, P; Hemochromatosis and Iron Overload Screening (HEIRS) Study Research, Investigators (28 April 2005). "Hemochromatosis and iron-overload screening in a racially diverse population". The New England Journal of Medicine. 352 (17): 1769–78. doi:10.1056/nejmoa041534. PMID 15858186.
43. ^ Dadone MM, Kushner JP, Edwards CQ, Bishop DT, Skolnick MH (August 1982). "Hereditary hemochromatosis. Analysis of laboratory expression of the disease by genotype in 18 pedigrees". American Journal of Clinical Pathology. 78 (2): 196–207. doi:10.1093/ajcp/78.2.196. PMID 7102818.
44. ^ MedlinePlus Encyclopedia: Ferritin Test Measuring iron in the body
45. ^ St Pierre; Clark, PR; Chua-Anusorn, W; Fleming, AJ; Jeffrey, GP; Olynyk, JK; Pootrakul, P; Robins, E; Lindeman, R (2005). "Non-invasive measurement and imaging of liver iron concentrations using proton magnetic resonance". Blood. 105 (2): 855–61. doi:10.1182/blood-2004-01-0177. PMID 15256427.
46. ^ Gordeuk V, Caleffi A, Corradini E, Ferrara F, Jones R, Castro O, Onyekwere O, Kittles R, Pignatti E, Montosi G, Garuti C, Gangaidzo I, Gomo Z, Moyo V, Rouault T, MacPhail P, Pietrangelo A (2003). "Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene". Blood Cells Mol Dis. 31 (3): 299–304. doi:10.1016/S1079-9796(03)00164-5. PMID 14636642.
47. ^ "Summaries for patients. Screening for hereditary hemochromatosis: recommendations from the American College of Physicians". Ann. Intern. Med. 143 (7): I-46. 2005. doi:10.7326/0003-4819-143-7-200510040-00004. PMID 16204158. S2CID 53088428.
48. ^ U.S. Preventive Services Task Force (2006). "Screening for haemochromatosis: recommendation statement". Ann. Intern. Med. 145 (3): 204–8. doi:10.7326/0003-4819-145-3-200608010-00008. PMID 16880462.
49. ^ Screening for Hemochromatosis U.S. Preventive Services Task Force (2006). Summary of Screening Recommendations and Supporting Documents. Retrieved 18 March 2007
50. ^ "Hemochromatosis: Treatments and drugs". Mayo Foundation for Medical Education and Research (MFMER).
51. ^ European Association For The Study Of The Liver. (2010). "EASL clinical practice guidelines for HFE hemochromatosis". Journal of Hepatology. 53 (1): 3–22. doi:10.1016/j.jhep.2010.03.001. PMID 20471131.
52. ^ Kowdley, KV; Bennett, RL; Motulsky, AG; Pagon, RA; Adam, MP; Ardinger, HH; Wallace, SE; Amemiya, A; Bean, LJH; Bird, TD; Dolan, CR; Fong, CT; Smith, RJH; Stephens, K (1993). "HFE-Associated Hereditary Hemochromatosis". University of Washington, Seattle. PMID 20301613. Retrieved 25 May 2015. Cite journal requires `|journal=` (help)
53. ^ Plaut, David; McLellan, William (2009). "Hereditary hemochromatosis". Journal of Continuing Education Topics & Issues. 11 (1). Archived from the original on 2016-10-11. Retrieved 11 October 2016.
54. ^ http://dynaweb.ebscohost.com/Detail.aspx?id=116469&sid=14aa79e5-a881-407c-94e7-339b81c4cd18@sessionmgr3[permanent dead link] accessed October 15, 2008.
55. ^ Polomoscanik, Steven C.; Cannon, C. Pat; Neenan, Thomas X.; Holmes-Farley, S. Randall; Mandeville, W. Harry; Dhal, Pradeep K. (2005). "Hydroxamic Acid-Containing Hydrogels for Nonabsorbed Iron Chelation Therapy: Synthesis, Characterization, and Biological Evaluation". Biomacromolecules. 6 (6): 2946–2953. doi:10.1021/bm050036p. ISSN 1525-7797. PMID 16283713.
56. ^ Qian, Jian; Sullivan, Bradley P.; Peterson, Samuel J.; Berkland, Cory (2017). "Nonabsorbable Iron Binding Polymers Prevent Dietary Iron Absorption for the Treatment of Iron Overload". ACS Macro Letters. 6 (4): 350–353. doi:10.1021/acsmacrolett.6b00945. ISSN 2161-1653.
57. ^ a b c Groborz, Ondřej; Poláková, Lenka; Kolouchová, Kristýna; Švec, Pavel; Loukotová, Lenka; Miriyala, Vijay Madhav; Francová, Pavla; Kučka, Jan; Krijt, Jan; Páral, Petr; Báječný, Martin; Heizer, Tomáš; Pohl, Radek; Dunlop, David; Czernek, Jiří; Šefc, Luděk; Beneš, Jiří; Štěpánek, Petr; Hobza, Pavel; Hrubý, Martin (2020). "Chelating Polymers for Hereditary Hemochromatosis Treatment". Macromolecular Bioscience. 20 (12): 2000254. doi:10.1002/mabi.202000254. ISSN 1616-5187. PMID 32954629.
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## External links[edit]
* GeneReview/NIH/UW entry on HFE-Associated Hereditary Hemochromatosis
* Hereditary haemochromatosis at Curlie
Classification
D
* ICD-10: E83.1
* ICD-9-CM: 275.0
* OMIM: 235200
* MeSH: D006432
* DiseasesDB: 5490
External resources
* eMedicine: med/975 derm/878
* GeneReviews: HFE-Associated Hereditary Hemochromatosis
* v
* t
* e
Metal deficiency and toxicity disorders
Iron
excess:
* Iron overload
* Hemochromatosis
* Hemochromatosis/HFE1
* Juvenile/HFE2
* HFE3
* African iron overload/HFE4
* Aceruloplasminemia
* Atransferrinemia
* Hemosiderosis
deficiency:
* Iron deficiency
Copper
excess:
* Copper toxicity
* Wilson's disease
deficiency:
* Copper deficiency
* Menkes disease/Occipital horn syndrome
Zinc
excess:
* Zinc toxicity
deficiency:
* Acrodermatitis enteropathica
Other
* Inborn errors of metabolism
* v
* t
* e
Cell membrane protein disorders (other than Cell surface receptor, enzymes, and cytoskeleton)
Arrestin
* Oguchi disease 1
Myelin
* Pelizaeus–Merzbacher disease
* Dejerine–Sottas disease
* Charcot–Marie–Tooth disease 1B, 2J
Pulmonary surfactant
* Surfactant metabolism dysfunction 1, 2
Cell adhesion molecule
IgSF CAM:
* OFC7
Cadherin:
* DSG1
* Striate palmoplantar keratoderma 1
* DSG2
* Arrhythmogenic right ventricular dysplasia 10
* DSG4
* LAH1
* DSC2
* Arrhythmogenic right ventricular dysplasia 11
Integrin:
* cell surface receptor deficiencies
Tetraspanin
* TSPAN7
* X-Linked mental retardation 58
* TSPAN12
* Familial exudative vitreoretinopathy 5
Other
* KIND1
* Kindler syndrome
* HFE
* HFE hereditary haemochromatosis
* DYSF
* Distal muscular dystrophy
* Limb-girdle muscular dystrophy 2B
See also other cell membrane 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
| Hereditary haemochromatosis | c0018995 | 1,089 | wikipedia | https://en.wikipedia.org/wiki/Hereditary_haemochromatosis | 2021-01-18T18:54:09 | {"gard": ["10746"], "mesh": ["D006432"], "umls": ["C0018995"], "orphanet": ["139498", "220489"], "wikidata": ["Q3144934"]} |
Retinal hemorrhage
SpecialtyOphthalmology
Retinal haemorrhage is a disorder of the eye in which bleeding occurs in the retina, the light sensitive tissue, located on the back wall of the eye.[1] There are photoreceptor cells in the retina called rods and cones, which transduce light energy into nerve signals that can be processed by the brain to form visual images.[2] Retinal hemorrhage can affect adults, and newborn babies and infants may also suffer from this disorder.
A retinal hemorrhage can be caused by several medical conditions such as hypertension, retinal vein occlusion (a blockage of a retinal vein), anemia, leukemia or diabetes.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Signs and symptoms[edit]
At the early stage, a retinal hemorrhage may not show any symptom at all.
Some symptoms may include:
* Seeing floaters in the vision
* Seeing cobwebs in the vision
* Seeing haze or shadows
* Distorted vision
* Rapid flashes of light in peripheral vision
* Red tint to vision
* Blurryness
* Sudden blindness
Other symptoms may include head aches, pain at the temple.
## Causes[edit]
Retinal hemorrhages commonly occur in high altitude climbers, most likely due to the effects of systemic hypoxia on the eye. Risk is correlated with the maximum altitude reached, duration of exposure to high altitude conditions, and climb rate.[3]
Retinal hemorrhages are significantly associated with abusive head traumas (AHT). The mechanism of the trauma is believed to be repeated acceleration and deceleration with or without blunt impact (shaken baby syndrome).[4] Around 85% of victims suffer from AHT will have retinal hemorrhages and it increases in severity with increasing likelihood of abuse.[5] However, claims regarding Shaken Baby Syndrome are not universally agreed upon and have conflicting scientific evidence.[6]
## Diagnosis[edit]
A retinal hemorrhage is generally diagnosed by using an ophthalmoscope or fundus camera in order to examine the inside of the eye. A fluorescein angiography test may be conducted, in which a fluorescent dye is often injected into the patient's bloodstream beforehand so the administering ophthalmologist can have a more detailed view and examination on the blood vessels in the retina.[7] The fluorescent dye can have dangerous side effects: see Fluorescein
Eye examination may be done to check the eye(s) conditions, for instance to check how well the patient sees straight ahead, off to the sides and at different distances.
Blood tests may provide information about the patient's overall health and may also reveal the medical condition that may have caused retinal hemorrhage.[1]
## Prevention[edit]
It is recommended to consult with ophthalmologist or optometrist as early as possible, particularly for people with vision problems, these includes floaters, flashes, cobwebs or spots in their vision. Preventive measures such as regular prenatal care and monitoring of infants with high risks of the disorder may be done to avoid further complications of retinal hemorrhages in infants. For retinal hemorrhages associated with hypertension, blood pressure can be controlled by having regular blood pressure check ups, frequent exercise, monitor daily food intakes and to practice a stress-free lifestyle.[7]
## Treatment[edit]
Retinal hemorrhages, especially mild ones not associated with chronic disease, will normally reabsorb without treatment. Laser surgery is a treatment option which uses a laser beam to seal off damaged blood vessels in the retina.[8] Anti-vascular endothelial growth factor (VEGF) drugs like Avastin and Lucentis have also been shown to repair retinal hemorrhaging in diabetic patients and patients with hemorrhages associated with new vessel growth.[9][10]
Alternative treatments may include providing necessary nutrients to strengthen and heal damaged blood vessels, through the consumption of dietary supplements such as Vitamins A, B, C and E. Also, the essential fatty acids including omega-3 from fish oil and flaxseed oil.[11]
## See also[edit]
* Visual impairment
## References[edit]
1. ^ a b "Retinal Hemorrhage - What You Need to Know". Drugs.com. Retrieved 2018-09-13.
2. ^ Yarfitz S, Hurley JB (May 1994). "Transduction mechanisms of vertebrate and invertebrate photoreceptors". The Journal of Biological Chemistry. 269 (20): 14329–32. PMID 8182033.
3. ^ Bosch MM, Barthelmes D, Landau K (December 2012). "High altitude retinal hemorrhages--an update" (PDF). High Altitude Medicine & Biology. 13 (4): 240–4. doi:10.1089/ham.2012.1077. PMID 23270439.
4. ^ Levin AV (2011). "Eye Injuries in Child Abuse". Child Abuse and Neglect. pp. 402–412. doi:10.1016/B978-1-4160-6393-3.00044-0. ISBN 978-1-4160-6393-3.
5. ^ Binenbaum G, Mirza-George N, Christian CW, Forbes BJ (June 2009). "Odds of abuse associated with retinal hemorrhages in children suspected of child abuse". Journal of AAPOS. 13 (3): 268–72. doi:10.1016/j.jaapos.2009.03.005. PMC 2712730. PMID 19541267.
6. ^ Lynoe et al. 2017
7. ^ a b "Retinal Hemorrhage". TheFreeDictionary.com. Retrieved 2018-09-13.
8. ^ Sparks KO. "Retinal Bleeding". LARetinaSurgeon.com.
9. ^ Spaide RF, Fisher YL (March 2006). "Intravitreal bevacizumab (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage". Retina. 26 (3): 275–8. doi:10.1097/00006982-200603000-00004. PMID 16508426. S2CID 8262505.
10. ^ "Age-Related Macular Degeneration Treatment". WebMD.
11. ^ Pilyugina S. "Retinal Physician - Ocular Dietary Supplementation — Food For Thought". Retinal Physician. Retrieved 2018-09-13.
## Further reading[edit]
* Currie AD, Bentley CR, Bloom PA (March 2001). "Retinal haemorrhage and fatal stroke in an infant with fibromuscular dysplasia". Archives of Disease in Childhood. 84 (3): 263–4. doi:10.1136/adc.84.3.263. PMC 1718691. PMID 11207180.
* Zuccoli G, Panigrahy A, Haldipur A, Willaman D, Squires J, Wolford J, Sylvester C, Mitchell E, Lope LA, Nischal KK, Berger RP (July 2013). "Susceptibility weighted imaging depicts retinal hemorrhages in abusive head trauma". Neuroradiology. 55 (7): 889–93. doi:10.1007/s00234-013-1180-7. PMC 3713254. PMID 23568702.
## External links[edit]
Classification
D
* ICD-10: H35.6
* ICD-9-CM: 362.81
* MeSH: D012166
* DiseasesDB: 29369
*[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
| Retinal haemorrhage | c0035317 | 1,090 | wikipedia | https://en.wikipedia.org/wiki/Retinal_haemorrhage | 2021-01-18T18:35:33 | {"mesh": ["D012166"], "umls": ["C0035317"], "icd-9": ["362.81"], "icd-10": ["H35.6"], "wikidata": ["Q3144957"]} |
Palmar erythema
SpecialtyDermatology
Palmar erythema is reddening of the palms at the thenar and hypothenar eminences.[1]:139
## Contents
* 1 Causes
* 2 Diagnosis
* 3 See also
* 4 References
* 5 External links
## Causes[edit]
It is associated with various physiological as well as pathological changes, or may be a normal finding:
* Portal hypertension
* Chronic liver disease (including chronic hepatitis[2])
* Pregnancy
* Polycythemia
* Thyrotoxicosis
* Rheumatoid arthritis (especially in patients with polycythaemia)[3]
* Eczema and psoriasis
* Deep telangiectasias
* Coxsackievirus A infection (Hand, foot and mouth disease)[4]
* Rocky Mountain spotted fever[4]
* Secondary syphilis[4]
* Kawasaki disease
* Adverse drug reaction: palmoplantar erythrodysesthesia (acral erythema)
Because circulating levels of estrogen increase in both cirrhosis and pregnancy, estrogen was thought to be the main cause for the increased vascularity. More recently, nitric oxide has also been implicated in the pathogenesis of palmar erythema.[5]
## Diagnosis[edit]
Palmar erythema has no specific treatment. Management is based on the underlying cause. When its cause is treated then patients get relief. If it is attributable to a particular drug then the drug should be withdrawn.
## See also[edit]
* Toxic erythema
* 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. ^ Basic pathology 8th edition p 646
3. ^ Saario R, Kalliomaki JL (Dec 1985), "Palmar erythema in rheumatoid arthritis", Clin Rheumatol., 4 (4), pp. 449–51, doi:10.1007/BF02031898, PMID 3830522
4. ^ a b c Le T, Bhushan V, Vasan N (2010), First Aid for the USMLE Step 1, p. 156, mhid: 0-07-163340
5. ^ Nevzati E, Shafighi M, Bakhtian KD, Treiber H, Fandino J, Fathi AR (2015). "Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells". Neurovascular Events After Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement. 120. pp. 141–145. doi:10.1007/978-3-319-04981-6_24. ISBN 978-3-319-04980-9. PMID 25366614.
## External links[edit]
Classification
D
* ICD-10: L53.8 (ILDS L53.840)
* ICD-9-CM: 695.0
* DiseasesDB: 24070
* v
* t
* e
Urticaria and erythema
Urticaria
(acute/chronic)
Allergic urticaria
* Urticarial allergic eruption
Physical urticaria
* Cold urticaria
* Familial
* Primary cold contact urticaria
* Secondary cold contact urticaria
* Reflex cold urticaria
* Heat urticaria
* Localized heat contact urticaria
* Solar urticaria
* Dermatographic urticaria
* Vibratory angioedema
* Pressure urticaria
* Cholinergic urticaria
* Aquagenic urticaria
Other urticaria
* Acquired C1 esterase inhibitor deficiency
* Adrenergic urticaria
* Exercise urticaria
* Galvanic urticaria
* Schnitzler syndrome
* Urticaria-like follicular mucinosis
Angioedema
* Episodic angioedema with eosinophilia
* Hereditary angioedema
Erythema
Erythema multiforme/
drug eruption
* Erythema multiforme minor
* Erythema multiforme major
* Stevens–Johnson syndrome, Toxic epidermal necrolysis
* panniculitis (Erythema nodosum)
* Acute generalized exanthematous pustulosis
Figurate erythema
* Erythema annulare centrifugum
* Erythema marginatum
* Erythema migrans
* Erythema gyratum repens
Other erythema
* Necrolytic migratory erythema
* Erythema toxicum
* Erythroderma
* Palmar erythema
* Generalized erythema
This medical sign article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
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
| Palmar erythema | c0014745 | 1,091 | wikipedia | https://en.wikipedia.org/wiki/Palmar_erythema | 2021-01-18T18:51:29 | {"umls": ["C0014745"], "icd-9": ["695.0"], "icd-10": ["L53.8"], "wikidata": ["Q1755849"]} |
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Denys–Drash syndrome" – news · newspapers · books · scholar · JSTOR (August 2020) (Learn how and when to remove this template message)
Denys–Drash syndrome
SpecialtyOncology, endocrinology, urology, obstetrics and gynaecology, medical genetics
Denys–Drash syndrome (DDS) or Drash syndrome is a rare disorder or syndrome characterized by gonadal dysgenesis, nephropathy, and Wilms' tumor.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Prognosis
* 4 History
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
Clinically, Denys–Drash is characterized by the triad of pseudohermaphroditism, mesangial renal sclerosis, and Wilms' tumor. The condition first manifests as early nephrotic syndrome and progresses to mesangial renal sclerosis, and ultimately kidney failure—usually within the first three years of life.
The presenting characteristics of DDS include loss of playfulness, decreased appetite, weight loss, growth delay, abnormal skeletal development, insomnia, abdominal pain, constipation, and anuria.
## Causes[edit]
The cause of DDS is most commonly (96% of patients) an abnormality in the WT1 gene (Wilms tumor suppressor gene). These abnormalities include changes in certain exons (9 and 8) and mutations in some alleles of the WT1 gene. Genetically, the syndrome is due to mutations in the Wilms tumor suppressor gene, WT1, which is on chromosome 11 (11p13). These mutations are usually found in exons 8 or 9, but at least one has been reported in exon 4.[1]
## Prognosis[edit]
A 1994 review of 150 cases reported in the literature found that 38% had died with a mean age of death of 2 years. 32% were still alive at the time of the report with a mean age of 4.65. No data were available for the remainder. The author described living with DDS as "walking a multidimensional tight rope".[2]
## History[edit]
P. Denys[3] and Allan L. Drash[4] first described the syndrome.
## See also[edit]
* Beckwith–Wiedemann syndrome
* WAGR syndrome
* Wilms' tumor
## References[edit]
1. ^ da Silva TE, Nishi MY, Costa EM, et al. (August 2011). "A novel WT1 heterozygous nonsense mutation (p.K248X) causing a mild and slightly progressive nephropathy in a 46,XY patient with Denys–Drash syndrome". Pediatr. Nephrol. 26 (8): 1311–5. doi:10.1007/s00467-011-1847-4. PMID 21559934. S2CID 42090144.
2. ^ Mueller, R F (1994-06-01). "The Denys-Drash syndrome". Journal of Medical Genetics. 31 (6): 471–477. doi:10.1136/jmg.31.6.471. ISSN 0022-2593. PMC 1049926. PMID 8071974.
3. ^ Denys P, Malvaux P, Van Den Berghe H, Tanghe W, Proesmans W (1967). "[Association of an anatomo-pathological syndrome of male pseudohermaphroditism, Wilms' tumor, parenchymatous nephropathy and XX/XY mosaicism]". Arch. Fr. Pediatr. (in French). 24 (7): 729–739. PMID 4292870.
4. ^ Drash A, Sherman F, Hartmann WH, Blizzard RM (1970). "A syndrome of pseudohermaphroditism, Wilms' tumor, hypertension, and degenerative renal disease". J. Pediatr. 76 (4): 585–593. doi:10.1016/S0022-3476(70)80409-7. PMID 4316066.
## External links[edit]
* 00527 at CHORUS
Classification
D
* OMIM: 194080
* MeSH: D030321
* DiseasesDB: 31499
External resources
* eMedicine: ped/564
* Orphanet: 220
* v
* t
* e
Genetic disorders relating to deficiencies of transcription factor or coregulators
(1) Basic domains
1.2
* Feingold syndrome
* Saethre–Chotzen syndrome
1.3
* Tietz syndrome
(2) Zinc finger
DNA-binding domains
2.1
* (Intracellular receptor): Thyroid hormone resistance
* Androgen insensitivity syndrome
* PAIS
* MAIS
* CAIS
* Kennedy's disease
* PHA1AD pseudohypoaldosteronism
* Estrogen insensitivity syndrome
* X-linked adrenal hypoplasia congenita
* MODY 1
* Familial partial lipodystrophy 3
* SF1 XY gonadal dysgenesis
2.2
* Barakat syndrome
* Tricho–rhino–phalangeal syndrome
2.3
* Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome
* Denys–Drash syndrome
* Duane-radial ray syndrome
* MODY 7
* MRX 89
* Townes–Brocks syndrome
* Acrocallosal syndrome
* Myotonic dystrophy 2
2.5
* Autoimmune polyendocrine syndrome type 1
(3) Helix-turn-helix domains
3.1
* ARX
* Ohtahara syndrome
* Lissencephaly X2
* MNX1
* Currarino syndrome
* HOXD13
* SPD1 synpolydactyly
* PDX1
* MODY 4
* LMX1B
* Nail–patella syndrome
* MSX1
* Tooth and nail syndrome
* OFC5
* PITX2
* Axenfeld syndrome 1
* POU4F3
* DFNA15
* POU3F4
* DFNX2
* ZEB1
* Posterior polymorphous corneal dystrophy
* Fuchs' dystrophy 3
* ZEB2
* Mowat–Wilson syndrome
3.2
* PAX2
* Papillorenal syndrome
* PAX3
* Waardenburg syndrome 1&3
* PAX4
* MODY 9
* PAX6
* Gillespie syndrome
* Coloboma of optic nerve
* PAX8
* Congenital hypothyroidism 2
* PAX9
* STHAG3
3.3
* FOXC1
* Axenfeld syndrome 3
* Iridogoniodysgenesis, dominant type
* FOXC2
* Lymphedema–distichiasis syndrome
* FOXE1
* Bamforth–Lazarus syndrome
* FOXE3
* Anterior segment mesenchymal dysgenesis
* FOXF1
* ACD/MPV
* FOXI1
* Enlarged vestibular aqueduct
* FOXL2
* Premature ovarian failure 3
* FOXP3
* IPEX
3.5
* IRF6
* Van der Woude syndrome
* Popliteal pterygium syndrome
(4) β-Scaffold factors
with minor groove contacts
4.2
* Hyperimmunoglobulin E syndrome
4.3
* Holt–Oram syndrome
* Li–Fraumeni syndrome
* Ulnar–mammary syndrome
4.7
* Campomelic dysplasia
* MODY 3
* MODY 5
* SF1
* SRY XY gonadal dysgenesis
* Premature ovarian failure 7
* SOX10
* Waardenburg syndrome 4c
* Yemenite deaf-blind hypopigmentation syndrome
4.11
* Cleidocranial dysostosis
(0) Other transcription factors
0.6
* Kabuki syndrome
Ungrouped
* TCF4
* Pitt–Hopkins syndrome
* ZFP57
* TNDM1
* TP63
* Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8
Transcription coregulators
Coactivator:
* CREBBP
* Rubinstein–Taybi syndrome
Corepressor:
* HR (Atrichia with papular lesions)
*[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
| Denys–Drash syndrome | c0950121 | 1,092 | wikipedia | https://en.wikipedia.org/wiki/Denys%E2%80%93Drash_syndrome | 2021-01-18T18:35:30 | {"gard": ["5576"], "mesh": ["D030321"], "umls": ["C0950121"], "orphanet": ["220"], "wikidata": ["Q774016"]} |
Absence of the mammary gland
Not to be confused with Amaziah.
Amazia refers to a condition where one or both of the mammary glands is absent (the nipple and areola remain present).[1] This may occur either congenitally or iatrogenically (typically the result of surgical removal and/or radiation therapy). Amazia can be treated with breast implants.
Amazia differs from amastia (the complete absence of breast tissue, nipple, and areola), although the two conditions are often (erroneously) thought to be identical. The terms "amazia" and "amastia" are thus often used interchangeably, even though the two conditions are medically different.
## See also[edit]
* Amastia
* Athelia
* Micromastia
## References[edit]
1. ^ Ozsoy Z, Gozu A, Ozyigit MT, Genc B (2007). "Amazia with midface anomaly: case report". Aesthetic Plast Surg. 31 (4): 392–4. doi:10.1007/s00266-006-0251-0. PMID 17576506.
* v
* t
* e
Breast disease
Inflammation
* Mastitis
* Nonpuerperal mastitis
* Subareolar abscess
* Granulomatous mastitis
Physiological changes
and conditions
* Benign mammary dysplasia
* Duct ectasia of breast
* Chronic cystic mastitis
* Mammoplasia
* Gynecomastia
* Adipomastia (lipomastia, pseudogynecomastia)
* Breast hypertrophy
* Breast atrophy
* Micromastia
* Amastia
* Anisomastia
* Breast engorgement
Nipple
* Nipple discharge
* Galactorrhea
* Inverted nipple
* Cracked nipples
* Nipple pigmentation
Masses
* Galactocele
* Breast cyst
* Breast hematoma
* Breast lump
* Pseudoangiomatous stromal hyperplasia
Other
* Pain
* Tension
* Ptosis
* Fat necrosis
* Amazia
*[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
| Amazia | c0432357 | 1,093 | wikipedia | https://en.wikipedia.org/wiki/Amazia | 2021-01-18T18:36:54 | {"mesh": ["C562989", "C535565"], "umls": ["C0432357"], "icd-10": ["Q83.0"], "wikidata": ["Q4740761"]} |
Byssinosis
Other namesBrown lung disease, Monday fever
SpecialtyPulmonology
Byssinosis is an occupational lung disease caused by exposure to cotton dust in inadequately ventilated working environments.[1] Byssinosis commonly occurs in workers who are employed in yarn and fabric manufacture industries. It is now thought that the cotton dust directly causes the disease and some believe that the causative agents are endotoxins that come from the cell walls of gram-negative bacteria that grow on the cotton. Although bacterial endotoxin is a likely cause, the absence of similar symptoms in workers in other industries exposed to endotoxins makes this uncertain.[2]
Of the 81 byssinosis-related fatalities reported in the United States between 1990 and 1999, 48% included an occupation in the yarn, thread, and fabric industry on the victim's death certificate.[3] This disease often occurred in the times of the industrial revolution. Most commonly young girls working in mills or other textile factories would be afflicted with this disease. In the United States, from 1996 to 2005, North Carolina accounted for about 37% of all deaths caused by byssinosis, with 31, followed by South Carolina (8) and Georgia (7).[4]
The term "brown lung" is a misnomer, as the lungs of affected individuals are not brown.[5]
## Contents
* 1 Symptoms
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 Further reading
* 6 External links
## Symptoms[edit]
* Breathing difficulties
* Chest tightness
* Wheezing
* Cough
Byssinosis can ultimately result in narrowing of the airways, lung scarring and death from infection or respiratory failure.[citation needed]
## Diagnosis[edit]
Patient history should reveal exposure to cotton, flax, hemp, or jute dust. Diagnostic tests include a lung function test and a chest x ray or CT scan. Measurable change in lung function before and after working shifts is key to diagnosis. Patients suffering from byssinosis show a significant drop in FEV1 over the course of work shift. Chest radiographs show areas of opacity due to fibrosis of the pulmonary parenchyma.[citation needed]
## Treatment[edit]
Affected workers should be offered alternative employment. Continued exposure leads to development of persistent symptoms and progressive decline in FEV1.[citation needed]
## References[edit]
1. ^ Hollander, AG (December 1953). "Byssinosis". Chest. American College of Chest Physicians. 24 (6): 674–678. doi:10.1378/chest.24.6.674. PMID 13107566. Archived from the original on 2007-10-24. Retrieved 2008-01-31.
2. ^ Newman, Lee S. (June 2008). "Byssinosis". Merck Manuals: online medical dictionary. Merck & Co. Retrieved 2009-06-15.
3. ^ "Section 4. Byssinosis and Related Exposures". The Work-Related Lung Disease Surveillance Report, 2002. National Institute for Occupational Safety and Health. 2003.
4. ^ "Byssinosis: Number of deaths by state, U.S. residents age 15 and over, 1996-2005". National Institute for Occupational Safety and Health. March 2009. Retrieved 2013-02-14.
5. ^ Barry S. Levy; David H. Wegman; Sherry L. Baron; Rosemary K. Sokas (2011). Occupational and environmental health recognizing and preventing disease and injury (6th ed.). New York: Oxford University Press. p. 416. ISBN 9780199750061.
## Further reading[edit]
* Snyder, Rachel Louise (2007). Fugitive Denim: A Moving Story of People and Pants in the Borderless World of Global Trade. W. W. Norton. ISBN 978-0-393-06180-2.
## External links[edit]
Classification
D
* ICD-10: J66.0
* ICD-9-CM: 504
* MeSH: D002095
* DiseasesDB: 1819
External resources
* MedlinePlus: 001089
Look up byssinosis in Wiktionary, the free dictionary.
* Byssinosis: MedlinePlus Medical Encyclopedia (NIH)
* Work-Related Lung Disease Surveillance System (eWoRLD): Work-Related Respiratory Diseases | CDC/NIOSH
* 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
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nasal septum
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tonsil
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pharynx
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vocal cords
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epiglottis
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trachea
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(including LRTIs)
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obstructive
acute
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chronic
COPD
Chronic bronchitis
Acute exacerbation of COPD)
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unspecified
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restrictive
(fibrosis)
External agents/
occupational
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Other
* ARDS
* Combined pulmonary fibrosis and emphysema
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* Löffler's syndrome/Eosinophilic pneumonia
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By pathogen
* Viral
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IIP
* UIP
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Other
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| Byssinosis | c0006542 | 1,094 | wikipedia | https://en.wikipedia.org/wiki/Byssinosis | 2021-01-18T18:41:58 | {"gard": ["5976"], "mesh": ["D002095"], "icd-9": ["504"], "wikidata": ["Q1018652"]} |
A number sign (#) is used with this entry because autosomal recessive agenesis of the corpus callosum with peripheral neuropathy (ACCPN), also known as Andermann syndrome, is caused by homozygous or compound heterozygous mutation in the SLC12A6 gene (604878) on chromosome 15q14.
Description
Andermann syndrome is an autosomal recessive motor and sensory neuropathy with agenesis of the corpus callosum associated with developmental and neurodegenerative defects and dysmorphic features. It has a high prevalence in the French Canadian population in the Charlevoix and Saguenay-Lac-Saint-Jean region of Quebec (Uyanik et al., 2006).
Dupre et al. (2003) provided a comprehensive review of the disorder. Dobyns (1996) reviewed the many genetic causes of agenesis of the corpus callosum.
Clinical Features
Naiman and Fraser (1955) described 2 sisters, and Ziegler (1958) described 2 brothers with agenesis of the corpus callosum associated with mental and physical retardation. Andermann et al. (1972) observed 2 brothers with mental retardation, areflexia and paraparesis. The authors postulated an anterior horn cell disease. The clinical picture was the same as in the sisters reported by Naiman and Fraser (1955) and the 2 families were French Canadian from the Charlevoix County in Quebec. Andermann et al. (1977) extended these studies to identify 45 patients in 24 sibships, descendants from a couple married in Quebec City, Charlevoix County, in 1657. Brain CT imaging demonstrated agenesis of the corpus callosum.
Cao et al. (1977) reported 3 sibs, a male and 2 females, with severe mental retardation, spastic quadriplegia, microcephaly, and infantile spasms. Two sibs had agenesis of the corpus callosum on pneumoencephalogram. Other reports of familial agenesis of the corpus callosum consistent with autosomal recessive inheritance were published by Shapira and Cohen (1973) and Castro Gago et al. (1982). The former report concerned 2 affected sisters whose parents were more closely related than first cousins. The latter report concerned 2 sisters and 2 daughters of a paternal uncle of their father. The 2 sisters, studied at 6 years and 15 months of age, respectively, had progressive psychomotor regression, microcephaly, optic atrophy and seizures. CT scan showed absence of the corpus callosum, subcortical atrophy and gray substance heterotopy at the level of the ventricles.
Larbrisseau et al. (1984) studied 15 cases and described a characteristic dysmorphic facies. The authors observed that progressive motor neuropathy led to loss of ambulation by adolescence and progressive scoliosis. Hauser et al. (1993) reported cases of agenesis of the corpus callosum with neuronopathy in a brother and sister in Vienna.
Uyanik et al. (2006) reported 3 unrelated patients with Andermann syndrome; 1 was German and 2 Turkish. The German child presented at age 13 days with feeding difficulties and hypotonia. Over the next few months, she was found to have complete absence of the corpus callosum with ventricular enlargement and areflexia with an axonal and demyelinating peripheral neuropathy. Lumbar puncture showed increased CSF protein. At age 3 years, she had marked psychomotor retardation with inability to walk or speak. Mild facial dysmorphism was present, including hypertelorism, short nose, broad nasal root, and downplaced first toe and thumb. The second child, born of consanguineous Turkish parents, presented with diffuse hypotonic weakness, psychomotor retardation, and afebrile seizures. She had mild mental retardation, high-arched palate, elongated facies, esotropia of the right eye, ptosis, facial diplegia, areflexia, and distal wasting of the limbs. She had complete ACC and an axonal/demyelinating motor and sensory neuropathy with decreased nerve conduction velocities. The third child, born of second-degree Turkish cousins, had hypotonia and psychomotor retardation. He could walk with support at age 5 years and developed some speech. He had complete ACC and peripheral neuropathy but was less severely affected in the upper limbs. He also had bilateral diffuse white matter abnormalities, which had not previously been reported in this syndrome.
Mapping
Casaubon et al. (1996) performed linkage studies with 120 microsatellite DNA markers to position the ACCPN gene to a 5-cM region on 15q13-q15, flanked by markers D15S1040 and D15S118. A maximum 2-point lod score of 11.1 was obtained with the markers D15S971 at a recombination fraction of 0.0. Haplotype analysis and linkage disequilibrium supported the existence of the previously suspected founder effect. The authors stated that this finding was the first step in the identification of the gene responsible for ACCPN, which may shed light on numerous conditions associated with progressive peripheral neuropathy or agenesis of the corpus callosum.
Howard et al. (2002) typed 11 polymorphic markers on chromosome 15 in 231 individuals from 50 seemingly unrelated French Canadian ACCPN families. Haplotype analysis confirmed the presence of a founder haplotype, and recombination events reduced the ACCPN candidate interval to a region of approximately 2 cM or 1000 kb between markers D15S1040 and ACTC.
Molecular Genetics
The K-Cl cotransporter KCC3, encoded by the SLC12A6 gene, maps within the ACCPN candidate region, prompting Howard et al. (2002) to screen that gene for mutations in individuals with ACCPN. Four distinct protein-truncated mutations (604878.0001-604878.0004) were found: 2 in the French Canadian population and 2 in non-French Canadian families. A 1-bp deletion (2436delG; 604878.0001) was determined to be a founder mutation in the French Canadian population.
In 3 unrelated patients with Andermann syndrome, Uyanik et al. (2006) identified 4 different mutations in the SLC12A6 gene (604878.0005-604878.0008). Two were of Turkish descent, and 1 was German.
Salin-Cantegrel et al. (2007) identified 2 mutations in exon 22 of the SLC12A6 gene (604878.0003; 604878.0009) in non-French Canadian patients with ACCPN, including families from Turkey, South Africa, Sudan, and the Netherlands.
Population Genetics
De Braekeleer et al. (1993) estimated that in the Saguenay-Lac-Saint-Jean region of northeastern Quebec the incidence at birth was 1 in 2,117 liveborns, and the carrier rate was 1 in 23 inhabitants. Remote consanguinity was found in several families, while the mean kinship coefficient was 2.7 times higher in the polyneuropathic group than in control groups. Genealogic reconstruction suggested that the high incidence is probably the result of founder effect and that a unique mutation accounts for most, if not all, of the cases known in this region.
Howard et al. (2002) determined that a 1-bp deletion (2436delG) was a founder mutation in the French Canadian population.
Animal Model
Howard et al. (2002) found that mice with a targeted deletion of the Slc12a6 gene had a locomotor deficit, peripheral neuropathy, and a sensorimotor gating deficit, similar to the human disease. The findings suggested a critical role for SLC12A6 in the development and maintenance of the nervous system.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Brachycephaly Face \- Narrow forehead \- Hypoplastic maxilla \- Facial asymmetry \- Facial diplegia \- Long face Ears \- Large ears Eyes \- Hypertelorism \- Ptosis \- Gaze palsies Nose \- Broad nasal root \- Short nose Mouth \- High-arched palate \- Protruding, fissured tongue RESPIRATORY \- Restrictive respiratory disease SKELETAL \- Joint contractures Spine \- Scoliosis Hands \- Long tapered fingers Feet \- Syndactyly of the second and third toes \- Overriding of the first toe SKIN, NAILS, & HAIR Hair \- Low hairline MUSCLE, SOFT TISSUES \- Progressive distal and proximal symmetric limb weakness \- Neonatal hypotonia \- Amyotrophy \- EMG shows denervation NEUROLOGIC Central Nervous System \- Delayed motor milestones \- Developmental delay \- Hypotonia, generalized \- Mental retardation, mild to severe \- Individuals can stand or walk with support by 4 to 6 years of age \- Seizures \- Agenesis of the corpus callosum \- Enlarged ventricles \- Axonal swelling of spinal nerve roots and cranial nerves Peripheral Nervous System \- Peripheral motor neuropathy, severe \- Peripheral sensory neuropathy, severe \- Areflexia \- Limb tremor \- Sural nerve biopsy shows absence of large myelinated fibers \- Axonal neuropathy \- Axonal degeneration/regeneration \- Demyelinating neuropathy \- 'Onion bulb' formations \- Hypomyelinated fibers \- Decreased motor and sensory nerve conduction velocities Behavioral Psychiatric Manifestations \- Hallucinatory psychosis develops during adolescence LABORATORY ABNORMALITIES \- Increased CSF protein MISCELLANEOUS \- Onset within the first year of life \- Progressive disorder \- Most individuals are wheelchair-bound or bedridden by adolescence \- Death in third or fourth decades, usually due to respiratory infection \- Increased frequency in the Charlevoix and Saguenat-Lac-St-Jean regions of Quebec, Canada (1 in 2,117 live births, carrier rate 1 in 23) MOLECULAR BASIS \- Caused by mutation in the solute carrier family 12 (sodium/chloride transporter), member 6 gene (SLC12A6, 604878.0001 ) ▲ 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
| AGENESIS OF THE CORPUS CALLOSUM WITH PERIPHERAL NEUROPATHY | c0795950 | 1,095 | omim | https://www.omim.org/entry/218000 | 2019-09-22T16:29:19 | {"doid": ["0090003"], "mesh": ["C536446"], "omim": ["218000"], "orphanet": ["1496"], "synonyms": ["Alternative titles", "CHARLEVOIX DISEASE", "ANDERMANN SYNDROME", "POLYNEUROPATHY, SENSORIMOTOR, WITH OR WITHOUT AGENESIS OF THE CORPUS CALLOSUM", "CORPUS CALLOSUM, AGENESIS OF, WITH NEURONOPATHY"], "genereviews": ["NBK1372"]} |
## Description
Congnital aplastic deformities of the breast include amastia (total absence of breasts and nipple), athelia (absence of the nipple), and amazia (absence of the mammary gland). Most common is amastia. Bilateral absence of the breasts may occur as an isolated anomaly or may be associated with a syndrome or a cluster of other anomalies, including anhidrotic ectodermal dysplasia (305100) and Poland syndrome (173800) (summary by Papadimitriou et al., 2009).
### Genetic Heterogeneity of Aplasia or Hypoplasia of Breasts and/or Nipples
An autosomal recessive form of breast and/or nipple aplasia or hypoplasia (BNAH2; 616001) is caused by mutation in the PTPRF gene (179590) on chromosome 1p34.
Clinical Features
Goldenring and Crelin (1961) described absence of breast and nipples in a mother and daughter, as did Trier (1965).
Greenberg (1987) described a female infant with athelia and choanal atresia, born to a woman treated for hyperthyroidism throughout pregnancy with methimazole and propranolol. The possibility of methimazole teratogenicity was raised.
Papadimitriou et al. (2009) reported a 13.5-year-old Greek girl, born of nonconsanguineous parents, who had bilateral amazia, hypoplastic areolae, and normal nipple formation. In addition, bilateral choanal atresia had been detected soon after birth and surgically corrected. Physical examination of the patient was otherwise unremarkable, and renal ultrasonography and chest radiography were normal.
Inheritance
Pedigrees consistent with dominant inheritance have been reported. Fraser (1956) found absent breasts in 7 members of 3 generations.
Wilson et al. (1972) described 7 persons with absence or hypoplasia of the breasts in 4 generations. The observations to date did not permit distinction between autosomal and X-linked inheritance.
INHERITANCE \- Autosomal dominant HEAD & NECK Nose \- Choanal atresia (in some patients) CHEST Breasts \- Amastia \- Nipple hypoplasia or aplasia (athelia, in some patients) \- Hypoplastic areolae (in some patients) \- Absent breast tissue (amazia, in some patients) ▲ 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
| BREASTS AND/OR NIPPLES, APLASIA OR HYPOPLASIA OF, 1 | c0432357 | 1,096 | omim | https://www.omim.org/entry/113700 | 2019-09-22T16:43:56 | {"mesh": ["C562989"], "omim": ["113700"], "icd-10": ["Q83.0"], "orphanet": ["180188"], "synonyms": ["Alternative titles", "AMASTIA", "ATHELIA", "AMAZIA"]} |
Pressure-induced localized lipoatrophy is a rare, acquired, localized lipodystrophy characterized by band-like, horizontal, asymptomatic, lipoatrophic depressions with clinically normal overlying skin usually involving the anterolateral aspect of the thighs. An identifiable history of the repeated mechanical microtrauma due to occupational or postural habits is present.
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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
| Pressure-induced localized lipoatrophy | c1260961 | 1,097 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90160 | 2021-01-23T17:40:57 | {"icd-10": ["E88.1"], "synonyms": ["Lipoatrophia semicircularis", "Semicircular lipoatrophy"]} |
Laryngotracheal stenosis
This condition can also be referred to as subglottic or tracheal stenosis.
SpecialtyOtorhinolaryngology
Diagnostic methodPatient history, CT scan of neck and chest, fibre-optic bronchoscopy
Laryngotracheal stenosis refers to abnormal narrowing of the central air passageways.[1] This can occur at the level of the larynx, trachea, carina or main bronchi.[2] In a small number of patients narrowing may be present in more than one anatomical location.
## Contents
* 1 Presentation
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 Nomenclature
* 6 See also
* 7 References
* 8 External links
## Presentation[edit]
The most common symptom of laryngotracheal stenosis is gradually-worsening breathlessness (dyspnea) particularly when undertaking physical activities (exertional dyspnea). The patient may also experience added respiratory sounds which in the more severe cases can be identified as stridor but in many cases can be readily mistaken for wheeze. This creates a diagnostic pitfall in which many patients with laryngotracheal stenosis are incorrectly diagnosed as having asthma and are treated for presumed lower airway disease.[3][4][5][6][7][8] This increases the likelihood of the patient eventually requiring major open surgery in benign disease[9] and can lead to tracheal cancer presenting too late for curative surgery to be performed.
## Causes[edit]
Laryngotracheal stenosis is an umbrella term for a wide and heterogeneous group of very rare conditions. The population incidence of adult post-intubation laryngotracheal stenosis which is the commonest benign sub-type of this condition is approximately 1 in 200,000 adults per year.[10] The main causes of adult laryngotracheal stenosis are:
Main causes of laryngotracheal stenosis Benign causes Malignant causes
Extrinsic compression
* Thyroid goitre
* Thymoma
* Mediastinal lymphadenopathy (e.g. TB)[11]
* Vascular anomalies
* Thyroid cancer[12]
* Lung cancer/lymphomas-related mediastinal lymphadenopathy
Intrinsic narrowing
* At the level of the larynx (glottis)
* Bilateral vocal fold paralysis
* Blunt/sharp laryngeal trauma
* Foreign body inhalation
* Sarcoidosis
* Amyloidosis[13]
* Bilateral vocal fold mobility impairment
* Crico-arytenoid joint fixation
* Rheumatoid arthritis
* Intubation-related joint fixation
* Inter-arytenoid scarring
* Intubation-related
* Infections (e.g. Diphtheria, epiglottitis)
* Respiratory papillomatosis[14][15]
* Large ball-valving vocal polyps
* Congenital laryngeal stenosis
* Laryngeal atresia
* Congenital laryngeal webs
* At the level of subglottis/trachea
* Intubation/tracheostomy-related (most common cause)[16][17]
* Granulomatosis with polyangiitis[18]
* Idiopathic Progressive Subglottic Stenosis
* Amyloidosis
* Tracheopathia osteoplastica
* Tracheomalacia
* Expiratory Dynamic Airway Collapse (EDAC)
* Tracheobronchomalacia
* Relapsing polychondritis[19][20]
* Tracheal ring damage due to COPD
* Tracheal ring weakness
* Benign tumors (e.g. Carcinoid)
* Tracheal trauma / rupture[21]
* Congenital subglottic/tracheal anomalies
* Complete tracheal rings
* Congenital subglottic/tracheal webs
* Subglottic haemangioma
* Subglottic / tracheal cysts[6]
* At the level of carina or main bronchi
* Granulomatosis with polyangiitis
* Foreign body inhalation
* Tuberculosis
* Following Photodynamic Therapy
* Head and neck (especially laryngeal or supraglottic) cancers
* Primary tracheal cancers
* Erosive thyroid cancer
* Erosive esophageal cancer[22]
* Lung cancer causing central airway obstruction[11]
## Diagnosis[edit]
Patient history, CT scan of neck and chest, fiberoptic bronchoscopy, and spirometry are all several ways to assess for laryngotracheal stenosis and effectively develop preoperational approaches to treating the disease. In addition, a methodology called the Cotton-Myer system is commonly used to evaluate the degree of severity of the laryngotracheal stenosis based on the percentage of obstruction; other systems have also been proposed to fill potential shortcomings of the Cotton-Myer classification and help capture the full complexity of the illness.[23]
## Treatment[edit]
The optimal management of laryngotracheal stenosis is not well defined, depending mainly on the type of the stenosis.[24] General treatment options include
1. Tracheal dilation using rigid bronchoscope
2. Laser surgery and endoluminal stenting[25]
3. Tracheal resection and laryngotracheal reconstruction[21][26]
Tracheal dilation is used to temporarily enlarge the airway. The effect of dilation typically lasts from a few days to 6 months. Several studies have shown that as a result of mechanical dilation (used alone) may occur a high mortality rate and a rate of recurrence of stenosis higher than 90%.[24] Thus, many authors treat the stenosis by endoscopic excision with laser (commonly either the carbon dioxide or the neodymium: yttrium aluminum garnet laser) and then by using bronchoscopic dilatation and prolonged stenting with a T-tube (generally in silicone).[27][28][29]
There are differing opinions on treating with laser surgery.
In very experienced surgery centers, tracheal resection and reconstruction (anastomosis complete end-to-end with or without laryngotracheal temporary stent to prevent airway collapse) is currently the best alternative to completely cure the stenosis and allows to obtain good results. Therefore, it can be considered the gold standard treatment and is suitable for almost all patients.[30]
The narrowed part of the trachea will be cut off and the cut ends of the trachea sewn together with sutures. For stenosis of length greater than 5 cm a stent may be required to join the sections.
Late June or early July 2010, a new potential treatment was trialed at Great Ormond Street Hospital in London, where Ciaran Finn-Lynch (aged 11) received a transplanted trachea which had been injected with stem cells harvested from his own bone marrow. The use of Ciaran's stem cells was hoped to prevent his immune system from rejecting the transplant,[31] but there remain doubts about the operation's success, and several later attempts at similar surgery have been unsuccessful.
## Nomenclature[edit]
Laryngotracheal stenosis (Laryngo-: Glottic Stenosis; Subglottic Stenosis; Tracheal: narrowings at different levels of the windpipe) is a more accurate description for this condition when compared, for example to subglottic stenosis which technically only refers to narrowing just below vocal folds or tracheal stenosis. In babies and young children however, the subglottis is the narrowest part of the airway and most stenoses do in fact occur at this level. Subglottic stenosis is often therefore used to describe central airway narrowing in children, and laryngotracheal stenosis is more often used in adults.
## See also[edit]
* Hermes Grillo pioneer in tracheal resection surgery
* Laryngospasm
## References[edit]
1. ^ Gelbard, A (2014). "Causes and Consequences of Laryngotracheal Stenosis". The Laryngoscope. 125 (5): 1137–1143. doi:10.1002/lary.24956. PMC 4562418. PMID 25290987.
2. ^ Armstrong WB, Netterville JL (August 1995). "Anatomy of the larynx, trachea, and bronchi". Otolaryngol. Clin. North Am. 28 (4): 685–99. PMID 7478631.
3. ^ Catenacci MH (July 2006). "A case of laryngotracheal stenosis masquerading as asthma". South. Med. J. 99 (7): 762–4. doi:10.1097/01.smj.0000217498.70967.77. PMID 16866062.
4. ^ Ricketti PA, Ricketti AJ, Cleri DJ, Seelagy M, Unkle DW, Vernaleo JR (2010). "A 41-year-old male with cough, wheeze, and dyspnea poorly responsive to asthma therapy". Allerg Asthma Proc. 31 (4): 355–8. doi:10.2500/aap.2010.31.3344. PMID 20819328.
5. ^ Scott PM, Glover GW (1995). "All that wheezes is not asthma". Br J Clin Pract. 49 (1): 43–4. PMID 7742187.
6. ^ a b Kokturk N, Demircan S, Kurul C, Turktas H (October 2004). "Tracheal adenoid cystic carcinoma masquerading asthma: a case report". BMC Pulm Med. 4: 10. doi:10.1186/1471-2466-4-10. PMC 526771. PMID 15494074.
7. ^ Parrish RW, Banks J, Fennerty AG (December 1983). "Tracheal obstruction presenting as asthma". Postgrad Med J. 59 (698): 775–6. doi:10.1136/pgmj.59.698.775. PMC 2417814. PMID 6318209.
8. ^ Galvin IF, Shepherd DR, Gibbons JR (1990). "Tracheal stenosis caused by congenital vascular ring anomaly misinterpreted as asthma for 45 years". Thorac Cardiovasc Surg. 38 (1): 42–4. doi:10.1055/s-2007-1013990. PMID 2309228.
9. ^ Nouraei SA, Singh A, Patel A, Ferguson C, Howard DJ, Sandhu GS (August 2006). "Early endoscopic treatment of acute inflammatory airway lesions improves the outcome of postintubation airway stenosis". Laryngoscope. 116 (8): 1417–21. doi:10.1097/01.mlg.0000225377.33945.14. PMID 16885746.
10. ^ Nouraei SA, Ma E, Patel A, Howard DJ, Sandhu GS (October 2007). "Estimating the population incidence of adult post-intubation laryngotracheal stenosis". Clin Otolaryngol. 32 (5): 411–2. doi:10.1111/j.1749-4486.2007.01484.x. PMID 17883582.
11. ^ a b Lu MS, Liu YH, Ko PJ, Wu YC, Hsieh MJ, Liu HP, Lin PJ (April 2003). "Preliminary experience with bronchotherapeutic procedures in central airway obstruction". Chang Gung Med J. 26 (4): 240–9. PMID 12846523.
12. ^ Tsutsui H, Kubota M, Yamada M, Suzuki A, Usuda J, Shibuya H, Miyajima K, Sugino K, Ito K, Furukawa K, Kato H (September 2008). "Airway stenting for the treatment of laryngotracheal stenosis secondary to thyroid cancer". Respirology. 13 (5): 632–8. doi:10.1111/j.1440-1843.2008.01309.x. PMID 18513246.
13. ^ Peña J, Cicero R, Marín J, Ramírez M, Cruz S, Navarro F (October 2001). "Laryngotracheal reconstruction in subglottic stenosis: an ancient problem still present". Otolaryngol Head Neck Surg. 125 (4): 397–400. doi:10.1067/mhn.2001.117372. PMID 11593179.
14. ^ Bent J (July 2006). "Pediatric laryngotracheal obstruction: current perspectives on stridor". Laryngoscope. 116 (7): 1059–70. doi:10.1097/01.mlg.0000222204.88653.c6. PMID 16826038.
15. ^ Perkins JA, Inglis AF, Richardson MA (March 1998). "Iatrogenic airway stenosis with recurrent respiratory papillomatosis". Arch. Otolaryngol. Head Neck Surg. 124 (3): 281–7. doi:10.1001/archotol.124.3.281. PMID 9525512.
16. ^ Wood DE, Mathisen DJ (September 1991). "Late complications of tracheotomy". Clin. Chest Med. 12 (3): 597–609. PMID 1934960.
17. ^ Lorenz RR (December 2003). "Adult laryngotracheal stenosis: etiology and surgical management". Curr Opin Otolaryngol Head Neck Surg. 11 (6): 467–72. doi:10.1097/00020840-200312000-00011. PMID 14631181.
18. ^ Filocamo, G; Torreggiani, S; Agostoni, C; Esposito, S (April 2017). "Lung involvement in childhood onset granulomatosis with polyangiitis". Pediatric Rheumatology Online Journal. 15 (1): 28. doi:10.1186/s12969-017-0150-8. PMC 5391594. PMID 28410589.
19. ^ Chang SJ, Lu CC, Chung YM, Lee SS, Chou CT, Huang DF (June 2005). "Laryngotracheal involvement as the initial manifestation of relapsing polychondritis". J Chin Med Assoc. 68 (6): 279–82. doi:10.1016/S1726-4901(09)70151-0. PMID 15984823.
20. ^ Kim CM, Kim BS, Cho KJ, Hong SJ (April 2003). "Laryngotracheal involvement of relapsing polychondritis in a Korean girl". Pediatr. Pulmonol. 35 (4): 314–7. doi:10.1002/ppul.10247. PMID 12629631.
21. ^ a b Mostafa BE, El Fiky L, El Sharnoubi M (July 2006). "Non-intubation traumatic laryngotracheal stenosis: management policies and results". Eur Arch Otorhinolaryngol. 263 (7): 632–6. doi:10.1007/s00405-006-0036-8. PMID 16633824.
22. ^ Wassermann K, Mathen F, Edmund Eckel H (October 2000). "Malignant laryngotracheal obstruction: a way to treat serial stenoses of the upper airways". Ann. Thorac. Surg. 70 (4): 1197–201. doi:10.1016/s0003-4975(00)01614-3. PMID 11081870.
23. ^ Rosow, David E.; Barbarite, Eric (December 2016). "Review of Adult Laryngotracheal Stenosis: Pathogenesis, Management, and Outcomes". Ovid. Current Opinion in Otolaryngology & Head and Neck Surgery. pp. 489–493. Retrieved 2020-12-05.
24. ^ a b Brichet A, Verkindre C, Dupont J, Carlier ML, Darras J, Wurtz A, Ramon P, Marquette CH (April 1999). "Multidisciplinary approach to management of postintubation tracheal stenoses". Eur. Respir. J. 13 (4): 888–93. doi:10.1034/j.1399-3003.1999.13d32.x. PMID 10362058.
25. ^ Ciccone AM, De Giacomo T, Venuta F, Ibrahim M, Diso D, Coloni GF, Rendina EA (October 2004). "Operative and non-operative treatment of benign subglottic laryngotracheal stenosis". Eur J Cardiothorac Surg. 26 (4): 818–22. doi:10.1016/j.ejcts.2004.06.020. PMID 15450579.
26. ^ Duncavage JA, Koriwchak MJ (August 1995). "Open surgical techniques for laryngotracheal stenosis". Otolaryngol. Clin. North Am. 28 (4): 785–95. PMID 7478638.
27. ^ Shapshay SM, Beamis JF, Hybels RL, Bohigian RK (1987). "Endoscopic treatment of subglottic and tracheal stenosis by radial laser incision and dilation". Ann. Otol. Rhinol. Laryngol. 96 (6): 661–4. doi:10.1177/000348948709600609. PMID 3688753.
28. ^ Shapshay SM, Beamis JF, Dumon JF (November 1989). "Total cervical tracheal stenosis: treatment by laser, dilation, and stenting". Ann. Otol. Rhinol. Laryngol. 98 (11): 890–5. doi:10.1177/000348948909801110. PMID 2817681.
29. ^ Mehta AC, Lee FY, Cordasco EM, Kirby T, Eliachar I, De Boer G (September 1993). "Concentric tracheal and subglottic stenosis. Management using the Nd-YAG laser for mucosal sparing followed by gentle dilatation". Chest. 104 (3): 673–7. doi:10.1378/chest.104.3.673. PMID 8365273. Archived from the original on 2014-06-18.
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Bibliography
* Ongkasuwan, Julina (2006-02-09). "Tracheal Stenosis". Baylor College of Medicine. Archived from the original on 2007-02-20. Retrieved 2007-03-17.
## External links[edit]
Classification
D
* ICD-10: Q31.1, Q32.1, J38.6, J39.8, J95.5
* ICD-9-CM: 519.19, 748.3
* MeSH: D014135
* 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
* t
* e
Congenital malformations and deformations of respiratory system
Upper RT
Nose
* Choanal atresia
* Arrhinia
Larynx
* Laryngeal cyst
* Laryngocele
* Laryngomalacia
Lower RT
Trachea and bronchus
* Tracheomalacia
* Tracheal stenosis
* Bronchomalacia
* Tracheobronchomegaly
Lung
* Bronchiectasis
* Pulmonary hypoplasia
* Pulmonary sequestration
* Congenital cystic adenomatoid malformation
*[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
| Laryngotracheal stenosis | c0040583 | 1,098 | wikipedia | https://en.wikipedia.org/wiki/Laryngotracheal_stenosis | 2021-01-18T18:43:31 | {"mesh": ["D014135"], "umls": ["C0040583"], "icd-9": ["748.3", "519.19"], "icd-10": ["J39.8", "Q31.1", "J38.6", "Q32.1", "J95.5"], "wikidata": ["Q4116448"]} |
17q11 microdeletion syndrome is a rare severe form of neurofibromatosis type 1 (NF1; see this term) characterized by mild facial dysmorphism, developmental delay, intellectual disability, increased risk of malignancies, and a large number of neurofibromas.
## Epidemiology
The prevalence of 17q11 microdeletion syndrome is not known. About 5% of NF1 cases are reported to have deletions of the entire NF1 gene. More than 170 affected patients have been reported to date.
## Clinical description
Affected individuals often have unusual body habitus and facial dysmorphism including facial coarsening, prominent forehead, ptosis, down-slanting palpebral fissures, hypertelorism, broad nose and nasal bridge, low set ears, and micrognathia. Patients develop a large number of neurofibromas, often with early onset, including multiple cutaneous neurofibromas, and less commonly plexiform neurofibromas. Other characteristic features include attention deficit/hyperactivity disorder (AD/HD), delayed cognitive development and intellectual disability. Some patients are reported to have microcephaly or macrocephaly, optic pathway glioma, iris coloboma (see these terms), heart defects (mitral valve prolapse, aortic dilatation), large hands and feet, connective tissue dysplasia (joint hyperflexibility, soft palm skin), muscular hypotonia, scoliosis, pectus excavatum, and bone cysts. A higher risk of malignancy for NF1 and non-NF1 tumors is reported: malignant peripheral nerve sheath tumors (lifetime risk of 16-26%), retroperitoneal fibrosarcoma, and medulloblastoma with extensive nodularity (see this term).
## Etiology
Germline and mosaic microdeletions of the NF1 gene and its flanking regions caused by non-allelic homologous recombination are reported in patients with this disorder. Most occur de novo.
## Genetic counseling
As most cases are de novo, recurrence risk for offspring of unaffected parents is very low. Affected individuals have a 50% risk of transmitting the microdeletion, and prenatal and preimplantation genetic diagnosis is possible.
*[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
| 17q11 microdeletion syndrome | c3150928 | 1,099 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97685 | 2021-01-23T19:10:25 | {"gard": ["5408"], "mesh": ["C563524"], "omim": ["613675"], "umls": ["C3150928"], "icd-10": ["Q85.0"], "synonyms": ["Del(17)(q11)", "Monosomy 17q11", "NF1 microdeletion syndrome", "Neurofibromatosis type 1 microdeletion syndrome"]} |
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