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A rare genetic disease characterized by the triad of adult-onset moderate to severe bilateral sensorineural hearing loss, premature graying of scalp hair, and essential tremor manifesting as involuntary shaking of the head. Additional pigmentation abnormalities have not been reported in this syndrome.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Sensorineural hearing loss-early graying-essential tremor syndrome
|
None
| 7,700 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=66633
| 2021-01-23T17:12:55 |
{"synonyms": ["Sensorineural deafness-early graying-essential tremor syndrome"]}
|
A number sign (#) is used with this entry because Peutz-Jeghers syndrome (PJS) is caused by heterozygous mutation in the serine/threonine kinase STK11 gene (602216) on chromosome 19p13.
Description
Peutz-Jeghers syndrome is an autosomal dominant disorder characterized by melanocytic macules of the lips, buccal mucosa, and digits; multiple gastrointestinal hamartomatous polyps; and an increased risk of various neoplasms.
Clinical Features
In the syndrome named for Peutz (1921) and Jeghers (Jeghers et al., 1949), polyps may occur in any part of the gastrointestinal tract but jejunal polyps are a consistent feature. Intussusception and bleeding are the usual symptoms. Melanin spots of the lips, buccal mucosa, and digits represent the second part of the syndrome. Malignant degeneration of the small intestinal polyps is rare. Metastases from a malignant polyp in Peutz-Jeghers syndrome was reported by Williams and Knudsen (1965). Dodds et al. (1972) found 15 cases of gastrointestinal carcinoma in Peutz-Jeghers syndrome: 5 in colon, 4 in duodenum, 4 in stomach, 1 in ileum, and 1 in both jejunum and stomach. In the family reported by Farmer et al. (1963), the father had only polyps, the son apparently only pigmentation, and the daughter both polyps and pigmentation. Kieselstein et al. (1969), who found polycystic kidney disease in the same family, also noted a dissociation of signs. Brigg et al. (1976) observed a case of presumed Peutz-Jeghers syndrome without spots or positive family history. Hamartomatous polyps were limited to the jejunum and caused bleeding. Griffith and Bisset (1980) reported 3 cases. In 2 of them, the family history was negative; in the third, the father and a paternal uncle had melanin spots of the lips but no history of intestinal disorder.
Sommerhaug and Mason (1970) added the ureter to the sites of polyps described in the Peutz-Jeghers syndrome. Previously described extraintestinal sites include esophagus, bladder, renal pelvis, bronchus and nose. Burdick and Prior (1982) reported nonresectable adenocarcinoma of the jejunum arising in a Peutz-Jeghers polyp and accompanied by metastases in mesenteric lymph nodes. Two developed breast carcinoma of which 1 arose in a fibroadenoma. Three had benign ovarian tumors, 1 had a benign breast tumor and 1 had a benign colloid thyroid nodule. One of the cases (case 7) reported by Jeghers et al. (1949) died of pancreatic cancer. Bowlby (1986) reported pancreatic cancer in an adolescent boy with PJS.
Affected females are prone to develop ovarian tumor, especially granulosa cell tumor (Christian et al., 1964). Wilson et al. (1986) described gynecomastia and multifocal and bilateral testicular tumors in a 6-year-old boy with PJS. The testicular tumors appear to be of Sertoli cell origin and most are calcifying. Two previously reported cases were found. Coen et al. (1991) reported the case of a 4-year-old boy with Peutz-Jeghers syndrome and bilateral sex-cord testicular tumors resulting in gynecomastia. Studies led to the conclusion that increase in aromatase activity (107910) in the gonadal tumors was responsible for estrogen excess and gynecomastia. Three other reported male patients with Peutz-Jeghers syndrome and gonadal tumors had presented with gynecomastia between birth and 6 years of age. They pointed out that multifocal sex-cord tumors were found in palpably normal testes. The occurrence of ovarian tumors far exceeds that of testicular tumors in this disorder. The production of estrogen by ovarian tumors is indicated by the reported appearance of isosexual precocity in girls with PJS (Solh et al., 1983). Young et al. (1995) reported 2 boys, aged 3.5 and 5.5 years, who were evaluated for gynecomastia and found to have multicentric Sertoli cell testicular tumors responsible for their feminization. Both had rapid growth and advanced bone age, and serum levels of estradiol were markedly elevated.
Bergada et al. (2000) described a 7-year-old boy with Peutz-Jeghers syndrome, gynecomastia, and bilateral neoplastic Sertoli cell proliferation in whom the only abnormal hormonal profile was increased concentration of inhibin-beta (see 147290), which was biologically active, and pro-alpha C of insulin, which was biologically inactive.
In a patient with both psoriasis and Peutz-Jeghers syndrome (sine polyps), Banse-Kupin and Douglass (1986) described a peculiar phenomenon: the development of characteristic pigmented macules within preexisting psoriatic plaques in sites highly unusual for PJS, e.g., on the elbow, back of the neck and occipital scalp, buttocks, and legs. Sommerhaug and Mason (1970) suggested that patients with PJS develop polyps in areas of frequent trauma. Banse-Kupin and Douglass (1986) proposed that pigmented macules may likewise be located in areas of frequent trauma or areas of inflammation. Inflammation may induce blockage of pigment transfer from melanocyte to keratinocyte, resulting in a macule. As the inflammation or trauma subsides, so may the blockage and the lesion may fade. Histologically, the oral mucosal lesions resemble lentigo simplex, but the acral lesions are distinctive (Yamada et al., 1981). There is an increased number of melanocytes with long dendrites filled with melanosomes but few melanosomes in keratocytes, suggesting a pigment block.
Giardiello et al. (1987) investigated the occurrence of cancer in 31 patients with PJS followed from 1973 to 1985. Gastrointestinal carcinoma developed in 4, nongastrointestinal carcinoma in 10, and multiple myeloma in 1. Adenomatous polyps of the stomach and colon occurred in 3 other patients. There were 4 cases of pancreatic cancer. Foley et al. (1988) provided a 49-year follow-up of the 'Harrisburg family,' 3 affected members of which were reported by Jeghers et al. (1949). The family had also been studied earlier by Bartholomew et al. (1962). In all, 12 affected members have been identified, making this the largest PJS kindred reported. One member of the family had developed a duodenal carcinoma and a hamartoma with adenomatous changes. Another member developed short bowel syndrome. In the follow-up of 72 patients with PJS in the St. Mark's Polyposis Registry, Spigelman et al. (1989) found that malignant tumors had developed in 16 (22%), of whom all but 1 had died. There were 9 gastrointestinal and 7 nongastrointestinal tumors. The chance of dying of cancer by age 57 was 48%.
Westerman and Wilson (1999) reviewed the literature on PJS, with particular emphasis on the risks for PJS gene carriers. The risks imposed by polyps included surgical emergencies like small bowel intussusception, and chronic or acute bleeding from the polyps. Many reports, however, suggested an association of PJS with both gastrointestinal and nongastrointestinal malignancies, often at a young age. The frequent occurrence of rare tumors of the ovary, cervix, and testis indicated a general susceptibility for the development of malignancies. The PJS gene was therefore thought to act as a tumor suppressor gene. The authors suggested that a surveillance protocol should be developed for the prevention of cancer in PJS.
Unusually early age of onset was observed by Fernandez Seara et al. (1995) in a 15-day-old girl who was found to have generalized gastrointestinal polyposis manifested by abdominal distention, hematemesis, bloody diarrhea, and edema. At 15 days of age, ileocecal intussusception causing intestinal obstruction was diagnosed radiologically and reduced by hydrostatic enema; ileocecal surgical resection was required, however. Rectal prolapse due to a large polyp occurred at one month of age. Esophagogastroscopy showed polyps in the stomach; one in the antrum partially obstructed the lumen. No hyperpigmentation of the lips or oral mucosa was observed at any time and none was present in her relatives. The histologic appearance of the polyps removed during life and at autopsy was consistent with Peutz-Jeghers syndrome.
Gruber et al. (1998) noted that the histopathologic appearance of hamartomas in PJS is distinct from that of other types of gastrointestinal polyps and likely reflects a different pathogenetic sequence for their development. PJS hamartomas show an elongated, frond-like epithelium with cystic dilatation of glands overlying an arborizing network of smooth muscle bundles. Hypermucinous goblet cells are often prominent. In addition, pseudoinvasion by histopathologically benign epithelium is common in PJS hamartomas. These characteristic features are easily distinguished from the cytologic atypia and lack of differentiation seen in typical adenomas, and it is not surprising that PJS tumors seem to share few of the earliest genetic events observed in the transition of normal epithelium to dysplastic adenomas. Hamartomatous polyps arising in the juvenile polyposis syndrome (174900) originate through yet another mechanism as a consequence of germline mutations in the SMAD4/DPC4 gene (600993). The hamartomas of juvenile polyposis are histologically distinct from those of PJS, and the risk of malignancy also differs in these 2 syndromes.
Some patients with PJS may be disturbed by the appearance of lentigines. Kato et al. (1998) described ruby laser therapy of labial lentigines in 2 children with this disorder. They stated that the response to treatment was excellent, with no sequelae or recurrence of the lesions.
Boardman et al. (2000) pointed out that diagnosing PJS, even in an individual from a known PJS kindred, can be difficult. Oral pigmentation tends to fade and be forgotten with time, and polyps can often be asymptomatic. Additionally, other syndromes may mimic the pigmentation of PJS, occurring in individuals with an occult malignancy (Babin et al., 1978; Eng et al., 1991; Gass and Glatzer, 1991) or in individuals with Laugier-Hunziker syndrome, a condition characterized by oral hyperpigmentation without polyposis (Veraldi et al., 1991).
Familial hamartomatous polyps of the small intestine resembling those of PJS were recognized as a feature of Bannayan-Zonana syndrome (BRRS; see 158350), which is caused by mutation in the PTEN gene (601728), by DiLiberti et al. (1983) and others. Pigmented spots occur also in BRRS but characteristically on the glans penis in males and not on the lips.
In connection with the possibility that the melanin spots of the lips represent a benign neoplasm, the observations of Jeghers et al. (1949) may be significant: clinically, some of the spots could be seen to have a somewhat stippled appearance under magnification, which, it was thought, could be explained by a curious histologic pattern observed on biopsy. The pigmentation occurred mainly in vertical bands interrupted by unpigmented areas. The change suggested the possibility of clonality.
Mapping
Studying 2 extended families, Bali et al. (1995) found positive evidence for linkage with several microsatellite markers on chromosome 1. Seldin (1997) reported that addition of more family members in the 2 largest families decreased the lod scores substantially as did the addition of more markers in the region. Indeed, in the original study, the maximum 2-point lod was below 2.0. Multipoint linkage analysis yielded a maximum lod score of 4.00 at D1S220. This is located in the distal region of 1p, where the human homolog of the putative modifier of multiple intestinal neoplasias (172411) had previously been mapped.
In a patient with Peutz-Jeghers syndrome, Markie et al. (1996) demonstrated a pericentric inversion in chromosome 6. Using fluorescence in situ hybridization with YAC clones selected to contain genetic markers from chromosome 6 and with a probe for the centromeric alphoid array, they located 1 inversion breakpoint within the alphoid repeat array, in a 1-cM interval between D6S257 and D6S402, and the other in a 4-cM interval between D6S403 and D6S311.
To localize the susceptibility locus for Peutz-Jeghers syndrome, Hemminki et al. (1997) used comparative genomic hybridization (CGH) and targeted linkage analysis, combined with loss of heterozygosity (LOH) study. They demonstrated a high-penetrance locus in distal 19p with a multipoint lod score of 7.00 at marker D19S886 without evidence of genetic heterogeneity. The study demonstrated the power of CGH combined with LOH analysis in identifying putative tumor suppressor loci. In comparative genomic hybridization, a single hybridization allows DNA copy number changes in the whole genome of a tumor to be assessed in comparison with normal tissue DNA (Kallioniemi et al., 1992). The findings of Hemminki et al. (1997) suggested that in most or all of the families they studied, the PJS was caused by a defect in a single locus on 19p. That the Peutz-Jeghers syndrome is genetically homogeneous required, however, confirmation by linkage analysis in further families. Amos et al. (1997) confirmed the mapping of PJS to the telomeric region of 19p. In the 5 families examined, there were no recombinants with the marker D19S886. The multipoint lod score at D19S886 was 7.52, and they found no evidence for genetic heterogeneity or of reduced penetrance.
Mehenni et al. (1997) performed a genomewide linkage analysis, using DNA polymorphisms in 6 families (2 from Spain, 2 from India, 1 from the U.S., and 1 from Portugal), including 39 affected individuals and 6 individuals of unknown status. Marker D19S886 yielded a maximum lod score of 4.74 at a recombination fraction of 0.45; multipoint linkage analysis resulted in a lod score of 7.51 for the interval between D19S886 and 19pter. However, markers on 19q13.4 also showed significant evidence for linkage. For example, D19S880 resulted in a maximum lod score of 3.8 at theta = 0.13. Most of this positive linkage was contributed by a single family. Thus, the results confirmed the mapping of a common PJS locus on 19p13.3, but also suggested the existence, in a minority of families, of a potential PJS locus on 19q13.4. Buchet-Poyau et al. (2002) excluded several candidate genes as a second PJS locus in the 19q13.3-q13.4 region.
Molecular Genetics
Within a distance of 190 kb proximal to D19S886, the marker with the highest lod score in the study of Hemminki et al. (1997), Jenne et al. (1998) identified and characterized a novel human gene encoding the serine/threonine kinase STK11. In a 3-generation PJS family, they found an STK11 allele with a deletion of exons 4 and 5 and an inversion of exons 6 and 7 (602216.0001) segregating with the disease. Sequence analysis of STK11 exons in 4 unrelated PJS patients identified 3 nonsense mutations (602216.0002, 602216.0003, 602216.0004) and 1 acceptor splice site mutation (602216.0005). All 5 germline mutations were predicted to disrupt the function of the kinase domain. Jenne et al. (1998) concluded that germline mutations in STK11, probably in conjunction with acquired genetic defects of the second allele in somatic cells, caused the manifestations of PJS.
Independently and simultaneously, Hemminki et al. (1998), the group that identified the linkage of PJS to chromosome 19, demonstrated mutations in the serine/threonine kinase gene in 11 of 12 unrelated patients with PJS.
Jenne (1998) speculated that cellular context between melanocytes and keratinocytes are regulated by STK11 activity. He pointed to the wide tissue distribution of STK11 and suggested that effects in melanocytes may be observed preferentially at sites of mechanical and physical stress.
Gruber et al. (1998) studied 6 families with PJS from the Johns Hopkins Polyposis Registry to identify the molecular basis of PJS and to characterize the pathogenesis of gastrointestinal hamartomas and adenocarcinomas in these patients. Linkage analysis in the family studied by McKusick, who contributed to the publication of Jeghers et al. (1949), and in 5 other families confirmed linkage to 19p13.3. Germline mutations in STK11 were identified in all 6 families by sequencing genomic DNA. Analysis of hamartomas and adenocarcinomas from patients with PJS identified LOH of 19p markers near STK11 in 70% of tumors. Haplotype analysis indicated that the retained allele carried a germline mutation (602216.0012), confirming that STK11 is a tumor suppressor gene. LOH of 17p and 18q was identified in an adenocarcinoma but not in hamartomas, implying that allelic loss of these 2 regions corresponds to late molecular events in the pathogenesis of cancer in PJS. The adenocarcinomas showing 17p LOH also demonstrated altered p53 by immunohistochemistry. None of the 18 PJS tumors showed microsatellite instability, LOH on 5q near APC (611731), or mutations in codons 12 or 13 of the KRAS2 (190070) protooncogene. These data provided evidence that STK11 is a tumor suppressor gene that acts as an early gatekeeper regulating the development of hamartomas in PJS and suggested that hamartomas may be pathogenetic precursors of adenocarcinoma. Additional somatic mutation events underlie the progression of hamartomas to adenocarcinomas, and some of these somatic mutations are common to the later stages of tumor progression seen in the majority of colorectal carcinomas.
Miyaki et al. (2000) presented findings suggesting that gastrointestinal hamartomatous polyps in PJS patients develop through inactivation of the STK11 gene by germline mutation plus somatic mutation or LOH of the unaffected STK11 allele, and that additional mutations of the beta-catenin gene (CTNNB1; 116806) and the p53 gene (TP53; 191170) convert hamartomatous polyps into adenomatous and carcinomatous lesions.
Westerman et al. (1999) found novel STK11 mutations in 12 of 19 predominantly Dutch families with PJS. No mutation was found in the remaining 7 families. None of the mutations occurred in more than 1 family, and a number were demonstrated to have arisen de novo. The likelihood of locus heterogeneity was raised.
Jiang et al. (1999) conducted a detailed investigation of germline STK11 alterations by protein truncation test and genomic DNA sequence analysis in 10 unrelated PJS families. A novel truncating deletion in a single patient and several known polymorphisms were identified. The results suggested that STK11 mutations account for only some cases of PJS.
Boardman et al. (2000) searched for mutations in the STK11 gene in 5 kindreds with more than 2 family members affected by PJS, 5 PJS probands with only 1 other affected family member, and 23 individuals with sporadic PJS. Conformation-sensitive gel electrophoresis was used for the initial screen, followed by direct sequence analysis for characterization. Long-range PCR was used for the detection of larger genetic insertions or deletions. Genetic alterations in the gene were found in 2 probands who had a family history of PJS. Mutations were detected in the gene in only 4 of the 23 patients with sporadic PJS. The authors interpreted these data as suggesting the presence of significant genetic heterogeneity in PJS and the involvement of other loci in this syndrome. They pointed to the report by Mehenni et al. (1997) of a possible second susceptibility locus on 19q in 2 PJS Indian families and to that by Olschwang et al. (1998), in which no evidence of linkage was found in 3 of 20 PJS kindreds.
Olschwang et al. (2001) studied 34 families with PJS. Mutations in the STK11 gene were identified in 24 families. In the 10 families in which mutations were not identified, there was a significantly increased risk of proximal biliary adenocarcinoma.
Westerman et al. (1999) traced the Dutch family reported by Peutz (1921) and determined that the affected members carried a previously unidentified germline mutation in the STK11 gene (602216.0014). The pedigree, published by Westerman et al. (1999), showed affected individuals in 4 generations and, by inference, in an earlier fifth generation. In total, 22 persons (9 females and 13 males) were affected and 31 were unaffected. Nasal polyposis was present in 2 members of 1 generation and in 4 members of another. Colicky abdominal pain occurred in all 22 affected members, paralytic ileus in 16, chronic anemia in 9, and acute or chronic blood loss in 14. Rectal prolapse due to polyps occurred in 7. In 4 patients, the nasal polyposis was severe, obstructing the nasal cavity and sinuses, requiring repeated surgery. In 1 woman who had had extremely severe nasal polyposis since childhood, a squamous cell carcinoma of the nasal cavity developed. She died of this tumor 4 years later. Three of the 5 cases of gastrointestinal cancer were in the colon, 1 was in the stomach, and 1 was of unknown primary origin. Breast cancer occurred in a female patient at the age of 47 years. Premenopausal breast cancer was diagnosed in a sib at the age of 44; it was not known whether this patient was affected by PJS. No other cancers of the reproductive tract were found in this family.
Keller et al. (2002) reported molecular genetic evidence of an association between nasal polyposis and PJS. They studied 12 nasal polyps from 4 patients with PJS who came from 3 families with known germline mutations in STK11, and 28 sporadic nasal polyps from 28 subjects without evidence of PJS, Kartagener syndrome (244400), cystic fibrosis (CF; 219700), or aspirin sensitivity. In 2 unrelated patients with PJS, 4 of 8 nasal polyps showed loss of heterozygosity at 19p13.3. In contrast, loss of heterozygosity was not found in 23 sporadic nasal polyps. Haplotype analysis showed that loss of heterozygosity comprised deletion of the wildtype allele. Loss of heterozygosity at 19p13.3 in nasal polyps of affected patients corresponded with reports of loss of heterozygosity in gastrointestinal hamartomatous polyps (Entius et al., 2001). In his original publication, Peutz (1921) suggested that nasal polyps represent an extraintestinal manifestation of PJS.
Le Meur et al. (2004) reported a family with typical features of PJS, including melanin spots of the oral mucosa, gastrointestinal hamartomatous polyps, and breast and colon cancer. The authors noted that the proband had neurofibromatosis type I (162200) of paternal origin as well as PJS of maternal origin. Using quantitative multiplex PCR of short fluorescent fragments of the 19p13 region, they identified an approximately 250-kb heterozygous deletion that completely removed the STK11 locus. Le Meur et al. (2004) stated that this was the first report of a complete germline deletion of STK11 and suggested that the presence of such large genomic deletions should be considered in PJS families without detectable point mutations of STK11.
Amos et al. (2004) screened 42 independent probands for mutations in the STK11 gene and detected mutations in 22 of 32 (69%) probands with PJS and 0 of 10 probands referred to rule out PJS. In a total of 51 participants with PJS, the authors found gastric polyps to be very common, with a median age at onset of 16 years. Individuals with missense mutations had a significantly later time to onset of first polypectomy (p = 0.04) and of other symptoms compared with those participants with either truncating mutations or no detectable mutation. Amos et al. (2004) concluded that STK11 mutation analysis should be restricted to individuals who meet PJS criteria or their close relatives, and suggested that mutation characterization might be of value in disease management. They also noted that the common occurrence of gastric polyps might facilitate chemopreventive studies for this disorder.
In a 20-year-old female patient with PJS and gastrointestinal hamartomatous polyps, Hernan et al. (2004) identified a de novo heterozygous germline tyr246-to-ter mutation of the STK11 gene (602216.0023). Comparison of melting curve profiles obtained from DNA from the patient's lymphocytes and hamartomatous polyps showed no differences, indicative of a heterozygous mutation rather than loss of heterozygosity in the polyps. Hernan et al. (2004) suggested that biallelic inactivation of STK11 is not necessarily required for hamartoma formation in PJS patients.
In a patient with PJS and a primary gastric cancer (137215), Shinmura et al. (2005) identified heterozygosity for a deletion mutation of the STK11 gene (602216.0022), resulting in a truncated protein. No inactivation of the wildtype allele by somatic mutation, chromosomal deletion, or hypermethylation at the 5-prime CpG site of STK11 was detected in the gastric carcinoma. The patient's sister also had PJS and died of gastric carcinoma in her twenties. Shinmura et al. (2005) stated that this was the first report of an STK11 germline mutation in a PJS patient with gastric carcinoma.
### Genetic Heterogeneity
Alhopuro et al. (2008) identified a heterozygous germline mutation in the MYH11 gene (160745) in 1 of 33 PJS patients who did not have STK11 mutations, and the mutation was not identified in 1,015 controls. The patient had a cystic astrocytoma at age 13 years. At age 23 years, he developed intussusception and was diagnosed with typical PJS. His unaffected father also carried the mutation; there was no family history of the disorder. The authors postulated autosomal recessive inheritance and the presence of a second unidentified MYH11 mutation. In an unrelated patient with colorectal tumor showing microsatellite instability, Alhopuro et al. (2008) identified the same mutation in the somatic state.
Genotype/Phenotype Correlations
In a study of 132 PJS patients with or without cancer who had mutations in the STK11 gene, Schumacher et al. (2005) found that mutations in the part of the gene involved in ATP binding and catalysis were rarely associated with cancer, whereas mutations in the part of the gene involved in substrate recognition were more frequently associated with malignancies. PJS patients with breast cancers had predominantly truncating mutations.
History
Although Peutz (1921) was the first to recognize the familial association of gastrointestinal polyposis and mucocutaneous pigmentation, cases of gastrointestinal and, in particular, polyposis of the small intestine had been described before him. Many of these may have been instances of Peutz-Jeghers syndrome in which the characteristic pigmentation was not noticed or its significance was not appreciated. Two extensive reviews put the polyps-and-spots syndrome 'on the map': the review by Jeghers et al. (1949) in 2 successive weekly issues of the New England Journal of Medicine, and, describing 10 personal cases, the review by Dormandy (1957) in 3 successive weekly issues of the same journal. The designation Peutz-Jeghers syndrome appears to have first been used (at least in the title of an article) by Bruwer et al. (1954) of the Mayo Clinic. If in several early reports of small intestinal polyposis the characteristic pigmentation of PJS may have passed unnoticed, the reverse is certainly true. Jeghers et al. (1949) called attention to the first account of such cases, in female twins, by Hutchinson (1896). Hutchinson (1896) stated that the pigmented spots 'remain nonaggressive and their subjects remain in good health.' Weber (1919) reported that 'one of the twins had died at the age of 20 years of intussusception at the Metropolitan Hospital.' Jeghers et al. (1949) obtained follow-up information on Hutchinson's twins of the family name Howard. They were daughters of the official rat catcher of city of London. The second twin died childless of breast cancer at the age of 52 years. The breast cancer was considered coincidental at the time of the follow-up, but the findings of Giardiello et al. (1987) and the demonstration that the gene that is mutant in PJS is a tumor suppressor gene, make the cause of death in the second twin highly significant.
Keller et al. (2002) provided a history of the Peutz-Jeghers syndrome, with biographic information concerning both Jan Peutz and Harold Jeghers.
INHERITANCE \- Autosomal dominant HEAD & NECK Nose \- Nasal polyps Mouth \- Hyperpigmented macules of lips \- Hyperpigmented macules of buccal mucosa RESPIRATORY Airways \- Bronchial polyps CHEST Breasts \- Gynecomastia with Sertoli cell tumors ABDOMEN Biliary Tract \- Biliary tract polyps Gastrointestinal \- Hamartomatous polyps (stomach to rectum) \- Recurrent colicky abdominal pain \- Intussusception \- Rectal prolapse \- Intestinal bleeding GENITOURINARY Internal Genitalia (Female) \- Ovarian cysts Ureters \- Ureteral polyps Bladder \- Bladder polyps SKELETAL Hands \- Clubbing of fingers SKIN, NAILS, & HAIR Skin \- Hyperpigmented spots on hands (especially palms), arms, feet (especially plantar areas), legs, and lips ENDOCRINE FEATURES \- Precocious puberty with Sertoli cell tumor HEMATOLOGY \- Iron deficiency anemia NEOPLASIA \- Gastrointestinal carcinoma \- Breast cancer (ductal) \- Thyroid cancer \- Lung \- Pancreatic cancer \- Uterine cancer \- Sertoli cell testicular tumors \- Ovarian sex cord tumors MISCELLANEOUS \- Pigmented spots appear in infancy through childhood and fade in adulthood \- Spots occur in 95% of patients but can be absent MOLECULAR BASIS \- Caused by mutations in the serine/threonine protein kinase 11 gene (STK11, 602216.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
PEUTZ-JEGHERS SYNDROME
|
c0031269
| 7,701 |
omim
|
https://www.omim.org/entry/175200
| 2019-09-22T16:36:00 |
{"doid": ["3852"], "mesh": ["D010580"], "omim": ["175200"], "icd-10": ["Q85.8"], "orphanet": ["2869"], "synonyms": ["Alternative titles", "POLYPOSIS, HAMARTOMATOUS INTESTINAL", "POLYPS-AND-SPOTS SYNDROME"], "genereviews": ["NBK1266"]}
|
Schrander-Stumpel et al. (1990) described newborn brother and sister who died shortly after birth from respiratory failure. They showed growth retardation with a Potter-like face, complete phocomelia of the upper limbs, severe hypoplasia of the 6 upper ribs, renal dysplasia and abnormalities of the external genitalia. They suggested that these cases represent the same entity reported by Ulbright et al. (1984). The syndrome appears to be lethal because of severe renal dysplasia which causes oligohydramnios and pulmonary hypoplasia. Schrander-Stumpel et al. (1990) suggested the designations 'renal dysplasia--limb defects syndrome (RL syndrome).'
INHERITANCE \- Autosomal recessive GROWTH Height \- Birth length below 5th percentile Weight \- Birth weight below 5th percentile Other \- Intrauterine growth retardation (IUGR) HEAD & NECK Head \- Prominent occiput Face \- Micrognathia \- 'Potter-like' facies Ears \- Low-set ears \- Dysplastic ears Nose \- Depressed nasal root \- Beaked nose Mouth \- Small mouth \- High palate \- Long-tented upper lip \- Thin vermilion borders Neck \- Short neck RESPIRATORY \- Respiratory distress \- Respiratory failure Lung \- Hypoplastic lungs \- Pneumothorax CHEST Ribs Sternum Clavicles & Scapulae \- Short sternum \- Long, thin ribs \- Hypoplastic ribs GENITOURINARY External Genitalia (Male) \- Circumferential penile groove External Genitalia (Female) \- Prominent labia minora \- Hypertrophic clitoris Internal Genitalia (Male) \- Cryptorchidism Kidneys \- Renal hypoplasia SKELETAL Spine \- Anterior rounding of lumbar vertebrae Pelvis \- Wide alar wing Limbs \- Short forearms \- Phocomelia \- Absent ulnae \- Aplastic-hypoplastic radius \- Aplastic humeri \- Absent fibulae \- Thin legs \- Humeroradial fusion Hands \- Short metacarpals Feet \- Talipes equinovarus PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios Placenta & Umbilical Cord \- Single umbilical artery Maternal \- Gestational diabetes MISCELLANEOUS \- Neonatal death ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
RENAL DYSPLASIA-LIMB DEFECTS SYNDROME
|
c1849438
| 7,702 |
omim
|
https://www.omim.org/entry/266910
| 2019-09-22T16:22:47 |
{"mesh": ["C537754"], "omim": ["266910"], "orphanet": ["3404"], "synonyms": ["Alternative titles", "RL SYNDROME"]}
|
X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome is a rare X-linked syndromic intellectual disability disorder characterized by profound intellectual disability, global developmental delay with absent speech, seizures, large joint contractures, abnormal position of thumbs and middle-age onset of cardiomegaly and atrioventricular valve abnormalities, resulting in subsequent congestive heart failure. Additional features include variable facial dysmorphism (notably large ears with overfolded helix) and large testes.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome
|
c3550913
| 7,703 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=324410
| 2021-01-23T19:11:44 |
{"omim": ["300886"]}
|
Primary peritoneal carcinoma (PPC) is a rare malignant tumor of the peritoneal cavity of extra-ovarian origin, clinically and histologically similar to advanced-stage serous ovarian carcinoma (see this term).
## Epidemiology
PPC accounts for about 10% of pelvic serous carcinomas.
## Clinical description
It is almost exclusively found in women. PPC can occur many years after oophorectomy performed for benign diseases or prophylactic oophorectomy. The tumor appears during adulthood with a mean age at diagnosis of 60 years. Clinical features include abdominal swelling, constipation, gastrointestinal disorders, nausea, vomiting, anorexia and weight loss. The tumor develops in the peritoneum and spreads to the abdomen, pelvis and ovaries.
## Etiology
Primary peritoneal carcinoma has an epithelial origin and probably derives from coelomatic embryonal epithelium. The fallopian tubes are suspected as the primary site. Women with breast cancer type 1 (BRCA1) gene mutations present an increased risk of developing a PPC.
## Diagnostic methods
Diagnosis is based on elevated cancer markers, with elevated cancer antigen 125 (CA125), and on imaging examinations such as ultrasound and chest-abdominal computed tomography (CAP-CT). Diagnosis is confirmed by biopsies performed during laparotomy or laparoscopy, especially when ovaries are normal or absent.
## Differential diagnosis
The main differential diagnosis is epithelial ovarian cancer. PPC and serous ovarian carcinoma are histologically similar, and it is often impossible to determine the organ of origin at late stages when the ovaries, abdominal cavity and fallopian tubes are all involved.
## Management and treatment
Management should be multidisciplinary and must be discussed by a panel of physicians in a specialized center. There are currently no validated recommendations on clinical management and no cytotoxic agents have been granted a European Marketing Authorization (MA) in this indication. Combination of cytoreductive surgery (visceral resections and peritonectomy procedures) with hyperthermic intraperitoneal chemotherapy (HIPEC) (off-label use) has been considered in specific patients (i.e. young patients with good general status and low tumor volume) before or after systemic chemotherapy (off-label use) if the disease does not respond to optimal cytoreductive surgery.
## Prognosis
Prognosis is poor, similar to or worse than that of ovarian carcinoma.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Primary peritoneal carcinoma
|
c1514428
| 7,704 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=168829
| 2021-01-23T18:47:18 |
{"icd-10": ["C48.2"], "synonyms": ["EOPPC", "Extra-ovarian primary peritoneal carcinoma", "PPC", "Primary peritoneal serous carcinoma", "Serous surface papillary carcinoma"]}
|
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "CNS demyelinating autoimmune diseases" – news · newspapers · books · scholar · JSTOR (June 2019)
CNS demyelinating autoimmune diseases
The demyelination of the Central Nervous System
SpecialtyNeurology, immunology
CNS demyelinating autoimmune diseases are autoimmune diseases which primarily affect the central nervous system.[1]
## Contents
* 1 Types
* 2 Presentation
* 3 Causes
* 4 Nervous System
* 5 Pathogenesis
* 6 See also
* 7 References
* 8 External links
## Types[edit]
Examples include:
* Diffuse cerebral sclerosis of Schilder
* Acute disseminated encephalomyelitis
* Acute hemorrhagic leukoencephalitis
* Multiple sclerosis (though the cause is unknown, it is sure that immune system is involved)
* Transverse myelitis
* Neuromyelitis optica
## Presentation[edit]
Since the neural impulse is inhibited in this condition it may lead to paresthesia, muscle weakness, unsteady gait, paralysis, vision loss and other motor dysfunctions.
## Causes[edit]
CNS demyelination autoimmune disease causes the myelin sheath to deteriorate since the sense of recognition of self is lost. The loss of the myelin insulation either disrupts or prevents neural conduction along the nerve cell's axon.
## Nervous System[edit]
The brain and the spinal cord are the essential components of the central nervous system and it is responsible for the integration of the signals received from the afferent nerves and initiates action. The nerve cells, known as neurons, carry impulses throughout the body and the nerve impulses are carried along the axon. These microscopic nerve fibers, where the action potential occurs, are protected by a white, fatty tissue that surrounds and insulates it, known as the myelin sheath. This insulation helps the axon of a nerve cell with the conduction and speed of the signal along the axon.
## Pathogenesis[edit]
The pathogenesis of the demyelination can vary. Some of the factors that contribute to the deteriorating of the myelin are due to inflammatory processes, acquired metabolic derangements, viral demyelination, and hypoxic-ischaemic demyelination.
## See also[edit]
* Idiopathic inflammatory demyelinating diseases \- A wider group of diseases which includes also the non-autoimmune demyelinating diseases.
* Demyelinating diseases \- Group including them all, regardless of their autoimmunity or idiopathic and inflammatory status.
## References[edit]
1. ^ "Demyelinating Autoimmune Diseases, CNS - MeSH - NCBI". Cite journal requires `|journal=` (help)
## External links[edit]
Classification
D
* MeSH: D020278
* v
* t
* e
Multiple sclerosis and other demyelinating diseases of the central nervous system
Signs and symptoms
* Ataxia
* Depression
* Diplopia
* Dysarthria
* Dysphagia
* Fatigue
* Incontinence
* Nystagmus
* Optic neuritis
* Pain
* Uhthoff's phenomenon
Investigations and diagnosis
* Multiple sclerosis diagnosis
* McDonald criteria
* Poser criteria
* Clinical
* Clinically isolated syndrome
* Expanded Disability Status Scale
* Serological and CSF
* Oligoclonal bands
* Radiological
* Radiologically isolated syndrome
* Lesional demyelinations of the central nervous system
* Dawson's fingers
Approved[by whom?] treatment
* Management of multiple sclerosis
* Alemtuzumab
* Cladribine
* Dimethyl fumarate
* Fingolimod
* Glatiramer acetate
* Interferon beta-1a
* Interferon beta-1b
* Mitoxantrone
* Natalizumab
* Ocrelizumab
* Ozanimod
* Siponimod
* Teriflunomide
Other treatments
* Former
* Daclizumab
* Multiple sclerosis research
Demyleinating diseases
Autoimmune
* Multiple sclerosis
* Neuromyelitis optica
* Diffuse myelinoclastic sclerosis
Inflammatory
* Acute disseminated encephalomyelitis
* MOG antibody disease
* Balo concentric sclerosis
* Marburg acute multiple sclerosis
* Neuromyelitis optica
* Diffuse myelinoclastic sclerosis
* Tumefactive multiple sclerosis
* Experimental autoimmune encephalomyelitis
Hereditary
* Adrenoleukodystrophy
* Alexander disease
* Canavan disease
* Krabbe disease
* Metachromatic leukodystrophy
* Pelizaeus–Merzbacher disease
* Leukoencephalopathy with vanishing white matter
* Megalencephalic leukoencephalopathy with subcortical cysts
* CAMFAK syndrome
Other
* Central pontine myelinolysis
* Marchiafava–Bignami disease
* Mitochondrial DNA depletion syndrome
Other
* List of multiple sclerosis organizations
* List of people with multiple sclerosis
* Multiple sclerosis drug pipeline
* Pathophysiology
This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CNS demyelinating autoimmune diseases
|
c0751873
| 7,705 |
wikipedia
|
https://en.wikipedia.org/wiki/CNS_demyelinating_autoimmune_diseases
| 2021-01-18T18:46:57 |
{"mesh": ["D020278"], "wikidata": ["Q5013186"]}
|
Pauci-immune glomerulonephritis (GN) without antineutrophilic cytoplasmic antibodies (ANCA) is a form of rapidly progressive glomerulonephritis comprising 10-43% of pauci-immune glomerulonephritis (see this term) and characterized by the absence of ANCA. In comparison with pauci-immune GN with ANCA (see this term), patients lacking ANCA may be younger at onset of the disease and have a shorter interval from onset of the disease to diagnosis. They have fewer extra renal manifestations (e.g. involvement of lung, eye, ear, nose and throat), fewer constitutional symptoms (e.g. fever, weight loss, muscle pain and arthralgia) and a high prevalence of nephrotic syndrome and chronic renal lesions. Their prognosis is generally poorer.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pauci-immune glomerulonephritis without ANCA
|
None
| 7,706 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97564
| 2021-01-23T17:29:43 |
{"icd-10": ["N05.7"], "synonyms": ["Antineutrophil cytoplasmic antibody-negative pauci-immune glomerulonephritis", "Pauci-immune glomerulonephritis without antineutrophil cytoplasmic antibody"]}
|
Vitreoretinopathy may refer to:
* Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a rare inherited autoimmune uveitis, first identified in 1990
* Familial exudative vitreoretinopathy, a genetic eye disorder
* Proliferative vitreoretinopathy, a disease that develops as a complication to rhegmatogenous retinal detachment
Disambiguation page providing links to topics that could be referred to by the same search term
This disambiguation page lists articles associated with the title Vitreoretinopathy.
If an internal link led you here, you may wish to change the link to point directly to the intended article.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Vitreoretinopathy
|
c1850109
| 7,707 |
wikipedia
|
https://en.wikipedia.org/wiki/Vitreoretinopathy
| 2021-01-18T19:08:16 |
{"orphanet": ["98668"], "synonyms": [], "wikidata": ["Q7937231"]}
|
Tropical theileriosis or Mediterranean theileriosis is a theileriosis of cattle from the Mediterranean and Middle East area, from Morocco to Western parts of India and China. It is a tick-borne disease, caused by Theileria annulata. The vector ticks are of the genus Hyalomma.
The most prominent symptoms are fever and lymph node enlargement. But there is a wide range of clinical manifestations, especially in enzootic areas. Among them, the Doukkala area of Morocco, where the epidemiology and symptomatology of the disease were minutely studied. [1]
The disease was once considered as "benign" in the literature, in comparison to East Coast fever. With the introduction of European breeds into the region, however, it could become of major economic incidence. [2] An efficient treatment with parvaquone, then buparvaquone became available in many countries from the mid-1990s. Animals native to endemic areas appear more tolerant to the disease, buffalos especially, appear less susceptible.[3]
## Contents
* 1 Clinical signs
* 2 Diagnosis
* 3 Treatment and control
* 4 References
* 5 External links
## Clinical signs[edit]
A high temperature (41.2°C) is a common feature in acute cases.
Body temperature is regularly higher than in any other cattle disease. Fever from 41 to 42°C is common in acute stages. Later on (day 5 to day 10 from the clinical onset), temperature will lower to a normal range (38.0–39.5°C), but the disease will continue to progress, despite a possible apparent clinical improvement (appetite comes back). Afterwards, from D10 to D15, there is a downfall stage, with hypothermia (37 to 38°C), anemia, jaundice, and heart failure. Such animals rarely recover, even with intensive treatment.
Lymph nodes are commonly enlarged and there may be episodes of blood from the nose, difficulty breathing and weight loss.[3]
Other signs, but not present in all cases are :
* Blood-tinged diarrhea, or with obvious blood clots.
* Bruxism(grinding of teeth) can be seen
* Circular raised patches of hair all over the body
* Haemorrhages in the ocular and vaginal mucous membranes
* A degree of anaemia
Diarrhea with blood clots in a calf
## Diagnosis[edit]
Lymph node enlargement in six-months-old calves in asymptomatic infestation
Lymph node enlargement and even hyperthermia can occur asymptomatically in enzootic area, during the disease season.
Clinical signs, including lymph node enlargement, anaemia, hyperthermia and history of tick infestation can lead to a suspicion of theileriosis
Definitive diagnosis relies on the observation of the pirolplasm stages of the organism in the erythrocytes in blood smears stained with Romanowsky stains. Lymph node aspirates can also be examined for the presence of 'Kock's Blue Bodies' which are schizont stages in lymphocytes. Necropsy reveals 'punched out ulcers' in the abomasum and greyish raised 'infarcts' on kidneys. Numerous serological tests like ELISA, and indirect immunofluorescence test and PCR can also help diagnosis.[3]
Theileria-annulata-piroplasms-cattle
## Treatment and control[edit]
Buparvaquone, halofuginone and tetracycline and butalex and oxytetracycline have all shown to be effective. Tick control should be considered, but resistance to parasiticide products may be increasing.[3] There are various options for controlling ticks of domestic animals, including: topical application of parasiticidal chemicals in dip baths or spray races or pour-on formulations, spraying parasiticides on walls of cattle pens, and rendering the walls of cattle pens smooth with mortar to stop ticks molting there. Selection of cattle for good ability to acquire immune resistance to ticks is potentially effective.
Endemic stability is a state where animals are affected at a low levels or not as susceptible to the disease, and this may be encouraged in endemic areas.[3]
Vaccination is available and should be performed in breeds that are susceptible to infection.[3]
Live attenuated vaccine are being used in many countries like India, Iran, Turkey etc. Which is a basically a Lymphocyte infected with Theileria annulata schizont stage and passaged for attenuation.
## References[edit]
1. ^ N. EL HAJ, M. KACHANI, M. BOUSLIKHANE, H. OUHELLI, A.T. AHAMI, J. KATENDE et S.P. MORZARIA. Séro-épidémiologie de la theilériose à Theileria annulata et de la babésiose à Babesia bigemina au Maroc[permanent dead link].
2. ^ With mortalities up to 50 to 80 percent in the 1980s (L. Mahin).
3. ^ a b c d e f Theileriosis - Cattle reviewed and published by WikiVet, accessed 11 October 2011.
* Chakraborty, S.; Roy, S.; Mistry, H.U.; Murthy, S.; George, N.; Bhandari, V.; Sharma, P. (2017). "Potential Sabotage of Host Cell Physiology by Apicomplexan Parasites for Their Survival Benefits". Frontiers in Immunology. 8: 1261. doi:10.3389/fimmu.2017.01261. PMC 5645534. PMID 29081773.
## External links[edit]
* The disease in the Merck Veterinary Manual
* Lucien Mahin's web-page on his clinical experience with Theileria annulata disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Tropical theileriosis
|
c0276858
| 7,708 |
wikipedia
|
https://en.wikipedia.org/wiki/Tropical_theileriosis
| 2021-01-18T18:54:08 |
{"wikidata": ["Q6103315"]}
|
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (November 2017)
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Suppurative granuloma" – news · newspapers · books · scholar · JSTOR (February 2017) (Learn how and when to remove this template message)
Supperative granuloma are chronic inflammatory cells at periphery with central abscess formation composed of histiocytes and multinucleated giant cells with central collections of neutrophils.
Often caused by Bartonella henselae (cat scratch disease).
This article related to pathology is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Suppurative granuloma
|
c3887677
| 7,709 |
wikipedia
|
https://en.wikipedia.org/wiki/Suppurative_granuloma
| 2021-01-18T18:36:10 |
{"umls": ["C3887677"], "wikidata": ["Q7644427"]}
|
Hypertrichosis-acromegaloid facial appearance syndrome (HAFF) is a very rare multiple congenital abnormality syndrome manifesting from birth with progressive hypertrichosis congenita terminalis (thick scalp hair extending onto the forehead with generalized increased body hair) associated with a typical acromegaloid facial appearance (thick eyebrows, prominent supraorbital ridges, broad nasal bridge, anteverted nares, long and large philtrum, and prominent mouth with full lips) appearing during childhood. HAFF seems to belong to a spectrum of phenotypes with the clinically overlapping acromegaloid facial appearance syndrome and hypertrichotic osteochondrodysplasia, Cantù type (see these terms).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hypertrichosis-acromegaloid facial appearance syndrome
|
c0268700
| 7,710 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=966
| 2021-01-23T18:35:05 |
{"icd-10": ["Q87.0"], "synonyms": ["HAFF", "Hypertrichosis-acromegaloid facial features syndrome", "Hypertrichosis-coarse face syndrome"]}
|
A number sign (#) is used with this entry because congenital secretory chloride diarrhea, referred to here as DIAR1, is caused by homozygous mutation in the SLC26A3 gene (126650) on chromosome 7q31.
Description
Congenital secretory chloride diarrhea is an autosomal recessive form of severe chronic diarrhea characterized by excretion of large amounts of watery stool containing high levels of chloride, resulting in dehydration, hypokalemia, and metabolic alkalosis. The electrolyte disorder resembles the renal disorder Bartter syndrome (see 607364), except that chloride diarrhea is not associated with calcium level abnormalities (summary by Choi et al., 2009).
### Genetic Heterogeneity of Diarrhea
Other forms of diarrhea include DIAR2 (251850), caused by mutation in the MYO5B gene (606540) on 18q21; DIAR3 (270420), caused by mutation in the SPINT2 gene (605124) on 19q13; DIAR4 (610370), caused by mutation in the NEUROG3 gene (604882) on 10q21; DIAR5 (613217), caused by mutation in the EPCAM gene (185535) on 2p21; DIAR6 (614616), caused by mutation in the GUCY2C gene (601330) on 12p12; DIAR7 (615863) caused by mutation in the DGAT1 gene (604900) on 8q24; DIAR8 (616868), caused by mutation in the SLC9A3 gene (182307) on 5p15; DIAR9 (618168), caused by mutation in the WNT2B gene (601968) on 1p13; and DIAR10 (618183), caused by mutation in the PLVAP gene (607647) on 19p13.
Clinical Features
This disorder was first described by Gamble et al. (1945) and Darrow (1945). Voluminous watery stools containing an excess of chloride are present from a few weeks of age. The children are often premature. Hydramnios, presumably due to intrauterine diarrhea (Holmberg et al., 1975), may complicate pregnancy. Indeed, polyhydramnios is probably an invariant feature.
Pasternack and Perheentupa (1966) described vascular changes resembling those of hypertensive angiopathy in 7 children, aged 1 to 42 months at the time of biopsy. All were normotensive. Kidney and muscle were biopsied.
Lubani et al. (1989) identified 16 affected Kuwaiti children over a 7-year period. All children had a shortened gestational period, abdominal distention, and chronic diarrhea. The serum electrolytes in all patients before treatment showed hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis. Diagnosis was confirmed by a stool chloride content that exceeded the sum of fecal sodium and potassium. In chloride diarrhea, juxtaglomerular hyperplasia, hyperreninemia and hyperaldosteronism, leading to hyperkaluria and hypokalemia, simulate the Bartter syndrome (see 241200). As in the latter disorder, inhibitors of prostaglandin synthetase have beneficial effects (Minford and Barr, 1980). In the intestinal brush border there is both an Na+/H+ and a chloride/bicarbonate exchange mechanism. A defect in either can impede NaCl absorption and lead to secretory diarrhea. The latter exchange mechanism is defective in chloride diarrhea; the former is deranged in sodium diarrhea (270420).
Inheritance
Both sexes have been affected and 2 sibs appear to have been affected in several families (Kelsey, 1954; Perheentupa et al., 1965), suggesting autosomal recessive inheritance.
Hoglund et al. (1994) reported paternal isodisomy for chromosome 7 in a female with congenital chloride diarrhea. She had inherited only paternal alleles at 10 loci and was homozygous for another 10 chromosome 7 loci studied. Physical status and laboratory tests were normal except for mild high-frequency sensorineural hearing loss. Most remarkable was the fact that she was of normal stature. Maternal uniparental disomy for chromosome 7 has been identified in 3 patients with recessive diseases: 2 patients with cystic fibrosis (Spence et al., 1988 and Voss et al., 1989) and 1 patient with osteogenesis imperfecta (Spotila et al., 1992). Both patients with CF had uniparental isodisomy for the complete chromosome, whereas the third patient displayed heterozygosity at the IGFBP1 locus (146730), consistent with uniparental heterodisomy. Severe growth retardation, present in all 3 patients with maternal uniparental disomy for chromosome 7, suggested that there may be imprinted growth-related genes on the maternal chromosome 7. Alternatively, although less likely, short stature could be due to homozygosity for a recessive mutation that occurs at sufficient frequency to be seen in all 3 patients. The lack of growth retardation in the patient reported by Hoglund et al. (1994) suggests that the paternal chromosome 7 lacks the suggested maternal imprinting effect on growth. The patient reported by Hoglund et al. (1994) was a 23-year-old female attending business school. The mother and father were 39 and 44 years of age, respectively, at the time of her birth. CLD was diagnosed at the age of 8 days on the basis of a high fecal chloride content.
Clinical Management
In patients with congenital chloridorrhea, the oral intake of chloride, sodium, and potassium must exceed fecal output (i.e., there must be a positive gastrointestinal balance) so that obligatory losses in sweat can be replaced. A positive balance can best be insured by a high intake of chloride, even though it exacerbates diarrhea. Aichbichler et al. (1997) concluded that suppression of gastric chloride secretion by a proton-pump inhibitor, omeprazole, reduces fecal electrolyte losses in patients with this disorder and thus promotes a positive gastrointestinal balance. However, this treatment does not reduce the need for careful monitoring of dietary intake, serum electrolyte concentrations, and urinary chloride excretion. Their patient was a 34-year-old man who had had severe diarrhea since birth. In early childhood he had been hospitalized many times because of volume depletion and hypokalemia. Early growth and physical development were delayed. His sibs were highly antagonistic toward him, because he would have diarrhea at any time and smelled bad. After the age of 4 years, he was raised by foster parents. As an adult, he had great difficulty obtaining and keeping a job because of diarrhea, fecal incontinence, and the need for frequent hospitalizations. He had an average of 6 stools per day, with as many as 12 on some days. The stools were large in volume and liquid. Most bowel movements were associated with urgency and many with fecal incontinence. During 8 months of follow-up on omeprazole, the number of stools decreased to 2 to 4 per day, with no fecal incontinence. With potassium supplementation he had only occasional episodes of hypokalemia and the patient returned to work.
Mapping
By studies of linkage disequilibrium as well as genetic linkage in a small number of Finnish families, Kere et al. (1993) obtained initial results suggestive of linkage between CLD and the CFTR gene (602421), which is mutant in cystic fibrosis (219700). However, extended analyses in 8 families established close linkage to chromosome 7 markers proximal to CFTR. Multipoint analyses mapped CLD at D7S496 with a maximum lod score of 9.33. Kere et al. (1993) concluded that the CLD gene is close to but distinct from CFTR. Strong allelic association (linkage disequilibrium) with D7S496 in Finnish patients was consistent with the hypothesis of a single founder.
To identify the CLD gene, Hoglund et al. (1996) constructed and refined a physical map based on a 2.7-Mb YAC contig around D7S496 and identified 2 candidate genes. Four known genes were established: SLC26A3 (126650), PRKAR2B (176912), LAMB1 (150240), and DLD (238331). SLC26A3 is expressed in the gut and encodes a protein with sequence homology to anion transporters; PRKAR2B encodes a regulatory subunit for protein kinase A. Both genes map within 450 kb of D7S496 (which is linked to CLD), making them functionally and positionally relevant candidates for the site of the mutation in CLD.
Molecular Genetics
Hoglund et al. (2001) stated that a total of 3 founder and 17 private mutations in the SLC26A3 gene (see, e.g., 126650.0001) underlying congenital chloride diarrhea had been described in various ethnic groups. They screened for mutations in 7 unrelated families with CLD and found 7 novel mutations as well as 2 previously identified ones. They reported for the first time rearrangement mutations in SLC26A3 (see, e.g., 126650.0004). Molecular features predisposing SLC26A3 for the 2 rearrangements may include repetitive elements and palindromic-like sequences.
Makela et al. (2002) noted that the only extraintestinal tissues showing SLC26A3 expression are eccrine sweat glands and seminal vesicles. They presented a summary of published mutations and polymorphisms of the SLC26A3 gene and reported 2 novel mutations of the gene: a 13-bp deletion (126650.0007) and a trp462-to-ter change (W462X; 126650.0008).
Choi et al. (2009) used whole-exome capture and massively parallel DNA sequencing to identify a homozygous pathogenic mutation in the SLC26A3 gene in a Turkish infant with congenital chloride diarrhea who was initially thought to have renal Bartter syndrome. Sequencing this gene in 39 additional patients referred with a suspected diagnosis of Bartter syndrome identified recessive SLC26A3 mutations in 5 patients. All except 1 presented in infancy with watery diarrhea associated with hypokalemia, increased serum bicarbonate, and high aldosterone; the last patient presented at age 6 years. High stool chloride was documented in 2 patients studied. Choi et al. (2009) emphasized the utility of this novel approach for the identification of pathogenic mutations.
Population Genetics
Holmberg and Perheentupa (1980) estimated that 31 cases of congenital chloride diarrhea in 21 families have been identified in Finland as compared with 30 cases in 24 families elsewhere. Lubani et al. (1989) identified 16 affected Kuwaiti children over a 7-year period, giving an estimated incidence of 7.6 per 100,000 live births.
Hoglund et al. (1996) demonstrated that the Finnish form of congenital chloride diarrhea is caused by a homozygous mutation in the SLC26A3 gene. Homozygosity for the same mutation, deletion of GGT(val) of codon 317 (126650.0001), was found in all 32 patients studied. The reverse use of the Luria-Delbruck equation resulted in an estimation of the age of the mutation. The calculation gave an average age of 19 generations, with a range of 13 to 25. This estimate was in agreement with the population history and suggested that the spread of the val317-to-del mutation in the expanding subpopulation in eastern Finland started 400 to 450 years ago.
Makela et al. (2002) described the geographic and population distributions of 3 founder mutations in the SLC26A3 gene: the Finnish V317del mutation (126650.0001), the Polish I675-676ins mutation (126650.0005), and the Arabic gly187-to-ter mutation (G187X; 126650.0006). They also tabulated genetic disorders with congenital or neonatal diarrhea as a main symptom.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive \- Poor growth CARDIOVASCULAR Vascular \- Hypotension due to volume depletion ABDOMEN External Features \- Abdominal distention Gastrointestinal \- Diarrhea, watery \- Diarrhea contains high chloride levels GENITOURINARY Kidneys \- Juxtaglomerular hyperplasia due to activation of the renin-aldosterone axis METABOLIC FEATURES \- Dehydration \- Metabolic alkalosis PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios Delivery \- Premature birth LABORATORY ABNORMALITIES \- Hypokalemia \- Hyponatremia \- Hypochloremia \- Increased serum bicarbonate \- Increased aldosterone \- Increased plasma renin activity MISCELLANEOUS \- Onset in first weeks to months of life \- Chronic disorder \- Electrolyte imbalances can mimic renal Bartter syndrome ( 601678 ) MOLECULAR BASIS \- Caused by mutation in the solute carrier family 26, member 3 gene (SLC26A3, 126650.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
DIARRHEA 1, SECRETORY CHLORIDE, CONGENITAL
|
c0267662
| 7,711 |
omim
|
https://www.omim.org/entry/214700
| 2019-09-22T16:29:46 |
{"doid": ["0060296"], "mesh": ["C536210"], "omim": ["214700"], "orphanet": ["53689"], "synonyms": ["Alternative titles", "CHLORIDE DIARRHEA, CONGENITAL, FINNISH TYPE", "CHLORIDORRHEA, CONGENITAL"]}
|
X-linked Charcot-Marie-Tooth disease type 1 is a rare, genetic, peripheral sensorimotor neuropathy characterized by an X-linked dominant inheritance pattern and the childhood-onset (within the first decade in males) of progressive, distal, moderate to severe muscle weakness and atrophy in lower extremities and intrinsic hand muscles, pes cavus, bilateral foot drop, reduced or absent tendon reflexes, as well as mild to moderate sensory impairment in lower extremities. Females tend to have milder manifestations or may be asymptomatic. Sensorineural deafness and central nervous system involvement have also been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
X-linked Charcot-Marie-Tooth disease type 1
|
c0393808
| 7,712 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101075
| 2021-01-23T17:30:36 |
{"gard": ["1258"], "mesh": ["C535919"], "omim": ["302800"], "umls": ["C0393808"], "icd-10": ["G60.0"], "synonyms": ["CMT1X", "CMTX1"]}
|
Spastic hemiplegia
Spastic hand
SpecialtyNeurology
Spastic hemiplegia is a neuromuscular condition of spasticity that results in the muscles on one side of the body being in a constant state of contraction. It is the "one-sided version" of spastic diplegia. It falls under the mobility impairment umbrella of cerebral palsy. About 20–30% of people with cerebral palsy have spastic hemiplegia.[1] Due to brain or nerve damage, the brain is constantly sending action potentials to the neuromuscular junctions on the affected side of the body. Similar to strokes, damage on the left side of the brain affects the right side of the body and damage on the right side of the brain affects the left side of the body. Other side can be effected for lesser extent. The affected side of the body is rigid, weak and has low functional abilities.[2] In most cases, the upper extremity is much more affected than the lower extremity. This could be due to preference of hand usage during early development. If both arms are affected, the condition is referred to as double hemiplegia. Some patients with spastic hemiplegia only suffer minor impairments, where in severe cases one side of the body could be completely paralyzed. The severity of spastic hemiplegia is dependent upon the degree of the brain or nerve damage.[1]
## Contents
* 1 Causes
* 2 Diagnosis
* 3 Treatment
* 4 Complications
* 5 Epidemiology
* 6 References
## Causes[edit]
There are many different brain dysfunctions that can account for the cause for spastic hemiplegia. Spastic hemiplegia occurs either at birth or in the womb. The cause can be all types of strokes, head injuries, hereditary diseases, brain injuries and infections.[3] Malformations of the veins or arteries in any part of the body can lead to spastic hemiplegia. The artery most commonly affected is the middle cerebral artery. Unborn and newborn babies are susceptible to strokes.[1] Leukodystrophies are a group of hereditary diseases that are known to cause spastic hemiplegia. Brain infections that cause spastic hemiplegia are meningitis, multiple sclerosis, and encephalitis.[4] The spasticity occurs when the afferent pathways in the brain are compromised and the communication between the brain to the motor fibers is lost. When the inhibitory signals to deactivate the stretch reflex is lost the muscle remains in a constantly contracted state. With spastic hemiplegia, one upper extremity and one lower extremity is affected, so cervical, lumbar and sacral segments of the spinal column can be affected.[1]
## Diagnosis[edit]
Infants with spastic hemiplegia may develop a hand preference earlier than is typical.[5]
## Treatment[edit]
Main article: Management of cerebral palsy
There is no known cure for cerebral palsy, however, there is a large array of treatments proven effective at improving quality of life and relieving some of the symptoms associated with CP, especially SHCP. Some treatments are aimed at improving mobility, strengthening muscle and improving coordination. Although CP is due to permanent damage and is not progressive in nature, without treatment the symptoms can become worse, intensifying in pain and severity, and create complications that were not initially present. Some treatments are preventative measures to help prevent further complications, such as complete paralysis of the arm due to non-use and subsequent worsening hypertonia and joint contracture. Others forms of treatment are corrective in nature. Many treatments target symptoms that are indirectly related to or caused by the SHCP. Many of these treatments are common for other forms of CP as well.[6] Treatment is individualized based on each case and the specific needs of the patient. Treatments are often combined with other forms of treatment and a long term treatment plan is created and continuously evaluated. Treatment can include the following:
* Physical therapy – Physical therapy is the most common form of treatment (source needed). It may include sensory stimulation, stretching, strengthening and positioning. Constraint-induced movement therapy is a newer form of physical therapy for SHCP that involves casting or splinting the unaffected arm to promote the use of the affected arm (Taub). The theory behind constraint-induced movement therapy is that new neural pathways are created. Alternative forms of physical therapy include yoga and dance. Physical therapy may also include the use of braces while not actively involved with the therapist.
* Occupational therapy – Occupational therapy evaluates and treats patients through selected activities in order to enable people to function as effectively and independently as possible in daily life. Occupational therapy is geared toward the individual to achieve optimal results and performance while learning to cope with their disability.
* Speech therapy – Due to difficulties in speech, speech therapy is often necessary. Aside from helping with understanding language and increasing communication skills, speech therapists can also assist children that have difficulty eating and drinking.
* Behavioral therapy — Psychotherapy and counseling are heavily used in the treatment of individuals with SHPD to help them cope emotionally with their needs and frustrations. Counseling through social work can be very beneficial for social issues and adjustments to society. Psychotherapy becomes a more important aspect of therapy when more serious issues such as depression become problematic. Play therapy is a common treatment for all young children with or without disabilities but can be very useful in helping children with SHCP. This therapy again is individualized geared to improve emotional and social development; reduce aggression; improve cooperation with others; assist a child in processing a traumatic event or prepare for an upcoming event such as surgery.
* Surgery – Although surgery may become necessary in some cases, physical therapy and the consistent use of braces can help mitigate the need for surgery. Surgical procedures are painful with long and difficult recoveries and do not cure the condition. Most common is a surgery that effectively lengthens the muscle. This type of surgery is usually performed on the legs, but can be performed on the arms as well. Surgeries also may be necessary to realign joints. Other, less popular surgical techniques try to reduce spasticity by severing selected overactive nerves that control muscles. This procedure, known as selective dorsal root rhizotomy, is still somewhat controversial and is generally used only on the lower extremities of severe cases. Other experimental surgical techniques are also being investigated. The benefits of surgery can also be negated or reversed if the patient does not participate in physical therapy and braces (or casts) are not worn regularly.
* Medicinal – Medication targeting symptoms associated with spasticity is also a relatively new treatment that is utilized but is still in the early stages of development. Drugs such as baclofen, benzodiazepines (e.g., diazepam), tizanidine, and sometimes dantrolene have shown promise in the effort to diminish spasticity.[7] Botulinum toxin ("Botox") type A may reduce spasticity a few months at a time and has frequently been considered a beneficial treatment for children with SHCP and other forms of CP. Botox has been shown to be especially beneficial to reducing spasticity in the gastrocnemius (calf) muscle. This therapy can improve range of motion, reduce deformity, improve response to occupational and physical therapy, and delay the need for surgery. Botox injections have also shown advantages for upper extremities. There is still some doubt for the effectiveness, and some side effects to the relaxed muscles have been a loss of strength for patients with some muscle control. Casting, in conjunction with Botox injections, maybe an additional option for better results.[7] Research is constantly investing in new improvements and more experimental therapy and treatment.
## Complications[edit]
The muscle spasticity can cause gait patterns to be awkward and jerky. The constant spastic state of the muscle can lead to bone and tendon deformation, further complicating the patient's mobility. Many patients with spastic hemiplegia are subjected to canes, walkers and even wheelchairs. Due to the decrease in weight bearing, patients are at a higher risk of developing osteoporosis.[8] An unhealthy weight can further complicate mobility. Patients with spastic hemiplegia are a high risk for experiencing seizures.[9] Oromotor dysfunction puts patients at risk for aspiration pneumonia. Visual field deficits can cause impaired two-point discrimination. Many patients experience the loss of sensation in the arms and legs on the affected side of the body.[8] Nutrition is essential for the proper growth and development for a child with spastic hemiplegia.
## Epidemiology[edit]
The incidence of cerebral palsy has increased in the past 40 years. It has been estimated that in the United States cerebral palsy occurs in 4 out every 1000 births.[10] Of these births about 20–30% of them have spastic hemiplegia. Spasticity overall, is the more common type of cerebral palsy, whereas non-spastic cerebral palsy is less common. Studies show that spastic type cerebral palsy is on the rise, and the occurrence of diplegia type is decreasing. The prevalence of cerebral palsy is higher in areas of low socioeconomic status. This could potentially be because cerebral palsy incidence increases as birth weight decreases.[11]
## References[edit]
1. ^ a b c d Cerebral palsy at eMedicine
2. ^ Brashear, Allison (2010). Spasticity: Diagnosis and Management. New York: Demos Medical.
3. ^ Tardieu C, Huet de la Tour E, Bret MD, Tardieu G (March 1982). "Muscle hyperextensibility in children with cerebral palsy: I. Clinical and experimental observations". Arch Phys Med Rehabil. 63 (3): 97–102. PMID 7073456.
Tardieu G, Tardieu C, Colbeau-Justin P, Lespargot A (March 1982). "Muscle hyperextensibility in children with cerebral palsy: II. Therapeutic implications". Arch Phys Med Rehabil. 63 (3): 103–7. PMID 7073451.
4. ^ Green LB, Hurvitz EA (November 2007). "Cerebral palsy". Phys Med Rehabil Clin N Am. 18 (4): 859–82, vii. doi:10.1016/j.pmr.2007.07.005. PMID 17967366.
5. ^ "Facts About Cerebral Palsy - United Cerebral Palsy of the Golden Gate - UCPGG". United Cerebral Palsy of the Golden Gate - UCPGG. Retrieved 28 February 2017.
6. ^ Miller, Freeman; Steven J. Bachrach, eds. (2006). Cerebral Palsy: The Complete Guide for Caregiving 2nd Edition. Baltimore: Johns Hopkins University Press. ISBN 0-8018-8354-7.
7. ^ a b Taub E, Ramey SL, DeLuca S, Echols K (February 2004). "Efficacy of constraint-induced movement therapy for children with cerebral palsy with asymmetric motor impairment". Pediatrics. 113 (2): 305–12. doi:10.1542/peds.113.2.305. PMID 14754942.
8. ^ a b Cerebral Palsy~clinical at eMedicine
9. ^ el-Abd MA, Ibrahim IK (March 1994). "Impaired afferent control in patients with spastic hemiplegia at different recovery stages: contribution to gait disorder". Arch Phys Med Rehabil. 75 (3): 312–7. doi:10.1016/0003-9993(94)90035-3. PMID 8129585.
10. ^ https://www.cdc.gov/ncbddd/cp/data.html
11. ^ Odding E, Roebroeck ME, Stam HJ (February 2006). "The epidemiology of cerebral palsy: incidence, impairments and risk factors". Disabil Rehabil. 28 (4): 183–91. doi:10.1080/09638280500158422. PMID 16467053.
* v
* t
* e
Cerebral palsy
Symptoms and signs
Spasticity
* Upper motor neuron lesion
* Spastic cerebral palsy
* Scissor gait
* Spastic diplegia
* Spastic hemiplegia
* Spastic quadriplegia
Ataxia and others
* Ataxic cerebral palsy
* Dyskinetic cerebral palsy
Diagnosis
General movements assessment
Measurement scales
* Gross Motor Function Classification System - Expanded & Revised (gross motor function)
* Manual Ability Classification System (manual dexterity)
* Communication Function Classification System (communication)
* Modified Ashworth scale (spasticity)
Management
* Management of cerebral palsy
* Selective percutaneous myofascial lengthening
* Rhizotomy
Other
* People with cerebral palsy
* Cerebral palsy organizations
* Works about cerebral palsy and other paralytic syndromes
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Spastic hemiplegia
|
c0154694
| 7,713 |
wikipedia
|
https://en.wikipedia.org/wiki/Spastic_hemiplegia
| 2021-01-18T18:40:51 |
{"gard": ["10448"], "mesh": ["D006429"], "umls": ["C0154694"], "wikidata": ["Q7573994"]}
|
A rare bone development disorder characterized by abnormal bowing of the ulna and subsequent non-healing fracture with formation of a false joint (pseudoarthrosis), instability and angulation at the pseudoarthrosis site, and shortening of the forearm. Additional signs and symptoms include concomitant bowing of the radius, abnormalities of the humeroulnar joint, and limited pronation or supination of the forearm. Neurofibromatosis type 1 and osteofibrous dysplasia are frequently associated.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Congenital pseudoarthrosis of the ulna
|
None
| 7,714 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=295026
| 2021-01-23T17:00:33 |
{"icd-10": ["Q74.0"], "synonyms": ["Congenital pseudarthrosis of the ulna"]}
|
Warmblood Fragile Foal Syndrome (WFFS) is a genetically induced disorder seen in horses. At first it was studied in Warmblood horses, but it is also present in Thoroughbreds, and potentially in any breed with Thoroughbred ancestry or outcrossing such as Quarter Horses, Standardbreds, and Morgans. It is autosomal recessive, so both sire and dam must be carriers for a foal to be affected. Foals with WFFS are naturally aborted, stillborn, or euthanized. WFFS is a genetic defect of connective tissue and foals born with it have hyper-extendible, abnormally thin, fragile skin that rips easily (similar to epidermolysis bullosa in humans).[1]
It is associated with mutations in the gene coding for Lysyl hydroxylase 1 that result in a non functional enzyme.
A genetic test for Warmblood Fragile Foal Syndrome Type 1 was made commercially available in 2013. Approximately 9–11% of Warmblood horses are carriers, and a lower carrier frequency in Thoroughbreds and Knabstruppers.[2]
Horses heterogynous for WFFS are phenotypically normal, so genetic testing is necessary to prevent breeding carriers.
## References[edit]
1. ^ Monthoux C, de Brot S, Jackson M, Bleul U, Walter J (January 2015). "Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome". BMC Veterinary Research. 11: 12. doi:10.1186/s12917-015-0318-8. PMC 4327794. PMID 25637337.
2. ^ "WFFS". www.vgl.ucdavis.edu. Retrieved 2019-05-03.
## External links[edit]
* "Warmblood Fragile Foal Syndrome Type 1". University of California/UCDavis.
This equine-related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Warmblood fragile foal syndrome
|
None
| 7,715 |
wikipedia
|
https://en.wikipedia.org/wiki/Warmblood_fragile_foal_syndrome
| 2021-01-18T19:03:38 |
{"wikidata": ["Q30314412"]}
|
Synovial sarcoma is a rare and aggressive soft tissue sarcoma. In the early stages of the condition, it may cause no noticeable signs or symptoms. However, as the tumor grows larger, affected people may notice a lump or swelling. In some cases, the tumor can limit range of motion or cause numbness and/or pain if it presses on nearby nerves. Although synovial sarcoma does not have a clearly defined cause, genetic factors are believed to influence the development of this disease. Cells in these tumors are usually characterized by the presence of a translocation involving chromosomes X and 18. This translocation is specific to synovial sarcoma and is often used to diagnose the condition. Treatment generally includes a combination of surgery, radiation therapy and/or chemotherapy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Synovial sarcoma
|
c0039101
| 7,716 |
gard
|
https://rarediseases.info.nih.gov/diseases/7721/synovial-sarcoma
| 2021-01-18T17:57:26 |
{"mesh": ["D013584"], "omim": ["300813"], "umls": ["C0039101"], "orphanet": ["3273"], "synonyms": ["Synovial cell sarcoma", "Synovialosarcoma"]}
|
Ichthyosis acquisita
Other namesAcquired ichthyosis
SpecialtyDermatology
Ichthyosis acquisita is a disorder clinically and histologically similar to ichthyosis vulgaris.[1]:565
## Contents
* 1 Presentation
* 1.1 Associated conditions
* 2 See also
* 3 References
* 4 External links
## Presentation[edit]
### Associated conditions[edit]
The development of ichthyosis in adulthood can be a manifestation of systemic disease, and it has been described in association with malignancies, drugs, endocrine and metabolic disease, HIV, infection, and autoimmune conditions.[2]:494
It usually is associated with people who have Hodgkin's disease but it is also occurs in people with mycosis fungoides, other malignant sarcomas, Kaposi's sarcoma and visceral carcinomas. It can occur in people suffering from leprosy, AIDS, tuberculosis, and typhoid fever.[citation needed]
## See also[edit]
* Ichthyosis
* Confluent and reticulated papillomatosis of Gougerot and Carteaud
* 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. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
## External links[edit]
Classification
D
* ICD-10: L85.0
* ICD-9-CM: 701.1
* MeSH: C538175
* v
* t
* e
Cutaneous keratosis, ulcer, atrophy, and necrobiosis
Epidermal thickening
* keratoderma: Keratoderma climactericum
* Paraneoplastic keratoderma
* Acrokeratosis paraneoplastica of Bazex
* Aquagenic keratoderma
* Drug-induced keratoderma
* psoriasis
* Keratoderma blennorrhagicum
* keratosis: Seborrheic keratosis
* Clonal seborrheic keratosis
* Common seborrheic keratosis
* Irritated seborrheic keratosis
* Seborrheic keratosis with squamous atypia
* Reticulated seborrheic keratosis
* Dermatosis papulosa nigra
* Keratosis punctata of the palmar creases
* other hyperkeratosis: Acanthosis nigricans
* Confluent and reticulated papillomatosis
* Callus
* Ichthyosis acquisita
* Arsenical keratosis
* Chronic scar keratosis
* Hyperkeratosis lenticularis perstans
* Hydrocarbon keratosis
* Hyperkeratosis of the nipple and areola
* Inverted follicular keratosis
* Lichenoid keratosis
* Multiple minute digitate hyperkeratosis
* PUVA keratosis
* Reactional keratosis
* Stucco keratosis
* Thermal keratosis
* Viral keratosis
* Warty dyskeratoma
* Waxy keratosis of childhood
* other hypertrophy: Keloid
* Hypertrophic scar
* Cutis verticis gyrata
Necrobiosis/granuloma
Necrobiotic/palisading
* Granuloma annulare
* Perforating
* Generalized
* Subcutaneous
* Granuloma annulare in HIV disease
* Localized granuloma annulare
* Patch-type granuloma annulare
* Necrobiosis lipoidica
* Annular elastolytic giant-cell granuloma
* Granuloma multiforme
* Necrobiotic xanthogranuloma
* Palisaded neutrophilic and granulomatous dermatitis
* Rheumatoid nodulosis
* Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction
Foreign body granuloma
* Beryllium granuloma
* Mercury granuloma
* Silica granuloma
* Silicone granuloma
* Zirconium granuloma
* Soot tattoo
* Tattoo
* Carbon stain
Other/ungrouped
* eosinophilic dermatosis
* Granuloma faciale
Dermis/
localized CTD
Cutaneous lupus
erythematosus
* chronic: Discoid
* Panniculitis
* subacute: Neonatal
* ungrouped: Chilblain
* Lupus erythematosus–lichen planus overlap syndrome
* Tumid
* Verrucous
* Rowell's syndrome
Scleroderma/
Morphea
* Localized scleroderma
* Localized morphea
* Morphea–lichen sclerosus et atrophicus overlap
* Generalized morphea
* Atrophoderma of Pasini and Pierini
* Pansclerotic morphea
* Morphea profunda
* Linear scleroderma
Atrophic/
atrophoderma
* Lichen sclerosus
* Anetoderma
* Schweninger–Buzzi anetoderma
* Jadassohn–Pellizzari anetoderma
* Atrophoderma of Pasini and Pierini
* Acrodermatitis chronica atrophicans
* Semicircular lipoatrophy
* Follicular atrophoderma
* Linear atrophoderma of Moulin
Perforating
* Kyrle disease
* Reactive perforating collagenosis
* Elastosis perforans serpiginosa
* Perforating folliculitis
* Acquired perforating dermatosis
Skin ulcer
* Pyoderma gangrenosum
Other
* Calcinosis cutis
* Sclerodactyly
* Poikiloderma vasculare atrophicans
* Ainhum/Pseudo-ainhum
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ichthyosis acquisita
|
c0263386
| 7,717 |
wikipedia
|
https://en.wikipedia.org/wiki/Ichthyosis_acquisita
| 2021-01-18T18:29:55 |
{"gard": ["476"], "mesh": ["C538175"], "umls": ["C0263386"], "icd-9": ["701.1"], "icd-10": ["L85.0"], "orphanet": ["454"], "wikidata": ["Q5986446"]}
|
This is a red furrow which extends across the nose just proximal to the alae nasi. It is usually noticed early in childhood and at that stage may have a rose color. Anderson (1961) observed 2 extensively affected families. An instance of male-to-male transmission occurred in one.
Nose \- Red furrow across the nose proximal to the alae nasi Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
NASAL GROOVE, FAMILIAL TRANSVERSE
|
c1834370
| 7,718 |
omim
|
https://www.omim.org/entry/161500
| 2019-09-22T16:37:37 |
{"omim": ["161500"]}
|
## Clinical Features
Brown et al. (1979) described longstanding, multiple, subcutaneous nodules with the histopathologic characteristics of rheumatoid nodules, in 2 males without clinical or serologic evidence of rheumatic disease. No abnormality of leukocyte function was found. One patient had a positive family history with 7 persons (5 males) in 4 sibships of 3 generations affected. The nodules were located on the elbows, hands, heels and shin. Seemingly, only the proband was studied in the multiply affected family.
Joints \- No clinical evidence of rheumatoid arthritis Limbs \- Longstanding, multiple, subcutaneous nodules Lab \- Histopathology characteristic of rheumatoid nodules \- No serologic evidence of rheumatic disease \- No abnormality of leukocyte function Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
RHEUMATOID NODULOSIS
|
c0035450
| 7,719 |
omim
|
https://www.omim.org/entry/180350
| 2019-09-22T16:35:08 |
{"mesh": ["D012218"], "omim": ["180350"], "icd-10": ["M06.3"]}
|
A number sign (#) is used with this entry because of evidence that Wiskott-Aldrich syndrome-2 (WAS2) is caused by homozygous mutation in the WIPF1 gene (602357) on chromosome 2q31. One such patient has been reported.
For a discussion of genetic heterogeneity of Wiskott-Aldrich syndrome, see WAS (301000).
Clinical Features
Conley et al. (1992) raised the possibility of the existence of an autosomal recessive form of Wiskott Aldrich syndrome. They observed an 8-year-old girl with a disorder phenotypically identical to the disorder in males with an X-linked mutation (WAS; 301000). Cytogenetic studies showed no structural abnormalities of the X chromosome and X-chromosome inactivation analysis showed that both X chromosomes could function as the active X.
Lanzi et al. (2012) reported an 11-day-old female Moroccan infant with Wiskott-Aldrich syndrome-2. She was born to consanguineous parents who had previously lost a daughter at age 4 months with recurrent infections. The WAS2 patient presented with features of Wiskott-Aldrich syndrome, including recurrent infections, eczema, and thrombocytopenia. Immunologic analysis showed low numbers of B cells and T cells, particularly CD8 (see 186910)-positive T cells. The number and percentage of natural killer (NK) cells were increased, but NK-cell functional activity was drastically reduced. IL2 (147680) corrected the partial proliferation defect in T cells from a WAS patient, but it failed to correct the complete T-cell proliferation defect in the WAS2 patient. Unlike patients with WAS, who show impaired T-cell chemotaxis, the WAS2 patient showed no response to IP10 (CXCL10; 147310), in association with poor expression of IP10 receptor (CXCR3; 300574). Platelet volume was normal. The WAS2 patient had undetectable WASP (300392), like WAS patients, but normal WASP sequence and mRNA levels. WIPF1, which is required for stabilization of WASP, was also undetectable. Unrelated cord blood transplantation at age 4.5 months restored immunologic function, and the WAS2 patient was healthy 16 months after the procedure.
Mapping
Wiskott-Aldrich syndrome-2 is caused by mutation in the WIPF1 gene, which maps to chromosome 2q31.1 (Gross, 2012).
Molecular Genetics
In a Moroccan infant with WAS2, Lanzi et al. (2012) identified a homozygous ser434-to-ter (S434X; 602357.0001) mutation in the WIPF1 gene. The parents were heterozygous for the mutation. Expression of WIPF1 in the patient's T cells corrected the defect in WASP expression.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
WISKOTT-ALDRICH SYNDROME 2
|
c0043194
| 7,720 |
omim
|
https://www.omim.org/entry/614493
| 2019-09-22T15:55:04 |
{"mesh": ["D014923"], "omim": ["614493"], "orphanet": ["906"], "synonyms": ["Alternative titles", "WIPF1 DEFICIENCY"]}
|
Reddy (1977) informed me of a case of threoninemia. The patient, an 8-month-old male offspring of a consanguineous marriage, had growth retardation and convulsions. The serum level of threonine was about 10 times normal and urinary excretion was increased. Oral loading with threonine increased the concentration in serum and urine. Threonine levels were normal in both parents (Reddy, 1978).
Growth \- Growth retardation Neuro \- Seizures Lab \- Hyperthreoninemia \- Hyperthreoninuria 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
THREONINEMIA
|
c1848861
| 7,721 |
omim
|
https://www.omim.org/entry/273770
| 2019-09-22T16:21:44 |
{"omim": ["273770"], "synonyms": ["Alternative titles", "HYPERTHREONINEMIA"]}
|
A number sign (#) is used with this entry because of evidence that congenital reticular ichthyosiform erythroderma (CRIE) is caused by heterozygous mutation in the KRT10 gene (148080) on chromosome 17q21.
Description
Congenital reticular ichthyosiform erythroderma (CRIE), also known as ichthyosis with confetti (IWC), is a rare skin condition characterized by slowly enlarging islands of normal skin surrounded by erythematous ichthyotic patches in a reticulated pattern. The condition starts in infancy as a lamellar ichthyosis, with small islands of normal skin resembling confetti appearing in late childhood and at puberty. Histopathologic findings include band-like parakeratosis, psoriasiform acanthosis, and vacuolization of keratinocytes with binucleated cells in the upper epidermis, sometimes associated with amyloid deposition in the dermis. Ultrastructural abnormalities include perinuclear shells formed from a network of fine filaments in the upper epidermis (summary by Krunic et al., 2003).
Clinical Features
Camenzind et al. (1984) reported 2 unrelated children with what the authors designated as 'confetti-type' ichthyosis. The first was a 14-year-old French boy with congenital ichthyosiform erythroderma who after treatment with topical retinoids in early childhood began to develop islands of white skin on his upper chest that gradually spread downward. The flat white spots were 1 to 2 cm in diameter, with predominance on the trunk and proximal limbs and sparing of the face, as if the patient had been 'sprayed with confetti.' The authors also noted that the boy had a foul odor reminiscent of butyric acid. Treatment with oral retinoids increased the number of white spots, with extension to the lower extremities. Histologic examination was similar for both erythrodermic and white skin, with an irregularly acanthotic epidermis overlaid by orthokeratotic and parakeratotic hyperkeratosis; the granular layer was present in all examined epidermis. The second patient was a 12-year-old Italian girl with congenital ichthyosiform erythroderma who prior to being treated with retinoids had white confetti-like macules of normal-appearing skin similar to the French boy's, except that her macules were clearly depressed relative to adjacent skin. The patient also developed hypertrichosis on her legs at 3 years of age. Histologic examination of erythematous skin showed epidermal hyperplasia, absence of the granular layer, and parakeratotic hyperkeratosis. Examination of a white macule revealed normal skin, with a granular layer, orthokeratotic horny layer, and normal thickness of the epidermis. Treatment with retinoids resulted in an increase in the number and area of white macules.
Brusasco et al. (1994) restudied the Italian girl originally described by Camenzind et al. (1984). At 18 years of age, she had bright red skin with discrete hyperkeratosis and pityriasiform desquamation, as well as striking patches of apparently normal skin on the trunk enclosed by the erythematous scaling skin. The areas of normal skin, which did not follow any particular distribution, were slightly elevated and the adjacent red ichthyotic skin had a reticulate pattern. Small white patches were also present on the limbs and face. Palmoplantar surfaces were orange-red and hyperkeratotic with increased markings, and there was clubbing of the nails. In addition, the patient had remarkable hypertrichosis, especially on the limbs, and also presented a mild ectropion. Extracutaneous abnormalities were not detected, and all laboratory tests, including hormonal levels, were normal. Punch biopsy of a patch of normal skin showed only mild orthokeratotic hyperkeratosis, whereas the erythrokeratotic skin showed parakeratotic hyperkeratosis, absence of the stratum granulosum, acanthosis, several mitoses, perinuclear vacuolization of some keratinocytes in the superficial layers of the epidermis, a few binuclear keratinocytes, dilation of dermal vessels, and a mononuclear infiltrate in the superficial dermis. Ultrastructurally, the most significant finding was the presence of granular material deposited in the form of cup- or bowl-like perinuclear masses in the vacuolized superficial keratinocytes and binuclear keratinocytes. This material, which closely resembled glycoproteins, was composed of very thin interlacing filaments with the prominent cross-points causing the granular appearance. Brusasco et al. (1994) noted that the ultrastructural findings in this patient presented strong similarities to those of CRIE, defined by a peculiar pattern involving a 3-dimensional network of fine interdigitating filaments forming perinuclear shells in vacuolized keratinocytes of the upper epidermis. Based on clinical, light microscopic, and ultrastructural features, they concluded that 'ichthyosis with confetti' and CRIE are the same disorder. In a further report of this Italian woman at age 23, Brusasco et al. (1998) noted that she had developed several hyperpigmented 3- to 5-mm macules on the extensor surfaces of her limbs. These lesions were almost black and had a tendency to coalesce into dark irregular areas. They were localized on the red ichthyotic skin only, and not on the small patches of normal skin. This feature had not been observed in the other patients with this disorder or in other ichthyotic disorders. Light microscopy showed typical features of CRIE, as well as a perivascular lymphohistiocytic infiltrate in the superficial dermis. Electron microscopy and immunohistochemistry demonstrated that the lesions were strictly related to the ichthyotic skin, and that the dark color was due to melanosome accumulation in activated dendritic melanocytes. No amyloid deposits were observed. Brusasco et al. (1998) postulated an unusual postinflammatory hyperpigmentation reaction in response to a continuous inflammatory process in CRIE. The lack of pigment deposition in the keratinocytes may have resulted from a transfer defect, or the finding may have reflected hyperplastic stimulation of the epidermis.
Krunic et al. (2003) reported a 32-year-old white man with a history of red, scaly skin since birth. At age 10 years, he developed enlarging white spots on the trunk and extremities. Physical examination showed diffuse intense erythema on the face, trunk, and extremities, with fine scaling and discrete hyperkeratotic patches on the upper trunk and back. There were patches of apparently normal skin on the abdomen, upper chest, and back. On the limbs, the areas of normal unaffected skin were interspersed with erythematous scaly patches forming a reticulated pattern. Histopathologic study of the affected erythematous skin showed hyperkeratosis, a thick granular layer, acanthosis, and paranuclear vacuolization in some keratinocytes. Ultrastructural study showed binuclear cells and granular filamentous paranuclear material within the vacuolized keratinocytes.
Choate et al. (2010) summarized the clinical features of ichthyosis with confetti (IWC), a very rare, sporadic severe skin disease in which affected subjects are born with erythroderma owing to defective skin barrier function, prominent scale, and palmoplantar keratoderma. Poor skin integrity leads to bacterial infections and, frequently, impaired growth and development. Early in life, hundreds to thousands of pale confetti-like spots appear across the body surface and increase in number and size with time. Histology of ichthyotic skin shows epidermal thickening and disordered differentiation above the basal layer, with perinuclear vacuolization, lack of a granular layer, and hyperkeratosis with retained nuclei in the stratum corneum. Choate et al. (2010) studied 7 kindreds with characteristic IWC. Biopsy of confetti spots in different kindreds revealed that these have normal histology, consistent with each representing a revertant from clonal expansion of a normal stem cell.
### Aarau Disease
In Aarau, Switzerland, Itin et al. (2003) described a 12-year-old girl with what they considered to be a 'new' disorder of cornification. The patient developed an ichthyosis vulgaris (146700)-like skin disorder 6 months after birth. Several years later, the clinical features changed considerably. The patient had developed streaks of hyperkeratotic, slightly scaling skin with underlying erythema distributed in a reticulate, occasionally annular pattern on the trunk and extremities. Lesions were stable and had not changed significantly in size or distribution over the ensuing years. The initial generalized skin lesions in this patient resolved, and erythrokeratodermic streaks and plaques developed, which was considered distinct from patients with CRIE. Histopathologic and ultrastructural findings were nonspecific, and there was no evidence of a metabolic disorder. Specifically, the pathognomonic features of CRIE, such as keratinocyte vacuolization, binucleate cells, and perinuclear shells, were not observed. The parents of the patient were nonconsanguineous, and no family members had this or any similar skin disorder. Itin et al. (2003) noted that the disorder in their patient shared several clinical features with CRIE (Marghescu et al., 1984), but was nonetheless distinct. Because of partial clinical overlap with erythrokeratodermia variabilis (EKV; 133200), Itin et al. (2003) screened for mutations in several connexin genes but found none. Itin et al. (2003) speculated that this disorder of cornification represented a separate new entity, which they proposed to call 'Aarau disease.'
Inheritance
In a review of CRIE, Krunic et al. (2003) noted that only a small number of patients with sporadic occurrence have been documented, suggesting new dominant mutation as a cause of the condition.
Mapping
Choate et al. (2010) compared genotypes of DNA from blood and cultured keratinocytes from biopsies of diseased and revertant skin of 1 subject. In contrast to blood and disease keratinocytes, revertant DNA showed a single large segment of copy-neutral loss of heterozygosity on chromosome 17q extending from 34.5 Mb to the telomere at 78.7 Mb. Three additional revertant spots from this subject also showed copy-neutral loss of heterozygosity extending from proximal 17q to the telomere, each with different inferred start sites for loss of heterozygosity, which excluded simple genetic mosaicism. In each revertant, the same parental haplotype was lost, consistent with loss of dominant mutation. Choate et al. (2010) then analyzed 28 revertant spots from 5 additional patients. All revertants showed copy-number loss of heterozygosity on 17q extending to the telomere. These observations confined the disease locus to an interval on 17q containing a gene cluster encoding 28 type 1 keratins and 24 keratin-associated proteins.
Molecular Genetics
Choate et al. (2010) sequenced the entire critical interval for IWC in a parent-child trio and identified a de novo mutation in the keratin-10 gene (KRT10; 148080) in the affected subject. The mutation abolished the canonical splice acceptor site of intron 6 (148080.0015) and was absent in revertant spots. Sequencing of KRT10 from genomic DNA and disease keratinocyte cDNA in the 6 other IWC kindreds identified de novo mutations in all 4 simplex kindreds and transmitted mutations in the 2 multiplex kindreds (see, e.g., 148080.0016-148080.0018). All mutations resulted in cDNAs encoding frameshifts that entered the same alternative C-terminal reading frame. Mutations included 2 additional intron 6 splice acceptor mutations, an intron 6 splice donor site mutation that results in skipping of exon 6, 2 frameshift mutations in exon 7, and an exon 6 mutation that creates a premature splice donor site. All of these mutations were absent in control chromosomes, and each was lost in revertant spots. On the basis of these findings, Choate et al. (2010) concluded that mutations in KRT10 cause ichthyosis with confetti.
INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Erythematous ichthyotic skin with reticulate pattern \- Numerous 'confetti-like' scattered patches of normal skin \- Palmoplantar hyperkeratosis Skin Histology \- Absence of stratum granulosum \- Retained nuclei in stratum corneum Nails \- Clubbing (rare) Hair \- Hypertrichosis (rare) IMMUNOLOGY \- Susceptibility to bacterial infections due to poor skin integrity MISCELLANEOUS \- At birth, there is generalized red scaly skin \- Hundreds to thousands of patches of pale normal skin appear during childhood and increase in number and size over time MOLECULAR BASIS \- Caused by mutation in the keratin 10 gene (KRT10, 148080.0015 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ERYTHRODERMA, ICHTHYOSIFORM, CONGENITAL RETICULAR
|
c3665704
| 7,722 |
omim
|
https://www.omim.org/entry/609165
| 2019-09-22T16:06:35 |
{"omim": ["609165"], "orphanet": ["281190"], "synonyms": ["CRIE", "Ichthyosis variegata", "ICHTHYOSIS WITH CONFETTI", "Ichthyosis with confetti", "IWC", "Alternative titles", "ICHTHYOSIS VARIEGATA"]}
|
A wide spectrum of malformations involving the distal anus and rectum as well as the urinary and genital tracts, which can affect boys and girls.
## Epidemiology
They occur in approximately 1 in 5000 live births.
## Clinical description
Defects range from mild anal anomalies to complex cloacal malformations. They can therefore be classified into the following groups: imperforated anus without fistula, ARM with rectourinary or rectogenital fistula and complex ARM (cloaca). Associated anomalies include genitourinary defects (in approximately 50% of patients) and spinal anomalies. A cloaca is associated with a urological problem (such as obstructive uropathy) in 90% of babies and with hydrocolpos in 50%. Sacral anomalies (hemisacrum and sacral hemivertebrae) have been described; hemivertebrae may also affect the lumbar and thoracic spine, leading to scoliosis. A tethered spinal cord (in 25% of patients) may result in motor and sensory disturbances of the lower extremities. Syringomyelia and myelomeningocele can occur.
## Etiology
The etiology remains unclear and is likely multifactorial. Familial cases have been described.
## Diagnostic methods
The radiological evaluation of a newborn with imperforate anus should include an abdominal and pelvic ultrasound to evaluate for genitourinary defects as they need to be dealt with in the newborn period to avoid serious complications. Spinal ultrasound in the first three months of life and magnetic resonance imaging thereafter are useful radiological modalities for detecting spinal anomalies.
## Differential diagnosis
ARM can occur in association with multisystem syndromes, such as Townes-Brocks syndrome, Currarino syndrome, Pallister-Hall syndrome, and Down syndrome (see these terms).
## Genetic counseling
The risk of ARM for a sibling of a patient with ARM can reach 1%.
## Management and treatment
Patients can either undergo a primary repair procedure (anoplasty) or a protective colostomy and definitive repair at a later date, depending on the malformation. The surgical approach to repairing these defects changed dramatically in 1980 with the introduction of the posterior sagittal approach, which allowed surgeons to view the anatomy of these defects clearly, to repair them under direct vision, and to learn about the complex anatomic arrangement between the rectum and genitourinary tract.
## Prognosis
Early diagnosis, management of associated anomalies and efficient meticulous surgical repair can ensure a good functional outcome in terms of bowel and urinary control, and sexual function. However, fecal and urinary incontinence can occur due mainly to associated problems such as a poorly developed sacrum, deficient nerve supply, and spinal cord anomalies. For these patients, an effective bowel management program, including enema and dietary restrictions improves the quality of life.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Isolated anorectal malformation
|
c3495676
| 7,723 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=557
| 2021-01-23T17:27:46 |
{"mesh": ["D000071056", "C537771"], "omim": ["107100", "207500", "301800"], "umls": ["C3495676"], "icd-10": ["Q42.0", "Q42.1", "Q42.2", "Q42.3"]}
|
For a general phenotypic description and a discussion of genetic heterogeneity of FG syndrome, see FGS1 (305450).
Clinical Features
Jehee et al. (2005) reported a Brazilian boy with FG syndrome born to a young and nonconsanguineous couple. The boy was severely hypotonic and mentally retarded. He had trigonocephaly due to premature metopic closure, bilateral epicanthic folds, upslanted palpebral fissures, short nose with depressed bridge and upturned nares, long philtrum, diastema of upper central incisors, strabismus, and hypospadias. He had severe constipation, requiring enemas on 5 different occasions. He died at age 4 years, apparently due to generalized infection and multiple organ failure; autopsy was not performed. The proband had 3 healthy younger sibs.
Mapping
In a Brazilian boy with FG syndrome, Jehee et al. (2005) detected an inherited duplication at Xq22.3 by comparative genomic hybridization microarray; the patient's mother was found to be heterozygous for the duplication. Jehee et al. (2005) stated that the duplication maps outside the 4 known loci for FG syndrome, and designated this locus FGS5.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
FG SYNDROME 5
|
c1845119
| 7,724 |
omim
|
https://www.omim.org/entry/300581
| 2019-09-22T16:20:03 |
{"mesh": ["C564480"], "omim": ["300581"]}
|
Christianson and Fourie (1996) described an Afrikaner family in which 6 persons in 3 generations showed an association of hair and nail defects. The proband had short, thin, sparse, pale scalp hair; her eyebrows were absent, and her eyelashes were short and sparse. There was almost no hair in her axillae and pubic area. Her nails were dystrophic and thickened; the distal half of the nail was not attached to the nail bed, resulting in a gap between the center of the free edge and the nail bed. Her sweating, skin, and teeth were normal. Similar manifestations, but varying in their severity, were found in her brother, mother, grandfather, aunt, and first cousin. The proband and her aunt had episodes of supraventricular tachycardia, and the proband's brother and mother had bradycardia. Christianson and Fourie (1996) suggested that this association is a 'new' autosomal dominant type of ectodermal dysplasia, involving hair and nails. The absence of skin defects distinguishes this form from Clouston syndrome (129500).
Inheritance \- Autosomal dominant Nails \- Dystrophic thickened nails \- Unattached distal half of nails Skin \- No skin defects \- Normal sweating Hair \- Short, thin, sparse, pale scalp hair \- Absent eyebrows \- Short, sparse eyelashes \- Sparse axillary and pubic hair Teeth \- Normal teeth Cardiac \- Episodic supraventricular tachycardia \- Bradycardia ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ECTODERMAL DYSPLASIA, HIDROTIC, CHRISTIANSON-FOURIE TYPE
|
c1832411
| 7,725 |
omim
|
https://www.omim.org/entry/601375
| 2019-09-22T16:14:56 |
{"mesh": ["C536180"], "omim": ["601375"], "orphanet": ["1808"]}
|
A number sign (#) is used with this entry because of evidence that congenital disorder of glycosylation type Icc (CDG1CC) is caused by hemizygous mutation in the MAGT1 gene (300715) on chromosome Xq13.
Hemizygous mutation in the MAGT1 gene can also cause immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN; 300853).
For a general discussion of CDGs, see CDG1A (212065).
Clinical Features
Blommaert et al. (2019) reported 2 unrelated boys, 11 and 13 years of age, with developmental delay, impaired intellectual development, and mild facial dysmorphism associated with abnormal serum transferrin isoelectic focusing consistent with a type 1 pattern. One patient had behavioral abnormalities and the other had hepatomegaly; neither had recurrent infections or an immunologic phenotype.
Inheritance
The transmission pattern of CDG1CC in the family reported by Blommaert et al. (2019) was consistent with X-linked recessive inheritance.
Molecular Genetics
In 2 unrelated boys with CDG1CC, Blommaert et al. (2019) identified hemizygous mutations in the MAGT1 gene (K356N, 300715.0008 and R331X, 300715.0009). The patients were genetically screened using a CDG candidate gene panel; neither mutation was found in the gnomAD database. In patient 1, the mutation was inherited from the unaffected mother; her X chromosome carrying the mutation showed 98% skewed X inactivation. In patient 2, the mutation occurred de novo. Patient fibroblasts and MAGT1-null HEK293 cells showed compensatory upregulation of TUSC3. Analysis of patient fibroblasts showed an N-glycosylation defect, with variable hypoglycosylation of STT3B (608605)-dependent substrates, including SHBG (182205) and CTSC (602365). Expression of the mutations into MAGT1-null HEK293 cells was unable to rescue the glycosylation defect.
INHERITANCE \- X-linked recessive HEAD & NECK Face \- Dysmorphic features, mild, nonspecific NEUROLOGIC Central Nervous System \- Developmental delay \- Impaired intellectual development Behavioral Psychiatric Manifestations \- Behavioral abnormalities LABORATORY ABNORMALITIES \- Type 1 pattern of abnormal serum transferrin isoelectric focusing consistent with a glycosylation defect MISCELLANEOUS \- Two unrelated boys have been reported (last curated August 2019) MOLECULAR BASIS \- Caused by mutation in the magnesium transporter 1 gene (MAGT1, 300715.0008 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Icc
|
None
| 7,726 |
omim
|
https://www.omim.org/entry/301031
| 2019-09-22T16:18:57 |
{"omim": ["301031"]}
|
Myophosphorylase deficiency (McArdle's disease), or glycogen storage disease type 5 (GSD5) , is a severe form of glycogen storage disease characterized by exercise intolerance.
## Epidemiology
Prevalence is unknown.
## Clinical description
Onset occurs in childhood. Patients present with a syndrome of muscular exercise intolerance with myalgia, cramps, fatigue, and muscle weakness. Massive elevation of creatine-kinase and rhabdomyolysis with myoglobinuria (dark urine) after exercise is noted in around 50% of patients, potentially leading to acute kidney failure. A 'second wind' phenomenon with relief of myalgia and fatigue after a few minutes of rest is observed in many patients. The clinical presentation is usually very classical, but some patients may have very moderate forms. In a few cases, onset very early in life with hypotonia, generalized muscle weakness and progressive respiratory failure has been described.
## Etiology
The condition is caused by mutations in the PYGM gene (11q13), leading to muscle phosphorylase deficiency. Mutation p.R50X may account for 40% to 50% of the alleles in Caucasian populations.
## Diagnostic methods
The diagnosis is based on biological findings revealing a lack of lactate elevation in blood during ischemic forearm test, excess glycogen, and deficient phosphorylase activity in the muscle biopsy.
## Differential diagnosis
The differential diagnosis should include GSD type 7 (see this term).
## Genetic counseling
The condition is autosomal recessive.
## Management and treatment
Treatment is based on controlled physical training in order to develop mitochondrial oxidation capacities in muscles, and programmed glucose intake according to exercising periods. Diets with high protein intake have yielded variable results.
## Prognosis
Prognosis is favorable when severe rhabdomyolysis is avoided. However, myoglobinuria may lead to potentially life-threatening renal failure.
*[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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Glycogen storage disease due to muscle glycogen phosphorylase deficiency
|
c0017924
| 7,727 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=368
| 2021-01-23T18:31:49 |
{"gard": ["6528"], "mesh": ["D006012", "C537276"], "omim": ["232600"], "umls": ["C0017924", "C2936916"], "icd-10": ["E74.0"], "synonyms": ["GSD due to muscle glycogen phosphorylase deficiency", "GSD type 5", "GSD type V", "Glycogen storage disease type 5", "Glycogen storage disease type V", "Glycogenosis due to muscle glycogen phosphorylase deficiency", "Glycogenosis type 5", "Glycogenosis type V", "McArdle disease", "Myophosphorylase deficiency"]}
|
Autosomal dominant optic atrophy plus syndrome (ADOA plus) is a rare syndrome that causes vision loss, hearing loss, and symptoms affecting the muscles. The syndrome is associated with degeneration of the optic nerve (optic atrophy). The optic nerve sends signals about what the eyes are seeing to the brain. When there is optic nerve damage, it causes vision loss. Other symptoms of ADOA plus include sensorineural hearing loss and symptoms affecting the muscles such as muscle pain and weakness.
ADOA plus is caused by changes (mutations) in the OPA1 gene. The syndrome is inherited in an autosomal dominant manner. A diagnosis of ADOA plus is suspected when an eye exam finds degeneration of the optic nerve (optic atrophy). The diagnosis can be confirmed with a muscle biopsy and genetic testing of the OPA1 gene. Treatment options include visual and hearing aids. Certain medications have been found to help improve vision loss in some people.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Autosomal dominant optic atrophy plus syndrome
|
c2931235
| 7,728 |
gard
|
https://rarediseases.info.nih.gov/diseases/5243/autosomal-dominant-optic-atrophy-plus-syndrome
| 2021-01-18T18:01:57 |
{"mesh": ["C536544"], "omim": ["125250"], "umls": ["C2931235"], "orphanet": ["1215"], "synonyms": ["Dominant optic atrophy, deafness, ptosis, ophthalmoplegia, dystaxia, and myopathy", "OPTIC ATROPHY WITH OR WITHOUT DEAFNESS, OPHTHALMOPLEGIA, MYOPATHY, ATAXIA, AND NEUROPATHY", "DOMINANT OPTIC ATROPHY PLUS SYNDROME", "Treft-Sanborn-Carey syndrome", "Optic atrophy - deafness- polyneuropathy - myopathy", "Optic atrophy-deafness-polyneuropathy-myopathy syndrome"]}
|
Idiopathic panuveitis is a rare inflammatory eye disease, of unknown etiology, characterized by generalized inflammation of the uvea (iris, ciliary body, choroid), retina and vitreous with consequent ciliary spasm and posterior synechiae formation, leading to acute or chronic, unilateral or bilateral visual impairment and ocular discomfort or pain. Patients present an increased risk of development of cataracts, secondary glaucoma, cystoid macular edema and/or retinal detachment. It could potentially result in vision loss.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Idiopathic panuveitis
|
c4707884
| 7,729 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=280921
| 2021-01-23T18:16:01 |
{"icd-10": ["H44.1"]}
|
A number sign (#) is used with this entry because of evidence that Fuchs endothelial corneal dystrophy-8 (FECD8) is caused by heterozygous mutation in the AGBL1 gene (615496) on chromosome 15q25.
Description
Fuchs endothelial corneal dystrophy (FECD) is the most common genetic disorder of the corneal endothelium. Late-onset FECD is marked by thickening of Descemets membrane and excrescences, called guttae, that typically appear in the fourth or fifth decade. Disease progression results in decreased visual acuity as a result of increasing corneal edema, and end-stage disease is marked by painful epithelial bullae (summary by Riazuddin et al., 2013).
For a discussion of genetic heterogeneity of FECD, see FECD1 (136800).
Clinical Features
Riazuddin et al. (2013) studied a large 3-generation family in which 12 members, the majority of whom were in the sixth or seventh decade of life, fulfilled the phenotypic criteria for Fuchs corneal dystrophy but exhibited variable severity.
Molecular Genetics
Riazuddin et al. (2013) studied a large 3-generation family in which 12 members, the majority of whom were in the sixth or seventh decade of life, fulfilled the phenotypic criteria for Fuchs corneal dystrophy but exhibited variable severity. After excluding linkage to known FECD loci and mutation in 3 FECD-associated genes, Riazuddin et al. (2013) performed genomewide linkage analysis that did not yield significant linkage, although 2 loci on chromosomes 3p and 15q showed positive signals under a multilocus model. Next-generation exome sequencing in 1 unaffected and 2 affected members of the family identified a heterozygous nonsense mutation in the AGBL1 gene (R1028X; 615496.0001) on chromosome 15q that segregated with disease in the family under the multilocus model. The R1028X variant was also found in 2 of 384 ethnically matched controls and in the NHLBI Exome Variant Server database; Riazuddin et al. (2013) noted, however, that the respective minor allele frequencies (MAFs) of 0.0026 and 0.0035 were below the greater than 4% prevalence of late-onset FECD in the US population. Sequencing of the AGBL1 gene in an unselected FECD cohort identified 2 additional unrelated individuals with the R1028X mutation as well as 3 unrelated FECD patients who were heterozygous for a missense mutation in the AGBL1 gene (C990S; 615496.0002). The C990S variant was not found in 384 ethnically matched controls, but was present in the NHLBI Exome Variant Server at a low MAF of 0.0025 in the European American population. Riazuddin et al. (2013) concluded that AGBL1 is a causative locus for late-onset FECD.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Central guttae, unilateral or bilateral MISCELLANEOUS \- Twelve or more lesions per eye in individuals over 60 years of age \- Intrafamilial variability in severity MOLECULAR BASIS \- Caused by mutation in the ATP/GTP-binding protein-like-1 gene (AGBL1, 615496.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CORNEAL DYSTROPHY, FUCHS ENDOTHELIAL, 8
|
c0016781
| 7,730 |
omim
|
https://www.omim.org/entry/615523
| 2019-09-22T15:51:50 |
{"doid": ["11555"], "mesh": ["D005642"], "omim": ["615523"], "orphanet": ["98974"]}
|
A number sign (#) is used with this entry because of evidence that autosomal recessive mental retardation-36 (MRT36) is caused by homozygous mutation in the ADAT3 gene (615302) on chromosome 19p13.
Clinical Features
Alazami et al. (2013) reported 8 consanguineous Arab families from various geographic regions in which multiple individuals had mental retardation that was often associated with esotropia and failure to thrive. Other more variable features included microcephaly, hypotonia, and mild brain abnormalities on MRI, such as dilated ventricles or delayed myelination.
El-Hattab et al. (2016) reported 15 individuals from 11 apparently unrelated Arab families with features similar to those of the patients reported by Alazami et al. (2013). All of the patients had moderate to severe intellectual disability, and most had strabismus, growth failure, and brain abnormalities on neuroimaging. Previously unreported features included variable dysmorphic facial features (prominent forehead, upslanting palpebral fissures, epicanthus, hypertelorism, telecanthus, depressed nasal bridge) in 10 patients, behavioral problems (aggressiveness, hyperactivity) in 5, and endocrine abnormalities (low IGF1, growth hormone deficiency, hypothyroidism) in 3.
Salehi Chaleshtori et al. (2018) described a 6-year-old girl, born to consanguineous Iranian parents, with mild to moderate cognitive impairment, neurodevelopmental delay, attention-deficit/hyperactivity disorder, asymmetric face, and depressed nasal bridge. She did not have strabismus.
Inheritance
The transmission pattern of MRT36 in the families reported by Alazami et al. (2013) was consistent with autosomal recessive inheritance.
Mapping
By homozygosity mapping of a large consanguineous family with MRT36, Alazami et al. (2013) found linkage to a locus on chromosome 19p13.3 (maximum lod score greater than 4.3 near the proximal telomere).
Molecular Genetics
In affected members of 8 consanguineous Arab families with autosomal recessive mental retardation, Alazami et al. (2013) identified a homozygous mutation in the ADAT3 gene (V128M; 615302.0001). Molecular modeling indicated that the mutation occurs in a hook that protrudes from the surface of the protein and would disrupt this protrusion. The mutation, which was found by homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in all families and was not found in the 1000 Genomes Project or Exome Variant Server databases or in 580 ethnically matched alleles. Haplotype analysis indicated a founder effect, which was estimated to have occurred between 65 and 111 generations ago. The ADAT3 gene is involved in the regulation of protein translation.
By whole-exome sequencing, El-Hattab et al. (2016) identified homozygosity for the same V128M founder mutation in the ADAT3 gene in affected members of 11 apparently unrelated Arab families with MRT36.
In a 6-year-old Iranian girl, born to consanguineous parents, with MRT36, Salehi Chaleshtori et al. (2018) identified homozygosity for an 8-bp duplication in the ADAT3 gene (615302.0002) that segregated with the phenotype in the family. The mutation was not found in the ExAC, 1000 Genomes Project, or EVS databases.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Failure to thrive HEAD & NECK Head \- Microcephaly Face \- Dysmorphic facial features (in some patients) \- Prominent forehead \- High forehead Ears \- Recurrent otitis media (in 1 family) Eyes \- Strabismus (in most patients) \- Esotropia \- Upslanting palpebral fissures \- Epicanthus \- Telecanthus Nose \- Depressed nasal bridge NEUROLOGIC Central Nervous System \- Mental retardation \- Hypotonia \- Epilepsy (in some patients) \- Spasticity (in some patients) \- Brain anomalies seen on MRI (in some patients) \- Delayed myelination \- Reduced white matter volume \- Brain atrophy \- Corpus callosum agenesis Behavioral Psychiatric Manifestations \- Aggressive behavior (in some patients) \- Hyperactive behavior (in some patients) ENDOCRINE FEATURES \- Endocrine abnormalities (rare) Hypothyroidism (in 1 patient) \- Growth hormone deficiency (in 1 patient) LABORATORY ABNORMALITIES \- Low IGF-1 (in 1 family) MISCELLANEOUS \- Onset in infancy \- Variable features may be present MOLECULAR BASIS \- Caused by mutation in the tRNA-specific adenosine deaminase 3 gene (ADAT3, 615302.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 36
|
c3809039
| 7,731 |
omim
|
https://www.omim.org/entry/615286
| 2019-09-22T15:52:41 |
{"omim": ["615286"], "orphanet": ["363528"], "synonyms": []}
|
## Clinical Features
Ensink et al. (2001) reported a large 4-generation Dutch family with nonsyndromic progressive mid- to high-frequency sensorineural hearing loss. Most of those affected presented with hearing impairment after 30 years of age, but hearing impairment was noted at about 10 years of age in 2. After correction for presbycusis, hearing impairment was most marked at 1 to 2 kHz and showed an annual progression of 0.8 dB per year. Vestibular function was intact.
Inheritance
The transmission pattern of nonsyndromic hearing loss in the Dutch family reported by Ensink et al. (2001) was consistent with autosomal dominant inheritance.
Mapping
Ensink et al. (2001) stated that linkage analysis in the Dutch family they reported with postlingual progressive nonsyndromic hearing loss mapped the phenotype to the DFNA13 locus (601868). However, by linkage analysis in this family, in which no mutations were found in the COL11A2 gene (120290), Snoeckx et al. (2004) identified a novel dominant locus for postlingual nonsyndromic sensorineural hearing loss (DFNA31). The DFNA31 locus is located in a 7.5-cM region of 6p21.3, telomeric to the DFNA13 locus. DNA sequencing of coding regions and exon/intron boundaries of 2 candidate genes in this interval, POU5F1 (164177) and GABBR1 (603540), revealed no disease-causing mutations.
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural (0.5 - 2.0 kHz) \- Presbycusis MISCELLANEOUS \- Age of onset between 5 and 10 years of age \- Based on one large Dutch family (last curated August 2015) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
DEAFNESS, AUTOSOMAL DOMINANT 31
|
c1837617
| 7,732 |
omim
|
https://www.omim.org/entry/608645
| 2019-09-22T16:07:26 |
{"doid": ["0110561"], "mesh": ["C563888"], "omim": ["608645"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"]}
|
Pancreatic injury
SpecialtyEmergency medicine
A pancreatic injury is some form of trauma sustained by the pancreas. The injury can be sustained through either blunt forces, such as a motor vehicle accident, or penetrative forces, such as that of a gunshot wound.[1] The pancreas is one of the least commonly injured organs in abdominal trauma.[2]
## Contents
* 1 Management
* 1.1 Diagnosis
* 1.2 Classification
* 1.3 Surgical treatment
* 2 History
* 3 References
* 4 External links
* 5 External links
## Management[edit]
Diagram of the pancreas, showing its relation to the duodenum and the mesenteric veins and arteries
### Diagnosis[edit]
The diagnosis of this form of injury can be challenging because of the pancreas' location inside the abdomen.[3] The use of ultrasound can reveal fluid around the site of injury.[1] Computed tomography (CT) can also be utilized as a non-invasive diagnostic tool,[3] but its reliability is low; one retrospective case review found that computed tomography had either failed to find injuries or had underestimated the severity of injury in more than half of 17 pancreatic injury patients.[4] Serum amylase has also been shown to be of limited diagnostic utility within the first three hours following injury.[4] Management of a pancreatic injury can be difficult because other abdominal organs, such as the liver, usually have sustained trauma as well.[3][5] Several common symptoms manifest hours after the injury such as tachycardia, abdominal distension, and midepigastric tenderness.[5] Indications for surgical intervention include: peritonitis based on physical examination; hypotension in combination with a positive focussed assessment with sonography (ultrasound) for trauma (FAST); and pancreatic duct disruption based on the results of thin-cut computed tomography or endoscopic retrograde cholangiopancreatography (ERCP).[3] Commonly, a laparotomy is done in order to directly visualize the injury, and generally this approach is the most accurate diagnostic method.[1][5]
### Classification[edit]
1: Head of pancreas
2: Uncinate process of pancreas
3: Pancreatic notch
4: Body of pancreas
5: Anterior surface of pancreas
6: Inferior surface of pancreas
7: Superior margin of pancreas
8: Anterior margin of pancreas
9: Inferior margin of pancreas
10: Omental tuber
11: Tail of pancreas
12: Duodenum
Pancreatic injuries are classified according to the criteria of the American Association for the Surgery of Trauma (AAST). The grade of the trauma should be increased by one level for multiple injuries to the same organ. The description of the injury is that "based on most accurate assessment at autopsy, laparotomy, or radiological study." The pancreatic organ injury scale, as minimally modified, is:[4][6]
The Pancreatic Injury Scale classification Grade Subcapsular hematoma Laceration
I Minor contusion without ductal injury Superficial laceration without ductal injury
II Major contusion without duct injury or tissue loss Major laceration without duct injury or tissue loss
III Distal transection or parenchymal injury with duct injury
IV Proximal transection or parenchymal injury, involving ampulla
V Laceration-Massive disruption of pancreatic head
### Surgical treatment[edit]
When there is no pancreatic duct injury, typically hemostasis and surgical drainage are the main form of treatment.[1][3][4] Surgical repair is undertaken when there is evidence or suspicion of ductal injury.[4] The type of surgery depends on the degree of the injury and its proximity to the mesenteric blood vessels that serve the pancreas. When injuries are not close to the mesenteric vessels, a distal pancreatectomy may be done; this procedure preserves much of the pancreas and usually avoids loss of its endocrine and exocrine functions.[4] In severe cases of pancreaticoduodenal injury, a pancreaticoduodenectomy can be used.[4][7] Common complications after surgery include pancreatitis, pancreatic fistula, abscess, and pseudocyst formation.[2] Initial management of hemorrhage includes controlling it by packing the wound.[5][7]
## History[edit]
The first recorded case of pancreatic injury was published in The Lancet in 1827.[8] At the time, death as a result of injury was deemed to be "universal".[8] The first successful surgery to repair a transected pancreas was performed in 1904 by Garré, who reported the case the following year.[5][9][10]
## References[edit]
1. ^ a b c d Degiannis E, Glapa M, Loukogeorgakis SP, Smith MD (January 2008). "Management of pancreatic trauma". Injury. 39 (1): 21–9. doi:10.1016/j.injury.2007.07.005. PMID 17996869.
2. ^ a b Brooks, A.; Shukla, A.; Beckingham, I. (2003). "Pancreatic trauma". Trauma. 5: 1–8. doi:10.1191/1460408603ta261oa.
3. ^ a b c d e Subramanian, A.; Feliciano, D. V. (2007). "Pancreatic Trauma Revisited*". European Journal of Trauma and Emergency Surgery. 34 (1): 3–10. doi:10.1007/s00068-007-7079-4. PMID 26815484.
4. ^ a b c d e f g Boffard K, Brooks A (2001). "Pancreatic, splenic and duodenal injuries". In Holzheimer RG, Mannick JA (eds.). Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt. NBK6884.
5. ^ a b c d e Khan MA, Cameron I (December 2010). "The management of pancreatic trauma". Journal of the Royal Army Medical Corps. 156 (4): 221–7. doi:10.1136/jramc-156-04-03. PMID 21275354.
6. ^ American Association for the Surgery of Trauma (from Moore EE, Cogbill TH, Malangoni MA et al. (1990) J Trauma 30: 1427–1429)
7. ^ a b Stawicki SP, Schwab CW (December 2008). "Pancreatic trauma: demographics, diagnosis, and management". The American Surgeon. 74 (12): 1133–45. PMID 19097525. Retrieved 2012-08-04.
8. ^ a b Hess, Walter; Howard, John R. (2002). History of the pancreas: mysteries of a hidden organ. Kluwer Academic. pp. 363–96. ISBN 978-0-306-46742-4.
9. ^ "Abstracts of Current Literature". Surgery, Gynecology & Obstetrics. Franklin H. Martin Memorial Foundation, American College of Surgeons. 1: 285. September 1905.
10. ^ Demetrios Demetriades; Beat Schnüriger; Galinos Barmparas (2010). "49: Pancreatic injury". Surgical Management of Hepatobiliary and Pancreatic Disorders (Second ed.). doi:10.3109/9781841847603. ISBN 9781841847603. "In 1904, Garre operated successfully on a patient with a transected pancreas."
## External links[edit]
Classification
D
* ICD-10: S36.209
* ICD-9-CM: 863.84
External resources
* eMedicine: article/433177
## External links[edit]
* v
* t
* e
Nonmusculoskeletal injuries of abdomen and pelvis
Abdomen / GI
* Ruptured spleen
* Blunt splenic trauma
* Traumatic diaphragmatic hernia
* Gastrointestinal perforation
* Liver injury
* Pancreatic injury
Pelvic
* Uterine perforation
* Penile fracture
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pancreatic injury
|
c0273163
| 7,733 |
wikipedia
|
https://en.wikipedia.org/wiki/Pancreatic_injury
| 2021-01-18T19:03:06 |
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## Summary
### Clinical characteristics.
The spectrum of COL4A1-related disorders includes: small-vessel brain disease of varying severity including porencephaly, variably associated with eye defects (retinal arterial tortuosity, Axenfeld-Rieger anomaly, cataract) and systemic findings (kidney involvement, muscle cramps, cerebral aneurysms, Raynaud phenomenon, cardiac arrhythmia, and hemolytic anemia). On imaging studies, small-vessel brain disease is manifest as diffuse periventricular leukoencephalopathy, lacunar infarcts, microhemorrhage, dilated perivascular spaces, and deep intracerebral hemorrhages. Clinically, small-vessel brain disease manifests as infantile hemiparesis, seizures, single or recurrent hemorrhagic stroke, ischemic stroke, and isolated migraine with aura. Porencephaly (fluid-filled cavities in the brain detected by CT or MRI) is typically manifest as infantile hemiparesis, seizures, and intellectual disability; however, on occasion it can be an incidental finding. HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome usually associates asymptomatic small-vessel brain disease, cerebral large vessel involvement (i.e., aneurysms), and systemic findings involving the kidney, muscle, and small vessels of the eye. Two additional phenotypes include isolated retinal artery tortuosity and nonsyndromic autosomal dominant congenital cataract.
### Diagnosis/testing.
Diagnosis is based on clinical findings and molecular genetic testing of COL4A1.
### Management.
Treatment of manifestations: Supportive care tailored to the individual’s specific medical needs and including practical help and emotional support for affected individuals and their families. Hypertension should be treated to reduce the overall risk of stroke.
Prevention of primary and secondary complications: Avoiding head trauma and anticoagulant exposure may decrease the risk for intracerebral hemorrhage.
Surveillance: Depends on the severity and type of symptoms.
Agents/circumstances to avoid: Smoking and hypertension because these factors increase the risk for stroke; sustained head pressure or physical activities that may cause head trauma; anticoagulant use.
### Genetic counseling.
COL4A1-related disorders are inherited in an autosomal dominant manner. Most individuals diagnosed with a COL4A1-related disorder have an affected parent. The proportion of cases caused by a de novo pathogenic variant is estimated to be at least 27%. Each child of an individual with a COL4A1-related disorder has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis is possible for pregnancies at increased risk if the pathogenic variant in the family is known.
## Diagnosis
COL4A1-related disorders cover a spectrum of overlapping phenotypes characterized by a small-vessel brain disease of varying severity including porencephaly, variably associated with eye defects (congenital cataract, retinal arterial tortuosity, eye anterior segment anomaly of Axenfeld-Rieger type) and systemic findings (muscle cramps and/or serum creatine kinase (CK) elevation, kidney involvement, cerebral aneurysms, Raynaud phenomenon, cardiac arrhythmia, and hemolytic anemia).
### Suggestive Findings
A COL4A1-related disorder should be suspected in individuals with any of the following phenotypes that have overlapping features:
* Porencephaly type 1 [Gould et al 2005, Breedveld et al 2006, van der Knaap et al 2006, Yoneda et al 2013, Meuwissen et al 2015]
* Brain small-vessel disease with or without ocular anomalies [Gould et al 2006, Sibon et al 2007, Vahedi et al 2007, Coupry et al 2010, Shah et al 2012, Rødahl et al 2013, Meuwissen et al 2015]
* HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome [Plaisier et al 2007, Plaisier et al 2010]
* Tortuosity of retinal arteries [Zenteno et al 2014]
* Nonsyndromic autosomal dominant congenital cataract [Xia et al 2014]
Clinical features of COL4A1-related disorders vary widely and can include the following:
* Neurologic
* Infantile hemiplegia
* Developmental delay
* Migraines with or without aura
* Seizures
* Dementia
* Intellectual disability
* Intracerebral hemorrhage at any age including antenatal, neonatal, and recurrent episodes
* Ischemic stroke
* Typically on neuroimaging: features of brain small-vessel disease (Figure 1)
* Ophthalmic
* Transient visual loss caused by retinal hemorrhage
* Cataract, glaucoma, microphthalmia/anophthalmia
* Other systemic findings
* Hematuria
* Raynaud phenomenon
* Supraventricular arrhythmia
* Muscle cramps
#### Figure 1.
Spectrum of brain imaging abnormalities in COL4A1-related disorders A. Axial FLAIR showing right paraventricular porencephalic cyst and extensive white-matter abnormalities [van der Knaap et al 2006]
Family history is consistent with autosomal dominant inheritance. Findings and age of onset vary within and between families.
### Establishing the Diagnosis
The diagnosis of a COL4A1-related disorder is established in a proband with suggestive findings and the identification of a heterozygous pathogenic variant in COL4A1 (see Table 1).
Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing.
* Single-gene testing. Sequence analysis of COL4A1 is performed first followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found. To date, no deletions or duplications involving COL4A1 as causative of COL4A1-related disorders have been reported. Because these disorders usually result from a COL4A1 pathogenic missense variant that disrupts the collagen triple helix (see Molecular Genetics), a screening test for large duplications/deletions may have a very low yield.
* A multigene panel that includes COL4A1 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
* More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if single-gene testing (and/or use of a multigene panel that includes COL4A1) fails to confirm a diagnosis in an individual with features of a COL4A1-related disorder. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). 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 COL4A1-Related Disorders
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
COL4A1Sequence analysis 3100%
Deletion/duplication analysis 4Unknown 5
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods 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.
5\.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
## Clinical Characteristics
### Clinical Description
COL4A1-related disorders cover a spectrum of overlapping phenotypes characterized by a small-vessel brain disease of varying severity including porencephaly, variably associated with eye defects (congenital cataract, retinal arterial tortuosity, eye anterior segment anomaly of Axenfeld-Rieger type) and systemic findings (muscle cramps and/or serum CK elevation, kidney involvement, cerebral aneurysms, Raynaud phenomenon, cardiac arrhythmia, hemolytic anemia).
#### Autosomal Dominant Familial Porencephaly
Autosomal dominant familial porencephaly related to COL4A1 pathogenic variants has been reported in more than 50 individuals [Gould et al 2005, Breedveld et al 2006, van der Knaap et al 2006, Yoneda et al 2013, Meuwissen et al 2015]. This condition is characterized by the presence of fluid-filled cavities in the brain, caused by antenatal or perinatal parenchymal hemorrhage and detected by either brain CT, MRI (Figure 1A), or fetal ultrasound imaging. In addition to porencephalic cavities, brain imaging shows various degrees of periventricular leukoencephalopathy, microbleeds, lacunar infarct, and calcifications [Vahedi et al 2007, Livingston et al 2011, Ayrignac et al 2015, Meuwissen et al 2015].
The spectrum of neurologic clinical symptoms varies in degree of severity and age of onset, with wide intrafamilial heterogeneity. Typically, affected individuals may present with infantile hemiparesis, seizures, intellectual disability, dystonia, stroke, and migraine. First manifestations (including intracerebral hemorrhages) may occur in previously asymptomatic adults, and MRI brain anomalies can be clinically silent.
Congenital cataract is frequently observed in affected individuals. Retinal arteriolar tortuosity is more rarely associated with porencephaly [van der Knaap et al 2006].
#### Autosomal Dominant Brain Small-Vessel Disease with Hemorrhage
Autosomal dominant brain small-vessel disease with hemorrhage differs from autosomal dominant familial porencephaly by the absence of porencephalic cavities, while brain imaging demonstrates characteristic brain small-vessel involvement, including diffuse periventricular leukoencephalopathy (Figure 1B), lacunar infarcts, microbleeds, dilated perivascular spaces, deep intracerebral hemorrhages, and intracerebral calcifications (Figure 1C) [Vahedi et al 2007, Yoneda et al 2013, Meuwissen et al 2015].
Neurologic manifestations are also heterogeneous within families, and vary from infantile hemiparesis with seizure to isolated migraine with aura to absence of clinical symptoms. Single or recurrent intracerebral hemorrhage may occur in non-hypertensive adults who are younger than age 50 years. Such hemorrhages can occur spontaneously, after trauma, or as a result of anticoagulant use; some are fatal. Antenatal intracerebral and intraventricular hemorrhage may be observed using fetal ultrasound examination. Mild cognitive impairment has also been reported in one family [Sibon et al 2007]; however, it is unclear whether this is a separate finding or a manifestation of recurrent stroke.
Concomitant eye anomalies including retinal arteriolar tortuosity, congenital cataract, and/or anterior segment anomalies of the Axenfeld-Rieger type may be observed [Sibon et al 2007, Coupry et al 2010].
More rarely, systemic symptoms including serum CK elevation with or without muscle cramps [Yoneda et al 2013, Meuwissen et al 2015] and renal involvement including hematuria, unilateral renal atrophy [John et al 2015], renal cysts, and hemolytic anemia [Meuwissen et al 2015] are observed.
#### HANAC Syndrome
HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome has been well characterized in six families [Plaisier et al 2007, Plaisier et al 2010].
The small-vessel brain disease of HANAC is usually clinically asymptomatic [Alamowitch et al 2009]. By contrast, the systemic symptoms usually observed in HANAC – including muscle cramps, renal involvement, retinal arterial tortuosity, and Raynaud phenomenon – are rarely reported in COL4A1-related porencephaly or small-vessel brain disease [Gould et al 2006, Meuwissen et al 2015].
Brain involvement
* Half of affected individuals have: cerebral small-vessel disease characterized by leukoencephalopathy affecting subcortical, periventricular, or pontine regions; dilated perivascular spaces; lacunar infarcts; and microbleeds. None have porencephaly. Only two of the 14 affected individuals have clinical cerebrovascular symptoms: a minor ischemic stroke and a mild post-traumatic intracerebral hemorrhage while on anticoagulants [Alamowitch et al 2009].
* Single or multiple intracranial aneurysms, all located on the carotid siphon, have been observed in six individuals, with no rupture episode (Figure 1D).
Renal manifestations
* One family presented with isolated microscopic hematuria (i.e., without proteinuria or hypertension) and intermittent episodes of gross hematuria. Kidney biopsy was normal by light microscopy, but ultrastructural examination disclosed irregular and abnormal thickening of the basement membranes of the tubules, Bowman’s capsule, and interstitial capillaries. Small renal cysts were variably observed.
* Three families had renal findings of bilateral cortical and medullary renal cysts without hematuria. Cysts were large, but the overall kidney size was normal (Figure 2). Mild renal failure without proteinuria or hypertension may develop in individuals after age 50 years.
#### Figure 2.
Abdominal MRI showing bilateral renal cysts in a patient with HANAC syndrome [Plaisier et al 2007]
Muscle cramps involving a variety of muscles usually occur in affected individuals, with first episodes occurring before age three years. Muscle strength was slightly affected in only two individuals. Electromyography does not show a specific abnormality, and muscle biopsy, available in one person only, is normal. All affected individuals have persistent elevation of serum CK concentration.
Bilateral retinal arteriolar tortuosity is observed in all individuals with HANAC syndrome (see Ocular manifestations below).
Other manifestations. Raynaud phenomenon, supraventricular arrhythmia, and liver cyst are variably reported.
#### Additional Findings in COL4A1-Related Disorders
Ocular manifestations are variably observed in COL4A1-related disorders. Three distinct ocular features have been reported:
* Bilateral retinal arterial tortuosity is variably present in individuals with small-vessel brain disease with hemorrhage [Gould et al 2006] or with porencephaly [van der Knaap et al 2006], whereas all individuals with HANAC syndrome exhibited this finding [Plaisier et al 2007]. Additionally, one COL4A1 pathogenic variant has been characterized in individuals with familial retinal arteriolar tortuosity without cerebral or systemic symptoms [Zenteno et al 2014]. Fundus examination shows marked tortuosity of second- and third-order retinal arteries, with normal first-order arteries and retinal veins (Figure 3). No leakage or staining is observed on fluorescein angiography. Affected individuals experience episodic transient visual loss as a result of retinal hemorrhage occurring spontaneously or after minor stress or trauma. Visual prognosis has been excellent, without retinal sequelae.
* Congenital cataract is reported either as an isolated ocular feature [van der Knaap et al 2006, Shah et al 2010] or associated with other eye anterior segment abnormalities of Axenfeld-Rieger type in families with small-vessel brain disease and porencephaly [Sibon et al 2007, Coupry et al 2010, Rødahl et al 2013, Yoneda et al 2013, Meuwissen et al 2015]. Nonsyndromic congenital cataract has also been associated with a COL4A1 pathogenic variant in a large family [Xia et al 2014].
* Anterior segment anomaly of Axenfeld-Rieger type comprises a spectrum of ocular findings affecting the anterior chamber including congenital iris abnormalities, posterior embryotoxon, microcornea, increased intraocular pressure, and glaucoma. It has been described in families presenting with small-vessel brain disease and porencephaly [Sibon et al 2007, Meuwissen et al 2015].
#### Figure 3.
Fluorescein angiography. Typical retinal arteriolar tortuosity (arrows) in a patient with HANAC syndrome [Plaisier et al 2007].
Renal manifestations
* Bilateral renal cysts are very frequently observed in individuals with HANAC, and more rarely in affected individuals with small-vessel brain disease. In one family, renal cysts represent the main clinical manifestation, together with hematuria and glomerular filtration rate decrease [Gale et al 2016].
* Hematuria has been reported in individuals with porencephaly, small-vessel brain disease, and HANAC [Meuwissen et al 2015].
* Unilateral renal atrophy has been reported in two individuals [John et al 2015].
* Glomerular filtration rate decrease (usually affecting individuals age >40 years) has been observed in individuals with HANAC, as well as in affected individuals from one family presenting with renal cysts and hematuria without brain or extracerebral involvement [John et al 2015, Gale et al 2016].
Muscle manifestations. Serum CK elevation and painful muscle cramps, seen in all individuals with HANAC syndrome [Plaisier et al 2010], are only variably present in other affected individuals [Meuwissen et al 2015]. Muscle biopsy was performed in one affected individual with myopathic defects [Yoneda et al 2013].
Cardiac manifestations. Mitral valve prolapse and supraventricular arrythmia have been characterized in four patients [Plaisier et al 2010, Meuwissen et al 2015].
Ultrastructural basement membrane abnormalities have been demonstrated in skin vessels, at the dermo-epidermal junction, and in kidney.
* In individuals with HANAC syndrome with hematuria, ultrastructural examination disclosed irregular and abnormal thickening of the basement membranes of the tubules, Bowman’s capsule, and interstitial capillaries [Plaisier et al 2007]. In the skin, similar alterations including duplication of the basement membrane are seen at the dermo-epidermal junction and in dermal arterioles; vascular smooth muscle cells are dissociated due to abnormal spreading of basement membrane [Plaisier et al 2010].
* In one individual with autosomal dominant porencephaly, focal disruption and a major increase in thickness of the basement membrane of skin capillaries were found [van der Knaap et al 2006].
### Genotype-Phenotype Correlations
The number of COL4A1 pathogenic variants is too small to explore genotype-phenotype relationships.
However, all six COL4A1 pathogenic variants associated with hereditary angiopathy, nephropathy, aneurysms, and muscle cramps (i.e., HANAC syndrome) are localized in exons 24 and 25 [Plaisier et al 2007, Plaisier et al 2010]. They affect glycine residues localized in a short 30-amino acid region of the protein, whereas all but one pathogenic variant responsible for more severe brain disease, including porencephaly and small-vessel brain disease, are mostly distributed through exons 25 to 51 [Meuwissen et al 2015].
### Penetrance
Penetrance of COL4A1-related disorders is probably close to 100%, with expression varying in age of onset and severity of the clinical symptoms, even in the same family; however, these data need verification in larger cohort studies.
### Prevalence
Prevalence of COL4A1-related disorders cannot be established as fewer than 100 families have been described.
No data on the prevalence of COL4A1 pathogenic variants in persons with microscopic hematuria or renal cysts are available.
To date pathogenic variants have been reported in individuals of Dutch, Italian, French, German, American, Chinese, Spanish, and Japanese origin.
## Differential Diagnosis
COL4A2-related porencephaly and intracerebral hemorrhages. Seven heterozygous COL4A2 pathogenic variants have been characterized in individuals with either porencephaly (porencephaly type 2; OMIM 614483) or intracerebral hemorrhage (OMIM 614519). Neurologic presentation of individuals with porencephaly type 2 was similar to that observed in COL4A1-related porencephaly [Yoneda et al 2012, Meuwissen et al 2015]. Four patients presented with adult-onset intracerebral hemorrhage [Jeanne et al 2012]. Variably present extracerebral symptoms included cerebellar and optic atrophy, cataracts, intracranial aneurysms, nephropathy, and myopathy [Verbeek et al 2012, Gunda et al 2014].
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is characterized by a history of migraine headaches with aura (30%-40% of individuals), mid-adult (30s-60s) onset of cerebrovascular disease, mood disturbance, apathy, cognitive disturbance progressing to dementia, and diffuse white-matter lesions and subcortical infarcts on neuroimaging. The pathologic hallmark of CADASIL is electron-dense granules in the media of arterioles that can often be identified by electron microscopic evaluation of skin biopsies. Mutation of NOTCH3 causes CADASIL [Joutel et al 1996]. Inheritance is autosomal dominant.
Autosomal dominant retinal vasculopathy with cerebral leukodystrophy (RVCL) (OMIM 192315) is a microvascular endotheliopathy, which variably associates a retinal vasculopathy, migraine, Raynaud phenomenon, stroke, and dementia with onset in middle age [Ophoff et al 2001].
Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS), a distinctive subtype of RVCL, is characterized by brain disease, kidney disease (hematuria and proteinuria), and Raynaud phenomenon. Ultrastructural alterations affecting the glomerular basement membrane and the basement membrane of capillaries in the brain and other tissues have been observed in HERNS [Jen et al 1997].
C terminus pathogenic variants in TREX1 cause RVCL [Richards et al 2007]. Inheritance is autosomal dominant.
Porencephalic cysts may occur after antenatal or neonatal parenchymal hemorrhagic infarction in the context of neonatal alloimmune thrombocytopenia; a coagulopathy like von Willebrand disease, factor V deficiency (OMIM 227400), or factor X deficiency (OMIM 227600); maternal warfarin use; or thrombophilia (most often heterozygosity for factor V Leiden mutation) (see Factor V Leiden Thrombophilia).
CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leucoencephalopathy; Maeda-syndrome) is characterized by early-onset changes in the deep white matter of the brain observed on MRI and associated neurologic findings. The most frequent initial symptom is gait disturbance from spasticity beginning between ages 20 and 30 years; 23% of affected individuals have stroke-like episodes before age 40 years. Mood changes (apathy and irritability), pseudobulbar palsy, and cognitive dysfunction begin between ages 20 and 50 years. The disease progresses slowly over the five to 20 years following the onset of neurologic symptoms. This rare disease is caused by pathogenic variants in HTRA1; inheritance is autosomal recessive. CARASIL has been reported mostly in Japanese and Chinese families. See HTRA1 Disorder.
Anophthalmia/microphthalmia (A/M). Microphthalmia refers to a globe with a total axial length that is at least two standard deviations below the mean for age. Anophthalmia refers to complete absence of the globe in the presence of ocular adnexa (eyelids, conjunctiva, and lacrimal apparatus). A/M is a genetically heterogenous disorder that has been associated with pathogenic variants in more than 70 genes. SOX2, OTX2, and FOXE3 are among the genes most commonly associated with A/M [Chassaing et al 2014].
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with COL4A1-related disorders, the following are recommended:
* Brain MRI including T1-weighted saggital, T2-weighted axial, and FLAIR axial images
* Brain angiographic CT scan
* Ophthalmologic examination including fundoscopic examination and slit-lamp examination
* Kidney and liver ultrasound examination or CT
* Measurement of serum CK concentration
* Measurement of serum creatinine concentration and estimation of the glomerular filtration rate
* Evaluation for the presence of hematuria
* Electrocardiogram (ECG); echocardiography and ambulatory ECG monitoring in individuals presenting with palpitations
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Hypertensive individuals must be treated to reduce the global risk of stroke.
Supportive care including practical help, emotional support, and counseling are appropriate for affected individuals and their families.
No specific support exists for individuals with COL4A1-related disorders.
* Seizures are managed using standard protocols.
* Cataract surgery may be required for individuals with severe lens opacities.
* Glaucoma is initially treated with topical anti-glaucoma medication. Surgery is reserved for eyes that do not respond to medical therapy.
* Symptomatic paroxysmal supraventricular arrhythmia should be treated with antiarrhythmic drugs (beta blockers).
* Surgical or endovascular treatment should be discussed for asymptomatic intracranial aneurysms >10.0 mm in diameter.
### Prevention of Primary Manifestations
Avoidance of anticoagulant exposure and activities that involve an increased risk for head trauma may decrease the risk for intracerebral hemorrhage.
### Prevention of Secondary Complications
See Prevention of Primary Manifestations.
### Surveillance
The interval at which individuals with COL4A1-related disorders should be seen for follow up depends on the severity and type of symptoms.
Annual clinical evaluation is reasonable.
Regular brain imaging can be proposed, especially to evaluate the size of asymptomatic cerebral aneurysms.
### Agents/Circumstances to Avoid
The following should be avoided:
* Smoking because it increases the global risk of stroke
* Hypertension because it increases the risk of stroke
* Sustained head pressure during birth or postnatal physical activities that may cause head trauma [Gould et al 2006]
* Anticoagulant use [Gould et al 2006]
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Cesarean delivery for pregnancies in which the fetus is at risk for a COL4A1-related disorder is recommended to prevent brain vascular injury attributable to birth trauma in newborns [Gould et al 2006].
### 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
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*[ND]: No data
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*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
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*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
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*[CEEs]: conjugated estrogens
*[Diff]: Difference
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*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
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*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
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*[COL]: Colombia
*[KAZ]: Kazakhstan
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*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
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COL4A1-Related Disorders
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None
| 7,734 |
gene_reviews
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https://www.ncbi.nlm.nih.gov/books/NBK7046/
| 2021-01-18T21:37:30 |
{"synonyms": []}
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For a discussion of the genetic heterogeneity in age at natural menopause, see MENOQ1 (300488).
Mapping
Stolk et al. (2009) conducted a 2-stage genomewide association study for age at natural menopause in 2,979 European women and identified 4 SNPs on chromosome 19q13.4 that were significant: rs1172822 (p = 6.28 x 10(-11)), rs2384687 (p = 1.39 x 10(-10)), rs1551562 (p = 1.04 x 10(-9)), and rs897798 (p = 3.91 x 10(-8)). The authors stated that the 4 SNPs were likely to report the same signal because they were in high linkage disequilibrium. Stolk et al. (2009) subsequently conducted fine mapping using metaanalysis of imputed data from the stage 1 study and found 2 additional SNPs with higher significance compared to that of the initially reported SNPs, located in the same LD block on chromosome 19 as the genomewide-significant SNPs (rs4806660 and rs11668344; p = 1.00 x 10(-7) for both).
In a genomewide association study of 17,438 women, He et al. (2009) found significant association with age at natural menopause for 6 SNPs on chromosome 19q13.42: rs1172822 (p = 1.8 x 10(-19)), rs2384687 (p = 2.4 x 10(-18)), rs897798 (p = 1.1 x 10(-14)), rs7246479 (p = 2.3 x 10(-12)), rs1551562 (p = 2.6 x 10(-12)), and rs12611091 (p = 6.6 x 10(-10)). He et al. (2009) stated that the nearest gene to all 6 SNPs is BRSK1 (609235) and that other nearby genes include SUV420H2 (613198) and HSPBP1 (612939).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MENOPAUSE, NATURAL, AGE AT, QUANTITATIVE TRAIT LOCUS 2
|
c2752068
| 7,735 |
omim
|
https://www.omim.org/entry/612884
| 2019-09-22T16:00:24 |
{"omim": ["612884"]}
|
Hand-foot-genital syndrome (HFGS) is a very rare multiple congenital abnormality syndrome characterized by distal limb malformations and urogenital defects.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hand-foot-genital syndrome
|
c1841679
| 7,736 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2438
| 2021-01-23T18:31:02 |
{"gard": ["2594"], "mesh": ["C535627"], "omim": ["140000"], "umls": ["C1841679"], "icd-10": ["Q51.2"], "synonyms": ["HFGS", "Hand-foot-uterus syndrome"]}
|
White forelock with malformations is a multiple congenital anomalies syndrome characterized by poliosis, distinct facial features (epicanthal folds, hypertelorism, posterior rotation of ears, prominent philtrum, high-arched palate) and congenital anomalies/malformations of the eye (blue sclera), cardiopulmonary (atrial septal defect, prominent thoracic and abdominal veins), and skeletal (clinodactyly, syndactyly of the fingers and 2nd and 3rd toes) systems. There have been no further descriptions in the literature since 1980.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
White forelock with malformations
|
c1848463
| 7,737 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2475
| 2021-01-23T19:12:25 |
{"gard": ["10081"], "mesh": ["C536700"], "omim": ["277740"], "umls": ["C1848463"], "icd-10": ["Q87.8"]}
|
Silent sinus syndrome
Other namesImploding antrum syndrome
SpecialtyENT surgery
Silent sinus syndrome is a spontaneous, asymptomatic collapse of the maxillary sinus and orbital floor associated with negative sinus pressures. It can cause painless facial asymmetry, diplopia and enophthalmos. Usually the diagnosis is suspected clinically, and it can be confirmed radiologically by characteristic imaging features that include maxillary sinus outlet obstruction, sinus opacification, and sinus volume loss caused by inward retraction of the sinus walls. Treatment is surgical involving making an outlet for mucous drainage from the obstructed sinus, and, in some cases, paired with reconstruction of the orbital floor.
## References[edit]
* Illner A, Davidson HC, Harnsberger HR, Hoffman J (2002). "The silent sinus syndrome: clinical and radiographic findings". AJR Am J Roentgenol. 178 (2): 503–6. doi:10.2214/ajr.178.2.1780503. PMID 11804926. Full text
* Numa WA, Desai U, Gold DR, Heher KL, Annino DJ (2005). "Silent sinus syndrome: a case presentation and comprehensive review of all 84 reported cases". Ann Otol Rhinol Laryngol. 114 (9): 688–94. PMID 16240931.
* Habicht ME, Eppenberger PE, Galassi FM, Rühli FJ, Henneberg M (2018). "Queen Meresankh III – the oldest case of bilateral Silent Sinus Syndrome (c. 2620/10 - 2570 BC)?". Anthropologie. 56 (2): 103–113. doi:10.26720/anthro.17.09.25.2.
## External links[edit]
Classification
D
External resources
* Orphanet: 71276
This article about a disease, disorder, or medical condition is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Silent sinus syndrome
|
c3698095
| 7,738 |
wikipedia
|
https://en.wikipedia.org/wiki/Silent_sinus_syndrome
| 2021-01-18T18:30:09 |
{"umls": ["C3698095"], "orphanet": ["71276"], "wikidata": ["Q7514763"]}
|
## Clinical Features
Abidi et al. (1999) reported a family with X-linked mental retardation in which there were 8 affected males in 3 generations. Somatic manifestations were variable and mild; these included short stature (4 of 8), small head circumference (5 of 8), sloping forehead (5 of 8), hearing loss (3 of 8), cupped ears (2 of 8), and small testes (4 of 6). The somatic manifestations were sufficiently variable to limit their usefulness in clinical diagnosis of this disorder.
Mapping
By linkage studies in a family with a syndromic form of mental retardation, Abidi et al. (1999) obtained a lod score of 4.41 with zero recombination at locus DXS1166 in Xq13.2. Given the broad range of somatic manifestations, the authors concluded that further molecular study of other X-linked mental retardation entities with similar clinical manifestations will be necessary to determine if this entity is allelic to them.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ABIDI X-LINKED MENTAL RETARDATION SYNDROME
|
c1846056
| 7,739 |
omim
|
https://www.omim.org/entry/300262
| 2019-09-22T16:20:36 |
{"doid": ["0060818"], "mesh": ["C535556"], "omim": ["300262"], "orphanet": ["85273"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, X-LINKED, SYNDROMIC, ABIDI TYPE"]}
|
An extremely rare arthrogryposis syndrome, described in only two pairs of siblings from two unrelated families to date, and characterized by the association of arthrogryposis, congenital torticollis, dysmorphic facial features (i.e. asymmetry of the face, myopathic facial movements, ptosis, posteriorly rotated ears, cleft palate), progressive scoliosis and episodes of malignant hyperthermia. There have been no further descriptions in the literature since 1988.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Multiple pterygium-malignant hyperthermia syndrome
|
c1857576
| 7,740 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2215
| 2021-01-23T18:17:44 |
{"gard": ["3361"], "mesh": ["C565679"], "omim": ["217150"], "umls": ["C1857576"], "icd-10": ["G71.8"], "synonyms": ["Froster-Iskenius-Waterson-Hall syndrome", "Malignant hyperthermia-arthrogryposis-torticollis syndrome"]}
|
Hypertryptophanemia
Other namesFamilial hypertryptophanemia[1]
Tryptophan
SpecialtyEndocrinology
Hypertryptophanemia, is a rare autosomal recessive[2] metabolic disorder that results in a massive buildup of the amino acid tryptophan in the blood, with associated symptoms and tryptophanuria (-uria denotes "in the urine").[3][4]
Elevated levels of tryptophan are also seen in Hartnup disease,[5] a disorder of amino acid transport.[6] However, the increase of tryptophan in that disorder is negligible when compared to that of hypertryptophanemia.[1][5]
## Contents
* 1 Symptoms and signs
* 2 Genetics
* 3 Pathophysiology
* 4 Diagnosis
* 5 Management
* 6 See also
* 7 References
* 8 External links
## Symptoms and signs[edit]
A number of abnormalities and symptoms have been observed with hypertryptophanemia.
Musculoskeletal effects include: joint contractures of the elbows and interphalangeal joints of the fingers and thumbs (specifically the distal phalanges), pes planus (fallen arches), an ulnar drift affecting the fingers of both hands (an unusual, yet correctible feature where the fingers slant toward the ulnar side of the forearm), joint pain and laxity, and adduction of the thumbs (where the thumb appears drawn into the palm, related to contracture of the adductor pollicis).[1][2]
Behavioral, developmental and other anomalies often include: hypersexuality, perceptual hypersensitivity, emotional lability (mood swings),[3] hyperaggressive behavior;[2] hypertelorism (widely-set eyes), optical strabismus (misalignment) and myopia.[1][2]
Metabolically, hypertryptophanemia results in tryptophanuria and exhibits significantly elevated serum levels of tryptophan, exceeding 650% of maximum (normal range: 25-73 micromole/l) in some instances.[2][3]
A product of the bacterial biosynthesis of tryptophan is indole.[7][8] The excess of tryptophan in hypertryptophanemia also results in substantial excretion of indoleic acids. These findings suggest a possible congenital defect in the metabolic pathway where tryptophan is converted to kynurenine.[3]
Kynurenine, a metabolite of tryptophan.
## Genetics[edit]
Familial Hypertryptophanemia has an autosomal recessive pattern of inheritance.
Hypertryptophanemia is believed to be inherited in an autosomal recessive manner.[2] This means a defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.[citation needed]
## Pathophysiology[edit]
At present, no specific enzyme deficiency nor genetic mutation has been implicated as the cause of hypertryptophanemia.[1][2] Several known factors regarding tryptophan metabolism and kynurenines, however, may explain the presence of behavioral abnormalities seen with the disorder.
Tryptophan is an essential amino acid, and is required for protein synthesis.[9] Aside from this crucial role, the remainder of tryptophan is primarily metabolized along the kynurenine pathway in most tissues, including those of the brain and central nervous system.[10][11][12][13]
As the main defect behind hypertryptophanemia is suspected to alter and disrupt the metabolic pathway from tryptophan to kynurenine,[2] a possible correlation between hypertryptophanemia and the known effects of kynurenines on neuronal function, physiology and behavior may be of interest.[14][15]
One of these kynurenines, aptly named kynurenic acid, serves as a neuroprotectant through its function as an antagonist at both nicotinic and glutamate receptors (responsive to the neurotransmitters nicotine and glutamate, respectively).[11][12] This action is in opposition to the agonist quinolinic acid, another kynurenine, noted for its potential as a neurotoxin.[10][13] Quinolinic acid activity has been associated with neurodegenerative disorders such as Huntington's disease, the neuroprective abilities of kynurenic acid forming a counterbalance against this process, and the related excitotoxicity and similar damaging effects on neurons.[13][14]
Indoleic acid excretion is another indicator of hypertryptophanemia.[2][3] Indirectly related to kynurenine metabolism, indole modifies neural function and human behavior by interacting with voltage-dependent sodium channels (integral membrane proteins that form ion channels, allowing vital synaptic action potentials).[15]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (February 2018)
## Management[edit]
This section is empty. You can help by adding to it. (July 2017)
## See also[edit]
* Blue diaper syndrome
* Tryptamine
* Serotonin
## References[edit]
1. ^ a b c d e Online Mendelian Inheritance in Man (OMIM): 600627
2. ^ a b c d e f g h i Martin JR, Mellor CS, Fraser FC (April 1995). "Familial hypertryptophanemia in two siblings". Clin. Genet. 47 (4): 180–183. doi:10.1111/j.1399-0004.1995.tb03956.x. PMID 7628119.
3. ^ a b c d e Snedden W, Mellor CS, Martin JR (July 1983). "Familial hypertryptophanemia, tryptophanuria and indoleketonuria". Clinica Chimica Acta. 131 (3): 247–256. doi:10.1016/0009-8981(83)90094-3. ISSN 0009-8981. PMID 6883719.
4. ^ Snedden W, Mellor CS, Martin JR (November 1982). "Hypertryptophanemia and indoleketonuria in two mentally subnormal siblings" (Free full text). The New England Journal of Medicine. 307 (22): 1405. doi:10.1056/NEJM198211253072219. ISSN 0028-4793. PMID 7133092.
5. ^ a b Online Mendelian Inheritance in Man (OMIM): 234500
6. ^ Seow HF, Bröer S, Bröer A, Bailey CG, Potter SJ, Cavanaugh JA, Rasko JE (September 2004). "Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19". Nature Genetics. 36 (9): 1003–1007. doi:10.1038/ng1406. PMID 15286788.
7. ^ Dunn MF, Niks D, Ngo H, Barends TR, Schlichting I (June 2008). "Tryptophan synthase: the workings of a channeling nanomachine". Trends in Biochemical Sciences. 33 (6): 254–264. doi:10.1016/j.tibs.2008.04.008. PMID 18486479.
8. ^ Houben KF, Dunn MF (March 1990). "Allosteric effects acting over a distance of 20-25 A in the Escherichia coli tryptophan synthase bienzyme complex increase ligand affinity and cause redistribution of covalent intermediates". Biochemistry. 29 (9): 2421–2429. doi:10.1021/bi00461a028. ISSN 0006-2960. PMID 2186812.
9. ^ Reeds PJ (1 July 2000). "Dispensable and indispensable amino acids for humans" (Free full text). The Journal of Nutrition. 130 (7): 1835S–1840S. doi:10.1093/jn/130.7.1835S. ISSN 0022-3166. PMID 10867060.
10. ^ a b Stone TW (January 2001). "Endogenous neurotoxins from tryptophan". Toxicon. 39 (1): 61–73. doi:10.1016/S0041-0101(00)00156-2. ISSN 0041-0101. PMID 10936623.
11. ^ a b Stone TW, Mackay GM, Forrest CM, Clark CJ, Darlington LG (July 2003). "Tryptophan metabolites and brain disorders". Clinical Chemistry and Laboratory Medicine. 41 (7): 852–859. doi:10.1515/CCLM.2003.129. PMID 12940508. S2CID 21169913.
12. ^ a b Stone TW, Forrest CM, Mackay GM, Stoy N, Darlington LG (December 2007). "Tryptophan, adenosine, neurodegeneration and neuroprotection". Metabolic Brain Disease. 22 (3–4): 337–352. doi:10.1007/s11011-007-9064-3. PMID 17712616. S2CID 5823156.
13. ^ a b c Stone TW (April 2001). "Kynurenic acid antagonists and kynurenine pathway inhibitors". Expert Opin Investig Drugs. 10 (4): 633–645. doi:10.1517/13543784.10.4.633. PMID 11281814. S2CID 30077788.
14. ^ a b Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA (August 2006). "Tryptophan metabolism in the central nervous system: medical implications". Expert Reviews in Molecular Medicine. 8 (20): 1–27. doi:10.1017/S1462399406000068. PMID 16942634.
15. ^ a b Moroni F (June 1999). "Tryptophan metabolism and brain function: focus on kynurenine and other indole metabolites". European Journal of Pharmacology. 375 (1–3): 87–100. doi:10.1016/S0014-2999(99)00196-X. ISSN 0014-2999. PMID 10443567.
## External links[edit]
Classification
D
* ICD-10: E70.8
* ICD-9-CM: 270.2
* OMIM: 600627
* MeSH: C538393
External resources
* Orphanet: 2224
* 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hypertryptophanemia
|
c2931837
| 7,741 |
wikipedia
|
https://en.wikipedia.org/wiki/Hypertryptophanemia
| 2021-01-18T18:47:28 |
{"gard": ["2871"], "mesh": ["C538393", "C563467"], "umls": ["C2931837"], "icd-9": ["270.2"], "icd-10": ["E70.8"], "orphanet": ["2224"], "wikidata": ["Q5958803"]}
|
A rare, genetic, syndromic, neurological disorder characterized by early infantile-onset of the progressive brain and spinal cord calcification, growth retardation, psychomotor deterioration, deafness, microcytic hypochromic anemia, and variable distal renal tubular acidosis. There have been no further descriptions in the literature since 1997.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Central nervous system calcification-deafness-tubular acidosis-anemia syndrome
|
None
| 7,742 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3240
| 2021-01-23T18:26:48 |
{"synonyms": ["Central nervous system calcification-hearing loss-tubular acidosis-anemia syndrome", "Yoshimura-Takeshita syndrome"]}
|
Penoscrotal transposition (PST) is a rare congenital genital anomaly in which the scrotum is positioned superior and anterior to the penis. PST may present with a broad spectrum of anomalies ranging from simple shawl scrotum (doughnut scrotum) to very complex extreme transposition with craniofacial, central nervous system, cardiac, gastrointestinal, urological, and other genital (undescended testicles, hypospadias, chordee) malformations. Growth deficiency and intellectual disability may also be noticed (60% 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Penoscrotal transposition
|
c1868854
| 7,743 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2842
| 2021-01-23T17:15:34 |
{"gard": ["4273"], "mesh": ["C536650"], "umls": ["C1868854"], "icd-10": ["Q55.8"]}
|
Concha bullosa on both sides (marked with asterisks), coronal orientated image from CT
A concha bullosa is a pneumatized (air-filled) cavity within a nasal concha, also known as a turbinate.[1] Bullosa refers to the air-filled cavity within the turbinate.[1] It is a normal anatomic variant seen in up to half the population. Occasionally, a large concha bullosa may cause it to bulge sufficiently to obstruct the opening of an adjacent sinus, possibly leading to recurrent sinusitis.[1] In such a case the turbinate can be reduced in size by endoscopic nasal surgery (turbinectomy). The presence of a concha bullosa is often associated with deviation of the nasal septum toward the opposite side of the nasal cavity.[2] Although it is thought that sinusitis or sinus pathology has relation to concha bullosa, no strong statistical correlation has been demonstrated.[1]
## Additional image[edit]
## References[edit]
1. ^ a b c d Hatipoğlu, HG; Cetin, MA; Yüksel, E (Sep 2005). "Concha bullosa types: their relationship with sinusitis, ostiomeatal and frontal recess disease" (PDF). Diagnostic and Interventional Radiology. 11 (3): 145–9. PMID 16206055.
2. ^ Stallman, JS; Lobo, JN; Som, PM (Oct 2004). "The incidence of concha bullosa and its relationship to nasal septal deviation and paranasal sinus disease". American Journal of Neuroradiology. 25 (9): 1613–8. PMID 15502150.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Concha bullosa
|
c0339821
| 7,744 |
wikipedia
|
https://en.wikipedia.org/wiki/Concha_bullosa
| 2021-01-18T18:44:18 |
{"umls": ["C0339821"], "wikidata": ["Q5158611"]}
|
Phobophobia
SpecialtyPsychology
Phobophobia is the fear of phobias and, more specifically, of the internal sensations associated with that phobia and anxiety,[1] which binds it closely to other anxiety disorders, especially with generalized anxiety disorders (free floating fears) and panic attacks. It is a condition in which anxiety disorders are maintained in an extended way, which combined with the psychological fear generated by phobophobia of encountering the feared phobia would ultimately lead to the intensifying of the effects of the feared phobia that the patient might have developed, such as agoraphobia, and specially with it,[2] and making them susceptible to having an extreme fear of panicking.[2] Phobophobia comes in between the stress the patient might be experiencing and the phobia that the patient has developed as well as the effects on his/her life, or in other words, it is a bridge between anxiety/panic the patient might be experiencing and the type of phobia he/she fears, creating an intense and extreme predisposition to the feared phobia. Nevertheless, phobophobia is not necessarily developed as part of other phobias, but can be an important factor for maintaining them.[2]
Phobophobia differentiates itself from other kinds of phobias by the fact that there is no environmental stimulus per se, but rather internal dreadful sensations similar to psychological symptoms of panic attacks.[2] The psychological state of the mind creates an anxious response that has itself a conditioned stimuli leading to further anxiety,[2] resulting in a vicious cycle. Phobophobia is a fear experienced before actually experiencing the fear of the feared phobias its somatic sensations that precede it, which is preceded by generalized anxiety disorders and can generate panic attacks. Like all the phobias, the patients avoids the feared phobia in order to avoid the fear of it.
## Contents
* 1 Cause and symptoms
* 2 Association with generalized anxiety disorder
* 3 Association with panic attacks
* 4 Treatment
* 5 Etymology
* 6 See also
* 7 References
## Cause and symptoms[edit]
Phobophobia is mainly linked with internal predispositions. It is developed by the unconscious mind which is linked to an event in which phobia was experienced with emotional trauma and stress, which are closely linked to anxiety disorders and by forgetting and recalling the initiating trauma.[3] Phobophobia might develop from other phobias, in which the intense anxiety and panic caused by the phobia might lead to fearing the phobia itself, which triggers phobophobia before actually experiencing the other phobia. The extreme fear towards the other phobia can lead the patient to believe that their condition may develop into something worse, intensifying the effects of the other phobia by fearing it. Also, phobophobia can be developed when anxiety disorders are not treated, creating an extreme predisposition to other phobias. The development of phobophobia can also be attributed to characteristics of the patient itself, such as phylogenetic influence, the prepotency of certain stimuli, individual genetic inheritance, age incidence, sex incidence, personality background, cultural influence inside and outside the family, physiological variables and biochemical factors.[3] Phobophobia shares the symptoms of many other anxiety disorders, more specifically panic attacks and generalized anxiety disorder:
1. Dizziness
2. Heart pounding
3. An excess of perspiration
4. Slight paresthesia
5. Tension
6. Hyperventilation
7. Angst
8. Faintness
9. Avoidance
## Association with generalized anxiety disorder[edit]
Generalized anxiety disorder is when our minds are troubled about some uncertain event,[4] or in other words, when we feel threatened, although the source of the threat might not be obvious to us.[4] It is a disorder when it happens frequently, and disables people from accomplishing some of their daily activities. Generalized anxiety disorder always comes before phobophobia, and some of its symptoms are listed below:
1. Paleness of skin
2. Sweating
3. Dilation of pupils
4. Rapid pounding of heart
5. Rise in blood pressure
6. Tension in the muscles
7. Trembling
8. Readiness to be startled
9. Dryness and tightness of the throat and mouth
10. Rapid breathing
11. Desperation
12. A sinking feeling in the stomach
13. A strong desire to cry, run or hide
The main problem with this disorder is that we do not know what we are troubled about, which may lead to our desire to escape. Anxiety becomes a disorder only when we experience psychological trauma, in which our knowledge of past events trigger a fear of uncertain danger in the future. In other words, the primarily event is anxiety which arises for no accountable reason, panic might develop from anxiety[4] and the phobophobia is developed in the very end as a consequence of both of them,[3] sharing some of the symptoms. If either of these initiating disorders are not treated, phobophobia can be developed because an extended susceptibility and experience of this feelings can create an extreme predisposition to other phobias. Anxiety is mainly fixed to a certain specific event or specific events, a strong learned drive which is situationally evoked which is stressful to one person but not to another, and this makes it much easier for phobophobia to develop, as well as other phobias.[5]
## Association with panic attacks[edit]
When people experience panic attacks, they are convinced that they are about to die or suffer some extreme calamity[6] in which some kind of action is done by the individual (such as fleeing or screaming). In case of phobophobia, a panic attack might be encountered as the fear that they will in fact experience the calamities of the feared phobia and see it as something inevitable. Also, the nature of the panic is of profound personal significance to the individual, on a similar way phobophobia is related to the individual.[6] This is why panic attacks are closely related to phobophobia. Nevertheless, they can differentiate themselves by the fact that phobophobia is a psychological fear of the phobia itself that intensifies it, while panic attacks are extreme fear of encountering the calamities of an imminent disaster, and in this particular case, of encountering other phobias, which can be often accompanied by the at least four of the following common symptoms of panic attacks:
1. Dyspnea
2. Palpitations
3. Chest pain or discomfort
4. Choking or smothering sensations
5. Vertigo or unsteady feelings
6. Feelings of unreality (depersonalization or derealization)
7. Paresthesias (tingling in hands or feet)
8. Hot and cold flushes
9. Faintness
10. Trembling or shaking
11. Difficult breathing
12. Sweating
Panic attacks can also be accompanied by disturbance in heart action and feelings of desperation and angst.[6] Being closely related, phobophobia and panic attacks, the first one can be treated like a panic attack with psychological therapy. Moreover, in combination with phobophobia, a patient might be more susceptible to believe that their continuing anxiety symptoms will eventually culminate in a much more severe mental disorder, such as schizophrenia.[6]
## Treatment[edit]
There are many ways to treat phobophobia, and the methods used to treat panic disorders have been shown to be effective to treat phobophobia, because panic disorder patients will present in a similar fashion to conventional phobics and perceive their fear as totally irrational.[6] Also, exposure based techniques have formed the basis of the armamentarium of behaviour therapists in the treatment of phobic disorders for many years, they are the most effective forms of treatment for phobic avoidance behavior.[7] Phobics are treated by exposing them to the stimuli which they specially fear,[6] and in case of phobophobia, it is both the phobia they fear and their own sensations. There are two ways to approach interoceptive exposure on patients:
* Paradoxical intention: This method is especially useful to treat the fear towards the phobophobia and the phobia they fear, as well as some of the sensations the patient fears. This method exposes the patient to the stimuli that causes the fear,[7] which they avoid. The patient is directly exposed to it bringing them to experience the sensations that they fear, as well as the phobia. This exposure based technique helps the doctor by guiding the patient to encounter their fears and overcome them by feeling no danger around them.
* Symptoms artificially produced: This method is very useful to treat the fear towards the sensations encountered when experiencing phobophobia, the main feared stimuli of this anxiety disorder. By ingestion of different chemical agents, such as caffeine, CO2-O2 or adrenaline, some of the symptoms the patient feels when encountering phobophobia and other anxiety disorders are triggered, such as hyperventilation, heart pounding, blurring of vision and paresthesia,[2] which can lead to the controlling of the sensations by the patients. At first, panic attacks will be encountered, but eventually, as the study made by Doctor Griez and Van den Hout shows, the patient shows no fear to somatic sensations and panic attacks and eventually of the phobia feared.[2]
Cognitive modification is another method that helps considerably to treat phobophobics. When treating the patients with the method, doctors correct some wrong information the patient might have about his disease, such as their catastrophic beliefs or imminent disaster by the feared phobia. Some doctors have even agreed that this is the most helpful component, since it has shown to be very effective especially if combined with other methods, like interoceptive exposure. The doctor seeks to convince patients that their symptoms do not signify danger or loss of control,[7] for example, if combined with the interoceptive exposure, the doctor can show them that there is no unavoidable calamity and if the patient can keep themselves under control, they learn by themselves that there is no real threat and that it is just in their mind. Cognitive modification also seeks to correct other minor misconceptions, such as the belief that the individual will go crazy and may need to be "locked away forever" or that they will totally lose control and perhaps "run amok".[6] Probably, the most difficult aspect of cognitive restructuring for the majority of the patients will simply be to identify their aberrant beliefs and approach them realistically.[6]
Relaxation and breathing control techniques are used to produce the symptoms naturally. The somatic sensations, the feared stimuli of phobophobia, are sought to be controlled by the patient to reduce the effects of phobophobia.[6] One of the major symptoms encountered is that of hyperventilation, which produce dizziness, faintness, etc. So, hyperventilation is induced in the patients in order to increase their CO2 levels that produce some of this symptoms. By teaching the patients to control this sensations by relaxing and controlling the way they breathe, this symptoms can be avoided and reduce phobophobia. This method is useful if combined with other methods, because alone it doesn't treat other main problems of phobophobia.
## Etymology[edit]
The word phobophobia is an English adaptation of the Greek φόβος, phobos, "fear". Phobophobia literally translates to "fear of fear".
## See also[edit]
* Anxiety sensitivity
* First inauguration of Franklin D. Roosevelt, the speech for which contained the line "the only thing we have to fear is fear itself"
## References[edit]
1. ^ Griez, E. J. and Van den Hout, M. A. . Treatment of Phobophobia by Exposure to CO2-Induced Anxiety Symptoms. The Journal of Nervous and Mental Disease 171 (1983): 506-508. ISSN 0022-3018.
2. ^ a b c d e f g Griez, E. J. and Van den Hout, M. A. . Treatment of Phobophobia by Exposure to CO2-Induced Anxiety Symptoms. The Journal of Nervous and Mental Disease 171 (1983): 506-508. ISSN 0022-3018.
3. ^ a b c Mark, Isaac M. Fear and Phobias. Great Britain: Academic Press, 1969, LCCN 75084222.
4. ^ a b c Mark, Isaac M. Living with fear: understanding and coping with anxiety. USA: McGraw Hill, 1978, ISBN 0-07-040395-3.
5. ^ Levitt, Eugene E. The psychology of Anxiety. USA: The Bobbs-Merrill Company, 1967, LCCN 67-19654.
6. ^ a b c d e f g h i Baker, Roger. Panic Disorder: Theory, Research and Therapy. Ed. Roger Baker. Great Britain: John Wiley and Son Ltd., 1989, ISBN 0-471-92319-2.
7. ^ a b c Wolfe, Barry E., et al. Treatment of panic disorder: A Consensus Development Disorder. Ed. Barry E. Wolfe and Jack D. Maser. USA: American Psychiatric Press, 1994, ISBN 0-88048-685-6.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
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Phobophobia
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wikipedia
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https://en.wikipedia.org/wiki/Phobophobia
| 2021-01-18T18:58:05 |
{"wikidata": ["Q1644478"]}
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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: "Zamzam–Sheriff–Phillips syndrome" – news · newspapers · books · scholar · JSTOR (April 2008) (Learn how and when to remove this template message)
Zamzam–Sheriff–Phillips syndrome
SymptomsAniridia, Intellectual disability
Risk factorsfamily history.
Zamzam–Sheriff–Phillips syndrome is a rare[1] autosomal recessive congenital disorder. It is characterized by aniridia, ectopia lentis, abnormal upper incisors and intellectual disability.[2] Not a lot of research has been undertaken of this particular disease so thus far there is no known gene that affects this condition. However it has been hypothesised that the symptoms described are found at a particular gene, though intellectual disability is believed to be due to a different genetic cause.
Consanguinuity (intermarrying among relatives such as cousins), often associated with autosomal recessive inheritance, has been attributed to the inheritance of this disease.[3]
## References[edit]
1. ^ Zazam Sheriff Phillips syndrome; Aniridia, lens luxation, mental retardation at NIH's Office of Rare Diseases
2. ^ Birth Disorder Information Directory - Z
3. ^ Zamzam AM, Sheriff SM, Phillips CI (1988). "Aniridia, ectopia lentis, abnormal upper incisors and mental retardation--an autosomal recessive syndrome". Jpn. J. Ophthalmol. 32 (4): 375–8. PMID 3266265.
* v
* t
* e
Congenital malformations and deformations of eyes
Adnexa
Eyelid
* Ptosis
* Ectropion
* Entropion
* Distichia
* Blepharophimosis
* Ablepharon
* Marcus Gunn phenomenon
Lacrimal apparatus
* Congenital lacrimal duct obstruction
Globe
Entire eye
* Anophthalmia (Cystic eyeball, Cryptophthalmos)
* Microphthalmia
Lens
* Ectopia lentis
* Aphakia
Iris
* Aniridia
Anterior segment
* Axenfeld–Rieger syndrome
Cornea
* Keratoglobus
* Megalocornea
Other
* Buphthalmos
* Coloboma (Coloboma of optic nerve)
* Hydrophthalmos
* Norrie disease
This genetic disorder article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Zamzam–Sheriff–Phillips syndrome
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c2931300
| 7,746 |
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https://en.wikipedia.org/wiki/Zamzam%E2%80%93Sheriff%E2%80%93Phillips_syndrome
| 2021-01-18T19:03:55 |
{"gard": ["339"], "mesh": ["C536723"], "umls": ["C2931300"], "wikidata": ["Q167868"]}
|
"Mendes da Costa" redirects here. For people with this name, see Mendes (name). "Mendes da Costa syndrome" redirects here. It is not to be confused with Da Costa's syndrome.
Erythrokeratodermia variabilis
Other namesProgressive symmetric erythrokeratodermia, Gottron type
Erythrokeratodermia variabilis is inherited in an autosomal dominant manner of inheritance
SpecialtyDermatology, medical genetics
Erythrokeratodermia variabilis (also known as "erythrokeratodermia figurata variabilis", "keratosis extremitatum progrediens", "keratosis palmoplantaris transgrediens et progrediens",[2]:509 "Mendes da Costa syndrome",[3] "Mendes da Costa type erythrokeratodermia", and "progressive symmetric erythrokeratoderma") is a rare autosomal dominant disorder that usually presents at birth or during the first year of life.[4] To date, it is thought to be caused by mutations in genes encoding for connexin channels proteins in the epidermis, leading to the misregulation of homeostasis in keratinocytes.[5]
One type is characterized by generalized, persistent, brown hyperkeratosis with accentuated skin markings, while a second type is localized, with involvement that is limited in extent and characterized by sharply demarcated, hyperkeratotic plaques.[2][6]:565
It can be associated with GJB3[7] and GJB4.[8]
It was characterized in 1925.[9]
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ "OMIM Entry - # 133200 - ERYTHROKERATODERMIA VARIABILIS ET PROGRESSIVA 1; EKVP1". omim.org. Retrieved 3 September 2017.
2. ^ a b Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
4. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). Page 497. McGraw-Hill. ISBN 0-07-138076-0.
5. ^ Richard, Gabriela. (2000). Exp Dermatol. Page 77-96. ISSN 0906-6705.
6. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
7. ^ Richard G, Smith LE, Bailey RA, et al. (December 1998). "Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis". Nat. Genet. 20 (4): 366–9. doi:10.1038/3840. PMID 9843209. S2CID 841727.
8. ^ Macari F, Landau M, Cousin P, et al. (November 2000). "Mutation in the Gene for Connexin 30.3 in a Family with Erythrokeratodermia Variabilis". Am. J. Hum. Genet. 67 (5): 1296–301. doi:10.1016/S0002-9297(07)62957-7. PMC 1288569. PMID 11017804.
9. ^ Mendes da Costa, S. Erythro- et keratodermia variabilis in a mother and a daughter. Acta Derm. Venerol. 6: 255-261, 1925.
Classification
D
* ICD-10: Q82.8
* OMIM: 133200
* MeSH: D056266
External resources
* Orphanet: 316
* v
* t
* e
Diseases of ion channels
Calcium channel
Voltage-gated
* CACNA1A
* Familial hemiplegic migraine 1
* Episodic ataxia 2
* Spinocerebellar ataxia type-6
* CACNA1C
* Timothy syndrome
* Brugada syndrome 3
* Long QT syndrome 8
* CACNA1F
* Ocular albinism 2
* CSNB2A
* CACNA1S
* Hypokalemic periodic paralysis 1
* Thyrotoxic periodic paralysis 1
* CACNB2
* Brugada syndrome 4
Ligand gated
* RYR1
* Malignant hyperthermia
* Central core disease
* RYR2
* CPVT1
* ARVD2
Sodium channel
Voltage-gated
* SCN1A
* Familial hemiplegic migraine 3
* GEFS+ 2
* Febrile seizure 3A
* SCN1B
* Brugada syndrome 6
* GEFS+ 1
* SCN4A
* Hypokalemic periodic paralysis 2
* Hyperkalemic periodic paralysis
* Paramyotonia congenita
* Potassium-aggravated myotonia
* SCN4B
* Long QT syndrome 10
* SCN5A
* Brugada syndrome 1
* Long QT syndrome 3
* SCN9A
* Erythromelalgia
* Febrile seizure 3B
* Paroxysmal extreme pain disorder
* Congenital insensitivity to pain
Constitutively active
* SCNN1B/SCNN1G
* Liddle's syndrome
* SCNN1A/SCNN1B/SCNN1G
* Pseudohypoaldosteronism 1AR
Potassium channel
Voltage-gated
* KCNA1
* Episodic ataxia 1
* KCNA5
* Familial atrial fibrillation 7
* KCNC3
* Spinocerebellar ataxia type-13
* KCNE1
* Jervell and Lange-Nielsen syndrome
* Long QT syndrome 5
* KCNE2
* Long QT syndrome 6
* KCNE3
* Brugada syndrome 5
* KCNH2
* Short QT syndrome
* KCNQ1
* Jervell and Lange-Nielsen syndrome
* Romano–Ward syndrome
* Short QT syndrome
* Long QT syndrome 1
* Familial atrial fibrillation 3
* KCNQ2
* BFNS1
Inward-rectifier
* KCNJ1
* Bartter syndrome 2
* KCNJ2
* Andersen–Tawil syndrome
* Long QT syndrome 7
* Short QT syndrome
* KCNJ11
* TNDM3
* KCNJ18
* Thyrotoxic periodic paralysis 2
Chloride channel
* CFTR
* Cystic fibrosis
* Congenital absence of the vas deferens
* CLCN1
* Thomsen disease
* Myotonia congenita
* CLCN5
* Dent's disease
* CLCN7
* Osteopetrosis A2, B4
* BEST1
* Vitelliform macular dystrophy
* CLCNKB
* Bartter syndrome 3
TRP channel
* TRPC6
* FSGS2
* TRPML1
* Mucolipidosis type IV
Connexin
* GJA1
* Oculodentodigital dysplasia
* Hallermann–Streiff syndrome
* Hypoplastic left heart syndrome
* GJB1
* Charcot–Marie–Tooth disease X1
* GJB2
* Keratitis–ichthyosis–deafness syndrome
* Ichthyosis hystrix
* Bart–Pumphrey syndrome
* Vohwinkel syndrome)
* GJB3/GJB4
* Erythrokeratodermia variabilis
* Progressive symmetric erythrokeratodermia
* GJB6
* Clouston's hidrotic ectodermal dysplasia
Porin
* AQP2
* Nephrogenic diabetes insipidus 2
See also: ion channels
This genetic disorder article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Erythrokeratodermia variabilis
|
c0265961
| 7,747 |
wikipedia
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https://en.wikipedia.org/wiki/Erythrokeratodermia_variabilis
| 2021-01-18T18:45:41 |
{"gard": ["10923"], "mesh": ["D056266"], "umls": ["C0265961", "C1851480"], "orphanet": ["317"], "wikidata": ["Q3591493"]}
|
A number sign (#) is used with this entry because of evidence that this disorder can be caused by mutations in the integrin-beta-4 gene (ITGB4; 147557) or the integrin-alpha-6 gene (ITGA6; 147556).
See also epidermolysis bullosa simplex with pyloric atresia (EBSPA), which is caused by mutations in the PLEC1 gene (601282).
Description
Traditionally, EB-PA has been classified as a form of junctional epidermolysis bullosa. Uitto et al. (1997) and Pulkkinen and Uitto (1998) proposed reclassification of the disorder as a 'hemidesmosomal' variant because ultrastructural findings can indicate cleavage in the hemidesmosomal region of the skin. However, in subsequent reports of consensus conferences, Fine et al. (2000, 2008) eliminated the term 'hemidesmosomal' because it added undue confusion. The disorder is considered to be a form of junctional EB because skin cleavage occurs within the lamina lucida. Hemidesmosome may be abnormal because the integrins span this region.
In a study involving 265 cases of junctional or hemidesmosomal EB, Varki et al. (2006) reviewed the clinical and molecular heterogeneity of these subtypes of EB, discussed exceptions to the general rules on genotype-phenotype correlations, and noted unusual phenotypes and genetics observed in patients and families with EB.
Clinical Features
Bull et al. (1980, 1983) reported a sister and brother with epidermolysis bullosa and pyloric atresia at birth. Both died in early infancy of complications related to the skin disorder. An older stillborn sister was probably affected. Both sibs also had bilateral stenosis at the ureterovesical junctions with bilateral pyelonephrosis; this feature was present in an earlier-reported case. Electron microscopic studies of skin biopsy specimens disclosed findings consistent with a diagnosis of epidermolysis bullosa letalis, or the Herlitz form of JEB (226700). The authors found 10 previously reported cases and 2 instances in which sibs were affected, suggesting autosomal recessive inheritance.
Similar cases were reported by Adashi et al. (1980) and Berger et al. (1986). Death usually occurred in the first few months of life despite surgical management of the pyloric abnormality.
Carmi et al. (1982) described 2 sibs from consanguineous Bedouin parents with extensive aplasia cutis congenita. Only 1 had pyloric atresia. Elevated amniotic fluid alpha-fetoprotein was noted by Carmi et al. (1982) and by Leschot and Treffers (1975). Carey et al. (1983) described a pair of dizygotic twins, a boy and girl, with extensive skin changes similar to the changes observed in the patients of Carmi et al. (1982). Carey et al. (1983) suggested that the designation 'aplasia cutis congenita' was inappropriate because it usually entails involvement of the scalp predominantly or exclusively; they suggested the eponymic designation Carmi syndrome. One of the twins had axillary pterygia and bilateral lower lid ectropion, whereas the other showed esophageal atresia.
Toriello et al. (1983) reported affected brother and sister, and Leschot (1983) called attention to the similar case reported by Leschot et al. (1980). Frieden (1986) reported arthrogryposis and ear and nose deformities.
Vivona et al. (1987) described a sister and brother with lethal congenital cutis aplasia. Only 1 had esophageal atresia with complete absence of the pyloris. In the view of Vivona et al. (1987), the similarity between their cases and those of Carmi et al. (1982) strongly supported the existence of a unique EB-like mutation, i.e., an autosomal recessive disorder with variable involvement of skin, nails, and mucosa, with variable effects on the digestive system.
Rosenbloom and Ratner (1987) reported premature sibs with lethal epidermolysis bullosa associated with congenital pyloric atresia. A review of other cases indicated that it is usually a lethal condition with death due to the septic complications of EB.
Ishigami et al. (1990) described congenital pyloric atresia in a female infant with junctional EB who, despite successful early surgical correction of the obstruction, died from intractable diarrhea and protein-losing gastroenteropathy at the age of 4.5 months.
Lacour et al. (1992) described a case of lethal JEB in a newborn girl who also had pyloric stenosis. Immunohistologic and electron microscopic studies showed cleavage through the lamina lucida of the digestive basement membrane, as for the localized skin blisters. There was normal immunostaining of the laminin glycoprotein BM600 at the dermoepidermal junction.
Vidal et al. (1995) reported an infant who presented at birth with pyloric atresia and cutaneous aplasia of the left hand. Perioral blistering and erosions of the mucosa of the mouth, upper esophagus and cornea were noted shortly after birth. Gastric erosions were found later. The infant died at the age of 8 months as the result of infection of skin blisters and generalized infection.
Chavanas et al. (1999) reported a patient who represented a rare instance in which JEB-PA showed improvement with age. The proband was a 14-year-old boy, the child of nonconsanguineous parents, who at birth presented all the hallmarks of severe JEB-PA, including extensive skin blistering, pyloric atresia, and urethrovesical occlusion. However, as the child grew, the blistering tendency decreased and his skin and epithelia acquired resistance to trauma. At the age of 14, induction of blisters required prolonged rubbing of the skin.
Pathogenesis
Lestringant et al. (1992) found that the GB3 monoclonal antibody, which reacts to laminin-5 subunits, was normally expressed in skin biopsies from 3 of 3 cases of JEB-PA, thus excluding it as a form of Herlitz JEB, which is due to mutations in genes encoding laminin-5 subunits. Lestringant et al. (1992) concluded that the pyloric atresia/epidermolysis bullosa association represents an autosomal recessive entity of JEB, and that pyloric atresia is a primary manifestation rather than a scarring process secondary to JEB. The authors noted that patients with JEB-PA often have erosions and/or subepithelial cleavage in the respiratory, gastrointestinal, and urinary tracts. Obstruction of the ureterovesical junction and a high incidence of a peculiar form of aplasia cutis congenita were considered to be additional features.
Maman et al. (1998) provided detailed clinical and histopathologic information on 8 cases of the triple syndrome epidermolysis bullosa/pyloric atresia/aplasia cutis congenita (EB-PA-ACC). The affected individuals were members of the extended Bedouin family first described by Carmi et al. (1982). All affected infants were found to have mixed skin lesions, including blisters and patchy lack of skin. In 7 of the 8, intestinal obstructions, especially pyloric atresia or stenosis, were found. Skin lesions involved all layers with marked dystrophic changes. The intestinal obstruction was the result of overproliferation of connective tissue. In view of the clinical and histopathologic findings, Maman et al. (1998) postulated that the condition is caused by an autosomal recessive mutation affecting the integrity of the basement membrane and hemidesmosomes and the control of the normal process of fibrosis occurring during wound healing. The sequence of events appeared to be initiated by the separation of the epidermis or the intestinal mucosal layer. An inflammatory reaction then takes place and proceeds with massive fibrosis penetrating the deep layers and causing damage to skin and obstruction of the intestinal lumen. Maman et al. (1998) postulated a mutation in one of the integrin genes.
Diagnosis
### Prenatal Diagnosis
Nazzaro et al. (1990) made the prenatal diagnosis of JEB-PA by ultrastructural demonstration of dermal-epidermal separation at the lamina lucida level in fetal skin obtained at 18 weeks of gestation. Fetal ultrasound showed marked gastric dilatation, and light microscopy of pyloric tissue obtained after termination showed that the pyloric lumen was replaced by loose connective tissue with no inflammatory reaction. Skin biopsy studies showed a positive reaction with the GB3 antibody, thus excluding the Herlitz form of JEB. In the family studied, 2 previous children had died during the first months of life of the same disorder despite surgery for the pyloric abnormality.
Although AFP and skin biopsy had been used for prenatal diagnosis of this condition, Achiron et al. (1992) found normal levels of amniotic AFP at 16 weeks' gestation in a woman at risk for this disorder in her fetus. However, 10 weeks later, ultrasonography showed hydramnios, dilated stomach, deformed external ear, and contracted fisted hand, all of which were confirmed postnatally.
Molecular Genetics
In an infant with JEB-PA, Vidal et al. (1995) demonstrated compound heterozygosity for 2 mutations in the integrin beta-4 gene (147557.0001, 147557.0002).
In a patient with nonlethal JEB-PA and survival until 14 years of age, Chavanas et al. (1999) found compound heterozygosity for 2 splice site mutations in the ITGB4 gene (147557.0007 and 147557.0011).
In an infant with epidermolysis bullosa with pyloric atresia and esophageal stenosis, Ruzzi et al. (1997, 1997) identified a homozygous deletion in the ITGA6 gene (147556.0001).
In members of the original inbred Bedouin kindred from southern Israel with EB-PA-ACC described by Carmi et al. (1982) and Maman et al. (1998), Birnbaum et al. (2008) identified a homozygous 2,279-bp in-frame deletion in exons 27-30 of the ITBG4 gene (147557.0016). They stated that this was the largest deletion in the ITBG4 gene to date and included the first pair of fibronectin III repeats.
Genotype/Phenotype Correlations
Pulkkinen et al. (1998) identified novel lesions of both ITGB4 alleles in the probands of 5 families with JEB-PA, 2 of them with lethal and 3 of them with nonlethal variants of the disease. Of the 2 patients with lethal JEB-PA, one was a compound heterozygote for premature termination codon mutations, and the other was homozygous for a missense mutation involving a cysteine residue (C61Y; 147557.0005). The 3 patients with nonlethal JEP-PA had missense mutations on both alleles.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Rudimentary ears Mouth \- Oral lesions Teeth \- Enamel hypoplasia ABDOMEN Gastrointestinal \- Esophageal atresia \- Esophageal lesions \- Pyloric atresia GENITOURINARY Kidneys \- Pyelonephrosis Bladder \- Urethrovesical occlusion \- Stenosis at the ureterovesical junctions SKELETAL \- Joint contractures SKIN, NAILS, & HAIR Skin \- Epidermolysis bullosa junctional \- Blistering, generalized \- Congenital absence of skin on some areas (aplasia cutis) \- Extreme skin fragility \- Atrophic scarring \- Milia Electron Microscopy \- Cleavage occurs within the lamina lucida \- Hemidesmosomes may be disrupted Nails \- Absent nails \- Dystrophic nails PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios LABORATORY ABNORMALITIES \- Increased alpha-fetoprotein in the mother during early pregnancy while carrying an affected fetus MISCELLANEOUS \- Onset in utero \- Death usually in infancy \- See also simplex EB with pyloric atresia ( 612138 ) MOLECULAR BASIS \- Caused by mutation in the integrin-beta-4 gene (ITGB4, 147557.0001 ) \- Caused by mutation in the integrin-alpha-6 gene (ITGA6, 147556.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
EPIDERMOLYSIS BULLOSA JUNCTIONALIS WITH PYLORIC ATRESIA
|
c1856934
| 7,748 |
omim
|
https://www.omim.org/entry/226730
| 2019-09-22T16:28:12 |
{"doid": ["0060733"], "mesh": ["C535377"], "omim": ["226730"], "orphanet": ["79403"], "synonyms": ["Alternative titles", "EPIDERMOLYSIS BULLOSA, JUNCTIONAL, WITH PYLORIC ATRESIA", "JUNCTIONAL EPIDERMOLYSIS BULLOSA WITH PYLORIC ATRESIA", "JEB-PA", "EPIDERMOLYSIS BULLOSA, JUNCTIONAL, WITH PYLORIC ATRESIA AND APLASIA CUTIS CONGENITA", "EB-PA-ACC", "CARMI SYNDROME", "APLASIA CUTIS CONGENITA WITH GASTROINTESTINAL ATRESIA"], "genereviews": ["NBK1157", "NBK1125"]}
|
Camptodactyly-tall stature-scoliosis-hearing loss syndrome is characterised by camptodactyly, tall stature, scoliosis, and hearing loss (CATSHL). It has been described in around 30 individuals from seven generations of the same family. The syndrome is caused by a missense mutation in the FGFR3 gene, leading to a partial loss of function of the encoded protein, which is a negative regulator of bone growth.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Camptodactyly-tall stature-scoliosis-hearing loss syndrome
|
c1864852
| 7,749 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85164
| 2021-01-23T18:56:26 |
{"gard": ["10012"], "mesh": ["C537975"], "omim": ["610474"], "umls": ["C1864852"], "icd-10": ["Q87.2"], "synonyms": ["CATSHL syndrome", "Camptodactyly-tall stature-scoliosis-deafness syndrome"]}
|
Hypoglossia
SpecialtyMedical genetics
Hypoglossia is a short, incompletely developed tongue. It can occur either as an isolated malformation or in association with other deformities,[1] particularly limb defects in a syndrome known as oromandibular limb hypogenesis syndrome.
## References[edit]
1. ^ Amor DJ, Craig JE (January 2001). "Situs inversus totalis and congenital hypoglossia". Clin. Dysmorphol. 10 (1): 47–50. doi:10.1097/00019605-200101000-00010. PMID 11152148.
## External links[edit]
Classification
D
* ICD-10: Q38.3
* v
* t
* e
Congenital malformations and deformations of digestive system
Upper GI tract
Tongue, mouth and pharynx
* Cleft lip and palate
* Van der Woude syndrome
* tongue
* Ankyloglossia
* Macroglossia
* Hypoglossia
Esophagus
* EA/TEF
* Esophageal atresia: types A, B, C, and D
* Tracheoesophageal fistula: types B, C, D and E
* esophageal rings
* Esophageal web (upper)
* Schatzki ring (lower)
Stomach
* Pyloric stenosis
* Hiatus hernia
Lower GI tract
Intestines
* Intestinal atresia
* Duodenal atresia
* Meckel's diverticulum
* Hirschsprung's disease
* Intestinal malrotation
* Dolichocolon
* Enteric duplication cyst
Rectum/anal canal
* Imperforate anus
* Rectovestibular fistula
* Persistent cloaca
* Rectal atresia
Accessory
Pancreas
* Annular pancreas
* Accessory pancreas
* Johanson–Blizzard syndrome
* Pancreas divisum
Bile duct
* Choledochal cysts
* Caroli disease
* Biliary atresia
Liver
* Alagille syndrome
* Polycystic liver disease
This medical sign article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hypoglossia
|
c0025988
| 7,750 |
wikipedia
|
https://en.wikipedia.org/wiki/Hypoglossia
| 2021-01-18T18:36:50 |
{"mesh": ["D014060"], "umls": ["C0025988"], "icd-10": ["Q38.3"], "orphanet": ["156212", "141152"], "wikidata": ["Q5959625"]}
|
Micro syndrome
Other namesWarburg–Sjo–Fledelius syndrome
Warburg Micro syndrome (WARBM), also known as Micro syndrome, is a rare autosomal recessive genetic disorder characterized by microcephaly, microcornea, congenital cataract, intellectual or developmental disability, optic atrophy, and hypogenitalism.[1]
## Contents
* 1 Genetics
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Genetics[edit]
The rare cases that have been examined are often within families, or the people that have cases of Warburg Micro syndrome have a mutation in their genes.[citation needed]
It can be associated with RAB3GAP.[2]
## Diagnosis[edit]
Warburg Micro syndrome can be identified in people several ways, one of the most common is ocular problems or other physical traits that don't appear natural. It is especially easy to identify micro syndrome in infants and in younger children. Intellectual or developmental disabilities can seriously affect a patient in the way they think and move. So far according to studies all patients have had serious intellectual or developmental disabilities, and hypotonia is found in all the patients during infancy.[citation needed]
## Treatment[edit]
There is no specific treatment for Warburg Micro syndrome, but there are ways to help the disorders, and illnesses that come with it. Many individuals with Warburg Micro syndrome need permanent assistance from their disorders and inabilities to move and support themselves. Seizures are not uncommon and patients should get therapy to help control them, and many patients also require wheelchairs to move, so an assistant would be needed at all times.[3]
Those with Warburg Micro syndrome are born appearing normal. At the age of one, mental and physical delays become apparent, along with some limb spasms. By the age of eight, Warburg Micro syndrome has already set in, and the patient will have joint contractures, Ocular Atrophy will become noticeable, the patient will most likely lose ability to walk, speak, and sometimes move at all.[citation needed]
## References[edit]
1. ^ "WARBURG Micro Syndrome." https://www.ncbi.nlm.nih.gov/ 10 Mar. 2008 <https://www.ncbi.nlm.nih.gov/omim/?term=600118>.
2. ^ Morris-Rosendahl DJ, Segel R, Born AP, et al. (October 2010). "New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish". Eur. J. Hum. Genet. 18 (10): 1100–6. doi:10.1038/ejhg.2010.79. PMC 2987448. PMID 20512159.
3. ^ "Micro Syndrome." http://www.orpha.net 13 Mar. 2008 <http://www.orpha.net/data/patho/GB/uk-MicroSyndrome.pdf>.
## External links[edit]
Classification
D
* OMIM: 600118
* MeSH: C536681
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Warburg Micro syndrome
|
c1838625
| 7,751 |
wikipedia
|
https://en.wikipedia.org/wiki/Warburg_Micro_syndrome
| 2021-01-18T19:08:10 |
{"gard": ["5534"], "mesh": ["C536681"], "umls": ["C1838625"], "orphanet": ["2510"], "wikidata": ["Q6839205"]}
|
Rare genetic disease
Spinal muscular atrophy with lower extremity predominance 2B
Other namesLower extremity-predominant spinal muscular atrophy type 2B, SMALED2B
Spinal muscular atrophy with lower extremity predominance 2B is inherited in an autosomal dominant manner.
SpecialtyNeurology
SymptomsGeneralised severe hypotonia at birth
Usual onsetInfancy
DurationLifetime
CausesMutations in BICD2 gene
Diagnostic methodMolecular test
PrognosisLife limiting
Spinal muscular atrophy with lower extremity predominance 2B (SMALED2B) is a rare neuromuscular disorder characterised by generalised muscle weakness. Decreased foetal movement is apparent already before birth. The child is born with a generalised muscle weakness (hypotonia) and contractures resembling arthrogryposis multiplex congenita, respiratory insufficiency and sometimes facial deformations.[1][2] The disorder is frequently fatal in early childhood.[1]
The disease is caused by a mutation in the BICD2 gene and is passed on in an autosomal dominant manner.[1]
There is no known cure to SMALED2B.
## References[edit]
1. ^ a b c Online Mendelian Inheritance in Man (OMIM): 618291
2. ^ Koboldt, Daniel C.; Kastury, Rama D.; Waldrop, Megan A.; Kelly, Benjamin J.; Mosher, Theresa Mihalic; McLaughlin, Heather; Corsmeier, Don; Slaughter, Jonathan L.; Flanigan, Kevin M.; McBride, Kim L.; Mehta, Lakshmi (2018). "In-frame de novo mutation in BICD2 in two patients with muscular atrophy and arthrogryposis". Molecular Case Studies. 4 (5): a003160. doi:10.1101/mcs.a003160. ISSN 2373-2865. PMC 6169820. PMID 30054298.
Classification
D
* OMIM: 618291
## See also[edit]
* Spinal muscular atrophies
* Spinal muscular atrophy with lower extremity predominance 1
* Spinal muscular atrophy with lower extremity predominance 2A
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic
Brain and spinal cord
* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis
Brain/
encephalopathy
Degenerative
Extrapyramidal and
movement disorders
* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA
* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
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* Akathisia
* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person
Dementia
* Tauopathy
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* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Dementia with Lewy bodies
* Posterior cortical atrophy
* Vascular dementia
Mitochondrial disease
* Leigh syndrome
Demyelinating
* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS
Episodic/
paroxysmal
Seizures and epilepsy
* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy
Headache
* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache
Cerebrovascular
* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases
Other
* Sleep disorders
* For more detailed coverage, see Template:Sleep
CSF
* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension
Other
* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
Both/either
Degenerative
SA
* Friedreich's ataxia
* Ataxia–telangiectasia
MND
* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia
* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
This genetic disorder article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Spinal muscular atrophy with lower extremity predominance 2B
|
None
| 7,752 |
wikipedia
|
https://en.wikipedia.org/wiki/Spinal_muscular_atrophy_with_lower_extremity_predominance_2B
| 2021-01-18T18:29:15 |
{"wikidata": ["Q102296550"]}
|
The large number of distinct types of the Ehlers-Danlos syndrome that have already been identified indicates great heterogeneity, but clearly that heterogeneity is not exhausted by the present classification. Some of the unclassified families are apparently recessive (see 225320); some, such as that reported by Friedman and Harrod (1982), are seemingly dominant. These authors reported a mother and son with large hernias, positional foot deformities, thoracic deformity, asthma, and eczematoid dermatitis. Both had facial asymmetry, prominent nasal bridge and small jaw. The mother had severe thoracolumbar kyphoscoliosis and 'cigarette paper' scars over the legs. She died of dissecting aortic aneurysm and at autopsy had cystic medial necrosis of the aorta and myxomatous degeneration and elongation of the mitral and tricuspid valves. McKusick (1972) observed dissecting aortic aneurysm in type VI EDS (225400). Loose-jointedness, stretchable skin, Gorlin sign (tip of tongue to tip of nose) and a few papyraceous scars occurred in a man who died of dissecting aneurysm, as did his sister and mother who showed similar systemic signs.
Limbs \- Positional foot deformities Inheritance \- Autosomal dominant form(s) \- genetic heterogeneity Spine \- Thoracolumbar kyphoscoliosis Vascular \- Dissecting aortic aneurysm Facies \- Facial asymmetry \- Prominent nasal bridge \- Small jaw \- Gorlin sign (tip of tongue to tip of nose) Joints \- Loose-jointedness Abdomen \- Hernias Lab \- Cystic medial necrosis of the aorta \- Myxomatous valvular degeneration Skin \- Eczematoid dermatitis \- Stretchable skin \- Cigarette-paper scars Pulmonary \- Asthma Thorax \- Thoracic deformity ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
EHLERS-DANLOS SYNDROME, AUTOSOMAL DOMINANT, TYPE UNSPECIFIED
|
c0220679
| 7,753 |
omim
|
https://www.omim.org/entry/130090
| 2019-09-22T16:41:47 |
{"mesh": ["C562424"], "omim": ["130090"], "synonyms": ["Alternative titles", "EDS, UNSPECIFIED TYPE", "EHLERS-DANLOS SYNDROME, FRIEDMAN-HARROD TYPE"]}
|
Multiple carboxylase deficiency
SpecialtyMedical genetics, endocrinology
Multiple carboxylase deficiency is a form of metabolic disorder involving failures of carboxylation enzymes.
The deficiency can be in biotinidase or holocarboxylase synthetase.[1]
These conditions respond to biotin.[2]
Forms include:
* Holocarboxylase synthetase deficiency \- neonatal;
* Biotinidase deficiency \- late onset;
If left untreated, the symptoms can include feeding problems, decreased body tone, generalized red rash with skin exfoliation and baldness, failure to thrive, seizure, coma, developmental delay, foul smelling urine, lactic acidosis, and high levels of ketones and ammonia in the blood.
## References[edit]
1. ^ "Multiple Carboxylase Deficiency". Archived from the original on 2008-08-28.
2. ^ "Definition: multiple carboxylase deficiency from Online Medical Dictionary".
## External links[edit]
Classification
D
* MeSH: D009100
* SNOMED CT: 62151000119109
External resources
* Orphanet: 148
* http://www.pmh.health.wa.gov.au/services/newborn/health_professionals/disorders/mcd_prof.htm
* v
* t
* e
Metabolic disorders of vitamins, coenzymes, and cofactors
B7 Biotin/MCD
* Biotinidase deficiency
* Holocarboxylase synthetase deficiency
Other B
* B5 (Pantothenate kinase-associated neurodegeneration)
* B12 (Methylmalonic acidemia)
Other vitamin
* Familial isolated vitamin E deficiency
Nonvitamin cofactor
* Tetrahydrobiopterin deficiency
* Molybdenum cofactor deficiency
This article about an endocrine, nutritional, or metabolic disease is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Multiple carboxylase deficiency
|
c0026755
| 7,754 |
wikipedia
|
https://en.wikipedia.org/wiki/Multiple_carboxylase_deficiency
| 2021-01-18T18:44:34 |
{"gard": ["3824"], "mesh": ["D009100"], "umls": ["C0026755"], "orphanet": ["148"], "wikidata": ["Q6934914"]}
|
Onychomycosis
Other namesDermatophytic onychomycosis[1] tinea unguium[1]
A toenail affected by onychomycosis
SpecialtyInfectious disease
SymptomsWhite or yellow nail discoloration, thickening of the nail[2][3]
ComplicationsLower leg cellulitis[3]
Usual onsetOlder males[2][3]
CausesFungal infection[3]
Risk factorsAthlete's foot, other nail diseases, exposure to someone with the condition, peripheral vascular disease, poor immune function[3]
Diagnostic methodBased on appearance, confirmed by laboratory testing[2]
Differential diagnosisPsoriasis, chronic dermatitis, chronic paronychia, nail trauma[2]
TreatmentNone, anti-fungal medication, trimming the nails[2][3]
MedicationTerbinafine, ciclopirox[2]
PrognosisOften recurs[2]
Frequency~10% of adults[2]
Onychomycosis, also known as tinea unguium,[4] is a fungal infection of the nail.[2] Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed.[2][3] Toenails or fingernails may be affected, but it is more common for toenails to be affected.[3] Complications may include cellulitis of the lower leg.[3] A number of different types of fungus can cause onychomycosis, including dermatophytes and Fusarium.[3] Risk factors include athlete's foot, other nail diseases, exposure to someone with the condition, peripheral vascular disease, and poor immune function.[3] The diagnosis is generally suspected based on the appearance and confirmed by laboratory testing.[2]
Onychomycosis does not necessarily require treatment.[3] The antifungal medication terbinafine taken by mouth appears to be the most effective but is associated with liver problems.[2][5] Trimming the affected nails when on treatment also appears useful.[2] There is a ciclopirox-containing nail polish, but it does not work as well.[2] The condition returns in up to half of cases following treatment.[2] Not using old shoes after treatment may decrease the risk of recurrence.[3]
It occurs in about 10 percent of the adult population.[2] Older people are more frequently affected.[2] Males are affected more often than females.[3] Onychomycosis represents about half of nail disease.[2] It was first determined to be the result of a fungal infection in 1853 by Georg Meissner.[6]
## Contents
* 1 Etymology
* 2 Signs and symptoms
* 3 Causes
* 3.1 Dermatophytes
* 3.2 Other
* 3.3 Risk factors
* 4 Diagnosis
* 4.1 Classification
* 4.2 Differential diagnosis
* 5 Treatment
* 5.1 Medications
* 5.2 Other
* 5.3 Cost
* 5.3.1 United States
* 6 Prognosis
* 7 Epidemiology
* 8 Research
* 9 References
* 10 External links
## Etymology[edit]
The term is from Greek ὄνυξ onyx "nail", μύκης mykēs "fungus",[7] and the suffix -ωσις -ōsis "functional disease".
## Signs and symptoms[edit]
A case of fungal infection of the big toe
Advanced fungal infection of the big toe
The most common symptom of a fungal nail infection is the nail becoming thickened and discoloured: white, black, yellow or green. As the infection progresses the nail can become brittle, with pieces breaking off or coming away from the toe or finger completely. If left untreated, the skin underneath and around the nail can become inflamed and painful. There may also be white or yellow patches on the nailbed or scaly skin next to the nail,[8] and a foul smell.[9] There is usually no pain or other bodily symptoms, unless the disease is severe.[10] People with onychomycosis may experience significant psychosocial problems due to the appearance of the nail, particularly when fingers – which are always visible – rather than toenails are affected.[11] Dermatophytids are fungus-free skin lesions that sometimes form as a result of a fungus infection in another part of the body. This could take the form of a rash or itch in an area of the body that is not infected with the fungus. Dermatophytids can be thought of as an allergic reaction to the fungus.
## Causes[edit]
The causative pathogens of onychomycosis are all in the fungus kingdom and include dermatophytes, Candida (yeasts), and nondermatophytic molds.[2] Dermatophytes are the fungi most commonly responsible for onychomycosis in the temperate western countries; while Candida and nondermatophytic molds are more frequently involved in the tropics and subtropics with a hot and humid climate.[12]
### Dermatophytes[edit]
When onychomycosis is due to a dermatophyte infection, it is termed tinea unguium. Trichophyton rubrum is the most common dermatophyte involved in onychomycosis. Other dermatophytes that may be involved are T. interdigitale, Epidermophyton floccosum, T. violaceum, Microsporum gypseum, T. tonsurans, and T. soudanense. A common outdated name that may still be reported by medical laboratories is Trichophyton mentagrophytes for T. interdigitale. The name T. mentagrophytes is now restricted to the agent of favus skin infection of the mouse; though this fungus may be transmitted from mice and their danders to humans, it generally infects skin and not nails.
### Other[edit]
Other causative pathogens include Candida and nondermatophytic molds, in particular members of the mold genus Scytalidium (name recently changed to Neoscytalidium), Scopulariopsis, and Aspergillus. Candida species mainly cause fingernail onychomycosis in people whose hands are often submerged in water. Scytalidium mainly affects people in the tropics, though it persists if they later move to areas of temperate climate.
Other molds more commonly affect people older than 60 years, and their presence in the nail reflects a slight weakening in the nail's ability to defend itself against fungal invasion.
### Risk factors[edit]
Aging is the most common risk factor for onychomycosis due to diminished blood circulation, longer exposure to fungi, and nails which grow more slowly and thicken, increasing susceptibility to infection. Nail fungus tends to affect men more often than women and is associated with a family history of this infection.
Other risk factors include perspiring heavily, being in a humid or moist environment, psoriasis, wearing socks and shoes that hinder ventilation and do not absorb perspiration, going barefoot in damp public places such as swimming pools, gyms and shower rooms, having athlete's foot (tinea pedis), minor skin or nail injury, damaged nail, or other infection, and having diabetes, circulation problems, which may also lead to lower peripheral temperatures on hands and feet, or a weakened immune system.[13]
## Diagnosis[edit]
The diagnosis is generally suspected based on the appearance and confirmed by laboratory testing.[2] The four main tests are a potassium hydroxide smear, culture, histology examination, and polymerase chain reaction.[2][3] The sample examined is generally nail scrapings or clippings.[2] These being from as far up the nail as possible.[3]
Nail plate biopsy with periodic acid-Schiff stain appear more useful than culture or direct KOH examination.[14] To reliably identify nondermatophyte molds, several samples may be necessary.[15]
### Classification[edit]
There are five classic types of onychomycosis:[16][17]
* Distal subungual onychomycosis is the most common form of tinea unguium[2] and is usually caused by Trichophyton rubrum, which invades the nail bed and the underside of the nail plate.
* White superficial onychomycosis (WSO) is caused by fungal invasion of the superficial layers of the nail plate to form "white islands" on the plate. It accounts for around 10 percent of onychomycosis cases. In some cases, WSO is a misdiagnosis of "keratins granulations" which are not a fungus, but a reaction to nail polish that can cause the nails to have a chalky white appearance. A laboratory test should be performed to confirm.[18]
* Proximal subungual onychomycosis is fungal penetration of the newly formed nail plate through the proximal nail fold. It is the least common form of tinea unguium in healthy people, but is found more commonly when the patient is immunocompromised.[2]
* Endonyx onychomycosis is characterized by leukonychia along with a lack of onycholysis or subungual hyperkeratosis.[17]
* Candidal onychomycosis is Candida species invasion of the fingernails, usually occurring in persons who frequently immerse their hands in water. This normally requires the prior damage of the nail by infection or trauma.
### Differential diagnosis[edit]
In many cases of suspected nail fungus there is actually no fungal infection, but only nail deformity.[19][20]
To avoid misdiagnosis as nail psoriasis, lichen planus, contact dermatitis, nail bed tumors such as melanoma, trauma, or yellow nail syndrome, laboratory confirmation may be necessary.[2]
Other conditions that may appear similar to onychomycosis include: psoriasis, normal aging, yellow nail syndrome, and chronic paronychia.[21]
## Treatment[edit]
A person's foot with a fungal nail infection ten weeks into a course of terbinafine oral medication. Note the band of healthy (pink) nail growth behind the remaining infected nails.
### Medications[edit]
Most treatments are with antifungal medications either topically or by mouth.[2] Avoiding use of antifungal therapy by mouth (e.g. terbinafine) in persons without a confirmed infection is recommended because of the possible side effects of that treatment.[19]
Topical agents include ciclopirox nail paint, amorolfine, and efinaconazole.[22][23][24] Some topical treatments need to be applied daily for prolonged periods (at least 1 year).[23] Topical amorolfine is applied weekly.[25] Topical ciclopirox results in a cure in 6% to 9% of cases; amorolfine might be more effective.[2][23] Ciclopirox when used with terbinafine appears to be better than either agent alone.[2] In trials, about 17% of people were cured using efinaconazole as opposed to 4% of people using placebo.[26] Although eficonazole, P-3051 (ciclopirox 8% hydrolacquer), and tavaborole are effective at treating fungal infection of toenails, complete cure rates are low.[27]
Medications that may be taken by mouth include terbinafine (76% effective), itraconazole (60% effective) and fluconazole (48% effective).[2] They share characteristics that enhance their effectiveness: prompt penetration of the nail and nail bed,[28] and persistence in the nail for months after discontinuation of therapy.[29] Ketoconazole by mouth is not recommended due to side effects.[30] Oral terbinafine is better tolerated than itraconazole.[31] For superficial white onychomycosis, systemic rather than topical antifungal therapy is advised.[32]
### Other[edit]
Chemical (keratolytic) or surgical debridement of the affected nail appears to improve outcomes.[2]
As of 2014 evidence for laser treatment is unclear as the evidence is of low quality[33] and varies by type of laser.[34]
Tea tree oil is not recommended as a treatment, since it is not effective and can irritate the surrounding skin.[35]
### Cost[edit]
#### United States[edit]
According to a 2015 study, the cost in the United States of testing with the periodic acid–Schiff stain (PAS) was about $148. Even if the cheaper KOH test is used first and the PAS test is used only if the KOH test is negative, there is a good chance that the PAS will be done (because of either a true or a false negative with the KOH test). But the terbinafine treatment costs only $10 (plus an additional $43 for liver function tests). In conclusion the authors say that terbinafine has a relatively benign adverse effect profile, with liver damage very rare, so it makes more sense cost-wise for the dermatologist to prescribe the treatment without doing the PAS test. (Another option would be to prescribe the treatment only if the potassium hydroxide test is positive, but it gives a false negative in about 20% of cases of fungal infection.) On the other hand, as of 2015 the price of topical (non-oral) treatment with efinaconazole was $2307 per nail, so testing is recommended before prescribing it.[20]
## Prognosis[edit]
Following effective treatment, recurrence is common (10–50%).[2] Nail fungus can be painful and cause permanent damage to nails. It may lead to other serious infections if the immune system is suppressed due to medication, diabetes or other conditions. The risk is most serious for people with diabetes and with immune systems weakened by leukemia or AIDS, or medication after organ transplant. Diabetics have vascular and nerve impairment, and are at risk of cellulitis, a potentially serious bacterial infection; any relatively minor injury to feet, including a nail fungal infection, can lead to more serious complications.[36] Infection of the bone is another rare complication.[8]
## Epidemiology[edit]
A 2003 survey of diseases of the foot in 16 European countries found onychomycosis to be the most frequent fungal foot infection and estimates its prevalence at 27%.[37][38] Prevalence was observed to increase with age. In Canada, the prevalence was estimated to be 6.48%.[39] Onychomycosis affects approximately one-third of diabetics[40] and is 56% more frequent in people suffering from psoriasis.[41]
## Research[edit]
Research suggests that fungi are sensitive to heat, typically 40–60 °C (104–140 °F). The basis of laser treatment is to try to heat the nail bed to these temperatures in order to disrupt fungal growth.[42] As of 2013 research into laser treatment seems promising.[2] There is also ongoing development in photodynamic therapy, which uses laser or LED light to activate photosensitisers that eradicate fungi.[43]
## References[edit]
1. ^ a b Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1135. ISBN 978-1-4160-2999-1.
2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af Westerberg DP, Voyack MJ (December 2013). "Onychomycosis: Current trends in diagnosis and treatment". American Family Physician. 88 (11): 762–70. PMID 24364524.
3. ^ a b c d e f g h i j k l m n o p "Onychomycosis – Dermatologic Disorders". Merck Manuals Professional Edition. February 2017. Retrieved 2 June 2018.
4. ^ Rodgers P, Bassler M (February 2001). "Treating onychomycosis". American Family Physician. 63 (4): 663–72, 677–8. PMID 11237081.
5. ^ Kreijkamp-Kaspers S, Hawke K, Guo L, Kerin G, Bell-Syer SE, Magin P, et al. (July 2017). "Oral antifungal medication for toenail onychomycosis". The Cochrane Database of Systematic Reviews. 7: CD010031. doi:10.1002/14651858.CD010031.pub2. PMC 6483327. PMID 28707751.
6. ^ Rigopoulos D, Elewski B, Richert B (2018). Onychomycosis: Diagnosis and Effective Management. John Wiley & Sons. ISBN 9781119226505.
7. ^ ὄνυξ, μύκης. Liddell, Henry George; Scott, Robert; A Greek–English Lexicon at the Perseus Project.
8. ^ a b NHS Choices: Symptoms of fungal nail infection
9. ^ Mayo clinic: Nail fungus
10. ^ Onychomycosis at eMedicine
11. ^ Szepietowski JC, Reich A (July 2009). "Stigmatisation in onychomycosis patients: a population-based study". Mycoses. 52 (4): 343–9. doi:10.1111/j.1439-0507.2008.01618.x. PMID 18793262.
12. ^ Chi CC, Wang SH, Chou MC (November 2005). "The causative pathogens of onychomycosis in southern Taiwan". Mycoses. 48 (6): 413–20. doi:10.1111/j.1439-0507.2005.01152.x. PMID 16262878.
13. ^ Mayo Clinic – Nail fungus – risk factors
14. ^ Velasquez-Agudelo V, Cardona-Arias JA (February 2017). "Meta-analysis of the utility of culture, biopsy, and direct KOH examination for the diagnosis of onychomycosis". BMC Infectious Diseases. 17 (1): 166. doi:10.1186/s12879-017-2258-3. PMC 5320683. PMID 28222676.
15. ^ Shemer A, Davidovici B, Grunwald MH, Trau H, Amichai B (January 2009). "New criteria for the laboratory diagnosis of nondermatophyte moulds in onychomycosis". The British Journal of Dermatology. 160 (1): 37–9. doi:10.1111/j.1365-2133.2008.08805.x. PMID 18764841. S2CID 42320540.
16. ^ James WD, Berger TG (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
17. ^ a b Tosti, Antonella (31 Jul 2018). Elston, Dirk M; Vinson, Richard P (eds.). "Onychomycosis". Medscape. Retrieved 18 Jun 2020.
18. ^ "AAPA". Cmecorner.com. Retrieved 2010-08-05.
19. ^ a b American Academy of Dermatology (February 2013), "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, American Academy of Dermatology, retrieved 5 December 2013. Which cites:* Roberts DT, Taylor WD, Boyle J (March 2003). "Guidelines for treatment of onychomycosis" (PDF). The British Journal of Dermatology. 148 (3): 402–10. doi:10.1046/j.1365-2133.2003.05242.x. PMID 12653730. S2CID 33750748.
20. ^ a b Mikailov A, Cohen J, Joyce C, Mostaghimi A (March 2016). "Cost-effectiveness of Confirmatory Testing Before Treatment of Onychomycosis". JAMA Dermatology. 152 (3): 276–81. doi:10.1001/jamadermatol.2015.4190. PMID 26716567.
21. ^ Hall B (2012). Sauer's Manual of Skin Diseases (10 ed.). Lippincott Williams & Wilkins. p. Chapter 33. ISBN 9781451148688.
22. ^ Rodgers P, Bassler M (February 2001). "Treating onychomycosis". American Family Physician. 63 (4): 663–72, 677–8. PMID 11237081.
23. ^ a b c Crawford F, Hollis S (July 2007). Crawford F (ed.). "Topical treatments for fungal infections of the skin and nails of the foot". The Cochrane Database of Systematic Reviews (3): CD001434. doi:10.1002/14651858.CD001434.pub2. PMC 7073424. PMID 17636672.
24. ^ Gupta AK, Paquet M (2014). "Efinaconazole 10% nail solution: a new topical treatment with broad antifungal activity for onychomycosis monotherapy". Journal of Cutaneous Medicine and Surgery. 18 (3): 151–5. doi:10.2310/7750.2013.13095. PMID 24800702. S2CID 10079807.
25. ^ Loceryl (5% amorolfine) package labelling
26. ^ "Drugs at FDA: JUBLIA" (PDF). Retrieved 26 June 2014.
27. ^ Foley K, Gupta AK, Versteeg S, Mays R, Villanueva E, John D, et al. (Cochrane Skin Group) (January 2020). "Topical and device-based treatments for fungal infections of the toenails". The Cochrane Database of Systematic Reviews. 1: CD012093. doi:10.1002/14651858.CD012093.pub2. PMC 6984586. PMID 31978269.
28. ^ Elewski BE (July 1998). "Onychomycosis: pathogenesis, diagnosis, and management". Clinical Microbiology Reviews. 11 (3): 415–29. doi:10.1128/CMR.11.3.415. PMC 88888. PMID 9665975.
29. ^ Elewski BE, Hay RJ (August 1996). "Update on the management of onychomycosis: highlights of the Third Annual International Summit on Cutaneous Antifungal Therapy". Clinical Infectious Diseases. 23 (2): 305–13. doi:10.1093/clinids/23.2.305. PMID 8842269.
30. ^ "Nizoral (ketoconazole) Oral Tablets: Drug Safety Communication - Prescribing for Unapproved Uses including Skin and Nail Infections Continues; Linked to Patient Death". FDA. 19 May 2016. Retrieved 20 May 2016.
31. ^ Haugh M, Helou S, Boissel JP, Cribier BJ (July 2002). "Terbinafine in fungal infections of the nails: a meta-analysis of randomized clinical trials". The British Journal of Dermatology. 147 (1): 118–21. doi:10.1046/j.1365-2133.2002.04825.x. PMID 12100193. S2CID 19682557.
32. ^ Baran R, Faergemann J, Hay RJ (November 2007). "Superficial white onychomycosis--a syndrome with different fungal causes and paths of infection". Journal of the American Academy of Dermatology. 57 (5): 879–82. doi:10.1016/j.jaad.2007.05.026. PMID 17610995.
33. ^ Bristow IR (2014). "The effectiveness of lasers in the treatment of onychomycosis: a systematic review". Journal of Foot and Ankle Research. 7: 34. doi:10.1186/1757-1146-7-34. PMC 4124774. PMID 25104974.
34. ^ Liddell LT, Rosen T (April 2015). "Laser Therapy for Onychomycosis: Fact or Fiction?". Journal of Fungi. 1 (1): 44–54. doi:10.3390/jof1010044. PMC 5770012. PMID 29376898.
35. ^ Halteh P, Scher RK, Lipner SR (November 2016). "Over-the-counter and natural remedies for onychomycosis: do they really work?". Cutis. 98 (5): E16–E25. PMID 28040821.
36. ^ Mayo clinic – Nail fungus: complications
37. ^ Burzykowski T, Molenberghs G, Abeck D, Haneke E, Hay R, Katsambas A, et al. (December 2003). "High prevalence of foot diseases in Europe: results of the Achilles Project". Mycoses. 46 (11–12): 496–505. doi:10.1046/j.0933-7407.2003.00933.x. hdl:1942/429. PMID 14641624.
38. ^ Verma S, Heffernan MP (2008). Superficial fungal infection: Dermatophytosis, onychomycosis, tinea nigra, piedra. In K Wolff et al., eds., Fitzpatrick's Dermatology in General Medicine, 7th ed., vol 2, pp. 1807–1821. New York: McGraw Hill.
39. ^ Vender, Ronald B.; Lynde, Charles W.; Poulin, Yves (2006). "Prevalence and epidemiology of onychomycosis". Journal of Cutaneous Medicine and Surgery. 10 Suppl 2 (6_suppl): S28–S33. doi:10.2310/7750.2006.00056. PMID 17204229. S2CID 74819774.
40. ^ Gupta AK, Konnikov N, MacDonald P, Rich P, Rodger NW, Edmonds MW, et al. (October 1998). "Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: a multicentre survey". The British Journal of Dermatology. 139 (4): 665–71. doi:10.1046/j.1365-2133.1998.02464.x. PMID 9892911. S2CID 22038748.
41. ^ Gupta AK, Lynde CW, Jain HC, Sibbald RG, Elewski BE, Daniel CR, et al. (May 1997). "A higher prevalence of onychomycosis in psoriatics compared with non-psoriatics: a multicentre study". The British Journal of Dermatology. 136 (5): 786–9. doi:10.1046/j.1365-2133.1997.6771624.x. PMID 9205520. S2CID 5969796.
42. ^ "Device-based Therapies for Onychomycosis Treatment". Retrieved 23 December 2012.
43. ^ Piraccini BM, Alessandrini A (March 2015). "Onychomycosis: A Review". Journal of Fungi. 1 (1): 30–43. doi:10.3390/jof1010030. PMC 5770011. PMID 29376897.
## External links[edit]
Classification
D
* ICD-10: B35.1
* ICD-9-CM: 110.1
* MeSH: D014009
* DiseasesDB: 13125
External resources
* MedlinePlus: 001330
* eMedicine: derm/300
* Patient UK: Onychomycosis
* 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
Fungal infection and mesomycetozoea
Superficial and
cutaneous
(dermatomycosis):
Tinea = skin;
Piedra (exothrix/
endothrix) = hair
Ascomycota
Dermatophyte
(Dermatophytosis)
By location
* Tinea barbae/tinea capitis
* Kerion
* Tinea corporis
* Ringworm
* Dermatophytids
* Tinea cruris
* Tinea manuum
* Tinea pedis (athlete's foot)
* Tinea unguium/onychomycosis
* White superficial onychomycosis
* Distal subungual onychomycosis
* Proximal subungual onychomycosis
* Tinea corporis gladiatorum
* Tinea faciei
* Tinea imbricata
* Tinea incognito
* Favus
By organism
* Epidermophyton floccosum
* Microsporum canis
* Microsporum audouinii
* Trichophyton interdigitale/mentagrophytes
* Trichophyton tonsurans
* Trichophyton schoenleini
* Trichophyton rubrum
* Trichophyton verrucosum
Other
* Hortaea werneckii
* Tinea nigra
* Piedraia hortae
* Black piedra
Basidiomycota
* Malassezia furfur
* Tinea versicolor
* Pityrosporum folliculitis
* Trichosporon
* White piedra
Subcutaneous,
systemic,
and opportunistic
Ascomycota
Dimorphic
(yeast+mold)
Onygenales
* Coccidioides immitis/Coccidioides posadasii
* Coccidioidomycosis
* Disseminated coccidioidomycosis
* Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis
* Histoplasma capsulatum
* Histoplasmosis
* Primary cutaneous histoplasmosis
* Primary pulmonary histoplasmosis
* Progressive disseminated histoplasmosis
* Histoplasma duboisii
* African histoplasmosis
* Lacazia loboi
* Lobomycosis
* Paracoccidioides brasiliensis
* Paracoccidioidomycosis
Other
* Blastomyces dermatitidis
* Blastomycosis
* North American blastomycosis
* South American blastomycosis
* Sporothrix schenckii
* Sporotrichosis
* Talaromyces marneffei
* Talaromycosis
Yeast-like
* Candida albicans
* Candidiasis
* Oral
* Esophageal
* Vulvovaginal
* Chronic mucocutaneous
* Antibiotic candidiasis
* Candidal intertrigo
* Candidal onychomycosis
* Candidal paronychia
* Candidid
* Diaper candidiasis
* Congenital cutaneous candidiasis
* Perianal candidiasis
* Systemic candidiasis
* Erosio interdigitalis blastomycetica
* C. auris
* C. glabrata
* C. lusitaniae
* C. tropicalis
* Pneumocystis jirovecii
* Pneumocystosis
* Pneumocystis pneumonia
Mold-like
* Aspergillus
* Aspergillosis
* Aspergilloma
* Allergic bronchopulmonary aspergillosis
* Primary cutaneous aspergillosis
* Exophiala jeanselmei
* Eumycetoma
* Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa
* Chromoblastomycosis
* Geotrichum candidum
* Geotrichosis
* Pseudallescheria boydii
* Allescheriasis
Basidiomycota
* Cryptococcus neoformans
* Cryptococcosis
* Trichosporon spp
* Trichosporonosis
Zygomycota
(Zygomycosis)
Mucorales
(Mucormycosis)
* Rhizopus oryzae
* Mucor indicus
* Lichtheimia corymbifera
* Syncephalastrum racemosum
* Apophysomyces variabilis
Entomophthorales
(Entomophthoramycosis)
* Basidiobolus ranarum
* Basidiobolomycosis
* Conidiobolus coronatus/Conidiobolus incongruus
* Conidiobolomycosis
Microsporidia
(Microsporidiosis)
* Enterocytozoon bieneusi/Encephalitozoon intestinalis
Mesomycetozoea
* Rhinosporidium seeberi
* Rhinosporidiosis
Ungrouped
* Alternariosis
* Fungal folliculitis
* Fusarium
* Fusariosis
* Granuloma gluteale infantum
* Hyalohyphomycosis
* Otomycosis
* Phaeohyphomycosis
* 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
* Clear Nails Plus Reviews
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Onychomycosis
|
c0040261
| 7,755 |
wikipedia
|
https://en.wikipedia.org/wiki/Onychomycosis
| 2021-01-18T19:10:38 |
{"mesh": ["D014009"], "umls": ["C0040261"], "icd-9": ["681.9"], "icd-10": ["B35.1"], "wikidata": ["Q917620"]}
|
## Description
Hyperhidrosis palmaris et plantaris (HYPRPP) is characterized by excessive perspiration of the eccrine sweat gland in the palm, sole, and axilla. Perspiration in those affected may be aggravated by emotional stimuli (summary by Higashimoto et al., 2006).
Stolman (1998) noted that hyperhidrosis may be complicated by skin maceration as well as secondary microbial infections, and that treatment modalities are associated with complications.
Pathogenesis
Nejsum et al. (2002) demonstrated that the presence of aquaporin-5 (AQP5; 600442) in plasma membranes of sweat glands is essential for secretion of sweat. Immunohistochemical labeling showed abundant AQP5 in secretory parts of rat and mouse sweat glands, and immunoelectron microscopy demonstrated abundant AQP5 labeling in the apical plasma membrane. AQP5 immunolabeling of human sweat glands yielded a similar pattern. Aqp5-deficient mice demonstrated a marked reduction in pilocarpine-induced sweat response. Nejsum et al. (2002) speculated that dysregulation of AQP5 may be involved in hyperhidrosis and that AQP5 inhibition may provide a therapeutic option in this clinical disorder.
Inheritance
German (1988) reported a Chinese family with hyperhidrosis of the palms and soles in at least 4 generations.
Higashimoto et al. (2006) stated that 40 to 65% of patients with primary palmar hyperhidrosis have a positive family history. They considered autosomal dominant inheritance with incomplete penetrance likely because patients of both sexes are affected and the condition is sometimes directly and vertically transmitted through 3 or more generations within a family.
Population Genetics
German (1988) indicated that primary palmar hyperhidrosis may be unusually frequent in Chinese.
Cloward (1957) stated that primary palmar hyperhidrosis occurred over 20 times more frequently in Japanese than in other Asians or Caucasians in Hawaii.
Mapping
Higashimoto et al. (2006) performed a genomewide linkage analysis in 11 families with palmar hyperhidrosis, including 42 affected and 40 unaffected members. Data from 3 of the families showed a combined maximum 2-point lod score of 3.08 and 3.16 (theta = 0.0) at markers D14S283 and D14S264, respectively, on chromosome 14q11.2-q13. These regions were ruled out in the 8 other families. Haplotype analysis of the 3 families narrowed the locus to a 6- to 30-cM interval between D14S1070 and D14S990 at minimum and D14S1070 and D14S70 at maximum.
Inheritance \- Autosomal dominant Skin \- Hyperhidrosis of palms and soles ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
HYPERHIDROSIS PALMARIS ET PLANTARIS
|
c1274743
| 7,756 |
omim
|
https://www.omim.org/entry/144110
| 2019-09-22T16:40:05 |
{"mesh": ["C563185"], "omim": ["144110"], "synonyms": ["Alternative titles", "HYPERHIDROSIS, PRIMARY PALMAR"]}
|
Hereditary thrombophilia due to congenital antithrombin deficiency is a rare, genetic, hematological disease characterized by decreased levels of antithrombin activity in plasma resulting in impaired inactivation of thrombin and factor Xa. Patients have an increased risk for venous thromboembolism, usually in the deep veins of the arms, legs and pulmonary system and, on occasion, in other venous territories (e.g. cerebral veins or sinus, mesenteric, portal, hepatic, renal and/or retinal veins).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hereditary thrombophilia due to congenital antithrombin deficiency
|
c0272375
| 7,757 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=82
| 2021-01-23T17:45:28 |
{"gard": ["6148"], "mesh": ["D020152"], "omim": ["613118"], "icd-10": ["D68.5"], "synonyms": ["Hereditary thrombophilia due to congenital antithrombin 3 deficiency"]}
|
Primary pulmonary coccidioidomycosis
SpecialtyInfectious disease
Primary pulmonary coccidioidomycosis is an infection caused by inhalation of Coccidioides immitis.[1]:314 Once pulmonary symptoms subside, about 30% of women and 15% of men will have allergic skin manifestations in the form of erythema nodosum.[1]:314 A coccidioidoma is a benign localized residual granulomatous lesion or scar that can remain in the lung's tissues following primary pulmonary coccidioidomycosis.[2]
## See also[edit]
* Coccidioidomycosis
* List of cutaneous conditions
## References[edit]
1. ^ a b James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
2. ^ "Coccidioidoma". Dictionary.com. Retrieved 6 January 2010.
This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Primary pulmonary coccidioidomycosis
|
c0375046
| 7,758 |
wikipedia
|
https://en.wikipedia.org/wiki/Primary_pulmonary_coccidioidomycosis
| 2021-01-18T19:07:15 |
{"umls": ["C0375046"], "icd-9": ["114.0"], "icd-10": ["B38.2"], "wikidata": ["Q7243158"]}
|
## Description
The Osebold-Remondini syndrome is a bone dysplasia with mesomelic shortness of limbs and, hence, shortness of stature, absence or hypoplasia of second phalanges with synostosis of the remaining phalanges, carpal and tarsal coalitions, and apparently no other anomalies (summary by Opitz and Gilbert, 1985).
Clinical Features
Osebold et al. (1985) described a kindred in which 7 members had a constellation of skeletal anomalies which appeared to constitute a distinct syndrome. The middle phalanges of the hands and feet were hypoplastic or absent. The limbs showed mesomelic shortening, and the affected persons were in general somewhat short. The terminal phalanges of the index fingers deviated radially. In younger members, x-rays showed delayed coalescence of bipartite calcanei. All were of normal intelligence. In the wrist the hamate and capitate bones were joined. Sheffield et al. (1987) pointed to similarities between the Osebold-Remondini syndrome and the mild type of chondrodysplasia punctata, and Osebold (1987) reviewed differences between the two.
Inheritance
Male-to-male transmission and affected persons in 3 generations in the family reported by Osebold et al. (1985) suggested autosomal dominant inheritance of the disorder.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature SKELETAL Spine \- Normal spine Limbs \- Mesomelic limb shortening \- Short radii \- Dysplastic distal radial epiphyses \- Short ulnae \- Short tibiae \- Short fibulae Hands \- Decreased finger mobility \- Short, broad fingers \- Single interphalangeal joint \- Absent/hypoplastic middle phalanges \- Radially deviated fingers \- Carpal fusion Feet \- Short, broad toes \- Absent/hypoplastic middle phalanges \- Abnormal tarsals \- Delayed fusion of bipartite calcanci \- Tarsal fusion ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
OSEBOLD-REMONDINI SYNDROME
|
c1862130
| 7,759 |
omim
|
https://www.omim.org/entry/112910
| 2019-09-22T16:44:05 |
{"doid": ["0110968"], "mesh": ["C537092"], "omim": ["112910"], "orphanet": ["93382"], "synonyms": ["Alternative titles", "BRACHYMESOPHALANGY WITH MESOMELIC SHORT LIMBS AND CARPAL AND TARSAL OSSEOUS ABNORMALITIES", "BRACHYDACTYLY, TYPE A6"]}
|
A number sign (#) is used with this entry because X-linked erythropoietic protoporphyria (XLEPP) is caused by gain-of-function mutations in the ALAS2 gene (301300) on chromosome Xp11.
Loss-of-function mutations in the ALAS2 gene cause X-linked sideroblastic anemia (300751).
Description
X-linked erythropoietic protoporphyria (XLEPP) is a metabolic disorder of heme biosynthesis characterized by onset in early childhood of severe photosensitivity associated with decreased iron stores and increased erythrocyte zinc- and metal-free protoporphyrin. Some patients may develop liver disease or gallstones (summary by Ducamp et al., 2013).
For a discussion of genetic heterogeneity of erythropoietic protoporphyria, see EPP1 (177000).
Clinical Features
In a subgroup of families with FECH (612386) mutation-negative protoporphyria, Whatley et al. (2008) studied 8 families in which at least 1 member had acute photosensitivity clinically indistinguishable from that seen in autosomal recessive erythropoietic protoporphyria-1 (EPP1; 177000). Four families were of western European ancestry, and the others were of Jewish, North African, Indo-Asian, and Sudanese ancestry. In these 8 families, both sexes were affected. Patients had neither anemia nor iron overload. Instead there was some evidence of diminished iron stores, particularly in males. Five patients (17%) had overt liver disease, which was more common in males (0.008), and 1 obligate carrier was asymptomatic. These families showed an apparent X-linked pattern of inheritance with an absence of father-to-son transmission.
Ducamp et al. (2013) reported 5 XLEPP patients from 4 unrelated families referred for a history of skin photosensitivity associated with increased levels of zinc- and metal-free protoporphyrin in erythrocytes. Two patients had elevated liver enzymes and 1 had gallstones. Most had evidence of iron deficiency, but only some patients had anemia.
Brancaleoni et al. (2016) reported 6 unrelated families of European descent with XLP confirmed by genetic analysis. Five of the families carried the common ALAS2 4-bp deletion (c.1706_1709delAGTG; 301300.0015). Among the families, there were 7 affected males with a hemizygous mutation and 10 females who had the mutation in the heterozygous state. In 1 family (family C), there was only 1 affected male who had a de novo mutation; his mother was not a carrier. There was heterogeneity among the females with the mutation: 2 were fully affected with photosensitivity from childhood and increased erythrocyte protoporphyrin IX (PPIX), 7 had later onset of symptoms and/or only mildly increased PPIX, and 1 was completely asymptomatic with normal laboratory values. X-chromosome inactivation studies on the females with mutations were consistent with the clinical and biochemical heterogeneity: the 2 photosensitive females had a skewed pattern with over 73% of the wildtype allele inactivated, the asymptomatic female had 88.4% inactivation of the mutant allele, and the 7 females with no or late-onset photosensitivity and/or mildly increased PPIX values had relatively balanced X-inactivation patterns with preferential expression of the wildtype ALAS2 allele.
Inheritance
The transmission pattern of erythropoietic porphyria in the families reported by Whatley et al. (2008) was consistent with X-linked dominant inheritance.
Ducamp et al. (2013) reported a French girl with XLEPP whose mother was mildly affected and was demonstrated to be germline and somatic mosaic for an ALAS2 mutation (301300.0015).
Brancaleoni et al. (2016) determined that clinical and biochemical heterogeneity in females who are heterozygous for pathogenic ALAS2 mutations is associated with X-chromosome inactivation patterns. Females with full symptoms of the disorder tend to have a skewed pattern with most of the wildtype allele inactivated, whereas those without symptoms have most of the mutant allele inactivated. Those with intermediate or mild symptoms have relatively balanced X-inactivation patterns with preferential expression of the wildtype ALAS2 allele. The findings indicated that the disorder should be considered to have X-linked inheritance with penetrance and severity in females related to the level of X-chromosome inactivation, and that the term 'X-linked dominant' inheritance be discontinued.
Molecular Genetics
The observation of apparent X linkage of EPP in 8 families prompted Whatley et al. (2008) to investigate 2 candidate genes on the X chromosome that are involved in heme formation, GATA1 (305371) and ALAS2 (301300). Protoporphyrin accumulation segregated with an X chromosome haplotype defined by microsatellite markers around ALAS2 in 3 families. Sequencing of genomic DNA identified 2 different deletions in the last exon (exon 11) of ALAS2. The frameshifts produced by these deletions led to replacement or deletion of the approximately 20 C-terminal amino acids of the ALAS2 enzyme. These mutations segregated with photosensitivity (lod score 7.8) and were absent from 129 unrelated EPP patients (106 with dominant EPP, 23 with FECH mutation-negative EPP), and 100 normal chromosomes. The delAGTG mutation (301300.0015), present in 6 families, occurred on 5 different haplotypes, indicating that it had arisen on at least 5 separate occasions, whereas the 2 families with delAT (301300.0016), both from southwest England, had the same background haplotype and may have come from a single extended family. The ALAS2 gene encodes erythroid-specific mitochondrial aminolevulinate synthase-2, which catalyzes the first committed step of heme biosynthesis. Expression studies showed that both deletions markedly increased ALAS2 activity and that some of the 5-aminolevulinate (ALA) that was produced was further metabolized to porphyrin. Whatley et al. (2008) concluded that deletions in ALAS2 cause a theretofore unrecognized X-linked protoporphyria that, in contrast to autosomal dominant porphyrias, has close to 100% penetrance.
In 4 unrelated girls with X-linked dominant erythropoietic protoporphyria, Ducamp et al. (2013) identified 3 different heterozygous mutations in the ALAS2 gene. One was recurrent (delAGTG; 301300.0015) and the other 2 were novel (301300.0019 and 301300.0020). All occurred in the last exon of the ALAS2 gene, and all were shown in vitro to result in increased ALAS2 catalytic activity, consistent with a gain of function. By generating a series of ALAS2 variants, Ducamp et al. (2013) found that the 'gain-of-function domain' contains a minimum of 33 amino acids between residues 544 and 576 in the C terminus of the protein.
INHERITANCE \- X-linked ABDOMEN Liver \- Abnormal liver function (in some patients) Biliary Tract \- Gallstones (in some patients) SKIN, NAILS, & HAIR Skin \- Photosensitivity, severe HEMATOLOGY \- Iron deficiency \- Iron-deficiency anemia (in some patients) \- Increased erythrocyte zinc- and metal-free protoporphyrin MISCELLANEOUS \- Onset in early childhood \- Some females with the mutation may be unaffected or mildly affected due to skewed X-chromosome inactivation MOLECULAR BASIS \- Caused by mutation in the delta-aminolevulinate synthase 2 gene (ALAS2, 301300.0015 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
PROTOPORPHYRIA, ERYTHROPOIETIC, X-LINKED
|
c2677889
| 7,760 |
omim
|
https://www.omim.org/entry/300752
| 2019-09-22T16:19:46 |
{"doid": ["13270"], "mesh": ["C567464"], "omim": ["300752"], "orphanet": ["443197"], "synonyms": ["Alternative titles", "PROTOPORPHYRIA, ERYTHROPOIETIC, X-LINKED DOMINANT", "ERYTHROHEPATIC PROTOPORPHYRIA, X-LINKED"], "genereviews": ["NBK121284"]}
|
Coccygodynia is a rare condition in that causes pain in and around the coccyx (tailbone). Although various causes have been described for the condition, the more common causes are direct falls and injury.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Coccygodynia
|
c0009193
| 7,761 |
gard
|
https://rarediseases.info.nih.gov/diseases/5168/coccygodynia
| 2021-01-18T18:01:15 |
{"umls": ["C0009193"], "synonyms": ["Coccydynia"]}
|
Keshan disease
SpecialtyCardiology
Keshan disease is a congestive cardiomyopathy caused by a combination of dietary deficiency of selenium and the presence of a mutated strain of Coxsackievirus, named after Keshan County of Heilongjiang province, Northeast China, where symptoms were first noted. These symptoms were later found prevalent in a wide belt extending from northeast to southwest China, all due to selenium-deficient soil. The disease peaked in 1960–1970, killing thousands of people.[1][2]
Often fatal, the disease afflicts children and women of child-bearing age, characterized by heart failure and pulmonary edema. Over decades, supplementation with selenium reduced this affliction.[3]
It had been linked to the coxsackie B virus. Current research suggests that the lack of selenium results in a more virulent strain of the coxsackievirus becoming the dominant viral species present in the population of virus, but the mechanism of this selection event is unclear.[4][5]
Keshan disease can also lead to higher rates of cancer, cardiovascular disease, hypertension, and strokes. In addition, an individual can experience eczema, psoriasis, arthritis, cataracts, alcoholism, and infections.
## Contents
* 1 Diagnosis
* 2 Prevention
* 3 Treatments
* 3.1 Living with Keshan disease
* 4 See also
* 5 References
* 6 External links
## Diagnosis[edit]
This section is empty. You can help by adding to it. (October 2017)
## Prevention[edit]
It is hard to consider Keshan disease extremely preventable because the only way to ensure that the individual is getting enough selenium would be to test the soil in the area. However, one way that selenium intake can be improved is to increase intake of foods that are rich with selenium. Examples include Brazil nuts, onions, canned tuna, beef, cod, turkey, chicken breast, enriched pasta, egg, cottage cheese, oatmeal, white or brown rice, and garlic. If the individual lives in an area that does not have selenium enriched soil, dietary supplementation should be considered. To determine whether or not an individual is selenium deficient, blood testing is performed.
## Treatments[edit]
The treatment for Keshan disease is selenium supplementation. The recommended amounts are fifty-five micrograms of selenium per day for adult men and women, sixty micrograms a day for women during pregnancy and seventy micrograms per day for women after pregnancy. A doctor may insist that if a man is sexually active, he may have to take up to seventy micrograms of selenium per day. A doctor may also recommend that the individual take vitamin E; selenium and vitamin E are medically linked and seem to work to together. An individual will also be advised to have a diet that includes seafood, meats such as kidney, and liver, and some grains and seeds; all of these are high in selenium. Brewer's yeast and wheat germ both contain high levels of selenium. Garlic, onions, mushroom, broccoli, tomatoes, radishes, and Swiss chard may be good sources of selenium if the soil in which they are grown contains it. An individual will have to be monitored once they begin to take the selenium supplements, due to the fact that too much of it can cause balding, intestinal distress, weakness, and slow mental functioning. Individuals in China with the disease treat it with a herb called Astragalus, which accumulates selenium from the soil.[6]
### Living with Keshan disease[edit]
An individual will most likely be prescribed selenium supplements (in the form of selenomethionine) or have injections of this mineral. Other recommendations for managing Keshan disease are to increase consumption of foods rich in selenium in addition to supplements, avoid alcohol, monitor side effects to medications, and increase sleep. Cardiac surgery (implants, stents or full heart transplant) may be advised. [7]
## See also[edit]
* Selenium deficiency
* Kashin–Beck disease
## References[edit]
1. ^ "C&en: It's Elemental: The Periodic Table - Selenium".
2. ^ Westgate, Tom (1 November 2006). "A little selenium goes a long way". Education in Chemistry. Royal Society of Chemistry. Archived from the original on 27 June 2019. Retrieved 30 June 2018.
3. ^ "Office of Dietary Supplements - Selenium".
4. ^ Beck MA, Levander OA, Handy J (May 2003). "Selenium deficiency and viral infection". J. Nutr. 133 (5 Suppl 1): 1463S–7S. doi:10.1093/jn/133.5.1463S. PMID 12730444.
5. ^ Ren LQ, Li XJ, Li GS, Zhao ZT, Sun B, Sun F (November 2004). "Coxsackievirus B3 infection and its mutation in Keshan disease". World J. Gastroenterol. 10 (22): 3299–302. doi:10.3748/wjg.v10.i22.3299. PMC 4572299. PMID 15484304. Archived from the original on 2008-09-15.
6. ^ "Vitamins Diary". VitaminsDiary.com. Retrieved 2011-11-08.
7. ^ "Vital Health Zone". Retrieved 2011-11-08.
## External links[edit]
Classification
D
* ICD-10: E59
* ICD-9-CM: 269.3
* MeSH: C536166
* DiseasesDB: 11941
* v
* t
* e
Infectious diseases – viral systemic diseases
Oncovirus
DNA virus
HBV
Hepatocellular carcinoma
HPV
Cervical cancer
Anal cancer
Penile cancer
Vulvar cancer
Vaginal cancer
Oropharyngeal cancer
KSHV
Kaposi's sarcoma
EBV
Nasopharyngeal carcinoma
Burkitt's lymphoma
Hodgkin lymphoma
Follicular dendritic cell sarcoma
Extranodal NK/T-cell lymphoma, nasal type
MCPyV
Merkel-cell carcinoma
RNA virus
HCV
Hepatocellular carcinoma
Splenic marginal zone lymphoma
HTLV-I
Adult T-cell leukemia/lymphoma
Immune disorders
* HIV
* AIDS
Central
nervous system
Encephalitis/
meningitis
DNA virus
Human polyomavirus 2
Progressive multifocal leukoencephalopathy
RNA virus
MeV
Subacute sclerosing panencephalitis
LCV
Lymphocytic choriomeningitis
Arbovirus encephalitis
Orthomyxoviridae (probable)
Encephalitis lethargica
RV
Rabies
Chandipura vesiculovirus
Herpesviral meningitis
Ramsay Hunt syndrome type 2
Myelitis
* Poliovirus
* Poliomyelitis
* Post-polio syndrome
* HTLV-I
* Tropical spastic paraparesis
Eye
* Cytomegalovirus
* Cytomegalovirus retinitis
* HSV
* Herpes of the eye
Cardiovascular
* CBV
* Pericarditis
* Myocarditis
Respiratory system/
acute viral
nasopharyngitis/
viral pneumonia
DNA virus
* Epstein–Barr virus
* EBV infection/Infectious mononucleosis
* Cytomegalovirus
RNA virus
* IV: Human coronavirus 229E/NL63/HKU1/OC43
* Common cold
* MERS coronavirus
* Middle East respiratory syndrome
* SARS coronavirus
* Severe acute respiratory syndrome
* SARS coronavirus 2
* Coronavirus disease 2019
* V, Orthomyxoviridae: Influenza virus A/B/C/D
* Influenza/Avian influenza
* V, Paramyxoviridae: Human parainfluenza viruses
* Parainfluenza
* Human orthopneumovirus
* hMPV
Human
digestive system
Pharynx/Esophagus
* MuV
* Mumps
* Cytomegalovirus
* Cytomegalovirus esophagitis
Gastroenteritis/
diarrhea
DNA virus
Adenovirus
Adenovirus infection
RNA virus
Rotavirus
Norovirus
Astrovirus
Coronavirus
Hepatitis
DNA virus
HBV (B)
RNA virus
CBV
HAV (A)
HCV (C)
HDV (D)
HEV (E)
HGV (G)
Pancreatitis
* CBV
Urogenital
* BK virus
* MuV
* Mumps
* v
* t
* e
Malnutrition
Protein-energy
malnutrition
* Kwashiorkor
* Marasmus
* Catabolysis
Vitamin deficiency
B vitamins
* B1
* Beriberi
* Wernicke–Korsakoff syndrome
* Wernicke's encephalopathy
* Korsakoff's syndrome
* B2
* Riboflavin deficiency
* B3
* Pellagra
* B6
* Pyridoxine deficiency
* B7
* Biotin deficiency
* B9
* Folate deficiency
* B12
* Vitamin B12 deficiency
Other
* A: Vitamin A deficiency
* Bitot's spots
* C: Scurvy
* D: Vitamin D deficiency
* Rickets
* Osteomalacia
* Harrison's groove
* E: Vitamin E deficiency
* K: Vitamin K deficiency
Mineral deficiency
* Sodium
* Potassium
* Magnesium
* Calcium
* Iron
* Zinc
* Manganese
* Copper
* Iodine
* Chromium
* Molybdenum
* Selenium
* Keshan disease
Growth
* Delayed milestone
* Failure to thrive
* Short stature
* Idiopathic
General
* Anorexia
* Weight loss
* Cachexia
* Underweight
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Keshan disease
|
c0268095
| 7,762 |
wikipedia
|
https://en.wikipedia.org/wiki/Keshan_disease
| 2021-01-18T18:40:29 |
{"gard": ["8761"], "mesh": ["C536166"], "umls": ["C0268095"], "icd-9": ["269.3"], "icd-10": ["E59"], "wikidata": ["Q1739759"]}
|
Schöpf-Schulz-Passarge syndrome (SSPS) is a rare autosomal recessive ectodermal dysplasia characterized by multiple eyelid apocrine hidrocystomas, palmoplantar keratoderma, hypotrichosis, hypodontia and nail dystrophy.
## Epidemiology
More than 25 cases with SSPS have been described so far.
## Clinical description
SSPS refers to a discrete phenotype of ectodermal dysplasia with a relatively benign course and late diagnosis, often established in adulthood. The onset of symptoms occurs in childhood and early adolescence, but they consist of relatively unspecific features, including various degrees of hypodontia, hypotrichosis, palmoplantar keratoderma and nail dystrophy. Telangiectatic rosacea is a further relatively common feature. Multiple eyelid apocrine hidrocystomas commonly appear in (late) adulthood. Palmoplantar keratoderma with histologic features of eccrine syringofibroadenoma is observed in nearly half of cases and occasionally develops a malignant potential. Other adnexal tumors described include basal cell carcinoma, eccrine poroma, benign acanthoma and follicular infundibulum tumor. Some patients have been described to have a bird-like facies. Within the WNT10A mutational spectrum, odonto-onycho-dermal dysplasia and SSPS are regarded as discrete entities, while an increasing number of patients are described with incomplete phenotypes of the odonto-onychial, tricho-odonto and tricho-odonto-onychial types.
## Etiology
SSPS is due to homozygous or compound heterozygous mutations in WNT10A. Incomplete/localized disease expression in heterozygous carriers and multiple instances of consanguinity occasionally lead to a pseudodominant transmission.
## Genetic counseling
Transmission is autosomal recessive.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Schöpf-Schulz-Passarge syndrome
|
c1857069
| 7,763 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=50944
| 2021-01-23T19:02:05 |
{"mesh": ["C565607"], "omim": ["224750"], "umls": ["C1857069"], "icd-10": ["Q82.8"], "synonyms": ["Eccrine tumors-ectodermal dysplasia", "Keratosis palmoplantaris-cystic eyelids-hypodontia-hypotrichosis syndrome", "Palmoplantar hyperkeratosis-cystic eyelids-hypodontia-hypotrichosis syndrome", "Palmoplantar keratoderma-cystic eyelids-hypodontia-hypotrichosis syndrome", "SSPS"]}
|
An autosomal dominant cerebellar ataxia type II that is characterized by progressive ataxia, motor system abnormalities, dysarthria, dysphagia and retinal degeneration leading to progressive blindness.
## Epidemiology
The disorder is estimated worldwide prevalence is less than 1/100,000 and it is thought to account for 2-4% of all forms of the disease(up to 7% in Asian populations). Higher prevalence is described in some populations such as in Scandinavia or South Africa.
## Clinical description
Onset of Spinocerebellar ataxia type 7 (SCA7) is generally in the second to fourth decade but can range from infancy to the sixth decade of life. Manifestations that present in infancy and early childhood include muscle weakness, wasting, hypotonia, poor feeding, failure to thrive and loss of motor milestones. Changes in visual acuity and color vision (tritanopia) may be the earliest signs of the disease, especially in younger-onset patients. In those where initial symptoms occur before adolescence, the disease progresses much faster and blindness can occur within a few years. In those with adult-onset disease, manifestations include dysmetria, poor coordination and dysdiadokinesia with progression into severe dysarthria, dysphagia and loss of motor control. Visual symptoms (hemeralopia, photophobia, abnormalities in color vision and central visual acuity) may precede, accompany or follow cerebellar ataxia in those with adult-onset SCA7 but progression is slower, with blindness occurring 10 or more years after initial symptom onset. Psychosis and cognitive decline has also been reported in some cases. Patients eventually become bedridden.
## Etiology
SCA7 is due to a CAG trinucleotide repeat in the ataxin 7 (ATXN7) gene (3p21.1-p12). This mutation leads to degeneration in the cells of the retina, cerebellum and brainstem. A larger CAG-repeat expansion is associated with an earlier onset and more severe disease course.
## Diagnostic methods
Diagnosis is based on characteristic clinical findings (progressive incoordination and cone-rod retinal dystrophy) as well as molecular genetic testing. A CAG trinucleotide expansion (usually 36 or more CAG repeats) in the ATXN7 gene confirms diagnosis of SCA7. Magnetic resonance imaging usually shows severe atrophy of the cerebellum and the brainstem. Electroretinogram testing reveals rod and cone abnormalities and fundoscopic examination shows macular changes later in the disease course.
## Differential diagnosis
Differential diagnoses include lipid storage diseases (such as neuronal ceroid lipofuscinosis) and Leber hereditary optic neuropathy. Other forms of ADCA should also be considered but can be excluded based on the absence of retinal degeneration, which is unique to SCA7.
## Antenatal diagnosis
Antenatal diagnosis is possible in families with a known ATXN7 mutation.
## Genetic counseling
The disorder is inherited autosomal dominantly and genetic anticipation is observed. Genetic counseling can inform parents with the disease of the 50% risk of passing it on to their children.
## Management and treatment
There is no cure for SCA7 and treatment is supportive. Activity should be maintained as much as possible with the help of canes and walkers. Motorized chairs may eventually be necessary. Speech therapy and communication devices should be offered to those with dysarthria. UV exposure should be limited and sunglasses worn in order to limit damage to the retina. Low vision aids may also be beneficial. Ophthalmological follow-up is essential to monitor visual acuity. Dysphagia must also be monitored and a feeding tube may be required in those with advanced disease, in order to lower the risk of aspiration pneumonia (most common cause of death).
## Prognosis
The prognosis depends on the age of symptom onset. An earlier onset is associated with a more severe and rapidly progressive disease. Mean age when aid walking needed is about 35 years, and mean age when wheelchair needed is approximately 37 years.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Spinocerebellar ataxia type 7
|
c0752125
| 7,764 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=94147
| 2021-01-23T18:21:47 |
{"gard": ["4955"], "mesh": ["D020754"], "omim": ["164500"], "umls": ["C0752125"], "icd-10": ["G11.8"], "synonyms": ["Ataxia with pigmentary retinopathy", "Cerebellar syndrome-pigmentary maculopathy syndrome", "SCA7"]}
|
Craniosynostosis is the premature closure of one or more of the joints that connect the bones of a baby's skull (cranial sutures). Normally, the bones remain separate until about age 2, while the brain is growing. They then fuse together and stay connected throughout life. The closure is premature when it occurs before brain growth is complete.
Symptoms and severity vary depending on how many sutures close prematurely. For example, if only one closes prematurely (which is most common), brain growth may continue in other parts of the skull, leading only to an abnormally-shaped skull and no other health problems or complications. If multiple sutures close prematurely, brain growth can be restricted. This can lead to increased pressure in the skull, impaired brain development, seizures, blindness, and/or intellectual disability.
Craniosynostosis may occur as a single abnormality (isolated craniosynostosis) or it may occur as one feature of one of many syndromes. Most cases of isolated craniosynostosis occur randomly (sporadically) and have no known cause. In some cases, isolated craniosynostosis is due to a mutation in any of several genes, with autosomal dominant inheritance. When craniosynostosis is a feature of a larger syndrome (syndromic craniosynostosis), the cause and inheritance pattern depend on the syndrome the person has. However, most syndromic causes of craniosynostosis are autosomal dominant. Craniosynostosis can also be associated with a metabolic disease such as rickets, or hyperthyroidism.
Treatment for craniosynostosis depends on the severity in each child and may involve surgery in infancy to relieve pressure within the skull, allow for brain growth, and improve the appearance of the shape of the head. However, not all children with craniosynostosis will need surgery. The long-term outlook depends on how many sutures are involved and whether the child has a larger syndrome or other health problems. Children who have surgery and are otherwise healthy generally do not experience long-term complications, especially when only one suture is involved.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Craniosynostosis
|
c0010278
| 7,765 |
gard
|
https://rarediseases.info.nih.gov/diseases/6209/craniosynostosis
| 2021-01-18T18:01:03 |
{"mesh": ["D003398"], "omim": ["123100"], "umls": ["C0010278"], "orphanet": ["1531"], "synonyms": ["Craniostenosis", "CSO"]}
|
"Granulomatous" and "Granulomatous reactions" redirect here. For the Interstitial granulomatous drug reaction, see Interstitial granulomatous drug reaction.
Not to be confused with Granulation tissue.
Granuloma
Picture of a granuloma (without necrosis) as seen through a microscope on a glass slide. The tissue on the slide is stained with two standard dyes (hematoxylin: blue, eosin: pink) to make it visible. The granuloma in this picture was found in a lymph node of a patient with Mycobacterium avium infection
SpecialtyPathology
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances which it is unable to eliminate.[1] Such substances include infectious organisms including bacteria and fungi, as well as other materials such as foreign objects, keratin and suture fragments.[2][3][4][5]
## Contents
* 1 Definition
* 2 Diseases with granulomas
* 2.1 Tuberculosis
* 2.2 Leprosy
* 2.3 Schistosomiasis
* 2.4 Histoplasmosis
* 2.5 Cryptococcosis
* 2.6 Cat-scratch disease
* 2.7 Rheumatic Fever
* 2.8 Sarcoidosis
* 2.9 Crohn's disease
* 2.10 Listeria monocytogenes
* 2.11 Leishmania spp
* 2.12 Pneumocystis pneumonia
* 2.13 Aspiration pneumonia
* 2.14 Rheumatoid arthritis
* 2.15 Granuloma annulare
* 2.16 Foreign-body granuloma
* 2.17 Childhood granulomatous periorificial dermatitis
* 3 Granulomas associated with vasculitis
* 4 Etymology
* 5 See also
* 6 References
* 7 External links
## Definition[edit]
In pathology, a granuloma is an organized collection of macrophages.[1][6]
In medical practice, doctors occasionally use the term "granuloma" in its more literal meaning: "a small nodule". Since a small nodule can represent anything from a harmless nevus to a malignant tumor, this usage of the term is not very specific. Examples of this use of the term granuloma are the lesions known as vocal cord granuloma (known as contact granuloma), pyogenic granuloma and intubation granuloma, all of which are examples of granulation tissue, not granulomas. "Pulmonary hyalinizing granuloma" is a lesion characterized by keloid-like fibrosis in the lung, and is not granulomatous. Similarly, radiologists often use the term granuloma when they see a calcified nodule on X-ray or CT scan of the chest. They make this assumption since granulomas usually contain calcium, although the cells that form a granuloma are too tiny to be seen by a radiologist. The most accurate use of the term "granuloma" requires a pathologist to examine surgically removed and specially colored (stained) tissue under a microscope.
Histiocytes (specifically macrophages) are the cells that define a granuloma. They often, but not invariably, fuse to form multinucleated giant cells (Langhans giant cell).[7] The macrophages in granulomas are often referred to as "epithelioid". This term refers to the vague resemblance of these macrophages to epithelial cells. Epithelioid macrophages differ from ordinary macrophages in that they have elongated nuclei that often resemble the sole of a slipper or shoe. They also have larger nuclei than ordinary macrophages and their cytoplasm is typically more pink when stained with eosin. These changes are thought to be a consequence of "activation" of the macrophage by the offending antigen.
The other key term in the above definition is the word "organized" that refers to a tight, ball-like formation. The macrophages in these formations are typically so tightly clustered that the borders of individual cells are difficult to appreciate. Loosely dispersed macrophages are not considered to be granulomas.
All granulomas, regardless of cause, may contain additional cells and matrix. These include lymphocytes, neutrophils, eosinophils, multinucleated giant cells, fibroblasts and collagen (fibrosis). The additional cells are sometimes a clue to the cause of the granuloma. For example, granulomas with numerous eosinophils may be a clue to coccidioidomycosis or allergic bronchopulmonary fungal disease, and granulomas with numerous neutrophils suggest blastomycosis, granulomatosis with polyangiitis, aspiration pneumonia or cat-scratch disease.
In terms of the underlying cause, the difference between granulomas and other types of inflammation is that granulomas form in response to antigens that are resistant to "first-responder" inflammatory cells such as neutrophils and eosinophils. The antigen causing the formation of a granuloma is most often an infectious pathogen or a substance foreign to the body, but sometimes the offending antigen is unknown (as in sarcoidosis).[citation needed]
Granulomas are seen in a wide variety of diseases, both infectious and non-infectious.[2][3] Infections that are characterized by granulomas include tuberculosis, leprosy, histoplasmosis, cryptococcosis, coccidioidomycosis, blastomycosis and cat scratch disease. Examples of non-infectious granulomatous diseases are sarcoidosis, Crohn's disease, berylliosis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, pulmonary rheumatoid nodules and aspiration of food and other particulate material into the lung.
An important feature of granulomas is whether or not they contain necrosis. Necrosis refers to dead cells that, under the microscope, appear as a mass of formless debris with no nuclei present. A related term, "caseation" (literally: turning to cheese) refers to a form of necrosis that, to the unaided eye (i.e., without a microscope), appears cheese-like ("caseous"), and is typically (but not uniquely) a feature of the granulomas of tuberculosis. The identification of necrosis in granulomas is important because granulomas with necrosis tend to have infectious causes.[2] There are several exceptions to this general rule, but it nevertheless remains useful in day-to-day diagnostic pathology.
* Necrosis in granulomas
* Granuloma without necrosis in a lymph node of a person with sarcoidosis.
* Granuloma with central necrosis in a lung of a person with tuberculosis. Note the Langhans-type giant cells (with many nuclei arranged in a horseshoe-like pattern at the edge of the cell) around the periphery of the granuloma. Langhans-type giant cells are seen in many types of granulomas, and are not specific for tuberculosis.
## Diseases with granulomas[edit]
### Tuberculosis[edit]
The granulomas of tuberculosis tend to contain necrosis ("caseating tubercules"), but non-necrotizing granulomas may also be present. Multinucleated giant cells with nuclei arranged like a horseshoe (Langhans giant cell) and foreign body giant cells[8] are often present, but are not specific for tuberculosis. A definitive diagnosis of tuberculosis requires identification of the causative organism by microbiologic cultures.[9]
### Leprosy[edit]
In leprosy, granulomas are found in the skin and tend to involve nerves. The appearance of the granulomas differs according to the precise type of leprosy.
### Schistosomiasis[edit]
Some schistosome ova that are laid in intestinal and urinary venules backwash into the liver via the portal vein causing granuloma formation in the liver.
### Histoplasmosis[edit]
Granulomas are seen in most forms of histoplasmosis (acute histoplasmosis, histoplasmoma, chronic histoplasmosis). Histoplasma organisms can sometimes be demonstrated within the granulomas by biopsy or microbiological cultures.[2]
### Cryptococcosis[edit]
When Cryptococcus infection occurs in persons whose immune systems are intact, granulomatous inflammation is typically encountered. The granulomas can be necrotizing or non-necrotizing. Using a microscope and appropriate stains, organisms can be seen within the granulomas.[9]
### Cat-scratch disease[edit]
Cat-scratch disease is an infection caused by the bacterial organism Bartonella henselae, typically acquired by a scratch from a kitten infected with the organism. The granulomas in this disease are found in the lymph nodes draining the site of the scratch. They are characteristically "suppurative", i.e., pus forming, containing large numbers of neutrophils. Organisms are usually difficult to find within the granulomas using methods routinely used in pathology laboratories.
### Rheumatic Fever[edit]
Rheumatic fever is a systemic disease affecting the peri-arteriolar connective tissue and can occur after an untreated Group A Beta-hemolytic streptococcal pharyngeal infection. It is believed to be caused by antibody cross-reactivity.
### Sarcoidosis[edit]
Two asteroid bodies in sarcoidosis. H&E stain.
Sarcoidosis is a disease of unknown cause characterized by non-necrotizing ("non-caseating") granulomas in multiple organs and body sites,[10] most commonly the lungs and lymph nodes within the chest cavity. Other common sites of involvement include the liver, spleen, skin and eyes. The granulomas of sarcoidosis are similar to the granulomas of tuberculosis and other infectious granulomatous diseases. However, in most cases of sarcoidosis, the granulomas do not contain necrosis and are surrounded by concentric scar tissue (fibrosis). Sarcoid granulomas often contain star-shaped structures termed asteroid bodies or lamellar structures termed Schaumann bodies. However, these structures are not specific for sarcoidosis.[9] Sarcoid granulomas can resolve spontaneously without complications or heal with residual scarring. In the lungs, this scarring can cause a condition known as pulmonary fibrosis that impairs breathing. In the heart, it can lead to rhythm disturbances, heart failure, and even death.
### Crohn's disease[edit]
Crohn's disease is an inflammatory condition of uncertain cause characterized by severe inflammation in the wall of the intestines and other parts of the abdomen. Within the inflammation in the gut wall, granulomas are often found and are a clue to the diagnosis.[11]
### Listeria monocytogenes[edit]
Listeria monocytogenes infection in infants can cause potentially fatal disseminated granulomas, called granulomatosis infantiseptica, following in utero infection.
### Leishmania spp[edit]
Leishmaniases are a group of human diseases caused by Leishmania genus and transmitted by a sandfly bite can lead to granulomatous inflammation[12] in skin (cutaneous form of the disease) and liver (visceral form) with research suggesting effective granuloma formation to be desirable in the resolution of the disease.[13]
### Pneumocystis pneumonia[edit]
Pneumocystis infection in the lungs is usually not associated with granulomas, but rare cases are well documented to cause granulomatous inflammation. The diagnosis is established by finding Pneumocystis yeasts within the granulomas on lung biopsies.[14]
### Aspiration pneumonia[edit]
Aspiration pneumonia is typically caused by aspiration of bacteria from the oral cavity into the lungs, and does not result in the formation of granulomas. However, granulomas may form when food particles or other particulate substances like pill fragments are aspirated into the lungs. Patients typically aspirate food because they have esophageal, gastric or neurologic problems. Intake of drugs that depress neurologic function may also lead to aspiration. The resultant granulomas are typically found around the airways (bronchioles) and are often accompanied by foreign-body-type multinucleated giant cells, acute inflammation or organizing pneumonia. The finding of food particles in lung biopsies is diagnostic.[15]
### Rheumatoid arthritis[edit]
Necrotizing granulomas can develop in patients with rheumatoid arthritis, typically manifesting as bumps in the soft tissues around the joints (so-called rheumatoid nodules) or in the lungs.[9]
### Granuloma annulare[edit]
Granuloma annulare is a skin disease of unknown cause in which granulomas are found in the dermis of the skin. However, it is not a true granuloma. Typically there is a central zone of necrobiotic generation of collagen with surrounding inflammation and mucin deposition on pathology.
### Foreign-body granuloma[edit]
Granulomatous reaction to nylon suture material
A foreign-body granuloma occurs when a foreign body (such as a wood splinter, piece of metal, glass etc.) penetrates the body's soft tissue followed by acute inflammation and formation of a granuloma.[16] In some cases the foreign body can be found and removed even years after the precipitating event.[17]
### Childhood granulomatous periorificial dermatitis[edit]
Childhood granulomatous periorificial dermatitis is a rare granulomatous skin disorder of unknown cause. It is temporary and tends to affect children, usually of African descent.
## Granulomas associated with vasculitis[edit]
Certain inflammatory diseases are characterised by a combination of granulomatous inflammation and vasculitis (inflammation of the blood vessels). Both the granulomas as well as the vasculitis tend to occur in association with necrosis. Classic examples of such diseases include granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis.
## Etymology[edit]
The term is from granule \+ -oma. The plural is granulomas or granulomata. The adjective granulomatous means characterized by granulomas.
## See also[edit]
* Lick granuloma, a skin disorder in dogs that results from dog's urge to lick the lower portion of its leg
* Sperm granuloma
* Contact granuloma, i.e. "throat granuloma"
## References[edit]
1. ^ a b Williams, Olivia; Fatima, Saira (5 April 2020). "Granuloma". StatPearls. Treasure Island: StatPearls Publishing. PMID 32119473.
2. ^ a b c d Mukhopadhyay S, Farver CF, Vaszar LT, Dempsey OJ, Popper HH, Mani H, Capelozzi VL, Fukuoka J, Kerr KM, Zeren EH, Iyer VK, Tanaka T, Narde I, Nomikos A, Gumurdulu D, Arava S, Zander DS, Tazelaar HD (Jan 2012). "Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries". Journal of Clinical Pathology. 65 (1): 51–57. doi:10.1136/jclinpath-2011-200336. PMID 22011444. S2CID 28504428.
3. ^ a b Woodard BH, Rosenberg SI, Farnham R, Adams DO (1982). "Incidence and nature of primary granulomatous inflammation in surgically removed material". American Journal of Surgical Pathology. 6 (2): 119–129. doi:10.1097/00000478-198203000-00004. PMID 7102892. S2CID 12907076.
4. ^ Hunter DC, Logie JR (1988). "Suture granuloma". British Journal of Surgery. 75 (11): 1149–1150. doi:10.1002/bjs.1800751140. PMID 3208057. S2CID 12804852.
5. ^ Chen KT, Kostich ND, Rosai J (1978). "Peritoneal foreign body granulomas to keratin in uterine adenocanthoma". Archives of Pathology and Laboratory Medicine. 102 (4): 174–177. PMID 580709.
6. ^ Adams DO (1976). "The granulomatous inflammatory response. A review". American Journal of Pathology. 84 (1): 164–191. PMC 2032357. PMID 937513.
7. ^ Murphy, Kenneth; Paul, Travers; Mark, Walport (2008). Janeway's immunobiology (7th ed.). New York: Garland Science. p. 372. ISBN 978-0815341239.
8. ^ dental decks part II Edited by Nour
9. ^ a b c d Mukhopadhyay S, Gal AA (2010). "Granulomatous lung disease: an approach to the differential diagnosis". Archives of Pathology and Laboratory Medicine. 134 (5): 669–690. doi:10.1043/1543-2165-134.5.667 (inactive 2020-12-26). PMID 20441499.CS1 maint: DOI inactive as of December 2020 (link)
10. ^ Iannuzzi M, Rybicki BA, Teirstein AS (2007). "Sarcoidosis". New England Journal of Medicine. 357 (21): 2153–2165. doi:10.1056/NEJMra071714. PMID 18032765.
11. ^ Cohen, Elizabeth (June 11, 2009). "Teen diagnoses her own disease in science class". CNN Health. Cable News Network.
12. ^ Ridley, M. J.; Ridley, D. S. (April 1986). "Monocyte recruitment, antigen degradation and localization in cutaneous leishmaniasis". British Journal of Experimental Pathology. 67 (2): 209–218. ISSN 0007-1021. PMC 2013155. PMID 3707851.
13. ^ Kaye, Paul M.; Beattie, Lynette (2016-03-01). "Lessons from other diseases: granulomatous inflammation in leishmaniasis". Seminars in Immunopathology. 38 (2): 249–260. doi:10.1007/s00281-015-0548-7. ISSN 1863-2300. PMC 4779128. PMID 26678994.
14. ^ Hartel PH, Shilo K, Klassen-Fischer M, et al. (2010). "Granulomatous reaction to Pneumocystis jirovecii. clinicopathologic review of 20 cases". American Journal of Surgical Pathology. 34 (5): 730–734. doi:10.1097/PAS.0b013e3181d9f16a. PMID 20414100. S2CID 25202257.
15. ^ Mukhopadhyay S, Katzenstein AL (2007). "Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens". American Journal of Surgical Pathology. 31 (5): 752–759. doi:10.1097/01.pas.0000213418.08009.f9. PMID 17460460. S2CID 45207101.
16. ^ Joyce, S; Rao Sripathi, BH; Mampilly, MO; Firdoose Nyer, CS (September 2014). "Foreign Body Granuloma". J Maxillofac Oral Surg. 13 (3): 351–4. doi:10.1007/s12663-010-0113-9. PMC 4082545. PMID 25018614.
17. ^ El Bouchti, I.; Ait Essi, F.; Abkari, I.; Latifi, M.; El Hassani, S. (2012). "Foreign Body Granuloma: A Diagnosis Not to Forget". Case Reports in Orthopedics. Hindawi Publishing Corporation. 2012: 1–2. doi:10.1155/2012/439836. PMC 3505897. PMID 23259122.
## External links[edit]
Classification
D
* ICD-10: L92
* ICD-9-CM: 686.1, 709.4
* MeSH: D006099
* SNOMED CT: 45647009
* v
* t
* e
Inflammation
Symptoms
* Flushing (Rubor)
* Fever (Calor)
* Swelling (Tumor)
* Pain (Dolor)
* Malaise
Mechanism
Acute
Plasma-derived mediators
* Bradykinin
* complement
* C3
* C5a
* MAC
* coagulation
* Factor XII
* Plasmin
* Thrombin
Cell-derived mediators
preformed:
* Lysosome granules
* biogenic amines
* Histamine
* Serotonin
synthesized on demand:
* cytokines
* IFN-γ
* IL-8
* TNF-α
* IL-1
* eicosanoids
* Leukotriene B4
* Prostaglandins
* Nitric oxide
* Kinins
Chronic
* Macrophage
* Epithelioid cell
* Giant cell
* Granuloma
Other
* Acute-phase reaction
* Vasodilation
* Increased vascular permeability
* Exudate
* Leukocyte extravasation
* Chemotaxis
Tests
* Full blood count
* Leukocytosis
* C-reactive protein
* Erythrocyte sedimentation rate
General
* Lymphadenopathy
* List of inflammed body part states
* v
* t
* e
Cutaneous keratosis, ulcer, atrophy, and necrobiosis
Epidermal thickening
* keratoderma: Keratoderma climactericum
* Paraneoplastic keratoderma
* Acrokeratosis paraneoplastica of Bazex
* Aquagenic keratoderma
* Drug-induced keratoderma
* psoriasis
* Keratoderma blennorrhagicum
* keratosis: Seborrheic keratosis
* Clonal seborrheic keratosis
* Common seborrheic keratosis
* Irritated seborrheic keratosis
* Seborrheic keratosis with squamous atypia
* Reticulated seborrheic keratosis
* Dermatosis papulosa nigra
* Keratosis punctata of the palmar creases
* other hyperkeratosis: Acanthosis nigricans
* Confluent and reticulated papillomatosis
* Callus
* Ichthyosis acquisita
* Arsenical keratosis
* Chronic scar keratosis
* Hyperkeratosis lenticularis perstans
* Hydrocarbon keratosis
* Hyperkeratosis of the nipple and areola
* Inverted follicular keratosis
* Lichenoid keratosis
* Multiple minute digitate hyperkeratosis
* PUVA keratosis
* Reactional keratosis
* Stucco keratosis
* Thermal keratosis
* Viral keratosis
* Warty dyskeratoma
* Waxy keratosis of childhood
* other hypertrophy: Keloid
* Hypertrophic scar
* Cutis verticis gyrata
Necrobiosis/granuloma
Necrobiotic/palisading
* Granuloma annulare
* Perforating
* Generalized
* Subcutaneous
* Granuloma annulare in HIV disease
* Localized granuloma annulare
* Patch-type granuloma annulare
* Necrobiosis lipoidica
* Annular elastolytic giant-cell granuloma
* Granuloma multiforme
* Necrobiotic xanthogranuloma
* Palisaded neutrophilic and granulomatous dermatitis
* Rheumatoid nodulosis
* Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction
Foreign body granuloma
* Beryllium granuloma
* Mercury granuloma
* Silica granuloma
* Silicone granuloma
* Zirconium granuloma
* Soot tattoo
* Tattoo
* Carbon stain
Other/ungrouped
* eosinophilic dermatosis
* Granuloma faciale
Dermis/
localized CTD
Cutaneous lupus
erythematosus
* chronic: Discoid
* Panniculitis
* subacute: Neonatal
* ungrouped: Chilblain
* Lupus erythematosus–lichen planus overlap syndrome
* Tumid
* Verrucous
* Rowell's syndrome
Scleroderma/
Morphea
* Localized scleroderma
* Localized morphea
* Morphea–lichen sclerosus et atrophicus overlap
* Generalized morphea
* Atrophoderma of Pasini and Pierini
* Pansclerotic morphea
* Morphea profunda
* Linear scleroderma
Atrophic/
atrophoderma
* Lichen sclerosus
* Anetoderma
* Schweninger–Buzzi anetoderma
* Jadassohn–Pellizzari anetoderma
* Atrophoderma of Pasini and Pierini
* Acrodermatitis chronica atrophicans
* Semicircular lipoatrophy
* Follicular atrophoderma
* Linear atrophoderma of Moulin
Perforating
* Kyrle disease
* Reactive perforating collagenosis
* Elastosis perforans serpiginosa
* Perforating folliculitis
* Acquired perforating dermatosis
Skin ulcer
* Pyoderma gangrenosum
Other
* Calcinosis cutis
* Sclerodactyly
* Poikiloderma vasculare atrophicans
* Ainhum/Pseudo-ainhum
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Granuloma
|
c0018188
| 7,766 |
wikipedia
|
https://en.wikipedia.org/wiki/Granuloma
| 2021-01-18T19:04:19 |
{"mesh": ["D006099"], "icd-9": ["686.1", "709.4"], "icd-10": ["L92"], "wikidata": ["Q1129338"]}
|
Laplane et al. (1972) reported 2 brothers of Kabylian ancestry (the Kabyle are Berber people of northern Algeria) with a disorder they termed syndesmodysplasic dwarfism. Features were severe dwarfism and progressive stiff joints, including spine and hips. The skin was said to be normal.
Joints \- Progressive stiff joints Growth \- Syndesmodysplasic dwarfism 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SYNDESMODYSPLASIC DWARFISM
|
c2931647
| 7,767 |
omim
|
https://www.omim.org/entry/272450
| 2019-09-22T16:21:56 |
{"mesh": ["C537869"], "omim": ["272450"], "orphanet": ["2654"]}
|
Papilloma of the choroid plexus is a rare benign type of choroid plexus tumor (see this term), accounting for 1% of all brain tumors, often occurring in the fourth ventricle (in adults) and the lateral ventricle (in children) but sometimes arising ectopically in the brain parenchyma, and presenting with nausea, vomiting, papilledema, abnormal eye movements, as well as enlarged head circumference, seizures and gait impairment due to an increase in intracranial pressure.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Papilloma of choroid plexus
|
c0205770
| 7,768 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2807
| 2021-01-23T17:59:37 |
{"gard": ["4214"], "mesh": ["D020288"], "omim": ["260500"], "umls": ["C0205770"], "icd-10": ["D33.0"], "synonyms": ["CPP", "Choroid plexus papilloma"]}
|
A heart defect present at birth in which blood can flow through an opening between the top chambers of the heart
Atrial septal defect
Illustration of an atrial septal defect.
SpecialtyCardiac surgery
Symptomsasymptomatic
Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this does not naturally close after birth it is referred to as a patent (open) foramen ovale (PFO). It is common in patients with a congenital atrial septal aneurysm (ASA).
After PFO closure the atria normally are separated by a dividing wall, the interatrial septum. If this septum is defective or absent, then oxygen-rich blood can flow directly from the left side of the heart to mix with the oxygen-poor blood in the right side of the heart; or the opposite, depending on whether the left or right atrium has the higher blood pressure.[1] In the absence of other heart defects, the left atrium has the higher pressure. This can lead to lower-than-normal oxygen levels in the arterial blood that supplies the brain, organs, and tissues. However, an ASD may not produce noticeable signs or symptoms, especially if the defect is small. Also, in terms of health risks, people who have had a cryptogenic stroke are more likely to have a PFO than the general population.[2]
A cardiac shunt is the presence of a net flow of blood through a defect, either from left to right or right to left. The amount of shunting present, if any, determines the hemodynamic significance of the ASD. A right-to-left-shunt results in venous blood entering the left side of the heart and into the arterial circulation without passing through the pulmonary circulation to be oxygenated. This may result in the clinical finding of cyanosis, the presence of bluish-colored skin, especially of the lips and under the nails.
During development of the baby, the interatrial septum develops to separate the left and right atria. However, a hole in the septum called the foramen ovale allows blood from the right atrium to enter the left atrium during fetal development. This opening allows blood to bypass the nonfunctional fetal lungs while the fetus obtains its oxygen from the placenta. A layer of tissue called the septum secundum acts as a valve over the foramen ovale during fetal development. After birth, the pressure in the right side of the heart drops as the lungs open and begin working, causing the foramen ovale to close entirely. In about 25% of adults,[3] the foramen ovale does not entirely seal.[4] In these cases, any elevation of the pressure in the pulmonary circulatory system (due to pulmonary hypertension, temporarily while coughing, etc.) can cause the foramen ovale to remain open.
## Contents
* 1 Types
* 1.1 Ostium secundum
* 1.1.1 Natural history
* 1.2 Patent foramen ovale
* 1.3 Ostium primum
* 1.4 Sinus venosus
* 1.5 Common or single atrium
* 1.6 Mixed
* 2 Presentation
* 2.1 Complications
* 2.1.1 Decompression sickness
* 2.1.2 Eisenmenger's syndrome
* 2.1.3 Paradoxical embolus
* 2.1.4 Migraine
* 3 Causes
* 4 Mechanisms
* 5 Diagnosis
* 5.1 Physical examination
* 5.2 Echocardiography
* 5.3 Transcranial doppler bubble study
* 5.4 Electrocardiogram
* 6 Treatment
* 6.1 Patent Foramen Ovale
* 6.1.1 PFO Closure
* 6.1.2 Medical Therapy
* 6.2 Atrial Septal Defect
* 6.2.1 Evaluation prior to correction
* 6.2.2 Surgical closure
* 6.2.3 Catheter procedure
* 7 Epidemiology
* 8 References
* 8.1 Additional references
* 9 External links
## Types[edit]
Schematic drawing showing the location of different types of ASD, the view is into an opened right atrium.
HV: right ventricle; VCS: superior vena cava; VCI: inferior vena cava
1: upper sinus venosus defect; 2: lower sinus venosus defect; 3: secundum defect; 4: defect involving coronary sinus; 5; primum defect.
The six types of atrial septal defects are differentiated from each other by whether they involve other structures of the heart and how they are formed during the developmental process during early fetal development.
### Ostium secundum[edit]
The ostium secundum atrial septal defect is the most common type of atrial septal defect and comprises 6–10% of all congenital heart diseases.
The secundum atrial septal defect usually arises from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum. About 10 to 20% of individuals with ostium secundum ASDs also have mitral valve prolapse.[5]
An ostium secundum ASD accompanied by an acquired mitral valve stenosis is called Lutembacher's syndrome.[6]
#### Natural history[edit]
Most individuals with an uncorrected secundum ASD do not have significant symptoms through early adulthood. More than 70% develop symptoms by about 40 years of age. Symptoms are typically decreased exercise tolerance, easy fatigability, palpitations, and syncope.
Complications of an uncorrected secundum ASD include pulmonary hypertension, right-sided heart failure, atrial fibrillation or flutter, stroke, and Eisenmenger's syndrome.
While pulmonary hypertension is unusual before 20 years of age, it is seen in 50% of individuals above the age of 40. Progression to Eisenmenger's syndrome occurs in 5 to 10% of individuals late in the disease process.[6]
### Patent foramen ovale[edit]
Patent-foramen-ovale-en
A patent foramen ovale (PFO) is a remnant opening of the fetal foramen ovale, which normally closes after a person's birth. In medical use, the term "patent" means open or unobstructed.[7] In about 25% of people, the foramen ovale fails to close properly, leaving them with a PFO or at least with what some physicians classify as a "pro-PFO", which is a PFO that is normally closed, but can open under increased blood pressure. On echocardiography, shunting of blood may not be noted except when the patient coughs.
PFO is linked to stroke, sleep apnea, migraine with aura, and decompression sickness. No cause is established for a foramen ovale to remain open instead of closing naturally, but heredity and genetics may play a role.[8][9] PFO is not treated in the absence of other symptoms.
The mechanism by which a PFO may play a role in stroke is called paradoxical embolism. In the case of PFO, a blood clot from the venous circulatory system is able to pass from the right atrium directly into the left atrium via the PFO, rather than being filtered by the lungs, and thereupon into systemic circulation toward the brain.[10][11] PFO is common in patients with an atrial septal aneurysm (ASA), a much rarer condition, which is also linked to cryptogenic (i.e., of unknown cause) stroke.[12]
PFO is more common in people with cryptogenic stroke than in those with a stroke of known cause.[13] While PFO is present in 25% in the general population, the probability of someone having a PFO increases to about 40 to 50% in those who have had a cryptogenic stroke, and more so in those who have a stroke before the age of 55.[14] Treatment with anticoagulant and antiplatelet medications in this group appear similar.[15]
### Ostium primum[edit]
Main article: Ostium primum atrial septal defect
A defect in the ostium primum is occasionally classified as an atrial septal defect,[16] but it is more commonly classified as an atrioventricular septal defect.[17][18] Ostium primum defects are less common than ostium secundum defects.[19] This type of defect is usually associated with Down syndrome.
### Sinus venosus[edit]
A sinus venosus ASD is a type of atrial septum defect in which the defect involves the venous inflow of either the superior vena cava or the inferior vena cava.
A sinus venosus ASD that involves the superior vena cava makes up 2 to 3% of all interatrial communication. It is located at the junction of the superior vena cava and the right atrium. It is frequently associated with anomalous drainage of the right-sided pulmonary veins into the right atrium (instead of the normal drainage of the pulmonary veins into the left atrium).[20]
Ultrasound picture of the heart, seen in a subcostal view: The apex is towards the right, the atria are to the left. ASD secundum seen as a discontinuation of the white band of the atrial septum. The enlarged right atrium is below. The enlarged pulmonary veins are seen entering the left atrium above.
### Common or single atrium[edit]
Common (or single) atrium is a failure of development of the embryologic components that contribute to the atrial septal complex. It is frequently associated with heterotaxy syndrome.[21]
### Mixed[edit]
The interatrial septum can be divided into five septal zones. If the defect involves two or more of the septal zones, then the defect is termed a mixed atrial septal defect.[22]
## Presentation[edit]
### Complications[edit]
Due to the communication between the atria that occurs in ASDs, disease entities or complications from the condition are possible. Patients with an uncorrected atrial septal defect may be at increased risk for developing a cardiac arrhythmia, as well as more frequent respiratory infections.[19]
#### Decompression sickness[edit]
ASDs, and particularly PFOs, are a predisposing venous blood carrying inert gases, such as helium or nitrogen does not pass through the lungs.[23][24] The only way to release the excess inert gases from the body is to pass the blood carrying the inert gases through the lungs to be exhaled. If some of the inert gas-laden blood passes through the PFO, it avoids the lungs and the inert gas is more likely to form large bubbles in the arterial blood stream causing decompression sickness.
#### Eisenmenger's syndrome[edit]
Main article: Eisenmenger's syndrome
If a net flow of blood exists from the left atrium to the right atrium, called a left-to-right shunt, then an increase in the blood flow through the lungs happens. Initially, this increased blood flow is asymptomatic, but if it persists, the pulmonary blood vessels may stiffen, causing pulmonary hypertension, which increases the pressures in the right side of the heart, leading to the reversal of the shunt into a right-to-left shunt. Reversal of the shunt occurs, and the blood flowing in the opposite direction through the ASD is called Eisenmenger's syndrome, a rare and late complication of an ASD.
#### Paradoxical embolus[edit]
Venous thrombus (clots in the veins) are quite common. Embolizations (dislodgement of thrombi) normally go to the lung and cause pulmonary emboli. In an individual with ASD, these emboli can potentially enter the arterial system, which can cause any phenomenon attributed to acute loss of blood to a portion of the body, including cerebrovascular accident (stroke), infarction of the spleen or intestines, or even a distal extremity (i.e., finger or toe).
This is known as a paradoxical embolus because the clot material paradoxically enters the arterial system instead of going to the lungs.
#### Migraine[edit]
Main article: Migraine surgery § Patent foramen ovale closure
Some recent research has suggested that a proportion of cases of migraine may be caused by PFO. While the exact mechanism remains unclear, closure of a PFO can reduce symptoms in certain cases.[25][26] This remains controversial; 20% of the general population has a PFO, which for the most part, is asymptomatic. About 20% of the female population has migraines, and the placebo effect in migraine typically averages around 40%. The high frequency of these facts make finding statistically significant relationships between PFO and migraine difficult (i.e., the relationship may just be chance or coincidence). In a large randomized controlled trial, the higher prevalence of PFO in migraine patients was confirmed, but migraine headache cessation was not more prevalent in the group of migraine patients who underwent closure of their PFOs.[27]
## Causes[edit]
* Down syndrome – patients with Down syndrome have higher rates of ASDs, especially a particular type that involves the ventricular wall.[28] As many as one half of Down syndrome patients have some type of septal defect.[28]
* Ebstein's anomaly[29] – about 50% of individuals with Ebstein anomaly have an associated shunt between the right and left atria, either an atrial septal defect or a patent foramen ovale.[30]
* Fetal alcohol syndrome – about one in four patients with fetal alcohol syndrome has either an ASD or a ventricular septal defect.[31]
* Holt–Oram syndrome – both the osteium secundum and osteum primum types of ASD are associated with Holt–Oram syndrome[32]
* Lutembacher's syndrome – the presence of a congenital ASD along with acquired mitral stenosis[6]
## Mechanisms[edit]
In unaffected individuals, the chambers of the left side of the heart are under higher pressure than the chambers of the right side because the left ventricle has to produce enough pressure to pump blood throughout the entire body, while the right ventricle needs only to produce enough pressure to pump blood to the lungs.
In the case of a large ASD (> 9 mm), which may result in a clinically remarkable left-to-right shunt, blood shunts from the left atrium to the right atrium. This extra blood from the left atrium may cause a volume overload of both the right atrium and the right ventricle. If untreated, this condition can result in enlargement of the right side of the heart and ultimately heart failure.[22]
Any process that increases the pressure in the left ventricle can cause worsening of the left-to-right shunt. This includes hypertension, which increases the pressure that the left ventricle has to generate to open the aortic valve during ventricular systole, and coronary artery disease which increases the stiffness of the left ventricle, thereby increasing the filling pressure of the left ventricle during ventricular diastole. The left-to-right shunt increases the filling pressure of the right heart (preload) and forces the right ventricle to pump out more blood than the left ventricle. This constant overloading of the right side of the heart causes an overload of the entire pulmonary vasculature. Eventually, pulmonary hypertension may develop.
The pulmonary hypertension will cause the right ventricle to face increased afterload. The right ventricle is forced to generate higher pressures to try to overcome the pulmonary hypertension. This may lead to right ventricular failure (dilatation and decreased systolic function of the right ventricle).
If the ASD is left uncorrected, the pulmonary hypertension progresses and the pressure in the right side of the heart becomes greater than the left side of the heart. This reversal of the pressure gradient across the ASD causes the shunt to reverse - a right-to-left shunt. This phenomenon is known as Eisenmenger's syndrome. Once right-to-left shunting occurs, a portion of the oxygen-poor blood gets shunted to the left side of the heart and ejected to the peripheral vascular system. This causes signs of cyanosis.
* Heart of human embryo of about 35 days
* Atrial septal defect with left-to-right shunt
* Illustration depicting atrial septal defect
## Diagnosis[edit]
Abnormal chest X-ray as seen in a patient of atrial septal defect
Most individuals with a significant ASD are diagnosed in utero or in early childhood with the use of ultrasonography or auscultation of the heart sounds during physical examination.
Some individuals with an ASD have surgical correction of their ASD during childhood. The development of signs and symptoms due to an ASD are related to the size of the intracardiac shunt. Individuals with a larger shunt tend to present with symptoms at a younger age.
Adults with an uncorrected ASD present with symptoms of dyspnea on exertion (shortness of breath with minimal exercise), congestive heart failure, or cerebrovascular accident (stroke). They may be noted on routine testing to have an abnormal chest X-ray or an abnormal ECG and may have atrial fibrillation. If the ASD causes a left-to-right shunt, the pulmonary vasculature in both lungs may appear dilated on chest X-ray, due to the increase in pulmonary blood flow.[33]
### Physical examination[edit]
The physical findings in an adult with an ASD include those related directly to the intracardiac shunt and those that are secondary to the right heart failure that may be present in these individuals.
Upon auscultation of the heart sounds, a systolic ejection murmur may be heard that is attributed to the pulmonic valve, due to the increased flow of blood through the pulmonic valve rather than any structural abnormality of the valve leaflets.
In unaffected individuals, respiratory variations occur in the splitting of the second heart sound (S2). During respiratory inspiration, the negative intrathoracic pressure causes increased blood return into the right side of the heart. The increased blood volume in the right ventricle causes the pulmonic valve to stay open longer during ventricular systole. This causes a normal delay in the P2 component of S2. During expiration, the positive intrathoracic pressure causes decreased blood return to the right side of the heart. The reduced volume in the right ventricle allows the pulmonic valve to close earlier at the end of ventricular systole, causing P2 to occur earlier.
In individuals with an ASD, a fixed splitting of S2 occurs because the extra blood return during inspiration gets equalized between the left and right atria due to the communication that exists between the atria in individuals with ASD.
The right ventricle can be thought of as continuously overloaded because of the left-to-right shunt, producing a widely split S2. Because the atria are linked via the atrial septal defect, inspiration produces no net pressure change between them, and has no effect on the splitting of S2. Thus, S2 is split to the same degree during inspiration as expiration, and is said to be “fixed”.
### Echocardiography[edit]
In transthoracic echocardiography, an atrial septal defect may be seen on color flow imaging as a jet of blood from the left atrium to the right atrium.
If agitated saline is injected into a peripheral vein during echocardiography, small air bubbles can be seen on echocardiographic imaging. Bubbles traveling across an ASD may be seen either at rest or during a cough. (Bubbles only flow from right atrium to left atrium if the right atrial pressure is greater than left atrial). Because better visualization of the atria is achieved with transesophageal echocardiography, this test may be performed in individuals with a suspected ASD which is not visualized on transthoracic imaging. Newer techniques to visualize these defects involve intracardiac imaging with special catheters typically placed in the venous system and advanced to the level of the heart. This type of imaging is becoming more common and involves only mild sedation for the patient typically.
If the individual has adequate echocardiographic windows, use of the echocardiogram to measure the cardiac output of the left ventricle and the right ventricle independently is possible. In this way, the shunt fraction can be estimated using echocardiography.
### Transcranial doppler bubble study[edit]
A less invasive method for detecting a PFO or other ASDs than transesophagal ultrasound is transcranial Doppler with bubble contrast.[34] This method reveals the cerebral impact of the ASD or PFO.
### Electrocardiogram[edit]
The ECG findings in atrial septal defect vary with the type of defect the individual has. Individuals with atrial septal defects may have a prolonged PR interval (a first-degree heart block). The prolongation of the PR interval is probably due to the enlargement of the atria common in ASDs and the increased distance due to the defect itself. Both of these can cause an increased distance of internodal conduction from the SA node to the AV node.[35]
In addition to the PR prolongation, individuals with a primum ASD have a left axis deviation of the QRS complex, while those with a secundum ASD have a right axis deviation of the QRS complex. Individuals with a sinus venosus ASD exhibit a left axis deviation of the P wave (not the QRS complex).
A common finding in the ECG is the presence of incomplete right bundle branch block, which is so characteristic that if it is absent, the diagnosis of ASD should be reconsidered.
* Play media
ASD with pulmonary embolism resulting in a right-to-left shunting of blood[36]
* Play media
ASD with pulmonary embolism resulting in a right-to-left shunting of blood[36]
* Play media
ASD with pulmonary embolism resulting in a right-to-left shunting of blood[36]
## Treatment[edit]
### Patent Foramen Ovale[edit]
Most patients with a PFO are asymptomatic and do not require any specific treatment.[37] However, those who develop a stroke require further workup to identify the etiology. In those where a comprehensive evaluation is performed and an obvious etiology is not identified, they are defined as having a cryptogenic stroke. The mechanism for stroke is such individuals is likely embolic due to paradoxical emboli, a left atrial appendage clot, a clot on the inter-atrial septum, or within the PFO tunnel.[38]
#### PFO Closure[edit]
The Amplatzer Septal Occluder is a device specifically designed to close an ASD
Until recently, patients with PFO and cryptogenic stroke were treated with antiplatelet therapy only. Previous studies did not identify a clear benefit of PFO closure over antiplatelet therapy in reducing recurrent ischemic stroke. However, based on new evidence [39][40][41] and systematic review in the field,[38] percutaneous PFO closure in addition to antiplatelet therapy is suggested for all who meet all the following criteria:[42]
* Age ≤ 60 years at onset of first stroke,
* Embolic-appearing cryptogenic ischemic stroke (i.e., no evident source of stroke despite a comprehensive evaluation), and
* PFO with a right-to-left interatrial shunt detected by bubble study (echocardiogram)[43][44]
A variety of PFO closure devices may be implanted via catheter-based procedures.[45][46]
Amplazer PFO Occluder in heart
#### Medical Therapy[edit]
Based on the most up to date evidence, PFO closure is more effective at reducing recurrent ischemic stroke when compared to medical therapy. In most of these studies, antiplatelet and anticoagulation were combined in the medical therapy arm. Although there is limited data on the effectiveness of anticoagulation in reducing stroke in this population, it is hypothesized that based on the embolic mechanism, that anticoagulation should be superior to antiplatelet therapy at reducing risk of recurrent stroke. A recent review of the literature supports this hypothesis recommending anticoagulation over the use of antiplatelet therapy in patients with PFO and cryptogenic stroke.[38] However, more evidence is required comparing of PFO closure with anticoagulation or anticoagulation with antiplatelet therapy.
### Atrial Septal Defect[edit]
Once someone is found to have an atrial septal defect, a determination of whether it should be corrected is typically made. If the atrial septal defect is causing the right ventricle to enlarge a secundum atrial septal defect should generally be closed.[47] If the ASD is not causing problems the defect may simply be checked every two or three years.[47] Methods of closure of an ASD include surgical closure and percutaneous closure.
#### Evaluation prior to correction[edit]
Prior to correction of an ASD, an evaluation is made of the severity of the individual's pulmonary hypertension (if present at all) and whether it is reversible (closure of an ASD may be recommended for prevention purposes, to avoid such a complication in the first place. Pulmonary hypertension is not always present in adults who are diagnosed with an ASD in adulthood).
If pulmonary hypertension is present, the evaluation may include a right heart catheterization. This involves placing a catheter in the venous system of the heart and measuring pressures and oxygen saturations in the superior vena cava, inferior vena cava, right atrium, right ventricle, and pulmonary artery, and in the wedge position. Individuals with a pulmonary vascular resistance (PVR) less than 7 wood units show regression of symptoms (including NYHA functional class). However, individuals with a PVR greater than 15 wood units have increased mortality associated with closure of the ASD.
If the pulmonary arterial pressure is more than two-thirds of the systemic systolic pressure, a net left-to-right shunt should occur at least 1.5:1 or evidence of reversibility of the shunt when given pulmonary artery vasodilators prior to surgery. (If Eisenmenger's physiology has set in, the right-to-left shunt must be shown to be reversible with pulmonary artery vasodilators prior to surgery.)
Surgical mortality due to closure of an ASD is lowest when the procedure is performed prior to the development of significant pulmonary hypertension. The lowest mortality rates are achieved in individuals with a pulmonary artery systolic pressure less than 40 mmHg. If Eisenmenger's syndrome has occurred, a significant risk of mortality exists regardless of the method of closure of the ASD. In individuals who have developed Eisenmenger's syndrome, the pressure in the right ventricle has raised high enough to reverse the shunt in the atria. If the ASD is then closed, the afterload that the right ventricle has to act against has suddenly increased. This may cause immediate right ventricular failure, since it may not be able to pump the blood against the pulmonary hypertension.
#### Surgical closure[edit]
Illustration depicting surgical patch closure of ASD
Surgical closure of an ASD involves opening up at least one atrium and closing the defect with a patch under direct visualization.
#### Catheter procedure[edit]
Illustration depicting surgical device closure of ASD
Percutaneous device closure involves the passage of a catheter into the heart through the femoral vein guided by fluoroscopy and echocardiography.[12] An example of a percutaneous device is a device which has discs that can expand to a variety of diameters at the end of the catheter. The catheter is placed in the right femoral vein and guided into the right atrium. The catheter is guided through the atrial septal wall and one disc (left atrial) is opened and pulled into place. Once this occurs, the other disc (right atrial) is opened in place and the device is inserted into the septal wall. This type of PFO closure is more effective than drug or other medical therapies for decreasing the risk of future thromboembolism.[12][48][49] The most common adverse effect of PFO device closure is new-onset atrial fibrillation. [50] Other complications, all rare, include device migration, erosion and embolization and device thrombosis or formation of an inflammatory mass with risk for recurrent ischemic stroke. [51][52]
Percutaneous closure of an ASD is currently only indicated for the closure of secundum ASDs with a sufficient rim of tissue around the septal defect so that the closure device does not impinge upon the superior vena cava, inferior vena cava, or the tricuspid or mitral valves. The Amplatzer Septal Occluder (ASO) is commonly used to close ASDs. The ASO consists of two self-expandable round discs connected to each other with a 4-mm waist, made up of 0.004– to 0.005-inch Nitinol wire mesh filled with Dacron fabric. Implantation of the device is relatively easy. The prevalence of residual defect is low. The disadvantages are a thick profile of the device and concern related to a large amount of nitinol (a nickel-titanium compound) in the device and consequent potential for nickel toxicity.
Percutaneous closure is the method of choice in most centres.[53] Studies evaluating percutaneous ASD closure among pediatric and adult population show that this is relatively safer procedure and has better outcomes with increasing hospital volume.[54][55]
## Epidemiology[edit]
As a group, atrial septal defects are detected in one child per 1500 live births. PFOs are quite common (appearing in 10–20% of adults), but when asymptomatic go undiagnosed. ASDs make up 30 to 40% of all congenital heart diseases that are seen in adults.[56]
The ostium secundum atrial septal defect accounts for 7% of all congenital heart lesions. This lesion shows a male:female ratio of 1:2.[57]
## References[edit]
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This article incorporates public domain material from the United States Department of Health and Human Services document: "National Heart, Lung, and Blood Institute".
### Additional references[edit]
* Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. pp. 270, 400–401. ISBN 978-1437727883.
## External links[edit]
* Atrial septal defect information for parents.
Classification
D
* ICD-10: Q21.1
* ICD-9-CM: 745.5-745.6
* OMIM: 108800
* MeSH: D006344
* DiseasesDB: 1089
External resources
* MedlinePlus: 000157
* eMedicine: med/3519 article/894813
* v
* t
* e
Congenital heart defects
Heart septal defect
Aortopulmonary septal defect
* Double outlet right ventricle
* Taussig–Bing syndrome
* Transposition of the great vessels
* dextro
* levo
* Persistent truncus arteriosus
* Aortopulmonary window
Atrial septal defect
* Sinus venosus atrial septal defect
* Lutembacher's syndrome
Ventricular septal defect
* Tetralogy of Fallot
Atrioventricular septal defect
* Ostium primum
Consequences
* Cardiac shunt
* Cyanotic heart disease
* Eisenmenger syndrome
Valvular heart disease
Right
* pulmonary valves
* stenosis
* insufficiency
* absence
* tricuspid valves
* stenosis
* atresia
* Ebstein's anomaly
Left
* aortic valves
* stenosis
* insufficiency
* bicuspid
* mitral valves
* stenosis
* regurgitation
Other
* Underdeveloped heart chambers
* right
* left
* Uhl anomaly
* Dextrocardia
* Levocardia
* Cor triatriatum
* Crisscross heart
* Brugada syndrome
* Coronary artery anomaly
* Anomalous aortic origin of a coronary artery
* Ventricular inversion
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Atrial septal defect
|
c0018817
| 7,769 |
wikipedia
|
https://en.wikipedia.org/wiki/Atrial_septal_defect
| 2021-01-18T18:52:26 |
{"mesh": ["D006344"], "umls": ["C0018817"], "icd-9": ["745.5", "745.6"], "orphanet": ["1478"], "wikidata": ["Q757749"]}
|
## Description
Perifolliculitis capitis abscedens et suffodiens is a chronic inflammatory disease of the scalp characterized by the presence of large and small nodules that suppurate and intercommunicate by sinus formation. It may be more frequent in black males than in others (summary by McMullan and Zeligman, 1956).
Clinical Features
Bjellerup and Wallengren (1990) described typical perifolliculitis capitis abscedens et suffodiens in 2 brothers. One, a 20-year-old man, had a 3-month history of tender, suppurating nodules on the scalp and developed small areas of alopecia. The 33-year-old brother had itching of the scalp and hair loss. In both patients, the only microorganism isolated was S. epidermidis. Treatment with oral isotretinoin was successful in both.
INHERITANCE \- Isolated cases SKIN, NAILS, & HAIR Skin \- Suppurative scalp nodules \- Scalp sinus formation \- Small areas of alopecia \- Scalp itching \- S. epidermidis only microorganism isolated MISCELLANEOUS \- Successful treatment with oral isotretinoin ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
PERIFOLLICULITIS CAPITIS ABSCEDENS ET SUFFODIENS, FAMILIAL
|
c0263506
| 7,770 |
omim
|
https://www.omim.org/entry/260910
| 2019-09-22T16:23:35 |
{"mesh": ["C562486"], "omim": ["260910"], "icd-10": ["L66.3"], "orphanet": ["345"], "synonyms": ["Alternative titles", "DISSECTING CELLULITIS OF THE SCALP"]}
|
Ectrodactyly–ectodermal dysplasia–cleft syndrome
Other namesEEC syndrome
Ectrodactyly–ectodermal dysplasia–cleft syndrome is autosomal dominant
SpecialtyMedical genetics
Ectrodactyly–ectodermal dysplasia–cleft syndrome, or EEC, and also referred to as EEC syndrome[1] and split hand–split foot–ectodermal dysplasia–cleft syndrome[2]:520 is a rare form of ectodermal dysplasia, an autosomal dominant disorder inherited as a genetic trait.[3]:571 EEC is characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefts.[4] Other features noted in association with EEC include vesicoureteral reflux, recurrent urinary tract infections,[5] obstruction of the nasolacrimal duct,[6] decreased pigmentation of the hair and skin, missing or abnormal teeth, enamel hypoplasia, absent punctae in the lower eyelids, photophobia, occasional cognitive impairment and kidney anomalies, and conductive hearing loss.[7][8]
## Contents
* 1 Presentation
* 1.1 Ectrodactyly
* 1.2 Ectodermal dysplasia
* 1.3 Facial clefting
* 1.4 Speech deficits
* 2 Embryology
* 3 Management
* 4 Research
* 4.1 Genetics
* 4.1.1 Mutations
* 4.1.2 Genetic expression
* 4.1.3 In vitro model of EEC
* 5 Notable people
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Presentation[edit]
### Ectrodactyly[edit]
Ectrodactyly involves the deficiency or absence of one or more central digits of the hand or foot and is also known as split hand–split foot malformation (SHFM).[9] The hands and feet of people with ectrodactyly are often described as "claw-like" and may include only the thumb and one finger (usually either the little finger, ring finger, or a syndactyly of the two) with similar abnormalities of the feet.[6]
Ectodermal dysplasia describes abnormalities of structures derived from the embryonic ectoderm.[6] These abnormalities affect both the superficial ectodermal layer, as well as the mesectodermal layer constituted by the neural crest.[10]
### Ectodermal dysplasia[edit]
Ectodermal dysplasia is characterized by absent sweat glands resulting in dry (hypohydrotic), often scale-like skin, sparse and usually coarse scalp hair that is often blonde, sparse eyebrows and eyelashes, and small brittle nails.[6] In addition, abnormalities of ectodermal derivatives, neuroectodermal derivatives, and mesectodermal derivatives are often found. The ectodermal derivative abnormalities can affect the epidermis including mammary, pituitary and sweat glands, as well as hairs, dental enamel, nails, lens, and the internal ear. Neuroectodermal derivatives that can be affected include sensory placodes, cutaneous pigmental cells, and hair buds. Mesectodermal derivatives affected can include the dermis, hypodermis, dentin, head muscles and conjunctival cells, cervicofacial vascular endothelial cells, and part of the maxillofacial skeleton.[10]
The hypohydrotic symptoms of ectodermal dysplasia described above are evidenced not only in the skin of affected individuals, but also in their phonation and voice production.[8] Because the vocal folds may not be as hydrated as is necessary during the adduction phase of vocal fold vibration (due to lack of lubrication), a complete seal may not be accomplished between the folds and mucosal wave movement may be disrupted.[11] This results in air escapement between the folds and the production of breathy voice, which often accompanies the skin abnormalities of ectodermal dysplasia.[6]
### Facial clefting[edit]
There is much discrepancy in the literature regarding the exact nature of the facial clefting involved in EEC. Some authors claim that the clefting involved in EEC is always cleft lip +/- palate and use this marker as a means of distinguishing EEC from other syndromes, such as AEC syndrome (ankyloblepharon, ectodermal dysplasia, and clefting) in which other types of clefting are found.[7] Other authors include cleft palate only (CPO) in conjunction with ectrodactyly and ectodermal dysplasia as sufficient for a diagnosis of EEC.[8][12][13]
### Speech deficits[edit]
The speech deficits associated with EEC syndrome are numerous. The clefting often causes hypernasal speech and velopharyngeal incompetence. Because of this, compensatory articulation strategies including retruded articulation and glottal compensation are often incorporated into the patient's speech. Articulation is further impaired by the numerous dental anomalies, including missing or malformed teeth found in EEC syndrome.[8]
Language deficits are also associated with EEC syndrome and are attributed to two factors. Conductive hearing loss due to ossicular anomalies is often encountered in patients with EEC syndrome, which can have significant impacts on language acquisition. Also, the impaired cognitive functioning that sometimes accompanies EEC can inhibit language acquisition.[8]
## Embryology[edit]
The ectodermal dysplasia associated with EEC syndrome arises from abnormalities in the embryonic ectoderm, as described above.[6] Very early in embryonic development, the embryonic stem cells differentiate into three types of cells: the ectoderm, mesoderm, and endoderm. It is from these three types of cells that all body organs originate. In general terms, ectodermal cells generate the skin, spinal cord, and teeth (as well as the numerous derivatives mentioned above). Mesodermal cells generate blood vessels, muscle and bone, and endodermal cells generate the lungs, the digestive system and the urinary system.[14]
There are two layers of mesoderm; intraembryonic and extraembryonic. As the intraembryonic layer grows laterally, it becomes continuous with the extraembryonic layer, forming the chorion (contributing to the blood supply). At the same time during embryonic development, the ectoderm begins to thicken and fold upward, forming the neural folds, which eventually meet to form the neural tube and neural crest.[15] Because these two events occur at roughly the same time in embryological development, abnormalities found in this syndrome can involve not only the ectodermal cells, but also disruption to development in the mesectodermal layer constituted by the neural crest.[4][10]
"What these structures have in common is that their development and morphogenesis depends on the signaling between specialized ectodermal cells and the underlying mesoderm. Epithelial-mesenchymal interactions between the apical ectodermal ridge (AER) and the underlying mesenchyme, denoted the progress zone, are required for normal morphogenesis of the limb.[4]
## Management[edit]
This section is empty. You can help by adding to it. (March 2017)
## Research[edit]
Current research regarding EEC syndrome is focused on the genetic components contributing to the presented traits found in patients with EEC. A normal human karyotype includes 22 pairs of autosomal or non-sex chromosomes and one pair of sex chromosomes, constituting a total of 46 chromosomes. During reproduction, each parent contributes 23 chromosomes; 22 autosomal chromosomes and one sex chromosome.[16] As stated above, EEC syndrome is an autosomal dominant disorder.[4] This means that there is an abnormal gene on one of the autosomal (non-sex) chromosomes from either parent. Because the gene is dominant, only one parent must contribute the abnormal gene for the child to inherit the disease and the contributing parent will usually have the disease, due to the expression of the dominant gene in the parent.[16] Some characteristics of autosomal dominant inheritance patterns include a vertical transmission pattern, meaning that the disease phenotype is seen in generation after generation. Also, the recurrence risk is 50% and there are an equal number of affected males and females. Though we can calculate the chance of inheritance of the gene, the degree of expression cannot be calculated.[8]
### Genetics[edit]
Genetics research relating to EEC has made great strides in recent years, but many findings are currently being debated in the literature. Chromosome 19, within the region of D19S894 and D19S416 has been postulated as the locus for the abnormalities found in EEC syndrome. This is supported by reports (though conflicting) regarding an association of cleft lip +/- palate on locus 19q, which suggests that EEC could be an allelic variant.[13]
More recently, the p63 gene has been targeted in numerous studies.[4][5][7][12] The p63 gene is a homologue of the tumor suppressor gene p53,[12] though this is not indicative that patients with EEC are more likely to develop tumors. p63 mutations have been implicated in other human malformation conditions as well, including AEC or Hay–Wells syndrome, limb–mammary syndrome, ADULT syndrome, and non-syndromic split hand–split foot malformation. When comparing the data for these syndromes, each syndrome has a distinct pattern and type of mutations, with extensive genotype–phenotype correlations. Brunner and colleagues found that most of the p63 mutations associated with EEC "involve amino acid substitutions in the DNA binding domain common to all known p63 isoforms". The findings of their study propose that the most frequently mutated arginine codons associated with EEC are 204, 227, 279, 280, and 304, with these five amino acid mutations accounting for 75% of all reported cases of EEC syndrome.[7] Other studies have had similar findings. One study found three of the five listed amino acid mutations in their subjects and noted that when 200 control chromosomes were tested, these three mutant alleles were not present.[12]
#### Mutations[edit]
The mutations found in EEC are missense mutations,[7] meaning that there is a single amino acid change in the protein, as opposed to premature termination of protein synthesis, known as a nonsense mutation.[4] The frameshift mutation introduces a premature stop codon that affected the α isotope, but does not affect the β and γ isotopes of p63. From this, it can be concluded that mutant p63α isotopes seem to play a major role in the pathogenesis of EEC syndrome.[4] It seems that p63α is the predominant p63 isotope in epithelial basal cell layers,[12] which are the cell type often associated with the anomalies found in patients with EEC syndrome.[citation needed]
#### Genetic expression[edit]
EEC can be both familial and sporadic, both cases relating back to abnormalities of the p63 gene. This means that in some cases, EEC expresses de novo in a child of unaffected parents (sporadic) due to spontaneous mutation, in addition to the existing autosomal dominant inherited form. There seems to be significant interfamilial and intrafamilial variability in expressivity, more noticeably between rather than within families. Because of this variability, it is possible that there is more than one genetic locus involved in the actual manifestation of the syndrome in any given person.[12] Other notably proposed sections of the involved chromosome include 3q27,[4][7][12] and more highly disputed areas, including 7q11.2–q21.3[12][13]
A study supports the hypothesis of the p63 gene as the locus for the mutations associated with EEC syndrome. The study is known as the p63 knockout mice study, in which the phenotypes of p63-deficient mice are described. The description of the mice is as follows:[citation needed]
> P63-deficient mice lack all squamous epithelia and their derivatives, including hair, whiskers, teeth, as well as the mammary, lacrimal, and salivary glands. Particularly striking are severe limb truncations with forelimbs showing a complete absence of the phalanges and carpals, and variable defects of ulnae and radiae and hindlimbs that are lacking altogether…The p63 mutations act in a dominant fashion in humans, giving rise to a phenotype that resembles that of p63 knockout mice.[4]
This striking data offers convincing support for the p63 gene hypothesis. This study is also cited in the demonstration that the growth and patterning of the underlying mesenchyme is highly dependent on the apical ectodermal ridge of the limbs, as well as the maxillary and mandibular branchial ectoderm that are so prominently disturbed in these mice.[12] All of these findings are consistent with the clinical presentation of EEC in humans and may explain the association of limb malformation and clefting that are found in this syndrome.[citation needed]
#### In vitro model of EEC[edit]
Modeling EEC syndrome in vitro has been achieved by reprogramming EEC fibroblasts carrying mutations R304W and R204W into induced pluripotent stem cell (iPSC) lines. EEC-iPSC recapitulated defective epidermal and corneal fates. This model further identified PRIMA-1MET, a small compound that was identified as a compound targeting and reactivating p53 mutants based on a cell-based screening for rescuing the apoptotic activity of p53, as efficient to rescue R304W mutation defect.[17] Of interest, similar effect had been observed on keratinocytes derived from the same patients.[18] PRIMA-1MET could become an effective therapeutic tool for EEC patients.[19]
Further genetic research is necessary to identify and rule out other possible loci contributing to EEC syndrome, though it seems certain that disruption of the p63 gene is involved to some extent. In addition, genetic research with an emphasis on genetic syndrome differentiation should prove to be very useful in distinguishing between syndromes that present with very similar clinical findings. There is much debate in current literature regarding clinical markers for syndromic diagnoses. Genetic findings could have great implications in clinical diagnosis and treatment of not only EEC, but also many other related syndromes.[citation needed]
## Notable people[edit]
These people are noted as having this condition.
* Francesca Jones \- tennis player, UK
## See also[edit]
* Limb–mammary syndrome
* List of cutaneous conditions
* Cleft hand
* List of dental abnormalities associated with cutaneous conditions
## References[edit]
1. ^ Buss PW, Hughes HE, Clarke A (September 1995). "Twenty-four cases of the EEC syndrome: clinical presentation and management". Journal of Medical Genetics. 32 (9): 716–723. doi:10.1136/jmg.32.9.716. PMC 1051673. PMID 8544192.
2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
3. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
4. ^ a b c d e f g h i Celli J, Duijf P, Hamel BC, et al. (1999). "Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome" (PDF). Cell. 99 (2): 143–153. doi:10.1016/S0092-8674(00)81646-3. PMID 10535733. S2CID 18193864.
5. ^ a b Ramirez D, Lammer EJ (2004). "Lacrimoauriculodentodigital syndrome with cleft lip/palate and renal manifestations". Cleft Palate-Craniofacial Journal. 41 (5): 501–506. doi:10.1597/03-080.1. PMID 15352854. S2CID 20874635.
6. ^ a b c d e f Peterson-Falzone, Sally J.; Mary A. Hardin-Jones; Michael P. Karnell; Betty Jane McWilliams (2001). Cleft Palate Speech. Mosby. ISBN 978-0-8151-3153-3.
7. ^ a b c d e f Brunner HG, Hamel BC, Van Bokhoven H (2002). "The p63 gene in EEC and other syndromes". Journal of Medical Genetics. 39 (6): 377–381. doi:10.1136/jmg.39.6.377. PMC 1735150. PMID 12070241.
8. ^ a b c d e f Shprintzen, Robert J. (1997). Genetics, Syndromes, and Communication Disorders. Singular Pub. Group. ISBN 978-1-56593-620-1.
9. ^ Moerman P, Fryns JP (1996). "Ectodermal dysplasia, Rapp–Hodgkin type in a mother and severe ectrodactyly–ectodermal dysplasia–clefting syndrome (EEC) in her child". American Journal of Medical Genetics. 63 (3): 479–481. doi:10.1002/(SICI)1096-8628(19960614)63:3<479::AID-AJMG12>3.0.CO;2-J. PMID 8737656.
10. ^ a b c Ruhin B, Martinot V, Lafforgue P, Catteau B, Manouvrier-Hanu S, Ferri J (2001). "Pure ectodermal dysplasia: retrospective study of 16 cases and literature review". Cleft Palate-Craniofacial Journal. 38 (5): 504–518. doi:10.1597/1545-1569(2001)038<0504:PEDRSO>2.0.CO;2. PMID 11522173.
11. ^ Peterson-Falzone SJ, Caldarelli DD, Landahl KL (1981). "Abnormal laryngeal vocal quality in ectodermal dysplasia". Archives of Otolaryngology. 107 (5): 300–304. doi:10.1001/archotol.1981.00790410038010. PMID 7224950.
12. ^ a b c d e f g h i Barrow LL, van Bokhoven H, Daack-Hirsch S, et al. (2002). "Analysis of the p63 gene in classical EEC syndrome, related syndromes, and non-syndromic orofacial clefts". Journal of Medical Genetics. 39 (8): 559–566. doi:10.1136/jmg.39.8.559. PMC 1735218. PMID 12161593.
13. ^ a b c O'Quinn JR, Hennekam RC, Jorde LB, Bamshad M (1998). "Syndromic ectrodactyly with severe limb, ectodermal, urogenital, and palatal defects maps to chromosome 19". American Journal of Human Genetics. 62 (1): 130–135. doi:10.1086/301687. PMC 1376811. PMID 9443880.
14. ^ Batshaw, Mark L. (2002). Children with Disabilities. Baltimore: Paul H. Brookes. ISBN 978-1-55766-581-2.
15. ^ Zemlin, Willard R. (1981). Speech and Hearing Science: Anatomy and Physiology. Prentice-Hall.
16. ^ a b Hall, Judith G. (August 2007). "Chromosomes and Genes". Merck. Retrieved 2008-10-01.
17. ^ Shalom Feuerstein R.; et al. (2012). "Impaired epithelial differentiation of induced pluripotent stem cells from EEC patients is rescued by APR-246/PRIMA-1MET". Proceedings of the National Academy of Sciences, USA. 110 (6): 2152–2156. doi:10.1073/pnas.1201753109. PMC 3568301. PMID 23355677.
18. ^ Shen J, van den Bogaard EH, Kouwenhoven EN, Bykov VJ, Rinne T, Zhang Q, Tjabringa GS, Gilissen C, van Heeringen SJ, Schalkwijk J, van Bokhoven H, Wiman KG, Zhou H (2013). "APR-246/PRIMA-1(MET) rescues epidermal differentiation in skin keratinocytes derived from EEC syndrome patients with p63 mutations". Proceedings of the National Academy of Sciences, USA. 110 (6): 2157–2162. Bibcode:2013PNAS..110.2157S. doi:10.1073/pnas.1201993110. PMC 3568378. PMID 23355676.
19. ^ Zhou H, Aberdam D (2013). "A step closer toward therapies for p63-related disorders". Rare Diseases. 1: e24247. doi:10.4161/rdis.24247. PMC 3932939. PMID 25002990.
## Further reading[edit]
* GeneReviews/NCBI/NIH/UW entry on Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Syndrome or AEC Syndrome, Hay-Wells Syndrome. Includes: Rapp-Hodgkin Syndrome
## External links[edit]
Classification
D
* OMIM: 129900
* MeSH: C536189
* DiseasesDB: 34402
* OMIM entries on AEC
* 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ectrodactyly–ectodermal dysplasia–cleft syndrome
|
c0406704
| 7,771 |
wikipedia
|
https://en.wikipedia.org/wiki/Ectrodactyly%E2%80%93ectodermal_dysplasia%E2%80%93cleft_syndrome
| 2021-01-18T18:57:41 |
{"gard": ["2076"], "mesh": ["C536189"], "umls": ["C0406704"], "orphanet": ["1896"], "wikidata": ["Q5334319"]}
|
A rare, syndromic, hereditary optic neuropathy disorder characterized by early-onset, severe, progressive visual impairment, optic disc pallor and central scotoma, variably associated with dyschromatopsia, auditory neuropathy (e.g. mild progressive sensorineural hearing loss), sensorimotor axonal neuropathy and, occasionally, moderate hypertrophic cardiomyopathy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Autosomal recessive optic atrophy, OPA7 type
|
c2751812
| 7,772 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=227976
| 2021-01-23T16:59:47 |
{"mesh": ["C567833"], "omim": ["612989"], "icd-10": ["H47.2"]}
|
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (September 2015)
Retrocuspid papilla (RCP) is a small elevated nodules mostly behind the lower canine teeth in humans(Fig.1,2).[1] It is sometimes associated with reactive arthritis.[2]
## Contents
* 1 Epidemiology
* 2 Clinical appearance
* 3 Histology
* 4 References
## Epidemiology[edit]
The RCP are first reported in 1947 and 1965.[3][4] In a Swedish population it was first reported 1994. Among 1150 consecutively examined patients aged 20 –75 years, 10 showed RCP. Among 2000 biopsy cases from 1989 - 1992 in Department of Oral Pathology Lund University, 15 biopsies met the criteria of RCP. [5]
## Clinical appearance[edit]
The lesions are bilaterally situated in the attached gingiva or close to the border of the mucosa lingual to the two mandibular canines (Fig.1).[6]
Fig.1.Retrucuspid papillae lingual to both lower canines.
However, they could in a few individuals also be seen simultaneously in the molar region and on the lingual side (Fig.2).[7] They were 2–3 mm wide and high and covered with normal mucosa. Their tips were erected or could be folded down, mimicking the entrance of a periodontal abscess, but no duct was present.
Fig.2. Retrocuspid papilla in molar region labial gingiva mimicking a periodontal abscess
Radiographs showed no bone destruction and the depths of the periodontal pockets could not explain the presence of the lesions. They were nonsymptomatic and were not noticed by the patients.[8]
## Histology[edit]
Fig.3. Hematoxylin Eosin staining of the attached gingiva with a Retrocuspid papilla.
Immunohistochemical staining with FXIIIa [9] antibody disclosed a population of reactive spindle- or stellate-shaped cells[10] in 11 of 15 cases, located in connective tissue papillae and in a few cases also distributed throughout the lesion. The FXIIIa-stained cells appeared together with the frequently observed stellate, "young" occasionally multinucleated fibroblastic cells observed in more than 50% of patients aged 10–69 years. It is likely that FXIIIA-expressing "mucosal dendrocytes" are pathologically involved in some way.[11][12][13]
## References[edit]
1. ^ Rajendran A; Sundaram S (10 February 2014). Shafer's Textbook of Oral Pathology (7th ed.). Elsevier Health Sciences APAC. p. 27. ISBN 978-81-312-3800-4.
2. ^ Ghom AG; Ghom SA (30 September 2014). Textbook of Oral Medicine. JP Medical Ltd. p. 25. ISBN 978-93-5152-303-1.
3. ^ Hirschfeld I: The retrocuspid papilla. Am J Orthod 1947;33:447-57.
4. ^ Everett FG, Hall WB, Bennet JS: Retrocuspid papillae. Periodontics 1965;3:81-3.
5. ^ Hedin CA, Gerner L, Larsson Å: The retrocuspid papilla and factor XIIIa: an epidemiologic and histomorphologic study. Scand J Dent 1994; 102:290-4.
6. ^ Hedin CA, Gerner L, Larsson Å: The retrocuspid papilla and factor XIIIa: an epidemiologic and histomorphologic study. Scand J Dent 1994; 102:290-4.
7. ^ Hedin CA, Gerner L, Larsson Å: The retrocuspid papilla and factor XIIIa: an epidemiologic and histomorphologic study. Scand J Dent 1994; 102:290-4.
8. ^ Hedin CA, Gerner L, Larsson Å: The retrocuspid papilla and factor XIIIa: an epidemiologic and histomorphologic study. Scand J Dent 1994; 102:290-4.
9. ^ Nemeth AJ, Penneys NS: Factor XIIIa is expressed by fibroblasts in fibrovascular tumors. J Cutan Pathol 1989;16:266-71.
10. ^ Regezi JA, Courtney RM, Kerr DA: Fibous lesions of the skin and mucous membranes which contain stellkate and multinucleated cells. Oral Surg Oral Med Oral Pathol 1975;39:605-14.
11. ^ Hedin CA, Gerner L, Larsson Å: The retrocuspid papilla and factor XIIIa: an epidemiologic and histomorphologic study. Scand J Dent 1994; 102:290-4.
12. ^ Nickoloff BJ, Griffiths CEM: The spindle-shaped cells in cutaneous Kaposi´s sarcoma. Am J Pathol 1989;135:793-800
13. ^ Cerio R, Spaull J, Oliver GF, Wilson Jones E: A study of factor XIIIa and MAC 387 immunolabeling in normal and pathological skin. Am J Dermatopathol 1990;12:221-33.
* v
* t
* e
Oral and maxillofacial pathology
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* Agnathia
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* Odontogenic: periapical
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* Benign: Basal cell adenoma
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* Malignant: Acinic cell carcinoma
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* Orofacial granulomatosis
* Perioral dermatitis
* Pyostomatitis vegetans
Other
* Eagle syndrome
* Hemifacial hypertrophy
* Facial hemiatrophy
* Oral manifestations of systemic disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Retrocuspid papilla
|
None
| 7,773 |
wikipedia
|
https://en.wikipedia.org/wiki/Retrocuspid_papilla
| 2021-01-18T18:53:00 |
{"wikidata": ["Q25111468"]}
|
Congenitally uncorrected transposition of the great arteries (congenitally uncorrected TGA), also referred to as complete transposition, is a congenital cardiac malformation characterized by atrioventricular concordance and ventriculoarterial (VA) discordance.
## Epidemiology
The incidence is estimated at 1 in 3,500-5,000 live births, with a male-to-female ratio of 1.5 to 3.2:1.
## Clinical description
In 50% of cases, the VA discordance is an isolated finding. In 10% of cases, TGA is associated with noncardiac malformations. The association with other cardiac malformations such as ventricular septal defect (VSD) and left ventricular outflow tract obstruction is frequent and dictates the timing and clinical presentation, which consists of cyanosis with or without congestive heart failure. The onset and severity depend on anatomical and functional variants that influence the degree of mixing between the two circulatory systems. If no obstructive lesions are present and there is a large VSD, cyanosis may go undetected and only be perceived during episodes of crying or agitation. In these cases, signs of congestive heart failure prevail.
## Etiology
The exact etiology remains unknown. Some associated risk factors (gestational diabetes mellitus, maternal exposure to rodenticides and herbicides, and maternal use of antiepileptic drugs) have been proposed. Mutations in the growth differentiation factor-1 gene (GDF1), the mediator complex subunit 13-like gene (MED13L) and the gene encoding the cryptic protein (CFC1) have been shown to be implicated in discordant VA connections, but they account for only a small minority of congenitally uncorrected TGA cases.
## Diagnostic methods
The diagnosis is confirmed by echocardiography, which also provides information about the morphological details required for future surgical management.
## Differential diagnosis
The differential diagnosis should include other causes of central neonatal cyanosis.
## Antenatal diagnosis
Prenatal diagnosis by fetal echocardiography is feasible and useful as it may improve early neonatal management and reduce morbidity and mortality.
## Management and treatment
Palliative treatment with prostaglandin E1 and balloon atrial septostomy are usually required soon after birth. Surgical correction is performed at a later stage. Usually, the Jatene arterial switch operation is the procedure of choice. Whenever this operation is not feasible, an adequate alternative surgical approach should be implemented.
## Prognosis
With the advent of newer and improved surgical techniques and improved post-operative intensive care, the long-term survival is approximately 90% at 15 years of age. However, exercise performance, cognitive function and quality of life may be impaired.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Congenitally uncorrected transposition of the great arteries
|
c1837341
| 7,774 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=860
| 2021-01-23T18:41:37 |
{"mesh": ["C563853"], "omim": ["608808", "613854"], "icd-10": ["Q20.3"], "synonyms": ["Congenitally uncorrected transposition of the great vessels", "D-transposition of the great arteries", "Dextro-transposition of the great arteries", "Isolated ventriculoarterial discordance", "Ventriculoarterial discordance with atrioventricular concordance"]}
|
FBXL4-related encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome is a severe condition that begins in infancy and affects multiple body systems. It is primarily associated with brain dysfunction combined with muscle weakness (encephalomyopathy).
Infants with FBXL4-related encephalomyopathic mtDNA depletion syndrome have weak muscle tone (hypotonia) and a failure to grow or gain weight at the expected rate (failure to thrive). Children with FBXL4-related encephalomyopathic mtDNA depletion syndrome have delayed development of mental and motor skills and severely impaired speech development. Many affected individuals have seizures, movement abnormalities, and an unusually small head size (microcephaly) with a loss of nerve cells in the brain (cerebral atrophy).
All individuals with FBXL4-related encephalomyopathic mtDNA depletion syndrome have a buildup of a chemical called lactic acid in the body (lactic acidosis), and about half of individuals have an accumulation of ammonia in the blood. Buildup of these substances can be life-threatening. Many affected individuals also have heart abnormalities, such as congenital heart defects or heart rhythm abnormalities (arrhythmias). In addition, individuals with this condition can have vision problems, hearing loss, liver abnormalities (hepatopathy), and immune deficiency due to a decrease in white blood cells. Many children with FBXL4-related encephalomyopathic mtDNA depletion syndrome have distinctive facial features that can include thick eyebrows; outside corners of the eyes that point upward (upslanting palpebral fissures); a broad nasal bridge and tip; and a long, smooth space between the upper lip and nose (philtrum).
Because the encephalomyopathy and other signs and symptoms are so severe, people with FBXL4-related encephalomyopathic mtDNA depletion syndrome usually live only into early childhood.
## Frequency
FBXL4-related encephalomyopathic mtDNA depletion syndrome is a rare condition; the exact prevalence is unknown. At least 50 affected individuals have been described in the medical literature.
## Causes
As its name suggests, FBXL4-related encephalomyopathic mtDNA depletion syndrome is caused by mutations in the FBXL4 gene. This gene provides instructions for producing a protein that is found within cell structures called mitochondria. Mitochondria are involved in a wide variety of cellular activities, including energy production, chemical signaling, and regulation of cell growth and division (proliferation) and cell death (apoptosis). Mitochondria contain their own DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. The FBXL4 protein is likely involved in the maintenance of mtDNA. Having an adequate amount of mtDNA is essential for normal energy production within cells.
FBXL4 gene mutations that cause FBXL4-related encephalomyopathic mtDNA depletion syndrome lead to a loss of FBXL4 protein function. A lack of this protein's activity leads to problems with the maintenance of mtDNA, which can reduce the amount of mtDNA in cells (known as mtDNA depletion). Depletion of mtDNA impairs mitochondrial function in many of the body's cells and tissues. Reduced mitochondrial function eventually leads to cell dysfunction, most noticeably affecting the brain, muscles, and other tissues that have high-energy requirements. This cell dysfunction leads to encephalomyopathy and other features of FBXL4-related encephalomyopathic mtDNA depletion syndrome.
### Learn more about the gene associated with FBXL4-related encephalomyopathic mitochondrial DNA depletion syndrome
* FBXL4
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
FBXL4-related encephalomyopathic mitochondrial DNA depletion syndrome
|
c3809592
| 7,775 |
medlineplus
|
https://medlineplus.gov/genetics/condition/fbxl4-related-encephalomyopathic-mitochondrial-dna-depletion-syndrome/
| 2021-01-27T08:24:56 |
{"omim": ["615471"], "synonyms": []}
|
X-linked creatine deficiency is an inherited disorder that primarily affects the brain. People with this disorder have intellectual disability, which can range from mild to severe, and delayed speech development. Some affected individuals develop behavioral disorders such as attention-deficit/hyperactivity disorder (ADHD) or autistic behaviors that affect communication and social interaction. They may also experience seizures. Children with X-linked creatine deficiency may experience slow growth and exhibit delayed development of motor skills such as sitting and walking. Affected individuals tend to tire easily.
A small number of people with X-linked creatine deficiency have additional signs and symptoms including abnormal heart rhythms, an unusually small head (microcephaly), or distinctive facial features such as a broad forehead and a flat or sunken appearance of the middle of the face (midface hypoplasia).
## Frequency
The prevalence of X-linked creatine deficiency is unknown. More than 150 affected individuals have been identified. The disorder has been estimated to account for between 1 and 2 percent of males with intellectual disability.
## Causes
Mutations in the SLC6A8 gene cause X-linked creatine deficiency. The SLC6A8 gene provides instructions for making a protein that transports the compound creatine into cells. Creatine is needed for the body to store and use energy properly.
SLC6A8 gene mutations impair the ability of the transporter protein to bring creatine into cells, resulting in a creatine shortage (deficiency). The effects of creatine deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.
### Learn more about the gene associated with X-linked creatine deficiency
* SLC6A8
## Inheritance Pattern
This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell may or may not cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In most cases of X-linked inheritance, males experience more severe symptoms of the disorder than females. About half of females with one mutated copy of the SLC6A8 gene in each cell have intellectual disability, learning difficulties, or behavioral problems. Other females with one mutated copy of the SLC6A8 gene in each cell have no noticeable neurological problems.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
X-linked creatine deficiency
|
c1845862
| 7,776 |
medlineplus
|
https://medlineplus.gov/genetics/condition/x-linked-creatine-deficiency/
| 2021-01-27T08:24:35 |
{"gard": ["1608"], "mesh": ["C535598"], "omim": ["300352"], "synonyms": []}
|
With an estimated 120,000 people living with HIV/AIDS, the HIV/AIDS epidemic in Colombia is consistent with the epidemic in much of Latin America as a whole, both in terms of prevalence of infection and characteristics of transmission and affected populations.[1] Colombia has a relatively low rate of HIV infection at 0.4%, though certain groups, particularly men who have sex with men, bear the burden of significantly higher rates of infection than the general population.[2] Colombia's health care system and conception of a "right to health," created by the T-760 decision of 2008, have revolutionized access to HIV treatment. Despite this, the quality of health insurance and treatment for HIV has often been disputed.[3]
## Contents
* 1 Prevalence
* 2 Testing and Treatment
* 3 Government Policies
* 3.1 Needle and Syringe Program
* 3.2 Opioid substitution therapy
* 4 AIDS Activism in Colombia
* 5 Affected Populations
* 5.1 HIV in MSM (Men who have sex with men)
* 5.2 HIV in Intravenous Drug Users
* 5.3 HIV in Sex Workers
* 6 References
* 7 External links
## Prevalence[edit]
Approximately 120,000 people in Colombia are living with HIV, according to UNAIDS.[4] Colombia's rate of HIV prevalence, which is 0.4%, is on par with HIV prevalence in other Latin American and Caribbean nations.[5] New HIV infections in Colombia peaked between the years of 1993–1997, and have since dropped off. In recent years, the estimated number of new HIV infections in the country has dropped gradually, with an estimated 5,600 new infections in 2016.[6]
HIV is more common among men than women in Colombia. Men have an HIV prevalence rate of about 0.6%, whereas women have a prevalence rate of about 0.2%.[7]
## Testing and Treatment[edit]
A 2012 study that surveyed the records of almost 30,000 Colombians between the ages of 18 and 69 found that 19.7% had been tested for HIV. People living in rural areas, people with less education, men, and people over the age of 65 were less likely to have been tested than the general population. On the other hand, women, urbanites, people with more education, and young people were more likely to have been tested than the general population. Consistent with factors throughout the region and the world, common reasons given for not seeking HIV testing included a low-risk perception of becoming infected, feeling healthy, stigma associated with HIV, and feeling unprepared, both financially and emotionally, for the possibility of an HIV diagnosis.[8] In Colombia, 36% of people living with AIDS have virally suppressed loads.[9]
## Government Policies[edit]
Two landmark decisions, one in 1993 and one in 2008, significantly altered access to HIV treatment in Colombia. At the beginning of the HIV epidemic, about 20% of Colombia's population was on private healthcare, with the rest relying on public health care.[10]
In 1993, the passage of Law 100 created a system of privatized but regulated universal health care — under the new system, private insurance companies competed for clients with government oversight. Insurance companies were mandated only to cover treatment listed under Colombia's obligatory health plan. There were two types of insurance schemes under the new system — one to which employees and employers contributed, and one which was subsidized by the government. Although the contributory scheme offered more comprehensive health care overall, the antiretroviral medication used to treat HIV (AZT) was not covered under either version of the government's obligatory health plan. Individuals seeking AZT were forced to file tutelas, or pleas, in order to access it.[11] One activist action, called Operation Wasp, involved filing seven tutelas in seven different courts in Bogotá so as to occupy the court dockets for ten days. All of the judges targeted by Operation Wasp ruled in favor of the tutelas.[12]
In 2008, with annual tutelas totaling around 100,000 the Constitutional Court of Colombia reached the T-760 decision, which made the obligatory government health plan more generous and provided for measures to be taken to decrease the incidence of arbitrary denial of health coverage.[13] The T-760 decision fundamentally reframed how health care was viewed in Colombia, and is commonly viewed as having created a "right to health" conception of health care in which health care is viewed as a human right.[14]
Today, almost 100% of Colombians are insured. However, the quality of that insurance has often been disputed, with reports of individuals being denied healthcare due to administrative or bureaucratic reasons.[15]
### Needle and Syringe Program[edit]
In 2014, the Colombian Ministry of Health launched needle and syringe programs (NSPs) in five Colombian cities: Medellín, Bogotá, Cali, Cucuta, and Armenia. At its launch, the government allotted 100,000 syringes for distribution to people who inject drugs, in most cases heroin.[16]
### Opioid substitution therapy[edit]
Colombia is one of only five countries in Latin America and the Caribbean to offer opioid substitution therapy, a drug therapy that involves replacing a drug such as heroin with another, less harmful opioid. In theory, OST would reduce rates of infection among intravenous drug users by decreasing the use of injection drugs. OST services are available in seven Colombian cities, but it is unknown how widely used these services are.[17]
## AIDS Activism in Colombia[edit]
Influenced by the emergence of similar groups in the U.S, early AIDS activism in Colombia initially consisted of support groups for people with AIDS. These groups, such as Seguro Social, El Club de la Alegría, and El Cartel de la Vida, focused initially on issues such as self-care and support for people with AIDS. Later, the groups would shift their focus towards access to treatment for HIV and AIDS.[18] Consistent with AIDS activism in other countries, early AIDS activism in Colombia was closely linked to LGBTQ organizations and the LGBTQ community as a whole.[19]
## Affected Populations[edit]
### HIV in MSM (Men who have sex with men)[edit]
Men who have sex with men in Colombia experience significantly higher rates of HIV infection than does the general population. The prevalence of HIV among MSM in Colombia ranges from 6% to 24%,[20] and is highest in Cali, Bogotá, and Barranquilla.[21] Bogotá's rate of HIV among MSM is 15%, and the rate of HIV among MSM in Colombia as a whole is 17%.[22]
In a survey of seven Colombian cities, between 14% and 31% of men who have sex with men reported ever being tested for HIV.
### HIV in Intravenous Drug Users[edit]
In Colombia, people who inject drugs have an HIV prevalence rate of 2.8%.[23] Although additional studies are needed, recent epidemiological studies have shown an increase in both heroin usage and heroin injection in Colombia. Of particular note is the fact that though exported heroin in Colombia is of high quality, the heroin that is not exported and remains in Colombia to be sold to Colombian drug users tends to be of low quality and therefore tends to be water-soluble, which makes it more likely to be injected. A primary concern about the rise in the rate of drug injection in Colombia is the spread of HIV, both among drug-injecting and non drug-injecting populations.[24] A 2014 study found that heroin production in the country had formed "injection networks" which have the potential to spread HIV, particularly among young men.[25]
### HIV in Sex Workers[edit]
The prevalence of HIV among sex workers in Colombia is 1.2%. Over 90% of sex workers are aware of their HIV status, and over 94% report condom usage.[26] At the same time, many sex workers say that the see HIV testing as pointless, because they lack access to adequate treatment should they test positive.[27]
## References[edit]
1. ^ "Colombia". UNAIDS. UNAIDS. Retrieved 11 December 2017.
2. ^ Ballvé, Teo. "Colombia: AIDS in the Time of War". nacla.org. Retrieved 14 December 2017.
3. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (Dec 2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18 (2): 157–169. PMC 5395009. PMID 28559683.
4. ^ "Colombia". UNAIDS. UNAIDS. Retrieved 11 December 2017.
5. ^ García, Patricia J, Bayer, Angela, Cárcamo, César P (1974). "The Changing Face of HIV in Latin America and the Caribbean". Electroencephalogr Clin Neurophysiol. 37 (2): 393–8. doi:10.1007/s11904-014-0204-1. PMC 4136548. PMID 24824881.CS1 maint: multiple names: authors list (link)
6. ^ "Colombia". UNAIDS. UNAIDS. Retrieved 11 December 2017.
7. ^ "Colombia". UNAIDS. UNAIDS. Retrieved 11 December 2017.
8. ^ Arrivillaga M1, Hoyos PA, Tovar LM, Varela MT, Correa D, Zapata H. (2012). "HIV testing and counselling in Colombia: evidence from a national health survey and recommendations for health-care services". International Journal of STD & AIDS. 23 (11): 815–21. doi:10.1258/ijsa.2012.011468. hdl:11522/3551. PMID 23155103.CS1 maint: multiple names: authors list (link)
9. ^ "Colombia". UNAIDS. UNAIDS. Retrieved 11 December 2017.
10. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (Dec 2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18 (2): 157–169. PMC 5395009. PMID 28559683.
11. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (Dec 2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18 (2): 157–169. PMC 5395009. PMID 28559683.
12. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (Dec 2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18 (2): 157–169. PMC 5395009. PMID 28559683.
13. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (Dec 2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18 (2): 157–169. PMC 5395009. PMID 28559683.
14. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (Dec 2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18 (2): 157–169. PMC 5395009. PMID 28559683.
15. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (Dec 2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18 (2): 157–169. PMC 5395009. PMID 28559683.
16. ^ McKenzie, Victoria (2014-07-04). "Colombia kicks off 1st clean needle program for drug addicts". Colombia Reports. Retrieved 8 November 2017.
17. ^ "HIV AND AIDS IN LATIN AMERICA THE CARIBBEAN REGIONAL OVERVIEW". Avert. 2015-07-21. Retrieved 13 December 2017.
18. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18: 157–169. PMC 5395009. PMID 28559683.
19. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (Dec 2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18 (2): 157–169. PMC 5395009. PMID 28559683.
20. ^ Carol A. Reisen, Maria Cecilia Zea, Fernanda T. Bianchi, Paul J. Poppen, Ana Maria del Río González, Rodrigo A. Aguayo Romero, and Carolin Pérez (2014). "HIV testing among MSM in Bogotá, Colombia: The role of structural and individual characteristics". AIDS Educ Prev. 26 (4): 328–44. doi:10.1521/aeap.2014.26.4.328. PMC 4121962. PMID 25068180.CS1 maint: multiple names: authors list (link)
21. ^ Martha Lucía Rubio Mendoza, Jerry Owen Jacobson, Sonia Morales-Miranda, Clara Ángela Sierra Alarcón, Ricardo Luque Núñez (2015). "High HIV Burden in Men Who Have Sex with Men across Colombia's Largest Cities: Findings from an Integrated Biological and Behavioral Surveillance Study". PLOS ONE. 10 (8): e0131040. Bibcode:2015PLoSO..1031040R. doi:10.1371/journal.pone.0131040. PMC 4529092. PMID 26252496.CS1 maint: multiple names: authors list (link)
22. ^ "Colombia". UNAIDS. UNAIDS. Retrieved 11 December 2017.
23. ^ "Colombia". UNAIDS. UNAIDS. Retrieved 11 December 2017.
24. ^ Maria José Miguez'Correspondence information about the author Maria José Miguez, Bryan Page, Marianna K Baum (1997). "Illegal drug use and HIV-1 infection in Colombia". The Lancet. 350 (9091): 1635. doi:10.1016/S0140-6736(05)64059-7. PMID 9393372.CS1 maint: multiple names: authors list (link)
25. ^ P. Mateu-Gelabert1, D. Berbesi2, I.E.M. Motta3,4, H. Guarino1, S. Harris (2014). "Heroin production in Colombia: A time-bomb for a drug injection-driven HIV epidemic in Colombia?". National Institute of Drug Abuse. Retrieved 16 November 2017.CS1 maint: multiple names: authors list (link)
26. ^ "Colombia". UNAIDS. UNAIDS. Retrieved 11 December 2017.
27. ^ Corey Prachniak-rincóncorresponding author and Jimena Villar de Onís (Dec 2016). "HIV and the Right to Health in Colombia". Health and Human Rights Journal. 18 (2): 157–169. PMC 5395009. PMID 28559683.
## External links[edit]
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* t
* e
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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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
HIV/AIDS in Colombia
|
None
| 7,777 |
wikipedia
|
https://en.wikipedia.org/wiki/HIV/AIDS_in_Colombia
| 2021-01-18T19:04:18 |
{"wikidata": ["Q17001419"]}
|
Gerald and Bruns (1978) reported that E11S mapped separately from polio sensitivity (173850) on chromosome 19 and is therefore determined by a separate gene. Coxsackievirus B3 susceptibility (120050) is also determined by a gene on chromosome 19. By analysis of human-mouse hybrid cells, Kaneda et al. (1987) assigned E11S to 19q13.1-qter.
Immunology \- Echo 11 sensitivity Inheritance \- Autosomal dominant (19q13.1-qter) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ECHO VIRUS 11 SENSITIVITY
|
c1851888
| 7,778 |
omim
|
https://www.omim.org/entry/129150
| 2019-09-22T16:41:56 |
{"mesh": ["C565071"], "omim": ["129150"]}
|
A group of rare arteriovenous malformations characterized by unilateral vascular malformations in a metameric distribution involving the craniofacial region. Subtypes differ according to the distribution of lesions, with cerebrofacial arteriovenous metameric syndrome (CAMS) 1 (medial prosencephalic group) involving the hypothalamus and nasal region, Wyburn-Mason syndrome (lateral prosencephalic group) involving the occipital lobe, thalamus, and maxilla, and CAMS 3 (lateral rhombencephalic group) involving the cerebellum, pons, and mandible.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Cerebrofacial arteriovenous metameric syndrome
|
c3839265
| 7,779 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141189
| 2021-01-23T18:56:30 |
{"icd-10": ["Q28.2"], "synonyms": ["CAMS"]}
|
A number sign (#) is used with this entry because of evidence that immunodeficiency-centromeric instability-facial anomalies syndrome-3 (ICF3) is caused by homozygous mutation in the CDCA7 gene (609937) on chromosome 2q31.
Description
Immunodeficiency-centromeric instability-facial anomalies syndrome-3 is an autosomal recessive disorder characterized by recurrent infections in childhood and variable dysmorphic facial features. Laboratory studies show hypomethylation of certain chromosomal regions. Additional features, including delayed development, are variable (summary by Thijssen et al., 2015).
For a discussion of genetic heterogeneity of immunodeficiency-centromeric instability-facial anomalies syndrome, see ICF1 (242860).
Clinical Features
Thijssen et al. (2015) reported 5 patients from 4 unrelated families with an immunodeficiency syndrome characterized by recurrent upper respiratory infections and associated with hypo- or agammaglobulinemia with normal B cells. Cytogenetic studies showed abnormalities of chromosomes 1, 9, and 16, and hypomethylation of alpha-satellite DNA and pericentromeric satellite type II. One of the patients (family A) had previously been reported by Kloeckener-Gruissem et al. (2005) (as patient 2) and Braegger et al. (1991). This patient was born of consanguineous Turkish parents and had ischiadic hypoplasia, renal dysgenesis, polydactyly, and severe hypogammaglobulinemia with normal T-cell function. Other features included intrauterine growth retardation, microcephaly, psychomotor retardation, conductive hearing loss, craniofacial anomalies including flat face, hypertelorism, epicanthic folds, strabismus, short nose, and low-set ears, hypospadias, and cryptorchidism. Kloeckener-Gruissem et al. (2005) found that this patient later developed scoliosis, tapetoretinal degeneration, mental handicap, and suspected bilateral focal cortical heterotopy. Cytogenetic and Southern blot analysis showed that the patient had hypomethylation and centromeric instability of chromosomes 1 and 16, but did not have mutations in the DNMT3B gene (602900) or in genes encoding the DNMT3B-interacting proteins SUMO1 (601912) and UBC9 (UBE2I; 601661). Thijssen et al. (2015) noted that this patient died at 26 years of age. Of the other 4 patients reported by Thijssen et al. (2015), all had recurrent infections, 3 had facial anomalies, and 3 had gastrointestinal problems; only 1 had delayed psychomotor development. Two families were of Turkish origin and 2 were of French origin; 3 families were confirmed consanguineous.
Inheritance
The transmission pattern of ICF3 in the family reported by Thijssen et al. (2015) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 5 patients from 4 unrelated families with ICF3, Thijssen et al. (2015) identified 4 different homozygous missense mutations in the CDCA7 gene (609937.0001-609937.0004). The mutations were found by a combination of homozygosity mapping and whole-exome sequencing. Segregation of the mutations was confirmed in 1 family only. All the mutations occurred at residues in the conserved C-terminal zinc finger domain, but functional studies of the variants were not performed. Knockdown of the CDCA7 gene in mouse embryonic fibroblasts resulted in decreased CpG methylation at centromeric repeats.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Hypertelorism \- Epicanthal folds Nose \- Flat nasal bridge ABDOMEN Gastrointestinal \- Gastrointestinal problems NEUROLOGIC Central Nervous System \- Delayed psychomotor development (in some patients) \- Intellectual disability (in some patients) IMMUNOLOGY \- Recurrent infections \- Hypo- or agammaglobulinemia \- Normal B cells LABORATORY ABNORMALITIES \- Hypomethylation of alpha-satellite repeats on chromosome 9 \- Hypomethylation of satellite repeats on chromosome 1, 9, and 16 Cytogenetic abnormalities MISCELLANEOUS \- Onset at birth MOLECULAR BASIS \- Caused by mutation in the cell division cycle-associated protein 7 gene (CDCA7, 609937.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
IMMUNODEFICIENCY-CENTROMERIC INSTABILITY-FACIAL ANOMALIES SYNDROME 3
|
c4310799
| 7,780 |
omim
|
https://www.omim.org/entry/616910
| 2019-09-22T15:47:29 |
{"doid": ["0090010"], "omim": ["616910"], "orphanet": ["2268"], "synonyms": ["Immunodeficiency-centromeric instability-facial anomalies syndrome"]}
|
Pseudohypoaldosteronism type 1 (PHA1) is a condition characterized by problems regulating the amount of sodium in the body. Sodium regulation, which is important for blood pressure and fluid balance, primarily occurs in the kidneys. However, sodium can also be removed from the body through other tissues, such as the sweat glands and colon. Pseudohypoaldosteronism type 1 is named for its characteristic signs and symptoms, which mimic (pseudo) low levels (hypo) of a hormone called aldosterone that helps regulate sodium levels. However, people with PHA1 have high levels of aldosterone.
There are two types of PHA1 distinguished by their severity, the genes involved, and how they are inherited. One type, called autosomal dominant PHA1 (also known as renal PHA1) is characterized by excessive sodium loss from the kidneys. This form of the condition is relatively mild and often improves in early childhood. The other type, called autosomal recessive PHA1 (also known as generalized or systemic PHA1) is characterized by sodium loss from the kidneys and other organs, including the sweat glands, salivary glands, and colon. This type of PHA1 is more severe and does not improve with age.
The earliest signs of both types of PHA1 are usually the inability to gain weight and grow at the expected rate (failure to thrive) and dehydration, which are typically seen in infants. The characteristic features of both types of PHA1 are excessive amounts of sodium released in the urine (salt wasting), which leads to low levels of sodium in the blood (hyponatremia), and high levels of potassium in the blood (hyperkalemia). Infants with PHA1 can also have high levels of acid in the blood (metabolic acidosis). Hyponatremia, hyperkalemia, or metabolic acidosis can cause nonspecific symptoms such as nausea, vomiting, extreme tiredness (fatigue), and muscle weakness in infants with PHA1.
Infants with autosomal recessive PHA1 can have additional signs and symptoms due to the involvement of multiple organs. Affected individuals may experience episodes of abnormal heartbeat (cardiac arrhythmia) or shock because of the imbalance of salts in the body. They may also have recurrent lung infections or lesions on the skin. Although adults with autosomal recessive PHA1 can have repeated episodes of salt wasting, they do not usually have other signs and symptoms of the condition.
## Frequency
PHA1 is a rare condition that has been estimated to affect 1 in 80,000 newborns.
## Causes
Mutations in one of four different genes involved in sodium regulation cause autosomal dominant or autosomal recessive PHA1. Mutations in the NR3C2 gene cause autosomal dominant PHA1. This gene provides instructions for making the mineralocorticoid receptor protein. Mutations in the SCNN1A, SCNN1B, or SCNN1G genes cause autosomal recessive PHA1. Each of these three genes provides instructions for making one of the pieces (subunits) of a protein complex called the epithelial sodium channel (ENaC).
The mineralocorticoid receptor regulates specialized proteins in the cell membrane that control the transport of sodium or potassium into cells. In response to signals that sodium levels are low, such as the presence of the hormone aldosterone, the mineralocorticoid receptor increases the number and activity of these proteins at the cell membrane of certain kidney cells. One of these proteins is ENaC, which transports sodium into the cell; another protein simultaneously transports sodium out of the cell and potassium into the cell. These proteins help keep sodium in the body through a process called reabsorption and remove potassium from the body through a process called secretion.
Mutations in the NR3C2 gene lead to a nonfunctional or abnormally functioning mineralocorticoid receptor protein that cannot properly regulate the specialized proteins that transport sodium and potassium. As a result, sodium reabsorption and potassium secretion are both decreased, causing hyponatremia and hyperkalemia.
Mutations in the SCNN1A, SCNN1B, and SCNN1G genes result in reduced functioning or nonfunctioning ENaC channels. As in autosomal dominant PHA1, the reduction or absence of ENaC function in the kidneys leads to hyponatremia and hyperkalemia. In addition, nonfunctional ENaC channels in other body systems lead to additional signs and symptoms of autosomal recessive PHA1, including lung infections and skin lesions.
### Learn more about the genes associated with Pseudohypoaldosteronism type 1
* NR3C2
* SCNN1A
* SCNN1B
* SCNN1G
## Inheritance Pattern
PHA1 can have different inheritance patterns. When the condition is caused by mutations in the NR3C2 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When PHA1 is caused by mutations in the SCNN1A, SCNN1B, or SCNN1G genes, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pseudohypoaldosteronism type 1
|
c1449842
| 7,781 |
medlineplus
|
https://medlineplus.gov/genetics/condition/pseudohypoaldosteronism-type-1/
| 2021-01-27T08:24:46 |
{"gard": ["9145", "4552"], "mesh": ["D011546"], "omim": ["177735", "264350"], "synonyms": []}
|
A teratoma with malignant transformation (TMT) is a tumor that develops from germ cells when they grow and divide abnormally, forming a mass. Approximately 6% of teratomas develop into TMTs by a process called malignant transformation, when some of the cells in the teratoma become cancerous. TMTs can occur anywhere in the body, but most are located in the testes in men or ovaries in women. The cause of TMT is unknown. Treatment may include surgery and chemotherapy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Teratoma with malignant transformation
|
c0039538
| 7,782 |
gard
|
https://rarediseases.info.nih.gov/diseases/10646/teratoma-with-malignant-transformation
| 2021-01-18T17:57:23 |
{"mesh": ["D013724"], "umls": ["C0039538"], "synonyms": []}
|
Dysmorphopsia
SpecialtyOphthalmology
Dysmorphopsia, in a broad sense, is a condition in which a person is unable to correctly perceive objects. It is a visual distortion, used to denote a variant of metamorphopsia in which lines appear wavy.[1] These illusions may be restricted to certain visuals areas, or may affect the entire visual field.[2]
It has been associated with meningioma tumors[3] and bilateral lateral occipital corital damage, e.g. after carbon monoxide poisoning or drug abuse.[4]
## Contents
* 1 Etymology
* 2 See also
* 3 References
* 4 Further reading
## Etymology[edit]
The term dysmorphopsia comes from the Greek words dus (bad), morphè (form) and opsis (seeing).[1]
## See also[edit]
* Hallucination
* Macropsia
* Metamorphopsia
* Micropsia
* Occipital lobe
* Visual perception
## References[edit]
1. ^ a b "dysmorphopsia".
2. ^ M.D, Orrin Devinsky; M.D, Mark D'Esposito (16 October 2003). Neurology of Cognitive and Behavioral Disorders. Oxford University Press. ISBN 9780198031482 – via Google Books.
3. ^ Safran, Avinoam B.; Sanda, Nicolae; Sahel, José-Alain (22 March 2018). "A neurological disorder presumably underlies painter Francis Bacon distorted world depiction". Frontiers in Human Neuroscience. 8: 581. doi:10.3389/fnhum.2014.00581. PMC 4148635. PMID 25221491.
4. ^ Blom, Jan Dirk (8 December 2009). A Dictionary of Hallucinations. Springer Science & Business Media. ISBN 9781441912237 – via Google Books.
## Further reading[edit]
* A Dictionary of Hallucinations
* A neurological disorder presumably underlies painter Francis Bacon distorted world depiction
* Dysmorphopsia: a notable variant of the "thin man" phenomenon?
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Dysmorphopsia
|
None
| 7,783 |
wikipedia
|
https://en.wikipedia.org/wiki/Dysmorphopsia
| 2021-01-18T18:44:06 |
{"wikidata": ["Q25312802"]}
|
A very rare syndrome characterized by a combination of blepharochalasis, double lip, and non-toxic thyroid enlargement (seen in 10-50% of cases), although the occurrence of all three signs at presentation is uncommon. Hypertrophy of the mucosal zone of the lip with persistence of the horizontal sulcus between cutaneous and mucosal zones gives an appearance of double lip, with the upper lip being frequently involved. Blepharochalasis, or episodic edema of eyelid, appears around puberty, is present in 80% of cases, is usually bilateral, and can rarely lead to vision impairment and other ocular complications. Most cases are sporadic, but familial cases (with a possible autosomal dominant inheritance) have also been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ascher syndrome
|
c0339085
| 7,784 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1253
| 2021-01-23T18:47:01 |
{"gard": ["201"], "mesh": ["C562742"], "omim": ["109900"], "umls": ["C0339085"], "icd-10": ["Q87.0"], "synonyms": ["Blepharochalasis-double lip syndrome"]}
|
A number sign (#) is used with this entry because of evidence that the Stanescu type of spondyloepiphyseal dysplasia (SEDSTN) is caused by heterozygous mutation in the COL2A1 gene (120140) on chromosome 12q13.
Description
Spondyloepiphyseal dysplasia with accumulation of glycoprotein in chondrocytes has been designated the 'Stanescu type.' Clinical hallmarks include progressive joint contracture with premature degenerative joint disease, particularly in the knee, hip, and finger joints. Interphalangeal joints of the hands are swollen due to osseous distention of the metaphyseal ends of the phalanges. Affected individuals may be relatively tall despite the presence of a short trunk. Radiologically, there is generalized platyspondyly with mild modification of the endplates, hypoplastic pelvis, epiphyseal flattening with metaphyseal splaying of the long bones, and enlarged phalangeal epimetaphyses of the hands. In addition, the proximal femora are characteristically broad and elongated with striking coxa valga (summary by Nishimura et al., 1998).
Clinical Features
Stanescu et al. (1984) reported a French boy who presented with difficulty in walking. Examination at 10.5 years of age showed normal height with mild genu valgum. Joints were enlarged, especially the elbows and knees, hip flexion was limited except on external rotation, and he had a waddling gait. Other features included hearing loss, which required hearing aids by age 20 years, and mild myopia. His parents were nonconsanguineous, and he had 2 healthy brothers. X-rays showed massive enlargement of long bone epiphyses with enlargement of the adjacent metaphyses as well. The most striking finding, however, involved the femoral necks, which were very enlarged, particularly distally, and showed valgus deformation. The iliac wings appeared small in comparison, with poor coverage of the femoral heads. The metacarpal metaphyses were also enlarged, with epiphyses that were increased in size and mildly flattened. The height of all vertebral bodies was slightly reduced. Tibial growth cartilage biopsy showed significant cellularity and irregularly arranged chondrocytes, with moderate hypertrophy along the ossification line. Histochemical analysis revealed metachromasia in the growth zone, which was reduced in the resting zone. Cells in all zones were larger than normal and contained what appeared to be glycoprotein inclusions. Electrophoretic analysis of proteoglycans was normal, but analysis of noncollagenous protein bands showed some alterations, with significant reduction in P1 and a mild decrease in P4 and P5. Stanescu et al. (1984) concluded that the disorder in this patient represented an unusual form of spondyloepiphyseal dysplasia with normal stature.
Nishimura et al. (1998) examined 3 affected individuals from 2 unrelated Japanese families segregating a bone dysplasia in an autosomal dominant fashion. The proband of the first family had an unsteady gait from 2 years of age, with a tendency to fall on ambulation; he was referred for evaluation of knee deformity and back pain at age 10 years. His father reported flexion contractures of the fingers and knees in childhood that gradually worsened. The proband in the second family noted painful knees and ankles after athletic activity at 7 years of age, and at age 14 presented for evaluation of left hip pain while walking. All 3 patients had painful large joints with joint restriction, progressive contracture of the finger joints with osseous expansion, and normal height despite the presence of a short trunk. Moderate platyspondyly, hypoplastic ilia, epiphyseal flattening with metaphyseal splaying of the tubular bones, and characteristically broad elongated femoral necks were identical in all 3 patients. However, the proband from the second family exhibited severe brachydactyly, which was not seen in the father and son from the first family. Histologic examination of an iliac crest biopsy showed PAS-positive, amylase-resistant intracytoplasmic inclusion bodies in the chondrocytes, corresponding to dilated rough endoplasmic reticulum filled with moderately electron-dense material on electron microscopy. Nishimura et al. (1998) stated that the clinical and radiologic features in these patients were identical to those seen in the spondyloepiphyseal dysplasia reported by Stanescu et al. (1984).
Jurgens et al. (2015) studied 3 affected individuals from 2 unrelated families with spondyloepiphyseal dysplasia of the Stanescu type. The 38-year-old proband of the first family was originally reported by Hurvitz et al. (1999) as having progressive pseudorheumatoid dysplasia (208230), but was negative for mutation in the WISP3 gene (603400). She had a daughter who was also affected. The proband of the second family was a Korean boy born of unaffected nonconsanguineous parents. All 3 patients were noted to have a waddling gait in early childhood. They developed progressive joint stiffness and pain with flexion contractures of the hips and knees resulting in difficulty with mobility and a 'Z' posture upon standing. Spine radiographs showed platyspondyly and anterior wedging, as well as generalized joint space narrowing and metaphyseal irregularity. The mother underwent bilateral hip and knee replacements at ages 25 and 26, respectively. She developed progressive thoracolumbar kyphosis with severe spinal stenosis by age 35 requiring laminectomy and spinal fusion, after which she remained ambulatory. Her daughter, who developed kyphosis and progressive scoliosis in adolescence, had severe pain with ambulation and could only walk short distances with crutches by her third decade of life. At 10.5 years of age, the Korean boy could walk only with assistance due to joint pain and limb muscle weakness from prolonged disuse, and had 20-degree flexion contractures at the hips and knees. Jurgens et al. (2015) noted phenotypic overlap between their patients and previously reported patients with Stanescu SED; however, because they did not have access to the patients' chondrocytes, they were unable to test for the characteristic cytoplasmic inclusions.
Hammarsjo et al. (2015) examined 6 affected members of a 3-generation family with the Stanescu type of spondyloepiphyseal dysplasia. All affected individuals presented with progressive joint disease of varying severity, with age of onset ranging from 1 to 20 years. The most prominent sign was early onset of pain and deformities, particularly involving the knee, hip, and finger joints. Skeletal survey of the 25-year-old male proband revealed features consistent with SEDSTN, including moderate platyspondyly with elongated vertebral bodies and endplate irregularities, mild iliac hypoplasia, mild epiphyseal flattening of hip and knee, and bulbous ends of short tubular bones. Hammarsjo et al. (2015) noted that elongation of the femoral neck, seen on x-ray of the proband at age 15 years, was not observed in pelvic films from 4 affected adults, indicating that this is an age-dependent feature.
Molecular Genetics
In a mother and daughter with the Stanescu type of spondyloepiphyseal dysplasia, Jurgens et al. (2015) performed whole-exome sequencing and identified a heterozygous missense mutation in the COL2A1 gene (G207R; 120140.0055). The mutation was not present in the unaffected maternal grandmother; DNA from the maternal grandfather was unavailable. Jurgens et al. (2015) sequenced COL2A1 in a similarly affected Korean boy and identified heterozygosity for the same missense mutation. The mutation was not present in either of his unaffected parents, indicating de novo occurrence in the proband.
In an affected member of a 3-generation family with SEDSTN, Hammarsjo et al. (2015) analyzed a skeletal gene panel including 347 genes, and identified heterozygosity for a missense mutation in the COL2A1 gene (D1219H; 120140.0056). Sanger sequencing confirmed that the mutation segregated with disease in the family, and the mutation was not found in 249 exomes from a local ethnically mixed population or in public variant databases.
INHERITANCE \- Autosomal dominant GROWTH Height \- Normal height HEAD & NECK Mouth \- Limited mouth opening (in some patients) Neck \- Neck stiffness SKELETAL \- 'Z'-posture (due to hip and knee flexion) \- Accumulation of glycoprotein in chondrocytes Spine \- Stiffness \- Kyphoscoliosis \- Platyspondyly \- Anterior wedging \- Elongated vertebral bodies Pelvis \- Hypoplastic ilia \- Flat acetabulum \- Coxa valga Limbs \- Joint stiffness \- Joint pain \- Joint space narrowing \- Flexion contractures, especially at hip and knee \- Epiphyseal flattening of long bones \- Metaphyseal splaying or irregularity \- Flattened and irregular femoral head \- Broadening of proximal femora \- Elongation of proximal femora (seen in some children but not in adults) Hands \- Prominent metaphyses \- Contractures of finger joints \- Bulbous ends of short tubular bones MISCELLANEOUS \- Symptoms appear in early childhood and are progressive MOLECULAR BASIS \- Caused by mutation in the collagen II, alpha-polypeptide gene (COL2A1, 120140.0055 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SPONDYLOEPIPHYSEAL DYSPLASIA, STANESCU TYPE
|
c4225273
| 7,785 |
omim
|
https://www.omim.org/entry/616583
| 2019-09-22T15:48:25 |
{"omim": ["616583"], "orphanet": ["459051"], "synonyms": ["Alternative titles", "SED, STANESCU TYPE", "SED, Stanescu type"]}
|
Autosomal recessive polycystic kidney disease (ARPKD) is a genetic condition that is characterized by the growth of cysts in the kidneys (which lead to kidney failure) and liver and problems in other organs, such as the blood vessels in the brain and heart. The severity varies from person to person. The signs of ARPKD frequently begin before birth, so it is often called “infantile PKD” but some people do not develop symptoms until later in childhood or even adulthood. Children born with ARPKD often, but not always, develop kidney failure before reaching adulthood; babies with the worst cases die hours or days after birth due to respiratory difficulties or respiratory failure. Liver scarring occurs in all patients. The condition is caused by a mutation in the PKHD1 gene and is inherited in an autosomal recessive manner. Some symptoms of the condition may be controlled by medicines, antibiotics, healthy diet, and growth hormones.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Autosomal recessive polycystic kidney disease
|
c0085548
| 7,786 |
gard
|
https://rarediseases.info.nih.gov/diseases/8378/autosomal-recessive-polycystic-kidney-disease
| 2021-01-18T18:01:55 |
{"mesh": ["D017044"], "omim": ["263200"], "umls": ["C0085548"], "orphanet": ["731"], "synonyms": ["ARPKD", "Polycystic kidney disease, infantile type"]}
|
A number sign (#) is used with this entry because of evidence that variation in the IRF5 gene (607218) influences susceptibility to systemic lupus erythematosus.
For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.
Mapping
Systemic lupus erythematosus is a complex systemic autoimmune disease caused by both genetic and environmental factors. Increased production of type I interferon (IFN) and expression of IFN-inducible genes are commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disorder. Sigurdsson et al. (2005) analyzed 44 SNPs in 13 genes from the type I IFN pathway of 679 Swedish, Finnish, and Icelandic patients with SLE, 798 unaffected family members, and 438 unrelated control individuals for joint linkage and association with SLE. The authors identified SNPs in IRF5 (e.g., rs2004640, 607218.0002) that displayed strong signals in joint analysis of linkage and association with SLE.
Graham et al. (2006) replicated association of the T allele of rs2004640 in 4 independent case-control cohorts and by family-based transmission disequilibrium test analysis, and also studied an independent cis-acting variant (rs2280714) associated with elevated expression of IRF5 (Morley et al., 2004) and linked to the exon 1B splice site. Haplotypes carrying the cis-acting variant and lacking the exon 1B donor site did not confer risk of SLE. Thus, a common IRF5 haplotype driving elevated expression of multiple unique isoforms of IRF5 is an important genetic risk factor for SLE.
Cunninghame Graham et al. (2007) identified 2 overtransmitted IRF5 haplotypes and a single undertransmitted haplotype among 380 UK SLE nuclear families; see 607218.0003.
Sigurdsson et al. (2008) genotyped 47 polymorphisms in the IRF5 gene in 485 Swedish SLE patients and 563 controls and found that 18 showed significant association even after Bonferroni correction, with particularly strong association (p = 4.6 x 10(-9); OR, 1.69) for a diallelic CGGGG indel promoter polymorphism (607218.0001). Logistic regression analysis conditioned on the CGGGG indel abolished association signals from 10 SNPs, including 2 that were previously suggested to be functional (rs2004640 and rs10954213; see 607218.0002 and 607218.0003, respectively). Conditioning on another strongly associated SNP, rs10488631 (p = 9.4 x 10(-10); OR, 2.07), abolished association signals from 2 other SNPs, and conditional analysis using the CGGGG indel and rs10488631 together abolished the association signals from all markers in the IRF5 gene. Logistic regression analysis conditional on either CGGGG or rs10488631 suggested that they are independently associated with SLE.
To identify risk loci for SLE susceptibility, Gateva et al. (2009) selected SNPs from 2,466 regions that showed nominal evidence of association with SLE (P less than 0.05) in a genomewide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. Gateva et al. (2009) showed an association with the IRF5 gene at rs2070197 (combined P value = 5.8 x 10(-24), odds ratio = 1.88, 95% confidence interval = 1.78-1.95).
Han et al. (2009) performed a genomewide association study of SLE in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina-Human610-Quad BeadChips and replicating 78 SNPs in 2 additional cohorts (3,152 cases and 7,050 controls). Han et al. (2009) found association with rs4728142 with the IRF5 gene (combined P value = 8.14 x 10(-19), odds ratio = 1.43, 95% confidence interval 1.32-1.54).
Population Genetics
Mexican individuals with SLE appear to have a more severe disease and a lower age of onset than Europeans, as well as a higher frequency of disease activity flares, renal manifestations, and organ damage. Among Mexican SLE patients, Reddy et al. (2007) found a significant disease association with 3 different SNPs in the IRF5 gene. The strongest association was for allele C of rs2070197 (607218.0004), which tagged the risk haplotype. The frequency of the risk haplotype in healthy Mexican mestizo individuals (0.201) was significantly higher than that found in healthy individuals with European ancestry (0.09); the frequency was even higher in the healthy Mexican Indian group (0.31). Further, a much higher frequency of the risk haplotype and of individual homozygosity for it was found among Mexican SLE patients. The high frequency of the C allele of rs2070197 in Mexican Indians (Mazateco) suggested to the authors that the Indian genetic background in Mexicans clearly contributes to the high frequency of the risk haplotype in Mexican mestizos. The low frequency of homozygosity for the risk haplotype (4% in mestizo controls and 6.5% in healthy Mazatecos) led Reddy et al. (2007) to hypothesize that individuals homozygous for the risk haplotype will develop SLE.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SYSTEMIC LUPUS ERYTHEMATOSUS, SUSCEPTIBILITY TO, 10
|
c2677097
| 7,787 |
omim
|
https://www.omim.org/entry/612251
| 2019-09-22T16:02:02 |
{"omim": ["612251"]}
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## Clinical Features
Wolach et al. (1990) described this combination in a 5-year-old daughter of first-cousin, Sephardic Jewish parents. Diffuse skin pigmentation had been present from birth and biopsy confirmed the diagnosis of diffuse cutaneous mastocytosis (see 154800). There was no mental retardation associated with the microcephaly. Wolach et al. (1990) favored autosomal recessive inheritance.
Hennekam and Beemer (1992) studied a girl, born of nonconsanguineous parents in the Netherlands, who at birth was noted to have diffuse hyperpigmented, slightly elevated macules on her whole body, especially on the trunk and extremities, with exaggerated dermatographism. She had a large anterior fontanel, slight proptosis, upward slanting palpebral fissures, highly arched palate, receding chin, and clinodactyly of the fifth fingers. Neurologic examination revealed generalized hypotonia, decreased deep tendon reflexes, and absent swallowing reflex; she required lifelong feeding by gavage. Funduscopy showed slightly pale optic nerve heads, which remained unchanged over the next 8 years; visual evoked potentials were normal. She had bilateral mixed hearing loss of 60 to 70 dB. At 7 months of age, she began to have generalized seizures and continued to have 10 to 15 convulsions per day despite extensive antiseizure medication. She had very severe developmental retardation, reacting to tactile stimuli and able to smile, but with no other motor abilities. At 2 years of age, her length was in the 10th centile and weight in the 25th centile, and she remained in those centiles until her death at 8 years of age from bronchopneumonia. Hennekam and Beemer (1992) noted similarities to the patient described by Wolach et al. (1990).
Salpietro et al. (2009) reported a 16-year-old girl, born of nonconsanguineous parents, who at 3 years of age developed diffuse macules and papules on the neck and trunk, but did not have pruritus, feeding difficulties, or recurrent infections. She had mild mental retardation and hypotonia. Examination at 16 years of age revealed diffuse hyperpigmented macules and papules on the trunk, with fewer over the limbs; however, her face, scalp, palms, and soles were spared. Dermatographism was also present. She had microcephaly and a triangular face, with prominent supraorbital ridges, upward-slanting palpebral fissures, wide nasal bridge, long and prominent nose, hypoplastic nares, full lips, high-arched palate, micrognathia, bilateral short ears, long slender fingers, left complete distal palmar crease, camptodactyly of the right fifth finger, and small asymmetric feet, with the left foot being 2 cm shorter than the right. Laboratory studies, abdominal ultrasound, cardiologic evaluation, and ophthalmologic and audiologic examinations were all normal. Radiographs demonstrated a dislocation of the right proximal fifth finger interphalangeal joint, and skin biopsy showed prominent mast cell infiltration and confirmed the diagnosis of cutaneous mastocytosis. Salpietro et al. (2009) noted similarities to the patients previously reported by Wolach et al. (1990) and Hennekam and Beemer (1992), except for lack of feeding problems or hearing loss in the present patient.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly Face \- Micrognathia Ears \- Microtia \- Hearing loss, conductive or mixed Eyes \- Upslanting palpebral fissures Nose \- Wide nasal bridge \- Hypoplastic nares Mouth \- High-arched palate ABDOMEN Gastrointestinal \- Feeding problems SKELETAL Spine \- Scoliosis Hands \- Clinodactyly of fifth fingers SKIN, NAILS, & HAIR Skin \- Cutaneous mastocytosis \- Dermatographism (dermatographic urticaria) Skin Histology \- Mast cell infiltration MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Hypotonia \- Mental retardation ▲ 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
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*[OCD]: Obsessive-compulsive disorder
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*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
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*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
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*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
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*[ITA]: Italy
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CUTANEOUS MASTOCYTOSIS, CONDUCTIVE HEARING LOSS AND MICROTIA
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c3151493
| 7,788 |
omim
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https://www.omim.org/entry/248910
| 2019-09-22T16:25:31 |
{"omim": ["248910"], "orphanet": ["2135"], "synonyms": ["Mastocytosis-short stature-hearing loss syndrome"]}
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A number sign (#) is used with this entry because the velocardiofacial syndrome and DiGeorge syndrome (DGS; 188400) are caused by a 1.5- to 3.0-Mb hemizygous deletion of chromosome 22q11.2. Haploinsufficiency of the TBX1 gene (602054) in particular is responsible for most of the physical malformations. There is evidence that point mutations in the TBX1 gene can also cause the disorder.
Clinical Features
The del22q11 syndrome is associated with a highly variable phenotype despite the uniformity of the chromosomal deletion that causes the syndrome in most patients.
Shprintzen et al. (1981) reported on 39 patients with a syndrome characterized by the following frequent features: cleft palate, cardiac anomalies, typical facies, and learning disabilities. Less frequent features included microcephaly, mental retardation, short stature, slender hands and digits, minor auricular anomalies, and inguinal hernia. The Pierre Robin syndrome was present in 4. The heart malformation was most often ventricular septal defect. In the group studied, mother and daughter were affected in 2 instances, mother and son in 1, and mother and both daughter and son in 1.
Fitch (1983) found small optic discs with tortuous vessels in an affected 6-year-old girl, the offspring of first-cousin parents.
Wraith et al. (1985) reported a male infant with holoprosencephaly and tetralogy of Fallot with death at 32 days. The mother had the same heart lesion, tetralogy of Fallot (totally corrected by surgery at age 12 years), and a large submucous cleft palate causing nasal voice. Her face was considered typical of VCF syndrome: prominent tubular nose, narrow palpebral fissures, and slightly retruded mandible. She was mildly retarded. Another child, female, may have been affected. The authors suggested that the association of tetralogy of Fallot and prosencephaly should prompt search for signs of VCF syndrome in relatives.
Shprintzen et al. (1985) claimed that VCFS is the most frequent clefting syndrome, accounting for 8.1% of children with palatal clefts seen in their center. Learning disabilities characterized by difficulty with abstraction, reading comprehension, and mathematics is found in all cases as is a characteristic facial dysmorphia. Cardiac anomalies were found in 82%. Platybasia occurred in 85%. Ophthalmologic abnormalities, including tortuous retinal vessels, small optic discs, posterior embryotoxon, or bilateral cataracts, were observed in 70%. Neonatal hypocalcemia requiring treatment occurred in almost 13%. Small or absent lymphoid tissue was documented by nasopharyngoscopic examination in a great majority. Most patients had frequent infections, and T-lymphocyte dysfunction was found. Male-to-male transmission established autosomal dominant inheritance.
Marked tortuosity of the retinal vessels, as noted in earlier reports, was commented on by Beemer et al. (1986).
Meinecke et al. (1986) reported 8 patients with the VCF syndrome; 3 cases were sporadic and 5 others occurred in 2 families. The authors concluded that the frequency of cardiovascular anomalies and cleft palate has been incorrectly estimated to be high, 98% and 82%, respectively, because patients have been ascertained in cardiac or cleft palate clinics. Their 8 patients were diagnosed mainly through their pattern of facial dysmorphism and only 2 and 4 of the 8, respectively, had clefts and heart defects. Furthermore, mental retardation, noted in all cases in previous publications, was not present in any of these 8 patients. They suspected that the rate of fresh mutations may not be as high as previously assumed because of mild expression in some family members.
Williams et al. (1987) found evidence for congenital hypoplasia of the adenoids in over four-fifths of patients with the VCF syndrome. They suggested that this feature contributes to the hypernasal speech found in persons with this condition because normally velopharyngeal closure during speech is aided by the adenoids.
Lipson et al. (1991) reported on 38 cases including 2 familial cases. They emphasized the frequent delay in diagnosis and treatment for the hypernasal speech and velopharyngeal insufficiency. Overt cleft palate was present in 7 of the cases and submucous cleft in 15. Congenital heart disease was present in 16. Velopharyngeal insufficiency was present in all but one; pharyngoplasty was performed in all but 6 of the cases and results were good in all of these. Lipson et al. (1991) published photographs illustrating the main facial features: almond-shaped palpebral fissures, deficient nasal alae, bulbous nasal tip in older children, myopathic facies, and small open mouth. Hypernasal speech was often the finding that brought the children to attention.
Goldberg et al. (1993) reviewed the full spectrum of the velocardiofacial syndrome on the basis of 120 patients. Learning disability, cleft palate, and pharyngeal hypotonia were present in 90% or more of the patients; cardiac anomalies in 82%; slender hands and digits in 63%; medial displacement of internal carotid arteries in 25%; umbilical hernia in 23%; and hypospadias in 10% of males.
Nickel et al. (1994) reported 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of VCFS; both also had bifid uvula. The third child had DiGeorge sequence.
Kousseff (1984) described 3 sibs with a syndrome of sacral meningocele, conotruncal cardiac defects, unilateral renal agenesis (in 1 sib), low-set and posteriorly angulated ears, retrognathia, and short neck with low posterior hairline. Kousseff (1984) suggested autosomal recessive inheritance. Toriello et al. (1985) reported a similar, isolated case and designated the disorder Kousseff syndrome. Forrester et al. (2002) restudied the family reported by Kousseff (1984) and identified a 22q11-q13 deletion in the proband, his deceased brother, and his father. The proband had spina bifida, shunted hydrocephalus, cleft palate, short stature, cognitive impairment, and the typical craniofacial features of velocardiofacial syndrome, including low-set and dysplastic ears, broad base of the nose, narrow alae nasi, and retrognathia. His brother had died at 2 weeks of age with myelomeningocele, hydrocephalus, transposition of the great vessels, and unilateral renal agenesis, and his sister had died at 22 days of age with myelomeningocele, truncus arteriosus, hypocalcemia, and autopsy findings of absent thymus and parathyroid glands, consistent with DiGeorge anomaly.
Maclean et al. (2004) reported 2 patients with Kousseff syndrome, 1 with a 22q11.2 deletion and the other without. The first was a 4-year-old girl with a sacral myelomeningocele, tetralogy of Fallot, microcephaly, hydrocephalus, hypoplasia of the corpus callosum, and moderate developmental delay, who had a normal chromosome 22q11.2 FISH test and did not exhibit the facial phenotype of VCFS. The second patient, a male infant who died at 10 days of age, had a large sacral myelomeningocele, hydrocephalus, Arnold-Chiari malformation, atrial septal defect, conoventricular ventricular septal defect, type B interrupted aortic arch, hypocalcemia, and suspected duodenal stenosis; FISH testing revealed a 22q11.2 microdeletion. Maclean et al. (2004) concluded that Kousseff syndrome is a distinct clinical entity that is genetically heterogeneous.
Lynch et al. (1995) reported the case of a 34-year-old man who presented for neurologic evaluation for cerebellar atrophy of unknown etiology. By history, he had had neonatal hypocalcemia, an atrial septal defect, and a corrected cleft palate. Physical examination showed the characteristic facies of velocardiofacial syndrome, as well as dysmetria and dysdiadochokinesia consistent with cerebellar degeneration. An MRI scan of his head performed by the authors showed vermian and hemispheric cerebellar atrophy, calcification of the basal ganglia, a small brainstem without focal loss of volume, and multiple white matter lucencies on T2-weighted images. The white matter lesions were suggestive of axonal loss, ischemia, or demyelination. Molecular cytogenetic studies showed a deletion of 22q11.2, del(22)(q11.21-q11.23). This case represented the first report of the association of a neurodegenerative disorder with velocardiofacial syndrome or DiGeorge syndrome.
Ryan et al. (1997) reported a European collaborative study of 558 patients with deletions of 22q11. In 204 of the 285 patients for whom parental deletion status was available, neither parent had the deletion. Of the 81 inherited deletions, the sex of the parent with the deletion was known in 79 cases, with 61 maternal and 18 paternal deletions. Growth data were available for 131 of 158 patients whose heights and/or weights were less than the 50th centile; 57 of 158 were below the 3rd centile for either height or weight. Forty-four patients had died, and of the 29 for whom age of death was available, 16 had died within 1 month and 25 within 6 months as a consequence of congenital heart disease. There was 1 death from severe immune deficiency. A total of 107 of 338 cases were developmentally normal, although 37 of these had speech delay. Of 231 patients with abnormal development, 102 had mild delay and 60 had either moderate or severe learning difficulties. Twenty-two of 252 children in the study had behavioral or psychiatric problems, including 2 with episodes of psychosis; 11 of 61 adults had a psychiatric disorder, 4 of whom had had at least 1 episode of psychosis. Cardiac studies were recorded in 545 patients, of whom 409 had significant cardiac pathology, most commonly tetralogy of Fallot, ventricular septal defect, interrupted aortic arch, pulmonary atresia/ventricular septal defect, and truncus arteriosus. A total of 242 of 496 patients had otolaryngeal abnormalities, with 72 having either an overt cleft palate or submucous cleft; 161 patients had velopharyngeal insufficiency without clefting. Of 159 patients in whom data on hearing were available, 52 had abnormal hearing, with data on the type of hearing loss available in only 17, in all of whom this was conductive in type. A total of 49 of 136 patients had renal abnormalities, with absent, dysplastic, or multicystic kidneys in 23, obstructive abnormalities in 14, and vesicoureteric reflux in 6. A total of 203 of 340 had recorded hypocalcemia; 108 of this group had a history of seizures, and 42 of these had had seizures secondary to hypocalcemia. Most hypocalcemia was reported in the neonatal period, but 1 patient presented at 18 years of age. Laboratory and clinical immune function and thymus status were available in 218 patients. Only 4 of these were classified as having a major immune function abnormality. Two of these had died, with severe immunodeficiency being the cause of death in 1. A total of 94 of 548 patients had minor abnormalities of the skeletal system, and 39 of 548 had ocular anomalies. Ten offspring comparisons showed that 27 of 35 children had more severe congenital heart disease than their parents, with 8 of 35 having the same degree of severity. Developmental status was worse in 9 of 17 and the same in 7 of 17. Palatal abnormalities were better in 10 of 22 children and similar to the parents in 12 of 22 children. Sibship comparisons in 26 sibs from 12 families showed considerable variation in heart abnormalities between sibs, and development status was similar in most cases. Ryan et al. (1997) concluded that most of the clinical findings in their study reflected previous reports; however, fewer immunologic problems and more renal problems than were expected were found. Ryan et al. (1997) therefore recommended that abdominal ultrasound be carried out in all patients with 22q11 deletions. They also recommended that both parents be studied when a child is found to have a deletion.
Vincent et al. (1999) reported the case of female monozygotic twins with 22q11 deletions. The twins shared facial characteristics of DGS/VCFS and immunologic defect. However, only one, who died on day 5, had a cardiac defect, comprised of an interrupted aortic arch with a ventricular septal defect, a truncus arteriosus, and a large arterial duct. The authors stated that this was the fourth report of a discrepant cardiac status between monozygotic twins harboring 22q11 deletions.
Worthington et al. (1997) reported 3 cases of VCFS with anal anomalies (2 cases of anal stenosis and one of a covered anus with a perineal fistula) and confirmed deletions of the 22q11 region by FISH. They presented an additional case of a child with clinical VCFS whose father was born with an imperforate anus and had mental retardation presumably because of VCFS; this family had been lost to follow-up.
Devriendt et al. (1997) reported a female fetus with Potter sequence caused by unilateral renal agenesis and contralateral multicystic renal dysplasia. Additionally, there was agenesis of the uterus and oviducts (Von Mayer-Rokitansky-Kuster anomaly). The father had dysmorphic features typical of VCFS, and fluorescence in situ hybridization analysis confirmed deletions of chromosome 22q11 in both father and fetus. The fetus had no dysmorphic features suggestive of VCFS and no cardiovascular abnormalities.
Sundaram et al. (2007) described 2 patients with 22q11.2 deletion who had absent uterus and unilateral renal agenesis. One patient also had mild developmental delay, hypoparathyroidism, and psychiatric symptoms; the other patient also had high-arched palate, bulbous nasal tip, bicuspid aortic valve, short stature, and primary amenorrhea. Sundaram et al. (2007) suggested that mullerian or uterine/vaginal agenesis be included as part of the clinical spectrum of 22q11.2 deletion syndrome.
Van Geet et al. (1998) studied a family in which all 3 members with a 22q11 microdeletion and VCFS had giant platelets and a mild decrease in platelet number. Platelet function, however, tested by aggregation and by adherence to collagen in a whole blood perfusion system, was normal. They studied the files of 35 other patients with 22q11 deletion and also found that their platelets had an increased size compared with cardiac controls. Moreover, their platelet size correlated negatively with platelet number. Since patients with 22q11 deletion are expected to be heterozygous for deletion of the GP1BB gene (138720), they can be considered to be carriers of the Bernard-Soulier syndrome (231200). A significant increase in platelet size may be a positive predictor for the clinical diagnosis of VCFS.
Digilio et al. (2001) reported on the growth parameters of 73 patients with the 22q11 deletion. In general, these patients were characterized by weight deficiency in the first years of life, weight normalization in the following years, development of obesity in adolescence, short stature in 10% of the patients, normal height in adolescents, slight delay in bone age in infancy, and microcephaly in 10% of the patients.
Jawad et al. (2001) studied 195 patients with chromosome 22q11.2 deletion syndrome and found that diminished T-cell counts in the peripheral blood are common. The pattern of changes seen with aging in normal control patients was also seen in patients with the chromosome 22q11.2 deletion syndrome, although the decline in T cells was blunted. Autoimmune disease was seen in most age groups, although the types of disorders varied according to age. Infections were also common in older patients, although they were seldom life-threatening. Juvenile rheumatoid arthritis with onset between 1.5 and 6 years of age was seen in 4 of the 195 patients; idiopathic thrombocytopenia purpura with onset at 1 to 8 years of age was seen in 8 of 195 patients; autoimmune hemolytic anemia, psoriasis, vitiligo, inflammatory bowel disease, adult rheumatoid arthritis, and rheumatic fever with chorea were each seen in 1 patient of the 195 patients sampled.
Kawame et al. (2001) reported 5 patients with chromosome 22q11.2 deletion that manifested Graves disease between the ages of 27 months and 16 years, and suggested that Graves disease may be part of the clinical spectrum of this disorder.
McElhinney et al. (2001) studied 29 patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age to determine the incidence of cardiovascular anomalies. In 11 of 29 (38%) patients, cardiovascular anomalies were detected, including 3 with a vascular ring, 3 with a right aortic arch with mirror-image branching of the brachiocephalic arteries (no vascular ring; one with a patent ductus arteriosus; see 607411), and 4 with a left aortic arch with an aberrant right subclavian artery (no vascular ring; 1 with a patent ductus), and 1 with a left superior vena cava draining to the coronary sinus. All 3 patients with vascular rings and 1 with a patent ductus arteriosus required intervention, giving an incidence of 14% in this study.
Kessler-Icekson et al. (2002) examined myocardial tissues removed after corrective surgery of 31 patients with congenital heart defects (21 with tetralogy of Fallot and 10 with a double-chamber right ventricle) using a set of 9 polymorphic short tandem repeat markers along the 22q11.2 region. Ten (48%) of the tetralogy of Fallot patients had homozygosity for 3 or more consecutive markers, suggesting possible 22q11.2 deletions. None of the patients with double-chamber right ventricle had this finding.
Martin et al. (2004) identified an altered dermatoglyphic profile in 22q deletion syndrome patients, which involved (1) ATD angle and amplitude, (2) the presence of radial loops in the hypothenar area, and (3) fluctuating asymmetry. Martin et al. (2004) noted that the first 2 features are similar to those found in other genetic syndromes associated with low IQ, whereas high levels of fluctuating asymmetry have often been reported in schizophrenia.
Sandrin-Garcia et al. (2002) described a family in which a patient had the clinical diagnosis of VCFS and his sister had a suggestive phenotype. Both were found to carry a deletion in 22q11.2 of maternal origin. The mother and other unaffected relatives did not show the deletion, suggesting that the mother had gonadal mosaicism with a normal DNA profile in the blood cells.
Conway et al. (2002) described a child with the typical craniofacial manifestations of VCFS and unilateral pulmonary agenesis. They suggested that the patient's pulmonary agenesis was related to a disruption of the dorsal aortic arch development that selectively interfered with lung bud growth and, further, that pulmonary agenesis should be considered part of the spectrum of malformations seen in 22q11.2 deletion. Cunningham et al. (2003) reported a second patient with VCFS, confirmed by genetic detection of 22q11.2 deletion, and unilateral primary pulmonary agenesis. High-resolution CT imaging showed a hypoplastic left lung comprising a single lobe, small left bronchus, hypoplastic left pulmonary artery, and hypoplastic left chest wall with complete shift of the trachea and mediastinum into the left hemithorax. The patient also had congenital conductive hearing loss due to malformation and subluxation of the left stapes, and hypoplasia of the left mandible.
Bassett et al. (2005) described the phenotypic features of 78 adults with 22q11 deletion syndrome and identified 43 distinct features present in more than 5% of patients. Common characteristic features included intellectual disabilities (92.3%), hypocalcemia (64%), palatal anomalies (42%), and cardiovascular anomalies (25.8%). Other less commonly appreciated features included obesity (35%), hypothyroidism (20.5%), hearing deficits (28%), cholelithiasis (19%), scoliosis (47%), and dermatologic abnormalities (severe acne, 23%; seborrhea, 35%). Significantly, schizophrenia was present in 22.6% of patients.
### Neuropsychologic Features
Golding-Kushner et al. (1985) observed that children with VCFS had 'characteristic personality features,' which were described as blunt or inappropriate affect, and that a greater than expected number of these children developed severe psychiatric illnesses as they approached adolescence.
Shprintzen et al. (1992) pointed out that psychotic illness is a feature of VCFS in adolescents or adults. In a pilot study of patients diagnosed with VCFS and their relatives, Pulver et al. (1994) found a high rate of psychosis among the patients and their relatives, suggesting that there may be a gene associated with schizophrenia (see 181500) on chromosome 22q or that a DNA rearrangement in this region may be important to the etiology of some forms of schizophrenia.
Kok and Solman (1995) emphasized the usefulness of interactive computer-based instruction for the development of reading, language, spelling, and numeracy skills in VCFS individuals.
Woodin et al. (2001) reported updated findings of neuropsychologic data from 80 children with the 22q11 deletion. The subjects showed higher verbal than nonverbal IQ scores, assets in verbal memory, and deficits in the areas of attention, story memory, visuospatial memory, arithmetic performance relative to other areas of achievement, and psychosocial functioning.
Gothelf et al. (2004) studied 43 patients with VCFS for obsessive-compulsive symptoms, using the Yale-Brown obsessive compulsive scale and a semistructured psychiatric interview. Fourteen of the subjects (32.6%) met DSM-IV criteria for obsessive-compulsive disorder (OCD; see 164230); in these patients, the symptoms began at an early age and generally responded to fluoxetine treatment. Additionally, 16 of the patients (37.2%) had attention-deficit hyperactivity disorder (ADHD; see 143465) and 7 (16.2%) had a psychotic disorder.
Gothelf et al. (2004) investigated the association of familial, developmental, and physical factors with the occurrence of ADHD in 51 patients with nonfamilial VCFS. Twenty-one patients (41.2%) were diagnosed with ADHD. There was a significantly greater prevalence of ADHD in the first-degree relatives of patients with ADHD than in those without (odds ratio, 5.9, 95% CI, 1.6-22.1; p = 0.006). ADHD and non-ADHD groups had similar IQ scores (total, verbal, and performance) and had a similar average degree of severity of facial dysmorphism and cardiac and cleft anomalies. Gothelf et al. (2004) suggested that there is a genetic contribution to ADHD in VCFS.
Evers et al. (2006) reported a 52-year-old man with 22q11.2 deletion. As a child he showed learning disabilities and behavioral problems. As a young adult, he exhibited aggressive outbursts, apathy, echolalia, perseverations, and psychotic features, including delusional thoughts and hallucinations, necessitating long-term care in a psychiatric facility. Since then, he has demonstrated aggressive behavior, periods of withdrawal, and progressive cognitive decline consistent with dementia, particularly since the age of 36 years. An affected autistic sister also had the deletion.
Evers et al. (2009) reported 7 unrelated adult patients with the 22q11.2 deletion and low cognitive function. Most had psychotic episodes in their young adult lives followed by intellectual decline. Other variable features included paranoia, aggression, mood swings, destructive behavior, autistic disorder, and dementia. At the time of the report, all were living in long-term residential care. All presented with intellectual disability, which later developed into more severe psychiatric illnesses, leading to the correct molecular diagnosis later in life.
Butcher et al. (2012) used the Vineland Adaptive Behavior Scales to assess functioning in 100 adults with 22q11.2 deletion syndrome (46 males; mean age = 28.8 (SD = 9.7) years) where intellect ranged from average to borderline (57 individuals) to mild intellectual disability (43 individuals). More than 75% of the subjects scored in the functional deficit range. Although personal, vocational, and financial demographics confirmed widespread functional impairment, daily living skills and employment were relative strengths. Intelligence quotient was a significant predictor (p less than 0.001) of overall and domain-specific adaptive functioning skills. A diagnosis of schizophrenia was a significant predictor (p less than 0.05) of overall adaptive functioning, daily living skills, and socialization scores. Notably, congenital heart disease, history of mood/anxiety disorders, sex, and age were not significant predictors of functioning. Butcher et al. (2012) concluded that, despite functional impairment in adulthood that is primarily mediated by cognitive and psychiatric phenotypes, relative strengths in activities of daily living and employment have important implications for services and long-term planning in patients with 22q11.2 deletion syndrome.
Van et al. (2016) investigated the relationship of small for gestational age (SGA) birth weight (less than 3rd percentile for sex and gestational age) and prematurity (less than 37 weeks' gestation) to expression of schizophrenia in a well-characterized cohort of 123 adults with 22q11 deletion syndrome. SGA birth weight (OR = 3.52, 95% CI 1.34-9.22) and prematurity (OR = 5.38, 95% CI = 1.63-17.75), but not maternal factors, were significant risk factors for schizophrenia in 22q11.2 deletion syndrome. Being born SGA or premature resulted in a positive predictive value of 46% for schizophrenia; negative predictive value in the absence of both features was 83%. Post hoc analyses suggested that these perinatal complications were also associated with factors indicative of increased severity of schizophrenia. Van et al. (2016) concluded that in 22q11.2 deletion syndrome, fetal growth and gestation may have a clinically significant impact on future risk of schizophrenia.
Biochemical Features
Goodman et al. (2000) reported that 8 of 15 patients with deletions in the VCF critical region 22q11.2 had elevated proline levels ranging from 278 to 849 micromol/l while 7 were in the normal range of 51 to 271 micromol/l. Goodman et al. (2000) suggested that the hyperprolinemia (239500) is caused by the hemizygous deletion of the proline oxidase gene (606810) that maps to this region. Goodman et al. (2000) concluded that elevations in plasma proline levels should be considered a biochemical feature of the chromosome 22q11.2 deletion syndromes and suggested that patients with isolated hyperprolinemia should be studied for the microdeletion at 22q11.2.
Diagnosis
VCFS is the most common syndrome that has palatal anomalies as a major feature. A possible strategy for early detection of VCFS is the routine screening for 22q11 deletions in all infants with cleft palate (CP). Ruiter et al. (2003) evaluated this strategy as opposed to testing on clinical suspicion alone. At the Nijmegen Cleft Palate Craniofacial Center in the Netherlands, they routinely tested 58 new patients with overt CP, using FISH, for the 22q11 deletion. One deletion was identified in a newborn girl with an overt CP who was clinically not suspected of having VCFS. Based on this study and the literature, they estimated the prevalence of 22q11 deletions among children with CP, but without any other symptoms of VCFS, to be 1 in 99. They concluded that routine FISH testing for 22q11 deletions in infants with overt CP is not indicated, provided clinical follow-up is guaranteed.
Cytogenetics
The large clinical overlap between DiGeorge syndrome and velocardiofacial syndrome suggested an etiologic connection. DiGeorge syndrome is associated with microdeletions of chromosome 22q11 and is thought to be caused by reduced dosage of genes within this region, i.e., monosomy. Scambler et al. (1992) presented preliminary evidence of similar microdeletions in 22q11 in patients with VCF syndrome. Kelly et al. (1993) found monosomy for a region of 22q11 in all 12 patients with VCFS who were examined by use of DNA probes. By high-resolution banding techniques, Driscoll et al. (1992) detected an interstitial deletion of 22q11.21-q11.23 in 3 of 15 patients with VCFS. The remaining 12 patients had apparently normal chromosomes. Molecular analysis with probes from the DiGeorge chromosome region (DGCR) within 22q11 detected DNA deletions in 14 of the 15 patients. In 2 families, deletions were detected in the affected parent as well as the proband, suggesting autosomal dominant transmission of VCFS due to segregation of a deletion. Thus, further support is provided that VCFS and DGS may be the result of mutation in the same gene.
Karayiorgou et al. (1995) reported the results of 2 studies examining the genetic overlap between schizophrenia and VCFS. In the first study, they characterized 2 interstitial deletions identified on 22q11 in a sample of schizophrenic patients. The size of the deletions were estimated to be between 1.5 and 2 Mb. In the second study, they investigated whether variations in deletion size are associated with the schizophrenic phenotype in VCFS patients. The results suggested that a region of the genome that had previously been implicated by genetic linkage analysis may harbor genetic lesions that increase the susceptibility to schizophrenia. See 600850.
To ascertain the relationship between psychiatric illness, VCFS, and chromosome 22 deletions, Carlson et al. (1997) evaluated 26 VCFS patients by clinical and molecular biologic methods. The VCFS children and adolescents were found to share psychiatric disorders, including bipolar spectrum disorders and attention-deficit disorder with hyperactivity. The adult patients (more than 18 years of age) were affected with bipolar spectrum disorders. Four of 6 adult patients had psychotic symptoms manifested by paranoid and grandiose delusions. Loss of heterozygosity (LOH) analysis of all 26 patients revealed that all but 3 had a large 3-Mb common deletion. One patient had a nested distal deletion and 2 did not have a detectable deletion, even when analyzed with a large number of sequence tagged sites (STSs) at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remarkably high prevalence of bipolar spectrum disorders, in association with the congenital anomalies of VCFS and its occurrence among nondeleted VCFS patients, suggested a common genetic etiology.
Morrow et al. (1995) used 11 short tandem-repeat polymorphic (STRP) markers to study 15 VCFS individuals and their unaffected parents. Haplotypes generated by these markers revealed that 82% of the patients had deletions. All patients who had a deletion shared a common proximal breakpoint, while there were 2 distinct distal breakpoints. Markers D22S941 and D22S944 appeared to be consistently hemizygous in patients with deletions. Both of these markers are located on a single nonchimeric YAC that is 400 kb long. Parental origin of the deleted chromosome had no effect on the phenotypic manifestations.
By genotyping 151 VCFS patients and performing haplotype analysis on 105, using 15 consecutive polymorphic markers in 22q11, Carlson et al. (1997) found that 83% had a deletion and more than 90% of these had a similar deletion of approximately 3 Mb, suggesting that sequences flanking the common breakpoints are susceptible to rearrangement. They found no correlation between the presence or size of the deletion and the phenotype. To define further the chromosomal breakpoints among the VCFS patients, they developed somatic hybrid cell lines from a set of VCFS patients. An 11-kb resolution physical map of a 1,080-kb region that included deletion breakpoints was constructed, incorporating genes and ESTs isolated by the hybridization selection method. The ordered markers were used to examine the 2 separated copies of chromosome 22 in the somatic hybrid cell lines. In some cases, they could map the chromosome breakpoints within a single cosmid.
Edelmann et al. (1999) developed hamster-human somatic hybrid cell lines from VCFS/DGS patients and showed by use of haplotype analysis with a set of 16 ordered genetic markers on 22q11 that the breakpoints occurred within similar low copy repeats, designated LCR22s. Models were presented to explain how the LCR22s can mediate different homologous recombination events, thereby generating a number of rearrangements that are associated with congenital anomaly disorders.
Shaikh et al. (2000) completed sequencing of the 3-Mb typically deleted region (TDR) and identified 4 LCRs within it. Although the LCRs differed in content and organization of shared modules, those modules that were common between them shared 97 to 98% sequence identity with one another. Sequence analysis of rearranged junction fragments from variant deletions in 3 DGS/VCFS patients implicated the LCRs directly in the formation of 22q11.2 deletions. FISH analysis of nonhuman primates suggested that the duplication events which generated the nest of LCRs may have occurred at least 20 to 25 million years ago.
Saitta et al. (2004) traced the grandparental origin of regions flanking de novo 3-Mb deletions in 20 informative 3-generation families with DiGeorge or velocardiofacial syndromes. Haplotype reconstruction of the flanking regions showed an unexpectedly high number of proximal interchromosomal exchanges between homologs, occurring in 19 of 20 families, whereas the normal chromosome 22 in these probands showed interchromosomal exchanges in 2 of 15 informative meioses, a rate consistent with the genetic distance. Immunostaining with MLH1 (120436) antibody localized meiotic exchanges to the distal region of chromosome 22q in 75% of human spermatocytes tested, also reflecting the genetic map. There was no effect of proband gender or parental age on crossover frequency, and parental origin studies in 65 de novo 3-Mb deletions demonstrated no bias. Unlike Williams syndrome (194050), FISH analysis showed no chromosomal inversions flanked by LCRs in 22 sets of parents of 22q11-deleted patients or in 8 nondeleted patients with a DGS/VCFS phenotype. Saitta et al. (2004) concluded that significant aberrant interchromosomal exchange events during meiosis I in the proximal region of the affected chromosome 22 are the likely etiology for these deletions. Since this type of exchange occurs more often for 22q11 deletions than for deletions of 7q11, 15q11, 17p11, and 17q11, they suggested that there is a difference in the meiotic behavior of chromosome 22.
Sahoo et al. (2011) analyzed 38,779 individuals referred to the diagnostic laboratory for microarray testing for the presence of copy number variants encompassing 20 putative schizophrenia susceptibility loci. They also analyzed the indications for study for individuals with copy number variants overlapping those found in 6 individuals referred for schizophrenia. After excluding larger gains or losses that encompassed additional genes outside the candidate loci (e.g., whole-arm gains/losses), Sahoo et al. (2011) identified 1,113 individuals with copy number variants encompassing schizophrenia susceptibility loci and 37 individuals with copy number variants overlapping those present in the 6 individuals referred for schizophrenia. Of these, 1,035 had a copy number variant of 1 of 6 recurrent loci: 1q21.1 (612474, 612475), 15q11.2 (608636), 15q13.3 (612001), 16p11.2 (611913), 16p13.11 (610543, 613458), and 22q11.2 (see also 608363). The indications for study for these 1,150 individuals were diverse and included developmental delay, intellectual disability, autism spectrum, and multiple congenital anomalies. Sahoo et al. (2011) identified the 22q11.2 microdeletion in 186 individuals; 38 were de novo, 4 maternally inherited, 4 paternally inherited, and 140 of unknown inheritance. The average age at diagnosis was 7.1 years with an age range of 0.2 to 50.1 years, and the indications for study included development delay, behavioral abnormalities, dysmorphic features, multiple congenital anomalies, congenital heart defect, failure to thrive, autism, hypocalcemia, seizure disorder, postaxial polydactyly, and clubfeet. This deletion was seen in 115 of 23,250 cases referred to their laboratory for a frequency of 0.49%, and not at all in 5,674 controls for a p value of less than 0.0001 (see Itsara et al., 2009). The incidence in a schizophrenia population reported by Kirov et al. (2009) was 0.2% compared to 0.0% in their controls. Sahoo et al. (2011) concluded that the results from their study, the largest genotype-first analysis of schizophrenia susceptibility loci to that time, suggested that the phenotypic effects of copy number variants associated with schizophrenia are pleiotropic and implied the existence of shared biologic pathways among multiple neurodevelopmental conditions.
Heterogeneity
Tsai et al. (1999) reported a child with congenital heart disease (atrial septal defect, ventricular septal defect, pulmonic stenosis), submucosal cleft palate, hypernasal speech, learning difficulties, and right fifth finger anomaly, features consistent with velocardiofacial syndrome. The child did not have a 22q deletion based on FISH analysis using the probe D22S75; however, cytogenetic analysis demonstrated a terminal deletion of 4q34.2-qter. The authors suggested that a distal 4q deletion may lead to a syndrome similar to velocardiofacial syndrome and emphasized the importance of searching for other chromosome abnormalities when a phenotype of velocardiofacial syndrome is present and a 22q deletion is not detected.
Van Esch et al. (1999) reviewed 35 cases of del10p13-p14 plus one of their own (see 601362) and compared the phenotypic spectrum with that of classic DGS/VCFS associated with del22q11 as defined by Ryan et al. (1997). Both groups of patients may have facial dysmorphism, renal anomalies, hypoparathyroidism, and immune defect. However, severe growth and mental retardation were noted in almost all patients with del10p but not in those with del22q11. Heart defects were less frequent in del10p. A distinct feature in del10p was the presence of progressive sensorineural deafness, whereas in del22q11 the hearing loss was mostly conductive due to palate deformities and velopharyngeal insufficiency. In both groups, the full clinical picture was rarely seen.
Inheritance
Carelle-Calmels et al. (2009) noted that deletion of 22q11.2, resulting in DGS or VCFS, is usually sporadic but has been reported to be inherited in 6 to 28% of patients with these syndromes. They performed cytogenetic studies of the parents of a girl with DGS (or VCFS) who had a deletion of 22q11.2 and found an unexpected rearrangement of both 22q11.2 regions in the unaffected father. He carried a 22q11.2 deletion on one copy of chromosome 22 and a reciprocal 22q11.2 duplication (see 608363) on the other copy of chromosome 22. Genetic compensation, which is consistent with the normal phenotype of the father, was shown through quantitative-expression analyses of genes located within the genetic region associated with the 22q11 deletion syndrome. Carelle-Calmels et al. (2009) noted that this finding has implications for genetic counseling.
Delio et al. (2013) genotyped a total of 389 DNA samples from 22q11 deletion syndrome-affected families. A total of 219 (56%) individuals with 22q11 deletion had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, similar to data for the general population in 11 countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6 to 1.7 times greater than that for males, suggesting that for this region in the genome enhanced meiotic recombination rates, as well as other 22q11.2-specific features, could be responsible for the observed excess in maternal origin.
Molecular Genetics
Using a YAC clone containing the VCFS critical region on chromosome 22q11 as a substrate for cDNA selection, Sirotkin et al. (1996) derived a cDNA that encodes a clathrin heavy chain gene (CLTD; 601273). FISH studies revealed that a cosmid containing the CLTD gene mapped to chromosome 22q11 and was deleted from 2 patients with VCFS who had previously been shown to have deletions of chromosome 22q11. Sirotkin et al. (1996) noted that because VCFS is a complex disorder with significant variability in phenotype and penetrance, it is likely that a number of genes in the commonly deleted region contribute to the phenotype.
Sirotkin et al. (1997) identified a novel gene, termed transmembrane protein deleted in VCFS (TMVCF; 602101), in the VCFS critical region. They localized the TMVCF gene between polymorphic markers D22S944 and D22S941, both of which are deleted in more than 80% of VCFS patients.
Carlson et al. (1997) delineated a 480-kb critical region for VCFS, including the genes for GSCL (601845), SLC25A1 (190315), CLTD, HIRA (600237), and TMVCF, as well as a number of novel ordered ESTs.
Dunham et al. (1992) pointed out that the HP500 sequence often deleted in VCFS is located within the same 450-kb yeast artificial chromosome (YAC) as the catechol-O-methyltransferase (COMT; 116790) gene, which might, therefore, be deleted also in this disorder.
Murphy et al. (1999) examined 50 adults with VCFS using a structured clinical interview to establish a DSM-IV diagnosis. Twelve percent of this sample of 50 patients were referred from a psychiatry clinic; the remainder came from genetics or cardiology. Fifteen individuals with VCFS (30%) had a psychotic disorder, with 12 (24%) fulfilling DSM-IV criteria for schizophrenia. In addition, 6 (12%) had major depression without psychotic features. The individuals with schizophrenia had fewer negative symptoms and a relatively later age of onset compared with those with schizophrenia without VCFS. Murphy et al. (1999) found no evidence that possession of the low-activity COMT allele (val158-to-met; 116790.0001) was associated with schizophrenia in their sample.
Baker et al. (2005) studied 2 hypotheses: first, that individuals with 22q11 deletion syndrome would manifest specific cognitive and neurophysiologic abnormalities in common with individuals at high risk for schizophrenia in the general population; and second, that the COMT val108/158met polymorphism would modify the severity of endophenotypic features. Adolescents and young adults with 22q11 deletion syndrome, aged 13-21, were compared with age- and IQ-matched control subjects on measures that were associated with risk for idiopathic schizophrenia. These individuals displayed poorer verbal working memory and expressive language performance than control subjects. Auditory mismatch negativity event-related potentials were reduced at frontal electrodes but intact at temporal sites. The presence of the COMT val108/158met allele on the single intact chromosome 22 was associated with more marked auditory mismatch negativity amplitude reduction and poorer neuropsychologic performance. Neither allele influenced psychiatric symptoms.
Glaser et al. (2006) tested measures of executive function, IQ, and memory in 34 children and young adults with the 22q11.2 deletion syndrome (14 hemizygous for COMT val158 and 30 for met158). No significant differences were detected between met- and val-hemizygous participants on measures of executive function. The groups did not differ on full-scale, performance, and verbal IQ or on verbal and visual memory. Glaser et al. (2006) suggested that either the COMT polymorphism has a small effect on executive function in 22q11.2 deletion syndrome or no effect exists at all.
Yagi et al. (2003) demonstrated mutations in the TBX1 gene in patients with the conotruncal anomaly face syndrome (217095)/velocardiofacial syndrome (602054.0001 and 602054.0003).
Paylor et al. (2006) identified a heterozygous 23-bp deletion in the TBX1 gene (602054.0004) in a mother and 2 sons with velocardiofacial syndrome. The mother had major depression (608516) and 1 of the sons was diagnosed with Asperger syndrome (see, e.g., 608638 and 209850). Paylor et al. (2006) suggested that the Tbx1 gene is a candidate for psychiatric disease in patients with VCFS and DiGeorge syndrome.
Kaminsky et al. (2011) presented the largest copy number variant case-control study to that time, comprising 15,749 International Standards for Cytogenomic Arrays cases and 10,118 published controls, focusing on recurrent deletions and duplications involving 14 copy number variant regions. Compared with controls, 14 deletions and 7 duplications were significantly overrepresented in cases, providing a clinical diagnosis as pathogenic. The 22q11.2 deletion was identified in 93 cases and no controls for a p value of 9.15 x 10(-21) and a frequency in cases of 1 of 169.
Genotype/Phenotype Correlations
McDonald-McGinn et al. (2001) reported on 30 individuals with the 22q11 deletion that were identified following the diagnosis in a relative. Sixty percent of patients had no visceral anomalies. In fact, only 6 of the 19 adults (32%) and 6 of the 11 children (55%) had major findings which would have brought them to medical attention. Deletion sizing demonstrated the same large 3- to 4-Mb deletion in most families despite wide inter- and intrafamilial variability, and there was no difference in clinical findings based on the parent of origin. Thus, no genotype-phenotype correlations could be made.
Pathogenesis
By analyzing head profile radiographs, Molsted et al. (2010) found an increased frequency of abnormalities in the morphology of the sella turcica in 33 patients with VCFS, including 30 with either velopharyngeal insufficiency or palatal abnormalities, compared to controls. VCFS patients showed deviations mostly in the posterior part of the dorsum sellae, and patients had increased cranial base angles compared to controls. Molsted et al. (2010) noted that abnormal morphology of the cranial base and the sella turcica should be considered a cranial malformation. Taking into account that the main features of the disorder are palatal abnormalities, thymic hypoplasia, hypothyroidism, and cardiac defects, the findings of Molsted et al. (2010) suggested a defect in the neural crest developmental field that includes the thyroid, thymus, and conotruncal septum of the heart.
Animal Model
Jerome and Papaioannou (2001) investigated the potential role of the Tbx1 gene (602054) in the causation of the DiGeorge/velocardiofacial syndrome (DGS/VCFS) phenotype. This gene, which encodes a transcription factor of the T-box family, maps to 22q11. They produced a null mutation of the Tbx1 gene in mice and found that mice heterozygous for the mutation had a high incidence of cardiac outflow tract anomalies, thus modeling one of the major abnormalities of the human syndrome. Moreover, Tbx1 -/- mice displayed a wide range of developmental anomalies encompassing almost all of the common DGS/VCFS features, including hypoplasia of the thymus and parathyroid glands, cardiac outflow tract abnormalities, abnormal facial structures, abnormal vertebrae, and cleft palate. On the basis of this phenotype in mice, Jerome and Papaioannou (2001) proposed that TBX1 in humans has a role in the etiology of DGS/VCFS.
Merscher et al. (2001) used a Cre-loxP strategy to generate mice that were hemizygous for a 1.5-Mb deletion corresponding to that on 22q11 in VCFS/DGS patients. These mice exhibited significant perinatal lethality and had conotruncal and parathyroid defects. The conotruncal defects could be partially rescued by a human BAC containing the TBX1 gene. Mice heterozygous for a null mutation in Tbx1 developed conotruncal defects. These results together with the expression patterns of TBX1 suggested a major role for the TBX1 gene in the molecular etiology of VCFS/DGS.
Funke et al. (2001) reported that mice overexpressing 4 transgenes (PNUTL1, 602724; GP1BB, 138720; TBX1; and WDR14, 610778) had chronic otitis media, a hyperactive circling behavior, and sensorineural hearing loss. This was associated with middle and inner ear malformations analogous to human Mondini dysplasia, reported to occur in VCFS/DGS patients. Based upon its pattern of expression in the ear and functional studies of the gene, the authors hypothesized that Tbx1 likely plays a central role in the etiology of ear defects in these mice, and that haploinsufficiency of TBX1 may be responsible for ear disorders in VCFS/DGS patients.
The CRKL gene (602007) encodes an SH2-SH3-SH3 adaptor protein closely related to the Crk (164762) gene products. CRKL maps within the common deletion region for DGS/VCFS. Guris et al. (2001) reported that mice homozygous for a targeted null mutation at the Crkl locus exhibited defects in multiple cranial and cardiac neural crest derivatives including the cranial ganglia, aortic arch arteries, cardiac outflow tract, thymus, parathyroid glands, and craniofacial structures. They showed that the migration and early expansion of the neural crest cells is unaffected in Crkl -/- embryos. Guris et al. (2001) concluded that the similarity between the Crkl -/- phenotype and the clinical manifestations of DGS/VCFS implicate defects in CRKL-mediated signaling pathways as part of the molecular mechanism underlying this syndrome.
Schinke and Izumo (2001) reviewed the genetic structure of the 22q11 region associated with DGS and the syntenic region of mouse chromosome 16. The gene order is inverted between human and mouse in a segment of this region. A table accompanying the figure summarized the phenotypes of mice homozygous or heterozygous mutant for chromosomal deletions or gene mutations of specific regions.
Df1/+ mice, which model del22q11, present with reduced penetrance of cardiovascular defects similar to those seen in deleted patients but not with other del22q11-like findings. The reduced penetrance of cardiovascular defects is caused by the ability of mutant embryos to recover from a fourth pharyngeal arch artery growth abnormality that is fully penetrant in early embryos. Taddei et al. (2001) showed that genetic background has a major effect on the penetrance of cardiovascular defects by affecting this embryonic recovery process. This effect could not be explained by allelic variation at the haploid locus, and is likely to be caused by genetic modifiers elsewhere in the genome. Taddei et al. (2001) also showed that genetic factors control extension of the Df1/+ phenotype to include thymic and parathyroid anomalies, establishing the Df1 mouse as a model for the genetic analysis of 3 major features of human del22q11 syndrome. They found that in Df1/+ mice, as in human patients, expression of the heart and thymic phenotypes are essentially independent of each other, suggesting that they may be controlled by different genetic modifiers.
Stalmans et al. (2003) reported that absence of the 164-amino acid isoform of Vegf (Vegf164; see 192240), the only one that binds neuropilin-1 (602069), causes birth defects in mice reminiscent of those found in patients with deletion of 22q11. The close correlation of birth and vascular defects indicated that vascular dysgenesis may pathogenetically contribute to the birth defects. Vegf interacted with Tbx1 (602054), as Tbx1 expression was reduced in Vegf164-deficient embryos and knocked-down Vegf levels enhanced the pharyngeal arch artery defects induced by Tbx1 knockdown in zebrafish. Moreover, initial evidence suggested that a Vegf promoter haplotype was associated with an increased risk for cardiovascular birth defects in del22q11 individuals. Stalmans et al. (2003) concluded that genetic data in mouse, fish, and human indicated that VEGF is a modifier of cardiovascular birth defects in the del22q11 syndrome.
Liao et al. (2004) reported that mice hemizygous for a null allele of Tbx1 had mild malformations, while homozygotes had severe malformations in the affected structures. Neither pattern of malformation precisely modeled VCFS or DGS. Furthermore, bacterial artificial chromosome (BAC) transgenic mice overexpressing human TBX1 and 3 other transgenes had similar malformations to VCFS/DGS patients. By employing genetic complementation studies, the authors demonstrated that altered TBX1 dosage, rather than overexpression of the other transgenes, was responsible for most of the defects in the BAC transgenic mice. Furthermore, the full spectrum of VCFS/DGS malformations was elicited in a TBX1 dose-dependent manner, thus providing a molecular basis for the pathogenesis and varied expressivity of the syndrome.
Sigurdsson et al. (2010) studied Df(16)A(+/-) mice, which model a microdeletion on human chromosome 22q11.2 that constitutes one of the largest known genetic risk factors for schizophrenia. To examine functional connectivity in these mice, Sigurdsson et al. (2010) measured the synchronization of neural activity between the hippocampus and the prefrontal cortex during the performance of a task requiring working memory, which is one of the cognitive functions disrupted in the disease. In wildtype mice, hippocampal-prefrontal synchrony increased during working memory performance, consistent with previous reports in rats. Df(16)A(+/-) mice, which are impaired in the acquisition of the task, showed drastically reduced synchrony, measured both by phase-locking of prefrontal cells to hippocampal theta oscillations and by coherence of prefrontal and hippocampal local field potentials. Furthermore, the magnitude of hippocampal-prefrontal coherence at the onset of training could be used to predict the time it took the Df(16)A(+/-) mice to learn the task and increased more slowly during task acquisition. Sigurdsson et al. (2010) concluded that their data suggested how the deficits in functional connectivity observed in patients with schizophrenia may be realized at the single-neuron level, and further suggested that impaired long-range synchrony of neural activity is one consequence of the 22q11.2 deletion and may be a fundamental component of the pathophysiology underlying schizophrenia.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly Face \- Long \- Pierre Robin syndrome \- Retrognathia Ears \- Minor auricular anomalies Eyes \- Narrow palpebral fissures \- Small optic discs \- Tortuous retinal vessels \- Posterior embryotoxon Nose \- Square nasal root \- Decreased nasopharyngeal lymphoid tissue \- Prominent tubular nose \- Hypoplastic nasal alae \- Bulbous nasal tip Mouth \- Cleft palate \- Velopharyngeal insufficiency \- Small open mouth \- Pharyngeal hypotonia CARDIOVASCULAR Heart \- Congenital abnormality in 85% \- Ventricular septal defect \- Tetralogy of Fallot Vascular \- Right aortic arch \- Aberrant left subclavian \- Internal carotid artery abnormalities RESPIRATORY Lung \- Primary pulmonary dysgenesis, unilateral (reported in 2 unrelated patients) ABDOMEN External Features \- Inguinal hernia \- Umbilical hernia SKELETAL Hands \- Slender hands and digits NEUROLOGIC Central Nervous System \- Learning disability \- Mental retardation Behavioral Psychiatric Manifestations \- Blunt or inappropriate affect \- Psychotic illness \- Paranoia \- Autistic features \- Aggression \- Mood swings VOICE \- Nasal voice ENDOCRINE FEATURES \- Neonatal hypocalcemia, rare IMMUNOLOGY \- Frequent infections T-lymphocyte dysfunction, rare LABORATORY ABNORMALITIES \- Monosomy for 22q11 MISCELLANEOUS \- Overlapping features of DiGeorge syndrome \- Incidence is estimated to be between 1 in 2,000 to 1 in 7,000 live births MOLECULAR BASIS \- A contiguous gene syndrome caused by deletion (1.5Mb - 3.0Mb) of 22q11.2 ▲ 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
VELOCARDIOFACIAL SYNDROME
|
c0012236
| 7,789 |
omim
|
https://www.omim.org/entry/192430
| 2019-09-22T16:32:02 |
{"doid": ["12583"], "mesh": ["D004062"], "omim": ["192430"], "icd-9": ["758.32"], "icd-10": ["Q93.81"], "orphanet": ["567"], "synonyms": ["Alternative titles", "CHROMOSOME 22q11.2 DELETION SYNDROME", "VCF SYNDROME", "SHPRINTZEN VCF SYNDROME"], "genereviews": ["NBK1523"]}
|
Paroxysmal kinesigenic choreoathetosis
Other namesFamilial PKD
Paroxysmal kinesigenic choreoathetosis is inherited in an autosomal dominant manner
SpecialtyNeurology
Paroxysmal kinesigenic choreoathetosis (PKC) also called paroxysmal kinesigenic dyskinesia (PKD) is a hyperkinetic movement disorder characterized by attacks of involuntary movements, which are triggered by sudden voluntary movements. The number of attacks can increase during puberty and decrease in a person's 20s to 30s. Involuntary movements can take many forms such as ballism, chorea or dystonia and usually only affect one side of the body or one limb in particular. This rare disorder only affects about 1 in 150,000 people,[1] with PKD accounting for 86.8% of all the types of paroxysmal dyskinesias,[2] and occurs more often in males than females. There are two types of PKD, primary and secondary. Primary PKD can be further broken down into familial and sporadic. Familial PKD, which means the individual has a family history of the disorder, is more common, but sporadic cases are also seen.[3] Secondary PKD can be caused by many other medical conditions such as multiple sclerosis (MS), stroke, pseudohypoparathyroidism,[4] hypocalcemia, hypoglycemia, hyperglycemia,[3] central nervous system trauma, or peripheral nervous system trauma.[5] PKD has also been linked with infantile convulsions and choreoathetosis (ICCA) syndrome, in which patients have afebrile seizures during infancy (benign familial infantile epilepsy) and then develop paroxysmal choreoathetosis later in life.[6] This phenomenon is actually quite common, with about 42% of individuals with PKD reporting a history of afebrile seizures as a child.[6]
## Contents
* 1 Genetics
* 2 Pathophysiology
* 2.1 SPECT studies
* 2.2 fMRI studies
* 2.3 Diffusion tensor imaging
* 3 Diagnosis
* 4 Treatment
* 5 History
* 6 See also
* 7 References
* 8 External links
## Genetics[edit]
Paroxysmal kinesigenic dyskinesias are often inherited in an autosomal dominant fashion and several genes have now been identified where mutations can cause this disease. The genes typically code for proteins known to be involved in synaptic transmission, ion channels or ion transporters.[7] The first gene to be identified was the PRRT2 gene on chromosome 16, found in 2011 to be the cause of the disease in some patients.[8] The mutations in this gene included a nonsense mutation identified in the genome of one family and an insertion mutation identified in the genome of another family.[9] Researchers found PRRT2 mutations in 10 of 29 sporadic cases affected with PKD, thus suggests PRRT2 is the gene mutated in a subset of PKD and PKD is genetically heterogeneous.[10] Later reports have identified the genes SCN8A, CHRNA4, and SLC16A2 as further causes of PKD.[7]
## Pathophysiology[edit]
The pathophysiology of PKD is not fully explained. A few mechanisms have been suggested thus far:
1. GABA dysregulation
2. Abnormal breakdown of dopamine in the basal ganglia
3. Dysfunction of the substantia nigra[11]
4. A form of epilepsy[2]
Multiple methods are being used to study the potential brain abnormalities of individuals with PKD compared with “normal” individuals. These methods include SPECT studies, fMRI studies, and diffusion tensor imaging. The main problem with many of the studies concerned with the pathophysiology of the disorder is the small sample size. Because the studies normally only include about 7-10 patients with PKD, the results cannot be generalized to the entire population of patients. However, the studies do bring up possibilities for further study.
### SPECT studies[edit]
In a study by Joo et al., the researchers performed interictal studies, meaning they scanned the patient's brain between attacks to find an underlying abnormality, rather than ictal scans, which look at the abnormalities that present themselves during an attack.[11] The researchers found interictally decreased cerebral blood flow in the posterior parts of the bilateral caudate nucleus.[11] However, the literature does state that although this could be a cause of PKD, it could also be a result of PKD.[11] Another SPECT study showed an increase in the cerebral blood flow in the left posterior thalamus in a PKD patient during an attack.[12] The researchers also subtracted the ictal from the postictal scans, and saw increased blood flow in the thalamus. They ultimately suggested that hyperactive blood flow in this area could be causing the pathophysiology of PKD. This study, however, was only performed on one patient, and would need to be replicated many more times in order to be generalized to the population of PKD patients. Other SPECT studies have been cited showing hyperactivity in the basal ganglia.[13]
### fMRI studies[edit]
In a study by Zhou et al.,[14] the researchers performed fMRI studies on PKD patients, and analyzed the differences between the amplitude low frequency fluctuations (ALFF) of the patients. They found that the left postcentral gyrus and the bilateral putamen had increased ALFF in PKD patients.[14] The researchers concluded that the hyperactivity in these regions suggested that there is a dysfunction in the basal ganglia-thalamo-cortical circuit in PKD. This circuit is part of the motor control circuit in the brain, making it a reasonable place for abnormality in a movement disorder, but again, researchers are still unsure of the role these differences they found play in the disease pathology.
### Diffusion tensor imaging[edit]
Diffusion tensor imaging (DTI) displays physical alterations in the brain that may not be seen on regular MRI.[13] In one study researchers found that some of the patients had abnormalities in their thalamus. However, this does not prove that all patients have abnormalities in their thalamus. Other cases are cited, including a patient who developed a similar paroxysmal dyskinesia after a thalamic infarction,[13] implicating that an abnormality in the thalamus of individuals could contribute to PKD. It is not fully known, however, what role a thalamic abnormality plays in the disease pathophysiology.
## Diagnosis[edit]
Paroxysmal kinesigenic dyskinesia is diagnosed using a strict set of guidelines. These criteria were studied and confirmed by Bruno et al. in a study of 121 individuals with PKD.[3] The age at onset is between 1 and 20 years old. The attacks of involuntary movements last less than one minute and have a known trigger, usually a sudden voluntary movement. For example, if a PKD patient stands up or begins walking after being sedentary for a period of time, or a person goes from a walk to a run, it can trigger an attack. Persons with PKD do not lose consciousness during attacks and have a full memory of the entire attack. Lastly, people with the disorder have a good response to medication and are usually prescribed anticonvulsants. The study also found that patients with familial PKD exhibit symptoms that follow the diagnostic criteria closely, while sporadic PKD individuals may deviate slightly.[5] Prior to criteria for diagnosis being set out, many patients with PKD were often diagnosed with some form of epilepsy. Many patients also experience an aura, similar to those experienced with epilepsy, preceding their attacks. Some patients describe it as a tingling sensation in the affected limb or “butterflies in their stomach.” Some individuals also have precipitants, such as stress and anxiety, that make it more likely for attacks to occur.
The above diagnostic criteria also set PKD apart from the other paroxysmal dyskinesias, which include paroxysmal nonkinesigenic dyskinesia (PNKD) and paroxysmal exercise-induced dyskinesia (PED). While PKD attacks last less than one minute, PNKD attacks last a few minutes to a few hours, and as the name suggests, the attacks do not occur because of a sudden voluntary movement like PKD.[5] Additionally, PKD can almost always be managed with drug therapy, while PNKD is not as responsive to anticonvulsants. PED, on the other hand, separates itself from PKD in that it is caused by prolonged exercise. Attacks from PED will cease soon after exercise is stopped.[5]
## Treatment[edit]
Almost all patients respond positively to antiepileptic (anticonvulsant) drugs. One of the drugs most often mentioned in the literature is carbamazepine, and is the most widely used drug for treating PKD. Other anticonvulsants like valproic acid, phenytoin and clonazepam are common alternatives. Other categories of drugs have also been used, such as dopamine affecting drugs like Levodopa or Tetrabenazine.[5] Individuals with the disorder can also modify their behavior to lessen their attacks without the influence of drug therapy. For example, decreasing stress to avoid precipitants can help patients decrease the number of attacks. In addition, avoiding any sudden movements can also prevent an attack. In order to prevent an attack, some individuals use their auras as a warning, while others purposefully perform slow gestures or movements prior to a triggering movement.[2] Many, if not most, individuals end up growing out of the attacks with age, even without medicinal therapy, but some patients will go back to having attacks after a period of remission.[3] In regards to secondary PKD, treatment of the primary condition can lessen the PKD attacks in those individuals.[5]
## History[edit]
A movement order similar to PKD first mentioned in research literature in 1940 by Mount and Reback. They described a disorder consisting of attacks of involuntary movements but unlike PKD, the attacks lasted minutes to hours and were found to be caused by alcohol or caffeine intake.[15] They named it paroxysmal dystonic choreoathetosis. Kertesz later described another new movement disorder in 1967. He described a disorder that was induced by sudden movements, and responded to anticonvulsants, naming it paroxysmal kinesigenic choreoathetosis. Finally in a review in 1995 Demirkiran and Jankovic stated the disease should be called paroxysmal kinesigenic dyskinesia instead, pointing out that the attacks could manifest as any form of dyskinesia, not just choreoathetosis.[15]
## See also[edit]
* Paroxysmal dyskinesia
* Paroxysmal nonkinesogenic dyskinesia
* Paroxysmal exercise-induced dystonia
## References[edit]
1. ^ Khan, W. U.; Staios, G.; Rana, A. Q. (2010). "Paroxysmal kinesigenic dyskinesia in a mother and daughter". Acta Neurologica Belgica. 110 (2): 201–202. PMID 20873453.
2. ^ a b c Zhou, J. Q.; Zhou, L. M.; Fang, Z. Y.; Wang, Q.; Chen, Z. Y.; Yang, L. B.; Chen, S. D.; Cai, X. D. (2011). "Analyzing clinical and electrophysiological characteristics of Paroxysmal Dyskinesia". Journal of Research in Medical Sciences. 16 (1): 110–114. PMC 3063430. PMID 21448393.
3. ^ a b c d Bruno, M. K.; Hallett, M.; Gwinn-Hardy, K.; Sorensen, B.; Considine, E.; Tucker, S.; Lynch, D. R.; Mathews, K. D.; Swoboda, K. J.; Harris, J.; Soong, B. W.; Ashizawa, T.; Jankovic, J.; Renner, D.; Fu, Y. H.; Ptacek, L. J. (2004). "Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: New diagnostic criteria". Neurology. 63 (12): 2280–2287. doi:10.1212/01.WNL.0000147298.05983.50. PMID 15623687.
4. ^ Thomas, K. P.; Muthugovindan, D.; Singer, H. S. (2010). "Paroxysmal Kinesigenic Dyskinesias and Pseudohypo-parathyroidism Type Ib". Pediatric Neurology. 43 (1): 61–64. doi:10.1016/j.pediatrneurol.2010.03.012. PMID 20682207.
5. ^ a b c d e f Mehta, S. H.; Morgan, J. C.; Sethi, K. D. (2009). "Paroxysmal dyskinesias". Current Treatment Options in Neurology. 11 (3): 170–178. doi:10.1007/s11940-009-0020-x. PMID 19364451.
6. ^ a b Weber, Y. G.; Lerche, H. (2009). "Genetics of paroxysmal dyskinesias". Current Neurology and Neuroscience Reports. 9 (3): 206–211. doi:10.1007/s11910-009-0031-8. PMID 19348709.
7. ^ a b Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA (February 2020). "The expanding spectrum of movement disorders in genetic epilepsies". Developmental Medicine and Child Neurology. 62 (2): 178–191. doi:10.1111/dmcn.14407. PMID 31784983.
8. ^ Chen, W. J.; Lin, Y.; Xiong, Z. Q.; Wei, W.; Ni, W.; Tan, G. H.; Guo, S. L.; He, J.; Chen, Y. F.; Zhang, Q. J.; Li, H. F.; Lin, Y.; Murong, S. X.; Xu, J.; Wang, N.; Wu, Z. Y. (2011). "Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia". Nature Genetics. 43 (12): 1252–1255. doi:10.1038/ng.1008. PMID 22101681.
9. ^ Wang, J. -L.; Cao, L.; Li, X. -H.; Hu, Z. -M.; Li, J. -D.; Zhang, J. -G.; Liang, Y.; San-a; Li, N.; Chen, S. -Q.; Guo, J. -F.; Jiang, H.; Shen, L.; Zheng, L.; Mao, X.; Yan, W. -Q.; Zhou, Y.; Shi, Y. -T.; Ai, S. -X.; Dai, M. -Z.; Zhang, P.; Xia, K.; Chen, S. -D.; Tang, B. -S. (2011). "Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias". Brain. 134 (12): 3493–3501. doi:10.1093/brain/awr289. PMC 3235563. PMID 22120146.
10. ^ Li J, Zhu X, Wang X et al. J Med Genet. 2012 Feb;49(2):76-8. Epub 2011 Nov 30. Targeted genomic sequencing identifies PRRT2 mutations as a cause of paroxysmal kinesigenic choreoathetosis.
11. ^ a b c d Joo, E. Y.; Hong, S. B.; Tae, W. S.; Kim, J. H.; Han, S. J.; Seo, D. W.; Lee, K. H.; Kim, M. H.; Kim, S.; Lee, M. H.; Kim, B. T. (2005). "Perfusion abnormality of the caudate nucleus in patients with paroxysmal kinesigenic choreoathetosis". European Journal of Nuclear Medicine and Molecular Imaging. 32 (10): 1205–1209. doi:10.1007/s00259-005-1814-z. PMID 15948007.
12. ^ Shirane, S.; Sasaki, M; Kogure, D; Matsuda, H; Hashimoto, T (2001). "Increased ictal perfusion of the thalamus in paroxysmal kinesigenic dyskinesia". Journal of Neurology, Neurosurgery & Psychiatry. 71 (3): 408–410. doi:10.1136/jnnp.71.3.408. PMC 1737540. PMID 11511723.
13. ^ a b c Zhou, B.; Chen, Q.; Gong, Q.; Tang, H.; Zhou, D. (2009). "The thalamic ultrastructural abnormalities in paroxysmal kinesigenic choreoathetosis: A diffusion tensor imaging study". Journal of Neurology. 257 (3): 405–409. doi:10.1007/s00415-009-5334-9. PMID 20012544.
14. ^ a b Zhou, B.; Chen, Q.; Zhang, Q.; Chen, L.; Gong, Q.; Shang, H.; Tang, H.; Zhou, D. (2010). "Hyperactive putamen in patients with paroxysmal kinesigenic choreoathetosis: A resting-state functional magnetic resonance imaging study". Movement Disorders. 25 (9): 1226–1231. doi:10.1002/mds.22967. PMID 20629125.
15. ^ a b Bhatia, K. P. (2011). "Paroxysmal dyskinesias". Movement Disorders. 26 (6): 1157–1165. doi:10.1002/mds.23765. PMID 21626559.
## External links[edit]
Classification
D
* ICD-10: G24.8
* OMIM: 128200
External resources
* Orphanet: 98809
* GeneReviews/NIH/NCBI/UW entry on Familial Paroxysmal Kinesigenic Dyskinesia
* OMIM entries on Familial Paroxysmal Kinesigenic Dyskinesia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Paroxysmal kinesigenic choreoathetosis
|
c1868682
| 7,790 |
wikipedia
|
https://en.wikipedia.org/wiki/Paroxysmal_kinesigenic_choreoathetosis
| 2021-01-18T18:42:43 |
{"gard": ["8721"], "orphanet": ["98809"], "wikidata": ["Q3042113"]}
|
Pelizaeus-Merzbacher like disease (PMLD) is an autosomal recessive leukodystrophy sharing identical clinical and radiological features as X-linked Pelizaeus-Merzbacher disease (PMD; see this term).
## Epidemiology
Prevalence is unknown.
## Clinical description
It is characterized by early-onset nystagmus, delayed motor milestones, progressive spasticity, ataxia, and diffuse leukodystrophy on MRI.
## Etiology
One PMLD form is due to mutations in the GJC2 gene encoding the gap junction protein C2. There are very likely other PMLD forms that have not been defined but that are caused by mutations affecting other genes involved in myelination. Other syndromes have also been referred to as PMLD but their inclusion as PMLD has been debated because of their severity and of the evidence of neuronal, besides white matter, involvement on MRI. These syndromes include an autosomal recessive syndrome due to mutations in the HSPD1 gene, encoding the heat shock protein 1, that resembles severe PMD (nystagmus, developmental delay, spasticity, feeding and breathing problems, early-onset lethality) and that is associated with acquired microcephaly, as well as a syndrome due to mutations in the AIMP1 gene, encoding the aminoacyl tRNA synthetase complex-interacting multifunctional protein 1, and characterized by nystagmus, axial hypotonia, spastic paraparesis, severe developmental delay, kyphoscoliosis, microcephaly, intellectual deficit, and absence of speech. An X-linked syndrome, allelic to Allan-Herndon-Dudley syndrome (see this term), has also been referred to as a PMLD. This syndrome is characterized by neonatal hypotonia, nystagmus, progressive spastic paraplegia, ataxia and developmental delay, and is due to mutations in the SLC16A2 gene encoding the monocarboxylate transporter 8 involved in thyroid hormone transport. However, MRI findings are not as severe as those of PMD (diffuse hypomyelination), and tend to improve over time, making this more of a delayed myelination disorder that is probably secondary to a neuronal dysfunction related to impaired thyroid hormone transport.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pelizaeus-Merzbacher-like disease
|
c1850053
| 7,791 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=280270
| 2021-01-23T17:17:50 |
{"gard": ["12300"], "mesh": ["C536319"], "omim": ["260600", "300523", "608804", "612233"], "icd-10": ["E75.2"], "synonyms": ["PMLD"]}
|
Abnormally increased distance between two body parts, usually the eyes
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: "Hypertelorism" – news · newspapers · books · scholar · JSTOR (October 2009) (Learn how and when to remove this template message)
Hypertelorism
Other namesOcular hypertelorism,[1] orbital hypertelorism,[1] hypertelorbitism[2]
Hypertelorism as seen in craniofrontonasal dysplasia
SpecialtyMedical genetics
Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as well as the distance between the pupils is greater than normal. Hypertelorism should not be confused with telecanthus, in which the distance between the inner eye corners is increased but the distances between the outer eye corners and the pupils remain unchanged.[3]
Hypertelorism is a symptom in a variety of syndromes, including Edwards syndrome (trisomy 18), 1q21.1 duplication syndrome, basal cell nevus syndrome, DiGeorge syndrome and Loeys–Dietz syndrome. Hypertelorism can also be seen in Apert syndrome, Autism spectrum disorder, craniofrontonasal dysplasia, Noonan syndrome, neurofibromatosis,[4] LEOPARD syndrome, Crouzon syndrome, Wolf–Hirschhorn syndrome, Andersen–Tawil syndrome, Waardenburg syndrome and cri du chat syndrome, along with piebaldism, prominent inner third of the eyebrows, irises of different color, spondyloepiphyseal dysplasia, mucopolysaccharide metabolism disorders (Morquio syndrome and Hurler's syndrome), deafness and also in hypothyroidism. Some links have been found between hypertelorism and attention deficit/hyperactivity disorder.
## Contents
* 1 Embryology
* 2 Treatment
* 2.1 Box osteotomy
* 2.2 Facial bipartition
* 2.3 Soft tissue reconstruction
* 2.4 Complications from surgery
* 3 See also
* 4 References
* 5 External links
## Embryology[edit]
Because hypertelorism is an anatomic condition associated with a heterogeneous group of congenital disorders, it is believed that the underlying mechanism of hypertelorism is also heterogeneous. Theories include too early ossification of the lower wings of the sphenoid, an increased space between the orbita, due to increasing width of the ethmoid sinuses, field defects during the development, a nasal capsule that fails to form, leading to a failure in normal medial orbital migration and also a disturbance in the formation of the cranial base, which can be seen in syndromes like Apert and Crouzon.[3]
## Treatment[edit]
The craniofacial surgery to correct hypertelorism is usually done between five and eight years of age. This addresses the psychosocial aspects in the child's early school years. Another reason for correction age five or older is that the surgery should be delayed until the tooth buds have grown out low enough into the maxilla, thus preventing damage to them. Also, before age five the craniofacial bones are thin and fragile, which can make surgical correction difficult. In addition, it is possible that orbital surgery during infancy may inhibit midface growth.[3]
For the treatment of hypertelorism there are two main operative options: The box osteotomy and the facial bipartition (also referred to as median fasciotomy).[5]
Box osteotomy
Facial bipartition
Hypertelorism correction
### Box osteotomy[edit]
This treatment of orbital hypertelorism was first performed by Paul Tessier.[6] The surgery starts off by various osteotomies that separate the entire bony part of the orbit from the skull and surrounding facial bones. One of the osteotomies consists of removing the bone between the orbits. The orbits are then mobilized and brought towards each other. Because this often creates excessive skin between the orbits a midline excision of skin is frequently necessary. This approximates the eyebrows and eye corners and provides a more pleasing look.[3]
### Facial bipartition[edit]
The standard procedure (box osteotomy) was modified by Jacques van der Meulen and resulted in the development of the facial bipartition (or median faciotomy).[7][8] Facial bipartition first involves splitting the frontal bone from the supraorbital rim. Then the orbits and the midface are released from the skull-base using monoblock osteotomy. Then a triangular shaped piece of bone is removed from the midline of the midface. The base of this triangular segment lies above the orbita and the apex lies between the upper incisor teeth. After removing this segment it is possible to rotate the two halves of the midface towards each other, thus resulting in reduction of the distance between the orbits. It also results in leveling out the V-shaped maxilla and therefore widening of it. Because hypertelorism is often associated with syndromes like Apert, hypertelorism is often seen in combination with midface dysplasia. If this is the case, facial bipartition can be combined with distraction osteogenesis. The aim of distraction osteogenesis of the midface is to normalize the relationship between orbital rim to eye and also normalize the position of zygomas, nose and maxilla in relation to the mandible.[9]
### Soft tissue reconstruction[edit]
To create an acceptable aesthetic result in the correction of orbital hypertelorism, it is also important to take soft-tissue reconstruction in consideration. In this context, correction of the nasal deformities is one of the more difficult procedures. Bone and cartilage grafts may be necessary to create a nasal frame and local rotation with for example forehead flaps, or advancement flaps can be used to cover the nose.[3]
### Complications from surgery[edit]
As with almost every kind of surgery, the main complications in both treatments of hypertelorism include excessive bleeding, risk of infection and CSF leaks and dural fistulas. Infections and leaks can be prevented by giving perioperative antibiotics and identifying and closing of any dural tears. The risk of significant bleeding can be prevented by meticulous technique and blood loss is compensated by transfusions. Blood loss can also be reduced by giving hypotensive anesthesia. Rarely major eye injuries, including blindness, are seen. Visual disturbances can occur due to the eye muscle imbalance after orbital mobilization. Ptosis and diplopia can also occur postoperatively, but this usually self-corrects. A quite difficult problem to correct postoperatively is canthal drift, which can be managed best by carefully preserving the canthal tendon attachments as much as possible. Despite the extensiveness in these procedures, mortality is rarely seen in operative correction of hypertelorism.[3]
## See also[edit]
* Hypotelorism
* Telecanthus
## References[edit]
1. ^ a b "ocular hypertelorism, orbital hypertelorism". TheFreeDictionary.com. Retrieved 2020-01-08.
2. ^ Weinzweig, Jeffrey (2010-04-13). Plastic Surgery Secrets Plus E-Book. Elsevier Health Sciences. p. 331. ISBN 978-0-323-08590-8.
3. ^ a b c d e f Michael L. Bentz: Pediatric Plastic Surgery; Chapter 9 Hypertelorism by Renato Ocampo, Jr., MD/ John A. Persing, MD
4. ^ Mautner, V (June 2010). "Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions" (PDF). Journal of Medical Genetics. 47 (9): 623–630. doi:10.1136/jmg.2009.075937. PMID 20543202. S2CID 5781561.
5. ^ Donald Serafin, M.D., F.A.C.S. & Nicholas G. Georgiade, D.D.S., M.D., PACS: Pediatric Plastic Surgery Volume I, 1984; Chapter 28 Orbital Hypertelorism by Ian T. Jackson
6. ^ Tessier P, Guiot G, Derome P. Orbital hypertelorism: II. Definite treatment of hypertelorism (OR.H.) by craniofacial or by extracranial osteotomies. Scand J Plast Reconstr Surg 7: 39-58, 1973
7. ^ van der Meulen, JC. The pursuit of symmetry in cranio-facial surgery. Br J Plast Surg 29: 84-91, 1976
8. ^ van der Meulen, JC. Medial faciotomy. Br J Plast Surgery 32: 339-342, 1976
9. ^ D Richardson and J K Thiruchelvam: Review Craniofacial surgery for orbital malformations http://www.nature.com/eye/journal/v20/n10/full/6702475a.html
## External links[edit]
Classification
D
* ICD-10: Q75.2
* ICD-9-CM: 376.41 756.0
* OMIM: 145400
* MeSH: D006972
* DiseasesDB: 29328
Wikimedia Commons has media related to Hypertelorism.
* v
* t
* e
Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality
Appendicular
limb / dysmelia
Arms
clavicle / shoulder
* Cleidocranial dysostosis
* Sprengel's deformity
* Wallis–Zieff–Goldblatt syndrome
hand deformity
* Madelung's deformity
* Clinodactyly
* Oligodactyly
* Polydactyly
Leg
hip
* Hip dislocation / Hip dysplasia
* Upington disease
* Coxa valga
* Coxa vara
knee
* Genu valgum
* Genu varum
* Genu recurvatum
* Discoid meniscus
* Congenital patellar dislocation
* Congenital knee dislocation
foot deformity
* varus
* Club foot
* Pigeon toe
* valgus
* Flat feet
* Pes cavus
* Rocker bottom foot
* Hammer toe
Either / both
fingers and toes
* Polydactyly / Syndactyly
* Webbed toes
* Arachnodactyly
* Cenani–Lenz syndactylism
* Ectrodactyly
* Brachydactyly
* Stub thumb
reduction deficits / limb
* Acheiropodia
* Ectromelia
* Phocomelia
* Amelia
* Hemimelia
multiple joints
* Arthrogryposis
* Larsen syndrome
* RAPADILINO syndrome
Axial
Skull and face
Craniosynostosis
* Scaphocephaly
* Oxycephaly
* Trigonocephaly
Craniofacial dysostosis
* Crouzon syndrome
* Hypertelorism
* Hallermann–Streiff syndrome
* Treacher Collins syndrome
other
* Macrocephaly
* Platybasia
* Craniodiaphyseal dysplasia
* Dolichocephaly
* Greig cephalopolysyndactyly syndrome
* Plagiocephaly
* Saddle nose
Vertebral column
* Spinal curvature
* Scoliosis
* Klippel–Feil syndrome
* Spondylolisthesis
* Spina bifida occulta
* Sacralization
Thoracic skeleton
ribs:
* Cervical
* Bifid
sternum:
* Pectus excavatum
* Pectus carinatum
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hypertelorism
|
c0020534
| 7,792 |
wikipedia
|
https://en.wikipedia.org/wiki/Hypertelorism
| 2021-01-18T18:48:01 |
{"mesh": ["D006972"], "umls": ["C0020534"], "icd-9": ["756.0", "376.41"], "icd-10": ["Q75.2"], "wikidata": ["Q1641128"]}
|
A number sign (#) is used with this entry because von Hippel-Lindau syndrome (VHL) is caused by heterozygous mutation in the VHL gene (608537) on chromosome 3p25.
Evidence suggests that variation in the cyclin D1 gene (CCND1; 168461) on chromosome 11q13 may modify the phenotype.
Homozygous or compound heterozygous mutations in the VHL gene cause familial erythrocytosis-2 (ECYT2; 263400).
Description
Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors.
Neumann and Wiestler (1991) classified VHL as type 1 (without pheochromocytoma) and type 2 (with pheochromocytoma). Brauch et al. (1995) further subdivided VHL type 2 into type 2A (with pheochromocytoma) and type 2B (with pheochromocytoma and renal cell carcinoma). Hoffman et al. (2001) noted that VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. McNeill et al. (2009) proposed that patients with VHL syndrome caused by large VHL deletions that include the HSPC300 gene (C3ORF10; 611183) have a specific subtype of VHL syndrome characterized by protection from renal cell carcinoma, which the authors proposed be named VHL type 1B.
Nordstrom-O'Brien et al. (2010) provided a review of the genetics of von Hippel-Lindau disease.
Clinical Features
The cardinal features of von Hippel-Lindau syndrome are angiomata of the retina and hemangioblastoma of the cerebellum. Hemangioma of the spinal cord has also been observed. Pheochromocytoma occurs in some patients. The combination of hypertension with angioma may lead to subarachnoid hemorrhage. Hypernephroma-like renal tumors occur in some patients. Polycythemia may be due to either the hemangioblastoma of the cerebellum or the hypernephroma. Hemangiomas of the adrenals, lungs, and liver, and multiple cysts of the pancreas and kidneys, have been observed in some instances.
Although there were many earlier reports of this syndrome (see HISTORY), Melmon and Rosen (1964) introduced the term 'von Hippel-Landau' syndrome and described a large kindred with multiple features of the disorder. The condition of arteriovenous aneurysm of retina and midbrain with facial nevus, described by Bonnet et al. (1938) and by Wyburn-Mason (1943), is of uncertain relationship to this condition. Metastatic renal cancer occurs in some instances (Kranes and Balogh, 1966). Goldberg and Duke (1968) examined the eyes of an affected 51-year-old black male whose mother died of cerebellar tumor at age 26 years. The same case was described by McKusick (1961). In addition to the association of tumors of the brain and adrenal medulla that occurs in neurofibromatosis and in von Hippel-Lindau disease, cerebellar tumors sometimes produce paroxysmal hypertension similar to that of pheochromocytoma. Urinary catecholamines are normal in such cases (Cameron and Doig, 1970).
Cysts and 'hypernephroid' tumors of the epididymis have been described in VHL patients (Grossman and Melmon, 1972). Male patients may have papillary cystadenoma of the epididymis, an unusual tumor that is bilateral when it occurs in von Hippel-Lindau disease and is not familial when unilateral (Price, 1971). The experience of Lamiell (1987) differed, however; 7 of 21 affected males in 1 kindred had an epididymal mass and 5 of these were unilateral. Tsuda et al. (1976) observed the occurrence of bilateral papillary cystadenoma of the epididymis in 3 brothers with VHL syndrome. Bilateral papillary cystadenomas of the broad ligament, presumably of mesonephric origin, is the probable homologous tumor of the female (Erbe, 1978).
In von Hippel-Lindau disease with pheochromocytoma, Atuk et al. (1979) reported hypercalcemia which was corrected in all by removal of the tumor. In several patients, pheochromocytoma antedated development of retinal lesions. Fishman and Bartholomew (1979) described 3 related patients with striking pancreatic involvement. One had exocrine pancreatic insufficiency. In an extensively affected kindred, Fill et al. (1979) found renal cell carcinoma in 16 of 42 cases and carcinoma of the pancreas in 4 of 42.
Griffiths et al. (1987) found reports of 6 patients with von Hippel-Lindau syndrome, pheochromocytoma, and islet cell tumor. A further 11 patients showed pheochromocytoma and islet cell tumor. No patient with von Hippel-Lindau syndrome had a carcinoid tumor, which is a feature of neurofibromatosis with pheochromocytoma (see 162200). No cases of neurofibromatosis had islet cell tumor. In Cardiff, Wales, 20 patients with cerebellar hemangioblastoma were seen between 1972 and 1985. In 8 of these, Huson et al. (1986) subsequently established the diagnosis of von Hippel-Lindau disease. Although the diagnosis had not previously been considered, in retrospect, 7 of the 8 cases were known to be at risk for the syndrome.
Jennings et al. (1988) demonstrated the usefulness of family studies in determining asymptomatic lesions requiring treatment, such as renal cell carcinoma. They also reported the occurrence of a spermatic cord mesenchymal hamartoma in this disorder. Lamiell et al. (1989) identified 43 affected members in a large kindred, which was exceptional for absence of pheochromocytoma and erythrocythemia, for more renal and pancreatic cysts and malignancies, and for somewhat fewer eye or central nervous system lesions. Bilateral renal adenocarcinoma was found presymptomatically in 5 young subjects who had bilateral nephrectomy and hemodialysis. Three survived long-term after renal transplants. Five members of the family had pancreatic malignancy.
Horbach et al. (1989) suggested that the combination of adrenal pheochromocytoma and ipsilateral renal cell carcinoma may represent a forme fruste of von Hippel-Lindau disease.
Neumann and Wiestler (1991) found a striking tendency for familial clustering of particular VHL features. Both angiomatosis retinae and hemangioblastoma of the CNS occurred in most families, whereas the occurrence of renal lesions and/or pancreatic cysts was mutually exclusive with pheochromocytoma. The authors interpreted these findings to indicate that the VHL locus is complex, with the existence of different mutations in different families or the occurrence of additional genetic lesions that cooperate with the VHL gene on chromosome 3p. They suggested a linear sequence of features as follows: pheochromocytoma, angiomatosis retinae, hemangioblastoma of the CNS, renal lesions, pancreatic cysts, and epididymal cystadenoma.
In the course of an evaluation of 41 families with this disorder from the United States and Canada, Glenn et al. (1991) found 1 large family with a distinctive phenotype: the most common disease manifestation was pheochromocytoma occurring in 57% (27 of 47) of affected members; few (4 of 47) had symptomatic spinal or cerebellar hemangioblastomas; no affected family member had renal cell carcinoma or pancreatic cysts. Genetic analysis demonstrated, however, that the disorder in this family was linked to the same markers found to be linked to typical VHL. The observations are clearly relevant to the descriptions of families with 'pure' pheochromocytoma (171300); they may be instances of allelism at the VHL locus.
Keeler and Klauber (1992) described renal cell carcinoma in a 16-year-old boy, probably the youngest reported example of hypernephroma in VHL disease.
Lenz et al. (1992) demonstrated that norepinephrine-producing adrenal pheochromocytoma in von Hippel-Lindau disease can produce the clinical syndrome of hypertension associated with severe hypokalemia and hyperreninemic hyperaldosteronism. The hyperreninemic hyperaldosteronism was rapidly improved by beta-blockade and was completely reversed by tumor removal. Kerr et al. (1995) described hemangioblastoma of the optic nerve in a 27-year-old woman with von Hippel-Lindau syndrome, the tenth such reported case.
Davies et al. (1994) described a 65-year-old woman who was an obligate carrier of the gene for von Hippel-Lindau disease. Her father, 2 brothers, 2 sisters, and 3 sons had hemangioblastomas and renal carcinomas. Careful examination of the woman showed only a small benign renal cyst. Such cysts are very common in the general population. Therefore, obligate gene carriers may not exhibit any features of the disease beyond the age of 60 years.
Using a VHL register set up in the northwest of England in 1990 containing information on 83 affected persons, Maddock et al. (1996) studied population statistics, clinical features, age at onset, and survival. The mean age at onset of first symptoms was 26.25 years, with cerebellar hemangioblastoma being the most common presenting manifestation (34.9% of cases). The mean age at diagnosis of VHL was 30.87 years. Overall, 50 patients (60.2%) developed a cerebellar hemangioblastoma, 34 (41%) a retinal angioma, 21 (25.3%) a renal cell carcinoma, 12 (14.5%) a spinal hemangioblastoma, and 12 (14.5%) a pheochromocytoma. Mean age at death was 40.9 years with cerebellar hemangioblastoma being the most common cause (47.7% of deaths). In addition to the 83 clinically affected subjects, Maddock et al. (1996) identified 3 obligate carriers who were considered to be lesion free on extensive screening tests. In the regionally based cancer registry, 14% of all CNS hemangioblastomas were found to occur as part of VHL, but investigations for VHL in apparently sporadic cases appeared to have been limited.
Endolymphatic sac tumors (ELSTs) are highly vascular, benign, but locally aggressive neoplasms of the endolymphactic system that often destroy the surrounding temporal bone. They are very rare and generally occur sporadically, but occur with increased frequency in patients with VHL. Manski et al. (1997) found MRI evidence of 15 ELSTs in 13 (11%) of 121 patients with VHL, but in none of 253 patients without evidence of VHL (P less than 0.001). Clinical findings in these 13 patients included hearing loss in 13, tinnitus in 12, vertigo in 8, and facial paresis in 1. Mean age at onset of hearing loss was 22 years (range, 12 to 50 years).
Lonser et al. (2004) described 3 cases of von Hippel-Lindau disease that illustrated the following features of endolymphatic sac tumors: morbid hearing loss due to a radiologically undetectable microscopic tumor in the endolymphatic sac or duct; initial symptoms caused by hemorrhage, endolymphatic hydrops, or both; an origin in the endolymphatic duct or sac; and molecular evidence of an association with von Hippel-Lindau disease. Complete surgical resection of the endolymphatic sac tumors is curative and can be performed with the preservation of hearing and the alleviation of vestibular symptoms.
Butman et al. (2007) reported 35 VHL patients with ELSTs; 3 had bilateral tumors. Mean age at symptom onset was 31 years (range, 11 to 63 years). In additional to hearing loss, tinnitus, and vertigo, other features included aural fullness, aural pain, and facial nerve weakness. Detailed CT and MRI studies showed that 7 (18%) ears had otic capsule invasion, which was always associated with hearing loss. Tumors with otic capsule invasion were larger (2.2 cm) than those without capsule invasion (1.2 cm). However, there was not a significant association between tumor size and hearing loss. Intralabyrinthine hemorrhage was detected in 79% of ears with sudden hearing loss. Butman et al. (2007) concluded that hearing loss associated with ELSTs can result from otic capsule invasion, intralabyrinthine hemorrhage, or endolymphatic hydrops.
James (1998) tabulated reports of 4 women with VHL and broad ligament papillary cystadenoma published between 1988 and 1994 (Gersell and King, 1988; Funk and Heiken, 1989; Korn et al., 1990; Gaffey et al., 1994; Karsdorp et al., 1994) and added a fifth case. These are mesosalpinx cysts, which are the equivalent of epididymal cysts in the male. The cysts were unilateral in at least 3 of the 5 cases. They occurred along the full course of the mesonephric duct, in the mesosalpinx close to the ovary, over the uterine tubes, and near the vaginal fornix in a remnant of the Gartner duct (the female counterpart to the duct of the epididymis). At least 3 of the patients had multiple renal cysts and bilateral renal cell carcinoma. In the patient reported by Korn et al. (1990), screening for VHL after the papillary cystadenomas were diagnosed revealed pancreatic cysts and lesions of the cerebellum and kidney; renal cell carcinoma was diagnosed during follow-up surgery. The unilateral cyst in the patient reported by Gaffey et al. (1994) was preceded by the finding of a middle ear papillary tumor. The combined presentation of mesonephric cystadenoma and ear tumor was noted in reports of epididymal cysts in men (Price, 1971). Gaffey et al. (1994) suggested that the ear tumor and the adnexal tumor may represent 'major visceral manifestations of VHL.' (Nomenclature: According to the VHL Family Alliance, a genetic support group, the approved terminology is 'adnexal papillary cystadenoma of probable mesonephric origin,' abbreviated APMO (Graff, 1998).)
Fukino et al. (2000) described a Japanese VHL family in which 2 of the 3 affected members developed acute occlusive hydrocephalus that necessitated emergency surgery for ventricular shunting or drainage. In both cases, the occlusion of the cerebrospinal canal was caused by cerebellar hemangioblastoma. The 2 patients with hydrocephalus were sisters aged 8 and 19 at the time of development of obstructive hydrocephalus. They inherited VHL from their mother, who also suffered from cerebellar hemangioblastoma requiring surgery as well as from retinal angiomas.
McCabe et al. (2000) described the clinical features, association with von Hippel-Lindau disease, and visual acuity outcomes of patients with juxtapapillary capillary hemangioma, on or adjacent to the optic nerve. Because of their location, a hamartoma on the lesions could potentially be misdiagnosed as papilledema, papillitis, choroidal neovascularization, or choroiditis. Endophytic, exophytic, and sessile forms were described. On long-term follow-up, visual acuity generally worsened. Patients with VHL and juxtapapillary hemangioma more often presented at a younger age, had tumors with an endophytic growth pattern, and had bilateral, multiple tumors. Tumor treatment with laser photocoagulation resulted in variable visual acuity outcomes in the patients reported.
Raja et al. (2004) reported that external beam radiotherapy (EBRT) was a useful option in the treatment of retinal hemangiomas secondary to VHL disease that progressed despite standard therapy. EBRT led to improvement of visual acuity, reduction in tumor volume, and stabilization of retinal detachment in most patients treated.
Eisenhofer et al. (2001) examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in MEN2 (171400) and VHL to underlying differences in the expression of tyrosine hydroxylase (TH; 191290), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT; 171190), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN2 patients and 30 VHL patients with adrenal pheochromocytomas. MEN2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than VHL patients. MEN2 patients all had elevated plasma concentrations of the epinephrine metabolite metanephrine, whereas VHL patients showed specific increases in the norepinephrine metabolite normetanephrine. The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN2 patients.
Taouli et al. (2003) discussed abdominal imaging findings, including pictorial images, from more than 150 patients with VHL syndrome. The most common findings were renal and pancreatic masses.
In a prospective study of 406 VHL patients from 199 families seen at 1 institution in a 12-year period, Chew (2005) found that 205 of the patients had ocular involvement. Patients with complete deletion of the VHL gene were less likely to have ocular involvement than those with partial deletion, missense, or nonsense mutations (9% vs 45%; p less than 0.0001). Chew (2005) identified a previously unreported ocular feature, retinal neovascularization, in 17 patients. Chew (2005) also found 11 cases of intraorbital/intracranial hemangioblastoma, previously reported to be rare in VHL, accounting for 5.3% of all vision-threatening lesions in this study group.
In surgically excised retinal hemangioblastomas associated with von Hippel-Lindau disease, Liang et al. (2007) demonstrated high levels of VEGF (192240) and CXCR4 (162643) mRNA and protein but low levels of CXCL12 (600835). Increased expression of VEGF and CXCR4 was also detected in more active hemangioblastomas.
Binderup et al. (2016) performed a retrospective analysis of a national cohort study that included 52 VHL mutation carriers. The analysis spanned a total of 799 person-years. From birth to time of the report, 581 manifestations were diagnosed during 2,583 examinations in the study subjects. The rate of new tumor development varied significantly with age and was highest at 30 to 34 years (0.4 new tumors/year). Tumor location further influenced the rate. The risk of retinal tumors was highest in subjects during the teenage years but was highest for cerebellar tumors in subjects during their 30s. Truncating VHL mutation carriers had a significantly higher manifestation rate compared with missense mutation carriers (hazard ratio = 1.85, 95% confidence interval 1.06-3.24, p = 0.031). The authors concluded that the rate of new manifestation development is not constant throughout the life span of VHL patients. They recommended careful retinal surveillance during the teenage years and increased cerebellar surveillance in adulthood.
Pathogenesis
Interfamilial differences in predisposition to pheochromocytoma in VHL reflect allelic heterogeneity such that there is a strong association between missense mutations and risk of pheochromocytoma. Prowse et al. (1997) investigated the mechanism of tumorigenesis in VHL tumors to determine whether there were differences between tumor types or classes of germline mutations. They studied 53 tumors (30 renal cell carcinomas, 15 hemangioblastomas, 5 pheochromocytomas, and 3 pancreatic tumors) from 33 patients (27 kindreds) with VHL. Overall, 51% of 45 informative tumors showed LOH at the VHL locus. In 11 cases, it was possible to distinguish between loss of the wildtype and mutant alleles, and in each case the wildtype allele was lost. LOH was detected in all tumor types and occurred in the presence of both germline missense mutations and other types of germline mutation associated with a low risk of pheochromocytoma. Intragenic somatic mutations were detected in 3 tumors (all hemangioblastomas) and in 2 of these could be shown to occur in the wildtype allele. Their study provided the first example of homozygous inactivation of the VHL gene by small intragenic mutations in this type of tumor. Hypermethylation of the VHL gene was detected in 33% (6 of 18) of tumors without LOH, including 2 renal cell carcinomas and 4 hemangioblastomas. Prowse et al. (1997) stated that although hypermethylation of the VHL gene had been reported previously in nonfamilial RCC and although methylation of tumor-suppressor genes had been implicated in the pathogenesis of other sporadic cancers, this was the first report of somatic methylation in a familial cancer syndrome. Herman et al. (1994) observed hypermethylation of the VHL gene in 19% of sporadic RCCs. Versteeg (1997) provided a general discussion of aberrant methylation in cancer.
By using comparative genomic hybridization (CGH), Lui et al. (2002) characterized the genetic profiles of 36 VHL-related pheochromocytomas. They found loss of chromosome 3 or chromosome 11 in 34 tumors (94%) and 31 tumors (86%), respectively. There was significant concordance of deletions in chromosomes 3 and 11, suggesting that they are involved in 2 different but necessary and complementary genetic pathways. The loss of chromosome 11 appeared to be specific for VHL-related pheochromocytoma as it was not present in any of the 10 VHL-related CNS hemangioblastomas studied and was significantly less common when compared with sporadic and MEN2-related pheochromocytomas. The authors stated that this was the first report of a novel consistent genetic alteration that is selected and specific for VHL-related pheochromocytoma.
Population Genetics
Maher et al. (1991) estimated the point prevalence of heterozygotes in East Anglia to be 1 in 53,000, with an estimated birth incidence of 1 in 36,000 live births. Reproductive fitness was 0.83. Direct and indirect estimates of the mutation rate were 4.4 per million gametes per generation and 2.32 per million gametes per generation, respectively. No significant association was found between parental age or birth order and new mutations. In the Freiburg district of Germany, Neumann and Wiestler (1991) calculated the prevalence of this disorder to be 1 in 38,951.
Maddock et al. (1996) reported on a VHL register set up in the northwest of England in 1990. There was information on 83 affected persons. In addition, the effectiveness of the screening program used and the occurrence of CNS hemangioblastomas in the general populations were examined. The diagnostic point prevalence of heterozygotes in the region was 1 in 85,000 persons, with an estimated birth incidence of 1 in 45,500 live births. The mutation rate was estimated directly to be 1.4 x 10(-6)/gene/generation (1 in 714,200).
Wu et al. (2012) identified mutations in the VHL gene in 12 (75%) of 16 Chinese probands with clinically diagnosed VHL syndrome. PCR-direct sequencing detected 12 mutations, 1 of which was novel, in 12 patients (75%). Use of universal primer quantitative fluorescent multiplex PCR (UPQFM-PCR) enabled detection of 2 large deletions in 2 (12.5%) patients. The 2 remaining patients carried atypical variations in the VHL gene that could not definitively be called pathogenic. Nine (56.3%) probands did not have a family history of the disorder, suggesting a high frequency of de novo mutations among Chinese patients. Clinically, 15 families were classified as type 1 (without pheochromocytoma) and 1 as type 2 (with pheochromocytoma). The most common manifestations were CNS hemangioblastoma, clear cell renal cell carcinoma, and pancreatic cysts and tumors. Combining this information with previous reports of Chinese VHL patients indicated that the clinical features and spectrum of VHL mutations among the Chinese are comparable to those found in large-scale investigations from other countries.
Diagnosis
Seizinger et al. (1991) pointed out that visceral cysts of the kidney, pancreas, and epididymis occur not only as features of VHL but also in the general population, and that the presence of such cysts, unaccompanied by other more typical lesions such as retinal and cerebellar hemangioblastoma, may represent a major diagnostic problem. The application of flanking markers for the VHL gene for presymptomatic diagnostic testing confirmed that epididymal cysts are indeed not suitable as a diagnostic criterion. The genetic studies suggested that VHL with or without pheochromocytomas is caused by defects within the same gene. Renal cell carcinoma occurs as part of VHL; a second more proximal region of chromosome 3, 3p14.2, is responsible for 'pure familial renal cell carcinoma' (144700).
Webster et al. (2000) calculated the likelihood of VHL in an individual presenting with a single ocular angioma conditional upon the age of presentation, results of DNA analysis, family history of VHL, and results of systemic screening, and produced a risk estimate table for individuals with combinations of these variables.
Hes et al. (2003) noted that in the presence of a positive family history, VHL disease can be diagnosed clinically in a patient with at least 1 typical VHL tumor. Typical VHL tumors are retinal, spinal, and cerebellar hemangioblastoma; renal cell carcinoma; and pheochromocytoma. Endolymphatic sac tumors and multiple pancreatic cysts suggest a positive carriership in the presence of a positive VHL family history because they are uncommon in the general population. In contrast, renal and epididymal cysts occur very frequently in the general population and are, as sole manifestations, not reliable indicators for VHL disease. In patients with a negative family history of VHL-associated tumors, a diagnosis of VHL disease can also be made on the basis of 2 or more hemangioblastomas or a single hemangioblastoma in association with a visceral manifestation (e.g., pheochromocytoma or renal cell carcinoma). Hes et al. (2003) suggested the following criteria for eligibility for VHL gene mutation analysis: a patient with classic VHL disease (meeting clinical diagnostic criteria) and/or first-degree family members; a person from a family in which a germline VHL gene mutation has been identified (presymptomatic test); a VHL-suspected patient, i.e., one with multicentric tumors in 1 organ, bilateral tumors, 2 organ systems affected, or 1 VHL-associated tumor at a young age (less than 50 years for hemangioblastoma and pheochromocytoma or less than 30 years for renal cell carcinoma); or a patient from a family with hemangioblastoma, renal cell carcinoma, or pheochromocytoma only.
### Mutation Analysis
Using DNA polymorphic markers, Glenn et al. (1992) studied 16 families with VHL disease. Of 48 asymptomatic persons at risk of developing this illness because of an affected parent or sib, DNA polymorphism analysis predicted that 9 were carriers of the disease gene and 33 had the wildtype allele. The test was not informative in 6 persons. All 9 persons predicted to carry the VHL gene had evidence of occult disease on clinical examination. There was no clinical evidence of VHL disease in 32 of 33 persons predicted to carry the wildtype allele.
Richards et al. (1993, 1994) found that large germline deletions could be detected by Southern analysis and pulsed field gel electrophoresis in 19% and 3% of VHL patients, respectively.
To determine whether the pheochromocytoma-associated syndromes VHL and MEN2 play a role in the development of thoracic functioning paragangliomas, Bender et al. (1997) analyzed germline DNA from 5 unselected patients with this tumor for mutations in the genes that predispose to VHL and MEN2. Molecular and clinical data revealed that 3 (60%) had VHL, with 2 different germline mutations of the VHL gene, but no individual was affected by MEN2. Two of these 3 patients with VHL did not show any additional VHL-associated lesions. Bender et al. (1997) suggested that VHL should be considered in the differential diagnosis of thoracic pheochromocytoma, and that in VHL patients suspected of a catecholamine-secreting tumor, thoracic localization should be considered if an adrenal pheochromocytoma cannot be detected.
Pack et al. (1999) stated that the reported frequency of detection of VHL germline mutations had varied from 39 to 80%. Stolle et al. (1998) found that a quantitative Southern blotting procedure improved this frequency. Pack et al. (1999) reported the use of fluorescence in situ hybridization as a method to detect and characterize VHL germline deletions. They reexamined a group of VHL patients shown previously by SSCP and sequencing analysis not to harbor point mutations in the VHL locus. They found constitutional deletions in 29 of 30 VHL patients in this group, using cosmid and P1 probes that covered the VHL locus. They then tested 6 phenotypically normal offspring from 4 of these VHL families: 2 were found to carry the deletion and the other 4 were deletion-free. In addition, germline mosaicism of the VHL gene was identified in 1 family. Thus, FISH was found to be a simple and reliable method to detect VHL germline deletions and to be practically useful in cases where other methods of screening fail to detect abnormalities in the VHL gene.
Hes et al. (2000) performed mutation analysis of the VHL gene in 84 patients presenting with a single CNS hemangioblastoma and 4 with multiple hemangioblastomas, but no other features of VHL. A VHL germline mutation was found in 3 of 69 (4.3%) of those with single hemangioblastomas presenting at less than 50 years of age (3 of 84 (3.6%) in total) and 2 of the 4 patients with multiple hemangioblastomas. A VHL mutation was found in a 44-year-old woman presenting with a single cerebellar hemangioblastoma, in 4 clinically unaffected relatives, and in 2 single cases presenting at 29 and 36 years. Hes et al. (2000) recommended that in addition to conventional clinical and radiologic investigations, VHL mutation analysis be offered to those presenting with CNS hemangioblastomas before the age of 50 years.
Sgambati et al. (2000) presented 2 cases of VHL mosaicism. In each of 2 families, standard testing methods (Southern blot analysis and direct sequencing) identified the germline mutation in the VHL gene of the offspring, but not in their clinically affected parent. Additional methods of analysis of the affected parents' blood detected the VHL gene mutation in a portion of their peripheral blood lymphocytes. In one case, detection of the deleted allele was by FISH, and, in the second case, a 3-bp deletion was detected by conformational sensitive gel electrophoresis and DNA sequencing of cloned genomic DNA. Sgambati et al. (2000) concluded that mosaicism in VHL is important to search for and recognize when an individual without a family history of VHL has VHL. Patients diagnosed without family histories of the disease have been reported in as many as 23% of kindreds. Identification of individuals potentially mosaic for VHL will affect counseling of families, and these individuals should themselves be included in clinical screening programs for occult disease.
Cytogenetics
Kiechle-Schwarz et al. (1989) found rearrangements resulting in partial or total trisomy of chromosome 3p in 3 cell clones from pheochromocytomas derived from patients with von Hippel-Lindau syndrome.
Kovacs and Kung (1991) analyzed the DNA from 28 nonpapillary renal cell carcinomas arising in 2 patients with VHL disease. They used both karyotypic and RFLP analyses for evidence of allelic recombination on chromosomes 3 and 5. Two distinct breakpoint clusters were identified, each associated with different karyotypic alterations. The first type involves a breakpoint at chromosome 3p13, with the common nonreciprocal translocations occurring between 3p and 5q or 1q, resulting in the net loss of 3p and gain of 5q or 1q segments. In the second form of translocation, which was less common, the breakpoint on 3p and on the partner chromosome is near the centromere at bands p11 or q11. This kind of rearrangement was observed in 10 tumors with a nonrandom involvement of chromosome 3. In each case the derivative chromosome carrying the translocated 3p segment was preferentially eliminated from the tumor cells.
Mapping
Go et al. (1984) found no linkage of VHL with any of 31 marker loci by studying 41 affected persons among 220 descendants of an ancestral couple. Wells et al. (1987) found linkage with a segregating minisatellite band at a recombination fraction of 0.15 (lod score of about 3.0). In studies of 9 families, Seizinger et al. (1988) found linkage with RAF1 (164760) on chromosome 3; the combined maximum lod score was 4.38 at theta = 0.11 (1 lod unit confidence interval, the approximate equivalent of 95% confidence interval, of theta = 0.04 to 0.23). The finding of recombination between VHL and RAF1 indicated that the site of the VHL mutation is not in the RAF1 gene.
Seizinger et al. (1989) reported a multipoint linkage analysis of the VHL gene using a battery of polymorphic markers in the region 3p26-p25. Vance et al. (1990) confirmed the linkage of VHL to 3p. Hosoe et al. (1990) concluded that VHL is located between RAF1 (3p25) and D3S18 (3p26).
Maher et al. (1990) confirmed the assignment to 3p by linkage studies in 12 British families. They suggested that the VHL locus is telomeric to the THRB gene (190160). No evidence for genetic heterogeneity was found. Seizinger et al. (1991) reported the location of the VHL locus at 3p26-p25 on the basis of studies in 28 pedigrees comprising 164 affected persons. By multipoint linkage analysis, Maher et al. (1991) demonstrated flanking markers. They found no evidence of locus heterogeneity; families with and without pheochromocytoma showed linkage to D3S18 with which no recombination was observed (maximum lod score = 6.6 at theta = 0.0; CI, 0.00-0.06). By multipoint linkage analysis, Richards et al. (1993) narrowed the target region for isolation of the VHL disease gene by positional cloning techniques to a 4-cM interval between D3S1250 and D3S18.
Richards et al. (1993) constructed a long-range physical map around D3S601, which had been shown to be tightly linked to the VHL locus, and screened 91 VHL patients from 80 kindreds for germline rearrangements using pulsed field gel electrophoresis. Two patients were found to have germline deletions within this region, approximately 120 kb and 50 kb, respectively, telomeric to D3S601. The results established the position of the VHL locus with respect to D3S601, refined its localization to a small region of approximately 50 kb, and excluded the plasma membrane Ca(2+)-transporting ATPase-2 gene (108733) as the site of the VHL mutation.
Molecular Genetics
In 28 of 221 kindreds with von Hippel-Lindau syndrome, Latif et al. (1993) identified rearrangements of the VHL gene. Eighteen of these rearrangements were due to deletion in the VHL gene: 1 of these was an in-frame 3-nucleotide deletion (608537.0001).
In 55 of 94 unrelated VHL kindreds, Crossey et al. (1994) identified 40 different mutations in the VHL gene. The 2 most frequent mutations were arg238-to-gln (608537.0005) and arg238-to-trp (608537.0003), which were detected in 5 and 4 unrelated kindreds, respectively.
Ciotti et al. (2009) identified mutations in the VHL gene in 9 (100%) of 9 unrelated families and in 16 (88.9%) of 18 isolated patients presenting with the classic phenotype of VHL syndrome. VHL mutations were also found in 2 (66.7%) of 3 patients who met the diagnostic criteria for VHL syndrome, but who also had multiple cerebellar hemangioblastomas. Of those with mutations, 6 (22%) of 27 were found to have complete or partial deletions of the gene. No VHL mutations were found in 13 additional patients who did not meet the full diagnostic criteria of the disorder, but who had some suggestive features.
### Modifiers of VHL
To assess the influence of variation in CCND1 (168461) on the retinal, renal, and central nervous system (CNS) manifestations of von Hippel-Lindau disease (193300), Zatyka et al. (2002) genotyped 118 patients for the codon 242 G-A SNP (168461.0001). The number of retinal angiomas was significantly higher in individuals harboring the G allele compared with AA homozygotes (p of 0.04). Possession of 1 or more G alleles was associated with earlier diagnosis of CNS hemangioblastoma by almost 2-fold, although the difference did not attain statistical significance (p of 0.05). A similar analysis for onset of renal cell carcinoma showed no evidence of an association with CCND1 genotype.
In a retrospective analysis of 123 patients from 55 families with VHL, including 13 with complete germline deletion of the VHL gene and 42 with partial gene deletions, Maranchie et al. (2004) observed a paradoxically lower prevalence of renal cell carcinoma in those with complete gene deletions. RCC occurred more frequently in patients with partial germline VHL deletions relative to complete deletions (48.9% vs 22.6%, p = 0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p = 0.22), pancreas (p = 0.72), or pheochromocytoma (p = 0.34). Deletion mapping demonstrated that development of RCC had an even greater correlation with retention of HSPC300 (C3ORF10; 611183), located within the 30-kb region of 3p immediately telomeric to the VHL gene (52.3% vs 18.9%, p less than 0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC.
Cascon et al. (2007) found that 6 of 8 VHL patients without RCC had large germline deletion of the VHL gene including deletion of HSPC300. In contrast, 9 of the 10 with RCC had retention of the HSPC300 gene. Analysis of 9 sporadic RCC tumors showed that all retained an HSPC300 allele. Cascon et al. (2007) concluded that loss of the HSPC300 gene confers protection against renal clear cell carcinoma.
Genotype/Phenotype Correlations
Although pheochromocytoma occurs in only about 7% of VHL patients, marked interfamilial differences are often observed. Examining the relationship between VHL gene mutations and phenotype in 65 VHL kindreds, Crossey et al. (1994) found that large deletions or intragenic mutations predicted to cause a truncated protein were found in 36 of 53 families without pheochromocytoma but in only 2 of 12 families with pheochromocytoma (P less than 0.01). Of 12 families with pheochromocytoma, 10 had missense mutations compared with 13 of 53 kindreds without pheochromocytoma (P less than 0.001). In particular, the arg238-to-trp and arg238-to-gln mutations were associated with a high risk (62%) of pheochromocytoma.
Chen et al. (1995) identified germline mutations in 85 of 114 VHL families (75%). They found that the types of mutations responsible for VHL without pheochromocytoma (VHL type 1) differed from those responsible for VHL with pheochromocytoma (VHL type 2). Microdeletions/insertions, nonsense mutations, or deletions were found in 56% of families with VHL type 1; missense mutations accounted for 96% of those responsible for VHL type 2. Specific mutations in codon 238 accounted for 43% of the mutations responsible for VHL type 2 (see 608537.0003-608537.0005).
Zbar et al. (1996) performed germline mutation analysis in 469 VHL families from North America, Europe, and Japan. Germline mutations were identified in 300 (63%) of the families tested; a total of 137 distinct intragenic germline mutations were detected. Most (124 of 137) of the mutations occurred in 1 or 2 families; a few occurred in 4 or more families. In this large series, it was possible to compare the effects of identical germline mutations in different populations. Germline VHL mutations produce similar cancer phenotypes in Caucasian and Japanese VHL families. Germline VHL mutations were identified that produced 3 distinct cancer phenotypes: (1) renal carcinoma without pheochromocytoma, (2) renal carcinoma with pheochromocytoma (e.g., 608537.0003), and (3) pheochromocytoma alone (e.g., 608537.0012). Zbar et al. (1996) provided a catalog of VHL germline mutations with associated phenotype information.
In a patient with von Hippel-Lindau syndrome due to a 505T-C transition (608537.0009) in the VHL gene, Schimke et al. (1998) found a secretory carotid body paraganglioma, the first such instance; a nonfunctional malignant carotid body tumor had been described in a patient with VHL by Hull et al. (1982).
Gallou et al. (1999) analyzed the occurrence of RCC in VHL families, based on the nature of the VHL mutations. They observed RCC in at least 1 member of the VHL families in 77% of cases with mutations leading to truncated proteins, and in 55% of cases with missense mutations (P less than 0.05). Thus, mutations resulting in truncated proteins may carry a higher risk of RCC in VHL patients.
Bradley et al. (1999) described a family with VHL disease and a mutation in the VHL protein (608537.0017). Of 13 affected individuals, 7 had renal cell carcinoma and 1 had pheochromocytoma. The authors contrasted this family with 2 families reported by Chen et al. (1996) that had a mutation at the same position but causing a different amino acid change (608537.0012). In these families, 19 of 22 affected individuals had pheochromocytoma and none had renal cell carcinoma. Bradley et al. (1999) concluded that different amino acid changes at the same position can cause very distinct clinical phenotypes.
Hes et al. (2000) described 5 VHL families in which direct sequencing of the coding region of the VHL gene failed to identify the family-specific mutation. Further molecular analysis revealed deletions involving the VHL gene in each of these families. In 4 families, partial deletions of 1 or more exons were detected by Southern blot analysis. In the fifth family, FISH analysis demonstrated the deletion of the entire VHL gene. The data supported the previously established observation that families with a germline deletion have a low risk for pheochromocytoma. Further unraveling of the genotype-phenotype correlations in VHL disease revealed that families with a full or partial deletion of the VHL gene exhibited a phenotype with a preponderance of central nervous system hemangioblastoma.
Friedrich (2001) reviewed genotype/phenotype correlations in von Hippel-Lindau syndrome.
Hoffman et al. (2001) noted that a type 2C VHL mutant, L188V (608537.0014), which had been associated with a pheochromocytoma-only phenotype (and had been shown to retain the ability to promote HIF (603348) ubiquitylation), retained the ability to suppress cyclin D1 (CCND1; 168461) expression, suggesting that loss of VHL-mediated suppression of cyclin D1 is not necessary for pheochromocytoma development in VHL disease. Other studies had suggested that (1) genetic modifiers influence the phenotypic expression of VHL disease (Webster et al., 1998); and (2) polymorphic variation at the CCND1 codon 242 A/G SNP (168461.0001) may influence cancer susceptibility or prognosis in some situations. Therefore, Zatyka et al. (2002) analyzed the relationship between CCND1 genotype and phenotypic expression of VHL disease. They found an association between the G allele and multiple retinal angiomas (p = 0.04), and risk of central nervous system hemangioblastoma (p = 0.05). The findings suggested that a variety of HIF-independent mechanisms may contribute to the tumor suppressor activity of the VHL protein and that polymorphic variation at one VHL protein target influences the phenotypic expression of VHL disease.
In a study of 573 individuals with VHL syndrome from 200 unrelated families, Ong et al. (2007) found that age at disease onset was significantly earlier, and age-related risks of retinal angiomas and RCC were higher in individuals with nonsense or frameshift mutations compared to those with deletions or missense mutations. The results also confirmed the association of pheochromocytomas with missense mutations, particularly those that resulted in surface amino acid substitutions.
Wong et al. (2007) characterized the germline mutations found in 335 patients with VHL disease associated with retinal capillary hemangioblastomas (RCHs) and sought to establish genotype-phenotype correlations between genotype category (amino acid substitutions, protein-truncating mutations, and complete deletions) and ocular phenotype. The prevalence of RCHs was lowest (14.5%) among patients with complete deletions; the overall prevalence of retinal angiomatosis was 37.2%. Genotype category had no correlation with unilaterality or bilaterality of ocular disease or with the number or extent of peripheral RCHs. The prevalence of RCHs at the juxtapapillary location was lower among patients with protein-truncating mutations than in patients with amino acid substitutions. Complete deletions were associated with the highest mean visual acuity.
Franke et al. (2009) identified germline deletions in the VHL gene ranging from 0.5 to 250 kb in 54 families with VHL syndrome. In 28 of these families, at least 1 additional gene was deleted including FANCD2 (227646), HSPC300 (C3ORF10;611183), and IRAK2 (603304). The precise breakpoints were determined in 33 index patients. Of the 66 breakpoints, 90% occurred in Alu elements, indicating that Alu-mediated recombination is a major mechanism for germline deletions of the VHL gene. Among all 54 families with VHL syndrome resulting from germline deletions of the VHL gene, Franke et al. (2009) found a higher occurrence of renal cell carcinomas and CNS hemangioblastomas compared to patients with other types of mutations. There was an independent association between renal cell carcinoma and retinal angiomas and retention of the HSPC300 gene, which confirmed the findings of Cascon et al. (2007).
McNeill et al. (2009) reviewed the molecular and clinical characteristics of 127 individuals from 62 kindreds with germline deletions in the VHL gene. Large VHL gene deletions associated with a contiguous loss of HSPC300 (10 patients) were associated with a significantly lower lifetime risk of RCC than deletions that did not involve HSPC300 (42 patients). The age-related risk of RCC at age 60 was 0% in the first group and 72% in the second group. Patients with exon 1 VHL deletions and retention of FANCD2 were excluded as the status of HSPC300 was uncertain. The risks of hemangioblastomas and pheochromocytomas were similar in both groups. These findings further supported the growing body of evidence indicating that patients with VHL syndrome caused by large VHL deletions that include the HSPC300 gene have a specific subtype of VHL syndrome with protection from RCC, which McNeill et al. (2009) proposed be named VHL type 1B.
History
Cushing and Bailey (1928) pointed out that Lindau (1927) was mainly responsible for showing the connection between retinal angiomas and CNS lesions. They reported the rather long-term follow-up of a patient named Frank McA. who had the full syndrome. The family history of involvement in several generations was obtained by John F. Fulton (1899-1960), Yale neurophysiologist who worked with Cushing for a year in the 1920s, and drawings of the fundus lesions were obtained by W. H. Wilmer of Johns Hopkins. As pointed out by Cushing and Bailey (1928), Treacher Collins (1894) was the first to recognize the angiomatous nature of the retinal lesions; he reported brother and sister. Then, von Hippel (1904) reported his 2 patients. In his biography of Cushing, Fulton (1946) gave an interesting account of the 'young Swedish pathologist named Arvid Lindau (who) had attracted Cushing's attention in 1927 [Lindau, 1927] through his description of an important new disease entity, which Cushing appropriately christened Lindau's disease.'
Melmon and Rosen (1964) reviewed the literature and reported studies of an extensively affected kindred. They pointed out that von Hippel's first publication on this subject concerned 2 patients, Otto Meyer and Otto Mobius by name, who figured in several later publications as well. Following this historic lead, Melmon and Rosen (1964) gave the full name of each of their patients beginning with the proband Bruno Bernardini.
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Endolymphatic sac tumors (ELSTs) \- Hearing loss, sensorineural, associated with ELSTs \- Tinnitus \- Vertigo Eyes \- Retinal angiomata RESPIRATORY Lung \- Pulmonary hemangiomas ABDOMEN Liver \- Liver hemangiomas Pancreas \- Multiple pancreatic cysts \- Pancreatic hemangioblastoma GENITOURINARY Internal Genitalia (Male) \- Bilateral papillary cystadenoma of the epididymis \- Bilateral papillary cystadenomas of the broad ligament \- Epididymal cyst Kidneys \- Renal hemangioblastoma \- Renal cell carcinoma (e.g., 193300.0002 ) \- Multiple renal cysts NEUROLOGIC Central Nervous System \- Cerebellar hemangioblastoma Peripheral Nervous System \- Spinal cord hemangioblastoma ENDOCRINE FEATURES \- Hypertension \- Adrenal hemangiomas HEMATOLOGY \- Polycythemia NEOPLASIA \- Pheochromocytoma \- Hemangioblastoma, sporadic cerebellar (e.g., 193300.0007 ) \- Hypernephroma \- Pancreatic cancer \- Paraganglioma \- Adenocarcinoma of ampulla of Vater MISCELLANEOUS \- Incidence of 1 in 39,000 \- Highly variable phenotype, even within families \- VHL type 1 - renal carcinoma and hemangioblastoma \- VHL type 2A - hemangioblastoma and pheochromocytoma \- VHL type 2B - renal carcinoma and pheochromocytoma \- VHL type 2C - pheochromocytoma only MOLECULAR BASIS \- Caused by mutation in the von Hippel-Lindau gene (VHL, 608537.0001 ) ▲ 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
VON HIPPEL-LINDAU SYNDROME
|
c0019562
| 7,793 |
omim
|
https://www.omim.org/entry/193300
| 2019-09-22T16:31:54 |
{"doid": ["14175"], "mesh": ["D006623"], "omim": ["193300"], "icd-10": ["Q85.8"], "orphanet": ["892"], "genereviews": ["NBK1463"]}
|
For a general phenotypic description and a discussion of genetic heterogeneity of Carney complex, see CNC1 (160980).
Mapping
Stratakis et al. (1995, 1996) studied 101 patients from 11 North American kindreds with Carney complex. Skin myxomas, cardiac myxomas, Cushing syndrome, and acromegaly were present in, respectively, 62%, 30%, 31%, and 8% of the patients. They demonstrated linkage to markers on the short arm of chromosome 2 (2p16) with a maximum 2-point lod score of 5.97 at theta = 0.03 for linkage to a (CA)n dinucleotide repeat polymorphism (Leach et al., 1994). Candidate genes in the proximity, including the proopiomelanocortin gene (176830) and the DNA-mismatch repair gene MSH2 (609309), were excluded.
Stratakis et al. (1996) examined 15 tumor and normal tissue specimens from 13 patients with Carney complex. DNA was extracted from peripheral blood, tumor cell lines, and frozen or paraffin-embedded tissues and subjected to PCR amplification with primers from 64 microsatellite locations covering chromosomes 1 and 3 to 22 and 14 loci on chromosome 2. The alterations detected were loss and gain of heterozygosity (LOH and GOH; 49% and 26%, respectively), deletions of both alleles (DEL; 10%), and microsatellite length instability (15%). GOH and LOH were the most frequent changes, with telomeric markers significantly overrepresented (p less than 0.05). Chromosomes 6, 11, 22, 10, and 19 demonstrated mostly LOH, GOH, or DEL in over 40% of the informative loci tested (73, 59, 47, 46, and 44%, respectively), whereas markers on chromosome 2 showed only microsatellite length instability (10%). The authors concluded that tumors and tumor cell lines from patients with Carney complex demonstrate significant genomic, but not microsatellite length, instability. Thus, the Carney complex gene or genes on chromosome 2p16 are different from the MSH2 and MSH6 genes and have a dominant, rather than recessive, tumor function. These genes appear to be involved in the regulation of genomic stability of dividing cells, in particular the structure of telomeres in replicating chromosomes and/or the function of the mitotic apparatus.
Basson et al. (1997) presented evidence from linkage studies that the Carney complex is genetically heterogeneous. They studied a kindred with 7 affected individuals in 4 generations. All 6 living affected individuals exhibited pleomorphic spotty skin pigmentation typical of the Carney complex. All 4 of the 6 affected individuals who had reached adulthood had had left and/or right atrial myxomas. Three individuals whose atrial myxomas were resected had recurrence at least once, distant from the operative site. Three of them had histories of extracardiac myxomas, 2 in the breast and 1 in the vagina. Endocrine abnormalities were present in 3, 2 showed thyroid dysfunction, and 1 required adrenalectomy for Cushing syndrome. Linkage studies yielded lod scores of less than -2.0 over the 10-cM interval between D2S391 and D2S393, where the Carney complex had previously been mapped by Stratakis et al. (1996).
Basson (1999) pointed out that one of the 'chromosome 2' families of Stratakis et al. (1996) was in fact found to be linked to chromosome 17.
Stratakis (1999) evaluated genetic heterogeneity in Carney complex as follows: whereas there are several families with individual lod scores over 3 that mapped to chromosome 17, there are also several families for which the chromosome 17 locus can definitely be excluded. Most of these families (although not all, perhaps leaving room for a third locus) mapped to 2p16 with an aggregate lod score over 5.
Analysis of chromosome rearrangements in tumors is a useful tool for uncovering genes with a role in tumorigenesis and/or tumor progression. Matyakhina et al. (2003) used comparative genomic hybridization (CGH) to demonstrate a low level 2p amplification in 4 of 8 CNC tumors; 1 tumor showed specific amplification of the 2p16-p23 region only. To define more precisely the 2p amplicon in these and other tumors, they completed the genomic mapping of the CNC2 region, and analyzed 46 tumor samples from CNC patients with and without PRKAR1A mutations by FISH using BACs. Consistent cytogenetic changes in the region were detected in 40 (87%) of the samples analyzed. Amplification of the region represented as homogeneously stained regions (HSRs) was found in 24 samples (60%). Three tumors (8%) showed both amplification and deletion of the region in their cells. Thirteen tumors (32%) showed deletion only. Matyakhina et al. (2003) concluded that cytogenetic changes of the 2p16 region that harbors the CNC2 locus are frequently observed in tumors from CNC patients, including those with germline, inactivating PRKAR1A mutations. These changes are mostly amplifications of the 2p16 region that overlap with a previously identified amplicon in sporadic thyroid cancer, and an area often deleted in sporadic adrenal tumors. Both thyroid and adrenal tumors constitute part of CNC indicating that the responsible gene(s) in the area may indeed be involved in both inherited and sporadic endocrine tumor pathogenesis and/or progression.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CARNEY COMPLEX, TYPE 2
|
c2607929
| 7,794 |
omim
|
https://www.omim.org/entry/605244
| 2019-09-22T16:11:27 |
{"doid": ["0050471"], "mesh": ["D056733"], "omim": ["605244"], "orphanet": ["1359"], "synonyms": ["Alternative titles", "CARNEY MYXOMA-ENDOCRINE COMPLEX, TYPE 2"], "genereviews": ["NBK1286"]}
|
McCune-Albright syndrome (MAS) is a disorder that affects the skin, skeleton, and certain endocrine organs (hormone-producing tissues). Cafe-au-lait spots of the skin are common and are usually the first apparent sign of MAS. The main skeletal feature is fibrous dysplasia, which ranges in severity and can cause various complications. Early skeletal symptoms may include limping, pain, or fracture. Endocrinous features may include precocious puberty especially in girls (resulting of estrogen excess from ovarian cysts), excess growth hormone; thyroid lesions with possible hyperthyroidism; renal phosphate wasting, and, rarely, Cushing syndrome caused by an excess of the hormone cortisol produced by the adrenal glands, which are small glands located on top of each kidney. MAS is not inherited. MAS is caused by a somatic mutation in a gene called GNAS, which is acquired after an egg is fertilized and only affects some of the body's cells and tissues. Management depends on the symptoms in each person and may include optimizing function related to fractures and deformities; medications; and surgery.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
McCune-Albright syndrome
|
c0242292
| 7,795 |
gard
|
https://rarediseases.info.nih.gov/diseases/6995/mccune-albright-syndrome
| 2021-01-18T17:59:13 |
{"mesh": ["D005359"], "omim": ["174800"], "orphanet": ["562"], "synonyms": ["MAS", "Albright syndrome", "Albright's disease", "PFD", "POFD", "McCune Albright syndrome", "Polyostotic fibrous dysplasia"]}
|
Baker (1937) and others have reported families with numerous persons with appendicitis in a pattern consistent with dominant inheritance with irregular penetrance. Barker and Morris (1988) and Barker et al. (1988) reported results of epidemiologic studies in the U.K. demonstrating a relationship between housing conditions and the consumption of green vegetables in the frequency of acute appendicitis. These results remind us that familial aggregation may have a nongenetic basis. Basta et al. (1990) found that a positive family history for appendectomy was significantly more frequent in families of 80 consecutive patients with histopathologically proven acute appendicitis than in families of surgical controls matched for sex, age, and number of sibs. The relative risk was 10.0. Analysis of a collection of pedigrees supported a polygenic or multifactorial model with a total heritability of 56%. There is no evidence to support a major gene, although a rare gene could not be ruled out as the cause of a small proportion of cases.
Shamis et al. (1994) studied 2-generation families containing a total of 2,331 persons. Aggregation of acute appendicitis in 782 families indicated a familial factor in predisposition.
GI \- Appendicitis proneness Inheritance \- Polygenic or multifactorial with heritability of 56% ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
APPENDICITIS, PRONENESS TO
|
c1862632
| 7,796 |
omim
|
https://www.omim.org/entry/107700
| 2019-09-22T16:44:48 |
{"omim": ["107700"]}
|
Prostatic stromal tumour of uncertain malignant potential
Other namesProstatic stromal proliferation of uncertain malignant potential (PSPUMP)[1]
Prostatic stromal tumour of uncertain malignant potential. H&E stain.
Prostatic stromal tumour of uncertain malignant potential (PSTUMP) is a rare tumour of the prostate gland stroma that may behave benign or like cancer.
It can be abbreviated STUMP;[2] an abbreviation used for a uterine lesion of uncertain malignant potential.
## References[edit]
1. ^ Gaudin, PB.; Rosai, J.; Epstein, JI. (1998). "Sarcomas and related proliferative lesions of specialized prostatic stroma: a clinicopathologic study of 22 cases". Am J Surg Pathol. 22 (2): 148–62. doi:10.1097/00000478-199802000-00002. PMID 9500215.
2. ^ De Berardinis, E.; Busetto, GM.; Antonini, G.; Giovannone, R.; Di Placido, M.; Magliocca, FM.; Di Silverio, A.; Gentile, V. (2012). "Incidental prostatic stromal tumor of uncertain malignant potential (STUMP): histopathological and immunohistochemical findings". Urologia. 79 (1): 65–8. doi:10.5301/RU.2012.9099. PMID 22388992. S2CID 14922067.
## External links[edit]
Classification
D
* ICD-10: D40.0
* MeSH: C537245
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Prostatic stromal tumour of uncertain malignant potential
|
c1514517
| 7,797 |
wikipedia
|
https://en.wikipedia.org/wiki/Prostatic_stromal_tumour_of_uncertain_malignant_potential
| 2021-01-18T18:28:00 |
{"gard": ["9405"], "mesh": ["C537245"], "umls": ["C1514517", "C2931458"], "wikidata": ["Q28439761"]}
|
Acute uric acid nephropathy
SpecialtyNephrology
Acute uric acid nephropathy (AUAN, also acute urate nephropathy) is a rapidly worsening (decreasing) kidney function (acute kidney injury) that is caused by high levels of uric acid in the urine (hyperuricosuria).
## Contents
* 1 Causes
* 2 Pathophysiology
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 6 References
## Causes[edit]
Acute uric acid nephropathy is usually seen as part of the acute tumour lysis syndrome in patients undergoing chemotherapy or radiation therapy for the treatment of malignancies with rapid cell turnover, such as leukemia and lymphoma. It may also occur in these patients before treatment is begun, due to spontaneous tumor cell lysis (high incidence in Burkitt's lymphoma).
Acute uric acid nephropathy can also be caused by an acute attack of gout.
## Pathophysiology[edit]
Acute uric acid nephropathy is caused by deposition of uric acid crystals within the kidney interstitium and tubules, leading to partial or complete obstruction of collecting ducts, renal pelvis, or ureter. This obstruction is usually bilateral, and patients follow the clinical course of acute kidney failure.
## Diagnosis[edit]
The picture of acute kidney failure is observed: decreased urine production and rapidly rising serum creatinine levels. Acute uric acid nephropathy is differentiated from other forms of acute kidney failure by the finding of a urine uric acid/creatinine ratio > 1 in a random urine sample.
## Prevention[edit]
Patients at risk for acute uric acid nephropathy can be given allopurinol or rasburicase (a recombinant urate oxidase) prior to treatment with cytotoxic drugs.
## Treatment[edit]
Treatment is focused on preventing deposition of uric acid within the urinary system by increasing urine volume with potent diuretics such as furosemide. Raising the urinary pH to a level higher than 7 (alkalinization) is often difficult to attain, although sodium bicarbonate and/or acetazolamide are sometimes used in an attempt to increase uric acid solubility.
Dialysis (preferably hemodialysis) is started if the above measures fail.
## References[edit]
* Conger JD (1990). "Acute uric acid nephropathy". Med Clin North Am. 74 (4): 859–71. PMID 2195258.
* Robinson RR, Yarger WE (1977). "Acute uric acid nephropathy". Arch Intern Med. 137 (7): 839–40. doi:10.1001/archinte.137.7.839. PMID 879920.
* Yu AS, Brenner BM (2005). "Chapter 266: Tubulointerstitial diseases of the kidney". In Kasper DL, Braunwald E, Fauci A, Hauser S, Longo D, Jameson JL (eds.). Harrison's Principles of Internal Medicine (16th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-140235-4
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Acute uric acid nephropathy
|
c0558595
| 7,798 |
wikipedia
|
https://en.wikipedia.org/wiki/Acute_uric_acid_nephropathy
| 2021-01-18T19:00:38 |
{"umls": ["C0558595"], "wikidata": ["Q4677952"]}
|
Hereditary geniospasm is a movement disorder that causes episodes of involuntary tremors of the chin and lower lip. The episodes may last anywhere from a few seconds to hours and may occur spontaneously or be brought on by stress. The episodes usually first appear in infancy or childhood and tend to lessen in frequency with age. Hereditary geniospasm is believed to be inherited in an autosomal dominant pattern. Although the exact gene that causes the condition is unknown, it has been suggested that mutations in a gene on chromosome 9 may be responsible in some families.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hereditary geniospasm
|
c2931589
| 7,799 |
gard
|
https://rarediseases.info.nih.gov/diseases/9501/hereditary-geniospasm
| 2021-01-18T18:00:03 |
{"mesh": ["C537682"], "omim": ["190100"], "orphanet": ["53372"], "synonyms": ["Trembling chin", "GSM 1", "Hereditary chin tremor/myoclonus", "Geniospasm"]}
|
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