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High-grade serous carcinoma
Immunohistochemistry micrograph of androgen receptors on a HGSC tumour sample
High-grade serous carcinoma (HGSC) is a type of tumour that arises from the serous epithelial layer in the abdominopelvic cavity and is mainly found in the ovary. HGSCs make up the majority of ovarian cancer cases[1] and have the lowest survival rates.[2] HGSC is distinct from low-grade serous carcinoma (LGSC) which arises from ovarian tissue, is less aggressive and is present in stage I ovarian cancer where tumours are localised to the ovary.
Although originally thought to arise from the squamous epithelial cell layer covering the ovary, HGSC is now thought to originate in the Fallopian tube epithelium. HGSC is much more invasive than LGSC with a higher fatality rate - although it is more sensitive to platinum-based chemotherapy,[3][4] possibly due to its rapid growth rate. In rare cases, HGSCs can develop from LGSCs,[5][6] but generally the two types arise independently of each other.
## Contents
* 1 Risk factors
* 1.1 Environmental risk factors
* 1.2 Genetic risk factors
* 2 Pathophysiology
* 2.1 Cell origin
* 2.2 Pathogenesis
* 3 Diagnosis
* 3.1 Screening
* 4 Prevention
* 5 Treatment
* 6 Epidemiology
* 7 References
## Risk factors[edit]
### Environmental risk factors[edit]
The ‘incessant ovulation’ theory is suggested by the strong correlation between the number of ovulatory cycles of an individual and their risk of ovarian cancer.[7]
This trend is reflected in the protective effects of pregnancy, parity and breastfeeding against ovarian cancer,[8][9] and similar findings in epidemiological studies that have indicated a reduction of risk associated with use of oral contraceptive pills.[10][7]
Ovulation is accepted as the cause of ovarian cortical inclusion cysts, the precursor lesions of serous carcinomas, and lower numbers of these cortical inclusion cysts are thought to be the mechanism by which reducing lifetime ovulations can lower the risk of developing HGSC.[11]
Conversely, a temporal association with menopausal hormone therapy and incidence of HGSC was found,[12] and polycystic ovarian syndrome (PCOS) was shown to contribute to a doubling of the risk of ovarian cancer.[13]
Endometriosis can increase risk for other ovarian cancer subtypes, but is not associated with HGSC.[14]
### Genetic risk factors[edit]
More than 20% of ovarian cancer tumours have hereditary origin. The majority of these feature mutations in the tumour suppressor BRCA genes, which tend to give rise to HGSC.[15] A mutation in BRCA1 or BRCA2 can confer a lifetime ovarian cancer risk of 40-50% and 10-20% respectively,[16] with BRCA2 mutations strongly associated with better clinical outcomes.
A specific tumour protein 53 (TP53) expression pattern in the Fallopian tube epithelium – the ‘p53 signature’ - is thought to be a precursor marker of HGSC. TP53-/- mice (in which the TP53 gene has been deleted) do not develop ovarian carcinomas.[17] However, TP53 mutations were found in 96% of HGSC cases.[18] A local abnormal TP53 expression may thus be indicative of HGSC.[19] In women, pelvic HGSC show either a complete absence of P53 expression, or overexpression, suggesting that any aberration of P53 leads to tumour development.[20] Additionally, overexpression of TP53 is associated with better clinical outcome whereas an absence of the p53 protein is linked to an increased risk of HGSC tumour recurrence.[20]
A recent mouse model suggest that a p53 mutation may induce HGSC arising from the ovary rather than the Fallopian tube.[21]
## Pathophysiology[edit]
### Cell origin[edit]
HGSC are further distinguished from LGSC by ‘type I/II’ ovarian tumour nomenclature;[22] type I referring to tumour types (e.g. LGSCs) where precursor lesions within the ovary have been characterised, and type II referring to tumour types (e.g. HGSCs) without association of such lesions, tumours understood to develop de novo from the tubal and/or ovarian surface epithelium. This classification has more relevance to research rather than to clinical practice.[23]
The serous membrane is a particular type of secretory epithelium which covers organs in body cavities and secretes serous fluid to reduce friction from muscle movement. Serous membrane lining the abdominopelvic cavity is called the peritoneum; that lining heart and mediastinum is the pericardium, and that lining the thoracic cavity and lungs is the pleura. Technically a ‘serous carcinoma’ can occur anywhere on these membranes, but high-grade serous carcinoma is generally limited to the peritoneal area.
While until recently HGSC was thought to arise from simple differentiation of cortical inclusion cysts (CICs) of ovarian surface epithelium (OSE), the cell origin of HGSC is now understood to be much more complex, with evidence for other sites of origin, both intra- and extra-ovarian, having come to light.
Tissue Evidence for role as HGSC cell of origin
Ovary Supporting:
1. Metastatic HGSC arose in the ovaries of mouse triple knockouts of p53, PTEN and Dicer in which the Fallopian tubes had been removed, as well as in double murine knockouts of PTEN and p53 with intact Fallopian tubes.[21]
2. The stem-cell-rich hilum region of the ovarian surface epithelium is a cancer-prone area.[24]
Opposing:
1. A convincing precursor of HGSC in the ovary has not yet been identified.[25]
Coelomic epithelium Supporting:
'Coelomic hypothesis' [25]
1. Due to the embryological relationship between the coelomic epithelium and the Müllerian ducts, the coelomic epithelium is predisposed to differentiation via Müllerian metaplasia into the different epithelial tumour tissue types (e.g. serous, endometrioid, clear cell and mucinous). Cortical inclusion cysts of the OSE can thus undergo differentiation into neoplasms.
2. This hypothesis can account for primary peritoneal carcinomas by implying that extra-ovarian coelomic epithelium can similarly undergo Müllerian metaplasia.
Opposing:
1. There has so far been an absence of precursor lesions of ovarian carcinomas on the OSE despite extensive histopathology.[10]
Fallopian tube Supporting:
1. Precursor lesions (serous tubal intraepithelial carcinomas or ‘STICs’) found on the fimbrial ends of the Fallopian tube of BRCA 1/2 women.[26]
2. There is physical contact between the fimbriae and the ovary during ovulation (supports ‘incessant ovulation’ hypothesis).
3. The fringes of the fimbriae come into contact with the pro-inflammatory follicular fluid.[27]
4. Identical TP53 mutations in STIC and concurrent HGSC were reported, suggesting a clonal relationship.[28]
5. In the triple p53-PTEN-Dicer knockout mice earlier mentioned, where the Fallopian tubes were intact, HGSC arose from the tubes 100% of the time, eclipsing the tumourgenicity of the ovary.[21] Identical findings were found from PTEN-Dicer knockouts.
6. A 2012 clinical trial of a screening technique found that 7 out of 9 identified HGSC cases arose from the Fallopian tube fimbriae[29]
7. Transfer of transformed serous Fallopian tube secretory epithelium into the peritoneum of severe combined immunodeficiency (SCID) mice induced tumours which resemble human HGSC.[30]
8. Reliable HGSC precursors were found on the Fallopian tubes in the form of abnormal TP53 expression patterns.[31]
9. Serous fimbrial cells are less able to correct DNA damage and reverse mutations than their ciliated counterparts, indicating how they might be particularly vulnerable to the mutagenicity of the follicular fluid at ovulation.[32]
Opposing:
1. A 2013 study shows that STICs only advance to form HGSC in the presence of a BRCA mutation, remaining uninvasive in models without such mutations – suggesting that HGSCs may arise from Fallopian tube tissue in individuals with BRCA mutations, but not generally.[33]
Extra-uterine Müllerian epithelium (EUME) All epithelia of the female genital tract – Fallopian tubes, endometrium, endocervix, ectocervix, upper vagina - are derived from the embryonal Müllerian ducts. Extra-uterine Müllerian epithelium includes the distal end of the Fallopian tubes (the fimbriae), and instances of endosalpingiosis, endometriosis and endocervicosis.
Supporting:
1. High-grade serous extra-uterine carcinomas have been reported.[25][34]
2. Intraovarian Müllerian cysts can be explained as examples of endosalpingiosis within the ovary, rather than as results of Müllerian metaplasia in pre-existing cortical inclusion cysts as per the coelomic hypothesis.
3. This hypothesis can also account for primary peritoneal carcinomas, as EUME can be found far away enough from the ovary and fimbriae to give rise to tumors without input from those organs.
4. The extensiveness of EUME can also explain the presence of paratubal and paraovarian tumours.
5. Endosalpingiosis - a condition where Fallopian tube epithelium is found outside the Fallopian tube - supports the likelihood of HGSC arising in the wider peritoneum.
6. Endosalpingiosis is associated with high incidence of borderline serous carcinoma (38%) and HGSC (18%).[35]
7. A central role of EUME in HGS carcinogenesis would account for cases of HGSC that do not involve precursor STICs.
Opposing:
1. This is a relatively new hypothesis and requires further research using appropriate models before conclusions can be drawn.
Border between ovary and Fallopian tube (transition zone) Supporting:
1. Transition zones in other epithelia are frequent sites of stem cells.
2. Such an epithelial transition zone may have more ambiguous stem cell fate signalling, and thus may be vulnerable to carcinogenesis.[27]
3. A number of epithelial transition zones, e.g. ectocervix junction, gastro-duodenal junction, are implicated in the development of different epithelial cancers.[36]
Opposing:
1. This is a relatively new hypothesis and requires further research using appropriate models before conclusions can be drawn.
The common Müllerian origin of the Fallopian tubes, uterus, cervix, and upper vagina has resulted in the proposal that peritoneal high-grade serous carcinoma is a spectrum of a single disease.[23]
Relevant animal models of HGSC can only be developed when the cell origin is properly understood. However, as HGSC tends to have the same clinical behaviour, regardless of its primary cell origin, determining cell origin is less important for clinical treatment, but may be of relevance when looking for biomarkers.
The specific process by which a HGSC arises may be related to the BRCA mutation status of the individual,[33][37] as well as the p53 mutation status.[21]
A 2007 paper describes the process of determining cell of origin as “Tumour origin is typically assigned to the organ presenting with the dominant tumour mass. The one exception is the peritoneum, which is classified as a primary site only if a candidate origin is not found in the endometrium, tube or ovary”.[38]
It is recognised that HGSC can have variable and complex primary origins, but understanding and determining this will give insight into its pathogenesis.
Diagram of HGSC theories of origin
### Pathogenesis[edit]
Assuming a fimbrial origin, as observed in the majority of HGSC cases,[29] the current understanding of HGSC genesis suggests a process by which STIC fimbrial cells implant into the ovary as cortical inclusion cysts through the ovulation rupture site.
To account for instances where there is no STIC involvement, endosalpingiosis or de novo metaplasia of ovarian surface epithelium inclusions are also possible. A much rarer occurrence is the differentiation of HGSC from LGSC.[5][6]
## Diagnosis[edit]
Symptoms include persistent bloating, postmenopausal bleeding, and/or appetite loss.[39]
Transvaginal ultrasonography as well as cancer marker CA125 level analysis is often used to determine potential malignancy of suspect pelvic masses.[40]
Surgical staging is the procedure by which the abdominal cavity and lymph nodes are examined for malignant tissue, usually via laparoscopy. Tissue biopsies may be taken for further analysis. It is not until this histological analysis stage that actual diagnosis of HGSC can be made.[40]
If glands are seen to fuse with intricate, extensive papillae featuring epithelial tufting with solid nests surrounded by a space alongside irregular slit-like spaces, then serous carcinoma is suspected.
Distinguishing between LGSC and HGSC:[41]
1. Necrosis is common in HGSC and absent in LGSC, as are giant (multi- or mononucleated) tumour cells.
2. Psammoma bodies are more frequent in low-grade serous carcinoma.
3. Tp53 expression is assessed for mutations, overexpression or absence – common features of high-grade serous carcinomas.
4. LGSCs are generally limited to micropapillary growth patterns, whereas HGSCs can exhibit admixed patterns.
Distinction of HGSC from high-grade endometrioid carcinoma is not always possible.[41]
The progression of HGSC may also be determined from examining the cadherin expression profile.[42]
### Screening[edit]
As ovarian cancer is rarely symptomatic until an advanced stage,[43] regular pre-emptive screening is a particularly important tool for avoiding the late stage at which most patients present. However, A 2011 US study found that transvaginal ultrasound and cancer marker CA125 screening did not reduce ovarian cancer mortality.[44] In contrast, a more recent UK study found that up to 20% of ovarian cancer deaths could be prevented through annual performance of these procedures.[45]
## Prevention[edit]
Prevention for an individual deemed at risk of HGSC has, up until recently, been (bilateral or unilateral) removal of both the ovary and the Fallopian tube (salpingo-oophorectomy).
With hormonal and even morbidity issues resulting from ovary removal, and the increased evidence for the role of the Fallopian tubes HGSC pathogenesis, optimisation of this procedure has been to remove just the Fallopian tube(s) (salpingectomy) with the ovaries remaining until age of menopause [46][47] \- although critics of this argue that a reduced blood supply to the ovaries may induce premature menopause regardless.[48]
Prophylactic salpingo-oophorectomy is frequently performed in carriers of BRCA1 or BRCA2 mutations,[49] although the benefits conferred by this procedure may vary dependent on the specific mutation.[50]
Tubal ligation is a less invasive prophylactic treatment shown to significantly reduce the risk of HGSC.[51]
## Treatment[edit]
Cytoreductive “debulking” surgery may be performed prior to chemotherapy treatment in order to decrease the physical mass of the tumour and thus reduce the number of chemotherapy cycles needed.[40] The typical advanced presentation as well as extra-ovarian spread seen in HGSC can require aggressive debulking procedures.[52] In some cases total abdominal hysterectomy will be performed, in other cases where the patient intends to bear children a salpingo-oophorectomy is performed instead.
Typical chemotherapy is six cycles of intraperitoneally-delivered platinum-base adjuvant chemotherapy with agents such as carboplatin.[40] Measurements of blood CA125 levels are used to determine patient response to the treatment.
Between 20% and 30% of patients relapse within six months of treatment.[53]
Poly ADP ribose polymerase (PARP) inhibitors are another possible treatment, with carriers of BRCA1/2 mutations being the most responsive [54][55]
## Epidemiology[edit]
A study of incidence rates in the US between 1992 and 1999 found that the age-specific incidence rate for HGSC doubles every 10 years up until age 55, where it plateaus at approximately 20 cases per 100,000 women - before dropping dramatically after age 75.[56]
Ovarian cancer incidence rates are low in East Asia[57] and highest in Europe, the United States, and Australia/New Zealand.[58]
Since 1975, survival rates for ovarian cancer have steadily improved with a mean decrease of 51% by 2006 of risk of death from ovarian cancer for an advanced stage tumour.[59] The increase has mainly been due to successful extended life expectancy of affected patients rather than an improvement in cure rates.
A racial disparity exists between black and white women in the US, where black women experience a higher mortality risk from ovarian cancer.[59][60]
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|
High-grade serous carcinoma
|
c3839280
| 8,000 |
wikipedia
|
https://en.wikipedia.org/wiki/High-grade_serous_carcinoma
| 2021-01-18T18:36:45 |
{"umls": ["C3839280"], "wikidata": ["Q28134897"]}
|
A number sign (#) is used with this entry because of evidence that one form of primary open angle glaucoma (POAG), designated GLC1A, is caused by heterozygous mutation in the MYOC gene (601652) on chromosome 1q.
Heterozygous mutations in the CYP1B1 gene (601771) may also contribute to the phenotype by digenic inheritance.
For a general phenotypic description and a discussion of genetic heterogeneity of POAG, see 137760.
Clinical Features
Impressive 'dominant' pedigrees of juvenile glaucoma were reported by Stokes (1940), Allen and Ackerman (1942), and others. In a Scottish family that settled in Virginia, Courtney and Hill (1931) described 18 cases (10 males, 8 females) in 5 generations with 2 instances of failure of penetrance in the third generation. Onset was usually in the second or third decade and the course was rapid.
Crombie and Cullen (1964) described juvenile open angle glaucoma in 11 members of 5 generations (see 601652.0009 for a description of the gln337-to-arg mutation in the MYOC gene in that kindred). Harris (1965) observed 16 cases in 3 generations. The age of onset in 8 of these averaged 26 years. The angles of the anterior chambers were open in 1 patient on whom gonioscopy was performed early in the progress of the disease.
Juvenile glaucoma of the form present in the kindreds studied by Sheffield et al. (1993) and Richards et al. (1994) is an uncommon form of open angle glaucoma, usually recognized during childhood or early adulthood and often showing a strong family history. Johnson et al. (1993) found that the average age at diagnosis was 18 years. Affected family members tended to be myopic, but lacked other ocular or systemic abnormalities. The intraocular pressures of affected individuals were commonly more than 50 mm Hg when they were first examined. Gonioscopy showed open angles, with no abnormal pigmentation, iris processes, or embryonic tissue. Topical medications were initially effective in controlling intraocular pressure, but surgery was usually required for long-term pressure control.
Wiggs et al. (1995) reported the clinical features of 5 pedigrees in which primary juvenile glaucoma showed linkage to 1q21-q31. In the 23 affected patients, the average age of diagnosis was 18.5 years (range, 5 to 30 years), and the average initial intraocular pressure was 38.5 mm Hg (range, 30 to 53 mm Hg). Myopia was present in 87% of affected individuals, and 83% required surgical treatment for glaucoma. A difference in phenotypic expression was observed in a pair of monozygotic twins who carried the affected haplotype. In one twin, the diagnosis of severe glaucoma was made at the age of 19 years. Because of this diagnosis, his twin brother was examined and found to have somewhat elevated intraocular pressures but minimal optic nerve deterioration and full visual fields. Linkage to 1q21-q31 was excluded in 2 other families with juvenile glaucoma. One of these families was African American. In the other family, early onset of the disease was associated with severe optic nerve deterioration before 10 years of age, despite only moderate elevations of intraocular pressures.
Lotufo et al. (1989) found that juvenile-onset open angle glaucoma is more frequent among Americans of African ancestry. Johnson et al. (1996) described the clinical phenotype of juvenile-onset primary open angle glaucoma in a previously unpublished family showing linkage to 1q. The family included 22 affected individuals over 5 generations, of whom 12 were still living. The average age of diagnosis for living affected individuals was 26 years. An association between myopia and glaucoma was observed in this family, but the glaucoma was not associated with iris processes or other structural anomalies. The clinical course and response to treatment were similar to those in other families with this disease. The phenotype can range from mild ocular hypertension to blindness, with age of diagnosis ranging from 6 to 62 years. However, most affected individuals display a characteristic phenotype that includes onset in the first 3 decades of life, unusually high intraocular pressures, and the need for surgical therapy to prevent loss of vision.
Mapping
In a family in which 22 persons were affected with an autosomal dominant form of juvenile-onset open angle glaucoma (Johnson et al., 1993), Sheffield et al. (1993) used short tandem repeat markers in linkage analysis to map the gene to 1q21-q31. The highest lod score was provided by D1S212; lod = 6.5 at theta = 0.0. They noted that one of the atrial natriuretic peptide receptor genes (108960) maps to 1q21-q22. Richards et al. (1994) extended the linkage studies in a different family, confirming the assignment to 1q21-q31. Wiggs et al. (1994) confirmed the assignment to 1q by the study of 3 affected pedigrees. Meyer et al. (1994) confirmed linkage to 1q21-q23 in 2 large French kindreds; maximum lod = 7.60 with D1S212 at theta = 0.44.
In a Danish 5-generation dominant juvenile-onset glaucoma family, Graff et al. (1995) confirmed linkage to 1q; a maximum 2-point lod score of 6.67 was obtained for linkage to D1S210. However, multipoint linkage analysis in a 9-generation Swedish family with dominant juvenile-onset glaucoma and iris hypoplasia excluded linkage to the region of approximately 18 cM between loci D1S104 and D1S218, shown to contain the previously mapped glaucoma gene. The diagnosis in the Swedish family that failed to show linkage to 1q may be 'iris hypoplasia with early onset glaucoma, autosomal dominant' (see 137600), which in some instances has been mapped to chromosome 4q.
Morissette et al. (1995) studied 142 members of a huge multigenerational French-Canadian family affected with autosomal dominant primary open angle glaucoma. In 40 patients, either juvenile open angle glaucoma (JOAG) or chronic open angle glaucoma (COAG) with diagnosis after age 40 years was identified. In 6 subjects, ocular hypertension, a possible precursor of primary open angle glaucoma, was found. JOAG/COAG was tightly linked to 7 microsatellite markers on 1q23-q25. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or ocular hypertension, but did not occur in unaffected spouses or in normal family members more than 35 years of age, except for 3 obligatory carriers. From these observations, Morissette et al. (1995) concluded that the GLC1A gene is responsible for both adult-onset and juvenile glaucoma.
Wiggs et al. (1996) suggested that although the findings of Morissette et al. (1995) may indicate that variable expressivity of the GLC1A gene may lead to a broader range of onset for the form of juvenile glaucoma that maps to 1q, it does not follow that the GLC1A gene is an important cause of adult-onset primary open angle glaucoma (137760). Wiggs et al. (1996) noted that the adult-onset primary open angle glaucoma usually has its onset after the age of 50 and is probably inherited as a complex trait, without an obvious segregation pattern. The rare juvenile form, inherited as an autosomal dominant with high penetrance, almost always develops before the age of 40. Morissette et al. (1995) studied 40 members of the family who showed a common haplotype derived from microsatellite markers located in the 1q21-q31 region and found that 36 developed the disease before the age of 40. The remaining 4 were first diagnosed at ages 44, 47, 53, and 62. However, because of the insidious character of glaucoma, pinpointing the actual onset of the disease is difficult.
Richards et al. (1996) appeared to have excluded mutation at the GLC1A locus as the cause of primary open angle glaucoma with onset in middle age (between 42 and 57 years) in a large affected family.
Brezin et al. (1997) tested linkage to the GLC1A locus in 8 French families with open angle glaucoma and ocular hypertension. The median age at diagnosis was 28.5 years. When analysis was based on a phenotype consisting of both open angle glaucoma and ocular hypertension, linkage to the GLC1A locus was found in 4 families and excluded in 3 families. When the phenotype was limited to only those with open angle glaucoma, linkage to the GLC1A locus was excluded in 2 families. Brezin et al. (1997) also demonstrated that while there was no difference in peak intraocular pressure between the linked and unlinked families, those linked to GLC1A had an increased risk of developing open angle glaucoma and of having severe glaucomatous optic neuropathy. Belmouden et al. (1997) used recombinant haplotypes to reduce the GLC1A interval to a maximum of 3 cM in the region 1q23-q25. Findings in a contig from this region were compatible with its cytogenetic location on 1q24 G-band.
Molecular Genetics
Stone et al. (1997) used analyses of sequence tagged site (STS) content and haplotype sharing between families affected with the 1q-linked form of glaucoma to prioritize candidate genes for mutation screening. A gene encoding the trabecular meshwork protein myocilin (MYOC; 601652) mapped to the narrowest disease interval by both STS content and radiation hybrid mapping. In 13 glaucoma probands, including the proband from the family with 22 affected members originally described by Johnson et al. (1993) and in which Sheffield et al. (1993) demonstrated linkage to 1q, Stone et al. (1997) identified heterozygosity for 1 of 3 different mutations in the MYOC gene (601652.0001-601652.0003). Initially, a search for mutations in the MYOC gene by Stone et al. (1997) was applied to the screening of affected members of 4 different 1q-linked glaucoma families and affected members of 4 smaller families implicated by haplotype data. Amino acid-altering mutations were detected in 5 of the 8 families. A tyrosine-to-histidine mutation in codon 430 (601652.0001) was detected in all 22 affected members of the original family in which 1q linkage was demonstrated (Sheffield et al., 1993). A lysine-to-valine mutation in codon 357 (601652.0002) was detected in 2 families, including 1 previously unreported adult-onset open angle glaucoma family with 15 affected members. A nonsense mutation (gln361 to ter; 601652.0003), which would be expected to result in a 136-amino acid truncation of the gene product, was detected in 2 families. The prevalence of these mutations was then estimated by screening 4 different populations: glaucoma patients with a family history of the disease; unselected primary open angle glaucoma probands seen in a single clinic; the general population (approximated by patients with heritable retinal disease and spouses from families who participated in prior linkage studies); and unrelated volunteers over the age of 40 with normal intraocular pressures and no personal or family history of glaucoma. These experiments revealed 8 additional individuals harboring the gln361-to-ter mutation and 1 additional individual harboring the tyr430-to-his mutation. Overall, missense or nonsense mutations were found in 13 of 330 unrelated glaucoma patients (3.9%) and 1 of 471 controls (0.2%). Stone et al. (1997) speculated that the MYOC gene product may cause increased intraocular pressure by obstruction of aqueous outflow. Its expression in trabecular meshwork and ciliary body (structures of the eye involved in the regulation of intraocular pressure) is consistent with this hypothesis. The prevalence of the sequence changes observed in this study, coupled with the prevalence of glaucoma in the general population, suggested to the authors that mutations in GLC1A cause glaucoma in nearly 100,000 individuals in the U.S. This would make GLC1A the most common molecularly recognizable form of blindness. For comparison, only 2,000 people in the U.S. would be expected to harbor mutations in the rhodopsin gene (180380), which is the most common form of molecularly recognizable retinitis pigmentosa.
Alward et al. (1998) screened 716 patients with primary open angle glaucoma and 596 control subjects for sequence changes in the GLC1A gene. They identified 16 sequence variations that met the criteria for probable disease-causing mutations because they altered the predicted amino acid sequence and were found in one or more patients with glaucoma and in less than 1% of the control subjects. These 16 mutations were found in 33 patients (4.6%). Six of the mutations were found in more than 1 subject (total, 99). Clinical features associated with these 6 mutations included an age at diagnosis ranging from 8 to 77 years and maximal recorded intraocular pressures ranging from 12 to 77 mm Hg. The spectrum of disease, as indicated by this survey, can range from juvenile glaucoma to typical late-onset primary open angle glaucoma. Quigley (1996) commented on the fact that glaucoma is the second leading cause of blindness in the world after cataract, affecting approximately 70 million people, about half of whom are estimated to have open angle glaucoma. Nearly as many people have angle-closure glaucoma, a disorder that is particularly prevalent among Asians. Among persons of European and African ancestry in the United States, open angle glaucoma affects an estimated 2.5 million, half of whom are unaware of their disease. The disorder is present in 2% of those over the age of 40 years, and the prevalence increases with age. The risk among blacks is 4 times that among whites. Quigley (1998) stated that it is premature to suggest that screening of genetic loci for open angle glaucoma will be widely useful, however.
Yoon et al. (1999) described a Korean case of apparent autosomal recessive inheritance of juvenile-onset POAG (601652.0011).
Wiggs and Vollrath (2001) examined a patient with a complex deletion of the maternal copy of chromosome 1 that included the entire TIGR/MYOC gene. Neither the patient nor her family showed evidence of glaucoma. The authors concluded that haploinsufficiency of the TIGR/MYOC protein is not the cause of early-onset glaucoma associated with mutations in TIGR/MYOC even though missense and nonsense mutations in the gene have been associated with juvenile- and adult-onset primary open angle glaucoma.
Craig et al. (2001) studied the phenotype and age-related penetrance of primary open angle glaucoma in families with the most common myocilin mutation in Australia (gln368 to ter; Q368X; 601652.0003). They found that the Q368X mutation was associated with primary open angle glaucoma with younger onset and higher peak intraocular pressure than nonmutation glaucoma cases. In addition, Q368X mutation glaucoma cases were more likely to have undergone glaucoma drainage surgery. They did not observe simple autosomal dominant inheritance patterns for POAG in the 8 pedigrees studied. They concluded that other factors were involved in expression of the POAG phenotype in Q368X pedigrees.
Approximately 10 to 20% of all cases of JOAG are caused by mutations in the MYOC gene. Wiggs et al. (2004) identified 25 pedigrees with typical JOAG, demonstrating autosomal dominant inheritance. They sequenced the myocilin gene in probands from each family and found mutations in 8%.
In 2 of 100 unrelated Indian patients with glaucoma, Sripriya et al. (2004) identified a heterozygous mutation in the MYOC gene (601652.0014). One patient with juvenile-onset glaucoma was from northern India; 4 affected family members with JOAG had the same mutation.
Baird et al. (2005) studied a large 6-generation Tasmanian family of British ancestry with POAG originally described by Craig et al. (2001), in which 9 of 24 affected individuals had a Q368X mutation in the MYOC gene (601652.0003), but the remaining 15 patients did not. Using Markov chain Monte Carlo multipoint estimations of identity-by-descent sharing and allele-sharing methods, they identified a second disease region in this family on the short arm of chromosome 3. The disease locus was initially mapped to D3S1298 and subsequently narrowed to a minimum 9-cM region between markers D3S1298 and D3S1289. A multiplicative relative risk model revealed a positive association between this region and the Q368X mutation on chromosome 1 in affected individuals. Baird et al. (2005) concluded that there is an autosomal dominant glaucoma locus (GLC1L) on chromosome 3p.
Bhattacharjee et al. (2007) screened 315 Indian patients with POAG for mutation in the MYOC gene and identified 7 mutations in 11 patients, indicating that MYOC mutations account for 2.2% of POAG cases in this population.
Hewitt et al. (2007) compared findings in 66 patients heterozygous for a range of MYOC mutations with those of 105 patients with open angle glaucoma known not to have an MYOC mutation. Patients with an MYOC mutation had glaucoma diagnosed earlier (P less than 0.001) and had higher maximum recorded intraocular pressures (P less than 0.001) than those without an MYOC mutation. There were no significant structural or morphologic differences between the 2 groups. Disc hemorrhages were identified more frequently in those without MYOC mutations (14/209 vs 1/129) but this was not significant after correction for multiple hypothesis testing.
In affected members of a US family segregating POAG, Wirtz et al. (2007) identified an asp380-to-his (D380H; 601652.0017) mutation in the MYOC gene. The disease presented in this family with extremely high IOPs requiring trabeculectomies to control the pressure. The age at diagnosis ranged from 30 to 45 years. Wirtz et al. (2007) cited reports of 3 other substitutions at asp380 to ala, asn, and gly, all of which resulted in a similar presentation of POAG that was intermediate between the more severe clinical presentations observed in individuals with the pro370-to-leu (601652.0004) or lys423-to-glu (601652.0010) variant and the milder findings observed in patients with the gln368-to-ter (601652.0003) mutation.
### Digenic Inheritance
Vincent et al. (2002) described a Canadian family segregating both primary adult-onset and juvenile forms of open angle glaucoma, which were associated with digenic mutations in the MYOC (601652.0013) and the CYP1B1 (601771.0012) genes. All affected family members carried the MYOC mutation; those who also carried the CYP1B1 mutation had juvenile glaucoma, whereas those with only the MYOC mutation had the adult-onset form. The mean age at onset of disease among carriers of the MYOC mutation alone was 51 years, whereas carriers of both MYOC and CYP1B1 mutations had an average age at onset of only 27 years. Individuals carrying only the CYP1B1 mutation were not clinically affected. Thus, in this family, CYP1B1 appeared to be acting as a modifier of MYOC.
### Reviews
Kwon et al. (2009) reviewed the clinical features of primary open-angle glaucoma and the mechanisms of elevated intraocular pressure and optic nerve damage, focusing on mutations in the MYOC gene.
Animal Model
Gould et al. (2004) found that mice overexpressing Myoc to a level similar to that induced by corticosteroids did not develop elevated intraocular pressure or glaucoma. They hypothesized that disease pathogenesis in primary open-angle glaucoma patients may depend upon expression of abnormal mutant MYOC protein.
Zillig et al. (2005) used the chicken beta-B1-crystallin promoter to overexpress human wildtype and Y437H (601652.0001)-mutated myocilin in the lenses of transgenic mice. They found that increasing amounts of myocilin were not secreted in vivo but remained in the rough endoplasmic reticulum, causing severe alterations of cellular structure and function. Lenses expressing mutated Y437H myocilin developed nuclear cataracts, completely lost transparency, and eventually ruptured.
Shepard et al. (2007) demonstrated that mutations in human MYOC induce exposure of a cryptic peroxisomal targeting sequence, which must interact with PTS1R (PEX5; 600414) to elevate intraocular pressure (IOP). They noted that the lack of a PTS1 signal on mouse myocilin explains why IOP was unchanged in mice overexpressing mouse wildtype myocilin (Gould et al., 2004) and in knockin mice expressing the mouse ortholog of human Y437H myocilin (Gould et al., 2006). In contrast, expression of human MYOC glaucomatous mutations in mouse eyes did cause elevation of IOP. Shepard et al. (2007) stated that this was the first disease-gene-based animal model of human primary open-angle glaucoma.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Glaucoma, open-angle \- Myopia MOLECULAR BASIS \- Caused by mutation in the myocilin gene (MYOC, 601652.0001 ) ▲ 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
|
GLAUCOMA 1, OPEN ANGLE, A
|
c2981140
| 8,001 |
omim
|
https://www.omim.org/entry/137750
| 2019-09-22T16:40:43 |
{"doid": ["1068", "1067"], "omim": ["137750"], "orphanet": ["98977"], "synonyms": ["Alternative titles", "GLAUCOMA, PRIMARY OPEN ANGLE, JUVENILE-ONSET, 1"]}
|
Haemochromatosis type 4
Other namesFerroportin disease
SpecialtyHepatology, Medical genetics
CausesMutation in ferroportin gene
Differential diagnosisHereditary hemochromatosis
TreatmentPhlebotomy, Iron chelation
FrequencyRare
Hemochromatosis type 4, is a hereditary iron overload disorder that affects ferroportin, an iron transport protein needed to export iron from cells into circulation.[1] Although the disease is rare, it is found throughout the world and affects people from various ethnic groups. While the majority of individuals with type 4 hemochromatosis have a relatively mild form of the disease, some affected individuals have a more severe form. As the disease progresses, iron may accumulate in the tissues of affected individuals over time, potentially resulting in organ damage.[2]
## Contents
* 1 Signs and Symptoms
* 2 Genetics
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and Symptoms[edit]
Symptoms vary greatly between individuals with type 4 hemochromatosis. This difference in symptoms is likely due to the different types of SLC40A1 mutations patients may have.[3] In general, signs and symptoms of type 4 hemochromatosis are caused by excess iron in cells, which leads to tissue damage. The damage is largely due to iron-catalyzed oxidative reactions. Iron can exchange electrons with a variety of substrates, which can lead to generation of reactive oxygen species. This can lead to oxidative stress, lipid peroxidation, and DNA damage, which may result in cell death.[4] Two main forms of hemochromatosis type 4 exist (A and B), and the symptoms of these forms are distinct from one another.[5]
Type 4A hemochromatosis typically has milder symptoms than other types of hemochromatosis. Individuals with type 4A hemochromatosis tend to have hyperferritinemia (elevated ferritin in the blood plasma) and low saturated transferrin levels. These individuals are likely to have liver and spleen iron overload, primarily in Kupffer cells and other macrophages.[6] Because iron export is impaired, iron is unavailable for transport by circulating transferrin. This iron unavailability potentially leads to mild anemia in type 4A hemochromatosis patients because iron is necessary for hemoglobin synthesis, and red blood cells have a relatively high turnover rate.[7] Over time, iron stores increase, and individuals with type 4A hemochromatosis may develop hepatic fibrosis.[8]
The symptoms of type 4B hemochromatosis tend to be more severe. They resemble the symptoms of hemochromatosis types 1, 2, and 3. Plasma iron concentration is elevated, and symptoms include joint pain, diabetes, and arrhythmia. Liver iron deposition tends to be greater in type 4B than in type 4A.[9] Liver damage occurs more frequently in this form of hemochromatosis than in type 4A, and some individuals develop cirrhosis of the liver.[10]
## Genetics[edit]
Type 4 hemochromatosis is caused by mutations of the SLC40A1 gene, located on the long arm of chromosome 2, specifically at 2q32.2. The SLC40A1 gene encodes ferroportin, a protein responsible for exporting iron from cells in the intestine, liver, spleen, and kidney, as well as from reticuloendothelial macrophages and the placenta.[11][12] More than 39 mutations to the SLC40A1 gene have been identified in patients with type 4 hemochromatosis.[13] All reported SLC40A1 mutations are deletions or missense mutations, which lead to amino acid substitution.[14]
Mutations to SLC40A1 that change the amino acid sequence can result in loss of function or gain of function for the resulting ferroportin protein. The loss of function mutation results in a phenotype that is different from that of a gain of function mutation, and these phenotypes are associated with two different forms of type 4 hemochromatosis. Loss-of-function mutations are more frequent and are associated with type 4A hemochromatosis. These mutations lead to a defect in the localization of ferroportin. Gain-of-function mutations are associated with type 4B and lead to production of ferroportin that resists negative regulation by hepcidin.[15][16]
Unlike other forms of hemochromatosis, which have a recessive pattern of inheritance, type 4 is an autosomal dominant disorder. The dominant inheritance pattern occurs in hemochromatosis type 4 because ferroportin is multimeric. Consequently, mutant ferroportin can associate with wild-type ferroportin in multimers and interfere with the function of normal ferroportin proteins.[17]
## Pathophysiology[edit]
In normal iron regulation, iron is absorbed in the intestine, and ferroportin transports iron from the cells of the intestinal lining into the bloodstream. Iron in the bloodstream is then bound by transferrin, which carries the iron to target cells. Iron is stored in cells and blood serum in a protein called ferritin. Reticuloendothelial macrophages, which can phagocytose red blood cells, are important in the iron recycling process. Ferroportin is upregulated in the reticuloendothelial macrophages after phagocytosis occurs so that iron from the degraded red blood cells can be released into the bloodstream and transported to other types of cells as needed. Hepcidin, a protein synthesized in the liver in response to iron or inflammation, is a regulator of ferroportin expression. When hepcidin binds ferroportin, ferroportin is phosphorylated, endocytosed, tagged with ubiquitin, and degraded.[18][19] More than 39 mutations to the SLC40A1 gene have been identified in patients with type 4 hemochromatosis.[20] The misregulation of ferroportin in type 4 hemochromatosis can involve a failure of ferroportin to be properly expressed at the cell membrane, or it can involve a failure of ferroportin to respond to negative regulation by hepcidin.[21]
Hemochromatosis type 4A is characterized by impaired iron export in cells. Reticuloendothelial macrophages are most affected. Iron accumulates preferentially in Kupffer cells, which are located in the liver, and serum ferritin increases; less iron is available for circulating transferrin, a protein that binds iron and transports it through the bloodstream to cell receptors.[22][23] This means that, while iron is trapped in certain types of tissues, it cannot be transported to tissues where it is needed. The accumulation of iron in tissues due to impaired iron export can lead to increasing transferrin iron saturation and liver parenchymal iron overload in advanced stages of the disease.[24] More ferritin is produced to suppress oxidative cell damage, although the amount of ferritin that cells can accumulate is limited.[25]
Hemochromatosis type 4B is characterized by abnormal iron release from macrophages and enterocytes because the mutant ferroportin is resistant to the hepcidin protein, which serves a regulatory function in wild-type ferroportin.[26] Intestinal iron absorption and release of iron from macrophages is increased.[27] Thus, this form of the disease leads to elevated transferrin saturation levels.[28] Systemic iron overload results, and liver iron deposition is primarily in the hepatocytes.[29]
## Diagnosis[edit]
Diagnosis is based upon identification of symptoms, medical history, family history, and laboratory tests. Blood tests may show high levels of ferritin and low, normal, or high levels of transferrin saturation, depending on the form of hemochromatosis. The diagnosis must be confirmed by genetic testing for SLC40A1 mutations.[30]
## Treatment[edit]
Treatment is based on the symptoms and severity of the disease. Iron chelators may be used to bind excess iron in tissues and allow for excretion of the excess metal.[31] Individuals with hemochromatosis type 4B may be treated with therapeutic phlebotomy. However, individuals with hemochromatosis type 4A may not require treatment. Additionally, therapeutic phlebotomy may not be tolerated in individuals with type 4A because anemia may develop despite the elevated serum ferritin levels typically found in these individuals.[32]
## Epidemiology[edit]
Ferroportin disease is rare.[33]
## References[edit]
1. ^ Roetto, A.; Camaschella, C. (2005). "New insights into iron homeostasis through the study of non-HFE hereditary haemochromatosis". Best Practice & Research Clinical Haematology. 18 (2): 235–250. doi:10.1016/j.beha.2004.09.004. PMID 15737887.
2. ^ Pietrangelo, A. (2004). "Non-HFE hemochromatosis". Hepatology. 39 (1): 21–29. doi:10.1002/hep.20007. PMID 14752817.
3. ^ Wallace, D.F.; Subramaniam, V.N. (2007). "Non-HFE haemochromatosis". World Journal of Gastroenterology. 13 (35): 4690–4698. doi:10.3748/wjg.v13.i35.4690. PMC 4611190. PMID 17729390.
4. ^ Gozzelino, R.; Arosio, P. (2016). "Iron homeostasis in health and disease". International Journal of Molecular Sciences. 17 (1): 130. doi:10.3390/ijms17010130. PMC 4730371. PMID 26805813.
5. ^ Wallace, D.F.; Subramaniam, V.N. (2007). "Non-HFE haemochromatosis". World Journal of Gastroenterology. 13 (35): 4690–4698. doi:10.3748/wjg.v13.i35.4690. PMC 4611190. PMID 17729390.
6. ^ Porto, G.; Brissot, P.; Swinkels, D.W.; Zoller, H.; Kamarainen, O.; Patton, S.; Alonso, I.; Morris, M.; Keeney, S. (2016). "EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)". European Journal of Human Genetics. 24 (4): 479–495. doi:10.1038/ejhg.2015.128. PMC 4929861. PMID 26153218.
7. ^ Gozzelino, R.; Arosio, P. (2016). "Iron homeostasis in health and disease". International Journal of Molecular Sciences. 17 (1): 130. doi:10.3390/ijms17010130. PMC 4730371. PMID 26805813.
8. ^ Wallace, D.F.; Subramaniam, V.N. (2007). "Non-HFE haemochromatosis". World Journal of Gastroenterology. 13 (35): 4690–4698. doi:10.3748/wjg.v13.i35.4690. PMC 4611190. PMID 17729390.
9. ^ Porto, G.; Brissot, P.; Swinkels, D.W.; Zoller, H.; Kamarainen, O.; Patton, S.; Alonso, I.; Morris, M.; Keeney, S. (2016). "EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)". European Journal of Human Genetics. 24 (4): 479–495. doi:10.1038/ejhg.2015.128. PMC 4929861. PMID 26153218.
10. ^ Wallace, D.F.; Subramaniam, V.N. (2007). "Non-HFE haemochromatosis". World Journal of Gastroenterology. 13 (35): 4690–4698. doi:10.3748/wjg.v13.i35.4690. PMC 4611190. PMID 17729390.
11. ^ MacKenzie, E.L.; Iwasaki, K.; Tsuji, Y. (2008). "Intracellular iron transport and storage: from molecular mechanisms to health implications". Antioxid. Redox Signal. 10 (6): 997–1030. doi:10.1089/ars.2007.1893. PMC 2932529. PMID 18327971.
12. ^ Chen, S.R.; Yang, L.Q.; Chong, Y.T.; Jie, Y.S.; Wu, Y.K.; Yang, J.; Lin, G.L.; Li, X.H. (2015). "Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4". Internal Medicine Journal. 45 (6): 672–676. doi:10.1111/imj.12764. PMID 26059880.
13. ^ Chen, S.R.; Yang, L.Q.; Chong, Y.T.; Jie, Y.S.; Wu, Y.K.; Yang, J.; Lin, G.L.; Li, X.H. (2015). "Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4". Internal Medicine Journal. 45 (6): 672–676. doi:10.1111/imj.12764. PMID 26059880.
14. ^ Domenico, I.; Ward, D.M.; Nemeth, E.; Vaughan, M.B.; Musci, G.; Ganz, T.; Kaplan, J.; Kornfeld, S.A. (2005). "The molecular basis of ferroportin-linked hemochromatosis". Proceedings of the National Academy of Sciences of the United States of America. 102 (25): 8955–8960. doi:10.1073/pnas.0503804102. PMC 1157058. PMID 15956209.
15. ^ Domenico, I.; Ward, D.M.; Nemeth, E.; Vaughan, M.B.; Musci, G.; Ganz, T.; Kaplan, J.; Kornfeld, S.A. (2005). "The molecular basis of ferroportin-linked hemochromatosis". Proceedings of the National Academy of Sciences of the United States of America. 102 (25): 8955–8960. doi:10.1073/pnas.0503804102. PMC 1157058. PMID 15956209.
16. ^ Callebaut, I.; Joubrel, R.; Pissard, S.; Kannengiesser, C.; Gerolami, V.; Ged, C.; Cadet, E.; Cartault, F.; Ka, C.; Gourlaouen, I.; Gourhant, L.; Oudin, C.; Goossens, M.; Grandchamp, B.; De Verneuil, H.; Rochette, J.; Ferec, C.; LeGac, G. (2014). "Comprehensive functional annotationof 18 missense mutations found in suspected hemochromatosis type 4 patients". Human Molecular Genetics. 23 (17): 4479–4490. doi:10.1093/hmg/ddu160. PMID 24714983. Retrieved 9 November 2016.
17. ^ Domenico, I.; Ward, D.M.; Nemeth, E.; Vaughan, M.B.; Musci, G.; Ganz, T.; Kaplan, J.; Kornfeld, S.A. (2005). "The molecular basis of ferroportin-linked hemochromatosis". Proceedings of the National Academy of Sciences of the United States of America. 102 (25): 8955–8960. doi:10.1073/pnas.0503804102. PMC 1157058. PMID 15956209.
18. ^ MacKenzie, E.L.; Iwasaki, K.; Tsuji, Y. (2008). "Intracellular iron transport and storage: from molecular mechanisms to health implications". Antioxid. Redox Signal. 10 (6): 997–1030. doi:10.1089/ars.2007.1893. PMC 2932529. PMID 18327971.
19. ^ Chen, S.R.; Yang, L.Q.; Chong, Y.T.; Jie, Y.S.; Wu, Y.K.; Yang, J.; Lin, G.L.; Li, X.H. (2015). "Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4". Internal Medicine Journal. 45 (6): 672–676. doi:10.1111/imj.12764. PMID 26059880.
20. ^ Chen, S.R.; Yang, L.Q.; Chong, Y.T.; Jie, Y.S.; Wu, Y.K.; Yang, J.; Lin, G.L.; Li, X.H. (2015). "Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4". Internal Medicine Journal. 45 (6): 672–676. doi:10.1111/imj.12764. PMID 26059880.
21. ^ Domenico, I.; Ward, D.M.; Nemeth, E.; Vaughan, M.B.; Musci, G.; Ganz, T.; Kaplan, J.; Kornfeld, S.A. (2005). "The molecular basis of ferroportin-linked hemochromatosis". Proceedings of the National Academy of Sciences of the United States of America. 102 (25): 8955–8960. doi:10.1073/pnas.0503804102. PMC 1157058. PMID 15956209.
22. ^ Goodsell, D.S. (2002). "Ferritin and transferrin". Rcsb Protein Data Bank. doi:10.2210/rcsb_pdb/mom_2002_11. Retrieved 9 November 2016.
23. ^ Franchini, M. (2006). "Hereditary iron overload: update on pathophysiology, diagnosis, and treatment". Am. J. Hematol. 81 (3): 202–209. doi:10.1002/ajh.20493. PMID 16493621.
24. ^ Wallace, D.F.; Subramaniam, V.N. (2007). "Non-HFE haemochromatosis". World Journal of Gastroenterology. 13 (35): 4690–4698. doi:10.3748/wjg.v13.i35.4690. PMC 4611190. PMID 17729390.
25. ^ Eaton, J.W.; Qian, M. (2002). "Molecular bases of cellular iron toxicity". Free Radical Biology and Medicine. 32 (9): 833–840. doi:10.1016/s0891-5849(02)00772-4.
26. ^ Callebaut, I.; Joubrel, R.; Pissard, S.; Kannengiesser, C.; Gerolami, V.; Ged, C.; Cadet, E.; Cartault, F.; Ka, C.; Gourlaouen, I.; Gourhant, L.; Oudin, C.; Goossens, M.; Grandchamp, B.; De Verneuil, H.; Rochette, J.; Ferec, C.; LeGac, G. (2014). "Comprehensive functional annotationof 18 missense mutations found in suspected hemochromatosis type 4 patients". Human Molecular Genetics. 23 (17): 4479–4490. doi:10.1093/hmg/ddu160. PMID 24714983. Retrieved 9 November 2016.
27. ^ Wallace, D.F.; Subramaniam, V.N. (2007). "Non-HFE haemochromatosis". World Journal of Gastroenterology. 13 (35): 4690–4698. doi:10.3748/wjg.v13.i35.4690. PMC 4611190. PMID 17729390.
28. ^ Callebaut, I.; Joubrel, R.; Pissard, S.; Kannengiesser, C.; Gerolami, V.; Ged, C.; Cadet, E.; Cartault, F.; Ka, C.; Gourlaouen, I.; Gourhant, L.; Oudin, C.; Goossens, M.; Grandchamp, B.; De Verneuil, H.; Rochette, J.; Ferec, C.; LeGac, G. (2014). "Comprehensive functional annotationof 18 missense mutations found in suspected hemochromatosis type 4 patients". Human Molecular Genetics. 23 (17): 4479–4490. doi:10.1093/hmg/ddu160. PMID 24714983. Retrieved 9 November 2016.
29. ^ Kasvosve, I. (2013). "Effect of ferroportin polymorphism on iron homeostasis and infection". Clinica Chimica Acta. 416: 20–25. doi:10.1016/j.cca.2012.11.013. PMID 23178444.
30. ^ "Ferroportin Disease". National Organization for Rare Disorders. Retrieved 9 November 2016.
31. ^ Santos, P.C.J.L.; Dinardo, C.L.; Cancado, R.D.; Schettert, I.T.; Krieger, J.E.; Periera, A.C. (2012). "Non-HFE hemochromatosis". Revista Brasileira de Hematologia e Hemoterapia. 34 (4): 311–6. doi:10.5581/1516-8484.20120079. PMC 3460409. PMID 23049448.
32. ^ Franchini, M. (2006). "Hereditary iron overload: update on pathophysiology, diagnosis, and treatment". Am. J. Hematol. 81 (3): 202–209. doi:10.1002/ajh.20493. PMID 16493621.
33. ^ Palmer, WC; Vishnu, P; Sanchez, W; Aqel, B; Riegert-Johnson, D; Seaman, LAK; Bowman, AW; Rivera, CE (December 2018). "Diagnosis and Management of Genetic Iron Overload Disorders". Journal of general internal medicine. 33 (12): 2230–2236. doi:10.1007/s11606-018-4669-2. PMID 30225768.
## External links[edit]
Classification
D
* OMIM: 606069
* MeSH: C537249 C537249, C537249
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Hemochromatosis type 4
|
c1853733
| 8,002 |
wikipedia
|
https://en.wikipedia.org/wiki/Hemochromatosis_type_4
| 2021-01-18T19:11:02 |
{"gard": ["10094"], "mesh": ["C537249"], "umls": ["C1853733"], "orphanet": ["139491"], "wikidata": ["Q28448698"]}
|
Rippling muscle disease with myasthenia gravis is a rare, acquired, neuromuscular disease characterized by CAV3 mutation-negative rippling muscle disease in association with acetylcholine receptor antibody-mediated myasthenia gravis. Patients typically present exercise-induced, electrically-silent muscle rippling with myalgia, in combination with generalized myasthenia gravis symptoms (ptosis, diplopia, neck weakness, dysphagia and dyspnea).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Rippling muscle disease with myasthenia gravis
|
None
| 8,003 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=206575
| 2021-01-23T18:49:03 |
{"icd-10": ["G70.8"], "synonyms": ["Acquired rippling muscle disease", "Immune-mediated rippling muscle disease"]}
|
Enlarged parietal foramina (EPF) is a developmental defect, characterized by variable intramembranous ossification defects of the parietal bones, which is either asymptomatic, symptomatic (headaches, nausea, vomiting, intellectual disability) or associated with other pathologies.
## Epidemiology
Prevalence is estimated to be 1/15,000-1/50,000.
## Clinical description
EPF is a congenital disorder characterized by symmetrical, paired persistent foramina (openings) in the parietal bones (diameter >5 mm), located close to the intersection of the sagittal and lambdoid sutures. In infants, EPF presents as a persistent enlargement extending forward from the posterior fontanelle, caused by a single large central parietal bone defect, termed cranium bifidum. The latter tends to resolve in early childhood leaving two distinct, large parietal foramina through the ossification of a midline bridge. EPF is usually asymptomatic, but may be associated with headaches, nausea, vomiting, intense local pain and intellectual disability. EPF can also be accompanied by meningeal, cortical, and vascular malformations of the posterior fossa (that may predispose to epilepsy), and Duane retraction syndrome (see this term). Craniofacial anomalies including cleft palate, myelomeningocele and isolated encephalocele are rarely associated (see these terms). Clavicular hypoplasia may lead to confusion with cleidocranial dysplasia (see this term).
## Etiology
EPF is caused by insufficient ossification around the parietal notch. In most cases this results from heterozygous loss of function mutations in human homeobox genes, MSX2 (5q35.2) and ALX4 (11p11.2), which encode transcription factors involved in skeletal development. A possible third locus on 4q21-q23 has also been reported in a large Chinese pedigree. EPF may also be seen in aminopterin/methotrexate embryofetopathy (see this term), which is caused by exposure to folic acid antagonists during the first trimester of preganancy.
## Diagnostic methods
Diagnosis of EPF is based on family history and on clinical examination. Radiographically, EPF presents as symmetric radiolucencies. Computed tomography (CT) imaging with 3D reconstructions can delineate the osseous defect and magnetic resonance (MR) imaging may demonstrate associated intracranial changes. If EPF is associated with anomalies of the cerebral vasculature, additional vascular imaging like CT, MR, or digital subtraction angiography may be warranted. Diagnosis is confirmed by screening for the pathogenic mutation.
## Differential diagnosis
Differential diagnosis includes Potocki-Shaffer syndrome; distal monosomy 15q; cleidocranial dysplasia; acromelic frontonasal dysplasia; craniosynostosis-anal anomalies-porokeratosis; and frontonasal dysplasia with alopecia and genital anomaly (see these terms).
## Antenatal diagnosis
Preimplantation genetic testing, or prenatal diagnosis during pregnancy from 10 weeks gestation, is available for families with a known genetic defect.
## Genetic counseling
Transmission is autosomal dominant with high but incomplete penetrance.
## Management and treatment
Treatment for EPF is generally conservative, since the natural history of the defect is to close progressively with age. Protective helmets can be considered in young, active children with particularly large defects, but surgery is not usually recommended. Imaging to assess for any accompanying venous anomalies is imperative prior to any surgical intervention.
## Prognosis
There is no known correlation between the size of the defect and the likelihood of having an associated brain abnormality. A spontaneous closure of the defect with growth of the infant has been observed, but it is frequently incomplete.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Enlarged parietal foramina
|
c1868598
| 8,004 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=60015
| 2021-01-23T18:47:08 |
{"mesh": ["C566826"], "omim": ["168500", "609566", "609597"], "umls": ["C1868598"], "icd-10": ["Q75.8"], "synonyms": ["Catlin marks", "Fenestrae parietales symmetricae", "Foramina parietalia permagna", "Hereditary cranium bifidum", "Symmetric parietal foramina"]}
|
A number sign (#) is used with this entry because autosomal dominant tubular aggregate myopathy-1 (TAM1) is caused by heterozygous mutation in the STIM1 gene (605921) on chromosome 11p15.
Heterozygous mutation in the STIM1 gene can also cause Stormorken syndrome (STRMK; 185070), a similar disorder with additional features.
Description
Tubular aggregates in muscle, first described by Engel (1964), are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They are a nonspecific pathologic finding that may occur in a variety of circumstances, including alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness, and inherited myopathies. Tubular aggregates are derived from the sarcoplasmic reticulum (Salviati et al., 1985) and are believed to represent an adaptive mechanism aimed at regulating an increased intracellular level of calcium in order to prevent the muscle fibers from hypercontraction and necrosis (Martin et al., 1997; Muller et al., 2001).
### Genetic Heterogeneity of Tubular Aggregate Myopathy
See also TAM2 (615883), caused by mutation in the ORAI1 gene (610277) on chromosome 12q24.
Clinical Features
Rohkamm et al. (1983) described a family in which 7 persons in 3 generations had slowly progressive weakness without atrophy, myalgia, cramps, or episodic weakness. Creatine kinase was normal, and EMG showed only slight myopathic changes. Neuromuscular transmission was undisturbed. Muscle biopsy showed that 60 to 90% of all fibers contained tubular aggregates. There was marked variation in fiber size and marked atrophy of type II fibers. Male-to-male transmission was observed, and the authors postulated autosomal dominant inheritance.
Pierobon-Bormioli et al. (1985) reported a family in which 5 persons in 3 generations showed tubular aggregates on muscle biopsy associated with mild weakness and muscle aching. Type 1 fiber predominance and type 2 hypotrophy were noted. Electron-microscopic studies confirmed that tubular aggregates originated from the sarcoplasmic reticulum of muscle.
Cameron et al. (1992) observed tubular aggregate myopathy in a father and daughter who presented with slowly progressive proximal weakness, limitation of eye movement, Achilles tendon contractures, and increased serum creatine kinase.
Martin et al. (1997) reported a 19-year-old man with exercise-induced myalgia, easy fatigability, and increased serum creatine kinase. Muscle biopsy showed very large amounts of subsarcolemmal and intermyofibrillar tubular aggregates. The aggregates consisted of closely packed vesicles and tubules filled with electron-dense material or with smaller tubules. Although neither his father nor paternal grandfather had clinical symptoms, both showed increased serum creatine kinase and similar muscle biopsy findings, consistent with autosomal dominant inheritance.
Muller et al. (2001) reported a father and 2 sons with myopathy with tubular aggregates. All had onset in middle age of slowly progressive muscle weakness associated with fatigue, muscle cramps, and myalgia. Muscle biopsy of the 2 sons showed type 2 fiber atrophy and tubular aggregates.
Bohm et al. (2013) reported 4 unrelated families with autosomal dominant tubular aggregate myopathy associated with heterozygous mutations in the STIM1 gene (605921.0004-605921.0007). In 3 families, the onset of disease was variable, occurring during childhood, adolescence, or even early adulthood in 1 patient. All presented with mild and slowly progressive lower limb muscle weakness causing frequent falls and difficulty running. More variable features included ophthalmoparesis without ptosis and contractures of the elbows, wrist and fingers, heel cords, and neck. Four patients had mild respiratory insufficiency, but none had cardiac involvement. Three affected individuals from 1 family were asymptomatic, but had a slight myopathic pattern on EMG and increased serum creatine kinase. Muscle biopsies from all patients showed type II fiber atrophy and tubular aggregates of a reticular origin. Ultrastructural analysis showed massive tubular aggregation with single- or double-walled membranes of different diameters. The aggregates appeared to originate from the sarcoplasmic reticulum.
Hedberg et al. (2014) reported 3 unrelated Caucasian females with TAM1. All had normal early motor development, but showed difficulties walking, running, and climbing stairs due to proximal muscle weakness between 3 and 4 years of age. All had a positive Gowers sign; upper limb girdle muscles were also weakened. Two patients had no dysarthria or ophthalmoplegia at ages 7 and 15 years, but 1 developed mild manifestations of these symptoms at age 31 years. Muscle biopsies showed type 1 fiber predominance, hypotrophic fibers, and an increased number of centralized nuclei. The biopsies showed tubular aggregates with uneven staining for myophosphorylase (PYGM; 608455) in 2 patients.
Bohm et al. (2014) reported 7 patients from 6 families with TAM1 confirmed by genetic analysis. All patients were adults at the time of the report except 1, who was 13 years old. Five patients had onset of symptoms in childhood, whereas 2 had onset as adults. The phenotype was somewhat variable: some patients presented with myalgia or postexercise fatigability and increased serum creatine kinase and later developed muscle weakness mostly affecting the proximal lower limbs, whereas others presented with limb-girdle muscle weakness and later developed myalgia. Three patients had walking difficulties associated with heel contractures. Two patients had only myalgia or postexercise fatigability without muscle weakness or walking difficulties. One patient had eye movement deficits. Muscle biopsy of all patients showed tubular aggregates consisting of single- or double-walled membranes and originating from the endoplasmic reticulum. The aggregates were observed in both fiber types and were often accompanied by internal nuclei and fiber size variability. There was no correlation between tubular aggregate types and mutation, age of onset, or disease severity.
Inheritance
The transmission pattern of tubular aggregate myopathy in the families reported by Bohm et al. (2013) was consistent with autosomal dominant inheritance.
Molecular Genetics
In affected members from 4 unrelated families with autosomal dominant tubular aggregate myopathy, Bohm et al. (2013) identified 4 different heterozygous mutations in the intraluminal EF hand domains of the STIM1 gene (605921.0004-605921.0007). The initial mutations were identified by whole-exome sequencing. In vitro studies showed that the mutations induced STIM1 clustering, indicating that calcium sensing was impaired and resulting in a gain-of-function effect. TAM myoblasts showed a higher level of basal calcium and dysregulation of intracellular calcium homeostasis compared to controls. Because recessive STIM1 loss-of-function mutations are associated with immunodeficiency (612783), Bohm et al. (2013) concluded that the tissue-specific impact of STIM1 loss or constitutive activation is different, and that a tight regulation of STIM1-dependent calcium entry is fundamental for normal skeletal muscle structure and function. None of the patients with TAM had evidence of immune dysfunction.
In 3 unrelated Caucasian females with TAM1, Hedberg et al. (2014) identified a de novo heterozygous mutation in the STIM1 gene. Two patients had the same mutation (H109R; 605921.0006) previously identified by Bohm et al. (2013), whereas the third had a novel mutation (I115F; 605921.0009).
In 7 patients from 6 families with TAM1, Bohm et al. (2014) identified 5 different heterozygous missense mutations in the STIM1 gene (see, e.g., 605921.0005 and 605921.0010). In vitro functional expression studies in myoblasts showed that the mutations resulted in constitutive clustering of STIM1 independent of intraluminal calcium levels. The 6 families were ascertained from a larger cohort of 38 unrelated families with features suggestive of tubular aggregate myopathy who underwent direct sequencing of the STIM1 gene.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- External ophthalmoplegia (in some patients) \- Pupillary abnormalities (reported in 1 family) \- Difficulties with night vision (reported in 1 family) RESPIRATORY \- Respiratory insufficiency (in some patients) SKELETAL \- Contractures (in some patients) MUSCLE, SOFT TISSUES \- Frequent falls \- Difficulty running \- Exercise-induced myalgia \- Muscle cramps at rest \- Muscle stiffness \- Easy fatigability \- Proximal muscle atrophy \- Proximal muscle weakness \- Weakness of the intrinsic hand muscles (in some patients) \- Hyporeflexia, lower limbs \- Areflexia, lower limbs \- Increased fiber size variation seen on muscle biopsy \- Internal nuclei seen on muscle biopsy \- Fatty infiltration seen on muscle biopsy \- Type 2 fiber atrophy \- Tubular aggregates mainly in type 2 fibers and are subsarcolemmal or intermyofibrillar and stain for NADH-tetrazolium reductase LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Childhood or young adult onset \- Mild phenotype \- Slowly progressive \- Some patients may be asymptomatic MOLECULAR BASIS \- Caused by mutation in the stromal interaction molecule 1 gene (STIM1, 605921.0004 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MYOPATHY, TUBULAR AGGREGATE, 1
|
c0410207
| 8,005 |
omim
|
https://www.omim.org/entry/160565
| 2019-09-22T16:37:41 |
{"doid": ["0080089"], "mesh": ["D020914"], "omim": ["160565"], "orphanet": ["2593"], "synonyms": ["Alternative titles", "MYOPATHY, TUBULAR AGGREGATE", "TUBULAR AGGREGATE MYOPATHY"]}
|
Non-islet cell tumor hypoglycemia
SpecialtyOncology
Non-islet cell tumor hypoglycemia is a condition in which a tumor secretes hormones into the bloodstream that cause hypoglycemia. The is most commonly insulin-like growth factor 2, which stimulates insulin receptors to uptake glucose into cells.[1]
Many types of non-islet cell tumors can cause this phenomenon, but not all act through the same mechanism. Rarely, non-islet tumors can secrete IGF-1 or insulin.[1]
## References[edit]
1. ^ a b "UpToDate". www.uptodate.com. Retrieved 22 April 2019.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Non-islet cell tumor hypoglycemia
|
None
| 8,006 |
wikipedia
|
https://en.wikipedia.org/wiki/Non-islet_cell_tumor_hypoglycemia
| 2021-01-18T18:43:37 |
{"wikidata": ["Q7049134"]}
|
Autosomal recessive spastic paraplegia type 43 is a rare, complex hereditary spastic paraplegia characterized by a childhood to adolescent onset of progressive lower limb spasticity, associated with mild to severe gait disturbances, extensor plantar responses, muscle weakness and severe distal atrophy, frequently with upper limb involvement. Additional features may include joint contractures, distal sensory loss and brisk or absent deep tendon reflexes. Other signs, such as depression, memory loss, optic atrophy (with vision loss) and brain iron deposition (revealed by brain imagery), 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
|
Autosomal recessive spastic paraplegia type 43
|
c2680446
| 8,007 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=320370
| 2021-01-23T17:01:52 |
{"omim": ["615043"], "icd-10": ["G11.4"], "synonyms": ["SPG43"]}
|
Trisomy 13 is a type of chromosome disorder characterized by having 3 copies of chromosome 13 in cells of the body, instead of the usual 2 copies. In some people, only a portion of cells contains the extra chromosome 13 (called mosaic trisomy 13), whereas other cells contain the normal chromosome pair. Trisomy 13 causes severe intellectual disability and many physical abnormalities, such as congenital heart defects; brain or spinal cord abnormalities; very small or poorly developed eyes (microphthalmia); extra fingers or toes; cleft lip with or without cleft palate; and weak muscle tone (hypotonia). Most cases are not inherited and result from a random error during the formation of eggs or sperm in healthy parents. Trisomy 13 is diagnosed based on the symptoms, clinical exam, and confirmed by the results of a chromosome test. Due to various life-threatening medical problems, many infants with trisomy 13 do not survive past the first days or weeks 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
|
Trisomy 13
|
c2936830
| 8,008 |
gard
|
https://rarediseases.info.nih.gov/diseases/7341/trisomy-13
| 2021-01-18T17:57:18 |
{"mesh": ["D000073839"], "orphanet": ["3378"], "synonyms": ["Patau syndrome", "Chromosome 13, trisomy 13 complete", "Complete trisomy 13 syndrome", "D trisomy syndrome (formerly)"]}
|
A rare cutaneous paraneoplastic disease characterized by the presence of excessive lanugo-type hair on the glabrous skin of face, neck, trunk and limbs that can be associated with additional clinical features such as burning glossitis, papillary hypertrophy of the tongue, diarrhea, dysgeusia, and/or weight loss. It is associated with lymphoma or cancer of the gastrointestinal system, urinary tract, lung, breast, uterus or ovary.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Acquired hypertrichosis lanuginosa
|
c0343072
| 8,009 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2221
| 2021-01-23T18:49:18 |
{"gard": ["2864"], "icd-10": ["L68.1"]}
|
For other uses, see Pneumonia (disambiguation).
Inflammation of the alveoli of the lungs
Pneumonia
Other namesPneumonitis
Chest X-ray of a pneumonia caused by influenza and Haemophilus influenzae, with patchy consolidations, mainly in the right upper lobe (arrow)
Pronunciation
* /njuːˈmoʊniə/ new-MOHN-ee-ə
SpecialtyPulmonology, Infectious disease
SymptomsCough, difficulty breathing, rapid breathing, fever[1]
DurationFew weeks[2]
CausesBacteria, virus, aspiration[3][4]
Risk factorsCystic fibrosis, COPD, sickle cell disease, asthma, diabetes, heart failure, history of smoking, older age[5][6][7]
Diagnostic methodBased on symptoms, chest X-ray[8]
Differential diagnosisCOPD, asthma, pulmonary edema, pulmonary embolism[9]
PreventionVaccines, handwashing, not smoking[10]
MedicationAntibiotics, antivirals, oxygen therapy[11][12]
Frequency450 million (7%) per year[12][13]
DeathsFour million per year[12][13]
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli.[3][14] Symptoms typically include some combination of productive or dry cough, chest pain, fever and difficulty breathing.[1] The severity of the condition is variable.[1] Pneumonia is usually caused by infection with viruses or bacteria, and less commonly by other microorganisms.[a] Identifying the responsible pathogen can be difficult. Diagnosis is often based on symptoms and physical examination.[8] Chest X-rays, blood tests, and culture of the sputum may help confirm the diagnosis.[8] The disease may be classified by where it was acquired, such as community- or hospital-acquired or healthcare-associated pneumonia.[17]
Risk factors for pneumonia include cystic fibrosis, chronic obstructive pulmonary disease (COPD), sickle cell disease, asthma, diabetes, heart failure, a history of smoking, a poor ability to cough (such as following a stroke), and a weak immune system.[5][7]
Vaccines to prevent certain types of pneumonia (such as those caused by Streptococcus pneumoniae bacteria or that linked to influenza) are available.[10] Other methods of prevention include hand washing to prevent infection, and not smoking.[10]
Treatment depends on the underlying cause.[18] Pneumonia believed to be due to bacteria is treated with antibiotics.[11] If the pneumonia is severe, the affected person is generally hospitalized.[18] Oxygen therapy may be used if oxygen levels are low.[11]
Each year, pneumonia affects about 450 million people globally (7% of the population) and results in about 4 million deaths.[12][13] With the introduction of antibiotics and vaccines in the 20th century, survival has greatly improved.[12] Nevertheless, pneumonia remains a leading cause of death in developing countries, and also among the very old, the very young, and the chronically ill.[12][19] Pneumonia often shortens the period of suffering among those already close to death and has thus been called "the old man's friend".[20]
Play media
Video summary (script)
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Bacteria
* 2.2 Viruses
* 2.3 Fungi
* 2.4 Parasites
* 2.5 Noninfectious
* 3 Mechanisms
* 3.1 Bacterial
* 3.2 Viral
* 4 Diagnosis
* 4.1 Diagnosis in children
* 4.2 Diagnosis in adults
* 4.3 Physical exam
* 4.4 Imaging
* 4.5 Microbiology
* 4.6 Classification
* 4.6.1 Community
* 4.6.2 Healthcare
* 4.7 Differential diagnosis
* 5 Prevention
* 5.1 Vaccination
* 5.2 Medications
* 5.3 Other
* 6 Management
* 6.1 Bacterial
* 6.2 Viral
* 6.3 Aspiration
* 6.4 Follow-up
* 7 Prognosis
* 7.1 Clinical prediction rules
* 7.2 Pleural effusion, empyema, and abscess
* 7.3 Respiratory and circulatory failure
* 8 Epidemiology
* 8.1 Children
* 9 History
* 10 Society and culture
* 10.1 Awareness
* 10.2 Costs
* 11 References
* 11.1 Bibliography
* 12 External links
## Signs and symptoms
Symptoms frequency[21]
Symptom Frequency
Cough 79–91%
Fatigue 90%
Fever 71–75%
Shortness of breath 67–75%
Sputum 60–65%
Chest pain 39–49%
Main symptoms of infectious pneumonia
People with infectious pneumonia often have a productive cough, fever accompanied by shaking chills, shortness of breath, sharp or stabbing chest pain during deep breaths, and an increased rate of breathing.[9] In elderly people, confusion may be the most prominent sign.[9]
The typical signs and symptoms in children under five are fever, cough, and fast or difficult breathing.[22] Fever is not very specific, as it occurs in many other common illnesses and may be absent in those with severe disease, malnutrition or in the elderly. In addition, a cough is frequently absent in children less than 2 months old.[22] More severe signs and symptoms in children may include blue-tinged skin, unwillingness to drink, convulsions, ongoing vomiting, extremes of temperature, or a decreased level of consciousness.[22][23]
Bacterial and viral cases of pneumonia usually result in similar symptoms.[24] Some causes are associated with classic, but non-specific, clinical characteristics. Pneumonia caused by Legionella may occur with abdominal pain, diarrhea, or confusion.[25] Pneumonia caused by Streptococcus pneumoniae is associated with rusty colored sputum.[26] Pneumonia caused by Klebsiella may have bloody sputum often described as "currant jelly".[21] Bloody sputum (known as hemoptysis) may also occur with tuberculosis, Gram-negative pneumonia, lung abscesses and more commonly acute bronchitis.[23] Pneumonia caused by Mycoplasma pneumoniae may occur in association with swelling of the lymph nodes in the neck, joint pain, or a middle ear infection.[23] Viral pneumonia presents more commonly with wheezing than bacterial pneumonia.[24] Pneumonia was historically divided into "typical" and "atypical" based on the belief that the presentation predicted the underlying cause.[27] However, evidence has not supported this distinction, therefore it is no longer emphasized.[27]
## Cause
The bacterium Streptococcus pneumoniae, a common cause of pneumonia, imaged by an electron microscope
Pneumonia is due to infections caused primarily by bacteria or viruses and less commonly by fungi and parasites. Although more than 100 strains of infectious agents have been identified, only a few are responsible for the majority of cases. Mixed infections with both viruses and bacteria may occur in roughly 45% of infections in children and in 15% of infections in adults.[12] A causative agent may not be isolated in about half of cases despite careful testing.[20] In an active population-based surveillance for community-acquired pneumonia requiring hospitalization in five hospitals in Chicago and Nashville from January 2010 through June 2012, 2259 patients were identified who had radiographic evidence of pneumonia and specimens that could be tested for the responsible pathogen.[28] Most patients (62%) had no detectable pathogens in their sample, and unexpectedly, respiratory viruses were detected more frequently than bacteria.[28] Specifically, 23% had one or more viruses, 11% had one or more bacteria, 3% had both bacterial and viral pathogens, and 1% had a fungal or mycobacterial infection. "The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%)."[28]
The term pneumonia is sometimes more broadly applied to any condition resulting in inflammation of the lungs (caused for example by autoimmune diseases, chemical burns or drug reactions); however, this inflammation is more accurately referred to as pneumonitis.[15][16]
Factors that predispose to pneumonia include smoking, immunodeficiency, alcoholism, chronic obstructive pulmonary disease, sickle cell disease (SCD), asthma, chronic kidney disease, liver disease, and biological aging.[23][29][7] Additional risks in children include not being breastfed, exposure to cigarette smoke and other air pollution, malnutrition, and poverty.[30] The use of acid-suppressing medications – such as proton-pump inhibitors or H2 blockers – is associated with an increased risk of pneumonia.[31] Approximately 10% of people who require mechanical ventilation develop ventilator-associated pneumonia,[32] and people with a gastric feeding tube have an increased risk of developing aspiration pneumonia.[33] For people with certain variants of the FER gene, the risk of death is reduced in sepsis caused by pneumonia. However, for those with TLR6 variants, the risk of getting Legionnaires' disease is increased.[34]
### Bacteria
Main article: Bacterial pneumonia
Cavitating pneumonia due to MRSA as seen on a CT scan
Bacteria are the most common cause of community-acquired pneumonia (CAP), with Streptococcus pneumoniae isolated in nearly 50% of cases.[35][36] Other commonly isolated bacteria include Haemophilus influenzae in 20%, Chlamydophila pneumoniae in 13%, and Mycoplasma pneumoniae in 3% of cases;[35] Staphylococcus aureus; Moraxella catarrhalis; and Legionella pneumophila.[20] A number of drug-resistant versions of the above infections are becoming more common, including drug-resistant Streptococcus pneumoniae (DRSP) and methicillin-resistant Staphylococcus aureus (MRSA).[23]
The spreading of organisms is facilitated by certain risk factors.[20] Alcoholism is associated with Streptococcus pneumoniae, anaerobic organisms, and Mycobacterium tuberculosis; smoking facilitates the effects of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Legionella pneumophila. Exposure to birds is associated with Chlamydia psittaci; farm animals with Coxiella burnetti; aspiration of stomach contents with anaerobic organisms; and cystic fibrosis with Pseudomonas aeruginosa and Staphylococcus aureus.[20] Streptococcus pneumoniae is more common in the winter,[20] and it should be suspected in persons aspirating a large number of anaerobic organisms.[23]
### Viruses
Main article: Viral pneumonia
A chest x-ray of a patient with severe viral pneumonia due to SARS
In adults, viruses account for about one third of pneumonia cases,[12] and in children for about 15% of them.[37] Commonly implicated agents include rhinoviruses, coronaviruses, influenza virus, respiratory syncytial virus (RSV), adenovirus, and parainfluenza.[12][38] Herpes simplex virus rarely causes pneumonia, except in groups such as newborns, persons with cancer, transplant recipients, and people with significant burns.[39] After organ transplantation or in otherwise immunocompromised persons, there are high rates of cytomegalovirus pneumonia.[37][39] Those with viral infections may be secondarily infected with the bacteria Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae, particularly when other health problems are present.[23][37] Different viruses predominate at different times of the year; during flu season, for example, influenza may account for more than half of all viral cases.[37] Outbreaks of other viruses also occur occasionally, including hantaviruses and coronaviruses.[37] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can also result in pneumonia.[40]
### Fungi
Main article: Fungal pneumonia
Fungal pneumonia is uncommon, but occurs more commonly in individuals with weakened immune systems due to AIDS, immunosuppressive drugs, or other medical problems.[20][41] It is most often caused by Histoplasma capsulatum, Blastomyces, Cryptococcus neoformans, Pneumocystis jiroveci (pneumocystis pneumonia, or PCP), and Coccidioides immitis. Histoplasmosis is most common in the Mississippi River basin, and coccidioidomycosis is most common in the Southwestern United States.[20] The number of cases of fungal pneumonia has been increasing in the latter half of the 20th century due to increasing travel and rates of immunosuppression in the population.[41] For people infected with HIV/AIDS, PCP is a common opportunistic infection.[42]
### Parasites
Main article: Parasitic pneumonia
A variety of parasites can affect the lungs, including Toxoplasma gondii, Strongyloides stercoralis, Ascaris lumbricoides, and Plasmodium malariae.[43] These organisms typically enter the body through direct contact with the skin, ingestion, or via an insect vector.[43] Except for Paragonimus westermani, most parasites do not specifically affect the lungs but involve the lungs secondarily to other sites.[43] Some parasites, in particular those belonging to the Ascaris and Strongyloides genera, stimulate a strong eosinophilic reaction, which may result in eosinophilic pneumonia.[43] In other infections, such as malaria, lung involvement is due primarily to cytokine-induced systemic inflammation.[43] In the developed world, these infections are most common in people returning from travel or in immigrants.[43] Around the world, parasitic pneumonia is most common in the immunodeficient.[44]
### Noninfectious
Main article: Idiopathic interstitial pneumonia
Idiopathic interstitial pneumonia or noninfectious pneumonia[45] is a class of diffuse lung diseases. They include diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and usual interstitial pneumonia.[46] Lipoid pneumonia is another rare cause due to lipids entering the lung.[47] These lipids can either be inhaled or spread to the lungs from elsewhere in the body.[47]
## Mechanisms
Pneumonia fills the lung's alveoli with fluid, hindering oxygenation. The alveolus on the left is normal, whereas the one on the right is full of fluid from pneumonia.
Pneumonia frequently starts as an upper respiratory tract infection that moves into the lower respiratory tract.[48] It is a type of pneumonitis (lung inflammation).[49] The normal flora of the upper airway give protection by competing with pathogens for nutrients. In the lower airways, reflexes of the glottis, actions of complement proteins and immunoglobulins are important for protection. Microaspiration of contaminated secretions can infect the lower airways and cause pneumonia. The progress of pneumonia is determined by the virulence of the organism; the amount of organism required to start an infection; and the body's immune response against the infection.[34]
### Bacterial
Most bacteria enter the lungs via small aspirations of organisms residing in the throat or nose.[23] Half of normal people have these small aspirations during sleep.[27] While the throat always contains bacteria, potentially infectious ones reside there only at certain times and under certain conditions.[27] A minority of types of bacteria such as Mycobacterium tuberculosis and Legionella pneumophila reach the lungs via contaminated airborne droplets.[23] Bacteria can also spread via the blood.[24] Once in the lungs, bacteria may invade the spaces between cells and between alveoli, where the macrophages and neutrophils (defensive white blood cells) attempt to inactivate the bacteria.[50] The neutrophils also release cytokines, causing a general activation of the immune system.[51] This leads to the fever, chills, and fatigue common in bacterial pneumonia.[51] The neutrophils, bacteria, and fluid from surrounding blood vessels fill the alveoli, resulting in the consolidation seen on chest X-ray.[52]
### Viral
Viruses may reach the lung by a number of different routes. Respiratory syncytial virus is typically contracted when people touch contaminated objects and then they touch their eyes or nose.[37] Other viral infections occur when contaminated airborne droplets are inhaled through the nose or mouth.[23] Once in the upper airway, the viruses may make their way into the lungs, where they invade the cells lining the airways, alveoli, or lung parenchyma.[37] Some viruses such as measles and herpes simplex may reach the lungs via the blood.[53] The invasion of the lungs may lead to varying degrees of cell death.[37] When the immune system responds to the infection, even more lung damage may occur.[37] Primarily white blood cells, mainly mononuclear cells, generate the inflammation.[53] As well as damaging the lungs, many viruses simultaneously affect other organs and thus disrupt other body functions. Viruses also make the body more susceptible to bacterial infections; in this way, bacterial pneumonia can occur at the same time as viral pneumonia.[38]
## Diagnosis
Crackles
Crackles heard in the lungs of a person with pneumonia using a stethoscope.
* * *
Problems playing this file? See media help.
Pneumonia is typically diagnosed based on a combination of physical signs and often a chest X-ray.[54] In adults with normal vital signs and a normal lung examination, the diagnosis is unlikely.[55] However, the underlying cause can be difficult to confirm, as there is no definitive test able to distinguish between bacterial and non-bacterial cause.[12][54] The overall impression of a physician appears to be at least as good as decision rules for making or excluding the diagnosis.[56]
### Diagnosis in children
The World Health Organization has defined pneumonia in children clinically based on either a cough or difficulty breathing and a rapid respiratory rate, chest indrawing, or a decreased level of consciousness.[57] A rapid respiratory rate is defined as greater than 60 breaths per minute in children under 2 months old, greater than 50 breaths per minute in children 2 months to 1 year old, or greater than 40 breaths per minute in children 1 to 5 years old.[57]
In children, low oxygen levels and lower chest indrawing are more sensitive than hearing chest crackles with a stethoscope or increased respiratory rate.[58] Grunting and nasal flaring may be other useful signs in children less than five years old.[59]
Lack of wheezing is an indicator of Mycoplasma pneumoniae in children with pneumonia, but as an indicator it is not accurate enough to decide whether or not macrolide treatment should be used.[60] The presence of chest pain in children with pneumonia doubles the probability of Mycoplasma pneumoniae.[60]
### Diagnosis in adults
In general, in adults, investigations are not needed in mild cases.[61] There is a very low risk of pneumonia if all vital signs and auscultation are normal.[62] C-reactive protein (CRP) may help support the diagnosis.[63] For those with CRP less than 20 mg/L without convincing evidence of pneumonia, antibiotics are not recommended.[34]
Procalcitonin may help determine the cause and support defcisions about who should receive antibiotics.[64] Antibiotics are encouraged if the procalcitonin level reaches 0.25 μg/L, strongly encouraged if it reaches 0.5 μg/L, and strongly discouraged if the level is below 0.10 μg/L.[34] In people requiring hospitalization, pulse oximetry, chest radiography and blood tests – including a complete blood count, serum electrolytes, C-reactive protein level, and possibly liver function tests – are recommended.[61]
The diagnosis of influenza-like illness can be made based on the signs and symptoms; however, confirmation of an influenza infection requires testing.[65] Thus, treatment is frequently based on the presence of influenza in the community or a rapid influenza test.[65]
### Physical exam
Physical examination may sometimes reveal low blood pressure, high heart rate, or low oxygen saturation.[23] The respiratory rate may be faster than normal, and this may occur a day or two before other signs.[23][27] Examination of the chest may be normal, but it may show decreased expansion on the affected side. Harsh breath sounds from the larger airways that are transmitted through the inflamed lung are termed bronchial breathing and are heard on auscultation with a stethoscope.[23] Crackles (rales) may be heard over the affected area during inspiration.[23] Percussion may be dulled over the affected lung, and increased, rather than decreased, vocal resonance distinguishes pneumonia from a pleural effusion.[9]
### Imaging
A chest X-ray showing a very prominent wedge-shape area of airspace consolidation in the right lung characteristic of acute bacterial lobar pneumonia
CT of the chest demonstrating right-side pneumonia (left side of the image)
A chest radiograph is frequently used in diagnosis.[22] In people with mild disease, imaging is needed only in those with potential complications, those not having improved with treatment, or those in which the cause is uncertain.[22][61] If a person is sufficiently sick to require hospitalization, a chest radiograph is recommended.[61] Findings do not always match the severity of disease and do not reliably separate between bacterial and viral infection.[22]
X-ray presentations of pneumonia may be classified as lobar pneumonia, bronchopneumonia, lobular pneumonia, and interstitial pneumonia.[66] Bacterial, community-acquired pneumonia classically show lung consolidation of one lung segmental lobe, which is known as lobar pneumonia.[35] However, findings may vary, and other patterns are common in other types of pneumonia.[35] Aspiration pneumonia may present with bilateral opacities primarily in the bases of the lungs and on the right side.[35] Radiographs of viral pneumonia may appear normal, appear hyper-inflated, have bilateral patchy areas, or present similar to bacterial pneumonia with lobar consolidation.[35] Radiologic findings may not be present in the early stages of the disease, especially in the presence of dehydration, or may be difficult to interpret in the obese or those with a history of lung disease.[23] Complications such as pleural effusion may also be found on chest radiographs. Laterolateral chest radiographs can increase the diagnostic accuracy of lung consolidation and pleural effusion.[34]
A CT scan can give additional information in indeterminate cases.[35] CT scans can also provide more details in those with an unclear chest radiograph (for example occult pneumonia in chronic obstructive pulmonary disease) and can exclude pulmonary embolism and fungal pneumonia and detect lung abscess in those who are not responding to treatments.[34] However, CT scans are more expensive, have a higher dose of radiation, and cannot be done at bedside.[34]
Lung ultrasound may also be useful in helping to make the diagnosis.[67] Ultrasound is radiation free and can be done at bedside. However, ultrasound requires specific skills to operate the machine and interpret the findings.[34] It may be more accurate than chest X-ray.[68]
* Play media
Pneumonia seen by ultrasound[69]
* Play media
Pneumonia seen by ultrasound[69]
* Pneumonia seen by ultrasound[69]
* Right middle lobe pneumonia in a child as seen on plain X ray
### Microbiology
In people managed in the community, determining the causative agent is not cost-effective and typically does not alter management.[22] For people who do not respond to treatment, sputum culture should be considered, and culture for Mycobacterium tuberculosis should be carried out in persons with a chronic productive cough.[61] Microbiological evaluation is also indicated in severe pneumonia, alcoholism, asplenia, immunosuppression, HIV infection, and those being empirically treated for MRSA of pseudomonas.[34][70] Although positive blood culture and pleural fluid culture definitively establish the diagnosis of the type of micro-organism involved, a positive sputum culture has to be interpreted with care for the possibility of colonisation of respiratory tract.[34] Testing for other specific organisms may be recommended during outbreaks, for public health reasons.[61] In those hospitalized for severe disease, both sputum and blood cultures are recommended,[61] as well as testing the urine for antigens to Legionella and Streptococcus.[71] Viral infections, can be confirmed via detection of either the virus or its antigens with culture or polymerase chain reaction (PCR), among other techniques.[12] Mycoplasma, Legionella, Streptococcus, and Chlamydia can also be detected using PCR techniques on bronchoalveolar lavage and nasopharyngeal swab.[34] The causative agent is determined in only 15% of cases with routine microbiological tests.[9]
### Classification
Main article: Classification of pneumonia
Pneumonitis refers to lung inflammation; pneumonia refers to pneumonitis, usually due to infection but sometimes non-infectious, that has the additional feature of pulmonary consolidation.[72] Pneumonia is most commonly classified by where or how it was acquired: community-acquired, aspiration, healthcare-associated, hospital-acquired, and ventilator-associated pneumonia.[35] It may also be classified by the area of the lung affected: lobar pneumonia, bronchial pneumonia and acute interstitial pneumonia;[35] or by the causative organism.[73] Pneumonia in children may additionally be classified based on signs and symptoms as non-severe, severe, or very severe.[74]
The setting in which pneumonia develops is important to treatment,[75][76] as it correlates to which pathogens are likely suspects,[75] which mechanisms are likely, which antibiotics are likely to work or fail,[75] and which complications can be expected based on the person's health status.
#### Community
Main article: Community-acquired pneumonia
Community-acquired pneumonia (CAP) is acquired in the community,[75][76] outside of health care facilities. Compared with health care–associated pneumonia, it is less likely to involve multidrug-resistant bacteria. Although the latter are no longer rare in CAP,[75] they are still less likely.
#### Healthcare
Health care–associated pneumonia (HCAP) is an infection associated with recent exposure to the health care system,[75] including hospitals, outpatient clinics, nursing homes, dialysis centers, chemotherapy treatment, or home care.[76] HCAP is sometimes called MCAP (medical care–associated pneumonia).
People may become infected with pneumonia in a hospital; this is defined as pneumonia not present at the time of admission (symptoms must start at least 48 hours after admission).[76][75] It is likely to involve hospital-acquired infections, with higher risk of multidrug-resistant pathogens. People in a hospital often have other medical conditions, which may make them more susceptible to pathogens in the hospital.
Ventilator-associated pneumonia occurs in people breathing with the help of mechanical ventilation.[75][32] Ventilator-associated pneumonia is specifically defined as pneumonia that arises more than 48 to 72 hours after endotracheal intubation.[76]
### Differential diagnosis
Several diseases can present with similar signs and symptoms to pneumonia, such as: chronic obstructive pulmonary disease, asthma, pulmonary edema, bronchiectasis, lung cancer, and pulmonary emboli.[9] Unlike pneumonia, asthma and COPD typically present with wheezing, pulmonary edema presents with an abnormal electrocardiogram, cancer and bronchiectasis present with a cough of longer duration, and pulmonary emboli present with acute onset sharp chest pain and shortness of breath.[9] Mild pneumonia should be differentiated from upper respiratory tract infection (URTI). Severe pneumonia should be differentiated from acute heart failure. Pulmonary infiltrates that resolved after giving mechanical ventilation should point to heart failure and atelectasis rather than pneumonia. For recurrent pneumonia, underlying lung cancer, metastasis, tuberculosis, a foreign bodies, immunosuppression, and hypersensitivity should be suspected.[34]
## Prevention
Prevention includes vaccination, environmental measures and appropriate treatment of other health problems.[22] It is believed that, if appropriate preventive measures were instituted globally, mortality among children could be reduced by 400,000; and, if proper treatment were universally available, childhood deaths could be decreased by another 600,000.[24]
### Vaccination
Vaccination prevents against certain bacterial and viral pneumonias both in children and adults. Influenza vaccines are modestly effective at preventing symptoms of influenza,[12][77] The Center for Disease Control and Prevention (CDC) recommends yearly influenza vaccination for every person 6 months and older.[78] Immunizing health care workers decreases the risk of viral pneumonia among their patients.[71]
Vaccinations against Haemophilus influenzae and Streptococcus pneumoniae have good evidence to support their use.[48] There is strong evidence for vaccinating children under the age of 2 against Streptococcus pneumoniae (pneumococcal conjugate vaccine).[79][80][81] Vaccinating children against Streptococcus pneumoniae has led to a decreased rate of these infections in adults, because many adults acquire infections from children. A Streptococcus pneumoniae vaccine is available for adults, and has been found to decrease the risk of invasive pneumococcal disease by 74%, but there is insufficient evidence to suggest using the pneumococcal vaccine to prevent pneumonia or death in the general adult population.[82] The CDC recommends that young children and adults over the age of 65 receive the pneumococcal vaccine, as well as older children or younger adults who have an increased risk of getting pneumococcal disease.[81] The pneumococcal vaccine has been shown to reduce the risk of community acquired pneumonia in people with chronic obstructive pulmonary disease, but does not reduce mortality or the risk of hospitalization for people with this condition.[83] People with COPD are recommended by a number of guidelines to have a pneumococcal vaccination.[83] Other vaccines for which there is support for a protective effect against pneumonia include pertussis, varicella, and measles.[84]
### Medications
When influenza outbreaks occur, medications such as amantadine or rimantadine may help prevent the condition, but they are associated with side effects.[85] Zanamivir or oseltamivir decrease the chance that people who are exposed to the virus will develop symptoms; however, it is recommended that potential side effects are taken into account.[86]
### Other
Smoking cessation[61] and reducing indoor air pollution, such as that from cooking indoors with wood, crop residues or dung, are both recommended.[22][24] Smoking appears to be the single biggest risk factor for pneumococcal pneumonia in otherwise-healthy adults.[71] Hand hygiene and coughing into one's sleeve may also be effective preventative measures.[84] Wearing surgical masks by the sick may also prevent illness.[71]
Appropriately treating underlying illnesses (such as HIV/AIDS, diabetes mellitus, and malnutrition) can decrease the risk of pneumonia.[24][84][87] In children less than 6 months of age, exclusive breast feeding reduces both the risk and severity of disease.[24] In people with HIV/AIDS and a CD4 count of less than 200 cells/uL the antibiotic trimethoprim/sulfamethoxazole decreases the risk of Pneumocystis pneumonia[88] and is also useful for prevention in those that are immunocompromised but do not have HIV.[89]
Testing pregnant women for Group B Streptococcus and Chlamydia trachomatis, and administering antibiotic treatment, if needed, reduces rates of pneumonia in infants;[90][91] preventive measures for HIV transmission from mother to child may also be efficient.[92] Suctioning the mouth and throat of infants with meconium-stained amniotic fluid has not been found to reduce the rate of aspiration pneumonia and may cause potential harm,[93] thus this practice is not recommended in the majority of situations.[93] In the frail elderly good oral health care may lower the risk of aspiration pneumonia.[94] Zinc supplementation in children 2 months to five years old appears to reduce rates of pneumonia.[95]
For people with low levels of vitamin C in their diet or blood, taking vitamin C supplements may be suggested to decrease the risk of pneumonia, although there is no strong evidence of benefit.[96] There is insufficient evidence to recommend that the general population take vitamin C to prevent pneumonia.[97]
For adults and children in the hospital who require a respirator, there is no strong evidence indicating a difference between heat and moisture exchangers and heated humidifiers for preventing pneumonia.[98] There is no good evidence that one approach to mouth care is better than others in preventing nursing home acquired pneumonia.[99] There is tentative evidence that laying flat on the back compared to semi-raised increases pneumonia risks in people who are intubated.[100]
## Management
CURB-65
Symptom Points
Confusion 1
Urea>7 mmol/l 1
Respiratory rate>30 1
SBP<90mmHg, DBP<60mmHg 1
Age>=65 1
Antibiotics by mouth, rest, simple analgesics, and fluids usually suffice for complete resolution.[61] However, those with other medical conditions, the elderly, or those with significant trouble breathing may require more advanced care. If the symptoms worsen, the pneumonia does not improve with home treatment, or complications occur, hospitalization may be required.[61] Worldwide, approximately 7–13% of cases in children result in hospitalization,[22] whereas in the developed world between 22 and 42% of adults with community-acquired pneumonia are admitted.[61] The CURB-65 score is useful for determining the need for admission in adults.[61] If the score is 0 or 1, people can typically be managed at home; if it is 2, a short hospital stay or close follow-up is needed; if it is 3–5, hospitalization is recommended.[61] In children those with respiratory distress or oxygen saturations of less than 90% should be hospitalized.[101] The utility of chest physiotherapy in pneumonia has not yet been determined.[102][103] Over-the-counter cough medicine has not been found to be effective,[104] nor has the use of zinc in children.[105] There is insufficient evidence for mucolytics.[104] There is no strong evidence to recommend that children who have non-measles related pneumonia take vitamin A supplements.[106] Vitamin D, as of 2018 is of unclear benefit in children.[107]
Pneumonia can cause severe illness in a number of ways, and pneumonia with evidence of organ dysfunction may require intensive care unit admission for observation and specific treatment.[108] The main impact is on the respiratory and the circulatory system. Respiratory failure not responding to normal oxygen therapy may require heated humidified high-flow therapy delivered through nasal cannulae,[108] non-invasive ventilation,[109] or in severe cases invasive ventilation through an endotracheal tube.[108] Regarding circulatory problems as part of sepsis, evidence of poor blood flow or low blood pressure is initially treated with 30 ml/kg of crystalloid infused intravenously.[34] In situations where fluids alone are ineffective, vasopressor medication may be required.[108]
For adults with moderate or severe acute respiratory distress syndrome (ARDS) undergoing mechanical ventilation, there is a reduction in mortality when people lay on their front for at least 12 hours a day. However, this increases the risk of endotracheal tube obstruction and pressure sores.[110]
### Bacterial
Antibiotics improve outcomes in those with bacterial pneumonia.[13] The first dose of antibiotics should be given as soon as possible.[34] Increased use of antibiotics, however, may lead to the development of antimicrobial resistant strains of bacteria.[111] Antibiotic choice depends initially on the characteristics of the person affected, such as age, underlying health, and the location the infection was acquired. Antibiotic use is also associated with side effects such as nausea, diarrhea, dizziness, taste distortion, or headaches.[111] In the UK, treatment before culture results with amoxicillin is recommended as the first line for community-acquired pneumonia, with doxycycline or clarithromycin as alternatives.[61] In North America, amoxicillin, doxycycline, and in some areas a macrolides (such as azithromycin or erythromycin) is the first-line outpatient treatment in adults.[36][112][70] In children with mild or moderate symptoms, amoxicillin taken by mouth is the first line.[101][113][114] The use of fluoroquinolones in uncomplicated cases is discouraged due to concerns about side-effects and generating resistance in light of there being no greater benefit.[36][115]
For those who require hospitalization and caught their pneumonia in the community the use of a β-lactam such as cephazolin plus macrolide such as azithromycin is recommended.[116][70] A fluoroquinolone may replace azithromycin but is less preferred.[70] Antibiotics by mouth and by injection appear to be similarly effective in children with severe pneumonia.[117]
The duration of treatment has traditionally been seven to ten days, but increasing evidence suggests that shorter courses (3–5 days) may be effective for certain types of pneumonia and may reduce the risk of antibiotic resistance.[118][119][120][121] For pneumonia that is associated with a ventilator caused by non-fermenting Gram-negative bacilli (NF-GNB), a shorter course of antibiotics increases the risk that the pneumonia will return.[120] Recommendations for hospital-acquired pneumonia include third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and vancomycin.[76] These antibiotics are often given intravenously and used in combination.[76] In those treated in hospital, more than 90% improve with the initial antibiotics.[27] For people with ventilator-acquired pneumonia, the choice of antibiotic therapy will depend on the person's risk of being infected with a strain of bacteria that is multi-drug resistant.[32] Once clinically stable, intravenous antibiotics should be switched to oral antibiotics.[34] For those with Methicillin resistant Staphylococcus aureus (MRSA) or Legionella infections, prolonged antibiotics may be beneficial.[34]
The addition of corticosteroids to standard antibiotic treatment appears to improve outcomes, reducing death and morbidity for adults with severe community acquired pneumonia, and reducing death for adults and children with non-severe community acquired pneumonia.[122][123] A 2017 review therefore recommended them in adults with severe community acquired pneumonia.[122] A 2019 guideline however recommended against there general use, unless refractory shock was present.[70] Side effects associated with the use of corticosteroids include high blood sugar.[122] There is some evidence that adding corticosteroids to the standard PCP pneumonia treatment may be beneficial for people who are infected with HIV.[42]
The use of granulocyte colony stimulating factor (G-CSF) along with antibiotics does not appear to reduce mortality and routine use for treating pneumonia is not supported by evidence.[124]
### Viral
Neuraminidase inhibitors may be used to treat viral pneumonia caused by influenza viruses (influenza A and influenza B).[12] No specific antiviral medications are recommended for other types of community acquired viral pneumonias including SARS coronavirus, adenovirus, hantavirus, and parainfluenza virus.[12] Influenza A may be treated with rimantadine or amantadine, while influenza A or B may be treated with oseltamivir, zanamivir or peramivir.[12] These are of most benefit if they are started within 48 hours of the onset of symptoms.[12] Many strains of H5N1 influenza A, also known as avian influenza or "bird flu", have shown resistance to rimantadine and amantadine.[12] The use of antibiotics in viral pneumonia is recommended by some experts, as it is impossible to rule out a complicating bacterial infection.[12] The British Thoracic Society recommends that antibiotics be withheld in those with mild disease.[12] The use of corticosteroids is controversial.[12]
### Aspiration
In general, aspiration pneumonitis is treated conservatively with antibiotics indicated only for aspiration pneumonia.[125] The choice of antibiotic will depend on several factors, including the suspected causative organism and whether pneumonia was acquired in the community or developed in a hospital setting. Common options include clindamycin, a combination of a beta-lactam antibiotic and metronidazole, or an aminoglycoside.[126] Corticosteroids are sometimes used in aspiration pneumonia, but there is limited evidence to support their effectiveness.[125]
### Follow-up
The British Thoracic Society recommends that a follow-up chest radiograph be taken in people with persistent symptoms, smokers, and people older than 50.[61] American guidelines vary, from generally recommending a follow-up chest radiograph[127] to not mentioning any follow-up.[71]
## Prognosis
With treatment, most types of bacterial pneumonia will stabilize in 3–6 days.[2] It often takes a few weeks before most symptoms resolve.[2] X-ray findings typically clear within four weeks and mortality is low (less than 1%).[23][128] In the elderly or people with other lung problems, recovery may take more than 12 weeks. In persons requiring hospitalization, mortality may be as high as 10%, and in those requiring intensive care it may reach 30–50%.[23] Pneumonia is the most common hospital-acquired infection that causes death.[27] Before the advent of antibiotics, mortality was typically 30% in those that were hospitalized.[20] However, for those whose lung condition deteriorates within 72 hours, the problem is usually due to sepsis.[34] If pneumonia deteriorates after 72 hours, it could be due to nosocomial infection or excerbation of other underlying comorbidities.[34] About 10% of those discharged from hospital are readmitted due to underlying co-morbidities such as heart, lung, or neurological disorders, or due to new onset of pneumonia.[34]
Complications may occur in particular in the elderly and those with underlying health problems.[128] This may include, among others: empyema, lung abscess, bronchiolitis obliterans, acute respiratory distress syndrome, sepsis, and worsening of underlying health problems.[128]
### Clinical prediction rules
Clinical prediction rules have been developed to more objectively predict outcomes of pneumonia.[27] These rules are often used to decide whether to hospitalize the person.[27]
* Pneumonia severity index (or PSI Score)[27]
* CURB-65 score, which takes into account the severity of symptoms, any underlying diseases, and age[129]
### Pleural effusion, empyema, and abscess
A pleural effusion: as seen on chest X-ray. The A arrow indicates fluid layering in the right chest. The B arrow indicates the width of the right lung. The volume of the lung is reduced because of the collection of fluid around the lung.
In pneumonia, a collection of fluid may form in the space that surrounds the lung.[130] Occasionally, microorganisms will infect this fluid, causing an empyema.[130] To distinguish an empyema from the more common simple parapneumonic effusion, the fluid may be collected with a needle (thoracentesis), and examined.[130] If this shows evidence of empyema, complete drainage of the fluid is necessary, often requiring a drainage catheter.[130] In severe cases of empyema, surgery may be needed.[130] If the infected fluid is not drained, the infection may persist, because antibiotics do not penetrate well into the pleural cavity. If the fluid is sterile, it must be drained only if it is causing symptoms or remains unresolved.[130]
In rare circumstances, bacteria in the lung will form a pocket of infected fluid called a lung abscess.[130] Lung abscesses can usually be seen with a chest X-ray but frequently require a chest CT scan to confirm the diagnosis.[130] Abscesses typically occur in aspiration pneumonia, and often contain several types of bacteria. Long-term antibiotics are usually adequate to treat a lung abscess, but sometimes the abscess must be drained by a surgeon or radiologist.[130]
### Respiratory and circulatory failure
Pneumonia can cause respiratory failure by triggering acute respiratory distress syndrome (ARDS), which results from a combination of infection and inflammatory response. The lungs quickly fill with fluid and become stiff. This stiffness, combined with severe difficulties extracting oxygen due to the alveolar fluid, may require long periods of mechanical ventilation for survival.[37] Other causes of circulatory failure are hypoxemia, inflammation, and increased coagulability.[34]
Sepsis is a potential complication of pneumonia but usually occurs in people with poor immunity or hyposplenism. The organisms most commonly involved are Streptococcus pneumoniae, Haemophilus influenzae, and Klebsiella pneumoniae. Other causes of the symptoms should be considered such as a myocardial infarction or a pulmonary embolism.[131]
## Epidemiology
Main article: Epidemiology of pneumonia
Deaths from lower respiratory infections per million persons in 2012
24–120
121–151
152–200
201–241
242–345
346–436
437–673
674–864
865–1,209
1,210–2,085
Disability-adjusted life year for lower respiratory infections per 100,000 inhabitants in 2004[132]
no data
less than 100
100–700
700–1,400
1,400–2,100
2,100–2,800
2,800–3,500
3,500–4,200
4,200–4,900
4,900–5,600
5,600–6,300
6,300–7,000
more than 7,000
Pneumonia is a common illness affecting approximately 450 million people a year and occurring in all parts of the world.[12] It is a major cause of death among all age groups resulting in 4 million deaths (7% of the world's total death) yearly.[12][13] Rates are greatest in children less than five, and adults older than 75 years.[12] It occurs about five times more frequently in the developing world than in the developed world.[12] Viral pneumonia accounts for about 200 million cases.[12] In the United States, as of 2009, pneumonia is the 8th leading cause of death.[23]
### Children
In 2008, pneumonia occurred in approximately 156 million children (151 million in the developing world and 5 million in the developed world).[12] In 2010, it resulted in 1.3 million deaths, or 18% of all deaths in those under five years, of which 95% occurred in the developing world.[12][22][133] Countries with the greatest burden of disease include India (43 million), China (21 million) and Pakistan (10 million).[134] It is the leading cause of death among children in low income countries.[12][13] Many of these deaths occur in the newborn period. The World Health Organization estimates that one in three newborn infant deaths is due to pneumonia.[135] Approximately half of these deaths can be prevented, as they are caused by the bacteria for which an effective vaccine is available.[136] In 2011, pneumonia was the most common reason for admission to the hospital after an emergency department visit in the U.S. for infants and children.[137]
## History
WPA poster, 1936/1937
Pneumonia has been a common disease throughout human history.[138] The word is from Greek πνεύμων (pneúmōn) meaning "lung".[139] The symptoms were described by Hippocrates (c. 460–370 BC):[138] "Peripneumonia, and pleuritic affections, are to be thus observed: If the fever be acute, and if there be pains on either side, or in both, and if expiration be if cough be present, and the sputa expectorated be of a blond or livid color, or likewise thin, frothy, and florid, or having any other character different from the common... When pneumonia is at its height, the case is beyond remedy if he is not purged, and it is bad if he has dyspnoea, and urine that is thin and acrid, and if sweats come out about the neck and head, for such sweats are bad, as proceeding from the suffocation, rales, and the violence of the disease which is obtaining the upper hand."[140] However, Hippocrates referred to pneumonia as a disease "named by the ancients". He also reported the results of surgical drainage of empyemas. Maimonides (1135–1204 AD) observed: "The basic symptoms that occur in pneumonia and that are never lacking are as follows: acute fever, sticking pleuritic pain in the side, short rapid breaths, serrated pulse and cough."[141] This clinical description is quite similar to those found in modern textbooks, and it reflected the extent of medical knowledge through the Middle Ages into the 19th century.
Edwin Klebs was the first to observe bacteria in the airways of persons having died of pneumonia in 1875.[142] Initial work identifying the two common bacterial causes, Streptococcus pneumoniae and Klebsiella pneumoniae, was performed by Carl Friedländer[143] and Albert Fraenkel[144] in 1882 and 1884, respectively. Friedländer's initial work introduced the Gram stain, a fundamental laboratory test still used today to identify and categorize bacteria. Christian Gram's paper describing the procedure in 1884 helped to differentiate the two bacteria, and showed that pneumonia could be caused by more than one microorganism.[145]
Sir William Osler, known as "the father of modern medicine", appreciated the death and disability caused by pneumonia, describing it as the "captain of the men of death" in 1918, as it had overtaken tuberculosis as one of the leading causes of death in this time. This phrase was originally coined by John Bunyan in reference to "consumption" (tuberculosis).[146][147] Osler also described pneumonia as "the old man's friend" as death was often quick and painless when there were much slower and more painful ways to die.[20]
Viral pneumonia was first described by Hobart Reimann in 1938. Reimann, Chairman of the Department of Medicine at Jefferson Medical College, had established the practice of routinely typing the pneumoccocal organism in cases where pneumonia presented. Out of this work, the distinction between viral and bacterial strains was noticed.[148]
Several developments in the 1900s improved the outcome for those with pneumonia. With the advent of penicillin and other antibiotics, modern surgical techniques, and intensive care in the 20th century, mortality from pneumonia, which had approached 30%, dropped precipitously in the developed world. Vaccination of infants against Haemophilus influenzae type B began in 1988 and led to a dramatic decline in cases shortly thereafter.[149] Vaccination against Streptococcus pneumoniae in adults began in 1977, and in children in 2000, resulting in a similar decline.[150]
## Society and culture
See also: List of notable pneumonia cases
### Awareness
Due to the relatively low awareness of the disease, 12 November was declared as the annual World Pneumonia Day, a day for concerned citizens and policy makers to take action against the disease, in 2009.[151][152]
### Costs
The global economic cost of community-acquired pneumonia has been estimated at $17 billion annually.[23] Other estimates are considerably higher. In 2012 the estimated aggregate costs of treating pneumonia in the United States were $20 billion;[153] the median cost of a single pneumonia-related hospitalization is over $15,000.[154] According to data released by the Centers for Medicare and Medicaid Services, average 2012 hospital charges for inpatient treatment of uncomplicated pneumonia in the U.S. were $24,549 and ranged as high as $124,000. The average cost of an emergency room consult for pneumonia was $943 and the average cost for medication was $66.[155] Aggregate annual costs of treating pneumonia in Europe have been estimated at €10 billion.[156]
## References
Footnotes
1. ^ The term pneumonia is sometimes more broadly applied to any condition resulting in inflammation of the lungs (caused for example by autoimmune diseases, chemical burns or certain medications),[3][4] although this inflammation is more accurately referred to as pneumonitis.[15][16]
Citations
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12. ^ 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 Ruuskanen O, Lahti E, Jennings LC, Murdoch DR (April 2011). "Viral pneumonia". Lancet. 377 (9773): 1264–75. doi:10.1016/S0140-6736(10)61459-6. PMC 7138033. PMID 21435708.
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144. ^ Fraenkel A (21 April 1884). "Über die genuine Pneumonie, Verhandlungen des Congress für innere Medicin". Dritter Congress. 3: 17–31.
145. ^ Gram C (15 March 1884). "Über die isolierte Färbung der Schizomyceten in Schnitt- und Trocken-präparaten". Fortschr. Med. 2 (6): 185–89.
146. ^ Tomashefski Jr JF, ed. (2008). Dail and Hammar's pulmonary pathology (3rd ed.). New York: Springer. p. 228. ISBN 978-0-387-98395-0.
147. ^ Osler W, McCrae T (1920). The principles and practice of medicine: designed for the use of practitioners and students of medicine (9th ed.). D. Appleton. p. 78. "One of the most widespread and fatal of all acute diseases, pneumonia has become the "Captain of the Men of Death", to use the phrase applied by John Bunyan to consumption."
148. ^ John H, Hodges MD (1989). Wagner, MD, Frederick B (ed.). "Thomas Jefferson University: Tradition and Heritage". Jefferson Digital Commons. Part III, Chapter 9: Department of Medicine. p. 253.
149. ^ Adams WG, Deaver KA, Cochi SL, Plikaytis BD, Zell ER, Broome CV, Wenger JD (January 1993). "Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era". JAMA. 269 (2): 221–6. doi:10.1001/jama.1993.03500020055031. PMID 8417239.
150. ^ Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, et al. (Active Bacterial Core Surveillance of the Emerging Infections Program Network) (May 2003). "Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine". The New England Journal of Medicine. 348 (18): 1737–46. doi:10.1056/NEJMoa022823. PMID 12724479.
151. ^ "World Pneumonia Day Official Website". Fiinex. Archived from the original on 2 September 2011. Retrieved 13 August 2011.
152. ^ Hajjeh R, Whitney CG (November 2012). "Call to action on world pneumonia day". Emerging Infectious Diseases. 18 (11): 1898–9. doi:10.3201/eid1811.121217. PMC 3559175. PMID 23092708.
153. ^ "Household Component Summary Data Tables". Archived from the original on 20 February 2017.
154. ^ "Household Component Summary Data Tables". Archived from the original on 20 February 2017.
155. ^ "One hospital charges $8,000 – another, $38,000". The Washington Post.
156. ^ Welte T, Torres A, Nathwani D (January 2012). "Clinical and economic burden of community-acquired pneumonia among adults in Europe". Thorax. 67 (1): 71–9. doi:10.1136/thx.2009.129502. PMID 20729232.
### Bibliography
* Murray JF (2010). Murray and Nadel's textbook of respiratory medicine (5th ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 978-1-4160-4710-0.
* Cunha BA, ed. (2010). Pneumonia essentials (3rd ed.). Sudbury, MA: Physicians' Press. ISBN 978-0-7637-7220-8.
## External links
Wikiquote has quotations related to: Pneumonia
Look up pneumonia in Wiktionary, the free dictionary.
Classification
D
* ICD-10: J12, J13, J14, J15, J16, J17, J18, P23
* ICD-9-CM: 480-486, 770.0
* MeSH: D011014
* DiseasesDB: 10166
* SNOMED CT: 233604007
External resources
* Curlie: Pneumonia
* MedlinePlus: 000145
* eMedicine: search/pneumonia
* Patient UK: Pneumonia
* Scholia: Q12192
* v
* t
* e
Pneumonia
Infectious pneumonias
* Bacterial pneumonia
* Viral pneumonia
* Fungal pneumonia
* Parasitic pneumonia
* Atypical pneumonia
* Community-acquired pneumonia
* Healthcare-associated pneumonia
* Hospital-acquired pneumonia
* Ventilator-associated pneumonia
* Severe acute respiratory syndrome
Pneumonias caused by
infectious or noninfectious agents
* Aspiration pneumonia
* Lipid pneumonia
* Eosinophilic pneumonia
* Bronchiolitis obliterans organizing pneumonia
Noninfectious pneumonia
* Chemical pneumonitis
* Idiopathic pneumonia syndrome
* v
* t
* e
Diseases of the respiratory system
Upper RT
(including URTIs,
common cold)
Head
sinuses
Sinusitis
nose
Rhinitis
Vasomotor rhinitis
Atrophic rhinitis
Hay fever
Nasal polyp
Rhinorrhea
nasal septum
Nasal septum deviation
Nasal septum perforation
Nasal septal hematoma
tonsil
Tonsillitis
Adenoid hypertrophy
Peritonsillar abscess
Neck
pharynx
Pharyngitis
Strep throat
Laryngopharyngeal reflux (LPR)
Retropharyngeal abscess
larynx
Croup
Laryngomalacia
Laryngeal cyst
Laryngitis
Laryngopharyngeal reflux (LPR)
Laryngospasm
vocal cords
Laryngopharyngeal reflux (LPR)
Vocal fold nodule
Vocal fold paresis
Vocal cord dysfunction
epiglottis
Epiglottitis
trachea
Tracheitis
Laryngotracheal stenosis
Lower RT/lung disease
(including LRTIs)
Bronchial/
obstructive
acute
Acute bronchitis
chronic
COPD
Chronic bronchitis
Acute exacerbation of COPD)
Asthma (Status asthmaticus
Aspirin-induced
Exercise-induced
Bronchiectasis
Cystic fibrosis
unspecified
Bronchitis
Bronchiolitis
Bronchiolitis obliterans
Diffuse panbronchiolitis
Interstitial/
restrictive
(fibrosis)
External agents/
occupational
lung disease
Pneumoconiosis
Aluminosis
Asbestosis
Baritosis
Bauxite fibrosis
Berylliosis
Caplan's syndrome
Chalicosis
Coalworker's pneumoconiosis
Siderosis
Silicosis
Talcosis
Byssinosis
Hypersensitivity pneumonitis
Bagassosis
Bird fancier's lung
Farmer's lung
Lycoperdonosis
Other
* ARDS
* Combined pulmonary fibrosis and emphysema
* Pulmonary edema
* Löffler's syndrome/Eosinophilic pneumonia
* Respiratory hypersensitivity
* Allergic bronchopulmonary aspergillosis
* Hamman-Rich syndrome
* Idiopathic pulmonary fibrosis
* Sarcoidosis
* Vaping-associated pulmonary injury
Obstructive / Restrictive
Pneumonia/
pneumonitis
By pathogen
* Viral
* Bacterial
* Pneumococcal
* Klebsiella
* Atypical bacterial
* Mycoplasma
* Legionnaires' disease
* Chlamydiae
* Fungal
* Pneumocystis
* Parasitic
* noninfectious
* Chemical/Mendelson's syndrome
* Aspiration/Lipid
By vector/route
* Community-acquired
* Healthcare-associated
* Hospital-acquired
By distribution
* Broncho-
* Lobar
IIP
* UIP
* DIP
* BOOP-COP
* NSIP
* RB
Other
* Atelectasis
* circulatory
* Pulmonary hypertension
* Pulmonary embolism
* Lung abscess
Pleural cavity/
mediastinum
Pleural disease
* Pleuritis/pleurisy
* Pneumothorax/Hemopneumothorax
Pleural effusion
Hemothorax
Hydrothorax
Chylothorax
Empyema/pyothorax
Malignant
Fibrothorax
Mediastinal disease
* Mediastinitis
* Mediastinal emphysema
Other/general
* Respiratory failure
* Influenza
* Common cold
* SARS
* Coronavirus disease 2019
* Idiopathic pulmonary haemosiderosis
* Pulmonary alveolar proteinosis
Authority control
* GND: 4036659-5
* NDL: 00562778
* NSK: 002275398
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Pneumonia
|
c0032285
| 8,010 |
wikipedia
|
https://en.wikipedia.org/wiki/Pneumonia
| 2021-01-18T18:35:39 |
{"mesh": ["D011014"], "umls": ["C0032285"], "icd-9": ["480", "484", "481", "770.0", "483", "482", "486", "485"], "icd-10": ["J12", "J16", "J13", "P23", "J15", "J14", "J18", "J17"], "wikidata": ["Q12192"]}
|
A number sign (#) is used with this entry because this phenotype can be caused by homozygous mutation in the FOXN1 gene (600838) on chromosome 17q11-q12.
Clinical Features
Pignata et al. (1996) reported 2 sisters with an association of congenital alopecia, severe T-cell immunodeficiency, and ridging and pitting of all nails. A decrease of mature T lymphocytes was mainly due to a low number of helper T cells, whereas the number of suppressor/cytotoxic T cells was relatively normal. Mitogen stimulation did not produce an adequate proliferative response. Since a normal proliferative response was seen following phorbol myristate acetate and ionomycin stimulation of T cells, the authors suggested that in these girls there was a block in the signal transmission upstream to protein kinase C. One sister died at the age of 1 year. Another girl underwent bone marrow transplantation (BMT) at 5 months and was alive 1 year after BMT. Pignata et al. (1996) suggested this association is a new syndrome presumably with autosomal recessive inheritance. Although alopecia has been reported in several patients with Omenn syndrome (603554), the sisters reported by Pignata et al. (1996) had alopecia at birth, before clinical evidence of erythrodermia, and the alopecia persisted after BMT. Frank et al. (1999) noted that the 2 sisters originated from a geographically isolated small community in southern Italy.
Vigliano et al. (2011) reported studies of a human fetus with the homozygous R255X mutation from the high-risk southern Italian village. There was total blockage of CD4+ T-cell maturation and severe impairment of CD8+ cells, although a few nonfunctional CD8+ cells lacking CD3 were found. Some diversity of the T-cell receptor generation occurred, but it was impaired compared to controls, and there were low levels of alpha/beta TCRs. No thymic tissue was found in the fetus. There were no abnormalities in the development of B cells or natural killer cells. The findings indicated that FOXN1 is crucial for in utero T-cell development in humans. The identification of a limited number of CD8+ cells suggested an extrathymic origin for these cells, implying FOXN1-independent lymphopoiesis.
Molecular Genetics
In the 2 sisters described by Pignata et al. (1996), Frank et al. (1999) identified homozygosity for a mutation (R255X; 600838.0001) in FOXN1 gene. The sister who had received a bone marrow transplant from her brother was alive and free of infection 4 years after the transplant (Frank et al., 1999). Detection of the haplotype specific for the wildtype FOXN1 allele as well as the mutant allele was indicative of chimerism and provided evidence of long-term engraftment and expansion of the bone marrow graft. Frank et al. (1999) identified this phenotype as a human homolog of the 'nude' mouse.
During a genetic screening of the village population from which the patients reported by Frank et al. (1999) originated, Amorosi et al. (2008) identified a female fetus who was homozygous for the R255X mutation. Post-termination examination at 15 weeks' gestation showed that the fetus lacked a thymus and the skin was grossly abnormal, being tighter than usual and showing basal hyperplasia and dysmaturity, suggesting impaired differentiation. The phenotype was identical to that of the Nude/SCID phenotype of mice. In addition, the fetus had multiple neural tube defects, including anencephaly and spina bifida.
Population Genetics
Adriani et al. (2004) reported 4 additional children from the same Italian community reported by Pignata et al. (1996) and Frank et al. (1999) who were affected with congenital alopecia and died from severe infections in early childhood. Screening for the R255X mutation in 843 inhabitants representing 30% of the village population resulted in identification of 55 (6.52%) heterozygous carriers. A genealogic study revealed that these individuals belonged to 39 families that were linked in an extended 7-generation pedigree comprising 483 individuals. Archival research identified a single ancestral couple born at the beginning of the 19th century, and haplotype analysis was consistent with a single ancestral origin for the mutation.
Animal Model
The mouse and rat 'nude' phenotype (see Flanagan, 1966) consists of disruption of normal hair growth and thymus development, causing nude mice and rats to be immunodeficient. The mouse 'nude' locus was localized to mouse chromosome 11 within a less than 1-Mb critical region. Nehls et al. (1994) showed that Foxn1 gene, which is in this critical region, was disrupted on nude mouse and rat mutant alleles.
Hair \- Congenital alopecia Nails \- Ridging and pitting of all nails Immunol \- Severe T-cell immunodeficiency Lab \- Decreased mature T lymphocytes \- Decreased helper T cells \- Normal number of suppressor/cytotoxic T cells \- Decreased proliferative response to mitogen stimulation \- Normal proliferative response to phorbol myristate acetate and ionomycin 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
|
T-CELL IMMUNODEFICIENCY, CONGENITAL ALOPECIA, AND NAIL DYSTROPHY
|
c1866426
| 8,011 |
omim
|
https://www.omim.org/entry/601705
| 2019-09-22T16:14:24 |
{"doid": ["0060769"], "mesh": ["C536781"], "omim": ["601705"], "orphanet": ["169095"], "synonyms": ["FOXN1 deficiency", "Severe T-cell immunodeficiency-congenital alopecia-nail dystrophy syndrome", "Winged helix deficiency"]}
|
Dissecting cellulitis of the scalp is a rare chronic suppurative dermatosis of the scalp that mainly affects black men and that is characterized by multiple painful inflammatory follicular and perifollicular nodules, pustules, and abscesses that interconnect via sinus tracts and eventually result in scarring alopecia.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Dissecting cellulitis of the scalp
|
c0263506
| 8,012 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=345
| 2021-01-23T18:20:06 |
{"gard": ["1883"], "mesh": ["C562486"], "omim": ["260910"], "icd-10": ["L08.8"]}
|
## Summary
### Clinical characteristics.
Baller-Gerold syndrome (BGS) can be suspected at birth in an infant with craniosynostosis and upper limb abnormality. The coronal suture is most commonly affected; the metopic, lambdoid, and sagittal sutures may also be involved alone or in combination. Upper limb abnormality can include a combination of thumb hypo- or aplasia and radial hypo- or aplasia and may be asymmetric. Malformation or absence of carpal or metacarpal bones has also been described. Skin lesions may appear anytime within the first few years after birth, typically beginning with erythema of the face and extremities and evolving into poikiloderma. Slow growth is apparent in infancy with eventual height and length typically at 4 SD below the mean.
### Diagnosis/testing.
The diagnosis of BGS is established in a proband with typical clinical findings and/or the identification of biallelic pathogenic variants in RECQL4 by molecular genetic testing.
### Management.
Treatment of manifestations: Surgery before age six months to repair bilateral craniosynostosis; pollicization of the index finger as needed to create a functional grasp; sunscreen use with poikiloderma to protect against skin cancer.
Surveillance: Because individuals with allelic RECQL4 disorders are at increased risk for osteosarcoma and lymphoma, attention to clinical findings (e.g., bone pain, swelling, and/or limp) for osteosarcoma and lymph node enlargement or generalized symptoms (e.g., fever or unexplained weight loss) for lymphoma is recommended for those with BGS.
Agents/circumstances to avoid: Sun exposure because of risk for skin cancer.
### Genetic counseling.
Baller-Gerold syndrome is inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes and therefore carry one pathogenic variant. Heterozygotes (carriers) are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members, prenatal diagnosis for pregnancies at increased risk, and preimplantation genetic diagnosis are possible if both pathogenic variants in the family have been identified.
## Diagnosis
### Suggestive Findings
Baller-Gerold syndrome should be suspected in individuals with a combination of the following findings:
* Coronal craniosynostosis, manifest clinically as abnormal shape of the skull (brachycephaly) with ocular proptosis and prominent forehead and confirmed by skull x-ray or (preferably) 3D-CT reconstruction
When the coronal sutures are fused, the orbit is pulled forward. The coronal sutures cannot be discerned on the frontal view, and the same holds true for the lambdoidal sutures.
* Radial ray defect, manifest as aplasia or hypoplasia of the thumb, and/or aplasia or hypoplasia of the radius
Note: Radiographs may be necessary for confirmation of minor radial ray malformations.
* Growth restriction
* Poikiloderma consisting of hyper- and hypopigmentation of the skin with punctate atrophy and telangiectases
### Establishing the Diagnosis
The diagnosis of Baller-Gerold syndrome is established in a proband with typical clinical findings and/or by identification of biallelic pathogenic variants in RECQL4 on molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of Baller-Gerold syndrome is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with craniosynostosis or those in whom the diagnosis of Baller-Gerold syndrome has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and laboratory findings suggest the diagnosis of Baller-Gerold syndrome, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
* Single-gene testing. Sequence analysis of RECQL4 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected.
Perform sequence analysis first. If only one or no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.
* A multigene panel that includes RECQL4 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
A multigene panel that also includes deletion/duplication analysis should be considered if only one or no pathogenic variant is found on the multigene panel sequence analysis (see Table 1).
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the phenotype is indistinguishable from many other inherited disorders characterized by craniosynostosis or when the diagnosis of Baller-Gerold syndrome is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
Exome array (when clinically available) may be considered if exome sequencing is not diagnostic.
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 Baller-Gerold Syndrome
View in own window
Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
RECQL4Sequence analysis 3>95% 4
Gene-targeted deletion/duplication analysis 5Rare 6, 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants.
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\.
Larizza et al [2013]
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
6\.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
7\.
A large homozygous intragenic deletion was reported in a single individual of Japanese ethnicity with Baller-Gerold syndrome [Kaneko et al 2017].
## Clinical Characteristics
### Clinical Description
Since the original description of Baller-Gerold syndrome (BGS) by Baller [1950] and Gerold [1959], fewer than 40 individuals with BGS have been reported [Mégarbané et al 2000, Van Maldergem et al 2006, Debeljak et al 2009, Siitonen et al 2009, Piard et al 2015, Kaneko et al 2017]. BGS can be suspected at birth in an infant with craniosynostosis and upper limb abnormality. The coronal suture is most commonly affected; the metopic, lambdoid, and sagittal sutures may also be involved alone or in combination [Van Maldergem et al 2016].
Craniofacial findings associated with craniosynostosis
* Brachycephaly
* Proptosis
* Prominent forehead
* Large fontanelles
Additional craniofacial features
* Concave nasal ridge
* Short nose
* Narrow mouth with thin vermilion of the lips
* High arched palate
Skeletal anomalies
* Upper limb anomalies. A combination of thumb hypo- or aplasia and radial hypo- or aplasia is present and may be asymmetric. Malformation or absence of carpal or metacarpal bones has also been described.
* Knee abnormality. Patellar hypo- or aplasia becomes apparent in childhood.
* Late ossification of the patella may be misinterpreted as absence of the patella in infants.
* Absence of patella may result in genu recurvatum and knee instability.
Skin findings. Skin lesions may appear anytime within the first few years after birth.
* Lesions typically begin with erythema of the face and extremities.
* Findings later evolve into poikiloderma (mottled hypo-and hyper-pigmentation, atrophy, and telangiectasias).
Growth. Slow growth is apparent in infancy with eventual height and length typically at 4 SD below the mean.
Development/intelligence. Although intellectual deficiency has been reported [Ramos Fuentes et al 1994], most if not all patients have normal intelligence. No formal studies on intellectual development have been performed.
Other findings
* Imperforate or anterior displacement of the anus has been reported in several individuals.
* Cardiovascular defects such as ventricular septal defects, tetralogy of Fallot, and congenital portal venous malformations have been occasionally described.
Cancer risk. One case of lymphoma was reported in an individual with Baller-Gerold syndrome [Debeljak et al 2009]. However, an increased risk for osteosarcoma, lymphoma, and skin cancer in other disorders associated with pathogenic variants in RECQL4 (see Genetically Related Disorders) has been reported. Therefore, individuals with Baller-Gerold syndrome with symptoms suggestive of cancer should have prompt evaluation.
### Genotype-Phenotype Correlations
No formal genotype-phenotype correlations have been made owing to the small number of patients reported to date.
### Nomenclature
The name Baller-Gerold syndrome was coined by Cohen [1975] based on descriptions of three affected individuals reported by Baller and Gerold from the German literature.
* Baller [1950] described a woman with short stature, oxycephaly, hypoplasia of the left radius, and aplasia of the right radius; her parents were remotely consanguineous.
* Gerold [1959] described male and female sibs with coronal craniosynostosis, radial and thumb aplasia, and bowing of the ulnae.
Since 1975 the designation Baller-Gerold syndrome has been used to refer to any type of craniosynostosis associated with any type of radial ray defect; this is likely an incorrect use of the term, and has led some authors to consider metopic ridging and radial ray defects observed in valproate embryopathy sufficient for a diagnosis of BGS [Santos de Oliveira et al 2006].
### Prevalence
The prevalence of Baller-Gerold syndrome is unknown; it is probably less than 1:1,000,000 [Mo et al 2018].
## Differential Diagnosis
The major differential diagnosis for Baller-Gerold syndrome (BGS) comprises the allelic disorders Rothmund-Thomson syndrome and RAPADILINO syndrome (OMIM 266280). (See Genetically Related Disorders.) See Figure 1.
#### Figure 1.
Diagram showing overlapping and unique clinical features of the RECQL4-associated disorders. Note: "Mutated cases" refers to cases with a molecular diagnosis. From Van Maldergem et al [2016]
Additional conditions to consider are included in Table 2.
### Table 2.
Disorders to Consider in the Differential Diagnosis of BGS
View in own window
DisorderGene(s)MOIClinical Features of This Disorder
Overlapping with BGSDistinguishing from BGS
Fanconi anemia (FA)Various 1AR
AD
XL
* Radial ray defects
* Craniosynostosis in some
* Cardiac malformation & hematologic anomalies often present
* Chromosome breakage after incubation w/clastogens
Fetal valproate syndrome
(OMIM 609442)N/AN/A
* Radial hypo-or aplasia
* Craniosynostosis (metopic)
* History of maternal use of valproate during pregnancy
* Facial dysmorphia
* Cleft palate
* Neural tube defect
VACTERL
(OMIM 192350)UnknownSporadicThumb hypo- or aplasia
* Cranial nerves palsies
* Cardiac malformation
* Choanal atresia
* Coloboma
* Outer &/or inner ear abnormality
* Orofacial cleft
SALL4-related disordersSALL4ADRadial ray malformations
* Shape of pinnae
* Anorectal anomalies
Holt-Oram syndromeTBX5ADUpper-extremity malformations may involve radial bones.
* Cardiac malformation &/or conduction defect present
* No craniosynostosis
Thrombocytopenia-absent radius (TAR) syndromeSee footnote 2See footnote 2Shortening of upper limbs, sometimes severe
* No craniosynostosis
* Thumbs present in TAR
Saethre-Chotzen syndromeTWISTAD
* Craniosynostosis
* Occasional radial defects (radioulnar synostosis or hypoplastic radius)
* Facial asymmetry
* Small ears w/prominent crus
* Brachydactyly
* Partial 2-3 syndactyly of hand
Roberts syndromeESCO2AR
* Radial aplasia/hypoplasia
* Occasional craniosynostosis
* Shortening of 4 limbs
* Intellectual disability
CDAGS syndrome
(OMIM 603116)UnknownAR
* Craniosynostosis
* Porokeratosis resembling poikiloderma
* Clavicular hypoplasia
* Hearing loss
AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; XL = X-linked
CDAGS = craniosynostosis and clavicular hypoplasia; delayed fontanelle closure, cranial defects and deafness; anal anomalies; genitourinary malformations; and skin eruption [Mendoza-Londono et al 2005]
1\.
The diagnosis of FA rests on the detection of chromosomal aberrations (breaks, rearrangements, radials, exchanges) in cells after culture with a DNA interstrand cross-linking agent such as diepoxybutane (DEB) or mitomycin C (MMC). Approximately 20 genes have been associated with FA.
2\.
Previously thought to be autosomal recessive, the mode of inheritance of TAR syndrome is complex, with a microdeletion in 1q21.1 being necessary but not sufficient to determine the phenotype [Klopocki et al 2007].
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with Baller-Gerold syndrome (BGS), the following are recommended if they have not already been completed:
* Consultation with a clinical geneticist and/or genetic counselor
* Neurosurgery or craniofacial specialist consultation for evaluation of craniosynostosis
* Orthopedic surgery and occupational therapy assessment to evaluate hand and arm function and need for surgery
* Dermatology evaluation if poikiloderma develops
### Treatment of Manifestations
Craniosynostosis should be managed by neurosurgical/craniofacial specialists. When craniosynostosis is bilateral, surgery is usually performed before age six months.
Pollicization of the index finger to restore a functional grasp has had satisfactory results in a number of persons with absence of the thumb [Foucher et al 2005]. However, many children with aplasia of the thumb are able to function without orthopedic surgical intervention.
If poikiloderma is present, sensible use of sunscreens may protect against potential risk for skin cancer due to UV exposure.
If cancer arises, medical care should be sought from an oncologist familiar with the type of cancer.
### Surveillance
Although lymphoma has only been described in one individual with BGS to date [Debeljak et al 2009], it is known that individuals with RECQL4 pathogenic variants associated with both Rothmund-Thomson syndrome and RAPADILINO syndrome are at increased risk for developing osteosarcoma and lymphoma. Given the potential risk, it would be reasonable for affected individuals with BGS and RECQL4 pathogenic variants (or their guardians) to be aware of the signs and symptoms associated with these malignancies. These signs and symptoms may include bone pain, swelling, and/or limp for osteosarcoma, and lymph node enlargement or generalized symptoms such as fever or unexplained weight loss for lymphoma.
### Agents/Circumstances to Avoid
Excessive sun exposure should be avoided because of the theoretic increased risk for skin cancer.
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Baller-Gerold Syndrome
|
c0265308
| 8,013 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1204/
| 2021-01-18T21:40:20 |
{"mesh": ["C536788"], "synonyms": []}
|
Epispadias
SpecialtyMedical genetics
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: "Epispadias" – news · newspapers · books · scholar · JSTOR (March 2013) (Learn how and when to remove this template message)
An epispadias is a rare type of malformation in which the urethra ends, in males, in an opening on the upper aspect of the penis,[1] and in females when the urethra develops too far anteriorly. It occurs in around 1 in 120,000 male and 1 in 500,000 female births.[citation needed]
## Contents
* 1 Signs and symptoms
* 1.1 Relationship to other conditions
* 2 Causes
* 3 Treatment
* 4 Prognosis
* 5 References
* 6 External links
## Signs and symptoms[edit]
Most cases involve a small and bifid penis, which requires surgical closure soon after birth, often including a reconstruction of the urethra. Where it is part of a larger exstrophy, not only the urethra but also the bladder (bladder exstrophy) or the entire perineum (cloacal exstrophy) are open and exposed on birth, requiring closure. Many parts of this article are incorrect.[citation needed]
### Relationship to other conditions[edit]
Despite the similarity of name, an epispadias is not a type of hypospadias, and involves a problem with a different set of embryologic processes.[citation needed]
Women can also have this type of congenital malformation. Epispadias of the female may occur when the urethra develops too far anteriorly, exiting in the clitoris or even more forward. For females, this may not cause difficulty in urination but may cause problems with sexual satisfaction. Frequently, the clitoris is bifurcated at the site of urethral exit, and therefore clitoral sensation is less intense during sexual intercourse due to frequent stimulation during urination. However, with proper stimulation, using either manual or positional techniques, clitoral orgasm is definitely possible.[citation needed]
## Causes[edit]
Epispadias is an uncommon and partial form of a spectrum of failures of abdominal and pelvic fusion in the first months of embryogenesis known as the exstrophy - epispadias complex. While epispadias is inherent in all cases of exstrophy it can also, much less frequently, appear in isolation as the least severe form of the complex spectrum. It occurs as a result of defective migration of the genital tubercle primordii to the cloacal membrane, and so malformation of the genital tubercle, at about the 5th week of gestation.[citation needed]
## Treatment[edit]
The main treatment for isolated epispadias is a comprehensive surgical repair of the genito-urinary area usually during the first 7 years of life, including reconstruction of the urethra, closure of the penile shaft and mobilisation of the corpora. The most popular and successful technique is known as the modified Cantwell-Ransley approach. In recent decades however increasing success has been achieved with the complete penile disassembly technique despite its association with greater and more serious risk of damage.[citation needed]
## Prognosis[edit]
Even with successful surgery, patients may have long-term problems with:[citation needed]
* incontinence, where serious usually treated with some form of continent urinary diversion such as the Mitrofanoff
* depression and psycho-social complications
* sexual dysfunction
## References[edit]
Wikimedia Commons has media related to Epispadias.
1. ^ "Epispadias: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2017-07-13.
## External links[edit]
Classification
D
* ICD-10: Q64.0
* ICD-9-CM: 752.62
* MeSH: D004842
* DiseasesDB: 33378
External resources
* MedlinePlus: 001285
* v
* t
* e
Congenital malformations and deformations of urinary system
Abdominal
Kidney
* Renal agenesis/Potter sequence, Papillorenal syndrome
* cystic
* Polycystic kidney disease
* Meckel syndrome
* Multicystic dysplastic kidney
* Medullary sponge kidney
* Horseshoe kidney
* Renal ectopia
* Nephronophthisis
* Supernumerary kidney
* Pelvic kidney
* Dent's disease
* Alport syndrome
Ureter
* Ectopic ureter
* Megaureter
* Duplicated ureter
Pelvic
Bladder
* Bladder exstrophy
Urethra
* Epispadias
* Hypospadias
* Posterior urethral valves
* Penoscrotal transposition
Vestigial
Urachus
* Urachal cyst
* Urachal fistula
* Urachal sinus
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Epispadias
|
c0563449
| 8,014 |
wikipedia
|
https://en.wikipedia.org/wiki/Epispadias
| 2021-01-18T19:05:10 |
{"mesh": ["D004842"], "umls": ["C0563449", "C0014588"], "icd-9": ["752.62"], "icd-10": ["Q64.0"], "orphanet": ["93928"], "wikidata": ["Q1347416"]}
|
Monoclonal mast cell activation syndrome (MMAS) is a rare immunological disorder characterized by recurrent episodes of allergy, flushing, stomach and intestinal cramping, diarrhea, wheezing, fatigue and a temporary loss of consciousness caused by a fall in blood pressure (hypotension). MMAS is very similar to systemic mastocytosis but without the itchy skin patches known as urticaria pigmentosa. Symptoms may be triggered by a number of factors, including eating, exertion, environmental conditions, emotional stress, or insect stings. It is caused by a very small change (mutation) in the KIT gene which results in a defect of the mast cells. Treatment may include antihistamines and other medications, as needed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Monoclonal mast cell activation syndrome
|
c4267893
| 8,015 |
gard
|
https://rarediseases.info.nih.gov/diseases/12980/monoclonal-mast-cell-activation-syndrome
| 2021-01-18T17:59:00 |
{"icd-10": ["D89.41 "], "orphanet": ["529468"], "synonyms": ["MMAS", "Monoclonal MCAD"]}
|
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: "Pulmonary carcinoid tumour" – news · newspapers · books · scholar · JSTOR (February 2014) (Learn how and when to remove this template message)
Pulmonary carcinoid tumour
SpecialtyOncology/pulmonology
Pulmonary carcinoid tumour is a neuroendocrine tumour of the lung.
There are two types:
* Typical pulmonary carcinoid tumour
* Atypical pulmonary carcinoid tumour
## References[edit]
## External links[edit]
Classification
D
External resources
* eMedicine: article/426400
* Lung carcinoids (cancer.org)
* v
* t
* e
Cancer involving the respiratory tract
Upper RT
Nasal cavity
Esthesioneuroblastoma
Nasopharynx
Nasopharyngeal carcinoma
Nasopharyngeal angiofibroma
Larynx
Laryngeal cancer
Laryngeal papillomatosis
Lower RT
Trachea
* Tracheal tumor
Lung
Non-small-cell lung carcinoma
* Squamous-cell carcinoma
* Adenocarcinoma (Mucinous cystadenocarcinoma)
* Large-cell lung carcinoma
* Rhabdoid carcinoma
* Sarcomatoid carcinoma
* Carcinoid
* Salivary gland–like carcinoma
* Adenosquamous carcinoma
* Papillary adenocarcinoma
* Giant-cell carcinoma
Small-cell carcinoma
* Combined small-cell carcinoma
Non-carcinoma
* Sarcoma
* Lymphoma
* Immature teratoma
* Melanoma
By location
* Pancoast tumor
* Solitary pulmonary nodule
* Central lung
* Peripheral lung
* Bronchial leiomyoma
Pleura
* Mesothelioma
* Malignant solitary fibrous tumor
This article about a medical condition affecting the respiratory system is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
This article about a neoplasm 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
|
Pulmonary carcinoid tumour
|
c0280089
| 8,016 |
wikipedia
|
https://en.wikipedia.org/wiki/Pulmonary_carcinoid_tumour
| 2021-01-18T19:02:35 |
{"umls": ["C0280089"], "wikidata": ["Q16893452"]}
|
Cutis laxa (CL) is an inherited or acquired connective tissue disorder characterized by wrinkled, redundant and sagging inelastic skin associated with skeletal and developmental anomalies and, in some cases, with severe systemic involvement. Several different forms of inherited CL have been described, differentiated on the basis of the mode of inheritance and differences in the extent of internal organ involvement, associated anomalies and disease severity.
## Epidemiology
Most cases of CL are inherited, with prevalence at birth being estimated at around 1/1,000,000 and only around 200 families being reported in the literature so far.
## Clinical description
Autosomal recessive types of CL (ARCL) appear to be the most common forms with two subtypes being described: ARCL1 and ARCL2 (see these terms). ARCL1 is the most severe form of CL with generalized involvement leading to life-threatening complications (lung atelectesias and emphysema, vascular anomalies, and gastrointestinal and genitourinary tract diverticuli). ARCL2 appears to cover a spectrum of disorders ranging in severity from the wrinkly skin syndrome (see this term) to more severe disease associated with growth and developmental delay, and skeletal anomalies (classic ARCL2, Debré type; see this term). De Barsy syndrome and geroderma osteodysplastica (see these terms) also show significant clinical overlap with ARCL2. Occipital horn syndrome (X-linked cutis laxa (XRCL); see this term) is very similar to ARCL2; however, several patients present a more severe phenotype and systemic involvement. Autosomal dominant CL (ADCL) is generally a mild cutaneous disorder but systemic manifestations (hernias, cardiac valve anomalies, cardiovascular manifestations, gastrointestinal diverticuli and emphysema) have been noted in some cases.
## Etiology
Although the underlying etiology remains unknown in many patients with the inherited forms of CL, several genes have been implicated: FBLN5 , EFEMP2 and LTBP4 in ARCL1 (14q32.1, 11q13 and 19q13.1-q13.2) , ATP6V0A2 and PYCR1 in ARCL2 (12q24.3 and 17q25.3), and ELN and FBLN5 in ADCL (7q11.2 and 14q32.1)). Homozygous ELNmutations have also been indentified in four patients with a mild form of ARCL.
## Diagnostic methods
Diagnosis is often problematic due to the considerable clinical overlap between the hereditary forms. The diagnostic approach should include a detailed physical examination, family history, skeletal survey, developmental assessment, imaging studies, histological analysis, liver function tests and biochemical analysis, kidney ultrasound, and ophthalmological and cardiac evaluation.
## Differential diagnosis
The main differential diagnosis is the Ehlers-Danlos syndromes (see these terms) but similar skin manifestations may also occur in patients with Williams syndrome, pseudoxanthoma elasticum, Hutchinson Gilford syndrome, Barber Say syndrome, Costello syndrome, Cardio-Facio-Cutaneous syndrome and Kabuki syndrome (see these terms). Inherited forms of CL should also be distinguished from acquired CL which is commonly preceded by urticaria, angioedema, local or generalized inflammatory skin disease or drug hypersensitivity reactions.
## Antenatal diagnosis
Prenatal diagnosis is feasible by molecular testing for families in which the genetic anomaly has been identified.
## Genetic counseling
Correct diagnosis of the hereditary forms is essential for providing adapted genetic counseling to affected families.
## Management and treatment
There is no efficient treatment for CL and management is symptomatic. Plastic surgery is not generally indicated for the cutaneous manifestations in inherited forms.
## Prognosis
Prognosis is variable, ranging from a usually fatal outcome in childhood in ARCL1 to a normal life expectancy in less severe forms.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Cutis laxa
|
c0010495
| 8,017 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=209
| 2021-01-23T16:55:09 |
{"gard": ["6227"], "mesh": ["D003483"], "umls": ["C0010495"], "icd-10": ["Q82.8"]}
|
Nablus mask-like facial syndrome is a rare microdeletion syndrome that is characterized by a mask-like facial appearance. Facial features include narrowing of the eye opening (blepharophimosis); tight appearing glistening facial skin; and flat and broad nose. Other features include malformed ears; unusual scalp hair pattern; permanently bent fingers and toes (camptodactyly); joint deformities (contractures) that restrict movement in the hands and feet; unusual dentition; mild developmental delay; undescended testicles in males (cryptorchidism); and a happy disposition. This condition is caused by a deletion at chromosome 8q22.1.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Nablus mask-like facial syndrome
|
c1842464
| 8,018 |
gard
|
https://rarediseases.info.nih.gov/diseases/4722/nablus-mask-like-facial-syndrome
| 2021-01-18T17:58:48 |
{"mesh": ["C536110"], "omim": ["608156"], "umls": ["C1842464"], "orphanet": ["178303"], "synonyms": ["8q22.1 microdeletion syndrome"]}
|
A number sign (#) is used with this entry because of evidence that Joubert syndrome-9 (JBTS9) is caused by homozygous or compound heterozygous mutation in the CC2D2A gene (612013) on chromosome 4p15. Digenic inheritance has also been reported; see MOLECULAR GENETICS.
Meckel syndrome-6 (MKS6; 612284) is an allelic disorder.
For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see JBST1 (213300).
Clinical Features
Noor et al. (2008) ascertained a highly consanguineous Pakistani family segregating autosomal recessive mild to moderate mental retardation and retinitis pigmentosa (RP), with 4 living affected individuals; an additional family member with mental retardation was determined to be a 48,XXXX phenocopy. Height, weight, and occipitofrontal circumference were within the normal range in all affected individuals, and there was no facial dysmorphism. The 3 older patients all had retinitis pigmentosa, astigmatism, and nystagmus; the youngest, at age 3 years, did not have RP but did have astigmatism and nystagmus. RP was not present in other members of the family. The oldest affected individual also had early cataract. Gorden et al. (2008) reviewed the brain MRIs of the patients reported by Noor et al. (2008) and determined that they had findings consistent with Joubert syndrome. In an erratum, Noor et al. (2008) agreed.
Gorden et al. (2008) reported 7 families with Joubert syndrome linked to chromosome 4p. The clinical features were variable, but common features included the molar tooth sign, cerebellar vermis hypoplasia, and abnormal eye movements. Two patients had retinal dystrophy and 2 had a history of encephalocele. One patient had abnormal renal ultrasound and hepatosplenomegaly, and another had renal disease. One additional patient was a 22-year-old woman with agenesis of the corpus callosum, hydrocephalus, cerebellar vermis hypoplasia, abnormal eye movements, coloboma, mild renal disease, and hepatic fibrosis requiring liver transplant at age 10 years. Gorden et al. (2008) noted that the features in this patient were reminiscent of COACH syndrome (216360), which in some cases may be a variant representing a transitional phenotype between Joubert syndrome and Meckel syndrome (249000).
Mapping
In a consanguineous Pakistani family segregating Joubert syndrome, Noor et al. (2008) performed homozygosity mapping using Affymetrix 500K microarrays and identified an 11.2-Mb homozygous and haploidentical region on chromosome 4p15.33-p15.2. Linkage analysis across this region yielded a maximum 2-point lod score of 3.59 at marker D4S419.
Molecular Genetics
In affected members of a consanguineous Pakistani family with Joubert syndrome, Noor et al. (2008) identified homozygosity for a splice site mutation in the CC2D2A gene (612013.0001) that segregated with the phenotype. The mutation was not found in 460 Pakistani control chromosomes.
Gorden et al. (2008) identified 7 different mutations in the CC2D2A gene (see, e.g., 612013.0003-612013.0006) in 6 (9%) of 70 families with clinical features consistent with Joubert syndrome.
Lee et al. (2012) reported 2 patients with Joubert syndrome who had a heterozygous mutation in the CC2D2A gene, consistent with JBTS9 (see 612013.0007 and 612013.0009), and a heterozygous mutation in the CEP41 gene (see 612013.0005 and 612013.0006), consistent with JBTS15 (614464), indicating digenic inheritance.
Genotype/Phenotype Correlations
Bachmann-Gagescu et al. (2012) identified biallelic pathogenic mutations in the CC2D2A gene in 20 patients from 17 unrelated families with Joubert syndrome. The patients were ascertained from a larger cohort of 209 families with the disorder, yielding a prevalence of about 8% for those with CC2D2A mutations. Patients with CC2D2A-related Joubert syndrome were more likely to have ventriculomegaly and seizures compared to Joubert syndrome patients without CC2D2A mutations. Although mutation-specific genotype-phenotype correlations could not be identified, most Joubert syndrome patients had at least 1 missense mutation, compared to those with the more severe Meckel syndrome, which tends to be associated with nonsense mutations (see 612013.0002).
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Retinitis pigmentosa \- Astigmatism \- Nystagmus \- Cataract NEUROLOGIC Central Nervous System \- Mental retardation, mild to moderate \- Seizures (in some patients) \- Ventriculomegaly \- Molar tooth sign MOLECULAR BASIS \- Caused by mutation in the coiled-coil and C2 domains-containing protein 2A (CC2D2A, 612013.0001 ) ▲ 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
|
JOUBERT SYNDROME 9
|
c1855675
| 8,019 |
omim
|
https://www.omim.org/entry/612285
| 2019-09-22T16:01:58 |
{"doid": ["0111004"], "mesh": ["C537430"], "omim": ["612285"], "orphanet": ["2318"], "genereviews": ["NBK1325"]}
|
Zimmermann-Laband syndrome (ZLS) is a rare disorder characterized by gingival fibromatosis, coarse facial appearance, and absence or hypoplasia of nails or terminal phalanges of hands and feet.
## Epidemiology
Forty-four patients have been reported to date.
## Clinical description
Coarse facial appearance includes bulbous soft nose, thickened lips, thick and floppy ears and gingival hypertrophy or fibromatosis. The syndrome has a highly variable clinical expression, and other possible features include hyperextensibility of joints, hepatosplenomegaly, hypertrichosis and hearing loss. Intellectual deficit is occasional and usually mild to moderate. The overgrown gingival tissues can affect the ability to speak.
## Etiology
The genetic basis is unknown. Mapping of breakpoints of two translocations t(3;8) and t(3;17) found in two patients with the typical clinical features of Zimmermann-Laband syndrome defined a common breakpoint region located in 3p14.3 but the lack of a specific coding-sequence lesion in the common region suggests that either some other type of genetic defect in this vicinity, or an alteration elsewhere in the genome, could be responsible for ZLS. Autosomal dominant inheritance has been suggested.
## Differential diagnosis
The differential diagnosis includes other defined syndromes of hirsutism and coarsening of the face. Isolated gingival fibromatosis has been documented as a dominantly transmissible trait.
## Management and treatment
Treatment consists of surgical removal of the hyperplasic fibrous tissue and appropriate orthodontic treatment to improve esthetic appearance and eruption of the non-erupted teeth.
## Prognosis
Prognosis is dominated by the risk of recurrence, which is high. Physical systemic evaluation is essential. The syndrome is not life-threatening.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Zimmermann-Laband syndrome
|
c0796013
| 8,020 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3473
| 2021-01-23T18:39:06 |
{"gard": ["385"], "mesh": ["C536725"], "omim": ["135500", "616455", "618658"], "umls": ["C0796013"], "icd-10": ["Q87.8"], "synonyms": ["Gingival fibromatosis-hepatosplenomegaly-other anomalies syndrome", "Laband syndrome"]}
|
## Clinical Features
The DSM-IV (American Psychiatric Association, 1994) describes specific phobias, also known as simple phobias, as being characterized by a marked persistent, excessive, and unreasonable fear caused by the presence of a specific object or situation (e.g., flying, heights, animals, injections, blood). Exposure to the phobic stimulus provokes an immediate anxiety response often resembling panic (see panic disorder, 167870). An adult recognizes that the fear is excessive, but a child may not. The phobic situation is either avoided or endured with intense anxiety or distress, and the avoidance or anxiety interferes with the individual's life activities. Vasovagal fainting may occur and is particularly common with blood-injection-injury phobia. Epidemiology studies indicate that women are more likely to have specific phobias than men. The overall 1-year prevalence is 9%, with a lifetime prevalence of 10 to 11.3%. A genetic component to simple phobias has been hypothesized because the illness, especially blood injury phobias, may aggregate in families, and because most phobias are not associated with a previous traumatic event involving the phobic stimulus.
Mapping
In a genomewide linkage analysis of 57 European American patients with simple phobia from 14 families ascertained through probands with panic disorder, Gelernter et al. (2003) found evidence for linkage to chromosome 14. Parametric analysis yielded a maximum lod score of 3.17 (dominant model) and 2.86 (recessive model) at marker D14S75. Using a simple parametric model, the lod scores at D14S75 increased to 3.70 (dominant model) and 3.30 (recessive model). Gelernter et al. (2003) noted that several anxiety disorders segregated in these families and that several individuals with simple phobia also had other comorbid anxiety disorders. They also noted that the homologous genomic region has been implicated in a mouse model for fear.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
PHOBIA, SPECIFIC
|
c0236801
| 8,021 |
omim
|
https://www.omim.org/entry/608251
| 2019-09-22T16:07:59 |
{"doid": ["599"], "mesh": ["C562465"], "omim": ["608251"], "icd-10": ["F40.2"], "synonyms": ["Alternative titles", "PHOBIA, SIMPLE"]}
|
## Clinical Features
Golla et al. (2002) reported a family in which 4 males had mild to moderate nonspecific X-linked mental retardation, with no intellectual impairment in their obligate carrier mothers.
Mapping
By linkage analysis in a family in which 4 affected males had nonsyndromic mental retardation, Golla et al. (2002) obtained the same multipoint lod score of 2.08 for 2 intervals on the X chromosome: one in the pericentromeric region and the other at Xq26. Since the responsible gene was not characterized, haplotyping was the only means available for carrier and prenatal testing for this form of MRX, which they designated MRX42. Carrier risk estimation using pedigree and haplotype data for 5 females at risk was presented, and the difficulties of prenatal diagnosis given linkage to 2 different regions was discussed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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, X-LINKED 42
|
c2931498
| 8,022 |
omim
|
https://www.omim.org/entry/300372
| 2019-09-22T16:20:24 |
{"doid": ["0050776"], "mesh": ["C567906"], "omim": ["300372"], "orphanet": ["777"]}
|
Gestational diabetes is a disorder characterized by abnormally high blood sugar levels during pregnancy. Affected women do not have diabetes before they are pregnant, and most of these women go back to being nondiabetic soon after the baby is born. The disease has a 30 to 70 percent chance of recurring in subsequent pregnancies. Additionally, about half of women with gestational diabetes develop another form of diabetes, known as type 2 diabetes, within a few years after their pregnancy.
Gestational diabetes is often discovered during the second trimester of pregnancy. Most affected women have no symptoms, and the disease is discovered through routine screening at their obstetrician's office. If untreated, gestational diabetes increases the risk of pregnancy-associated high blood pressure (called preeclampsia) and early (premature) delivery of the baby.
Babies of mothers with gestational diabetes tend to be large (macrosomia), which can cause complications during birth. Infants whose mothers have gestational diabetes are also more likely to develop dangerously low blood sugar levels soon after birth. Later in life, these individuals have an increased risk of developing obesity, heart disease, and type 2 diabetes.
## Frequency
In the United States, up to 14 percent of all pregnancies are affected by gestational diabetes. The prevalence of gestational diabetes has been increasing rapidly over the past few decades (a trend similar to the increase in obesity and type 2 diabetes).
The risk of developing gestational diabetes varies by ethnic background. Women of Native American, Asian, Hispanic, or African American heritage are more likely to be diagnosed with the disease than are non-Hispanic white women.
## Causes
The causes of gestational diabetes are complex. This condition results from a combination of genetic, health, and lifestyle factors, some of which have not been identified.
A hormone called insulin is important in the development of gestational diabetes. Insulin, which is produced in the pancreas, controls how much glucose (a type of sugar) is passed from the blood into cells to be used as an energy source. Under normal conditions, when blood sugar levels are high (such as after a meal), the pancreas releases insulin to move the excess glucose into cells, which reduces the amount of glucose in the blood.
As a normal part of pregnancy, women develop a reduced ability to respond to the effects of insulin, known as insulin resistance. This process ensures that there is enough glucose to provide energy for the growing fetus. As insulin resistance develops, more and more insulin is needed to keep blood sugar levels within the normal range. As a result, insulin-producing cells in the pancreas (called beta cells) make larger amounts of insulin. These cells are usually able to keep up with the body's demand for insulin, and so most pregnant women do not develop gestational diabetes. However, in some women, pancreatic beta cells are unable to increase production of insulin enough to keep blood sugar levels within the normal range. The result is a rise in blood sugar levels (hyperglycemia) that characterizes gestational diabetes.
Common variations (polymorphisms) in several genes have been associated with the risk of developing gestational diabetes. Because they are common, these variations can be present in people with gestational diabetes and in those without. It is the combination of these changes that helps determine a woman's likelihood of developing the disease. Although little is known about the genetics of gestational diabetes, studies suggest that the genes associated with this form of diabetes overlap with those associated with type 2 diabetes. These genes are involved in the development or function of insulin-producing beta cells in the pancreas or play a role in insulin resistance.
Genetic variations likely act in combination with health and lifestyle factors to influence a woman's overall risk of developing gestational diabetes. Risk factors include having a previous pregnancy affected by gestational diabetes, being older (particularly over age 35) during pregnancy, or having previously had a baby who was large (over 9 pounds) at birth. Other health conditions that predispose to the disease include overweight or obesity, a hormonal imbalance called polycystic ovary syndrome (PCOS), and prediabetes (higher-than-normal blood sugar levels that do not reach the cutoff for diabetes). Many of the risk factors for gestational diabetes are the same factors that increase the risk of developing type 2 diabetes.
### Learn more about the genes associated with Gestational diabetes
* GCK
* KCNJ11
* KCNQ1
Additional Information from NCBI Gene:
* CDKAL1
* IGF2BP2
* IRS1
* MTNR1B
* TCF7L2
## Inheritance Pattern
Gestational diabetes is a complex disease without a clear pattern of inheritance. However, many affected individuals have at least one close family member, such as a parent or sibling, with this disease or another form of diabetes (most commonly type 2 diabetes).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Gestational diabetes
|
c1833104
| 8,023 |
medlineplus
|
https://medlineplus.gov/genetics/condition/gestational-diabetes/
| 2021-01-27T08:25:44 |
{"mesh": ["C563425"], "omim": ["606176", "610374", "610582"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic paraplegia-9B (SPG9B) is caused by homozygous or compound heterozygous mutation in the ALDH18A1 gene (138250) on chromosome 10q24.
Heterozygous mutation in the ALDH18A1 gene can cause autosomal dominant spastic paraplegia-9A (SPG9A; 601162).
Description
Autosomal recessive SPG9B is a neurologic disorder characterized by early-onset complex spastic paraplegia. Affected individuals had delayed psychomotor development, intellectual disability, and severe motor impairment. More variable features include dysmorphic facial features, tremor, and urinary incontinence (summary by Coutelier et al., 2015).
For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
Clinical Features
Coutelier et al. (2015) reported 6 adult patients from 2 unrelated families (FSP856 from Spain and SR45 from Portugal) with early-onset autosomal recessive complex spastic paraplegia. Four affected individuals in 1 family presented in the first decade (less than 1 year to 7 years of age) with intellectual disability and/or delayed motor development. They had severe spasticity and gait instability associated with hyperreflexia of the upper and lower limbs and extensor plantar responses; 1 lost ambulation at age 30. Three had limb muscle weakness, including 2 with tetraplegia and foot drop. All patients also had mild microcephaly, and 3 had nonspecific dysmorphic facial features. Additional more variable features included postural tremor, dysarthria, mildly decreased vibration sense at the ankles, and urinary symptoms. Two brothers in the other family had onset of severely delayed psychomotor development in the first year of life. As adults, both had lost ambulation due to severe spasticity. They had severe intellectual disability; 1 never acquired speech. One patient likely had cataracts. Brain imaging of 1 patient showed atrophy of the corpus callosum, periventricular white matter abnormalities, and mild cortical atrophy. Both were incontinent. None of the 6 patients had evidence of skin abnormalities. The parents of the Spanish sibs were unaffected; the Portuguese parents were not available for evaluation.
Inheritance
The transmission pattern of SPG9B in the families reported by Coutelier et al. (2015) was consistent with autosomal recessive inheritance.
Molecular Genetics
In affected members of 2 unrelated families with autosomal recessive spastic paraplegia-9B, Coutelier et al. (2015) identified homozygous or compound heterozygous missense mutations in the ALDH18A1 gene (138250.0010-138250.0012) affecting conserved residues. The mutations were found by whole-exome or panel sequencing. Functional studies of the variants were not performed.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Growth retardation HEAD & NECK Head \- Microcephaly Face \- Dysmorphic facial features Eyes \- Cataract (1 patient) GENITOURINARY Bladder \- Urinary retention \- Incontinence MUSCLE, SOFT TISSUES \- Muscle atrophy NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Poor or absent speech \- Dysarthria \- Spasticity \- Tetraplegia (in some patients) \- Foot drop (in some patients) \- Pseudobulbar palsy (in some patients) \- Impaired gait \- Loss of ambulation (in some patients) \- Hyperreflexia \- Extensor plantar responses \- Tremor (in some patients) Peripheral Nervous System \- Distal vibration sense (in some patients) MISCELLANEOUS \- Two unrelated families have been reported (last curated October 2015) \- Onset in first decade (range 1 to 7 years) \- Progressive disorder \- No skin abnormalities MOLECULAR BASIS \- Caused by mutation in the aldehyde dehydrogenase 18 family, member A1 gene (ALDH18A1, 138250.0010 ) ▲ 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
|
SPASTIC PARAPLEGIA 9B, AUTOSOMAL RECESSIVE
|
c4225272
| 8,024 |
omim
|
https://www.omim.org/entry/616586
| 2019-09-22T15:48:25 |
{"doid": ["0110825"], "omim": ["616586"], "orphanet": ["447760"], "synonyms": ["AR-SPG9B"]}
|
Based on personal examination or history of 11 members of a Japanese family, Inoue et al. (1998) described a distinctive disorder characterized by facial, especially perioral, pigmented follicular atrophoderma, with numerous milia and epidermoid cysts. They suggested that the diagnosis could be made at a glance because of the perioral cutaneous manifestations. Histopathologic examination of the follicular atrophoderma showed proliferation of basaloid cells continuous with the epidermis and coarse collagen fibers, with a decreased density of elastic fibers around the basaloid cells. In 2 of the 8 individuals who were examined, generalized hypohidrosis was also present. Inoue et al. (1998) pictured the pigmentation and multiple depressed pits in the perioral area. In none of the patients was there a history of basal cell carcinoma or tendency to hair loss. The onset of symptoms was thought to be about 20 years, but 2 individuals in the most recent generation also showed follicular atrophoderma and epidermoid cysts that they had thought represented acne scars on the forehead and perioral region. Affected individuals occurred in 4 generations, with 1 instance of male-to-male transmission. Autosomal dominant inheritance was suggested by the authors. The patients' manifestations resembled those of Bazex-Dupre-Christol syndrome (BZX; 301845), but BZX is an X-linked disorder, has a different distribution of follicular atrophoderma, and has basal cell carcinoma and hypotrichosis as features.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
FOLLICULAR ATROPHODERMA, PERIORAL PIGMENTED, WITH MILIA AND EPIDERMOID CYSTS
|
c1863692
| 8,025 |
omim
|
https://www.omim.org/entry/603587
| 2019-09-22T16:12:50 |
{"mesh": ["C566360"], "omim": ["603587"]}
|
Piglet with dipygus at Ukrainian National Chernobyl Museum in Kiev
Dysmelia (from Gr. δυσ- dys, "bad" + μέλ|ος mél|os, "limb" + Eng. suff. -ia) is a congenital disorder of a limb resulting from a disturbance in embryonic development.[1]
## Contents
* 1 Types
* 2 Occurrence rate
* 3 Causes
* 4 Syndromes with dysmelia
* 5 References
* 6 External links
## Types[edit]
Syndactyly of the second and third toes
Dysmelia can refer to[citation needed]
* missing (aplasia) limbs: amelia, oligodactyly, congenital amputation e.g. Tibial or Radial aplasia
* malformation of limbs: shortening (micromelia, rhizomelia or mesomelia), ectrodactyly, phocomelia, meromelia, syndactyly, brachydactyly, club foot
* too many limbs: polymelia, polydactyly, polysyndactyly
* others: Tetraamelia, hemimelia, Symbrachydactyly
Bilateral polydactyly with short fingers in Ellis-van Creveld syndrome patient
## Occurrence rate[edit]
Birth defects involving limbs occur in 1 per 1000.[citation needed]
## Causes[edit]
Dysmelia can be caused by[citation needed]
* inheritance of abnormal genes, e.g. polydactyly, ectrodactyly or brachydactyly, symptoms of deformed limbs then often occur in combination with other symptoms (syndromes)
* external causes during pregnancy (thus not inherited), e.g. via amniotic band syndrome
* teratogenic drugs (e.g. thalidomide, which causes phocomelia) or environmental chemicals
* ionizing radiation (nuclear weapons, radioiodine, radiation therapy)
* infections
* metabolic imbalance
## Syndromes with dysmelia[edit]
This section needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Dysmelia" – news · newspapers · books · scholar · JSTOR (October 2020)
Main page: Category:Syndromes with dysmelia
* 2p15-16.1 microdeletion syndrome
* Achard syndrome
* Ackerman syndrome
* Acrocallosal syndrome
* Acropectoral syndrome
* Adams-Oliver syndrome
* Aglossia adactylia
* Amniotic band syndrome
* Apert syndrome
* Autosomal recessive Robinow syndrome
* Basel-Vanagaite-Sirota syndrome (Microlissencephaly-Micromelia syndrome)
* Campomelic dysplasia
* Cardiofaciocutaneous syndrome
* Catel–Manzke syndrome
* Cenani-Lenz syndrome
* Corneodermatoosseous syndrome
* Diploid triploid mosaic
* Ectrodactyly–ectodermal dysplasia–cleft syndrome
* Edwards syndrome
* Ellis–van Creveld syndrome
* Fibular dimelia diplopodia syndrome (Leg duplication mirror foot syndrome)
* Greig cephalopolysyndactyly syndrome
* Haas syndrome
* Hanhart syndrome
* Holt-Oram syndrome
* Humeroradial synostosis
* Johnson–Munson syndrome
* Joubert syndrome
* McKusick–Kaufman syndrome
* Mermaid syndrome
* Mesomelia-Synostoses syndrome (8q13 microdeletion syndrome)
* Microgastria
* Myhre syndrome
* Nager acrofacial dysostosis
* Neu-Laxova syndrome
* Patau syndrome
* Pfeiffer syndrome
* Poland syndrome
* Radial aplasia
* Roberts SC-Phocomelia syndrome (Phocomelia syndrome)
* Rubinstein–Taybi syndrome
* Silver–Russell syndrome
* Split-hand split-foot malformation (SHFM)
* TAR syndrome (thrombocytopenia with absent radius)
* Tetra-amelia syndrome
* Ulbright-Hodes syndrome
* VACTERL association
* Wallis–Zieff–Goldblatt syndrome
## References[edit]
1. ^ (2006) Dysmelia (Limb Deficiency/Reduction). pp 312-322. In: Atlas of Genetic Diagnosis and Counseling. Humana Press.
## External links[edit]
* DysNet: An organisation for people affected by Dysmelia (congenital limb difference)
* Reach: Association for Children with Upper Limb Deficiency)
* 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
|
Dysmelia
|
c4073131
| 8,026 |
wikipedia
|
https://en.wikipedia.org/wiki/Dysmelia
| 2021-01-18T19:10:44 |
{"umls": ["C4073131"], "wikidata": ["Q1269288"]}
|
Finger hyperphalangy-toe anomalies-severe pectus excavatum syndrome is a rare, genetic, congenital limb malformation syndrome characterized by bilateral short broad thumbs, short deviated index fingers, clinodactyly of the fifth fingers, broad, valgus-deviated halluces and laterally-deviated, overlapping second toe, associated with severe pectus excavatum and craniofacial dysmorphism (including brachycephaly, low anterior hairline, flat supraorbital ridges, telecanthus, upslanting palpebral fissures, maxillary hypoplasia, posteriorly rotated ears, microsomia and micrognathia). Radiological findings include thumb, index, and middle finger hyperphalangy, with severe delta phalanxes in affected fingers and halluces.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Finger hyperphalangy-toe anomalies-severe pectus excavatum syndrome
|
None
| 8,027 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=369979
| 2021-01-23T18:20:38 |
{"icd-10": ["Q87.2"]}
|
A number sign (#) is used with this entry because of evidence that immunodeficiency-12 (IMD12) is caused by homozygous mutation in the MALT1 gene (604860) on chromosome 18q21.
Clinical Features
Jabara et al. (2013) reported 2 sibs, born of consanguineous Lebanese parents, with a primary immunodeficiency characterized by onset in infancy of recurrent bacterial and candidal infections resulting in bronchiectasis and growth delay. Manifestations included mastoiditis, aphthous ulcers, cheilitis, gingivitis, esophagitis, gastritis, duodenitis, and meningitis. Organisms included Pseudomonas, Streptococcus, Haemophilus influenza, Klebsiella, and cytomegalovirus (CMV), among others. The patients died at ages 7 and 13.5 years. Laboratory studies showed normal levels of absolute lymphocytes and serum immunoglobulins, but specific antibody titers were low despite immunization, and T cells showed impaired proliferative responses to mitogens.
McKinnon et al. (2014) reported a 15-year-old girl, born of consanguineous Kurdish parents, with a severe primary immunodeficiency apparent since infancy. She had recurrent chronic dermatitis, inflammatory gastrointestinal disease, and recurrent pneumonia resulting in bronchiectasis and digital clubbing. Organisms included Staphylococcus aureus, varicella virus, herpes simplex virus, Streptococcus, and CMV. The patient also had nonspecific dysmorphic facial features and delayed bone age with osteoporosis. Immunophenotyping of patient B cells showed increased numbers of naive B cells, absent marginal zone B cells, and decreased switched memory B cells, consistent with an arrest of B-cell development. However, serum Ig levels were normal except for increased IgE, and the patient was able to mount antibodies against vaccines. CD3+ T cells were increased, with skewing toward the CD4+ T helper subset. Although absolute lymphocyte numbers were normal, stimulation testing showed an absence of proliferation and blast formation in CD3+ T cells.
Inheritance
The transmission pattern of immunodeficiency-12 in the family reported by Jabara et al. (2013) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 2 sibs, born of consanguineous Lebanese parents, with primary immunodeficiency-12, Jabara et al. (2013) identified a homozygous mutation in the MALT1 gene (604860.0001). The mutation, which was found by homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. The mutation was not present in the dbSNP or 1000 Genomes databases, or in 150 ethnically matched controls. Patient T cells showed impaired degradation of the NFKB inhibitor I-kappa-B-alpha (NFKB1A; 164008) and decreased IL2 (147680) expression after T-cell activation, and the mutant cDNA failed to rescue defective activation of T cells from Malt1-null mice, consistent with a loss of function. The clinical and laboratory findings were similar to those of patients with IMD11 (615206), caused by loss-of-function mutations in the CARD11 gene (607210), another member of the CBM complex.
In a 15-year-old girl, born of consanguineous Kurdish parents, with IMD12, McKinnon et al. (2014) identified a homozygous missense mutation in the MALT1 gene (W580S; 604860.0002). The mutation was found by whole-exome sequencing and segregated with the disorder. Functional studies showed that the mutant protein had lost both paracaspase and scaffolding activity. CD3+ T cells showed impaired degradation of NFKB1A and decreased phosphorylation of NFKB3 (164014).
INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth SKELETAL \- Delayed bone age (1 patient) \- Osteoporosis (1 patient) IMMUNOLOGY \- Primary immunodeficiency \- Recurrent bacterial infections \- Recurrent candidal infections \- Recurrent viral infections \- Opportunistic infections \- Normal numbers of lymphocytes \- Impaired B-cell differentiation \- Poor antibody response \- Decreased T-cell proliferative response to mitogens MISCELLANEOUS \- One patient from a consanguineous Lebanese family and one patient from a consanguineous Kurdish family have been reported (last curated April 2014) \- Death may occur in late childhood MOLECULAR BASIS \- Caused by mutation in the mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1, 604860.0001 ) ▲ 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 12
|
c3809583
| 8,028 |
omim
|
https://www.omim.org/entry/615468
| 2019-09-22T15:51:59 |
{"omim": ["615468"], "orphanet": ["397964"], "synonyms": []}
|
A rare autosomal anomaly syndrome, with a highly variable phenotype, typically characterized by short length, joint abnormalities (e.g. dysplasia, hyperextensibility, contractures, dislocation), congenital cardiac defects, and craniofacial dysmorphism (incl. microcephaly, a high, prominent, narrow and/or hairy forehead, epicanthus, upward-slanting and/or small palpebral fissures, broad, high or depressed nasal bridge and malformed ears). Delayed motor development and intellectual disability is observed in patients not presenting early demise.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Monosomy 22
|
c0795878
| 8,029 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96123
| 2021-01-23T18:54:10 |
{"icd-10": ["Q93.0"], "synonyms": ["Del(22)", "Deletion 22"]}
|
Ruvalcaba syndrome is an extremely rare malformation syndrome, described in less than 10 patients to date, characterized by microcephaly with characteristic facies (downslanting parpebral fissures, microstomia, beaked nose, narrow maxilla), very short stature, narrow thoracic cage with pectus carinatum, hypoplastic genitalia and skeletal anomalies (i.e. characteristic brachydactyly and osteochondritis of the spine) as well as intellectual and developmental delay.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Ruvalcaba syndrome
|
c0265248
| 8,030 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3121
| 2021-01-23T17:06:55 |
{"gard": ["4748"], "mesh": ["C579395"], "omim": ["180870"], "umls": ["C0265248"], "icd-10": ["Q87.8"]}
|
Rombo syndrome
Other namesVermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, basal cell carcinomas and peripheral vasodilation with cyanosis
Rombo syndrome is inherited in an autosomal dominant manner[1]
Rombo syndrome is a very rare genetic disorder characterized mainly by atrophoderma vermiculatum of the face,[2]:580 multiple milia, telangiectases, acral erythema,[3] peripheral vasodilation with cyanosis[4] and a propensity to develop basal cell carcinomas.[3] The lesions become visible in late childhood, began at ages 7 to 10 years and are most pronounced on the face, At that time a pronounced, somewhat cyanotic redness of the lips and hands was evident as well as moderate follicular atrophy of the skin on the cheeks. In adulthood, whitish-yellow, milia-like papules and telangiectatic vessels developed. The papules were present particularly on the cheeks and forehead, gradually becoming very conspicuous and dominating the clinical picture. Trichoepitheliomas were found in 1 case. In adults, the eyelashes and eyebrows were either missing or irregularly distributed with defective and maldirected growth. Basal cell carcinomas were a frequent complication. The skin atrophy was referred to as vermiculate atrophoderma. Basal cell carcinomas may develop around the age of 35. Histological observations during the early stage include irregularly distributed and atrophic hair follicles, milia, dilated dermal vessels, lack of elastin or elastin in clumps. After light irradiation a tendency to increased repair activity was observed both in epidermis and in the dermal fibroblasts.[4] Histologic sections showed the dermis to be almost devoid of elastin in most areas with clumping of elastic material in other areas. The disorder had been transmitted through at least 4 generations with instances of male-to-male transmission.[4]
## See also[edit]
* Tricho–rhino–phalangeal syndrome
* List of cutaneous conditions
* List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer
* List of cutaneous neoplasms associated with systemic syndromes
## References[edit]
1. ^ "OMIM Entry - 180730 - ROMBO SYNDROME". omim.org. Retrieved 7 August 2017.
2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
3. ^ a b van Steensel MA, Jaspers NG, Steijlen PM (June 2001). "A case of Rombo syndrome". Br. J. Dermatol. 144 (6): 1215–8. doi:10.1046/j.1365-2133.2001.04235.x. PMID 11422044. S2CID 24195995.
4. ^ a b c Michaëlsson G, Olsson E, Westermark P (1981). "The Rombo syndrome: a familial disorder with vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, basal cell carcinomas and peripheral vasodilation with cyanosis". Acta Derm. Venereol. 61 (6): 497–503. PMID 6177160.
## External links[edit]
Classification
D
* ICD-10: L98.8
* OMIM: 180730
* MeSH: C535870
* DiseasesDB: 33487
External resources
* Orphanet: 3110
This Genodermatoses 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
|
Rombo syndrome
|
c1867147
| 8,031 |
wikipedia
|
https://en.wikipedia.org/wiki/Rombo_syndrome
| 2021-01-18T18:41:33 |
{"gard": ["4738"], "mesh": ["C535870"], "umls": ["C1867147"], "orphanet": ["3110"], "wikidata": ["Q7362935"]}
|
15q11.2 microdeletion syndrome is a rare partial autosomal monosomy with a variable phenotypic expression and reduced penetrance associated with an increased susceptibility to neuropsychiatric or neurodevelopmental disorders including delayed psychomotor development, speech delay, autism spectrum disorder, attention deficit-hyperactivity disorder, obsessive-compulsive disorder, epilepsy or seizures. It may also include mild non-specific dysmorphic features (such as dysplastic ears, broad forehead, hypertelorism), cleft palate, neurological and neuroimaging abnormalities (such as ataxia and muscular hypotonia).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
15q11.2 microdeletion syndrome
|
c3180937
| 8,032 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261183
| 2021-01-23T19:10:29 |
{"gard": ["10525"], "mesh": ["C557830"], "omim": ["615656"], "umls": ["C3180937"], "icd-10": ["Q93.5"], "synonyms": ["15q11.2 BP1-BP2 microdeletion syndrome", "Del(15)(q11.2)", "Monosomy 15q11.2"]}
|
## Summary
### Clinical characteristics.
Congenital deafness with labyrinthine aplasia, microtia, and microdontia (LAMM syndrome) is characterized by: profound bilateral congenital sensorineural deafness associated with inner ear anomalies (most often bilateral complete labyrinthine aplasia); microtia (type I) that is typically bilateral (although unilateral microtia and normal external ears are observed on occasion); and microdontia (small teeth). Individuals with LAMM syndrome commonly have motor delays during infancy presumably due to impaired balance from inner ear (vestibular) abnormalities. Growth, physical development, and cognition are normal.
### Diagnosis/testing.
The diagnosis of LAMM syndrome is established in a proband by identification of biallelic pathogenic variants in FGF3 on molecular genetic testing.
### Management.
Treatment of manifestations: Enrollment in appropriate early-intervention programs and educational programs for the hearing impaired; consideration of vibrotactile hearing devices or brain stem implants for individuals with complete labyrinthine aplasia; consideration of cochlear implantation for those with a cochleovestibular nerve and a cochlear remnant; routine ophthalmologic management of strabismus.
Prevention of secondary complications: Attention to the increased risk for accidents secondary to delayed gross motor development and deafness.
Surveillance: Yearly evaluations with a physician familiar with LAMM syndrome or other forms of hereditary deafness; regular ENT and dental evaluations.
Agents/circumstances to avoid: Individuals with residual cochlear function should avoid noise exposure. Because of the high risk for disorientation when submerged in water, swimming needs to be undertaken with caution.
Evaluation of relatives at risk: It is recommended that sibs have hearing screening to allow early diagnosis and treatment of hearing impairment.
### Genetic counseling.
LAMM syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the FGF3 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.
## Diagnosis
### Suggestive Findings
The diagnosis of congenital deafness with labyrinthine aplasia, microtia, and microdontia (LAMM syndrome) should be suspected in individuals with the following:
* Profound congenital sensorineural deafness
* Severe inner ear anomalies diagnosed by CT scan or MRI of the inner ear. The most common inner ear anomaly is complete labyrinthine aplasia with no recognizable structure in the inner ear (also referred to as Michel aplasia) (Figure 1C).
* Microtia with shortening of the upper part of the auricles (also referred to as type I microtia) (Figure 1A)
* Microdontia (small teeth) with widely spaced teeth (Figure 1B)
#### Figure 1.
Congenital deafness with labyrinthine aplasia, microtia, and microdontia A. Microtia with anteverted ears
Some individuals may also show gross motor developmental delay during infancy (presumably due to the absence of vestibular system) accompanied by additional features that include:
* Hypoplasia/dysplasia of middle ear anatomic structures identified by imaging studies;
* Stenosis of the jugular foramen with enlarged emissary vein identified by imaging studies.
### Establishing the Diagnosis
The diagnosis of LAMM syndrome is established in a proband by identification of biallelic pathogenic variants in FGF3 on molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of LAMM syndrome is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of LAMM syndrome has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and laboratory findings suggest the diagnosis of LAMM syndrome, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
* Single-gene testing. Sequence analysis of FGF3 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If only one or no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.
* A multigene panel that includes FGF3 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the diagnosis of LAMM syndrome is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia
View in own window
Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
FGF3Sequence analysis 315 reported 4
Gene-targeted deletion/duplication analysis 53 reported 6
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Tekin et al [2007], Tekin et al [2008], Alsmadi et al [2009], Ramsebner et al [2010], Dill et al [2011], Riazuddin et al [2011], Sensi et al [2011], Singh et al [2014], Basdemirci et al [2019]
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
6\.
Gregory-Evans et al [2007]
## Clinical Characteristics
### Clinical Description
Labyrinthine aplasia, microtia, and microdontia (LAMM syndrome) was originally described by Tekin et al [2007]. Since then more than 60 individuals with homozygous and compound heterozygous FGF3 pathogenic variants from more than 20 families (consanguineous and nonconsanguineous) have been reported [Sensi et al 2011]. Age at diagnosis is typically age 50 years or younger (range: 1 month to 50 years).
Profound congenital sensorineural deafness is bilateral in all individuals reported to date. Most have bilateral complete labyrinthine aplasia, some have unilateral complete labyrinthine aplasia and visible but severely malformed inner ear structures in the other ear, and a few have some inner ear structure present bilaterally [Tekin et al 2007, Ramsebner et al 2010, Riazuddin et al 2011].
Type I microtia with shortening of auricles above the crura of the antihelix tends to be bilateral in most. Unilateral microtia and bilateral normal external ears have been reported in individuals with the p.Arg95Trp pathogenic variant. Anteverted ears and large skin tags or lobulation of the upper side of the auricle can be seen in some [Tekin et al 2008].
Small teeth have been observed in all reported individuals. Dental anomalies include conical shape and decreased tooth diameter resulting in widely spaced teeth. Loss of tooth height and peg-shaped lateral incisors have been seen. Supernumerary upper lateral incisors and absence of the first premolars have been observed.
Mild micrognathia and excessive caries were noted in one adult.
Hypodontia or dental root anomalies have not been observed [Tekin et al 2007].
Other
* Motor delays during infancy, presumably the result of impaired balance; commonly seen
* Stenosis of the jugular foramen with enlarged emissary vein diagnosed by cranial imaging with no clinical manifestations
* Normal growth and physical development
* Average or above-average cognition; affected individuals often attend and thrive at schools for the hearing impaired.
* Absence of limb anomalies and lacrimal findings (seen in some FGFR-related syndromes)
Findings that may be incidental to LAMM syndrome include: mild anatomic defects including unilateral stenosis of the uretero-pelvic junction, ocular abnormalities such as strabismus-hypermetropia; brain anomalies such as pontocerebellar arachnoid cysts; cardiovascular findings such as prominent azygos vein; and mildly distinctive facial features such as long facies, downslanting palpebral fissures, deep-set eyes, high nasal bridge, hypoplastic alae nasi, and mild micrognathia.
Life span is not typically altered in individuals with LAMM syndrome. Healthy adults in their 40s and 50s have been reported [Tekin et al 2007, Alsmadi et al 2009].
### Genotype-Phenotype Correlations
The variant p.Arg95Trp is associated with a less severe phenotype than the other FGF3 pathogenic variants [Ramsebner et al 2010, Riazuddin et al 2011].
* Microtia was not observed in eight of 11 individuals homozygous for p.Arg95Trp; in contrast, none of the persons reported with other pathogenic variants had normal-appearing external ears.
* Inner ear structures were identified in seven of 20 individuals homozygous for p.Arg95Trp; in contrast, persons reported with other pathogenic variants had either no inner ear components or primitive vesicle-like structures.
### Prevalence
LAMM syndrome is very rare; no prevalence estimates have been established. It has been reported in more than 60 individuals from more than 20 unrelated families.
## Differential Diagnosis
### Table 2.
Other Genes of Interest in the Differential Diagnosis of LAMM Syndrome
View in own window
Gene(s)DisorderMOIClinical Features of Differential Diagnosis Disorder
Overlapping w/LAMM syndromeDistinguishing from LAMM syndrome
FGF10
FGFR2
FGFR3Lacrimo-auriculo-dento-digital (LADD) syndrome
(OMIM 149730)AD
* Hearing loss
* Dental anomalies
* Aplasia, atresia, or hypoplasia of the lacrimal & salivary systems
* Cup-shaped ears
* Digital (particularly thumb) anomalies
EYA1
SIX1
SIX5Branchiootorenal spectrum disorderADHearing loss
* Branchial fistulae & cysts
* Renal malformations
KMT2D
KDM6AKabuki syndromeAD
XL
* Hearing loss
* Strabismus
* Skeletal anomalies
* Typical facial features
* Dermatoglyphic abnormalities
* Congenital heart defects
* Mild-to-moderate intellectual disability
SALL1Townes-Brocks syndromeAD
* Microtia
* Hearing loss
* Imperforate anus or anal stenosis
* Typical thumb malformations w/out hypoplasia of the radius
AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; XL = X-linked; LAMM = labyrinthine aplasia, microtia, and microdontia
Other single-gene disorders or microdeletion/microduplication syndromes should be considered in individuals who have intellectual disability in addition to typical anomalies seen in LAMM syndrome [Dill et al 2011].
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with congenital deafness with labyrinthine aplasia, microtia, and microdontia (LAMM syndrome), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 3.
Recommended Evaluations Following Initial Diagnosis in Individuals with Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia
View in own window
System/
ConcernEvaluationComment
ENTCT &/or MRI of the temporal bonesEvaluate inner ear anomalies
HearingAudiologic evaluationEvaluate for sensorineural hearing loss
DentalDental evaluationEvaluate for dental anomalies
RenalConsider renal ultrasound.Evaluate for kidney anomalies incl unilateral stenosis of the uretero-pelvic junction
OtherConsultation w/clinical geneticist &/or genetic counselor
### Treatment of Manifestations
Ideally, the team evaluating and treating a deaf individual should include an otolaryngologist with expertise in the management of early-childhood otologic disorders, an audiologist experienced in the assessment of hearing loss in children, a clinical geneticist, and a pediatrician. The expertise of an educator of the Deaf, a neurologist, and a pediatric ophthalmologist may also be required.
* Enrollment in appropriate early-intervention programs and educational programs for the hearing impaired is appropriate.
* An important part of the evaluation is determining the appropriate habilitation option. Possibilities include hearing aids, vibrotactile devices, brain stem implants, and cochlear implantation:
* Consideration of vibrotactile hearing devices or brain stem implants for individuals with complete labyrinthine aplasia [Riazuddin et al 2011]
* Evaluation for cochlear implantation in those individuals with a cochleovestibular nerve and a cochlear remnant. Cochlear implantation can be considered in children over age 12 months with severe-to-profound hearing loss.
* Routine ophthalmologic management of strabismus, if present, is indicated.
### Prevention of Secondary Complications
Regardless of its etiology, uncorrected hearing loss has consistent sequelae: Auditory deprivation through age two years is associated with poor reading performance, poor communication skills, and poor speech production. Educational intervention is insufficient to completely remediate these deficiencies.
In contrast, early auditory intervention (whether through amplification or cochlear implantation) is effective (see Hereditary Hearing Loss and Deafness Overview). However, the presence of severe inner ear anomalies and Michel aplasia in individuals with LAMM syndrome limits auditory habilitation options.
Delayed gross motor development (presumably the result of impaired balance and profound deafness) increases the risk for accidents and trauma.
* The risk for accidents can be addressed in part by use of visual or vibrotactile alarm systems in homes and schools.
* The risk for pedestrian injury can be reduced by choosing routes with visual displays of crosswalks.
* Anticipatory education of parents, health providers, and educational programs about hazards can help address the risk for falls [Gaebler-Spira & Thornton 2002, Chakravarthy et al 2007].
### Surveillance
### Table 4.
Recommended Surveillance for Individuals with Deafness with Congenital Labyrinthine Aplasia, Microtia, and Microdontia
View in own window
System/ConcernEvaluationFrequency
DeafnessENT evaluationAnnually
StrabismusOphthalmologic evaluationAnnually
DentalDental evaluationAs necessary
Yearly evaluations by the multidisciplinary team mentioned in Treatment of Manifestations is appropriate.
### Agents/Circumstances to Avoid
Noise exposure is a well-recognized environmental cause of hearing loss. Since this risk can be minimized by avoidance, individuals with LAMM syndrome and a residual cochlea should be counseled appropriately.
Because of the high risk for disorientation when submerged in water, swimming needs to be undertaken with caution.
### Evaluation of Relatives at Risk
It is appropriate to clarify the genetic status of apparently asymptomatic sibs of an affected individual by molecular genetic testing for the FGF3 pathogenic variant in the family in order to allow early diagnosis and treatment of hearing impairment. (Note: Affected sibs may have normal-appearing ears.)
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia
|
c1853144
| 8,033 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK100664/
| 2021-01-18T21:33:39 |
{"mesh": ["C565195"], "synonyms": ["Congenital Deafness with Inner Ear Agenesis", "Microtia", "and Microdontia; LAMM Syndrome"]}
|
A number sign (#) is used with this entry because of evidence that selective tooth agenesis-8 (STHAG8) is caused by heterozygous mutation in the WNT10B gene (601906) on chromosome 12q13.
For a general phenotypic description and a discussion of genetic heterogeneity of selective tooth agenesis, see STHAG1 (106600).
Clinical Features
Yu et al. (2016) studied a Chinese family in which a mother and her daughter and son exhibited oligodontia, with 12 to 24 missing teeth. The existing teeth were small and/or cone-shaped. All 3 affected individuals had sparse eyebrows, and the children also had sparse light-brown hair as well as dry skin. The authors stated that there were no obvious developmental abnormalities of the ears, hands, or feet in the affected members of the family.
Molecular Genetics
In a Chinese family in which a mother and her daughter and son exhibited oligodontia but had no mutation in known oligodontia-associated genes, Yu et al. (2016) performed whole-exome sequencing and identified heterozygosity for a missense mutation in the WNT10B gene (R211Q; 601906.0003) that segregated fully with disease in the family. Screening the WNT10B gene in a cohort of 145 probands with oligodontia revealed 3 more patients with heterozygous mutations, including 2 missense and 1 nonsense mutation (W262X; 601906.0004). Functional analysis demonstrated that the mutants could not efficiently induce endothelial differentiation of dental pulp stem cells. Yu et al. (2016) observed that the most frequently missing permanent teeth in WNT10B-associated oligodontia were the lateral incisors (83.3%), whereas premolars were missing only 51.4% of the time, which they noted was a pattern 'clearly different' from the oligodontia patterns resulting from WNT10A (606268) mutations (see STHAG4, 150400); however, they suggested that an overlapping phenotype in some individuals with WNT10A or WNT10B mutations was likely.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Sparse eyebrows (in some patients) Teeth \- Selective tooth agenesis of permanent dentition \- Small teeth \- Cone-shaped teeth \- Shovel-shaped teeth SKIN, NAILS, & HAIR Skin \- Dry skin (in some patients) Hair \- Sparse eyebrows (in some patients) \- Sparse hair (in some patients) \- Lighter-colored hair (in some patients) MISCELLANEOUS \- Lateral incisors are the most frequently missing teeth MOLECULAR BASIS \- Caused by mutation in the wingless-type MMTV integration site family, member-10B gene (WNT10B, 601906.0003 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
TOOTH AGENESIS, SELECTIVE, 8
|
c4310730
| 8,034 |
omim
|
https://www.omim.org/entry/617073
| 2019-09-22T15:46:57 |
{"omim": ["617073"], "orphanet": ["99798"], "synonyms": ["Selective tooth agenesis"]}
|
A number sign (#) is used with this entry because Sandhoff disease is caused by mutation in the beta subunit of hexosaminidase (HEXB; 606873) on chromosome 5q13.
Description
Sandhoff disease is a progressive neurodegenerative disorder characterized by an accumulation of GM2 gangliosides, particularly in neurons, and is clinically indistinguishable from Tay-Sachs disease (272800).
Clinical Features
Sandhoff et al. (1968) gave the initial description of the disorder that bears his name. O'Brien (1971) studied 2 Mexican-American sisters and a boy of Anglo-Saxon extraction. Most patients have been non-Jewish; however, the clinical and pathologic picture is very similar to Tay-Sachs disease (272800). Weakness begins in the first 6 months of life. Startle reaction, early blindness, progressive mental and motor deterioration, doll-like face, cherry red spots, and macrocephaly are all present as in Tay-Sachs disease. Death usually occurs by age 3 years.
In the case reported by Krivit et al. (1972), signs of heart involvement preceded those of nervous system change. A pansystolic murmur and cardiomegaly were discovered at 3 months. Neurologic deterioration was first noted at 8 months. Coarse facies, macroglossia, megalencephaly, minimal hepatosplenomegaly and high lumbar gibbus suggested Hurler syndrome.
Der Kaloustian et al. (1981) described 7 cases in Lebanon. The largest collection of cases is represented by the 36 patients in 15 families described in a Creole population of Argentina (Dodelson de Kremer et al., 1985).
Frey et al. (2005) reported 3 adult patients, including 2 sisters, with late-onset GM2-gangliosidosis diagnosed in childhood. All had learning difficulties in school, and all had been hospitalized for either emotional lability, intermittent psychosis, or confusional state. As adults, neurologic evaluations showed variable features of muscle weakness, muscle atrophy, fasciculations, supranuclear gaze palsy, muscular atrophy, hyperreflexia, and extensor plantar responses. Serial neuropsychologic examination in 1 of the 2 sisters showed significant declines in cognitive and executive function over 10 years. In a literature review of 62 patients, Frey et al. (2005) found that 44% had some degree of cognitive dysfunction, 62% of whom showed progressive dementia. Cerebellar and cortical atrophy were common. Frey et al. (2005) concluded that patients with late-onset GM2 gangliosidosis have a high risk of dementia, and that patients with dementia often have other neurologic manifestations.
Heterogeneity
### Clinical Heterogeneity
Spence et al. (1974) described a case of clinically, histologically, and chemically typical Sandhoff disease in a black male. Total hexosaminidase activity in the blood was 20 to 24% of normal (compared with the usual value of less than 5%), whereas in the liver the level was less than 2% of normal. This may be an allelic variant of Sandhoff disease.
In a 10-year-old male with progressive cerebellar ataxia and psychomotor retardation, Wood and MacDougall (1976) found almost complete absence of total hexosaminidase activity in serum, leukocytes, and cultured skin fibroblasts. In spite of disparate clinical findings, this disorder may be allelic to the classic infantile form of Sandhoff disease in view of the similarity of the enzyme deficiency. Studies of residual hexosaminidase isozymes in the juvenile and infantile forms suggested that the defects may be different allelic modifications of the beta subunit common to Hex-A and Hex-B (Wood and MacDougall, 1976). Wood (1978) found no complementation of Sandhoff and juvenile Sandhoff cells, suggesting allelism.
Johnson and Chutorian (1978) found a new form of hexosaminidase deficiency characterized clinically by mild, juvenile-onset, slowly progressive cerebellar ataxia, and macular cherry red spots. Hexosaminidase B appeared to be absent, resulting in a relative increase in Hex-A in screening tests. They suggested that this condition may be due to a mutation allelic to that for Sandhoff disease.
In one of its mutant forms, Hex-A deficiency can lead to late-onset, progressive motor neuron disease. Cashman et al. (1986) presented a case demonstrating that the same is true for Hex-B deficiency. Their female patient had a progressive motor neuron syndrome that began at age 7 years and was characterized by dysarthria, muscle wasting, fasciculations, and pyramidal tract dysfunction. Rectal biopsy at age 24 showed membranous cytoplasmic bodies in submucosal ganglion cells.
Diagnosis
Lowden et al. (1978) described Sandhoff disease in a Metis kindred of northern Saskatchewan and discussed carrier detection. Chamoles et al. (2002) described methods for enzymatic detection of Tay-Sachs and Sandhoff disease in newborns using dried blood spots on filter paper.
### Differential Diagnosis
Kaback (1985) knew of no case of Sandhoff disease in a Jewish child. It may be that the rare cases are confused with Tay-Sachs disease; however, the hepatosplenomegaly should distinguish them as it did in Sandhoff's original case.
Pathogenesis
Tay-Sachs disease (272800) results from a mutation in the alpha subunit (HEXA; 606869) of the hexosaminidase A enzyme, and Sandhoff disease results from mutation in the beta subunit (HEXB; 606873) of the hexosaminidase A and B enzymes. Thus, hexosaminidases A and B are both deficient in Sandhoff disease. Srivastava and Beutler (1973) maintained that hexosaminidases A and B share a common subunit that is lacking in Sandhoff disease, whereas a subunit unique to hexosaminidase A is deficient in Tay-Sachs disease. Galjaard et al. (1974), Thomas et al. (1974), and Rattazzi et al. (1975) showed that Hex-A activity appears after fusion of Tay-Sachs and Sandhoff cells, suggesting genetic complementation. Abnormal radioactive-sulfate kinetics and mucopolysacchariduria are observed in Sandhoff disease but not in Tay-Sachs disease.
Through serial analysis of gene expression (SAGE), Myerowitz et al. (2002) determined gene expression profiles in cerebral cortex from a Tay-Sachs patient, a Sandhoff disease patient, and a pediatric control. Examination of genes that showed altered expression in both patients revealed molecular details of the pathophysiology of the disorders relating to neuronal dysfunction and loss. A large fraction of the elevated genes in the patients could be attributed to activated macrophages/microglia and astrocytes, and included class II histocompatibility antigens, the proinflammatory cytokine osteopontin (SPP1; 166490), complement components, proteinases and inhibitors, galectins, osteonectin (SPARC; 182120), and prostaglandin D2 synthase (PTGDS; 176803). The authors proposed a model of neurodegeneration that includes inflammation as a factor leading to the precipitous loss of neurons in individuals with these disorders.
Mapping
The HEXB locus (606873) has been assigned to chromosome 5 (Gilbert et al., 1975). In a child with a de novo balanced translocation t(5;13)(q11;p11), Mattei et al. (1984) found decreased levels of Hex-B, suggesting to these workers that the HEXB gene assignment can be narrowed to 5q11.
Chern et al. (1976) studied heteropolymeric hexosaminidase A formed by human-mouse hybrid cells that contained an X;15 translocation chromosome but lacked human chromosome 5. Tests with specific antisera suggested that the hybrid molecule had human alpha units and mouse beta units. The findings are consistent with hexosaminidase A being composed of alpha and beta subunits coded by genes on chromosomes 15 and 5, respectively.
Molecular Genetics
O'Dowd et al. (1986) concluded that the primary gene defect in the majority of Sandhoff cases is in the HEXB gene itself. They studied 5 juvenile cell lines, all of which were found to have normal or reduced levels of pre-beta-chain mRNA and no gross abnormalities in the HEXB gene. Of the 11 infantile type cell lines examined, 4 were found to contain no detectable pre-beta-chain mRNA. Two of the 4 contained partial gene deletions located to the 5-prime end of the HEXB genes. One of these cell lines had previously been assigned to the single complementation group in Sandhoff disease. Thus, the clinical heterogeneity in Sandhoff disease appears to be related to different allelic HEXB mutations.
Oonk et al. (1979) reported the cases of 2 adult sisters with spinocerebellar degeneration and very low activities of both Hex-A and Hex-B. Bolhuis et al. (1987) reported the autopsy findings of one of the sisters. She had suffered from progressive disabling spinocerebellar disease with motor neuron involvement, but had no dementia, seizures, or ophthalmologic abnormalities. She died of severe urosepsis at age 39. GM2-ganglioside storage was most pronounced in the cerebellum. Only very small amounts of mature beta chain were synthesized. Bolhuis et al. (1987) concluded that the disorder was the result of a 'destabilizing mutation' in the HEXB locus. Bolhuis et al. (1993) demonstrated that these 2 sisters were compound heterozygotes for an mRNA-negative allele on 1 chromosome 5 and an R505Q mutation (606873.0009) on the homologous chromosome. Transfection of COS cells with a cDNA construct containing the R505Q mutation resulted in the expression of a labile form of beta-hexosaminidase, thus confirming their earlier conclusion.
Brown et al. (1992) and Kleiman et al. (1994) gave updates on the HEXB mutations in the Argentinian deme described by Dodelson de Kremer et al. (1985).
Neufeld (1989) provided a review of the disorders related to mutations in the HEXA and HEXB genes. Mahuran (1998) stated that he maintains a database of published hexosaminidase and GM2A (613109) mutations and that the database contains 23 HEXB mutations, 86 HEXA (606869) mutations, and 4 GM2A mutations.
Among 12 unrelated Italian patients with Sandhoff disease, 11 of whom had the infantile type, Zampieri et al. (2009) identified 11 different mutations in the HEXB gene, including 6 novel mutations (see, e.g., 606873.0017 and 606873.0018). The common 16-kb deletion (606873.0001) was not identified in this patient cohort.
Population Genetics
Cantor and Kaback (1985) stated that the gene frequency for Sandhoff disease was about 1/1000 in Jews and 1/600 in non-Jews.
Drousiotou et al. (2000) noted that in the previous 15 years, 4 patients with the infantile form of Sandhoff disease had been identified in 4 different families in Cyprus (population, 703,000; birth rate, 1.7%). Three of these cases came from the Christian Maronite community (less than 1% of the population) and 1 from the Greek community (84% of the population). This relatively large number of patients prompted Drousiotou et al. (2000) to initiate an epidemiologic study to establish the frequency of the mutant gene in Cyprus. Measuring beta-hexosaminidases A and B in both leukocytes and serum, they identified 35 carriers among 244 random Maronite samples and 15 among 28 Maronites with a family history of Sandhoff disease, but only 1 carrier out of 115 random samples from the Greek community. Of 50 Maronite carriers examined, 42 were found to have deletion of adenine at nucleotide 76 (606873.0016).
Animal Model
Sango et al. (1995) found that mice generated through disruption of the HEXB gene have severe neurologic involvement, representing a satisfactory model of Sandhoff disease. In contrast, disruption of the HEXA gene with the intent of producing a model of Tay-Sachs disease resulted in no neurologic abnormality, although the mice exhibited biochemical and pathologic features of the disease. Differences in the ganglioside degradative pathway between mice and humans were revealed by the studies. Phaneuf et al. (1996) likewise found that mice with disruption of the Hexa gene suffered no obvious behavioral or neurologic deficit while those homozygous for a disruption of the Hexb gene developed a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor, and ataxia. They proposed that homozygous Hexa deficient mice escaped disease through particle catabolism of accumulated GM2 via GA2 through the combined action of sialidase and beta-hexosaminidase B.
Huang et al. (1997) found that neuron death in HEXB-/- mice is associated with apoptosis occurring throughout the central nervous system, while HEXA-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. Huang et al. (1997) suggested that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.
The mucopolysaccharidosis phenotype is not seen in patients with either Tay-Sachs disease or Sandhoff disease and is also not seen in the knockout mice that have been created as a model of these 2 disorders by homozygosity for a defect in either HEXA or HEXB. However, double knockout mice lacking both subunits of lysosomal beta-hexosaminidase were found by Sango et al. (1996) to display both gangliosidosis and mucopolysaccharidosis. Lack of mucopolysaccharide storage in Tay-Sachs and Sandhoff diseases is presumably due to functional redundancy in the beta-hexosaminidase enzyme system.
Liu et al. (1999) explored a new treatment paradigm for glycosphingolipid storage disorders, namely substrate depletion therapy, by constructing a genetic model in mice. Sandhoff disease mice, which abnormally accumulate glycosphingolipids, were bred with mice that were blocked in their synthesis of GSLs. The mice with simultaneous defects in GSL synthesis and degradation no longer accumulated GSLs, had improved neurologic function, and had a much longer life span; however, these mice eventually developed a late-onset neurologic disease because of accumulation of another class of substrate, oligosaccharides. The results supported the validity of substrate deprivation therapy, but also highlighted limitations.
A possible therapeutic strategy for treating Sandhoff disease and related disorders is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N-butyldeoxynojirimycin, which had been in clinical trials for the potential treatment of type I Gaucher disease (230800), a related disorder that involves glycosphingolipid storage in peripheral tissues but not in the central nervous system. It had also been used in the treatment of Tay-Sachs disease in mice (Platt et al., 1997). Jeyakumar et al. (1999) evaluated whether this drug could also be applied to the treatment of diseases for central nervous system storage and pathology. They found that in the mouse model of Sandhoff disease there was delay of symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offered a potentially general therapy for this family of lysosomal storage diseases, including those with central nervous system disease.
Yamaguchi et al. (2004) found that the progressive neurologic disease induced in Hexb -/- mice, the animal model for Sandhoff disease, was associated with the appearance of antiganglioside autoantibodies. Both elevation of serum antiganglioside autoantibodies and IgG deposition to CNS neurons were found in the advanced stages of the disease in Hexb -/- mice; serum transfer from these mice showed IgG binding to neurons. To determine the role of these autoantibodies, the Fc receptor gamma gene (FCER1G; 147139) was additionally disrupted in Hexb -/- mice, as it plays a key role in immune complex-mediated autoimmune diseases. Clinical symptoms were improved and life spans were extended in the double-null mice; the number of apoptotic cells was also decreased. The level of ganglioside accumulation, however, did not change. IgG deposition was also confirmed in the brain of an autopsied Sandhoff disease patient. Taken together, these findings suggested that the production of autoantibodies plays an important role in the pathogenesis of neuropathy in Sandhoff disease and therefore provides a target for therapy.
GU \- Impotence \- Mild urinary incontinence Neuro \- Startle reaction \- Progressive mental and motor deterioration \- Cerebellar ataxia \- Dysarthria \- Fasciculations \- Pyramidal tract dysfunction \- Hyperreflexia \- Impaired thermal sensitivity \- Orthostatic hypotension \- Postural dizziness Inheritance \- Autosomal recessive with multiple alleles and compounds Skel \- High lumbar gibbus Lab \- Hexosaminidase B beta chain deficiency Tongue \- Macroglossia Muscle \- Infantile muscle weakness \- Muscle wasting GI \- Chronic diarrhea \- Episodic abdominal pain \- Hepatosplenomegaly Eyes \- Early blindness \- Cherry red spots Facies \- Doll-like face \- Coarse facies Misc \- Lethal usually by age 3 years \- Intolerance to heat Cranium \- Macrocephaly Skin \- Impaired sweating Cardiac \- Cardiomegaly ▲ Close
*[v]: View this template
*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[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
|
SANDHOFF DISEASE
|
c0751489
| 8,035 |
omim
|
https://www.omim.org/entry/268800
| 2019-09-22T16:22:31 |
{"doid": ["3323"], "mesh": ["D012497"], "omim": ["268800"], "icd-10": ["E75.01"], "orphanet": ["309169", "309162", "796", "309155"], "synonyms": ["Alternative titles", "GM2-GANGLIOSIDOSIS, TYPE II", "HEXOSAMINIDASES A AND B DEFICIENCY"]}
|
A number sign (#) is used with this entry because variants of the PHF11 gene (607796), located on chromosome 13, are related to serum level of IgE, which in turn is related to atopy, including asthma.
Polymorphism in the IL21R gene (605383) has been associated with elevated IgE levels. Polymorphisms in the PLA2G7 (601690), MS4A2 (147138), and IL4R (147781) genes have been associated with susceptibility to atopy.
Polymorphisms in the MS4A2 gene (147138) on chromosome 11q13 have been associated with susceptibility to atopy.
Asthma (600807), hay fever, and eczema are embraced under the general term atopic hypersensitivity. The genetics of atopic hypersensitivity is complex. Tips (1954) thought that each of the 3 forms of atopy is determined by homozygosity at a single and separate locus. The study of Lubs (1972) suggested, however, a more general increased risk of allergic manifestations. Others (Cooke and Vander Veer, 1916; Clarke et al., 1928; Schwartz, 1952) proposed dominant inheritance. Demonstration of immune response genes in man (146850) gives support to the heritability of atopy (and tends to support dominant inheritance). Bottazzo and Lendrum (1976) reported a strong association between HLA W6 and intrinsic asthma. The early history of the genetics of asthma was reviewed by Bias et al. (1978), beginning with the perceptive observation of Salter in 1864. Bias et al. (1978) reviewed the evidence for genetic control of the several steps in the allergic process.
From determinations of IgE levels in 29 families, Bias et al. (1973) suggested the existence of 'an autosomal dominant gene coding for a substance which represses the biosynthesis or controls the metabolism of IgE.' Complex segregation analysis, as developed by Morton and MacLean (1974), can detect major genes in the presence of polygenic heritability and sib environmental correlation. Gerrard et al. (1978) applied the method to data on IgE levels in 173 nuclear families. They concluded that these data were consistent with a regulatory locus for IgE occupied by 2 alleles, RE and re, with the dominant allele suppressing persistently high levels of IgE. The displacement of mean IgE level in re-re homozygotes was estimated to be 1.67 standard deviations. The frequency of the re gene was estimated to be 0.489 in their population of Saskatchewan white families. Blumenthal et al. (1981) suggested that the genetics may be more complex than previously reported. Hasstedt et al. (1983) supported this view; their analysis did not show evidence of a major gene effect. Eiberg et al. (1985) found a strong suggestion of linkage to ESD (133280) which would put this locus on chromosome 13. The maximum lod score (male and female) was 2.67 at theta 0.00. Borecki et al. (1985) presented data that appear to corroborate an hypothesis relating IgE production and liability to allergy. Homozygous individuals (rr) have persistently elevated levels of IgE. Heterozygotes (Rr), although showing normal IgE levels, have an increased frequency of hypersensitivity, at least to some allergens. Cookson and Hopkin (1988) studied the familial occurrence of atopy, defined by skin prick test responses and serum immunoglobulin-E titers to common inhaled allergens, in 239 members of 40 nuclear and 3 extended families. Ninety percent of the atopic children in the nuclear families had at least 1 demonstrably atopic parent. In each of the extended families, atopy was vertically transmitted, and 31 of 47 (66%) offspring of marriages between atopic and unaffected parents were atopic. Of the designated atopic subjects, 83% admitted to symptoms suggesting atopic disease, but only 30% regarded themselves as having any such disorder. Cookson and Hopkin (1988) suggested that the propensity to produce IgE in response to common, usually inhaled, allergens is inherited as an autosomal dominant, but that its clinical expression depends on interaction with other factors. Hanson et al. (1991) showed that monozygotic twins reared apart or together showed greater concordance than dizygotic twins reared apart or together, in prevalence of asthma and seasonal rhinitis, skin-test response, total serum IgE levels, and specific IgE, as measured by the radioallergosorbent test (RAST). Maximum-likelihood tests of genetic and environmental components of the variation of total IgE levels showed a substantial genetic component and a negligible contribution from common familial environmental effects. Cookson et al. (1989) reexamined the genetics of atopy, using a definition based on specific IgE responses to common antigens or on an abnormally raised total serum IgE. They followed the premise that atopic persons have a propensity to produce prolonged exuberant IgE responses to minute amounts of antigen and that the general state of enhanced IgE responsiveness may cause an increase in antigen-specific IgE antibody levels with or without a high total serum IgE. In linkage studies they found linkage to a hypervariable minisatellite probe (Jeffreys et al., 1985) that had been assigned to chromosome 11 in the region 11q12-q13. These studies gave a maximum lod score of 6.39 at a theta of 0.10 (Cookson et al., 1989). In studies of 64 nuclear families recruited through symptomatic children, the linkage to a marker locus at 11q13, or D11S97, was again confirmed. In 4 Japanese families, Shirakawa et al. (1991) and Shirakawa et al. (1994) reported a lod score of 4.88 at theta = 0.07 for linkage to D11S97. In a linkage study of 64 nuclear families, Young et al. (1992) found a 2-point lod score of 3.8 at theta = 0.07 for linkage to D11S97. A test of genetic heterogeneity showed that atopic IgE responses are linked to this locus in 60 to 100% of families, these values representing the approximate 95% confidence limits. Since previous studies had suggested that the risk of atopy is higher for children of atopic mothers than for those of atopic fathers, Cookson et al. (1992) sought differences between maternal and paternal patterns of transmission at the 11q13 locus among pairs of sibs in families affected by atopy. When they defined atopy as the presence of a positive skinprick test (equal to or larger than 2 mm) to any of a panel of common allergens, a higher than normal concentration of total serum IgE, or a positive radioallergosorbent test for a specific IgE, Cookson et al. (1992) found that 125 (62%) of the sib-pairs affected by atopy shared the maternal 11q13 allele (and D11S97 marker) and 78 (38%) did not. This distribution differed significantly from the expected 50/50 distribution (p = 0.001). Of paternally derived alleles, 83 (46%) were shared and 96 (54%) were not (not significantly different from 50/50). The result was similar whatever definition of atopy was used and with other genetic markers on 11q. The pattern of inheritance through the maternal line is consistent either with paternal genomic imprinting or with maternal modification of developing immune responses. Lympany et al. (1992) could not demonstrate significant linkage between D11S97 and either atopy or bronchial hyperreactivity to methacholine. The use of either a positive skin prick test or a positive RAST as the definition of atopy did not significantly alter the lod scores. Hizawa et al. (1992) and Rich et al. (1992) failed to find linkage of atopy and 11q13. Amelung et al. (1992) were unable to find linkage between atopy or bronchial hyperresponsiveness and markers on 11q or 6p. Moffatt et al. (1992) concluded that affected sib-pair analysis supported linkage, giving evidence that was not dependent on the definition of atopy or the specification of model.
Using sib pair analysis in 51 English families with asthma and atopy, Wheatley et al. (2002) described significant association (p = 0.008) for a polymorphism in the SART1 gene (605941) with atopy, but not with asthma. The authors hypothesized that polymorphic variation within the SART1 gene may account for some individuals developing atopy.
Hargrave et al. (2003) reviewed the records of 84 consecutive patients who underwent penetrating keratoplasty for keratoconus (148300). Because an association between keratoconus and atopic disease had been documented in the literature and had been considered significant since 1937, careful attention was paid to the clinical history of atopy in this study. Atopic patients have been shown to have a 'Th2 immune bias.' Of the 7 patients who rejected their corneal allografts, 4 had repeat penetrating keratoplasty. Of these 4 repeat corneal allografts, 3 showed eosinophilia when compared with rejected grafts in control (nonkeratoconic, nonatopic) patients. Atopic keratoconus patients had a mixed inflammatory cellular infiltrate in the rejected corneal tissue specimen with a significantly greater density of eosinophils compared with patients who did not have a preexisting Th2 bias. The histopathology was comparable to the authors' murine model of rejection in TH2 mice, characterized by a predominantly eosinophilic infiltrate when compared with wildtype (Th1) mice that had a predominantly mononuclear infiltrate in the rejected corneal graft bed.
Marsh and Meyers (1992) reviewed the evidence for a major gene for atopy on 11q and concluded that the evidence cannot be considered convincing. They quoted Risch (1992) as suggesting that, especially in complex diseases like atopy, one should always be willing to consider that a 'significant' lod score (equal to or more than 3.0) may represent a false positive. They discussed several possible reasons for the failure to replicate the earlier linkage results. Coleman et al. (1993) studied genetic linkage in 95 multiplex families recruited through probands with active atopic eczema. Linkage analyses between atopy and markers on 11q13 excluded a major susceptibility locus for atopy in that region. There was no significant deviation from the expected proportion of alleles shared by affected sib-pairs. When they analyzed families according to parental atopic phenotype, they observed a positive lod score (0.8) in 19 families with unaffected fathers, in contrast to markedly negative scores for other combinations of affected parental phenotype. The possibility of a maternal influence on the inheritance of atopy could not, therefore, be excluded.
Sandford et al. (1993) demonstrated that a Ca microsatellite repeat in the fifth intron of the FCER1B gene (MS4A2; 147138) is located on 11q13. Sandford et al. (1993) also found that the FCER1B gene was linked to clinical atopy. Maternally derived alleles were used in the analysis. The known roles of the high-affinity IgE receptor in antigen-induced mast-cell degranulation and in the release of cytokines that enhance IgE production, along with the map location, made the FCER1B gene a candidate for the chromosome 11 atopy locus. However, in a study of allele sharing in sibs with asthma and atopy, Collee et al. (1993) could find no significantly increased proportion of shared alleles at the FCER1B locus. They also found no significant difference in the proportion of maternal and paternal alleles shared at 2 other loci in 11q13. Their results did support linkage of atopy to this region.
In Japanese families, Hizawa et al. (1995) could not confirm the existence of a major gene for atopy located at 11q13 under the model of autosomal dominant inheritance. However, they observed a significant association between serum total IgE levels and genetic markers at this locus both in 14 Japanese atopic families and in 120 unrelated Japanese subjects. For these association studies they detected 8 alleles at the D11S97 locus and 8 alleles in the CA/GT repeat region in the fifth intron of the FCER1B gene.
Using maximum likelihood analysis of variance components estimates in an Australian population-based sample of 232 Caucasian nuclear families, Palmer et al. (2000) found a narrow-sense heritability of total serum IgE levels of 47.3%, i.e., additive genetic effects contributed just under half of the total variance. Specific serum IgE levels against house dust mite and Timothy grass, measured as a combined RAST index, showed a narrow-sense heritability of 33.8% and with environmental effects common to sibs contributing approximately 15% of the total phenotypic variance, explained by childhood exposure to domestic allergens. The study suggested the presence of important genetic determinants of the pathophysiologic traits associated with asthma. The authors proposed that total and specific serum IgE levels are appropriate phenotypes for molecular investigations of the genetic susceptibility to asthma.
Moffatt et al. (2001) examined the association between the HLA-DRB1 locus (142857) and quantitative traits underlying asthma in a population sample consisting of 1,004 individuals from 230 families from the rural Australian town of Busselton. They detected strong associations between HLA-DRB1 alleles and the total serum IgE concentration and IgE titers against individual antigens, with the HLA-DRB1 locus accounting for 4% of the variation in total serum IgE level and 2 to 3% of the variation in specific IgE titers. Alleles associated with elevations of the total serum IgE were different from those associated with specific allergens, suggesting that specific and total serum IgE concentrations may have separate genetic controls.
Milgrom et al. (1999) showed that the role of immune responses mediated by IgE in the pathogenesis of allergic asthmas is reflected in the successful use of recombinant 'humanized' monoclonal antibody against IgE in the treatment of moderate to severe allergic asthma. The antibody forms complexes with free IgE and blocks its interaction with mast cells and basophils.
Allergists are frequently faced with patients simultaneously suffering from asthma, atopic dermatitis, and allergic rhinitis, a constellation recognized as the 'atopic triad.' Oettgen and Geha (1999) reviewed the role of IgE in asthma and atopy.
Finn (1992) suggested a relationship between environmental factors and genetic factors in hay fever. History suggests that in the United Kingdom hay fever was unknown until after the advent of the Industrial Revolution with its accompanying chemical pollution. Indeed, it was first described by John Bostock (1773-1846), who practiced in Liverpool for 20 years before moving to London in 1817. Remarkably, hay fever seems to have been unknown, for all practical purposes, before Bostock's description of his personal case in 1819. Bostock (1828) noted that 'one of the most remarkable circumstances respecting this complaint is its not being noticed as a specific affection, until the last 10 or 12 years.' Finn (1992) suggested that chemical damage to the mucous membrane of the nose is a primary event in hay fever and that without such damage, hay fever would not occur or would occur only very rarely. The nasal mucosa has evolved to prevent the entry of antigens, but the sudden onset of massive chemical pollution overwhelms the natural resistance of the nasal mucous membrane.
Anderson et al. (2002) constructed a BAC/PAC contig physical map of the 1.5 Mb region surrounding the D13S273 microsatellite marker at the chromosome 13q14 atopy locus. Association testing between total serum IgE concentration in 172 sib pairs and microsatellite markers across the contig detected a highly significant association with a novel microsatellite marker within 200 kb of D13S273. The association remained significant when corrected for multiple testing (P less than 0.005). Adjoining microsatellites in the D13S273 vicinity showed weaker association, suggesting that an atopy gene is located within this interval.
Other studies had shown consistent linkage of 13q14 to atopy and total serum IgE concentration (Eiberg et al., 1985; Kimura et al., 1999). Zhang et al. (2003) used serum IgE concentration as a quantitative trait to map susceptibility gene(s) for atopy and asthma in the 13q14 region. They localized the quantitative trait locus (QTL) in a comprehensive single-nucleotide polymorphism (SNP) map. They found replicated association to IgE levels that was attributed to several alleles in a single gene, PHF11 (607796). They also found association with these variants to severe clinical asthma. The gene product contains 2 plant homeodomain (PHD) zinc fingers and probably regulates transcription. Distinctive splice variants were expressed in immune tissues and cells.
Hecker et al. (2003) identified a SNP in the promoter region of the IL21R gene, -83T-C (605383.0001), that was significantly associated with elevated IgE levels in females, but not in males.
The eotaxin gene family (eotaxin 1, 601156; eotaxin 2, 602495; and eotaxin 3, 604697) recruits and activates CCR3 (601268)-bearing cells such as eosinophils, mast cells, and Th2 lymphocytes that play a major role in allergic disorders. Shin et al. (2003) genotyped a 721-member asthma cohort at 17 polymorphisms among the 3 eotaxin loci. Statistical analysis revealed that the eotaxin 2 +1272A-G G* allele showed significantly lower frequency in asthmatics than in normal healthy controls (0.14 vs 0.23, P = 0.002), and that distribution of the eotaxin 2 +1272A-G G* allele-containing genotypes was also much lower in asthmatics (26.3 vs 40.8%, P = 0.003). In addition, a nonsynonymous SNP in eotaxin 1, +123Ala to Thr, showed significant association with total serum IgE levels (P = 0.002-0.02). The effect of eotaxin 1 +123Ala to Thr on total serum IgE appeared in a gene dose-dependent manner. The authors suggested that the development of asthma may be associated with eotaxin 2 +1272A-G polymorphisms, and the susceptibility to high IgE production may be attributed to the eotaxin 1 +123Ala to Thr polymorphism. In an erratum, the authors noted that the first base of the translation start site of the eotaxin 2 genomic reference sequence had been denoted as +1, introducing some errors in the numbering of the eotaxin 2 SNPs.
Tumor necrosis factors TNFA (191160) and TNFB (LTA; 153440) are major proinflammatory cytokines that are thought to be important in the pathogenesis of asthma. Shin et al. (2004) genotyped 550 Korean asthmatics and 171 Korean controls at 5 SNPs in TNFA and 2 SNPs in TNFB. Six common haplotypes could be constructed in the TNF gene cluster due to very strong linkage disequilibrium between TNFA and TNFB, which are located 13 kb apart on chromosome 6p21. The TNFA-308G-A SNP (191160.0004) showed a significant association with the risk of asthma (p = 0.0004). The frequency of TNFA-308A allele-containing genotype in asthmatics (9.8%) was much lower than that in normal controls (22.9%). The protective effects of this polymorphism on asthma were also evident in separated subgroups by atopic status (p = 0.05 in nonatopic subjects and p = 0.003 in atopic subjects). The most common haplotype of the TNF gene cluster, TNF-ht1-GGTCCGG, was associated with total serum IgE levels in asthma patients, especially in nonatopic patients (p = 0.004). Shin et al. (2004) concluded that genetic variants of TNF may be involved in the development of asthma and total serum IgE level in bronchial asthma patients.
Mathias et al. (2005) studied the inheritance of total serum IgE in the isolated Tangier Island population in the Chesapeake Bay where Tangier disease (205400) was first described. All 664 current Tangier Island residents belonged to 1 large extended pedigree spanning 13 generations, with an average inbreeding coefficient of 0.009. Familial correlations and heritability calculations revealed a significant genetic component to total IgE (heritability = 26%).
Sharma et al. (2005) studied the association of a polymorphism in the CMA1 gene (118938), -1903G-A, and a (TG)n(GA)n repeat polymorphism located 254 bp downstream of the gene with asthma and IgE levels in Indian asthmatic patients with a family history of asthma and atopy. A significant association was observed between -1903G-A genotype and serum IgE levels (p = 0.003 and p = 0.0004 for a northern and a western cohort, respectively). Comparing major haplotypes with respect to log total serum IgE levels, a significant difference was obtained between patients and controls (p = 0.018 and p = 0.046 for the northern and western cohorts, respectively). Sharma et al. (2005) suggested that the CMA1 gene contributes to asthma susceptibility and may be involved in regulating IgE levels in atopic asthma.
Hysi et al. (2005) found an insertion-deletion polymorphism (ND1+32656) near the beginning of intron 9 in the NOD1 gene (605980) that accounted for approximately 7% of the variation in total serum IgE in 2 panels of families. The insertion allele was associated with high IgE levels as well as with asthma in an independent study of 600 asthmatic children and 1,194 super-normal controls. Hysi et al. (2005) hypothesized that intracellular recognition of specific bacterial products may affect the presence of childhood asthma.
Pulmonary \- Asthma \- Hay fever Inheritance \- Autosomal dominant Immunology \- Atopic hypersensitivity Lab \- IgE level control Skin \- Eczema ▲ 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
|
IgE RESPONSIVENESS, ATOPIC
|
c1840253
| 8,036 |
omim
|
https://www.omim.org/entry/147050
| 2019-09-22T16:39:35 |
{"mesh": ["C564133"], "omim": ["147050"], "synonyms": ["Alternative titles", "IMMUNOGLOBULIN E, BASIC LEVEL OF, IN SERUM", "IgE, LEVEL OF", "IgE RESPONSE UNDERLYING ALLERGIC ASTHMA AND RHINITIS"]}
|
Scedosporiosis
SpecialtyInfectious disease
Scedosporiosis is an infection caused by fungi from the genus Scedosporium[1] which includes two hyphomycetes of emerging medical importance, Scedosporium apiospermum and Scedosporium prolificans.[2]
Pseudallescheria boydii is the teleomorph (sexual state) distinguished from its anamorph (asexual state) S. apiospermum. During the past decades, both states have undergone several sequential name changes having been referred to as Petriellidium boydii, Allescheria boydii, Pseudallescheria sheari and Monosporium apiospermum.[2]
Pulmonary scedosporiosis, caused by Allescheria boydii is also a very rare fungal involvement of the lungs.[3]
## See also[edit]
* Pseudallescheriasis
## References[edit]
1. ^ Pseudallescheria / Scedosporium: emerging therapy-refractory opportunists in humans
2. ^ a b Immunotherapy Against Invasive Mold Infections Immunotherapy. 2012;4(1):107-120. © 2012 Future Medicine Ltd. Available on Medscape: here
3. ^ Meshram, Sushant; Mishra Gyanshankar (December 2011). "Pulmonary scedosporiosis–A rare entity" (PDF). Asian Pacific Journal of Tropical Disease. 1 (4): 330–332. doi:10.1016/S2222-1808(11)60076-5. Retrieved 14 February 2013.
## External links[edit]
Classification
D
* ICD-10: B48.7
External resources
* Orphanet: 449280
This infectious disease 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
|
Scedosporiosis
|
None
| 8,037 |
wikipedia
|
https://en.wikipedia.org/wiki/Scedosporiosis
| 2021-01-18T19:09:08 |
{"orphanet": ["449280"], "synonyms": [], "wikidata": ["Q25098926"]}
|
Trisomy 22
SpecialtyMedical genetics
Trisomy 22 is a chromosomal disorder in which there are three copies of chromosome 22 rather than two. It is a frequent cause of spontaneous abortion during the first trimester of pregnancy. Progression to the second trimester and live birth are rare. This disorder is found in individuals with an extra copy or a variation of chromosome 22 in some or all cells of their body. There are many kinds of disorders associated with Trisomy 22:
* Emanuel syndrome[1] is named after the genetic contributions made by researcher Dr. Beverly Emanuel. This condition is assigned to individuals born with an unbalanced 11/22 translocation. That is, a fragment of chromosome 11 is moved, or translocated, to chromosome 22.
* 22q11 deletion syndrome[2] is a rare condition which occurs in approximately 1 in 4000 births. This condition is identified when a band in the q11.2 section of the arm of chromosome 22 is missing or deleted. This condition has several different names: 22q11.2 deletion syndrome, Velocardiofacial syndrome, DiGeorge syndrome, conotruncal anomaly face syndrome, Opitz G/BBB syndrome, and Cayler cardiofacial syndrome. The effects of this disorder are different in each individual but similarities exist such as heart defects, immune system problems, a distinctive facial appearance, learning challenges, cleft palate, hearing loss, kidney problems, hypocalcemia, and sometimes psychiatric issues.
* 22q11 microduplication syndrome[3] is the opposite of the 22q11 deletion syndrome: in this condition, a band of q.11.2 section of chromosome 22 is duplicated. Individuals carrying this deficiency are relatively “normal” as in they don’t possess any major birth defects or major medical illnesses. This microduplication is more common than the deletion; this might be due to the milder phenotype of the individuals.
* 22q13 deletion syndrome (Phelan–McDermid syndrome)[4] is a condition caused by the deletion of the tip of the q arm on chromosome 22. Most individuals with this disorder experience cognitive delays; low muscle tone; and sleeping, eating, and behavioural issues.
* Chromosome ring 22[5] is a rare disorder caused by the break and re-join of both ends of chromosome 22, forming a ring. The effects on the individual with this disorder are dependent on the amount of genetic information lost during the break/re-join. Major characteristics for this disorder are intellectual disability, muscle weakness and lack of coordination.
* Cat eye syndrome (Schmid Fraccaro syndrome)[6] is a condition caused by a partial trisomy or tetrasomy in chromosome 22. A small extra chromosome is found, made up of the top half of chromosome 22 and a portion of the q arm at the q11.2 break. This chromosome can be found three or four times. This syndrome is referred as “Cat Eye” due to the eye appearance of reported affected individuals who have coloboma of the iris; however, this feature is only seen in about half of the cases.
* Mosaic trisomy 22[7] is a disorder in which an extra chromosome 22 is found only in some cells of the body. The severity of each case is determined by the number of cells with this extra copy. Some characteristics of individuals with this condition are cardiac abnormalities, growth retardation, mental delay, etc.
* Complete trisomy 22[8] is in contrast with Mosaic trisomy 22; this disorder is characterized by an extra copy of chromosome 22 which is found in each cell of the body of the affected individual. As of 2014, 29 live-born human cases have been reported, with all of them dying before the age of 12 months.[9]
## Contents
* 1 See also
* 2 Notes
* 3 References
* 4 External links
## See also[edit]
* Cat eye syndrome
## Notes[edit]
1. ^ "EmanuelSyndrome.org". chromosome 22 central. Retrieved 10 November 2011.
2. ^ "22q11 Deletion Syndrome". chromosome 22 central. Retrieved 10 November 2011.
3. ^ "22q11 Microduplication". Chromosome 22 central. Retrieved 10 November 2011.
4. ^ "Phelan-McDermid Syndrome / 22q13 Deletion Syndrome". Chromosome 22 Central. Retrieved 10 November 2011.
5. ^ "Chromosome 22 Ring". Chromosome 22 Central. Retrieved 10 November 2011.
6. ^ "Cat Eye Syndrome / Schmid Fraccaro Syndrome". Chromosome 22 Central. Retrieved 10 November 2011.
7. ^ "Mosaic Trisomy 22". Chromosome 22 Central. Retrieved 10 November 2011.
8. ^ "Complete Trisomy 22". Chromosome 22 Central. Retrieved 10 November 2011.
9. ^ Kehinde, FI (December 2014). "Co-occurrence of non-mosaic trisomy 22 and inherited balanced t(4;6)(q33;q23.3) in a liveborn female: case report and review of the literature". American Journal of Medical Genetics. Part A. PubMed. 164A (12): 3187–93. doi:10.1002/ajmg.a.36778. PMID 25257307.
## References[edit]
* Mokate T, Leask K, Mehta S, et al. (2006). "Non-mosaic trisomy 22: a report of 2 cases". Prenat. Diagn. 26 (10): 962–5. doi:10.1002/pd.1537. PMID 16906599.
## External links[edit]
Classification
D
* DiseasesDB: 32684
* Humpath 6236
* v
* t
* e
Chromosome abnormalities
Autosomal
Trisomies/Tetrasomies
* Down syndrome
* 21
* Edwards syndrome
* 18
* Patau syndrome
* 13
* Trisomy 9
* Tetrasomy 9p
* Warkany syndrome 2
* 8
* Cat eye syndrome/Trisomy 22
* 22
* Trisomy 16
Monosomies/deletions
* (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome)
* 1
* Wolf–Hirschhorn syndrome
* 4
* Cri du chat syndrome/Chromosome 5q deletion syndrome
* 5
* Williams syndrome
* 7
* Jacobsen syndrome
* 11
* Miller–Dieker syndrome/Smith–Magenis syndrome
* 17
* DiGeorge syndrome
* 22
* 22q11.2 distal deletion syndrome
* 22
* 22q13 deletion syndrome
* 22
* genomic imprinting
* Angelman syndrome/Prader–Willi syndrome (15)
* Distal 18q-/Proximal 18q-
X/Y linked
Monosomy
* Turner syndrome (45,X)
Trisomy/tetrasomy,
other karyotypes/mosaics
* Klinefelter syndrome (47,XXY)
* XXYY syndrome (48,XXYY)
* XXXY syndrome (48,XXXY)
* 49,XXXYY
* 49,XXXXY
* Triple X syndrome (47,XXX)
* Tetrasomy X (48,XXXX)
* 49,XXXXX
* Jacobs syndrome (47,XYY)
* 48,XYYY
* 49,XYYYY
* 45,X/46,XY
* 46,XX/46,XY
Translocations
Leukemia/lymphoma
Lymphoid
* Burkitt's lymphoma t(8 MYC;14 IGH)
* Follicular lymphoma t(14 IGH;18 BCL2)
* Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH)
* Anaplastic large-cell lymphoma t(2 ALK;5 NPM1)
* Acute lymphoblastic leukemia
Myeloid
* Philadelphia chromosome t(9 ABL; 22 BCR)
* Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1)
* Acute promyelocytic leukemia t(15 PML,17 RARA)
* Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1)
Other
* Ewing's sarcoma t(11 FLI1; 22 EWS)
* Synovial sarcoma t(x SYT;18 SSX)
* Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB)
* Myxoid liposarcoma t(12 DDIT3; 16 FUS)
* Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS)
* Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1)
Other
* Fragile X syndrome
* Uniparental disomy
* XX male syndrome/46,XX testicular disorders of sex development
* Marker chromosome
* Ring chromosome
* 6; 9; 14; 15; 18; 20; 21, 22
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Trisomy 22
|
c0265490
| 8,038 |
wikipedia
|
https://en.wikipedia.org/wiki/Trisomy_22
| 2021-01-18T19:06:51 |
{"gard": ["5335"], "mesh": ["C536799"], "umls": ["C0265490"], "wikidata": ["Q1426698"]}
|
## Clinical Features
Pearlman et al. (1964) described mother and daughter with multiple carpal and tarsal synostoses (carpal and tarsal coalition) as well as radial-head subluxation, aplasia or hypoplasia of the middle phalanges, and metacarpophalangeal synostoses. The latter synostoses seem comparable to those that occur in the 2 more distal joints in the 2 forms of symphalangism (185700, 185800). Although the authors felt this to be the disorder described by Nievergelt (see Nievergelt syndrome, 163400), this is almost certainly not the case but a distinct entity is involved.
Bersani and Samilson (1957) described a mother and her daughter and son with massive synostosis of tarsal bones. No specific statement was made about the state of the carpal bones. Wray and Herndon (1963) observed calcaneonavicular coalition in 3 generations. Isolated fusion of carpal and tarsal bones was described by Kewesch (1934). Diamond (1974) observed talocalcaneal coalition in a mother and 3 of her 8 children. It is probable that this is a disorder distinct from the more common calcaneonavicular bridges.
Limbs \- Carpal synostosis \- Tarsal synostosis \- Digital synostosis \- Radial-head subluxation \- Aplasia/hypoplasia of middle phalanges \- Metacarpophalangeal synostoses \- Absent phalanges \- Short metacarpals Inheritance \- Autosomal dominant Nails \- Absent nails Nose \- Hypoplastic alae nasae ▲ 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
|
SYNOSTOSES, TARSAL, CARPAL, AND DIGITAL
|
c1861305
| 8,039 |
omim
|
https://www.omim.org/entry/186400
| 2019-09-22T16:32:55 |
{"doid": ["14762"], "mesh": ["C536943"], "omim": ["186400"], "orphanet": ["1412"], "synonyms": ["Alternative titles", "CALCANEONAVICULAR COALITION"]}
|
A number sign (#) is used with this entry because of evidence that congenital nuclear cataract-41 (CTRCT41) is caused by heterozygous mutation in the WFS1 gene (606201) on chromosome 4p16. One such family has been reported.
Description
Cataract is an opacification of the lens or lens capsule in the eye and is the most common cause of childhood blindness in the world, with an incidence of 1 to 3 per 10,000 live births. If untreated in infancy or childhood, it frequently causes visual impairment and can result in irreversible amblyopia. Nuclear cataract refers to opacification within the embryonal and/or fetal nuclei of the lens (summary by Berry et al., 2013).
Mapping
In a 4-generation family of Irish descent segregating autosomal dominant congenital nuclear cataract without other ocular or systemic features, Berry et al. (2013) performed genotyping with SNP and microsatellite markers and identified a candidate interval on chromosome 4p16, obtaining a 2-point lod score of 2.62 with marker D4S432 (theta = 0). Recombination events narrowed the interval to a 6.6-Mb region at 4p16.1.
Cytogenetics
Reese et al. (1987) described congenital cataract in father and infant son, both of whom had translocation t(3;4)(p26.2;p15). In the child, the cataracts were not found by an examining physician at age 4 weeks, but 'milky' pupils were noted by the mother at 7 weeks, and at 9 weeks both lenses showed fully mature cataracts with no retinal reflex. The father had dense bilateral cataracts diagnosed at birth and underwent uneventful lens aspirations at 3 and 8 months of age; thus, it is possible that the cause of this cataract is a genetic change at or near one of the breakpoints, 3p26.2 or 4p15.
Molecular Genetics
In a 4-generation family of Irish descent segregating autosomal dominant congenital nuclear cataract mapping to chromosome 4p16.1, Berry et al. (2013) sequenced 13 positional candidate genes but found no mutations. Exome sequencing in an affected family member identified a heterozygous missense mutation in the WFS1 gene (E462G; 606201.0023), and direct genomic sequencing confirmed that the mutation cosegregated completely with disease in the family. Screening of the WFS1 gene in a panel of 50 unrelated individuals with autosomal dominant cataract did not reveal any other mutations.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Cataract, congenital nuclear MISCELLANEOUS \- One family has been reported (last curated January 2014) MOLECULAR BASIS \- Caused by mutation in the WFS1 gene (WFS1, 606201.0032 ) ▲ 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
|
CATARACT 41
|
c0392557
| 8,040 |
omim
|
https://www.omim.org/entry/116400
| 2019-09-22T16:43:36 |
{"doid": ["0110241"], "mesh": ["C535342"], "omim": ["116400"], "icd-10": ["Q12.0"], "orphanet": ["98992", "91492", "98995", "98991"], "synonyms": ["Alternative titles", "CATARACT 41, CONGENITAL NUCLEAR TYPE"]}
|
Czeizel (1983) described a lethal syndrome in 3 daughters of normal unrelated parents: one died at 2 months with omphalocele, posterior cleft palate, and uterus bicornis; the second died at 4 months with omphalocele, uvula duplex, and hydrocephalus internus; the third died at 1 year with omphalocele and cleft palate.
HEENT \- Posterior cleft palate \- Cleft uvula \- Hydrocephalus GU \- Bicornuate uterus Misc \- Lethal in infancy Abdomen \- Omphalocele 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
|
OMPHALOCELE-CLEFT PALATE SYNDROME, LETHAL
|
c1850317
| 8,041 |
omim
|
https://www.omim.org/entry/258320
| 2019-09-22T16:24:07 |
{"mesh": ["C537747"], "omim": ["258320"], "orphanet": ["2736"], "synonyms": ["Alternative titles", "CLEFT PALATE-OMPHALOCELE SYNDROME, LETHAL"]}
|
A rare immune disease characterized by progressive immunodeficiency leading to recurrent and opportunistic infections, autoimmunity and malignancy as well as neurologic manifestations.
## Epidemiology
To date, more than 70 patients have been reported with Purine nucleoside phosphorylase (PNP) deficiency in the world literature. PNP deficiency accounts for less than 4% of patients with severe combined immunodeficiency (SCID).
## Clinical description
PNP deficiency typically manifests in the 1st years of life, with recurrent, opportunistic infections caused by bacterial, viral (such as varicella zoster virus), and fungal (such as Pneumocystis carinii) pathogens. The susceptibility to infections is variable ranging from classical SCID in infancy to infrequent infections during childhood and even the 2nd decade of life. Failure to thrive has also been reported. Up to 2/3 of patients have neurologic involvement including motor system dysfunction, hyper/hypotonia, spastic paresis, ataxia, hyperactivity, and behavioral problems. Cerebrovascular accidents and sensorineural deafness are less commonly observed. The neurologic involvement often precedes immune abnormalities. Autoimmune manifestations are reported in 1/3 of cases and include autoimmune hemolytic anemia, immune thrombocytopenic purpura and systemic lupus erythematosus.
## Etiology
PNP deficiency is caused by loss-of-function mutations in the PNP gene (14q11.2) which encodes a key enzyme (PNP) in the purine salvage pathway. PNP is vital for removal of metabolites of DNA breakdown and promotes recycling of purine bases. Lack of PNP allows intracellular accumulation of such metabolites which are particularly toxic to immature lymphoid cells, leading to lymphopenia and impaired cell-mediated immunity. Intracellular accumulation of purine bases has also been suggested to cause neuronal cell apoptosis.
## Diagnostic methods
Diagnosis is based on the clinical examination and on laboratory findings showing leukopenia, severe lymphopenia with low CD3, CD4, and CD8 counts and variable B cell function and immunoglobulin levels. Neutropenia has also been reported. Hallmark diagnostic markers of PNP deficiency include hypouricemia, complete or near complete absence of PNP activity in red blood cell lysate and increased urine or blood levels of inosine, guanosine and their deoxy forms. Diagnosis is confirmed by genetic screening of PNP.
## Differential diagnosis
Differential diagnosis includes aplastic anemias, SCID, severe combined immunodeficiency due to adenosine deaminase deficiency, ataxia-telangiectasia, and viral meningoencephalitis.
## Antenatal diagnosis
Measurement of T cell receptor excision circles during newborn screening for SCID can detect some patients suffering from PNP deficiency, although removal of metabolites by maternal PNP may delay the deleterious effects on PNP-deficient lymphocytes. Few newborn screening programs also measure purine metabolites in dried blood spots.
## Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be proposed to affected families informing them of a 25% risk of transmitting the disease where both parents are unaffected carriers.
## Management and treatment
Specific enzyme replacement is not available for PNP deficiency, although frequent red blood cells transfusions rich in PNP have been shown to provide temporary benefit. Hematopoietic stem cell transplantation (HSCT) is the only treatment option for the severe immune deficiency. Transplanted cells deliver the missing enzyme, thereby improving purine homeostasis. Supportive treatment, including intravenous immunoglobulin therapy, prophylaxis for Pneumocystis carinii, and physical, occupational, and speech therapy, reduces the risk of infection and may encourage optimal neurologic development for patients.
## Prognosis
If left untreated, prognosis is poor and patients usually die in the first decade of life, often succumbing to infections. Few patients have reached the 2nd and even 3rd decade of life. After HSCT from family or unrelated donors, patients may achieve successful immune reconstitution and are free from infections. Nevertheless, even with HSCT, improvement of neurological deficits is not definite.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Purine nucleoside phosphorylase deficiency
|
c0268125
| 8,042 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=760
| 2021-01-23T17:05:12 |
{"gard": ["4606"], "mesh": ["C562587"], "omim": ["613179"], "umls": ["C0268125"], "icd-10": ["D81.5"], "synonyms": ["PNP deficiency", "PNPase deficiency"]}
|
Tubular aggregate myopathy is a disorder that affects the skeletal muscles. Signs and symptoms typically begin in childhood and worsen over time. The leg muscles are most often affected, but the arm muscles may also be involved. Symptoms include muscle pain, cramping, weakness or stiffness; and exercise-induced muscle fatigue. Affected individuals may have an unusual walking style (gait) or difficulty running, climbing stairs, or getting up from a squatting position. Some individuals develop contractures. This condition may be caused by mutations in the STIM1 or ORAI1 genes. It is usually inherited in an autosomal dominant manner, but autosomal recessive inheritance has 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
|
Tubular aggregate myopathy
|
c0410207
| 8,043 |
gard
|
https://rarediseases.info.nih.gov/diseases/3884/tubular-aggregate-myopathy
| 2021-01-18T17:57:16 |
{"mesh": ["D020914"], "omim": ["160565", "615883"], "umls": ["C0410207"], "orphanet": ["2593"], "synonyms": ["Myopathy, tubular aggregate"]}
|
A rare superficial pemphigus disease characterized by severe intractable pruritus with erythematous or urticarial plaques and sometimes vesicles organized in a herpetiform pattern. Mucosae are generally spared. Eosinophilia in peripheral blood and low titers of circulating autoantibodies are observed in many cases. Histology can show an aspect of either pemphigus (superficial or deep), or an intraepidermal infiltrate rich in eosinophils (eosinophilic spongiosis).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Herpetiform pemphigus
|
None
| 8,044 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=208524
| 2021-01-23T17:45:21 |
{"icd-10": ["L10.8"]}
|
A type of nemaline myopathy (NM) only observed in several families of the Amish community.
## Clinical description
It has a neonatal onset and patients present with hypotonia associated to contractures, a severe pectus carinatum, and tremor that subsides after 2-3 months of age.
## Etiology
TNNT1 (19q13.4) is the causative gene of the Amish NM.
## Genetic counseling
Transmission follows an autosomal recessive pattern.
## Prognosis
Life expectancy rarely exceeds 2 years as a consequence of severe respiratory insufficiency.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Amish nemaline myopathy
|
c1854380
| 8,045 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98902
| 2021-01-23T17:43:11 |
{"gard": ["8334"], "mesh": ["C538397"], "omim": ["605355"], "icd-10": ["G71.2"]}
|
Chondrolysis [ICD Code M94.3] is the process of breakdown of cartilage. It can occur due to effect of various anesthetic agents like bupivacaine, lidocaine, ropivacaine and levobupivacaine are all toxic to cartilage and their intra-articular infusions can lead to this toxic effect.[1]
## See also[edit]
* Chondritis
* Osteochondritis
* Relapsing polychondritis
## References[edit]
1. ^ Gulihar, Abhinav; Robati, Shibby; Twaij, Haider; Salih, Alan; Taylor, Grahame J.S. (December 2015). "Articular cartilage and local anaesthetic: A systematic review of the current literature". Journal of Orthopaedics. 12 (Suppl 2): S200–S210. doi:10.1016/j.jor.2015.10.005. PMC 4796530. PMID 27047224.
## External links[edit]
* Chondrolysis at Radiopedia
* v
* t
* e
Bone and joint disease
Bone
Inflammation
endocrine:
* Osteitis fibrosa cystica
* Brown tumor
infection:
* Osteomyelitis
* Sequestrum
* Involucrum
* Sesamoiditis
* Brodie abscess
* Periostitis
* Vertebral osteomyelitis
Metabolic
* Bone density
* Osteoporosis
* Juvenile
* Osteopenia
* Osteomalacia
* Paget's disease of bone
* Hypophosphatasia
Bone resorption
* Osteolysis
* Hajdu–Cheney syndrome
* Ainhum
* Gorham's disease
Other
* Ischaemia
* Avascular necrosis
* Osteonecrosis of the jaw
* Complex regional pain syndrome
* Hypertrophic pulmonary osteoarthropathy
* Nonossifying fibroma
* Pseudarthrosis
* Stress fracture
* Fibrous dysplasia
* Monostotic
* Polyostotic
* Skeletal fluorosis
* bone cyst
* Aneurysmal bone cyst
* Hyperostosis
* Infantile cortical hyperostosis
* Osteosclerosis
* Melorheostosis
* Pycnodysostosis
Joint
Chondritis
* Relapsing polychondritis
Other
* Tietze's syndrome
Combined
Osteochondritis
* Osteochondritis dissecans
Child
leg:
* hip
* Legg–Calvé–Perthes syndrome
* tibia
* Osgood–Schlatter disease
* Blount's disease
* foot
* Köhler disease
* Sever's disease
spine
* * Scheuermann's_disease
arm:
* wrist
* Kienböck's disease
* elbow
* Panner disease
* 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
This article about a disease of musculoskeletal and connective tissue 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
|
Chondrolysis
|
c0343263
| 8,046 |
wikipedia
|
https://en.wikipedia.org/wiki/Chondrolysis
| 2021-01-18T18:36:19 |
{"umls": ["CL468866", "C0343263"], "icd-10": ["M94.3"], "wikidata": ["Q9845798"]}
|
For a discussion of genetic heterogeneity of quantitative trait loci for intelligence, see INTLQ1 (603783).
Mapping
To identify chromosomal regions that explain variation in intelligence, Posthuma et al. (2005) conducted a genomewide scan involving 634 sib pairs. Model-free multipoint linkage analysis revealed evidence for a significant QTL (INTLQ2) for performance IQ at 2q24.1-q31.1 (lod score of 4.42), which overlaps a region previously shown to be associated with autism. A second region of suggestive linkage (INTLQ3; 610295) for both full-scale and verbal IQs was located at 6p25.3-p22.3 (lod score of 3.20 for full-scale IQ and 2.33 for verbal IQ).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
INTELLIGENCE QUANTITATIVE TRAIT LOCUS 2
|
c1853204
| 8,047 |
omim
|
https://www.omim.org/entry/610294
| 2019-09-22T16:04:45 |
{"omim": ["610294"], "synonyms": ["Alternative titles", "INTLQ2"]}
|
Genetic X-linked recessive bleeding disorder
Haemophilia B
Other namesHemophilia B
This condition is inherited in an X-linked recessive manner.
SpecialtyHaematology
SymptomsEasy bruising[1]
CausesFactor IX deficiency[1]
Diagnostic methodBleeding scores, Coagulation factor assays[2]
TreatmentFactor IX concentrate[1]
Haemophilia B, also spelled Hemophilia B is a blood clotting disorder causing easy bruising and bleeding due to an inherited mutation of the gene for factor IX, and resulting in a deficiency of factor IX. It is less common than factor VIII deficiency (haemophilia A).[3]
Haemophilia B was first recognized as a distinct disease entity in 1952.[4] It is also known by the eponym Christmas disease,[1] named after Stephen Christmas, the first patient described with haemophilia B. In addition, the first report of its identification was published in the Christmas edition of the British Medical Journal.[4][5]
## Contents
* 1 Signs and symptoms
* 1.1 Complications
* 2 Genetics
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Differential diagnosis
* 5 Treatment
* 5.1 Dental considerations
* 6 History
* 7 Society
* 8 See also
* 9 References
* 10 Further reading
* 11 External links
## Signs and symptoms[edit]
Symptoms include easy bruising, urinary tract bleeding (haematuria), nosebleeds (epistaxis), and bleeding into joints (haemarthrosis).[1]
### Complications[edit]
Patients with bleeding disorders show a higher incidence of periodontal disease as well as dental caries, concerning the fear of bleeding which leads to a lack of oral hygiene and oral health care. The most prominent oral manifestation of a mild haemophilia B would be gingival bleeding during exfoliation of primary dentition, or prolonged bleeding after an invasive procedure/tooth extraction; In severe haemophilia, there may be spontaneous bleeding from the oral tissues (e.g. soft palate, tongue, buccal mucosa), lips and gingiva, with ecchymoses. In rare cases, haemarthrosis (bleeding into joint space) of the temporomandibular joint (TMJ) may be observed.[6]
Patients with haemophilia will experience many episodes of oral bleeding over their lifetime. Average 29.1 bleeding events per year are serious enough to require factor replacement in F VIII-deficient patients which 9% involved oral structures. Children with severe haemophilia have significant lower prevalence of dental caries and lower plaque scores compared with matched, healthy controls.[7]
## Genetics[edit]
X chromosome
The factor IX gene is located on the X chromosome (Xq27.1-q27.2). It is an X-linked recessive trait, which explains why males are affected in greater numbers.[8][9]
In 1990, George Brownlee and Merlin Crossley showed that two sets of genetic mutations were preventing two key proteins from attaching to the DNA of people with a rare and unusual form of haemophilia B – haemophilia B Leyden – where sufferers experience episodes of excessive bleeding in childhood but have few bleeding problems after puberty.[9] This lack of protein attachment to the DNA was thereby turning off the gene that produces clotting factor IX, which prevents excessive bleeding.[9]
## Pathophysiology[edit]
Coagulation (FIX is on left)
Factor IX deficiency leads to an increased propensity for haemorrhage, which can be either spontaneously or in response to mild trauma.[10]
Factor IX deficiency can cause interference of the coagulation cascade, thereby causing spontaneous haemorrhage when there is trauma. Factor IX when activated activates factor X which helps fibrinogen to fibrin conversion.[10]
Factor IX becomes active eventually in coagulation by cofactor factor VIII (specifically IXa). Platelets provide a binding site for both cofactors. This complex (in the coagulation pathway) will eventually activate factor X.[11]
## Diagnosis[edit]
The diagnosis for haemophilia B can be done via the following tests/methods:[2]
* Coagulation screening test
* Bleeding scores
* Coagulation factor assays
### Differential diagnosis[edit]
The differential diagnosis for this inherited condition is the following: haemophilia A, factor XI deficiency, von Willebrand disease, fibrinogen disorders and Bernard–Soulier syndrome[9]
## Treatment[edit]
Treatment is given intermittently, when there is significant bleeding. It includes intravenous infusion of factor IX and/or blood transfusions. NSAIDS should be avoided once the diagnosis is made since they can exacerbate a bleeding episode. Any surgical procedure should be done with concomitant tranexamic acid.[4][12]
### Dental considerations[edit]
Surgical treatment, including a simple dental extraction, must be planned to minimize the risk of bleeding, excessive bruising, or haematoma formation. Soft vacuum-formed splints can be used to provide local protection following a dental extraction or prolonged post-extraction bleed.[13]
## History[edit]
Factor IX
In the 1950s and 1960s, with newfound technology and gradual advances in medicine, pharmaceutical scientists found a way to take the factor IX from fresh frozen plasma (FFP) and give it to those with haemophilia B. Though they found a way to treat the disease, the FFP contained only a small amount of factor IX, requiring large amounts of FFP to treat an actual bleeding episode, which resulted in the person requiring hospitalization. By the mid-1960s scientists found a way to get a larger amount of factor IX from FFP. By the late 1960s, pharmaceutical scientists found methods to separate the factor IX from plasma, which allows for neatly packaged bottles of factor IX concentrates. With the rise of factor IX concentrates it became easier for people to get treatment at home.[14] Although these advances in medicine had a significant positive impact on the treatment of haemophilia, there were many complications that came with it. By the early 1980s, scientists discovered that the medicines they had created were transferring blood-borne viruses, such as hepatitis, and HIV, the virus that causes AIDS. With the rise of these deadly viruses, scientists had to find improved methods for screening the blood products they received from donors. In 1982, scientists made a breakthrough in medicine and were able to clone factor IX gene. With this new development it decreased the risk of the many viruses. Although the new factor was created, it wasn't available for haemophilia B patients until 1997.[citation needed]
## Society[edit]
Main article: Haemophilia in European royalty
In 2009, an analysis of genetic markers revealed that haemophilia B was the blood disease affecting many European royal families of Great Britain, Germany, Russia and Spain: so-called "Royal Disease".[15][16]
## See also[edit]
* Haemophilia C
* Haemophilia in European royalty
## References[edit]
1. ^ a b c d e "Hemophilia B: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2016-09-21.
2. ^ a b Konkle, Barbara A.; Josephson, Neil C.; Nakaya Fletcher, Shelley (1 January 1993). "Hemophilia B". GeneReviews. Retrieved 7 October 2016.update 2014
3. ^ Kliegman, Robert (2011). Nelson textbook of pediatrics (19th ed.). Philadelphia: Saunders. pp. 1700–1. ISBN 978-1-4377-0755-7.
4. ^ a b c "Haemophilia B (Factor IX Deficiency) information | Patient". Patient. Retrieved 2016-04-21.
5. ^ Biggs R, Douglas AS, MacFarlane RG, Dacie JV, Pitney WR, Merskey C, O'Brien JR (1952). "Christmas disease: a condition previously mistaken for haemophilia". Br Med J. 2 (4799): 1378–82. doi:10.1136/bmj.2.4799.1378. PMC 2022306. PMID 12997790.
6. ^ "Hemophilia A" (PDF). College of Dental Hygienists of Ontario. September 2, 2015.
7. ^ Glick, Michael (2015). Burket's Oral Medicine. USA: People's Medical Publishing House. pp. 473, 475, 481, 482. ISBN 978-1-60795-188-9.
8. ^ "OMIM Entry - # 306900 - HEMOPHILIA B; HEMB". omim.org. Retrieved 2016-10-07.
9. ^ a b c d "Hemophilia".
10. ^ a b "Hemophilia B: Practice Essentials, Background, Pathophysiology". eMedicine. Medscape. 24 August 2016. Retrieved 7 October 2016.
11. ^ "Factor IX Deficiency: Background, Pathophysiology, Epidemiology". eMedicine. Medscape. 24 August 2016. Retrieved 7 October 2016.
12. ^ Beck, Norman (2009). Diagnostic hematology. London: Springer. p. 416. ISBN 9781848002951. Retrieved 7 October 2016.
13. ^ Andrew Brewer, Maria Elvira Correa (May 2006). "Guildelines for Dental Treatment of Patients with Inherited Bleeding Disorders" (PDF). Treatment of Hemophilia. 40: 9 – via World Federation of Hemophilia (WFH).
14. ^ Schramm, Wolfgang (November 2014). "The history of haemophilia – a short review". Thrombosis Research. 134: S4–S9. doi:10.1016/j.thromres.2013.10.020. ISSN 1879-2472. PMID 24513149. – via ScienceDirect (Subscription may be required or content may be available in libraries.)
15. ^ Michael Price (8 October 2009). "Case Closed: Famous Royals Suffered From Hemophilia". ScienceNOW Daily News. AAAS. Retrieved 9 October 2009.
16. ^ Evgeny I. Rogaev; et al. (8 October 2009). "Genotype Analysis Identifies the Cause of the "Royal Disease"". Science. 326 (5954): 817. Bibcode:2009Sci...326..817R. doi:10.1126/science.1180660. PMID 19815722. S2CID 206522975.subscription required
## Further reading[edit]
* Franchini, Massimo; Frattini, Francesco; Crestani, Silvia; Sissa, Cinzia; Bonfanti, Carlo (1 January 2013). "Treatment of hemophilia B: focus on recombinant factor IX". Biologics: Targets and Therapy. 7: 33–38. doi:10.2147/BTT.S31582. ISSN 1177-5475. PMC 3575125. PMID 23430394.
* Nathwani, Amit C.; Reiss, Ulreke M.; Tuddenham, Edward G.D.; Rosales, Cecilia; Chowdary, Pratima; McIntosh, Jenny; Della Peruta, Marco; Lheriteau, Elsa; Patel, Nishal; Raj, Deepak; Riddell, Anne; Pie, Jun; Rangarajan, Savita; Bevan, David; Recht, Michael; Shen, Yu-Min; Halka, Kathleen G.; Basner-Tschakarjan, Etiena; Mingozzi, Federico; High, Katherine A.; Allay, James; Kay, Mark A.; Ng, Catherine Y.C.; Zhou, Junfang; Cancio, Maria; Morton, Christopher L.; Gray, John T.; Srivastava, Deokumar; Nienhuis, Arthur W.; Davidoff, Andrew M. (20 November 2014). "Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B". New England Journal of Medicine. 371 (21): 1994–2004. doi:10.1056/NEJMoa1407309. ISSN 0028-4793. PMC 4278802. PMID 25409372.
## External links[edit]
Classification
D
* ICD-10: D67
* ICD-9-CM: 286.1
* OMIM: 306900
* MeSH: D002836
* DiseasesDB: 5561
External resources
* MedlinePlus: 000539
* eMedicine: emerg/240
* Patient UK: Haemophilia B
Scholia has a topic profile for Haemophilia B.
* v
* t
* e
Disorders of bleeding and clotting
Coagulation · coagulopathy · Bleeding diathesis
Clotting
By cause
* Clotting factors
* Antithrombin III deficiency
* Protein C deficiency
* Activated protein C resistance
* Protein S deficiency
* Factor V Leiden
* Prothrombin G20210A
* Platelets
* Sticky platelet syndrome
* Thrombocytosis
* Essential thrombocythaemia
* DIC
* Purpura fulminans
* Antiphospholipid syndrome
Clots
* Thrombophilia
* Thrombus
* Thrombosis
* Virchow's triad
* Trousseau sign of malignancy
By site
* Deep vein thrombosis
* Bancroft's sign
* Homans sign
* Lisker's sign
* Louvel's sign
* Lowenberg's sign
* Peabody's sign
* Pratt's sign
* Rose's sign
* Pulmonary embolism
* Renal vein thrombosis
Bleeding
By cause
Thrombocytopenia
* Thrombocytopenic purpura: ITP
* Evans syndrome
* TM
* TTP
* Upshaw–Schulman syndrome
* Heparin-induced thrombocytopenia
* May–Hegglin anomaly
Platelet function
* adhesion
* Bernard–Soulier syndrome
* aggregation
* Glanzmann's thrombasthenia
* platelet storage pool deficiency
* Hermansky–Pudlak syndrome
* Gray platelet syndrome
Clotting factor
* Haemophilia
* A/VIII
* B/IX
* C/XI
* von Willebrand disease
* Hypoprothrombinemia/II
* Factor VII deficiency
* Factor X deficiency
* Factor XII deficiency
* Factor XIII deficiency
* Dysfibrinogenemia
* Congenital afibrinogenemia
Signs and symptoms
* Bleeding
* Bruise
* Haematoma
* Petechia
* Purpura
* Nonthrombocytopenic purpura
By site
* head
* Epistaxis
* Haemoptysis
* Intracranial haemorrhage
* Hyphaema
* Subconjunctival haemorrhage
* torso
* Haemothorax
* Haemopericardium
* Pulmonary haematoma
* abdomen
* Gastrointestinal bleeding
* Haemobilia
* Haemoperitoneum
* Haematocele
* Haematosalpinx
* joint
* Haemarthrosis
* v
* t
* e
X-linked disorders
X-linked recessive
Immune
* Chronic granulomatous disease (CYBB)
* Wiskott–Aldrich syndrome
* X-linked severe combined immunodeficiency
* X-linked agammaglobulinemia
* Hyper-IgM syndrome type 1
* IPEX
* X-linked lymphoproliferative disease
* Properdin deficiency
Hematologic
* Haemophilia A
* Haemophilia B
* X-linked sideroblastic anemia
Endocrine
* Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy
* KAL1 Kallmann syndrome
* X-linked adrenal hypoplasia congenita
Metabolic
* Amino acid: Ornithine transcarbamylase deficiency
* Oculocerebrorenal syndrome
* Dyslipidemia: Adrenoleukodystrophy
* Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency
* Pyruvate dehydrogenase deficiency
* Danon disease/glycogen storage disease Type IIb
* Lipid storage disorder: Fabry's disease
* Mucopolysaccharidosis: Hunter syndrome
* Purine–pyrimidine metabolism: Lesch–Nyhan syndrome
* Mineral: Menkes disease/Occipital horn syndrome
Nervous system
* X-linked intellectual disability: Coffin–Lowry syndrome
* MASA syndrome
* Alpha-thalassemia mental retardation syndrome
* Siderius X-linked mental retardation syndrome
* Eye disorders: Color blindness (red and green, but not blue)
* Ocular albinism (1)
* Norrie disease
* Choroideremia
* Other: Charcot–Marie–Tooth disease (CMTX2-3)
* Pelizaeus–Merzbacher disease
* SMAX2
Skin and related tissue
* Dyskeratosis congenita
* Hypohidrotic ectodermal dysplasia (EDA)
* X-linked ichthyosis
* X-linked endothelial corneal dystrophy
Neuromuscular
* Becker's muscular dystrophy/Duchenne
* Centronuclear myopathy (MTM1)
* Conradi–Hünermann syndrome
* Emery–Dreifuss muscular dystrophy 1
Urologic
* Alport syndrome
* Dent's disease
* X-linked nephrogenic diabetes insipidus
Bone/tooth
* AMELX Amelogenesis imperfecta
No primary system
* Barth syndrome
* McLeod syndrome
* Smith–Fineman–Myers syndrome
* Simpson–Golabi–Behmel syndrome
* Mohr–Tranebjærg syndrome
* Nasodigitoacoustic syndrome
X-linked dominant
* X-linked hypophosphatemia
* Focal dermal hypoplasia
* Fragile X syndrome
* Aicardi syndrome
* Incontinentia pigmenti
* Rett syndrome
* CHILD syndrome
* Lujan–Fryns syndrome
* Orofaciodigital syndrome 1
* Craniofrontonasal dysplasia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Haemophilia B
|
c0008533
| 8,048 |
wikipedia
|
https://en.wikipedia.org/wiki/Haemophilia_B
| 2021-01-18T19:07:06 |
{"gard": ["8732"], "mesh": ["D002836"], "umls": ["C0008533"], "orphanet": ["98879"], "wikidata": ["Q2562598"]}
|
For a phenotypic description and a discussion of genetic heterogeneity of multiple exostoses, see (133700).
Mapping
In a child with multiple exostoses with an interstitial deletion of chromosome 11, Le Merrer et al. (1994) excluded linkage to markers in the region 11p12-p11. However, the locus they termed 'EXT2' was mapped to 19p by linkage to a microsatellite DNA marker at the D19S221 locus. In studies of 21 families, they found a maximum location score of 7.22 with a proportion of families (35%) linked to chromosome 19 and a proportion of families (65%) linked to chromosome 8. Their data supported the location of EXT1 distal to D8S198 and the location of the other gene, designated EXT3, between D19S413 and D19S221.
Le Merrer et al. (1994) suggested that the close linkage of EXT3 to the JUNB (165161) and JUND (165162) protooncogenes on 19p makes these genes possible candidate genes, because malignancy is a complication of multiple exostoses and because transgenic mice defective for a functionally related gene (FOS; 164810) have been shown to develop multiple exostoses of long bones (Wang et al., 1991).
Francannet et al. (2001) reported a clinical and molecular study of 42 French families representing 217 affected individuals with multiple exostoses. They confirmed linkage to EXT1 in 29 of the families, EXT2 (133701) in 9, and EXT3 in 1. Francannet et al. (2001) concluded that there must be at least 1 additional locus for the multiple exostoses phenotype to account for the 3 unlinked families.
Skel \- Multiple exostoses Inheritance \- Autosomal dominant (19p) ▲ 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
|
EXOSTOSES, MULTIPLE, TYPE III
|
c0206641
| 8,049 |
omim
|
https://www.omim.org/entry/600209
| 2019-09-22T16:16:28 |
{"doid": ["206"], "mesh": ["D018216"], "omim": ["600209"], "orphanet": ["321"]}
|
A number sign (#) is used with this entry because of evidence that autosomal dominant keratitis is caused by heterozygous mutation in the PAX6 gene (607108) on chromosome 11p13.
Description
Keratitis is a rare ocular disorder presenting with congenital and progressive features predominantly involving the anterior segment of the eye. The major clinical symptoms are anterior stromal corneal opacification and vascularization of the peripheral cornea. Progression of the opacification and vascularization into the central cornea may occur with corresponding reduction in visual acuity. Other anterior segment features include variable radial defects of the iris stroma and foveal hypoplasia (summary by Mirzayans et al., 1995).
Clinical Features
Kivlin et al. (1986) reported a unique form of hereditary childhood corneal clouding, characterized by recurrent stromal keratitis and vascularization. Male-to-male transmission as well as multiple affected generations without consanguinity indicated autosomal dominant inheritance. Male and female members of the family were equally affected. Nonpenetrance was encountered in several persons. Expressivity was also variable; some family members had only transient childhood episodes of ocular inflammation without sequelae. The extent and severity of the disease also varied between the 2 eyes of an affected individual. There was a marked propensity for early recurrence of the disorder after keratoplasty.
Pearce et al. (1995) reported a family in which 15 individuals were affected in 4 generations. All affected persons presented with, at a minimum, a circumferential 1- to 2-mm wide band of corneal opacification and vascularization at the level of Bowman membrane and in continuity with the limbus. There was considerable variation in the severity of the corneal changes, with generally more progressive keratitis among older affected persons. Foveal hypoplasia was found in all affected persons. There was no skin or mucous membrane involvement in patients with autosomal dominant keratitis, as has been shown to occur with keratitis in patients suffering from epidermolysis bullosa simplex (226670) by Granek and Baden (1980), in the EEC syndrome (129900) by Mawhorter et al. (1985), or the keratitis-ichthyosis-deafness syndrome (KID; 148210) by Wilson et al. (1991). Keratoendothelitis fugax hereditaria (148200) is distinct from autosomal dominant keratitis, as it is characterized by self-limiting intermittent attacks of keratoendothelitis affecting one or the other eye.
Inheritance
Keratitis is inherited as a fully penetrant autosomal dominant disease with variable clinical presentation (Mirzayans et al., 1995).
Mapping
Mirzayans et al. (1995) used the candidate gene approach to investigate whether mutations in the PAX6 gene are responsible for keratitis. Significant linkage was found between 2 polymorphic loci in the PAX6 region and keratitis in the family originally described by Pearce et al. (1995) (peak lod score = 4.45 at theta = 0.00 with D11S914).
Molecular Genetics
In affected members of a family with autosomal dominant keratitis, originally described by Pearce et al. (1995), Mirzayans et al. (1995) identified a splice site mutation in the PAX6 gene (607108.0011).
Eyes \- Hereditary childhood corneal clouding \- Recurrent stromal keratitis and vascularization Misc \- Propensity for early recurrence after keratoplasty 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
|
KERATITIS, HEREDITARY
|
c1835698
| 8,050 |
omim
|
https://www.omim.org/entry/148190
| 2019-09-22T16:39:19 |
{"mesh": ["C537022"], "omim": ["148190"], "orphanet": ["2334"]}
|
Primary mediastinal large B-cell lymphoma
Micrograph of a primary mediastinal large B-cell lymphoma. H&E stain.
SpecialtyHematology and oncology
Primary mediastinal B-cell lymphoma, abbreviated PMBL, is a rare type of lymphoma that forms in the mediastinum (the space in between the lungs) and predominantly affects young adults.[1][2]
It is a subtype of diffuse large B-cell lymphoma;[3] however, it generally has a significantly better prognosis.
## Contents
* 1 Diagnosis
* 2 Treatment
* 3 Prognosis
* 4 Epidemiology
* 5 See also
* 6 References
* 7 External links
## Diagnosis[edit]
Diagnosis requires a biopsy, so that the exact type of tissue can be determined by examination under a microscope. PMBL is generally considered a sub-type of diffuse large B-cell lymphoma, although it is also closely related to nodular sclerosing Hodgkin lymphoma (NSHL).[4] Tumors that are even more closely related to NSHL than typical for PMBL are called gray zone lymphoma.[4]
## Treatment[edit]
Treatment commonly begins with months of multi-drug chemotherapy regimen. Either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or DA-EPOCH-R (dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab) has been typical.[5] Other, more intense, regimens may be more effective.[4]
Radiation therapy may be added, especially if chemotherapy does not seem sufficient on its own.[5] Radiation may cause other health problems later, such as breast cancer, and there is some debate about the best approach to it.[4]
FDG-PET scanning is not as useful for predicting treatment success in PMBL as it is in other lymphomas.[4]
## Prognosis[edit]
Most people with PMBL are successfully treated and survive for many years. However, if the initial treatment is unsuccessful, or if it returns, the long-term prognosis is worse.[5] Relapses generally appear within 12 to 18 months after the completion of treatment.[4]
## Epidemiology[edit]
This lymphoma is most commonly seen in women between the age of 20 and 40.[4]
## See also[edit]
* Diffuse large B-cell lymphoma
* Primary mediastinal (thymic) large B cell lymphoma
## References[edit]
1. ^ Johnson PW, Davies AJ (2008). "Primary mediastinal B-cell lymphoma". Hematology. American Society of Hematology. Education Program. 2008: 349–58. doi:10.1182/asheducation-2008.1.349. PMID 19074109.
2. ^ Coso D, Rey J, Bouabdallah R (February 2010). "[Primary mediastinal B-cell lymphoma]". Revue de Pneumologie Clinique. 66 (1): 32–5. doi:10.1016/j.pneumo.2009.12.007. PMID 20207294.
3. ^ "Types of Non-Hodgkin Lymphoma". www.cancer.org. Retrieved 2017-09-28.
4. ^ a b c d e f g Dunleavy K, Wilson WH (January 2015). "Primary mediastinal B-cell lymphoma and mediastinal gray zone lymphoma: do they require a unique therapeutic approach?". Blood. 125 (1): 33–9. doi:10.1182/blood-2014-05-575092. PMC 4281829. PMID 25499450.
5. ^ a b c Lees C, Keane C, Gandhi MK, Gunawardana J (February 2019). "Biology and therapy of primary mediastinal B-cell lymphoma: current status and future directions". British Journal of Haematology. 185 (1): 25–41. doi:10.1111/bjh.15778. PMC 6594147. PMID 30740662.
## External links[edit]
Classification
D
* ICD-O: 9679/3
External resources
* eMedicine: article/203681
* v
* t
* e
Leukaemias, lymphomas and related disease
B cell
(lymphoma,
leukemia)
(most CD19
* CD20)
By
development/
marker
TdT+
* ALL (Precursor B acute lymphoblastic leukemia/lymphoma)
CD5+
* naive B cell (CLL/SLL)
* mantle zone (Mantle cell)
CD22+
* Prolymphocytic
* CD11c+ (Hairy cell leukemia)
CD79a+
* germinal center/follicular B cell (Follicular
* Burkitt's
* GCB DLBCL
* Primary cutaneous follicle center lymphoma)
* marginal zone/marginal zone B-cell (Splenic marginal zone
* MALT
* Nodal marginal zone
* Primary cutaneous marginal zone lymphoma)
RS (CD15+, CD30+)
* Classic Hodgkin lymphoma (Nodular sclerosis)
* CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma)
PCDs/PP
(CD38+/CD138+)
* see immunoproliferative immunoglobulin disorders
By infection
* KSHV (Primary effusion)
* EBV
* Lymphomatoid granulomatosis
* Post-transplant lymphoproliferative disorder
* Classic Hodgkin lymphoma
* Burkitt's lymphoma
* HCV
* Splenic marginal zone lymphoma
* HIV (AIDS-related lymphoma)
* Helicobacter pylori (MALT lymphoma)
Cutaneous
* Diffuse large B-cell lymphoma
* Intravascular large B-cell lymphoma
* Primary cutaneous marginal zone lymphoma
* Primary cutaneous immunocytoma
* Plasmacytoma
* Plasmacytosis
* Primary cutaneous follicle center lymphoma
T/NK
T cell
(lymphoma,
leukemia)
(most CD3
* CD4
* CD8)
By
development/
marker
* TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma)
* prolymphocyte (Prolymphocytic)
* CD30+ (Anaplastic large-cell lymphoma
* Lymphomatoid papulosis type A)
Cutaneous
MF+variants
* indolent: Mycosis fungoides
* Pagetoid reticulosis
* Granulomatous slack skin
aggressive: Sézary disease
* Adult T-cell leukemia/lymphoma
Non-MF
* CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
* Pleomorphic T-cell lymphoma
* Lymphomatoid papulosis type B
* CD30+: CD30+ cutaneous T-cell lymphoma
* Secondary cutaneous CD30+ large-cell lymphoma
* Lymphomatoid papulosis type A
Other
peripheral
* Hepatosplenic
* Angioimmunoblastic
* Enteropathy-associated T-cell lymphoma
* Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma)
* Subcutaneous T-cell lymphoma
By infection
* HTLV-1 (Adult T-cell leukemia/lymphoma)
NK cell/
(most CD56)
* Aggressive NK-cell leukemia
* Blastic NK cell lymphoma
T or NK
* EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma)
* Large granular lymphocytic leukemia
Lymphoid+
myeloid
* Acute biphenotypic leukaemia
Lymphocytosis
* Lymphoproliferative disorders (X-linked lymphoproliferative disease
* Autoimmune lymphoproliferative syndrome)
* Leukemoid reaction
* Diffuse infiltrative lymphocytosis syndrome
Cutaneous lymphoid hyperplasia
* Cutaneous lymphoid hyperplasia
* with bandlike and perivascular patterns
* with nodular pattern
* Jessner lymphocytic infiltrate of the skin
General
* Hematological malignancy
* leukemia
* Lymphoproliferative disorders
* Lymphoid leukemias
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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 mediastinal B-cell lymphoma
|
c1292754
| 8,051 |
wikipedia
|
https://en.wikipedia.org/wiki/Primary_mediastinal_B-cell_lymphoma
| 2021-01-18T19:07:20 |
{"umls": ["C0855152", "C1292754"], "orphanet": ["98838"], "wikidata": ["Q53660452"]}
|
In the course of studies of children with respiratory disease, Sturgess et al. (1980) identified a brother and sister, aged 22 and 19 years, respectively, with chronic sinopulmonary disease and transposition of the number 1 doublet microtubule. The anatomic defect was present in the nasal and bronchial cilia of both subjects and the sperm of the male. Since some motility of cilia was retained (as is true in dynein-defective cilia), the authors suggested ciliary dyskinesia as a designation alternative to 'immotile cilia syndrome.' See CILD1 (244400).
Respiratory \- Chronic sinopulmonary disease Lab \- Transposition of ciliary number 1 doublet microtubule 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
|
CILIARY DYSKINESIA WITH TRANSPOSITION OF CILIARY MICROTUBULES
|
c0022521
| 8,052 |
omim
|
https://www.omim.org/entry/215520
| 2019-09-22T16:29:33 |
{"mesh": ["D007619"], "omim": ["244400", "215520"], "orphanet": ["244"], "synonyms": ["PCD"]}
|
Radial aplasia
SpecialtyOrthopedic
Radial aplasia is a congenital defect which affects the formation of the radius bone in the arm. The radius is the lateral bone (thumb side) which connects the humerus of the upper arm to the wrist via articulation with the carpal bones. A child born with this condition has either a short or absent radius bone in one or both of his or her arms. Radial aplasia also results in the thumb being either partly formed or completely absent from the hand, which can result in difficulties performing activities of daily living. Radial aplasia is connected with the condition VACTERL association, under the 'L' for limb malformations.[citation needed]
Radial aplasia is not inherited. The cause for radial aplasia is unknown, but it widely believed to occur within the first ten weeks of gestation.[1]
## References[edit]
1. ^ Visser, Jan Douwes (2017-04-01). Pediatric Orthopedics: Symptoms, Differential Diagnosis, Supplementary Assessment and Treatment. Springer. p. 356. ISBN 9783319401782.
## External links[edit]
Classification
D
* OMIM: 312190
External resources
* Orphanet: 3016
This article about a disease of musculoskeletal and connective tissue is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
This article about a congenital malformation 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
|
Radial aplasia
|
c1838608
| 8,053 |
wikipedia
|
https://en.wikipedia.org/wiki/Radial_aplasia
| 2021-01-18T18:32:00 |
{"umls": ["C1838608"], "orphanet": ["3016"], "wikidata": ["Q7280260"]}
|
Warty dyskeratoma
Warty dyskeratoma, also known as an Isolated dyskeratosis follicularis,[1]:777 is a benign[2] epidermal proliferation with distinctive histologic findings that may mimic invasive squamous cell carcinoma[3] and commonly manifests as an umbilicated (Having a central mark or depression resembling a navel) lesion with a keratotic plug,[4] WD have some histopathologic similarities to viral warts but it's not caused by HPV and the majority of these lesions display overall histopathologic features consistent with a follicular adnexal neoplasm.[5] usually limited to the head, neck,[6] scalp[7] or face and vulva.[6] Lesions are generally solitary and sporadic and may be associated with a follicular unit. Oral involvement,[4] particularly the hard palate, and genital involvement have been reported. it can also be thought of as one of the manifestations of focal acantholytic dyskeratosis, an epidermal reaction pattern that can be seen in several disorders, including Darier's disease and Grover's disease.[8]:639 But the main Difference between Darier disease and Warty dyskeratoma, is that Darier disease inherited dermatosis (autosomal dominant) consisting of multiple keratotic papules on the face, trunk, and extremities, while WD occurs as an isolated, noninherited, single keratotic nodule mainly confined to the head and neck as mentioned earlier.[6]
## Differential Diagnosis[edit]
Warty dyskeratoma must be differentiated from vulvar dysplasia, Bowenoid papulosis, squamous carcinoma, condyloma, and other viral-induced squamous lesions.[6]
## See also[edit]
* Keratosis follicularis (disambiguation)
* Stucco keratosis
* List of cutaneous conditions
## References[edit]
1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
2. ^ Diallo M, Cribier B, Scrivener Y (2007). "[Warty dyskeratoma: infundibular histogenesis. Anatomoclinical study of 43 cases]". Ann Dermatol Venereol (in French). 134 (8–9): 633–6. doi:10.1016/S0151-9638(07)91823-2. PMID 17925685.
3. ^ Chau MN, Radden BG (October 1984). "Oral warty dyskeratoma". J. Oral Pathol. 13 (5): 546–56. doi:10.1111/j.1600-0714.1984.tb01455.x. PMID 6434720.
4. ^ a b Kaugars GE, Lieb RJ, Abbey LM (March 1984). "Focal oral warty dyskeratoma". Int. J. Dermatol. 23 (2): 123–30. doi:10.1111/j.1365-4362.1984.tb05686.x. PMID 6698687.
5. ^ Kaddu S, Dong H, Mayer G, Kerl H, Cerroni L (September 2002). "Warty dyskeratoma--"follicular dyskeratoma": analysis of clinicopathologic features of a distinctive follicular adnexal neoplasm". J. Am. Acad. Dermatol. 47 (3): 423–8. doi:10.1067/mjd.2002.122756. PMID 12196754.
6. ^ a b c d Duray PH, Merino MJ, Axiotis C (1983). "Warty dyskeratoma of the vulva". Int. J. Gynecol. Pathol. 2 (3): 286–93. doi:10.1097/00004347-198303000-00006. PMID 6642851.
7. ^ Griffiths TW, Hashimoto K, Sharata HH, Ellis CN (July 1997). "Multiple warty dyskeratomas of the scalp" (PDF). Clin. Exp. Dermatol. 22 (4): 189–91. doi:10.1111/j.1365-2230.1997.tb01059.x. hdl:2027.42/75672. PMID 9499610.
8. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
* v
* t
* e
Skin cancer of the epidermis
Tumor
Carcinoma
BCC
* Forms
* Aberrant
* Cicatricial
* Cystic
* Fibroepithelioma of Pinkus
* Infltrative
* Micronodular
* Nodular
* Pigmented
* Polypoid
* Pore-like
* Rodent ulcer
* Superficial
* Nevoid basal cell carcinoma syndrome
SCC
* Forms
* Adenoid
* Basaloid
* Clear cell
* Signet-ring-cell
* Spindle-cell
* Marjolin's ulcer
* Bowen's disease
* Bowenoid papulosis
* Erythroplasia of Queyrat
* Actinic keratosis
Adenocarcinoma
* Aggressive digital papillary adenocarcinoma
* Extramammary Paget's disease
Ungrouped
* Merkel cell carcinoma
* Microcystic adnexal carcinoma
* Mucinous carcinoma
* Primary cutaneous adenoid cystic carcinoma
* Verrucous carcinoma
* Malignant mixed tumor
Benign
tumors
Acanthoma
* Forms
* Large cell
* Fissuring
* Clear cell
* Epidermolytic
* Melanoacanthoma
* Pilar sheath acanthoma
* Seboacanthoma
* Seborrheic keratosis
* Warty dyskeratoma
Keratoacanthoma
* Generalized eruptive
* Keratoacanthoma centrifugum marginatum
* Multiple
* Solitary
Wart
* Verruca vulgaris
* Verruca plana
* Plantar wart
* Periungual wart
Other
Epidermal nevus
* Syndromes
* Epidermal nevus syndrome
* Schimmelpenning syndrome
* Nevus comedonicus syndrome
* Nevus comedonicus
* Inflammatory linear verrucous epidermal nevus
* Linear verrucous epidermal nevus
* Pigmented hairy epidermal nevus syndrome
* Systematized epidermal nevus
* Phakomatosis pigmentokeratotica
Other nevus
* Nevus unius lateris
* Patch blue nevus
* Unilateral palmoplantar verrucous nevus
* Zosteriform speckled lentiginous nevus
Ungrouped
* Cutaneous horn
* v
* t
* e
Oral and maxillofacial pathology
Lips
* Cheilitis
* Actinic
* Angular
* Plasma cell
* Cleft lip
* Congenital lip pit
* Eclabium
* Herpes labialis
* Macrocheilia
* Microcheilia
* Nasolabial cyst
* Sun poisoning
* Trumpeter's wart
Tongue
* Ankyloglossia
* Black hairy tongue
* Caviar tongue
* Crenated tongue
* Cunnilingus tongue
* Fissured tongue
* Foliate papillitis
* Glossitis
* Geographic tongue
* Median rhomboid glossitis
* Transient lingual papillitis
* Glossoptosis
* Hypoglossia
* Lingual thyroid
* Macroglossia
* Microglossia
* Rhabdomyoma
Palate
* Bednar's aphthae
* Cleft palate
* High-arched palate
* Palatal cysts of the newborn
* Inflammatory papillary hyperplasia
* Stomatitis nicotina
* Torus palatinus
Oral mucosa – Lining of mouth
* Amalgam tattoo
* Angina bullosa haemorrhagica
* Behçet's disease
* Bohn's nodules
* Burning mouth syndrome
* Candidiasis
* Condyloma acuminatum
* Darier's disease
* Epulis fissuratum
* Erythema multiforme
* Erythroplakia
* Fibroma
* Giant-cell
* Focal epithelial hyperplasia
* Fordyce spots
* Hairy leukoplakia
* Hand, foot and mouth disease
* Hereditary benign intraepithelial dyskeratosis
* Herpangina
* Herpes zoster
* Intraoral dental sinus
* Leukoedema
* Leukoplakia
* Lichen planus
* Linea alba
* Lupus erythematosus
* Melanocytic nevus
* Melanocytic oral lesion
* Molluscum contagiosum
* Morsicatio buccarum
* Oral cancer
* Benign: Squamous cell papilloma
* Keratoacanthoma
* Malignant: Adenosquamous carcinoma
* Basaloid squamous carcinoma
* Mucosal melanoma
* Spindle cell carcinoma
* Squamous cell carcinoma
* Verrucous carcinoma
* Oral florid papillomatosis
* Oral melanosis
* Smoker's melanosis
* Pemphigoid
* Benign mucous membrane
* Pemphigus
* Plasmoacanthoma
* Stomatitis
* Aphthous
* Denture-related
* Herpetic
* Smokeless tobacco keratosis
* Submucous fibrosis
* Ulceration
* Riga–Fede disease
* Verruca vulgaris
* Verruciform xanthoma
* White sponge nevus
Teeth (pulp, dentin, enamel)
* Amelogenesis imperfecta
* Ankylosis
* Anodontia
* Caries
* Early childhood caries
* Concrescence
* Failure of eruption of teeth
* Dens evaginatus
* Talon cusp
* Dentin dysplasia
* Dentin hypersensitivity
* Dentinogenesis imperfecta
* Dilaceration
* Discoloration
* Ectopic enamel
* Enamel hypocalcification
* Enamel hypoplasia
* Turner's hypoplasia
* Enamel pearl
* Fluorosis
* Fusion
* Gemination
* Hyperdontia
* Hypodontia
* Maxillary lateral incisor agenesis
* Impaction
* Wisdom tooth impaction
* Macrodontia
* Meth mouth
* Microdontia
* Odontogenic tumors
* Keratocystic odontogenic tumour
* Odontoma
* Dens in dente
* Open contact
* Premature eruption
* Neonatal teeth
* Pulp calcification
* Pulp stone
* Pulp canal obliteration
* Pulp necrosis
* Pulp polyp
* Pulpitis
* Regional odontodysplasia
* Resorption
* Shovel-shaped incisors
* Supernumerary root
* Taurodontism
* Trauma
* Avulsion
* Cracked tooth syndrome
* Vertical root fracture
* Occlusal
* Tooth loss
* Edentulism
* Tooth wear
* Abrasion
* Abfraction
* Acid erosion
* Attrition
Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures
* Cementicle
* Cementoblastoma
* Gigantiform
* Cementoma
* Eruption cyst
* Epulis
* Pyogenic granuloma
* Congenital epulis
* Gingival enlargement
* Gingival cyst of the adult
* Gingival cyst of the newborn
* Gingivitis
* Desquamative
* Granulomatous
* Plasma cell
* Hereditary gingival fibromatosis
* Hypercementosis
* Hypocementosis
* Linear gingival erythema
* Necrotizing periodontal diseases
* Acute necrotizing ulcerative gingivitis
* Pericoronitis
* Peri-implantitis
* Periodontal abscess
* Periodontal trauma
* Periodontitis
* Aggressive
* As a manifestation of systemic disease
* Chronic
* Perio-endo lesion
* Teething
Periapical, mandibular and maxillary hard tissues – Bones of jaws
* Agnathia
* Alveolar osteitis
* Buccal exostosis
* Cherubism
* Idiopathic osteosclerosis
* Mandibular fracture
* Microgenia
* Micrognathia
* Intraosseous cysts
* Odontogenic: periapical
* Dentigerous
* Buccal bifurcation
* Lateral periodontal
* Globulomaxillary
* Calcifying odontogenic
* Glandular odontogenic
* Non-odontogenic: Nasopalatine duct
* Median mandibular
* Median palatal
* Traumatic bone
* Osteoma
* Osteomyelitis
* Osteonecrosis
* Bisphosphonate-associated
* Neuralgia-inducing cavitational osteonecrosis
* Osteoradionecrosis
* Osteoporotic bone marrow defect
* Paget's disease of bone
* Periapical abscess
* Phoenix abscess
* Periapical periodontitis
* Stafne defect
* Torus mandibularis
Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities
* Bruxism
* Condylar resorption
* Mandibular dislocation
* Malocclusion
* Crossbite
* Open bite
* Overbite
* Overeruption
* Overjet
* Prognathia
* Retrognathia
* Scissor bite
* Maxillary hypoplasia
* Temporomandibular joint dysfunction
Salivary glands
* Benign lymphoepithelial lesion
* Ectopic salivary gland tissue
* Frey's syndrome
* HIV salivary gland disease
* Necrotizing sialometaplasia
* Mucocele
* Ranula
* Pneumoparotitis
* Salivary duct stricture
* Salivary gland aplasia
* Salivary gland atresia
* Salivary gland diverticulum
* Salivary gland fistula
* Salivary gland hyperplasia
* Salivary gland hypoplasia
* Salivary gland neoplasms
* Benign: Basal cell adenoma
* Canalicular adenoma
* Ductal papilloma
* Monomorphic adenoma
* Myoepithelioma
* Oncocytoma
* Papillary cystadenoma lymphomatosum
* Pleomorphic adenoma
* Sebaceous adenoma
* Malignant: Acinic cell carcinoma
* Adenocarcinoma
* Adenoid cystic carcinoma
* Carcinoma ex pleomorphic adenoma
* Lymphoma
* Mucoepidermoid carcinoma
* Sclerosing polycystic adenosis
* Sialadenitis
* Parotitis
* Chronic sclerosing sialadenitis
* Sialectasis
* Sialocele
* Sialodochitis
* Sialosis
* Sialolithiasis
* Sjögren's syndrome
Orofacial soft tissues – Soft tissues around the mouth
* Actinomycosis
* Angioedema
* Basal cell carcinoma
* Cutaneous sinus of dental origin
* Cystic hygroma
* Gnathophyma
* Ludwig's angina
* Macrostomia
* Melkersson–Rosenthal syndrome
* Microstomia
* Noma
* Oral Crohn's disease
* Orofacial granulomatosis
* Perioral dermatitis
* Pyostomatitis vegetans
Other
* Eagle syndrome
* Hemifacial hypertrophy
* Facial hemiatrophy
* Oral manifestations of systemic disease
This Epidermal nevi, neoplasms, cysts article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Warty dyskeratoma
|
c0334063
| 8,054 |
wikipedia
|
https://en.wikipedia.org/wiki/Warty_dyskeratoma
| 2021-01-18T18:33:36 |
{"umls": ["C0334063"], "orphanet": ["69745"], "wikidata": ["Q7971063"]}
|
Nocturnal epilepsy
SpecialtyNeurology
Nocturnal epilepsy is a seizure disorder in which seizures occur only while sleeping.[1] Several common forms of epilepsy, including frontal lobe epilepsy, can manifest in a nocturnal state.
Epilepsy can be nocturnal if the form of epilepsy triggers seizures only while one is asleep, or if one normally has seizures that occur at that time. In the latter example, if the subject stays awake at a time when he is normally sleeping, the subject may have the seizure while awake. Noting this, it is important for the subject to maintain a proper sleeping cycle. Diverting from proper sleep patterns can trigger more frequent epileptic symptoms in people who are diagnosed with nocturnal epilepsy and, as mentioned before, even while awake.[2]
## Contents
* 1 Diagnosis
* 1.1 Type
* 2 Treatment
* 3 References
* 4 Sources
## Diagnosis[edit]
The condition may be difficult to diagnose. The subject may be unaware they have a seizure disorder.[3] To others, the involuntary movements made during sleep may appear no different from those typical of normal sleep.[4] People who have nocturnal seizures may notice unusual conditions upon awakening in the morning, such as a headache, having wet the bed, having bitten the tongue, a bone or joint injury, muscle strains or weakness, fatigue, or lightheadedness. Others may notice unusual mental behaviors consistent with the aftermath of a seizure.[5] Objects near the bed may have been knocked to the floor, or the subject may be surprised to find themselves on the floor.
There are many risks associated with nocturnal seizures including concussion, suffocation and sudden unexpected death (SUDEP).
### Type[edit]
A person who suffers from epilepsy regardless of whether it is nocturnal or not, can be categorized into two different types of epilepsy either being generalized, or partial. A generalized epilepsy syndrome is associated with an overall hyperactivity in the brain, where electrical discharges occur all over the brain at once; this syndrome often has a genetic basis. While generalized epilepsy occurs all over the brain, partial epilepsy consists of a regional or localized hyperactivity, which means that the seizures occur conversely in one part of the brain or several parts at once.[2]
## Treatment[edit]
Like other forms of epilepsy, nocturnal epilepsy can be treated with anti-convulsants.[6] Despite the effectiveness of anti-convulsants in people who suffer from nocturnal epilepsy, the drugs are shown to disrupt a person's sleeping structure.[7] This may cause concern in people who suffer specifically from nocturnal epilepsy because undisrupted sleep is important for these people, as it lowers the likeliness of epileptic symptoms to arise.
One particular study by V. Bradley and D. O'Neill analysed the different forms of epilepsy, including nocturnal epilepsy and its relationship with sleep.[2] They found that some patients only experienced epileptic symptoms while they are asleep (nocturnal epilepsy), and that maintaining good sleep helped in reducing epileptic symptoms. Another study determined that anti-convulsant medications can minimize epilepsy not just in people who are awake, but also in people who are asleep. However, some of these anti-convulsant medications did also have adverse effects on subjects' sleeping structures, which can exacerbate epileptic symptoms in people who suffer from nocturnal epilepsy.
To minimize epileptic seizures in these people, it is important to find an anti-convulsant medication that does not disrupt a person's sleeping structure. The anti-convulsant medications that were tested to meet this criterion are: phenobarbital, phenytoin, carbamazepine, valproate, ethosuximide, felbamate, gabapentin, lamotrigine, topiramate, vigabatrin, tiagabine, levetiracetam, zonisamide, and oxcarbazepine.[2] Oxcarbazepine is shown to have the least amount of adverse effects on sleep. Another study shows that it enhances slow wave-sleep and sleep continuity in patients with epilepsy.[2][7]
## References[edit]
1. ^ "Nocturnal epilepsy definition" Drugs.com
2. ^ a b c d e Paul R. C., Richard B. B., James D. G. (2005) Clinical Sleep Disorders Philadelphia: Lippincott, Williams, and Wilkins.
3. ^ Winslow, Forbes. Obscure diseases of the brain and mind, p 311
4. ^ Shneerson, John M. (2005) Sleep Medicine: A Guide to Sleep and its Disorders, p 221
5. ^ Atkins, Ringrose. REPORT ON NERVOUS AND MENTAL DISEASE Dublin Journal of Medical Science, Volume 67
6. ^ Browne, Thomas R., Holmes, Gregory L. (2008) Handbook of Epilepsy, p 51
7. ^ a b Thorpy, Michael J., Plazzi, Giuseppe. (2010) The Parasomnias and Other Sleep-Related Movement Disorders Cambridge University Press, Cambridge Books Online
## Sources[edit]
* Manford, Mark (2003), Practical Guide to Epilepsy, Butterworth-Heinemann, ISBN 978-0-7506-4621-5
* v
* t
* e
Seizures and epilepsy
Basics
* Seizure types
* Aura (warning sign)
* Postictal state
* Epileptogenesis
* Neonatal seizure
* Epilepsy in children
Management
* Anticonvulsants
* Investigations
* Electroencephalography
* Epileptologist
Personal issues
* Epilepsy and driving
* Epilepsy and employment
Seizure types
Focal
Seizures
Simple partial
Complex partial
Gelastic seizure
Epilepsy
Temporal lobe epilepsy
Frontal lobe epilepsy
Rolandic epilepsy
Nocturnal epilepsy
Panayiotopoulos syndrome
Vertiginous epilepsy
Generalised
* Tonic–clonic
* Absence seizure
* Atonic seizure
* Automatism
* Benign familial neonatal seizures
* Lennox–Gastaut syndrome
* Myoclonic astatic epilepsy
* Epileptic spasms
Status epilepticus
* Epilepsia partialis continua
* Complex partial status epilepticus
Myoclonic epilepsy
* Progressive myoclonus epilepsy
* Dentatorubral–pallidoluysian atrophy
* Unverricht–Lundborg disease
* MERRF syndrome
* Lafora disease
* Juvenile myoclonic epilepsy
Non-epileptic seizure
* Febrile seizure
* Psychogenic non-epileptic seizure
Related disorders
* Sudden unexpected death in epilepsy
* Todd's paresis
* Landau–Kleffner syndrome
* Epilepsy in animals
Organizations
* Citizens United for Research in Epilepsy (US)
* Epilepsy Action (UK)
* Epilepsy Action Australia
* Epilepsy Foundation (US)
* Epilepsy Outlook (UK)
* Epilepsy Research UK
* Epilepsy Society (UK)
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Nocturnal epilepsy
|
c0393719
| 8,055 |
wikipedia
|
https://en.wikipedia.org/wiki/Nocturnal_epilepsy
| 2021-01-18T19:09:36 |
{"umls": ["C0393719"], "wikidata": ["Q7046514"]}
|
Rare genetic disease
Spinal muscular atrophy with lower extremity predominance 2A
Other namesLower extremity-predominant spinal muscular atrophy type 2A, SMALED2A
Spinal muscular atrophy with lower extremity predominance 2A is inherited in an autosomal dominant manner.
SpecialtyNeurology
SymptomsMuscle weakness in legs
Usual onsetInfancy
DurationLifetime
CausesMutations in BICD2 gene
Diagnostic methodMolecular test
Spinal muscular atrophy with lower extremity predominance 2A (SMALED2A) is a rare neuromuscular disorder characterised by muscle weakness predominantly in legs. The disorder is usually diagnosed shortly after birth; affected children have a delayed motor development, waddling gait, difficulties walking, sometimes develop spasticity.[1][2] Sensation, swallowing and cognitive development are not affected. The disorder is slowly progressive throughout the lifetime.[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 for SMALED2A.
## References[edit]
1. ^ a b c Online Mendelian Inheritance in Man (OMIM): 615290
2. ^ Frasquet, M.; Camacho, A.; Vílchez, R.; Argente‐Escrig, H.; Millet, E.; Vázquez‐Costa, J. F.; Silla, R.; Sánchez‐Monteagudo, A.; Vílchez, J. J.; Espinós, C.; Lupo, V. (2020). "Clinical spectrum of BICD2 mutations". European Journal of Neurology. 27 (7): 1327–1335. doi:10.1111/ene.14173. ISSN 1351-5101.
Classification
D
* OMIM: 615290
## See also[edit]
* Spinal muscular atrophies
* Spinal muscular atrophy with lower extremity predominance 1
* Spinal muscular atrophy with lower extremity predominance 2B
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic
Brain and spinal cord
* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis
Brain/
encephalopathy
Degenerative
Extrapyramidal and
movement disorders
* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA
* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
* Myoclonic epilepsy
* Akathisia
* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person
Dementia
* Tauopathy
* Alzheimer's
* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Dementia with Lewy bodies
* Posterior cortical atrophy
* Vascular dementia
Mitochondrial disease
* Leigh syndrome
Demyelinating
* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS
Episodic/
paroxysmal
Seizures and epilepsy
* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy
Headache
* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache
Cerebrovascular
* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases
Other
* Sleep disorders
* For more detailed coverage, see Template:Sleep
CSF
* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension
Other
* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
Both/either
Degenerative
SA
* Friedreich's ataxia
* Ataxia–telangiectasia
MND
* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia
* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
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 2A
|
None
| 8,056 |
wikipedia
|
https://en.wikipedia.org/wiki/Spinal_muscular_atrophy_with_lower_extremity_predominance_2A
| 2021-01-18T18:28:50 |
{"wikidata": ["Q102296729"]}
|
Rare symptom of brain damage where sufferers deny being blind
This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (September 2019) (Learn how and when to remove this template message)
Anton syndrome, also known as Anton's blindness and visual anosognosia, is a rare symptom of brain damage occurring in the occipital lobe. Those who have it are cortically blind, but affirm, often quite adamantly and in the face of clear evidence of their blindness, that they are capable of seeing. Failing to accept being blind, people with Anton syndrome dismiss evidence of their condition and employ confabulation to fill in the missing sensory input. It is named after the neurologist Gabriel Anton. Only 28 cases have been published.[1]
Although sometimes the two terms are used as synonymous, Anton syndrome must not be confused with Anton–Babinski syndrome,[citation needed] which is characterised clinically by contralateral sensory neglect, anosognosia with associated affective indifference toward the condition (anosodiaphoria), construction and dressing apraxia. Anton–Babinski syndrome is the right-hemisphere equivalent of Gerstmann syndrome and it is due to non-dominant inferior parietal lobule damage.
## Contents
* 1 Presentation
* 2 Causes
* 3 History
* 4 Culture
* 5 See also
* 6 References
* 7 Bibliography
## Presentation[edit]
Anton syndrome is mostly seen following a stroke, but may also be seen after head injury. Neurologist Macdonald Critchley describes it thus:
> The sudden development of bilateral occipital dysfunction is likely to produce transient physical and psychical effects in which mental confusion may be prominent. It may be some days before the relatives, or the nursing staff, stumble onto the fact that the patient has actually become sightless. This is not only because the patient ordinarily does not volunteer the information that they have become blind, but he furthermore misleads his entourage by behaving and talking as though they were sighted. Attention is aroused however when the patient is found to collide with pieces of furniture, to fall over objects, and to experience difficulty in finding his way around. They may try to walk through a wall or through a closed door on his way from one room to another. Suspicion is still further alerted when they begin to describe people and objects around them which, as a matter of fact, are not there at all.
>
> Thus we have the twin symptoms of anosognosia (or lack of awareness of defect) and confabulation, the latter affecting both speech and behaviour.[2]
Anton syndrome may be thought of ideally as the opposite of blindsight, blindsight occurring when part of the visual field is not consciously experienced, but some reliable perception does in fact occur.
## Causes[edit]
Why patients with Anton syndrome deny their blindness is unknown, although there are many theories. One hypothesis is that damage to the visual cortex results in the inability to communicate with the speech-language areas of the brain. Visual imagery is received but cannot be interpreted; the speech centers of the brain confabulate a response.[3]
Patients have also reported visual anosognosia after experiencing ischemic vascular cerebral disease. A 96-year-old man, who was admitted to an emergency department complaining of a severe headache and sudden loss of vision, was discovered to have had a posterior cerebral artery thrombosis with consequent loss of vision. He adamantly claimed he was able to see despite an ophthalmologic exam proving otherwise. An MRI of his brain proved that his right occipital lobe was ischemic. Similarly, a 56-year-old woman was admitted to the emergency department in a confused state and with severely handicapped psychomotor skills. Ocular movements and pupil reflexes were still intact, but the patient could not name objects and was not aware of light changes in the room, and seemed unaware of her visual deficit.[citation needed]
## History[edit]
Most cases of Anton syndrome are reported from adults. The European Journal of Neurology published an article in 2007 that examines a case study of a six-year-old child with Anton syndrome and early stages of adrenoleukodystrophy. The child reportedly had abnormal eye movements, would often fall, and would reach for things and often miss his target. When his sight was tested at 20/20 he was still unable to read the large letters on the chart. He denied having headaches, diplopia, or eye pain and seemed unconcerned and unaware of his poor eyesight. Upon examination, his pupils were equal in shape, round, and reactive to light. His mother commented that he developed unusual eye movements and that they had a "roving quality".[4]
## Culture[edit]
Anton syndrome was featured in a two-part episode of the television series House M.D., titled "Euphoria", although it was ascribed to primary amoebic meningoencephalitis, a disease that usually does not cause the syndrome in real life.
The syndrome features prominently in the Rupert Thomson novel The Insult. It is also mentioned in the science fiction novel Blindsight, by Peter Watts.
It is mentioned frequently as "Anton's Blindness" as one of the primary metaphors in Raj Patel's The Value of Nothing.
In Lars von Trier's film Dogville, the character Jack McKay acts as if he can see but gives many signs he cannot.
The syndrome is also the main theme of the Malaysian movie Desolasi (Desolation), where the patients live in their own world of imagination, while unable to see the real world.
It is also mentioned in Oliver Sacks's An Anthropologist on Mars.
## See also[edit]
* Prosopagnosia – Cognitive disorder of face perception
* Riddoch syndrome – Type of visual impairment
* Visual release hallucinations
## References[edit]
1. ^ Kim, Nina; Anbarasan, Deepti; Howard, Jonathan (April 2017). "Anton syndrome as a result of MS exacerbation". Neurology: Clinical Practice. 7 (2): e19–e22. doi:10.1212/CPJ.0000000000000273. PMC 5669417. PMID 29185543.
2. ^ Macdonald Critchley, "Modes of reaction to central blindness", in Critchley, 1979, p. 156
3. ^ Prigatano, George P.; Schacter, Daniel L (1991). Awareness of deficit after brain injury: clinical and theoretical issues. Oxford [Oxfordshire]: Oxford University Press. pp. 53–60. ISBN 978-0-19-505941-0.
4. ^ Trifiletti, R. R.; Syed, E. H. (2007). "Anton-Babinski Syndrome in a Child with Early-stage Adrenoleukodystrophy". European Journal of Neurology. 14 (2): e11–e12. doi:10.1111/j.1468-1331.2006.01581.x. PMID 17250706. S2CID 26141348.
## Bibliography[edit]
* Critchley, Macdonald, The Divine Banquet of the Brain, Raven, New York, 1979[ISBN missing]
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Anton–Babinski syndrome
|
None
| 8,057 |
wikipedia
|
https://en.wikipedia.org/wiki/Anton%E2%80%93Babinski_syndrome
| 2021-01-18T18:53:46 |
{"wikidata": ["Q15783653"]}
|
A number sign (#) is used with this entry because of evidence that myopathy due to myoadenylate deaminase deficiency (MMDD) is caused by homozygous or compound heterozygous mutation in the AMPD1 gene (102770) on chromosome 1p13.
Description
Myoadenylate deaminase deficiency (MMDD) is an autosomal recessive condition that can manifest as exercise-induced muscle pain, occasionally associated with rhabdomyolysis and/or increased serum creatine kinase, or even infantile hypotonia. However, the finding of homozygous mutations among asymptomatic individuals have suggested to some (e.g., Verzijl et al., 1998) that AMPD1 deficiency may be a harmless entity (summary by Castro-Gago et al., 2011).
Genetta et al. (2001) stated that AMPD1 deficiency is the most prevalent genetic disease in humans, the number of people heterozygous approaching 10% of Caucasians and individuals of African descent (Sabina et al., 1989). A small percentage of homozygous-deficient individuals, approximately 1.8% of the population, display symptoms of chronic fatigue and lost productivity as well as a predisposition to stress-related ailments, including heart disease and stroke, according to Genetta et al. (2001).
Clinical Features
Fishbein et al. (1978) reported 5 unrelated Caucasian men with muscle weakness and/or postexertional cramping associated with lack of muscle adenylate deaminase activity and protein levels. Red cell adenylate deaminase (AMPD3; 102772) was normal, suggesting that it is under different genetic control than muscle. This was consistent with evidence that myoadenylate deaminase is antigenically unique to muscle and that the isozyme from red cells has distinctive kinetic properties. Fishbein et al. (1978) suggested that this may be a common form of myopathy of the nonprogressive 'limp infant' and benign congenital hypotonia type.
Sabina et al. (1980) reported a 35-year-old woman who presented with easy fatigability, postexercise myalgia, and delayed recovery of muscle strength. Skeletal muscle biopsy showed less than 1% normal AMPD1 activity and lack of ammonia release in skeletal muscle after ischemic exercise. Further studies demonstrated that depletion and slow repletion of the muscle ATP pool were responsible for the symptoms. The findings suggested that disruption of the purine nucleotide cycle due to myoadenylate deaminase deficiency can result in marked alterations in ATP content of muscle, and that the changes could account for muscle dysfunction.
Shumate et al. (1980) reported an 18-month-old girl referred for delayed motor and speech development. She had always been hypotonic and was unable to stand unsupported. There was no muscle atrophy. Muscle biopsy showed severely decreased adenylate deaminase activity compared to controls.
Morisaki et al. (1992) reported an 18-year-old German woman who first noted calf pain at 4 years of age, usually related to exercise. Her symptoms persisted, and she also had weakness of the upper arms. Morisaki et al. (1992) also reported 10 additional unrelated patients ranging in age from 16 to 68 years, with onset of symptoms between 11 and 55 years. The most common presentation was muscle pain after exercise. Some also reported muscle weakness and/or fatigue; 1 had rhabdomyolysis following a viral infection. Muscle biopsies showed significantly decreased AMPD activity, and immunoblot analysis in some patients showed absence of the AMPD1 protein.
Morisaki et al. (2000) and Abe et al. (2000) reported a 46-year-old Japanese woman who had first noted muscle weakness of the legs at 40 years of age. She had occasional myalgia and cramps in the lower extremities after exercise, as well as muscle atrophy. Serum creatine kinase was slightly elevated. Computed tomography showed a characteristic distribution of skeletal muscle involvement, with proximal and flexor muscles more severely affected than distal and extensor muscles in the leg. In addition, the left sternocleidomastoid muscle showed marked atrophy with an asymptomatic weakness of over 20 years duration, suggesting abnormal development.
Castro-Gago et al. (2011) reported a 6-month-old Spanish girl who presented with weakness and hypotonia from the first month of life. She was conceived by in vitro fertilization with sperm donation. She had severe muscle weakness, hypotonia of the trunk and upper limbs, areflexia, and lacked muscle atrophy. Ocular movements were normal; she also had macrocephaly. EMG showed a myopathic pattern. Skeletal muscle biopsy showed normal levels of all skeletal proteins tested but loss of AMPD1 enzyme activity. Hypotonia persisted, and the child was unable to sit at age 18 months.
Diagnosis
Fishbein et al. (1978) noted that AMPD1 is 10 times higher in skeletal muscle than in any other tissue. Increased plasma ammonia (relative to lactate) after the exercise of sponge-squeezing may be low in this disorder, which could be a useful clinical test.
Valen et al. (1987) found decreased purine release after exercise in MMDD patients compared with that in normal subjects and pointed out that this finding increases the specificity of the forearm ischemic exercise test. Using the standardized ischemic forearm test, Sinkeler et al. (1988) studied 36 relatives of 9 unrelated patients with AMPD1 deficiency. Eight new cases of myoadenylate deaminase deficiency were detected, 5 of which were confirmed histochemically and biochemically. Obligate heterozygotes showed normal ammonia production and AMPD1 staining, but the mean activity of the enzyme was significantly less than in controls. Only 2 of the 8 newly found individuals complained of exertional myalgia.
Inheritance
In the mother of an affected child, Fishbein et al. (1979) observed intermediate values in the ischemic forearm exercise test, suggesting genetic transmission of the deficiency state. Biochemical studies of AMPD1 by Fishbein et al. (1984) demonstrated the existence of a carrier state for the deficiency, indicating an autosomal recessive pattern of transmission for the disorder.
Molecular Genetics
In a German woman and 10 other unrelated individuals with AMPD1 deficiency, Morisaki et al. (1992) identified the same homozygous 34C-T transition in the AMPD1 gene, resulting in a truncated protein (Q12X; 102770.0001). However, this variant was found at high frequency in control populations (see POPULATION GENETICS).
In a Japanese woman with adult-onset AMPD1 deficiency, Morisaki et al. (2000) and Abe et al. (2000) identified compound heterozygous missense mutations in the AMPD1 gene (R388W, 102770.0002 and R425H, 102770.0003).
Genetta et al. (2001) quoted Loh et al. (1999), who purportedly demonstrated a protective effect conferred by 1 AMPD allele on individuals at risk for congestive heart failure; people harboring at least 1 AMPD mutant allele had a significant probability of prolonged survival after the onset of symptoms of congestive heart failure.
In a Spanish infant with hypotonia, Castro-Gago et al. (2011) identified a homozygous Q12X mutation. The unaffected mother was heterozygous for the mutation; paternal DNA was unavailable.
Population Genetics
Fishbein et al. (1978) noted that deficiency of muscle-specific AMPD is apparently a common cause of exercise-induced myopathy and may be the most common cause of metabolic myopathy in humans. Most large screening centers reported that 1 to 2% of all muscle biopsies submitted for pathologic examination are deficient in AMPD enzyme activity.
In an analysis of genomic DNA from 59 Caucasians, 13 African Americans, and 106 Japanese, Morisaki et al. (1992) found that 17% of Caucasians and 23% of African Americans, but no Japanese, carried a Q12X mutant allele of AMPD1 (102770.0001); additionally, 2 Caucasians and 1 African American were found to be homozygous. Morisaki et al. (1992) concluded that the restricted distribution and high frequency of this allele suggested that it arose in a remote ancestor of individuals of western European descent. The frequency of the mutant allele would account for the 2% reported incidence of AMPD deficiency in muscle biopsies, even in the absence of clinical symptoms.
INHERITANCE \- Autosomal recessive MUSCLE, SOFT TISSUES \- Muscle pain after exercise \- Muscle fatigue \- Muscle weakness \- Hypotonia (in some patients) \- Rhabdomyolysis (in some patients) LABORATORY ABNORMALITIES \- Decreased activity of AMPD1 in skeletal muscle Increased serum creatine kinase MISCELLANEOUS \- Highly variable phenotype \- Variable age at onset (range infancy to late adulthood) \- Some patients may be asymptomatic MOLECULAR BASIS \- Caused by mutation in the adenosine monophosphate deaminase 1 gene (AMPD1, 102770.0001 ) ▲ 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
|
MYOPATHY DUE TO MYOADENYLATE DEAMINASE DEFICIENCY
|
c0268123
| 8,058 |
omim
|
https://www.omim.org/entry/615511
| 2019-09-22T15:51:51 |
{"omim": ["615511"], "orphanet": ["45"], "synonyms": ["Alternative titles", "ADENOSINE MONOPHOSPHATE DEAMINASE-1 DEFICIENCY, MYOPATHY DUE TO", "AMPD1 DEFICIENCY", "MYOADENYLATE DEAMINASE DEFICIENCY, MYOPATHY DUE TO"]}
|
Benign mesonephroma (Wolffian tumors or Wolffian duct adenomas) are rare tumors located anywhere along the length between the ovary and vagina in sites of remnant wolffian ducts. Wolffian ducts are structures in a developing embryo that get incorporated into the reproductive system in males and degenerate in females. Wolffian tumors are thought to have a low potential to become cancerous and tend to range from 0.8 to 25 centimeters in size. Surgery is the recommended treatment. In a small number of cases, recurrences or malignancy have been been reported. Close follow-up is advised.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Benign mesonephroma
|
c1520159
| 8,059 |
gard
|
https://rarediseases.info.nih.gov/diseases/8680/benign-mesonephroma
| 2021-01-18T18:01:49 |
{"mesh": ["C536741"], "umls": ["C1520159"], "synonyms": ["Wolffian adnexal tumor", "WAT", "Female adnexal tumor of probable Wolffian origin", "FATWO", "Wolffian adenoma", "Mesonephric adenoma", "Wolffian duct adenoma", "Wolffian tumor"]}
|
A rare primary bone dysplasia with increased bone density characterized by slowly progressive endosteal hyperostosis and osteosclerosis exclusively of the skull base and the calvaria, resulting in entrapment and dysfunction of cranial nerves I, II, V, VII, and VIII. First symptoms often appear during the second decade of life and include disturbances in smell, vision, facial sensation and expression, hearing, and balance, as well as headaches due to increased ocular and intracranial pressure. After the fourth decade, radiological progression is minimal, although decreased intracranial volume can lead to death in severe 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
|
Hyperostosis cranialis interna
|
c1840404
| 8,060 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=443098
| 2021-01-23T17:19:09 |
{"mesh": ["C564168"], "omim": ["144755"], "umls": ["C1840404"], "icd-10": ["M85.2"]}
|
A number sign (#) is used with this entry because of evidence that autosomal recessive spinocerebellar ataxia-17 (SCAR17) is caused by homozygous mutation in the CWF19L1 gene (616120) on chromosome 10q24.
Description
Autosomal recessive spinocerebellar ataxia-17 is a neurologic disorder characterized by onset of gait ataxia and cerebellar signs in early childhood. Patients also have variable intellectual disability (summary by Evers et al., 2016).
Clinical Features
Yapici and Eraksoy (2005) reported 2 sibs, born of consanguineous parents, with nonprogressive congenital cerebellar ataxia. Both had mildly delayed walking with an unsteady gait and frequent falls. At ages 12 and 6 years, respectively, physical examination showed dysarthria, dysmetria, hypotonia in the extremities, truncal ataxia, and increased reflexes in the lower extremities. IQ scores were 90 and 68, respectively. Brain MRI showed cerebellar hypoplasia predominantly affecting the vermis. Burns et al. (2014) noted that the sibs reported by Yapici and Eraksoy (2005) were born of consanguineous Turkish parents.
Nguyen et al. (2016) reported a Dutch girl, born of unrelated parents, with SCAR17. She had delayed psychomotor development and showed clumsiness at age 5 years. At age 10 years, she had slurred monotonic speech, oculomotor apraxia, a slight dystonic movement disorder, intention tremor, unsteady gait, and mild hypotonia. She was cooperative, but described as slow (IQ of 55). Brain imaging showed severe cerebellar hypoplasia with slow progression.
Evers et al. (2016) reported a 9-year-old boy, born of consanguineous Turkish parents, with SCAR17. He first walked at age 13 months with an unsteady gait, which later progressed to include gait ataxia, dysmetria, ataxic upper limb movements, intention tremor, and dysarthria. He also had mild microcephaly (-2.83 SD), mild intellectual disability, and delayed speech. Brain imaging showed mildly progressive cerebellar atrophy. He had thick bushy eyebrows and synophrys, but no other dysmorphic features. Ultrasound examination of a subsequent pregnancy in this family showed that the fetus had reduced cerebellar diameter, consistent with the fetus being affected with the same disorder. The pregnancy was terminated at 22 weeks' gestation. Evers et al. (2016) noted that the fetus had some additional abnormalities, including agenesis of the corpus callosum, duplication of the terminal phalange of the right thumb, and thoracic hemivertebrae, that may not have been related to the SCAR17 phenotype.
Inheritance
The transmission pattern of SCAR17 in the family reported by Yapici and Eraksoy (2005) was consistent with autosomal recessive inheritance.
Molecular Genetics
In the Turkish sibs with SCAR17 reported by Yapici and Eraksoy (2005), Burns et al. (2014) identified a homozygous splice site mutation in the CWF19L1 gene (616120.0001). The mutation was found by a combination of homozygosity mapping and exome sequencing. Studies of patient cells showed a lack of protein expression, consistent with the mutation being a null allele causing a loss of function. Direct sequencing of the CWF19L1 gene in 64 additional individuals with ataxia detected no mutations.
In a girl, born of unrelated Dutch parents, with SCAR17, Nguyen et al. (2016) identified compound heterozygous mutations in the CWF19L1 gene (616120.0002 and 616120.0003). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient fibroblasts showed normal expression levels of CWF19L; functional studies of the variant were not performed. Screening of the CWF19L1 gene in 27 additional patients with autosomal recessive cerebellar ataxia did not reveal any pathogenic variants.
In a boy, born of consanguineous Turkish parents, with SCAR17, Evers et al. (2016) identified a homozygous truncating mutation in the CWF19L1 gene (616120.0004). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells showed no detectable full-length CWF19L protein, consistent with a loss of function.
Animal Model
Burns et al. (2014) found that morpholino-mediated knockdown of cwf19l1 in zebrafish led to defective cerebellar structure and abnormal motor behavior.
INHERITANCE \- Autosomal recessive MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Spinocerebellar ataxia \- Truncal ataxia \- Extremity ataxia \- Unsteady gait \- Tremor \- Dysarthria \- Dysmetria \- Intellectual disability \- Delayed language \- Cerebellar hypoplasia predominantly affecting the vermis Peripheral Nervous System \- Hyperreflexia in the lower extremities MISCELLANEOUS \- Onset in infancy \- Slowly progressive disorder MOLECULAR BASIS \- Caused by mutation in the CWF19-like protein 1 gene (CWF19L1, 616120.0001 ) ▲ 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
|
SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 17
|
c4015301
| 8,061 |
omim
|
https://www.omim.org/entry/616127
| 2019-09-22T15:49:56 |
{"doid": ["0080064"], "omim": ["616127"], "orphanet": ["453521"], "synonyms": ["SCAR17", "Spinocerebellar ataxia autosomal recessive type 17"]}
|
Brachydactyly-mesomelia-intellectual disability-heart defects syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by developmental delay, intellectual disability, thin habitus with narrow shoulders, mesomelic shortness of the arms, craniofacial dysmorphism (e.g. long lower face, maxillary hypoplasia, beak nose, short columella, prognathia, high arched palate, obtuse mandibular angle), brachydactyly (mostly involving middle phalanges) and cardiovascular anomalies (i.e. aortic root dilatation, mitral valve prolapse).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Brachydactyly-mesomelia-intellectual disability-heart defects syndrome
|
None
| 8,062 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1277
| 2021-01-23T18:40:13 |
{"gard": ["5036"], "icd-10": ["Q87.8"], "synonyms": ["Stratton-Garcia-Young syndrome"]}
|
A rare, indolent primary cutaneous B-cell lymphoma characterized by multifocal, red to violaceous papules, plaques or nodules localized predominantly on the trunk and extremities. Histologically, these are dermis infiltrates consisting of small, marginal zone B cells, lymphoplasmacytic cells, and plasma cells. Marginal zone B cells express CD20, CD79a and Bcl-2, and are negative for CD5, CD10 and Bcl-6. Plasma cells are typically located at the periphery, and express CD138, CD79a, and monotypic light chains.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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 cutaneous marginal zone B-cell lymphoma
|
c1275321
| 8,063 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178536
| 2021-01-23T17:20:12 |
{"mesh": ["D018442"], "umls": ["C1275321"], "icd-10": ["C83.0"], "synonyms": ["PCMZL"]}
|
Burnside-Butler syndrome
Other names15q11.2 BP1-BP2 microdeletion
Burnside-Butler syndrome is a name that has been applied to the effects of microdeletion of DNA sequences involving four neurodevelopmental genes (TUBGCP5, CYFIP1, NIPA1, and NIPA2).[1] Varying developmental and psychiatric disorders have been attributed to the microdeletion; however, the great majority of people with the deletion do not have any clinical features associated with it. More studies are needed to delineate the range of clinical presentation.[2][3]
The 15q11.2 BP1–BP2 microdeletion (Burnside-Butler syndrome) was the most common cytogenetic abnormality found in a recent study using ultra-high resolution chromosomal microarray analysis optimized for neurodevelopmental disorders of 10,351 consecutive patients presenting for genetic laboratory testing who had autism spectrum disorders (ASD).[4] It may represent an under-recognized contributor to the global prevalence of ASD, which is a common clinical manifestation of many rare genetic disorders, many of which can be identified by chromosome microarray analysis. The 15q11.2 BP1-BP2 microdeletion was reported to account for 9% of the top 85 genetic findings associated with neurodevelopmental disorders followed by the proximal 16p11.2 deletion syndrome (5%).[4] However, the very high frequency of the deletion in unaffected population controls suggests that there is considerable ascertainment bias and that most people who have a neurodevelopmental condition and the deletion are likely to have an alternate cause for their symptoms. In a large population-based study,[5] 1 in 292 people in the general population had this deletion. While the deletion was over-represented in cases vs controls (1 in 126 cases had the deletion) suggesting that it likely does contribute to neurodevelopmental problems in some individuals, the penetrance is likely to be very low. To understand this point, it is important to remember that affected individuals make up only a small proportion of the population. Assuming that 1% have intellectual disability, for example, this would imply penetrance of ~1.3% for the deletion - i.e. 98.7% of people with the deletion would have no symptoms as a result.
This suggests that the term "Burnside-Butler syndrome" should be used with caution, if at all. In the context of low penetrance for a very common variant, it is not surprising that the features that have been attributed to the deletion are highly variable and inconsistent. No consistent set of features has been described that would meet the usual criteria for naming a syndrome, and the use of the term is likely to cause confusion.
## References[edit]
1. ^ Jerkovich, A. M.; Butler, M. G. (2014). "Further phenotypic expansion of 15q11.2 BP1-BP2 microdeletion (Burnside-Butler) syndrome - IOS Press". Journal of Pediatric Genetics. 3 (1): 41–44. doi:10.3233/pge-14082. PMC 4190059. PMID 25309804.
2. ^ Cox, Devin M.; Butler, Merlin G. (2015-02-13). "The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review". International Journal of Molecular Sciences. 16 (2): 4068–4082. doi:10.3390/ijms16024068. PMC 4346944. PMID 25689425.
3. ^ "OMIM Entry - # 615656 - CHROMOSOME 15q11.2 DELETION SYNDROME". www.omim.org. Retrieved 2015-10-02.[permanent dead link]
4. ^ a b Ho, Karen S.; Wassman, E. Robert; Baxter, Adrianne L.; Hensel, Charles H.; Martin, Megan M.; Prasad, Aparna; Twede, Hope; Vanzo, Rena J.; Butler, Merlin G. (2016-12-09). "Chromosomal Microarray Analysis of Consecutive Individuals with Autism Spectrum Disorders Using an Ultra-High Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders". International Journal of Molecular Sciences. 17 (12): 2070. doi:10.3390/ijms17122070. ISSN 1422-0067. PMC 5187870. PMID 27941670.
5. ^ Coe, Bradley P.; Witherspoon, Kali; Rosenfeld, Jill A.; van Bon, Bregje W. M.; Vulto-van Silfhout, Anneke T.; Bosco, Paolo; Friend, Kathryn L.; Baker, Carl; Buono, Serafino; Vissers, Lisenka E. L. M.; Schuurs-Hoeijmakers, Janneke H. (October 2014). "Refining analyses of copy number variation identifies specific genes associated with developmental delay". Nature Genetics. 46 (10): 1063–1071. doi:10.1038/ng.3092. ISSN 1546-1718. PMC 4177294. PMID 25217958.
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
|
Burnside-Butler syndrome
|
c3180937
| 8,064 |
wikipedia
|
https://en.wikipedia.org/wiki/Burnside-Butler_syndrome
| 2021-01-18T18:31:49 |
{"gard": ["10525"], "mesh": ["C557830"], "umls": ["C3810258"], "wikidata": ["Q21154057"]}
|
Microlissencephaly-micromelia syndrome is a syndrome of abnormal cortical development, characterized by severe prenatal polyhydramnios, postnatal microcephaly, lissencephaly, upper limb micromelia, dysmorphic facies (coarse face, hypertrichosis, and short nose with long philtrum), intractable seizures, and early death. Hypoparathyroidism was noted in one case.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Microlissencephaly-micromelia syndrome
|
None
| 8,065 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=50810
| 2021-01-23T19:07:37 |
{"icd-10": ["Q04.3"], "synonyms": ["Basel-Vanagaite-Sirota syndrome"]}
|
Multiple cutaneous leiomyoma
Other namesHereditary leiomyomatosis and renal cell cancer [1]
SpecialtyDermatology
Multiple cutaneous leiomyomas, also known as Pilar leiomyomas,[2] arise from the arrectores pilorum muscles, and are made up of a poorly circumscribed proliferation of haphazardly arranged smooth muscle fibers located in the dermis that appear to infiltrate the surrounding tissue and may extend into the subcutis.[2]
Sometimes associated with uterine leiomyomas (a combination known as multiple cutaneous and uterine leiomyomatosis, MCUL), these lesions may also be a manifestation of the hereditary leiomyomatosis and renal cell cancer syndrome.
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ "Hereditary leiomyomatosis and renal cell cancer | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 28 April 2019.
2. ^ a b Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). Page 1033. McGraw-Hill. ISBN 0-07-138076-0.
## External links[edit]
Classification
D
* ICD-10: C64
* OMIM: 150800
External resources
* Orphanet: 523
This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Multiple cutaneous leiomyoma
|
c0346065
| 8,066 |
wikipedia
|
https://en.wikipedia.org/wiki/Multiple_cutaneous_leiomyoma
| 2021-01-18T18:37:17 |
{"umls": ["C0346065"], "wikidata": ["Q6934921"]}
|
A number sign (#) is used with this entry because the Lutheran inhibitor (INLU) blood group phenotype of the Lutheran blood group (111200) results from heterozygous mutation in the KLF1 gene (600599) on chromosome 19p13.
Description
The Lutheran inhibitor blood group phenotype (In(Lu)) is characterized phenotypically by the apparent absence of the Lu antigen (BCAM; 612773) on red blood cells during serologic tests, i.e., Lu(a-b-). Since it is inherited as an autosomal dominant trait, it was initially postulated to result from an inhibitor of the Lu antigen. However, Singleton et al. (2008) found that the phenotype results from a mutation in the transcription factor KLF1 that regulates expression of the BCAM gene.
The Lu-null phenotype, or autosomal recessive true Lu(a-b-) (247420), is caused by homozygous or compound heterozygous inactivating mutations in the BCAM gene.
Clinical Features
By flow cytometry, Helias et al. (2013) demonstrated that the majority of red blood cells from individuals with the In(Lu) blood type completely lacked BCAM reactivity, although a small proportion showed some BCAM reactivity, suggesting weak expression of Lu(b). In addition, In(Lu) blood cells also showed low expression of CD44 (107269) compared to controls. These flow cytometric parameters allowed distinction of In(Lu) from recessive true Lu-null cells, or Lu(a-b-), that is caused by inactivating mutations in the BCAM gene. All 10 samples of In(Lu) carried heterozygous loss-of-function mutations in the KLF1 gene (see, e.g., 600599.0007-600599.0009). Helias et al. (2013) also found that In(Lu) individuals had increased levels of fetal hemoglobin (HbF) (mean of 2.14%) compared to controls (mean less than 1.0%), and slightly increased levels of HbA2 (141850). Finally, 9 In(Lu) individuals who were heterozygous for the P1 allele (607922.0007) did not express the P1 antigen (see 111400), whereas 1 who was homozygous for the P1 allele expressed only weak P1. These findings suggested that the expression of P1 is suppressed in the In(Lu) blood type. Helias et al. (2013) concluded that the KLF1 haploinsufficiency has different effects on the expression of different erythroid proteins, likely reflecting the variable dependence of their respective genes on the KLF1 transcription factor.
Inheritance
Race and Sanger (1975) described a dominant, independently segregating suppressor affecting the expression of Lutheran gene, which has been termed the Lutheran inhibitor, symbolized In(Lu). It influences the Lutheran, Auberger (see 111200), I (110800), and P (111400) blood group systems. The Auberger system belongs to the Lutheran system (Daniels et al., 1991).
Gibson (1976) described 2 families and confirmed the fact that In(Lu) also inhibits the full expression of the P1 antigen.
Mapping
Shaw et al. (1984) found that the dominant inhibitor of Lutheran antigens, In(Lu), is the usual cause of the Lutheran null phenotype in southeast England where they studied the families of 41 probands and found no proven case of the recessive background, LuLu. The only suggestion of linkage was with Rh (maximum lod = 1.169 in males at theta 0.1). Previously, INLU and CD44 (or MDU3; 107269) were thought to be the same. Telen (1992), however, knew of no evidence for this.
Rowe et al. (1992) investigated the families of 11 Lu-null probands to determine which of the 3 known genetic backgrounds, dominant, recessive (247420), or X-linked recessive (309050), was responsible for their Lu-null phenotype. In 10 of the 11 families, the Lu-null phenotype was caused by the dominant suppressor gene INLU. The family data permitted them to demonstrate for the first time independence of the INLU and LU genes. They also demonstrated suppression of the P1 antigen by the INLU gene. Close linkage of INLU and HLA was excluded.
Molecular Genetics
Karamatic Crew et al. (2007) noted that the autosomal dominant Lu(a-b-) is more common than autosomal recessive Lu(a-b-) (247420).
Singleton et al. (2008) identified 9 different heterozygous loss-of-function mutations in the KLF1 gene (see, e.g., 600599.0001-600599.0004) in 21 of 24 persons with the autosomal dominant In(Lu) phenotype. The individuals had no reported pathology, indicating that 1 functional KLF1 allele is sufficient to sustain human erythropoiesis.
In red blood cell samples from 10 probands with the dominant In(Lu) phenotype, Helias et al. (2013) identified 10 different heterozygous loss-of-function mutations in the KLF1 gene (see, e.g., 600599.0001-600599.0002 and 600599.0007-600599.0009).
Pathogenesis
In(Lu) was originally postulated to result from inheritance of a gene that inhibited or suppressed the Lutheran antigen gene (Gibson, 1976). The findings of Singleton et al. (2008) indicated that the lack of expression of the Lu antigen in this phenotype results from decreased transcription of erythroid-specific genes associated with red blood cell maturation. Although individuals with the In(Lu) phenotype serologically type as Lu(a-b-), further adsorption and elution techniques may show the presence of very weak Lutheran antigen expression.
Population Genetics
In South Wales, Rowe et al. (1992) found a frequency of 0.0002 for the Lu(a-b-) phenotype.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
BLOOD GROUP--LUTHERAN INHIBITOR
|
c1292231
| 8,067 |
omim
|
https://www.omim.org/entry/111150
| 2019-09-22T16:44:20 |
{"omim": ["111150"], "synonyms": ["Alternative titles", "DOMINANT LU (a-b-) PHENOTYPE"]}
|
## Description
Distal arthrogryposis type 4 (DA4) is distinguished by the presence of scoliosis (summary by Bamshad et al., 2009).
For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Clinical Features
Hall et al. (1982) reported a large Mexican family with distal arthrogryposis and severe scoliosis. The authors referred to the disorder as distal arthrogryposis type IID.
Baraitser (1982) reported a family in which 9 members spanning 4 generations had scoliosis inherited in an autosomal dominant pattern. Seven of the patients also had camptodactyly, 5 had torticollis, and 4 were unable to straighten the elbow. The scoliosis varied from mild to severe, and at least 5 members had fusion of cervical vertebrae. One boy was severely mentally retarded.
Pagnan and Gollop (1987) reported 3 members of a Brazilian family with autosomal dominant inheritance of DAIID. The proband, a 5-year-old girl, had congenital camptodactyly, bilateral equinovarus deformity, secondary muscle hypoplasia of both legs, and severe mental retardation. Other features included low frontal and posterior hairline, hypoplastic forehead, bilateral horizontal nystagmus, osteopenia, and asymmetry of the calvaria. Spine films were normal. The patient's father had camptodactyly, congenital clubfoot, talus valgus deformity, tibial or fibular deviation of the toes, and syndactyly of several toes. Spinal imaging showed lumbar scoliosis and osteophyte formation of several vertebrae. He also showed nystagmus. The proband's uncle had features similar to those of the proband's father, and photos of a paternal grandfather suggested that he also had the same syndrome.
Nomenclature
In a revised and extended classification scheme of the distal arthrogryposes, Bamshad et al. (1996) referred to this disorder as distal arthrogryposis type 4 (DA4).
INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Hypoplastic forehead \- Low anterior and posterior hairline Eyes \- Nystagmus, bilateral horizontal Nose \- Low nasal bridge Neck \- Torticollis SKELETAL Skull \- Cranial asymmetry Spine \- Accentuation of physiologic dorsal kyphosis \- Lumbar scoliosis \- Osteophyte formation of vertebrae Hands \- Camptodactyly (adults) \- Syndactyly \- Ulnar deviation (adults) Feet \- Club foot \- Talus valgus \- Syndactyly \- Fibular or tibial deviation of toes SKIN, NAILS, & HAIR Hair \- Low frontal hairline \- Low posterior hairline ▲ 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
|
ARTHROGRYPOSIS, DISTAL, TYPE 4
|
c1836756
| 8,068 |
omim
|
https://www.omim.org/entry/609128
| 2019-09-22T16:06:37 |
{"doid": ["0050646"], "mesh": ["C563791"], "omim": ["609128"], "orphanet": ["65720"], "synonyms": ["Alternative titles", "ARTHROGRYPOSIS WITH SEVERE SCOLIOSIS", "ARTHROGRYPOSIS, DISTAL, TYPE IID"]}
|
A rare malformation characterized by fixed narrowing of the tracheal lumen primarily due to complete tracheal cartilage rings and an absent membranous trachea, which causes breathing difficulty.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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 tracheal stenosis
|
c0265767
| 8,069 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141127
| 2021-01-23T16:59:52 |
{"gard": ["12008"], "mesh": ["C536975"], "omim": ["603569"], "umls": ["C0265767"], "icd-10": ["Q32.1"]}
|
A number sign (#) is used with this entry because of evidence that Holt-Oram syndrome (HOS) is caused by heterozygous mutation in the TBX5 gene (601620) on chromosome 12q24.
Description
Holt-Oram syndrome is an autosomal dominant disorder characterized by abnormalities of the upper limbs and shoulder girdle, associated with a congenital heart lesion. The typical combination is considered to be a triphalangeal thumb with a secundum atrial septal defect (ASD), but there is a great range in the severity of both the heart and skeletal lesions (summary by Hurst et al., 1991).
Clinical Features
Although the abnormality of the upper extremities is more extensive in some cases, the characteristic findings in the Holt-Oram syndrome are thumb anomaly and atrial septal defect. The thumb may be absent or may be a triphalangeal, nonopposable, finger-like digit. The thumb metacarpal has both a proximal and a distal epiphyseal ossification center (Temtamy and McKusick, 1978).
This syndrome was first clearly described by Holt and Oram (1960), who observed atrial septal defect in members of 4 generations of a family, associated with 'a congenital anomaly of the thumbs which lay in the same plane as the fingers, their terminal phalanges being curved inwards.' McKusick (1961) reported mother and daughter with atrial septal defect and absent or triphalangeal, fingerlike thumb. In 1966 the daughter gave birth to a male infant with upper extremity phocomelia and ventricular septal defect (VSD). The involvement of the arm was more extensive and the cardiovascular involvement more varied in the families described by Lewis et al. (1965) and Harris and Osborne (1966) than in the family of Holt and Oram (1960). However, it is not certain that these represented a separate mutation (McKusick, 1966). The family reported by Kuhn et al. (1963) may be an example of the Lewis type of heart-hand syndrome.
Lenz (1968) noted that the involvement of the arms in the Holt-Oram syndrome can be sufficiently severe to simulate thalidomide embryopathy.
Boehme and Shotar (1989) described a Jordanian family of normal intelligence in which members of 3 generations had complex malformations of the arms combined with variably expressed congenital heart disease. Because of the pedigree pattern, which included 1 instance of male-to-male transmission, they suggested autosomal dominant inheritance, but concluded that the disorder was distinct from HOS.
Poznanski et al. (1970) pointed out that carpal abnormalities, e.g., extra carpal bones, are more specific for the Holt-Oram syndrome than are changes in the thumb. Posteriorly and laterally, protuberant medial epicondyles of the humerus were seen in several patients. The left side was more severely affected in 27 of 39 cases (Smith et al., 1979). Cardiac involvement may be absent in patients with limb defects; 5 of 39 had normal clinical and EKG findings despite typical limb defects (Smith et al., 1979). Although a secundum atrial septal defect is most common, a wide variety of other cardiac defects occur, including ventricular septal defects and mitral valve prolapse. Patients with only limb defects may bear offspring with the complete syndrome.
Glauser et al. (1989) described a family in which the father had atrial septal defect and a hypoplastic thumb, and a son had triphalangeal thumb and syndactyly of digits 1 and 2 on the left with aplasia of the right thumb, and hypoplastic left heart syndrome with large atrial septal defect, coarctation of the aorta, patent ductus arteriosus (PDA), severe aortic stenosis, small left ventricle, and pulmonary hypertension. An older sister of this son had atrial septal defect but no clinically or radiologically apparent abnormalities of the upper limbs.
Moens et al. (1993) reported a 4-generation family with HOS. In addition to the typical changes in the thumb and atrial septal defect, there was postaxial/central polydactyly in some family members.
Basson et al. (1994) reported 2 extensively affected kindreds with HOS showing linkage to chromosome 12. The first family was previously reported by Gall et al. (1966). Of 49 at-risk family members in 5 generations, 26 (11 male and 15 female) were affected. Each affected member was the offspring of an affected parent, thereby confirming the high penetrance of the disease gene. All affected members had some skeletal abnormalities, although many of these were subtle and detected only by radiography. Skeletal deformities generally manifested as deformities of the thenar and carpal bones, occasionally in association with mildly hypoplastic clavicles and shortened radii. Thenar abnormalities included distal displacement of the thenar eminence in the presence or absence of a triphalangeal digit. Only one subject had an aplastic thumb on one side; the contralateral thumb was triphalangeal. None of the subjects had phocomelia or severe ectromelia. All affected members had cardiovascular disease. Septal defects were present in 15 of the surviving family members; 4 had atrial septal defects, 9 had ventricular septal defects, and 2 had both. The atrial septal defects were all of the ostium secundum type, except for one which involved an ostium primum defect. Four had required surgical correction of hemodynamically significant defects. One member of the family died of complications related to a complete atrioventricular canal defect. Eisenmenger syndrome, resulting from an uncorrected ventricular septal defect, was present in 1. Cardiac conduction disease, including bradycardia, atrioventricular block, atrial fibrillation, and sinus node dysfunction, was present in 11 of the surviving affected family members, and 6 required permanent pacemakers. The second family studied by Basson et al. (1994) had 18 affected members (10 male and 8 female) surviving with HOS. All had skeletal abnormalities, which were typically more severe than those found in the first family. Bilateral frank phocomelia or severe ectromelia characterized by hypoplastic humeri, radii, and clavicles, with thenar aplasia and carpal and digital deformities, was present in 7. On the other hand, congenital cardiovascular disease was milder and less frequent in the second family in which 6 had cardiac disease, all consisting of atrial septal defect of the ostium secundum type. Surgery for the septal defect had been required in 3 of these. Only one member of the family had conduction disease (incomplete right bundle branch block), and none had patent ductus arteriosus or superior vena cava anomaly, which were present in members of the first kindred. Since the 2 families showed the same linkage relationship to markers on 12q, the disorders are probably due to different mutations in the same gene, which is important to the development of both the limbs and the cardiovascular system.
Newbury-Ecob et al. (1996) reported a detailed study of a large cohort of patients that included 44 familial and 11 sporadic cases. Association of cardiac and radial abnormalities was a criterion for inclusion of familial cases. Limb defects were found in all affected persons. The thumb was the most commonly affected structure, although in 7 of 44 cases, the thumbs were normal. In most cases, the thumb defects (absence in 19/44, hypoplasia in 17/44, triphalangeal thumbs in 8/44) were associated with hypoplastic thenar or limited supination of the forearm. Radial hypoplasia (18/44) was more frequent than absence of radius (10/44). Ulnar hypoplasia occurred only in patients with radial defects. Most patients had narrow, sloping shoulders. Limb defects were always bilateral and often asymmetrical, the left side being more severely affected. Cardiac involvement was found in 95% of familial cases; secundum atrial septal defect (15) and ventricular septal defect (11) were the most common defects. In 17 of the familial cases, only ECG abnormalities were found. Both cardiac and limb abnormalities were more severe in the sporadic group. Newbury-Ecob et al. (1996) found a significant positive correlation (r = 0.49) between severity of the limb and cardiac defects. The patients with atrial septal defects had more severe limb abnormalities. Correlation between sibs was greater than that between parent and offspring.
Sletten and Pierpont (1996) described a family in which the proband had hypoplastic left thumb, hypoplastic left ventricle and endocardial cushion defect. His mother, aunt, uncle, grandfather and some other relatives had less pronounced manifestations of HOS. Analysis of the literature showed that single cardiovascular malformations (CVM) such as ASD, VSD, or PDA were reported in 125 of 189 cases (66%), and 33 patients (17.5%) had more complex cardiac defects (hypoplastic left heart, total anomalous pulmonary venous return, truncus arteriosus). Sletten and Pierpont (1996) emphasized that the proportion of severe CVM in patients with HOS has been underestimated and should be considered in counseling families with the disorder.
Kantaputra et al. (2002) described a Thai family in which the mother and 3 offspring were affected with a dominantly inherited malformation syndrome with short stature, upper limb anomaly, and minor craniofacial anomalies suggestive of HOS; however, molecular studies did not reveal any mutations in the TBX5 gene. One of the offspring, a 23-year-old man, was cardiologically asymptomatic, although echocardiography revealed he had a quadricuspid aortic valve associated with mild aortic regurgitation.
Tseng et al. (2007) reported a Taiwanese male infant with genetically confirmed HOS and right lung agenesis. He presented at birth with severe respiratory distress, sloping shoulder, and absence of bilateral thumbs and radii. Cardiac ultrasound showed atrial and ventricular septal defects, patent ductus arteriosus, and dextroposition of the heart. Chest CT scan showed absence of the right lung and bronchial tree. He also had absence of the right pulmonary artery and vein. Tseng et al. (2007) noted that pulmonary anomalies are uncommon in HOS, but may expand the phenotypic abnormalities associated with the disorder.
Diagnosis
Brons et al. (1988) discussed the prenatal diagnosis of HOS in 2 pregnancies. More severe forms of the disorder were excluded early in gestation. In the first fetus, ventricular septal defect, atrial septal defect, and a minor skeletal defect were found at 22 weeks. In a second fetus in the same sibship, no structural abnormalities were discovered until the thirtieth week, when a small atrial septal defect was detected.
Cytogenetics
Rybak et al. (1971) described many cases in 4 generations of a Polish family and concluded that partial deletion of the long arm of a B-group chromosome was related to the abnormality. They suggested that the single case of Ockey et al. (1967) had the Holt-Oram syndrome; a similar deletion of the long arm of a group B chromosome was present. Rybak (1981) reported that the family refused to be restudied with banding techniques.
Turleau et al. (1984) described de novo deletion of the q23-q24.2 region of chromosome 14 in a boy with arm and cardiac abnormalities possibly consistent with the Holt-Oram syndrome. In addition, he had mental retardation, synophrys, strabismus, thin upper lip, bilateral pretragian skin tags, and cryptorchidism. Using linkage studies, Ruiz et al. (1994) excluded the 14q23-q24 region as the site of the HOS gene in a Belgian family with several affected persons in 4 generations.
Kristoffersson et al. (1987) found normal high-resolution karyotypes in 3 patients: a mother, her daughter, and an unrelated woman. Yang et al. (1990) described a sporadic case of HOS associated with a de novo pericentric inversion of chromosome 20. The breakpoints in chromosome 20 were at p13 and q13.2. They suggested that the HOS mutation is located at the site of one of these breakpoints.
Basson et al. (1999) described a child with a chromosome 5;12 translocation that caused severe skeletal and composite cardiac malformations. The affected child had left arm phocomelia, right radial hypoplasia, and right thumb aplasia. Cardiac angiography demonstrated a common atrium and a complete atrioventricular canal defect.
Mapping
Terrett et al. (1994) studied linkage between microsatellite DNA markers and HOS in 7 families. In 5, linkage between HOS and markers on 12q was found, whereas the 2 remaining families, phenotypically indistinguishable from the others, did not show this linkage. Analysis of the family data with the computer program HOMOG indicated that HOS is a heterogeneous disorder. In the five 12q-linked families, Terrett et al. (1994) narrowed the assignment to a 21-cM interval in the distal region.
In each of 2 extensively affected kindreds, Basson et al. (1994) demonstrated linkage of HOS to markers in the 12q2 region; combined multipoint lod score = 16.8. Judging by the location of the markers used, HOS probably is in the q21.3-q22 region.
Fryns et al. (1996) reported a family in which linkage to 12q was excluded, thus demonstrating genetic heterogeneity in the Holt-Oram syndrome.
Inheritance
The Holt-Oram syndrome is inherited as an autosomal dominant trait (Hurst et al., 1991).
Braulke et al. (1991) reported a probable instance of germinal mosaicism: an unaffected man fathered 4 offspring with HOS by 3 different women.
Molecular Genetics
Li et al. (1997) and Basson et al. (1997) demonstrated mutations in the TBX5 gene as the basis of Holt-Oram syndrome (see, e.g., 601620.0001-601620.0005). The dominant phenotype of HOS appears to result from haploinsufficiency of TBX5. The glu69-to-ter mutation (601620.0002) identified by Basson et al. (1997) in affected members of one kindred was predicted to encode a markedly truncated TBX5 protein that lacked most T-box residues.
Basson et al. (1999) showed that TBX5 mutations predicted to create null alleles caused substantial abnormalities in both limb and heart. In contrast, missense mutations of the TBX5 gene produced distinct phenotypes: gly80 to arg (601620.0004) caused significant cardiac malformations but only minor skeletal abnormalities, whereas 2 mutations of codon 237, arg237 to gln (601620.0003) and arg237 to trp (601620.0005), caused extensive upper limb malformations but less significant cardiac abnormalities. They noted that residue 80 is highly conserved within T-box sequences that interact with the major groove of target DNA, whereas residue 237 is located in the T-box domain that selectively binds to the minor groove of DNA.
Yang et al. (2000) analyzed 11 Chinese patients with Holt-Oram syndrome using SSCP analysis of TBX5. The authors identified 3 novel mutations, including a frameshift mutation caused by a deletion of 1 basepair (601620.0006), and 2 missense mutations (601620.0007 and 601620.0008). The patients with the frameshift mutation had more severe upper limb anomalies, including aplasia/hypoplasia of the arm and thumbs, while those with missense mutations had milder anomalies, such as absent or hypoplastic thumbs, without arm abnormalities.
In 2 unrelated families with HOS, Gruenauer-Kloevekorn and Froster (2003) found the same truncation mutation in all affected members (601620.0009). The phenotype was similar in both families and included ASD, hypoplastic deltoid muscles, and hypoplastic or absent thumbs extending to radial defects in 1 patient.
Borozdin et al. (2006) reported a Czech mother and 2 daughters who were diagnosed with Holt-Oram syndrome, in whom they identified a 2.19 to 2.27-Mb contiguous deletion encompassing the TBX5 and TBX3 (601621) genes. Clinical reexamination confirmed the presence of features of ulnar-mammary syndrome (UMS; 181450) that were previously unrecognized. Borozdin et al. (2006) noted that the contiguous deletion also included the RBM19 gene (616444), but commented that it was unlikely to contribute to or modify the phenotype since all the anomalies present in the affected individuals could be explained by either TBX5 or TBX3 haploinsufficiency.
In affected members of a 5-generation family segregating an atypical form of HOS, consisting predominantly of nonseptal cardiac defects and mild limb anomalies, Patel et al. (2012) identified a 48-kb duplication encompassing exons 2 through 9 of the TBX5 gene. The duplication, which was identified by array CGH and multiplex ligation-dependent probe amplification, segregated with the disorder in the family.
Nomenclature
McKusick (1961) suggested the alternative designations atriodigital dysplasia and Holt-Oram syndrome; the latter 'caught on.'
History
An obituary of Samuel Oram (1913-1991) was provided by Davies (1992).
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Atrial septal defect (ostium secundum type) \- Ventricular septal defect \- Hypoplastic left heart syndrome Vascular \- Patent ductus arteriosus CHEST External Features \- Absent pectoralis major muscle Ribs Sternum Clavicles & Scapulae \- Pectus excavatum or carinatum SKELETAL Spine \- Vertebral anomalies \- Thoracic scoliosis Limbs \- Absent thumb \- Bifid thumb \- Triphalangeal thumb \- Carpal bone anomalies \- Upper extremity phocomelia \- Radial-ulnar anomalies \- Asymmetric involvement MOLECULAR BASIS \- Caused by mutations in the T-Box 5 gene (TBX5, 601620.0001 ) ▲ 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
|
HOLT-ORAM SYNDROME
|
c0265264
| 8,070 |
omim
|
https://www.omim.org/entry/142900
| 2019-09-22T16:40:10 |
{"doid": ["0060468"], "mesh": ["C535326"], "omim": ["142900"], "icd-10": ["Q87.2"], "orphanet": ["392"], "synonyms": ["Alternative titles", "HOS1", "HEART-HAND SYNDROME", "ATRIODIGITAL DYSPLASIA"], "genereviews": ["NBK1111"]}
|
Rare autosomal dominant multi-system genetic condition
Noonan syndrome with multiple lentigines (NSML)
Other namesLEOPARD syndrome, cardiocutaneous syndrome, Gorlin syndrome II, lentiginosis profusa syndrome, progressive cardiomyopathic lentiginosis,[1]:550 Capute-Rimoin-Konigsmark-Esterly-Richardson syndrome, Moynahan syndrome
Three-quarter facial view, first-generation patient showing slight prognathism and low set ears
SpecialtyMedical genetics
Noonan syndrome with multiple lentigines (NSML) which is part of a group called Ras/MAPK pathway syndromes,[2] is a rare autosomal dominant,[3] multisystem disease caused by a mutation in the protein tyrosine phosphatase, non-receptor type 11 gene (PTPN11). The disease is a complex of features, mostly involving the skin, skeletal and cardiovascular systems, which may or may not be present in all patients. The nature of how the mutation causes each of the condition's symptoms is not well known; however, research is ongoing. It is a RASopathy.
Noonan syndrome with multiple lentigines is caused by a different missense mutation of the same gene. Noonan syndrome is fairly common (1:1,000 to 1:2,500 live births), and neurofibromatosis 1 (which was once thought to be related to NSML) is also common (1:3500); however, no epidemiological data exists for NSML.[4]
## Contents
* 1 Signs and symptoms
* 2 Pathophysiology
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 History
* 8 See also
* 9 References
* 10 External links
## Signs and symptoms[edit]
An alternative name of the condition, LEOPARD syndrome, is a mnemonic, originally coined in 1969,[5] as the condition is characterized by some of the following seven conditions, the first letters of which spell LEOPARD, along with the characteristic "freckling" of the skin, caused by the lentigines that is reminiscent of the large cat.
* Lentigines — Reddish-brown to dark brown macules (surface skin lesion) generally occurring in a high number (10,000+) over a large portion of the skin, at times higher than 80% coverage. These can even appear inside the mouth (buccal), or on the surface of the eye (scleral). These have irregular borders and range in size from 1 mm in diameter to café-au-lait spots, several centimeters in diameter. Also, some areas of vitiligo-like hypopigmentation may be observed.
* Electrocardiographic conduction abnormalities: Generally observed on an electrocardiograph as a bundle branch block.
* Ocular hypertelorism: Wideset eyes, which lead to a similar facial resemblance between patients. Facial abnormalities are the second highest occurring symptom after the lentigines. Abnormalities also include: broad nasal root, prognathism (protruding lower jaw), or low-set, possibly rotated, ears.
* Pulmonary stenosis: Narrowing of the pulmonary artery as it exits the heart. Other cardiac abnormalities may be present, including aortic stenosis, or mitral valve prolapse.
* Abnormal genitalia: usually cryptorchidism (retention of testicles in body) or monorchism (single testicle). In female patients, this presents as missing or single ovaries, much harder by nature to detect. Ultrasound imaging is performed at regular intervals, from the age of 1 year, to determine if ovaries are present.
* Retarded growth: Slow, or stunted growth. Most newborns with this syndrome are of normal birth weight and length, but will often slow within the first year.
* Deafness: Sensorineural (nerve deafness).
The presence of all of these hallmarks is not needed for a diagnosis. A clinical diagnosis is considered made when, with lentigines present there are 2 other symptoms observed, such as ECG abnormalities and ocular hypertelorism, or without lentigines, 3 of the above conditions are present, with a first-degree relative (i.e. parent, child, sibling) with a clinical diagnosis.[6]
* Additional dermatologic abnormalities (axillary freckling, localized hypopigmentation, interdigital webbing, hyperelastic skin)
* Mild mental retardation is observed in about 30% of those affected with the syndrome
* Nystagmus (involuntary eye movements), seizures, or hyposmia (reduced ability to smell) has been documented in a few patients
* In 2004, a patient was reported with recurrent upper extremity aneurysms that required surgical repairs.[7]
* In 2006, a NSML patient was reported with acute myelogenous leukemia.[8]
Due to the rarity of the syndrome itself, it is hard to determine whether certain additional diseases are actually part of the syndrome. With a base population of possibly less than one thousand individuals, one or two outlying cases can skew the statistical population very quickly.
* Hand of 37-year-old patient showing interdigital webbing
* 37-year-old patient (second generation), exhibiting hypertelorism, broad nasal root, slight ptosis
* Thirty-seven-year-old patient demonstrating hyperelasticity
* 21-month-old, third generation patient, confirmed by genetic tests as Y279C, exhibiting ocular hyperteliorism, cephalofacial similarity.
* Torso of thirty-seven-year-old, second-generation patient, exhibiting lentiginosis.
## Pathophysiology[edit]
NSML is inherited in an autosomal dominant fashion, although it can also arise due to spontaneous mutation.
In the two predominant mutations of NSML (Y279C and T468M) the mutations cause a loss of catalytic activity of the SHP2 protein (the gene product of the PTPN11 gene), which is a previously unrecognized behavior for this class of mutations.[9] This interferes with growth factor and related signalling. While further research confirms this mechanism,[10][11] additional research is needed to determine how this relates to all of the observed effects of NSML.
## Diagnosis[edit]
The presence of the disease can be confirmed with a genetic test. In a study of 10 infants with clinical indications of NSML prior to their first birthday, 8 (80%) patients were confirmed to have the suspected mutation. An additional patient with the suspected mutation was subsequently found to have NF1, following evaluation of the mother.[12]
There are 5 identified allelic variants responsible for NSML. Y279C, T468M, A461T, G464A, and Q510P which seems to be a unique familial mutation, in that all other variants are caused by transition errors, rather than transversion.
## Treatment[edit]
It is suggested that, once diagnosed, individuals be routinely followed by a cardiologist, endocrinologist, dermatologist, and other appropriate specialties as symptoms present.
It is recommended that those with the syndrome who are capable of having children seek genetic counseling before deciding to have children. As the syndrome presents frequently as a forme fruste (incomplete, or unusual form) variant, an examination of all family members must be undertaken.[13] As an autosomal dominant trait there is a fifty percent chance with each child that they will also be born with the syndrome. Although fully penetrant, since the syndrome has variable expressivity, one generation may have a mild expression of the syndrome, while the next may be profoundly affected.
Once a decision to have children is made, and the couple conceives, the fetus is monitored during the pregnancy for cardiac evaluation. If a gross cardiac malformation is found, parents receive counseling on continuing with the pregnancy.
Other management is routine care as symptoms present:[13]
1. For those with endocrine issues (low levels of thyrotopin [a pituitary hormone responsible for regulating thyroid hormones], follicle stimulating hormone) drug therapy is recommended.
2. For those who are disturbed by the appearance of lentigines, cryosurgery may be beneficial. Due to the large number of lentigines this may prove time-consuming. An alternative treatment with tretinoin or hydroquinone creams may help.
3. Drug therapies for those with cardiac abnormalities, as those abnormalities become severe enough to warrant the use of these therapies. ECG's are mandatory prior to any surgical interventions, due to possible arrythmia.
## Prognosis[edit]
In itself, NSML is not a life-threatening diagnosis, most people diagnosed with the condition live normal lives. Obstructive cardiomyopathy and other pathologic findings involving the cardiovascular system may be a cause of death in those whose cardiac deformities are profound.[13]
## Epidemiology[edit]
Various literature describes the syndrome as being "rare"[13] or "extremely rare".[14] There is no epidemiologic data available regarding how many individuals suffer from the syndrome worldwide; however, there are approximately 200 cases described in medical literature.[15]
## History[edit]
Zeisler and Becker first described a syndrome with multiple lentigines, hypertelorism, pectus carinatum (protruding breastbone) and prognathism (protrusion of lower jaw) in 1936.[16] Sporadic descriptions were added through the years. In 1962, cardiac abnormalities and short stature were first associated with the condition.[17] In 1966, three familial cases were added, a mother, her son and daughter.[18] Another case of mother to two separate children, with different paternity of the two children, was added in 1968.[19]
It was believed as late as 2002[20] that Noonan Syndrome with Multiple Lentigines (NSML) was related to neurofibromatosis type I (von Recklinghausen syndrome). In fact, since both ICD9 and ICD10 lack a specific diagnosis code for NSML, the diagnosis code for NF1 is still sometimes used for diagnostic purposes, although it has been shown that the gene is not linked to the NF1 locus.[21]
## See also[edit]
* Neurofibromatosis
* Noonan syndrome
## 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. ^ Tidyman WE, Rauen KA (June 2009). "The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation". Current Opinion in Genetics & Development. 19 (3): 230–6. doi:10.1016/j.gde.2009.04.001. PMC 2743116. PMID 19467855.
3. ^ Coppin BD, Temple IK (1997). "Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis)". Journal of Medical Genetics. 34 (7): 582–6. doi:10.1136/jmg.34.7.582. PMC 1051000. PMID 9222968.
4. ^ Tullu MS, Muranjan MN, Kantharia VC, et al. (1 April 2000). "Neurofibromatosis-Noonan syndrome or LEOPARD Syndrome? A clinical dilemma". J Postgrad Med. 46 (2): 98–100. PMID 11013475.
5. ^ Gorlin RJ, Anderson RC, Blaw M (1969). "Multiple lentigenes syndrome". Am. J. Dis. Child. 117 (6): 652–62. doi:10.1001/archpedi.1969.02100030654006. PMID 5771505.
6. ^ Voron DA, Hatfield HH, Kalkhoff RK (1976). "Multiple lentigines syndrome. Case report and review of the literature". Am. J. Med. 60 (3): 447–56. doi:10.1016/0002-9343(76)90764-6. PMID 1258892.
7. ^ Yagubyan M, Panneton JM, Lindor NM, Conti E, Sarkozy A, Pizzuti A (April 2004). "LEOPARD syndrome: a new polyaneurysm association and an update on the molecular genetics of the disease". J. Vasc. Surg. 39 (4): 897–900. doi:10.1016/j.jvs.2003.11.030. PMID 15071461.
8. ^ Uçar C, Calýskan U, Martini S, Heinritz W (March 2006). "Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive)". J. Pediatr. Hematol. Oncol. 28 (3): 123–5. doi:10.1097/01.mph.0000199590.21797.0b. PMID 16679933. S2CID 21559684.
9. ^ Tartaglia M, Martinelli S, Stella L, et al. (2006). "Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease". American Journal of Human Genetics. 78 (2): 279–90. doi:10.1086/499925. PMC 1380235. PMID 16358218.
10. ^ Hanna N, Montagner A, Lee WH, et al. (2006). "Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1". FEBS Lett. 580 (10): 2477–82. doi:10.1016/j.febslet.2006.03.088. PMID 16638574. S2CID 27676871.
11. ^ Kontaridis MI, Swanson KD, David FS, Barford D, Neel BG (2006). "PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects". J. Biol. Chem. 281 (10): 6785–92. doi:10.1074/jbc.M513068200. PMID 16377799.
12. ^ Digilio MC, Sarkozy A, de Zorzi A, et al. (2006). "LEOPARD syndrome: clinical diagnosis in the first year of life". American Journal of Medical Genetics. 140 (7): 740–6. doi:10.1002/ajmg.a.31156. PMID 16523510. S2CID 19570040.
13. ^ a b c d LEOPARD Syndrome at eMedicine
14. ^ "LEOPARD Syndrome". NORD — National Organization for Rare Disorders.
15. ^ "Noonan syndrome with multiple lentigines". U.S. National Library of Medicine.
16. ^ Zeisler EP, Becker SW (1936). "Generalized lentigo: its relation to systemic nonelevated nevi". Arch Dermatol Syphilol. 33: 109–125. doi:10.1001/archderm.1936.01470070112010.
17. ^ Moynahan EJ (1962). "Multiple symmetrical moles, with psychic and somatic infantilism and genital hypoplasia: first male case of a new syndrome". Proceedings of the Royal Society of Medicine. 55 (11): 959–960. doi:10.1177/003591576205501112. PMC 1896920. PMID 19994192.
18. ^ Walther RJ, Polansky BJ, Grotis IA (1966). "Electrocardiographic abnormalities in a family with generalized lentigo". N. Engl. J. Med. 275 (22): 1220–5. doi:10.1056/NEJM196612012752203. PMID 5921856.
19. ^ Matthews NL (1968). "Lentigo and electrocardiographic changes". N. Engl. J. Med. 278 (14): 780–1. doi:10.1056/NEJM196804042781410. PMID 5638719.
20. ^ National Library of Medicine MeSH: C05.660.207.525
21. ^ Ahlbom BE, Dahl N, Zetterqvist P, Annerén G (1995). "Noonan syndrome with café-au-lait spots and multiple lentigines syndrome are not linked to the neurofibromatosis type 1 locus". Clin. Genet. 48 (2): 85–9. doi:10.1111/j.1399-0004.1995.tb04061.x. PMID 7586657. S2CID 31291484.
## External links[edit]
Classification
D
* OMIM: 151100 164757 164760 176876 611554
* MeSH: D044542
* DiseasesDB: 7387
External resources
* MedlinePlus: 001473
* eMedicine: article/1096445
* GeneReviews: LEOPARD Syndrome
Wikimedia Commons has media related to LEOPARD syndrome.
* NSML at NIH/UW GeneTests
* Gorlin's syndrome II at Who Named It?
* DermAtlas 981603547
* Dermnetnz
* DermIS
* v
* t
* e
Deficiencies of intracellular signaling peptides and proteins
GTP-binding protein regulators
GTPase-activating protein
* Neurofibromatosis type I
* Watson syndrome
* Tuberous sclerosis
Guanine nucleotide exchange factor
* Marinesco–Sjögren syndrome
* Aarskog–Scott syndrome
* Juvenile primary lateral sclerosis
* X-Linked mental retardation 1
G protein
Heterotrimeic
* cAMP/GNAS1: Pseudopseudohypoparathyroidism
* Progressive osseous heteroplasia
* Pseudohypoparathyroidism
* Albright's hereditary osteodystrophy
* McCune–Albright syndrome
* CGL 2
Monomeric
* RAS: HRAS
* Costello syndrome
* KRAS
* Noonan syndrome 3
* KRAS Cardiofaciocutaneous syndrome
* RAB: RAB7
* Charcot–Marie–Tooth disease
* RAB23
* Carpenter syndrome
* RAB27
* Griscelli syndrome type 2
* RHO: RAC2
* Neutrophil immunodeficiency syndrome
* ARF: SAR1B
* Chylomicron retention disease
* ARL13B
* Joubert syndrome 8
* ARL6
* Bardet–Biedl syndrome 3
MAP kinase
* Cardiofaciocutaneous syndrome
Other kinase/phosphatase
Tyrosine kinase
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* ZAP70 deficiency
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* CHEK2
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* IKBKG
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* STK11
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* DMPK
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* ATR
* Seckel syndrome 1
* GRK1
* Oguchi disease 2
* WNK4/WNK1
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Tyrosine phosphatase
* PTEN
* Bannayan–Riley–Ruvalcaba syndrome
* Lhermitte–Duclos disease
* Cowden syndrome
* Proteus-like syndrome
* MTM1
* X-linked myotubular myopathy
* PTPN11
* Noonan syndrome 1
* LEOPARD syndrome
* Metachondromatosis
Signal transducing adaptor proteins
* EDARADD
* EDARADD Hypohidrotic ectodermal dysplasia
* SH3BP2
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Other
* NF2
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* NOTCH3
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* PRKAR1A
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* PRKAG2
* Wolff–Parkinson–White syndrome
* PRKCSH
* PRKCSH Polycystic liver disease
* XIAP
* XIAP2
See also intracellular signaling peptides and proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[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
|
Noonan syndrome with multiple lentigines
|
c0175704
| 8,071 |
wikipedia
|
https://en.wikipedia.org/wiki/Noonan_syndrome_with_multiple_lentigines
| 2021-01-18T19:02:17 |
{"gard": ["1100"], "mesh": ["D044542"], "umls": ["C0175704"], "orphanet": ["500"], "wikidata": ["Q1798016"]}
|
Levy et al. (2003) described 3 sibs, a boy and 2 girls, with congenital myopathy, bullous eruption of the skin, secretory diarrhea, apparent zinc deficiency, failure to thrive, deafness, and microcephaly. The joint contractures resolved with age. Cryptorchidism was present in the male, and congenital heart disease was present in 1 of the 3 sibs. Myopathy improved with age and the blistering disappeared in the neonatal period without recurrence. The parents, of Italian ancestry, were not consanguineous and there were no other affected relatives. The disorder was thought to be autosomal recessive.
The syndrome in the sibs reported by Levy et al. (2003) appeared to be distinct from known syndromes of secretory diarrhea, myopathy, deafness, microcephaly, and zinc deficiency. Linkage analysis performed on DNA from the patients and their parents showed no linkage to markers on chromosome 12p12 flanking the GUCY2C gene (601330), which is a candidate gene for secretory diarrhea; to markers on chromosome 7q22-q31.1 flanking the DRA gene (126650), which is mutated in a form of secretory diarrhea (214700); or to markers on chromosome 15q22-qter flanking the MPI gene (154550), which is mutated in type Ib carbohydrate-deficient glycoprotein syndrome (602579). Because of the association of myopathy and blistering skin lesions in the sibs they reported, Levy et al. (2003) considered a recessive form of congenital muscular dystrophy in epidermolysis bullosa simplex (226670), which is caused by mutations in the PLEC1 gene (PLEC1; 601282). They excluded this disorder because of lack of histopathologic evidence for epidermolysis bullosa and the absence of PLEC1 gene mutations in 1 of the patients. Moreover, secretory diarrhea had not been reported in the epidermolysis bullosa-muscular dystrophy syndrome, and the myopathy in the patients reported by Levy et al. (2003) tended to improve with age rather than progress, as in epidermolysis bullosa-muscular dystrophy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[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
|
SECRETORY DIARRHEA, MYOPATHY, AND DEAFNESS
|
c1843757
| 8,072 |
omim
|
https://www.omim.org/entry/607540
| 2019-09-22T16:09:02 |
{"mesh": ["C564382"], "omim": ["607540"]}
|
Tyrosinemia type 1 (HTI) is an inborn error of tyrosine catabolism caused by defective activity of fumarylacetoacetate hydrolase (FAH) and is characterized by progressive liver disease, renal tubular dysfunction, porphyria-like crises and a dramatic improvement in prognosis following treatment with nitisinone.
## Epidemiology
Birth incidence is 1/100,000 in most areas but is more common is some regions, notably in Québec, Canada.
## Clinical description
HT1 is clinically heterogenous. Symptoms may start during the first few months (acute type), in second half of the first year (subacute type) or in the following years up to adulthood (chronic type). In the acute type, manifestations of hepatic failure predominate (bleeding diathesis, hypoglycemia, ascites etc) with frequent sepsis and rapid deterioration. Mild proximal tubular disease is usually present. Subacute type manifests a similar but less severe clinical picture presenting usually with hepatomegaly or hypophosphatemic rickets (due to tubular dysfunction). Intercurrent illness may precipitate hepatic crisis. Chronic type presents with hepatomegaly secondary to cirrhosis and often tubulopathy, leading to rickets and renal failure. Neurological crises are infrequent presenting symptoms; however they can complicate any type of the disease when untreated. The crises resemble those of acute intermittent porphyria, manifesting with painful parasthesias (causing patients to assume ophisthotonic position, self mutilation), autonomic signs (hypertension, tachycardia, ileus) and respiratory decompensation. All patients stand a high risk of developing hepatocellular carcinoma (HCC) secondary to cirrhosis.
## Etiology
The deficiency of fumarylacetoacetate hydrolase, FAH(15q23-q25) results in accumulation of fumaryl- and maleyl-acetoacetate that cause hepatorenal damage. The accumulation of their derivatives (succinyl-acetone (SA) and succinyl-acetoacetate (SAA)) leads to accumulation of delta-aminolevulinate (δ-ALA) resulting in inhibition of porphobilinogen synthesis and porphyria-like crises.
## Diagnostic methods
Liver synthetic functions are usually severely affected with coagulopathy and hypoalbuminemia. Elevated levels of SA in dried blood spots, plasma or urine are pathognomonic. Other abnormalities include elevated α -fetoprotein (especially in acutely ill infants), increased plasma levels of tyrosine, phenylalanine and methionine, increased urinary δ-ALA excretion and features of Fanconi tubulopathy. Confirmation of diagnosis is usually by mutation analysis.
## Differential diagnosis
Differential metabolic diagnoses include classic galactosemia, hereditary fructose intolerance, and fructose 1,6 diphosphatase deficiency, Wilson's disease and some mitochondrial disorders (see these terms).
## Antenatal diagnosis
Prenatal diagnosis is feasible by mutation analysis on chorionic villus sampling (CVS), if the familial causative mutations are known or alternatively by FAH assay on CVS or amniocytes and determination of SA levels in amniotic fluid. Newborn screening is available in many countries.
## Genetic counseling
HT1 is an autosomal recessive disorder with a 25% risk of recurrence within a family.
## Management and treatment
As soon as the diagnosis is confirmed (or even highly suspected) start nitisinone (NTBC) orally in a dose of 1-2 mg/kg once a day along with the emergency treatment for acute liver failure if necessary. A protein-restricted diet must also be started in parallel. Patients should be referred to a specialist center for long term management. Liver transplantation should be considered in acutely ill infants (if liver function fails to respond to nitisinone within a week), suspected or diagnosed HCC, and non-compliance or unavailability of medical treatment.
## Prognosis
Nitisinone treatment, combined with a low-protein diet allows most the patients to survive in good health. The prognosis is dominated by the risk of HCC.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Tyrosinemia type 1
|
c0268490
| 8,073 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=882
| 2021-01-23T19:05:19 |
{"gard": ["2658"], "mesh": ["D020176"], "omim": ["276700"], "umls": ["C0268490"], "icd-10": ["E70.2"], "synonyms": ["FAH deficiency", "Fumarylacetoacetase deficiency", "Fumarylacetoacetate hydrolase deficiency", "Hepatorenal tyrosinemia", "Tyrosinemia type I"]}
|
A rare subtype of axonal hereditary motor and sensory neuropathy characterized by distal muscle weakness and atrophy (principally of peroneal muscles) associated with distal sensory loss (tactile, vibration), pes cavus present since infancy or childhood, and axonal swelling with neurofilament accumulation on nerve biopsy. Other features may include hand muscle involvement, hypo/arreflexia, gait disturbances, muscle cramps, toe abnormalities and mild 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 dominant Charcot-Marie-Tooth disease type 2 with giant axons
|
c4013360
| 8,074 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=401964
| 2021-01-23T17:36:50 |
{"gard": ["12447"], "omim": ["610100"], "icd-10": ["G60.0"], "synonyms": ["Autosomal dominant hereditary motor and sensory neuropathy type 2 with giant axons", "CMT2 with giant axons", "HMSN2 with giant axons"]}
|
Nägele's obliquity is the presentation of the anterior parietal bone to the birth canal during vaginal delivery with the biparietal diameter being oblique to the brim of the pelvis.[1] The synonym for this presentation is anterior asynclitism.[2] It was first described in 1777 by German Karl Nägele.[3][4]
## References[edit]
1. ^ "Naegele obliquity | definition of Naegele obliquity by Medical dictionary". medical-dictionary.thefreedictionary.com. Retrieved 2017-04-11.
2. ^ "Anterior asynclitism definition | Drugs.com". drugs.com. Retrieved 2017-04-11.
3. ^ The American Illustrated Medical Dictionary. W.B. Saunders Company. 1916. p. 694; digitized by The Ohio State University
4. ^ Mosby (2016). Mosby's Medical Dictionary. p. 1191. ISBN 9780323414258.
* v
* t
* e
Pregnancy and childbirth
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* Birth control
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Conception
* Assisted reproductive technology
* Artificial insemination
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Testing
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Prenatal
Anatomy
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Delivery
* Bloody show
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* Position
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Postpartum
Maternal
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* Doula
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Infant
* Adaptation to extrauterine life
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Obstetric history
* Gravidity and parity
This human reproduction 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
|
Naegele obliquity
|
None
| 8,075 |
wikipedia
|
https://en.wikipedia.org/wiki/Naegele_obliquity
| 2021-01-18T18:48:49 |
{"wikidata": ["Q30314531"]}
|
## Clinical Features
In 2 distantly related Amish boys, McKusick et al. (1968) observed absence deformity of the left leg, congenital cataract, and progressive scoliosis. One of the boys had also partial duplication of the left foot, imperforate anus, and partial paralysis of muscles supplied by the third cranial nerve. Roentgenographic evidence of generalized spondyloepiphyseal dysplasia was present in both, and both were shorter of stature than was accounted for solely by the spinal curvature. Both had dysplasia of the optic nerve and serious visual impairment even after extraction of the cataracts. Intellectual capacity was unimpaired.
Inheritance
All 4 parents of the boys with this rare disorder shared at least 2 ancestral couples in common, strongly suggesting autosomal recessive inheritance (McKusick et al., 1968).
Spine \- Progressive scoliosis Limbs \- Absent leg Eyes \- Congenital cataract 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
|
LEG, ABSENCE DEFORMITY OF, WITH CONGENITAL CATARACT
|
c1855523
| 8,076 |
omim
|
https://www.omim.org/entry/246000
| 2019-09-22T16:25:58 |
{"mesh": ["C565442"], "omim": ["246000"], "orphanet": ["2310"]}
|
## Clinical Features
Both proximal symphalangism (185800) and distal symphalangism (185700) are autosomal dominant disorders characterized by fusion of the proximal or distal interphalangeal joints, respectively. Kantaputra et al. (2002) described a seemingly novel form of distal symphalangism. A Thai mother and son had brachydactyly, especially at the distal segment of the digits, fusion of the distal interphalangeal joints, and absence of digital phalanges 3 and 4. They also had cone-shaped epiphyses of middle phalanges 2 and 4, radial-ray carpal-bone anomalies, narrowing of the zygomatic arch, and dental pulp stones. The second fingers were predominantly affected. Proximal symphalangism was ruled out because of the pattern of the symphalangism and because no mutation in the NOG gene (602991) was found. Distal symphalangism shares many features with brachydactyly type B (113000), including aplasia/hypoplasia of the middle and distal phalanges of fingers 2 to 5 and fingernail dysplasia. This diagnosis was ruled out by the absence of mutation in the ROR2 gene (ROR2; 602337), which has been found in cases of type B brachydactyly.
INHERITANCE \- Autosomal dominant HEAD & NECK Teeth \- Dental pulp stones \- Microdontia SKELETAL Skull \- Narrowed zygomatic arch Hands \- Short fingers \- Distal symphalangism \- Aplastic/hypoplastic middle phalanges (fingers 2-5) \- Aplastic/hypoplastic distal phalanges (fingers 2-5) \- Cone-shaped epiphyses of middle phalanges \- Absent scaphoid bone \- Absent trapezium bone \- Absent trapezoid bone \- Absent pisiform bone Feet \- Distal symphalangism \- Aplastic/hypoplastic middle phalanges (toes 2-5) \- Aplastic/hypoplastic distal phalanges (toes 2-5) SKIN, NAILS, & HAIR Nails \- Absent nails \- Hypoplastic nails ▲ 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
|
SYMPHALANGISM, DISTAL, WITH MICRODONTIA, DENTAL PULP STONES, AND NARROWED ZYGOMATIC ARCH
|
c1847185
| 8,077 |
omim
|
https://www.omim.org/entry/606895
| 2019-09-22T16:09:50 |
{"mesh": ["C538148"], "omim": ["606895"]}
|
MERRF (Myoclonic Epilepsy with Ragged Red Fibers) syndrome is a mitochondrial encephalomyopathy characterized by myoclonic seizures.
## Epidemiology
The prevalence in the general population of Europe has been estimated at 0.9 in 100 000, but the disease seems to be more common in the USA.
## Clinical description
Patients usually present during adolescence or early adulthood with myoclonic epilepsy, sometimes with neurosensory deafness, optic atrophy, short stature or peripheral neuropathy. A few cases have been associated with lipomatosis, cardiomyopathy, pigmentary retinopathy, ophthalmoparesis and/or pyramidal signs. The disease is progressive with worsening of the epilepsy and onset of additional symptoms including ataxia, deafness, muscle weakness, and dementia. Magnetic resonance imaging of the brain may show cortical atrophy, basal ganglia calcifications and leucodystrophy. Clinical manifestations may vary greatly between patients from the same family and between families.
## Etiology
MERRF syndrome is caused by mutations in the mitochondrial DNA. Over 80% of individuals with MERRF syndrome carry the 8344A>G mutation in the lysine transfer RNA (tRNA Lys) gene (MTTK). Other mutations have been found in other transfer RNA genes or in the MTND5 gene. They may be associated with MERRF/MELAS overlap syndrome, in which affected individuals also suffer from stroke-like episodes.
## Diagnostic methods
The diagnosis of MERRF syndrome relies on the demonstration of abnormal lactate accumulation in blood or, more often, in the cerebrospinal fluid, and on the muscle biopsy, which reveals the presence of cytochrome c oxidase negative muscle fibers and ragged red fibers. Biochemical analysis of muscle often shows cytochrome c oxidase deficiency or combined respiratory chain defect. Heteroplasmy (i.e. coexistence of the mutant form with a residual population of wild type mitochondrial DNA) should be taken into account during identification of the causal. The proportion of the mutation may differ considerably between tissues. However, in MERRF syndrome, this proportion is most often very high (above 90%) in every tissue and the mutation may therefore be investigated in blood.
## Antenatal diagnosis
The possibility of heterogeneous proportions of the mutation between tissues theoretically hampers prenatal diagnosis.
## Genetic counseling
The heteroplasmy makes genetic counseling very arduous in MERRF syndrome. Mitochondrial DNA mutations are transmitted through maternal inheritance. An affected man cannot transmit the disease. The mutation will be transmitted along the maternal lineage but its proportion is essentially unpredictable. Although higher proportions of the mutation in the blood of the mother result in a higher risk of having a child with severe phenotype, there are many examples of extreme segregation of the mutation from mother to child, which prevent efficient genetic counseling at an individual level.
## Management and treatment
As with other mitochondrial encephalomyopathies, there is no specific treatment for MERRF syndrome. Seizures can be treated with conventional anticonvulsant therapies but valporic acid should be administered with care and in association with L-carnitine. In the absence of proper clinical trials, it is difficult to evaluate the effect of proposed supportive treatment such as coenzyme Q10 and its analogue idebenone, carnitine, etc.
## Prognosis
The prognosis for patients with MERRF syndrome is globally poor because of the progressive nature of the disease. However, the severity varies greatly and some patients, mainly those with non-cerebral presenting symptoms, may have a prolonged survival with relatively little handicap.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
MERRF
|
c0162672
| 8,078 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=551
| 2021-01-23T17:55:46 |
{"gard": ["7144"], "mesh": ["D017243"], "omim": ["545000"], "umls": ["C0162672"], "icd-10": ["G71.3"], "synonyms": ["Fukuhara syndrome", "Myoclonus epilepsy associated with ragged-red fibres"]}
|
Accommodative infacility
SpecialtyOphthalmology
Accommodative infacility also known as accommodative inertia[1] is the inability to change the accommodation of the eye with enough speed and accuracy to achieve normal function. This can result in visual fatigue, headaches, and difficulty reading.[2] The delay in accurate accommodation also makes vision blurry for a moment when switching between distant and near objects. The duration and extent of this blurriness depends on the extent of the deficit.[3]
## Signs and symptoms[edit]
Most common symptom of accommodative infacility is difficulty in changing focus from one distance to other.[1]
## Treatment[edit]
Vision assessment and cycloplegic refraction should be done. If there is any refractive errors, it should be corrected before considering orthoptic treatments. The accommodative infacility is commonly treated with vision therapy/orthoptics; one study found that 12 weeks of treatment had a significant effect on visual accommodation.[4]
## References[edit]
1. ^ a b William J., Benjamin (2006). "Accommodation, the Pupil, and Presbyopia". Borish's clinical refraction (2nd ed.). St. Louis Mo.: Butterworth Heinemann/Elsevier. p. 112. ISBN 978-0-7506-7524-6.
2. ^ Cacho-Martínez, Pilar; Cantó-Cerdán, Mario; Carbonell-Bonete, Stela; García-Muñoz, Ángel (2015-08-16). "Characterization of Visual Symptomatology Associated with Refractive, Accommodative, and Binocular Anomalies". Journal of Ophthalmology. 2015 (2015): 895803. doi:10.1155/2015/895803. PMC 4553196. PMID 26351575.
3. ^ Hennessey, Daniel; Iosue, Richard A.; Rouse, Michael W. (1984). "Relation of Symptoms to Accommodative Infacility of School-Aged Children". Optometry and Vision Science. 61 (3): 177–183. ISSN 1538-9235. PMID 6720863.
4. ^ Scheiman, Mitchell; Cotter, Susan; Kulp, Marjean Taylor; Mitchell, G. Lynn; Cooper, Jeffrey; Gallaway, Michael; Hopkins, Kristine B.; Bartuccio, Mary; Chung, Ida (2011). "Treatment of Accommodative Dysfunction in Children: Results from an Random Clinical Trial". Optometry and Vision Science. 88 (11): 1343–1352. doi:10.1097/OPX.0b013e31822f4d7c. ISSN 1040-5488. PMC 3204163. PMID 21873922.
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* 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
|
Accommodative infacility
|
c0729255
| 8,079 |
wikipedia
|
https://en.wikipedia.org/wiki/Accommodative_infacility
| 2021-01-18T18:39:41 |
{"umls": ["C0729255", "C2938955"], "wikidata": ["Q16001577"]}
|
A number sign (#) is used with this entry because thyroid dyshormonogenesis-6 (TDH6) is caused by homozygous or compound heterozygous mutation in the DUOX2 gene (606759) on chromosome 15q21.
For a general phenotypic description and a discussion of genetic heterogeneity of thyroid dyshormonogenesis, see TDH1 (274400).
Clinical Features
Moreno et al. (2002) described a patient with permanent and severe thyroid hormone deficiency and a complete iodide organification defect who was one of a group of 9 identified through a screening program for congenital hypothyroidism. At screening, this patient had thyroxine levels below the limit of detection and very high thyrotropin levels. The other 8 patients studied had mild transient congenital hypothyroidism and a partial iodide organification defect.
Molecular Genetics
Moreno et al. (2002) analyzed DNA of 9 patients with idiopathic congenital hypothyroidism and an iodide organification defect for mutations in the genes for DUOX1 (606758) and DUOX2. In a patient with permanent and severe thyroid hormone deficiency and a complete iodide organification defect, Moreno et al. (2002) detected homozygosity for a nonsense mutation (606759.0001) in the DUOX2 gene that eliminated all functional domains of the protein. Three of the 8 patients with mild transient congenital hypothyroidism and a partial iodide organification defect had heterozygous mutations in the DUOX2 gene that prematurely terminated the protein, thus abolishing its functional domains. Moreno et al. (2002) observed that monoallelic mutations, associated with mild, transient hypothyroidism, resulted in insufficient thyroid production of hydrogen peroxide, which prevented the synthesis of sufficiently large quantities of thyroid hormones required at the beginning of life.
In 2 brothers with congenital hypothyroidism, Vigone et al. (2005) identified compound heterozygosity for mutations in the DUOX2 gene (606759.0003 and 606759.0004). The euthyroid parents were heterozygous for the mutations. The brothers were reevaluated at age 4 after 1 month of levothyroxine withdrawal, at which time they had mildly increased serum thyroid-stimulating hormone levels and normal free thyroid hormone levels. They were at the 75th centile in both height and weight and had adequate cognitive development (IQs of 103 and 112, respectively) and normal hearing. Due to persistent hyperthyrotropinemia, levothyroxine was restarted in both children.
Park and Chatterjee (2005) reviewed the genetics of primary congenital hypothyroidism, summarizing the different phenotypes associated with known genetic defects and proposing an algorithm for investigating the genetic basis of the disorder.
INHERITANCE \- Autosomal recessive ENDOCRINE FEATURES \- Hypothyroidism, congenital LABORATORY ABNORMALITIES \- Iodide organification defect \- Low T3 \- Low T4 \- Elevated TSH \- Increased RAI (radioactive iodine) uptake MISCELLANEOUS \- Heterozygotes have mild, transient hypothyroidism in infancy MOLECULAR BASIS \- Caused by mutation in the dual oxidase 2 gene (DUOX2, 606759.0001 ) ▲ 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
|
THYROID DYSHORMONOGENESIS 6
|
c1848805
| 8,080 |
omim
|
https://www.omim.org/entry/607200
| 2019-09-22T16:09:32 |
{"mesh": ["C564766"], "omim": ["274400", "607200"], "orphanet": ["95716"], "synonyms": ["THYROID HORMONOGENESIS, GENETIC DEFECT IN, 6", "Alternative titles", "Thyroid dyshormonogenesis", "HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 6"]}
|
Sight-threatening emergency
Retrobulbar bleeding
Other namesRetrobulbar hemorrhage
Anatomy of the orbit
SpecialtyOphthalmology
FrequencyRare[1]
Retrobulbar bleeding, also known as retrobulbar hemorrhage, is when bleeding occurring behind the eye.[1] Symptoms may include pain, bruising around the eye, the eye bulging outwards, vomiting, and vision loss.[1]
Retrobulbar bleeding can occur as a result of trauma to the eye, surgery to the eye, blood thinners, or an arteriovenous malformation.[1]
In those with significant symptoms lateral canthotomy with cantholysis is indicated.[1] This is recommended to be carried out within two hours.[1] The condition is rare.[1]
## References[edit]
1. ^ a b c d e f g "Retrobulbar hemorrhage". EyeWiki. Retrieved 7 May 2020.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Retrobulbar bleeding
|
c0302497
| 8,081 |
wikipedia
|
https://en.wikipedia.org/wiki/Retrobulbar_bleeding
| 2021-01-18T19:02:48 |
{"mesh": ["D019315"], "wikidata": ["Q42263577"]}
|
Pseudohypoparathyroidism type 1c (PHP1c) is a rare type of pseudohypoparathyroidism (PHP; see this term) characterized by resistance to parathyroid hormone (PTH) and other hormones, which manifests with hypocalcemia, hyperphosphatemia and elevated PTH levels, a constellation of clinical features collectively termed Albright's hereditary osteodystrophy (AHO; see this term), but normal activity of the stimulatory protein G (Gs alpha).
## Epidemiology
The prevalence is unknown.
## Clinical description
Clinical manifestations of PHP1c are similar to those seen in pseudohypoparathyroidism type 1a (PHP1a; see this term). They display the symptoms and signs of AHO (brachydactyly (most often the shortening of the 3, 4 and 5th metacarpals), rounded face, short stature, central obesity, subcutaneous ossifications and variable development delay) as well as PTH-resistance leading to hypocalcemia and hyperphosphatemia, and resistance towards TSH and, sometimes, other hormones.
## Etiology
The exact etiology is unknown as mutations in the GNAS gene (20q13) are only rarely found. Other components of the cAMP-dependent signaling pathway, such as adenylyl cyclase, inhibitory G proteins, or phosphodiesterases might be impaired.
## Genetic counseling
In familial cases the disease is inherited autosomal dominantly and genetic counseling is possible.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[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
|
Pseudohypoparathyroidism type 1C
|
c2932716
| 8,082 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79444
| 2021-01-23T16:54:25 |
{"gard": ["10681"], "mesh": ["C548076"], "omim": ["612462"], "umls": ["C2932716"], "icd-10": ["E20.1"]}
|
A group of rare inherited non-syndromic ichthyoses characterized by mutations in keratin genes. Mutations in KRT1 and KRT10 cause most cases of epidermolytic ichthyosis (EI), as well as congenital reticular ichthyosiform erythroderma (CRIE). EI manifests at birth with generalized blistering, which later transforms into hyperkeratosis. Severe palmoplantar involvement is suggestive of the presence of a KRT1 mutation. CRIE patients present at birth with erythroderma and scaling, often with a collodion membrane, and gradually develop confetti-like clear areas of normal skin. KRT2 mutations are associated with superficial epidermolytic ichthyosis (SEI), which is clinically similar to EI, but generally milder and more localized.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Keratinopathic ichthyosis
|
c4511307
| 8,083 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=281103
| 2021-01-23T18:34:52 |
{"synonyms": ["KPI"]}
|
A number sign (#) is used with this entry because of evidence that contractures, pterygia, and variable skeletal fusions syndrome-1A (CPSKF1A) is caused by heterozygous mutation in the MYH3 gene (160720) on chromosome 17p13.
Heterozygous mutation in the MYH3 gene can also cause distal arthrogryposes, including DA2A (193700) and DA2B3 (618436).
Description
Contractures, pterygia, and variable skeletal fusions syndrome-1A (CPSKF1) is characterized by contractures of proximal and distal joints, pterygia involving the neck, axillae, elbows, and/or knees, as well as variable vertebral, carpal, and tarsal fusions and short stature. Progression of vertebral fusions has been observed, and inter- and intrafamilial variability has been reported (Carapito et al., 2016; Zieba et al., 2017; Cameron-Christie et al., 2018).
An autosomal recessive form of CPSKF (CPSKF1B; 618469) is caused by compound heterozygous mutation in the MYH3 gene.
Clinical Features
McKeown and Harris (1988) described a multiple pterygium syndrome in 3 children and their mother. Great variability in severity was observed among the affected subjects. Ptosis and severe scoliosis due to hemivertebrae were present in some. The mother had vertebral fusions, and 2 of the children exhibited both vertebral and carpal fusions; radiographs of the feet were not reported. The mildest case was similar to distal arthrogryposis type IIB (108145), in which joint contractures are associated with ptosis. The most severely affected case closely resembled the autosomal recessive Escobar variant of multiple pterygium syndrome (EVMPS; 265000). The authors speculated that some isolated cases may in fact represent this dominant disorder. The most severely affected members of the family were exposed to phenobarbitone and phenytoin during pregnancy. Several of the affected members had a functional palate abnormality producing nasal speech.
Wiles et al. (1992) described a 12-year-old Australian girl with short-trunk short stature and scoliosis, who had a rigid spine and mild lumbar lordosis. Respiratory function tests showed a mild restrictive pattern. X-rays showed delayed bone age, platyspondyly, fusion of vertebral bodies in the cervical, thoracic, and lumbar spine, fusion of posterior elements in the thoracic and lumbar spine, foreshortened lordotic thoracic spine with scoliosis, kyphosis of lumbar spine, and horizontal sacrum. In addition, she had unilateral carpal coalition with fusion of the lunate and triquetrum bones. Tarsal findings were not reported. Cameron-Christie et al. (2018) restudied the girl reported by Wiles et al. (1992) and tabulated additional findings, including tarsal fusion, short webbed neck, and elbow contractures.
Prontera et al. (2006) reported a 3-year-old girl with classic clinical features of EVMPS, including vertebral fusions and multiple anterior vertebral clefts. Clinical examination of the father showed subtle minor signs of the disorder, including difficulty in opening the mouth widely, scoliosis, pectus excavatum, slight cutaneous syndactyly, malformed carpal bones, and an altered metacarpal-phalangeal pattern. The authors suggested that either this family shows autosomal dominant inheritance or the father is a manifesting heterozygote. Molecular studies were not performed.
Prontera et al. (2006) reviewed the features of mildly affected members of 3 previously reported families with dominant multiple pterygium syndrome and noted that one or more of the following features were present: ptosis, posteriorly rotated ears, webbing of the neck, axillae, elbows, or knees, vertebral anomalies such as vertebral fusion or hemivertebrae, carpal bone anomalies and carpal fusion, fusion of tarsal bones, and pelvic dysplasia.
Isidor et al. (2008) reported a 30-year-old French mother and her 9-year-old son with a clinical diagnosis of spondylocarpotarsal synostosis syndrome (SCT; 272460). Both exhibited short stature, progressive scoliosis, hearing loss, cleft palate, and short neck. The mother had fusion of cervical vertebrae in childhood that progressed to include thoracic vertebrae by age 26, abnormal segmentation of thoracic vertebrae, limited extension of both elbows, and carpal and tarsal synostosis. Evaluation of her son at age 8.5 years showed scoliosis with fusion of thoracic bodies and a carpal bone age of 3 years; no carpal bone fusion was observed, which was attributed to the major bone age delay.
Carapito et al. (2016) studied the mother and son originally reported by Isidor et al. (2008) (family 1) as well as an unrelated 27-year-old mother and her 6-year-old daughter (family 2) who had been clinically diagnosed with SCT. In family 2, both mother and daughter had carpal and tarsal fusions, but otherwise showed intrafamilial variability; the mother had normal stature and mobility, whereas the daughter was severely disabled with short stature, major orthopedic malformations, and pterygia of the neck, knees, and ankles. The daughter also had cardiovascular anomalies, including bicuspid aortic valve with mild aortic insufficiency and slight supravalvular stenosis as well as patent ductus arteriosus requiring surgery, and she experienced an episode of respiratory failure due to restrictive lung disease. Vertebral fusions had been diagnosed prenatally in the daughter and she showed severe scoliosis with diffuse vertebral segmentation abnormalities; the mother had fusions of C1-C2 and C6-C7 but did not show scoliosis. All 4 patients exhibited mild dysmorphic features, including downslanting palpebral fissures, low-set ears, and low hairline. Carapito et al. (2016) noted phenotypic overlap between SCT and multiple pterygium syndrome.
Zieba et al. (2017) studied 3 probands clinically diagnosed with SCT from the International Skeletal Dysplasia Registry: a 3-year-old boy (R06-109A) and 2 adult women (R07-183B and R12-336A). There were vertebral fusions in the cervical, thoracic, lumbar, and sacral regions of the spine, as well as carpal and tarsal coalitions. X-rays demonstrated the progressive nature of the vertebral fusions, ranging from mild disc space narrowing in the boy to vertebral fusions and severe scoliosis in the women. All 3 patients had bilateral fifth-finger clinodactyly. The boy had a cleft palate. One woman (R07-183B) had mild hand contractures with syndactyly as well as elbow and knee dislocations, and underwent surgery as a child to correct overlapping fifth toes. She was a member of a large family in which her brother, father, 2 paternal uncles, and her son were also affected. Most affected relatives reported only scoliosis and vertebral fusions, some had mild hand contractures, and the proband's son had cleft palate. None of the affected individuals were reported to have congenital pterygium, severe camptodactyly, or equinovarus deformities.
Scala et al. (2018) studied an 8.5-year-old Italian boy who exhibited severely limited extension of the elbows, wrists, knees, and ankles, as well as facial features consistent with Sheldon-Hall syndrome (see DA2B3, 618436), including triangular face, prominent nasolabial folds and chin, low-set ears with uplifted earlobes, downslanting palpebral fissures, and wide philtrum. In addition, he had unilateral carpal bone fusion, multiple cervical and thoracic vertebral fusions, and mild thoracolumbar scoliosis. The authors stated that this was the first report of a typical Sheldon-Hall syndrome phenotype accompanied by vertebral and carpal fusions.
Cameron-Christie et al. (2018) reported 4 patients from 3 families, including the Australian girl (family 9) originally described by Wiles et al. (1992), who were heterozygous for mutations in the MYH3 gene. All of the patients exhibited vertebral fusions with scoliosis, carpal/tarsal fusions, and variable joint contractures. Other features included facial dysmorphism, short neck, absent finger flexion creases, and webbing of the neck and fingers. In a Dutch family (family 2), an affected brother and sister had inherited the mutation from their mother, who exhibited only camptodactyly.
Molecular Genetics
By exome sequencing in 3 families in which affected individuals had contractures, pterygia of the knees and neck, and vertebral fusions, which Bamshad et al. (1996) had classified as distal arthrogryposis-8 (DA8), Chong et al. (2015) excluded mutation in 8 genes previously identified in patients with multiple pterygium syndromes and identified heterozygous mutations in the MYH3 gene (160720.0009-160720.0011). The mutations, which segregated with disease in the respective families, involved highly conserved residues and were not found in public databases.
In a French mother and son (family 1) with joint mobility limitation and vertebral and carpal fusions, who were previously studied by Isidor et al. (2008) and found to be negative for mutation in the FLNB (603381) and NOG (602991) genes, Carapito et al. (2016) performed exome sequencing and identified heterozygosity for a missense mutation in the MYH3 gene (T333R; 160720.0013). An unrelated mother and daughter (family 2) with multiple pterygia and vertebral, carpal, and tarsal fusions were found to be heterozygous for a different missense mutation in MYH3 (L1344P; 160720.0014).
By exome sequencing in 3 probands from the International Skeletal Dysplasia Registry who had vertebral, carpal, and tarsal fusions, Zieba et al. (2017) identified heterozygosity for mutations in the MYH3 gene (see, e.g., 160720.0011).
In an 8.5-year-old Italian boy with multiple joint contractures and facial dysmorphism reminiscent of DA2B3, as well as wide neck, mild scoliosis, and vertebral and carpal fusions, who was negative for mutation in Noonan syndrome (see 163950)-associated genes, Scala et al. (2018) sequenced the MYH3 gene and identified heterozygosity for a missense mutation (F287V; 160720.0015).
From a cohort of 16 patients with multiple contractures, pterygia, vertebral fusions, and variable carpal and/or tarsal fusions, who were known to be negative for mutation in the FLNB gene, Cameron-Christie et al. (2018) identified 4 patients from 3 families with heterozygous mutations in the MYH3 gene, including the Australian girl described by Wiles et al. (1992) (see, e.g., 160720.0016). In another 6 patients from 4 unrelated families from the same cohort, Cameron-Christie et al. (2018) identified compound heterozygosity for MYH3 mutations (see CPSKF1B, 618469).
### Exclusion Studies
In a family diagnosed with distal arthrogryposis-8, in which an affected father and daughter lacked popliteal or antecubital pterygia as well as vertebral fusions and had ventricular septal defects, Chong et al. (2015) found no mutation in the MYH3 gene. The authors suggested that the phenotype in this family might represent a distinct mendelian condition.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly (in some patients) Ears \- Low-set posteriorly rotated ears \- Hearing loss (in some patients) Eyes \- Ptosis \- Downslanting palpebral fissures Nose \- Long nasal bridge Mouth \- Cleft palate Neck \- Short neck \- Webbing of neck CHEST External Features \- Short trunk \- Pectus carinatum (rare) \- Barrel-shaped chest (rare) SKELETAL \- Bone age delay (in some patients) Skull \- Craniosynostosis (in some patients) Spine \- Scoliosis \- Vertebral fusion \- Hemivertebrae \- Mild cervical spinal stenosis (rare) \- Spondylolisthesis (rare) Pelvis \- Sacral anomaly Limbs \- Elbow contractures \- Limited forearm supination \- Hip contractures (in some patients) \- Knee contractures Hands \- Carpal fusion \- Fifth-finger clinodactyly \- Camptodactyly Feet \- Tarsal fusion SKIN, NAILS, & HAIR Skin \- Multiple pterygia \- Hypoplastic flexion creases \- Antecubital webbing \- Popliteal webbing \- Webbing of fingers MISCELLANEOUS \- Inter- and intrafamilial phenotypic variability MOLECULAR BASIS \- Caused by mutation in the embryonic skeletal muscle myosin heavy chain-3 gene (MYH3, 160720.0009 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[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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CONTRACTURES, PTERYGIA, AND VARIABLE SKELETAL FUSIONS SYNDROME 1A
|
c1867440
| 8,084 |
omim
|
https://www.omim.org/entry/178110
| 2019-09-22T16:35:32 |
{"doid": ["0080110"], "mesh": ["C566739"], "omim": ["178110"], "orphanet": ["65743"], "synonyms": ["Alternative titles", "MULTIPLE PTERYGIUM SYNDROME, AUTOSOMAL DOMINANT", "PTERYGIUM SYNDROME, MULTIPLE", "ARTHROGRYPOSIS, DISTAL, TYPE 8, FORMERLY"]}
|
Skin disease
Stevens–Johnson syndrome
Man with characteristic skin lesions of
Stevens–Johnson syndrome
SpecialtyDermatology
SymptomsFever, skin blisters, skin peeling, painful skin, red eyes[1]
ComplicationsDehydration, sepsis, pneumonia, multiple organ failure.[1]
Usual onsetAge < 30[2]
CausesCertain medications, certain infections, unknown[2][1]
Risk factorsHIV/AIDS, systemic lupus erythematosus, genetics[1]
Diagnostic method<10% of the skin involved, skin biopsy[2]
Differential diagnosisChickenpox, staphylococcal epidermolysis, staphylococcal scalded skin syndrome, autoimmune bullous disease[3]
TreatmentHospitalization, stopping the cause[2]
MedicationPain medication, antihistamines, antibiotics, corticosteroids, intravenous immunoglobulins[2]
PrognosisMortality ~7.5%[1][4]
Frequency1–2 per million per year (together with TEN)[1]
Stevens–Johnson syndrome (SJS) is a type of severe skin reaction.[1] Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe.[1][3] Erythema multiforme (EM) is generally considered a separate condition.[5] Early symptoms of SJS include fever and flu-like symptoms.[1] A few days later, the skin begins to blister and peel, forming painful raw areas.[1] Mucous membranes, such as the mouth, are also typically involved.[1] Complications include dehydration, sepsis, pneumonia and multiple organ failure.[1]
The most common cause is certain medications such as lamotrigine, carbamazepine, allopurinol, sulfonamide antibiotics and nevirapine.[1] Other causes can include infections such as Mycoplasma pneumoniae and cytomegalovirus, or the cause may remain unknown.[2][1] Risk factors include HIV/AIDS and systemic lupus erythematosus.[1]
The diagnosis of Stevens–Johnson syndrome is based on involvement of less than 10% of the skin.[2] It is known as TEN when more than 30% of the skin is involved and considered an intermediate form when 10–30% is involved.[3] SJS/TEN reactions are believed to follow a type IV hypersensitivity mechanism.[6] It is also included with drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP) and toxic epidermal necrolysis in a group of conditions known severe cutaneous adverse reactions (SCARs).[7]
Treatment typically takes place in hospital such as in a burn unit or intensive care unit.[2] Efforts may include stopping the cause, pain medication, antihistamines, antibiotics, intravenous immunoglobulins or corticosteroids.[2] Together with TEN, SJS affects 1 to 2 people per million per year.[1] Typical onset is under the age of 30.[2] Skin usually regrows over two to three weeks; however, complete recovery can take months.[2] Overall, the risk of death with SJS is 5 to 10%.[1][4]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Medications
* 2.2 Infections
* 3 Pathophysiology
* 3.1 T-cell receptors
* 3.2 ADME
* 4 Diagnosis
* 4.1 Pathology
* 4.2 Classification
* 5 Prevention
* 6 Treatment
* 7 Prognosis
* 8 Epidemiology
* 9 History
* 10 Notable cases
* 11 Research
* 12 References
* 13 External links
## Signs and symptoms[edit]
SJS usually begins with fever, sore throat, and fatigue, which is commonly misdiagnosed and therefore treated with antibiotics. SJS, SJS/TEN, and TEN are often heralded by fever, sore throat, cough, and burning eyes for 1 to 3 days.[8] Patients with these disorders frequently experience burning pain of their skin at the start of disease.[8] Ulcers and other lesions begin to appear in the mucous membranes, almost always in the mouth and lips, but also in the genital and anal regions. Those in the mouth are usually extremely painful and reduce the patient's ability to eat or drink. Conjunctivitis occurs in about 30% of children who develop SJS.[9] A rash of round lesions about an inch across arises on the face, trunk, arms and legs, and soles of the feet, but usually not the scalp.[10]
* Mucosal desquamation in a person with Stevens–Johnson syndrome
* Inflammation and peeling of the lips—with sores presenting on the tongue and the mucous membranes in SJS.
* Conjunctivitis in SJS
## Causes[edit]
SJS is thought to arise from a disorder of the immune system.[10] The immune reaction can be triggered by drugs or infections.[11] Genetic factors are associated with a predisposition to SJS.[12] The cause of SJS is unknown in one-quarter to one-half of cases.[12] SJS, SJS/TEN, and TEN are considered a single disease with common causes and mechanisms.[8]
Individuals expressing certain human leukocyte antigen (i.e. HLA) serotypes (i.e. genetic alleles), genetical-based T cell receptors, or variations in their efficiency to absorb, distribute to tissues, metabolize, or excrete (this combination is termed ADME) a drug are predisposed to develop SJS.
### Medications[edit]
See also: List of SJS-inducing substances
Although SJS can be caused by viral infections and malignancies, the main cause is medications.[13] A leading cause appears to be the use of antibiotics, particularly sulfa drugs.[12][14] Between 100 and 200 different drugs may be associated with SJS.[15] No reliable test exists to establish a link between a particular drug and SJS for an individual case.[13] Determining what drug is the cause is based on the time interval between first use of the drug and the beginning of the skin reaction. Drugs discontinued more than 1 month prior to onset of mucocutaneous physical findings are highly unlikely to cause SJS and TEN.[8] SJS and TEN most often begin between 4 and 28 days after culprit drug administration.[8] A published algorithm (ALDEN) to assess drug causality gives structured assistance in identifying the responsible medication.[13][16]
SJS may be caused by the medications rivaroxaban,[17] vancomycin, allopurinol, valproate, levofloxacin, diclofenac, etravirine, isotretinoin, fluconazole,[18] valdecoxib, sitagliptin, oseltamivir, penicillins, barbiturates, sulfonamides, phenytoin, azithromycin, oxcarbazepine, zonisamide, modafinil,[19] lamotrigine, nevirapine,[8] pyrimethamine, ibuprofen,[20] ethosuximide, carbamazepine, bupropion, telaprevir,[21][22] and nystatin.[23][24]
Medications that have traditionally been known to lead to SJS, erythema multiforme, and toxic epidermal necrolysis include sulfonamide antibiotics,[8] penicillin antibiotics, cefixime (antibiotic), barbiturates (sedatives), lamotrigine, phenytoin (e.g., Dilantin) (anticonvulsants) and trimethoprim. Combining lamotrigine with sodium valproate increases the risk of SJS.[25]
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a rare cause of SJS in adults; the risk is higher for older patients, women, and those initiating treatment.[26] Typically, the symptoms of drug-induced SJS arise within a week of starting the medication. Similar to NSAIDs, paracetamol (acetaminophen) has also caused rare cases[27][28] of SJS. People with systemic lupus erythematosus or HIV infections are more susceptible to drug-induced SJS.[10]
### Infections[edit]
The second most common cause of SJS and TEN is infection, particularly in children. This includes upper respiratory infections, otitis media, pharyngitis, and Epstein–Barr virus, Mycoplasma pneumoniae and cytomegalovirus infections. The routine use of medicines such as antibiotics, antipyretics and analgesics to manage infections can make it difficult to identify if cases were caused by the infection or medicines taken.[29]
Viral diseases reported to cause SJS include: herpes simplex virus (possibly; is debated), AIDS, coxsackievirus, influenza, hepatitis, and mumps.[12]
In pediatric cases, Epstein-Barr virus and enteroviruses have been associated with SJS.[12]
Recent upper respiratory tract infections have been reported by more than half of patients with SJS.[12]
Bacterial infections linked to SJS include group A beta-hemolytic streptococci, diphtheria, brucellosis, lymphogranuloma venereum, mycobacteria, Mycoplasma pneumoniae, rickettsial infections, tularemia, and typhoid.[12]
Fungal infections with coccidioidomycosis, dermatophytosis and histoplasmosis are also considered possible causes.[12] Malaria and trichomoniasis, protozoal infections, have also been reported as causes.[12]
## Pathophysiology[edit]
SJS is a type IV hypersensitivity reaction in which a drug or its metabolite stimulates cytotoxic T cells (i.e. CD8+ T cells) and T helper cells (i.e. CD4+ T cells) to initiate autoimmune reactions that attack self tissues. In particular, it is a type IV, subtype IVc, delayed hypersensitivity reaction dependent in part on the tissue-injuring actions of natural killer cells.[30] This contrasts with the other types of SCARs disorders, i.e., the DRESS syndrome which is a Type IV, Subtype IVb, hypersensitivity drug reaction dependent in part on the tissue-injuring actions of eosinophils[30][31] and acute generalized exanthematous pustulosis which is a Type IV, subtype IVd, hypersensitivity reaction dependent in part on the tissue-injuring actions of neutrophils.[30][32]
Like other SCARs-inducing drugs, SJS-inducing drugs or their metabolites stimulate CD8+ T cells or CD4+ T cells to initiate autoimmune responses. Studies indicate that the mechanism by which a drug or its metabolites accomplishes this involves subverting the antigen presentation pathways of the innate immune system. The drug or metabolite covalently binds with a host protein to form a non-self, drug-related epitope. An antigen presenting cell (APC) takes up these alter proteins; digests them into small peptides; places the peptides in a groove on the human leukocyte antigen (i.e. HLA) component of their major histocompatibility complex (i.e. MHC); and presents the MHC-associated peptides to T-cell receptors on CD8+ T cells or CD4+ T cells. Those peptides expressing a drug-related, non-self epitope on one of their various HLA protein forms (HLA-A, HLA-B, HLA-C, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, or HLA-DR) can bind to a T-cell receptor and thereby stimulate the receptor-bearing parent T cell to initiate attacks on self tissues. Alternatively, a drug or its metabolite may stimulate these T cells by inserting into the groove on a HLA protein to serve as a non-self epitope or bind outside of this groove to alter a HLA protein so that it forms a non-self epitope. In all these cases, however, a non-self epitope must bind to a specific HLA serotype (i.e. variation) in order to stimulate T cells. Since the human population expresses some 13,000 different HLA serotypes while an individual expresses only a fraction of them and since a SJS-inducing drug or metabolite interacts with only one or a few HLA serotypes, a drug's ability to induce SCARs is limited to those individuals who express HLA serotypes targeted by the drug or its metabolite.[33][34] Accordingly, only rare individuals are predisposed to develop a SCARs in response to a particular drug on the bases of their expression of HLA serotypes:[35] Studies have identified several HLA serotypes associated with development of SJS, SJS/TEN, or TEN in response to certain drugs.[30][36] In general, these associations are restricted to the cited populations.[37]
In some East Asian populations studied (Han Chinese and Thai), carbamazepine\- and phenytoin-induced SJS is strongly associated with HLA-B*1502 (HLA-B75), an HLA-B serotype of the broader serotype HLA-B15.[38][39][40] A study in Europe suggested the gene marker is only relevant for East Asians.[41][42] This has clinical relevance as it is agreed upon that prior to starting a medication such as allopurinol in a patient of Chinese descent, HLA-B*58:01 testing should be considered.[8]
Based on the Asian findings, similar studies in Europe showed 61% of allopurinol-induced SJS/TEN patients carried the HLA-B58 (phenotype frequency of the B*5801 allele in Europeans is typically 3%). One study concluded: "Even when HLA-B alleles behave as strong risk factors, as for allopurinol, they are neither sufficient nor necessary to explain the disease."[43]
Other HLA associations with the development of SJS, SJS/TEN, or TEN and the intake of specific drugs as determined in certain populations are given in HLA associations with SCARs.
### T-cell receptors[edit]
In addition to acting through HLA proteins to bind with a T-cell receptor, a drug or its metabolite may bypass HLA proteins to bind directly to a T-cell receptor and thereby stimulate CD8+ T or CD4+ T cells to initiate autoimmune responses. In either case, this binding appears to develop only on certain T cell receptors. Since the genes for these receptors are highly edited, i.e. altered to encode proteins with different amino acid sequences, and since the human population may express more than 100 trillion different (i.e. different amino acid sequences) T-cell receptors while an individual express only a fraction of these, a drug's or its metabolite's ability to induce the DRESS syndrome by interacting with a T cell receptor is limited to those individuals whose T cells express a T cell receptor(s) that can interact with the drug or its metabolite.[33][44] Thus, only rare individuals are predisposed to develop SJS in response to a particular drug on the bases of their expression of specific T-cell receptor types.[35] While the evidence supporting this T-cell receptor selectivity is limited, one study identified the preferential presence of the TCR-V-b and complementarity-determining region 3 in T-cell receptors found on the T cells in the blisters of patients with allopurinol-induced DRESS syndrome. This finding is compatible with the notion that specific types of T cell receptors are involved in the development of specific drug-induced SCARs.[36]
### ADME[edit]
Variations in ADME, i.e. an individual's efficiency in absorbing, tissue-distributing, metabolizing, or excreting a drug, have been found to occur in various severe cutaneous adverse reactions (SCARS) as well as other types of adverse drug reactions.[45] These variations influence the levels and duration of a drug or its metabolite in tissues and thereby impact the drug's or metabolite's ability to evoke these reactions.[7] For example, CYP2C9 is an important drug-metabolizing cytochrome P450; it metabolizes and thereby inactivates phenytoin. Taiwanese, Japanese, and Malaysian individuals expressing the CYP2C9*3[46] variant of CYP2C9, which has reduced metabolic activity compared to the wild type (i.e. CYP2c9*1) cytochrome, have increased blood levels of phenytoin and a high incidence of SJS (as well as SJS/TEN and TEN) when taking the drug.[7][47] In addition to abnormalities in drug-metabolizing enzymes, dysfunctions of the kidney, liver, or GI tract which increase a SCARs-inducing drug or metabolite levels are suggested to promote SCARs responses.[7][4] These ADME abnormalities, it is also suggested, may interact with particular HLA proteins and T cell receptors to promote a SCARs disorder.[7][48]
## Diagnosis[edit]
The diagnosis is based on involvement of less than 10% of the skin.[2] It is known as TEN when more than 30% of the skin is involved and an intermediate form with 10 to 30% involvement.[3] A positive Nikolsky's sign is helpful in the diagnosis of SJS and TEN.[8] A skin biopsy is helpful, but not required, to establish a diagnosis of SJS and TEN.[8]
### Pathology[edit]
Micrograph showing full-thickness epidermal necrosis with a basket weave-like stratum corneum and separation of the dermis and epidermis, skin biopsy, H&E stain
SJS, like TEN and erythema multiforme, is characterized by confluent epidermal necrosis with minimal associated inflammation. The acuity is apparent from the (normal) basket weave-like pattern of the stratum corneum.
### Classification[edit]
Stevens–Johnson syndrome (SJS) is a milder form of toxic epidermal necrolysis (TEN).[49] These conditions were first recognised in 1922.[26] A classification first published in 1993, that has been adopted as a consensus definition, identifies Stevens–Johnson syndrome, toxic epidermal necrolysis, and SJS/TEN overlap. All three are part of a spectrum of severe cutaneous reactions (SCAR) which affect skin and mucous membranes.[13] The distinction between SJS, SJS/TEN overlap, and TEN is based on the type of lesions and the amount of the body surface area with blisters and erosions.[13] It is agreed that the most reliable method to classify EM, SJS, and TEN is based on lesion morphology and extent of epidermal detachment.[8] Blisters and erosions cover between 3% and 10% of the body in SJS, 11–30% in SJS/TEN overlap, and over 30% in TEN.[13] The skin pattern most commonly associated with SJS is widespread, often joined or touching (confluent), papuric spots (macules) or flat small blisters or large blisters which may also join together.[13] These occur primarily on the torso.[13]
SJS, TEN, and SJS/TEN overlap can be mistaken for erythema multiforme.[50] Erythema multiforme, which is also within the SCAR spectrum, differs in clinical pattern and etiology.[13] Although both SJS and TEN can also be caused by infections, they are most often adverse effects of medications.[13]
## Prevention[edit]
Screening individuals for certain predisposing gene variants before initiating treatment with particular SJS-, TEN/SJS-, or TEN-inducing drugs is recommended or under study. These recommendations are typically limited to specific populations that show a significant chance of having the indicated gene variant since screening of populations with extremely low incidences of expressing the variant is considered cost-ineffective.[51] Individuals expressing the HLA allele associated with sensitivity to an indicated drug should not be treated with the drug. These recommendations include the following.[7][52] Before treatment with carbamazepine, the Taiwan and USA Food and Drug Administrations recommend screening for HLA-B*15:02 in certain Asian groups. This has been implemented in Taiwan, Hong Kong, Singapore, and many medical centers in Thailand and Mainland China. Before treatment with allopurinol, the American College of Rheumatology guidelines for managing gout recommend HLA-B*58:01 screening. This is provided in many medical centers in Taiwan, Hong Kong, Thailand, and Mainland China. Before treatment with abacavir, the USA Food and Drug Administration recommends screening for HLA-B*57:01 in Caucasian populations. This screening is widely implemented.[citation needed] It has also been suggested[by whom?] that all individuals found to express this HLA serotype avoid treatment with abacovir. Current trials are underway in Taiwan to define the cost-effectiveness of avoiding phenytoin in SJS, SJS/TEN, and TEN for individuals expressing the CYP2C9*3 allele of CYP2C9.[52]
## Treatment[edit]
SJS constitutes a dermatological emergency. Patients with documented Mycoplasma infections can be treated with oral macrolide or oral doxycycline.[10]
Initially, treatment is similar to that for patients with thermal burns, and continued care can only be supportive (e.g. intravenous fluids and nasogastric or parenteral feeding) and symptomatic (e.g., analgesic mouth rinse for mouth ulcer). Dermatologists and surgeons tend to disagree about whether the skin should be debrided.[10]
Beyond this kind of supportive care, no treatment for SJS is accepted. Treatment with corticosteroids is controversial. Early retrospective studies suggested corticosteroids increased hospital stays and complication rates. No randomized trials of corticosteroids were conducted for SJS, and it can be managed successfully without them.[10]
Other agents have been used, including cyclophosphamide and ciclosporin, but none has exhibited much therapeutic success. Intravenous immunoglobulin treatment has shown some promise in reducing the length of the reaction and improving symptoms. Other common supportive measures include the use of topical pain anesthetics and antiseptics, maintaining a warm environment, and intravenous analgesics.
An ophthalmologist should be consulted immediately, as SJS frequently causes the formation of scar tissue inside the eyelids, leading to corneal vascularization, impaired vision, and a host of other ocular problems. Those with chronic ocular surface disease caused by SJS may find some improvement with PROSE treatment (prosthetic replacement of the ocular surface ecosystem treatment).[53]
## Prognosis[edit]
SJS (with less than 10% of body surface area involved) has a mortality rate of around 5%. The mortality for toxic epidermal necrolysis (TEN) is 30–40%. The risk for death can be estimated using the SCORTEN scale, which takes a number of prognostic indicators into account.[54] It is helpful to calculate a SCORTEN within the first 3 days of hospitalization.[8] Other outcomes include organ damage/failure, cornea scratching, and blindness.[citation needed]. Restrictive lung disease may develop in patients with SJS and TEN after initial acute pulmonary involvement.[8] Patients with SJS or TEN caused by a drug have a better prognosis the earlier the causative drug is withdrawn.[8]
## Epidemiology[edit]
SJS is a rare condition, with a reported incidence of around 2.6[10] to 6.1[26] cases per million people per year. In the United States, about 300 new diagnoses are made each year. The condition is more common in adults than in children.
## History[edit]
SJS is named for Albert Mason Stevens and Frank Chambliss Johnson, American pediatricians who jointly published a description of the disorder in the American Journal of Diseases of Children in 1922.[55][56]
## Notable cases[edit]
* Ab-Soul, American hip hop recording artist and member of Black Hippy[57]
* Padma Lakshmi, actress, model, television personality, and cookbook writer[58]
* Manute Bol, former NBA player. Bol died from complications of Stevens–Johnson syndrome as well as kidney failure.[59]
* Gene Sauers, three-time PGA Tour winner[60]
* Samantha Reckis, a seven-year-old Plymouth, Massachusetts girl who lost the skin covering 95% of her body after taking children's Motrin in 2003. In 2013, a jury awarded her $63M in a lawsuit against Johnson & Johnson, one of the largest lawsuits of its kind.[61] The decision was upheld in 2015.[62]
* Karen Elaine Morton, a model and actress who appeared in Tommy Tutone's "867-5309/Jenny" video and was Playmate of the Month in the July 1978 issue of Playboy Magazine.[63]
## Research[edit]
In 2015, the NIH and the Food and Drug Administration (FDA) organized a workshop entitled "Research Directions in Genetically-Mediated Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis".[8]
## References[edit]
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## External links[edit]
* Bentley, John; Sie, David (8 October 2014). "Stevens-Johnson syndrome and toxic epidermal necrolysis". The Pharmaceutical Journal. 293 (7832). Retrieved 8 October 2014.
Classification
D
* ICD-10: L51.1
* ICD-9-CM: 695.13
* OMIM: 608579
* MeSH: D013262
* DiseasesDB: 4450
* SNOMED CT: 73442001
External resources
* MedlinePlus: 000851
* eMedicine: emerg/555 derm/405
* Patient UK: Stevens–Johnson syndrome
* v
* t
* e
Urticaria and erythema
Urticaria
(acute/chronic)
Allergic urticaria
* Urticarial allergic eruption
Physical urticaria
* Cold urticaria
* Familial
* Primary cold contact urticaria
* Secondary cold contact urticaria
* Reflex cold urticaria
* Heat urticaria
* Localized heat contact urticaria
* Solar urticaria
* Dermatographic urticaria
* Vibratory angioedema
* Pressure urticaria
* Cholinergic urticaria
* Aquagenic urticaria
Other urticaria
* Acquired C1 esterase inhibitor deficiency
* Adrenergic urticaria
* Exercise urticaria
* Galvanic urticaria
* Schnitzler syndrome
* Urticaria-like follicular mucinosis
Angioedema
* Episodic angioedema with eosinophilia
* Hereditary angioedema
Erythema
Erythema multiforme/
drug eruption
* Erythema multiforme minor
* Erythema multiforme major
* Stevens–Johnson syndrome, Toxic epidermal necrolysis
* panniculitis (Erythema nodosum)
* Acute generalized exanthematous pustulosis
Figurate erythema
* Erythema annulare centrifugum
* Erythema marginatum
* Erythema migrans
* Erythema gyratum repens
Other erythema
* Necrolytic migratory erythema
* Erythema toxicum
* Erythroderma
* Palmar erythema
* Generalized erythema
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Stevens–Johnson syndrome
|
c0014518
| 8,085 |
wikipedia
|
https://en.wikipedia.org/wiki/Stevens%E2%80%93Johnson_syndrome
| 2021-01-18T19:09:02 |
{"gard": ["7700"], "mesh": ["D013262"], "umls": ["C3658302", "C0014518", "C3658301", "C1274933", "C0038325"], "orphanet": ["537", "36426"], "wikidata": ["Q1053948"]}
|
Small cell carcinoma of the bladder (SCCB) is a very rare, poorly differentiated neuroendocrine epithelial bladder tumor characterized clinically by hematuria and/or dysuria and a highly aggressive course.
## Epidemiology
SCCB is extremely rare with an annual incidence of less than 1-9/1,000,000. Since 1980, fewer than 1,500 cases have been identified. The demographic profile of SCCB is similar to that of patients with bladder transitional cell carcinoma (TCC). The majority of patients are male, with a mean sex ratio of 5:1, and a range between 1:1 to 16:1. The vast majority of cases were reported in the Caucasian population.
## Clinical description
Most knowledge on SCCB is based on retrospective investigations and on a few prospective studies. Mean age at diagnosis is 67 years (range 32 to 91 years). The clinical features of SCCB are similar to those of bladder TCC and reflect the presence of a tumoral mass. The main symptom is gross hematuria (63 to 88% of cases) with dysuria as the second most common symptom. Urinary obstruction, abdominal pain, urinary tract infection and weigh loss are occasionally present. SCCB often occurs with other types of carcinoma and is frequently found combined with other histological forms of bladder cancer: TCC, adenocarcinoma and squamous cell carcinoma. SCCB is generally believed to have a high metastatic potential. Rare cases of paraneoplastic syndromes such as ectopic ACTH secretion and hypercalcemia have also been reported.
## Etiology
The etiology of the disease is unknown but a multipotent stem cell anomaly is thought to be a likely mechanism. A history of smoking is found in 65% to 79% of cases.
## Diagnostic methods
Histology and immunohistochemistry show a tumor that is indistinguishable from small cell lung cancer (SCLC; see this term). Diagnosis of SCCB relies mainly on histopathological data obtained by cystoscopy and transurethral resection of the bladder tumor. Immunochemistry staining is useful in establishing the diagnosis. Light microscopy reveals packed cells having scant cytoplasm containing few organelles. Tumors are composed of nests of small round malignant cells with pyknotic round to oval nuclei and evenly dispersed ''salt and pepper chromatin''. More than 95% of SCCB cases are diagnosed at muscle invasive stage T2 or later.
## Differential diagnosis
The differential diagnosis includes direct invasion of the bladder by SCC of the prostate, metastatic SCC from another source, usually the lung, and primary lymphomas of the bladder.
## Management and treatment
The staging system used is the TNM-staging of bladder transitional cell carcinoma. Treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease should be managed with multimodal therapy associating chemotherapy, surgery and/or radiotherapy. Neoadjuvant chemotherapy using 4 chemotherapy cycles followed by radical cystectomy is the most effective therapeutic sequence. Patients with unresectable disease should be managed with palliative chemotherapy based on neuroendocrine-type regimens comprising a platinum drug (cisplatin in fit patients). Prophylactic cranial irradiation should be considered in stages III/IV bladder SCC.
## Prognosis
The prognosis of the disease is poor mainly in the case of pure small cell 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
|
Small cell carcinoma of the bladder
|
None
| 8,086 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=284400
| 2021-01-23T17:24:50 |
{"gard": ["11923"], "icd-10": ["C67.0", "C67.1", "C67.2", "C67.3", "C67.4", "C67.5", "C67.6", "C67.7", "C67.8", "C67.9"], "synonyms": ["Poorly differentiated neuroendocrine carcinoma of the bladder", "SCCB", "Small cell bladder cancer", "Small cell bladder carcinoma", "Small cell carcinoma of the urinary bladder"]}
|
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome.
Description
The interstitial 16q22 deletion syndrome is a multiple congenital anomaly disorder associated with failure to thrive in infancy, poor growth, delayed psychomotor development, hypotonia, and dysmorphic features, including large anterior fontanel, high forehead, diastasis of the cranial sutures, broad nasal bridge, hypertelorism, low-set abnormal ears, and short neck. The phenotypic features and deletion sizes are variable, but deletion of 16q22 appears to be critical for manifestations of the syndrome (summary by Fujiwara et al., 1992).
Clinical Features
Fryns et al. (1977) reported an infant with an interstitial 16q21 deletion associated with craniofacial anomalies, cranial suture diastasis, and a narrow thorax who died at age 1 month of pneumonia. Postmortem examination showed intestinal malrotation and a ventricular septal defect. A review of this patient by Fujiwara et al. (1992) noted low birth weight, failure to thrive, hypotonia, and poor suck. The patient reported by Fryns et al. (1977) also had a large anterior fontanel, high forehead, prominent metopic suture, broad nasal bridge, hypertelorism, low-set abnormal ears, small upslanted palpebral fissures, micrognathia, short neck, and broad toes.
Rivera et al. (1985) reported an infant with a de novo interstitial deletion of chromosome 16q21-q23. He had very low birth weight and length, small head, joint contractures, and poor suck. Dysmorphic features included relatively large skull with brachycephaly, high forehead, prominent metopic suture, hypertelorism, small nose with flat bridge, long philtrum, thin lips, micrognathia, arched palate, low-set ears, short neck, and brachydactyly. Cardiac examination showed aortic coarctation. He died at age 6 months. Rivera et al. (1985) noted the similarities to the case reported by Fryns et al. (1977), who had a 16q21 deletion.
Naritomi et al. (1988) reported a girl with a de novo 16q13-q22 deletion. She had failure to thrive as a newborn and poor subsequent growth. She had a large anterior fontanel and widely patent cranial sutures at age 2 months. Brain CT showed mild hydrocephalus and an occipital meningoencephalocele. At age 18 months, the cranial sutures were still widely patent, and she had a high bossed forehead, epicanthal folds, hypertelorism, flat and broad nasal bridge, short nose, low-set, posteriorly rotated, deformed ears, high-arched palate, short neck, and widely spaced nipples. She was hypotonic and showed mild psychomotor retardation at age 3 years.
Fujiwara et al. (1992) reported a female infant with an interstitial deletion of chromosome 16q who had mild dysmorphic features, including prominent forehead, wide anterior fontanel, diastasis of the cranial sutures, hypertelorism, upslanting palpebral fissures, broad nasal bridge, narrow thorax, and widely spaced nipples. She had severe failure to thrive due to recurrent vomiting and watery diarrhea, developed convulsions and repeated cardiac arrest, and died on day 159 of life from repeated infections. High resolution banding showed a de novo deletion of chromosome 16q22.1-q22.3. Fujiwara et al. (1992) reviewed previous reports of 7 additional patients with different deletions of regions 16q21 to 16q24, including 1 patient with a 16q13-q22 deletion, and noted that there was a constellation of similar features. Affected individuals had low birth weight, failure to thrive, feeding disturbances, hypotonia, and delayed psychomotor development. Dysmorphic features included prominent forehead, wide anterior fontanel, diastasis of cranial sutures, blepharostenosis, hypertelorism, broad nasal bridge, low-set and deformed ears, and short neck. Less common features included narrow thorax and ectopic anus. The most common deleted region was 16q22.
Callen et al. (1993) reported the features of 4 unrelated patients with variable interstitial deletions of 16q21-q24. All the breakpoints were different. The phenotype was somewhat variable, but common features included failure to thrive, delayed psychomotor development, hypotonia, large anterior fontanel, high forehead, broad and flat nasal bridge, low-set dysmorphic ears, micrognathia, high-arched palate, flexed fingers, and broad first toe. Callen et al. (1993) also referred to a family in which 3 members had a deletion of 16q21 with a normal phenotype, suggesting that loss of 16q21 is not pathogenic.
Goto et al. (2004) reported a Japanese boy with an approximately 1.2-Mb deletion of chromosome 16q22 encompassing the CBFB gene (121360). At birth, he had low height, weight, and head circumference, but was noted to have a large and apparently bulging fontanel with delayed mineralization of the skull and no hydrocephalus. Radiographs showed open fontanel, multiple wormian bones along the sagittal suture, hypoplasia of the distal phalanges, and slightly narrow upper thorax. He later showed mild psychomotor retardation and dysmorphic features, including midface hypoplasia, upslanting palpebral fissures, epicanthal folds, prominent earlobes, broad nasal tip, and pointed chin. Goto et al. (2004) noted that the phenotype was reminiscent of cleidocranial dysplasia (119600), caused by mutation in the RUNX2 gene (600211), and that CBFB forms a heterodimer with RUNX2. The findings suggested that 1 feature of the 16q22 deletion syndrome, large fontanels, may be due to haploinsufficiency of CBFB.
Khan et al. (2006) reported a boy with a de novo 16q21-q22 deletion. He had a cleft soft palate, delayed mineralization of the parietal bones, and mild dysmorphic features including hypertelorism, upslanting palpebral fissures, midface hypoplasia, and micrognathia. He had hypoplastic distal phalanges of the hands and a ventricular septal defect that resolved by age 6 months. There was no evidence of bone marrow insufficiency. Despite a difficult period in infancy mainly due to feeding difficulties, he later showed developmental gains by age 15 months. Haploinsufficiency of the CBFB gene was detected by FISH analysis, and no mutations were found in the RUNX2 gene. Khan et al. (2006) noted the phenotypic similarities to a Cbfb-deficient mouse model (Kundu et al., 2002) and suggested that CBFB haploinsufficiency in their patient may have led to the cranial ossification defects.
INHERITANCE \- Isolated cases GROWTH Height \- Low birth length Weight \- Low birth weight Other \- Failure to thrive \- Postnatal growth retardation HEAD & NECK Head \- High forehead \- Frontal bossing Face \- Micrognathia Ears \- Low-set ears \- Posteriorly rotated ears \- Dysplastic ears Eyes \- Hypertelorism \- Epicanthal folds \- Upslanting palpebral fissures \- Short palpebral fissures Nose \- Broad flat nasal bridge Mouth \- High-arched palate Neck \- Short neck CHEST External Features \- Narrow thorax Breasts \- Widely spaced nipples ABDOMEN Gastrointestinal \- Poor suck SKELETAL Skull \- Large anterior fontanel \- Diastasis of cranial sutures \- Wormian bones Hands \- Flexed fingers Feet \- Broad first toe NEUROLOGIC Central Nervous System \- Hypotonia \- Delayed psychomotor development MISCELLANEOUS \- Contiguous gene deletion syndrome MOLECULAR BASIS \- A contiguous gene syndrome caused by deletion of chromosome 16q22 including the CBFB gene ( 121360 ) ▲ 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
|
CHROMOSOME 16q22 DELETION SYNDROME
|
c3281152
| 8,087 |
omim
|
https://www.omim.org/entry/614541
| 2019-09-22T15:54:54 |
{"omim": ["614541"]}
|
The term morbilliform refers to a rash that looks like measles. The rash consists of macular lesions that are red and usually 2–10 mm in diameter but may be confluent in places.[1] A morbilliform rash is a rose-red flat (macular) or slightly elevated (maculopapular) eruption, showing circular or elliptical lesions varying in diameter from 1 to 3 mm, with healthy-looking skin intervening.
Patients with measles will have the rash but there are other syndromes and infections that will display the same symptom such as patients with Kawasaki disease,[2] meningococcal petechiae or Waterhouse-Friderichsen syndrome,[2] Dengue, Roseola, congenital syphilis,[3] rubella,[2] Echovirus 9,[2] drug hypersensitivity reactions (in particular with certain classes of antiretroviral drugs, such as abacavir and nevirapine, and also the antiepileptic drug phenytoin), or other conditions may also have a morbilliform rash. It has also been mentioned as a possible manifestation of onset or recovery from COVID-19.[4]
One cause of morbilliform rash is an allergic reaction to transfused blood/blood components. In such a case, the skin lesions would develop within a few hours (Approx. 4hours) of transfusion along with pruritus. The condition may even present with other symptoms, such as conjunctival oedema, oedema in the lips and tongue, and even localised angioedema. On rare occasions, the condition may even escalate to anaphylactic shock where pulmonary restrictions are seen. The associated cause for this is a reaction against an allergen that is seldom identified during testing. Transfusing products with anti-IgA antibodies to IgA-deficient patients has also been a suspected cause for such reactions. Management usually relates to the stoppage of transfusion for around 30minutes, until given antihistamines take effect. Transfusion may even be continued after, if no further progression is seen.
## References[edit]
1. ^ Primary Care Dermatology Module. Nomenclature of Skin Lesions The University of Wisconsin. Department of Pediatrics. Retrieved on Nov 30, 2009
2. ^ a b c d thefreedictionary.com > morbilliform rash Retrieved on Nov 30, 2009
3. ^ American Family Physician Sept 1st 2012 Vol 86 No 5 pp381-482 Syphilis: A re-emerging infection.
4. ^ https://dermnetnz.org/topics/covid-19/
## External links[edit]
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Morbilliform
|
c0234918
| 8,088 |
wikipedia
|
https://en.wikipedia.org/wiki/Morbilliform
| 2021-01-18T18:58:01 |
{"umls": ["C0234918"], "wikidata": ["Q3061764"]}
|
A number sign (#) is used with this entry because of evidence that Fuhrmann syndrome is caused by homozygous mutation in the WNT7A gene (601570) on chromosome 3p25.
Clinical Features
In 2 boys and a girl of a Turkish-Arabian family working in Germany, Fuhrmann et al. (1980) described a 'new' syndrome consisting of bowing of the femurs, aplasia or hypoplasia of the fibula, and poly-, syn-, and oligodactyly. Parental consanguinity was denied. However, both parents belonged to the same Christian minority from the same province. Other findings included hypoplasia of pelvis, congenital dislocation of hips, absence or coalescence of tarsal bones, absence of various metatarsals, hypoplasia of fingers and fingernails, and postaxial polydactyly. The bowing of the femurs looked like that of camptomelia. Fuhrmann et al. (1982) provided follow-up, including the prenatal diagnosis of a fourth affected sib and the anatomic findings in the abortus.
In a male and female offspring of Turkish parents related as cousins once removed, Pfeiffer et al. (1988) observed a lethal syndrome consisting of absence of the fibula and ulna with oligodactyly, joint contractures, right-angle bowing of the femurs, cleft lip and palate, and, in the sib examined, an Arnold-Chiari anomaly with communicating hydrocephalus, caudally displaced cerebellum with absence of the velum medullare and of the posterior vermis, and focal microgyria in the frontal area. The first infant was delivered at 28 weeks by cesarean section because of premature labor and lived only a short period. The upper lip appeared attached to the nose because the tongue was squeezed into the cleft lip. The abnormalities in the second affected child were detected at 20 weeks of the pregnancy by ultrasonography and the pregnancy was terminated. The patients of Fuhrmann et al. (1980) and Pfeiffer et al. (1988) came from different parts of Turkey. Lipson et al. (1991) reported 2 unrelated cases, 1 from a consanguineous Vietnamese family and the second from a nonconsanguineous Polish family.
In an extensive and highly inbred Muslim family from Pakistan, Kumar et al. (1997) described 4 children with a similar pattern of skeletal abnormalities, including aplasia/hypoplasia of the ulnas, hypoplasia of the pelvis, aplasia/hypoplasia of the femurs, fibular aplasia, and variable digital abnormalities, as well as absent/dysplastic nails. Overlap was recognized with Fuhrmann syndrome and with the Al-Awadi/Raas-Rothschild syndrome (276820). It also had similarities to the femur-fibula-ulna syndrome, or FFU syndrome (228200).
Woods et al. (2006) analyzed the Pakistani Muslim family described by Kumar et al. (1997). Two further affected individuals had been born who conformed to the original phenotype. In the upper limbs hypoplasia/aplasia of the ulnar rays was identified, which was accompanied by shortening and bowing of the radius. The fifth digits were hypoplastic but all other elements were present. There was hypoplasia of the nails with a radial-ulnar gradient; the thumbs were the most severely affected, with complete absence of the nails. The pelvis was highly abnormal, with hypoplastic iliac wings and, in 1 case, absent os ischii. The patellae were absent and in 1 subject the knee joints were fused. There was complete absence of the toenails and loss of individual toes. In each affected person limb involvement was symmetrical, legs were more affected than arms, and the functional deficit was far greater than that expected because of limb shortening alone.
Aynaci et al. (2001) described a single case of presumed Fuhrmann syndrome in a male newborn in a consanguineous Turkish family.
Huber et al. (2003) described 2 unrelated boys with bilateral fibular aplasia, poly- and oligodactyly, and bowed tibiae in 2 nonconsanguineous Brazilian families. These cases were similar to those reported by Fuhrmann et al. (1980) and supported the view that this entity is a distinct combination of developmental limb anomalies.
Molecular Genetics
In the Pakistani Muslim family described by Kumar et al. (1997), Woods et al. (2006) found that affected individuals had 3 homozygous changes, all in exon 3 of the WNT7A gene: a missense mutation, 630G-A, that led to an alanine-to-threonine substitution (A109T; 601570.0002), and 2 known synonymous SNPs.
History
Vogel (1997) provided an obituary of Walter Fuhrmann (1924-1995), who was Professor of Human Genetics at Giessen University in Germany from 1967 until 1992.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature SKELETAL Pelvis \- Congenital hip dislocation \- Hypoplastic iliac wings Limbs \- Forearm bowing \- Hypoplastic/aplastic ulnae \- Short bowed radii \- Hypoplastic/aplastic femora \- Femoral bowing \- Absent patellae \- Hypoplastic/aplastic fibulae Hands \- Postaxial polydactyly \- Clinodactyly (4th and 5th fingers) \- Syndactyly \- Hypoplastic metacarpals (4th and 5th) Feet \- Talipes equinovarus \- Oligodactyly \- Aplastic/hypoplastic phalanges \- Aplastic/hypoplastic metatarsals \- Syndactyly SKIN, NAILS, & HAIR Skin \- Hypoplastic flexion creases dorsum of hand Nails \- Absent/hypoplastic finger nails (thumb most severely affected) \- Absent toenails ENDOCRINE FEATURES \- Amenorrhea MISCELLANEOUS \- Allelic to ulnar and fibula, absence of, with severe limb deficiency (Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome 276820 ) MOLECULAR BASIS \- Caused by mutation in the wingless-type MMTV integration site family, member 7A gene (WNT7A, 601570.0002 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
FIBULAR APLASIA OR HYPOPLASIA, FEMORAL BOWING AND POLY-, SYN-, AND OLIGODACTYLY
|
c1856728
| 8,089 |
omim
|
https://www.omim.org/entry/228930
| 2019-09-22T16:27:53 |
{"doid": ["0090067"], "mesh": ["C538189"], "omim": ["228930"], "orphanet": ["2854"], "synonyms": ["Alternative titles", "FUHRMANN SYNDROME"]}
|
## Description
Fetal hemoglobin (HbF) levels vary considerably in healthy normal adults. The distribution of HbF and F cells, erythrocytes that contain measurable HbF, in healthy adults is continuous, although most adults have HbF of less than 0.6% of total Hb. Approximately 10 to 15% of individuals have increases of HbF ranging from 0.8% to 5%, a trait often referred to as hereditary persistence of fetal hemoglobin (HPFH), usually distributed unevenly among red cells. When coinherited with beta-thalassemia (see 613985) or sickle cell anemia (603903), HPFH can increase HbF output to levels that are clinically beneficial (Thein et al., 2007).
For a general phenotypic description and a discussion of loci that may affect fetal hemoglobin levels, see HBFQTL1 (141749).
Clinical Features
Thein et al. (1994) reported a large family from the state of Gujarat in India in which members had beta-thalassemia and/or hereditary persistence of fetal hemoglobin. The presence of HbF-containing cells segregated as an independent trait from the beta-thalassemia. The proband had homozygous beta-thalassemia, but had a mild phenotype associated with high circulating levels of HbF. He married an unrelated woman with heterozygous beta-thalassemia. Two sons were homozygous for beta-thalassemia, but did not inherit HPFH from the father, as manifest by their severe disease. A detailed examination of the rest of the large kindred showed that many members had increased HbF at 0.8 to 3.4%, and that those heterozygous for beta-thalassemia had HbF levels ranging from 2.5 to 24%. F-cell levels ranged from 5.8 to 26%, consistent with a heterocellular form of HPFH.
Mapping
Thein et al. (1994) excluded linkage to the beta-globin gene cluster on chromosome 11p in a large Indian family with HPFH. An effect of a major gene was suspected when the effects of genetic modifiers, notably beta-thalassemia on 11p and a polymorphism in the promoter of the gamma-G gene (HBG2; 142250), were accounted for in the analysis. By follow-up of the large Indian kindred reported by Thein et al. (1994), Craig et al. (1996) found linkage to a locus determining fetal hemoglobin production on chromosome 6q22.3-q23.1.
Garner et al. (1998) extended the Asian-Indian kindred studied by Craig et al. (1996) by 57 members, bringing the total studied to 210, and saturated the 6q23 region with 26 additional markers. Linkage analysis showed tight linkage of the quantitative trait locus (QTL) to markers D6S976 (lod score 11.3 at theta = 0.0) and D6S270 (lod score = 7.4 at theta = 0.0). Key recombination events placed the QTL within a 1- to 2-cM interval spanning approximately 1.5 Mb between D6S270 and D6S1626. Furthermore, haplotype analysis led to a reevaluation of the genealogy and to the identification of additional relationships in the kindred.
By genotyping 2 panels of twin pairs of North European origin consisting of 824 and 1,217 individuals, respectively, Thein et al. (2007) found a strong association (combined p values of 10(-50) to 10(-75) for both panels) between fetal Hb levels, and a 24-kb segment on chromosome 6q23 starting 33 kb upstream of HBS1L (612450). The region was termed 'HMIP' for HBS1L-MYB (189990) intergenic polymorphism. These 12 markers showed very strong linkage disequilibrium. The marker with the highest value within this interval was rs9399137 (p = 10(-45)), which is in intron 1a of the HBS1L gene. Two other markers also showed significant values: rs52090901 (p = 10(-5)), located in the 5-prime untranslated region upstream of exon 1a of the HBS1L gene, and rs6929404 (p = 0.0002), which is between exon 1a of HBS1L and the first exon of the MYB gene. Based on haplotype analysis, Thein et al. (2007) estimated that the markers in this region account for 17.6% of the trait variance. The variants associated with high F-cell levels were also strongly correlated with increased expression of HBS1L in cultured erythroid cells.
By analyzing 1,794 European individuals, Menzel et al. (2007) found that haplotype-2 of the HMIP2 block could explain variance of several hematologic traits, including red blood cell count (0.6%), mean corpuscular volume (1.7%), mean corpuscular hemoglobin (2.1%), platelet count (0.6%), and monocyte number (1.6%). The findings suggested that variation at the HMIP locus on 6q23.3 has an impact on other peripheral blood cell indices besides hemoglobin.
In a cohort of 238 Chinese carriers of beta-thalassemia, So et al. (2008) identified 29 SNPs within the HMIP segment on chromosome 6q23 that were mildly associated with HbF levels (p values between 0.003 and 0.039 after multiple testing correction). None of the SNPs identified by Thein et al. (2007) were significantly associated with HbF levels in 93 normal Chinese individuals. So et al. (2008) nevertheless concluded that this intergenic region plays a role in the regulation of fetal hemoglobin expression.
In 2 independent cohorts of patients with sickle cell anemia, Lettre et al. (2008) found a significant association between several SNPs in the HBS1L-MYB interval and HbF levels. The most significant associations among 1,275 African Americans and 350 Brazilians were with rs9399137 (p = 5 x 10(-11)) and rs4895441 (p = 4 x 10(-7)), respectively. The associations with different SNPs in this region were independent of one another, but overall could explain 5% of variance in HbF levels.
To fine map HbF association signals at the BCL11A (606557), HBS1L-MYB, and beta-globin loci (see 141749), Galarneau et al. (2010) resequenced 175.2 kb from these loci in 190 individuals including the HapMap European CEU and Nigerian YRI founders and 70 African Americans with sickle cell anemia. The authors discovered 1,489 sequence variants, including 910 previously unreported variants. Using this information and data from HapMap, Galarneau et al. (2010) selected and genotyped 95 SNPs, including 35 at the HBS1L-MYB locus, in 1,032 African Americans with sickle cell anemia. Single-marker regression analysis identified rs9402686 as more strongly associated with HbF levels than rs9399137, the previous index HbF SNP at this locus (p = 1.9 x 10(-13) for rs9402686; p = 3.5 x 10(-10) for rs9399137).
Molecular Genetics
Pandit et al. (2008) provided evidence suggesting that a 32C-T SNP in the 5-prime untranslated region of the HBS1L gene (rs2297339) may influence HbF. The C allele was associated with increased HbF levels among Thai-Chinese patients with beta-thalassemia, particularly among those who were heterozygous for the HBG2 polymorphism (142250.0028). rs2297339 in HBS1L is predicted to confer a binding site for transcription factor AP4 (600743) and may influence gene expression.
Wahlberg et al. (2009) found 3 sites in the core intergenic HMIP2 block that were hypersensitive to DNase I cleavage, indicative of active chromatin, in erythroid cell lines. Chromatin immunoprecipitation with microarray (ChIP-chip) analysis showed strong histone acetylation in a 65-kb interval encompassing the HMIP2 and HMIP3 blocks in primary human erythroid cells, but not in non-MYB-expressing HeLa cells. Several potential cis-regulatory elements and strong GATA1 (305371) signals were identified in this area. The findings suggested that this region contains distal regulatory sequences that could be important in hematopoiesis by controlling MYB expression.
To establish the identity of the gene at the HBS1L-MYB locus that influences HbF levels, Galarneau et al. (2010) resequenced 70 individuals with sickle cell anemia and identified 6 and 4 rare missense variants in HBS1L and MYB, respectively. They genotyped these variants in 1,032 individuals with sickle cell anemia to assess their burden at the gene level by comparing normalized HbF levels in carriers and noncarriers. Results for HBS1L were not significant; however, a significant difference was observed for MYB (corrected p = 0.005), with the 25 carriers having on average 1.4% more HbF than the 937 noncarriers. These data suggested that MYB is the gene causally involved in controlling HbF production at the HBFQTL2 locus.
Inheritance \- Autosomal dominant Misc \- Only some cells have high fetal hemoglobin \- Interaction of HPFH with beta-thalassemia and SS disease Heme \- Heterocellular persistence of fetal hemoglobin ▲ 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
|
FETAL HEMOGLOBIN QUANTITATIVE TRAIT LOCUS 2
|
c1840598
| 8,090 |
omim
|
https://www.omim.org/entry/142470
| 2019-09-22T16:40:22 |
{"omim": ["142470"], "icd-10": ["D56.4"], "orphanet": ["46532", "251380"], "synonyms": ["HPFH-beta-thalassemia syndrome", "HPFH-sickle cell disease syndrome"]}
|
Cleidocranial dysplasia (CCD) is a rare genetic developmental abnormality of bone characterized by hypoplastic or aplastic clavicles, persistence of wide-open fontanels and sutures and multiple dental abnormalities.
## Epidemiology
The prevalence of CCD is 1/1,000,000, with higher rates in groups with a founder effect. The disorder is found in many ethnic groups and no sex predilection has been reported. It may be underdiagnosed because of the number of relatively mild cases.
## Clinical description
There is an extremely wide range of clinical manifestations (even within the same family) from isolated dental anomalies to severe malformations with functional repercussions. The main clinical signs are hypoplasia or aplasia of the clavicles with narrow, sloping shoulders that can be approximated anteriorly, delayed fusion of cranial sutures with large, wide-open fontanels at birth that may persist throughout life, and a wide spectrum of dental anomalies including abnormal dentition, uniform or chaotic supernumerary teeth (hyperdontia) in the primary and secondary dentition resulting in crowding and malocclusion, retention of deciduous teeth, delayed eruption of secondary dentition and failure to shed the primary teeth. The dental manifestations may affect articulation and mastication. Other signs include broad flat forehead, hypertelorism, midface hypoplasia, and a pointed jaw giving a characteristic facial appearance as well as brachydactyly, tapering fingers and short, broad thumbs. Associated skeletal abnormalities include short stature, scoliosis, genu valgum, pes planus, a wide pubic symphysis, dysplastic scapulae, and coxa vara, generally with little clinical significance. Secondary complications include recurrent infections of the upper respiratory tract, sleep apnea, mild motor delay and variable degrees of hearing loss. Cognitive and intellectual functions are normal. The proportion of women with CCD requiring cesarean section is higher than in the general population due to cephalopelvic disproportion.
## Etiology
CCD is caused by mutations in the RUNX2 gene (6p21) involved in differentiation of osteoblasts and bone formation. A wide range of mutations have been identified, with high penetrance and significant variability. No clear phenotype-genotype correlations have been established.
## Diagnostic methods
Diagnosis is based on clinical signs and on characteristic radiographic findings (wide-open sutures, patent fontanels, cone-shaped thorax with narrow upper thoracic diameter, hand deformities, abnormal dentition). Molecular genetic testing can be used to confirm the diagnosis in patients with atypical clinical and radiological diagnostic features.
## Differential diagnosis
Differential diagnoses include mandibuloacral dysplasia, Crane-Heise syndrome, Yunis-Varon syndrome, pycnodysostosis, CDAGS syndrome, and hypophosphatasia.
## Antenatal diagnosis
Prenatal diagnosis for pregnancies at increased risk is possible and requires identification of the disease-causing genetic mutation in the family.
## Genetic counseling
Cleidocranial dysplasia follows an autosomal dominant pattern of inheritance. Genetic counseling should be provided to affected families. The number of cases related to de novo mutations appears to be high.
## Management and treatment
Management of dental anomalies is very important with the aim of achieving optimal function and esthetics. Options include removal of retained deciduous, supernumerary and abnormal permanent teeth. Dental surgery should be considered for unerupted teeth and orthodontics for malocclusion. Speech therapy may be required. Antibiotics are recommended for recurrent infections. Because of the role of RUNX2 in bone maintenance and ossification, bone mineral density should be monitored and preventive treatment for osteoporosis considered.
## Prognosis
The malformations and complications of CCD rarely cause significant disability. The prognosis is generally good.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Cleidocranial dysplasia
|
c0008928
| 8,091 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1452
| 2021-01-23T17:33:08 |
{"gard": ["6118"], "mesh": ["D002973"], "omim": ["119600", "216330"], "umls": ["C0008928"], "icd-10": ["Q74.0"], "synonyms": ["Cleidocranial dysostosis"]}
|
Xanthogranulomatous osteomyelitis
Other namesXO
SpecialtyInfectious disease, orthopedic
Xanthogranulomatous osteomyelitis is a peculiar aspect of osteomyelitis characterized by prevalent histiocytic infiltrate and foamy macrophage clustering.[1]
## Contents
* 1 Pathology
* 2 Diagnosis
* 3 Management
* 4 References
## Pathology[edit]
See also: Xanthogranulomatous inflammation
The granulomatous tissue largely comprises foam cells of monocyte/macrophage origin positive for KP1, HAM56, CD11b and CD68. Neutrophils, hemorrhagic foci and numerous plasma cells are additional findings.[2][3][4][5] Staphylococcus aureus was isolated in the case reported by Kamat et al.[5] A delayed type hypersensitivity reaction in cell-mediated immunity has been suggested in this type of infiltrate that is composed of macrophages and T cells.[3] T cells are represented by a mixture of CD4\+ and CD8\+ lymphocytes. Macrophages and lymphocytes show marked expression of HLA-DR antigen.[6] Arguably XO is the bone localization of the xanthogranulomatous process occurring in several other locations.[2]
## Diagnosis[edit]
As of 2011 five cases had been reported, involving rib, tibial epiphysis, ulna, distal tibia and femur. Young individuals are prevalently affected but one case involved a 50-year-old woman. Pain, swelling of possibly long duration, fever and increased ESR are some of the main clinical findings. X-ray examination shows lytic foci with sclerotic margins.[2][3][4][5]
## Management[edit]
Antibiotics have been used with success for cases with positive cultures, Curettage, bone grafting, and resection has been described in few studies.[7][8][9]
## References[edit]
1. ^ Rosai J(2004). Rosai and Ackerman's Surgical Pathology. Philadelphia, Mosby, p. 2142.
2. ^ a b c Cozzutto C (1984) Xanthogranulomatous osteomyelitis. Arch Pathol Lab Med 108:973-976.
3. ^ a b c Vankalakunti M, Saikia UN, Mathew M, Kang M (2007). Xanthogranulomatous osteomyelitis of ulna mimicking a neoplasm. World J Surg Oncol 5(46):1-4.
4. ^ a b Kashani MM, Zakerian BZ, Shayan K, Riyasi F (2010). Xanthogranulomatous osteomyelitis of femur. Iran J Orthop Surg 8(4):187-190.
5. ^ a b c Kamat G, Gramapuroit V, Shettar C, Myageri A(2011). Xanthogranulomatous osteomyelitis presenting as swelling in right tibia. Case report. Case Rep Pathol, in press.
6. ^ Nakashiro S, Fujivara S, Harada S, Hisatsugu T, Watanabe T (1995). Xanthogranulomatous cholecystitis. Cell composition and possible pathogenetic role of cell-mediated immunity.Pathol Res Pract 183:395-482.
7. ^ Pathak S, Gautam R, Prince PC, Bagtharia P, Sharma A. A Rare Case Report on Xanthogranulomatous Osteomyelitis of Hip Mimicking Tuberculosis and Review of Literature. Cureus. 2019 Oct;11(10).
8. ^ Nalini G. Xanthogranulomatous osteomyelitis: a case report. Medicine Journal. 2014 Dec 16;1(6):45.
9. ^ Sapra R, Jain P, Gupta S, Kumar R. Multifocal bilateral xanthogranulomatous osteomyelitis. Indian J Orthop. 2015. Jul-Aug;49(4):482-484. doi: 10.4103/0019-5413.159682.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Xanthogranulomatous osteomyelitis
|
None
| 8,092 |
wikipedia
|
https://en.wikipedia.org/wiki/Xanthogranulomatous_osteomyelitis
| 2021-01-18T18:53:11 |
{"wikidata": ["Q8043030"]}
|
Du Bois sign
Symptomsshortened little fingers
Differential diagnosiscongenital syphilis
The du Bois sign is a medical finding of shortness of the little finger in congenital syphilis.[1][2]
## References[edit]
1. ^ Braun-Falco, O., 978-3540594529, Dermatology, 2000, Springer
2. ^ Voelpel, James H.; Muehlberger, Thomas (1 March 2011). "The du Bois Sign". Annals of Plastic Surgery. 66 (3): 241–244. doi:10.1097/SAP.0b013e3181ea1ed8.
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
|
Du Bois sign
|
c1842878
| 8,093 |
wikipedia
|
https://en.wikipedia.org/wiki/Du_Bois_sign
| 2021-01-18T18:57:30 |
{"umls": ["C1842878"], "wikidata": ["Q5311066"]}
|
Lamellar ichthyosis is a condition that mainly affects the skin. Infants with this condition are typically born with a tight, clear sheath covering their skin called a collodion membrane. This membrane usually dries and peels off during the first few weeks of life, and then it becomes obvious that affected babies have scaly skin, and eyelids and lips that are turned outward. People with lamellar ichthyosis typically have large, dark, plate-like scales covering their skin on most of their body. Infants with lamellar ichthyosis may develop infections, an excessive loss of fluids (dehydration), and respiratory problems. Affected individuals may also have hair loss (alopecia), abnormally formed fingernails and toenails (nail dystrophy), a decreased ability to sweat (hypohidrosis), an increased sensitivity to heat, and a thickening of the skin on the palms of the hands and soles of the feet (keratoderma). Less frequently, affected individuals have reddened skin (erythema) and joint deformities (contractures).
## Frequency
Lamellar ichthyosis is estimated to affect 1 in 100,000 individuals in the United States. This condition is more common in Norway, where an estimated 1 in 91,000 individuals are affected.
## Causes
Mutations in one of many genes can cause lamellar ichthyosis. These genes provide instructions for making proteins that are found in the outermost layer of the skin (the epidermis). The skin abnormalities associated with lamellar ichthyosis disrupt the normal formation of the epidermis, resulting in impaired regulation of body temperature, water retention, and resistance to infections.
Mutations in the TGM1 gene are responsible for approximately 90 percent of cases of lamellar ichthyosis. The TGM1 gene provides instructions for making an enzyme called transglutaminase 1. This enzyme is involved in the formation of the cornified cell envelope, which is a structure that surrounds skin cells and helps form a protective barrier between the body and its environment. TGM1 gene mutations lead to severely reduced or absent enzyme production, which prevents the formation of the cornified cell envelope.
Mutations in other genes associated with lamellar ichthyosis are each responsible for only a small percentage of cases. In some people with lamellar ichthyosis, the cause of the disorder is unknown. Researchers have identified multiple chromosome regions that contain genes that may be associated with lamellar ichthyosis, although the specific genes have not been identified.
### Learn more about the genes associated with Lamellar ichthyosis
* ABCA12
* TGM1
Additional Information from NCBI Gene:
* CYP4F22
* LIPN
* NIPAL4
## 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
|
Lamellar ichthyosis
|
c3536797
| 8,094 |
medlineplus
|
https://medlineplus.gov/genetics/condition/lamellar-ichthyosis/
| 2021-01-27T08:25:31 |
{"gard": ["10803"], "mesh": ["D017490"], "omim": ["242300", "606545", "601277", "604777"], "synonyms": []}
|
Squamous cell carcinoma of the corpus uteri is a rare cancer of corpus uteri composed of squamous cells of varying degree of differentiation that usually affects postmenopausal women and presents with abnormal vaginal discharge, dysfunctional bleeding, abdominal pain and distension. It is often associated with cervical stenosis and pyometra.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Squamous cell carcinoma of the corpus uteri
|
c1333396
| 8,095 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=213716
| 2021-01-23T18:47:29 |
{"icd-10": ["C54.9"], "synonyms": ["Endometrial squamous cell carcinoma"]}
|
Xp22.13p22.2 duplication syndrome is a rare syndromic intellectual disability characterized by developmental delay and intellectual disability, learning and behavioral problems, short stature, thin and sparse hair, mild dysmorphic features, tapering fingers and later onset of scoliosis, obesity and cardiovascular problems (cardiomegaly and cardiomyopathy). Females have normal intelligence.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Xp22.13p22.2 duplication syndrome
|
None
| 8,096 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=284180
| 2021-01-23T17:45:37 |
{"icd-10": ["Q99.8"], "synonyms": ["Dup(X)(p22)", "Dup(X)(p22.13p22.2)", "Duplication Xp22"]}
|
Unpleasant, abnormal sense of touch
Dysesthesia (or dysaesthesia) means "abnormal sensation". Its etymology comes from the Greek word "dys," meaning "not-normal," and "aesthesis," which means "sensation" (abnormal sensation). It is defined as an unpleasant, abnormal sense of touch. It often presents as pain[1] but may also present as an inappropriate, but not discomforting, sensation. It is caused by lesions of the nervous system, peripheral or central, and it involves sensations, whether spontaneous or evoked, such as burning, wetness, itching, electric shock, and pins and needles.[1] Dysesthesia can include sensations in any bodily tissue, including most often the mouth, scalp, skin, or legs.[1]
It is sometimes described as feeling like acid under the skin. Burning dysesthesia might accurately reflect an acidotic state in the synapses and perineural space. Some ion channels will open to a low pH, and the acid sensing ion channel has been shown to open at body temperature, in a model of nerve injury pain. Inappropriate, spontaneous firing in pain receptors has also been implicated as a cause of dysesthesia.[citation needed]
People with dysesthesia can become incapacitated with pain, despite no apparent damage to the skin or other tissue. Dysesthesia patients also often have psychological disorders.
## Contents
* 1 Types
* 2 Presentation
* 3 Causes
* 4 Diagnosis
* 4.1 Differential diagnosis
* 5 Treatment
* 6 Research
* 6.1 Studies
* 7 See also
* 8 References
* 9 Further reading
## Types[edit]
Dysesthesia can generally be described as a class of neurological disorders. It can be further classified depending on where it manifests in the body, and by the type of sensation that it provokes.
Cutaneous dysesthesia is characterized by discomfort or pain from touch to the skin by normal stimuli, including clothing. The unpleasantness can range from a mild tingling to blunt, incapacitating pain.
Scalp dysesthesia is characterized by pain or burning sensations on or under the surface of the cranial skin. Scalp dysesthesia may also present as excessive itching of the scalp.
Occlusal dysesthesia, or "phantom bite," is characterized by the feeling that the bite is "out of place" (occlusal dystopia) despite any apparent damage or instability to dental or oromaxillofacial structures or tissue. Phantom bite often presents in patients that have undergone otherwise routine dental procedures. Short of compassionate counseling, evidence for effective treatment regimes is lacking.
## Presentation[edit]
Chronic anxiety is often associated with dysesthesia.[2] Patients with this anxiety may experience numbness or tingling in the face. In one study, those patients that were examined psychologically had symptoms of anxiety, depression, obsessive-compulsive personality disorder, or somatoform disorder.[3]
## Causes[edit]
* Dysesthesia is commonly seen in diabetic patients, and can be relieved by using creams containing capsaicin.
* Dysesthesia may be seen in patients with Guillain–Barré syndrome.
* Dysesthesia is among symptoms of neuropathy (along with paresthesias, gait disturbance, weakness, and absent DTRs).
* Dysesthesia, along with polyneuropathy can be a symptom of nerve damage caused by Lyme disease.[4] The dysesthetic sensations continue after the successful antibiotic treatment of Lyme disease.
* Dysesthesia is a common symptom of a withdrawal from alcohol or other drugs.
* Dysesthesia is also a common symptom of multiple sclerosis. It is an effect of spinal cord injury.[5]
* Many patients with occlusal dysesthesia have reported recent oral surgery before the onset of dysesthetic pain.[3]
* Late-onset GM2 gangliosidosis may also present as burning dysesthesia.[6]
* Chemotherapy-induced peripheral neuropathy is a progressive, enduring and often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs caused by some chemotherapy agents.[7]
* Dysesthesia may be caused by a thalamic stroke involving the ventral postero-lateral (VPL) nucleus. It's typically seen in Dejerine-Roussy syndrome with hemi-sensory loss and severe dysesthesia of the affected area.
* Fibromyalgia may cause dysesthesia in all areas of the body, but mostly the extremities.[medical citation needed]
## Diagnosis[edit]
### Differential diagnosis[edit]
Although dysesthesia is similar to phantom limb syndrome, they should not be confused. In phantom limb, the sensation is present in an amputated or absent limb, while dysesthesia refers to discomfort or pain in a tissue that has not been removed or amputated. The dysesthetic tissue may also not be part of a limb, but part of the body, such as the abdomen. The majority of individuals with both phantom limb and dysesthesia experience painful sensations.
Phantom pain refers to dysesthetic feelings in individuals who are paralyzed or who were born without limbs. It is caused by the improper innervation of the missing limbs by the nerves that would normally innervate the limb. Dysesthesia is caused by damage to the nerves themselves, rather than by an innervation of absent tissue.
Dysesthesia should not be confused with anesthesia or hypoesthesia, which refer to a loss of sensation, or paresthesia which refers to a distorted sensation. Dysesthesia is distinct in that it can, but not necessarily, refer to spontaneous sensations in the absence of stimuli. In the case of an evoked dysesthetic sensation, such as by the touch of clothing, the sensation is characterized not simply by an exaggeration of the feeling, but rather by a completely inappropriate sensation such as burning.
## Treatment[edit]
Daily oral muscle physical therapy, or the administration of antidepressants have been reported as effective therapy for occlusal dysesthesia patients.[3] Tooth grinding, and the replacement or removal of all dental work should be avoided in patients with occlusal dysesthesia,[3] despite the frequent requests for further surgery often made by these patients.
Antidepressants are also often prescribed for scalp dysesthesia.
Prakash et al. found that many patients with burning mouth syndrome (BMS), one variant of occlusal dysesthesia, also report painful sensations in other parts of the body. Many of the patients with BMS met the classification of restless leg syndrome (RLS). About half of these patients also had a family history of RLS. These results suggest that some BMS symptoms may be caused by the same pathway as RLS in some patients, indicating that dopaminergic drugs regularly used to treat RLS may be effective in treating BMS as well.
## Research[edit]
There are a number of hypotheses regarding the basis of occlusal dysesthesia. Some researchers believe the disorder is a psychological one, while others believe it to be a psychosomatic disorder.[3] Joseph Marbach hypothesized that the symptoms were rooted in psychiatric disorders. Marbach suggested that occlusal dysesthesia would occur in patients with underlying psychological problems (such as schizophrenia) after having undergone dental treatment. More recently, two studies have found that occlusal dysesthesia is associated with somatoform disorders in which the patients obsess over the oral sensations.
Similarly, Marbach later proposed that occlusal dysesthesia may be caused by the brain “talking to itself,” causing abnormal oral sensations in the absence of external stimuli. According to this model, the symptoms of dysesthesia are catalyzed by dental “amputation,” for example the extraction of a tooth, whereby the brain loses the ability to distinguish between its memory of the bite and the actual, new bite. The patient, unable to recognize his or her own bite, becomes especially attentive to these perceived oral discrepancies. Finally and most recently, Greene and Gelb suggested that instead of having a psychological root, dysesthesia may be caused by a false signal being sent from the peripheral nervous system to the central nervous system. However, the reviewers note that no method exists for determining sensor nerve thresholds, and so sensory perception in the mouth is often measured by interdental thickness discrimination (ITD), or the ability to differentiate between the sizes of objects (thin blocks) placed between teeth. In one study, occlusal dysesthesia patients showed greater ability to differentiate these thicknesses than control, healthy individuals, but these differences were not statistically significant.
### Studies[edit]
* Bennett et al. produced an artificial peripheral mononeuropathy in rats by surgically constricting the sciatic nerve.[8] These rats showed an increased response to noxious radiant heat, were nocifensive when placed on a cold metal floor, protected their hind paws, and had suppressed appetite. Additionally, the paws of many of these rats were inappropriately warm or cool to the touch, and many of the rats overgrew claws on the affected paws as well. These results indicate that the rats exhibited hyperalgesia, allodynia, and dysesthesia.
* In a study in which researchers cut spinal nerves in rats, researchers found these rats exhibited a longer duration in spontaneous foot lifting, hypersensitivity to mechanical stimuli, allodynia, and hyperalgesia.[9] Additionally, the receptive field neurons in this nerve pathway showed spontaneous firing in low-threshold nociceptors, suggesting that nerve damage can cause dysesthesia.
* In women with chronic pain or itchy scalps without any apparent physical cause, about half had from psychiatric disorders. For the majority of these women, their symptoms of scalp dysesthesia were alleviated or removed by treatment with low doses of antidepressants.[10]
* Landerholm et al. hypothesized that dynamic mechanical allodynia (DMA) might be the hyperbole of dynamic mechanical dysesthesia (DMD), mediated by peripheral nerves. When the researchers artificially blocked nerves in patients with peripheral neuropathic pain or central post-stroke pain, DMA symptoms in many of the patients transitioned into DMD symptoms. Additionally, the researchers determined that the number of mechanocreceptive fibers associated with the nociceptive system was responsible for the differentiation of DMA to DMD.[11]
* Ochoa et al. recorded intraneural signals in subjects with post-ischaemic paraesthesiae. The researchers found the signals to be spontaneous. The frequency of the signals paralleled the intensity and timing of the paresthetic sensations reported by the patients. These results suggest that paresthetic sensations are the result of inappropriate firing frequency and timing by impulses from sensory cells.[12]
* Tuskiyama et al. assessed occlusal dysesthesia patients using an interdental thickness discrimination test and a psychological examination. The researchers found that occlusal dysesthesia patients could not discriminate the thickness of material in their bite any better than normal dental patients, but that the occlusal dysesthesia patients were significantly more likely to exhibit psychological disorders.[13]
## See also[edit]
* Paresthesia
* Scalp dysesthesia
* Dysaesthesia aethiopica, a pseudoscientific diagnosis
## References[edit]
1. ^ a b c IASP Pain Terminology Archived 2008-05-12 at the Wayback Machine.
2. ^ "How to Stop Chronic Anxiety From Dysesthesia". www.calmclinic.com.
3. ^ a b c d e Hara, E. S., Matsuka, Y., Minakuchi, H., Clark, G. T., & Kuboki, T. (2012). Occlusal dysesthesia: a qualitative systematic review of the epidemiology, aetiology and management. Journal of Oral Rehabilitation, 39(8): 630-638. [1]
4. ^ Klempner, M. S., Hu, L. T., Evans, J., Schmid, C. H., Johnson, G. M., Trevino, R. P., . . . Weinstein, A. (2001). Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. New England Journal of Medicine, 345(2), 85-92.
5. ^ "Understandng Dysesthesia in Multiple Sclerosis". about.com.
6. ^ Chow, G. C. S., Clarke, J. T. R., & Banwell, B. L. (2001). Late-onset GM2 gangliosidosis presenting as burning dysesthesias. Pediatric Neurology, 25(1).
7. ^ del Pino BM. Chemotherapy-induced Peripheral Neuropathy. NCI Cancer Bulletin. Feb 23, 2010 [archived 2011-12-11];7(4):6.
8. ^ Bennett, G. J., & Xie, Y. K. (1988). A PERIPHERAL MONONEUROPATHY IN RAT THAT PRODUCES DISORDERS OF PAIN SENSATION LIKE THOSE SEEN IN MAN. Pain, 33(1).
9. ^ Djouhri, L., Fang, X., Koutsikou, S., & Lawson, S. N. (2012). Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias. Pain, 153(9).
10. ^ Hoss, D., & Segal, S. (1998). Scalp dysesthesia. Archives of Dermatology, 134(3). doi: 10.1001/archderm.134.3.327
11. ^ Landerholm, A. H., & Hansson, P. T. (2011). Mechanisms of dynamic mechanical allodynia and dysesthesia in patients with peripheral and central neuropathic pain. European Journal of Pain, 15(5).
12. ^ Ochoa, J. L., & Torebjork, H. E. (1980). PARAESTHESIAE FROM ECTOPIC IMPULSE GENERATION IN HUMAN SENSORY NERVES. Brain, 103(DEC).
13. ^ Tsukiyama, Y., Yamada, A., Kuwatsuru, R., & Koyano, K. (2012). Bio-psycho-social assessment of occlusal dysaesthesia patients. Journal of Oral Rehabilitation, 39(8).
## Further reading[edit]
* Gale Encyclopedia of Neurological Disorders
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Dysesthesia
|
c0392699
| 8,097 |
wikipedia
|
https://en.wikipedia.org/wiki/Dysesthesia
| 2021-01-18T18:34:32 |
{"mesh": ["D010292"], "umls": ["C0392699"], "icd-10": ["R20.8"], "wikidata": ["Q1269376"]}
|
This article is about the fear of loud sounds. For the aversion to specific sounds, such as eating, coughing, or alarms, see Misophonia. For the fear of making or taking phone calls, see Telephone phobia.
Phonophobia
Other namesLigyrophobia, sonophobia, acousticophobia[1]
SpecialtyPsychiatry, neurology
Phonophobia, also called ligyrophobia or sonophobia, is a fear of or aversion to loud sounds (for example fireworks)—a type of specific phobia.[2] It is a very rare phobia which is often the symptom of hyperacusis. Sonophobia can refer to the hypersensitivity of a patient to sound and can be part of the diagnosis of a migraine. Occasionally it is called acousticophobia.[1]
The term phonophobia comes from Greek φωνή - phōnē, "sound"[3] and φόβος - phobos, "fear".[4]
Ligyrophobics may be fearful of devices that can suddenly emit loud sounds, such as computer speakers or fire alarms. When operating a device such as a home theater system, computer, television, or CD player, they may wish to have the volume turned down all the way before doing anything that would cause the speakers to emit sound, so that once the command to produce sound is given, the user can raise the volume of the speakers to a comfortable listening level. They may avoid parades and carnivals due to the loud instruments such as drums. As festive occasions are accompanied by music of over 120 decibels, many phobics develop agoraphobia. Other ligyrophobics also steer clear of any events in which fireworks are to be let off[citation needed] .
Another example is watching someone blow up a balloon beyond its normal capacity. This is often an unsettling, even disturbing thing for a person with ligyrophobia to observe, as he or she anticipates a loud sound when the balloon pops. When balloons pop, two types of reactions are heavy breathing and panic attacks. The sufferer becomes anxious to get away from the source of the loud sound and may get headaches.[1]
It may also be related to, caused by, or confused with "hyperacusis", extreme sensitivity to loud sounds.[5] Phonophobia also refers to an extreme form of misophonia.[6]
## See also[edit]
* Astraphobia – fear of thunder
* Misophonia – irrational 'hatred' or disgust expressed towards specific sounds
* List of phobias
## References[edit]
1. ^ a b c Swerdlow, Bernard (1998). Whiplash and Related Headaches. p. 526.
2. ^ "Home : Oxford English Dictionary". oed.com. Retrieved 2020-11-21.
3. ^ φωνή, Henry George Liddell, Robert Scott,A Greek-English Lexicon, on Perseus
4. ^ φόβος, Henry George Liddell, Robert Scott, A Greek-English Lexicon, on Perseus
5. ^ Roeser, Ross (2007). Audiology: Diagnosis. New York, NY: Thieme Medical Publishers, Inc. p. 331. ISBN 978-1-58890-542-0.
6. ^ "Decreased sound tolerance: hypersensitivity of hearing (hyperacusis, misophonia, phonophobia)", Jonathan Hazell FRCS, Director, Tinnitus and Hyperacusis Centre, London UK [1]
## External links[edit]
Classification
D
* MeSH: D012001
* DiseasesDB: 29099
* SNOMED CT: 313387002
* v
* t
* e
Diseases of the outer and middle ear
Outer ear
* Otitis externa
* Otomycosis
Middle ear
and mastoid
* Otitis media
* Mastoiditis
* Bezold's abscess
* Gradenigo's syndrome
* Tympanosclerosis
* Cholesteatoma
* Perforated eardrum
Symptoms
* Ear pain
* Hearing loss
Tests
* Otoscope
* pneumatic
* tympanometry
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: 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
|
Phonophobia
|
c0751466
| 8,098 |
wikipedia
|
https://en.wikipedia.org/wiki/Phonophobia
| 2021-01-18T18:39:50 |
{"mesh": ["D012001"], "wikidata": ["Q2434711"]}
|
A number sign (#) is used with this entry because of evidence that ectodermal dysplasia-7 (ECTD7) is caused by homozygous mutation in the KRT74 gene (608248) on chromosome 12q13. One such family has been reported.
Description
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Ectodermal dysplasia of the hair/nail type is a rare congenital condition characterized by hypotrichosis and nail dystrophy without nonectodermal or other ectodermal manifestations.
Clinical Features
Naeem et al. (2007) reported a consanguineous Pakistani family in which multiple members had a hair/nail type of ectodermal dysplasia. In those affected, hair was absent from the scalp, face, chest, arms, and legs. The patients were born completely devoid of eyebrows and eyelashes and never developed axillary and pubic hair. Nail abnormalities were present on all digits; both fingernails and toenails had a dystrophic appearance.
Rasool et al. (2010) described a large consanguineous Pakistani family in which 4 of 7 children had an autosomal recessive form of hair/nail ectodermal dysplasia. The affected individuals, 1 male and 3 females, had a generalized hypotrichosis present since birth. Eyebrows, eyelashes, and body hair were present but thin. The hairs appeared brittle and somewhat inflexible, with fragile shafts that broke relatively easily on mechanical stress. The hair was sparse and evenly distributed over the head in 3 patients, but 1 patient had hypotrichosis more pronounced on the scalp. Nail dystrophy was present in all 4, with a similar, relatively mild expression. All fingers and toes had a relative micronychia and mild distal onycholysis. The growth of both hair and nails was reduced compared to that in the healthy sibs. Affected family members had normal dentition and no skin abnormalities, and they reported normal sweating. Raykova et al. (2014) reported further on this family and noted that the clinical phenotype was relatively mild compared to previously reported forms of autosomal recessive hair/nail ectodermal dysplasia. They described hypotrichosis with 'shaggy' hair shafts as well as slightly spoon-shaped nails, mild micronychia, and distal onycholysis.
Inheritance
The transmission pattern of ectodermal dysplasia in the consanguineous Pakistani family reported by Naeem et al. (2007) was consistent with autosomal recessive inheritance.
Mapping
Naeem et al. (2007) performed linkage analysis by genotyping 8 members of a consanguineous Pakistani family (3 affected and 5 unaffected) segregating a hair/nail type of ectodermal dysplasia, using microsatellite markers linked to the related phenotype. The disease locus was mapped to chromosome 12p11.1-q21.1 between D12S2080 and D12S1040 (Zmax = 3.1).
In a Pakistani family with an autosomal recessive form of hair/nail ectodermal dysplasia, Rasool et al. (2010) performed linkage analysis using chromosome 12 markers and identified a linkage interval flanked by markers D12S2080 and D12S1686, with a maximum 2-point lod score of 2.92 (theta = 0.0) at locus D12S368.
Molecular Genetics
In 4 affected sibs from a consanguineous Pakistani family with hair/nail ectodermal dysplasia, originally studied by Rasool et al. (2010), Raykova et al. (2014) identified homozygosity for a missense mutation in the KRT74 gene (F274S; 608248.0004). The mutation, which was present in heterozygosity in their unaffected parents and an unaffected sib, was not found in 350 in-house exomes or in 200 Pakistani or 200 Swedish control chromosomes.
### Exclusion Studies
Naeem et al. (2007) performed DNA sequence analysis of the coding exons and splice sites of 6 hair keratin genes, including KRTHB5 (KRT85; 602767), located in the linkage interval (12p11.1-q21.1) identified in a family segregating a hair/nail type of ectodermal dysplasia and failed to detect any pathogenic mutation in the affected members of the family.
Rasool et al. (2010) performed bidirectional sequencing of all coding exons and splice junctions of 4 hair keratin genes on chromosome 12q13 (KRTHB1, KRTHB3, KRTHB5, and KRTHB6) on genomic DNA from 2 affected individuals from a Pakistani family with an autosomal recessive form of hair/nail ectodermal dysplasia. No sequence variants were identified.
INHERITANCE \- Autosomal recessive HEAD & NECK Teeth \- Normal teeth SKIN, NAILS, & HAIR Skin \- Normal skin \- Normal sweating Nails \- Dystrophic fingernails \- Dystrophic toenails \- Micronychia \- Hyponychia \- Onycholysis Hair \- Total alopecia at birth \- Hypotrichosis \- Brittle hair \- No eyebrows \- Thin eyebrows \- No eyelashes \- Sparse eyelashes \- No axillary hair \- No pubic hair MISCELLANEOUS \- Two Pakistani families reported (last curated July 2014) MOLECULAR BASIS \- Caused by mutation in the keratin 74 gene (KRT74, 608248.0004 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ECTODERMAL DYSPLASIA 7, HAIR/NAIL TYPE
|
c1865951
| 8,099 |
omim
|
https://www.omim.org/entry/614929
| 2019-09-22T15:53:40 |
{"mesh": ["C566592"], "omim": ["614929"], "orphanet": ["69084"]}
|
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