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A number sign (#) is used with this entry because of evidence that normophosphatemic familial tumoral calcinosis can be caused by mutation in the gene encoding the sterile alpha motif domain-containing-9 protein (SAMD9; 610456). Clinical Features Familial tumoral calcinosis (FTC) is an uncommon life-threatening disorder characterized by massive periarticular, and seldom visceral, deposition of calcified tumors (Metzker et al., 1988). When associated with hyperphosphatemia, the disorder is known as hyperphosphatemic FTC (HFTC; 211900). Topaz et al. (2004) identified a subset of patients with FTC who displayed normal circulating levels of phosphate. A total of 8 individuals were assessed in 5 families of Jewish Yemenite origin. All patients reported reddish-to-hyperpigmented skin lesions during the first year of life, which preceded the appearance of calcified nodules, distributed mainly over the extremities. In addition, severe conjunctivitis and gingivitis were observed in most of the affected individuals. Results of routine laboratory tests, including calcium, phosphate, vitamin D3 metabolites, and parathyroid-hormone levels, were normal. Histopathologic examination of lesional skin biopsies disclosed massive calcium deposition in the mid- and lower dermis. These individuals did not carry mutations in GALNT3 (601756) or FGF23 (605380), which suggested that HFTC and normophosphatemic FTC (NFTC) are nonallelic. Mapping Using the approach of homozygosity mapping, Topaz et al. (2006) identified a 7.6-Mb homozygous interval on 7q21-q21.3 that was shared by all patients in 5 Jewish Yemenite families. Molecular Genetics In 5 Jewish Yemenite families with NFTC, Topaz et al. (2006) screened the SAMD9 gene, found within the shared homozygous interval, and detected a substitution of a negatively charged glutamic acid residue for a positively charged lysine residue at amino acid position 1495 of the protein sequence (K1495E; 610456.0001). In a screening of 92 healthy, unrelated Jewish individuals born to couples who immigrated to Israel from Yemen, Topaz et al. (2006) found 1 individual who carried both K1495E and the disease haplotype in the heterozygous state, which corresponded to a carrier rate of approximately 0.01, fitting the expected prevalence of the disease in the Israeli Jewish Yemenite population. Whereas HFTC models metastatic calcinosis, which refers to deposition of calcified materials due to abnormal calcium phosphate metabolism, as seen in chronic renal failure, NFTC shows a striking resemblance to acquired dystrophic calcinosis, in which tissue calcification occurs as a consequence of tissue injury/inflammation, as observed in many unrelated conditions such as vascular disease, cancer, and autoimmune disorders (Topaz et al., 2006). The conspicuous inflammatory malformations reported in NFTC, which are absent in HFTC, suggest that the SAMD9 protein may be involved in physiologic responses to tissue injury. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Conjunctivitis Mouth \- Gingivitis SKIN, NAILS, & HAIR Skin \- Erythematous papular skin eruption (infancy) \- Calcified, ulcerating nodules Skin Histology \- Massive calcium deposition in mid- and lower dermis LABORATORY ABNORMALITIES \- Normal serum phosphate MISCELLANEOUS \- Present in Jewish Yemenite population MOLECULAR BASIS \- Caused by mutation in the sterile alpha motif domain-containing protein-9 gene (SAMD9, 610456.0001 ). ▲ 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	TUMORAL CALCINOSIS, NORMOPHOSPHATEMIC, FAMILIAL	c1864861	5,800	omim	https://www.omim.org/entry/610455	2019-09-22T16:04:29	{"doid": ["0080170"], "mesh": ["C566473"], "omim": ["610455"], "orphanet": ["306658", "53715"], "synonyms": ["Alternative titles", "CALCINOSIS, TUMORAL, WITH NORMOPHOSPHATEMIA"]}
Chromosome 16p13.3 deletion syndrome is a chromosome abnormality that can affect many parts of the body. People with this condition are missing a small piece (deletion) of chromosome 16 at a location designated p13.3. Although once thought to be a severe form of Rubinstein-Taybi syndrome, it is now emerging as a unique syndrome. Signs and symptoms may include failure to thrive, hypotonia (reduced muscle tone), short stature, microcephaly (unusually small head), characteristic facial features, mild to moderate intellectual disability, organ anomalies (i.e. heart and/or kidney problems), and vulnerability to infections. Chromosome testing of both parents can provide information about whether the deletion was inherited. In most cases, parents do not have any chromosome abnormalities. However, sometimes one parent has a balanced translocation where a piece of a chromosome has broken off and attached to another one with no gain or loss of genetic material. The balanced translocation normally does not cause signs or symptoms, but it increases the risk for having a child with a chromosome abnormality like a deletion. Treatment is based on the signs and symptoms present in each person. To learn more about chromosome abnormalities in general, view our GARD fact sheet on Chromosome 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	Chromosome 16p13.3 deletion syndrome	c1864648	5,801	gard	https://rarediseases.info.nih.gov/diseases/10754/chromosome-16p133-deletion-syndrome	2021-01-18T18:01:25	{"omim": ["610543"], "synonyms": ["16p13.3 deletion syndrome"]}
A rare, genetic, syndromic intellectual disability characterized by psychomotor delay, hypotonia, feeding difficulties, failure to thrive, anomalies of the hands and feet (clinodactyly, camptodactyly, brachydactyly, feet malposition), and craniofacial dysmorphism. Associated prenatal growth retardation, and gastrointestinal, heart and eye anomalies have been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	20q11.2 microdeletion syndrome	None	5,802	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=444051	2021-01-23T19:09:59	{"icd-10": ["Q93.5"], "synonyms": ["Del(20)(q11.2)", "Monosomy 20q11"]}
A number sign (#) is used with this entry because Hermansky-Pudlak syndrome-1 (HPS1) is caused by homozygous or compound heterozygous mutation in the HPS1 gene (604982) on chromosome 10q24. Description Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles: melanosomes, platelet-dense granules, and lysosomes (Oh et al., 1998). ### Genetic Heterogeneity of Hermansky-Pudlak Syndrome HPS2 (608233) is caused by mutation in the AP3B1 gene (603401) on chromosome 5q14. HPS3 (614072) is caused by mutation in the HSP3 gene (606118) on chromosome 3q24. HPS4 (614073) is caused by mutation in the HSP4 gene (606682) on chromosome 22q12. HPS5 (614074) is caused by mutation in the HPS5 gene (607521) on chromosome 11p14. HPS6 (614075) is caused by mutation in the HPS6 gene (607522) on chromosome 10q24. HPS7 (614076) is caused by mutation in the DTNBP1 gene (607145) on chromosome 6p22. HPS8 (614077) is caused by mutation in the BLOC1S3 gene (609762) on chromosome 19q13. HPS9 (614171) is caused by mutation in the PLDN gene (604310) on chromosome 15q21. HPS10 (617050) is caused by mutation in the AP3D1 gene (607246) on chromosome 19p13. Clinical Features Hermansky and Pudlak (1959) described 2 unrelated patients with albinism, a lifelong bleeding tendency, and peculiar pigmented reticular cells in the bone marrow as well as in lymph node and liver biopsies. One patient was male and the other female; both were 33 years old. After the woman's death, she was found to have large amounts of the pigment in reticuloendothelial cells everywhere and in the walls of small blood vessels (Hermansky, 1963). Two families, each with 2 sibs affected with this syndrome, had come to the attention of Hermansky (1963). This syndrome is clearly different from the Chediak-Higashi syndrome (214500) because no qualitative changes of leukocytes are found in Hermansky syndrome and no pigmented macrophages are found in Chediak-Higashi syndrome. Report of a family by Verloop et al. (1964) supports this conclusion. Logan et al. (1971) described a patient with albinism and bleeding diathesis in whom a defect in platelet ADP release was demonstrated. Prolonged bleeding time and defective platelet aggregation were found. Two other patients with albinism and a defect in ADP release had been reported, as well as 12 others with prolonged bleeding. In 6 of 7 in whom the bone marrow was studied, histiocytes were found to contain abnormal granules. Weiss et al. (1979) studied the platelet defect, which they called delta storage pool disease, in 7 patients; 6, including 3 sisters, were of Puerto Rican ancestry. Four other unrelated patients had the same platelet defect but did not have albinism. Depinho and Kaplan (1985) reported 3 affected sibs from a consanguineous Puerto Rican kindred. The proband, a 31-year-old woman with 2 children, had fatal restrictive lung disease, a complication pointed out by others (Davies and Tuddenham, 1976; Garay et al., 1979). Indeed, the first patient (Hermansky and Pudlak, 1959) was a 33-year-old farmer who developed chronic interstitial pulmonary fibrosis. Davies and Tuddenham (1976) described 4 sibs with HPS-associated pulmonary fibrosis. The onset of pulmonary fibrosis is most often in the third or fourth decade. Inflammatory bowel disease, with onset of symptoms between 12 and 30 years of age, in HPS patients has been reported by several authors (e.g., Schinella et al., 1980). Most of the patients with HPS-related bowel disease have been Puerto Rican. Response to medical therapy was said to be poor. Mahadeo et al. (1991) reported 2 children, aged 7 years and 3 years, with granulomatous colitis in association with HPS. One of the children was Puerto Rican. Epistaxis is the most frequent hemorrhagic manifestation. All 3 sibs studied by Depinho and Kaplan (1985) had recurrent infections and were anergic. Kinnear and Tuddenham (1985) reported 4 cases of Hermansky-Pudlak syndrome. Cutaneous malignant melanoma developed in 1. The ocular features were similar to those of tyrosinase-positive oculocutaneous albinism (203200). The triad of the syndrome is albinism, platelets lacking dense bodies, and storage of ceroid-like material in tissues. The manifestations of the storage disease include ulcerative colitis, restrictive lung disease, kidney failure, and cardiomyopathy. The autofluorescent material stored in HPS is histochemically similar to that stored in neuronal ceroid lipofuscinosis (204200). Sandberg-Gertzen et al. (1999) described HPS in a mentally retarded patient with albinism and mild bleeding diathesis; the course was complicated by granulomatous colitis refractory to medical treatment and progressive, fatal pulmonary fibrosis. Hearing (1993) reviewed the complexities of melanogenesis, including the parallels between mouse and the human. The complex nature of the process was anticipated since, in the mouse, more than 150 distinct mutations affect visible pigmentation, and those occur at more than 50 genetic loci. The Hermansky-Pudlak syndrome observed in the isolated Swiss Alps village (Lattion et al., 1983 and Schallreuter et al., 1993) usually shows a relatively mild clinical course with normal life expectancy, and the patients lack manifestations of ceroid storage. The 2 most common complications associated with ceroid deposition in the usual form of HPS are pulmonary fibrosis and granulomatous colitis; the major cause of death in HPS after 1 year of age is pulmonary fibrosis. There is striking variability in pigmentation, which can vary from an almost total absence of pigment to an amount that is nearly normal. Obligate heterozygotes are normally pigmented. The third feature of HPS is the absence of dense bodies in the platelets. Using immunofluorescence with antibodies against CD63 (155740), Nishibori et al. (1993) demonstrated deficiency of CD63 (155740) in HPS. Clinical Management Vitamin E was thought to be of some benefit for the hemorrhagic problem in patients with HPS (Depinho and Kaplan, 1985). Wijermans and van Dorp (1989) reported that 1-desamino-8D-arginine vasopressin (dDAVP) is useful in the treatment of some cases of HPS. The authors suggested that it be combined with drugs that inhibit fibrinolysis because dDAVP also increases plasminogen activator activity. Population Genetics HPS may be the most frequent single-gene disorder in Puerto Rico and is frequent in an isolated mountain village high in the Swiss Alps (Schallreuter et al., 1993). Witkop (1986) estimated a frequency of about 1 in 2,000 among Puerto Ricans. Wildenberg et al. (1995) stated that in Puerto Rico, HPS has a frequency of about 1 in 1,800, giving a carrier frequency estimated to be 1 in 21. The origin of HPS in Puerto Rico has been traced to a region of southern Spain, and a connection to cases in Holland was considered likely (King, 1987). Heterogeneity Evidence of locus heterogeneity for HPS was provided by findings of homozygosity analysis of 4 inbred non-Puerto Rican HPS patients in whom Oh et al. (1998) detected no mutations in the HPS1 gene. If these patients were homozygous (by descent) for occult HPS1 mutations, they should also have been homozygous for the polymorphic markers that Oh et al. (1998) had found immediately flanking the gene. However, 3 of these patients were heterozygous for these markers, thus apparently excluding the HPS1 locus in these cases. Furthermore, genetic linkage analysis of the extended family of 1 of these 4 patients, as well as in another non-inbred family, showed no evidence for linkage. Mapping Fukai et al. (1995) found that HPS maps to chromosome 10. They used the linkage disequilibrium mapping approach to localize the HPS1 gene (604982) in 2 groups in whom the disorder is particularly frequent: a group in Puerto Rico and a group in an isolated village in the Swiss Alps. They localized the HPS1 gene in both groups to a 0.6-cM interval in chromosome segment 10q23.1-q23.2. Wildenberg et al. (1995) likewise mapped the HPS1 gene to 10q. They collected blood samples from a relatively homogeneous population in Puerto Rico. Analysis of pooled DNA samples allowed them to screen the genome rapidly for candidate loci, and identify linkage with a marker on 10q. The result was verified with additional markers, and a maximum lod score of 5.07 at theta = 0.001 was calculated for marker D10S198. Haplotype analysis placed the HPS1 gene in a region of approximately 14 cM that contains the markers D10S198 and D10S1239. Molecular Genetics Oh et al. (1996) identified the HPS1 gene by positional cloning and found homozygous frameshifts in this gene in Puerto Rican, Swiss, Irish, and Japanese HPS patients. The HPS1 polypeptide is a novel transmembrane protein that is likely to be a component of multiple cytoplasmic organelles and is apparently crucial for their normal development and function. The different clinical phenotypes associated with different HPS1 frameshifts suggested that differentially truncated HPS1 polypeptides may have somewhat different consequences for subcellular function. Oh et al. (1998) performed mutation analysis on 44 unrelated Puerto Rican and 24 unrelated non-Puerto Rican HPS patients. A 16-bp frameshift duplication (604982.0001), the result of an apparent founder effect, was nearly ubiquitous among Puerto Rican patients. A frameshift at codon 322 (604982.0002) may be the most frequent HPS1 mutation in Europeans. Oh et al. (1998) also described 6 novel HPS1 mutations: a 5-prime splice-junction mutation of IVS5, 3 frameshifts, a nonsense mutation, and a 1-codon in-frame deletion. These mutations defined an apparent frameshift hotspot at codons 321-322. Overall, however, they detected mutations in the HPS1 gene in only about half of non-Puerto Rican patients, and presented evidence suggesting locus heterogeneity for HPS. Genotype/Phenotype Correlations All identified patients with HPS in northwest Puerto Rico were found to be homozygous for the 16-bp duplication in exon 15 of the HPS1 gene (604982.0001). Gahl et al. (1998) compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication. They studied 49 patients: 27 Puerto Ricans and 22 patients from mainland United States who were not of Puerto Rican descent. The diagnosis was based on the presence of albinism and the absence of platelet dense bodies. Homozygosity for the 16-bp duplication was found in 25 of the 27 Puerto Rican patients, whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80% of the predicted value. High-resolution computed tomography in all 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in 8 patients without the duplication revealed minimal fibrosis in 3 and no fibrosis in the rest. Inflammatory bowel disease developed in 8 patients (4 in each group) between 3 and 25 years of age. Thus, the 16-bp duplication in exon 15 of the HPS1 gene, which has been found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults. Iwata et al. (2000) studied 2 groups of patients with Hermansky-Pudlak syndrome: those with the 16-bp duplication in the HPS1 gene on chromosome 10q23 (604982.0001), and those without the duplication. The visual acuity in the better eye was not statistically significantly different between the 2 groups. Although the authors attempted to compare visual acuity and iris transillumination versus visual acuity and macular translucency, they concluded that the variability in visual acuity was too great. The associations studied were not large enough for useful prediction of vision based on the amount of pigmentation. Of 65 patients, aged 3 to 54 years, in whom the diagnosis of HPS had been made on the basis of absence of platelet dense bodies in individuals with albinism combined with a bleeding diathesis, Toro et al. (1999) found the 16-bp duplication in HPS1 by PCR amplification in 40 who were homozygous, whereas the other 25 lacked the duplication. All patients with the duplication were from northwest Puerto Rico; all patients without the duplication were non-Puerto Rican, except 4 from central Puerto Rico. Both groups displayed skin color ranging from white to light brown, hair color ranging from white to brown, and eye color ranging from blue to brown. New findings in both groups of patients with HPS were melanocytic nevi with dysplastic features, acanthosis nigricans-like lesions in the axilla and neck, and trichomegaly. In 80% of patients with the duplication, features of solar damage were found, including multiple freckles, stellate lentigines, actinic keratoses, and, occasionally, basal cell or squamous cell carcinomas. Only 8% of patients lacking the 16-bp duplication displayed these findings. As a group, the patients with the duplication lived closer to the equator than those without the duplication, but this was not thought to explain the difference entirely. Nomenclature In a review of the trafficking of organellar-specific proteins to melanosomes, lysosomes, and cytoplasmic granules, Spritz (1999) proposed that the Hermansky-Pudlak syndrome due to mutations in the AP3B1 gene be named HPS2 and the original syndrome be called HPS1. Hermansky-Pudlak syndrome due to mutation in a gene on 3q24 (606118) is known as HPS3 (Anikster et al., 2001). Animal Model Two genetically distinct mouse loci, 'pale ear' (ep) and 'ruby-eye' (ru), both with mutant phenotypes similar to human HPS, map close together in the homologous region of murine chromosome 19, which suggested that one of these loci might be homologous to human HPS1. Feng et al. (1997) characterized the mouse Hps1 cDNA and genomic locus, and identified pathologic Hps1 gene mutations in ep but not in ru mice, establishing mouse 'pale ear' as an animal model for human HPS. (The human homolog of mouse ru is HPS6, 607522). The phenotype of homozygous ep mutant mice encompasses those of both HPS and Chediak-Higashi syndrome, suggesting that these disorders may be closely related. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus \- Lifelong reduced visual acuity, legal blindness to low vision \- Iris transillumination (variable) \- Macular translucency (variable) \- Iris color blue to brown \- Ocular albinism Nose \- Epistaxis Mouth \- Gingival bleeding CARDIOVASCULAR Heart \- Cardiomyopathy RESPIRATORY Lung \- Interstitial pulmonary fibrosis \- Restrictive lung disease ABDOMEN Gastrointestinal \- Granulomatous colitis \- Abdominal pain \- Bloody diarrhea \- Inflammatory bowel disease GENITOURINARY Kidneys \- Renal failure SKIN, NAILS, & HAIR Skin \- Albinism \- Creamy white skin \- Tanning possible \- Freckles in sun-exposed areas \- Pigmented nevi Hair \- Hair color white to brown HEMATOLOGY \- Bleeding diathesis \- Absent dense bodies in platelets \- Easy bruisability \- Normal platelet counts \- Normal prothrombin and partial chromoplastin times \- Prolonged bleeding time \- Pigmented reticuloendothelial cells LABORATORY ABNORMALITIES \- Hair bulb tyrosinase present MISCELLANEOUS \- Genetic heterogeneity \- Gene frequency in Northwest Puerto Rico 1 in 18 MOLECULAR BASIS \- Caused by mutation in the HPS1 gene (HPS1, 203300 ) ▲ 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	HERMANSKY-PUDLAK SYNDROME 1	c0079504	5,803	omim	https://www.omim.org/entry/203300	2019-09-22T16:31:25	{"doid": ["0060539"], "mesh": ["D022861"], "omim": ["203300"], "orphanet": ["79430", "231500"], "synonyms": ["Alternative titles", "ALBINISM WITH HEMORRHAGIC DIATHESIS AND PIGMENTED RETICULOENDOTHELIAL CELLS", "DELTA STORAGE POOL DISEASE"], "genereviews": ["NBK1287"]}
Alopecia totalis (AT) is a condition characterized by the complete loss of hair on the scalp. It is an advanced form of alopecia areata a condition that causes round patches of hair loss. Although the exact cause of AT is unknown, it is thought to be an autoimmune condition in which the immune system mistakenly attacks the hair follicles. Roughly 20% of affected people have a family member with alopecia, suggesting that genetic factors may contribute to the development of AT. There is currently no cure for AT, but sometimes hair regrowth occurs on it's own, even after many years. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Alopecia totalis	c0263504	5,804	gard	https://rarediseases.info.nih.gov/diseases/613/alopecia-totalis	2021-01-18T18:02:11	{"orphanet": ["700"], "synonyms": ["Loss of all scalp hair"]}
The rare combination of muscle weakness with electrical myotonia but without clinical myotonia has been reported in acid maltase deficiency and in centronuclear myopathy. Juguilon et al. (1982) described 3 adult patients with profound selective muscle wasting and weakness, electrical myotonia, and unusual findings on muscle biopsy: vacuoles containing hematoxylinophilic granules, and in 30% of type I fibers, demarcation of the sarcoplasm into lobules due apparently to reorganization of myofibrillar elements. Two of the patients were sibs. The sister, aged 28 years, was well until age 18 years when difficulty climbing stairs and frequent tripping were noted. At age 19, discovery of myotonic discharges on EMG led to the diagnosis of dystrophia myotonica. The brother, aged 30, had similar history and findings. In both, the quadriceps femoris muscles were spared and no cataracts were found on slit-lamp examination. Muscle \- Muscle weakness. Selective muscle wasting. Neuro \- No clinical myotonia. Lab \- Electrical myotonia. Muscle biopsy shows vacuoles containing hematoxylinophilic granules, and in 30% of type I fibers, myofibrillar elements demarcate the sarcoplasm into lobules. 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	MYOPATHY, GRANULOVACUOLAR LOBULAR, WITH ELECTRICAL MYOTONIA	c1850745	5,805	omim	https://www.omim.org/entry/254950	2019-09-22T16:24:38	{"mesh": ["C564974"], "omim": ["254950"]}
Neuroendocrine tumor of the anal canal is an epithelial tumor of anal canal arising from enterochromaffin cells in the colorectal-type epithelium above the dentate line and in the anal transition zone. The tumors are slow growing and the majority of cases are diagnosed in later advanced stages. It may present with symptoms related to the anatomical location of the tumor (rectal mass, rectal bleeding and pain, tenesmus or changes in bowel habits), symptoms of carcinoid syndrome (flushing and increased gut motility) or nonspecific symptoms of advanced disease (hepatomegaly, fever, weight loss, anorexia, malaise). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Neuroendocrine tumor of anal canal	None	5,806	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100082	2021-01-23T18:14:17	{"synonyms": ["NET of anal canal"]}
Granulosa cell tumour Other namesGranulosa-theca cell tumours or Folliculoma Micrograph of a juvenile granulosa cell tumour with hyaline globules. H&E stain. SpecialtyGynecologic oncology, obstetrics and gynaecology, oncology, endocrinology Granulosa cell tumours are tumours that arise from granulosa cells. They are estrogen secreting tumors and present as large, complex, ovarian masses. These tumours are part of the sex cord-gonadal stromal tumour or non-epithelial group of tumours. Although granulosa cells normally occur only in the ovary, granulosa cell tumours occur in both ovaries and testicles (see ovarian cancer and testicular cancer). These tumours should be considered malignant and treated in the same way as other malignant tumours of ovary. The ovarian disease has two forms, juvenile and adult, both characterized by indolent growth,[1] and therefore has high recovery rates.[2][3] The staging system for these tumours is the same as for epithelial tumours and most present as stage I.[4] The peak age at which they occur is 50–55 years, but they may occur at any age. Juvenile granulosa cell tumour is a similar but distinct rare tumour. It too occurs in both the ovary and testis. In the testis it is extremely rare, and has not been reported to be malignant.[5] Although this tumour usually occurs in children (hence its name), it has been reported in adults.[6] ## Contents * 1 Presentation * 2 Genetics * 2.1 Adult Granulosa Cell Tumours * 2.2 Juvenile Granulosa Cell Tumours * 3 Diagnosis * 3.1 Gross appearance * 3.2 Tumour marker * 4 Treatment * 5 In animals * 6 See also * 7 References * 8 External links ## Presentation[edit] Estrogens are produced by functioning tumours, and the clinical presentation depends on the patient's age and sex. * Female * If the patient is postmenopausal, she usually presents with abnormal uterine bleeding, and in some cases hemoperitoneum. * If the patient is of reproductive age, she would present with menometrorrhagia. However, in some cases she may stop ovulating altogether. * If the patient has not undergone puberty, early onset of puberty may be seen. * these tumors tend to have late recurrencies ( even after 30 years ) ## Genetics[edit] ### Adult Granulosa Cell Tumours[edit] Ovarian tumours by incidence and risk of ovarian cancer, with adult granulosa cell tumour at right.[7] Using next generation DNA sequencing, 97% of adult granulosa cell tumours were found to contain an identical mutation in the FOXL2 gene [1]. This is a somatic mutation, meaning it is not usually transmitted to descendants. Mutation c.402C>G in the sequence of FOXL2 leads to the amino acid substitution p. C134W. It is believed that this mutation may be the cause of granulosa cell tumours.[citation needed] ### Juvenile Granulosa Cell Tumours[edit] Two recent studies show that the enzyme AKT1 is involved in juvenile granulosa cell tumours. In-frame duplications in the pleckstrin-homology domain of the protein were found in more than 60% of juvenile granulosa cell tumours occurring in girls under 15 years of age. The tumours without duplications carried point mutations affecting highly conserved residues. The mutated proteins carrying the duplications displayed a non-wild-type subcellular distribution, with a marked enrichment at the plasma membrane, leading to a strong activation of AKT1.[8] Analysis by RNA-Seq pinpointed a series of differentially expressed genes that are involved in cytokine and hormone signaling and cell division-related processes. Further analyses pointed to a possible dedifferentiation process, and suggested that most of the transcriptomic dysregulations might be mediated by a limited set of transcription factors perturbed by AKT1 activation. These results incriminate somatic mutations of AKT1 as probable driver events in the pathogenesis of juvenile granulosa cell tumours.[9] ## Diagnosis[edit] ### Gross appearance[edit] Tumours vary in size, from tiny spots to large masses, with an average of 10 cm in diameter. Tumours are oval and soft in consistency. On cut-section, histology reveals reticular, trabecular areas with interstitial haemorrhage and Call-Exner bodies-small cyst like spaces interspersed within a graafian follicle. ### Tumour marker[edit] Inhibin, a hormone, has been used as biomarker for granulosa cell tumours. ## Treatment[edit] This section is empty. You can help by adding to it. (February 2018) ## In animals[edit] In the ovaries of aging squirrel monkeys (Saimiri sciureus), clusters of granulosa cells occur that resemble granulosa cell tumours in humans.[10] These appear to be a normal change with age in this species. ## See also[edit] * Inhibin, alpha ## References[edit] 1. ^ "Prognostic factors in adult granulosa". 2. ^ Young RH, Dickersin GR, Scully RE (1984). "Juvenile granulosa cell tumor of the ovary. A clinic pathological analysis of 125 cases. Beth Israel Deaconess Medical Center, Boston". American Journal of Surgical Pathology. 8 (8): 575–596. doi:10.1097/00000478-198408000-00002. PMID 6465418. 3. ^ "Program in Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center, Boston". 4. ^ Gynaecology. 3rd Ed. 2003. Churchill Livingstone, pp. 690-691. 5. ^ Dudani R, Giordano L, Sultania P, Jha K, Florens A, Joseph T (April 2008). "Juvenile granulosa cell tumor of testis: case report and review of literature". American Journal of Perinatology. 25 (4): 229–231. doi:10.1055/s-2008-1066878. PMID 18548396. 6. ^ Lin KH, Lin SE, Lee LM (July 2008). "Juvenile granulosa cell tumor of adult testis: a case report". Urology. 72 (1): 230.e11–3. doi:10.1016/j.urology.2007.11.126. PMID 18313118. 7. ^ \- Vaidya, SA; Kc, S; Sharma, P; Vaidya, S (2014). "Spectrum of ovarian tumors in a referral hospital in Nepal". Journal of Pathology of Nepal. 4 (7): 539–543. doi:10.3126/jpn.v4i7.10295. ISSN 2091-0908. \- Minor adjustment for mature cystic teratomas (0.17 to 2% risk of ovarian cancer): Mandal, Shramana; Badhe, Bhawana A. (2012). "Malignant Transformation in a Mature Teratoma with Metastatic Deposits in the Omentum: A Case Report". Case Reports in Pathology. 2012: 1–3. doi:10.1155/2012/568062. ISSN 2090-6781. PMC 3469088. PMID 23082264. 8. ^ Bessière L, Todeschini AL, Auguste A, Sarnacki S, Flatters D, Legois B, Sultan C, Kalfa N, Galmiche L, Veitia RA (March 2015). "A Hot-spot of In-frame Duplications Activates the Oncoprotein AKT1 in Juvenile Granulosa Cell Tumors". EBioMedicine. 2 (5): 421–431. doi:10.1016/j.ebiom.2015.03.002. PMC 4485906. PMID 26137586. 9. ^ Auguste A, Bessière L, Todeschini AL, Caburet S, Sarnacki S, Prat J, D'angelo E, De La Grange P, Ariste O, Lemoine F, Legois B, Sultan C, Zider A, Galmiche L, Kalfa N, Veitia RA (Dec 2015). "Molecular analyses of juvenile granulosa cell tumors bearing AKT1 mutations provide insights into tumor biology and therapeutic leads". Human Molecular Genetics. 24 (23): 6687–6698. doi:10.1093/hmg/ddv373. PMID 26362254. 10. ^ Walker ML, Anderson DC, Herndon JG, Walker LC (2009). "Ovarian aging in squirrel monkeys (Saimiri sciureus)". Reproduction. 138 (4): 793–799. doi:10.1530/REP-08-0449. PMID 19656956. ## External links[edit] Classification D * ICD-10: C56 * ICD-9-CM: 236.2 183 236.2 * ICD-O: 8620 * MeSH: D006106 External resources * eMedicine: med/928 * v * t * e Tumors of the female urogenital system Adnexa Ovaries Glandular and epithelial/ surface epithelial- stromal tumor CMS: * Ovarian serous cystadenoma * Mucinous cystadenoma * Cystadenocarcinoma * Papillary serous cystadenocarcinoma * Krukenberg tumor * Endometrioid tumor * Clear-cell ovarian carcinoma * Brenner tumour Sex cord–gonadal stromal * Leydig cell tumour * Sertoli cell tumour * Sertoli–Leydig cell tumour * Thecoma * Granulosa cell tumour * Luteoma * Sex cord tumour with annular tubules Germ cell * Dysgerminoma * Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma/Struma ovarii * Choriocarcinoma Fibroma * Meigs' syndrome Fallopian tube * Adenomatoid tumor Uterus Myometrium * Uterine fibroids/leiomyoma * Leiomyosarcoma * Adenomyoma Endometrium * Endometrioid tumor * Uterine papillary serous carcinoma * Endometrial intraepithelial neoplasia * Uterine clear-cell carcinoma Cervix * Cervical intraepithelial neoplasia * Clear-cell carcinoma * SCC * Glassy cell carcinoma * Villoglandular adenocarcinoma Placenta * Choriocarcinoma * Gestational trophoblastic disease General * Uterine sarcoma * Mixed Müllerian tumor Vagina * Squamous-cell carcinoma of the vagina * Botryoid rhabdomyosarcoma * Clear-cell adenocarcinoma of the vagina * Vaginal intraepithelial neoplasia * Vaginal cysts Vulva * SCC * Melanoma * Papillary hidradenoma * Extramammary Paget's disease * Vulvar intraepithelial neoplasia * Bartholin gland carcinoma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Granulosa cell tumour	c0018206	5,807	wikipedia	https://en.wikipedia.org/wiki/Granulosa_cell_tumour	2021-01-18T18:57:00	{"mesh": ["D006106"], "umls": ["C0018206", "C0334401"], "icd-9": ["183", "236.2"], "icd-10": ["C56"], "wikidata": ["Q612093"]}
Neuroma cutis is a relatively rare type of neuroma, or tumor involving nervous tissue, in the skin.[1] There are three types of true neuromas of the skin and mucous membranes known to exist: traumatic neuromas, multiple mucosal neuromas, and solitary palisaded encapsulated neuromas.[2] ## See also[edit] * Skin lesion ## References[edit] 1. ^ Heidingsfield, M. L. (1907-02-16). "Myomata Cutis". The Journal of the American Medical Association: 562. 2. ^ William, James; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders. ISBN 978-0-7216-2921-6. 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	Neuroma cutis	c0346057	5,808	wikipedia	https://en.wikipedia.org/wiki/Neuroma_cutis	2021-01-18T18:49:16	{"umls": ["C0346057"], "wikidata": ["Q16937037"]}
Part of a series on Psychology * Outline * History * Subfields Basic types * Abnormal * Behavioral genetics * Biological * Cognitive/Cognitivism * Comparative * Cross-cultural * Cultural * Differential * Developmental * Evolutionary * Experimental * Mathematical * Neuropsychology * Personality * Positive * Quantitative * Social Applied psychology * Applied behavior analysis * Clinical * Community * Consumer * Counseling * Critical * Educational * Environmental * Ergonomics * Forensic * Health * Humanistic * Industrial and organizational * Legal * Medical * Military * Music * Occupational health * Political * Religion * School * Sport * Traffic Lists * Disciplines * Organizations * Psychologists * Psychotherapies * Publications * Research methods * Theories * Timeline * Topics * Psychology portal * v * t * e Cognitive disorders (CDs), also known as neurocognitive disorders (NCDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem solving. Neurocognitive disorders include delirium and mild and major neurocognitive disorder (previously known as dementia). They are defined by deficits in cognitive ability that are acquired (as opposed to developmental), typically represent decline, and may have an underlying brain pathology.[1] The DSM-5 defines six key domains of cognitive function: executive function, learning and memory, perceptual-motor function, language, complex attention, and social cognition. Although Alzheimer's disease accounts for the majority of cases of neurocognitive disorders, there are various medical conditions that affect mental functions such as memory, thinking, and the ability to reason, including frontotemporal degeneration, Huntington’s disease, Lewy body disease, traumatic brain injury (TBI), Parkinson’s disease, prion disease, and dementia/neurocognitive issues due to HIV infection.[2] Neurocognitive disorders are diagnosed as mild and major based on the severity of their symptoms. While anxiety disorders, mood disorders, and psychotic disorders can also have an effect on cognitive and memory functions, the DSM-IV-TR does not consider these cognitive disorders, because loss of cognitive function is not the primary (causal) symptom.[3] Additionally, developmental disorders such as autism spectrum disorder are typically developed at birth or early in life as opposed to the acquired nature of neurocognitive disorders. Causes vary between the different types of disorders but most include damage to the memory portions of the brain.[4][5][6] Treatments depend on how the disorder is caused. Medication and therapies are the most common treatments; however, for some types of disorders such as certain types of amnesia, treatments can suppress the symptoms but there is currently no cure.[5][6] ## Contents * 1 Cognitive mental disorder perspective * 2 Classifications * 2.1 Delirium * 2.2 Mild and major neurocognitive disorder * 3 Causes * 3.1 Delirium * 3.2 Mild and major neurocognitive disorder * 4 Treatment * 4.1 Delirium * 4.2 Mild and major neurocognitive disorder * 5 See also * 6 Notes * 7 References ## Cognitive mental disorder perspective[edit] In abnormal psychology, cognitive disorders are mental disorders that develop on the basis of cognitive mental disorder perspective. The cognitive mental disorder perspective is the theory that psychological disorders originate from an interruption, whether short or long, in our basic cognitive functions, i.e. memory processing, perception, problem solving and language. This perspective takes opposition to the psychodynamic mental disorder perspective, behavioral mental disorder perspective, sociocultural mental disorder perspective, interpersonal mental disorder perspective and neurological/biological mental disorder perspective. One pioneer of cognitive disorder perspective is Albert Ellis. In 1962, Ellis proposed that humans develop irrational beliefs/goals about the world; and therefore, create disorders in cognitive abilities.[7] Another pioneer of the cognitive disorder perspective is Aaron Beck. In 1967, Beck designed what is known as the "cognitive model" for emotional disorders, mainly depression.[7] His model showed that a blending of negative cognitive functions about the self, the world, and possible selves lead to cognitive mental disorders. ## Classifications[edit] The previous edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) included a section entitled "Delirium, Dementia and Amnestic and Other Cognitive Disorders," which was revised in DSM-5 to the broader "Neurocognitive Disorders." Neurocognitive disorders are described as those with “a significant impairment of cognition or memory that represents a marked deterioration from a previous level of function”.[3] The subsections include delirium and mild and major neurocognitive disorder. ### Delirium[edit] Delirium develops rapidly over a short period of time and is characterized by a disturbance in cognition, manifested by confusion, excitement, disorientation, and a clouding of consciousness. Hallucinations and illusions are common, and some individuals may experience acute onset change of consciousness. It is a disorder that makes situational awareness and processing new information very difficult for those diagnosed. It usually has a high rate of onset ranging from minutes to hours and sometimes days, but it does not last for very long, only a few hours to weeks.[3] Delirium can also be accompanied by a shift in attention, mood swings, violent or unordinary behaviors, and hallucinations. It can be caused by a preexisting medical condition.[4] Delirium during a hospital stay can result in a longer stay and more risk of complications and long terms stays.[8] ### Mild and major neurocognitive disorder[edit] Mild and major neurocognitive disorders are usually associated with but not restricted to the elderly. Unlike delirium, conditions under these disorders develop slowly and are characterized by memory loss. In addition to memory loss and cognitive impairment, other symptoms include aphasia, apraxia, agnosia, loss of abstract thought, behavioral/personality changes, and impaired judgment. There may also be behavioral disturbances including psychosis, mood, and agitation. Mild and major neurocognitive disorders are differentiated based on the severity of their symptoms. Previously known as dementia, major neurocognitive disorder is characterized by significant cognitive decline and interference with independence, while mild neurocognitive disorder is characterized by moderate cognitive decline and does not interfere with independence. To be diagnosed, it must not be due to delirium or other mental disorder. They are also usually accompanied by another cognitive dysfunction.[3] For non-reversible causes of dementia such as age, the slow decline of memory and cognition is lifelong.[3] It can be diagnosed by screening tests such as the Mini Mental State Examination (MMSE).[3] ## Causes[edit] ### Delirium[edit] Delirium can be caused by the worsening of previous medical conditions, substance abuse or withdrawal, mental illness, severe pain, immobilization, sleep deprivation and hypnosis.[4] Other common causes that may increase the risk of delirium include infections of urinary tract, skin and stomach, pneumonia, old age, and poor nutrition.[9] ### Mild and major neurocognitive disorder[edit] Neurocognitive disorders can have numerous causes: genetics, brain trauma, stroke, and heart issues. The main causes are neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease because they affect or deteriorate brain functions.[5] Other diseases and conditions that cause NCDs include vascular dementia, frontotemporal degeneration, Lewy body disease, prion disease, normal pressure hydrocephalus, and dementia/neurocognitive issues due to HIV infection. They may also include dementia due to substance abuse or exposure to toxins. Neurocognitive disorder may also be caused by brain trauma, including concussions and traumatic brain injuries, as well as post-traumatic stress and alcoholism. This is referred to as amnesia, and is characterized by damage to major memory encoding parts of the brain such as the hippocampus.[6] Difficulty creating recent term memories is called anterograde amnesia and is caused by damage to the hippocampus part of the brain, which is a major part of the memory process.[6] Retrograde amnesia is also caused by damage to the hippocampus, but the memories that were encoded or in the process of being encoded in long term memory are erased[6] ## Treatment[edit] ### Delirium[edit] Before delirium treatment, the cause must be established. Medication such as antipsychotics or benzodiazepines can help reduce the symptoms for some cases. For alcohol or malnourished cases, vitamin B supplements are recommended and for extreme cases, life-support can be used.[4] ### Mild and major neurocognitive disorder[edit] There is no cure for neurocognitive disorder or the diseases that cause it. Antidepressants, antipsychotics, and other medications that treat memory loss and behavioral symptoms are available and may help to treat the diseases. Ongoing psychotherapy and psychosocial support for patients and families are usually necessary for clear understanding and proper management of the disorder and to maintain a better quality of life for everyone involved. Speech therapy has been shown to help with language impairment, therefore improving long term development and academic outcome.[10] Studies suggest that diets with high Omega 3 content, low in saturated fats and sugars, along with regular exercise can increase the level of brain plasticity.[11] Other studies have shown that mental exercise such a newly developed “computerized brain training programs” can also help build and maintain targeted specific areas of the brain. These studies have been very successful for those diagnosed with schizophrenia and can improve fluid intelligence, the ability to adapt and deal with new problems or challenges the first time encountered, and in young people, it can still be effective in later life.[6] A person with amnesia may slowly be able to recall their memories or work with an occupational therapist to learn new information to replace what was lost, or to use intact memories as a basis for taking in new information. If it is caused by an underlying cause such as Alzheimer's disease or infections, the cause may be treated but the amnesia may not be.[citation needed] ## See also[edit] * List of cognitive disorders ## Notes[edit] 1. ^ Rosen, Allyson. "Neurocognitive Disorders of the DSM-5" (PDF). stanford.edu. Retrieved 2 October 2017. 2. ^ Simpson JR (2014). "DSM-5 and neurocognitive disorders". J. Am. Acad. Psychiatry Law. 42 (2): 159–64. PMID 24986342. 3. ^ a b c d e f Guerrero, Anthony (2008). Problem-Based Behavioral Science of Medicine. New York: Springer. pp. 367–79. 4. ^ a b c d Torpy, Janet (2008). "Delirium". The Journal of the American Medical Association. 300 (19): 2936. doi:10.1001/jama.300.24.2936. PMID 19109124. 5. ^ a b c Torpy, Janet (2010). "Dementia". The Journal of the American Medical Association. 304 (7): 1972. doi:10.1001/jama.304.17.1972. PMID 21045107. 6. ^ a b c d e f Cicerelli, Saundra. Psychology. Upper Saddle River: Pearson Prentice Hal. 7. ^ a b Alloy, et al., 2005 8. ^ McGohan (2005). "Clinical Updates. Delirium". The Journal of Continuing Education in Nursing. 36 (3): 102–103. doi:10.3928/0022-0124-20050501-05. PMID 16022028. 9. ^ "MayoClinic's Review". MayoClinic. 10. ^ Ullrich, Dieter; Ullrich, Katja; Marten, Magret (September 2014). "A longitudinal assessment of early childhood education with integrated speech therapy for children with significant language impairment in Germany: Longitudinal assessment of early childhood education with integrated speech therapy". International Journal of Language & Communication Disorders. 49 (5): 558–566. doi:10.1111/1460-6984.12092. PMID 24939594. 11. ^ Gomez-Pinilla, Fernando (2011). "The Combined Effects of Exercise and Foods in Preventing Neurological and Cognitive Disorders". Preventive Medicine. 52: S75–S80. doi:10.1016/j.ypmed.2011.01.023. PMC 3258093. PMID 21281667. ## References[edit] Alloy, Lauren; John Riskind; Margaret Manos (October 2005). Abnormal Psychology. McGraw Hill. pp. 88–89. ISBN 0-07-242298-X. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Cognitive disorder	c0029227	5,809	wikipedia	https://en.wikipedia.org/wiki/Cognitive_disorder	2021-01-18T18:47:05	{"mesh": ["D019965", "D003072"], "umls": ["C0029227"], "wikidata": ["Q3065932"]}
Psychomotor retardation Other namesPsychomotor impairment, motormental retardation, psychomotor slowing SpecialtyPsychiatry Psychomotor retardation involves a slowing-down of thought and a reduction of physical movements in an individual. Psychomotor retardation can cause a visible slowing of physical and emotional reactions, including speech and affect.[1] Psychomotor retardation is most-commonly seen in people with major depression and in the depressed phase of bipolar disorder;[2] it is also associated with the adverse effects of certain drugs, such as benzodiazepines.[3] Particularly in an inpatient setting, psychomotor retardation may require increased nursing care to ensure adequate food and fluid intake and sufficient personal care. Informed consent for treatment is more difficult to achieve in the presence of this condition.[citation needed] ## Contents * 1 Causes * 2 Examples * 3 See also * 4 References * 5 External links ## Causes[edit] * Psychiatric disorders – schizophrenia, severe depression, bipolar disorder, etc. * Psychological disorders – eating disorders, mood disorders, anxiety disorders, etc. * Psychiatric medicines (if taken improperly, overdosed, or mixed with alcohol) * Parkinson's disease[4] ## Examples[edit] Examples of psychomotor retardation include the following: * Unaccountable difficulty in carrying out what are usually considered "automatic" or "mundane" self-care tasks for healthy people (i.e., without depressive illness) such as taking a shower, dressing, self-grooming, cooking, brushing one's teeth and exercising. * Physical difficulty performing activities which normally would require little thought or effort such as walking up a flight of stairs, getting out of bed, preparing meals and clearing dishes from the table, household chores or returning phone calls. * Tasks requiring mobility suddenly (or gradually) may inexplicably seem to be "impossible." Activities such as shopping, getting groceries, caring for the daily needs of one's children and meeting the demands of employment or school are commonly affected. * Activities usually requiring little mental effort can become challenging. Balancing one's checkbook, making a shopping list or making decisions about mundane tasks (such as deciding what errands need to be done) are often difficult. In schizophrenia, activity level may vary from psychomotor retardation to agitation; the patient will experience periods of listlessness and may be unresponsive, and at the next moment be active and energetic.[5] ## See also[edit] * Psychomotor learning * Psychomotor agitation ## References[edit] 1. ^ Tryon, W.W. 1991.Activity Measurement in Psychology and Medicine. Springer Publishing 2. ^ Buyukdura JS, McClintock SM, Croarkin PE (2011). "Psychomotor retardation in depression: biological underpinnings, measurement, and treatment". Prog Neuropsychopharmacol Biol Psychiatry. 35 (2): 395–409. doi:10.1016/j.pnpbp.2010.10.019. PMC 3646325. PMID 21044654. 3. ^ Allgulander, C.; Bandelow, B.; Hollander, E.; Montgomery, SA.; Nutt, DJ.; Okasha, A.; Pollack, MH.; Stein, DJ.; et al. (Aug 2003). "WCA recommendations for the long-term treatment of generalized anxiety disorder". CNS Spectr. 8 (8 Suppl 1): 53–61. doi:10.1017/S1092852900006945. PMID 14767398. 4. ^ "Psychomotor retardation". Retrieved 11 March 2016. 5. ^ Christopher D. Frith (1 January 1995). The cognitive neuropsychology of schizophrenia. Lawrence Erlbaum. p. 53. ISBN 978-0-86377-334-1. Retrieved 13 December 2010. ## External links[edit] Classification D * ICD-9-CM: 308.2 * MeSH: D011596 * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Psychomotor retardation	c0424230	5,810	wikipedia	https://en.wikipedia.org/wiki/Psychomotor_retardation	2021-01-18T18:44:52	{"icd-9": ["308.2"], "wikidata": ["Q3064951"]}
Very rare, incurable and fatal neurodegenerative disorder that was formerly common among the Fore people of Papua New Guinea. Kuru is a form of transmissible spongiform encephalopathy (TSE) Not to be confused with Koro (medicine). Kuru A Fore child with advanced kuru. He is unable to walk or sit upright without assistance and is severely malnourished. SpecialtyNeuropathology SymptomsBody tremors, random outbursts of laughter, gradual loss of coordination ComplicationsInfection and pneumonia during the terminal stage. Usual onsetOften takes years or even decades for symptoms to appear after exposure Duration11–14 month life expectancy after onset of symptoms[1] CausesTransmission of infected prion proteins Risk factorsCannibalism Diagnostic methodAutopsy Differential diagnosisCreutzfeldt–Jakob disease PreventionAvoid practices of cannibalism TreatmentNone PrognosisAlways fatal Frequency2,700 (1957–2004) DeathsApproximately 2,700 Kuru is a very rare, incurable and fatal neurodegenerative disorder that was formerly common among the Fore people of Papua New Guinea. Kuru is a form of transmissible spongiform encephalopathy (TSE) caused by the transmission of abnormally folded proteins (prion proteins), which leads to symptoms such as tremors and loss of coordination from neurodegeneration. The term kuru derives from the Fore word kuria or guria ("to shake"),[2] due to the body tremors that are a classic symptom of the disease. Kúru itself means "trembling".[3] It is also known as the "laughing sickness" due to the pathologic bursts of laughter which are a symptom of the disease. It is now widely accepted that kuru was transmitted among members of the Fore tribe of Papua New Guinea via funerary cannibalism. Deceased family members were traditionally cooked and eaten, which was thought to help free the spirit of the dead.[4] Women and children usually consumed the brain, the organ in which infectious prions were most concentrated, thus allowing for transmission of kuru. The disease was therefore more prevalent among women and children. The epidemic likely started when a villager developed sporadic Creutzfeldt–Jakob disease and died. When villagers ate the brain, they contracted the disease, and it was then spread to other villagers who ate their infected brains.[5] While the Fore people stopped consuming human meat in the early 1960s, when it was first speculated to be transmitted via endocannibalism, the disease lingered due to kuru's long incubation period of anywhere from 10 to over 50 years.[6] The epidemic declined sharply after the tribe ended cannibalism, from 200 deaths per year in 1957 to no deaths from at least 2010 onwards, with sources disagreeing on whether the last known kuru victim died in 2005 or 2009.[7][8][9][10] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Prion * 2.2 Transmission * 3 Immunity * 4 History * 5 In literature and popular culture * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Kuru, a transmissible spongiform encephalopathy, is a disease of the nervous system that causes physiological and neurological effects which ultimately lead to death. It is characterized by progressive cerebellar ataxia, or loss of coordination and control over muscle movements.[11][12] The preclinical or asymptomatic phase, also called the incubation period, averages 10–13 years, but can be as short as five and has been estimated to last as long as 50 years or more after initial exposure.[13] The clinical stage, which begins at the first onset of symptoms, lasts an average of 12 months. The clinical progression of kuru is divided into three specific stages: the ambulant, sedentary and terminal stages. While there is some variation in these stages between individuals, they are highly conserved among the affected population.[11] Before the onset of clinical symptoms, an individual can also present with prodromal symptoms including headache and joint pain in the legs.[14] In the first (ambulant) stage, the infected individual may exhibit unsteady stance and gait, decreased muscle control, tremors, difficulty pronouncing words (dysarthria), and titubation. This stage is named the ambulant because the individual is still able to walk around despite symptoms.[14] In the second (sedentary) stage, the infected individual is incapable of walking without support and suffers ataxia and severe tremors. Furthermore, the individual shows signs of emotional instability and depression, yet exhibits uncontrolled and sporadic laughter. Despite the other neurological symptoms, tendon reflexes are still intact at this stage of the disease.[14] In the third and final (terminal) stage, the infected individual's existing symptoms, like ataxia, progress to the point where they are no longer capable of sitting without support. New symptoms also emerge: the individual develops dysphagia, which can lead to severe malnutrition. They may also become incontinent, lose the ability or will to speak and become unresponsive to their surroundings, despite maintaining consciousness.[14] Towards the end of the terminal stage, patients often develop chronic ulcerated wounds that can be easily infected. An infected person usually dies within three months to two years after the first terminal stage symptoms, often because of pneumonia or other secondary infections.[15] ## Causes[edit] Kuru is largely localized to the Fore people and people with whom they intermarried.[16] The Fore people ritualistically cooked and consumed body parts of their family members following their death to symbolize respect and mourning.[citation needed] Because the brain is the organ enriched in the infectious prion, women and children, who consumed brain and viscera, had much higher likelihood of being infected than men, who preferentially consumed muscles.[17] Normally folded prion protein PrPc subdomain-Residues 125–228. Note the presence of alpha helices (blue) ### Prion[edit] Cryoelectron Microscopy model of the misfolded PrPsc protein, enriched in beta sheets (center).[18] The infectious agent is a misfolded form of a host-encoded protein called prion (PrP). Prion proteins are encoded by the Prion Protein Gene (PRNP).[19] The two forms of prion are designated as PrPc, which is a normally folded protein, and PrPsc, a misfolded form which gives rise to the disease. The two forms do not differ in their amino acid sequence; however, the pathogenic PrPsc isoform differs from the normal PrPc form in its secondary and tertiary structure. The PrPsc isoform is more enriched in beta sheets, while the normal PrPc form is enriched in alpha helices.[17] The differences in conformation allow PrPsc to aggregate and be extremely resistant to protein degradation by enzymes or by other chemical and physical means. The normal form, on the other hand, is susceptible to complete proteolysis and soluble in non-denaturing detergents.[14] It has been suggested that pre-existing or acquired PrPsc can promote the conversion of PrPc into PrPsc, which goes on to convert other PrPc. This initiates a chain reaction that allows for its rapid propagation, resulting in the pathogenesis of prion diseases.[14] ### Transmission[edit] In 1961, Australian medical researcher Michael Alpers conducted extensive field studies among the Fore accompanied by anthropologist Shirley Lindenbaum.[9] Their historical research suggested the epidemic may have originated around 1900 from a single individual who lived on the edge of Fore territory and who is thought to have spontaneously developed some form of Creutzfeldt–Jakob disease.[20] Alpers and Lindenbaum's research conclusively demonstrated that kuru spread easily and rapidly in the Fore people due to their endocannibalistic funeral practices, in which relatives consumed the bodies of the deceased to return the "life force" of the deceased to the hamlet, a Fore societal subunit.[21] Corpses of family members were often buried for days, then exhumed once the corpses were infested with maggots, at which point the corpse would be dismembered and served with the maggots as a side dish.[22] The demographic distribution evident in the infection rates – kuru was eight to nine times more prevalent in women and children than in men at its peak – is because Fore men considered consuming human flesh to weaken them in times of conflict or battle, while the women and children were more likely to eat the bodies of the deceased, including the brain, where the prion particles were particularly concentrated. Also, the strong possibility exists that it was passed on to women and children more easily because they took on the task of cleaning relatives after death and may have had open sores and cuts on their hands.[17] Although ingestion of the prion particles can lead to the disease,[23] a high degree of transmission occurred if the prion particles could reach the subcutaneous tissue. With elimination of cannibalism because of Australian colonial law enforcement and the local Christian missionaries' efforts, Alpers' research showed that kuru was already declining among the Fore by the mid‑1960s. However, the mean incubation period of the disease is 14 years, and 7 cases were reported with latencies of 40 years or more for those who were most genetically resilient, continuing to appear for several more decades. Sources disagree on whether the last sufferer died in 2005 or 2009.[9][10][7][8] ## Immunity[edit] Cerebellum of a kuru victim. In 2009, researchers at the Medical Research Council discovered a naturally occurring variant of a prion protein in a population from Papua New Guinea that confers strong resistance to kuru. In the study, which began in 1996,[24] researchers assessed over 3,000 people from the affected and surrounding Eastern Highland populations, and identified a variation in the prion protein G127.[25] G127 polymorphism is the result of a missense mutation, and is highly geographically restricted to regions where the kuru epidemic was the most widespread. Researchers believe that the PrnP variant occurred very recently, estimating that the most recent common ancestor lived 10 generations ago.[25][26] Of the discovery, Professor John Collinge, director of the Medical Research Council's Prion Unit at University College London, has stated that: > It's absolutely fascinating to see Darwinian principles at work here. This community of people has developed their own biologically unique response to a truly terrible epidemic. The fact that this genetic evolution has happened in a matter of decades is remarkable. > > — John Collinge, Medical Research Council The findings of the study could help researchers better understand and develop treatments for other related prion diseases, such as Creutzfeldt–Jakob disease[24] and Alzheimer's disease.[27] ## History[edit] Kuru was first described in official reports by Australian officers patrolling the Eastern Highlands of Papua New Guinea in the early 1950s.[28] Some unofficial accounts place kuru in the region as early as 1910.[7] In 1951, Arthur Carey was the first to use the term 'kuru' in a report to describe a new disease afflicting the Fore tribes of Papua New Guinea. In his report, Carey noted that kuru mostly afflicted Fore women, eventually killing them. Kuru was noted in the Fore, Yate and Usurufa people in 1952-1953 by anthropologists Ronald Berndt and Catherine Berndt. [7] In 1953, kuru was observed by patrol officer John McArthur who provided a description of the disease in his report. McArthur believed that kuru was merely a psychosomatic episode resulting from the sorcery practices of the tribal people in the region.[28] After the disease had festered into a bigger epidemic the tribal people asked Charles Pfarr, a Lutheran Medical Officer to come to the area to report the disease to Australian authorities.[7] Initially, the Fore people believed the causes of kuru to be sorcery or witchcraft.[29] The Fore people also thought that the magic causing kuru was contagious. It was also called negi-nagi, which meant foolish person as the victims laughed at spontaneous intervals.[30] This disease, the Fore people believed, was caused by ghosts because of the shaking and strange behaviour that comes with kuru. Attempting to cure this, they would feed victims pork and casuarinas bark. When the Kuru disease had become an epidemic, Daniel Carleton Gajdusek, a virologist, and Vincent Zigas, a medical doctor, started research on the disease. In 1957, Zigas and Gajdusek published a report in the Medical Journal of Australia that suggested that Kuru had a genetic origin, and that "any ethnic-environmental variables that are operating in kuru pathogenesis have not yet been determined."[31] Cannibalism was suspected as a possible cause from the very beginning but wasn't formally put forth as a theory until 1967 by Glasse and more formally in 1968 by Mathews, Glasse, & Lindenbaum. [30] Even before cannibalism had been linked to kuru, it was banned by the Australian administration, and the practice was nearly eliminated by 1960. While the number of cases of kuru was decreasing, those in medical research were able to properly investigate kuru, which eventually led to the modern understanding of prions as the cause.[32] In an effort to understand the pathology of Kuru disease, Gajdusek established the first experimental tests on chimpanzees for Kuru at the National Institutes of Health (NIH). The method of the experiments was to introduce kuru brain material to the closest human relative, the chimpanzee, and to document the behaviors of the animal until death or a negative outcome occurred.[7] Michael Alpers, an Australian doctor, collaborated with Gajdusek by providing samples of brain tissues he had taken from an 11-year-old Fore girl who had died of Kuru. In his work, Gajdusek was also the first to compile a bibliography of the Kuru disease.[33][citation needed] Joe Gibbs joined Gajdusek to monitor and record the behavior of the apes and conduct autopsies. Within two years, one of the chimps, Daisy, had developed kuru, demonstrating that an unknown disease factor was transmitted through infected biomaterial and that it was capable of crossing the species barrier to other primates. After Elisabeth Beck confirmed that this experiment brought about the first conducted transmission of Kuru, the finding was deemed a very important advancement in human medicine leading to the award of the Nobel Prize in Physiology or Medicine to Daniel Carleton Gajdusek in 1976.[7] Subsequently, E. J. Field spent large parts of the late 1960s and early 1970s in New Guinea investigating the disease,[34] connecting it to scrapie and multiple sclerosis.[35] He noted similarities in the diseases interactions with glial cells, including the critical observation that the infectious process may depend on structural rearrangement of the host's molecules.[36] This was an early observation of what was to later become the prion hypothesis.[37] ## In literature and popular culture[edit] * The Czech immunologist-poet Miroslav Holub wrote 'Kuru, or the Smiling Death Syndrome' about the disease.[38] * In the post-apocalyptic film The Book of Eli, the protagonist notes shaky hands as a recognizable symptom of cannibalistic practices.[citation needed] * In the survival horror game Dead Island, the virus that produces zombies is suggested to be derived from Kuru.[citation needed] * In the survival horror game DayZ, the virus will always be contracted if the player consumes human flesh or human fat.[39] * In a season 1 Scrubs episode “My Balancing Act” Dr John ‘JD’ Dorian diagnoses a patient with Kuru and is mocked by both the patient and Dr Cox. * The X-Files episode "Our Town" features an outbreak of Creutzfeldt–Jakob disease in a cannibalistic society whose founding member visited New Guinea. * In the second season of the comedy-horror FOX series, Scream Queens, Dean Cathy Munsch is diagnosed with kuru, which is later revealed to be a misdiagnosis. * In the film We Are What We Are, the Medical examiner is able to identify the cannibal family when he realises he had misidentified Kuru as Parkinson's Disease * In the videogame Far Cry Primal, a cannibalistic enemy tribe, the Udam, is revealed to be dying out from Kuru, which their leader, Ull, calls "skull-fire". * In the Pathfinder Roleplaying Game, there exists a tribe of cannibals named the Kuru ## See also[edit] * Cannibalism * Donner Party * Endocannibalism * Exocannibalism * List of incidents of cannibalism ## References[edit] 1. ^ "The epidemiology of kuru in the period 1987 to 1995", Department of Health (Australia), retrieved February 5, 2019 2. ^ Hoskin, J.O.; Kiloh, L.G.; Cawte, J.E. (April 1969). "Epilepsy and guria: The shaking syndromes of New Guinea". Social Science & Medicine. 3 (1): 39–48. doi:10.1016/0037-7856(69)90037-7. PMID 5809623. 3. ^ Scott, Graham (1978). The Fore Language of Papua New Guinea. Pacific Linguistics. pp. 2, 6. doi:10.15144/PL-B47. hdl:1885/146489. ISBN 978-0-85883-173-5. 4. ^ Whitfield, Jerome T; Pako, Wandagi H; Collinge, John; Alpers, Michael P (27 November 2008). "Mortuary rites of the South Fore and kuru". Philosophical Transactions of the Royal Society B: Biological Sciences. 363 (1510): 3721–3724. doi:10.1098/rstb.2008.0074. PMC 2581657. PMID 18849288. 5. ^ Bichell, Rae Ellen (September 6, 2016). "When People Ate People, A Strange Disease Emerged". NPR.org. Retrieved 2018-04-08. 6. ^ "Kuru". MedlinePlus Medical Encyclopedia. Retrieved 2016-11-14. 7. ^ a b c d e f g Alpers, MP (2007). "A history of kuru". Papua and New Guinea Medical Journal. 50 (1–2): 10–9. PMID 19354007. 8. ^ a b Rense, Sarah (September 7, 2016). "Here's What Happens to Your Body When You Eat Human Meat". Esquire. 9. ^ a b c "A life of determination". Monash University — Faculty of Medicine, Nursing and Health Sciences. 2009-02-23. Archived from the original on 2015-12-10. Retrieved 20 January 2016. 10. ^ a b Collinge, John; Whitfield, Jerome; McKintosh, Edward; Beck, John; Mead, Simon; Thomas, Dafydd J; Alpers, Michael P (June 2006). "Kuru in the 21st century—an acquired human prion disease with very long incubation periods". The Lancet. 367 (9528): 2068–2074. doi:10.1016/S0140-6736(06)68930-7. PMID 16798390. S2CID 11506094. 11. ^ a b Alpers, Michael P (December 2005). "The epidemiology of kuru in the period 1987 to 1995". Communicable Diseases Intelligence. 29 (4): 391–399. PMID 16465931. Retrieved 2016-11-10. 12. ^ Liberski, Pawel P.; Sikorska, Beata; Lindenbaum, Shirley; Goldfarb, Lev G.; McLean, Catriona; Hainfellner, Johannes A.; Brown, Paul (February 2012). "Kuru". Journal of Neuropathology & Experimental Neurology. 71 (2): 92–103. doi:10.1097/NEN.0b013e3182444efd. PMC 5120877. PMID 22249461. 13. ^ Collinge, John; Whitfield, Jerome; McKintosh, Edward; Frosh, Adam; Mead, Simon; Hill, Andrew F; Brandner, Sebastian; Thomas, Dafydd; Alpers, Michael P (27 November 2008). "A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea". Philosophical Transactions of the Royal Society B: Biological Sciences. 363 (1510): 3725–3739. doi:10.1098/rstb.2008.0068. PMC 2581654. PMID 18849289. 14. ^ a b c d e f Imran, Muhammad; Mahmood, Saqib (24 December 2011). "An overview of human prion diseases". Virology Journal. 8 (1): 559. doi:10.1186/1743-422X-8-559. PMC 3296552. PMID 22196171. 15. ^ Wadsworth, Jonathan D. F.; Joiner, Susan; Linehan, Jacqueline M.; Desbruslais, Melanie; Fox, Katie; Cooper, Sharon; Cronier, Sabrina; Asante, Emmanuel A.; Mead, Simon; Brandner, Sebastian; Hill, Andrew F.; Collinge, John (11 March 2008). "Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice". Proceedings of the National Academy of Sciences of the United States of America. 105 (10): 3885–3890. Bibcode:2008PNAS..105.3885W. doi:10.1073/pnas.0800190105. PMC 2268835. PMID 18316717. 16. ^ Lindenbaum, Shirley (2001-01-01). "Kuru, Prions, and Human Affairs: Thinking About Epidemics". Annual Review of Anthropology. 30 (1): 363–385. doi:10.1146/annurev.anthro.30.1.363. S2CID 162196301. 17. ^ a b c Kuru at eMedicine 18. ^ Kupfer, L.; Hinrichs, W.; Groschup, M. (1 September 2009). "Prion Protein Misfolding". Current Molecular Medicine. 9 (7): 826–835. doi:10.2174/156652409789105543. PMC 3330701. PMID 19860662. 19. ^ Linden, Rafael; Martins, Vilma R.; Prado, Marco A. M.; Cammarota, Martín; Izquierdo, Iván; Brentani, Ricardo R. (April 2008). "Physiology of the Prion Protein". Physiological Reviews. 88 (2): 673–728. doi:10.1152/physrev.00007.2007. PMID 18391177. 20. ^ Kuru: The Science and the Sorcery (Siamese Films, 2010) 21. ^ Diamond J.M. (1997). Guns, germs, and steel: the fates of human societies. New York: W.W. Norton. p. 208. ISBN 978-0-393-03891-0.[page needed] 22. ^ Liberski, P.P.; Brown, P. (January 2009). "Kuru: Its ramifications after fifty years" (PDF). Experimental Gerontology. 44 (1–2): 63–69. doi:10.1016/j.exger.2008.05.010. PMID 18606515. S2CID 28215397. 23. ^ Gibbs, Clarence J.; Amyx, Herbert L.; Bacote, Alfred; Masters, Colin L.; Gajdnsek, D. Carleton (August 1980). "Oral Transmission of Kuru, Creutzfeldt-Jakob Disease, and Scrapie to Nonhuman Primates". The Journal of Infectious Diseases. 142 (2): 205–208. doi:10.1093/infdis/142.2.205. PMID 6997404. 24. ^ a b "Brain disease 'resistance gene' evolves in Papua New Guinea community; could offer insights into CJD". ScienceDaily. 2009-11-21. Retrieved 2016-11-12. 25. ^ a b Mead, Simon; Whitfield, Jerome; Poulter, Mark; Shah, Paresh; Uphill, James; Campbell, Tracy; Al-Dujaily, Huda; Hummerich, Holger; Beck, Jon; Mein, Charles A.; Verzilli, Claudio; Whittaker, John; Alpers, Michael P.; Collinge, John (19 November 2009). "A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure" (PDF). New England Journal of Medicine. 361 (21): 2056–2065. doi:10.1056/NEJMoa0809716. PMID 19923577. 26. ^ Mead, Simon; Whitfield, Jerome; Poulter, Mark; Shah, Paresh; Uphill, James; Campbell, Tracy; Al-Dujaily, Huda; Hummerich, Holger; Beck, Jon; Mein, Charles A.; Verzilli, Claudio; Whittaker, John; Alpers, Michael P.; Collinge, John (19 November 2009). "A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure" (PDF). New England Journal of Medicine. 361 (21): 2056–2065. doi:10.1056/NEJMoa0809716. PMID 19923577. 27. ^ "Natural genetic variation gives complete resistance in prion diseases". Ucl.ac.uk. 2015-06-11. Retrieved 2016-11-12. 28. ^ a b Shirley Lindenbaum (14 Apr 2015). "An annotated history of kuru". Medicine Anthropology Theory. 29. ^ "Kuru". Transmissible Spongiform Encephalopathies. Archived from the original on 2016-11-21. Retrieved 2016-11-21. 30. ^ a b Liberski, Paweł P.; Gajos, Agata; Sikorska, Beata; Lindenbaum, Shirley (7 March 2019). "Kuru, the First Human Prion Disease". Viruses. 11 (3): 232. doi:10.3390/v11030232. PMC 6466359. PMID 30866511. 31. ^ Zigas, Vincent; Gajdusek, Daniel (23 November 1957). "Kuru: Clinical study of a new syndrome resembling paralysis agitans of the eastern highlands of Australian New Guinea". Medical Journal of Australia. 2 (21): 745–754. doi:10.5694/j.1326-5377.1957.tb60287.x. PMID 13492772. S2CID 38647011. 32. ^ Kennedy, John (15 May 2012). "Kuru Among the Foré — The Role of Medical Anthropology in Explaining Aetiology and Epidermiology". ArcJohn.wordpress.com. Retrieved 2016-11-21. 33. ^ Liberski, P. P.; Brown, P. (2004). "Kuru: A half-opened window onto the landscape of neurodegenerative diseases". Folia Neuropathologica. 42 Suppl A: 3–14. PMID 15449456. 34. ^ "Kuru - To Tremble with Fear". Horizon. Season 8. Episode 6. 22 February 1971. BBC2. 35. ^ Field, EJ (7 Dec 1967). "The significance of astroglial hypertrophy in Scrapie, Kuru, Multiple Sclerosis and old age together with a note on the possible nature of the scrapie agent". Journal of Neurology. 192 (3): 265–274. doi:10.1007/bf00244170. S2CID 8855940. 36. ^ Field, EJ (Feb 1978). "Immunological assessment of ageing: emergence of scrapie-like antigens". Age Ageing. 7 (1): 28–39. doi:10.1093/ageing/7.1.28. PMID 416662. 37. ^ Peat, Ray. "BSE - mad cow - scrapie, etc.: Stimulated amyloid degeneration and the toxic fats". RayPeat.com. 38. ^ Holub, Miroslav,Vanishing Lung Syndrome, trans. David Young and Dana Habova (Oberlin College Press, 1990). ISBN 0-932440-52-5; (Faber and Faber, 1990). ISBN 0-571-14339-3[page needed] 39. ^ "Brain Prion Disease". DayZ Wiki. Retrieved 2020-12-27. ## External links[edit] Classification D * ICD-10: A81.8 * ICD-9-CM: 046.0 * OMIM: 245300 * MeSH: D007729 * DiseasesDB: 31861 External resources * MedlinePlus: 001379 * v * t * e Prion diseases and transmissible spongiform encephalopathy Prion diseases in humans inherited/PRNP: * fCJD * Gerstmann–Sträussler–Scheinker syndrome * Fatal familial insomnia sporadic: * sCJD * Sporadic fatal insomnia * Variably protease-sensitive prionopathy acquired/ transmissible: * iCJD * vCJD * Kuru Prion diseases in other animals * Bovine spongiform encephalopathy * Camel spongiform encephalopathy * Scrapie * Chronic wasting disease * Transmissible mink encephalopathy * Feline spongiform encephalopathy * Exotic ungulate encephalopathy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Kuru (disease)	c0022802	5,811	wikipedia	https://en.wikipedia.org/wiki/Kuru_(disease)	2021-01-18T18:32:10	{"gard": ["7617"], "mesh": ["D007729"], "umls": ["C0022802"], "orphanet": ["454745"], "wikidata": ["Q274615"]}
## Clinical Features Neuhauser et al. (1977) described a brother and sister, with nonconsanguineous parents, who had severe mental retardation, spastic cerebral palsy, seizures, progressive or intermittent jaundice, and recurrent infections. They died at ages 3 and 4 years. One showed a small brain with almost complete lack of myelin in cerebral white matter, brainstem, cerebellum, and anterolateral parts of the spinal cord. Hypoplastic bile ducts, hydroureter, and hydronephrosis were also found. The brain abnormality was considered primarily a dysmyelination. Neuhauser et al. (1977) suggested that the syndrome described by Waggoner et al. (1942) (202600) might be due to a similar pathogenic process. Inheritance Neuhauser et al. (1977) suggested autosomal recessive inheritance of this disorder because of its occurrence in sibs. INHERITANCE \- Autosomal recessive RESPIRATORY \- Recurrent infections ABDOMEN Liver \- Jaundice, progressive or intermittent \- Hepatic duct hypoplasia GENITOURINARY External Genitalia (Male) \- Hypoplasia of penis Internal Genitalia (Male) \- Cryptorchidism Kidneys \- Hydronephrosis Ureters \- Hydroureter NEUROLOGIC Central Nervous System \- Mental retardation \- Seizures \- Cerebral palsy, spastic \- Dysmyelination of the brain and spinal cord MISCELLANEOUS \- Based on one report of brother and sister ▲ 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	DYSMYELINATION WITH JAUNDICE	c1857143	5,812	omim	https://www.omim.org/entry/224250	2019-09-22T16:28:28	{"mesh": ["C565610"], "omim": ["224250"]}
Orofaciodigital syndromes refers to numerous conditions in which the oral cavity (mouth, tongue, teeth, and jaw), facial structures (head, eyes, and nose), and digits (fingers and toes) may be formed differently. When changes happen to many different parts of the body, this is called a syndrome. The literature reports up to thirteen types of orofaciodigital syndrome, but research is necessary to confirm and clarify all of these types. For most of the types the exact cause of the condition is unknown. Click here to read this and more by visiting an information page on this topic developed by the National Human Genome Research Institute. See below for a list of orofaciodigital syndromes. These types are defined by certain symptoms or characteristics in addition to the those affecting the oral cavity, facial structures, and digits. Click on the embedded links to learn more about each type: Orofaciodigital syndrome 1 Orofaciodigital syndrome 8 Orofaciodigital syndrome 2 Orofaciodigital syndrome 9 Orofaciodigital syndrome 3 Orofaciodigital syndrome 10 Orofaciodigital syndrome 4 Orofaciodigital syndrome 11 Orofaciodigital syndrome 5 Orofaciodigital syndrome 12 Orofaciodigital syndrome 6 Orofaciodigital syndrome 13 Orofaciodigital syndrome 7* now considered identical to type 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	Orofaciodigital syndromes	c0029294	5,813	gard	https://rarediseases.info.nih.gov/diseases/10692/orofaciodigital-syndromes	2021-01-18T17:58:33	{"mesh": ["D009958"], "orphanet": ["140997"], "synonyms": ["Orofaciodigital syndrome", "Oral-facial-digital syndromes", "Oral facial digital syndromes", "OFD", "Oral-facial-digital syndrome"]}
A number sign (#) is used with this entry because of evidence that Charcot-Marie-Tooth type 2B1 (CMT2B1) is caused by homozygous mutation in the lamin A/C gene (LMNA; 150330) on chromosome 1q22. Description Charcot-Marie-Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies. On the basis of electrophysiologic criteria, CMT is divided into 2 major types: type 1, the demyelinating form, characterized by a motor median nerve conduction velocity less than 38 m/s (see CMT1B; 118200); and type 2, the axonal form, with a normal or slightly reduced nerve conduction velocity. For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A1 (118210). Clinical Features Bouhouche et al. (1999) studied a large consanguineous Moroccan autosomal recessive CMT2 family with 9 affected sibs. Onset of CMT was in the second decade in all affected individuals, who had weakness and wasting of the distal lower limb muscles and lower limb areflexia. Pes cavus was present in 7 patients, and there was proximal muscle involvement in 6. Motor nerve conduction velocities were normal or slightly reduced in all patients, reflecting an axonal process. Mapping In the large Moroccan family with CMT2, Bouhouche et al. (1999) excluded linkage to known CMT loci. A genomewide search showed linkage of the disorder in this family to markers on 1q, specifically 1q21.2-q21.3. Molecular Genetics In 3 consanguineous Algerian families with autosomal recessive CMT2 linked to chromosome 1q21, De Sandre-Giovannoli et al. (2002) identified a homozygous mutation in the LMNA gene (R298C; 150330.0020). ### Exclusion Studies Bouhouche et al. (1999) excluded the myelin protein zero gene (MPZ; 159440) as a candidate for mutation in this disorder by physical mapping and direct sequencing. Animal Model De Sandre-Giovannoli et al. (2002) reported that Lmna null mice presented with an axonal clinical and pathologic phenotype that is highly similar to patients with autosomal recessive CMT2. INHERITANCE \- Autosomal recessive SKELETAL Spine \- Kyphoscoliosis may be present Feet \- Pes cavus \- Foot deformities NEUROLOGIC Peripheral Nervous System \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy \- Proximal muscle involvement may occur \- 'Steppage' gait \- Foot drop \- Distal sensory impairment \- Hyporeflexia \- Areflexia \- Normal or mildly decreased motor nerve conduction velocity (NCV) (greater than 38 m/s) \- Axonal atrophy on nerve biopsy \- Axonal degeneration/regeneration on nerve biopsy \- Small 'onion bulbs' may be present \- Decreased number of myelinated fibers may be found MISCELLANEOUS \- Onset in second decade \- Usually begins in feet and legs (peroneal distribution) \- Upper limb involvement may occur later \- Severe course \- Genetic heterogeneity (see CMT2B2, 605589 ) \- For autosomal dominant forms of axonal neuropathy, see CMT2A ( 118210 ) MOLECULAR BASIS \- Caused by mutation in the lamin A/C gene (LMNA, 150330.0020 ) ▲ 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	CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2B1	c1854154	5,814	omim	https://www.omim.org/entry/605588	2019-09-22T16:11:10	{"doid": ["0110156"], "mesh": ["C537990"], "omim": ["605588"], "orphanet": ["98856"], "synonyms": ["Alternative titles", "CHARCOT-MARIE-TOOTH DISEASE, NEURONAL, TYPE 2B1", "CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL RECESSIVE, TYPE 2B1", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2B1"]}
Frontometaphyseal dysplasia is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, Melnick-Needles syndrome, and terminal osseous dysplasia. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits). Frontometaphyseal dysplasia is distinguished from the other otopalatodigital spectrum disorders by the presence of joint deformities called contractures that restrict the movement of certain joints. People with frontometaphyseal dysplasia may also have bowed limbs, an abnormal curvature of the spine (scoliosis), and abnormalities of the fingers and hands. Characteristic facial features may include prominent brow ridges; wide-set and downward-slanting eyes; a very small lower jaw and chin (micrognathia); and small, missing or misaligned teeth. Some affected individuals have hearing loss. In addition to skeletal abnormalities, individuals with frontometaphyseal dysplasia may have obstruction of the ducts between the kidneys and bladder (ureters), heart defects, or constrictions in the passages leading from the windpipe to the lungs (the bronchi) that can cause problems with breathing. Males with frontometaphyseal dysplasia generally have more severe signs and symptoms of the disorder than do females, who may show only the characteristic facial features. ## Frequency Frontometaphyseal dysplasia is a rare disorder; only a few dozen cases have been reported worldwide. ## Causes Mutations in the FLNA gene cause frontometaphyseal dysplasia. The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A binds to another protein called actin, and helps the actin to form the branching network of filaments that make up the cytoskeleton. Filamin A also links actin to many other proteins to perform various functions within the cell. A small number of mutations in the FLNA gene have been identified in people with frontometaphyseal dysplasia. These mutations are described as "gain-of-function" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of frontometaphyseal dysplasia. ### Learn more about the gene associated with Frontometaphyseal dysplasia * FLNA ## Inheritance Pattern This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Frontometaphyseal dysplasia	c4281559	5,815	medlineplus	https://medlineplus.gov/genetics/condition/frontometaphyseal-dysplasia/	2021-01-27T08:24:47	{"gard": ["826"], "omim": ["305620"], "synonyms": []}
Hepatic veno-occlusive disease Other namesVeno-occlusive disease with immunodeficiency Sinusoidal obstruction syndrome SpecialtyGastroenterology SymptomsWeight gain, tender enlargement of the liver, ascites, jaundice Diagnostic methodLiver biopsy Differential diagnosisBudd–Chiari syndrome PreventionUrsodeoxycholic acid TreatmentDefibrotide Deaths10-20% Hepatic veno-occlusive disease or veno-occlusive disease with immunodeficiency is a potentially life-threatening condition in which some of the small veins in the liver are obstructed. It is a complication of high-dose chemotherapy given before a bone marrow transplant and/or excessive exposure to hepatotoxic pyrrolizidine alkaloids. It is classically marked by weight gain due to fluid retention, increased liver size, and raised levels of bilirubin in the blood.[1] The name sinusoidal obstruction syndrome is preferred if hepatic veno-occlusive disease happens as a result of chemotherapy or bone marrow transplantation.[1][2] Apart from chemotherapy, hepatic veno-occlusive disease may also occur after ingestion of certain plant alkaloids such as pyrrolizidine alkaloids (in some herbal teas),[1] and has been described as part of a rare hereditary disease called hepatic venoocclusive disease with immunodeficiency (which results from mutations in the gene coding for a protein called SP110).[3] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 History * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] Features of hepatic veno-occlusive disease include weight gain, tender enlargement of the liver, ascites, and yellow discoloration of the skin; it often is associated with acute kidney failure.[4] ## Pathophysiology[edit] In the bone marrow transplant setting, hepatic veno-occlusive disease is felt to be due to injury to the hepatic venous endothelium from the conditioning regimen. Toxic agents causing veno-occlusive disease include plants as well as the medication cyclophosphamide.[citation needed] ## Diagnosis[edit] Doppler ultrasound of the liver is typically utilized to confirm or suggest the diagnosis. Common findings on liver doppler ultrasound include increased phasicity of portal veins with eventual development of portal flow reversal. The liver is usually enlarged but maintained normal echogenicity. A liver biopsy is required for a definitive diagnosis.[citation needed] ## Treatment[edit] Treatment generally includes supportive care including pain management and possibly diuretics.[5] In those with severe disease due to a bone marrow transplant, defibrotide is a proposed treatment.[6] It has been approved for use in severe cases in Europe and the United States.[7][8] A placebo controlled trial, however, has not been done as of 2016.[5] ## Prognosis[edit] Mild disease has a risk of death of about 10% while moderate disease has a risk of death of 20%.[5] When it occurs as a result of bone marrow transplant and multiorgan failure is present, the risk of death is greater than 80%.[6] ## History[edit] The first report on veno-occlusive disease, in 1920, was as a result of senecio poisoning in South Africa.[9] Subsequent reports were mostly in Jamaicans who had consumed herbal teas.[1] With the advent of bone marrow transplantation, most cases since its introduction have been in those undergoing treatment for leukemia.[1] ## See also[edit] * Budd-Chiari syndrome (large liver vein obstruction due to hepatic vein thrombosis) ## References[edit] 1. ^ a b c d e Helmy A (January 2006). "Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome (SOS)". Aliment. Pharmacol. Ther. 23 (1): 11–25. doi:10.1111/j.1365-2036.2006.02742.x. PMID 16393276. S2CID 22462806. Archived from the original on 2012-12-09. 2. ^ DeLeve LD, Shulman HM, McDonald GB (February 2002). "Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease)". Semin. Liver Dis. 22 (1): 27–42. doi:10.1055/s-2002-23204. PMID 11928077. 3. ^ Roscioli T, Cliffe ST, Bloch DB (June 2006). "Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease" (PDF). Nat. Genet. 38 (6): 620–2. doi:10.1038/ng1780. PMID 16648851. S2CID 1466106. 4. ^ RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Hepatic veno occlusive disease". www.orpha.net. Retrieved 2016-12-26. 5. ^ a b c Dalle, JH; Giralt, SA (March 2016). "Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: Risk Factors and Stratification, Prophylaxis, and Treatment". Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 22 (3): 400–9. doi:10.1016/j.bbmt.2015.09.024. PMID 26431626. 6. ^ a b Fulgenzi, A; Ferrero, ME (2016). "Defibrotide in the treatment of hepatic veno-occlusive disease". Hepatic Medicine: Evidence and Research. 8: 105–113. doi:10.2147/HMER.S79243. PMC 5098529. PMID 27843363. 7. ^ Keating, GM (December 2014). "Defibrotide: a review of its use in severe hepatic veno-occlusive disease following haematopoietic stem cell transplantation". Clinical Drug Investigation. 34 (12): 895–904. doi:10.1007/s40261-014-0242-x. PMID 25351934. S2CID 21019656. 8. ^ "Press Announcements - FDA approves first treatment for rare disease in patients who receive stem cell transplant from blood or bone marrow". www.fda.gov. Retrieved 18 July 2017. 9. ^ Willmot, F; Robertson, George (1920). "Senecio disease, or cirrhosis of the liver due to senecio poisoning". The Lancet. 196 (5069): 848–849. doi:10.1016/S0140-6736(01)00020-4. ## Further reading[edit] * Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. ISBN 978-0-7216-0187-8. * Wingard JR, Nichols WG, McDonald GB (2004). "Supportive care". Hematology Am Soc Hematol Educ Program. 1: 372–89. doi:10.1182/asheducation-2004.1.372. PMID 15561693. * Dignan, Fiona L.; Wynn, Robert F.; Hadzic, Nedim; Karani, John; Quaglia, Alberto; Pagliuca, Antonio; Veys, Paul; Potter, Michael N. (1 November 2013). "BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation". British Journal of Haematology. 163 (4): 444–457. doi:10.1111/bjh.12558. ISSN 1365-2141. PMID 24102514. ## External links[edit] Classification D * ICD-10: K76.5 * OMIM: 235550 * MeSH: D006504 * DiseasesDB: 34365 * SNOMED CT: 65617004 External resources * eMedicine: ped/2396 * GeneReviews: Venous Occlusive Disease with Immunodeficiency * Orphanet: 890 * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Hepatic veno-occlusive disease	c0019156	5,816	wikipedia	https://en.wikipedia.org/wiki/Hepatic_veno-occlusive_disease	2021-01-18T18:37:01	{"gard": ["13004"], "mesh": ["D006504"], "umls": ["C0019156"], "icd-10": ["K76.5"], "orphanet": ["890"], "wikidata": ["Q5731687"]}
A vaccine-associated sarcoma (VAS) or feline injection-site sarcoma (FISS) is a type of malignant tumor found in cats (and often, dogs and ferrets) which has been linked to certain vaccines. VAS has become a concern for veterinarians and cat owners alike and has resulted in changes in recommended vaccine protocols. These sarcomas have been most commonly associated with rabies and feline leukemia virus vaccines, but other vaccines and injected medications have also been implicated.[1] ## Contents * 1 History * 2 Pathology * 3 Diagnosis * 4 Treatment * 5 Precautionary measures * 6 See also * 7 References * 8 External links ## History[edit] VAS was first recognized at the University of Pennsylvania School of Veterinary Medicine in 1991.[2] An association between highly aggressive fibrosarcomas and typical vaccine location (between the shoulder blades) was made. Two possible factors for the increase of VAS at this time were the introduction in 1985 of vaccines for rabies and feline leukemia virus (FeLV) that contained aluminum adjuvant, and a law in 1987 requiring rabies vaccination in cats in Pennsylvania.[3] In 1993, a causal relationship between VAS and administration of aluminum adjuvanted rabies and FeLV vaccines was established through epidemiologic methods, and in 1996 the Vaccine-Associated Feline Sarcoma Task Force was formed to address the problem.[4] In 2003, a study of ferret fibrosarcomas indicated that this species also may develop VAS. Several of the tumors were located in common injection sites and had similar histologic features to VAS in cats.[5] Also in 2003, a study in Italy compared fibrosarcomas in dogs from injection sites and non-injection sites to VAS in cats, and found distinct similarities between the injection site tumors in dogs and VAS in cats. This suggests that VAS may occur in dogs.[6] ## Pathology[edit] Inflammation in the subcutis following vaccination is considered to be a risk factor in the development of VAS, and vaccines containing aluminum were found to produce more inflammation.[7] Furthermore, particles of aluminum adjuvant have been discovered in tumor macrophages.[8] In addition, individual genetic characteristics can also contribute to these injection-site sarcomas.[9] The incidence of VAS is between 1 in 1,000 to 1 in 10,000 vaccinated cats and has been found to be dose-dependent.[1] The time from vaccination to tumor formation varies from three months to eleven years.[10] Fibrosarcoma is the most common VAS; other types include rhabdomyosarcoma, myxosarcoma, chondrosarcoma, malignant fibrous histiocytoma, and undifferentiated sarcoma.[11] Similar examples of sarcomas developing secondary to inflammation include tumors associated with metallic implants and foreign body material in humans, and sarcomas of the esophagus associated with Spirocerca lupi infection in dogs and ocular sarcomas in cats following trauma. Cats may be the predominant species to develop VAS because they have an increased susceptibility to oxidative injury, as evidenced also by an increased risk of Heinz body anemia and acetaminophen toxicity.[10] ## Diagnosis[edit] VAS appears as a rapidly growing firm mass in and under the skin. The mass is often quite large when first detected and can become ulcerated or infected. It often contains fluid-filled cavities, probably because of its rapid growth.[12] Diagnosis of VAS is through a biopsy. The biopsy will show the presence of a sarcoma, but information like location and the presence of inflammation or necrosis will increase the suspicion of VAS. It is possible for cats to have a granuloma form after vaccination, so it is important to differentiate between the two before radical surgery is performed. One guideline for biopsy is if a growth is present three months after surgery, if a growth is greater than two centimeters, or if a growth is becoming larger one month after vaccination.[1] X-rays are taken prior to surgery because about one in five cases of VAS will develop metastasis, usually to the lungs but possibly to the lymph nodes or skin.[8] ## Treatment[edit] Treatment of VAS is through aggressive surgery. As soon as the tumor is recognized, it should be removed with very wide margins to ensure complete removal. Treatment may also include chemotherapy or radiation therapy. The most significant prognostic factor is initial surgical treatment. One study showed that cats with radical (extensive) initial surgery had a median time to recurrence of 325 days versus 79 days for cats with marginal initial excision.[3] The expression of a mutated form of p53, a tumor suppressor gene, is found commonly in VAS and indicates a poorer prognosis.[13] ## Precautionary measures[edit] New vaccine protocols have been put forth by the American Association of Feline Practitioners that limit type and frequency of vaccinations given to cats.[14] Specifically, the vaccine for feline leukemia virus should only be given to kittens and high risk cats. Feline rhinotracheitis/panleukopenia/calicivirus vaccines should be given as kittens, a year later and then every three years. Also, vaccines should be given in areas making removal of VAS easier,[15] namely: as close as possible to the tip of the right rear paw for rabies, the tip of the left rear paw for feline leukemia (unless combined with rabies), and on the right shoulder—being careful to avoid the midline or interscapular space—for other vaccines (such as FVRCP).[16] There have been no specific associations between development of VAS and vaccine brand or manufacturer, concurrent infections, history of trauma, or environment.[17] ## See also[edit] * Vaccine injury ## References[edit] 1. ^ a b c "Vaccine-Associated Feline Sarcoma Task Force: Roundtable Discussion". Journal of the American Veterinary Medical Association. 226 (11). 2005. Retrieved 2006-08-27. 2. ^ Hendrick M, Goldschmidt M (1991). "Do injection site reactions induce fibrosarcomas in cats?". J Am Vet Med Assoc. 199 (8): 968. PMID 1748617. 3. ^ a b Kitchell, Barbara E. (2005). "Feline Vaccine-Associated Sarcomas". Proceedings of the 30th World Congress of the World Small Animal Veterinary Association. Retrieved 2006-08-27. 4. ^ Richards J, Elston T, Ford R, Gaskell R, Hartmann K, Hurley K, Lappin M, Levy J, Rodan I, Scherk M, Schultz R, Sparkes A (2006). "The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel report". J Am Vet Med Assoc. 229 (9): 1405–41. doi:10.2460/javma.229.9.1405. PMID 17078805. 5. ^ Munday J, Stedman N, Richey L (2003). "Histology and immunohistochemistry of seven ferret vaccination-site fibrosarcomas". Vet Pathol. 40 (3): 288–93. doi:10.1354/vp.40-3-288. PMID 12724570. 6. ^ Vascellari M, Melchiotti E, Bozza M, Mutinelli F (2003). "Fibrosarcomas at presumed sites of injection in dogs: characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal fibrosarcomas". J Vet Med a Physiol Pathol Clin Med. 50 (6): 286–91. doi:10.1046/j.1439-0442.2003.00544.x. PMID 12887620. 7. ^ O'Rourke, Kate (2004). "Researchers probe vaccine-associated feline sarcoma". Journal of the American Veterinary Medical Association. 225 (6). Retrieved 2006-08-27. 8. ^ a b Hershey A, Sorenmo K, Hendrick M, Shofer F, Vail D (2000). "Prognosis for presumed feline vaccine-associated sarcoma after excision: 61 cases (1986-1996)". J Am Vet Med Assoc. 216 (1): 58–61. doi:10.2460/javma.2000.216.58. PMID 10638320. 9. ^ Martano M, Morello E, Buracco P (May 2011). "Feline injection-site sarcoma: past, present and future perspectives". Veterinary Journal. 188 (2): 136–41. doi:10.1016/j.tvjl.2010.04.025. hdl:2318/73932. PMID 20510635. 10. ^ a b Martin M (2003). "Vaccine-associated fibrosarcoma in a cat". Can Vet J. 44 (8): 660–3. PMC 340241. PMID 13677599. 11. ^ Chang H, Ho S, Lo H, Tu Y, Jeng C, Liu C, Wang F, Pang V (2006). "Vaccine-associated rhabdomyosarcoma with spinal epidural invasion and pulmonary metastasis in a cat". Vet Pathol. 43 (1): 55–8. doi:10.1354/vp.43-1-55. PMID 16407487. S2CID 23721821. 12. ^ Couto S, Griffey S, Duarte P, Madewell B (2002). "Feline vaccine-associated fibrosarcoma: morphologic distinctions". Vet Pathol. 39 (1): 33–41. doi:10.1354/vp.39-1-33. PMID 12102217. S2CID 24469628. 13. ^ Hershey A, Dubielzig R, Padilla M, Helfand S (2005). "Aberrant p53 expression in feline vaccine-associated sarcomas and correlation with prognosis". Vet Pathol. 42 (6): 805–11. doi:10.1354/vp.42-6-805. PMID 16301577. S2CID 29956787. 14. ^ "Canine and Feline Vaccination Guidelines". UC Davis School of Veterinary Medicine. Retrieved 2012-06-23. 15. ^ Eigner, Diane R. "Feline Vaccine Guidelines". The Winn Feline Foundation. Retrieved 2006-08-27. 16. ^ "VAFSTF Vaccine Site Recommendations". Vaccine-Associated Feline Sarcoma Task Force of the American Association of Feline Practitioners (AAFP), American Animal Hospital Association (AAHA), American Veterinary Medical Association (AVMA), and Veterinary Cancer Society (VCS). Retrieved 2012-12-04. 17. ^ Kass P, Spangler W, Hendrick M, McGill L, Esplin D, Lester S, Slater M, Meyer E, Boucher F, Peters E, Gobar G, Htoo T, Decile K (2003). "Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats". J Am Vet Med Assoc. 223 (9): 1283–92. doi:10.2460/javma.2003.223.1283. PMID 14621215. ## External links[edit] * Vaccine-Associated Feline Sarcoma Task Force (VAFSTF) * Vaccines and Sarcomas Informational Brochure from the Cornell Feline Health Center * "Vaccine-Associated Fibrosarcoma in Cats" from Pet Cancer Center * 2006 Feline Vaccination Guidelines (Summary) * Cat Vaccines Can Lead to Cancer [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Vaccine-associated sarcoma	None	5,817	wikipedia	https://en.wikipedia.org/wiki/Vaccine-associated_sarcoma	2021-01-18T18:54:37	{"wikidata": ["Q7907937"]}
Fluid accumulation in the air spaces and parenchyma of the lungs tissue Pulmonary edema Other namesPulmonary oedema Pulmonary edema with small pleural effusions on both sides. SpecialtyCardiology, critical care medicine Pulmonary edema is fluid accumulation in the tissue and air spaces of the lungs.[1] It leads to impaired gas exchange and may cause respiratory failure. It is due to either failure of the left ventricle of the heart to remove blood adequately from the pulmonary circulation (cardiogenic pulmonary edema), or an injury to the lung tissue or blood vessels of the lung (non-cardiogenic pulmonary edema).[2] Treatment is focused on three aspects: firstly improving respiratory function, secondly, treating the underlying cause, and thirdly avoiding further damage to the lung. Pulmonary edema, especially when sudden (acute), can lead to respiratory failure or cardiac arrest due to hypoxia. It is a cardinal feature of congestive heart failure. The term edema is from the Greek οἴδημα (oídēma, "swelling"), from οἰδέω (oidéō, "I swell"). ## Contents * 1 Types * 1.1 Cardiogenic * 1.2 Non-cardiogenic * 2 Signs and symptoms * 3 Flash pulmonary edema * 4 Diagnosis * 5 Prevention * 6 Management * 6.1 Cardiogenic pulmonary edema * 7 References ## Types[edit] Classically it is cardiogenic (left ventricular) but fluid may also accumulate due to damage to the lung. This damage may be direct injury or injury mediated by high pressures within the pulmonary circulation. When directly or indirectly caused by increased left ventricular pressure pulmonary edema may form when mean pulmonary pressure rises from the normal of 15 mmHg[3] to above 25 mmHg.[4] Broadly, the causes of pulmonary edema can be divided into cardiogenic and non-cardiogenic. By convention cardiogenic refers to left ventricular causes. ### Cardiogenic[edit] * Congestive heart failure which is due to the heart's inability to pump the blood out of the pulmonary circulation at a sufficient rate resulting in elevation in wedge pressure and pulmonary edema – this may be due to left ventricular failure, arrhythmias, or fluid overload, e.g., from kidney failure or intravenous therapy. * Hypertensive crisis can cause pulmonary edema as the elevation in blood pressure and increased afterload on the left ventricle hinders forward flow and causes the elevation in wedge pressure and subsequent pulmonary edema. ### Non-cardiogenic[edit] * Negative pressure pulmonary edema[5] in which a significant negative pressure in the chest (such as from an inhalation against an upper airway obstruction) ruptures capillaries and floods the alveoli. Negative pressure pulmonary edema has an incidence in the range of 0.05-0.1% for general anesthesia. The negative pressure causes a significant increase in preload, thereby increasing pulmonary blood volume. There is also a significant increase in left ventricular afterload, which causes a decreased cardiac output. The increase in pulmonary blood volume along with a decrease in cardiac output will increase the pulmonary transudative pressures. With all this occurring, pulmonary vascular resistance increases causing a shift of the intraventricular septum. The ventricular septal shift to the left causes a left ventricular diastolic dysfunction, which further increases pulmonary hydrostatic pressures.[6] * Neurogenic causes[7] (seizures, head trauma, strangulation, electrocution). * Pulmonary embolism[8] Acute lung injury may also cause pulmonary edema through injury to the vasculature and parenchyma of the lung. Acute lung injury and acute respiratory distress syndrome.[9] (ALI-ARDS) cover many of these causes, but they may include: * Inhalation of hot or toxic gases * Pulmonary contusion, i.e., high-energy trauma (e.g. vehicle accidents) * Aspiration, e.g., gastric fluid * Reexpansion, i.e. post large volume thoracocentesis, resolution of pneumothorax, post decortication, removal of endobronchial obstruction, effectively a form of negative pressure pulmonary oedema. * Reperfusion injury, i.e. postpulmonary thromboendartectomy or lung transplantation * Swimming induced pulmonary edema also known as immersion pulmonary edema[10][11] * Transfusion Associated Circulatory Overload (TACO) occurs when multiple blood transfusions or blood-products (plasma, platelets, etc.) are transfused over a short period of time.[12] * Transfusion associated Acute Lung Injury (TRALI) is a specific type of blood-product transfusion injury that occurs when the donors plasma contained antibodies against the recipient,such as anti-HLA or anti-neutrophil antibodies.[13] * Severe infection or inflammation which may be local or systemic. This is the classical form of ALI-ARDS. Some causes of pulmonary edema are less well characterised and arguably represent specific instances of the broader classifications above. * Arteriovenous malformation * Hantavirus pulmonary syndrome * High altitude pulmonary edema (HAPE)[14][15] * Envenomation, such as with the venom of Atrax robustus[16] ## Signs and symptoms[edit] The most common symptom of pulmonary edema is difficulty breathing, but may include other symptoms such as coughing up blood (classically seen as pink, frothy sputum), excessive sweating, anxiety, and pale skin. Shortness of breath can manifest as orthopnea (inability to lie down flat due to breathlessness) and/or paroxysmal nocturnal dyspnea (episodes of severe sudden breathlessness at night). These are common presenting symptoms of chronic pulmonary edema due to left ventricular failure. The development of pulmonary edema may be associated with symptoms and signs of "fluid overload"; this is a non-specific term to describe the manifestations of right ventricular failure on the rest of the body and includes peripheral edema (swelling of the legs, in general, of the "pitting" variety, wherein the skin is slow to return to normal when pressed upon), raised jugular venous pressure and hepatomegaly, where the liver is enlarged and may be tender or even pulsatile. Other signs include end-inspiratory crackles (sounds heard at the end of a deep breath) on auscultation and the presence of a third heart sound.[2] ## Flash pulmonary edema[edit] Flash pulmonary edema (FPE), is rapid onset pulmonary edema. It is most often precipitated by acute myocardial infarction or mitral regurgitation, but can be caused by aortic regurgitation, heart failure, or almost any cause of elevated left ventricular filling pressures. Treatment of FPE should be directed at the underlying cause, but the mainstays are nitroglycerin, ensuring adequate oxygenation with non-invasive ventilation, and decrease of pulmonary circulation pressures.[17] Recurrence of FPE is thought to be associated with hypertension[18] and may signify renal artery stenosis.[19] Prevention of recurrence is based on managing hypertension, coronary artery disease, renovascular hypertension, and heart failure. ## Diagnosis[edit] X-Ray showing pulmonary oedema Pulmonary edema on CT-scan (coronal MPR) There is no single test for confirming that breathlessness is caused by pulmonary edema – there are many causes of shortness of breath. Low oxygen saturation and disturbed arterial blood gas readings support the proposed diagnosis by suggesting a pulmonary shunt. A chest X-ray will show fluid in the alveolar walls, Kerley B lines, increased vascular shadowing in a classical batwing peri-hilum pattern, upper lobe diversion (increased blood flow to the superior parts of the lung), and possibly pleural effusions. In contrast, patchy alveolar infiltrates are more typically associated with noncardiogenic edema[2] Lung ultrasound, employed by a healthcare provider at the point of care, is also a useful tool to diagnose pulmonary edema; not only is it accurate, but it may quantify the degree of lung water, track changes over time, and differentiate between cardiogenic and non-cardiogenic edema.[20] Especially in the case of cardiogenic pulmonary edema, urgent echocardiography may strengthen the diagnosis by demonstrating impaired left ventricular function, high central venous pressures and high pulmonary artery pressures. Blood tests are performed for electrolytes (sodium, potassium) and markers of renal function (creatinine, urea). Liver enzymes, inflammatory markers (usually C-reactive protein) and a complete blood count as well as coagulation studies (PT, aPTT) are also typically requested. B-type natriuretic peptide (BNP) is available in many hospitals, sometimes even as a point-of-care test. Low levels of BNP (<100 pg/ml) suggest a cardiac cause is unlikely.[2] ## Prevention[edit] In those with underlying heart disease, effective control of congestive symptoms prevents pulmonary edema.[21] Dexamethasone is in widespread use for the prevention of high altitude pulmonary edema. Sildenafil is used as a preventive treatment for altitude-induced pulmonary edema and pulmonary hypertension,[22][23] the mechanism of action is via phosphodiesterase inhibition which raises cGMP, resulting in pulmonary arterial vasodilation and inhibition of smooth muscle cell proliferation.[24] While this effect has only recently been discovered, sildenafil is already becoming an accepted treatment for this condition, in particular in situations where the standard treatment of rapid descent has been delayed for some reason.[25] ## Management[edit] The initial management of pulmonary edema, irrespective of the type or cause, is supporting vital functions. Therefore, if the level of consciousness is decreased it may be required to proceed to tracheal intubation and mechanical ventilation to prevent airway compromise. Hypoxia (abnormally low oxygen levels) may require supplementary oxygen, but if this is insufficient then again mechanical ventilation may be required to prevent complications.[citation needed] Treatment of the underlying cause is the next priority; pulmonary edema secondary to infection, for instance, would require the administration of appropriate antibiotics.[citation needed] ### Cardiogenic pulmonary edema[edit] Acute cardiogenic pulmonary edema often responds rapidly to medical treatment.[26] Positioning upright may relieve symptoms. A loop diuretic such as furosemide (Lasix®) is administered, often together with morphine to reduce respiratory distress.[26] Both diuretic and morphine may have vasodilator effects, but specific vasodilators may be used (particularly intravenous glyceryl trinitrate or ISDN) provided the blood pressure is adequate.[26] Continuous positive airway pressure and bilevel positive airway pressure (BIPAP/NIPPV) has been demonstrated to reduce mortality and the need of mechanical ventilation in people with severe cardiogenic pulmonary edema.[27] It is possible for cardiogenic pulmonary edema to occur together with cardiogenic shock, in which the cardiac output is insufficient to sustain an adequate blood pressure. This can be treated with inotropic agents or by intra-aortic balloon pump, but this is regarded as temporary treatment while the underlying cause is addressed.[26] ## References[edit] 1. ^ Dorland's illustrated medical dictionary (32nd ed.). Saunders/Elsevier. p. 593. ISBN 9781416062578. 2. ^ a b c d Ware LB, Matthay MA (December 2005). "Clinical practice. Acute pulmonary edema". N. Engl. J. Med. 353 (26): 2788–96. doi:10.1056/NEJMcp052699. PMID 16382065. 3. ^ What Is Pulmonary Hypertension? From Diseases and Conditions Index (DCI). National Heart, Lung, and Blood Institute. Last updated September 2008. Retrieved on 6 April 2009. 4. ^ Adair, Olivia Vynn (2001). Cardiology secrets (2nd ed.). Elsevier Health Sciences. Chapter 41, page 210. ISBN 1-56053-420-6. 5. ^ Papaioannou V, Terzi I, Dragoumanis C, Pneumatikos I (2009). "Negative-pressure acute tracheobronchial hemorrhage and pulmonary edema". J Anesth. 23 (3): 417–20. doi:10.1007/s00540-009-0757-0. PMID 19685125. 6. ^ Hines, Roberta L. and Marschall, Katherine. Stoelting's Anesthesia and Co-Existing Disease. 6th edition. 2012. pages 178 and 179. 7. ^ O'Leary, R.; McKinlay, J. (2011). "Neurogenic pulmonary oedema". Continuing Education in Anaesthesia, Critical Care & Pain. 11 (3): 87–92. doi:10.1093/bjaceaccp/mkr006. 8. ^ "Pulmonary edema". Mayo Clinic. 2018-08-08. 9. ^ Boyle, AJ; Mac Sweeney, R; McAuley, DF (August 2013). "Pharmacological treatments in ARDS; a state-of-the-art update". BMC Med. 11: 166. doi:10.1186/1741-7015-11-166. PMC 3765621. PMID 23957905. 10. ^ Hampson NB, Dunford RG (1997). "Pulmonary edema of scuba divers". Undersea Hyperb Med. 24 (1): 29–33. PMID 9068153. Retrieved 2008-09-04. 11. ^ Cochard G, Arvieux J, Lacour JM, Madouas G, Mongredien H, Arvieux CC (2005). "Pulmonary edema in scuba divers: recurrence and fatal outcome". Undersea Hyperb Med. 32 (1): 39–44. PMID 15796313. Retrieved 2008-09-04. 12. ^ "Adverse Reactions". Professional Education. 2016-06-02. Retrieved 2016-12-03. 13. ^ "Transfusion-related acute lung injury (TRALI)". Professional Education. 2016-06-17. Retrieved 2016-12-03. 14. ^ Luks AM (2008). "Do we have a "best practice" for treating high altitude pulmonary edema?". High Alt. Med. Biol. 9 (2): 111–4. doi:10.1089/ham.2008.1017. PMID 18578641. 15. ^ Bates, M (2007). "High altitude pulmonary edema". Altitude Physiology Expeditions. Retrieved 2008-09-04. 16. ^ White J, Gray M, Fisher M (1989). Atrax Robustus IPCS InChem 17. ^ Long, Brit; Koyfman, Alex; Gottlieb, Michael (2018). "Management of Heart Failure in the Emergency Department Setting: An Evidence-Based Review of the Literature". The Journal of Emergency Medicine. 55 (5): 635–646. doi:10.1016/j.jemermed.2018.08.002. PMID 30266198. 18. ^ Kramer K, Kirkman P, Kitzman D, Little WC. Flash pulmonary edema: association with hypertension and recurrence despite coronary revascularization. Am Heart J. 2000 Sep;140(3):451–5. doi:10.1067/mhj.2000.108828. PMID 10966547. 19. ^ Pickering TG, Herman L, Devereux RB, Sotelo JE, James GD, Sos TA, Silane MF, Laragh JH. Recurrent pulmonary oedema in hypertension due to bilateral renal artery stenosis: treatment by angioplasty or surgical revascularisation. Lancet. 1988;332(8610):551–2. doi:10.1016/S0140-6736(88)92668-2. PMID 2900930. 20. ^ Volpicelli, Giovanni; Elbarbary, Mahmoud; Blaivas, Michael; Lichtenstein, Daniel A.; Mathis, Gebhard; Kirkpatrick, Andrew W.; Melniker, Lawrence; Gargani, Luna; Noble, Vicki E. (2012-04-01). "International evidence-based recommendations for point-of-care lung ultrasound". Intensive Care Medicine. 38 (4): 577–591. doi:10.1007/s00134-012-2513-4. ISSN 1432-1238. PMID 22392031. 21. ^ Light, R. W.; Lee, Y. C. G. (2006-01-01), Laurent, Geoffrey J.; Shapiro, Steven D. (eds.), "PLEURAL EFFUSIONS \| Overview", Encyclopedia of Respiratory Medicine, Oxford: Academic Press, pp. 353–358, doi:10.1016/b0-12-370879-6/00299-4, ISBN 978-0-12-370879-3, retrieved 2020-12-11 22. ^ Richalet JP, Gratadour P, Robach P, et al. (2005). "Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension". Am. J. Respir. Crit. Care Med. 171 (3): 275–81. doi:10.1164/rccm.200406-804OC. PMID 15516532. 23. ^ Perimenis P (2005). "Sildenafil for the treatment of altitude-induced hypoxaemia". Expert Opin Pharmacother. 6 (5): 835–7. doi:10.1517/14656566.6.5.835. PMID 15934909. 24. ^ Clark, Michael; Kumar, Parveen J. (2009). Kumar and Clark's clinical medicine. St. Louis, Mo: Elsevier Saunders. p. 783. ISBN 978-0-7020-2993-6. 25. ^ Fagenholz PJ, Gutman JA, Murray AF, Harris NS (2007). "Treatment of high altitude pulmonary edema at 4240 m in Nepal". High Alt. Med. Biol. 8 (2): 139–46. doi:10.1089/ham.2007.3055. PMID 17584008. 26. ^ a b c d Cleland JG, Yassin AS, Khadjooi K (2010). "Acute heart failure: focusing on acute cardiogenic pulmonary oedema". Clin Med. 10 (1): 59–64. doi:10.7861/clinmedicine.10-1-59. PMC 4954483. PMID 20408310. 27. ^ Wang, Y; Brown, J; Godfrey, C; Ahmad, M; Vital, FMR; Lambiase, P; Banerjee, A; Bakhai, A; Chong, M. "Non‐invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema". Cochrane Database of Systematic Reviews (4): CD005351. doi:10.1002/14651858.CD005351.pub4. PMC 6449889. PMID 30950507. Classification D * ICD-10: J81 * ICD-9-CM: 514 518.4 506.1 * MeSH: D011654 * DiseasesDB: 11017 External resources * MedlinePlus: 000140 * eMedicine: article/157452 article/300813, article/360932 * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis * v * t * e Disorders of volume state Volume contraction * dehydration * hypovolemia Hypervolemia * Edema * Anasarca * Cerebral edema * Pulmonary edema * Angioedema * Lymphedema Other * Cause of fluid collection * Exudate * Transudate * By site * Hydrothorax * Ascites * Hydrosalpinx * Hyperemia Authority control * GND: 4134256-2 * NDL: 00575969 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Pulmonary edema	c0034063	5,818	wikipedia	https://en.wikipedia.org/wiki/Pulmonary_edema	2021-01-18T18:55:44	{"mesh": ["D011654"], "umls": ["C0034063"], "icd-9": ["518.4", "514"], "wikidata": ["Q857667"]}
Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (abbreviated POIKTMP), is a disorder that affects many parts of the body, particularly the skin, muscles, lungs, and pancreas. Signs and symptoms vary among affected individuals. People with POIKTMP have patchy changes in skin coloring and small clusters of blood vessels just under the skin (telangiectases), a combination known as poikiloderma. These skin changes begin in infancy and occur primarily on the face. They can also have red, scaly skin patches and mild swelling (lymphedema) of the arms and legs; thickened skin on the palms of the hands and soles of the feet (palmoplantar keratoderma); and abnormal hardening (sclerosis) of tissues in the fingers and toes. People with this disorder usually have sparse scalp hair, and their eyelashes and eyebrows can also be sparse or absent. Affected individuals have a decreased ability to sweat (hypohidrosis), which impairs their ability to tolerate heat. Reduced movement of joints (contractures) caused by shortening of the connective tissues that attach muscles to bone (tendons) usually develops during childhood in people with POIKTMP. These contractures often affect the calf, resulting in turning in (valgus deformity) of the feet. Contractures can also affect the elbows and wrists. In addition, people with POIKTMP usually develop muscle weakness (myopathy) in the arms and legs, and medical imaging shows abnormal fatty tissue in the muscles. Adults with POIKTMP can develop a condition called pulmonary fibrosis, in which scar tissue forms in the lungs. Pulmonary fibrosis eventually causes difficulty breathing and can be life-threatening within a few years after symptoms begin. In addition to the skin, muscle, and lung problems that give this condition its name, people with POIKTMP can also have a shortage (deficiency) of enzymes produced by the pancreas to aid in the digestion of fats. This deficiency can lead to diarrhea and poor absorption of fats and fat-soluble vitamins. Liver problems, short stature, and delayed puberty can also occur in affected individuals. Intellectual development is not affected by this disorder. ## Frequency The prevalence of POIKTMP is unknown. At least 25 affected individuals have been described in the medical literature. POIKTMP is thought to be under-diagnosed because affected individuals may have only one or a few features of the disorder, and health care providers may not recognize these features as part of POIKTMP. ## Causes POIKTMP is caused by mutations in the FAM111B gene. This gene provides instructions for making a protein whose function is not well understood. The FAM111B protein, which is found in many parts of the body, contains a functional region called a peptidase domain. Similar proteins containing such a domain are able to break down other proteins. However, the types of proteins the FAM111B protein interacts with and the roles it plays in the body are unknown. The FAM111B gene mutations that cause POIKTMP result in production of an abnormal FAM111B protein from one copy of the gene in each cell. Because most of the FAM111B mutations identified in people with POIKTMP result in changes in the peptidase domain, researchers think that the mutations alter the protein's function, and that these changes in FAM111B function underlie the varied signs and symptoms of POIKTMP. ### Learn more about the gene associated with Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis * FAM111B ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about half of cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis	c3810325	5,819	medlineplus	https://medlineplus.gov/genetics/condition/hereditary-fibrosing-poikiloderma-with-tendon-contractures-myopathy-and-pulmonary-fibrosis/	2021-01-27T08:25:01	{"gard": ["13218"], "omim": ["615704"], "synonyms": []}
Enterocutaneous fistula SpecialtyGastroenterology An enterocutaneous fistula (ECF) is an abnormal communication between the small or large bowel and the skin that allows the contents of the stomach or intestines to leak through an opening in the skin.[1] ## Contents * 1 Causes * 2 Diagnosis * 2.1 Classification * 2.2 Two categories * 2.3 Three categories * 3 Treatment * 4 References ## Causes[edit] The mnemonic FRIENDS can be used to memorize characteristics which impede the closure of ECF.[2] * F Foreign body * R Radiation * I Infection or Inflammatory bowel disease * E Epithelialization * N Neoplasm * D Distal obstruction * S Short tract (<2 cm) ## Diagnosis[edit] ### Classification[edit] Congenital types: tracheoesophageal, vitellointestinal duct, patent urachus, rectovaginal Acquired: trauma (postoperative), radiation, malignancy, infection ### Two categories[edit] Low-output fistula: < 500 mL/day High-output fistula: > 500 mL/day ### Three categories[edit] Low-output fistula: < 200 mL/day Moderate-output fistula: 200–500 mL/day High-output fistula: > 500 mL/day[3] ## Treatment[edit] The majority will close spontaneously within approximately 6 weeks. If it has not closed by 12 weeks, it is unlikely to do so and definitive surgery should be planned. The median time to definitive repair from fistula onset was 6 months (range 1 day to 28 months). The 6-month time course is commonly utilized by groups with significant experience treating fistulas, owing to the trend in encountering a less hostile abdomen than in the early phases.[4] Some evidence also suggests that somatostatin can be an effective treatment with respect to reducing closure time and improving the spontaneous closure rate of enterocutaneous fistulas.[5] ## References[edit] 1. ^ "Gastrointestinal fistula". MedlinePlus. Retrieved 5 November 2014. 2. ^ Lee SH (2012). "Surgical management of enterocutaneous fistula". Korean Journal of Radiology. 13 Suppl 1: S17–S20. doi:10.3348/kjr.2012.13.S1.S17. PMC 3341456. PMID 22563283. 3. ^ Galie KL, Whitlow CB (2006). "Postoperative enterocutaneous fistula: when to reoperate and how to succeed". Clinics in Colon and Rectal Surgery. 19: 237–246. doi:10.1055/s-2006-956446. PMC 2780112. PMID 20011327. 4. ^ Ross H (2010). "Operative surgery for enterocutaneous fistula". Clinics in Colon and Rectal Surgery. 23: 190–194. doi:10.1055/s-0030-1262987. PMC 2967319. PMID 21886469. 5. ^ Stevens, P; Foulkes, RE; Hartford-Beynon, JS; Delicata, RJ (October 2011). "Systematic review and meta-analysis of the role of somatostatin and its analogues in the treatment of enterocutaneous fistula". European Journal of Gastroenterology & Hepatology. 23 (10): 912–922. doi:10.1097/MEG.0b013e32834a345d. PMID 21814141. * Metcalf C (1999). "Enterocutaneous fistulae". Journal of Wound Care. 8 (3): 141–142. doi:10.12968/jowc.1999.8.3.25854. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Enterocutaneous fistula	c0341318	5,820	wikipedia	https://en.wikipedia.org/wiki/Enterocutaneous_fistula	2021-01-18T18:54:26	{"mesh": ["D007412"], "umls": ["C0341318"], "wikidata": ["Q1344610"]}
## Description Pediatric trigger thumb is caused by a mismatch between the flexor pollicis longus tendon and its sheath. Patients present with a hard, palpable nodule (Notta's node) at the base of the metacarpal and an inability to extend the thumb beyond 30 degrees, which can rarely be accompanied by triggering, snapping, or a digit locked in extension (summary by Wang et al., 2012). Clinical Features Weber (1979) observed a 2-year-old boy with stenosing tenovaginitis of the left thumb resulting in a flexion deformity of the interphalangeal joint of 30 degrees. The boy's father recalled that as a child he was unable to extend both thumbs. His condition had improved but at age 28 he still had weakness of both thumbs and definite 'triggering' bilaterally, with tendon nodules. Weber (1979) noted that a few familial cases had been reported but that this may have been the first report of affected parent and child. Van Genechten (1982) described a 1-year-old boy who could not extend the interphalangeal joint of his right thumb. A firm, nontender nodule was palpable at the level of the metacarpophalangeal joint in the region of the flexor pollicis longus. Surgery revealed a nodule in the volar aspect of the flexor pollicis longus proximal to the main flexor sheath pulley and a mild degree of thickening of this annulus and adjacent sheath. The mother of the child mentioned that she and 4 other relatives had this anomaly and that all had been operated on in infancy with good results. No other congenital anomalies were present. Wang et al. (2012) described monozygotic twin boys with mirror-image trigger thumbs. Inheritance The families with trigger thumb reported by Weber (1979) and Van Genechten (1982) suggested autosomal dominant inheritance. INHERITANCE \- Autosomal dominant SKELETAL Hands \- Limited flexion of the interphalangeal joint of the thumb \- Nodule on the flexor tendon at the level of the metarcarpal head (Notta's node) ▲ 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	TRIGGER THUMB	c0410060	5,821	omim	https://www.omim.org/entry/190410	2019-09-22T16:32:23	{"mesh": ["D052582"], "omim": ["190410"], "icd-10": ["M65.31"]}
A rare, hereditary amyloidosis with primary renal involvement characterized by renal interstitial and medullary deposition of amyloid, low plasma levels of ApoA-1 and slow disease progression. Main clinical signs and symptoms are hypertension, proteinuria, hematuria and edema due to chronic renal insufficiency leading to end stage renal disease. Hepatosplenomegaly, progressive cardiomyopathy and involvement of skin, testes and adrenals (hypergonadotropic hypogonadism) 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	AApoAI amyloidosis	None	5,822	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93560	2021-01-23T19:04:44	{"icd-10": ["E85.0"], "synonyms": ["Apolipoprotein A-I amyloidosis", "Familial amyloid nephropathy due to apolipoprotein A-I variant", "Familial renal amyloidosis due to apolipoprotein A-I variant", "Hereditary amyloid nephropathy due to apolipoprotein A-I variant", "Hereditary renal amyloidosis due to apolipoprotein A-I variant"]}
Olivopontocerebellar atrophy-deafness syndrome is characterised by infancy-onset olivopontocerebellar atrophy, sensorineural deafness and speech impairment. It has been described in less than 15 children. Most cases were sporadic, but autosomal recessive inheritance was suggested in three 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	Olivopontocerebellar atrophy-deafness syndrome	None	5,823	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2732	2021-01-23T18:12:53	{"gard": ["4070"], "icd-10": ["Q04.8"], "synonyms": ["Olivopontocerebellar atrophy-hearing loss syndrome"]}
A number sign (#) is used with this entry because this phenotype is associated with early embryonic postzygotic somatic activating mutations in the GNAS1 gene (139320). Description Activating or gain-of-function GNAS1 mutations in patients with the McCune-Albright syndrome are present in the mosaic state, resulting from a postzygotic somatic mutation appearing early in the course of development which yields a monoclonal population of mutated cells within variously affected tissues. The nonmosaic state for most activating mutations is presumably lethal to the embryo. The disorder is characterized clinically by the classic triad of polyostotic fibrous dysplasia (POFD), cafe-au-lait skin pigmentation, and peripheral precocious puberty. However, the disorder is clinically heterogeneous and can include various other endocrinologic anomalies such as thyrotoxicosis, pituitary gigantism, and Cushing syndrome (219080) (Lumbroso et al., 2004). Clinical Features This disorder is called McCune-Albright syndrome or simply Albright syndrome, but should not be confused with pseudohypoparathyroidism (103580), which includes a constellation of features termed Albright hereditary osteodystrophy (AHO). The predominant features of MAS occur in 3 areas: the bony skeleton, the skin, and the endocrine system. In all 3 systems, the extent of the abnormality and, in the case of the endocrine system, the nature of the abnormality, are highly variable from case to case, depending on the specific tissues involved in the mosaicism and the extent of involvement. ### Skeletal No bone is spared. There is a strong tendency to asymmetry. Involvement of the skull and facial bones can be striking, and in the case of these bones also, asymmetry is the rule. Pathologic fracture or bone deformity may be presenting manifestations and pseudarthrosis occurs frequently. Deafness and blindness can result from impingement of the bony process on the cranial foramina. Shepherd's crook deformity of the proximal femur is particularly characteristic of the bony involvement. (The bone lesions of neurofibromatosis are usually less extensive than are those in polyostotic fibrous dysplasia, but may be difficult to distinguish on radiologic grounds alone.) Hypophosphatemic osteomalacia ('rickets') has been observed in some cases of polyostotic fibrous dysplasia. Dent and Gertner (1976) suggested that this may represent a situation comparable to 'tumor rickets' which is associated with mesenchymal tumors and regresses when the tumor is removed. McArthur et al. (1979) described 4 patients with Albright syndrome, hypophosphatemia, and inappropriately low renal tubular reabsorption of phosphate. Three of the patients had radiologic evidence of rickets. They postulated that a substance elaborated by the dysplastic bone interfered with phosphate reabsorption in the renal tubule. Kaplan et al. (1988) reported the case of a 31-year-old woman with this disorder in whom bone lesions progressed rapidly during pregnancy. A study of these lesions showed the presence of estrogen and progesterone receptors in osteogenic cells. Whether estrogen receptors are unique to the McCune-Albright syndrome or, alternatively, a property of any activated, dedifferentiated, or neoplastic bone cells is unclear. Viljoen et al. (1988) described a severely affected man, aged about 30, with massive craniofacial hyperostosis. They raised the question of whether this represents the severe end of the scale for polyostotic fibrous dysplasia, or whether it is a distinct entity. It seems likely that this was a severe expression of polyostotic fibrous dysplasia (McCune-Albright syndrome). McKusick (1988) studied a patient with severe craniofacial hyperostosis who had other, more characteristic features of polyostotic fibrous dysplasia, including cafe-au-lait pigmentation, which was absent in the case of Viljoen et al. (1988); this patient was later found by Schwindinger et al. (1992) to have a mutation in the GNAS1 gene (139320.0009). There are other definite cases of patients with very severe craniofacial involvement (Nager et al., 1982; Nager and Holliday, 1984). Such is also evident from inspection of the descriptions in the classic monograph of Albright and Reifenstein (1948). For example, they produced a picture (their Figure 145) of a skeleton thought by von Recklinghausen (1891) to represent hyperparathyroidism (osteitis fibrosa generalisata of von Recklinghausen). That this was severe Albright polyostotic fibrous dysplasia was suggested by the shepherd's crook deformity of the femora and the asymmetric bulge of the occipital area of the skull. Taconis (1988) reported 2 cases of osteosarcomatous transformation, 1 in the skull of a 25-year-old man and 1 in the iliac bone of a 38-year-old man. Taconis (1988) stated that the incidence of malignancy of the bone lesions may be lower than previously suggested. Malignant transformation occurs in both monostotic and polyostotic disease but is more common in the latter form. Although radiation therapy is often an inciting cause, this was not the case in either of these patients, who had received no radiation therapy. Candeliere et al. (1995) reported a 7-year-old boy with McCune-Albright syndrome in whom they identified high levels of expression of the FOS (164810) oncogene in bone lesions. Increased expression of the FOS oncogene was presumably a consequence of increased adenylate cyclase activity and may have been important in the pathogenesis of the bone lesions. Genetic analysis identified the R201H mutation in the GNAS1 gene (139320.0013). ### Skin The involvement of the skin consists predominantly of large cafe-au-lait spots with irregular margins, giving them a 'coast of Maine' configuration as opposed to the more regularly outlined 'coast of California' cafe-au-lait spots of neurofibromatosis (162200). Like the bony lesions, the pigmentary lesions of the skin may be limited predominantly to one side and stop sharply at the midline. The nape of the neck is a commonly involved site. (The cafe-au-lait spots of neurofibromatosis are for the most part smaller, more regular, and more uniformly distributed, and are accompanied by axillary freckling and usually by skin tumors.) ### Endocrine The leading endocrinologic feature is precocious puberty, which occurs in over half of female cases. Menstruation may occur in the first months of life. Precocious puberty has been reported also in males with this syndrome; testicular biopsy has revealed the full process of spermatogenesis with mature sperm in patients as young as 6 years (Benedict, 1966; Giovannelli et al., 1978). Probably the second most common endocrinopathy is hyperthyroidism (Lichtenstein and Jaffe, 1942; Hamilton and Maloof, 1973). Excessive secretion of growth hormone (GH1; 139250) with gigantism, hyperadrenocorticism with Cushing syndrome, and gynecomastia have been observed. In specific instances, it has been demonstrated that the Cushing syndrome is due to multinodular change in the adrenals and the hyperthyroidism to multinodular toxic goiter (Hamilton and Maloof, 1973). Falconer et al. (1942) reported pituitary gigantism in association with McCune-Albright syndrome. Wrong (1992) stated that he saw this patient, a boy born in Nottingham in 1930, in 1954; the patient was still alive, though severely disabled by bone disease, in the late 1960s at the age of almost 40. Premawardhana et al. (1992) described a 26-year-old woman with acromegaly due to a pituitary adenoma who developed secondary hypothyroidism and hypoadrenalism, in a setting of McCune-Albright syndrome. Cremonini et al. (1992) described acromegaly and hyperprolactinemia due to pituitary adenoma in a 35-year-old woman with McCune-Albright syndrome. Malchoff et al. (1994) reported a 27-year-old woman with McCune-Albright syndrome who had an unusual clinical course. She presented at the age of 3 years with vaginal bleeding, had breast development at age 4 years, and had a second episode of vaginal bleeding at age 5 years 7 months. She had no pigmentary skin lesions, and 2 sets of radiographs of the chest, pelvis, skull, and long bones were normal. She was treated for 24 months with medroxyprogesterone acetate, and precocity resolved. She progressed normally through puberty, starting at age 10 years, and had normal menses, starting at age 12 years. At age 25 years, she delivered a normal daughter. A chest x-ray at age 27 years after minor trauma identified a single lesion of fibrous dysplasia in the left seventh rib. Radiographs of other bones were normal. Studies of the GNAS1 gene showed an R201H mutation. Tinschert et al. (1999) reported a 37-year-old man with McCune-Albright syndrome causing gigantism and fibrous dysplasia with hypersecretion of growth hormone and prolactin (176760), with no evidence of pituitary tumor. The patient had an R201H mutation which ranged from 0% in buccal mucosa, blood, and skin melanocytes to 45% in a frozen section of the middle nasal concha. Coutant et al. (2001) reported a 3.8-year-old boy with McCune-Albright syndrome associated with abnormal prepubertal testis enlargement and no sexual precocity. Other endocrine tests showed excessive GH secretion and moderate adrenal androgen hypersecretion. These findings were consistent with the occurrence of an activating mutation of the GNAS1 gene mainly expressed in Sertoli cells and weakly expressed or absent in Leydig cells. Abnormal prepubertal testicular enlargement extends the clinical spectrum of MAS, suggesting that determination of serum inhibin B (see 147290) and anti-mullerian hormone (600957) should be considered in boys with this syndrome. DNA sequence analysis from bone and testis tissues detected the R201H mutation. Akintoye et al. (2002) estimated the prevalence of GH excess in MAS, characterized the clinical and endocrine manifestations, and described the response to treatment. Twelve patients (21%) had GH excess, based on failure to suppress serum GH on oral glucose tolerance test. Vision and hearing deficits were more common in patients with GH excess (33%) than in those without (4%). Patients with a history of precocious puberty and GH excess who had reached skeletal maturity achieved normal adult height despite a history of early epiphyseal fusion. All 9 patients tested had an increase in serum GH after TRH (613879), 11 of 12 (92%) had hyperprolactinemia, and all 8 tested had detectable or elevated nighttime GH levels. Pituitary adenoma was detected in 4 of 12 (33%) patients. GH excess is common in MAS and results in a distinct clinical phenotype characterized by inappropriately normal stature, TRH responsiveness, prolactin (176760) cosecretion, small or absent pituitary tumors, a consistent but inadequate response to treatment with cabergoline, and an intermediate response to long-acting octreotide. Laven et al. (2001) presented the first longitudinal assessment of ovarian dysfunction in an adult patient with McCune-Albright syndrome. Their report provided evidence for persistent autonomous unilateral ovarian dysfunction during early adulthood in McCune-Albright syndrome not compatible with normal fertility. Laven et al. (2004) presented a case of an adult MAS patient with persistent unilateral autonomous ovarian activity whose ovarian and endometrial function was restored by removal of the affected ovary. Obuobie et al. (2001) studied the GH and insulin-like growth hormone I (IGF1; 147440) profiles in a patient with confirmed McCune-Albright syndrome and GH hypersecretion throughout a successful pregnancy and postpartum period. Prepregnancy, the IGF I level was 60.6 nmol/L (normal, 18.0-43.1) and the daytime GH profile measured using assay A was 9.6-14.0 mU/L. At 13 weeks' gestation there was a decline of IGF I to 33.9 nmol/L and in the daytime GH profile (assay A) to 5.4-6.8 mU/L. At 24 weeks, IGF I had risen to 51.6 nmol/L. At 36 weeks, IGF I was still elevated at 56.6 nmol/L, with a daytime GH profile of 16.6-17.7 mU/L using assay A. At 12 weeks postpartum, the daytime GH profile with assay B was 5.6-8.6 mU/L. The authors concluded that GH suppression during pregnancy in acromegaly associated with McCune-Albright syndrome is best shown with assay B, which discriminates between GH and human placental lactogen (HPL; 150200). They also stated that GH secretion in a pregnant acromegalic with the McCune-Albright syndrome may not be entirely autonomous, as seen in classic acromegaly, but may be associated with a degree of negative feedback control that could be exerted by a circulating factor of placental origin, probably HPL or placental GH (GH2; 139240). DiGeorge (1975) reviewed unusual features of the syndrome and the evidence that the endocrinopathy represents autonomous function of the endocrine glands. Two main hypotheses had been stated: (1) excessive secretion of the hypothalamic releasing hormones is involved in the endocrinopathy of this disorder (Hall and Warrick, 1972); and (2) this disorder represents multiple, circumscribed embryonic alterations in a variety of tissues resulting from clones of cells characterized by autonomous behavior, and perhaps aberrant behavior, toward otherwise normal stimuli. The latter hypothesis appeared to be the more compatible with the skeletal, cutaneous, and endocrinologic features and with the mosaic hypothesis of Happle (1986); its validity was proved by demonstration of mosaicism for mutations in the GNAS1 gene. Majzoub and Scully (1993) described a 6-year-old boy who had apocrine sweat, facial acne, Tanner stage 2 pubic hair, and midpubertal-sized testes and penis, all indicative of precocious puberty, in association with osseous changes of this disorder. A patient, aged 50 years, with McCune-Albright syndrome had a large syrinx (syringomyelia) causing neurologic manifestations in the arms and legs (McKusick, 1988). Because of a linear midline pigmentation in the high cervical area posteriorly, in the same area of the syrinx, the possibility can be raised that the syrinx, which extended from C2 to T11, was a primary manifestation of the syndrome. The patient also had extensive involvement of the base of the skull with Arnold-Chiari syndrome (i.e., extension of cerebellar tissue through the foramen magnum). He had had hyperthyroidism, as reported by Hamilton and Maloof (1973). (The same patient had severe craniofacial hyperostosis and was demonstrably mosaic for a specific GNAS1 mutation, i.e., arg201-to-his (139320.0009).) Abs et al. (1990) described a case of atypical McCune-Albright syndrome; a 36-year-old woman had acromegaly due to a pituitary adenoma, a toxic multinodular goiter that was associated with spontaneous normalization of thyroid function, and asymptomatic polyostotic fibrous dysplasia. There was no skin pigmentation and no sexual precocity. See 139320.0009 for discussion of the molecular basis of the association of pituitary tumor with McCune-Albright syndrome. Chanson et al. (1994) reported 5 patients with McCune-Albright syndrome and acromegaly. In all, acromegaly began before the age of 20 years and was recognized after the diagnosis of fibrous dysplasia, which was polyostotic in 3 and monostotic in 2. Bone fibrous dysplasia always involved the base of the skull and in 4 patients prevented surgical removal of the pituitary adenoma, which was visualized easily by MRI. Yoshimoto et al. (1991) described the extraordinary case of a female infant who at birth had cutaneous pigmentation, hyperthyroidism, and Cushing syndrome. Mastorakos et al. (1997) described a 6-year-old girl with MAS and hyperthyroidism and reviewed the previously reported 63 patients with MAS and thyroid disorders. Kirk et al. (1999) presented 5 children (4 girls) with features of McCune-Albright syndrome who had Cushing syndrome in the infantile period (under 6 months of age). In 2 children, spontaneous resolution occurred, but the remaining 3 required bilateral adrenalectomy. In addition, all 4 girls experienced precocious puberty, and 3 children demonstrated radiologic evidence of nephrocalcinosis. In 1 patient, laparotomy, performed at 7 weeks of age because of vomiting and abdominal distention, revealed multiloculated ovarian cysts. Bilateral adrenalectomy was performed at 3 months for nodular hyperplasia. Irregular vaginal bleeding in association with breast development occurred by 11 months of age. Thyrotoxicosis subsequently developed, and the patient had a number of pathologic fractures of both femurs through polyostotic lesions and had marked spinal deformity. Kirk et al. (1999) postulated that the hypercalcemia and hypercalciuria leading to renal stones are secondary to the effects of cortisol on bone turnover. Yang et al. (1999) reported a case of thyroid cancer in McCune-Albright syndrome. Collins et al. (2003) reported a second case and reviewed both cases, extending the phenotypic spectrum of the disorder. ### Phenotypic Variation Cole et al. (1983) reported the case of a French-Canadian boy, of nonconsanguineous parents, who had unusual facial appearance (depressed nasal bridge, synophrys, and forehead hirsutism), 'coast of Maine' pigmented patches, myelofibrosis, recurrent femoral fractures and widespread fibrous dysplasia of bone leading to the suggested designation 'panostotic fibrous dysplasia.' Biochemical findings included elevated serum alkaline phosphatase (bone isozyme) and 1,25-(OH)2 vitamin D and low serum phosphorus levels. Increased turnover of bone was indicated by urinary excretion rates of hydroxyproline, glycylproline, and gamma-carboxyglutamic acid. Progressive cortical thinning and loss of bony trabeculae were demonstrated by serial x-rays and supported by bone biopsy. No precisely similar case was known. Candeliere et al. (1995) demonstrated that this patient, then a 14-year-old boy, had an arg201-to-cys mutation in the GNAS1 gene (139320.0008). Thus, this was an unusually severe form of McCune-Albright syndrome not fundamentally different from that disorder or perhaps from monostotic fibrous dysplasia. Cole (1996) pointed out that the patient with 'idiopathic hyperphosphatasia with dermal pigmentation' reported by Dohler et al. (1986) appears to have had the same disorder as the patient reported by Cole et al. (1983). De Sanctis et al. (1999) reported the diagnostic clinical features and their long-term evolution in 32 patients with McCune-Albright syndrome. Almost all patients had skin changes at birth. There was a 50% probability of bone dysplasia at 8 years of age and a 50% probability of precocious puberty in females at 4 years. Coutant et al. (2001) reported a 3.8-year-old boy with McCune-Albright syndrome associated with abnormal prepubertal testis enlargement and no sexual precocity. Physical examination showed cafe-au-lait skin lesions, enlarged testes, prepubertal sized penis, and no pubic or axillary hair. Skeletal radiography disclosed fibrous dysplasia. The serum testosterone level was 0.58 nmol/L and remained below 1.4 nmol/L during the 4-year follow-up. By contrast, serum inhibin B (see 147290) and anti-mullerian hormone (600957) concentrations were abnormally increased up to 255 pg/mL (childhood range, 35-180) and 792 pmol/L (childhood range, 309-566), respectively. The luteinizing hormone (LH; 152780) response to a gonadotropin-releasing hormone (GnRH; 152760) test was in the prepubertal range, whereas the follicle-stimulating hormone (FSH; 136530) response was blunted. This abnormal hormone concentration profile indicated autonomous hyperfunction of Sertoli cells, with no evidence of Leydig cell activation. Testicular histology showed tubules with marked Sertoli cell hyperplasia and very rare germinal cells, and interstitial tissue containing mesenchymal cells but no mature Leydig cells. DNA sequence analysis from bone and testis tissues detected the known activating mutation in MAS that results in the arg201-to-his mutation in the GNAS1 protein (139320.0009). Other Features Zacharin et al. (2011) reported 4 unrelated patients with MAS who had multiple hamartomatous gastrointestinal polyps in the stomach and/or duodenum. Two of the patients were noted to have perioral freckling in their early teens, reminiscent of Peutz-Jeghers syndrome (PJS; 175200) and were thus examined endoscopically. The polyps showed a branching pattern with prominent cores of smooth muscle covered by well-differentiated epithelium. Molecular analysis of peripheral blood identified activating mutations in the GNAS gene in 3 of the 4 patients; none of the patients had STK11 (602216) mutations. Molecular analysis of the gastrointestinal polyps showed no GNAS mutation in 1 patient, LOH of the GNAS locus in 1 patient, the same GNAS mutation as found in peripheral blood in 1 patient, and heterozygosity for a GNAS activating mutation only in the polyp in the patient without a mutation in peripheral blood. Zacharin et al. (2011) concluded that patients with MAS should undergo routine endoscopy, as gastrointestinal polyps may be a common manifestation of the disorder. Inheritance Few convincing instances of familial occurrence of POFD have been reported. Hibbs and Rush (1952) reported the case of a 50-year-old woman with typical skin pigmentation and involvement of multiple bones. The daughter had no skin pigmentation (which is absent in some cases) but had a pathologic fracture of the left radius and radiologic and histologic changes interpreted as those of fibrous dysplasia. Firat and Stutzman (1968) described hyperthyroidism in 1 patient who also had pituitary gigantism and hyperparathyroidism in 2 others. The last 2 cases were mother and daughter. The fibrous dysplasia was limited to the jaw. Reitzik and Lownie (1975) described a family in which many members had craniofacial POFD in an autosomal dominant pedigree pattern. This may have represented, however, an entity distinct from MAS. Alvarez-Arratia et al. (1983) presented a family that had several members in at least 3 generations with the bony and cutaneous lesions of polyostotic fibrous dysplasia. Happle (1986) made the intriguing suggestion that this disorder is caused by an autosomal dominant lethal gene that is compatible with viability of the conceptus only when it occurs in the mosaic state, having arisen by somatic mutation. Endo et al. (1991) described monozygotic twin girls of whom one showed major signs of MAS: precocious puberty, cafe-au-lait nevi, and polyostotic fibrous dysplasia. The lack of fully convincing familial cases, except for the occurrence in monozygotic twins (Lemli, 1977), is consistent with the Happle hypothesis. (In the twins reported by Lemli (1977), one had classic signs of McCune-Albright syndrome and the other had only radiologic signs of bone disease and elevated serum alkaline phosphatase.) The frequency of the disorder is about equal in males and females. Feuillan et al. (1991) reported the cases of 2 girls with precocious puberty initially diagnosed at the ages of 1 and 4 years. Both were unresponsive to treatment with the LHRH (luteinizing hormone-releasing hormone; 152760) agonist deslorelin for 5 years. In this respect they resembled patients with the McCune-Albright syndrome, but they had none of the other manifestations of MAS. Feuillan et al. (1991) suggested that although the underlying defect was absent in bone and skin, it was expressed in the ovaries of the 2 girls. This suggestion is consistent with the view that the McCune-Albright syndrome is a somatic mutation disorder. Clinical Management Plotkin et al. (2003) investigated the effects of intravenous pamidronate treatment in 18 children and adolescents with polyostotic fibrous dysplasia who were treated for 1.2 to 9.1 years. Although not quantitatively examined, pamidronate appeared to be effective in reducing bone pain. However, there was no radiographic evidence of filling of lytic lesions or thickening of the bone cortex surrounding the lesions in any patient. Feuillan et al. (2007) studied the effectiveness of the aromatase inhibitor letrozole in decreasing pubertal progression in girls with MAS and assessed the response of indices of bone turnover associated with the patients' polyostotic fibrous dysplasia. Girls had decreased rates of growth (p less than 0.01) and bone age advance (p less than 0.004) and cessation or slowing in their rates of bleeding over 12 to 36 months of therapy. Mean ovarian volume, estradiol, and indices of bone metabolism fell after 6 months (p less than 0.05) but tended to rise by 24 to 36 months. Feuillan et al. (2007) concluded that letrozole may be effective therapy in some girls with MAS and/or gonadotropin-independent precocious puberty. Possible adverse effects include ovarian enlargement and cyst formation. Mieszczak et al. (2008) determined the safety and efficacy of the aromatase inhibitor anastrozole for the treatment of precocious puberty in girls with McCune-Albright syndrome. Although it appeared safe, anastrozole for 1 year was ineffective in halting vaginal bleeding and attenuating rates of skeletal maturation and linear growth in girls with McCune-Albright syndrome. The authors concluded that pharmacologic strategies other than anastrozole should be pursued for the treatment of precocious puberty in this population. Molecular Genetics The mystery of the etiology and pathogenesis of polyostotic fibrous dysplasia appears to have been solved by the identification of activating mutations in the GNAS1 gene (139320) which render the gene functionally constitutive (Weinstein et al., 1991; Schwindinger et al., 1992). Similar mutations leading to constitutive activation of this gene had been identified in some human growth hormone secreting pituitary tumors and human thyroid tumors. Furthermore, the demonstration of the mutation in peripheral blood leukocytes but not in DNA from biopsies of clinically normal skin supports the proposal of Happle (1986) that this is a disorder of mosaicism resulting from postzygotic somatic cell mutation. Kitoh et al. (1999) found a mutation in GNAS1 in endosteal, but not in periosteal, cells taken from a cystic lesion of the humerus of an 11-year-old boy with polyostotic fibrous dysplasia. Bianco et al. (1998) isolated progenitor cells from the stromal system of the bone marrow involved in fibrous dysplasia in patients with McCune-Albright syndrome and analyzed these cells in culture. Analysis of the GNAS1 gene from individual colonies provided direct evidence for the presence of 2 different genotypes within single fibrous dysplastic lesions: marrow stromal cells containing 2 normal GNAS1 alleles, and those containing a normal allele and an allele with an activating mutation. Transplantation of clonal populations of normal cells into the subcutis of immunocompromised mice resulted in normal ossicle formation. In contrast, transplantation of clonal populations of mutant cells always led to the loss of transplanted cells from the transplantation site and no ossicle formation. However, transplantation of a mixture of normal and mutant cells reproduced an abnormal ectopic ossicle recapitulating human fibrous dysplasia and providing an in vivo cellular model of this disease. The results provided experimental evidence for the need of both normal and mutant cells in the development of McCune-Albright syndrome fibrous dysplastic lesions in bone. This study confirmed the hypothesis of Happle (1986). It also confirmed the editorial comment of DiGeorge (1975) concluding with the remark that MAS is 'a rare disorder, yes; an unimportant one, never' (Olsen, 1998). Bianco et al. (2000) analyzed a series of 8 consecutive cases of isolated fibrous dysplasia without the classic features of McCune-Albright syndrome and identified arg201 mutations in the GNAS1 gene in all of them. Histologic findings in these cases were not distinguishable from those observed in MAS-related fibrous dysplasia and included subtle changes in cell shape and collagen texture putatively ascribed to excess endogenous cAMP. Unmineralized osteoid changes characteristic of osteomalacia were prominent in lesional fibrous dysplasia. Bianco et al. (2000) concluded that the findings support the view that fibrous dysplasia, MAS, and nonskeletal isolated endocrine lesions associated with GNAS1 mutations represent a spectrum of phenotypic expressions, probably reflecting different patterns of somatic mosaicism, of the same basic disorder. Akintoye et al. (2002) noted that the molecular etiology of MAS is postzygotic activating mutations of the GNAS1 gene product, the alpha subunit of the Gs protein. The term 'GSP oncogene' has been assigned to these mutations due to their association with certain neoplasms. Collins et al. (2003) performed molecular analysis of thyroid carcinomas from 2 McCune-Albright syndrome patients and demonstrated that foci of malignancy and adjacent areas of hyperplasia and, in 1 case, some areas of normal thyroid harbored an activating mutation of GNAS1 at the arg201 codon (139320.0008 and 139320.0009, respectively). The authors concluded that these 2 cases of thyroid carcinoma in MAS supported the hypothesis that activation of the G(s) signaling cascade alone is insufficient for malignant transformation of thyroid or other endocrine cells. Using a PCR-based sensitive method, Lumbroso et al. (2004) reported a systematic search for Gs-alpha arg201 mutations in patients presenting with at least 1 of the signs of MAS. They studied 113 patients (98 girls and 15 boys), 24% presenting the classic triad, 33% with 2 signs, and 40% with only 1 classic sign. Overall, mutation of the arg201 codon was identified in 43% of the patients. When an affected tissue was available, the mutation was found in more than 90% of the patients, whatever the number of signs. Skin was a noteworthy exception because only 3 of 11 skin samples were positive. The mutation was detected in 46% of blood samples in patients presenting the classic triad, whereas this figure fell to 21% and 8% in patients with 2 and 1 sign, respectively. The authors concluded that affections as clinically different as monostotic fibrous dysplasia, isolated peripheral precocious puberty, neonatal liver cholestasis, and the classic MAS all appear to be components of a wide spectrum of diseases based on the same molecular defect. History This disorder was first described by McCune and Bruch (1937) and Albright et al. (1937, 1938). Affected persons came to the attention of Fuller Albright because of the similarity of the skeletal changes to those of osteitis fibrosa cystica resulting from hyperparathyroidism (Axelrod, 1970). Lichtenstein (1938) introduced the designation 'polyostotic fibrous dysplasia' for the skeletal aspect of the syndrome. Nerlich et al. (1991) suggested that Thomas Hasler, the 'Tegernsee giant,' had a combination of juvenile gigantism and polyostotic fibrous dysplasia. It would not be surprising if the two occurred together in light of the fact that the same somatic mutation is found in PFD and in growth hormone-secreting tumors of the pituitary (see 102200) (Schwindinger et al., 1991). INHERITANCE \- Somatic mosaicism HEAD & NECK Head \- Cranial foramen impingement \- Craniofacial hyperostosis Face \- Facial asymmetry Ears \- Deafness Eyes \- Blindness ABDOMEN Gastrointestinal \- Gastrointestinal polyps SKELETAL \- Polyostotic fibrous dysplasia \- Pathologic fracture SKIN, NAILS, & HAIR Skin \- Large cafe au lait spots with irregular margins ENDOCRINE FEATURES \- Hyperthyroidism \- Hyperparathyroidism \- Cushing syndrome \- Precocious puberty \- Acromegaly \- Hyperprolactinemia NEOPLASIA \- Pituitary adenoma MISCELLANEOUS \- Variable phenotype \- Activating or gain-of-function GNAS1 mutations in patients with the McCune-Albright syndrome are present in the mosaic state, resulting from a postzygotic somatic mutation appearing early in the course of development which yields a monoclonal population of mutated cells within variously affected tissues MOLECULAR BASIS \- Caused by somatic mutation in the guanine nucleotide-binding protein, alpha-stimulating activity polypeptide 1 gene (GNAS1, 139320.0008 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	MCCUNE-ALBRIGHT SYNDROME	c0242292	5,824	omim	https://www.omim.org/entry/174800	2019-09-22T16:36:01	{"doid": ["1858"], "mesh": ["D005359"], "omim": ["174800"], "icd-9": ["756.54"], "icd-10": ["Q78.1"], "orphanet": ["562"], "synonyms": ["Alternative titles", "ALBRIGHT SYNDROME"], "genereviews": ["NBK274564"]}
## Clinical Features Stanescu et al. (1963) described 9 members of a kindred with an apparently 'new' syndrome. The features included a peculiar form of craniofacial dysostosis with small skull, thin cranial bone, depressions over the frontoparietal and occipitoparietal sutures, poorly developed mandible, and exophthalmos. The limbs were short and by x-ray the cortices of the long bones were massively thickened. Maximilian et al. (1981) reexamined this family. In the period between reports, 3 additional affected persons had been born. Maximilian et al. (1981) noted that thickening of bone cortex occurs during or after puberty and increases with age. Dipierri and Guzman (1984) reported affected mother and infant daughter. The most striking features were short stature (144 cm in the mother), brachycephaly, brachydactyly, and dense cortices of long bones. The age of the unaffected father of 'the mother' in Dipierri and Guzman's report was 50 at the time of her birth. The patient reported by Hall (1974) had severe involvement of the spine and thorax with kyphoscoliosis and pectus excavatum; a different disorder may have been present. Horovitz et al. (1995) described an affected male and his affected mother. Both were short and had cortical sclerosis of the long bones, deficient facial sinus development, cranial bone malformations, and normal intelligence. The presence of wormian bones and calcification of the falx cerebri had not previously been observed. Both the 10-year-old son and the 37-year-old mother showed these 2 features. In the kindred reported by Horovitz et al. (1995) there were possibly affected individuals in 3 generations and several separate sibships with instances of male-to-male transmission. The diagnosis was based, however, not on personal examination but on information from the family and suggestive photographs. Inheritance The transmission pattern of craniofacial dysostosis with diaphyseal hyperplasia in the family reported by Stanescu et al. (1963) was consistent with autosomal dominant inheritance. Radiology \- Massively thickened long bone cortices \- Thin cranial bone Eyes \- Exophthalmos Growth \- Short stature Skull \- Craniofacial dysostosis \- Small skull \- Frontoparietal and occipitoparietal suture depressions \- Poorly developed mandible \- Brachycephaly Inheritance \- Autosomal dominant Spine \- Kyphoscoliosis Limbs \- Short limbs \- Brachydactyly Thorax \- Pectus excavatum ▲ 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	CRANIOFACIAL DYSOSTOSIS WITH DIAPHYSEAL HYPERPLASIA	c0432263	5,825	omim	https://www.omim.org/entry/122900	2019-09-22T16:42:46	{"mesh": ["C562974"], "omim": ["122900"], "orphanet": ["1798"], "synonyms": ["Alternative titles", "OSTEOSCLEROSIS, STANESCU TYPE"]}
Lichenoid eruption SpecialtyDermatology A lichenoid eruption is a skin disease characterized by damage and infiltration between the epidermis and dermis.[1] Examples include lichen planus, lichen sclerosus and lichen nitidus. It can also be associated with abrasion or drug use.[2] It has been observed in conjunction with the use of proton pump inhibitors, and might be a sign and/or symptom of lupus such as subacute cutaneous lupus erythematous, according to the case reports and reviews.[3][4][5][6] The term "lichenoid" derives from a resemblance to a lichen. ## References[edit] 1. ^ Lichenoid+eruptions at the US National Library of Medicine Medical Subject Headings (MeSH) 2. ^ "White : Diseases of the Skin - Lichen Planus and Lichenoid Disorders". 3. ^ Brauer, J; Votava, HJ; Meehan, S; Soter, NA (2009-08-15). "Lichenoid drug eruption". Dermatology Online Journal. 15 (8): 13. ISSN 1087-2108. PMID 19891921. 4. ^ Bong JL, Lucke TW, Douglas WS (January 2000). "Lichenoid drug eruption with proton pump inhibitors". BMJ. 320 (7230): 283. doi:10.1136/bmj.320.7230.283. PMC 27275. PMID 10650025. 5. ^ Tukenmez Demirci, Gulsen; Altunay, Ilknur Kivanc; Sarikaya, Sezgi; Sakiz, Damlanur (2011-11-25). "Lupus erythematosus and lichen planus overlap syndrome: a case report with a rapid response to topical corticosteroid therapy". Dermatology Reports. PAGEPress Publications. 3 (3): 48. doi:10.4081/dr.2011.e48. ISSN 2036-7406. PMC 4211510. PMID 25386300. 6. ^ Solhjoo, M; Ho, CH; Chauhan, K (2019), "article-24529", Drug-Induced Lupus Erythematosus, Treasure Island (FL): StatPearls Publishing, PMID 28722919, retrieved 2019-12-18 ## External links[edit] Classification D * ICD-10: L43-L44 * ICD-9-CM: 697 * MeSH: D017512 * v * t * e Papulosquamous disorders Psoriasis Pustular * Generalized pustular psoriasis (Impetigo herpetiformis) * Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid) * Annular pustular psoriasis * Localized pustular psoriasis Other * Guttate psoriasis * Psoriatic arthritis * Psoriatic erythroderma * Drug-induced psoriasis * Inverse psoriasis * Napkin psoriasis * Seborrheic-like psoriasis Parapsoriasis * Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica) * Lymphomatoid papulosis * Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans) * Large plaque parapsoriasis (Retiform parapsoriasis) Other pityriasis * Pityriasis rosea * Pityriasis rubra pilaris * Pityriasis rotunda * Pityriasis amiantacea Other lichenoid Lichen planus * configuration * Annular * Linear * morphology * Hypertrophic * Atrophic * Bullous * Ulcerative * Actinic * Pigmented * site * Mucosal * Nails * Peno-ginival * Vulvovaginal * overlap synromes * with lichen sclerosus * with lupus erythematosis * other: * Hepatitis-associated lichen planus * Lichen planus pemphigoides Other * Lichen nitidus * Lichen striatus * Lichen ruber moniliformis * Gianotti–Crosti syndrome * Erythema dyschromicum perstans * Idiopathic eruptive macular pigmentation * Keratosis lichenoides chronica * Kraurosis vulvae * Lichen sclerosus * Lichenoid dermatitis * Lichenoid reaction of graft-versus-host disease This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Lichenoid eruption	c0162848	5,826	wikipedia	https://en.wikipedia.org/wiki/Lichenoid_eruption	2021-01-18T19:04:17	{"mesh": ["D017512"], "icd-9": ["697"], "icd-10": ["L43"], "wikidata": ["Q6543234"]}
A rare large granular lymphocyte leukemia characterized by persistent (> 6 months) natural killer cell lymphocytosis in the absence of clinical diagnosis of leukemia/lymphoma, autoimmune disease, or chronic viral infections. The clinical course is variable, but generally indolent. Patients often remain asymptomatic, or may present with clinical manifestations including vasculitic skin lesions, neutropenic infections, musculoskeletal symptoms, peripheral neuropathy, or splenomegaly. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Chronic lymphoproliferative disorder of natural killer cells	c1512709	5,827	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=512017	2021-01-23T17:52:46	{"synonyms": ["CLPD-NK", "CNKL", "Chronic NK lymphocytosis", "Chronic NK-cell lymphocytosis", "Chronic lymphoproliferative disorder of NK-cells", "NK-cell lineage granular lymphocyte proliferative disorder"]}
A number sign (#) is used with this entry because susceptibility to the development of atypical hemolytic uremic syndrome-1 (AHUS1) can be conferred by variation in the gene encoding complement factor H (CFH; 134370) on chromosome 1q31. Deficiency of the CFH-related proteins CFHR1 (134371) and CFHR3 (605336) may be associated with development of the disorder due to autoantibodies. Other genes may play a role in modifying the phenotype (see MOLECULAR GENETICS). HUS can share overlapping clinical features with thrombotic thrombocytopenic purpura (TTP; 274150), which is caused by mutation in the von Willebrand factor-cleaving protease (VWFCP) gene (ADAMTS13; 604134). Description Typical hemolytic uremic syndrome is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia associated with distorted erythrocytes ('burr cells'). The vast majority of cases (90%) are sporadic, occur in children under 3 years of age, and are associated with epidemics of diarrhea caused by verotoxin-producing E. coli. The death rate is very low, about 30% of cases have renal sequelae, and there is usually no relapse of the disease. This form of HUS usually presents with a diarrhea prodrome (thus referred to as D+HUS) and has a good prognosis in most cases. In contrast, a subgroup of patients with HUS have an atypical presentation (aHUS or D-HUS) without a prodrome of enterocolitis and diarrhea and have a much poorer prognosis, with a tendency to relapse and frequent development of end-stage renal failure or death. These cases tend to be familial. Both autosomal recessive and autosomal dominant inheritance have been reported (Goodship et al., 1997; Taylor, 2001; Veyradier et al., 2003; Noris et al., 2003). Noris and Remuzzi (2009) provided a detailed review of atypical HUS. ### Genetic Heterogeneity of Atypical Hemolytic Uremic Syndrome Atypical HUS is a genetically heterogeneous condition. Susceptibility to the development of the disorder can be conferred by mutations in various components of or regulatory factors in the complement cascade system (Jozsi et al., 2008). See AHUS2 (612922), AHUS3 (612923), AHUS4 (612924), AHUS5 (612925), and AHUS6 (612926). AHUS7 (see 615008) is caused by mutation in the DGKE gene (601440), which is not part of the complement cascade system. Clinical Features Hagge et al. (1967) reported the hemolytic uremic syndrome in 2 sibs. Features included intravascular hemolysis, thrombocytopenia, and azotemia. One had repeated attacks ending in renal failure and death at age 8 years; the other recovered completely after one attack. Chan et al. (1969) reported HUS in 2 adopted, unrelated sibs. Kaplan et al. (1975) reported HUS in 3 sibs and reviewed reports of 21 sibships with 2 or more affected individuals. Two groups of families could be identified among 41 analyzed. Sibs whose onset was within a short time of each other had a relatively good prognosis (19% mortality). Those whose onset was more than a year apart had a poorer prognosis (68% mortality). Kaplan et al. (1975) suggested that an environmental agent was causative in the first group and that genetic factors were important in the second. Most of the first group of families came from an endemic area, whereas most of the second group came from a nonendemic area. Blattler et al. (1975) studied a family in which 4 sibs had died from HUS. The parents and 4 surviving sibs had normal renal function and normal platelet and fibrinogen survival. The mother and 3 sibs had an increased percentage of megathrombocytes. Two of them showed renal accumulation of Cr 51-platelet radioactivity and ultrastructural changes of the endothelium on renal biopsy. Edelsten and Tuck (1978) reported a family with HUS inherited in an autosomal dominant pattern. Thompson and Winterborn (1981) reported an 8-month-old Asian boy with very low levels of plasma factor H who presented with the hemolytic uremic syndrome. Complement component C3 (120700) was also depleted. A healthy 3-year-old brother had the same complement profile, suggesting activation of the alternative complement pathway. The parents, who were first cousins, had half-normal levels of factor H. Kirchner et al. (1982) described this disorder in mother and daughter. The daughter's illness, characterized primarily by renal insufficiency, was most compatible with adult hemolytic uremic syndrome and the mother's illness, with prominent neurologic findings, was most compatible with thrombotic thrombocytopenic purpura. Merrill et al. (1985) reported 2 certain cases and 3 possible case in 2 generations of a North Carolina black family. Neuhaus et al. (1997) reported clinical features of atypical D-HUS in 23 children. Features included requirement for dialysis (74%), hypertension (43%), cardiomyopathy (43%), and cerebral convulsions (48%). Only 5 patients (26%), including 4 infants, recovered completely. Six patients (32%) had 1 to 10 recurrences and 8 (42%) developed end-stage renal failure. Four children died. Warwicker et al. (1998) reported a 36-year-old man with sporadic relapsing aHUS. He had anemia, thrombocytopenia, hypertension, and acute renal failure. Renal biopsy showed a thrombotic microangiopathy and deposition of complement component C3 in vessel walls. He had half-normal serum levels of factor H and decreased levels of C3, consistent with activation of the alternative complement pathway. HUS recurred after renal transplantation. Molecular analysis revealed a heterozygous 4-bp deletion in the CFH gene (134370.0011). Ohali et al. (1998) reported a large consanguineous Bedouin family in which 10 infants had atypical HUS characterized by microangiopathic hemolytic anemia, acute renal failure, severe hypertension, edema, and increased serum triglycerides. All had very early onset with a median presentation at age 2 weeks. Two patients died during the first disease episode; the remaining 8 patients had a mean number of 4 relapses despite treatment. In total, 8 patients died at ages 3 weeks to 10 months. Factor H levels were low to undetectable in all 4 patients studied, and C3 levels were decreased in 9 of 10 infants tested. Four kidney biopsies showed marked arteriolar changes, including stenosis, edema, and thickening of the intima. Glomerular changes included swelling of endothelial cells with microvillus transformation and proliferation of mesangial cells with increased matrix deposition in the mesangium. Other changes included fibrotic changes in glomeruli and the tubulointerstitium, as well as C3 deposition in capillary walls. Rougier et al. (1998) reported 6 children with complement factor H deficiency and acute glomerular disease. Five of the 6 children presented with hemolytic uremic syndrome. Two of the children were from a consanguineous family from Turkey and exhibited a homozygous deficiency characterized by absence of the 150-kD form of factor H. Noris et al. (2003) reported a 21-year-old woman and her affected brother. Disease onset in the sister (the proband) was at age 16 months, when she developed fever, hemolytic anemia, and thrombocytopenia. At the time, renal function was normal. Thereafter she had 6 recurrences of thrombotic microangiopathy, all associated with deteriorating renal function. Treatment consisted of plasma exchange and infusions, steroids, and blood transfusions, which led to complete recovery of blood abnormalities and renal function. The last episode occurred at age 20 years and was characterized by anemia, thrombocytopenia, and severe impairment of renal function. Renal biopsy showed irreversible changes of chronic nephropathy with typical features of HUS, including diffuse narrowing/occlusion of vessels and severe glomerular ischemia. At the age of 21 years she was on chronic dialysis. The proband's brother had 2 episodes of HUS at age 9 years. Both were characterized by severe hemolytic anemia and acute renal insufficiency and resolved without plasma treatment, with no renal sequelae. Clinical Management Hazani et al. (1996) reported relapsing thrombotic microangiopathy in a 12-year-old girl and her 7-year-old brother. During 11 years of follow-up, the girl responded only to steroids; many other therapeutic modalities were ineffective. Following treatment with low-dose danazol, relapses became fewer and less severe, completely subsiding after 6 months. The brother's illness began with signs of hemolytic uremic syndrome, with later development of neurologic manifestations. During a 6-year follow-up he responded only to plasma exchange. Although chronic thrombocytopenia persisted during the last 3 years, the boy's clinical condition improved. Landau et al. (2001) described 2 patients with atypical HUS associated with factor H deficiency. One patient who underwent renal transplantation for end-stage renal disease later had an extensive nonhemorrhagic cerebral infarction on 2 occasions and died in spite of multiple plasma transfusions. A second patient, a 14-month-old boy, experienced numerous HUS episodes starting at the age of 2 weeks. Daily plasma transfusions during relapses brought about only a temporary state of remission. However, prophylactic twice-weekly plasma therapy had been successful in preventing relapses and preserving renal function. Landau et al. (2001) reported that with this regimen, serum factor H was increased from 6 mg/dL to subnormal values of 12 to 25 mg/dL (normal, greater than 60 mg/dL). Landau et al. (2001) concluded that aHUS recurs because factor H deficiency is not corrected by renal transplantation. A hypertransfusion protocol may be useful. Inheritance Concordant monozygotic twins have been reported (Campbell and Carre, 1965). Farr et al. (1975) described a family with several affected members, including a father and his son and daughter. A common symptom was hypertension. They reviewed reports of familial occurrence. Perret et al. (1979) described this disorder in 5 members of 3 generations of a kindred and suggested genetic predisposition with a dominant gene. In the study by Furlan et al. (1998), there were multiple patients with the familial form of HUS: patients 44 and 45 were sister and brother and had 8 sibs who had died of acute HUS; patient 46 (a male) had 3 brothers who had died of HUS; from 2 other unrelated families, patients 47 and 48 were sisters and patients 49 and 50 were brothers; 1 brother and 1 sister of patient 51 had died of HUS; patients 52 and 53 were brother and sister. Goodship et al. (1997) stated that most familial cases are recessive but dominant pedigrees had also been reported. In a review of thrombotic microangiopathies, Moake (2002) stated that 5 to 10% of cases of HUS are familial. The mortality rate (54%) is much higher in the familial form than in typical childhood HUS (3 to 5%). About half of the survivors have relapses and over one-third require long-term dialysis. Among patients with familial HUS who receive kidney allografts, 16% lose function in the engrafted kidney within 1 month. Pathogenesis ### Atypical Hemolytic Uremic Syndrome Low levels of factor H in patients with aHUS were reported by Roodhooft et al. (1990), Pichette et al. (1994), and others. Some patients, however, may have normal levels of factor H, suggesting a dysfunction of the protein (Warwicker et al., 1998). Reduced serum C3 levels have been reported in sporadic (Stuhlinger et al., 1974; Robson et al., 1992) and familial HUS (Zachwieja et al., 1992). In Italy, Noris et al. (1999) studied 6 families with HUS, 1 family with TTP, and 2 families with both disorders. Included in the study were 15 patients and 63 available healthy relatives as well as 25 age- and gender-matched healthy controls and 56 of their available relatives. Consanguinity was observed in 2 families. Seventy-three percent of the cases versus 16% of controls (P less than 0.001) as well as 24% of case-relatives versus 5% of control-relatives (P = 0.005) had decreased C3 levels, which were more marked in the actual cases. Factor H abnormalities were found in 4 of the 15 cases as compared with 3 of the 63 case-relatives and none of 17 healthy controls. All cases with factor H abnormalities had low C3 serum concentrations. Noris et al. (1999) concluded that reduced C3 in familial HUS is likely related to a genetically determined deficiency of factor H. Remuzzi et al. (2002) concluded that ADAMTS13 activity does not distinguish TTP from HUS, at least in the recurrent and familial forms, and that it is not the only determinant of VWF (613160) abnormalities in these conditions. In 41 children with D+HUS and 23 children with D-HUS, Veyradier et al. (2003) found that von Willebrand factor-cleaving protease activity was normal in over 50% of patients, but was undetectable in 1 D+HUS and 6 D-HUS children. After a 3-month remission, the D+HUS patient recovered 100% VWFCP activity, whereas the 6 D-HUS patients kept an undetectable level. In these 6 D-HUS patients, the disease was characterized by a neonatal onset and several relapses of hemolytic anemia, thrombocytopenia, acute renal failure, and cerebral ischemia. Arterial hypertension and end-stage renal failure sometimes occurred. Veyradier et al. (2003) concluded that a subgroup of patients with D-HUS is related to VWFCP and may actually correspond to TTP. Using in vitro expression studies, Manuelian et al. (2003) demonstrated that pathogenic mutations in the CFH gene (134370.0001; 134370.0017-134370.0018) resulted in mutant proteins with decreased binding to heparin, C3b/C3d, and human endothelial cells. The findings suggested that reduced interaction with the surface of endothelial cells is central to the pathophysiology of aHUS and that normal factor H has a protective role during tissue injury. Stahl et al. (2008) demonstrated that aHUS-associated mutant factor H (see, e.g., 134370.0022) exhibited decreased binding to normal platelets compared to wildtype factor H. Addition of patient serum containing mutant factor H to control platelets resulted in complement activation, deposition of C3 and C9, release of platelet-derived microparticles, and platelet aggregation, indicating platelet activation. Similar findings were obtained with other aHUS-associated CFH mutations. Preincubation of normal platelets with factor H reduced these effects. The findings indicated that mutant CFH results in complement activation on the surface of platelets and platelet activation, which may contribute to thrombocytopenia. ### Autoantibodies in aHUS Dragon-Durey et al. (2005) identified serum anti-CFH IgG autoantibodies in 3 (6%) of 48 children with recurrent aHUS. Plasma CFH activity was decreased, whereas plasma CFH antigen levels were normal and CFH gene analysis was normal, indicating an acquired functional CFH deficiency. The findings indicated that aHUS may occur in the context of an autoimmune disease, and suggested that plasma exchange or immunosuppression may be a beneficial treatment. Of 147 patients with aHUS, 121 of whom had previously been reported by Zipfel et al. (2007), Jozsi et al. (2008) identified serum anti-CFH autoantibodies in 16 (11%); 14 lacked CFHR1/CFHR3 completely and 2 showed extremely low CFHR1/CFHR3 plasma levels. These observations suggested that CFHR1/CFHR3 deficiency represents a risk factor for CFH autoantibody formation. Unaffected family members with decreased CFHR1/CFHR3 did not have CFH autoantibodies. The binding epitopes of all autoantibodies were localized to the C-terminal recognition region of factor H, which represents a hotspot for aHUS mutations. The authors thus defined a subgroup of aHUS, which they termed DEAP HUS (deficiency of CFHR proteins and CFH autoantibody positive), that is characterized by a combination of genetic and acquired factors. The findings illustrated a new combination of 2 susceptibility factors for the development of aHUS. Dragon-Durey et al. (2009) found a deletion of 1 or both CFHR1/CFHR3 alleles in 22.7% of 144 French aHUS patients and only 8.2% of 70 healthy controls. The highest deletion frequency was in the subgroup of aHUS patients with anti-factor H autoantibodies (92.9% had 1 or 2 deleted alleles) and in the group of patients with a CFI mutation (31.8% had 1 or 2 deleted alleles). Deletion of CFHR1/CFHR3 was not significantly more frequent in those patients in whom anti-CFH antibodies or CFI mutation were excluded. The findings indicated that genomic deletion of CFHR1/CFHR3 plays a role in the development of anti-CFH autoantibodies, but likely has only a secondary role in susceptibility to aHUS. ### Typical Hemolytic Uremic Syndrome Kaplan and Drummond (1978) noted that typical HUS is triggered by specific infection. Typical HUS follows a prodrome of acute afebrile gastroenteritis, often with bloody stools. HUS and a hitherto poorly recognized condition, haemorrhagic colitis, which is clinically and pathologically similar to the prodromal bloody diarrheal phase of classic HUS, are related in a causal way to verocytotoxin-producing Escherichia coli (VTEC) infection (Karmali et al., 1985). Verocytotoxin refers to the capacity of this family of potent protein exotoxins to produce an irreversible cytopathic effect in certain cultured cell lines, especially Vero and HeLa. The toxin is also lethal to laboratory animals, especially rabbits, in minute doses. E. coli O157:H7, the most frequently isolated serotype of verotoxin-producing E. coli in the United States, is capable of causing a broad spectrum of illness, including nonbloody diarrhea, bloody diarrhea, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura (Griffin et al., 1988). Proulx et al. (2002) compared the circulating concentrations of granulocyte colony-stimulating factor (GCSF; 138970) and several chemokines in the course of E. coli O157:H7 enteritis, hemorrhagic colitis (HC), and HUS. They found that GROA (155730), CCL4 (182284), and MCP1 (158105) are produced whether or not HC or HUS develops. They also found that children with O157:H7-associated HUS may present abnormally increased circulating levels of GCSF and decreased levels of ENA78 (CXCL5; 600324). The authors concluded that leukocytes may be involved in the pathogenesis of HUS. Mapping Goodship et al. (1997) undertook a candidate gene linkage study in 2 families with autosomal dominant HUS and in 1 family with a pedigree compatible with recessive inheritance or dominant inheritance with partial penetrance. The disease segregated with the region of 1q containing the candidate HF1 gene (CFH; 134370); maximum lod = 3.94. Warwicker et al. (1998) demonstrated that familial HUS segregated with the chromosome 1q region, bounded by the markers D1S212 and D1S306, containing the factor H gene. Molecular Genetics In affected members of a large family with autosomal dominant aHUS originally reported by Edelsten and Tuck (1978), Goodship et al. (1997) and Warwicker et al. (1998) identified a heterozygous mutation in the CFH gene (134370.0001). Although none of the patients had decreased levels of plasma factor H, Warwicker et al. (1998) postulated that the mutation disrupted the structure and function of the protein. In an adult with sporadic HUS, Warwicker et al. (1998) identified a heterozygous 4-bp deletion in the HF1 gene (134370.0011). In affected members of a Bedouin kindred with atypical HUS and factor H deficiency originally reported by Ohali et al. (1998), Ying et al. (1999) identified a homozygous mutation in the CFH gene (134370.0004). In this same family, Buddles et al. (2000) identified a different homozygous pathogenic mutation in the CFH gene (134370.0005). In 2 children from Turkey with relapsing HUS originally reported by Rougier et al. (1998), Dragon-Durey et al. (2004) identified a homozygous mutation in the CFH gene (134370.0012). Dragon-Durey et al. (2004) also identified heterozygous mutations in the CFH gene in 2 additional patients with atypical HUS reported by Rougier et al. (1998). Caprioli et al. (2003) analyzed the complete HF1 gene in 101 patients with HUS, 32 patients with TTP, and 106 controls in order to evaluate the frequency of HF1 mutations, the clinical outcome in mutation and nonmutation carriers, and the role of HF1 polymorphisms in the predisposition to HUS. They found 17 different HF1 mutations (16 heterozygous and 1 homozygous) in 33 HUS patients; 13 mutations were located in exons 22 and 23. No TTP patient carried HF1 mutations. HUS manifested earlier and the mortality rate was higher in mutation carriers than in noncarriers. Kidney transplants invariably failed for disease recurrences in patients with HF1 mutations, while in patients without HF1 mutations half of the grafts were functioning after 1 year. Three HF1 polymorphisms were strongly associated with aHUS: a -257T promoter allele, a 2089G allele in exon 14, and a 2881T allele in exon 19, resulting in an glu963-to-asp substitution. Two or 3 disease-associated variants led to a higher risk of HUS than 1 alone. Analysis of available relatives of mutation patients revealed a penetrance of 50%. In 5 of 9 families the proband inherited the mutation from 1 parent and 2 disease-associated variants from the other, while unaffected carriers inherited the protective variants. Caprioli et al. (2006) identified mutations in the CFH gene in 47 (30%) of 156 patients with aHUS. Most were heterozygous, but some families had homozygous mutations. Most of the mutations were spread over the 5 exons that encode the most C-terminal part of CFH, often clustering in SCR20, which is involved in binding to surface-bound C3b. In a comparison of 14 aHUS patients with MCP mutations and 42 with CFH mutations, Caprioli et al. (2006) found that patients with MCP mutations had an overall better prognosis. Complete remission was observed in 85.7% of patients with MCP mutations compared to 17.5% of patients with CFH mutations. Only 1 patient with an MCP mutation developed end-stage renal failure and none died during the acute episode, whereas end-stage renal failure and death occurred in 22% and 30%, respectively, of patients with CFH mutations. Most (85%) of the patients with MCP mutations retained normal renal function compared to 22.5% of patients with CFH mutations. ### Modifier Genes Zipfel et al. (2007) found that an 84-kb deletion of the CFHR1 (134371.0001) and CFHR3 (605336.0001) genes was associated with an increased risk of atypical hemolytic-uremic syndrome in 2 independent European cohorts. In the first group, 19 (16%) of 121 aHUS patients had the deletion compared to 2 of 100 control individuals. Three of the patients had a homozygous deletion. All patients had normal serum factor H levels. In the second group comprising 66 patients, 28% had the deletion compared to 6% of controls. Ten percent and 2% of patients and controls, respectively, were homozygous for the deletion. In vitro functional expression studies showed that CFHR1/CFHR3-deficient plasma had decreased protective activity against erythrocyte lysis, suggesting a defective regulation of complement activation. Of 147 patients with aHUS, 121 of whom had previously been reported by Zipfel et al. (2007), Jozsi et al. (2008) identified serum anti-CFH autoantibodies in 16 (11%); 14 lacked CFHR1/CFHR3 completely and 2 showed extremely low CFHR1/CFHR3 plasma levels. The findings illustrated a new combination of 2 susceptibility factors for the development of aHUS. Blom et al. (2008) identified an arg240-to-his (R240H) SNP in the C4BPA gene (120830) that was associated with aHUS. The heterozygous change was found in 6 of 166 patients with aHUS and in 5 of 542 healthy controls. Three of the 6 patients with this SNP carried mutations in other known aHUS susceptibility genes, including MCP and CFH. The findings were replicated in another sample. Functional expression studies showed that the C4BPA variant had impaired ability to bind C3b and to act as a cofactor in its degradation. The findings supported the hypothesis that dysregulation of the alternative complement pathway can lead to aHUS. ### Associations Pending Confirmation For discussion of a possible relationship between variation in the CFHR5 gene and atypical hemolytic uremic syndrome, see 608593.0003-608593.0005. Population Genetics ### Typical Hemolytic Uremic Syndrome Gianantonio et al. (1968) observed 75 cases of HUS in Argentina, where the disorder seems unusually frequent, and assembled some evidence for viral etiology. Endemic areas included Argentina, South Africa, the west coast of the United States, and the Netherlands. Tarr et al. (1989) reported an increase in the incidence of HUS in King County, Washington, during the previous 15 years. In Minnesota, Martin et al. (1990) reported an increase in mean annual incidence from 0.5 case per 100,000 child-years among children less than 18 in 1979 to 2.0 cases per 100,000 in 1988 (P = 0.000004). Of 28 patients, 13 (46%) showed E. coli O157:H7 in stool specimens. Patients were more likely than controls to attend large day-care centers, suggesting that such attendance is a risk factor for HUS. On the basis of the population-attributable risk, however, this factor could account for no more than 16% of the cases. History Remuzzi et al. (1979) suggested that deficiency of a vascular prostacyclin stimulator may underlie the disorder. Plasma from a 54-year-old woman with HUS had a low capacity to stimulate PGI2 production by rat aortic rings. Plasma treatment restored this activity. PGI2-stimulating activity was normal in 2 daughters of the proband but consistently low (20-50% of control) in both of her sons, neither of whom had a history or clinical signs of a microangiopathic disorder. INHERITANCE \- Autosomal recessive \- Autosomal dominant CARDIOVASCULAR Vascular \- Hypertension (especially in atypical hemolytic-uremic syndrome (aHUS)) ABDOMEN Gastrointestinal \- Prodrome of gastroenteric diarrhea, usually caused by E. coli 0157-H7 or shigella in young children (typical HUS) GENITOURINARY Kidneys \- Acute renal failure \- Anuria NEUROLOGIC Central Nervous System \- Global and focal neurologic abnormalities (less than 30%) \- Seizures \- Coma \- Hemiparesis \- Cognitive defects \- Visual defects \- Dysphasia METABOLIC FEATURES \- Fever HEMATOLOGY \- Microangiopathic hemolytic anemia \- Thrombocytopenia \- Thrombotic microangiopathy \- Reticulocytosis \- Schistocytes \- 'Burr cells' IMMUNOLOGY \- Complement component consumption \- Defective complement regulation \- Activation of the complement system \- Some patients may have autoantibodies to factor H, resulting in functional factor H deficiency LABORATORY ABNORMALITIES \- Decreased hemoglobin \- Increased blood urea nitrogen (BUN) \- Increased creatinine \- Decreased serum factor H (atypical HUS) \- Decreased serum factor I (atypical HUS) \- Decreased serum C3 (atypical HUS) \- Decreased serum factor B (atypical HUS) \- Hyperlipidemia \- Normal activity of von Willebrand factor-cleaving protease MISCELLANEOUS \- Diarrhea-associated (D+HUS), occurs in children younger than 3 years, associated with verotoxin-producing E. coli (90% of patients) (typical HUS) \- D+HUS (typical HUS) is usually sporadic, limited to 1 event, and has a good prognosis \- Diarrhea-negative subtype (D-HUS), or atypical HUS, is more severe and often relapses \- D-HUS is usually familial \- Phenotypic overlap with thrombotic thrombocytopenic purpura (TTP, 274150 ) \- May be triggered by medications, including antineoplastic agents, immunotherapeutic agents, and antiplatelet agents MOLECULAR BASIS \- Susceptibility conferred by mutation in the complement factor H gene (CHF, 134370.0001 ) \- Susceptibility conferred by deletion that includes the complement factor H-related 1 gene (CFHR1, 134371.0001 ) and complement factor H-related 3 gene (CFHR3, 605366.0001 ) ▲ 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	HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 1	c2931788	5,828	omim	https://www.omim.org/entry/235400	2019-09-22T16:27:10	{"mesh": ["D065766"], "omim": ["235400"], "icd-10": ["D59.3"], "orphanet": ["90038", "93581", "2134", "544472"], "synonyms": ["Atypical HUS with anti-factor H antibodies", "Stx-HUS", "Shiga-like toxin-associated HUS", "Alternative titles", "Hemolytic-uremic syndrome without diarrhea with anti-factor H antibodies", "AHUS, SUSCEPTIBILITY TO, 1", "D+HUS", "Typical HUS", "Hemolytic-uremic syndrome with diarrhea", "D-HUS with anti-factor H antibodies", "aHUS with anti-factor H antibodies"], "genereviews": ["NBK1367"]}
High bone mass osteogenesis imperfecta is a rare, genetic, primary bone dysplasia disorder characterized by increased bone fragility, manifesting with mutiple, childhood-onset, vertebral and peripheral fractures, associated with increased bone mass density on radiometric examination. Patients typically present normal or mild short stature and dentinogenesis, hearing, and sclerae are commonly normal. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	High bone mass osteogenesis imperfecta	None	5,829	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314029	2021-01-23T17:40:40	{"icd-10": ["Q78.0"], "synonyms": ["High bone mass OI"]}
Plasminogen activator inhibitor type 1 (PAI1) deficiency is a rare bleeding disorder that causes excessive or prolonged bleeding due to blood clots being broken down too early. PAI1 is a protein in the body needed for normal blood clotting. When the body does not have enough functional PAI1, the body's ability keep blood clots intact is impaired. Some people with PAI1 deficiency have some functional PAI1 (partial PAI1 deficiency), while others do not have any (complete PAI1 deficiency). Therefore, the severity of symptoms depends on how much functional PAI1 a person has. People with complete PAI1 deficiency may have symptoms in infancy, while those with partial PAI1 deficiency may not have symptoms until later in life, after an injury or surgery. Symptoms of PAI1 deficiency include excessive or prolonged bleeding after an injury, or after a medical or dental procedure. The bleeding may be delayed if clots initially form but are broken down too early. Internal bleeding after an injury can be life-threatening, particularly if it occurs around the brain. Other symptoms may include delayed wound healing, nosebleeds that last a long time, easy bruising, bleeding in the joints, and excessive bleeding in females during menstruation, pregnancy or childbirth. Some people with PAI1 deficiency may have scar tissue in the heart (cardiac fibrosis). PAI1 deficiency is caused by mutations in the SERPINE1 gene and inheritance typically is autosomal recessive. The specific mutations present determine whether a person has complete or partial PAI1 deficiency. In rare cases partial PAI1 deficiency has appeared to be autosomal dominant, but the genetic causes in these cases were not determined. In general, people with one SERPINE1 mutation (carriers) will not develop significant symptoms, if any. A diagnosis of PAI1 deficiency may be made based on evaluation of symptoms, various blood tests, and genetic testing of the SERPINE1 gene. Treatment for severe bleeding episodes may include intravenous antifibrinolytics (drugs that help the blood clot) and infusion of fresh frozen plasma. Antifibrinolytics may also be used for heavy menstrual bleeding or to prevent bleeding during an invasive procedure or childbirth. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Plasminogen activator inhibitor type 1 deficiency	c2750067	5,830	gard	https://rarediseases.info.nih.gov/diseases/4381/plasminogen-activator-inhibitor-type-1-deficiency	2021-01-18T17:58:17	{"mesh": ["C567640"], "omim": ["613329"], "orphanet": ["465"], "synonyms": ["Plasminogen activator inhibitor 1 deficiency", "PAI-1 deficiency", "Hyperfibrinolysis due to PAI1 deficiency", "PAI1 deficiency"]}
Subungual exostosis Other namesDupuytren subungual exostosis[1] Subungual exostosis (1/3), in a boy of 15 years old SpecialtyOrthopedic Subungual exostoses are bony projections which arise from the dorsal surface of the distal phalanx, most commonly of the hallux (the big toe).[2] ## Contents * 1 Presentation * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Presentation[edit] They tend to be painful due to the pressure applied to the nail bed and plate. They can involve destruction of the nail bed.[3] These lesions are not true osteochondromas, rather it is a reactive cartilage metaplasia. The reason it occurs on the dorsal aspect is because the periosteum is loose dorsally but very tightly adherent volarly.[4]Subungal malignant melanomas can also occur in canines. They are distinct from subungual osteochondroma.[5] ## Diagnosis[edit] This section is empty. You can help by adding to it. (September 2017) ## Treatment[edit] Surgical excision is common and is a very effective mode of treatment.[citation needed] * Subungual exostosis (2/3) * Subungual exostosis (3/3), after excision ## See also[edit] * Sternal cleft * List of cutaneous conditions ## References[edit] 1. ^ "Dupuytren subungual exostosis \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 11 October 2017. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 3. ^ Suga H, Mukouda M (2005). "Subungual exostosis: a review of 16 cases focusing on postoperative deformity of the nail". Annals of Plastic Surgery. 55 (3): 272–5. doi:10.1097/01.sap.0000174356.70048.b8. PMID 16106166. 4. ^ Murphey MD, Choi JJ, Kransdorf MJ, et al: Imaging of osteochondroma: variants and complications with radiologic-pathologic correlation. Radiographics 20:1407-1434, 2000 5. ^ Lee SK, Jung MS, Lee YH, Gong HS, Kim JK, Baek GH (2007). "Two distinctive subungual pathologies: subungual exostosis and subungual osteochondroma". Foot & Ankle International. 28 (5): 595–601. doi:10.3113/FAI.2007.0595. PMID 17559767. ## External links[edit] Classification D * OMIM: 603656 * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline 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	Subungual exostosis	c0038604	5,831	wikipedia	https://en.wikipedia.org/wiki/Subungual_exostosis	2021-01-18T18:46:22	{"gard": ["8280"], "mesh": ["C535723"], "umls": ["C0038604"], "wikidata": ["Q7632311"]}
Miller-Dieker Syndrome (MDS) is a contiguous gene deletion syndrome of chromosome 17p13.3, characterised by classical lissencephaly (lissencephaly type 1) and distinct facial features. Additional congenital malformations can be part of the condition. ## Epidemiology MDS is undoubtedly a rare condition with a reported estimate of 1 cases per 100 000 live births, although incidence and prevalence are probably higher. ## Clinical description Children with MDS present with severe developmental delay, usually have epilepsy, and feeding problems are common. The lissencephaly represents the severe end of the spectrum with generalized agyria, or agyria and some frontal pachygyria. ## Etiology Visible and submicroscopic deletions of 17p13.3, including the LIS1 gene, are found in almost 100% of patients. ## Management and treatment Management of children with MDS is symptomatic. To avoid the complications of feeding and swallowing problems (poor nutritional state, aspiration pneumonia), nasogastric tubes and gastrostomies (a more long-term solution) can be utilised. Seizure control is important. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Miller-Dieker syndrome	c0265219	5,832	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=531	2021-01-23T17:46:40	{"gard": ["3669"], "mesh": ["D054221"], "omim": ["247200"], "umls": ["C0265219"], "icd-10": ["Q04.3"], "synonyms": ["Lissencephaly due to 17p13.3 deletion", "Monosomy 17p13.3", "Telomeric deletion 17p"]}
Jalili syndrome is characterized by the association of amelogenesis imperfecta (AI; see this term) and cone-rod retinal dystrophy (CORD; see this term). ## Epidemiology It has been described in only one family with 29 affected individuals. ## Clinical description AI is a generic term for an inherited group of dental diseases in which the common clinical feature is an abnormality of tooth enamel. The enamel may be thin but normal, and/or hypomineralized. CORD is a rare retinal disorder that leads to an initial loss of central vision, color vision and photophobia before the age of 10 years with subsequent night blindness and visual field restriction. ## Etiology Mutations in the CNNM4 gene (2q11.2), which is implicated in metal ion transport, have been identified in several families. ## Genetic counseling Jalili syndrome is transmitted in an autosomal recessive manner. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Jalili syndrome	c2931074	5,833	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1873	2021-01-23T18:34:13	{"gard": ["1463"], "mesh": ["C535976"], "omim": ["217080"], "umls": ["C2931074", "C3495589"], "icd-10": ["H35.5"], "synonyms": ["Cone rod dystrophy-amelogenesis imperfecta syndrome"]}
Ganglioglioma is a rare, usually benign, well-circumscribed, often cystic, mixed neuronal-glial tumor (composed of both neoplastic glial and ganglionic elements) which is typically located in the temporal lobe and rarely invades the surrounding tissue. Patients usually present with seizures refractory to medical treatment. Association with neurofibromatosis type I and tuberous sclerosis has 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	Ganglioglioma	c0206716	5,834	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251949	2021-01-23T19:04:02	{"gard": ["2430"], "mesh": ["D018303"], "umls": ["C0206716"]}
## Description Cloverleaf skull, or Kleeblattschaedel, consists of a trilobular skull with craniosynostosis. The condition shows pathogenetic variability and etiologic heterogeneity. The cause of isolated cloverleaf skull is unknown (Cohen, 2009). Cohen (1975) pointed out that Kleeblattschaedel is a component of many syndromes, e.g., it is found in some cases of Crouzon syndrome (123500), Pfeiffer syndrome (101600), and Carpenter syndrome (201000). Cohen (2009) listed 12 monogenic disorders with cloverleaf skull as a feature, including type II thanatophoric dysplasia (187601), which accounts for 40% of all cloverleaf skull syndromes. Cohen (2009) published photographs of cloverleaf skull in various syndromes. History Kleeblattschaedel was first identified as an entity by Holtermuller and Wiedemann (1960). Aksu and Mietens (1979) reviewed 96 published cases. Limbs \- Elbow ankylosis Neuro \- Hydrocephalus Eyes \- Exophthalmos \- Corneal ulcerations Skull \- Trilobular skull \- Premature coronal and lambdoidal suture closure \- Craniosynostosis Inheritance \- Autosomal dominant \- all cases have been sporadic ▲ 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	KLEEBLATTSCHAEDEL	c1860050	5,835	omim	https://www.omim.org/entry/148800	2019-09-22T16:39:18	{"omim": ["148800"], "orphanet": ["2343"], "synonyms": ["Alternative titles", "KLEEBLATTSCHADEL", "CLOVERLEAF SKULL"]}
## Clinical Features Kozlowski et al. (1973) and Danks et al. (1974) reported 3 patients with precocious osteodysplasty, of whom 2 were sibs of Albanian extraction. All 3 died at less than 1 year of age. They suffered from a generalized disturbance of modeling of the long and tubular bones and pelvis with severe hypoplasia of the bones of the fingers and toes. Growth failure, striking susceptibility to respiratory infection, and fatal outcome suggested a widespread dysfunction. The authors noted that the disorder bore some clinical similarity to osteodysplasty of Melnick and Needles (309350), but with more severe skeletal changes and early death. Albrecht et al. (2002) reported 2 sibs, born of nonconsanguineous parents, with a precocious type of osteodysplasia. The proposita had severe shortness of all extremities, especially the fingers and toes, and a narrow thoracic cage. Radiologic examination revealed shortness of all long bones., with lack of diaphyseal constriction. The vertebral bodies were flat, with a ventral tongue. The ribs were thin and had irregular borders. There was poor ossification of the skull, hands, and feet. She required oxygen throughout her life. She had a flat face with depressed nasal bridge, a short, upturned nose, and a small chin with a longitudinal crease. She died of pneumonia at age 5 months. The second pregnancy was terminated at 23 weeks' gestation after ultrasound showed similar shortness of extremities. Inheritance The transmission pattern of precocious osteodysplasia in the families reported by Danks et al. (1974) and Albrecht et al. (2002) was consistent with autosomal recessive inheritance. Skel \- Abnormal long bone and tubular bone modeling \- Abnormal pelvis \- Hypoplastic finger and toe bones Growth \- Growth failure Misc \- Respiratory infection susceptibility 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	OSTEODYSPLASTY, PRECOCIOUS, OF DANKS, MAYNE, AND KOZLOWSKI	c1850185	5,836	omim	https://www.omim.org/entry/259270	2019-09-22T16:23:53	{"mesh": ["C564922"], "omim": ["259270"]}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Biotin deficiency" – news · newspapers · books · scholar · JSTOR (November 2013) This article possibly contains original research. Please improve it by verifying the claims made and adding inline citations. Statements consisting only of original research should be removed. (September 2015) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Biotin deficiency Biotin SpecialtyEndocrinology Biotin deficiency is a nutritional disorder which can become serious, even fatal, if allowed to progress untreated. It can occur in people of any age, ancestry, or gender. Biotin is part of the B vitamin family. Biotin deficiency rarely occurs among healthy people because the daily requirement of biotin is low, many foods provide adequate amounts of it, intestinal bacteria synthesize small amounts of it, and the body effectively scavenges and recycles it in the kidneys during production of urine. However, deficiencies can be caused by consuming raw egg whites over a period of weeks to months. Egg whites contain high levels of avidin, a protein that binds biotin strongly. When cooked, avidin is partially denatured and binding to biotin is reduced. However one study showed that 30-40% of the avidin activity was still present in the white after frying or boiling.[1] Genetic disorders such as biotinidase deficiency, multiple carboxylase deficiency, and holocarboxylase synthetase deficiency can also lead to inborn or late-onset forms of biotin deficiency.[citation needed] In all cases – dietary, genetic, or otherwise – supplementation with biotin is the primary method of treatment.[citation needed] ## Contents * 1 Signs and symptoms * 1.1 Psychological * 2 Causes * 2.1 Potential causes * 3 Biochemistry * 4 Diagnosis * 5 Treatment * 6 Epidemiology * 7 See also * 8 References * 9 Possible references * 10 External links ## Signs and symptoms[edit] * Rashes including red, patchy ones near the mouth (erythematous periorofacial macular rash) * Fine and brittle hair ### Psychological[edit] * Hallucinations[2] * Lethargy[2] * Mild depression, which may progress to profound fatigue and, eventually, to somnolence * Generalized muscular pains (myalgias) * Paresthesias ## Causes[edit] 1. Total parenteral nutrition without biotin supplementation: Several cases of biotin deficiency in patients receiving prolonged total parenteral nutrition (TPN) therapy without added biotin have been reported. Therefore, all patients receiving TPN must also receive biotin at the recommended daily dose, especially if TPN therapy is expected to last more than 1 week. All hospital pharmacies currently include biotin in TPN preparations. 2. Protein deficiency: A shortage of proteins involved in biotin homeostasis can cause biotin deficiency. The main proteins involved in biotin homeostasis are HCS, BTD (biotinidase deficiency) and SMVT 3. Anticonvulsant therapy: Prolonged use of certain drugs (especially highly common prescription anti-seizure medications such as phenytoin, primidone, and carbamazepine), may lead to biotin deficiency; however, valproic acid therapy is less likely to cause this condition.[3] Some anticonvulsants inhibit biotin transport across the intestinal mucosa. Evidence suggests that these anticonvulsants accelerate biotin catabolism, which means that it's necessary for people to take supplemental biotin, in addition to the usual minimum daily requirements, if they're treated with anticonvulsant medication(s) that have been linked to biotin deficiency. 4. Severe malnourishment 5. Prolonged oral antibiotic therapy: Prolonged use of oral antibiotics has been associated with biotin deficiency. Alterations in the intestinal flora caused by the prolonged administration of antibiotics are presumed to be the basis for biotin deficiency. 6. Genetic mutation: Mikati et al. (2006) reported a case of partial biotinidase deficiency (plasma biotinidase level of 1.3 nm/min/mL) in a 7-month-old boy. The boy presented with perinatal distress followed by developmental delay, hypotonia, seizures, and infantile spasms without alopecia or dermatitis. The child's neurologic symptoms abated following biotin supplementation and antiepileptic drug therapy. DNA mutational analysis revealed that the child was homozygous for a novel E64K mutation and that his mother and father were heterozygous for the novel E64K mutation. ### Potential causes[edit] 1. Smoking: Recent studies suggest that smoking can lead to marginal biotin deficiency because it speeds up biotin catabolism (especially in women). 2. Excessive alcohol consumption 3. Excessive consumption of antidiuretics or inadequate levels of antidiuretic hormone 4. Intestinal malabsorption caused by short bowel syndrome 5. Ketogenic diet ## Biochemistry[edit] Biotin is a coenzyme for five carboxylases in the human body (propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, pyruvate carboxylase, and 2 forms of acetyl-CoA carboxylase.) Therefore, biotin is essential for amino acid catabolism, gluconeogenesis, and fatty acid metabolism. Biotin is also necessary for gene stability because it is covalently attached to histones. Biotinylated histones play a role in repression of transposable elements and some genes. Normally, the amount of biotin in the body is regulated by dietary intake, biotin transporters (monocarboxylate transporter 1 and sodium-dependent multivitamin transporter), peptidyl hydrolase biotinidase (BTD), and the protein ligase holocarboxylase synthetase. When any of these regulatory factors are inhibited, biotin deficiency could occur.[4] ## Diagnosis[edit] The most reliable and commonly used methods for determining biotin status in the body are: * excretion of 3-hydroxyisovaleric acid and biotin in urine * activity of propionyl-CoA carboxylase in lymphocytes ## Treatment[edit] In the United States, biotin supplements are readily available without a prescription in amounts ranging from 300 to 10,000 micrograms (30 micrograms is identified as Adequate Intake). ## Epidemiology[edit] Since biotin is present in many foods at low concentrations, deficiency is rare except in locations where malnourishment is very common. Pregnancy, however, alters biotin catabolism and despite a regular biotin intake, half of the pregnant women in the U.S. are marginally biotin deficient. ## See also[edit] * Biotinidase deficiency * Holocarboxylase synthetase deficiency * Multiple carboxylase deficiency ## References[edit] 1. ^ Durance TD (1991). "Residual Avid in Activity in Cooked Egg White Assayed with Improved Sensitivity". Journal of Food Science. 56 (3): 707–709. doi:10.1111/j.1365-2621.1991.tb05361.x. 2. ^ a b Thompson et al. 2003, p. 315. 3. ^ Krause et al. 1982, p. 485. 4. ^ Said, H (2011). "Biotin: biochemical, physiological and clinical aspects". Subcellular Biochemistry. 56: 1–19. doi:10.1007/978-94-007-2199-9_1. ISBN 978-94-007-2198-2. PMID 22116691. Cite journal requires `\|journal=` (help) ## Possible references[edit] * Adhisivam B, Mahto D, Mahadevan S (March 2007). "Biotin responsive limb weakness". Indian Pediatr. 44 (3): 228–30. PMID 17413203. * Baykal T, Gokcay G, Gokdemir Y, Demir F, Seckin Y, Demirkol M, Jensen K, Wolf B (2005). "Asymptomatic adults and older siblings with biotinidase deficiency ascertained by family studies of index cases". J. Inherit. Metab. Dis. 28 (6): 903–12. doi:10.1007/s10545-005-0161-3. PMID 16435182. S2CID 22277450. * Boas MA (1927). "The Effect of Desiccation upon the Nutritive Properties of Egg-white". Biochem. J. 21 (3): 712–724.1. doi:10.1042/bj0210712. PMC 1251968. PMID 16743887. * Dobrowolski SF, Angeletti J, Banas RA, Naylor EW (February 2003). "Real time PCR assays to detect common mutations in the biotinidase gene and application of mutational analysis to newborn screening for biotinidase deficiency". Mol. Genet. Metab. 78 (2): 100–7. doi:10.1016/S1096-7192(02)00231-7. PMID 12618081. * Forbes GM, Forbes A (1997). "Micronutrient status in patients receiving home parenteral nutrition". Nutrition. 13 (11–12): 941–4. doi:10.1016/S0899-9007(97)00334-1. PMID 9433708. * Genc GA, Sivri-Kalkanoğlu HS, Dursun A, Aydin HI, Tokatli A, Sennaroglu L, Belgin E, Wolf B, Coşkun T (February 2007). "Audiologic findings in children with biotinidase deficiency in Turkey". Int. J. Pediatr. Otorhinolaryngol. 71 (2): 333–9. doi:10.1016/j.ijporl.2006.11.001. PMID 17161472. * González EC, Marrero N, Frómeta A, Herrera D, Castells E, Pérez PL (July 2006). "Qualitative colorimetric ultramicroassay for the detection of biotinidase deficiency in newborns". Clin. Chim. Acta. 369 (1): 35–9. doi:10.1016/j.cca.2006.01.009. PMID 16480705. * Hassan YI, Zempleni J (July 2006). "Epigenetic regulation of chromatin structure and gene function by biotin". J. Nutr. 136 (7): 1763–5. doi:10.1093/jn/136.7.1763. PMC 1479604. PMID 16772434. * Higuchi R, Mizukoshi M, Koyama H, Kitano N, Koike M (February 1998). "Intractable diaper dermatitis as an early sign of biotin deficiency". Acta Paediatr. 87 (2): 228–9. doi:10.1080/08035259850157732. PMID 9512215. * László A, Schuler EA, Sallay E, Endreffy E, Somogyi C, Várkonyi A, Havass Z, Jansen KP, Wolf B (2003). "Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies". J. Inherit. Metab. Dis. 26 (7): 693–8. doi:10.1023/B:BOLI.0000005622.89660.59. PMID 14707518. S2CID 12601233. * Mock DM (February 1999). "Biotin status: which are valid indicators and how do we know?". J. Nutr. 129 (2S Suppl): 498S–503S. doi:10.1093/jn/129.2.498S. PMID 10064317. * Mock DM (December 1991). "Skin manifestations of biotin deficiency". Semin Dermatol. 10 (4): 296–302. PMID 1764357. * Möslinger D, Mühl A, Suormala T, Baumgartner R, Stöckler-Ipsiroglu S (December 2003). "Molecular characterisation and neuropsychological outcome of 21 patients with profound biotinidase deficiency detected by newborn screening and family studies". Eur. J. Pediatr. 162 (Suppl 1): S46–9. doi:10.1007/s00431-003-1351-3. PMID 14628140. S2CID 6490712. * Neto EC, Schulte J, Rubim R, Lewis E, DeMari J, Castilhos C, Brites A, Giugliani R, Jensen KP, Wolf B (March 2004). "Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations". Braz. J. Med. Biol. Res. 37 (3): 295–9. doi:10.1590/S0100-879X2004000300001. PMID 15060693. * Schulpis KH, Gavrili S, Tjamouranis J, Karikas GA, Kapiki A, Costalos C (May 2003). "The effect of neonatal jaundice on biotinidase activity". Early Hum. Dev. 72 (1): 15–24. doi:10.1016/S0378-3782(02)00097-X. PMID 12706308. * Thompson, J, Manore M, Sheeshka J (2010). "Nutrients involved in energy metabolism and blood health". In Bennett G, Swieg C, et al. (eds.). Nutrition: A functional Approach. Toronto: Pearson Canada. p. 353. ISBN 9780321740212. * Velázquez A (1997). "Biotin deficiency in protein-energy malnutrition: implications for nutritional homeostasis and individuality". Nutrition. 13 (11–12): 991–2. doi:10.1016/S0899-9007(97)00345-6. PMID 9433719. * Weber P, Scholl S, Baumgartner ER (July 2004). "Outcome in patients with profound biotinidase deficiency: relevance of newborn screening". Dev Med Child Neurol. 46 (7): 481–4. doi:10.1111/j.1469-8749.2004.tb00509.x. PMID 15230462. * Welling DB (August 2007). "Long-term follow-up of hearing loss in biotinidase deficiency". J. Child Neurol. 22 (8): 1055. doi:10.1177/0883073807305789. PMID 17761663. S2CID 39911504. * Wiznitzer M, Bangert BA (July 2003). "Biotinidase deficiency: clinical and MRI findings consistent with myelopathy". Pediatr. Neurol. 29 (1): 56–8. doi:10.1016/S0887-8994(03)00042-0. PMID 13679123. * Wolf B (2001). "Disorders of biotin metabolism". In Scriver CR, Beaudet AL, et al. (eds.). The metabolic & molecular bases of inherited disease. New York: McGraw-Hill. pp. 3935–62. ISBN 978-0-07-913035-8. ## External links[edit] Classification D * ICD-10: E53.8 * ICD-9-CM: 266.2 * MeSH: C531633 C531633, C531633 External resources * eMedicine: ped/238 * GeneReviews/NCBI/NIH/UW entry on Biotinidase deficiency * OMIM entries on Biotinidasa deficiency * v * t * e Malnutrition Protein-energy malnutrition * Kwashiorkor * Marasmus * Catabolysis Vitamin deficiency B vitamins * B1 * Beriberi * Wernicke–Korsakoff syndrome * Wernicke's encephalopathy * Korsakoff's syndrome * B2 * Riboflavin deficiency * B3 * Pellagra * B6 * Pyridoxine deficiency * B7 * Biotin deficiency * B9 * Folate deficiency * B12 * Vitamin B12 deficiency Other * A: Vitamin A deficiency * Bitot's spots * C: Scurvy * D: Vitamin D deficiency * Rickets * Osteomalacia * Harrison's groove * E: Vitamin E deficiency * K: Vitamin K deficiency Mineral deficiency * Sodium * Potassium * Magnesium * Calcium * Iron * Zinc * Manganese * Copper * Iodine * Chromium * Molybdenum * Selenium * Keshan disease Growth * Delayed milestone * Failure to thrive * Short stature * Idiopathic General * Anorexia * Weight loss * Cachexia * Underweight [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Biotin deficiency	c0268680	5,837	wikipedia	https://en.wikipedia.org/wiki/Biotin_deficiency	2021-01-18T18:31:29	{"mesh": ["C531633"], "icd-9": ["266.2"], "icd-10": ["E53.8"], "wikidata": ["Q10264745"]}
A rare epidermal disease characterized by rough, dry skin with prominent, plate-like scaling. It is non-hereditary and usually arises during adulthood in the context of a variety of diseases or conditions, like various types of cancer, autoimmune diseases, endocrine disorders, nutritional deficiencies, but also as a side effect of certain medications. Severity depends on the underlying disease or 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	Acquired ichthyosis	c0263386	5,838	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=454	2021-01-23T18:49:16	{"mesh": ["C538175"], "icd-10": ["L85.0"]}
A rare genetic disorder of lipid metabolism characterized by neonatal to childhood onset of impaired absorption of dietary fat with greasy/oily and voluminous stools, but normal growth and development. Decreased levels of fecal elastase, as well as low serum levels of the fat-soluble vitamins A, D, and E, have been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Pancreatic triacylglycerol lipase deficiency	c0268240	5,839	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309031	2021-01-23T17:59:56	{"omim": ["614338"], "umls": ["C0268240"], "icd-10": ["K90.3"], "synonyms": ["Pancreatic triglyceride lipase deficiency"]}
Hereditary motor and sensory neuropathy Onion bulb formations in a nerve biopsy in a case of HMSN type I SpecialtyNeurology Hereditary motor and sensory neuropathies (HMSN) is a name sometimes given to a group of different neuropathies which are all characterized by their impact upon both afferent and efferent neural communication. HMSN are characterised by atypical neural development and degradation of neural tissue. The two common forms of HMSN are either hypertrophic demyelinated nerves or complete atrophy of neural tissue. Hypertrophic condition causes neural stiffness and a demyelination of nerves in the peripheral nervous system, and atrophy causes the breakdown of axons and neural cell bodies.[1] In these disorders, a patient experiences progressive muscle atrophy and sensory neuropathy of the extremities.[2] The term "hereditary motor and sensory neuropathy" was used mostly historically to denote the more common forms Charcot–Marie–Tooth disease (CMT). With the identification of a wide number of genetically and phenotypically distinct forms of CMT, the term HMSN is now used less frequently. ## Contents * 1 Symptoms * 2 Causes * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 Prognosis * 6 See also * 7 References * 8 Further reading * 9 External links ## Symptoms[edit] Foot showing symptoms of HMSN Neuropathy disorders usually have onset in childhood or young adulthood. Motor symptoms seem to be more predominant than sensory symptoms.[2] Symptoms of these disorders include: fatigue, pain, lack of balance, lack of feeling, lack of reflexes, and lack of sight and hearing, which result from muscle atrophy. Patients can also suffer from high arched feet, hammer toes, foot drop, foot deformities, and scoliosis. These symptoms are a result of severe muscular weakness and atrophy. In patients suffering from demyelinating neuropathy, symptoms are due to slow nerve conduction velocities, however people with axonal degradation have average to normal nerve conduction velocities.[citation needed] ## Causes[edit] All hereditary motor and sensory neuropathies are inherited. Chromosomes 17 and 1 seem to be the most common chromosomes with mutations.[1] The disease can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. ## Diagnosis[edit] Patients with hereditary motor and sensory neuropathies are diagnosed through a physical evaluation that looks for muscle atrophy, weakness, and sensory responses.[3] In addition to this, electromyography and motor nerve conduction tests can help clinicians decide what type of motor and sensory neuropathy it is and how severe the disease is. Final confirmation can come through genetic testing. ### Classification[edit] Charcot–Marie–Tooth disease was first described in 1886 by Jean-Martin Charcot, Pierre Marie, and independently Howard Henry Tooth.[2] In the 1950s, further classification occurred and separated patients into two distinct groups. Group one was characterized by slow nerve conduction velocities and demyelinating neuropathy. Group two was characterized by mostly normal nerve conduction velocities and degeneration of axons. In 1968, HMSN were classified again into seven groups:[1][4] Type Other names Diseases Database OMIM HMSN1 Charcot–Marie–Tooth disease type 1A and 1B 5815 (multiple) Hypertrophic demyelinating type: affected individuals experience weakness and atrophy in the lower legs in adolescence, and later develop weakness in the hands. This is the most common type of CMT. HMSN2 Charcot–Marie–Tooth disease type 2 2343 (multiple) Neuronal type: symptoms similar to type1, onset in adolescence. HMSN3 Dejerine–Sottas disease (Charcot–Marie–Tooth type 3) 5821 145900 Onset in infancy and results in delayed motor skills, much more severe than types 1 & 2\. HMSN4 Refsum disease 11213 266500 Spinal type: Muscle weakness and atrophy as in other types of CMT, but set apart by being autosomal recessive inheritance. HMSN5 Charcot–Marie–Tooth with pyramidal features — 600361 Pyramidal type: onset between ages 5–12. Lower legs are affected first by muscle weakness and atrophy followed by the upper extremities. Type 5 is also associated with visual and hearing loss. HMSN6 Charcot–Marie–Tooth type 6 32095 601152 Early onset muscular weakness and atrophy followed by optic atrophy resulting in vision loss and possibly blindness. HMSN7 HMSN+retinitis pigmentosa 32094 — Later onset with muscular weakness and atrophy mostly in the lower extremities. ## Treatment[edit] There is currently no known pharmacological treatment to hereditary motor and sensory neuropathy. However, the majority of people with these diseases are able to walk and be self-sufficient.[3] Some methods of relief for the disease include physical therapy, stretching, braces, and sometimes orthopedic surgery. Since foot disorders are common with neuropathy, precautions must be taken to strengthen these muscles and use preventative care and physical therapy to prevent injury and deformities. ## Prognosis[edit] Hereditary motor and sensory neuropathy are relatively common and are often inherited with other neuromuscular conditions, and these comorbidities cause an accelerated progression of the disease. Most forms HMSN affects males earlier and more severely than females, but others show no predilection to either sex. HMSN affects all ethnic groups. With the most common forms having no racial predilection, but other recessively inherited forms tend to impact specific ethnic groups. Onset of HMSN in most common in early childhood, with clinical effects occurring before the age of 10, but some symptoms are lifelong and progress slowly. Therefore, these symptoms do not appear until later in life.[1] ## See also[edit] * Hereditary motor and sensory neuropathy with proximal dominance * Charcot–Marie–Tooth disease * Hereditary motor neuropathies * Hereditary sensory and autonomic neuropathies * Spinal muscular atrophies ## References[edit] 1. ^ a b c d Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies at eMedicine 2. ^ a b c Vance, Jeffery M. (1991). "Hereditary motor and sensory neuropathies". Journal of Medical Genetics. 28 (1): 1–5. doi:10.1136/jmg.28.1.1. PMC 1016739. PMID 1999826. 3. ^ a b American Association of Neuromuscular & Electrodiagnostic Medicine. (2013). Hereditary Motor Sensory Neuropathy. http://www.aanem.org/Education/Patient-Resources/Disorders/Hereditary-Motor-Sensory-Neuropathy.aspx Accessed on 11/10/13. 4. ^ Dyck, Peter James; Lambert, Edward H. (1968). "Lower Motor and Primary Sensory Neuron Diseases With Peroneal Muscular Atrophy". Archives of Neurology. 18 (6): 603–18. doi:10.1001/archneur.1968.00470360025002. PMID 4297451. ## Further reading[edit] * Reilly MM (October 2000). "Classification of the hereditary motor and sensory neuropathies". Curr. Opin. Neurol. 13 (5): 561–4. doi:10.1097/00019052-200010000-00009. PMID 11073363. ## External links[edit] Classification D * ICD-10-CM: G60.0 * MeSH: D015417 External resources * eMedicine: neuro/468 * v * t * e Diseases relating to the peripheral nervous system Mononeuropathy Arm median nerve * Carpal tunnel syndrome * Ape hand deformity ulnar nerve * Ulnar nerve entrapment * Froment's sign * Ulnar tunnel syndrome * Ulnar claw radial nerve * Radial neuropathy * Wrist drop * Cheiralgia paresthetica long thoracic nerve * Winged scapula * Backpack palsy Leg lateral cutaneous nerve of thigh * Meralgia paraesthetica tibial nerve * Tarsal tunnel syndrome plantar nerve * Morton's neuroma superior gluteal nerve * Trendelenburg's sign sciatic nerve * Piriformis syndrome Cranial nerves * See Template:Cranial nerve disease Polyneuropathy and Polyradiculoneuropathy HMSN * Charcot–Marie–Tooth disease * Dejerine–Sottas disease * Refsum's disease * Hereditary spastic paraplegia * Hereditary neuropathy with liability to pressure palsy * Familial amyloid neuropathy Autoimmune and demyelinating disease * Guillain–Barré syndrome * Chronic inflammatory demyelinating polyneuropathy Radiculopathy and plexopathy * Brachial plexus injury * Thoracic outlet syndrome * Phantom limb Other * Alcoholic polyneuropathy Other General * Complex regional pain syndrome * Mononeuritis multiplex * Peripheral neuropathy * Neuralgia * Nerve compression syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Hereditary motor and sensory neuropathy	c0027888	5,840	wikipedia	https://en.wikipedia.org/wiki/Hereditary_motor_and_sensory_neuropathy	2021-01-18T18:50:32	{"gard": ["6634"], "mesh": ["D015417"], "umls": ["C0027888"], "wikidata": ["Q15270307"]}
Condition characterized by a loss of height of the nose, because of the collapse of the bridge Saddle nose Sketch of a saddle nose deformity SpecialtyPlastic surgery Saddle nose is a condition associated with nasal trauma, congenital syphilis, relapsing polychondritis, granulomatosis with polyangiitis, cocaine abuse, and leprosy, among other conditions.[1] The most common cause is nasal trauma. It is characterized by a loss of height of the nose, because of the collapse of the bridge. The depressed nasal dorsum may involve bony, cartilaginous or both bony and cartilaginous components of the nasal dorsum. ## Contents * 1 Diagnosis * 2 Treatment * 3 See also * 4 References * 5 External links ## Diagnosis[edit] Mainly a clinical diagnosis, made over time. ## Treatment[edit] Lateral view of the face with a saddle nose deformity far up on the bridge due to granulomatosis with polyangiitis using a nasal prosthesis It can usually be corrected with augmentation rhinoplasty[2] by filling the dorsum of nose with cartilage, bone or synthetic implant. If the depression is only cartilaginous, cartilage is taken from the nasal septum or auricle and laid in single or multiple layers. If deformity involves both cartilage and bone, cancellous bone from iliac crest is the best replacement. Autografts are preferred over allografts. Saddle deformity can also be corrected by synthetic implants of teflon or silicon, but they are likely to be extruded.[citation needed] ## See also[edit] * Saber shin * List of cutaneous conditions ## References[edit] 1. ^ Schreiber, BE; Twigg, S; Marais, J; Keat, AC (April–May 2014). "Saddle-nose deformities in the rheumatology clinic". Ear, Nose, & Throat Journal (Review). 93 (4–5): E45-7. PMID 24817241. 2. ^ Saddle Nose Rhinoplasty at eMedicine ## External links[edit] Classification D * ICD-10: A50.5, M95.0, Q67.4 * ICD-9-CM: 090.5, 754.0 * DiseasesDB: 11755 * v * t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis * v * t * e Diseases of joints General * Arthritis * Monoarthritis * Oligoarthritis * Polyarthritis Symptoms * Joint pain * Joint stiffness Inflammatory Infectious * Septic arthritis * Tuberculosis arthritis Crystal * Chondrocalcinosis * CPPD (Psudogout) * Gout Seronegative * Reactive arthritis * Psoriatic arthritis * Ankylosing spondylitis Other * Juvenile idiopathic arthritis * Rheumatoid arthritis * Felty's syndrome * Palindromic rheumatism * Adult-onset Still's disease Noninflammatory * Hemarthrosis * Osteoarthritis * Heberden's node * Bouchard's nodes * Osteophyte * 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 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	Saddle nose	c0264169	5,841	wikipedia	https://en.wikipedia.org/wiki/Saddle_nose	2021-01-18T18:44:04	{"icd-10": ["M95.0"], "wikidata": ["Q478112"]}
Glucocorticoid remediable aldosteronism Other namesGRA SpecialtyEndocrinology Glucocorticoid remediable aldosteronism also describable as aldosterone synthase hyperactivity, is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient. It is a cause of primary hyperaldosteronism.[1] ## Contents * 1 Symptoms and signs * 2 Normal Physiology * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 See also * 7 References * 8 External links ## Symptoms and signs[edit] Patients with GRA may be asymptomatic, but the following symptoms can be present:[citation needed] * Fatigue * Headache * High blood pressure * Hypokalemia * Intermittent or temporary paralysis * Muscle spasms * Muscle weakness * Numbness * Polyuria * Polydipsia * Tingling * Hypernatraemia * Metabolic alkalosis ## Normal Physiology[edit] Steroidogenesis, showing aldosterone synthase at right. Main article: Aldosterone synthase Aldosterone synthase is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone. It is localized to the mitochondrial inner membrane. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and other steroids. Aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex. Aldosterone synthase normally is not ACTH sensitive, and only activated by angiotensin II. Aldosterone causes the tubules of the kidneys to retain sodium and water. This increases the volume of fluid in the body, and drives up blood pressure. Steroid hormones are synthesized from cholesterol within the adrenal cortex. Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). Aldosterone synthesis is stimulated by several factors: by increase in the plasma concentration of angiotensin III. by increased plasma angiotensin II, ACTH, or potassium levels. The ACTH stimulation test is sometimes used to stimulate the production of aldosterone along with cortisol to determine if primary or secondary adrenal insufficiency is present. by plasma acidosis. by the stretch receptors located in the atria of the heart. by adrenoglomerulotropin, a lipid factor, obtained from pineal extracts. It selectively stimulates secretion of aldosterone. The secretion of aldosterone has a diurnal rhythm. Control of aldosterone release from the adrenal cortex: * The role of the renin–angiotensin system: Angiotensin is involved in regulating aldosterone and is the core regulator. Angiotensin II acts synergistically with potassium. * The role of sympathetic nerves: Aldosterone production is also affected to one extent or another by nervous control which integrates the inverse of carotid artery pressure, pain, posture, and probably emotion (anxiety, fear, and hostility)(including surgical stress). * The role of baroreceptors: Pressure in the carotid artery decreases aldosterone * The role of the juxtaglomerular apparatus * The plasma concentration of potassium: The amount of aldosterone secreted is a direct function of the serum potassium as probably determined by sensors in the carotid artery. * The plasma concentration of sodium: Aldosterone is a function of the inverse of the sodium intake as sensed via osmotic pressure. * Miscellaneous regulation: ACTH, a pituitary peptide, also has some stimulating effect on aldosterone probably by stimulating deoxycorticosterone formation which is a precursor of aldosterone. Aldosterone is increased by blood loss, pregnancy, and possibly by other circumstances such as physical exertion, endotoxin shock, and burns. Aldosterone feedback: Feedback by aldosterone concentration itself is of a non-morphological character (that is, other than changes in cell number or structure) and is relatively poor, so that electrolyte feedback predominates in the short term.[citation needed] ## Pathophysiology[edit] The genes encoding aldosterone synthase and 11β-hydroxylase are 95% identical and are close together on chromosome 8. In individuals with GRA, there is unequal crossing over so that the 5' regulatory region of the 11-hydroxylase gene is fused to the coding region of the aldosterone synthase.[citation needed] The product of this hybrid gene is aldosterone synthase that is ACTH-sensitive[2] in the zona fasciculata of the adrenal gland.[3] Although in normal subjects, ACTH accelerates the first step of aldosterone synthesis, ACTH normally has no effect on the activity of aldosterone synthase. However, in subjects with glucocorticoid-remediable aldosteronism, ACTH increases the activity of existing aldosterone synthase, resulting in an abnormally high rate of aldosterone synthesis and hyperaldosteronism.[citation needed] ## Diagnosis[edit] Genetic testing[citation needed] ## Treatment[edit] In GRA, the hypersecretion of aldosterone and the accompanying hypertension are remedied when ACTH secretion is suppressed by administering glucocorticoids.[citation needed] Dexamethasone, spironolactone and eplerenone have been used in treatment.[4] ## See also[edit] * Inborn errors of steroid metabolism * Hyperaldosteronism * Pseudohyperaldosteronism * Apparent mineralocorticoid excess syndrome * Aldosterone and aldosterone synthase ## References[edit] 1. ^ Vonend O, Altenhenne C, Büchner NJ, et al. (April 2007). "A German family with glucocorticoid-remediable aldosteronism". Nephrol. Dial. Transplant. 22 (4): 1123–30. doi:10.1093/ndt/gfl706. PMID 17277347. 2. ^ Ganong Physiology 3. ^ McMahon GT, Dluhy RG (2004). "Glucocorticoid-remediable aldosteronism". Cardiol Rev. 12 (1): 44–8. doi:10.1097/01.crd.0000096417.42861.ce. PMID 14667264. S2CID 2813697. 4. ^ McMahon GT, Dluhy RG (October 2004). "Glucocorticoid-remediable aldosteronism". Arq Bras Endocrinol Metabol. 48 (5): 682–6. doi:10.1590/S0004-27302004000500014. PMID 15761539. ## External links[edit] Classification D * ICD-10-CM: E26.02 * ICD-9-CM: 255.11 * OMIM: 103900 * MeSH: C563177 C563177, C563177 * v * t * e Adrenal gland disorder Hyperfunction Aldosterone * Hyperaldosteronism * Primary aldosteronism * Conn syndrome * Bartter syndrome * Glucocorticoid remediable aldosteronism * AME * Liddle's syndrome * 17α CAH * Pseudohypoaldosteronism Cortisol * Cushing's syndrome * Pseudo-Cushing's syndrome * Steroid-induced osteoporosis Sex hormones * 21α CAH * 11β CAH Hypofunction Aldosterone * Hypoaldosteronism * 21α CAH * 11β CAH Cortisol * CAH * Lipoid * 3β * 11β * 17α * 21α Sex hormones * 17α CAH * Inborn errors of steroid metabolism Adrenal insufficiency * Adrenal crisis * Adrenalitis * Xanthogranulomatous * Addison's disease * Waterhouse–Friderichsen syndrome * v * t * e Inborn errors of steroid metabolism Mevalonate pathway * HMG-CoA lyase deficiency * Hyper-IgD syndrome * Mevalonate kinase deficiency To cholesterol * 7-Dehydrocholesterol path: Hydrops-ectopic calcification-moth-eaten skeletal dysplasia * CHILD syndrome * Conradi-Hünermann syndrome * Lathosterolosis * Smith–Lemli–Opitz syndrome * desmosterol path: Desmosterolosis Steroids Corticosteroid (including CAH) * aldosterone: Glucocorticoid remediable aldosteronism * cortisol/cortisone: CAH 17α-hydroxylase * CAH 11β-hydroxylase * both: CAH 3β-dehydrogenase * CAH 21-hydroxylase * Apparent mineralocorticoid excess syndrome/11β-dehydrogenase Sex steroid To androgens * 17α-Hydroxylase deficiency * 17,20-Lyase deficiency * Cytochrome b5 deficiency * 3β-Hydroxysteroid dehydrogenase deficiency * 17β-Hydroxysteroid dehydrogenase deficiency * 5α-Reductase deficiency * Pseudovaginal perineoscrotal hypospadias To estrogens * Aromatase deficiency * Aromatase excess syndrome Other * X-linked ichthyosis * Antley–Bixler syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Glucocorticoid remediable aldosteronism	c1260386	5,842	wikipedia	https://en.wikipedia.org/wiki/Glucocorticoid_remediable_aldosteronism	2021-01-18T19:07:58	{"gard": ["2790"], "mesh": ["C563177"], "umls": ["C1260386"], "orphanet": ["403"], "wikidata": ["Q17149181"]}
A number sign (#) is used with this entry because persistent mullerian duct syndrome (PMDS) is caused by heterozygous mutation in the gene encoding anti-mullerian hormone (AMH; 600957) or in the AMH receptor gene (AMHR; 600956). These 2 forms of persistent mullerian duct syndrome are referred to as type I and type II, respectively. Description The persistent mullerian duct syndrome is characterized by the persistence of mullerian derivatives, uterus and tubes, in otherwise normally virilized males (summary by Knebelmann et al., 1991). Clinical Features The typical case is that of a male with bilateral cryptorchidism and inguinal hernias but normal male external genitalia otherwise. At the time of hernia repair, a uterus and fallopian tubes are found in the inguinal canal. The gonads are testes (Nilson, 1939). Harbison et al. (1991) reported a patient with PMDS who was born to healthy unrelated New York parents of Italian descent. A right inguinal hernia was noted at the age of 1 month. Surgery on the 79th day of life revealed that both gonads were within the right hernia sac. Attached to each gonad was an unremarkable epididymis, vas deferens, and fallopian tube. Between the fallopian tubes was what appeared to be an infantile uterus. No serum anti-mullerian hormone could be detected by enzyme-linked immunosorbent assay. Pathogenesis The AMH hormone, also known as mullerian inhibiting substance (MIS), is a glycoprotein homodimer produced by Sertoli cells not only during the period when it is responsible for regression of the mullerian ducts but also in late pregnancy, after birth, and even, although at a much reduced rate, in adulthood. In the female, low amounts of AMH are released into the follicular fluid by mature granulosa cells. (Sertoli cells, which produce AMH, require the presence of a Y chromosome; presumably it is the Sertoli cell alone that requires the presence of testis-determining factor (TDF). The Sertoli cell population in an XX/XY chimeric mouse is composed entirely of XY cells.) In a case of persistent mullerian duct syndrome, Rangnekar et al. (1990) found that 50% of metaphases showed premature centromeric divisions and hypoploid counts. The formation of sex cords populated by primordial germ cells precedes the differentiation of the gonads. Because granulosa and Sertoli cells both originate from bipotential sex-cord cells and produce MIS, Gustafson et al. (1992) hypothesized that sex-cord tumors might secrete large amounts of this hormone. In a woman with an ovarian sex-cord tumor with annular tubules, a rare tumor with the characteristics of both granulosa and Sertoli cells, they found a markedly elevated serum level of MIS and demonstrated the usefulness of measuring MIS in serum for detection of persistent or recurrent disease. The H-Y ('male') antigens were defined originally in the mouse by graft rejection (Eichwald and Silsmer, 1955); see histocompatibility Y antigen (426000). The H-Y antigen identified by graft rejection is different from that identified by antibody, the latter being referred to as 'serologic H-Y' or 'serologically detectable male' (SDM) antigen. SDM antibodies are raised by sensitizing female rodents with skin grafts or lymphoid cells from syngeneic males. Typing for SDM is then accomplished by absorption of SDM antibody and testing of the absorbed antibody for residual activity on male cells or cell extracts. There appear to be at least 2 SDM antigens. One is an integral part of the membrane of male cells and one is a soluble factor secreted by the Sertoli cells of the testis. Testis-secreted SDM can sex-reverse ovarian cells, causing them to form tubular structures in slow rotation cultures. These and other similar data implied a role for Sertoli-cell-secreted SDM in the development of the mammalian testis. Muller et al. (1993) presented evidence that testis-secreted H-Y is identical to mullerian inhibiting substance (AMH). Both are released by Sertoli cells; both evidently are encoded by autosomal genes under the control of the Y chromosome; both are found in the mature rat ovary; both induce sex reversal of ovarian cells in vitro; both are implicated in the sex reversal of ovarian cells in vivo; and both react specifically with the same antibodies. Inheritance Guell-Gonzalez et al. (1971), Morillo-Cucci and German (1971), and Armendares et al. (1973) described affected brothers. Von Seemen (1927) observed parental consanguinity. Affected sibs and parental consanguinity suggested autosomal recessive inheritance. Naguib et al. (1989) reported an Arab Bedouin family with 4 affected males, 2 brothers and 2 of their maternal uncles. Superficially the pedigree suggested X-linked recessive inheritance, but the consanguinity of the parents of the maternal uncles suggested autosomal recessive inheritance. Sloan and Walsh (1976) reported 2 affected half brothers with different fathers, suggesting X-linked recessive inheritance rather than autosomal recessive inheritance with male sex limitation. Molecular Genetics Knebelmann et al. (1991) demonstrated a missense mutation in the AMH gene in a patient with AMH-negative persistent mullerian duct syndrome (600957.0001). PMDS is biologically heterogeneous: in some cases, bioactive AMH is normally expressed by testicular tissue, while in others no AMH is produced. Imbeaud et al. (1994) performed molecular analysis of the AMH gene in 21 patients and their families. In 6 patients with normal serum concentration of AMH, the AMH was normal or contained only polymorphisms and silent mutations, supporting the hypothesis that the condition is due to end-organ resistance. In the 15 remaining patients with low or undetectable levels of serum AMH, 9 novel mutations were discovered. When present in homozygotes or compound heterozygotes, these mutations were associated with the PMDS phenotype, the same mutation never being observed in 2 different families. The first 3 exons of the AMH gene appeared particularly prone to mutation, although they are less GC rich than the last 2 exons and code for the N-terminal part of the AMH protein, which is not in itself essential to bioactivity. Imbeaud et al. (1995) demonstrated a mutation in the gene encoding the AMH receptor (600956.0001) in a 3-month-old boy of Pakistani extraction. The AMH gene was normal by sequencing and the production of normal AMH was demonstrated by the fact that normal regression of fetal rat mullerian ducts was elicited by coculture with a small fragment of testis from the patient. Imbeaud et al. (1996) reported results of molecular studies on 38 families with PMDS. They identified the basis of the condition, namely 16 AMH and 16 AMHR mutations in 32 families. Six of the patients were postpubertal and, since AMH production is normally repressed in these patients, determination of the level of AMH was no longer informative. In prepubertal patients, the type of genetic defect leading to PMDS could be predicted from the level of serum AMH, which is very low or undetectable in PMDS type I due to AMH mutations and at the upper limit of normal in receptor type II mutations. AMH mutations were extremely diverse. AMH mutations were identified in 16 families, including 9 previously reported families (Imbeaud et al., 1994). Imbeaud et al. (1996) reported that exon 1 and the 3-prime half of exon 5 of AMH are the main sites of deleterious changes including short deletions and missense mutations. AMH receptor mutations leading to type II PMDS were detected in 16 patients and 10 of these patients had a 27-bp deletion in exon 10 on at least one allele (600956.0002). This deletion was thus implicated in 25% of the PMDS patients analyzed by Imbeaud et al. (1996). This deletion was present in the homozygous state in 4 patients and it was coupled with missense mutations in 7 patients. Lang-Muritano et al. (2001) reported 2 brothers with bilateral cryptorchidism in whom the diagnosis of persistent mullerian duct syndrome was made on the basis of laparoscopic evidence of uterus and tubes, undetectable plasma levels of AMH, and homozygosity for a 23-bp insertion in exon 5 of the AMH gene (600957.0004). GU \- Bilateral cryptorchidism \- Normal penis Abdomen \- Inguinal hernias \- Inguinal uterus and fallopian tubes Lab \- Antimullerian hormone (AMH) defect \- Premature centromeric divisions and hypoploid counts Inheritance \- Autosomal recessive with male sex limitation ▲ 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	PERSISTENT MULLERIAN DUCT SYNDROME, TYPES I AND II	c1849930	5,843	omim	https://www.omim.org/entry/261550	2019-09-22T16:23:33	{"doid": ["0050791"], "mesh": ["C536665"], "omim": ["261550"], "orphanet": ["2856"], "synonyms": ["Alternative titles", "PSEUDOHERMAPHRODITISM, MALE INTERNAL", "HERNIA UTERI INGUINALE", "PERSISTENT OVIDUCT SYNDROME", "FEMALE GENITAL DUCTS IN OTHERWISE NORMAL MALE"]}
Carcinoma of the gallbladder (GBC) is the most common and aggressive form of biliary tract cancer (BTC; see this term) usually arising in the fundus of the gallbladder, rapidly metastasizing to lymph nodes and distant sites. ## Epidemiology Annual incidence rates vary from 1/100,000 to 1/ 4,350 between different ethnic groups and geographical regions. It is rare in developed Western countries but has a high incidence in Japan (1/19,000), northern India, Chile and certain regions of Eastern Europe. ## Clinical description GBC is a rare neoplasm occurring more often in females (3-4:1 female to male ratio) with an average age of onset of 65 years. Most patients are asymptomatic until the disease is advanced but presenting symptoms include abdominal pain (usually in the upper right quadrant), nausea, vomiting, jaundice, anorexia and weight loss. Gallstones are often present in patients with GBC. GBC is extremely aggressive and invasion of the lymph nodes, liver and other organs occurs rapidly in many cases. ## Etiology The exact etiology is unknown. Genetic susceptibility elicited by chronic inflammation of the gallbladder leading to dysplasia and malignant change is one possibility. Risk factors associated with GBC include a history of gallstones, cholelithiasis, porcelain gallbladder, bacterial infections, high caloric diet and an anomalous pancreaticobiliary junction. A family history of GBC is also a risk factor supporting the hypothesis that genetic and environmental factors both play a role in disease susceptibility. The APOB gene is the only gene identified so far with a direct link to GBC. Mutations in the genes KRAS, INK4a, p53 and EGFR have all been implicated in the pathogenesis of GBC. ## Diagnostic methods Diagnosis is based on laboratory tests and imaging studies. Blood tests measuring liver enzymes and tumor marker levels are conducted. There is often an increase in CEA and CA 19-9 tumor markers, especially at an advanced stage. Ultrasound and computed tomography (CT) scans show any masses or enlargement of the gallbladder. Tumor masses are usually found in the neck and body of the gallbladder. The TNM staging system is used to stage GBC and to determine the treatment and prognosis given. Patients are then given a stage based on the International Union Against Cancer (UICC) staging system. Histopathologically most GBCs are adenocarcinomas with various histopathological subtypes. Less frequently there can be squamous cell carcinoma, sarcoma, lymphoma (see this term) or melanoma. ## Differential diagnosis GBC is often misdiagnosed as other types of adenocarcinoma and other benign gallbladder diseases such as chronic cholecystitis and adenomyomatosis. ## Management and treatment The only curative treatment is complete surgical resection. If obstructive jaundice is present then biliary drainage with stenting is necessary. For T1 tumors a simple or radical (in T1b tumors) open cholecystectomy is recommended and is usually curative. Unfortunately GBC is rarely discovered at such an early stage. T2 tumors are best managed with an en bloc resection of the liver bed. T3 tumors require a selective radical resection depending on the organs affected. T4 tumors are considered unresectable or associated with high surgical morbidity. Chemotherapy can be given to those with unresectable T3 or T4 tumors or metastatic disease in hopes of improving survival and quality of life. Gemcitabine combined with cisplatin therapy is the standard treatment for unresectable biliary tract cancers. Less toxic molecular-targeted agents are now being tested as possible future treatments. ## Prognosis As GBC is often detected only at an advanced disease stage, the prognosis is poor with 5-year survival rates of approximately 20%. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Carcinoma of gallbladder and extrahepatic biliary tract	c0153452	5,844	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=56044	2021-01-23T18:50:25	{"mesh": ["D005706"], "umls": ["C0153452", "C0235782"], "synonyms": ["Carcinoma of gallbladder and EBT"]}
Kraus (1951) was of the opinion that homozygosity of a gene is responsible for a pronounced tubercle, whereas the heterozygote shows slight grooves, pits, tubercles or bulge. He provided good pictures of the anomaly. Lee and Goose (1972) studied the inheritance of this and four other common dental traits, namely, shovel incisors (147400), maxillary molar cusp number, mandibular molar cusp number, and fissure patterns. They concluded that all are probably multifactorial. Inheritance \- Autosomal dominant vs. multifactorial Teeth \- Grooves, pits, tubercles or bulges of maxillary molars ▲ 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	CARABELLI ANOMALY OF MAXILLARY MOLAR TEETH	c1861897	5,845	omim	https://www.omim.org/entry/114700	2019-09-22T16:43:43	{"mesh": ["C566175"], "omim": ["114700"]}
A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-39 (COXPD39) is caused by homozygous or compound heterozygous mutation in the GFM2 gene (606544) on chromosome 5q13. Description Combined oxidative phosphorylation deficiency-39 (COXPD39) is an autosomal recessive multisystem disorder resulting from a defect in mitochondrial energy metabolism. Affected individuals show global developmental delay, sometimes with regression after normal early development, axial hypotonia with limb spasticity or abnormal involuntary movements, and impaired intellectual development with poor speech. More variable features may include hypotonia, seizures, and features of Leigh syndrome (256000) on brain imaging. There are variable deficiencies of the mitochondrial respiratory chain enzyme complexes in patient tissues (summary by Glasgow et al., 2017). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). Clinical Features Dixon-Salazar et al. (2012) reported 2 sibs, born of consanguineous parents, with a severe neurodevelopmental disorder. The patients had microcephaly, simplified gyral pattern and pachygyria on brain imaging, and insulin-dependent diabetes. One of the affected sibs had died, but the age at death and cause of death were not provided. The patients were part of a large cohort of 188 probands from consanguineous unions with genetic forms of neurodevelopmental disorders who underwent exome sequencing. Fukumura et al. (2015) reported 2 Japanese sisters with a severe neurodevelopmental disorder. Both patients were born with arthrogryposis multiplex congenita and showed severe hypotonia. The older sib had enlarged lateral ventricles and hypoplasia of the corpus callosum, but no cortical malformations. She developed refractory seizures with hypsarrhythmia at age 3 months, and died at age 13 months after showing no developmental progress. Brain imaging of the younger sib showed progressive cerebellar atrophy and abnormal signals restricted to the midbrain suggestive of Leigh syndrome. By age 7 years, she was ventilator-dependent and bedridden with spasticity, bradycardia, and lack of developmental progress. Laboratory studies, including serum and cerebrospinal fluid (CSF) lactate, were normal, but magnetic resonance spectroscopy (MRS) showed a lactate peak. Fibroblasts from the second patient showed approximately 50% decreased activities of mitochondrial complexes III and IV compared to controls, but normal complexes I and II. Glasgow et al. (2017) reported 2 unrelated patients with COXPD39. Both were noted to have developmental delay and regression of developmental milestones around 2 years of age after normal early development. They acquired some speech, but later lost language skills and developed dysarthria (patient 1) or loss of language (patient 2). Both had loss of motor skills and lost the ability to walk in childhood. Patient 1 had intrauterine growth retardation and asymptomatic hypoglycemia in the newborn period. He was able to walk at 14 months and run at age 5, but developed dystonia and spasticity in the lower limbs. Patient 2 developed a severe seizure disorder and had myopathic facies with drooling, axial hypotonia with hypertonic limbs, and dystonic involuntary movements. Brain imaging in both patients showed T2-weighted abnormalities in the basal ganglia, consistent with Leigh syndrome, as well as abnormalities in other brain regions, including volume loss in the corpus callosum and cerebellum. Laboratory studies showed increased serum and CSF lactate. Analysis of patient fibroblasts and skeletal muscle showed variable decreases in several mitochondrial respiratory complexes, most notably complexes I and IV. These findings were consistent with tissue-specific manifestations. Inheritance The transmission pattern of COXPD39 in the families reported by Glasgow et al. (2017) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 sibs, born of consanguineous parents, with a neurodevelopmental disorder consistent with COXPD39, Dixon-Salazar et al. (2012) identified a homozygous missense mutation in the GFM2 gene (D576E; 606544.0001). The mutation, which was identified by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in 200 controls. The mutation occurred at a highly conserved residue and was predicted to damage the protein, but functional studies were not performed. In 2 Japanese sisters with COXPD39, Fukumura et al. (2015) identified compound heterozygous mutations in the GFM2 gene (606544.0002 and 606544.0003). Studies of patient cells confirmed that both mutations resulted in nonsense-mediated mRNA decay, consistent with a loss of function. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In 2 unrelated patients with COXPD39, Glasgow et al. (2017) identified biallelic mutations in the GFM2 gene (606544.0004-606544.0006). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. In vitro functional expression studies in patient fibroblasts did not show a defect in translation of mitochondrial proteins, but Glasgow et al. (2017) postulated that GFM2 acts later in the process. Patient skeletal muscle and fibroblasts showed variable decreased levels and activities of several subunits of mitochondrial complexes I, III, and IV. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation (in some patients) HEAD & NECK Head \- Microcephaly (in some patients) Face \- Myopathic facies Mouth \- Drooling SKELETAL \- Arthrogryposis multiplex congenita (in some patients) \- Contractures (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia, axial \- Hypertonia, limbs NEUROLOGIC Central Nervous System \- Developmental delay \- Developmental regression \- Loss of motor skills \- Speech delay \- Loss of language \- Loss of ambulation (in some patients) \- Poor fine motor skills \- Dysarthria \- Dystonia \- Involuntary movements \- Spasticity \- Seizures, refractory (in some patients) \- Hypsarrhythmia (in some patients) \- Brain imaging shows white matter abnormalities consistent with Leigh syndrome \- Corpus callosum abnormalities \- Cerebellar abnormalities \- Cerebral volume loss \- Enlarged ventricles \- Pachygyria (in some patients) \- Simplified gyral pattern (in some patients) METABOLIC FEATURES \- Hypoglycemia (in some patients) Diabetes mellitus (in some patients) LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased CSF lactate \- Decreased mitochondrial respiratory chain activities, variable, in multiple tissues MISCELLANEOUS \- Onset in first years of life \- Some patients may have normal early development and then show regression MOLECULAR BASIS \- Caused by mutation in the mitochondrial elongation factor G2 gene (GFM2, 606544.0001 ) ▲ 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	COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 39	None	5,846	omim	https://www.omim.org/entry/618397	2019-09-22T15:42:10	{"omim": ["618397"]}
Cleft lip - retinopathy is an exceedingly rare association characterized by cleft lip and progressive retinopathy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Cleft lip-retinopathy syndrome	c2931789	5,847	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1995	2021-01-23T17:35:39	{"gard": ["435"], "mesh": ["C538272"], "umls": ["C2931789"], "icd-10": ["Q87.8"], "synonyms": ["Ausems-Wittebol Post-Hennekam syndrome", "Cleft lip-cone rod dystrophy syndrome", "Cleft lip-progressive retinopathy syndrome"]}
A rare, hereditary nephrotic syndrome characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia, with an absence of response to an initial trial of corticosteroids (i.e. steroid-resistant nephrotic syndrome; SRNS) and a generally complicated course. ## Epidemiology The annual incidence is 1/ 200,000- 500,000 children. ## Clinical description Disease onset may occur anywhere between birth and adulthood but predominantly presents in younger populations. The nephrotic syndrome is defined by severe proteinuria (Urinary Protein/Creatinine ration > 200 mg/mmol) with low serum albumin (<30 g/l) and possible edema. Biopsy shows minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) or, more rarely, diffuse mesangial sclerosis (DMS), and podocyte foot process effacement by electron microscopy. It is multi-drug resistant and usually progresses to end-stage kidney failure; however, patients have a very low risk of recurrence after kidney transplantation. ## Etiology Causative pathogenic variants are identified in approximately 10-15% of young adults presenting with SRNS, 30% of children and at least 66% in congenital and infantile cases. Among these genes, NPHS1 (19q13.12) and NPHS2 (1q25.2) are by far the two main autosomal recessive genes implicated in SRNS while INF2 (14q32.33) and WT1 (11p13) are the leading cause of autosomal dominant SRNS. COQ8B (19q13.2) biallelic variants are commonly found in patients of Asian descent. So far, more than 60 single gene causes of SRNS have been reported, however most novel gene variants are rare and involve few families. ## Diagnostic methods Comprehensive gene panels to include all currently known SRNS genes; alternatively cascade testing starting with screening for pathogenic variants in NPHS2 and WT1, the most commonly mutated genes in children, can be performed at the initial stage and if negative expanded to large next generation sequencing based test. ## Differential diagnosis A number of hereditary renal disorders might present with persistent proteinuria, the hallmark of SRNS. These include defects in ciliary (eg. TTC21B) or tubular (eg. CLCN5, Dent disease) genes or atypical hemolytical syndrome (DGKE). There is also a number of syndromic (i.e. multiorgan) forms associated with defects in WT1, LMX1B, LAMB2, PAX2, etc. ## Antenatal diagnosis The decision regarding preimplantation genetic diagnosis and prenatal genetic testing should be discussed with the family in light of the local financial, social, and legal settings. ## Genetic counseling Recurrence risk counseling should be provided in all cases. Family members who are candidates for living-related kidney donation have to undergo genetic testing as part of evaluation; only heterozygous carriers of a recessive SRNS genetic variant may be considered as a potential donor, while a family member having a variant associated with a dominant inheritance should be dissuaded from kidney donation. ## Management and treatment International Pediatric Nephrology Association 2020 guidelines recommend discontinuing ineffective immunosuppressive therapies, and continuing non -immunosuppressive management, including RAASi and other supportive measures in patients with diagnosis of a hereditary nephrotic syndrome. There is high risk of progression to end-stage kidney disease; however, recurrence of the disease in the grafted kidney after transplantation is exceptional. ## Prognosis Life expectancy is not dramatically affected in SRNS patients, however individual outcome depends on prompt management and access to specific procedures, i.e. dialysis and kidney transplantation. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Genetic steroid-resistant nephrotic syndrome	c1868672	5,848	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=656	2021-01-23T18:52:24	{"gard": ["3946"], "mesh": ["C536404"], "omim": ["256370", "301028", "600995", "603278", "603965", "607832", "610725", "612551", "613237", "614131", "614196", "615244", "615573", "615861", "616002", "616032", "616220", "616730", "616892", "616893", "618176", "618177", "618178", "618179"], "umls": ["C1868672"], "icd-10": ["N04.1", "N04.3", "N04.8"], "synonyms": ["Familial idiopathic steroid-resistant nephrotic syndrome", "Genetic SRNS", "Hereditary steroid-resistant nephrotic syndrome"]}
A number sign (#) is used with this entry because of evidence that ectopia lentis et pupillae can be caused by homozygous or compound heterozygous mutation in the ADAMTSL4 gene (610113) on chromosome 1q21. Autosomal recessive isolated ectopia lentis-2 (ECTO2; 225100) is also caused by mutation in the ADAMTSL4 gene. Description Ectopia lentis et pupillae is a congenital hereditary disorder in which there is displacement of the lenses and the pupils, associated with other ocular anomalies, but without systemic manifestations. The condition is usually bilateral, with the lenses and pupils displaced in opposite directions (summary by Cruysberg and Pinckers, 1995). Additional signs include enlarged corneal diameter, increased corneal astigmatism, increased anterior chamber depth, thinning and flattening of the iris with loss of crypts, angle malformation caused by enlarged iris processes, persistent pupillary membrane, loss of zonular fibers, tilted disc, and increased axial length. Secondary manifestations include refractive errors, glaucoma, early cataract development, and retinal detachment. Membrane formation on the posterior aspect of the iris has been observed both in histologic sections and on ultrasound biomicroscopy (summary by Christensen et al., 2010). Clinical Features Colley et al. (1991) described 2 pairs of sibs and a fifth unrelated child with this disorder. The parents were nonconsanguineous in all cases. No skeletal, cardiac, or metabolic abnormalities were detected. Goldberg (1988) described the ophthalmologic features in 16 patients from 8 families. Characteristics in addition to displacement of the lens and pupil included high myopia, retinal detachment, enlarged corneal diameters, and cataract. Cruysberg and Pinckers (1995) described a kindred in which affected members were observed in 3 generations. In addition to ectopia lentis and ectopia pupillae, the patients had persistent pupillary membrane, iris transillumination, and poor pupillary dilatation. All developed bilateral cataracts before the age of 40 years, and 2 presented with intermittent acute intraocular hypertensive crises. Christensen et al. (2010) examined 10 affected individuals from 5 Norwegian families segregating autosomal recessive ectopia lentis et pupillae. Dislocation of the lens was seen in all individuals, although there was variability in the extent of dislocation, with minimal displacement in both eyes of 1 patient and 1 eye of another patient. Zonular fibers were missing in the area between the displaced pupil and the edge of the dislocated lens. Prominent displacement of the pupil was seen in 9 eyes of 5 individuals, 7 upward and 2 downward, and in 2 family members, the dislocated pupil was seen primarily in 1 eye. Mild pupillary dislocation was seen in 3 individuals, which was primarily in 1 eye in 2 of them, and in 1 patient, both pupils were centrally positioned. In eyes with prominent displacement of the pupil, the iris surface appeared flat and there were no well-developed crypts or clefts. Transillumination of the iris was seen in 5 patients, and a thin pupillary membrane was seen in 2 patients. Cataract developed relatively early, and all affected individuals over 45 years of age had undergone intracapsular cataract extraction. In contrast to earlier reports, only 2 of the 10 patients had myopia. All patients were of normal stature and none had features of Marfan (154700) or Weill-Marchesani syndromes (277600). Echocardiography was normal in the 2 patients who were studied, and plasma homocysteine levels were normal in the 2 patients tested. No ocular abnormalities were seen in 11 unaffected first-degree relatives who were examined. Inheritance The recessive inheritance of combined ectopia lentis and ectopia pupillae has been well established (Siemens, 1920). Whether simple ectopia lentis is a recessive entity separate from this is somewhat doubtful since simple and 'associated' forms are said to occur in the same family (Franceschetti, 1927; Diethelm, 1947). Walls and Heath (1959) described 3 affected sibs and an affected child of one of these sibs. It seems most likely that this was the familiar recessive disorder, the normal parent of the affected member in the later generation being a heterozygote. To invoke dominant inheritance, one must assume gonadal mosaicism or failure of expression in one of the parents of the affected sibs. These parents, it seems, were not examined. Cruysberg and Pinckers (1995) described a kindred in which affected members were observed in 3 generations. Although the parents of the first generation, in which there were 5 affected members of a sibship, were consanguineous, Cruysberg and Pinckers (1995) did not observe consanguinity in the next 2 generations. The authors raised the possibility of autosomal dominant inheritance with reduced penetrance. It seems more likely, however, that this was an instance of pseudodominance (McKusick, 1996). Mapping Christensen et al. (2010) performed homozygosity mapping in 5 Norwegian families with ectopia lentis et pupillae and identified a 0.67-cM (1.0 Mb) common segment on chromosome 1 in affected individuals, between SNP markers located 148,500,906 bp and 149,507,166 bp from chromosome 1pter (NCBI36). The findings were compatible with a common ancestor approximately 150 generations (4,000 years) earlier. Molecular Genetics In 10 affected individuals from 5 Norwegian families with ectopia lentis et pupillae mapping to chromosome 1p, Christensen et al. (2010) sequenced the candidate gene ADAMTSL4 and identified homozygosity for a 20-bp deletion (610113.0003). Obligate heterozygotes had no ocular abnormalities. Screening of 190 local blood donors identified 3 heterozygotes, corresponding to a prevalence for homozygosity of approximately 1:16,000 in this population. In an 8-year-old Swedish boy with ectopia lentis et pupillae, Aragon-Martin et al. (2010) identified compound heterozygosity for the 20-bp ADAMTSL4 deletion and an 11-bp ADAMTLS4 deletion (610113.0004). In a Caucasian British patient with ectopia lentis et pupillae, Chandra et al. (2012) identified compound heterozygosity for the 20-bp ADAMTSL4 deletion and a 1-bp insertion in the ADAMTSL4 gene (610113.0007). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Ectopic lens \- Ectopic pupil \- Flat-appearing iris \- Iris crypts and clefts underdeveloped \- Enlarged corneal diameters (in some patients) \- Persistent pupillary membrane (in some patients) \- Transillumination of the iris (in some patients) \- High myopia (in some patients) \- Cataract \- Retinal detachment (rare) \- Acute intraocular hypertension (rare) MISCELLANEOUS \- Variability in extent of dislocation of lens and/or displacement of pupil, both within families and between eyes in a single individual MOLECULAR BASIS \- Caused by mutation in the ADAMTS-like 4 gene (ADAMTSL4, 610113.0003 ) ▲ 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	ECTOPIA LENTIS ET PUPILLAE	c0013581	5,849	omim	https://www.omim.org/entry/225200	2019-09-22T16:28:25	{"mesh": ["D004479"], "omim": ["225200"], "orphanet": ["1885"], "synonyms": ["Alternative titles", "ECTOPIA LENTIS WITH ECTOPIA OF PUPIL"], "genereviews": ["NBK84111"]}
Hypertrichosis lanuginosa congenita is a rare congenital skin disease characterized by the presence of 3 to 5cm long lanugo-type hair on the entire body, with the exception of palms, soles, and mucous membranes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Hypertrichosis lanuginosa congenita	c0235864	5,850	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2222	2021-01-23T17:17:12	{"gard": ["12754", "2865"], "mesh": ["C538389"], "omim": ["145700", "145701", "307150"], "umls": ["C0235864", "C2936812"], "icd-10": ["Q84.2"], "synonyms": ["Hypertrichosis universalis"]}
## Clinical Features An historically notable example is the Scipion family in which the malformation was transmitted for over two thousand years (Manoiloff, 1931). The thumb is replaced by one or two triphalangeal digits, which may or may not be opposable (Swanson and Brown, 1962). The feet, in some cases, show preaxial polydactyly of the 1st or 2nd toes (Manoiloff, 1931; James and Lamb, 1963). A constant radiologic finding is distal epiphysis for the metacarpal of the accessory digits (Swanson and Brown, 1962). Limbs \- Preaxial polydactyly \- Thumb replaced by one or two triphalangeal digits \- Occasionl polydactyly of 1st or 2nd toes Radiology \- Distal epiphyses for metacarpals of accessory digits 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	POLYDACTYLY, PREAXIAL III	c1868113	5,851	omim	https://www.omim.org/entry/174600	2019-09-22T16:36:01	{"mesh": ["C566784"], "omim": ["174600"], "orphanet": ["93337"], "synonyms": ["Alternative titles", "INDEX FINGER POLYDACTYLY"]}
A number sign (#) is used with this entry because autosomal recessive nonsyndromic mental retardation-7 (MRT7) can be caused by homozygous mutation in the TUSC3 gene (601385) on chromosome 8p22. Clinical Features Garshasbi et al. (2008) reported a highly consanguineous Iranian kindred in which 7 individuals had nonsyndromic moderate to severe mental retardation. Brain MRI of 2 patients showed no abnormalities. Molinari et al. (2008) reported 2 sibs, born of second-cousin French parents, with nonsyndromic severe mental retardation. Al-Amri et al. (2016) reported a large consanguineous Omani family in which 4 children had MRT7. The patients had variable developmental delay with intellectual disability (IQ range, 40-50) and language delay. One patient had autism spectrum disorder. Three patients had poor overall growth with short stature and small head circumference (less than third percentile). The patients had mild dysmorphic features, including hypertelorism, long face, deep-set eyes, thin philtrum, and pointed chin, although some of these features were also observed in an unaffected family member. Three patients also had distal anomalies of the fingers and toes, including camptodactyly and syndactyly. Brain imaging of 1 patient was normal. A 7-year-old patient was in school, but with difficulties, whereas a 3-year-old girl had poor fine motor skills, only a few words, and difficulty chewing and swallowing. Mapping Najmabadi et al. (2007) reported a consanguineous Iranian family (M100) in which 4 individuals had nonsyndromic moderate mental retardation. Linkage analysis identified a candidate locus on chromosome 8p, termed MRT7, with a maximum lod score of 3.3. Haplotype analysis delineated a 6.5-Mb candidate region between SNPs rs1113990 and rs1534587. By genomewide linkage analysis of a consanguineous Iranian family with nonsyndromic mental retardation, Garshasbi et al. (2008) found linkage to a 4.6-Mb region on chromosome 8p22 (maximum lod score of 6.26). Molecular Genetics In affected members of a large consanguineous Iranian family with nonsyndromic mental retardation, Garshasbi et al. (2008) found a homozygous 120- to 150-kb deletion on chromosome 8p22 including the first exon of the TUSC3 gene. All unaffected parents of patients were heterozygous for this deletion, which was not detected among 192 unrelated Iranian controls. In 2 French sibs with nonsyndromic severe mental retardation, Molinari et al. (2008) identified a homozygous mutation in the TUSC3 gene (601385.0001). The findings implicated a role for N-glycosylation in higher brain functions. By genomewide linkage analysis followed by candidate gene sequencing, Garshasbi et al. (2011) identified a homozygous truncating mutation in the TUSC3 gene (Q55X; 601385.0002) in 3 Iranian sibs with autosomal recessive severe mental retardation. In affected members of a consanguineous Omani kindred with MRT7, Al-Amri et al. (2016) identified a homozygous frameshift mutation in the TUSC3 gene (c.222delA; 601385.0003). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to result in a complete loss of function. Nomenclature The HUGO Gene Nomenclature Committee (2011) assigned the designation MRT22 to a locus for autosomal recessive nonsyndromic mental retardation mapping to chromosome 8p22 without including a reference. Because this is the same location as the MRT7 locus, the MRT22 designation is also used in this entry. INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Mental retardation, mild to severe (IQ <35 in some patients) MOLECULAR BASIS \- Caused by mutation in the tumor suppressor candidate-3 gene (TUSC3, 601385.0001 ) ▲ 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	MENTAL RETARDATION, AUTOSOMAL RECESSIVE 7	c1970197	5,852	omim	https://www.omim.org/entry/611093	2019-09-22T16:03:39	{"doid": ["0060308"], "mesh": ["C567016"], "omim": ["611093"], "orphanet": ["88616"], "synonyms": ["MENTAL RETARDATION, AUTOSOMAL RECESSIVE 22", "Alternative titles", "NS-ARID", "AR-NSID"], "genereviews": ["NBK1332"]}
Joubert syndrome with orofaciodigital defect (or oral-facial-digital syndrome type 6, OFD6) is a very rare subtype of Joubert syndrome and related disorders (JSRD, see this term) characterized by the neurological features of JS associated with orofacial anomalies and often polydactyly. ## Epidemiology Prevalence is unknown. ## Clinical description Typical oral findings include bifid or lobulated tongue, lingual hamartomas and multiple oral frenulae, but cleft lip and/or palate can also be present. Polydactyly is typically mesaxial with Y-shaped metacarpals, but can also be preaxial or postaxial. A subset of patients present with hypothalamic hamartoma that has never been reported in other JSRD subgroups. ## Etiology Two OFD6 patients, including one fetus, were found to carry a homozygous mutation in the TMEM216 gene (11q13.1), but mutations in this gene were excluded in several other patients, and the genetic basis of this condition still remains elusive. ## Genetic counseling Males and females are equally affected and an autosomal recessive pattern of inheritance was observed in familial 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	Orofaciodigital syndrome type 6	c2745997	5,853	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2754	2021-01-23T18:29:01	{"gard": ["4412"], "mesh": ["C536531"], "omim": ["277170", "300804", "614815", "615665", "617127", "618763"], "umls": ["C2745997"], "icd-10": ["Q04.3"], "synonyms": ["Joubert syndrome with oral-facial-digital syndrome", "Joubert syndrome with orofaciodigital defect", "OFD6", "Oral-facial-digital syndrome type 6", "Polydactyly-cleft lip/palate-psychomotor retardation syndrome", "Váradi syndrome", "Váradi-Papp syndrome"]}
Horse with parrot mouth Brachygnathism or colloquially parrot mouth, is the uneven alignment of the upper and lower teeth in animals. In serious cases, the upper teeth protrude beyond the lower teeth. Problem with parrot mouth occur if the molars at the back of the mouth are also uneven, resulting in large hooks forming on the upper molars and the rear of the lower back molars. Horses with parrot mouth often require dental treatment at least every six months to remove the hooks and maintain alignment. The equivalent conditions in humans are termed retrognathism or prognathism depending on whether the lower jaw is too far back or too far forward respectively. ## See also[edit] * Horse teeth * Horse conformation * Veterinary dentistry ## References[edit] This equine-related article is a stub. You can help Wikipedia by expanding it. * v * t * e This veterinary medicine–related article is a stub. You can help Wikipedia by expanding it. * v * t * e This vertebrate anatomy–related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Brachygnathism	c1305740	5,854	wikipedia	https://en.wikipedia.org/wiki/Brachygnathism	2021-01-18T19:05:39	{"mesh": ["D057887"], "wikidata": ["Q4953452"]}
Dilated cardiomyopathy with ataxia (DCMA) syndrome is an inherited condition characterized by heart problems, movement difficulties, and other features affecting multiple body systems. Beginning in infancy to early childhood, most people with DCMA syndrome develop dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Some affected individuals also have long QT syndrome, which is a heart condition that causes the cardiac muscle to take longer than usual to recharge between beats. The irregular heartbeats (arrhythmia) can lead to fainting (syncope) or cardiac arrest and sudden death. Rarely, heart problems improve over time; however, in most cases of DCMA syndrome, affected individuals do not survive past childhood due to heart failure. A small percentage of people with DCMA syndrome have no heart problems at all. By age 2, children with DCMA syndrome have problems with coordination and balance (ataxia). These movement problems can result in delay of motor skills such as standing and walking, but most older children with DCMA syndrome can walk without support. In addition to heart problems and movement difficulties, most individuals with DCMA syndrome grow slowly before and after birth, which leads to short stature. Additionally, many affected individuals have mild intellectual disability. Many males with DCMA syndrome have genital abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). Other common features of DCMA syndrome include unusually small red blood cells (microcytic anemia), which can cause pale skin; an abnormal buildup of fats in the liver (hepatic steatosis), which can damage the liver; and the degeneration of nerve cells that carry visual information from the eyes to the brain (optic nerve atrophy), which can lead to vision loss. DCMA syndrome is associated with increased levels of a substance called 3-methylglutaconic acid in the urine. The amount of acid does not appear to influence the signs and symptoms of the condition. DCMA syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with DCMA syndrome also have high urine levels of another acid called 3-methylglutaric acid. ## Frequency DCMA syndrome is a very rare disorder. Approximately 30 cases have been identified in the Dariusleut Hutterite population of the Great Plains region of Canada. Only a few affected individuals have been identified outside this population. ## Causes Mutations in the DNAJC19 gene cause DCMA syndrome. The DNAJC19 gene provides instructions for making a protein found in structures called mitochondria, which are the energy-producing centers of cells. While the exact function of the DNAJC19 protein is unclear, it may regulate the transport of other proteins into and out of mitochondria. The DNAJC19 gene mutations that cause DCMA syndrome lead to the production of an abnormally shortened protein that likely has impaired function. Researchers speculate that a lack of functional DNAJC19 protein alters the transport of other proteins into and out of the mitochondria. When too many or too few proteins move in and out of the mitochondria, energy production and mitochondrial survival can be reduced. Tissues that have high energy demands, such as the heart and the brain, are especially susceptible to decreases in cellular energy production. It is likely that this loss of cellular energy damages these and other tissues, leading to heart problems, movement difficulties, and other features of DCMA syndrome. ### Learn more about the gene associated with Dilated cardiomyopathy with ataxia syndrome * DNAJC19 ## 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	Dilated cardiomyopathy with ataxia syndrome	c1857776	5,855	medlineplus	https://medlineplus.gov/genetics/condition/dilated-cardiomyopathy-with-ataxia-syndrome/	2021-01-27T08:25:38	{"gard": ["12964"], "mesh": ["C565706"], "omim": ["610198"], "synonyms": []}
## Clinical Features Esser (1939) reported 4 affected sibs (2 males, 2 females) and an affected male first cousin. Boo-Chai (1965) described 3 cases in sibs of Asiatic Indian descent. A dominant form of bifid nose without hypertelorism (109740) has been proposed. Ocular hypertelorism (sometimes a dominant) is occasionally associated with bifid nose but the genetics of the combination is unknown. Bifid nose may also be seen with frontonasal dysplasia (136760). Nose \- Bifid nose 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	BIFID NOSE, AUTOSOMAL RECESSIVE	c0221363	5,856	omim	https://www.omim.org/entry/210400	2019-09-22T16:30:27	{"mesh": ["C535441"], "omim": ["210400"], "orphanet": ["2695"], "synonyms": ["Alternative titles", "MEDIAN FISSURE OF NOSE", "NOSE, MEDIAN CLEFT OF"]}
Congenital fiber-type disproportion is a condition that primarily affects skeletal muscles, which are muscles used for movement. People with this condition typically experience muscle weakness (myopathy), particularly in the muscles of the shoulders, upper arms, hips, and thighs. Weakness can also affect the muscles of the face and muscles that control eye movement (ophthalmoplegia), sometimes causing droopy eyelids (ptosis). Individuals with congenital fiber-type disproportion generally have a long face, a high arch in the roof of the mouth (high-arched palate), and crowded teeth. Individuals with congenital fiber-type disproportion may have joint deformities (contractures) and an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Approximately 30 percent of people with this disorder experience mild to severe breathing problems related to weakness of muscles needed for breathing. Some people who experience these breathing problems require use of a machine to help regulate their breathing at night (noninvasive mechanical ventilation), and occasionally during the day as well. About 30 percent of affected individuals have difficulty swallowing due to muscle weakness in the throat. Rarely, people with this condition have a weakened and enlarged heart muscle (dilated cardiomyopathy). The severity of congenital fiber-type disproportion varies widely. It is estimated that up to 25 percent of affected individuals experience severe muscle weakness at birth and die in infancy or childhood. Others have only mild muscle weakness that becomes apparent in adulthood. Most often, the signs and symptoms of this condition appear by age 1. The first signs of this condition are usually decreased muscle tone (hypotonia) and muscle weakness. In most cases, muscle weakness does not worsen over time, and in some instances it may improve. Although motor skills such as standing and walking may be delayed, many affected children eventually learn to walk. These individuals often have less stamina than their peers, but they remain active. Rarely, people with this condition have a progressive decline in muscle strength over time. These individuals may lose the ability to walk and require wheelchair assistance. ## Frequency Congenital fiber-type disproportion is thought to be a rare condition, although its prevalence is unknown. ## Causes Mutations in multiple genes can cause congenital fiber-type disproportion. Mutations in the TPM3, RYR1 and ACTA1 genes cause 35 to 50 percent of cases, while mutations in other genes, some known and some unidentified, are responsible for the remaining cases. The genes that cause congenital fiber-type disproportion provide instructions for making proteins that are involved in the tensing of muscle fibers (muscle contraction). Changes in these proteins lead to impaired muscle contraction, resulting in muscle weakness. Skeletal muscle is made up of two types of muscle fibers: type I (slow twitch fibers) and type II (fast twitch fibers). Normally, type I and type II fibers are the same size. In people with congenital fiber-type disproportion, type I skeletal muscle fibers are significantly smaller than type II skeletal muscle fibers. It is unclear whether the small type I skeletal muscle fibers lead to muscle weakness or are caused by muscle weakness in people with congenital fiber-type disproportion. ### Learn more about the genes associated with Congenital fiber-type disproportion * ACTA1 * MYH7 * RYR1 * SELENON * TPM2 * TPM3 ## Inheritance Pattern Congenital fiber-type disproportion can have multiple inheritance patterns. When this condition is caused by mutations in the ACTA1 gene, it usually occurs in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Most other cases of congenital fiber-type disproportion, including those caused by mutations in the RYR1 gene, have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. When this condition is caused by mutations in the TPM3 gene, it can occur in either an autosomal dominant or autosomal recessive pattern. In rare cases, this condition can be inherited in an X-linked pattern, although the gene or genes associated with X-linked congenital fiber-type disproportion have not been identified. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. It is estimated that 40 percent of individuals with congenital fiber-type disproportion have an affected relative. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Congenital fiber-type disproportion	c0546264	5,857	medlineplus	https://medlineplus.gov/genetics/condition/congenital-fiber-type-disproportion/	2021-01-27T08:24:49	{"gard": ["6161"], "mesh": ["D020914"], "omim": ["255310"], "synonyms": []}
Renal hypouricemia is a kidney (renal) disorder that results in a reduced amount of urate in the blood. Urate is a byproduct of certain normal chemical reactions in the body. In the bloodstream it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. However, having too much urate in the body is toxic, so excess urate is removed from the body in urine. People with renal hypouricemia have little to no urate in their blood; they release an excessive amount of it in the urine. In many affected individuals, renal hypouricemia causes no signs or symptoms. However, some people with this condition develop kidney problems. After strenuous exercise, they can develop exercise-induced acute kidney injury, which causes pain in their sides and lower back as well as nausea and vomiting that can last several hours. Because an excessive amount of urate passes through the kidneys to be excreted in urine in people with renal hypouricemia, they have an increased risk of developing kidney stones (nephrolithiasis) formed from urate crystals. These urate stones can damage the kidneys and lead to episodes of blood in the urine (hematuria). Rarely, people with renal hypouricemia develop life-threatening kidney failure. ## Frequency The prevalence of renal hypouricemia is unknown; at least 150 affected individuals have been described in the scientific literature. This condition is thought to be most prevalent in Asian countries such as Japan and South Korea, although affected individuals have been found in Europe. Renal hypouricemia is likely underdiagnosed because it does not cause any symptoms in many affected individuals. ## Causes Mutations in the SLC22A12 or SLC2A9 gene cause renal hypouricemia. These genes provide instructions for making proteins called urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), respectively. These proteins are found in the kidneys, specifically in structures called proximal tubules. These structures help to reabsorb needed nutrients, water, and other materials into the blood and excrete unneeded substances into the urine. Within the proximal tubules, both the URAT1 and GLUT9 proteins reabsorb urate into the bloodstream or release it into the urine, depending on the body's needs. Most urate that is filtered through the kidneys is reabsorbed into the bloodstream; about 10 percent is released into urine. Mutations that cause renal hypouricemia lead to the production of URAT1 or GLUT9 protein with a reduced ability to reabsorb urate into the bloodstream. Instead, large amounts of urate are released in the urine. The specific cause of the signs and symptoms of renal hypouricemia is unclear. Researchers suspect that when additional urate is produced during exercise and passed through the kidneys, it could lead to tissue damage. Alternatively, without the antioxidant properties of urate, free radicals could cause tissue damage in the kidneys. Another possibility is that other substances are prevented from being reabsorbed along with urate; accumulation of these substances in the kidneys could cause tissue damage. It is likely that individuals with renal hypouricemia who have mild or no symptoms have enough protein function to reabsorb a sufficient amount of urate into the bloodstream to prevent severe kidney problems. ### Learn more about the genes associated with Renal hypouricemia * SLC22A12 * SLC2A9 ## Inheritance Pattern This condition is typically inherited in an autosomal recessive pattern, which means both copies of the SLC22A12 or SLC2A9 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 usually do not show signs and symptoms of the condition. Sometimes, individuals with one SLC2A9 gene mutation in each cell have reduced levels of urate. The levels usually are not as low as they are in people who have mutations in both copies of the gene, and they often do not cause any signs or symptoms. Rarely, people who carry one copy of the mutated gene will develop urate kidney stones. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Renal hypouricemia	c0473219	5,858	medlineplus	https://medlineplus.gov/genetics/condition/renal-hypouricemia/	2021-01-27T08:25:03	{"gard": ["9496"], "mesh": ["C537757"], "omim": ["220150", "612076"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that mitochondrial complex III deficiency nuclear type 3 (MC3DN3) is caused by homozygous mutation in the UQCRB gene (191330) on chromosome 8q22. For a general phenotypic description and a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (124000). Clinical Features Haut et al. (2003) reported a Turkish girl, born of consanguineous parents, with complex III deficiency. She developed normally until 8 months of age when she presented with an episode of acute gastroenteritis. Laboratory investigations showed hypoglycemia, metabolic acidosis, and, during metabolic crisis, hyperlactatemia. At the age of 4 years her growth was normal and there were no signs of psychomotor retardation or neurologic impairment. Liver enlargement at initial presentation disappeared progressively, and liver size was normal by 19 months of age. There had been 2 further episodes of hypoglycemia with metabolic acidosis at 2.5 years of age. Inheritance The transmission pattern of MC3DN3 in the family reported by Haut et al. (2003) was consistent with autosomal recessive inheritance. Molecular Genetics In a Turkish girl with complex III deficiency, Haut et al. (2003) identified a homozygous mutation in the UQCRB gene (191330.0001). Each unaffected parent was heterozygous for the mutation. INHERITANCE \- Autosomal recessive ABDOMEN Liver \- Hepatomegaly, transient NEUROLOGIC Central Nervous System \- Normal psychomotor development METABOLIC FEATURES \- Metabolic acidosis LABORATORY ABNORMALITIES \- Increased serum lactate during metabolic crisis \- Hypoglycemia \- Decreased mitochondrial complex III activity in liver and fibroblasts MISCELLANEOUS \- Onset in late infancy \- Episodic metabolic decompensation, usually associated with illness \- One Turkish girl has been reported (last curated April 2013) MOLECULAR BASIS \- Caused by mutation in the ubiquinol-cytochrome c reductase-protein gene (UQCRB, 191330.0001 ). ▲ 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	MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 3	c3554606	5,859	omim	https://www.omim.org/entry/615158	2019-09-22T15:53:00	{"doid": ["0080112"], "omim": ["615158"], "orphanet": ["1460"], "synonyms": ["Isolated CoQ-cytochrome C reductase deficiency", "Isolated coenzyme Q-cytochrome C reductase deficiency", "Isolated mitochondrial respiratory chain complex III deficiency", "Isolated ubiquinone-cytochrome C reductase deficiency"]}
Chitayat et al. (1991) described a combination of mental retardation with distal arthrogryposis in 2 sisters, one of whom died of respiratory failure due to hypoplastic lungs shortly after birth. The chin showed a grooving like that seen in the Freeman-Sheldon syndrome (193700) but the patients did not have other features of that syndrome. Clenched hands and narrow chest were present as well as increased subcutaneous fat and decreased muscle mass. Chitayat et al. (1991) concluded that the disorder is different from that reported by Chitayat et al. (1990); see 208080. With the exception of these 2 reports, previously reported families manifesting distal arthrogryposis of type II (the type with both limb involvement and manifestations elsewhere) have been autosomal dominant in their inheritance. Wortmann et al. (2007) reported a 16-month-old Turkish boy, born of consanguineous parents, who had severe encephalopathy, distal contractures, and growth retardation without hypopituitarism. He developed myoclonic and tonic-clonic seizures in the second week of life. His head had a 'cubical' shape with trigonocephaly, high narrow forehead, prominent metopic sutures, curved eyebrows, double lashes, rounded cheeks, small mouth, high-arched palate, retrognathia, small nose with pointed tip, and low-set ears. Generalized hirsutism, low nuchal hairline, a short narrow thorax, adducted thumbs, tapering fingers, camptodactyly/clinodactyly, and hammer toes were also noted. Muscle mass was decreased with a relative increase of subcutaneous fat, and he displayed axial hypotonia, poor spontaneous movements, and tetraspasticity. Cranial MRI revealed mild frontal atrophy and mild ventriculomegaly, bilateral symmetric periventricular lesions, and delayed myelinization. Muscle biopsy was normal, as was mitochondrial DNA analysis for common point mutations and deletions. Molecular genetic analysis ruled out a clinically similar disorder caused by reciprocal 6q/9p translocation, Haspeslagh syndrome (177980). Wortmann et al. (2007) stated that this patient was most similar to the patient described by Chitayat et al. (1991), although he had some features in common with the patient reported by Chitayat et al. (1990). Muscles \- Decreased muscle mass Limbs \- Hands clenched Thorax \- Narrow chest Neuro \- Mental retardation Facies \- Chin grooved Inheritance \- Autosomal recessive Joints \- Arthrogryposis, distal Misc \- Increased subcutaneous fat Lung \- Congenital hypoplasia \- Respiratory failure ▲ 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	ARTHROGRYPOSIS, DISTAL, WITH MENTAL RETARDATION AND CHARACTERISTIC FACIES	c1859723	5,860	omim	https://www.omim.org/entry/208081	2019-09-22T16:30:51	{"mesh": ["C565940"], "omim": ["208081"]}
Pfeiffer syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. Pfeiffer syndrome also affects bones in the hands and feet. Many of the characteristic facial features of Pfeiffer syndrome result from premature fusion of the skull bones. Abnormal growth of these bones leads to bulging and wide-set eyes, a high forehead, an underdeveloped upper jaw, and a beaked nose. More than half of all children with Pfeiffer syndrome have hearing loss; dental problems are also common. In people with Pfeiffer syndrome, the thumbs and first (big) toes are wide and bend away from the other digits. Unusually short fingers and toes (brachydactyly) are also common, and there may be some webbing or fusion between the digits (syndactyly). Pfeiffer syndrome is divided into three subtypes. Type 1, also known as classic Pfeiffer syndrome, has symptoms as described above. Most individuals with type 1 Pfeiffer syndrome have normal intelligence and a normal life span. Types 2 and 3 are more severe forms of Pfeiffer syndrome that often involve problems with the nervous system. The premature fusion of skull bones can limit brain growth, leading to delayed development and other neurological problems. In addition, individuals with type 2 or 3 can have fusion of the bones (ankylosis) in the elbow or other joints, limiting mobility, and abnormalities of the face and airways, which can cause life-threatening breathing problems. Type 2 is distinguished from type 3 by the presence of a cloverleaf-shaped head, which is caused by more extensive fusion of bones in the skull. ## Frequency Pfeiffer syndrome affects about 1 in 100,000 individuals. ## Causes Pfeiffer syndrome is most commonly caused by mutations in the FGFR2 gene. Mutations in the FGFR1 gene cause a small percentage of cases of type 1 Pfeiffer syndrome. Mutations in this gene have not been associated with type 2 or 3. The FGFR1 and FGFR2 genes provide instructions for making proteins known as fibroblast growth factor receptors 1 and 2, respectively. Among their multiple functions, these proteins signal immature cells to become bone cells during embryonic development. A mutation in either the FGFR1 or FGFR2 gene alters the function of the respective protein, causing prolonged signaling, which can promote the premature fusion of skull bones and affect the development of bones in the hands and feet. ### Learn more about the genes associated with Pfeiffer syndrome * FGFR1 * FGFR2 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Pfeiffer syndrome	c0220658	5,861	medlineplus	https://medlineplus.gov/genetics/condition/pfeiffer-syndrome/	2021-01-27T08:24:52	{"gard": ["7380"], "mesh": ["D000168"], "omim": ["101600"], "synonyms": []}
Multinucleate cell angiohistiocytoma SpecialtyDermatology Multinucleate cell angiohistiocytoma is a cutaneous condition that presents as slowly growing, multiple, discrete but grouped, red to violaceous papules[1] ## See also[edit] * Mast cell sarcoma * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Multinucleate cell angiohistiocytoma	c4049285	5,862	wikipedia	https://en.wikipedia.org/wiki/Multinucleate_cell_angiohistiocytoma	2021-01-18T18:30:39	{"umls": ["C4049285"], "wikidata": ["Q6934824"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Nonsyndromic deafness" – news · newspapers · books · scholar · JSTOR (November 2016) Nonsyndromic deafness Other namesNon-syndromic genetic deafness Treatmentvancomycin Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body. Genetic changes are related to the following types of nonsyndromic deafness. * DFNA: nonsyndromic deafness, autosomal dominant * DFNB: nonsyndromic deafness, autosomal recessive * DFNX: nonsyndromic deafness, X-linked * nonsyndromic deafness, mitochondrial Each type is numbered in the order in which it was described. For example, DFNA1 was the first described autosomal dominant type of nonsyndromic deafness. Mitochondrial nonsyndromic deafness involves changes to the small amount of DNA found in mitochondria, the energy-producing centers within cells.[1] Most forms of nonsyndromic deafness are associated with permanent hearing loss caused by damage to structures in the inner ear. The inner ear consists of three parts: a snail-shaped structure called the cochlea that helps process sound, nerves that send information from the cochlea to the brain, and structures involved with balance. Loss of hearing caused by changes in the inner ear is called sensorineural deafness. Hearing loss that results from changes in the middle ear is called conductive hearing loss. The middle ear contains three tiny bones that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic deafness involve changes in both the inner ear and the middle ear; this combination is called mixed hearing loss. The severity of hearing loss varies and can change over time. It can affect one ear (unilateral) or both ears (bilateral). Degrees of hearing loss range from mild (difficulty understanding soft speech) to profound (inability to hear even very loud noises). The loss may be stable, or it may progress as a person gets older. Particular types of nonsyndromic deafness often show distinctive patterns of hearing loss. For example, the loss may be more pronounced at high, middle, or low tones. Nonsyndromic deafness can occur at any age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs after the development of speech is classified as postlingual. ## Contents * 1 Genetics * 1.1 Genes related to nonsyndromic deafness * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 References * 6 Further reading * 7 External links ## Genetics[edit] Nonsyndromic deafness can have different patterns of inheritance. Between 75% and 80% of cases are inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Usually, each parent of an individual with autosomal recessive deafness is a carrier of one copy of the altered gene. These carriers do not have hearing loss. Another 20% to 25% of nonsyndromic deafness cases are autosomal dominant, which means one copy of the altered gene in each cell is sufficient to result in hearing loss. People with autosomal dominant deafness most often inherit an altered copy of the gene from a parent who has hearing loss. Between 1% and 2% of cases show an X-linked pattern of inheritance, which means the mutated gene responsible for the condition is located on the X chromosome. Males with X-linked nonsyndromic deafness tend to develop more severe hearing loss earlier in life than females who inherit a copy of the same gene mutation. Fathers will not pass X-linked traits to their sons since they do not pass on the X chromosome to their male offspring. Mitochondrial nonsyndromic deafness, which results from changes to the DNA in mitochondria, occurs in fewer than 1% of cases in the United States. The altered mitochondrial DNA is passed from a mother to her sons and daughters. This type of deafness is not inherited from fathers. Late onset progressive deafness is the most common neurological disability of the elderly. Although hearing loss of greater than 25 decibels is present in only 1% of young adults between the ages of 18–24 years of age, this increases to 10% in persons between 55–64 years of age and approximately 50% in octogenarians. The relative contribution of heredity to age-related hearing impairment is not known, however the majority of inherited late-onset deafness is autosomal dominant and non-syndromic (Van Camp et al., 1997). Over forty genes associated with autosomal dominant non-syndromic hearing loss have been localized and of these fifteen have been cloned. ### Genes related to nonsyndromic deafness[edit] Mutations in the ACTG1, CABP2, CDH23, CLDN14, COCH, COL11A2, DFNA5, ESPN, EYA4, GJB2, GJB6, KCNQ4, MYO15A, MYO6, MYO7A, OTOF, PCDH15, POU3F4, SLC26A4, STRC, TECTA, TMC1, TMIE, TMPRSS3, USH1C, and WFS1 genes cause nonsyndromic deafness, with weaker evidence currently implicating genes CCDC50, DIAPH1, DSPP, ESRRB, GJB3, GRHL2, GRXCR1, HGF, LHFPL5, LOXHD1, LRTOMT, MARVELD2, MIR96, MYH14, MYH9, MYO1A, MYO3A, OTOA, PJVK, POU4F3, PRPS1, PTPRQ, RDX, SERPINB6, SIX1, SLC17A8, TPRN, TRIOBP, SLC26A5, and WHRN. The causes of nonsyndromic deafness can be complex. Researchers have identified more than 30 genes that, when mutated, may cause nonsyndromic deafness; however, some of these genes have not been fully characterized. Many genes related to deafness are involved in the development and function of the inner ear. Gene mutations interfere with critical steps in processing sound, resulting in hearing loss. Different mutations in the same gene can cause different types of hearing loss, and some genes are associated with both syndromic and nonsyndromic deafness. In many families, the gene(s) involved have yet to be identified. Deafness can also result from environmental factors or a combination of genetic and environmental factors, including certain medications, peri-natal infections (infections occurring before or after birth), and exposure to loud noise over an extended period. Types include: OMIM Gene Type 124900 DIAPH1 DFNA1 600101 KCNQ4 DFNA2A 612644 GJB3 DFNA2B 601544 GJB2 DFNA3A 612643 GJB6 DFNA3B 600652 MYH14 DFNA4 600994 DFNA5 DFNA5 601543 TECTA DFNA8/12 601369 COCH DFNA9 601316 EYA4 DFNA10 601317 MYO7A DFNA11, neurosensory 601868 COL11A2 DFNA13 602459 POU4F3 DFNA15 603622 MYH9 DFNA17 604717 ACTG1 DFNA20/26 606346 MYO6 DFNA22 605192 SIX1 DFNA23 605583 SLC17A8 DFNA25 608641 GRHL2 DFNA28 606705 TMC1 DFNA36 605594 DSPP DFNA36, with dentinogenesis 607453 CCDC50 DFNA44 607841 MYO1A DFNA48 613074 MIR96 DFNA50 220290 GJB2 DFNB1A 612645 GJB6 DFNB1B 600060 MYO7A DFNB2, neurosensory (see also Usher syndrome) 600316 MYO15A DFNB3 600971 TMIE DFNB6 600974 TMC1 DFNB7 601072 TMPRSS3 DFNB8, childhood onset 601071 OTOF DFNB9 601386 CDH23 DFNB12 603720 STRC DFNB16 602092 USH1C DFNB18 603629 TECTA DFNB21 607039 OTOA DFNB22 609533 PCDH15 DFNB23 611022 RDX DFNB24 613285 GRXCR1 DFNB25 609823 TRIOBP DFNB28 607101 MYO3A DFNB30 607084 WHRN DFNB31 608565 ESRRB DFNB35 609006 ESPN DFNB36 607821 MYO6 DFNB37 608265 HGF DFNB39 610153 MARVELD2 DFNB49 609706 COL11A2 DFNB53 610220 PJVK DFNB59 611451 LRTOMT DFNB63 610265 LHFPL5 DFNB67 613079 LOXHD1 DFNB77 613307 TPRN DFNB79 613391 PTPRQ DFNB84 613453 SERPINB6 DFNB91 614899 CABP2 DFNB93 304500 PRPS1 DFNX1 304400 POU3F4 DFNX2 580000 MT-RNR1, COX1[2] deafness, aminoglycoside-induced 500008 (several mtDNA) DFN, sensorineural, mt ## Diagnosis[edit] This section is empty. You can help by adding to it. (December 2017) ## Treatment[edit] Treatment is supportive and consists of management of manifestations. User of hearing aids and/or cochlear implant, suitable educational programs can be offered. Periodic surveillance is also important.[3] ## Epidemiology[edit] About 1 in 1,000 children in the United States is born with profound deafness. By age 9, about 3 in 1,000 children have hearing loss that affects the activities of daily living. More than half of these cases are caused by genetic factors. Most cases of genetic deafness (70% to 80%) are nonsyndromic; the remaining cases are caused by specific genetic syndromes. In adults, the chance of developing hearing loss increases with age; hearing loss affects half of all people older than 80 years. ## References[edit] 1. ^ Reference, Genetics Home. "nonsyndromic hearing loss". Genetics Home Reference. Retrieved 14 April 2017. 2. ^ Usami, S; Nishio, S; Adam, MP; Ardinger, HH; Pagon, RA; Wallace, SE; Bean, LJH; Stephens, K; Amemiya, A (1993). "Nonsyndromic Hearing Loss and Deafness, Mitochondrial". PMID 20301595. Cite journal requires `\|journal=` (help) 3. ^ Smith, Richard JH; Jones, Mary-Kayt N. (1993). "Nonsyndromic Hearing Loss and Deafness, DFNB1". GeneReviews. University of Washington, Seattle. ## Further reading[edit] * Pandya, Arti (21 April 2011). Nonsyndromic Hearing Loss and Deafness, Mitochondrial. University of Washington, Seattle. PMID 20301595. NBK1422. In Pagon RA, Bird TD, Dolan CR, et al., eds. (1993). GeneReviews. Seattle WA: University of Washington, Seattle. * Smith, Richard JH; Sheffield, Abraham M; Camp, Guy Van (19 April 2012). Nonsyndromic Hearing Loss and Deafness, DFNA3. University of Washington, Seattle. PMID 20301708. NBK1536. In GeneReviews * Smith, Richard JH; Camp, Guy Van (2 January 2014). Nonsyndromic Hearing Loss and Deafness, DFNB1. University of Washington, Seattle. PMID 20301449. NBK1272. In GeneReviews * Huijun Yuan; Xue Z Liu (4 August 2011). DFNX1 Nonsyndromic Hearing Loss and Deafness. University of Washington, Seattle. PMID 21834172. NBK57098. In GeneReviews * Smith, Richard JH; Gurrola, II, Jose G; Kelley, Philip M (14 June 2011). "OTOF-Related Deafness". OTOF-Related Deafness. University of Washington, Seattle. PMID 20301429. NBK1251. In GeneReviews ## External links[edit] Classification D * ICD-10: H90.5 * MeSH: C580334 External resources * Orphanet: 87884 * v * t * e Disorders of hearing and balance Hearing Symptoms * Hearing loss * Excessive response * Tinnitus * Hyperacusis * Phonophobia Disease Loss * Conductive hearing loss * Otosclerosis * Superior canal dehiscence * Sensorineural hearing loss * Presbycusis * Cortical deafness * Nonsyndromic deafness Other * Deafblindness * Wolfram syndrome * Usher syndrome * Auditory processing disorder * Spatial hearing loss Tests * Hearing test * Rinne test * Tone decay test * Weber test * Audiometry * pure tone * visual reinforcement Balance Symptoms * Vertigo * nystagmus Disease * Balance disorder * Peripheral * Ménière's disease * Benign paroxysmal positional vertigo * Labyrinthitis * Labyrinthine fistula Tests * Dix–Hallpike test * Unterberger test * Romberg's test * Vestibulo–ocular reflex * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) * v * t * e Diseases of collagen, laminin and other scleroproteins Collagen disease COL1: * Osteogenesis imperfecta * Ehlers–Danlos syndrome, types 1, 2, 7 COL2: * Hypochondrogenesis * Achondrogenesis type 2 * Stickler syndrome * Marshall syndrome * Spondyloepiphyseal dysplasia congenita * Spondyloepimetaphyseal dysplasia, Strudwick type * Kniest dysplasia (see also C2/11) COL3: * Ehlers–Danlos syndrome, types 3 & 4 * Sack–Barabas syndrome COL4: * Alport syndrome COL5: * Ehlers–Danlos syndrome, types 1 & 2 COL6: * Bethlem myopathy * Ullrich congenital muscular dystrophy COL7: * Epidermolysis bullosa dystrophica * Recessive dystrophic epidermolysis bullosa * Bart syndrome * Transient bullous dermolysis of the newborn COL8: * Fuchs' dystrophy 1 COL9: * Multiple epiphyseal dysplasia 2, 3, 6 COL10: * Schmid metaphyseal chondrodysplasia COL11: * Weissenbacher–Zweymüller syndrome * Otospondylomegaepiphyseal dysplasia (see also C2/11) COL17: * Bullous pemphigoid COL18: * Knobloch syndrome Laminin * Junctional epidermolysis bullosa * Laryngoonychocutaneous syndrome Other * Congenital stromal corneal dystrophy * Raine syndrome * Urbach–Wiethe disease * TECTA * DFNA8/12, DFNB21 see also fibrous proteins * v * t * e Genetic disorder, membrane: Solute carrier disorders 1-10 * SLC1A3 * Episodic ataxia 6 * SLC2A1 * De Vivo disease * SLC2A5 * Fructose malabsorption * SLC2A10 * Arterial tortuosity syndrome * SLC3A1 * Cystinuria * SLC4A1 * Hereditary spherocytosis 4/Hereditary elliptocytosis 4 * SLC4A11 * Congenital endothelial dystrophy type 2 * Fuchs' dystrophy 4 * SLC5A1 * Glucose-galactose malabsorption * SLC5A2 * Renal glycosuria * SLC5A5 * Thyroid dyshormonogenesis type 1 * SLC6A19 * Hartnup disease * SLC7A7 * Lysinuric protein intolerance * SLC7A9 * Cystinuria 11-20 * SLC11A1 * Crohn's disease * SLC12A3 * Gitelman syndrome * SLC16A1 * HHF7 * SLC16A2 * Allan–Herndon–Dudley syndrome * SLC17A5 * Salla disease * SLC17A8 * DFNA25 21-40 * SLC26A2 * Multiple epiphyseal dysplasia 4 * Achondrogenesis type 1B * Recessive multiple epiphyseal dysplasia * Atelosteogenesis, type II * Diastrophic dysplasia * SLC26A4 * Pendred syndrome * SLC35C1 * CDOG 2C * SLC39A4 * Acrodermatitis enteropathica * SLC40A1 * African iron overload see also solute carrier family [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Nonsyndromic deafness	c3711374	5,863	wikipedia	https://en.wikipedia.org/wiki/Nonsyndromic_deafness	2021-01-18T19:10:19	{"gard": ["6410"], "mesh": ["C580334"], "icd-10": ["H90.5"], "orphanet": ["87884"], "synonyms": ["Isolated genetic deafness"], "wikidata": ["Q9079046"]}
Porencephaly is a rare condition that affects the central nervous system. People with porencephaly develop fluid-filled cysts or cavities in the brain either before or shortly after birth. The severity of the condition and the associated signs and symptoms vary significantly based on the size, location, and number of cysts. Common features include developmental delay, reduced muscle tone (hypotonia), seizures, macrocephaly (unusually large head size), spastic hemiplegia, speech problems, delayed growth, and intellectual disability. Porencephaly is usually the result of damage from infection or stroke after birth. In these cases, the condition occurs sporadically in people with no family history of the condition. There is an inherited form of the condition called familial porencephaly, which is caused by changes (mutations) in the COL4A1 or COL4A2 genes and is inherited in an autosomal dominant manner. Treatment is based on the signs and symptoms present in each person and may include physical therapy and medication for seizures. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Porencephaly	c0302892	5,864	gard	https://rarediseases.info.nih.gov/diseases/7430/porencephaly	2021-01-18T17:58:14	{"mesh": ["D065708"], "orphanet": ["2940"], "synonyms": []}
Billard et al. (1989) described apparently monozygotic twins (their patients 13 and 14) who suffered from mild and nonprogressive mental retardation without motor deficit or visual disorders, but with moderate dysmorphia, craniosynostosis, and small stature due to growth hormone deficiency. CT scan showed dense calcifications of the inner aspects of the lenticular nuclei and ventricular dilatation. Bonnemann et al. (1991) described 2 sibs with an encephalopathy, including intracerebral calcification and white matter lesions, dwarfism owing to growth hormone deficiency, and retinal degeneration. The onset of the disease in both sisters occurred with retardation of motor development during the first year of life. Later, dwarfism, mental retardation, spasticity, ataxia, and retinal degeneration became apparent. Differentiation from Cockayne syndrome (see 216400) is essential. Radiology \- Calcification of the lenticular nuclei and ventricular dilatation on CT scan Neuro \- Mild and nonprogressive mental retardation \- Spasticity \- Ataxia Inheritance \- Autosomal recessive Lab \- Growth hormone deficiency Growth \- Small stature \- Dwarfism HEENT \- Craniosynostosis \- Retinal degeneration ▲ 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	ENCEPHALOPATHY WITH INTRACRANIAL CALCIFICATION, GROWTH HORMONE DEFICIENCY, MICROCEPHALY, AND RETINAL DEGENERATION	c1856973	5,865	omim	https://www.omim.org/entry/225755	2019-09-22T16:28:15	{"mesh": ["C565594"], "omim": ["225755"], "orphanet": ["1261"]}
Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. Osteogenesis imperfecta type 1 is the mildest form of OI and is characterized by bone fractures during childhood and adolescence that often result from minor trauma. Fractures occur less frequently in adulthood. People with mild forms of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera), and may develop hearing loss in adulthood. Affected individuals are usually of normal or near normal height. Most of the mutations that cause osteogenesis imperfecta type 1 occur in the COL1A1 gene. These genetic changes reduce the amount of type I collagen produced in the body, which causes bones to be brittle and to fracture easily. OI type 1 exhibits an autosomal dominant pattern of inheritance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Osteogenesis imperfecta type I	c0023931	5,866	gard	https://rarediseases.info.nih.gov/diseases/8694/osteogenesis-imperfecta-type-i	2021-01-18T17:58:33	{"mesh": ["D010013"], "omim": ["166200"], "umls": ["C0023931"], "orphanet": ["216796"], "synonyms": ["OI type 1", "Osteogenesis imperfecta tarda", "Osteogenesis imperfecta with blue sclerae", "Adair-Dighton syndrome", "Mild osteogenesis imperfecta", "Non-deforming osteogenesis imperfecta", "Van der Hoeve syndrome", "Classic non-deforming OI with blue sclerae", "Osteogenesis imperfecta type 1"]}
Malouf syndrome Other namesDilated cardiomyopathy-hypergonadotropic hypogonadism syndrome Malouf syndrome (also known as "congestive cardiomyopathy-hypergonadotropic hypogonadism syndrome") is a congenital disorder that causes one or more of the following symptoms: mental retardation, ovarian dysgenesis, congestive cardiomyopathy, broad nasal base, blepharoptosis, and bone abnormalities, and occasionally marfanoid habitus (tall stature with long and thin limbs, little subcutaneous fat, arachnodactyly, joint hyperextension, narrow face, small chin, large testes, and hypotonia).[2] This disease is named after J. Malouf, who performed a case study on a family suffering from this disease in 1985.[citation needed] ## References[edit] 1. ^ McKusick, Victor A. (1998). Mendelian Inheritance in Man: A Catalog of Human Genes and Genetic Disorders. JHU Press. p. 2066. ISBN 9780801857423. 2. ^ "Dilated cardiomyopathy with hypergonadotropic hypogonadism \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. ## External links[edit] Classification D * ICD-10: ICD-10: Q87.8 * OMIM: 212112 External resources * Orphanet: 2229 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	Malouf syndrome	c0796083	5,867	wikipedia	https://en.wikipedia.org/wiki/Malouf_syndrome	2021-01-18T19:01:18	{"mesh": ["C535580"], "umls": ["C0796083", "C0796031"], "orphanet": ["2229"], "wikidata": ["Q6744557"]}
Autosomal recessive spastic paraplegia type 64 is an extremely rare and complex form of hereditary spastic paraplegia (see this term), reported in only 4 patients from 2 families to date, characterized by spastic paraplegia (presenting between the ages of 1 to 4 years with abnormal gait) associated with microcephaly, amyotrophy, cerebellar signs (e.g. dysarthria) aggressiveness, delayed puberty and mild to moderate intellectual disability. SPG64 is due to mutations in the ENTPD1 gene (10q24.1), encoding ectonucleoside triphosphate diphosphohydrolase 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	Autosomal recessive spastic paraplegia type 64	c3810289	5,868	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=401810	2021-01-23T17:00:54	{"omim": ["615683"], "icd-10": ["G11.4"], "synonyms": ["SPG64"]}
A number sign (#) is used with this entry because of evidence that multiple types of cataract (CTRCT39) are caused by heterozygous mutation in the CRYGB gene (123670) on chromosome 2q34. Description Mutations in the CRYGB gene have been found to cause multiple types of cataract, which have been described as lamellar, anterior polar, and complete. Clinical Features AlFadhli et al. (2012) studied a 3-generation consanguineous Kuwaiti family segregating congenital cataract of multiple types in an autosomal dominant pattern. Four family members had lamellar cataracts, including the proband and her father, her paternal grandfather, and a cousin; 2 family members had anterior polar cataracts in the pupillary region, including the paternal grandmother, who was of Egyptian origin, and another cousin; and the proband's paternal uncle had complete cataracts. There was no history of other ocular or systemic abnormalities in the family. Mapping In a 3-generation Kuwaiti family segregating autosomal dominant congenital cataract, AlFadhli et al. (2012) performed genomewide linkage analysis and identified a region of potential linkage with a maximum lod score of 1.5 on chromosome 2q34; however, no mutations were found in the candidate gene CRYBA2 (600836) located in that region. The second highest lod score, 1.49, was obtained at 2q33-q37 and spanned the gamma-crystallin gene cluster. Inheritance The transmission pattern of cataract in the Kuwaiti family reported by AlFadhli et al. (2012) was consistent with autosomal dominant inheritance. Molecular Genetics In a 3-generation Kuwaiti family with autosomal dominant congenital cataract mapping to chromosome 2q33-q37, AlFadhli et al. (2012) screened the 4 candidate gamma-crystallin genes, CRYGA (123660), CRYGB (123670), CRYGC (123680), and CRYGD (123690), and identified 2 different mutations in the CRYGB gene, each with an autosomal dominant mode of inheritance. The first was a 1-bp deletion in exon 2 (123670.0001) that was maternally inherited from the Egyptian grandmother and segregated with anterior polar cataracts, and the other was a 1-bp intronic deletion (123670.0002) that was paternally inherited from the Kuwaiti grandfather and segregated with the lamellar cataract phenotype. The patient with complete cataracts was the only family member who was compound heterozygous for both mutations. Neither mutation was found in 50 age-, gender-, and ethnicity-matched controls. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Cataract, congenital \- Cataract, lamellar \- Cataract, anterior polar \- Cataract, complete MOLECULAR BASIS \- Caused by mutation in the gamma-B crystallin gene (CRYGB, 123670.0001 ) ▲ 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	CATARACT 39, MULTIPLE TYPES	c3808800	5,869	omim	https://www.omim.org/entry/615188	2019-09-22T15:52:58	{"doid": ["0110236"], "omim": ["615188"], "icd-10": ["Q12.0"], "orphanet": ["91492"], "synonyms": []}
A number sign (#) is used with this entry because rare germline mutations have been found in the MSR1 (153622), ASCC1 (614215), and CTHRC1 (610635) genes in patients with Barrett esophagus and/or esophageal adenocarcinoma. Description Barrett esophagus, or Barrett metaplasia, describes the phenotypic change of normal esophageal squamous epithelium to a columnar and intestinal-type epithelium. This metaplastic change is important because patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The main cause of Barrett metaplasia is gastroesophageal reflux (GER; 109350). The retrograde movement of acid and bile salts from the stomach into the esophagus in this disease causes prolonged injury to the esophageal epithelium and induces chronic esophagitis, which in turn is believed to trigger the pathologic changes (summary by Wong et al., 2005). Clinical Features Barrett (1950) described a patient with chronic ulcerating esophagitis in which columnar rather than squamous epithelium surrounded the ulcers. Allison and Johnstone (1953), followed by many others, showed that the columnar epithelium-lined intrathoracic structure is anatomically and functionally esophagus. The proximal esophagus usually retains its normal squamous epithelium. The Barrett esophagus is a complication of gastroesophageal reflux. Why it develops only in some patients is not clear; Sjogren and Johnson (1983) suggested that it 'may be congenitally determined in part.' Familial occurrence was reported by Borrie and Goldwater (1976). Adenocarcinoma of the esophagus has an incidence of about 10% in the Barrett esophagus. Adenocarcinoma constitutes a minority of esophageal cancers but most of these originate in a Barrett esophagus. Inheritance Gelfand (1983) reported Barrett esophagus in identical twins. Everhart et al. (1978, 1983) described Barrett esophagus in 3 persons in 2 generations of a family. Crabb et al. (1985) described a family in which the proband had both GER and Barrett esophagus, 3 of 5 children also had both, the other 2 children had only GER, and 2 grandchildren had GER. One of the children with both developed adenocarcinoma of the esophagus. McKusick (1986) stated that he had seen adenocarcinoma of the esophagus in a man with the Barrett anomaly whose brother died of esophageal cancer. Prior and Whorwell (1986) observed 2 affected sisters, each of whom presented at age 66. Jochem et al. (1992) described a family with 6 cases of Barrett esophagus, all in males, in 3 successive generations. In 3 of the patients there was associated adenocarcinoma. Cameron (1992) reviewed the literature on the genetics of Barrett esophagus. Drovdlic et al. (2003) studied a large series of families with Barrett esophagus and esophageal adenocarcinoma in search of evidence that a subset of this combination is the result of a hereditary predisposition. Studying 957 individuals in 70 families, 173 had a reported diagnosis of Barrett esophagus or carcinoma of the esophagus or esophagogastric junction: 101 had Barrett esophagus only, 52 had carcinoma of the esophagus and esophagogastric junction, and 20 had both Barrett esophagus and carcinoma. There were 133 affected males and 40 affected females, for a male:female ratio of 3.3:1. In 124 participants (12.9%), a cancer other than esophageal was reported. Of these, 15 had a diagnosis of Barrett esophagus or esophageal carcinoma and 109 did not. Pathogenesis In endoscopic tissue biopsies, Wong et al. (2005) found that CDX1 (600746) mRNA and protein were universally expressed in all samples of Barrett metaplasia (BM) tested but not in normal esophageal squamous or gastric body epithelia. They attributed this tissue-specific expression pattern to the methylation status of the CDX1 promoter, which was completely methylated in normal squamous and gastric epithelia but demethylated in a majority of DNA clones from BM tissue. Conjugated bile salts and the inflammatory cytokines TNF-alpha (191160) and IL1-beta (147720) increased CDX1 mRNA expression via the NFKB (see 164011) pathway in vitro, but only when the CDX1 promoter was unmethylated or partially methylated. Wong et al. (2005) suggested that CDX1 is the molecular link between the etiologic agents that cause BM and the induction of an intestinal phenotype, and that CDX1 promoter demethylation is the key trigger for the development of BM. Molecular Genetics In a study of 116 patients of European descent with Barrett esophagus and/or esophageal adenocarcinoma, Orloff et al. (2011) identified rare germline mutations in 3 different genes. Candidate genomic regions were studied after being identified by genomewide linkage analysis of 21 concordant and 11 discordant sib pairs with the disorders. A mutation in the MSR1 gene on chromosome 8p22 (R293X; 153622.0001) was found in 8 (6.9%) patients in the initial cohort and in 2 (3.4%) of 58 patients in a replication study. A second MSR1 mutation (L254V; 153622.0003) was found in 2 patients (1.7%) in the initial cohort. A mutation in the CTHRC1 gene on 8q22 (Q44P; 610635.0001) was found in 1 (1.1%) patient in the initial cohort and in 1 (1.7%) in the replication cohort, and a mutation in the ASCC1 gene on 10q22 (N290S; 614215.0001) was found in 2 (2.1%) patients in the initial cohort. ### Associations Pending Confirmation The Esophageal Adenocarcinoma Genetics Consortium and Wellcome Trust Case Control Consortium (2012) presented the first genomewide association study of Barrett esophagus susceptibility comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at 2 loci were associated with disease risk: rs9257809 on chromosome 6p21, within the MHC locus (combined p = 4.09 x 10(-9); OR = 1.21; 95% CI, 1.13-1.28); and rs9936833 on chromosome 16q24 (combined p = 2.74 x 10(-10); OR = 1.14; 95% CI, 1.10-1.19). The SNP rs9936833 resides 141 kb centromeric to FOXF1 (601089), a forkhead transcription factor in the hedgehog signaling pathway that has a role in the development of the gastrointestinal tract and has been reported to cause esophageal structural alterations when inactivated. The region around rs9936833 contains multiple binding sites for specific transcription factors, such as FOXP2 (605317), that control FOXF1 expression. The SNP rs9257809 lies on the telomeric edge of the MHC region. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	BARRETT ESOPHAGUS	c0279628	5,870	omim	https://www.omim.org/entry/614266	2019-09-22T15:55:53	{"doid": ["9206"], "mesh": ["C562730"], "omim": ["614266"], "icd-9": ["530.85"], "icd-10": ["K22.7", "K22.70"], "orphanet": ["99976"], "synonyms": ["Alternative titles", "BARRETT METAPLASIA"]}
Eccrine carcinoma Other namesSyringoid carcinoma Eccrine carcinoma, alveolar type SpecialtyDermatology Eccrine carcinoma is a rare skin condition characterized by a plaque or nodule on the scalp, trunk, or extremities.[1]:669 It originates from the eccrine sweat glands of the skin, accounting for less than 0.01% of diagnosed cutaneous malignancies.[2] Eccrine carcinoma tumors are locally aggressive with a high rate of recurrence. Lack of reliable immunohistochemical markers and similarity to other common tumors has made identification of eccrine carcinoma difficult.[2] ## Contents * 1 Symptoms * 2 Complications * 3 Types * 4 Causes * 5 Diagnosis * 6 Treatment * 7 Prognosis * 8 Frequency * 9 See also * 10 References * 11 External links ## Symptoms[edit] Eccrine carcinoma results in brown, bluish, erythematous skin lesions across the body. Common regions where lesions are found are in the lower extremities (35%), head and neck (24%), and upper extremities (14%).[3][4] ## Complications[edit] Metastases and/or antagonistic side effects can occur after surgical excision of tumors.[2] ## Types[edit] Eccrine carcinoma tumors consist of two types: malignant and benign. Malignant tumors include porocarcinoma, hidradenocarcinoma, malignant spiradenoma carcinoma, malignant cylindroma, syringoid eccrine carcinoma, microcystic adnexal carcinoma, mucinous carcinoma, adenoid cystic carcinoma, and ductal papillary adenocarcinoma.[2] Benign tumors include poroma, hidradenoma, spiradenoma, cylindroma, syringometaplasia, syringoma, syringofibroadenoma, and chondroid syringoma.[2] Other tumors not classified include eccrine ductal carcinoma, basaloid eccrine carcinoma, clear cell eccrine carcinoma and non-specified sweat gland carcinomas.[2] ## Causes[edit] There is no research yet as to what causes Eccrine carcinoma.[2] ## Diagnosis[edit] A skin biopsy is the common test used to diagnose Eccrine Carcinoma.[2] The biopsy will detect growth of new or abnormal tissue. Another test that can be performed is using Immunohistochemistry, but it is inconsistent.[2] Markers used to detect Eccrine Carcinoma consist of carcinoembryonic antigen, progesterone receptors, estrogen receptors, epithelial membrane antigen, pancytokeratins, and cytokeratin 7.[5][6] ## Treatment[edit] Treatment requires surgical excision of tumors brought upon by Eccrine Carcinoma.[7] To treat lesions, chemotherapy and radiation therapy have been used.[8] ## Prognosis[edit] Eccrine carcinoma has a relative mortality rate of 80%, and the 10-year overall survival rate is 9%.[3] ## Frequency[edit] Eccrine carcinoma accounts for 0.005-0.01% of diagnosed cutaneous malignancies.[9] ## See also[edit] * Microcystic adnexal carcinoma * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 2. ^ a b c d e f g h i Kaseb, Hatem; Babiker, Hani M. (2020), "Cancer, An Overview of Eccrine Carcinoma", StatPearls, StatPearls Publishing, PMID 31082086, retrieved 2020-04-22 3. ^ a b Larson, Kristian; Babiker, Hani M.; Kovoor, Andrew; Liau, Joy; Eldersveld, Jordan; Elquza, Emad (2018). "Oral Capecitabine Achieves Response in Metastatic Eccrine Carcinoma". Case Reports in Oncological Medicine. 2018: 1–5. doi:10.1155/2018/7127048. ISSN 2090-6706. PMC 5852884. PMID 29686913. 4. ^ Idrissi Serhrouchni, Karima; Harmouch, Taoufiq; Chbani, Laila; El Fatemi, Hind; Sekal, Mohammed; Hammas, Nawal; Soughi, Meriem; Benchat, Loubna; Amarti, Afaf (2013-02-04). "Eccrine carcinoma: a rare cutaneous neoplasm". Diagnostic Pathology. 8 (1): 15. doi:10.1186/1746-1596-8-15. ISSN 1746-1596. PMC 3570399. PMID 23379908. 5. ^ Swanson, P. E.; Cherwitz, D. L.; Neumann, M. P.; Wick, M. R. (1987–2004). "Eccrine sweat gland carcinoma: an histologic and immunohistochemical study of 32 cases". Journal of Cutaneous Pathology. 14 (2): 65–86. doi:10.1111/j.1600-0560.1987.tb00477.x. ISSN 0303-6987. PMID 2439558. S2CID 1897717. 6. ^ Ohnishi, Takamitsu; Kaneko, Sakae; Egi, Motoko; Takizawa, Hajime; Watanabe, Shinichi (2002–2010). "Syringoid Eccrine Carcinoma". The American Journal of Dermatopathology. 24 (5): 409–413. doi:10.1097/00000372-200210000-00007. ISSN 0193-1091. PMID 12357203. S2CID 20147934. 7. ^ Moy, Ronald L.; Rivkin, Jonathan E.; Lee, Hyo; Brooks, Walter S.; Zitelli, John A. (1991–2005). "Syringoid eccrine carcinoma". Journal of the American Academy of Dermatology. 24 (5): 857–860. doi:10.1016/0190-9622(91)70133-m. ISSN 0190-9622. PMID 2050853. 8. ^ Sidiropoulos, M.; Sade, S.; Al-Habeeb, A.; Ghazarian, D. (2011-06-04). "Syringoid eccrine carcinoma: a clinicopathological and immunohistochemical study of four cases". Journal of Clinical Pathology. 64 (9): 788–792. doi:10.1136/jclinpath-2011-200069. ISSN 0021-9746. PMID 21642659. S2CID 46508699. 9. ^ Salih, Abdulwahid M.; Kakamad, F.H.; Essa, Rawand A.; Rauf, Goran M.; S.A., Masrur; H.M., Shvan; Q.S., Rawezh; A.H., Hunar; A.H., Dahat; Othman, Snur (2017). "Porocarcinoma: A systematic review of literature with a single case report". International Journal of Surgery Case Reports. 30: 13–16. doi:10.1016/j.ijscr.2016.10.051. ISSN 2210-2612. PMC 5128823. PMID 27898349. ## External links[edit] Classification D External resources eMedicine: article/1101796 * v * t * e Cancers of skin and associated structures Glands Sweat gland Eccrine * Papillary eccrine adenoma * Eccrine carcinoma * Eccrine nevus * Syringofibroadenoma * Spiradenoma Apocrine * Cylindroma * Dermal cylindroma * Syringocystadenoma papilliferum * Papillary hidradenoma * Hidrocystoma * Apocrine gland carcinoma * Apocrine nevus Eccrine/apocrine * Syringoma * Hidradenoma or Acrospiroma/Hidradenocarcinoma * Ceruminous adenoma Sebaceous gland * Nevus sebaceous * Muir–Torre syndrome * Sebaceous carcinoma * Sebaceous adenoma * Sebaceoma * Sebaceous nevus syndrome * Sebaceous hyperplasia * Mantleoma Hair * Pilomatricoma/Malignant pilomatricoma * Trichoepithelioma * Multiple familial trichoepithelioma * Solitary trichoepithelioma * Desmoplastic trichoepithelioma * Generalized trichoepithelioma * Trichodiscoma * Trichoblastoma * Fibrofolliculoma * Trichilemmoma * Trichilemmal carcinoma * Proliferating trichilemmal cyst * Giant solitary trichoepithelioma * Trichoadenoma * Trichofolliculoma * Dilated pore * Isthmicoma * Fibrofolliculoma * Perifollicular fibroma * Birt–Hogg–Dubé syndrome Hamartoma * Basaloid follicular hamartoma * Folliculosebaceous cystic hamartoma * Folliculosebaceous-apocrine hamartoma Nails * Neoplasms of the nailbed [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Eccrine carcinoma	c1302864	5,871	wikipedia	https://en.wikipedia.org/wiki/Eccrine_carcinoma	2021-01-18T18:36:18	{"umls": ["C1302864"], "wikidata": ["Q5332314"]}
Fragile XE syndrome (FRAXE) is a genetic condition associated with mild to borderline intellectual disabilities with physical features differing from person to person. The characteristic features are learning difficulties, often a consequence of communication problems (speech delay, poor writing skills), hyperactivity, and a shortened attention span. Nearly all cases of FRAXE are caused by a specific type of mutation, called a trinucleotide repeat expansion, in the AFF2 gene, which is located on the X chromosome. A trinucleotide repeat expansion occurs when there is an abnormally large number of repeats of a specific sequence of three nucleotides (building block of DNA) within our DNA. The repeating nucleotides in FRAXE syndrome are CCG. When the number of CCG repeats is over 200, people typically have the signs and symptoms seen in FRAXE. FRAXE is inherited in an X-linked manner. Although there is no specific treatment for FRAXE, there may be ways to manage the symptoms. A team of doctors or specialists is often needed to figure out the treatment options for each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Fragile XE syndrome	c0751157	5,872	gard	https://rarediseases.info.nih.gov/diseases/2378/fragile-xe-syndrome	2021-01-18T18:00:26	{"mesh": ["D005600"], "omim": ["309548"], "orphanet": ["100973"], "synonyms": ["X-linked mental retardation associated with fragile site FRAXE", "Fragile site, folic acid type", "Intellectual disability associated with fragile site FRAXE", "FRAXE syndrome"]}
Gates (1946) cited a family in which the grandfather showed bilaterally a radial artery that passed over the supinator longus muscle 3 to 4 cm above the wrist and ran over the radial extensors above the styloid process. All his children were said to have the same anomaly on the left side. Among his grandchildren the anomaly was found on both sides in 4, on one side in 4, and on neither side in 7. Barbosa Sueiro (1933-34) described the case of a man in whom the ulnar artery on the left arm ran along the medial border of the biceps, arising by precocious bifurcation of the branchial artery. There was also a superficial right interosseous artery. The latter condition was present also in the father and a brother and the former condition in the 2 brothers. Schneck (1879) described the Brown family in which 15 of 22 members of 3 generations showed an abnormal course of 1 or both radial arteries. Out of 44 arteries, the same abnormal course was taken 19 times. Both arteries were abnormal in 4 individuals; both were normal in 7. The right only was abnormal twice and the left only was abnormal 9 times. The artery took the usual course until within 3 to 4 cm of the wrist, according to the length of the arm, when suddenly it turned backwards over the supinator longus muscle, passing on the outside of the extensor tendons of the thumb and above the styloid process of the radius, thence behind the thumb into the palm, to form the palmar arch. Persons marrying into the family all showed radial arteries. This was clearly the family cited by Gates (1946). Inheritance \- Autosomal dominant Vascular \- Abnormal radial, ulnar, or interosseous artery ▲ 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	ARTERIES, ANOMALIES OF	c1876179	5,873	omim	https://www.omim.org/entry/108000	2019-09-22T16:44:45	{"omim": ["108000"]}
Cronkhite-Canada syndrome is a rare gastrointestinal disorder characterized by widespread colon polyps, unhealthy looking (dystrophic) nails, hair loss (alopecia), darkening skin (such as on the hands, arms, neck and face), diarrhea, weight loss, stomach pain, and/or excess fluid accumulation in arms and legs (peripheral edema). The cause of the condition is not known. Treatment aims to control symptoms and provide adequate nutrition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Cronkhite-Canada disease	c0282207	5,874	gard	https://rarediseases.info.nih.gov/diseases/4427/cronkhite-canada-disease	2021-01-18T18:01:02	{"mesh": ["D044483"], "omim": ["175500"], "orphanet": ["2930"], "synonyms": ["Polyposis skin pigmentation alopecia fingernail changes"]}
A rare acquired immunodeficiency disorder characterized by the appearance of susceptibility to disseminated opportunistic infections (in particular, disseminated nontuberculous mycobacterial infection, salmonellosis, penicillosis, and varicella zoster virus infection) in previously healthy (HIV-negative) adults, associated with the presence of acquired autoantibodies to interferon gamma. Typical clinical manifestation includes lymphadenopathy (cervical or generalized), fever, weight loss and/or reactive skin lesions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Adult-onset immunodeficiency with anti-interferon-gamma autoantibodies	None	5,875	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=306431	2021-01-23T18:52:48	{"gard": ["11992"], "icd-10": ["D84.8"], "synonyms": ["Acquired adult-onset immunodeficiency", "Adult-onset immunodeficiency with acquired anti-interferon-gamma autoantibodies"]}
For a phenotypic description and a discussion of genetic heterogeneity of familial thoracic aortic aneurysm, see 607086. Mapping Guo et al. (2001) reported a number of families with clear autosomal dominant inheritance of thoracic aneurysms and dissections. In 2 large families, linkage to FBN1 (134797) was excluded prior to a genomewide linkage analysis. Three loci showed a significant association with the disease. Subsequent multipoint analyses using a total of 15 families revealed a maximum lod score of 4.74 (theta = 0.0) at marker D5S2029, and haplotype analyses refined the disease interval to a 7.8-cM region between D5S806 and D5S641 at chromosome 5q13-q14. Candidate genes mapping to this interval were screened for mutations, but none were identified. Overall, of the 15 families included in the study, 9 showed linkage to this locus. A further family demonstrated evidence of linkage to chromosome 11q, although this could not be confirmed owing to a lack of affected family members. Kakko et al. (2003) genotyped 115 members of 11 Finnish families segregating thoracic aortic aneurysms and dissections and confirmed linkage to 5q13-q14. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	AORTIC ANEURYSM, FAMILIAL THORACIC 2	c1846837	5,876	omim	https://www.omim.org/entry/607087	2019-09-22T16:09:43	{"doid": ["14004"], "mesh": ["C564627"], "omim": ["607087"], "orphanet": ["91387"], "synonyms": ["FAA2", "Alternative titles", "Familial TAAD"], "genereviews": ["NBK1120"]}
## Clinical Features Rotenstein et al. (1982) described a family in which 4 females in 3 successive generations shared the clinical triad of fever, hypertension, and juvenile polyarthritis, along with the pathologic feature of noncaseating granulomas in vascular and extravascular distribution. The proband was a 5-year-old white girl who at age 8 months developed fever and a persistent macular erythematous rash. At 10 months nodules were noted on her wrists. At 18 months she had fever and symmetrical swelling, warmth and redness of hands, knees, and ankles, and pericardial effusion was noted. At age 4.5 years she had spiking fever, headache, and a seizure, with blood pressure of 200-140 mm Hg, bilateral iritis, papilledema, and pericardial friction rub. Abdominal aortograms showed beading of the splenic, renal and iliac arteries, proximal stenosis and poststenotic dilatation, and intrarenal arterial stenoses. Skin biopsy showed noncaseating granulomatous inflammation. After 1 year of therapy with prednisone and cyclophosphamide, aortograms showed dramatic improvement. In her mother, the diagnosis of rheumatoid arthritis with features of Still disease was made at age 8 years; in her twenties, she had 5 episodes of unexplained fever. At age 28, she developed fever, jaundice, and elevated alkaline phosphatase; liver biopsy showed noncaseating granulomas. At age 35 she had a pleural effusion. The proband's maternal grandmother, aged 62, had juvenile-onset polyarthritis, unexplained fever only during childhood, recent chronic iritis and noncaseating granulomas on conjunctival biopsy. The proband's maternal aunt, who died at age 24, had rheumatoid arthritis with features of Still disease beginning at age 8 years. Throughout her life, she had recurrent episodes of unexplained fever. In a final hospitalization she had seizures and severe hypertension. Autopsy showed systemic noncaseating granulomas. Di Liberti (1982) suggested that the patients reported by Rotenstein et al. (1982) had the same disorder as that in a family he and his associates presented at the 1974 Birth Defects Conference in Newport Beach, California. Five persons in 2 generations had arthritis beginning in early childhood and initially affecting the hands, wrists and ankles. The dorsal tendon sheaths of the hands and feet were particularly involved. By late childhood the swelling had diminished, but flexion contractures of the fingers and elbows were evident. Periarticular osteoporosis was also present. One child had iritis with prominent synechiae. He died suddenly at play, and at autopsy had granulomatous arteritis of the aorta, coronary arteries, kidneys, liver and other organs. The coronary arteries were almost totally occluded. Although some features suggested childhood sarcoidosis, the conspicuous arteritis is probably a differentiating feature. Malleson et al. (1981) reported a Mexican-American family in which the mother and a daughter and 3 sons had camptodactyly and arthritis. Another son had arthritis but no camptodactyly. One of the affected sons died at age 4.5 years and was shown to have granulomatous arteritis which affected the aorta, pericardium, myocardium, and coronary arteries. He had also had chronic bilateral iridocyclitis. Some of these features suggest Jabs syndrome (186580). INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Iritis \- Papilledema CARDIOVASCULAR Heart \- Pericardial effusion Vascular \- Granulomatous coronary arteritis \- Abdominal aortograms show beading of the splenic, renal and iliac arteries, proximal stenosis and poststenotic dilatation, and intrarenal arterial stenoses RESPIRATORY Lung \- Pleural effusion SKIN, NAILS, & HAIR Skin \- Macular erythematous rash \- Subcutaneous nodules \- Jaundice NEUROLOGIC Central Nervous System \- Headache \- Seizures METABOLIC FEATURES \- Fever ENDOCRINE FEATURES \- Hypertension IMMUNOLOGY \- Juvenile polyarthritis \- Rheumatoid arthritis \- Noncaseating granulomas, vascular and extravascular, especially hepatic LABORATORY ABNORMALITIES \- Elevated alkaline phosphatase ▲ 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	ARTERITIS, FAMILIAL GRANULOMATOUS, WITH JUVENILE POLYARTHRITIS	c1862510	5,877	omim	https://www.omim.org/entry/108050	2019-09-22T16:44:45	{"mesh": ["C566253"], "omim": ["108050"]}
For a phenotypic description and a discussion of genetic heterogeneity of absorptive hypercalciuria, see 143870. Imamura et al. (1998) reported the cases of 2 unrelated girls with multiple malformations, each of whom had an unbalanced translocation chromosome with deletion of the 4q33-qter segment and addition of a segment from another unidentified chromosome. One of the 2 girls had asymptomatic kidney stones. Both had excess urinary calcium excretion, exaggerated excretion on oral calcium load, and reduced but excessive excretion on restricted calcium intake. The urinary calcium excretion of their parents was normal. Both girls were thus diagnosed to have sporadic absorptive hypercalciuria. Imamura et al. (1998) suggested that the 4q33-qter segment contains the putative gene for absorptive hypercalciuria. Townes et al. (1979) recognized deletion of the terminal region of the long arm of chromosome 4 as a distinct syndrome. The syndrome comprises minor facial anomalies, cleft palate, limb and digital abnormalities (especially of the fifth finger), congenital heart defects, postnatal growth deficiency, and developmental delay. Giuffre et al. (2004) described a newborn girl with a de novo terminal 4q deletion (4q31.3-qter) and a characteristic phenotype of minor facial anomalies, cleft palate, congenital heart defect, abnormalities of hands and feet, and postnatal growth deficiency. Excessive urinary calcium excretion on standard milk formula and on oral calcium load was found. At 2 months of age, ultrasound showed kidney calcifications. Clinical and laboratory data supported the diagnosis of absorptive hypercalciuria or abnormal regulation of calcium-sensing receptors in the renal tubules. The findings supported the hypothesis that a putative gene for hypercalciuria is located on the terminal segment of 4q. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	HYPERCALCIURIA, ABSORPTIVE, 1	c0543800	5,878	omim	https://www.omim.org/entry/607258	2019-09-22T16:09:28	{"omim": ["607258"], "orphanet": ["2197"], "synonyms": ["Alternative titles", "HCA1"]}
Not to be confused with polydipsia. Dipsomania, an 18th-century woodcarving by Josef Stammel in the library of Admont Abbey. Dipsomania is a historical term describing a medical condition involving an uncontrollable craving for alcohol. In the 19th century, the term dipsomania was used to refer to a variety of alcohol-related problems, most of which are known today as alcoholism. Dipsomania is occasionally still used to describe a particular condition of periodic, compulsive bouts of alcohol intake. The idea of dipsomania is important for its historical role in promoting a disease theory of chronic drunkenness. The word comes from Greek dipso (Greek: "δίψα"= thirst) and mania. It is mentioned in the WHO ICD-10 classification as an alternative description for Alcohol Dependence Syndrome, episodic use F10.26. ## Contents * 1 History * 1.1 Examples in fiction * 1.2 Examples in science * 2 See also * 3 References * 4 External links ## History[edit] The term was coined by the German physician Christoph Wilhelm Hufeland in 1819, when, in a preface to an influential book by German-Russian doctor C. von Brühl-Cramer,[1] he translated Brühl-Cramer's term "trunksucht" as "dipsomania".[2] [3][4] Brühl-Cramer classified dipsomania in terms of continuous, remittent, intermittent, periodic and mixed forms, and in his book he discussed its cause, pathogenesis, sequelae, and treatment options, all influenced by prevailing ideas about the laws of chemistry and concepts of excitability.[5] Due to the influence of Brühl-Cramer's pioneering work, dipsomania became popular in medical circles throughout the 19th century.[6] Political scientist Mariana Valverde describes dipsomania as "the most medical" of the many terms used to describe habitual drunkenness in the 19th century.[7] Along with terms such as "inebriety", the idea of dipsomania was used as part of an effort of medical professionals and reformers to change attitudes about habitual drunkenness from being a criminally punishable vice to being a medically treatable disease.[8] As historian Roy MacLeod wrote about this dipsomania reform movement, it "illuminates certain features of the gradual transformation taking place in national attitudes towards the prevention and cure of social illnesses during the last quarter of the 19th century."[8] Although dipsomania was used in a variety of somewhat contradictory ways by different individuals, by the late 19th century the term was usually used to describe a periodic or acute condition, in contrast to chronic drunkenness.[9] In his 1893 book Clinical Lessons on Mental Diseases: The Mental State of Dipsomania, Magnan characterized dipsomania as a crisis lasting from one day to two weeks, and consisting of a rapid and huge ingestion of alcohol or whatever other strong, excitatory liquid was available.[9] Magnan further described dipsomania as solitary alcohol abuse, with loss of all other interests, and these crises recurred at indeterminate intervals, separated by periods when the subject was generally sober.[9] Similarly, in 1892 the influential English physician and mental health expert Daniel Hack Tuke defined dipsomania as a syndrome involving "an irresistible obsession and impulse to drink, coming on in attacks, during which the patients are in a condition of impotence of will and manifest great anguish."[10] Tuke clarifies that dipsomania can be distinguished from what was at the time considered alcoholism by six key factors. First, "an alcoholic patient becomes insane because he drinks; a dipsomaniac is insane before he commences to drink."[11] Second,"alcoholism is an intoxication which has as its cause alcohol; dipsomania has its cause in a defective mental condition, and alcohol is but a secondary factor, which may be replaced by any other poison, leaving to the syndrome all its psychological characters."[12] Third, "dipsomania proceeds in paroxysmal attacks, and the appetite for strong drink is absent during the intervals between the attacks. Alcoholism has no definite course." [12] Fourth, "a dipsomaniac satisfies a pathological and imperious want; he does not like alcohol, and takes it against his will," whereas "an alcoholic individual has no actual want; he only obeys a vice, a proclivity, and an alteration of his moral sense."[12] Fifth, a dipsomaniac is conscious and ashamed of his condition, whereas an alcoholic is sometimes unaware of, but more often indifferent to it. Finally, he concluded that "dipsomania is a syndrome, always identical with itself, whilst alcoholism is an intoxication varying much in its clinical symptoms."[12] Over time, the term dipsomania became less common, replaced by newer ideas and terms concerning chronic and acute drunkenness and alcoholism.[13] ### Examples in fiction[edit] * Sebastian Flyte, a character from the novel Brideshead Revisited by Evelyn Waugh, who sarcastically describes himself as a dipsomaniac * James O. Incandenza, a character in Infinite Jest by David Foster Wallace, described in the novel as having "crippling dipsomania" * Dwight Carson, a talented writer in The Fountainhead, who is turned into a dipsomaniac on the whim of Gail Wynand * Mrs. Ritchey (played by actress Charlotte Merriam in the 1931 movie Night Nurse) who exclaims that she is a dipsomaniac several times when confronted by Barbara Stanwyck's character (Lora Hart) with the fact that Ritchey's daughter is dying from malnutrition * Peter Morgan Sr., (played by actor Charles Coburn) in the 1938 movie Vivacious Lady, talks about his nephew Keith Morgan's (played by James Ellison) dipsomania ways * Richard Gilmore, a character in the TV series Gilmore Girls, refers to a fundraiser speaker as a dipsomaniac in the season one episode "P.S. I Lo..." * Susanna Conolly (alias Lalage Virtue, a talented singer and player), in GB Shaw's first novel The Irrational Knot.[14] * Raymond Reddington, a character played by actor James Spader in the TV series The Blacklist, uses the term while referring to a bogus DUI charge being used as blackmail in the season 4 episode "Lipet's Seafood Company (No. 111)". ### Examples in science[edit] * William Thomson, 1st Baron Kelvin writing to George FitzGerald on April 9, 1896:[15] "I have not had a moment's peace or happiness in respect to electromagnetic theory since Nov. 28, 1846 (see vol i. p. 80 M.P.P). "All this time I have been liable to fits of ether dipsomania, kept away at intervals only by rigorous abstention from thought on the subject." ## See also[edit] * Potomania * Zapoy ## References[edit] Citations 1. ^ Hasso Spode: Die Macht der Trunkenheit. Sozial- und Kulturgeschichte des Alkohols, Opladen 1993, pp. 125ff. 2. ^ Kielhorn, Friedrich-Wilhelm (January 1996). "The History of Alcoholism: Brühl-Cramer's Concepts and Observations". Addiction. 91 (1): 121–128. PMID 8822020. Archived from the original on 2012-09-10 – via Wiley Online Library. 3. ^ Valverde, Mariana (1998). Diseases of the Will. Cambridge: Cambridge University Press. pp. 48. ISBN 978-0-521-64469-3. "valentin magnan dipsomania." 4. ^ Peters, Uwe Henrik. Lexikon Psychiatrie, Psychotherapie, Medizinische Psychologie. Dipsomania entry at Google Books. 5. ^ Wiley.com journal 6. ^ NLA record 7. ^ Tracy, Sarah W. (2005). Alcoholism in America: From Reconstruction to Prohibition, Baltimore: Johns Hopkins University Press, p.31. 8. ^ a b "Extract at sagepub.com". Archived from the original on 2013-02-01. Retrieved 2009-04-26. 9. ^ a b c Dipsomania entry at Psychoanalysis Encyclopedia 10. ^ Tuke 1892, p. 389. 11. ^ Tuke 1892, p. 394 12. ^ a b c d Tuke 1892, p. 395. 13. ^ Tracy, Sarah (2005). Alcoholism in America. Baltimore: Johns Hopkins University Press. p. 31. ISBN 978-0-8018-8119-0. 14. ^ "The Irrational Knot". 15. ^ Thompson, Silvanius P. (1910). The Life of William Thomson: Baron Kelvin of Largs (First ed.). London: Macmillan and Co., Limited. p. 1065. Works cited * Tuke, Daniel Hack (1892). A Dictionary of Psychological Medicine: Giving the Definition, Etymology and Synonyms of the Terms Used in Medical Psychology with the Symptoms, Treatment, and Pathology of Insanity and the Law of Lunacy in Great Britain and Ireland. 1. Philadelphia: J. & A. Churchill.CS1 maint: ref=harv (link) ## External links[edit] * Bucknill, John Charles; Daniel Hack Tuke (1879). A Manual of Psychological Medicine: Containing the Lunacy Laws, the Nosology, Aetiology, Statistics, Description, Diagnosis, Pathology, and Treatment of Insanity (Fourth ed.). London: J. & A. Churchill. p. 287. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Dipsomania	c0001973	5,879	wikipedia	https://en.wikipedia.org/wiki/Dipsomania	2021-01-18T18:57:54	{"mesh": ["D000437"], "wikidata": ["Q2717096"]}
Coral dermatitis SpecialtyDermatology Coral dermatitis is a cutaneous condition caused by injury from the exoskeleton of certain corals.[1]:430 ## See also[edit] * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. * v * t * e Corals and coral reefs Stony corals * Blue * Brain * Elegance * Elkhorn * Hermatypic * Chalice * Pillar * Staghorn * Table Soft corals * Bamboo * Black * Organ pipe * Sea fans * Sea pens Coral reefs * Atoll * Cay * Coral * Fringing * Microatoll * Coral reef fish * Census of Coral Reefs * The Structure and Distribution of Coral Reefs * Catlin Seaview Survey * Spur and groove formation Coral regions * List of reefs * Deep-water coral * African coral reefs * Amazon Reef * Andros, Bahamas * Belize Barrier Reef * Coral Sea Islands * Coral Triangle * East African coral coast * Florida Keys National Marine Sanctuary * Great Barrier Reef * Maldives * Mesoamerican Barrier Reef System * New Caledonia barrier reef * Pulley Ridge * Raja Ampat Islands * Red Sea * Solomon Archipelago * Southeast Asian coral reefs Coral diseases * Coral bleaching * Black band disease * Skeletal eroding band * Stony coral tissue loss disease * White band disease * White pox disease Protection * Coral Reef Alliance * Coral reef protection * Green Fins * International Coral Reef Society * Project AWARE * Reef Check * Reef Ball Symbiotic algae * Zooxanthellae * Amphidinium * Symbiodinium Other * Artificial reef * Aquaculture of coral * Coral dermatitis * Precious coral * Coral in non-tropical regions * Coral rag * Coral reef organizations * Coral sand * Coralline algae * Environmental issues with coral reefs * Fire coral * Reef resilience * Rugosa (extinct) * Tabulata * v * t * e Animal bites and stings Arthropod bites and stings Arachnid * Demodex mite bite * Scorpion sting * Spider bite / Arachnidism * Latrodectism * Loxoscelism Insects * Ant sting * Bee sting * Cimicosis * Mosquito bite * Pulicosis * Reduviid bite Myriapoda * Centipede bite * Millipede burn Vertebrate * Alligator attack * Bear attack * Beaver attack * Boar attack * Cougar attack * Cat bite * Coyote attack * Crocodile attack * Dingo attack * Dog attack * Killer whale attack * Leopard attack * Lion attack * Monkey bite * Piranha fish attack * Shark attack * Snakebite * Stingray attack * Stonefish attack * Tiger attack * Venomous fish * Walrus attack * Wolf attack Other * Animal attacks * Bristleworm sting * Cephalopod attack * Cone snail sting * Coral dermatitis * Dog bite prevention * Hydroid dermatitis * Jellyfish dermatitis / Jellyfish sting * Leech bite * Man-eater * Portuguese man-of-war dermatitis * Sea anemone dermatitis * Sea urchin injury * Seabather's eruption This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Coral dermatitis	c0413141	5,880	wikipedia	https://en.wikipedia.org/wiki/Coral_dermatitis	2021-01-18T18:28:24	{"umls": ["C0413141"], "wikidata": ["Q5169523"]}
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-67 (RP67) is caused by homozygous mutation in the NEK2 gene (604043) on chromosome 1q32. One such family has been reported. Description Retinitis pigmentosa (RP) is the name given to a group of hereditary retinal conditions in which degeneration of rod photoreceptors, responsible for vision under dark conditions, is more pronounced than that of cone photoreceptors, which mediate daylight vision. Individuals with RP typically experience night blindness at first, followed by progressive and unstoppable visual impairment in daytime conditions as well. Their visual fields become reduced gradually and sight is lost from the midperiphery to the periphery, then from the midperiphery to the center, resulting eventually in complete or near-complete blindness if left untreated. Most patients show intraretinal pigment in a bone-spicule configuration around the fundus periphery as well as retinal arteriolar attenuation, elevated final dark-adapted thresholds, and reduced and delayed electroretinograms. Autosomal recessive RP is the most common form of hereditary retinal degeneration in humans (summary by Nishiguchi et al., 2013). For a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. Molecular Genetics Nishiguchi et al. (2013) performed whole-genome sequencing in 16 unrelated RP patients from diverse ethnic backgrounds, and in 1 Japanese female patient, who did not have any clear-cut mutations in known RP genes, they identified a homozygous frameshift mutation in the NEK2 gene (604043.0001). The mutation was not detected in 1,273 Japanese and 95 North American controls, and inactivation of Nek2 in zebrafish induced retinal photoreceptor defects that were rescued by human NEK2 mRNA. Analysis of the NEK2 gene in a mixed cohort of 192 American and 64 Japanese RP patients, as well as in 13 patients with retinal degeneration who had previously shown linkage to the NEK2 region, identified a Japanese male patient with apparent autosomal recessive RP who was heterozygous for the same NEK2 frameshift mutation. However, he also carried a frameshift mutation in the known RP-associated RPGR gene (312610.0026) that had previously been described as a sufficient cause of X-linked RP (see 300029) by Vervoort et al. (2000); studies in zebrafish suggested that the RPGR allele interacts in trans with the NEK2 locus to exacerbate photoreceptor defects. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Retinitis pigmentosa MISCELLANEOUS \- No clinical description given for 1 reported patient (last curated December 2013) MOLECULAR BASIS \- Caused by mutation in the never-in-mitosis gene A-related kinase-2 gene (NEK2, 604043.0001 ) ▲ 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	RETINITIS PIGMENTOSA 67	c0035334	5,881	omim	https://www.omim.org/entry/615565	2019-09-22T15:51:37	{"doid": ["0110359"], "mesh": ["D012174"], "omim": ["615565"], "orphanet": ["791"]}
Allochiria Allochiria is most frequently associated with a lesion of the right parietal lobe (in yellow, at top) SpecialtyNeurology Allochiria is a neurological disorder in which the patient responds to stimuli presented to one side of their body as if the stimuli had been presented at the opposite side.[1] It is associated with spatial transpositions, usually symmetrical, of stimuli from one side of the body (or of the space) to the opposite one. Thus a touch to the left side of the body will be reported as a touch to the right side, which is also known as somatosensory allochiria.[2] If the auditory or visual senses are affected, sounds (a person's voice for instance) will be reported as being heard on the opposite side to that on which they occur and objects presented visually will be reported as having been presented on the opposite side. Often patients may express allochiria in their drawing while copying an image. Allochiria often co-occurs with unilateral neglect and, like hemispatial neglect, the disorder arises commonly from damage to the right parietal lobe.[1] Allochiria is often confused with alloesthesia, also known as false allochiria.[3] True allochiria is a symptom of dyschiria and unilateral neglect.[4] Dyschiria is a disorder in the localization of sensation due to various degrees of dissociation and cause impairment in one side causing the inability to tell which side of the body was touched. The term is from the Greek meaning "other hand". ## Contents * 1 Definitional criteria * 2 Types * 2.1 Electromotor allochiria * 2.2 Motor allochiria * 2.3 Reflex allochiria * 2.4 Auditory allochiria * 2.5 Visual allochiria * 2.6 Gustatory allochiria * 3 Alloesthesia * 4 Dyschiria * 4.1 Achiria * 4.2 Allochiria * 4.3 Synchiria * 5 Experiences * 6 Diagnosis * 6.1 Diagnostic value * 7 Theory * 8 See also * 9 References ## Definitional criteria[edit] Animation. Parietal lobe (red). Allochiria has been observed mainly in the context of neglect which is usually due to a lesion that affects the right parietal lobe.[3] In patients with allochiria, their sensibility is retained completely but the patient is not clear as to which side of the body has been touched. Their power of localization is retained but error exists to the side touched and they often refer the irritation to the corresponding part of the limb.[5] In the patients' mind there is doubt or error as to which side of the body is touched. There are multiple definitions of allochiria. According to Musser, allochiria is the reference of a sensory stimulus to the corresponding location on the opposite location on the opposite side of the body.[6] Judson Bury says that a patient may refer to an impression on one side to a corresponding place on the opposite side of the body.[7] Thus, if a patient is pricked on one limb, he may say that he feels it on the other. Overall, even though different author's definition differs on points such as the type of stimulus, and the symmetry between the site of the stimulus and the seat of its localization, they all agree that an essential feature of allochiria is the deflection of a sensation to the wrong side of the body, which is true allochiria. In none of these definitions is any stress laid on the state of the patient's knowledge of a right or left side and the symptoms are seen as an error in localization. Obsersteiner laid stress that there is in allochiria no defect in vertical localization but merely confusion in the patient's mind between the opposite sides of the body and come to look upon the symptom as simply any form of bad mistake in localization.[8] There is in the patient's mind doubt or error as to the side touched while sensibility including the power of localization is otherwise retained. Allochiria has been described as occurring in nerve lesions, Hemiplegia, disseminated sclerosis Multiple sclerosis, tabes dorsalis, unilateral injury to the spinal cord, Ménière's disease, hysteria, symmetrical gangrene,[9] and in connection with touch, pain, the "muscle sense," the temperature sense, sight, smell, taste, hearing, and the electrical reactions.[10] Allochiria can occur in relation to any or every segment of the body. In some cases allochiria may be bilateral, and in others it may be restricted to certain regions of the body, or even only to one part of the body. Allochiria is marked to have connections with a variety of senses and sometimes only certain kinds of stimuli can arouse the appropriate feeling of one sidedness.[11] ## Types[edit] ### Electromotor allochiria[edit] This is seen when there is a cross of electrical reflexes as a muscle is stimulated. Electromotor allochiria has been observed in the face, lower limbs, and upper limbs.[10] In these cases, a stimulus presented on the affected side caused contraction of the opposite facial muscles with a current so weak that the healthy facial did not react. Another example is that pressure on one forearm caused movement of the opposite forearm. The central fact is that an electrical stimulus may manifest its effect at a distant part of the nervous system. This distant part may be on the same side of the body or on the opposite side, naturally it is more often on the opposite side because the representation of corresponding contralateral[12] limbs in the spinal cord are nearer to each other than homolateral limbs.[10] This has nothing to do with the confusion of the two sides that occurs in the patients mind when allochiria is present. ### Motor allochiria[edit] If patient asked to carry out a movement on effect side he does so with the corresponding part of the opposite side fully under the impression that he has correctly performed the required movement.[10] ### Reflex allochiria[edit] Patients with reflex allochiria respond to a stimulation of the sole of the foot or in the inner part of the thigh as being evoked as the corresponding reflex on the opposite side only.[10] ### Auditory allochiria[edit] In cases of auditory allochiria, observations recorded that when a tuning fork was held constantly to one ear, the patient responded with a series of symptoms, including pain and deafness, in the opposite ear.[10] ### Visual allochiria[edit] In visual allochiria, objects situated on one side of the visual field are perceived in the contralateral visual field.[13] In one of the two cases ever recorded, the visual impression received by the right open eye was regularly referred to the left eye, and the patient maintained that she perceived the impression with the left eye that in fact was shut. In the other case, a colored object held in front of the left eye was recognized and the patient maintained that she saw the color with the right eye.[10] ### Gustatory allochiria[edit] In a case of gustatory allochiria, a substance placed on one side of the tongue was said to have been tasted on the opposite side. Also, touches on that side of the tongue were also referred to the opposite side. In this type of allochiria, it is difficult to see how one can in this case dissociate the reference of taste from that of touch.[10] ## Alloesthesia[edit] Alloesthesia (i.e., allesthesia)[14] (Greek: allache = elsewhere + aistheesis = perception) is also known as "false allochiria" and many dictionaries list the same definition as allochiria and even give same Greek lexical roots. The term allesthesia was introduced by T. Grainger Stewart in an article published in the British Medical Journal in 1894.[15] The cases that Stewart found were mainly related to sensation and he observed consistent horizontal movement. Alloesthesia is a case of mistaken or incomplete perception of a stimulus and maybe accompanied by other failures in perception such as defective localization.[3] In a case-study, in which the condition was incorrectly described as allochiria, a stimulus applied to the inside of the cheek was referred to the outside. In another case, a touch to the index finger was referred to the thumb. False allochiria may occur in bilateral affections of nerves such as multiple neuritis, and although no such case has yet been recorded it is still clear that the condition above is not related to allochiria.[3][16][clarification needed] ## Dyschiria[edit] In dyschiria the failure to determine the correct side is a specific failure and is quite independent of any other failure as regards to perception of stimulus. In other words, the patient may recognize every single feature concerning a single stimulus—its precise nature, position, etc.—except the one point of its side. Evidence goes to show that there is present a mental defect of the specific feeling. Dyschiria has many forms which include achiria, allochiria, and synchiria.[10] ### Achiria[edit] Achiria is referred to as simple allochiria and is the term proposed to show the failure to regard feelings of sidedness or handedness. Achiria has sensory, motor, and introspective components. For the sensory achiria, a stimulus applied to the affected part arouses no feeling of sidedness. The stimulus is presented to the side of the body that the person with the disorder has no notion. For the motor component, if a patient is asked to carry out any movement with the limb in question he is unable to do so unless is indicated in some other way than by the use of the words right and left. Reason for this is that he has lost the knowledge of the meaning of these words either altogether or at all events when they are applied to limbs concerned. For the introspective component a patient loses memory for feeling of part of the body that the stimulus is presented and declares that though he knows he has a part he cannot feel it.[10] ### Allochiria[edit] Allochiria is when a stimuli presented on one side is constantly referred to the corresponding point of the opposite side. Allochiria has sensory, motor, and introspective manifestations. In sensory cases, a point to which they are referred on the opposite side corresponds exactly with the symmetrical point touched at fact which in itself disposes of the view that allochiria is in any way merely a disturbance of localization. For cases of motor allochiria, if a patient is asked to carry out a movement on effect side, he does so with the corresponding part of the opposite side fully under the impression that he has correctly performed the required movement. For the introspective cases the patient can appreciate a given feeling of sidedness only when the opposite limb is moved or stimulated.[10] ### Synchiria[edit] Synchiria[17] is a form of dyschiria in which a stimulus applied to one side of the body is felt on both sides. Synchiria has sensory, motor, and introspective signs. The sensory component refers to a stimulus applied to the affected part evokes two simultaneous sensations which are referred to the corresponding points on both sides of the body. The motor symptom is when a patient is asked to carry out movement on affected side he does so on both sides though in doing so he gets only the feeling of sidedness of the affected part. The introspective component shows that a patient is unable to appreciate the affected feeling of sidedness alone apart from the simultaneously appreciated feeling of the corresponding opposite side though he can appreciate it when he moves both limbs together under the impression that he is moving only the affected one.[10] ## Experiences[edit] Drawing of a clock by a subject with hemispatial neglect allochiria There are many cases that patients have shown symptoms of allochiria. Allochiria in constructional tasks is commonly seen when neglect patients transpose the elements on the left side to the right side but fail to see or fix their mistakes. Some cases in which patients have shown allochiria is in copying and drawing clocks from memory. A defect of mental representations may lead the patients to transpose all the elements to the ipsilesional side in drawing tasks.[2] In these drawing and memory tasks, patients with allochiria have a tendency to place all of the hours to the right half of the clock. There are different kinds of spatial transpositions that exist in these drawing tasks in patients with allochiria.[2] The figure shows an example of allochiria in the clock drawing of a patient with hemispatial neglect. The patient omitted the left side of objects when drawing a clock. Even though the patient could verbally express that the clock face has a left side, he or she would fail to notice that the drawing was incomplete. This implies that drawing tasks can play an important role in differentiating the specific impairment of the brain lesion, and not just saying that a patient has dementia.[18] Here is a case study of a patient that is showing neglect symptoms: https://www.youtube.com/watch?v=_1RPkp7rdnw ## Diagnosis[edit] When diagnosing allochiria, it is important to consider the sensory and the motor aspects of the problem. In absence of knowledge there are a number of ways in which the various symptoms may be overlooked or misinterpreted and as the condition goes frequently unrecognized. One rare example in medicine that causes a wrong diagnosis of allochiria is due to the unawareness of a few simple facts than to any failure in judgment. It is evident that the details of the sensory symptoms get overlooked when testing a patient's localizing capacity. The observer neglects to inquire expressly as to the side to which the sensation is referred. This is evident when patients with allochiria show no fault in sensorial perception and localization. However, even if the patient mentions the wrong side, it is sometimes being just regarded as a slip of the tongue and matter may not be pursued any further. Looking at the motor aspect of allochiria, the symptoms again are described in a misleading way because the symptoms are less obvious. Unless motor manifestations are carefully analyzed, they may be interpreted as clumsiness or weakness.[11] Moreover, when patients complained of weakness and awkwardness of right side—examinations apparently confirmed that the truth of this statement and defect was marked as acts consciously performed and was present only in relation to such acts. If a patient says that he cannot tell on which side the certain stimulus is applied—existence of allochiria is confirmed, provided that sensibility is intact.[19] ### Diagnostic value[edit] Allochiria represents a psychical[20] affection and the occurrence of any form of allochiria should be regarded as a positive indication of the presence of hysteria. Recognition of the allochiria may throw light upon a number of symptoms that would otherwise be misinterpreted as paresis, aboulia, and defective sensibility. This enables a correct analysis to be made of the precise defects present and serve as a guide toward the original focus of the whole affection and proving an important step in the exact psychological diagnosis that is an essential preliminary to the scientific treatment of hysteria.[21] ## Theory[edit] There are multiple theories that explain the outcome of allochiria. The current and most widely accepted explanation of allochiria is Hammond's Theory.[3] This theory assumes that there is an almost complete decussation of sensory fibers within the grey matter. He concludes that with a lesion on one posterior side, this would reach center in the corresponding hemisphere, and thus, the sensation is then referred by this hemisphere to the opposite side of the body.[10] Hammond goes on to say that if another unilateral lesion supervened at a different level from the first, the sensation that was previously deflected to the wrong hemisphere was now redirected by meeting with another obstacle and so arrived at its proper hemisphere. Allochiria occurs equally with unilateral and bilateral lesions as long as they are asymmetrical. Another theory is Huber's theory which assumes that an appearance of a new lesion on the opposite side from that of the block redirecting the impulse towards its original destination.[3] Disappearance of symptoms due to retrogression[22] of the lesion and track are cleared.[10] ## See also[edit] * Apraxia * Hemispatial neglect * Synesthesia * Hemiplegia * Hysteria * Agnosia * Brain damage ## References[edit] 1. ^ a b Halligan, P. W., Marshall, J., & Wade, D. (1992). 2. ^ a b c Lepore, M., Conson, M., Grossi, D., & Trojano, L. (2003). On the different mechanisms of spatial transpositions: a case of representational allochiria in clock drawing. Neuropsychologia, 41(10), 1290-1295. doi:10.1016/s0028-3932(03)00062-9. 3. ^ a b c d e f Meador, K. J., Allen, M. E., Adams, R. J., & Loring, D. W. (1991). ALLOCHIRIA VS ALLESTHESIA - IS THERE A MISPERCEPTION. Archives of Neurology, 48(5), 546-549. 4. ^ Halligan, P. W., Marshall, J., & Wade, D. (1992). Left on the right: Allochiria in a case of left visuo-spatial neglect.Journal of Neurology, Neurosurgery, and Psychiatry, 55, 717-719. Jones, E. (1907a). The clinical significance of Allochiria. 5. ^ Young, R. R., & Benson, D. F. (1992). WHERE IS THE LESION IN ALLOCHIRIA. [Letter]. Archives of Neurology, 49(4), 348-349. 6. ^ Musser. A Practical treatise on Medical Diagnosis. 5th ed., 1904, London, p. 289. 7. ^ Bury, Judson. Clinical Medicine. 2nd ed. 1899, London. P. 479 8. ^ Obersteiner H. On allochiria. Brain. 1882;4:153-168. 9. ^ http://medical.yourdictionary.com/symmetrical-gangrene 10. ^ a b c d e f g h i j k l m n Jones E. The precise diagnostic value of allochiria. Bravis. 1907;30:490-532 11. ^ a b Marcel, A., Postma, P., Gillmeister, H., Cox, S., Rorden, C., Nimmo-Smith, I., et al. (2004). Migration and fusion of tactile sensation - premorbid susceptibility to allochiria, neglect and extinction? [Article]. Neuropsychologia, 42(13), 1749-1767. doi:10.1016/j.neuropsychologia.2004.04.020. 12. ^ "Answers - The Most Trusted Place for Answering Life's Questions". Answers.com. 13. ^ Gonzalo-Fonrodona (2007). "Inverted or tilted perception disorder." REV NEUROL 44(3): 157-165. 14. ^ "allesthesia" – via The Free Dictionary. 15. ^ Stewart, TG. A clinical lecture on a case of perverted localization of sensation or allachaesthesia. BMH. 1984;1:1-4. 16. ^ Mario F. Mendez, J. W. Y. C. (2009). "Epilepsy partialis continua with visual allesthesia." Journal of Neurology 256(6): 1009-1011. 17. ^ "synchiria" – via The Free Dictionary. 18. ^ Kim, H. Y. S. C. E. Y.-L. D. (2010). "Context-bounded Refinement Filter Algorithm: Improving Recognizer Accuracy of Handwriting in Clock Drawing Test." Visual Representations and Reasoning 53-60 19. ^ Lancet, Lepore, M., Conson, M., Ferrigno, A., Grossi, D., & Trojano, L. (2004). Spatial transpositions across tasks and response modalities: Exploring representational allochiria. [Article]. Neurocase, 10(5), 386-392. 20. ^ "psychical" – via The Free Dictionary. 21. ^ Grossi, D., Di Cesare, G., & Trojano, L. (2004). Left on the right or viceversa: A case of "alternating" constructional allochiria. [Article]. Cortex, 40(3), 511-518. 22. ^ "the definition of retrogression". Dictionary.com. * Trojano, L., Grossi, D., & Flash, T. (2009). Cognitive neuroscience of drawing: Contributions of neuropsychological, experimental and neurofunctional studies. [Editorial Material]. Cortex, 45(3), 269-277. doi:10.1016/j.cortex.2008.11.015 * Kolb, B., & Whishaw, I. (1990).Fundamentals of human neuropsychology. Freeman: New York. * Leon Y. Deouell, D. D., Donatella Scabini, Nachum Soroker, Robert T Knight (2008). "No Disillusions in Auditory Extinction: Perceiving a Melody Comprised of Unperceived Notes." Front Hum Neurosci. 1(15): 1-15. * Pia, L., A. Folegatti, et al. (2009). "Are drawing perseverations part of the neglect syndrome?" Cortex 45(3): 293-299. * Blom, Jan Dirk. A Dictionary of Hallucinations, Springer, December 24, 2009 * Heath, M., Maraj, A., Maddigan, M., & Binsted, G. (2009). The Antipointing Task: Vector Inversion Is Supported by a Perceptual Estimate of Visual Space. Journal of Motor Behavior, 41(5), 383-392. Retrieved from Psychology and Behavioral Sciences Collection database. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Allochiria	c0422885	5,882	wikipedia	https://en.wikipedia.org/wiki/Allochiria	2021-01-18T18:44:41	{"mesh": ["D066190"], "umls": ["C0422885"], "wikidata": ["Q570126"]}
A number sign (#) is used with this entry because of evidence that brachydactyly-syndactyly syndrome is caused by heterozygous mutation in the HOXD13 gene (142989) on chromosome 2q31. One such family has been reported. Heterozygous mutation in HOXD13 can also cause brachydactyly and syndactyly in association with oligodactyly. One such patient has been reported. Clinical Features Zhao et al. (2007) described a Han Chinese family in which 23 affected individuals in 6 generations exhibited a complex brachydactyly-syndactyly syndrome. Digital photographs and radiographs were taken for 16 and 13 of them, respectively. Most of the patients exhibited generalized shortening of the hands and feet, 11 displayed broad and short distal phalanges of the thumbs, and 14 had mild cutaneous syndactyly of toes 2 and 3. Radiographs revealed a constant feature in all 13 patients: absence of middle phalanges of toes 2 through 5 and very marked short middle phalanges of the fifth finger. Combined shortening of the middle phalanges was noted, with the effect that the second and fifth fingers were most severely affected. In many cases the shortened middle phalanges were fused with the distal ones. Shortening of metacarpal 5, either alone or in combination with metatarsal 5 and/or other metacarpals/metatarsals, and short proximal phalanges of toes 1, 3, and 4 were noted in several patients. Other common limb anomalies included broad first metatarsals and hallux phalanges, often associated with hallux valgus. The proband also had small spurs of bone between the first and second metatarsals. These limb phenotypes overlapped those of brachydactyly types A4 (BDA4; 112800), D (113200), and E (113300), and syndactyly type I (185900). ### Brachydactyly/Syndactyly/Oligodactyly Syndrome Ibrahim et al. (2013) studied a girl with a complex brachydactyly-syndactyly-oligodactyly phenotype, who was born with normal measurements and had normal psychomotor development. Her hands had only 4 fingers each, as well as severe shortening of the digits and camptodactyly. The terminal phalanges and nails of the thumbs were absent. The left foot had only 3 shortened toes, and the nail of the great toe was absent. Partial cutaneous webbing (syndactyly) was present between the other toes, and the fibular toe was deviated to the tibial side. The right foot had only 4 shortened toes, with partial syndactyly of 2 toes, and the nail of the great toe was absent. X-rays showed missing and deformed metacarpals, metatarsals, and rudimentary phalangeal bones. There was no family history of congenital malformations. Molecular Genetics In a large Han Chinese family segregating brachydactyly-syndactyly syndrome, Zhao et al. (2007) found deletion of 21 basepairs in the HOXD13 gene (142989.0010) in affected members. The deletion was located in the imperfect GCN (where N denotes A-C, G, or T) triplet-containing exon 1 of HOXD13, and resulted in a polyalanine contraction of 7 residues. The site and length of the polyalanine tract in HOXD13, like that in the paralogous HOXA13 (142959), are highly conserved among mammals. In a girl exhibiting brachydactyly, syndactyly, and oligodactyly, who was negative for mutation in the ROR2 gene (602337), Ibrahim et al. (2013) identified heterozygosity for a de novo missense mutation in the HOXD13 gene (Q317K; 142989.0018) that was not found in the dbSNP database. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	BRACHYDACTYLY-SYNDACTYLY SYNDROME	c1853137	5,883	omim	https://www.omim.org/entry/610713	2019-09-22T16:04:11	{"doid": ["0050689"], "mesh": ["C565193"], "omim": ["610713"], "orphanet": ["93409"], "synonyms": []}
Serratia infection SpecialtyInfectious disease Serratia infection refers to a disease caused by a species in the genus Serratia. The species involved is usually Serratia marcescens. It can cause nosocomial infections.[1] ## References[edit] 1. ^ Hejazi A, Falkiner FR (November 1997). "Serratia marcescens". J. Med. Microbiol. 46 (11): 903–12. doi:10.1099/00222615-46-11-903. PMID 9368530. ## External links[edit] Classification D * MeSH: D016868 * v * t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis 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	Serratia infection	c0085394	5,884	wikipedia	https://en.wikipedia.org/wiki/Serratia_infection	2021-01-18T18:42:49	{"mesh": ["D016868"], "wikidata": ["Q16935263"]}
Coloboma of superior eyelid is a rare developmental defect during embryogenesis characterized by a typically unilateral, partial or full-thickness, variably sized defect of the superior eyelid, ranging from a small notch to complete absence of the entire lid, which is commonly triangular in shape (with base at eyelid margin) and located on the medial third of the lid. It can occur isolated, associated with other anomalies (e.g. ocular/orbital and facial), or as part of a syndrome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Coloboma of superior eyelid	c1863872	5,885	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=155884	2021-01-23T17:20:39	{"icd-10": ["Q10.3"], "synonyms": ["Superior palpebral coloboma"]}
## Summary ### Clinical characteristics. DYT-GNAL caused by a heterozygous GNAL pathogenic variant has been reported in more than 60 individuals to date. It is characterized by adult-onset isolated dystonia (i.e., no neurologic abnormalities other than tremor are evident on neurologic examination). The dystonia is most commonly focal and segmental, and rarely generalized. Dystonia is typically cervical in onset and commonly progresses to the cranial region (oromandibular/jaw, larynx, eyelids) and/or to one arm. Tremor reported in DYT-GNAL may be dystonic (i.e., occurring in a body part that shows at least minimal signs of dystonia) and may precede or follow the onset of dystonia. Intra- and interfamilial variability is considerable. DYT-GNAL caused by biallelic GNAL pathogenic variants, reported to date in two sibs from a consanguineous family, is characterized by mild intellectual disability and childhood-onset hypertonia that progresses to generalized dystonia. ### Diagnosis/testing. The diagnosis of DYT-GNAL is established in a proband with either isolated dystonia and a heterozygous GNAL pathogenic variant identified by molecular genetic testing or a more complex phenotype (intellectual disability, hypertonia, and generalized dystonia) and biallelic GNAL pathogenic variants. ### Management. Treatment of manifestations: While oral medication is usually the initial treatment of dystonia, experience in DYT-GNAL specifically is limited. Botulinum toxin intramuscular injections have improved cervical dystonia and dystonia affecting other sites in some patients with DYT-GNAL – as well as dystonia in selected muscles in patients with generalized dystonia. Deep-brain stimulation of the globus pallidus internus has been effective in a few patients with DYT-GNAL. Physical therapy may help prevent joint contractures and spine deformities. Treatment of depression and anxiety, commonly associated with cervical dystonia, is per standard practice. Surveillance: Follow up with a neurologist specializing in movement disorders several times a year is recommended to monitor for worsening of dystonia, development of new manifestations, and treatment effectiveness and side effects. Agents/circumstances to avoid: Dystonia of limbs can worsen if affected limbs are casted or braced. Similarly, neck collars should be avoided in persons with cervical dystonia. ### Genetic counseling. DYT-GNAL is typically inherited in an autosomal dominant manner (to date, 1 family with autosomal recessive inheritance of DYT-GNAL has been reported). Most individuals with autosomal dominant DYT-GNAL have an affected parent; the proportion of DYT-GNAL caused by a de novo pathogenic variant is unknown. Each child of an individual with DYT-GNAL has a 50% chance of inheriting the GNAL pathogenic variant; reduced penetrance and large intrafamilial clinical variability have been reported. Once the GNAL pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible. ## Diagnosis No formal diagnostic criteria have been established for DYT-GNAL. ### Suggestive Findings DYT-GNAL should be considered in individuals with the following clinical findings, neuroimaging findings, and family history. #### Clinical Findings Dystonia is defined as involuntary contractions of muscles that lead to abnormal movements and abnormal postures. Dystonic movements are typically repetitive, patterned, and often twisting. DYT-GNAL is characterized by the following: * Isolated; no neurologic abnormalities other than tremor evident on neurologic examination * Age at onset typically in adulthood; rarely in childhood [Fuchs et al 2013, LeDoux et al 2016, Masuho et al 2016] * Most commonly focal and segmental; rarely generalized [Fuchs et al 2013, Miao et al 2013, Vemula et al 2013, Masuho et al 2016]; and rarely laryngeal dystonia only [Putzel et al 2016] * Onset typically in the cervical region and commonly progressing to the cranial region (oromandibular/jaw, larynx, blepharospasm) and/or to one arm #### Neuroimaging Studies Brain magnetic resonance imaging and computed tomography results are normal, showing no structural intracranial lesions that could be considered a cause of acquired dystonia. #### Family History Consistent with autosomal dominant inheritance (i.e., includes both familial cases and simplex cases [a single occurrence in a family]). The one exception is autosomal recessive inheritance reported in two Turkish sibs [Masuho et al 2016]. ### Establishing the Diagnosis The diagnosis of DYT-GNAL is established in a proband with isolated dystonia and a heterozygous GNAL pathogenic variant identified by molecular genetic testing (see Table 1). A single report found a homozygous GNAL pathogenic variant, associated with a more complex and more severe phenotype (intellectual disability, hypertonia, and generalized dystonia) with age at onset in infancy [Masuho et al 2016]. #### Molecular Genetic Testing Because the phenotype of DYT-GNAL is indistinguishable from many other inherited disorders with dystonia, recommended molecular genetic testing approaches include use of a multigene panel or comprehensive genomic testing. Note: Single-gene testing (sequence analysis of GNAL, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended. * A dystonia multigene panel that includes GNAL 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) Multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * Comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is another good option. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in DYT-GNAL View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method GNALSequence analysis 332/32 4 Gene-targeted deletion/duplication analysis 5None reported to date 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. 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\. Fuchs et al [2013], Miao et al [2013], Vemula et al [2013], Dobričić et al [2014], Dufke et al [2014], Kumar et al [2014], Saunders-Pullman et al [2014], Zech et al [2014], Ziegan et al [2014], Zech et al [2015], Carecchio et al [2016], Dos Santos et al [2016], LeDoux et al [2016], Masuho et al [2016], Putzel et al [2016] 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\. Kumar et al [2014] used quantitative PCR of GNAL exon 9 to test for whole-gene deletions/duplications in 318 patients with dystonia; no deletions or duplications were found. No further data on detection rates of gene-targeted deletion/duplication analyses are available. ## Clinical Characteristics ### Clinical Description DYT-GNAL is a mostly adult-onset isolated dystonia (in which no additional neurologic abnormalities other than tremor are evident on neurologic examination). The dystonia is most commonly focal and segmental, and rarely generalized. Dystonia is typically cervical in onset and commonly progresses to the cranial region (oromandibular/jaw, larynx, eyelids) and/or to one arm. DYT-GNAL tremor may be dystonic (i.e., occurring in a body part that shows at least minimal signs of dystonia) and may precede or follow the onset of dystonia). Since its original description [Fuchs et al 2013, Vemula et al 2013], DYT-GNAL has been reported in: * 62 individuals with a heterozygous GNAL pathogenic variant [Miao et al 2013, Dobričić et al 2014, Dufke et al 2014, Kumar et al 2014, Saunders-Pullman et al 2014, Zech et al 2014, Ziegan et al 2014, Zech et al 2015, Carecchio et al 2016, Dos Santos et al 2016, LeDoux et al 2016, Putzel et al 2016]; * Two sibs (from a consanguineous union) homozygous for a GNAL pathogenic variant [Masuho et al 2016]. #### Heterozygous DYT-GNAL Age of onset. In the 28 individuals first described by Fuchs et al [2013], mean age at disease onset was 31.3 years (± 12.4 years); range: 7-54 years. Mean age at disease onset for an additional 29 individuals was 42.5 years (± 13.2 years); range: 8-68 years. Initial body region involved. DYT-GNAL most frequently starts as focal dystonia involving the neck (cervical dystonia, torticollis) with or without head tremor. Initial presentation can also occur in the oromandibular region or in the larynx (spasmodic dysphonia). Data available on 56 individuals revealed the following regarding the first body region affected by dystonia: * Cervical region: 78% * Larynx: 9% * Oromandibular region/jaw/tongue: 7% * Leg: two individuals * Face: one individual Other initial manifestations were dystonic arm tremor (2 individuals) and isolated head tremor (1 individual). Type of dystonia. Dystonia may remain focal (e.g., cervical dystonia is the only manifestation) or become segmental (e.g., cervical dystonia spreads to the cranial region or an upper limb). The trunk and the legs are rarely affected. Generalized dystonia is far less common. In a study of 28 individuals, dystonia remained focal in 12 and became segmental in 13 or generalized in three [Fuchs et al 2013]. The phenotypic variability within families was wide. In 62 individuals the sites involved during the disease course included the following: * Cervical dystonia: 84% * Oromandibular dystonia including dystonia of the jaw and tongue: 29% * Upper facial dystonia including blepharospasm: 22.6% * Dystonia of the arm or isolated dystonic tremor of the arm: 29% * Laryngeal dystonia: 21% * Truncal dystonia: 16% * Dystonia in a leg: 8% Tremor was also frequently reported, most commonly as dystonic head and/or arm tremor. Speech involvement was reported in 44% of 28 patients [Fuchs et al 2013]. Dystonic tremor. In a family with four affected individuals in whom the most disabling manifestation was tremor, age at onset in two family members was 36 and 58 years [Carecchio et al 2016]. EMG performed in two of the four showed the tremor to be dystonic. Other findings included focal speech-induced dystonia (likely due to intermittent oromandibular dystonia), isolated dystonic tremor of the right arm only, and jerky cervical dystonia with laryngeal involvement and arm tremor. Hyposmia. In one family with five affected individuals who were alive and available for a neurologic examination, two had hand-forearm dystonia and three had anosmia or microsmia [Vemula et al 2013]. It is possible that microsomia is more common than reported to date, since the olfactory dysfunction identified in this family was not self-reported but required specialized testing. Psychiatric comorbidities. While there are insufficient data on psychiatric manifestations in DYT-GNAL, it is known that psychiatric comorbidities, mainly depression and anxiety, are common in individuals with (cervical) dystonia. Of note, some medications may cause psychiatric side effects (see Management, Treatment of Manifestations). Intrafamilial phenotypic variability includes age at disease onset, initial body region involved, type of dystonia (focal versus segmental versus generalized), sites involved during the course of the disease, disease severity, and rate of progression [Fuchs et al 2013, Carecchio et al 2016]. In one family the following was observed in five living affected individuals who were examined: age at onset 45 to 63 years; generalized dystonia involving the arms, legs, and neck (1 individual), focal dystonia (torticollis) without progression (1 individual), and segmental dystonia (3 individuals); laryngeal involvement (3 individuals); and blepharospasm (1 individual) [Vemula et al 2013]. Of note, no information was available on the three other deceased individuals who were likely affected. #### Biallelic DYT-GNAL To date the only individuals known to have biallelic DYT-GNAL are two sibs from a consanguineous Turkish family reported by Masuho et al [2016], whose phenotype was more severe than that of heterozygous DYT-GNAL. The initial finding was increased muscle tone at age one year that progressed to generalized dystonia with involvement of the head, neck, trunk, and limbs. Action-induced spasms were observed. Both sibs had mild intellectual disability. ### Genotype-Phenotype Correlations No genotype-phenotype correlations are known for either heterozygous or biallelic GNAL pathogenic variants. ### Penetrance The penetrance for heterozygous DYT-GNAL is currently unknown. The following asymptomatic heterozygotes for a GNAL pathogenic variant have been reported: * 14 unaffected heterozygotes (mean age: 29 years, age range: 9-51 years) identified in three of four families [Vemula et al 2013] * One unaffected heterozygote who was a parent of two offspring with DYT-GNAL ages 50 and 59 years [Fuchs et al 2013] * One unaffected heterozygote who was the mother of a 40-year-old with laryngeal dystonia [Putzel et al 2016] ### Nomenclature Following the new naming system for the genetic dystonias in which the causative gene has been confirmed, the prefix "DYT" is followed by the gene symbol [Marras et al 2016]. Thus, the new designation for DYT25 isolated dystonia is DYT-GNAL. ### Prevalence DYT-GNAL is rare. To date 64 individuals (including two homozygotes) with DYT-GNAL have been reported. Studies in families of northern European descent with primary torsion dystonia of mixed European origin [Fuchs et al 2013] and in Swiss-German Amish-Mennonite families with primary dystonia [Saunders-Pullman et al 2014] found DYT-GNAL-causing variants in affected family members in 15% and 7.5%, respectively. In contrast, in studies including mostly simplex cases (i.e., a single occurrence in a family) with mostly isolated dystonia, the prevalence was about 0.5% (0-1.1%) [Miao et al 2013, Vemula et al 2013, Charlesworth et al 2014, Dobričić et al 2014, Dufke et al 2014, Zech et al 2014, Ziegan et al 2014, Ma et al 2015, Zech et al 2015, Dos Santos et al 2016, LeDoux et al 2016]. A study on 57 patients with isolated laryngeal dystonia found a slightly higher prevalence of 1.8% [Putzel et al 2016]. ## Differential Diagnosis See Hereditary Dystonia Overview. ### Table 2. Autosomal Dominant Disorders to Consider in the Differential Diagnosis of DYT-GNAL View in own window DisorderGeneClinical Features of Disorder That Overlap w/DYT-GNALFurther Details of This Disorder Age at onset of dystoniaSite of dystonia at onsetDystonia typeOther DYT-THAP1THAP1Craniocervical dystonia &/or laryngeal involvement may be presenting feature(s). * Median: 13 yrs (range: 2-49 yrs) 1 * Median: 13 yrs (range 2-62 yrs) 2 * Mean: 48 yrs (range: 8-69 yrs) 3 Cervical & laryngeal; upper limbCraniocervical involvement commonPenetrance of ~60% DYT-TOR1ATOR1AIsolated blepharospasm or craniocervical dystonia in some * Mean:14 yrs (range 4-44 yrs) 4 * Early onset, typically childhood; late onset in some Typically in 1 limb * 60% to 70% progress to generalized (or multifocal) dystonia. 5 * ~20% have focal dystonia, most frequently writer's cramp. * Ashkenazi Jewish ancestry common 4 * Reduced penetrance of ~30% * More rapid progression * Face & neck typically spared DYT-SGCE (see Myoclonus-Dystonia)SGCE * Cervical dystonia 6 * Myoclonic jerks typical of DYT-SGCE have been described in DYT-GNAL. 7 1st or 2nd decadeNeck, proximal arm, trunkMyoclonic jerks of mostly proximal muscles, typically cervical dystonia & writer's cramp * Action-induced, alcohol-responsive myoclonic jerks * Psychiatric features common (incl alcohol dependence) DYT-ANO3ANO3 * Adult-onset craniocervical dystonia * Laryngeal dystonia * Upper-limb dystonia (incl arm tremor) Early childhood to 6th decade (typically adult onset)Mostly craniocervicalSegmental/multifocal (craniocervical dystonia, head tremor, upper-limb dystonia, dystonic arm tremor, laryngeal dystonia)Most have dystonic tremor. 1\. Bressman et al [2009]; patients with familial dystonia 2\. Blanchard et al [2011]; review 3\. Xiao et al [2010]; cohort consisted mainly of individuals with late-onset focal dystonia (n = 1,210). 4\. Bressman et al [2000] 5\. See DYT1 Early-Onset Isolated Dystonia. 6\. Cervical dystonia may be the only presentation in DYT-SGCE. 7\. Carecchio et al [2016] CIZ1-related dystonia was described in a large family of northern European descent with adult-onset cervical dystonia and an otherwise normal neurologic examination [Xiao et al 2012]. Although Dufke et al [2015] also reported CIZ1 variants in individuals with or without a family history of predominantly cervical dystonia, the significance of these variants remains unknown. Thus, CIZ1 pathogenic variants as a cause for adult-onset cervical dystonia are currently unconfirmed. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with DYT-GNAL, 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 DYT-GNAL View in own window Organ SystemEvaluationComment NeurologicComplete neurologic exam performed by neurologist specializing in movement disordersAttention to blepharospasm, oromandibular dystonia, dystonia of jaw/tongue, (jerky) cervical dystonia, dystonia of arms/legs, truncal dystonia, tremor (head or extremities), laryngeal dystonia, hyposmia Eval using a dystonia rating scaleRating scale such as: * Burke-Fahn-Marsden dystonia rating scale (BFMDRS) * Unified Dystonia Rating Scale (UDRS) * Global Dystonia Rating Scale (GDS) For cervical dystonia: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) & Comprehensive Cervical Dystonia Rating Scale (CCDRS) Eval by physical therapistAttention to craniocervical dystonia, dystonia of extremities & trunk; geste antagoniste 1 ENT * Eval for botulinum toxin injections into laryngeal muscles by otorhinolaryngologist * Eval by speech therapist For those w/laryngeal dystonia Miscellaneous/ OtherConsultation w/clinical geneticist &/or genetic counselor 1\. Voluntary maneuver that temporarily reduces the severity of dystonic postures or movements ### Treatment of Manifestations #### Dystonia All treatment options are symptomatic. Oral medication. A trial with oral medication is usually first. Very few reports on the effect of oral medication specifically in DYT-GNAL are available. * Oral drugs currently used to treat dystonia: * Anticholinergics (trihexyphenidyl is most widely used; benztropine). These need to be monitored especially for cognitive side effects. * Baclofen * Benzodiazepines (diazepam, clonazepam, lorazepam) * Additional drugs that may be considered: * Levodopa. Note: Levodopa/carbidopa was not beneficial in patients with DYT-GNAL [Bressman et al 1994, Carecchio et al 2016]. * Antiepileptics; e.g., gabapentin [Esposito et al 2014, Sarva et al 2019] * Dopamine-depleting agents, most importantly tetrabenazine, which requires monitoring for psychiatric side effects (depressive episodes). Note: Tetrabenazine provided no benefit in one patient with DYT-GNAL [Carecchio et al 2016]. * Propanolol, cyclobenzaprine, trabenazine, and ethopropazine reported in a recent study [Sarva et al 2019] Botulinum toxin intramuscular injections, repeated in intervals of about three months, have improved cervical dystonia in some patients with DYT-GNAL [Dobričić et al 2014, Carecchio et al 2016, Dos Santos et al 2016] as well as dystonia affecting other sites (e.g., blepharospasm, oromandibular dystonia, focal dystonia of a limb) including selected muscles in individuals with generalized dystonia. Deep-brain stimulation of the globus pallidus internus has been effective in treatment of isolated dystonia in the following instances: * Two patients with DYT-GNAL cervical dystonia accompanied by severe head tremor had a very good response [Carecchio et al 2016]. * One patient with DYT-GNAL cervical and truncal dystonia showed a good response [Ziegan et al 2014]. * In three patients, cervical dystonia improved significantly, while cranial dystonia (including dysarthria) and limb dystonia did not improve or worsened [Sarva et al 2019]. Follow up includes more frequent visits in the first weeks and months after surgery in order to determine the best stimulation parameters. Physical therapy may help prevent joint contractures and spine deformities. #### Psychiatric Comorbidities Depression and anxiety are treated as per standard practice. Of note, dopamine-depleting agents, anticholinergics, and other drugs may cause or worsen psychiatric and cognitive features. ### Surveillance Follow up with a neurologist specializing in movement disorders several times a year is recommended to monitor for the following: * Worsening of dystonia * Development of new manifestations * Medication side effects * Issues related to DBS treatment including side effects such as hypokinesia and battery life Regular monitoring for psychiatric and cognitive features is indicated; medication adjustments and consultation with a psychiatrist may be necessary. ### Agents/Circumstances to Avoid Dystonia of limbs can worsen if affected limbs are casted or braced. Similarly, neck collars should be avoided in persons with cervical dystonia. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Controlled human studies on the safety of baclofen use during pregnancy have not been completed. Several case reports of baclofen use in the first trimester of pregnancy with normal fetal outcome have been published. Third-trimester exposure may lead to abnormalities in neonatal adaptation. The use of diazepam during the first trimester of pregnancy may be associated with an increased risk of cleft palate; thus, in situations where use of a benzodiazepine during pregnancy is required, other medications (e.g., lorazepam or clonazepam) may be preferable. Third-trimester use of a benzodiazepine may lead to neonatal complications, such as decreased tone and/or sedation. Botulinum toxin injections are typically avoided during pregnancy and breastfeeding. However, in several case reports of women who received botulinum toxin A injections in the first trimester of pregnancy, infants were born at full term with no complications. Data are insufficient to determine if the use of trihexyphenidyl during pregnancy has an effect on the developing fetus. See MotherToBaby for further information on medication use during pregnancy. ### Therapies Under Investigation The following clinical trials (identified by NCT number) on DBS in "primary dystonia" are listed in ClinicalTrials.gov. (The term "primary dystonia" currently is mainly used for genetic or idiopathic forms of isolated dystonia without a consistent pathologic/structural change.) Note that none is specifically recruiting patients with DYT-GNAL: * NCT02542839 evaluates repetitive transcranial magnetic stimulation (rTMS) delivered over each cerebellar hemisphere in addition to treatment with botulinum toxin injections in patients with primary cervical dystonia. Other rTMS studies conducted or recruiting: * NCT02073630 in patients with primary dystonia * NCT03369613 in patients with cervical dystonia * NCT03247868 evaluates the influence of motor learning techniques in patients with primary cervical dystonia. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	DYT-GNAL	c3554447	5,886	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK535640/	2021-01-18T21:31:14	{"synonyms": ["DYT25", "GNAL-Related Dystonia"]}
Clear-cell adenocarcinoma SpecialtyOncology/gynecology Clear-cell adenocarcinoma (CCA) of the vagina or cervix is a rare adenocarcinoma often linked to prenatal exposure to diethylstilbestrol (DES), a drug which was prescribed in high-risk pregnancy. ## Contents * 1 Presentation * 2 Diagnosis * 3 Treatment * 4 History * 5 See also * 6 References * 7 External links ## Presentation[edit] After age 30 it was thought that women exposed prenatally, "DES daughters", were no longer were at risk for the disease, but as they age into their 40s and 50, cases continue to be reported.[1] According to the Centers for Disease Control and Prevention (CDC), DES daughters should have a pap/pelvic exam every year because of their lifelong risk for clear-cell adenocarcinoma.[2][3] ## Diagnosis[edit] Clear-cell adenocarcinoma of the vagina is a rare cancer, occurring in up to 10% of primary vaginal malignancies. It is all but confirmed if maternal use of DES is established. Even though it was once thought to no longer occur past the age of 30, it is still seen into the 40s and 50s. Some of the main signs and symptoms for clear-cell adenocarcinoma of the vagina are spotting between menstrual cycles, bleeding post-menopause, abnormal bleeding, and malignant pericardial effusion or cardiac tamponade.[4] ## Treatment[edit] Low grade cancer is treated by surgical resection. High grade will require neoadjuvant chemotherapy and resection. Long-term surveillance will be required.[4] ## History[edit] The synthetic estrogen DES was given to millions of pregnant women in the United States and other countries. Use in the US was primarily from 1938-1971 but not limited to those years. Internationally, DES use continued until the early 1980s. DES was given if a woman had a previous miscarriage, diabetes, or a pregnancy with bleeding, threatened miscarriage or premature labor. Up until the mid to late 1950s some women were given DES shots. After that, DES was primarily prescribed in pill form. DES also was included in some prenatal vitamins.[citation needed] In the late 1960s through 1971 a cluster of young women, from their teens into their twenties, was mysteriously diagnosed with CCA, a cancer not generally found in women until after menopause. Doctors at Massachusetts General Hospital eventually linked DES exposure before birth to the development of CCA in these young women. They determined the risk for developing CCA among DES daughters is estimated at 1 in a 1,000.[5] ## See also[edit] * Glassy cell carcinoma of the cervix * Vaginal melanoma ## References[edit] 1. ^ Smith, Emily K.; White, Mary C.; Weir, Hannah K.; Peipins, Lucy A.; Thompson, Trevor D. (1 January 2012). "Higher incidence of clear cell adenocarcinoma of the cervix and vagina among women born between 1947 and 1971 in the United States". Cancer Causes & Control. SpringerLink. 23 (1): 207–211. doi:10.1007/s10552-011-9855-z. PMC 3230753. PMID 22015647. 2. ^ "Annual Exam for DES Daughters" (PDF). Centers for Disease Control and Prevention. Archived from the original (PDF) on 4 October 2013. Retrieved 18 June 2013. 3. ^ Moyer, Virginia A.; U.S. Preventive Services Task Force (19 June 2012). "Screening for Cervical Cancer: U.S. Preventive Services Task Force Recommendation Statement". Annals of Internal Medicine. 156 (12): 880–91, W312. doi:10.7326/0003-4819-156-12-201206190-00424. PMID 22711081. 4. ^ a b Gera S. Clear cell adenocarcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/vaginaclearcelladeno.html. Accessed May 25th, 2019 5. ^ Hatch EE, Palmer JR, Titus-Ernstoff L, et al. (August 1998). "Cancer risk in women exposed to diethylstilbestrol in utero". JAMA. 280 (7): 630–4. doi:10.1001/jama.280.7.630. PMID 9718055. ## External links[edit] * Clear cell adenocarcinoma entry in the public domain NCI Dictionary of Cancer Terms Classification D * ICD-O: 8310/3 * MeSH: D018262 * DiseasesDB: 2786 This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". * v * t * e Tumors of the female urogenital system Adnexa Ovaries Glandular and epithelial/ surface epithelial- stromal tumor CMS: * Ovarian serous cystadenoma * Mucinous cystadenoma * Cystadenocarcinoma * Papillary serous cystadenocarcinoma * Krukenberg tumor * Endometrioid tumor * Clear-cell ovarian carcinoma * Brenner tumour Sex cord–gonadal stromal * Leydig cell tumour * Sertoli cell tumour * Sertoli–Leydig cell tumour * Thecoma * Granulosa cell tumour * Luteoma * Sex cord tumour with annular tubules Germ cell * Dysgerminoma * Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma/Struma ovarii * Choriocarcinoma Fibroma * Meigs' syndrome Fallopian tube * Adenomatoid tumor Uterus Myometrium * Uterine fibroids/leiomyoma * Leiomyosarcoma * Adenomyoma Endometrium * Endometrioid tumor * Uterine papillary serous carcinoma * Endometrial intraepithelial neoplasia * Uterine clear-cell carcinoma Cervix * Cervical intraepithelial neoplasia * Clear-cell carcinoma * SCC * Glassy cell carcinoma * Villoglandular adenocarcinoma Placenta * Choriocarcinoma * Gestational trophoblastic disease General * Uterine sarcoma * Mixed Müllerian tumor Vagina * Squamous-cell carcinoma of the vagina * Botryoid rhabdomyosarcoma * Clear-cell adenocarcinoma of the vagina * Vaginal intraepithelial neoplasia * Vaginal cysts Vulva * SCC * Melanoma * Papillary hidradenoma * Extramammary Paget's disease * Vulvar intraepithelial neoplasia * Bartholin gland carcinoma * v * t * e Glandular and epithelial cancer Epithelium Papilloma/carcinoma * Small-cell carcinoma * Combined small-cell carcinoma * Verrucous carcinoma * Squamous cell carcinoma * Basal-cell carcinoma * Transitional cell carcinoma * Inverted papilloma Complex epithelial * Warthin's tumor * Thymoma * Bartholin gland carcinoma Glands Adenomas/ adenocarcinomas Gastrointestinal * tract: Linitis plastica * Familial adenomatous polyposis * pancreas * Insulinoma * Glucagonoma * Gastrinoma * VIPoma * Somatostatinoma * Cholangiocarcinoma * Klatskin tumor * Hepatocellular adenoma/Hepatocellular carcinoma Urogenital * Renal cell carcinoma * Endometrioid tumor * Renal oncocytoma Endocrine * Prolactinoma * Multiple endocrine neoplasia * Adrenocortical adenoma/Adrenocortical carcinoma * Hürthle cell Other/multiple * Neuroendocrine tumor * Carcinoid * Adenoid cystic carcinoma * Oncocytoma * Clear-cell adenocarcinoma * Apudoma * Cylindroma * Papillary hidradenoma Adnexal and skin appendage * sweat gland * Hidrocystoma * Syringoma * Syringocystadenoma papilliferum Cystic, mucinous, and serous Cystic general * Cystadenoma/Cystadenocarcinoma Mucinous * Signet ring cell carcinoma * Krukenberg tumor * Mucinous cystadenoma / Mucinous cystadenocarcinoma * Pseudomyxoma peritonei * Mucoepidermoid carcinoma Serous * Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma Ductal, lobular, and medullary Ductal carcinoma * Mammary ductal carcinoma * Pancreatic ductal carcinoma * Comedocarcinoma * Paget's disease of the breast / Extramammary Paget's disease Lobular carcinoma * Lobular carcinoma in situ * Invasive lobular carcinoma Medullary carcinoma * Medullary carcinoma of the breast * Medullary thyroid cancer Acinar cell * Acinic cell carcinoma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Clear-cell adenocarcinoma of the vagina	None	5,887	wikipedia	https://en.wikipedia.org/wiki/Clear-cell_adenocarcinoma_of_the_vagina	2021-01-18T18:43:25	{"wikidata": ["Q5130801"]}
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (classic 21-OHD CAH) affects the adrenal glands which are responsible for producing specific hormones. There are two types of classic 21-OHD CAH, the salt-wasting form and the simple-virilizing form. Symptoms include abnormal development of the external sex organs in females (ambiguous genitalia), early puberty, and short stature. The salt-wasting form also may include the inability to retain salt and water. This can lead to dehydration, low blood pressure, and a life-threatening adrenal crisis. Classic 21-OHD CAH is caused by a genetic pathogenic variant in the CYP21A2 gene and is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, blood hormone testing and may be confirmed by the results of genetic testing. Classic 21-OHD CAH can be diagnosed through a newborn screen. Treatment can prevent the more severe symptoms and may involve hormone replacement. in addition, some girls with abnormal genitalia may be offered surgery. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency	c2936858	5,888	gard	https://rarediseases.info.nih.gov/diseases/12665/classic-congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency	2021-01-18T18:01:17	{"mesh": ["C535979"], "orphanet": ["90794"], "synonyms": ["Classic 21-OHD CAH"]}
GRFoma is a type of pancreatic endocrine tumor (see this term) that hypersecretes growth hormone-releasing factor (GRF or GHRH) and that clinically resembles a pituitary adenoma (see this term) as patients present with acromegaly. In addition to the pancreas, this tumor can also occur in the lungs or small intestine, are usually large > 6cm and approximately 1/3 have metastasized at the time of diagnosis. It often co-occurs with Zollinger-Ellison syndrome or multiple endocrine neoplasia type 1 (MEN 1; see these terms). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	GRFoma	None	5,889	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97261	2021-01-23T18:00:47	{"icd-10": ["E16.8"], "synonyms": ["GRF tumor", "Growth hormone releasing factor tumor"]}
A rare benign follicular hamartoma that develops primarily on the face of adults, with a particular predilection for the back of the nose, but also on the neck or scalp. It presents as a solitary hemispheric flesh-colored nodule with a central pore or black dot that may contain a tuft of hair. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Trichofolliculoma	c0334262	5,890	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=864	2021-01-23T17:22:25	{"gard": ["5263"], "mesh": ["C536553"], "umls": ["C0334262"]}
A rare, congenital disorder of glycosylation-related bone disorder characterized by hypotonia, severe developmental delay, intellectual disability, seizures, increased serum alkaline phosphatase, short distal phalanges with hypoplastic nails, and dysmorphic facial features. In some cases, cleft palate, megacolon, anorectal malformations, and congenital heart defects have been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Hyperphosphatasia-intellectual disability syndrome	c1855923	5,891	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=247262	2021-01-23T18:33:53	{"mesh": ["C565495"], "omim": ["239300", "614207", "614749", "615716", "616025", "616809"], "umls": ["C1855923"], "synonyms": ["Mabry syndrome"]}
For a discussion of the genetic heterogeneity of quantitative trait loci (QTL) for mean platelet volume (MPV)/platelet count (PLT), see MPVCQTL1 (612573). Mapping Gieger et al. (2011) performed metaanalyses of genomewide association studies (GWAS) for MPV and PLT. Their analyses included 18,600 (13 studies, MPV) and 48,666 (23 studies, PLT) individuals of European descent, respectively, and up to approximately 2.5 million genotyped or imputed single-nucleotide polymorphisms (SNPs). Gieger et al. (2011) identified rs210134 located within the BAK1 gene (600516) on chromosome 6p21.3-p21.2 as significantly associated with PLT in an overall sample of 58,554 individuals, with a p value of 7.11 x 10(-36). The authors noted that ablation of Bak1 corrects thrombocytopenia due to reduced platelet life span induced by genetic ablation of Bclxl (see 600039) in mouse. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	MEAN PLATELET VOLUME/COUNT QUANTITATIVE TRAIT LOCUS 4	c3553339	5,892	omim	https://www.omim.org/entry/614644	2019-09-22T15:54:39	{"omim": ["614644"]}
Rare dental anomaly resulting in teeth having more than one cusp Talon cusp Other namesEagle's talon, dens evaginatus, interstitial cusp, tuberculated premolar, evaginated odontoma, supernumerary cusp[1] Periapical radiograph of talon cusp on a partially erupted upper left permanent maxillary incisor in an 8 year-old male of Arabic descent SpecialtyDentistry Talon cusp is a rare dental anomaly[2] resulting in an extra cusp or cusp-like projection on an anterior tooth, located on the inside surface of the affected tooth. The term 'talon cusp' refers to the same condition as dens evaginatus; however, talon cusp is more specifically the manifestation of dens evaginatus on the anterior teeth. Talon cusp can be simply defined as hyperplasia of the cingulum of an anterior tooth. Although talon cusp may not appear serious, and in some people may be completely benign, it can cause clinical, diagnostic and functional problems, and alters the appearance of a person's teeth. The condition was first described by W.H. Mitchell in 1982 and named by J. Kimball Mellor B.S., D.D.S. and Louis W. Ripa, D.D.S., M.S.[3] due to its similar appearance to an eagle's talon. Some sources define a talon cusp as an extra cusp which extends at least half the distance between the cementoenamel junction and the incisal edge of the tooth.[4] Other sources classify all enlarged cingula as talon cusps, and classify them according to the degree of enlargement.[4] The incidence of talon cusp has been found to range from 1% to 6% of the population.[vague][5] Talon cusp tends to occur on permanent teeth only,[4] being very rare in deciduous teeth.[4] In most cases, the involved teeth are the permanent maxillary lateral incisors (55%), followed by maxillary central incisors (33%), mandibular incisors (6%), and maxillary canines (4%).[4] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 Recent research * 7 References ## Signs and symptoms[edit] Talon cusp will show physical signs of the irregular dental formation of the teeth and cause other symptoms of the disease that could possibly lead to dental problems in the future, depending on severity of the deformity. Most commonly, the extra cusp is located on the lingual surface, giving a three-pronged appearance.[4] Rarely, however, the extra cusp may be situated on the facial surface, or there may be extra cusps on both lingual and facial surfaces.[4] There may be a deep groove between the talon cusp and the rest of the tooth. The extra cusp typically contains pulp tissue.[4] When viewing talon cusp from the occlusal, the projection will appear "x-shaped", as well as appears conical, and mimic the shape of an eagle's talon.[2] Symptoms of talon cusp include: * Interference with occlusion[2] or bite * Irritation of soft tissues and tongue[2] * Accidental cusp fracture[2] * Susceptible to dental caries[6] ## Cause[edit] The cause of talon cusp is unknown. The anomaly can occur due to genetic and environmental factors but the onset can be spontaneous. Prevention is difficult because the occurrence happens during the development of teeth. Talon cusp affects men and women equally, however the majority of reported cases are of the male gender.[4] Individuals of Asian, Arabic, Native American and Inuit descent are affected more commonly.[4] Talon cusp is also highly observed in patients with orofacial digital II syndrome and Rubinstein Taybi syndrome. Other anomalies that occur with talon cusp can include peg laterals, supernumerary teeth, dens envaginatus, agenesis and impaction.[4] A person belonging to one of these particular demographics or one who has any of these deformities or syndromes may have a higher risk of having a talon cusp. ## Mechanism[edit] The exact mechanism of the formation of dens evaginatus and talon cusp is unknown.[citation needed] It has been suggested that the anomaly is caused by an evagination. The formation of the "cusp" is due to excess layering of the internal enamel epithelium and dental papilla into the stellate reticulum. This occurs during the morphological differentiation stage of tooth development.[citation needed] During the developmental stages of tooth formation, certain dental follicle cells were differentiated incorrectly which formed the excess enamel and incorrect morphology of the affected tooth. Talon cusp can progress into severe dental problems if the severity of the cusp affects the person's hygiene and oral functions. Talon cusp may occur on its own or associated with other dental anomalies such as mesiodens, odontome, unerupted or impacted teeth, peg-shaped maxillary incisor, dens invaginatus, cleft lip, bilateral gemination, fusion, and supernumerary teeth. [7] ## Diagnosis[edit] This anomaly is large enough to be seen with the naked eye. One can see the projection on the incisal edge of a tooth looking into the mouth of the affected person. The structure is described to be "T'shaped" or "X-shaped" however will differ depending on its shape, size, structure, location and site of origin.[8] X-rays and radiographs can also show evidence of the abnormality. The digital images would show a tooth with talon cusp as if it were "double teeth".[4] When looking at a radiograph some features to look for would be location, edge, shape and number. The location would be on an anterior tooth, the edge would be clear and well defined and can be seen even by the naked eye, and the shape would appear "talon-like" over the top portion or crown of the affected tooth. There could potentially be one, two or multiple protrusions depending on the type of cusp. Talon cusp can fall under three categories: Type I, Type II and Type III. They are created based on the cusp formation shape and length of extension. * Type I - Talon: The additional cusp or talon projects from the palatal surface of a primary or permanent anterior (front) tooth that extends at least half of the distance from the cemento enamel junction to the incisal edge.[citation needed] * Type II - Semi Talon: The semi talon cusp measures about 1mm or more in length but extends less than half of the distance seen in Type I Talon.[6] * Type III - Trace Talon: The projection originates from the cingulum (also known as the "cervical third") of the root and is enlarged or prominent in any form (conical, bifid or tubercle-like)[6] Since many cases of Talon cusp go unreported, it is hard to draw linkage maps but it is safe to assume that dental formation is influenced by genetic factors.[4] Talon cusp is also seen in association with conditions such as Rubinstein-Taybi syndrome, Mohr syndrome, Ellis–van Creveld syndrome, Incontinentia pigmenti achromians, Berardinelli-Seip syndrome, and Sturge–Weber syndrome.[4] ## Treatment[edit] Treatment is only required if the occlusion or bite of the person is compromised and causing other dental problems. Multiple long-term clinical problems can arise such as occlusal interferences, aesthetic disturbances, loss of pulp vitality, irritation of tongue during mastication and speech, caries and displacement of the affected tooth. Most people with talon cusp will live their normal lives unless the case is severe and causes a cascade of other dental issues that lead to additional health problems. Generally talon cusps on lower teeth require no treatment, but talon cusps on upper teeth may interfere with the bite mechanics and may need to be removed or reduced.[4] Small talon cusps that produce no symptoms or complication for a person can remain untreated. However large talon cusps should not. Some common treatments include: * Fissure sealing[9] * Composite resin restoration[9] * Reduction of cusp * Pulpotomy * Root canal (endodontic treatment) * Extraction The condition is usually benign, but it can cause mild irritation to soft tissues around the teeth and the tongue, and if large enough, may pose an aesthetic problem. Talon cusps that are too large are filed down with a motorized file, and then endodontic therapy is administered. In order to prevent any future dental complications, when talon cusp is present due to an early diagnosis it would be best to see a dentist regularly every six months for routine dental checkups, remain under observation, brush and floss properly and undergo regular topical applications of fluoride gel to prevent caries and to promote enamel strength. ## Recent research[edit] Future studies will look further into the relationship of talon cusp and Rubinstein-Taybi syndrome and other oral-facial-digital syndromes. A former study showed a direct correlation in which 45 affected patients with Rubinstein-Taybi syndrome, 92% of these patients had talon cusp.[4][10] Other researchers are attempting to trace talon cusp to ancestors and comparing dentition to modern humans. Another study done in 2007 examined the dentition of 301 Native American Indian skeletons for the presence or absence of talon cusp. The results showed five skeletons (2 percent) in the population had the trait.[11] In 2011, only 21 cases of talon cusp have been reported and are in literature.[1] It appears that as of 2014 and 2015,[12] additional research continues in hopes of finding the cause and mechanism of talon cusp. With the majority of cases of talon cusp being unreported, it remains difficult to conduct tests, come up with conclusions, conduct surgery and perform research with small numbers. ## References[edit] 1. ^ a b Praveen, P (February 2011). "Talon Cusp in a Primary Tooth" (PDF). Journal of Dental Sciences and Research. 2 (1): 35–40. Retrieved November 1, 2015. 2. ^ a b c d e Ozcelik, Bahar; Atila, Burcu (2011-01-01). "Bilateral Palatal Talon Cusps on Permanent Maxillary Lateral Incisors: A Case Report". European Journal of Dentistry. 5 (1): 113–116. doi:10.1055/s-0039-1698866. ISSN 1305-7456. PMC 3019756. PMID 21228961. 3. ^ Mellor, J. Kimball; Ripa, Louis W. (1970-02-01). "Talon cusp: A clinically significant anomaly". Oral Surgery, Oral Medicine, Oral Pathology. 29 (2): 225–228. doi:10.1016/0030-4220(70)90089-7. PMID 5262843. 4. ^ a b c d e f g h i j k l m n o p Neville BW; Chi AC; Damm DD; Allen CA (13 May 2015). Oral and Maxillofacial Pathology. Head and Neck Pathology. 1. Elsevier Health Sciences. pp. 80–81. doi:10.1007/s12105-007-0007-4. ISBN 978-1-4557-7052-6. PMC 2807501. PMID 20614286. 5. ^ Neville, B.W., D. Damm, C. Allen, J. Bouquot. Oral & Maxillofacial Pathology. Second edition. 2002. Page 78. ISBN 0-7216-9003-3. 6. ^ a b c "Presentation and Management of Talon Cusp". www.jpma.org.pk. Retrieved 2015-11-02. 7. ^ Sharma, Gaurav; Nagpal, Archna (2014). "Talon Cusp: A Prevalence Study of Its Types in Permanent Dentition and Report of a Rare Case of Its Association with Fusion in Mandibular Incisor". Journal of Oral Diseases. 2014: 1–6. doi:10.1155/2014/595189. 8. ^ Sumer, A. P.; Zengin, A. Z. (2005-10-08). "An unusual presentation of talon cusp: A case report". British Dental Journal. 199 (7): 429–430. doi:10.1038/sj.bdj.4812741. ISSN 0007-0610. PMID 16215568. 9. ^ a b Oredugba, Folakemi A. (2005-12-08). "Mandibular facial talon cusp: Case report". BMC Oral Health. 5 (1): 9. doi:10.1186/1472-6831-5-9. ISSN 1472-6831. PMC 1334182. PMID 16336661. 10. ^ Hennekam, R. C.; Van Doorne, J. M. (1990-01-01). "Oral aspects of Rubinstein-Taybi syndrome". American Journal of Medical Genetics. Supplement. 6: 42–47. ISSN 1040-3787. PMID 2118777. 11. ^ Mayes, A. T. (2007). "Labial talon cusp - The Journal of the American Dental Association". Journal of the American Dental Association. 138 (4): 515–8. doi:10.14219/jada.archive.2007.0205. PMID 17403743. Retrieved 2015-12-10. 12. ^ Mallineni, Sreekanth-Kumar; Panampally, George-Kurian; Chen, Yong; Tian, Tian (2014-10-01). "Mandibular talon cusps: A Systematic review and data analysis". Journal of Clinical and Experimental Dentistry. 6 (4): e408–e413. doi:10.4317/jced.51476. ISSN 1989-5488. PMC 4282910. PMID 25593665. Classification D * ICD-10: K00.2 * ICD-9-CM: 520.2 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Talon cusp	c0399357	5,893	wikipedia	https://en.wikipedia.org/wiki/Talon_cusp	2021-01-18T18:40:42	{"icd-9": ["520.2"], "icd-10": ["K00.2"], "wikidata": ["Q7680290"]}
Monographella nivalis var. nivalis Pink snow mold in a lawn in Brno Komín, Czech Republic Scientific classification Kingdom: Fungi Phylum: Ascomycota Class: Sordariomycetes Subclass: Xylariomycetidae Order: Xylariales Family: Incertae sedis Genus: Monographella Species: M. nivalis var. nivalis Binomial name Monographella nivalis var. nivalis (Schaffnit) E. Müll., (1977) Synonyms * Calonectria graminicola * Calonectria nivalis * Fusarium nivale * Fusarium nivale * Fusarium nivale f.sp. graminicola * Fusarium nivale var. majus * Fusarium nivale var. nivale * Gerlachia nivalis * Gerlachia nivalis var. major * Gerlachia nivalis var. nivalis * Griphosphaeria nivalis * Lanosa nivalis * Melioliphila graminicola * Microdochium nivale * Microdochium nivale var. majus * Microdochium nivale var. nivale * Micronectriella nivalis * Monographella nivalis Fusarium patch is a disease in turf grass settings also called pink snow mold or Microdochium patch. Microdochium nivale is the pathogen that causes this disease in many cool season turf grass species in North America.[1] The white-pink mycelium on infected leaf blades is a distinguishing characteristic of the Microdochium nivale pathogen.[2] Fusarium patch is considered economically important in the turf grass industry because of its tendency to cause significant injury to golf greens, thereby decreasing putting surface quality.[3] Dissimilar from other snow molds, such as gray snow mold, Microdochium nivale does not need snow cover to cause widespread infection. ## Contents * 1 Hosts and symptoms * 2 Disease cycle * 3 Environment * 4 Management * 4.1 Cultural controls * 4.2 Chemical controls * 5 Importance * 6 See also * 7 References * 8 External links ## Hosts and symptoms[edit] M. nivale can infect all cool-season turf grass species.[4] Annual bluegrass (Poa annua), perennial ryegrass (Lolium perenne) and creeping bentgrass (Agrostis stolonifera) are more susceptible. In the fall, M.nivale infection begins as small, orange to red-brown spots, circular and only a few centimeters in diameter. During the winter and into the spring seasons, well-defined, clustered, circular patches 10-20 cm in diameter, of necrotic leaf tissues form on mown turf. Microdochium nivale is mostly seen on grasses mown at heights of three inches or greater.[5] On taller grass, patches often lack a circular pattern that is seen in shorter mown grass.[6] Pink snow mold patches usually follow drainage patterns since conidia spores are readily dislodged and transported by rainfall and water flowage.[7] Under prolonged cool and wet conditions, white-pink mycelium can be observed along the circumference of diseased patches.[8] ## Disease cycle[edit] M. nivale begins by oversummering (surviving the summer) in thatch or soil as haploid mycelium or spores. When cool, wet weather arrives in the fall or winter the mycelium grows from thatch or soil and infects leaves. These environmental conditions also favor the development of asexual spores called conidia on conidiophores. These conidia infect leaf sheaths and blades near the soil. Wind and surface water will help aid in the spread of this disease as it will allow for the spores to contact near by healthy plant. The disease becomes very severe if allowed to spread from the leaf blades to the crown of the plant.[9] This usually only happens under extreme circumstances, particularly if snowfall covers unfrozen ground.[10] ## Environment[edit] Microdochium nivale becomes problematic when turf experiences lengthy periods of cool, wet weather typical of fall or spring and into early summer in the Northern Hemisphere. The name is somewhat confusing because the presence of snow is not necessary for this pathogen to develop. The disease can thrive under snow cover, however, if it falls on unfrozen soil with thriving turf. In general this disease tends to develop proficiently when grass is growing at a slower than normal rate. Limiting fall N applications in an attempt to decrease the growth of grass and promote dormancy can help decrease the incidence of Pink Snow Mold. In regions of high humidity and temperatures ranging between 32 and 46 degrees Fahrenheit or 0 to 8 degrees Celsius, Pink Snow Mold will develop rapidly.[11] ## Management[edit] There are a number of different ways to manage diseases including cultural, chemical, and biological controls. Some of these controls are more effective than others, however, the best approach to a managing any disease, including Microdochium Patch, is an integrated approach called Integrated Pest Management or IPM. IPM uses a combination of chemical, cultural and biological controls to reduce spending on pesticides and to decrease pesticide resistance. The following are some of the most important cultural controls used in managing Microdochium Patch. ### Cultural controls[edit] Raising the mowing height is an easy way to reduce stress on a turfgrass plant and make the plant less susceptible to attack by disease, but there is a fine line. Turf mowed, less than 2.5 inches (64 mm) and above 3 inches (76 mm) makes the plant more susceptible to disease. Managing the moisture available to the plant is another way to help reduce the incidence of disease. The pathogen that causes Microdochium Patch requires and thrives in moist, cool conditions, therefore making sure that you aren't overwatering the turf when conditions are right for infection is very important. Giving the plant only enough water for normal plant function is the best way to ensure disease pressure is reduced as much as possible. Also, starving the turf of moisture can be damaging as this increases susceptibility to infection. Managing the amount of nitrogen available to the plant is another key to decreasing incidence of this disease. Avoiding excess fall nitrogen application will greatly reduce disease pressure of Microdochium nivale. On top of that excess nitrogen available to plant produces rapid growth of above ground tissue. This tissue often has thin cell walls and is prone to attack by disease. Managing thatch and soil drainage are two other important ways of controlling this disease as both of these affect the amount of moisture that is available to create a favorable environment to the disease,[12] giving the plant only enough water for normal plant function is the best way to ensure disease pressure is reduced as much as possible. Despite the fact that the above cultural controls cannot completely control Microdochium Patch, when they are all used to reduce disease pressure, they can have a noticeable impact and will help to reduce the amount of chemical control that is required. ### Chemical controls[edit] Chemical controls (i.e. the use of fungicides) to specifically control turf grass diseases have been around since 1891. Over the years better controls have been developed, all of which tend to be less toxic to animals and the environment when used properly. There is a wide variety of chemical groups that are labeled for control of Microdochium Patch. They include, but are not limited to the methyl benzimidazole carbamates (MBCs) such as thiophanate methyl, the dicarboximides such as iprodione and vinclozolin, the DMIs such as fenarimol and propiconazole, the QoIs such as azoxystrobin, pyraclostrobin, and trifloxystrobin, the phenylpyrroles such as fludioxonil, certain aromatic hydrocarbons such as PCNB, and the cholronitriles such as chlorothalonil.[13] There is a wide variety of chemical groups that are labeled for control of Microdochium Patch. They include, but are not limited to the methyl benzimidazole carbamates (MBCs) such as thiophanate methyl, the dicarboximides such as iprodione and vinclozolin, the DMIs such as fenarimol and propiconazole, the QoIs such as azoxystrobin, pyraclostrobin, and trifloxystrobin, the phenylpyrroles such as fludioxonil, certain aromatic hydrocarbons such as PCNB, and the cholronitriles such as chlorothalonil. These chemical classes should be rotated so that selection pressure on the disease in limited as to avoid resistant strains of this disease. The applicator should read and follow all label rates and directions. Breaking these directions and misuse of any labeled product is breaking the law. Remember that the label is the law. The best way to control Microdochium Patch especially going into winter is to use a three way spray right before the first snow fall. A combination of a dicarboximides such as iprodione, a chloronitrile such as chlorothalonil, and a DMI such as propiconazole will give sufficient control over the span of an average winter. ## Importance[edit] Microdochium Patch is a significant problem in the turfgrass management industry. Sports fields, sod farms and home lawns and golf courses can all be damaged by this the disease. The pathogen can be found in the Northern United States and all the way up into Canada, meaning that there is a large area where this pathogen can cause serious disease. The highest incidence of this disease in these areas occurs on golf courses due to the highly managed areas of susceptible turfgrass species such as Creeping Bentgrass (Agrostis stolonifera) and Annual Bluegrass (Poa annua). It is of particular concern because turf on golf courses is considered a high value crop. Diseases such a Microdochium Patch lower the value of the crop by decreasing its aesthetic value, affecting the playability, and decreasing the overall health of the turf. Because golf course budgets are often quite tight, the reduction of fungicide applications required in a season for snow mold will result in more money elsewhere in the budget. Being that the fungicide budget can be 10% of the maintenance budget, reductions in the use of fungicides can cause a significant increase in the amount of money to do other things. On top of that, reducing fungicide inputs helps keep the environment safe and reduces the chances of fungicide resistance development. ## See also[edit] * Fungi portal * Fusarium * Fusarium wilt ## References[edit] 1. ^ Chang, T., Chang, S., & Jung, G. (2011). Response of bentgrass cultivars to microdochium nivale isolates collected from golf courses. Plant Pathology Journal, 27(3), 232-241 2. ^ [1] Archived 2011-06-17 at the Wayback Machine Latin, R. (2007) Pink snow mold and Microdochium patch. Turfgrass Disease Profiles. Purdue Extension, Purdue University 3. ^ [2] Bertrand, A., Castonguay, Y., Azaiez, A., and Dionne, J. (2011). "Cold-induced responses in annual bluegrass genotypes with differential resistance to pink snow mold (Microdochium nivale).", Plant Science, 180(1), pp. 111-119. doi:10.1016/j.plantsci.2010.08.008 4. ^ [3] Archived 2011-06-17 at the Wayback Machine Latin, R. (2007) Pink snow mold and Microdochium patch. Turfgrass Disease Profiles. Purdue Extension, Purdue University 5. ^ [4] Archived 2011-06-17 at the Wayback Machine Latin, R. (2007) Pink snow mold and Microdochium patch. Turfgrass Disease Profiles. Purdue Extension, Purdue University 6. ^ [5] Archived 2011-06-17 at the Wayback Machine Latin, R. (2007) Pink snow mold and Microdochium patch. Turfgrass Disease Profiles. Purdue Extension, Purdue University 7. ^ [6] Archived 2011-06-17 at the Wayback Machine Latin, R. (2007) Pink snow mold and Microdochium patch. Turfgrass Disease Profiles. Purdue Extension, Purdue University 8. ^ Hsiang T. 2007. All you ever wanted to know about Fusarium Patch. AGSA Turf News, June 2007, pp. 13-16. 9. ^ Hsiang, Tom, and Pam Charbonneau. Controlling Fusarium Patch Disease. GreenMaster 2nd ser. 28.April/May (1994): 16+. Turfgrass Information File. Web. 23 Oct. 2011. 10. ^ Pink Snow Mold (Turfgrass) (Microdochium nivale) - Hort Answers - University of Illinois Extension. University of Illinois Extension-Urban Programs Resource Network - University of Illinois at Urbana-Champaign. Web. 23 Oct. 2011. 11. ^ Pink Snow Mold (Turfgrass) (Microdochium nivale) - Hort Answers - University of Illinois Extension. University of Illinois Extension-Urban Programs Resource Network - University of Illinois at Urbana-Champaign. Web. 23 Oct. 2011. 12. ^ Nick Christians.2007. Fundamentals of Turf grass Management. Wiley and Sons.Hoboken, NJ 13. ^ [Nick Christians.2007. Fundamentals of Turfgrass Management. Wiley and Sons.Hoboken, NJ] ## External links[edit] * More Information on Lawn Care and Fusarium Patch * Additional Information on Microdochium Patch * Additional Information on Microdochium Patch * Additional Information on Management of Microdochium Patch * Additional Information on Microdochium Patch * [7] Turfgrass disease profile * Index Fungorum * USDA ARS Fungal Database Taxon identifiers * Wikidata: Q15636098 * Fungorum: 445552 * GBIF: 7186642 * iNaturalist: 606963 * MycoBank: 445552 * NCBI: 594596 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Fusarium patch	None	5,894	wikipedia	https://en.wikipedia.org/wiki/Fusarium_patch	2021-01-18T18:39:49	{"wikidata": ["Q7548416"]}
Abortion in Finland is legal and free of charge under a broad range of circumstances. By international standards, political controversy is mild, and incidence is low. ## Contents * 1 Legal framework * 2 History * 3 See also * 4 References ## Legal framework[edit] According to law, approval for an abortion requires the signature of at least one physician (and in some cases, two), and in some cases additional permission from the National Supervisory Authority for Welfare and Health (Valvira). So officially abortion is not legal upon request, but in reality any pregnant individual gets an abortion that requests it before the 12th week of pregnancy.[1] One doctor's signature is enough in the case of terminations before the 12th week when the applicant is under 17 years old or has passed her 40th birthday, or if the applicant has already given birth to 4 or more children, regardless of age. Otherwise two doctors' signatures are required. Reasons for approval are the potential physical or mental distress if the pregnancy runs to term; or if the pregnancy arises from a serious crime (e.g. rape or incest) or if an illness of either parent would make it difficult to provide a normal upbringing for the child. Reference to Valvira for review and decision is needed in all cases between 13-20 weeks; or when there are grounds that the fetus is abnormal (in which case the 20 weeks is extended to 24 weeks); or in any case where the doctor has given a negative decision. Above 20 weeks, a threat to the physical life of the mother is the only valid reason for terminating a pregnancy. [2][3][4] ## History[edit] In Finland, abortion was illegal until 1950, when the Parliament of Finland legalized abortions to preserve the physical or mental health of the woman, if the woman was under 16, if the fetus might be deformed, or the woman had been raped.[5] Under pressure from the women's liberation movement and supportive editorials from most national newspapers, Finnish law was further liberalized in 1970.[6] The 1970 law allowed abortion up to 16 weeks of pregnancy for broad socio-economic reasons, if the woman was younger than 17, if the woman was older than 40, if the woman had already had four children, or if at least one parent would be unable to raise the child owing to disease or mental disturbance.[7] This time limit was lowered from 16 to 12 weeks in 1979.[8] The 1970 law also allowed abortion up to 20 weeks of pregnancy in the event of fetal deformity or physical threat to the woman's health. A 1985 bill allowed abortion up to 20 weeks of pregnancy for underage women and up to the 24th week if an amniocentesis or ultrasound found serious impairment in the fetus. In 2008, there were 10,423 abortions in Finland. There has been a gradual decrease in abortions over time, largely attributable to a decrease in the under 20 age group [9] As of 2010[update], the abortion rate was 10.4 abortions per 1000 women aged 15-44 years. [10] Abortions are provided free-of-charge in public hospitals. It is illegal to perform abortions in private clinics, though doctors are empowered to provide abortions outside of hospitals in emergency circumstances. Illegal abortions remain very rare because, due to the generality of the conditions specified in the law, in practice, a woman can get an abortion under almost any circumstance.[11] Political controversy since the 1970 law has been mild. Members of parliament from rightist parties, notably the Finns Party, periodically make statements decrying abortion as "immoral". Still, there has been no focused political campaign to significantly restrict abortion since legalization. ## See also[edit] * Abortion by country * Abortion debate * Abortion law * Religion and abortion ## References[edit] 1. ^ [1] (in Finnish) 2. ^ http://www.valvira.fi/terveydenhuolto/toimintaluvat/raskauden_keskeyttaminen/lupa_raskauden_keskeyttamiseen 3. ^ http://www.valvira.fi/terveydenhuolto/toimintaluvat/raskauden_keskeyttaminen 4. ^ http://www.infopankki.fi/en/living-in-finland/health/abortion 5. ^ Pirkko Niemelä. 1988. "Finland." Pg. 152-69 in International Handbook on Abortion. Ed. Paul Sachdev. New York: Greenwood Press. 6. ^ Helga Suutarinen. 1972. Vuoden 1970 aborttilaki sanomalehtien pääkirjoitukissa [The 1970 abortion law in newspaper editorials]. M.S. Thesis in Social Politics, University of Helsinki. 7. ^ Pirkko Niemelä. 1988. "Finland." Pg. 152-69 in International Handbook on Abortion. Ed. Paul Sachdev. New York: Greenwood Press. 8. ^ (in Finnish) Finnish Medical Society Duodecim. "Raskaudenkeskeytys." (August 20, 2001). Retrieved June 14, 2007. 9. ^ (in Finnish) Terveyden ja Hyvinvoinnin Laitos ""Archived copy". Archived from the original on 2010-04-27. Retrieved 2010-03-22.CS1 maint: archived copy as title (link)." (November 23, 2009). Raskaudenkeskeytykset Retrieved March 22, 2010. 10. ^ "World Abortion Policies 2013". United Nations. 2013. Retrieved 3 March 2014. 11. ^ Europe's Abortion Laws. (February 12, 2007). BBC News. Retrieved June 14, 2007. * v * t * e Abortion in Europe Sovereign states * Albania * Andorra * Armenia * Austria * Azerbaijan * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Cyprus * Czech Republic * Denmark * Estonia * Finland * France * Georgia * Germany * Greece * Hungary * Iceland * Ireland * * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Turkey * Ukraine * United Kingdom * England * Northern Ireland * Scotland * Wales * Vatican City States with limited recognition * Abkhazia * Artsakh * Kosovo * Northern Cyprus * South Ossetia * Transnistria * v * t * e Abortion Main topics * Definitions * History * Methods * Abortion debate * Philosophical aspects * Abortion law Movements * Abortion-rights movements * Anti-abortion movements Issues * Abortion and mental health * Beginning of human personhood * Beginning of pregnancy controversy * Abortion-breast cancer hypothesis * Anti-abortion violence * Abortion under communism * Birth control * Crisis pregnancy center * Ethical aspects of abortion * Eugenics * Fetal rights * Forced abortion * Genetics and abortion * Late-term abortion * Legalized abortion and crime effect * Libertarian perspectives on abortion * Limit of viability * Malthusianism * Men's rights * Minors and abortion * Natalism * One-child policy * Paternal rights and abortion * Prenatal development * Reproductive rights * Self-induced abortion * Sex-selective abortion * Sidewalk counseling * Societal attitudes towards abortion * Socialism * Toxic abortion * Unsafe abortion * Women's rights By country Africa * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde * Central African Republic * Chad * Egypt * Ghana * Kenya * Namibia * Nigeria * South Africa * Uganda * Zimbabwe Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor * Georgia * India * Iran * Israel * Japan * Kazakhstan * South Korea * Malaysia * Nepal * Northern Cyprus * Philippines * Qatar * Saudi Arabia * Singapore * Turkey * United Arab Emirates * Vietnam * Yemen Europe * Albania * Andorra * Austria * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Czech Republic * Denmark * Estonia * Finland * France * Germany * Greece * Hungary * Iceland * Ireland * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Ukraine * United Kingdom North America * Belize * Canada * Costa Rica * Cuba * Dominican Republic * El Salvador * Guatemala * Mexico * Nicaragua * Panama * Trinidad and Tobago * United States Oceania * Australia * Micronesia * Fiji * Kiribati * Marshall Islands * New Zealand * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu South America * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Law * Case law * Constitutional law * History of abortion law * Laws by country * Buffer zones * Conscientious objection * Fetal protection * Heartbeat bills * Informed consent * Late-term restrictions * Parental involvement * Spousal consent Methods * Vacuum aspiration * Dilation and evacuation * Dilation and curettage * Intact D&X * Hysterotomy * Instillation * Menstrual extraction * Abortifacient drugs * Methotrexate * Mifepristone * Misoprostol * Oxytocin * Self-induced abortion * Unsafe abortion Religion * Buddhism * Christianity * Catholicism * Hinduism * Islam * Judaism * Scientology * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Abortion in Finland	None	5,895	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Finland	2021-01-18T18:30:26	{"wikidata": ["Q4668458"]}
Hemoglobin E (HbE) disease is a mild, inherited blood disorder characterized by an abnormal form of hemoglobin, called hemoglobin E. People with this condition may have very mild anemia, but the condition typically does not cause any symptoms. It is inherited in an autosomal recessive manner and is caused by a mutation in the HBB gene. The mutation that causes hemoglobin E disease primarily occurs in Southeast Asian populations, and rarely in Chinese populations. Most people with HbE disease do not need any treatment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Hemoglobin E disease	c0238159	5,896	gard	https://rarediseases.info.nih.gov/diseases/2641/hemoglobin-e-disease	2021-01-18T18:00:07	{"umls": ["C0238159"], "orphanet": ["2133"], "synonyms": []}
Dissociative or psychogenic nonepileptic seizures (PNES) are involuntary episodes of movement, sensation, or behaviors (vocalizations, crying, and other expressions of emotion) that do not result from abnormal brain discharges. The seizures can look like any kind of epileptic seizure. They are somatic manifestations (physical symptoms) of psychologic distress. Psychiatric conditions associated with PNES include depression, anxiety, somatoform disorder, posttraumatic stress disorder, dissociative disorder, and personality disorders. Treatment depends on the cause of the psychologic distress, and may involve cognitive behavioral therapy or psychotherapy, as well as antidepressive medication. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Dissociative seizures	c0349245	5,897	gard	https://rarediseases.info.nih.gov/diseases/13028/dissociative-seizures	2021-01-18T18:00:51	{"synonyms": ["Psychogenic nonepileptic seizures", "Psychogenic seizures", "Pseudoseizures", "Functional seizures", "Non-epileptic attack disorder (NEAD)", "PNES"]}
Dyskeratosis congenita Other namesZinsser-Cole-Engman syndrome,[1][2]:570 Dyskeratosis congenital is inherited in an X-linked recessive manner SpecialtyMedical genetics Dyskeratosis congenita (DKC),also known as Zinsser-Engman-Cole syndrome, is a rare progressive congenital disorder with a highly variable phenotype.[3] The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, but these components do not always occur.[3] DKC is characterized by short telomeres. Some of the manifestations resemble premature ageing (similar to progeria). The disease initially mainly affects the skin, but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality.[3] ## Contents * 1 Presentation * 1.1 Predisposition to cancer * 2 Genetics * 2.1 X-linked * 2.2 Autosomal dominant * 2.3 Autosomal recessive * 3 Pathophysiology * 4 Diagnosis * 5 Management * 6 Prognosis * 7 Research * 8 See also * 9 References * 10 External links ## Presentation[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (January 2018) (Learn how and when to remove this template message) DKC can be characterized by cutaneous pigmentation, premature graying, dystrophy of the nails, leukoplakia of the oral mucosa, continuous lacrimation due to atresia of the lacrimal ducts, often thrombocytopenia, anemia, testicular atrophy in the male carriers, and predisposition to cancer. Many of these symptoms are characteristic of geriatrics, and those carrying the more serious forms of the disease often have significantly shortened lifespans. Also liver abnormalities are associated with this syndrome, Nodular Regenerative Hypoplasia of the liver, although rare, it is one of many manifestations of liver disorders short telomeres can cause. ### Predisposition to cancer[edit] Susceptibility to cancer seems counterintuitive because in many known cancers reactivation of telomerase is actually a required step for malignancy to evolve (see telomere). In a disease where telomerase is affected, it does not seem to follow that cancer would be a complication to result. The authors note the paradoxical nature of cancer predisposition in individuals who seem to lack one of the required components for cancer to form. It is thought [4] that without functional telomerase, chromosomes will likely be attached together at their ends through the non-homologous end joining pathway. If this proves to be a common enough occurrence, malignancy even without telomerase present is possible. Myelodysplastic Syndrome is associated with this syndrome usually presenting as a Hypoplastic Bone Marrow that can resemble Aplastic Anemia, but can be differentiated with >10% dysplasia in affected cell lines, sometimes not possible though because of the Hypoplastic marrow reducing blood cells to be observed, genetic clones are usually not present more often then not with Hypoplastic Myelodysplastic Disorder associated with Dyskeratosis Congenita. ## Genetics[edit] Of the components of the telomerase RNA component (TERC), one of key importance is the box H/ACA domain. This H/ACA domain is responsible for maturation and stability of TERC and therefore of telomerase as a whole. The mammalian H/ACA ribonucleoprotein contains four protein subunits: dyskerin, Gar1, Nop10, and Nhp2. Mutations in Nop10,[5] Nhp2[6] and dyskerin1[7] have all been shown to lead to DKC-like symptoms. ### X-linked[edit] The best characterized form of dyskeratosis congenita is a result of one or more mutations in the long arm of the X chromosome in the gene DKC1.[4][7] This results in the X-linked recessive form of the disease wherein the major protein affected is dyskerin. Of the five mutations described by Heiss and colleagues in Nature Genetics,[7] four were single nucleotide polymorphisms all resulting in the change of highly conserved amino acids. One case was an in-frame deletion resulting in the loss of a leucine residue, also conserved in mammals. In three of the cases, the specific amino acids affected (phenylalanine, proline, glycine) are found in the same locus in humans as they are in yeast (S. Cerevisiae) and the brown rat (R. Norvegicus).[7] This establishes the sequence conservation and importance of dyskerin within the eukaryotes. The relevant nature of dyskerin throughout most species is to catalyze the post-transcriptional pseudouridylation of specific uridines found in non-coding RNAs, such as ribosomal RNA (rRNA). Cbf5, the yeast analog of human dyskerin, is indeed known to be associated with the processing and maturation of rRNA.[4] In humans this role can be attributed to dyskerin.[7] Thus, the X-linked form of this disease may result in specific issues related to dysfunctional RNA and perhaps a graver phenotype. Within the vertebrates, as opposed to single celled eukaryotes, dyskerin is a key component of the telomerase RNA component (TERC) in the form of the H/ACA motif.[8] This X-linked variety, like the Nop10 and Nhp2 mutations, demonstrates shortened telomeres as a result of lower TERC concentrations.[citation needed] ### Autosomal dominant[edit] 3 genes: TERC, TERT, TINF2 The evidence supporting the importance of the H/ACA domain in human telomerase is abundant. At least one study[9] has shown that these mutations affect telomerase activity by negatively affecting pre-RNP assembly and maturation of human telomerase RNA. Nonetheless, mutations which directly affect the telomerase RNA components would presumably exist and should also cause premature aging or DKC-like symptoms. Indeed, three families with mutations in the human TERC gene have been studied with intriguing results.[4] In two of these families, two family-specific single nucleotide polymorphisms were present while in the other there persisted a large-scale deletion (821 base pairs of DNA) on chromosome 3 which includes 74 bases coding for a section of the H/ACA domain. These three different mutations result in a mild form of dyskeratosis congenita which uniquely follows an autosomal dominant pattern of inheritance. Premature graying, early dental loss, predisposition to skin cancer, as well as shortening of telomere length continue to be characteristic of this disease.[citation needed] ### Autosomal recessive[edit] 6 genes: The true phenotype of DKC individuals may depend upon which protein has incurred a mutation. One documented autosomal recessive mutation[5] in a family that carries DKC has been found in Nop10. Specifically, the mutation is a change of base from cytosine to thymine in a highly conserved region of the Nop10 sequence. This mutation, on chromosome 15, results in an amino acid change from arginine to tryptophan. Homozygous recessive individuals show the symptoms of dyskeratosis congenita in full. As compared to age-matched normal individuals, those suffering from DKC have telomeres of a much shorter length. Furthermore, heterozygotes, those who have one normal allele and one coding for the disease, also show relatively shortened telomeres. The cause of this was determined to be a reduction in TERC levels in those with the Nop10 mutation. With TERC levels down, telomere maintenance, especially in development, would be presumed to suffer accordingly. This would lead to the telomere shortening described.[5] Nhp2 mutations are similar in characterization to Nop10. These mutations are also autosomal recessive with three specific single-nucleotide polymorphisms being recognized which result in dyskeratosis congenita. Also like Nop10, individuals with these Nhp2 mutations have a reduction in the amount of telomerase RNA component (TERC) present in the cell. Again it can be presumed that a reduction in TERC results in aberrant telomere maintenance and thus shortened telomeres. Those homozygous recessive for mutations in Nhp2 do show shorter telomeres when compared with age-matched normal individuals.[6] ## Pathophysiology[edit] Main article: Ribosomopathy Dyskeratosis congenita is a disorder of poor telomere maintenance[4] mainly due to a number of gene mutations that give rise to abnormal ribosome function, termed ribosomopathy. Specifically, the disease is related to one or more mutations which directly or indirectly affect the vertebrate telomerase RNA component (TERC).[citation needed] Telomerase is a reverse transcriptase which maintains a specific repeat sequence of DNA, the telomere, during development. Telomeres are placed by telomerase on both ends of linear chromosomes as a way to protect linear DNA from general forms of chemical damage and to correct for the chromosomal end-shortening that occurs during normal DNA replication.[10] This end-shortening is the result of the eukaryotic DNA polymerases having no mechanism for synthesizing the final nucleotides present on the end of the "lagging strand" of double stranded DNA. DNA polymerase can only synthesize new DNA from an old DNA strand in the 5'→3' direction. Given that DNA has two strands that are complementary, one strand must be 5'→3' while the other is 3'→5'. This inability to synthesize in the 3'→5' directionality is compensated with the use of Okazaki fragments, short pieces of DNA that are synthesized 5'→3' from the 3'→5' as the replication fork moves. As DNA polymerase requires RNA primers for DNA binding in order to commence replication, each Okazaki fragment is thus preceded by an RNA primer on the strand being synthesized. When the end of the chromosome is reached, the final RNA primer is placed upon this nucleotide region, and it is inevitably removed. Unfortunately once the primer is removed, DNA polymerase is unable to synthesize the remaining bases.[10][11] Sufferers of DKC have been shown to have a reduction in TERC levels invariably affecting the normal function of telomerase which maintains these telomeres.[4][5][7] With TERC levels down, telomere maintenance during development suffers accordingly. In humans, telomerase is inactive in most cell types after early development (except in extreme cases such as cancer).[8] Thus, if telomerase is not able to efficiently affect the DNA in the beginning of life, chromosomal instability becomes a grave possibility in individuals much earlier than would be expected.[citation needed] A study shows that proliferative defects in DC skin keratinocytes are corrected by expression of the telomerase reverse transcriptase, TERT, or by activation of endogenous telomerase through expression of papillomavirus E6/E7 of the telomerase RNA component, TERC.[12] ## Diagnosis[edit] Since the disease has a wide variety of symptoms due to involvement of multiple systems of the body, diagnostic testing depends on the clinical findings in each individual patient. Commonly used tests include a complete blood count (CBC), bone marrow examination, leukocyte telomere length test (e.g. Flow FISH), pulmonary function test, and genetic testing.[13][14] ## Management[edit] The mainstay of treatment in dyskeratosis congenita is hematopoietic stem cell transplantation, best outcome with sibling donor. Short term therapy in initial stages is with anabolic steroids [oxymetholone, danazol] or with erythropoietin-like hormones or with granulocyte-colony stimulating factor [filgrastim) all these therapies are directed to cope with effects of bone marrow failure which manifests as low red and white blood cell counts. These medications help to increase the blood components and make up for the deficiencies caused due to bone marrow failure. Dyskeratosis Congenita in regards to stem cell transplantation have to be very carefully treated with low intensity radiation/chemo to avoid potentially catastrophic effects of Host versus graft disease and toxicity to other organs effected by short telomeres which makes them very sensitive to any radiation especially the lungs,and liver[citation needed] ## Prognosis[edit] DC is associated with shorter life expectancy, but many live to at least age 60.[15] Main cause of mortality in these patients are related to bone marrow failure. Nearly 80% of the patients of dyskeratosis congenita develop bone marrow failure.[citation needed] ## Research[edit] Recent research has used induced pluripotent stem cells to study disease mechanisms in humans, and discovered that the reprogramming of somatic cells restores telomere elongation in dyskeratosis congenita (DKC) cells despite the genetic lesions that affect telomerase. The reprogrammed DKC cells were able to overcome a critical limitation in TERC levels and restored function (telomere maintenance and self-renewal). Therapeutically, methods aimed at increasing TERC expression could prove beneficial in DKC.[16] ## See also[edit] * Cutaneous conditions * List of cutaneous conditions ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 305000 2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 3. ^ a b c Online Mendelian Inheritance in Man (OMIM): 127550 4. ^ a b c d e f Vulliamy T, Marrone A, Goldman F, et al. (September 2001). "The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita". Nature. 413 (6854): 432–435. Bibcode:2001Natur.413..432V. doi:10.1038/35096585. PMID 11574891. S2CID 4348062. 5. ^ a b c d Walne AJ, Vulliamy T, Marrone A, et al. (July 2007). "Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10". Hum Mol Genet. 16 (13): 1619–29. doi:10.1093/hmg/ddm111. PMC 2882227. PMID 17507419. 6. ^ a b Vulliamy T, Beswick R, Kirwan M, et al. (June 2008). "Mutations in the telomerase component Nhp2 cause the premature ageing syndrome dyskeratosis congenita". Proc Natl Acad Sci USA. 105 (23): 8073–8. doi:10.1073/pnas.0800042105. PMC 2430361. PMID 18523010. 7. ^ a b c d e f Heiss NS, Knight SW, Vulliamy TJ, et al. (May 1998). "X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions". Nat. Genet. 19 (1): 32–38. doi:10.1038/ng0598-32. PMID 9590285. S2CID 205342127. 8. ^ a b Wong J, Collins K (October 2006). "Telomerase RNA level limits telomere maintenance in X-linked dyskeratosis congenita". Genes Dev. 20 (20): 2848–2858. doi:10.1101/gad.1476206. PMC 1619937. PMID 17015423. 9. ^ Trahan C, Dragon F (February 2009). "Dyskeratosis congenita mutations in the H/ACA domain of human telomerase RNA affect its assembly into a pre-RNP". RNA. 15 (2): 235–43. doi:10.1261/rna.1354009. PMC 2648702. PMID 19095616. 10. ^ a b Greider, CW. (May 1996). "Telomere length regulation". Annu. Rev. Biochem. 65: 337–365. doi:10.1146/annurev.bi.65.070196.002005. PMID 8811183. 11. ^ Wason, James; et al. (2004). "Molecular Biology of the Gene. 5th ed". Annu. Rev. Biochem. 12. ^ Gourronc FA, Robertson MM, Herrig AK, Lansdorp PM, Goldman FD, Klingelhutz AJ (2010). "Proliferative defects in dyskeratosis congenita skin keratinocytes are corrected by expression of the telomerase reverse transcriptase, TERT, or by activation of endogenous telomerase through expression of papillomavirus E6/E7 or the telomerase RNA component, TERC". Experimental Dermatology. 19 (3): 279–288. doi:10.1111/j.1600-0625.2009.00916.x. PMC 2852488. PMID 19558498. 13. ^ Fernández García, M Soledad; Teruya-Feldstein, Julie (2014-08-21). "The diagnosis and treatment of dyskeratosis congenita: a review". Journal of Blood Medicine. 5: 157–167. doi:10.2147/JBM.S47437. ISSN 1179-2736. PMC 4145822. PMID 25170286. 14. ^ Savage, Sharon A. (2019-11-21), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Dyskeratosis Congenita", GeneReviews, Seattle (WA): University of Washington, Seattle, PMID 20301779, retrieved 2020-12-27 15. ^ Alter, Blanche P.; Rosenberg, Philip S.; Giri, Neelam; Baerlocher, Gabriela M.; Lansdorp, Peter M.; Savage, Sharon A. (2016-11-01). "Telomere length is associated with disease severity and declines with age in dyskeratosis congenita". Haematologica. 97 (3): 353–359. doi:10.3324/haematol.2011.055269. ISSN 0390-6078. PMC 3291588. PMID 22058220. 16. ^ Agarwal; et al. (2010). "Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients". Nature. 464 (7286): 292–296. Bibcode:2010Natur.464..292A. doi:10.1038/nature08792. PMC 3058620. PMID 20164838. ## External links[edit] * GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita * Dyskeratosis Congenita research study of Inherited Bone Marrow Failure Syndromes (IBMFS) Classification D * ICD-10: Q82.8 * ICD-9-CM: 757.39 * OMIM: 305000 * MeSH: D019871 * DiseasesDB: 30105 External resources * eMedicine: derm/111 * Orphanet: 1775 * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark * v * t * e X-linked disorders X-linked recessive Immune * Chronic granulomatous disease (CYBB) * Wiskott–Aldrich syndrome * X-linked severe combined immunodeficiency * X-linked agammaglobulinemia * Hyper-IgM syndrome type 1 * IPEX * X-linked lymphoproliferative disease * Properdin deficiency Hematologic * Haemophilia A * Haemophilia B * X-linked sideroblastic anemia Endocrine * Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy * KAL1 Kallmann syndrome * X-linked adrenal hypoplasia congenita Metabolic * Amino acid: Ornithine transcarbamylase deficiency * Oculocerebrorenal syndrome * Dyslipidemia: Adrenoleukodystrophy * Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency * Pyruvate dehydrogenase deficiency * Danon disease/glycogen storage disease Type IIb * Lipid storage disorder: Fabry's disease * Mucopolysaccharidosis: Hunter syndrome * Purine–pyrimidine metabolism: Lesch–Nyhan syndrome * Mineral: Menkes disease/Occipital horn syndrome Nervous system * X-linked intellectual disability: Coffin–Lowry syndrome * MASA syndrome * Alpha-thalassemia mental retardation syndrome * Siderius X-linked mental retardation syndrome * Eye disorders: Color blindness (red and green, but not blue) * Ocular albinism (1) * Norrie disease * Choroideremia * Other: Charcot–Marie–Tooth disease (CMTX2-3) * Pelizaeus–Merzbacher disease * SMAX2 Skin and related tissue * Dyskeratosis congenita * Hypohidrotic ectodermal dysplasia (EDA) * X-linked ichthyosis * X-linked endothelial corneal dystrophy Neuromuscular * Becker's muscular dystrophy/Duchenne * Centronuclear myopathy (MTM1) * Conradi–Hünermann syndrome * Emery–Dreifuss muscular dystrophy 1 Urologic * Alport syndrome * Dent's disease * X-linked nephrogenic diabetes insipidus Bone/tooth * AMELX Amelogenesis imperfecta No primary system * Barth syndrome * McLeod syndrome * Smith–Fineman–Myers syndrome * Simpson–Golabi–Behmel syndrome * Mohr–Tranebjærg syndrome * Nasodigitoacoustic syndrome X-linked dominant * X-linked hypophosphatemia * Focal dermal hypoplasia * Fragile X syndrome * Aicardi syndrome * Incontinentia pigmenti * Rett syndrome * CHILD syndrome * Lujan–Fryns syndrome * Orofaciodigital syndrome 1 * Craniofrontonasal dysplasia * v * t * e Metabolic disease: DNA replication and DNA repair-deficiency disorder DNA replication * Separation/initiation: RNASEH2A * Aicardi–Goutières syndrome 4 * Termination/telomerase: DKC1 * Dyskeratosis congenita DNA repair Nucleotide excision repair * Cockayne syndrome/DeSanctis–Cacchione syndrome * Thymine dimer * Xeroderma pigmentosum * IBIDS syndrome MSI/DNA mismatch repair * Hereditary nonpolyposis colorectal cancer * Muir–Torre syndrome * Mismatch repair cancer syndrome MRN complex * Ataxia telangiectasia * Nijmegen breakage syndrome Other * RecQ helicase * Bloom syndrome * Werner syndrome * Rothmund–Thomson syndrome/Rapadilino syndrome * Fanconi anemia * Li-Fraumeni syndrome * Severe combined immunodeficiency * v * t * e Progeroid syndromes DNA repair RecQ-associated * Werner syndrome * Bloom syndrome * Rothmund–Thomson syndrome NER protein-associated * Cockayne syndrome * Xeroderma pigmentosum * Trichothiodystrophy Lamin A/C * Hutchinson–Gilford progeria syndrome * Restrictive dermopathy Other/related disorders * Li–Fraumeni syndrome * Rapadilino syndrome * Baller–Gerold syndrome * DeSanctis–Cacchione syndrome * Nijmegen breakage syndrome * Fanconi anemia * Dyskeratosis congenita * Ataxia telangiectasia * De Barsy syndrome * PIBI(D)S syndrome * BIDS syndrome * Marfanoid–progeroid–lipodystrophy syndrome See also: DNA replication and repair-deficiency disorder [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Dyskeratosis congenita	c0265965	5,898	wikipedia	https://en.wikipedia.org/wiki/Dyskeratosis_congenita	2021-01-18T18:59:31	{"gard": ["10905"], "mesh": ["D019871"], "umls": ["C0265965"], "orphanet": ["1775"], "wikidata": ["Q3709312"]}
Necrolytic migratory erythema Other namesNME Necrolytic migratory erythema in the gluteal area SpecialtyDermatology Necrolytic migratory erythema is a red, blistering rash that spreads across the skin. It particularly affects the skin around the mouth and distal extremities; but may also be found on the lower abdomen, buttocks, perineum, and groin. It is strongly associated with glucagonoma, a glucagon-producing tumor of the pancreas, but is also seen in a number of other conditions including liver disease and intestinal malabsorption. ## Contents * 1 Signs and symptoms * 1.1 Clinical features * 1.2 Associated conditions * 2 Cause * 3 Mechanism * 4 Diagnosis * 4.1 Histology * 5 Management * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] ### Clinical features[edit] NME features a characteristic skin eruption of red patches with irregular borders, intact and ruptured vesicles, and crust formation.[1] It commonly affects the limbs and skin surrounding the lips, although less commonly the abdomen, perineum, thighs, buttocks, and groin may be affected.[1] Frequently these areas may be left dry or fissured as a result.[1] All stages of lesion development may be observed synchronously.[2] The initial eruption may be exacerbated by pressure or trauma to the affected areas.[1] ### Associated conditions[edit] William Becker first described an association between NME and glucagonoma in 1942[2][3] and since then, NME has been described in as many as 70% of persons with a glucagonoma.[4] NME is considered part of the glucagonoma syndrome,[5] which is associated with hyperglucagonemia, diabetes mellitus, and hypoaminoacidemia.[2] When NME is identified in the absence of a glucagonoma, it may be considered "pseudoglucagonoma syndrome".[6] Less common than NME with glucagonoma, pseudoglucagonoma syndrome may occur in a number of systemic disorders:[7] * Celiac disease * Ulcerative colitis * Crohn's disease * Hepatic cirrhosis * Hepatocellular carcinoma * Lung cancer, including small cell lung cancer * Tumors that secrete insulin\- or insulin-like growth factor 2 * Duodenal cancer ## Cause[edit] The cause of NME is unknown, although various mechanisms have been suggested. These include hyperglucagonemia, zinc deficiency, fatty acid deficiency, hypoaminoacidemia, and liver disease.[2] ## Mechanism[edit] The pathogenesis is also unknown. ## Diagnosis[edit] ### Histology[edit] The histopathologic features of NME are nonspecific[8] and include:[9] * epidermal necrosis * subcorneal pustules * confluent parakeratosis, epidermal hyperplasia, and marked papillary dermal hyperplasia in a psoriasiform pattern * angioplasia of papillary dermis * suppurative folliculitis The vacuolated, pale, swollen epidermal cells and necrosis of the superficial epidermis are most characteristic.[2] Immunofluorescence is usually negative.[2] ## Management[edit] Managing the original condition, glucagonoma, by octreotide or surgery. After resection, the rash typically resolves within days.[10] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ a b c d Thiers BH, Sahn RE, Callen JP (2009). "Cutaneous manifestations of internal malignancy". CA – A Cancer Journal for Clinicians. 59 (2): 73–98. doi:10.3322/caac.20005. PMID 19258446. 2. ^ a b c d e f Pujol RM, Wang CY, el-Azhary RA, Su WP, Gibson LE, Schroeter AL (January 2004). "Necrolytic migratory erythema: clinicopathologic study of 13 cases". International Journal of Dermatology. 43 (1): 12–8. doi:10.1111/j.1365-4632.2004.01844.x. PMID 14693015. 3. ^ Becker WS, Kahn D, Rothman S (1942). "Cutaneous manifestations of internal malignant tumors". Archives of Dermatology and Syphilology. 45 (6): 1069–1080. doi:10.1001/archderm.1942.01500120037004. 4. ^ van Beek AP, de Haas ER, van Vloten WA, Lips CJ, Roijers JF, Canninga-van Dijk MR (November 2004). "The glucagonoma syndrome and necrolytic migratory erythema: a clinical review". Eur. J. Endocrinol. 151 (5): 531–7. doi:10.1530/eje.0.1510531. PMID 15538929. 5. ^ Odom, Richard B.; Davidsohn, Israel; James, William D.; Henry, John Bernard; Berger, Timothy G.; Clinical diagnosis by laboratory methods; Dirk M. Elston (2006). Andrews' diseases of the skin: clinical dermatology. Saunders Elsevier. pp. 143. ISBN 978-0-7216-2921-6. 6. ^ Marinkovich MP, Botella R, Datloff J, Sangueza OP (April 1995). "Necrolytic migratory erythema without glucagonoma in patients with liver disease". Journal of the American Academy of Dermatology. 32 (4): 604–9. doi:10.1016/0190-9622(95)90345-3. PMID 7896950. 7. ^ Mignogna MD, Fortuna G, Satriano AR (December 2008). "Small-cell lung cancer and necrolytic migratory erythema". The New England Journal of Medicine. 359 (25): 2731–2. doi:10.1056/NEJMc0805992. PMID 19092164. 8. ^ Wilkinson DS (1973). "Necrolytic migratory erythema with carcinoma of the pancreas". Transactions of the St. John's Hospital Dermatological Society. 59 (2): 244–50. PMID 4793623. 9. ^ Kheir SM, Omura EF, Grizzle WE, Herrera GA, Lee I (July 1986). "Histologic variation in the skin lesions of the glucagonoma syndrome". The American Journal of Surgical Pathology. 10 (7): 445–53. doi:10.1097/00000478-198607000-00001. PMID 3014912. S2CID 19879900. 10. ^ Compton, Nicholas L.; Chien, Andy J. (May 2013). "A Rare but Revealing Sign: Necrolytic Migratory Erythema". The American Journal of Medicine. 126 (5): 387–389. doi:10.1016/j.amjmed.2013.01.012. PMID 23477490. ## External links[edit] Classification D * MeSH: D058568 * DiseasesDB: 8833 * SNOMED CT: 15576007 External resources * eMedicine: derm/168 * 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 * t * e Paraneoplastic syndromes Endocrine * Hypercalcaemia * SIADH * Zollinger–Ellison syndrome * Cushing's syndrome Hematological * Multicentric reticulohistiocytosis * Nonbacterial thrombotic endocarditis Neurological * Paraneoplastic cerebellar degeneration * Encephalomyelitis * Limbic encephalitis * Opsoclonus * Polymyositis * Transverse myelitis * Lambert–Eaton myasthenic syndrome * Anti-NMDA receptor encephalitis Musculoskeletal * Dermatomyositis * Hypertrophic osteopathy Mucocutaneous reactive erythema * Erythema gyratum repens * Necrolytic migratory erythema papulosquamous * Acanthosis nigricans * Ichthyosis acquisita * Acrokeratosis paraneoplastica of Bazex * Extramammary Paget's disease * Florid cutaneous papillomatosis * Leser-Trélat sign * Pityriasis rotunda * Tripe palms Other * Febrile neutrophilic dermatosis * Pyoderma gangrenosum * Paraneoplastic pemphigus [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) *[a.k.a.]: also known as	Necrolytic migratory erythema	c0221243	5,899	wikipedia	https://en.wikipedia.org/wiki/Necrolytic_migratory_erythema	2021-01-18T18:55:08	{"mesh": ["D058568"], "umls": ["C0221243"], "wikidata": ["Q776790"]}

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