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Congo floor maggot Scientific classification Kingdom: Animalia Phylum: Arthropoda Class: Insecta Order: Diptera Family: Calliphoridae Genus: Auchmeromyia Species: A. senegalensis Binomial name Auchmeromyia senegalensis Macquart, 1851 A Congo floor maggot. Coloured drawing by A.J.E. Terzi, ca 1919. The Congo floor maggot (Auchmeromyia senegalensis) is a species of blow-fly that is native to sub Saharan Africa and the Cape Verde Islands. A. sengalensis is an atypical myiasis species which does not live on or in the host, but sucks the blood of burrow-dwelling wild pigs, warthogs, aardvark, hyena and occasionally sleeping humans (sanguinivorous myiasis). Auchmeromyia is the only known genus of blood sucking maggot to feed on mammals although others feed on birds. There are five described species in the genus. Female flies lay their eggs on dry earth or the earthen floors of huts. Larvae feed for about twenty minutes, sometimes daily, and then fall to the ground. There are three larval instars and pupation lasts two weeks. The entire life cycle takes ten weeks and is continuous throughout the year. Fully grown maggots are 18 mm long. Male flies have an exceptionally long second segment and widely separated eyes. Whilst causing irritation and swelling Congo floor maggots are not known to transmit disease. Bites are easily avoided by providing beds. ## References[edit] * Goddard,J., 2007 Physician's Guide to Arthropods of Medical Importance Fifth Edition, 2007 ISBN 978-0-8493-8539-1 Taxon identifiers * Wikidata: Q5160521 * EoL: 709776 * GBIF: 1503531 * iNaturalist: 652122 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Congo floor maggot	None	6,100	wikipedia	https://en.wikipedia.org/wiki/Congo_floor_maggot	2021-01-18T18:39:06	{"wikidata": ["Q5160521"]}
Superficial epidermolytic ichthyosis (SEI) is a rare keratinopathic ichthyosis (KI; see this term) characterized by the presence of superficial blisters and erosions at birth. ## Epidemiology Less than 30 families have been reported in the literature. ## Clinical description Clinical features of SEI are similar but milder that those of epidermolytic ichthyosis (EI; see this term). SEI presents at birth or during the neonatal period with mild superficial blistering that is more frequent on flexures, shins, abdomen and extremities. After a few weeks, the skin starts to peel leaving characteristic denuded areas with normal skin (called molting/ mauserung phenomenon). A variable and mild grey rippled hyperkeratosis develops predominantly on the limbs, lower trunk and flexural areas. Blistering diminishes with age but persists through childhood and sometimes into adult life in response to trauma, heat or excessive sweating. Palmoplantar involvement is usually not observed but palmoplantar blistering, usually associated with hyperhidrosis, may sometimes occur. Skin odor is not present. ## Etiology SEI is caused by mutations in the KRT2 gene encoding keratin 2. These mutations impair keratin filament formation and weaken the structural stability of the keratinocyte cytoskeleton. ## Diagnostic methods Diagnosis is based on clinical and histological examination of skin lesions biopsies revealing acanthosis, a prominent granular layer, epidermolytic changes in the granular and upper spinous layers, hyperorthokeratosis and intracorneal blister formation. On electron microscopic examination, keratinocytes of the granular layer display structural alterations of tonofilaments. Molecular analysis, if available, reveals KRT2 mutations. ## Differential diagnosis Differential diagnosis includes epidermolytic ichthyosis, peeling skin syndrome, staphylococcal scalded skin syndrome, Alopecia-contractures-dwarfism-intellectual disability syndrome (see these terms), and atopic dermatitis. ## Antenatal diagnosis Genetic prenatal diagnosis is available for inherited ichthyoses (see this term) but it is generally not proposed for SEI due to its mild course. ## Genetic counseling Transmission is autosomal dominant. Genetic counseling should be offered to affected families. The risk for an affected parent to have an affected child is 50%. ## Management and treatment Treatment is symptomatic. Emollient and mild topical keratolytics may be used to reduce hyperkeratosis. Low dose of oral retinoids may also reduce hyperkeratosis, but must be used with caution because of their side effects and of their effect in the increase of skin fragility. Antibiotic therapy is required to treat secondary infection. ## Prognosis SEI is usually a mild disease. Life expectancy is normal and quality of life is not severely impaired. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Superficial epidermolytic ichthyosis	c0432306	6,101	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=455	2021-01-23T18:25:53	{"gard": ["2966"], "mesh": ["D053560"], "omim": ["146800"], "umls": ["C0432306"], "icd-10": ["Q80.8"], "synonyms": ["Ichthyosis bullosa of Siemens", "SEI"]}
A number sign (#) is used with this entry because of evidence that primary coenzyme Q10 deficiency-3 (COQ10D3) is caused by compound heterozygous mutation in the PDSS2 gene (610564) on chromosome 6q21. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of primary coenzyme Q10 deficiency, see COQ10D1 (607426). Clinical Features Lopez et al. (2006) described a male infant, born of unrelated white parents, who presented with neonatal pneumonia and hypotonia. At age 3 months, he developed refractory left-sided seizures with secondary generalization, despite various combinations of antiepileptic drugs. He became progressively floppy and had difficulties feeding because of exhaustion. At age 7 months, severe episodic vomiting prompted duodenal tube feeding, and he rapidly developed widespread edema. Low serum albumin of 4.3 g/liter and massive proteinuria led to the diagnosis of nephrotic syndrome. Serum lactate was markedly elevated. The absence of purposeful gaze and visual evoked-potential responses, together with normal funduscopic findings, suggested cortical blindness. Brain MRI showed changes in the basal ganglia consistent with Leigh syndrome (256000). Muscle biopsy and fibroblasts showed primary coenzyme Q10 deficiency, as well as a defect in activity of mitochondrial complex II+III. Oral therapy with CoQ10 supplementation did not lead to clinical improvement. The patient died at age 8 months due to severe status epilepticus. Molecular Genetics In an infant with a fatal encephalomyopathic form of CoQ10 deficiency with nephrotic syndrome, Lopez et al. (2006) found compound heterozygous mutations in the PDSS2 gene (610564.0001; 610564.0002), which encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of the CoQ10 biosynthetic pathway. Biochemical assays with radiolabeled substances indicated a severe defect in decaprenyl diphosphate synthase in the patient's fibroblasts. Each unaffected parent was heterozygous for 1 of the mutations. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Cortical blindness ABDOMEN Gastrointestinal \- Feeding difficulties GENITOURINARY Kidneys \- Nephrotic syndrome MUSCLE, SOFT TISSUES \- Coenzyme Q10 deficiency \- Decreased respiratory complex II+III activity \- Edema NEUROLOGIC Central Nervous System \- Hypotonia, neonatal \- Seizures, refractory \- Status epilepticus \- Bilateral signals in the basal ganglia \- Leigh syndrome LABORATORY ABNORMALITIES \- Increased serum lactate \- Proteinuria MISCELLANEOUS \- One patient has been reported (last curated May 2012) \- This patient died at age 8 months MOLECULAR BASIS \- Caused by mutation in the prenyl diphosphate synthase, subunit 2 gene (PDSS2, 610564.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	COENZYME Q10 DEFICIENCY, PRIMARY, 3	c3553358	6,102	omim	https://www.omim.org/entry/614652	2019-09-22T15:54:37	{"doid": ["0070240"], "omim": ["614652"], "orphanet": ["255249"], "synonyms": ["Infantile subacute necrotizing encephalopathy with nephrotic syndrome", "Leigh disease with nephrotic syndrome"], "genereviews": ["NBK410087"]}
A number sign (#) is used with this entry because hyperproinsulinemia is caused by heterozygous mutation in the INS gene (176730) on chromosome 11p15. Description Insulin (INS; 176730) is produced posttranslationally from its precursor molecule, proinsulin, by site-directed proteolysis in beta-cell granules. Conversion involves cleavage at pairs of basic residues that link both the insulin A and B chains to C-peptide. Human proinsulin conversion has a preferred sequential route, such that cleavage at the B-chain/C-peptide junction occurs first, producing des-31,32 split proinsulin as the major conversion intermediate. Under normal circumstances, proinsulin conversion is largely completed before secretion, and low plasma levels of intact proinsulin and conversion intermediates are found. Structural abnormalities in the proinsulin molecule can impair conversion, leading to the accumulation of proinsulin-like material in the circulation. Such defects show an autosomal dominant mode of inheritance and are the main cause of familial hyperproinsulinemia (summary by Warren-Perry et al., 1997). Clinical Features Gabbay et al. (1976) described a family in which many persons in an autosomal dominant pattern had proinsulin or a proinsulin-like material as the major fraction of circulating insulin immunoreactivity in both the fasting and the stimulated state. The hyperproinsulinemia was asymptomatic, with no evident relation to hypoglycemia or development of diabetes mellitus. In light of the dominant inheritance, the authors thought a structural abnormality of proinsulin to be more likely than deficiency of the proinsulin cleaving enzyme (or enzymes). Gabbay et al. (1979) presented data indicating that proinsulin in familial hyperproinsulinemia indeed has a structural abnormality such that cleavage at the B chain/C peptide site is impaired. Kanazawa et al. (1978) described the counterpart of the defect reported by Gabbay et al. (1976, 1979): hyperproinsulinemia due to mutation at the cleavage site connecting the A chain to the C peptide. Inheritance was again autosomal dominant. Shoelson et al. (1983) studied 3 unrelated patients, 1 of whom was previously reported by Tager et al. (1979) and 1 of whom was previously reported by Shoelson et al. (1983), with diabetes-type hyperglycemia and marked hyperinsulinemia suggestive of insulin resistance but with normal response to exogenously administered insulin. Because the opportunity to study pancreatic tissue was rare, the authors developed a method combining high pressure liquid chromatography and radioimmunoassay. By this method, each of the 3 patients was found to secrete a structurally variant and chemically distinct insulin. All 3 patients were heterozygous. Two patients came from families in which many members of several generations had the variant insulin in an autosomal dominant pedigree pattern and had either normal or very mildly impaired glucose tolerance. Gruppuso et al. (1984) identified a hyperproinsulinemia kindred in which the proband, a 14-year-old girl with a history of transient hyperglycemia at age 2 years, was studied for symptoms of hypoglycemia. Elevated levels of proinsulin were found in her and 2 sibs, her father, and her paternal grandfather, whereas 4 other close relatives were normal. Gruppuso et al. (1984) suggested that hyperproinsulinemia present in 5 persons in 3 consecutive generations with male-to-male transmission was due not to a structural defect of the proinsulin molecule but to a defect in the conversion mechanism in the pancreas. In 4 persons in 2 generations, Vinik et al. (1986) described a structural defect of insulin associated with hyperinsulinemia. The insulin was found to elute later than normal human insulin on reverse phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to isolated rat adipocytes and stimulate glucose metabolism in them. The proband, aged 45 years, had a 9-year history of syncopal attacks. He showed resistance to exogenous insulin. Plasma counterregulatory hormones (glucagon, growth hormone, cortisol, epinephrine, norepinephrine) showed normal concentrations. Binding of exogenous insulin by the patient's cells was normal. The abnormal insulin was demonstrated in 2 of 3 sons and in a sister but not in the mother, brother, or niece. Sensitivity to insulin was normal in the 2 sons who had abnormal insulin. The explanation for the insulin resistance in the proband was unclear. The authors thought that the change in the insulin molecule in this family was different from either the B24 phe-to-ser (176730.0002) or the B25 phe-to-leu (176730.0001) mutations previously described. Inheritance The transmission pattern of hyperproinsulinemia in the families reported by Shoelson et al. (1983) and Gruppuso et al. (1984) was consistent with autosomal dominant inheritance. Molecular Genetics Tager et al. (1979) studied insulin isolated from the pancreas of a diabetic patient and concluded that one of the allelic genes had undergone a mutation resulting in substitution of leucine for phenylalanine at position 23 or 24 in the insulin B chain. Occurring in the invariant portion of the molecule, the mutation resulted in reduced biologic activity (Given et al., 1980). Kwok et al. (1981) isolated genomic DNA from the leukocytes of a diabetic patient with the mutant insulin identified by Given et al. (1980). After digestion with restriction endonuclease MboII, electrophoresis, and hybridization with cloned human cDNA probes, one MboII cleavage site had been lost, which is consistent with the postulated replacement of phenylalanine by leucine at position 24 of the insulin gene. Shoelson et al. (1983) demonstrated that the substitution in the mutant insulin identified by Tager et al. (1979) and Given et al. (1980) is leucine for phenylalanine at B25 (176730.0001). In a patient with hyperproinsulinemia, Shoelson et al. (1983) identified a substitution of serine for phenylalanine at position 24 of the insulin B chain (176730.0002). In a patient with mild diabetes, marked fasting hyperinsulinemia, and a reduced fasting C-peptide:insulin molar ratio, Haneda et al. (1983, 1984) found heterozygosity for the ser24-to-phe mutation in the insulin B chain. The patient, who was found to have abnormal circulating insulin molecules that could be distinguished from each other and from normal insulin, responded normally to exogenous insulin. Five additional family members of both sexes in 3 generations were affected. In affected members of the family with hyperproinsulinemia reported by Gruppuso et al. (1984), Chan et al. (1987) identified a heterozygous missense mutation in the B chain of the INS gene (H10D; 176730.0003). INHERITANCE \- Autosomal dominant ENDOCRINE FEATURES \- Hyperproinsulinemia (asymptomatic in some patients) \- Hyperinsulinemia (in some patients) \- Hyperglycemia (in some patients) \- Normal response to exogenously administered insulin MOLECULAR BASIS \- Caused by mutation in the insulin gene (INS, 176730.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	HYPERPROINSULINEMIA	c0342283	6,103	omim	https://www.omim.org/entry/616214	2019-09-22T15:49:35	{"mesh": ["C562776"], "omim": ["616214"]}
For a general discussion of hereditary prostate cancer, see 176807. Mapping Xu et al. (1998) presented evidence for the location of a prostate cancer susceptibility gene, which they symbolized HPCX, on Xq27-q28. Heterogeneity estimates suggested that the gene accounts for approximately 16% of hereditary prostate cancer cases. The finding was consistent with the results of a previous population-based study suggesting an X-linked mode of inheritance of prostate cancer. Linkage to Xq27-q28 was observed in a combined study population of 360 prostate cancer families collected at 4 independent sites in North America, Finland, and Sweden. A maximum 2-point lod score of 4.60 was observed with DXS1113 at theta = 0.26 in the combined data set. Parametric multipoint and nonparametric analyses provided results consistent with the 2-point analysis. The estimation of the proportion of X-linked families appeared to be the same in each family collection. A candidate prostate cancer susceptibility gene on the X chromosome is the androgen receptor gene (AR; 313700). AR, however, is located at Xq12, over 50 cM from the region implicated in the study of Xu et al. (1998). Peters et al. (2001) reported on linkage analysis at the putative HPCX locus in an independent set of 186 prostate cancer families. In 81 families with no evidence of male-to-male transmission, they found a lod score of 1.062 at theta = 0.28 with DXS984. Although this analysis did not show statistically significant evidence for the linkage of prostate cancer susceptibility to Xq27-q28, the results were considered consistent with a small percentage of families being linked to this region. Cancel-Tassin et al. (2001) examined evidence for linkage to the HPCX locus in 64 (37 previously reported and 27 newly identified) families from southern and western Europe with at least 3 affected individuals with prostate cancer and an average age at diagnosis of 66.4 years. Using both parametric and nonparametric linkage methods, no significant evidence of linkage was observed. A subset of 18 pedigrees without male-to-male transmission showed negative or low positive 2-point lod scores and negative multipoint lod scores across the entire region. Farnham et al. (2005) performed linkage analysis on 143 Utah pedigrees for the HPCX prostate cancer susceptibility locus. In a dataset containing pedigrees having no more than 5 generations, a multipoint theta lod score of 2.74 (p = 0.0002) was observed, which was considered statistically significant after correction for multiple testing. Theta lod is a linkage statistic that is analogous to a 2-point lod score but utilizes full multipoint haplotype information. For both the full-structure pedigrees (up to 7 generations) and the smaller subpedigrees, the linkage evidence was much reduced. By linkage disequilibrium and haplotype analysis of Finnish families with X-linked prostate cancer with no male-to-male transmission, Baffoe-Bonnie et al. (2005) refined the HPCX locus to a 150-kb region on Xq27-q28 between markers D3S2390 and bG82i1.0. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	PROSTATE CANCER, HEREDITARY, X-LINKED 1	c2931456	6,104	omim	https://www.omim.org/entry/300147	2019-09-22T16:20:49	{"doid": ["10283"], "mesh": ["C537243"], "omim": ["300147"], "orphanet": ["1331"], "synonyms": ["Alternative titles", "PROSTATE CANCER SUSCEPTIBILITY, X-LINKED"]}
Doctors have documented numerous cases of insertion of foreign bodies into the urethra, typically as the result of auto-erotic activities. This can result in infections and serious internal bleeding.[1][2] A wide variety of solid objects have been reported to have been inserted into the urethra, including batteries, safety pins, straws,[2] and telephone wires.[3] Liquefied objects have also been inserted into the urethra, such as an injection of cocaine[4] (which, arguably, had harmful results[5]). The Chuck Palahniuk story "Guts", from the novel Haunted, includes the story of a boy in his early teens inserting candle wax into his urethra.[6] ## See also[edit] * Rectal foreign body * Urethral sounding * Urethral intercourse ## References[edit] 1. ^ Boscolo-Berto, R.; Iafrate, M.; Viel, G. (2010). "Forensic implications in self-insertion of urethral foreign bodies". The Canadian Journal of Urology. 17 (1): 5026–5027. PMID 20156386. 2. ^ a b Rahman, N. U.; Elliott, S. P.; McAninch, J. W. (2004). "Self-inflicted male urethral foreign body insertion: endoscopic management and complications". BJU International. 94 (7): 1051–1053. doi:10.1111/j.1464-410X.2004.05103.x. PMID 15541127. 3. ^ Trehan, R. K.; Haroon, A.; Memon, S.; Turner, D. (2007). "Successful removal of a telephone cable, a foreign body through the urethra into the bladder: a case report". Journal of Medical Case Reports. 1: 153. doi:10.1186/1752-1947-1-153. PMC 2211490. PMID 18042278. 4. ^ Rebecca Kolberg (June 3, 1988). "Some People Will Try Anything". 5. ^ Robert Wanderer (Spring 1989). "The Case of the Missing Penis". Et cetera. 6. ^ "Guts". Printed in Playboy magazine on March 2004. This article about a disease of the genitourinary system is a stub. You can help Wikipedia by expanding it. * v * t * e This sexuality-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Urethral foreign body	c0433676	6,105	wikipedia	https://en.wikipedia.org/wiki/Urethral_foreign_body	2021-01-18T18:55:21	{"icd-10": ["T19.0"], "wikidata": ["Q7900430"]}
Adenosarcoma of the uterus is a rare tumor of the uterus that typically originates in the lining of the uterus (endometrium). This type of tumor is characterized by both benign (noncancerous) and malignant components (low-grade sarcoma). Typical symptoms in affected individuals may include abnormal vaginal bleeding, an enlarged uterus, and tissue protruding from the external os (external opening of the uterus that leads into the cavity of the cervix). It is most common in post-menopausal women but can affect women of any age. Factors that may predisposed an individual to the condition include hyperestrogenemia (high blood estrogen levels), chemotherapy, or radiotherapy. Recommended treatment includes hysterectomy, usually accompanied by bilateral salpingo-oophorectomy (removal of fallopian tubes and ovaries). Ovarian conservation is an option for reproductive age women. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Adenosarcoma of the uterus	c2103110	6,106	gard	https://rarediseases.info.nih.gov/diseases/9636/adenosarcoma-of-the-uterus	2021-01-18T18:02:16	{"mesh": ["C538232"], "umls": ["C2103110"], "synonyms": ["Mullerian adenosarcoma of the uterus", "Uterine adenosarcoma"]}
Conversion disorder is a disorder in which a person experiences blindness, paralysis, or other symptoms affecting the nervous system that cannot be explained solely by a physical illness or injury. Symptoms usually begin suddenly after a period of emotional or physical distress or psychological conflict. Conversion disorder is thought to be caused by the body’s reaction to a stressful physical or emotional event. Some research has identified potential neurological changes that may be related to symptoms of the disorder. Diagnosis of conversion disorder is based on identifying particular signs that are common among people with the disorder, as well as performing tests to rule out other causes of the symptoms. Treatment may include psychotherapy, hypnosis, and stress management training to help reduce symptoms. Treatment of any underlying psychological disorder is also recommended. The affected body part may require physical or occupational therapy until symptoms resolve. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Conversion disorder	c0009946	6,107	gard	https://rarediseases.info.nih.gov/diseases/6191/conversion-disorder	2021-01-18T18:01:06	{"mesh": ["D003291"], "umls": ["C0009946"], "synonyms": ["Functional neurological disorder", "FND", "Functional movement disorder"]}
Microspherophakia - metaphyseal dysplasia is a very rare syndrome associating bone dysplasia with micromelic dwarfism and eye defects. ## Epidemiology It has been reported in a father and his son. ## Clinical description Bone dysplasia is characterized by diaphyseal thickening of the long bones, metaphyseal deformation and epiphyseal irregularities. Eye defects consisted of myopia, microspherophakia, lens coloboma and luxation, and retinal detachment. The affected patients have normal mental development. ## Etiology The condition is most probably hereditary, transmitted as an autosomal dominant trait. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Microspherophakia-metaphyseal dysplasia syndrome	c1834880	6,108	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2551	2021-01-23T17:26:28	{"gard": ["5481"], "mesh": ["C536540"], "omim": ["157151"], "umls": ["C1834880"], "icd-10": ["Q87.5"], "synonyms": ["Verloes-Van Maldergem-de Marneffe syndrome"]}
Gluszcz et al. (1963) described 4 sibs with cutaneous hemangiomatosis, acrocyanosis, hyperflexibility of joints, and phimosis. Some showed slight abnormalities of the vertebral bodies and ocular hypertelorism. In 2 (a female aged 15 and a male aged 19), tumors resembling cerebellar angioblastoma of von Hippel-Lindau disease (193300) were removed from the cervicothoracic portion of the spinal canal. See disseminated hemangiomatosis (106070). Skel \- Joint hyperflexibility \- Loosejointedness \- Abnormal vertebral bodies \- Cervicothoracic spinal tumor GU \- Phimosis Inheritance \- Autosomal recessive Facies \- Ocular hypertelorism Skin \- Acrocyanosis \- Hemangiomatosis ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	HEMANGIOMATOSIS, CUTANEOUS, WITH ASSOCIATED FEATURES	c0220738	6,109	omim	https://www.omim.org/entry/234800	2019-09-22T16:27:13	{"mesh": ["C562438"], "omim": ["234800"]}
Physiological anisocoria is when human pupils differ in size. It is generally considered to be benign, though it must be distinguished from Congenital Horner's syndrome, pharmacological dilatation or other conditions connected to the sympathetic nervous system.[1] The prevalence of physiological anisocoria has not been found to be influenced by the sex, age, or iris color of the subject. ## Presentation[edit] The main characteristic that distinguishes physiological anisocoria is an increase of pupil size with lower light or reduced illumination, such that the pupils differ in size between the two eyes. At any given eye examination, up to 41% of healthy patients can show an anisocoria of 0.4 mm or more at one time or another. It can also occur as the difference between both pupils varies from day to day.[2] A normal population survey showed that during poor light or near dark conditions, differences of 1 mm on average between pupils was found.[3] The presence of physiologic anisocoria has been estimated at 20% of the normal population, so some degree of pupil difference may be expected in at least 1 in 5 clinic patients.[citation needed] ## Causes[edit] When detected during childhood, without any other symptoms and when other disorders are discarded through clinical tests, it should be considered a developmental or genetic phenomenon. Asymmetric pupil or dyscoria, potential causes of anisocoria, refer to an abnormal shape of the pupil which can happens due to developmental and intrauterine anomalies.[4] When light is shined in the abnormal eye and it remains dilated then it’s a pathological small pupil. ## References[edit] 1. ^ Doetsch, H. (May 1950). "Anisocoria as a physiological phenomenon". Art Wochensch. 5. 26 (20): 331–3.[needs update] 2. ^ Corbett, J.; Lam BL; Thompson HS (15 July 1987). "The prevalence of simple anisocoria". Am J Ophthalmol. 104 (1): 69–73. doi:10.1016/0002-9394(87)90296-0. PMID 3605282. 3. ^ London, Richard; Ellen Richrer Erringer; Harry J. Wyafr (March 1991). "Variation and Clinical Observation With Different Conditions of Illumination and Accommodation". Investigative Ophthalmology & Visual Science. 32 (3): 501–9. 4. ^ Optometry College, . "Pupil Anomalies: Reaction and Red Flags". Pacifica University Oregon. Retrieved 25 November 2012.CS1 maint: numeric names: authors list (link) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Physiological anisocoria	None	6,110	wikipedia	https://en.wikipedia.org/wiki/Physiological_anisocoria	2021-01-18T18:35:31	{"wikidata": ["Q7189712"]}
Osteomyelitis Other namesBone infection Osteomyelitis of the 1st toe SpecialtyInfectious disease, orthopedics SymptomsPain in a specific bone, overlying redness, fever, weakness[1] ComplicationsAmputation[2] Usual onsetYoung or old[1] DurationShort or long term[2] CausesBacterial, fungal[2] Risk factorsDiabetes, intravenous drug use, prior removal of the spleen, trauma to the area[1] Diagnostic methodBlood tests, medical imaging, bone biopsy[2] Differential diagnosisCharcot's joint, rheumatoid arthritis, infectious arthritis, giant cell tumor, cellulitis[1][3] TreatmentAntimicrobials, surgery[4] PrognosisLow risk of death with treatment[5] Frequency2.4 per 100,000 per year[6] Osteomyelitis (OM) is an infection of bone.[1] Symptoms may include pain in a specific bone with overlying redness, fever, and weakness.[1] The long bones of the arms and legs are most commonly involved in children, while the feet, spine, and hips are most commonly involved in adults.[2] The cause is usually a bacterial infection,[1][2] but rarely can be a fungal infection.[7] It may occur by spread from the blood or from surrounding tissue.[4] Risks for developing osteomyelitis include diabetes, intravenous drug use, prior removal of the spleen, and trauma to the area.[1] Diagnosis is typically suspected based on symptoms.[2] This is then supported by blood tests, medical imaging, or bone biopsy.[2] Treatment of bacterial osteomyelitis often involves both antimicrobials and surgery.[4] In those with poor blood flow, amputation may be required.[2] Treatment of the relatively rare fungal osteomyelitis as mycetoma infections entails antifungal medications.[8] In contrast to bacterial osteomyelitis, amputation or large bony resections is a more common fate of neglected fungal osteomyelitis namely mycetoma where infections of the foot account for the majority of cases.[7][8] Treatment outcomes of bacterial osteomyelitis are generally good when the condition has only been present a short time.[2] About 2.4 per 100,000 people are affected a year.[6] The young and old are more commonly affected.[1] Males are more commonly affected than females.[3] The condition was described at least as early as the 300s BC by Hippocrates.[4] Before the availability of antibiotics the risk of death was significant.[9] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Pathogenesis * 4 Diagnosis * 4.1 Classification * 5 Treatment * 6 History * 6.1 Fossil record * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Symptoms may include pain in a specific bone with overlying redness, fever, and weakness.[1] Onset may be sudden or gradual.[1] Enlarged lymph nodes may be present.[10] In fungal infections like Mycetoma there is usually a history of walking bare footed especially in rural and farming areas. Contrary to the mode of infection in bacterial osteomyelitis which is mostly blood born/hematogenous, the mode of fungal osteomyelitis mycetoma originates from the skin then invades deeper tissues until it reaches the bones.[7] ## Cause[edit] Drawing of Staphylococcus bacteria Age group Most common organisms Newborns (younger than 4 mo) S. aureus, Enterobacter species, and group A and B Streptococcus species Children (aged 4 mo to 4 y) S. aureus, group A Streptococcus species, Haemophilus influenzae, and Enterobacter species Children, adolescents (aged 4 y to adult) S. aureus (80%), group A Streptococcus species, H. influenzae, and Enterobacter species Adult S. aureus and occasionally Enterobacter or Streptococcus species Sickle cell anemia patients Salmonella species are most common in patients with sickle cell disease.[11] In children, the long bones are usually affected. In adults, the vertebrae and the pelvis are most commonly affected.[citation needed] Acute osteomyelitis almost invariably occurs in children because of rich blood supply to the growing bones. When adults are affected, it may be because of compromised host resistance due to debilitation, intravenous drug abuse, infectious root-canaled teeth, or other disease or drugs (e.g., immunosuppressive therapy).[citation needed] Osteomyelitis is a secondary complication in 1–3% of patients with pulmonary tuberculosis.[12] In this case, the bacteria, in general, spread to the bone through the circulatory system, first infecting the synovium (due to its higher oxygen concentration) before spreading to the adjacent bone.[12] In tubercular osteomyelitis, the long bones and vertebrae are the ones that tend to be affected.[12] Staphylococcus aureus is the organism most commonly isolated from all forms of osteomyelitis.[12] Bloodstream-sourced osteomyelitis is seen most frequently in children, and nearly 90% of cases are caused by Staphylococcus aureus. In infants, S. aureus, Group B streptococci (most common[13]) and Escherichia coli are commonly isolated; in children from one to 16 years of age, S. aureus, Streptococcus pyogenes, and Haemophilus influenzae are common. In some subpopulations, including intravenous drug users and splenectomized patients, Gram-negative bacteria, including enteric bacteria, are significant pathogens.[14] The most common form of the disease in adults is caused by injury exposing the bone to local infection. Staphylococcus aureus is the most common organism seen in osteomyelitis, seeded from areas of contiguous infection. But anaerobes and Gram-negative organisms, including Pseudomonas aeruginosa, E. coli, and Serratia marcescens, are also common. Mixed infections are the rule rather than the exception.[14] Systemic mycotic (fungal) infections may also cause osteomyelitis. The two most common are Blastomyces dermatitidis and Coccidioides immitis.[citation needed] In osteomyelitis involving the vertebral bodies, about half the cases are due to S. aureus, and the other half are due to tuberculosis (spread hematogenously from the lungs). Tubercular osteomyelitis of the spine was so common before the initiation of effective antitubercular therapy, it acquired a special name, Pott's disease.[citation needed] The Burkholderia cepacia complex has been implicated in vertebral osteomyelitis in intravenous drug users.[15] ## Pathogenesis[edit] In general, microorganisms may infect bone through one or more of three basic methods * Via the bloodstream (haematogeneously) – the most common method[16] * From nearby areas of infection (as in cellulitis), or * Penetrating trauma, including iatrogenic causes such as joint replacements or internal fixation of fractures or secondary periapical periodontitis in teeth.[12] The area usually affected when the infection is contracted through the bloodstream is the metaphysis of the bone.[16] Once the bone is infected, leukocytes enter the infected area, and, in their attempt to engulf the infectious organisms, release enzymes that lyse the bone. Pus spreads into the bone's blood vessels, impairing their flow, and areas of devitalized infected bone, known as sequestra, form the basis of a chronic infection.[12] Often, the body will try to create new bone around the area of necrosis. The resulting new bone is often called an involucrum.[12] On histologic examination, these areas of necrotic bone are the basis for distinguishing between acute osteomyelitis and chronic osteomyelitis. Osteomyelitis is an infective process that encompasses all of the bone (osseous) components, including the bone marrow. When it is chronic, it can lead to bone sclerosis and deformity.[citation needed] Chronic osteomyelitis may be due to the presence of intracellular bacteria (inside bone cells).[17] Also, once intracellular, the bacteria are able to escape and invade other bone cells.[18] At this point, the bacteria may be resistant to some antibiotics.[19] These combined facts may explain the chronicity and difficult eradication of this disease, resulting in significant costs and disability, potentially leading to amputation. Intracellular existence of bacteria in osteomyelitis is likely an unrecognized contributing factor to its chronic form.[citation needed] In infants, the infection can spread to a joint and cause arthritis. In children, large subperiosteal abscesses can form because the periosteum is loosely attached to the surface of the bone.[12] Because of the particulars of their blood supply, the tibia, femur, humerus, vertebra, the maxilla, and the mandibular bodies are especially susceptible to osteomyelitis.[20] Abscesses of any bone, however, may be precipitated by trauma to the affected area. Many infections are caused by Staphylococcus aureus, a member of the normal flora found on the skin and mucous membranes. In patients with sickle cell disease, the most common causative agent is Salmonella, with a relative incidence more than twice that of S. aureus.[11] ## Diagnosis[edit] Mycobacterium doricum osteomyelitis and soft tissue infection. Computed tomography scan of the right lower extremity of a 21-year-old patient, showing abscess formation adjacent to nonunion of a right femur fracture. Extensive osteomyelitis of the forefoot Osteomyelitis in both feet as seen on bone scan The diagnosis of osteomyelitis is complex and relies on a combination of clinical suspicion and indirect laboratory markers such as a high white blood cell count and fever, although confirmation of clinical and laboratory suspicion with imaging is usually necessary.[21] Radiographs and CT are the initial method of diagnosis, but are not sensitive and only moderately specific for the diagnosis. They can show the cortical destruction of advanced osteomyelitis, but can miss nascent or indolent diagnoses.[21] Confirmation is most often by MRI. The presence of edema, diagnosed as increased signal on T2 sequences, is sensitive, but not specific, as edema can occur in reaction to adjacent cellulitis. Confirmation of bony marrow and cortical destruction by viewing the T1 sequences significantly increases specificity. The administration of intravenous gadolinium-based contrast enhances specificity further. In certain situations, such as severe Charcot arthropathy, diagnosis with MRI is still difficult.[21] Similarly, it is limited in distinguishing bone infarcts from osteomyelitis in sickle cell anemia.[22] Nuclear medicine scans can be a helpful adjunct to MRI in patients who have metallic hardware that limits or prevents effective magnetic resonance. Generally a triple phase technetium 99 based scan will show increased uptake on all three phases. Gallium scans are 100% sensitive for osteomyelitis but not specific, and may be helpful in patients with metallic prostheses. Combined WBC imaging with marrow studies have 90% accuracy in diagnosing osteomyelitis.[23] Diagnosis of osteomyelitis is often based on radiologic results showing a lytic center with a ring of sclerosis.[12] Culture of material taken from a bone biopsy is needed to identify the specific pathogen;[24] alternative sampling methods such as needle puncture or surface swabs are easier to perform, but do not produce reliable results.[25][26] Factors that may commonly complicate osteomyelitis are fractures of the bone, amyloidosis, endocarditis, or sepsis.[12] ### Classification[edit] The definition of OM is broad, and encompasses a wide variety of conditions. Traditionally, the length of time the infection has been present and whether there is suppuration (pus formation) or sclerosis (increased density of bone) is used to arbitrarily classify OM. Chronic OM is often defined as OM that has been present for more than one month. In reality, there are no distinct subtypes; instead there is a spectrum of pathologic features that reflect balance between the type and severity of the cause of the inflammation, the immune system and local and systemic predisposing factors.[citation needed] * Suppurative osteomyelitis * Acute suppurative osteomyelitis * Chronic suppurative osteomyelitis * Primary (no preceding phase) * Secondary (follows an acute phase) * Non-suppurative osteomyelitis * Diffuse sclerosing * Focal sclerosing (condensing osteitis) * Proliferative periostitis (periostitis ossificans, Garré's sclerosing osteomyelitis) * Osteoradionecrosis OM can also be typed according to the area of the skeleton in which it is present. For example, osteomyelitis of the jaws is different in several respects from osteomyelitis present in a long bone. Vertebral osteomyelitis is another possible presentation.[citation needed] ## Treatment[edit] Osteomyelitis often requires prolonged antibiotic therapy for weeks or months. A PICC line or central venous catheter can be placed for long-term intravenous medication administration. Some studies of children with acute osteomyelitis report that antibiotic by mouth may be justified due to PICC-related complications.[27][28] It may require surgical debridement in severe cases, or even amputation. Antibiotics by mouth and by intravenous appear similar.[29][30] Due to insufficient evidence it is unclear what the best antibiotic treatment is for osteomyelitis in people with sickle cell disease as of 2019.[31] Initial first-line antibiotic choice is determined by the patient's history and regional differences in common infective organisms. A treatment lasting 42 days is practiced in a number of facilities.[32] Local and sustained availability of drugs have proven to be more effective in achieving prophylactic and therapeutic outcomes.[33] Open surgery is needed for chronic osteomyelitis, whereby the involucrum is opened and the sequestrum is removed or sometimes saucerization[34] can be done. Hyperbaric oxygen therapy has been shown to be a useful adjunct to the treatment of refractory osteomyelitis.[35][36] Before the widespread availability and use of antibiotics, blow fly larvae were sometimes deliberately introduced to the wounds to feed on the infected material, effectively scouring them clean.[37][38] There is tentative evidence that bioactive glass may also be useful in long bone infections.[39] Support from randomized controlled trials, however, was not available as of 2015.[40] ## History[edit] The word is from Greek words ὀστέον osteon, meaning bone, μυελό- myelo- meaning marrow, and -ῖτις -itis meaning inflammation. In 1875, American artist Thomas Eakins depicted a surgical procedure for osteomyelitis at Jefferson Medical College, in an oil painting titled The Gross Clinic.[citation needed] ### Fossil record[edit] Main article: Paleopathology Evidence for osteomyelitis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. It has been reported in fossils of the large carnivorous dinosaur Allosaurus fragilis.[41] Osteomyelitis has been also associated with the first evidence of parasites in dinosaur bones.[42] ## See also[edit] * Brodie abscess * Chronic recurrent multifocal osteomyelitis * SAPHO syndrome * Garre's sclerosing osteomyelitis ## References[edit] 1. ^ a b c d e f g h i j k "Osteomyelitis". NORD (National Organization for Rare Disorders). 2005. Archived from the original on 11 February 2017. Retrieved 20 July 2017. 2. ^ a b c d e f g h i j "Osteomyelitis". Genetic and Rare Diseases Information Center (GARD). 2016. Archived from the original on 9 February 2017. Retrieved 20 July 2017. 3. ^ a b Ferri, Fred F. (2017). Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 924. ISBN 978-0323529570. Archived from the original on 2017-09-10. 4. ^ a b c d Schmitt, SK (June 2017). "Osteomyelitis". Infectious Disease Clinics of North America. 31 (2): 325–38. doi:10.1016/j.idc.2017.01.010. PMID 28483044. 5. ^ Bennett, John E.; Dolin, Raphael; Blaser, Martin J. (2014). Principles and Practice of Infectious Diseases. Elsevier Health Sciences. p. 2267. ISBN 978-1455748013. Archived from the original on 2017-09-10. 6. ^ a b Hochberg, Marc C.; Silman, Alan J.; Smolen, Josef S.; Weinblatt, Michael E.; Weisman, Michael H. (2014). Rheumatology E-Book. Elsevier Health Sciences. p. 885. ISBN 978-0702063039. Archived from the original on 2017-09-10. 7. ^ a b c El-Sobky, TA; Haleem, JF; Samir, S (2015). "Eumycetoma Osteomyelitis of the Calcaneus in a Child: A Radiologic-Pathologic Correlation following Total Calcanectomy". Case Reports in Pathology. 2015: 129020. doi:10.1155/2015/129020. PMC 4592886. PMID 26483983. 8. ^ a b van de Sande, Wendy; Fahal, Ahmed; Ahmed, Sarah Abdalla; Serrano, Julian Alberto; Bonifaz, Alexandro; Zijlstra, Ed (10 March 2018). "Closing the mycetoma knowledge gap". Medical Mycology. 56 (suppl_1): S153–S164. doi:10.1093/mmy/myx061. PMID 28992217. 9. ^ Brackenridge, R. D. C.; Croxson, Richard S.; Mackenzie, Ross (2016). Medical Selection of Life Risks 5th Edition Swiss Re branded. Springer. p. 912. ISBN 978-1349566327. Archived from the original on 2017-09-10. 10. ^ Root, Richard K.; Waldvogel, Francis; Corey, Lawrence; Stamm, Walter E. (1999). Clinical Infectious Diseases: A Practical Approach. Oxford University Press. p. 577. ISBN 978-0-19-508103-9. 11. ^ a b Burnett, M.W.; J.W. Bass; B.A. Cook (1998-02-01). "Etiology of osteomyelitis complicating sickle cell disease". Pediatrics. 101 (2): 296–97. doi:10.1542/peds.101.2.296. PMID 9445507. 12. ^ a b c d e f g h i j Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 810–11 ISBN 978-1-4160-2973-1 13. ^ Haggerty, Maureen (2002). "Streptococcal Infections". Gale Encyclopedia of Medicine. The Gale Group. Archived from the original on 2008-03-25. Retrieved 2008-03-14. 14. ^ a b Carek, P.J.; L.M. Dickerson; J.L. Sack (2001-06-15). "Diagnosis and management of osteomyelitis". Am Fam Physician. 63 (12): 2413–20. PMID 11430456. 15. ^ Weinstein, Lenny; Knowlton, Christin A.; Smith, Miriam A. (2007-12-16). "Cervical osteomyelitis caused by Burkholderia cepacia after rhinoplasty". J Infect Developing Countries. 2 (1): 76–77. doi:10.3855/jidc.327. ISSN 1972-2680. PMID 19736393. Archived from the original on January 7, 2009. 16. ^ a b Luqmani, Raashid; Robb, James; Daniel, Porter; Benjamin, Joseph (2013). Orthopaedics, Trauma and Rheumatology (second ed.). Mosby. p. 96. ISBN 978-0723436805. 17. ^ Ellington. "Microbial Pathogenesis" (1999).[page needed] 18. ^ Ellington Journal of Bone and Joint Surgery (2003).[page needed] 19. ^ Ellington. Journal of Orthopedic Research (2006).[page needed] 20. ^ King MD, Randall W, Johnson D (2006-07-13). "Osteomyelitis". eMedicine. WebMD. Archived from the original on 2007-11-09. Retrieved 2007-11-11. 21. ^ a b c Howe, B. M.; Wenger, D. E.; Mandrekar, J; Collins, M. S. (2013). "T1-weighted MRI imaging features of pathologically proven non-pedal osteomyelitis". Academic Radiology. 20 (1): 108–14. doi:10.1016/j.acra.2012.07.015. PMID 22981480. 22. ^ Delgado, J; Bedoya, M. A.; Green, A. M.; Jaramillo, D; Ho-Fung, V (2015). "Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease – can it differentiate bone infarcts from acute osteomyelitis?". Pediatric Radiology. 45 (13): 1981–87. doi:10.1007/s00247-015-3423-8. PMID 26209118. S2CID 7362493. 23. ^ Termaat, M. F.; Raijmakers, P. G.; Scholten, H. J.; Bakker, F. C.; Patka, P; Haarman, H. J. (2005). "The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: A systematic review and meta-analysis". The Journal of Bone and Joint Surgery. American Volume. 87 (11): 2464–71. doi:10.2106/JBJS.D.02691. PMID 16264122. 24. ^ Zuluaga AF; Galvis W; Saldarriaga JG; Agudelo M; Salazar BE; Vesga O (2006-01-09). "Etiologic diagnosis of chronic osteomyelitis: A prospective study". Archives of Internal Medicine. 166 (1): 95–100. doi:10.1001/archinte.166.1.95. ISSN 0003-9926. PMID 16401816. 25. ^ Zuluaga, Andrés F; Galvis, Wilson; Jaimes, Fabián; Vesga, Omar (2002-05-16). "Lack of microbiological concordance between bone and non-bone specimens in chronic osteomyelitis: An observational study". BMC Infectious Diseases. 2 (1): 8. doi:10.1186/1471-2334-2-8. PMC 115844. PMID 12015818. 26. ^ Senneville E, Morant H, Descamps D, et al. (2009). "Needle puncture and transcutaneous bone biopsy cultures are inconsistent in patients with diabetes and suspected osteomyelitis of the foot". Clinical Infectious Diseases. 48 (7): 888–93. doi:10.1086/597263. PMID 19228109. 27. ^ Keren, Ron; Shah, Samir S.; Srivastava, Rajendu; Rangel, Shawn; Bendel-Stenzel, Michael; Harik, Nada; Hartley, John; Lopez, Michelle; Seguias, Luis (2015-02-01). "Comparative Effectiveness of Intravenous vs Oral Antibiotics for Postdischarge Treatment of Acute Osteomyelitis in Children". JAMA Pediatrics. 169 (2): 120–28. doi:10.1001/jamapediatrics.2014.2822. ISSN 2168-6203. PMID 25506733. 28. ^ Norris, Anne H; Shrestha, Nabin K; Allison, Genève M; Keller, Sara C; Bhavan, Kavita P; Zurlo, John J; Hersh, Adam L; Gorski, Lisa A; Bosso, John A (2019-01-01). "2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapya". Clinical Infectious Diseases. 68 (1): e1–e35. doi:10.1093/cid/ciy745. ISSN 1058-4838. PMID 30423035. 29. ^ Sæterdal, I; Akselsen, PE; Berild, D; Harboe, I; Odgaard-Jensen, J; Reinertsen, E; Vist, GE; Klemp, M (2010). "Antibiotic Therapy in Hospital, Oral Versus Intravenous Treatment". Oslo, Norway: Knowledge Centre for the Health Services at The Norwegian Institute of Public Health. PMID 29319957. Cite journal requires `\|journal=` (help) 30. ^ Stengel, D; Bauwens, K; Sehouli, J; Ekkernkamp, A; Porzsolt, F (October 2001). "Systematic review and meta-analysis of antibiotic therapy for bone and joint infections". The Lancet. Infectious Diseases. 1 (3): 175–88. doi:10.1016/S1473-3099(01)00094-9. PMID 11871494. 31. ^ Martí-Carvajal, AJ; Agreda-Pérez, LH (7 October 2019). "Antibiotics for treating osteomyelitis in people with sickle cell disease". The Cochrane Database of Systematic Reviews. 10: CD007175. doi:10.1002/14651858.CD007175.pub5. PMC 6778815. PMID 31588556. 32. ^ Putland M.D, Michael S., Hyperbaric Medicine, Capital Regional Medical Center, Tallahassee, Florida, personal inquiry June 2008. 33. ^ Soundrapandian, C; Datta S; Sa B (2007). "Drug-eluting implants for osteomyelitis". Critical Reviews in Therapeutic Drug Carrier Systems. 24 (6): 493–545. doi:10.1615/CritRevTherDrugCarrierSyst.v24.i6.10. PMID 18298388. 34. ^ "Saucerization". 35. ^ Mader JT, Adams KR, Sutton TE (1987). "Infectious diseases: pathophysiology and mechanisms of hyperbaric oxygen". Journal of Hyperbaric Medicine. 2 (3): 133–40. Archived from the original on 2009-02-13. Retrieved 2008-05-16. 36. ^ Kawashima M, Tamura H, Nagayoshi I, Takao K, Yoshida K, Yamaguchi T (2004). "Hyperbaric oxygen therapy in orthopedic conditions". Undersea and Hyperbaric Medicine. 31 (1): 155–62. PMID 15233171. Archived from the original on 2009-02-16. Retrieved 2008-05-16. 37. ^ Baer M.D., William S. (1 July 1931). "The Treatment of Chronic Osteomyelitis with the Maggot (Larva of the Blow Fly)". Journal of Bone and Joint Surgery. 13 (3): 438–75. Archived from the original on 22 December 2007. Retrieved 2007-11-12. 38. ^ McKeever, Duncan Clark (June 2008). "The Classic: Maggots in Treatment of Osteomyelitis: A Simple Inexpensive Method". Clinical Orthopaedics and Related Research. 466 (6): 1329–35. doi:10.1007/s11999-008-0240-5. PMC 2384033. PMID 18404291. 39. ^ Aurégan, JC; Bégué, T (December 2015). "Bioactive glass for long bone infection: a systematic review". Injury. 46 Suppl 8: S3–7. doi:10.1016/s0020-1383(15)30048-6. PMID 26747915. 40. ^ van Gestel, NA; Geurts, J; Hulsen, DJ; van Rietbergen, B; Hofmann, S; Arts, JJ (2015). "Clinical Applications of S53P4 Bioactive Glass in Bone Healing and Osteomyelitic Treatment: A Literature Review". BioMed Research International. 2015: 684826. doi:10.1155/2015/684826. PMC 4609389. PMID 26504821. 41. ^ Molnar, R. E., 2001, '"Theropod paleopathology: a literature survey": In: Mesozoic Vertebrate Life, edited by Tanke, D. H., and Carpenter, K., Indiana University Press, pp. 337–63. 42. ^ "First Evidence of Parasites in Dinosaur Bones Found". smithsonianmag. Retrieved 2020-11-24. ## External links[edit] Wikimedia Commons has media related to Osteomyelitis. * 00298 at CHORUS * Acosta, Chin; et al. (2004). "Diagnosis and management of adult pyogenic osteomyelitis of the cervical spine" (PDF). Neurosurg Focus. 17 (6): E2. doi:10.3171/foc.2004.17.6.2. PMID 15636572. Classification D * ICD-10: M86 * ICD-9-CM: 730 * MeSH: D010019 * DiseasesDB: 9367 External resources * MedlinePlus: 000437 * eMedicine: ped/1677 * Patient UK: Osteomyelitis * v * t * e Bone and joint disease Bone Inflammation endocrine: * Osteitis fibrosa cystica * Brown tumor infection: * Osteomyelitis * Sequestrum * Involucrum * Sesamoiditis * Brodie abscess * Periostitis * Vertebral osteomyelitis Metabolic * Bone density * Osteoporosis * Juvenile * Osteopenia * Osteomalacia * Paget's disease of bone * Hypophosphatasia Bone resorption * Osteolysis * Hajdu–Cheney syndrome * Ainhum * Gorham's disease Other * Ischaemia * Avascular necrosis * Osteonecrosis of the jaw * Complex regional pain syndrome * Hypertrophic pulmonary osteoarthropathy * Nonossifying fibroma * Pseudarthrosis * Stress fracture * Fibrous dysplasia * Monostotic * Polyostotic * Skeletal fluorosis * bone cyst * Aneurysmal bone cyst * Hyperostosis * Infantile cortical hyperostosis * Osteosclerosis * Melorheostosis * Pycnodysostosis Joint Chondritis * Relapsing polychondritis Other * Tietze's syndrome Combined Osteochondritis * Osteochondritis dissecans Child leg: * hip * Legg–Calvé–Perthes syndrome * tibia * Osgood–Schlatter disease * Blount's disease * foot * Köhler disease * Sever's disease spine * * Scheuermann's_disease arm: * wrist * Kienböck's disease * elbow * Panner disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Osteomyelitis	c0008707	6,111	wikipedia	https://en.wikipedia.org/wiki/Osteomyelitis	2021-01-18T18:58:53	{"gard": ["7286"], "mesh": ["D010019"], "umls": ["C0008707", "C2242472", "C0029443"], "icd-10": ["M86"], "wikidata": ["Q938983"]}
Reticular pigmented anomaly of the flexures Other namesKitamura reticulate acropigmentation[1] SpecialtyDermatology Reticular pigmented anomaly of the flexures (also known as "dark dot disease", and "Dowling–Degos' disease") is a fibrous anomaly of the flexures or bending parts of the axillae, neck and inframammary/sternal areas.[2]:856 It is an autosomal-dominant pigmentary disorder that may appear in adolescence or adulthood. This condition is due to mutations in structural/desmosomal proteins found within stratified squamous epithelium.[3] Dark dot disease is associated with KRT5.[4] ## See also[edit] * List of cutaneous conditions * List of cutaneous conditions caused by mutations in keratins ## References[edit] 1. ^ "Dowling-Degos disease \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 23 April 2019. 2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 4. ^ Betz RC, Planko L, Eigelshoven S, et al. (March 2006). "Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease". Am. J. Hum. Genet. 78 (3): 510–9. doi:10.1086/500850. PMC 1380294. PMID 16465624. ## External links[edit] Classification D * OMIM: 179850 * MeSH: C562924 * 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 This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Reticular pigmented anomaly of the flexures	c3714534	6,112	wikipedia	https://en.wikipedia.org/wiki/Reticular_pigmented_anomaly_of_the_flexures	2021-01-18T18:46:19	{"gard": ["9775"], "mesh": ["C562924"], "umls": ["C3714534"], "orphanet": ["79145"], "wikidata": ["Q7316720"]}
Middle ear neuroendocrine tumor is a rare, otorhinolaryngologic tumor characterized by a mixed glandular and non-glandular histological features and positive immunostaining for pancytokeratin, vimentin, synaptophysin and islet-1 protein. Common signs and symptoms are hearing loss, mass, pain, discharge, equilibrium disturbances, tinnitus and nerve paralysis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Middle ear neuroendocrine tumor	None	6,113	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100084	2021-01-23T17:23:55	{}
Congenital stromal corneal dystrophy (CSCD) is an extremely rare form of stromal corneal dystrophy (see this term) characterized by opaque flaky or feathery clouding of the corneal stroma, and moderate to severe visual loss. ## Epidemiology The exact prevalence of this corneal dystrophy is not known but it is very rare: CSCD has been reported in 4 families to date in Germany, France, Belgium and Norway. ## Clinical description Patients develop bilateral corneal lesions before birth. The flakes and spots become more numerous with age, progressively increasing the effect on vision. Corneal erosions, photophobia and corneal vascularization are absent. Some patients have strabismus or primary open-angle glaucoma. ## Etiology The etiology of this condition is not known but mutations in the DCN gene (12q23) which codes for decorin have been identified in affected patients. DCN codes for a protein that may affect the rate of fibril formation. ## Diagnostic methods The morphologic abnormalities observed in CSCD include a peculiar arrangement of tightly packed lamellae having highly aligned collagen fibrils of an unusually small diameter. ## Genetic counseling Transmission appears to be autosomal dominant. ## Management and treatment A penetrating keratoplasty is the treatment of choice. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Congenital stromal corneal dystrophy	c1864738	6,114	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101068	2021-01-23T17:05:37	{"mesh": ["C566452"], "omim": ["610048"], "umls": ["C1864738"], "icd-10": ["H18.5"], "synonyms": ["CSCD", "Congenital hereditary stromal dystrophy", "Witschel dystrophy"]}
Dyck and Ohta (1975) classified four types of hereditary sensory neuropathy. Robinson et al. (1977) and Staal and Mechelse (1978) reported examples of hereditary sensory neuropathy apparently distinct from any of the four. Staal and Mechelse's report concerned 2 brothers with late-onset sensory ataxia without ulcerating acropathy or autonomic abnormality. The older patient had oculomotor dysfunction and extensor plantar responses. Limbs \- No ulcerating acropathy Neuro \- Sensory neuropathy \- Late-onset sensory ataxia \- No autonomic abnormality \- Oculomotor dysfunction \- Extensor plantar response Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	NEUROPATHY, HEREDITARY SENSORY, ATYPICAL	c1850384	6,115	omim	https://www.omim.org/entry/256860	2019-09-22T16:24:18	{"mesh": ["C564946"], "omim": ["256860"]}
Duplication of urethra is a very rare condition where there is an extra urethra, instead of the normal one. Urethral duplications can be classified into three types: incomplete urethral duplication (type 1), complete urethral duplication (type 2), and urethral duplication as a result of two bladdersThe urethra is the tube that connects the urinary bladder to the genitals for the removal of fluids from the body. In men, the urethra is a long tube that runs through the penis. In women, the urethra is shorter and emerges above the vaginal opening. Click here to view a picture of the male urinary tract. Click here to view a picture of the female urinary tract. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Duplication of urethra	c0266348	6,116	gard	https://rarediseases.info.nih.gov/diseases/1975/duplication-of-urethra	2021-01-18T18:00:48	{"umls": ["C0266348"], "orphanet": ["237"], "synonyms": ["Urethral duplication"]}
A number sign (#) is used with this entry because Hennekam lymphangiectasia-lymphedema syndrome-2 (HKLLS2) is caused by homozygous or compound heterozygous mutation in the FAT4 gene (612411) on chromosome 4q28. Biallelic mutation in the FAT4 gene can also cause Van Maldergem syndrome-2 (VMLDS2; 615546), a distinct disorder that shows overlapping features with HKLLS. Description Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by generalized lymphatic dysplasia affecting various organs, including the intestinal tract, pericardium, and limbs. Additional features of the disorder include facial dysmorphism and cognitive impairment (summary by Alders et al., 2014). For a discussion of genetic heterogeneity of Hennekam lymphangiectasia-lymphedema syndrome, see HKLLS1 (235510). Clinical Features Hennekam et al. (1989) described a syndrome of intestinal lymphangiectasia with severe lymphedema of the limbs, genitalia, and face, and severe mental retardation. Intestinal lymphangiectasia was accompanied by the usual hypoproteinemia, hypogammaglobulinemia, and lymphocytopenia. Facial anomalies included flat face, flat nasal bridge, hypertelorism, epicanthal folds, small mouth, tooth anomalies, and ear defects. The facial appearance was Oriental. Down syndrome had been suspected in some of the patients. The patients had seizures. Erysipelas was a problem complicating the edema of the legs. Autosomal recessive inheritance was strongly supported by the occurrence of the disorder in 2 males and 2 females of 2 sibships from parents who shared a common ancestral couple. Hennekam et al. (1989) reviewed genetic syndromes with lymphangiectasia and lymphedema as features. Alders et al. (2014) reported 9 patients from 5 unrelated families with Hennekam lymphangiectasia-lymphedema syndrome. Two of the families had previously been reported by Hennekam et al. (1989) and Al-Gazali et al. (2003). All patients had an unusual facial appearance, with flat face, flat nasal bridge, hypertelorism, epicanthus, blepharophimosis, small ears, small mouth, and irregular dentition. Two sibs had hearing loss. Most had poor overall growth, but only 1 had microcephaly. All had lymphedema of the limbs, and all but 1 had lymphangiectasia variably affecting the gut, pericardium, lungs, kidneys, and genitalia. Other features included camptodactyly and rare syndactyly. Borderline to mild cognitive impairment was common, although 2 sibs apparently had normal cognition. Alders et al. (2014) noted that the facial appearance was remarkably similar to that of Van Maldergem syndrome. Inheritance The transmission pattern of HKLLS2 in the families reported by Alders et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics In affected members of 5 unrelated families with Hennekam lymphangiectasia-lymphedema syndrome-2, Alders et al. (2014) identified homozygous or compound heterozygous mutations in the FAT4 gene (see, e.g., 612411.0003; 612411.0007-612411.0010). The mutation in the first family was found using a combination of homozygosity mapping and whole-exome sequencing. Subsequent mutations were identified in 4 of 24 Hennekam syndrome patients who underwent direct sequencing of the FAT4 gene. Overall, FAT4 mutations were present in 5 (20%) of 25 families with the disorder. One of the homozygous mutations (E2375K; 612411.0003) was identified in 3 affected members of the original family with Hennekam syndrome reported by Hennekam et al. (1989). Functional studies of the FAT4 variants were not performed. INHERITANCE \- Autosomal recessive GROWTH Other \- Growth retardation HEAD & NECK Face \- Dysmorphic facies \- Flat face Ears \- Small ears \- Thick helices \- Hearing loss (in some patients) Eyes \- Hypertelorism \- Epicanthus \- Blepharophimosis Nose \- Flat nasal bridge Mouth \- Small mouth Teeth \- Irregular dentition CARDIOVASCULAR Heart \- Pericardial lymphangiectasia RESPIRATORY Lung \- Pulmonary lymphangiectasia ABDOMEN Gastrointestinal \- Intestinal lymphangiectasia GENITOURINARY Kidneys \- Renal lymphangiectasia SKELETAL Hands \- Camptodactyly MUSCLE, SOFT TISSUES \- Lymphedema \- Lymphangiectasia NEUROLOGIC Central Nervous System \- Impaired cognition (in some patients) MOLECULAR BASIS \- Caused by mutation in the FAT atypical cadherin 4 gene (FAT4, 612411.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 2	c0340834	6,117	omim	https://www.omim.org/entry/616006	2019-09-22T15:50:13	{"doid": ["0060366"], "mesh": ["C537255"], "omim": ["616006"], "orphanet": ["2136"]}
A number sign (#) is used with this entry because of evidence that leukoencephalopathy with dystonia and motor neuropathy (LKDMN) is caused by homozygous mutation in the SCP2 gene (184755) on chromosome 1p32. One such patient has been reported. Clinical Features Ferdinandusse et al. (2006) described the first known patient with deficiency of sterol carrier protein-2 (SCPx), a peroxisomal enzyme with thiolase activity, which is required for the breakdown of branched-chain fatty acids. The patient was a 45-year-old white man with a 28-year history of dystonic head tremor and spasmodic torticollis. He had noticed a stutter for the first time when he was 7 years old. At age 17 years, he observed a spasmodic torticollis to the left side, with a dystonic head tremor in stressful situations. During a fertility checkup by a urologist at the age of 29 years, hypergonadotrophic hypogonadism and azoospermia were diagnosed. One of 2 brothers was reported to have similar neurologic complaints. Cranial magnetic resonance imaging (MRI) showed bilateral hyperintense signals in the thalamus, butterfly-like lesions in the pons, and lesions in the occipital region. Neurologic examination revealed hyposmia, pathologic saccadic eye movements, and a slight hypoacusis. Deep tendon reflexes were brisk in the arms but diminished in the lower extremities. There were slight cerebellar signs, with left-sided intention tremor and rebound phenomenon. Metabolite analyses of plasma revealed an accumulation of branched-chain pristanic acid, and abnormal bile alcohol glucuronides were excreted in urine. In cultured skin fibroblasts, the thiolytic activity of SCPx was deficient, and no SCPx protein could be detected by Western blotting. Molecular Genetics By mutation analysis of the SCP2 gene in a patient with leukoencephalopathy with dystonia and motor neuropathy, Ferdinandusse et al. (2006) identified a homozygous 1-bp insertion (545_546insA) (184755.0001). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Saccadic eye movements GENITOURINARY Internal Genitalia (Male) \- Hypergonadotrophic hypogonadism \- Azoospermia NEUROLOGIC Central Nervous System \- Dystonic head tremor \- Spasmodic torticollis \- Bilateral hyperintense signals seen on MRI \- Butterfly lesions of the pons MISCELLANEOUS \- Stressful situations can exacerbate symptoms \- One patient has been described (last curated May 2006) MOLECULAR BASIS \- Caused by mutation in the sterol carrier protein-2 gene (SCP2, 184755.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	LEUKOENCEPHALOPATHY WITH DYSTONIA AND MOTOR NEUROPATHY	c3150990	6,118	omim	https://www.omim.org/entry/613724	2019-09-22T15:57:42	{"omim": ["613724"], "orphanet": ["163684"], "synonyms": ["STEROL CARRIER PROTEIN 2 DEFICIENCY", "Alternative titles"]}
Galactocele SpecialtyGynaecology A galactocele (also called lacteal cyst or milk cyst) is a retention cyst containing milk or a milky substance that is usually located in the mammary glands. They can occur in women during or shortly after lactation. They present as a firm mass, often subareolar, and are caused by the obstruction of a lactiferous duct. Clinically, they appear similar to a cyst on examination.[1] The duct becomes more distended over time by epithelial cells and milk. It may rarely be complicated by a secondary infection and result in abscess formation. These cysts may rupture leading to formation of inflammatory reaction and may mimic malignancy. Once lactation has ended the cyst should resolve on its own without intervention. A galactocele is not normally infected as the milk within is sterile and has no outlet through which to become contaminated. Treatment is by aspiration of the contents or by excision of the cyst. Antibiotics are given to prevent infection.[2] Galactoceles may be associated with oral contraceptive use.[3] ## References[edit] 1. ^ Oxford Cases in Medicine and Surgery. 2. ^ Bhat Sriram, SRB's Manual of Surgery, 2010, New Delhi 3. ^ "Archived copy". Archived from the original on 2011-11-21. Retrieved 2011-10-31.CS1 maint: archived copy as title (link) Reference Robbins Basic Pathology ## External links[edit] Classification D * ICD-10: N64.8 * ICD-9-CM: 611.5 * MeSH: C535998 C535998, C535998 * DiseasesDB: 5053 * Case description and discussion at Harvard.edu * v * t * e Breast disease Inflammation * Mastitis * Nonpuerperal mastitis * Subareolar abscess * Granulomatous mastitis Physiological changes and conditions * Benign mammary dysplasia * Duct ectasia of breast * Chronic cystic mastitis * Mammoplasia * Gynecomastia * Adipomastia (lipomastia, pseudogynecomastia) * Breast hypertrophy * Breast atrophy * Micromastia * Amastia * Anisomastia * Breast engorgement Nipple * Nipple discharge * Galactorrhea * Inverted nipple * Cracked nipples * Nipple pigmentation Masses * Galactocele * Breast cyst * Breast hematoma * Breast lump * Pseudoangiomatous stromal hyperplasia Other * Pain * Tension * Ptosis * Fat necrosis * Amazia This women's health related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Galactocele	c0152243	6,119	wikipedia	https://en.wikipedia.org/wiki/Galactocele	2021-01-18T18:42:55	{"gard": ["8401"], "mesh": ["C535998"], "umls": ["C0152243"], "wikidata": ["Q686131"]}
A number sign (#) is used with this entry because of evidence that this form of pigmented hypomaturation-type amelogenesis imperfecta (AI2A2) is caused by homozygous mutation in the matrix metalloproteinase-20 gene (MMP20; 604629) on chromosome 11q22. For a discussion of genetic heterogeneity of the hypomaturation type of AI, see 204700. Description Autosomal recessive amelogenesis imperfecta pigmented hypomaturation type is characterized by enamel of normal thickness that is hypomineralized and has a mottled appearance. The slightly soft enamel detaches easily from the dentin, and radiographs show a lack of contrast between enamel and dentin (Witkop, 1988). Clinical Features Kim et al. (2005) reported a family in which 2 members had autosomal recessive pigmented hypomaturation AI. The enamel layer of the teeth was pigmented, showing an agar brown discoloration. The surface of the enamel was mottled and rough, but hard and brittle. Chunks of enamel had fractured away from several teeth. Radiographically, the enamel layer was usually more opaque then the underlying dentin, but not in all areas, and was never as radioopaque as normal enamel. The proband had an anterior open bite. Papagerakis et al. (2008) described an 11-year-old Chinese girl with hypoplastic-hypomaturation amelogenesis imperfecta and deep overbite. The enamel layer of her teeth was characterized by surface roughness and nonhomogeneous yellowish brown stain. Her tooth number and size were normal, but the enamel layer was thin and showed little contrast with the dentin. Wang et al. (2013) described a 14-year-old boy with generalized hypoplastic enamel that abraded easily and was sensitive to thermal change. The thin enamel layer was only slightly more radioopaque than the underlying dentin. ### Comparison of AI2A1 and AI2A2 Kim et al. (2005) compared the dental phenotypes of the KLK4 (Hart et al., 2004) and MMP20 (their study) probands and noted many similar features. The enamel crowns are normal in size and shape, have a rougher, duller, less reflective surface than normal enamel, and appear to be more brittle in that they show a tendency to fracture or chip, but do not appear to be particularly susceptible to dental caries. The radiodensity of the defective enamel is generally less than that of normal enamel but can still be distinguished from the underlying dentin on radiographs. The coloration of the teeth is different, but extrinsic staining since tooth eruption could have contributed to the current appearance. The KLK4 teeth have a more homogeneous dark yellow hue, while the MMP20 teeth have an irregular grayish brown discoloration and are a little more glossy. Overall, the dental phenotypes in the KLK4 and MMP20 probands are remarkably similar. Molecular Genetics In both affected members of a family segregating pigmented hypomaturation AI, Kim et al. (2005) identified homozygosity for a splice site mutation in the MMP20 gene (604629.0001). In a brother and sister, born to consanguineous Turkish parents, with hypomaturation AI and anterior open bite, Ozdemir et al. (2005) identified a homozygous missense mutation in the MMP20 gene (604629.0002) that segregated with the disorder. In an 11-year-old Chinese girl with hypoplastic-hypomaturation amelogenesis imperfecta and deep overbite, Papagerakis et al. (2008) identified a homozygous nonsense mutation in the MMP20 gene (604629.0003). In a 14-year-old boy with AI2A2, Wang et al. (2013) identified a homozygous missense mutation in the MMP20 gene (H204R; 604629.0004). INHERITANCE \- Autosomal recessive HEAD & NECK Teeth \- Amelogenesis imperfecta, hypomaturation type \- Yellowish-brown enamel \- Rough tooth surface \- Thin enamel layer \- Anterior open bite (in some patients) \- Increased sensitivity to thermal changes \- Enamel layer is slightly more radioopaque than dentin MOLECULAR BASIS \- Caused by mutation in the matrix metalloproteinase-20 gene (MMP20, 604629.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	AMELOGENESIS IMPERFECTA, HYPOMATURATION TYPE, IIA2	c0399372	6,120	omim	https://www.omim.org/entry/612529	2019-09-22T16:01:17	{"doid": ["0110060"], "mesh": ["C536606"], "omim": ["612529"], "orphanet": ["100033", "88661"], "synonyms": ["Alternative titles", "AMELOGENESIS IMPERFECTA, PIGMENTED HYPOMATURATION TYPE, 2"]}
Sclerema neonatorum SpecialtyPediatrics Sclerema neonatorum is a rare and severe skin condition that is characterized by diffuse hardening of the subcutaneous tissue with minimal inflammation.[1][2] It usually affects premature, ill newborns. Prognosis is poor. Minimal inflammation helps distinguish sclerema neonaturum from subcutaneous fat necrosis of the newborn. ## See also[edit] * Panniculitis * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ William D. James, Timothy G. Berger; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. p. 490. ISBN 978-0-7216-2921-6. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1515, 1524, 1525. ISBN 978-1-4160-2999-1. ## External links[edit] Classification D * ICD-10: P83.0 * ICD-9-CM: 778.1 * MeSH: D012593 * DiseasesDB: 31401 External resources * eMedicine: article/1112191 * v * t * e Disorders of subcutaneous fat Panniculitis Lobular * without vasculitis * Cold * Cytophagic histiocytic * Factitial * Gouty * Pancreatic * Traumatic * needle-shaped clefts * Subcutaneous fat necrosis of the newborn * Sclerema neonatorum * Post-steroid panniculitis * Lipodermatosclerosis * Weber–Christian disease * Lupus erythematosus panniculitis * Sclerosing lipogranuloma * with vasculitis: Nodular vasculitis/Erythema induratum Septal * without vasculitis: Alpha-1 antitrypsin deficiency panniculitis * Erythema nodosum * Acute * Chronic * with vasculitis: Superficial thrombophlebitis Lipodystrophy Acquired * generalized: Acquired generalized lipodystrophy * partial: Acquired partial lipodystrophy * Centrifugal abdominal lipodystrophy * HIV-associated lipodystrophy * Lipoatrophia annularis * localized: Localized lipodystrophy Congenital * Congenital generalized lipodystrophy * Familial partial lipodystrophy * Marfanoid–progeroid–lipodystrophy syndrome * Poland syndrome * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Sclerema neonatorum	c0036415	6,121	wikipedia	https://en.wikipedia.org/wiki/Sclerema_neonatorum	2021-01-18T18:29:49	{"mesh": ["D012593"], "umls": ["C0036415"], "icd-9": ["778.1"], "icd-10": ["P83.0"], "wikidata": ["Q3952465"]}
A number sign (#) is used with this entry because Omenn syndrome can be caused by mutation in the RAG1 (179615) and RAG2 (179616) genes on chromosome 11p and the Artemis gene (DCLRE1C; 605988) on chromosome 10p. See also T-, B-, NK+ severe combined immunodeficiency (SCID) (601457), a more severe form of immunodeficiency that can also be caused by mutation in the RAG1 and the RAG2 genes. Another distinct form of familial histiocytic reticulocytosis (267700) is caused by mutation in the perforin-1 gene (PRF1; 170280) on chromosome 10q22. Clinical Features Omenn (1965) described reticuloendotheliosis with eosinophilia in several individuals in related sibships from an inbred American family of Irish extraction. Barth et al. (1972) concluded that the familial reticuloendotheliosis with eosinophilia described by Omenn is a distinct entity. Pneumocystis carinii, responsible for eosinophilia in other immune deficiency disorders, was not detected in any of Omenn's cases. Velders et al. (1983) described an 18-month-old child with a widespread pruritic skin disorder and fever, lymphadenopathy, anemia, eosinophilia, and chronic diarrhea. The child had sharply demarcated erythematosquamous disseminated lesions on the head, trunk, and limbs. Biopsy of a nodule from one of his extremities revealed a dense infiltrate in the deep dermis consisting of histiocytes, lymphocytes, eosinophils, and mast cells. Ecto-5-nucleotidase was markedly reduced in the patient's lymph node tissue and peripheral blood lymphocytes compared to a control. The patient died of toxic shock syndrome at the age of 20 months. Cohen et al. (1980) observed a decreased presence of ecto-5-nucleotidase on the peripheral lymphocytes of a patient with Omenn syndrome, but concluded that this finding is not specific for the disease. Gelfand et al. (1984) also found absent or greatly diminished activity of ecto-5-prime-nucleotidase in Omenn syndrome. Hong et al. (1985) described Omenn disease terminating in lymphoma. Jouan et al. (1987) presented 9 cases of Omenn syndrome and suggested that pathologic lesions, particularly the skin and bone marrow changes, were reminiscent of those observed in acute graft-versus-host reaction (see 614395). Although blood chimerism had never been demonstrated, Jouan et al. (1987) supported a hypothesis of graft-versus-host disease in a primary cellular immunodeficiency and the persistence of proliferating maternal cells in peripheral target organs. Schofer et al. (1991) described an infant who had features compatible with Omenn syndrome, but who also had short-limbed dwarfism caused by metaphyseal chondrodysplasia. Gatti et al. (1969) described identical bone changes in 2 sibs who likewise had the features of Omenn syndrome. (See 200900 for discussion of metaphyseal chondrodysplasia associated with immune defect.) Rybojad et al. (1996) described a Moroccan male infant, born to consanguineous parents, who manifested nephrotic syndrome in addition to typical findings of Omenn syndrome. Renal biopsy confirmed minimal change glomerular disease. De Saint-Basile et al. (1991) studied 5 unrelated patients with Omenn syndrome; 2 were born of consanguineous parents. One of the patients had a brother and a sister who had died with the same syndrome, and the brother of another patient was said to have died with typical alymphocytosis-type T-, B- SCID (601457). The authors described the syndrome as being characterized by T-cell infiltration of skin, gut, liver, and spleen, leading to diffuse erythroderma, protracted diarrhea, failure to thrive, and hepatosplenomegaly. Although the lesions resembled those in graft-versus-host disease, the blood T cells were shown by DNA haplotype analysis to belong to the patients; the same was true of the T cells infiltrating the gut and skin in 1 patient. A restricted heterogeneity of the T-cell repertoire was indicated by oligoclonality of the T-cell receptor gene rearrangements. The occurrence of an alymphocytosis type of SCID in the brother of one of the patients suggested that the restricted heterogeneity of T-cell receptor gene usage in Omenn syndrome may rise from leakiness, within the context of a genetically determined faulty T-cell differentiation. Cavazzana-Calvo et al. (1993) presented further evidence that the Omenn syndrome is a leaky T-, B- SCID phenotype. Schwarz et al. (1999) illustrated the characteristic erythematous, scaly rash, involving the entire body in an infant with Omenn syndrome. The authors noted that some clinical hallmarks of the disease, including generalized erythrodermia, lymphadenopathy, massive inflammatory infiltrate leading to pachydermia, and alopecia, are reminiscent of graft-versus-host disease. The engraftment of maternal T cells in infants with SCID may result in clinically overt GVHD, mimicking Omenn syndrome (Pollack et al., 1982; Le Diest et al., 1987). Furthermore, transfusion of unirradiated blood products into SCID babies may also result in severe GVHD that resembles Omenn syndrome (Anderson and Weinstein, 1990). Ege et al. (2005) described a patient with Omenn syndrome who presented at the age of 5 months with septicemia, failure to thrive, generalized lymphadenopathy, hepatomegaly, splenomegaly, and erythrodermatitis. He exhibited alopecia and skin lesions, which consisted of large ichthyotic scales and scattered erythematous papules. Blood culture revealed Staphylococcus aureus; Pseudomonas aeruginosa was isolated from the feces. At the site of BCG vaccination, ulceration with lymph node involvement was observed. A lymph node taken from the left axilla showed numerous eosinophils, a marked proliferation of T cells, and a complete absence of B-cell lymphocytes. With immunosuppressive treatment, almost complete resolution of the dermatitis, alopecia, hepatosplenomegaly, and lymphadenopathy occurred, with significant weight gain. At the age of 10 months, peripheral blood stem cell transplantation after T-cell depletion and myoloablative conditioning was performed from the HLA-haploidentical mother. The therapy resulted in a complete donor chimerism and normal immune functions. Taken together, the patient presented with all of the clinical signs of Omenn syndrome, a T+, B-, NK+ SCID immunophenotype, and with elevated IgE levels and eosinophilia. Pathogenesis Using real-time PCR and immunohistochemistry, Cavadini et al. (2005) analyzed autoimmune regulator (AIRE; 607358) expression in the thymi of 2 Omenn syndrome patients and 1 T-, B-, NK+ SCID patient and found profound reduction of AIRE mRNA and protein compared to a normal control subject. There was no detectable mRNA for the self-antigens insulin (176730), cytochrome P450 1A2 (124060), or fatty acid-binding protein (see 134650) in the immunodeficient patients. Cavadini et al. (2005) concluded that deficiency of AIRE expression occurs in severe immunodeficiencies characterized by abnormal T-cell development and suggested that in Omenn syndrome, the few residual T-cell clones that develop may escape negative selection and thereafter expand in the periphery, causing massive autoimmune reactions. Clinical Management Gomez et al. (1995) reported the outcome of allogenic bone marrow transplant (BMT) in 9 consecutive patients with Omenn syndrome treated between 1980 and 1989. They concluded that both HLA-identical and haploidentical BMT can cure Omenn syndrome, provided that parenteral nutrition and immunosuppressive therapy are given before transplantation. Molecular Genetics Villa et al. (1998) reported that patients with Omenn syndrome had missense mutations in either the RAG1 (179615.0001-179615.0013) or the RAG2 (179616.0003; 179616.0004) gene that result in partial activity of the 2 proteins. Two of the amino acid substitutions mapped within the RAG1 homeodomain and decreased DNA-binding activity, whereas 3 others lowered the efficiency of RAG1/RAG2 interaction. The findings indicated that the immunodeficiency manifested in patients with Omenn syndrome arises from mutations that decrease the efficiency of V(D)J recombination. In a patient with T-, B- SCID, Corneo et al. (2001) identified compound heterozygosity for 2 mutations in the RAG2 gene (179616.0002; 179616.0008). A sib with Omenn syndrome had the same genotype. In 2 additional unrelated patients with T-, B- SCID, Corneo et al. (2001) identified mutations in the RAG1 gene (179615.0010; 179615.0015). Both mutations were also identified in patients with Omenn syndrome. The authors concluded that there was an additional factor required for the phenotypic expression of Omenn syndrome. Ege et al. (2005) described a family in which 2 brothers died with manifestations consistent with Omenn syndrome and a third brother with Omenn syndrome was shown to be a compound heterozygote for mutations (605988.0012; 605988.0013) in the DCLRE1C/Artemis gene. Animal Model Khiong et al. (2007) characterized mice with a spontaneous mutation in the Rag1 gene and concluded that these mice represent a model for Omenn syndrome. Marrella et al. (2007) generated a knockin mouse model in which endogenous Rag2 was replaced with Rag2 carrying the arg229-to-gln mutation (R229Q; 179616.0002) identified in patients with Omenn syndrome. They concluded that these mice mimic most symptoms of human Omenn syndrome. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive RESPIRATORY Lung \- Pneumonia ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly Gastrointestinal \- Diarrhea SKIN, NAILS, & HAIR Skin \- Generalized erythrodermia \- Pachydermia Skin Histology \- Lymphocytic infiltrates with occasional histiocytes and eosinophils Hair \- Alopecia HEMATOLOGY \- Anemia \- Thrombocytopenia \- Eosinophilia IMMUNOLOGY \- Lymphadenopathy \- Increased frequency of bacterial, viral, and fungal infections \- Lymph node architecture severely altered: lack of follicles, depletion of lymphocytes, and increased proportion of interdigitating reticular cells and eosinophils \- Very low B cells \- Absent B cells \- Variable (often increased) number of activated CD45RO+, DR+ circulating T cells \- Poor proliferative response of T lymphocytes to specific antigens \- Hypoplastic thymus which often lacks Hassal corpuscles \- Defect in V(D)J recombination process LABORATORY ABNORMALITIES \- Hypoproteinemia \- Very low IgG \- Very low IgA \- Very low IgM \- Increased IgE MOLECULAR BASIS \- Caused by mutation in the recombinase activating gene 1 (RAG1, 179615.0005 ) \- Caused by mutation in the recombinase activating gene 2 (RAG2, 179616.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	OMENN SYNDROME	c2700553	6,122	omim	https://www.omim.org/entry/603554	2019-09-22T16:13:02	{"doid": ["0060010"], "mesh": ["D016511"], "omim": ["603554"], "orphanet": ["39041"], "synonyms": ["Alternative titles", "RETICULOENDOTHELIOSIS, FAMILIAL, WITH EOSINOPHILIA", "SEVERE COMBINED IMMUNODEFICIENCY WITH HYPEREOSINOPHILIA"]}
Turcot syndrome is a condition characterized by multiple adenomatous colon polyps, an increased risk of colorectal cancer, and an increased risk of brain cancer. It may be associated with familial adenomatous polyposis (FAP) or Lynch syndrome (also known as hereditary non-polyposis colorectal cancer or HNPCC). The molecular basis of most Turcot syndrome is either a mutation in APC associated with FAP or a mutation in one of the mismatch repair genes associated with Lynch syndrome (MLH1 and PMS2). The brain tumors in individuals with APC mutations are typically medulloblastoma, whereas those with mismatch repair mutations are usually glioblastoma multiforme. Turcot syndrome typically follows an autosomal dominant inheritance pattern. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Turcot syndrome	c0265325	6,123	gard	https://rarediseases.info.nih.gov/diseases/420/turcot-syndrome	2021-01-18T17:57:15	{"mesh": ["C536928"], "omim": ["276300"], "umls": ["C0265325"], "synonyms": ["Malignant tumors of the central nervous system associated with familial polyposis of the colon", "CNS tumors with Familial polyposis of the colon", "Mismatch Repair Cancer Syndrome", "MMRCS", "Mismatch Repair Deficiency", "MMR Deficiency", "Brain tumor-polyposis syndrome", "Glioma-polyposis syndrome"]}
For phenotypic information on carotid artery intimal medial thickness, see entry 609338. Fox et al. (2004) performed a genomewide linkage analysis to localize a quantitative trait locus (QTL) influencing carotid intimal medial thickness (IMT). Carotid IMT was measured in 596 men and 629 women from 311 extended families (1,242 sib pairs) in the Framingham Heart Study Offspring cohort. B-mode carotid ultrasonography was used to define mean IMT of the carotid artery segments. They found evidence for significant linkage to internal carotid artery (ICA) IMT (2-point lod score = 4.1; multipoint lod score = 3.4) 161 cM from the tip of the short arm of chromosome 12. Association analysis of a single-nucleotide polymorphism (SNP) variant of SCARB1 (601040) showed a protective association of a missense variant allele in exon 1, with decreased ICA IMT compared with subjects homozygous for the common allele. The SCARB1 variant did not, however, account for the observed linkage. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	CAROTID INTIMAL MEDIAL THICKNESS 2	c1838020	6,124	omim	https://www.omim.org/entry/608447	2019-09-22T16:07:47	{"omim": ["608447"], "synonyms": ["Alternative titles", "CIMT2", "CAROTID INTIMAL MEDIAL THICKNESS QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 12"]}
A number sign (#) is used with this entry because of evidence that insulinomatosis and diabetes mellitus syndrome (INSDM) is caused by heterozygous mutation in the MAFA gene (610303) on chromosome 8q24. Description Insulinomatosis and diabetes mellitus syndrome is an autosomal dominant disorder in which affected individuals within a family present with either hyperinsulinemic hypoglycemia secondary to pancreatic neuroendocrine tumors, or a noninsulin-dependent form of diabetes mellitus. A few affected individuals show only impaired glucose tolerance. Some patients also exhibit congenital cataract and/or congenital glaucoma (Iacovazzo et al., 2018). Clinical Features Tragl and Mayr (1977) described a Yugoslavian father and daughter with multiple beta-cell adenomas of the pancreas. The father and daughter, who came to medical attention at age 38 years and 28 years, respectively, each underwent several pancreatic surgeries to remove insulinomas, but hypoglycemia always recurred; ultimately they were successfully treated with diazoxide and diet. The daughter had a 6-year-old son who had no abnormality of the endocrine system or indication of hyperinsulinism. The father's brother and 2 of the brother's children had diabetes mellitus. The authors suggested that an autosomal dominant gene is responsible for either one or the other trait by determining 'an abnormal sensitivity of the beta-cells.' Iacovazzo et al. (2018) studied 25 affected individuals from 2 unrelated white Caucasian families with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, 1 of which (family 2) was the Yugoslavian family originally reported by Tragl and Mayr (1977). Insulinomatosis was present in 10 patients, and 15 patients had a form of noninsulin-dependent DM resembling maturity-onset diabetes of the young (MODY); in addition, there were 2 family members with glucose intolerance. Diagnosis generally occurred between the third and fifth decades of life, although 2 individuals with DM were diagnosed in the second decade of life. In family 1, 4 patients with DM also exhibited congenital cataract and/or glaucoma. In individuals with hyperinsulinemic hypoglycemia who underwent surgery, histopathology revealed the presence of multifocal well-differentiated neuroendocrine tumors, including microadenomas and macrotumors, with a trabecular tissue architecture. The number of lesions was variable; the authors noted that the affected Yugoslavian daughter was reported to have had over 100 lesions in a surgical specimen (Anlauf et al., 2009). All tumors in these patients expressed insulin, and immunostaining for other pancreatic hormones was negative; local or distant metastases were not observed. All 6 patients who underwent surgery had persistent or recurrent disease. Inheritance Tragl and Mayr (1977) reported a 4-generation Yugoslavian family in which beta-cell adenomatosis or diabetes mellitus segregated as autosomal dominant traits. Molecular Genetics In a large white Caucasian family with insulinomatosis and diabetes mellitus, Iacovazzo et al. (2018) performed exome sequencing and identified a heterozygous missense mutation in the MAFA gene (S64F; 610303.0001) that segregated with disease and was not found in public variant databases. Targeted sequencing of MAFA in a Yugoslavian family with INSDM that was originally reported by Tragl and Mayr (1977) identified the same heterozygous S64F mutation in affected individuals. Haplotype analysis suggested that the mutation arose on separate alleles in the 2 families. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Congenital cataract (in some patients) \- Congenital glaucoma (in some patients) ABDOMEN Pancreas \- Multiple pancreatic beta-cell adenomas ENDOCRINE FEATURES \- Impaired glucose tolerance \- Diabetes mellitus \- Hyperinsulinemic hypoglycemia NEOPLASIA \- Multifocal well-differentiated beta-cell neuroendocrine tumors LABORATORY ABNORMALITIES \- Low serum glucose with inappropriately high insulin levels (in some patients) \- Elevated serum glucose (in some patients) MISCELLANEOUS \- Onset in third to fifth decade of life in most patients MOLECULAR BASIS \- Caused by mutation in the V-MAF avian musculoaponeurotic fibrosarcoma oncogene homolog A gene (MAFA, 610303.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	INSULINOMATOSIS AND DIABETES MELLITUS	c1578917	6,125	omim	https://www.omim.org/entry/147630	2019-09-22T16:39:24	{"mesh": ["C563258"], "omim": ["147630"], "synonyms": ["Alternative titles", "ISLET CELL ADENOMATOSIS"]}
## Description The KMT2A gene, or MLL, encodes a DNA-binding protein that methylates histone H3 (see 602810) lys4 (H3K4) and positively regulates expression of target genes, including multiple HOX genes (see 142980). MLL is a frequent target for recurrent translocations in acute leukemias that may be characterized as acute myeloid leukemia (AML; 601626), acute lymphoblastic leukemia (ALL), or mixed lineage (biphenotypic) leukemia (MLL). Leukemias with translocations involving MLL possess unique clinical and biologic characteristics and are often associated with poor prognosis. MLL rearrangements are found in more than 70% of infant leukemias, whether the immunophenotype is more consistent with ALL or AML6, but are less frequent in leukemias from older children. MLL translocations are also found in approximately 10% of AMLs in adults, as well as in therapy-related leukemias, most often characterized as AML, that develop in patients previously treated with topoisomerase II inhibitors for other malignancies. More than 50 different MLL fusion partners have been identified. Leukemogenic MLL translocations encode MLL fusion proteins that have lost H3K4 methyltransferase activity. A key feature of MLL fusion proteins is their ability to efficiently transform hematopoietic cells into leukemia stem cells (Krivtsov and Armstrong, 2007). Cloning and Expression Recurring chromosomal translocations involving chromosome 11q23 have been observed in both acute lymphoid leukemia and acute myeloid leukemia (AML; 601626), especially acute monoblastic leukemia (AML-M5) and acute myelomonocytic leukemia (AMML-M4). Rowley et al. (1990) demonstrated that the breakpoints in four 11q23 translocations associated with leukemia were contained within a yeast artificial chromosome (YAC) clone bearing the CD3D (186790) and CD3G (186740) genes. Within this YAC, Ziemin-van der Poel et al. (1991) identified a transcription unit spanning the breakpoint junctions of 3 of these translocations, 4;11, 9;11, and 11;19. They described 2 other related transcripts that were upregulated in a translocation cell line. Ziemin-van der Poel et al. (1991) named the gene MLL for myeloid/lymphoid, or mixed lineage, leukemia. Cimino et al. (1991) identified the same gene and called it ALL1. Gu et al. (1992) determined that the ALL1 gene encodes a protein of more than 3,910 amino acids containing 3 regions with homology to sequences within the Drosophila 'trithorax' gene, including cysteine-rich regions that can be folded into 6 zinc finger-like domains. Tkachuk et al. (1992) showed that the ALL1 gene, which they referred to as HRX (for 'homolog of trithorax'), codes for a 431-kD protein. Djabali et al. (1992) also cloned an 11.5-kb transcript spanning the 11q23 translocation breakpoint. Parry et al. (1993) showed that the sequence of a partial TRX1 cDNA contained an open reading frame encoding 1,012 amino acids with extensive homology to the Drosophila trithorax protein, particularly in the zinc finger-like domains. The TRX1 gene appears to be unique in the human genome and has been conserved during evolution. Butler et al. (1997) analyzed the distribution and localization of HRX proteins in cell lines and human tissues, using both polyclonal and monoclonal antibodies. Immunocytochemical analysis showed a punctate distribution of wildtype and chimeric HRX proteins within cell nuclei, suggesting that HRX localizes to nuclear structures in cells with and without 11q23 translocations. Nuclear staining was found in the majority of tissues studied, with the strongest reactivity in cerebral cortex, kidney, thyroid, and lymphoid tissues. Thus, Butler et al. (1997) concluded that HRX is widely expressed in most cell types, including hematopoietic cells, a finding that precludes an immunocytochemical approach for diagnosis of leukemias bearing 11q23 structural abnormalities. Using qRT-PCR analysis in mouse retina, Brightman et al. (2018) determined that Mll1 is widely expressed in neural progenitors and in developing and differentiated neurons, particularly in the inner retina. Gene Structure Gu et al. (1992) determined that the MLL gene spans approximately 100 kb and contains at least 21 exons. Mapping The MLL gene maps to chromosome 11q23 (Ziemin-van der Poel et al., 1991; Cimino et al., 1991). Gene Function Milne et al. (2002) showed that MLL regulates target HOX gene expression through direct binding to promoter sequences. They determined that the MLL SET domain is a histone H3 (see 601128) lys4 (K4)-specific methyltransferase whose activity is stimulated with acetylated H3 peptides. This methylase activity was found to be associated with HOX gene activation and H3 K4 methylation at cis regulatory sequences in vivo. A leukemogenic MLL fusion protein that activates HOX expression had no effect on histone methylation, suggesting a distinct mechanism for gene regulation by MLL and MLL fusion proteins. Nakamura et al. (2002) found that ALL1 is present within a stable multiprotein supercomplex composed of at least 29 proteins. The majority of the complex proteins are components of transcription complexes, including TFIID (see 604912). Other components are involved in RNA processing or histone methylation. The authors found that the complex remodels, acetylates, deacetylates, and methylates nucleosomes and/or free histones, and that the H3 K4 methylation activity of the complex is conferred by the ALL1 SET domain. Chromatin immunoprecipitations showed that ALL1 and other complex components examined were bound at the promoter of an active ALL1-dependent HOXA9 gene (142956). In parallel, H3 K4 was methylated, and histones H3 and H4 were acetylated at this promoter. The MLL gene encodes a large nuclear protein that is required for the maintenance of HOX gene expression. MLL is cleaved at 2 conserved sites to generate an N-terminal 320-kD fragment (N320) and a C-terminal 180-kD fragment (C180), which heterodimerize to stabilize the complex and confer its subnuclear destination. Hsieh et al. (2003) purified and cloned the protease responsible for cleaving MLL, which they entitled taspase-1 (608270). They determined that taspase-1 initiates a class of endopeptidases that utilize an N-terminal threonine as the active-site nucleophile to proteolyze polypeptide substrates following aspartate. RNA interference-mediated knockdown of taspase-1 in HeLa cells resulted in the appearance of unprocessed MLL and the loss of proper HOX gene expression. Lim et al. (2009) showed that Mll1 is required for neurogenesis in the mouse postnatal brain. Mll1-deficient subventricular zone neural stem cells survive, proliferate, and efficiently differentiate into glial lineages; however, neuronal differentiation is severely impaired. In Mll1-deficient cells, early proneural Mash1 (100790) and gliogenic Olig2 (606386) expression are preserved, but Dlx2 (126255), a key downstream regulator of subventricular zone neurogenesis, is not expressed. Overexpression of Dlx2 can rescue neurogenesis in Mll1-deficient cells. Chromatin immunoprecipitation demonstrates that Dlx2 is a direct target of MLL in subventricular zone cells. In differentiating wildtype subventricular zone cells, Mash1, Olig2, and Dlx2 loci have high levels of histone-3 trimethylated at lys4 (H3K4me3), consistent with their transcription. In contrast, in Mll1-deficient subventricular zone cells, chromatin at Dlx2 is bivalently marked by both H3K4me3 and H3K27me3, and the Dlx2 gene fails to properly activate. Lim et al. (2009) concluded that their data supported a model in which Mll1 is required to resolve key silenced bivalent loci in postnatal neural precursors to the actively transcribed state for the induction of neurogenesis, but not for gliogenesis. Liu et al. (2010) assigned MLL as a novel effector in the mammalian S-phase checkpoint network and identified checkpoint dysfunction as an underlying mechanism of MLL leukemias. MLL is phosphorylated at ser516 by ATR (601215) in response to genotoxic stress in the S phase, which disrupts its interaction with, and hence its degradation by, the SCF(Skp2) E3 ligase (see 601436), leading to its accumulation. Stabilized MLL protein accumulates on chromatin, methylates histone H3 lysine-4 at late replication origins, and inhibits the loading of CDC45 (603465) to delay DNA replication. Cells deficient in MLL showed radioresistant DNA synthesis and chromatid-type genomic abnormalities, indicative of S-phase checkpoint dysfunction. Reconstitution of Mll-null mouse embryonic fibroblasts with wildtype but not S516A or delta-SET mutant MLL rescued the S-phase checkpoint defects. Moreover, murine myeloid progenitor cells carrying an Mll-CBP (600140) knockin allele that mimics human t(11;16) leukemia showed a severe radioresistant DNA synthesis phenotype. Liu et al. (2010) demonstrated that MLL fusions function as dominant-negative mutants that abrogate the ATR-mediated phosphorylation/stabilization of wildtype MLL on damage to DNA, and thus compromise the S-phase checkpoint. Together, Liu et al. (2010) concluded that their results identified MLL as a key constituent of the mammalian DNA damage response pathway and showed that deregulation of the S-phase checkpoint incurred by MLL translocations probably contributes to the pathogenesis of human MLL leukemias. Zhu et al. (2015) demonstrated that p53 (191170) gain-of-function mutants bind to and upregulate chromatin regulatory genes, including the methyltransferases MLL1, MLL2 (KMT2D; 602113), and acetyltransferase MOZ (KAT6A; 601408), resulting in genomewide increases of histone methylation and acetylation. Analysis of The Cancer Genome Atlas showed specific upregulation of MLL1, MLL2, and MOZ in p53 gain-of-function patient-derived tumors, but not in wildtype p53 or p53-null tumors. Cancer cell proliferation was markedly lowered by genetic knockdown of MLL1 or by pharmacologic inhibition of the MLL1 methyltransferase complex. Zhu et al. (2015) concluded that their study revealed a novel chromatin mechanism underlying the progression of tumors with gain-of-function p53, and suggested possibilities for designing combinatorial chromatin-based therapies for treating individual cancers driven by prevalent gain-of-function p53 mutations. Li et al. (2016) demonstrated that a minimized human RBBP5 (600697)-ASH2L (604782) heterodimer is the structural unit that interacts with and activates all MLL family histone methyltransferases (MLL1; MLL2; MLL3, 606833; MLL4, 606834; SET1A, 611052; SET1B, 611055). Their structural, biochemical, and computational analyses revealed a 2-step activation mechanism of MLL family proteins. Li et al. (2016) concluded that their findings provided unprecedented insights into the common theme and functional plasticity in complex assembly and activity regulation of MLL family methyltransferases, and also suggested a universal regulation mechanism for most histone methyltransferases. Brightman et al. (2018) showed that mice with knockout of Mll1 in retinal progenitors display rod/cone dysfunction and deficits in visual signal transmission from photoreceptors to inner neurons. Mll1 deficiency resulted in thinner retinas, particularly affecting the inner layers, due to reduced progenitor cell proliferation and cell cycle progression. Immunostaining combined with RNAseq and histone modification analyses demonstrated that Mll1 deficiency altered retinal cell composition and caused a change in neuron-to-glia ratio. The gene expression profile of horizontal cells (HC) was one of the most severely affected in the knockout retinas, and detailed investigation revealed that Mll1 is indispensable for maintaining HC integrity, including identity, gene expression, and axon network. Mll1 knockout retinas failed to develop normal outer plexiform layer synapses, resulting in defects in visual signal transmission. ### MLL Fusion Proteins Human ML-2 leukemia cells lack a normal MLL gene and exclusively express an MLL/AF6 (MLLT4; 159559) fusion protein. Yokoyama et al. (2005) showed that MLL/AF6 associated with menin (MEN1; 613733) in ML-2 cells. Chromatin immunoprecipitation analysis showed both proteins present on upstream sites of the HOXA7 (142950), HOXA9 (142956), and HOXA10 (142957) promoters. Deletions and point mutations performed in the MLL portion of the MLL/ENL (MLLT1; 159556) fusion protein revealed a high affinity menin-binding motif (RXRFP) near the N terminus. Interaction between oncogenic MLL and menin was required for initiation of MLL-mediated leukemogenesis in mouse stem/progenitor cells, and menin was essential to maintain MLL-associated myeloid transformation. Acute genetic ablation of menin in mice reversed aberrant Hox gene expression mediated by MLL-menin promoter-associated complexes and specifically abrogated differentiation arrest and oncogenic properties of MLL-transformed leukemic blasts. By gel filtration, mass spectrometry, and Western blot analysis of human cell lines, Nie et al. (2003) identified unique low-abundance SWI/SWF complexes that contained ENL, several common SWI/SNF subunits, and either BAF250A (ARID1A; 603024) or BAF250B (ARID1B; 614556). Western blot analysis of HB(11;19) leukemia cells, which express the oncogenic MLL/ENL fusion protein, revealed that MLL/ENL also interacted with the BAF250B-containing complex. MLL/ENL-containing SWI/SNF complexes coactivated the HOXA7 promoter in a reporter gene assay. Biochemical Features ### Crystal Structure Huang et al. (2012) reported the crystal structures of human menin (613733) in its free form and in complexes with MLL1 or with JUND (165162), or with an MLL1-LEDGF (603620) heterodimer. These structures showed that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but that it can have opposite effects on transcription. The menin-JUND interaction blocks JUN N-terminal kinase-mediated JUND phosphorylation and suppresses JUND-induced transcription. In contrast, menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1. Cytogenetics ### MLL Breakpoint Cluster Region The ALL1 gene is rearranged in acute leukemias with interstitial deletions or reciprocal translocations between chromosome 11q23 and chromosomes 1, 4, 6, 9, 10, or 19. Gu et al. (1992) cloned translocation fragments from leukemic cells from t(4;11) and showed clustering of the breakpoints in areas of 7 to 8 kb on both chromosome 4 and 11. Sequencing indicated heptamer and nonamer-like sequences, associated with rearrangements of immunoglobulin and T-cell receptor genes, near the breakpoints. This suggested a direct involvement of the VDJ recombinase in the 11q23 translocations. Gu et al. (1992) determined that the breakpoint cluster region within ALL1 spans 8 kb and encompasses several small exons, most of which begin in the same phase of the open reading frame. McCabe et al. (1992) presented evidence that the breakpoints in all the translocations involving 11q23 in leukemia cells, e.g., t(4;11) t(6;11), t(9;11), and t(11;19), are clustered within a 9-kb BamHI genomic region of the MLL gene. McCabe et al. (1992) detected rearrangements of DNA in a fragment of the MLL gene by Southern blot hybridization. Djabali et al. (1992) concluded that most of the breakpoints in infant leukemias with t(4;11) and t(9;11) translocations lie within a 5-kb region. Using a human TRX1 cDNA as a probe, Parry et al. (1993) demonstrated that the gene is interrupted in both infant and adult acute myeloid (AML) and lymphoid (ALL) leukemia patients with 11q23 translocations. The structure of the TRX1 gene around the breakpoints show that this part of the human gene is interrupted by 9 introns. As a result of the rearrangement, zinc finger domains are translocated in both ALL and AML patients. Strout et al. (1998) analyzed the fusion sequences in genomic DNA from 9 patients with AML. Each had a partial tandem repeat spanning exons 2 to 6 of the ALL1 gene on 11q23. The breakpoint in intron 6 occurred in the breakpoint cluster region and the other near the 3-prime end of intron 1. In 7 cases, a distinct point of fusion could not be identified; instead, the sequence gradually diverged from an Alu element in intron 6 to an Alu element in intron 1 through heteroduplex fusion. The results supported the hypothesis that a recombination event between homologous Alu sequences is responsible for the partial tandem duplication of ALL1, probably through an intrastrand slipped-mispairing mechanism, in the majority of AML cases with this defect. This appeared to be the first demonstration identifying Alu element-mediated recombination as a consistent mechanism for gene rearrangement in somatic tissue. ### MLL/AF4 Fusion Gene Gu et al. (1992) determined that the t(4;11) chromosome translocation in leukemia results in 2 reciprocal fusion products coding for chimeric proteins derived from ALL1 and from a gene on chromosome 4 that they termed AF4 (MLLT2; 159557). Translocations involving 11q23 in leukemia result in the translocation of zinc finger domains with fusion to other genes on chromosome 4, chromosome 9, or chromosome 19. The gene on chromosome 19 with which it is fused is ENL (159556). Nakamura et al. (1993) showed that the genes with which it is fused on chromosome 4 (AF4) and chromosome 9 (AF9; 159558) show high homology of sequence to ENL. The protein products of the AF4, AF9, and ENL proteins contained nuclear targeting sequences as well as serine-rich and proline-rich regions. Independently, Domer et al. (1993) characterized the MLL/AF4 fusion product generated by the t(4;11) translocation. The sequence of the complete open reading frame for this fusion transcript revealed that the MLL protein is homologous to DNA methyltransferase. In the fusion gene, the 5-prime portion is derived from the MLL gene and the 3-prime portion from the AF4 gene. Gale et al. (1997) demonstrated that unique or clonotypic MLL-AF4 genomic fusion sequences were detectable in neonatal blood spots from individuals who developed ALL at ages 5 months to 2 years, thus providing unequivocal evidence for a prenatal initiation of acute leukemia in young patients. They stated that common subtypes due to other translocation fusion genes can be expected to have a similar prenatal initiation. In an infant diagnosed at the age of 3 weeks with ALL after presenting with hepatosplenomegaly and marked leukocytosis, Raffini et al. (2002) found a 3-way rearrangement of the MLL, AF4, and CDK6 (603368) genes. By reverse-panhandle PCR, they identified a breakpoint junction of CDK6 from band 7q21-q22 and MLL intron 9. Thus, the patient had an in-frame CDK6-MLL transcript along with an in-frame MLL-AF4 transcript. Wang et al. (2010) studied leukemia stem cells in mouse models of acute myelogenous leukemia induced by either coexpression of the Hoxa9 (142956) and Meis1a (601739) oncogenes or by the fusion oncoprotein MLL-AF9. The authors showed that the Wnt (see 164820)/beta-catenin (116806) signaling pathway is required for self-renewal of leukemia stem cells that are derived from either hematopoietic stem cells or more differentiated granulocyte-macrophage progenitors. Because the Wnt/beta-catenin pathway is normally active in hematopoietic stem cells but not in granulocyte-macrophage progenitors, Wang et al. (2010) concluded that reactivation of beta-catenin signaling is required for the transformation of progenitor cells by certain oncogenes. Beta-catenin is not absolutely required for self-renewal of adult hematopoietic stem cells; thus, targeting the Wnt/beta-catenin pathway may represent a new therapeutic opportunity in acute myelogenous leukemia. ### MLL/ENL Fusion Gene In studies of a t(11;19)-carrying cell line, Tkachuk et al. (1992) identified fusion transcripts expressed from both derivative chromosomes. The more abundant derivative 11 transcript coded for a chimeric protein containing the amino terminal 'AT-hook' motifs of the HRX gene fused to the ENL gene (MLLT1; 159556) from chromosome 19. (ENL was so named for '11-19 leukemia.') The HRX protein may have effects mediated by DNA binding within the minor groove at AT-rich sites. Tkachuk et al. (1992) referred to this type of leukemia as representing the multilineage leukemias rather than mixed lineage leukemias. The cell line carrying the t(11;19) was from a patient with T-cell precursor acute lymphocytic leukemia (Smith et al., 1989). Translocations involving 11q23 in leukemia result in the translocation of zinc finger domains with fusion to other genes on chromosome 4, chromosome 9, or chromosome 19. The gene on chromosome 19 with which it is fused is ENL. Nakamura et al. (1993) showed that the genes with which it is fused on chromosome 4 (AF4) and chromosome 9 (AF9; 159558) show high homology of sequence to ENL. The protein products of the AF4, AF9, and ENL proteins contained nuclear targeting sequences as well as serine-rich and proline-rich regions. ### MLL/AF9 Fusion Gene Translocations involving 11q23 in leukemia result in the translocation of zinc finger domains with fusion to other genes on chromosome 4, chromosome 9, or chromosome 19. The gene on chromosome 19 with which it is fused is ENL. Nakamura et al. (1993) showed that the genes with which it is fused on chromosome 4 (AF4) and chromosome 9 (AF9; 159558) show high homology of sequence to ENL. The protein products of the AF4, AF9, and ENL proteins contained nuclear targeting sequences as well as serine-rich and proline-rich regions. The human AF9 gene is one of the most common fusion partner genes with MLL, resulting in the t(9;11)(p22;q23). Strissel et al. (2000) identified several different structural elements in AF9, including a colocalizing DNA topo II cleavage site and a DNase I hypersensitive (DNase I HS) site. In addition, 2 scaffold-associated regions (SARs) are located centromeric to the topo II and DNase I HS cleavage sites and border breakpoint regions in 2 leukemic cell lines. The authors thus demonstrated that the patient breakpoint regions of AF9 share the same structural elements as the MLL BCR, and they proposed a DNA breakage and repair model for nonhomologous recombination between MLL and its partner genes, particularly AF9. ### MLL/AF6 Fusion Gene Prasad et al. (1993) identified AF6 (MLLT4; 159559) as the fusion partner of MLL in a common translocation, t(6;11)(q27;q23), associated with leukemia. The t(6;11)(q27;q23) translocation results in a chimeric MLL/AF6 protein with a calculated molecular mass of 325 kD. In the chimeric protein, the N-terminal portion of MLL, including 3 AT hook motifs, is fused to all of AF6 except the first 35 amino acids, leaving the Ras-interacting domain and the DHR motif of AF6 intact. By Western blot analysis of transfected COS cells and a human cell line with the t(6;11)(q27;q23) translocation, Joh et al. (1997) found that the MLL/AF6 fusion protein had an apparent molecular mass of 360 kD. Immunolocalization and cell fractionation followed by Western blot analysis indicated that MLL/AF6 was targeted to the nucleus, whereas AF6 itself was cytoplasmic. Mutation analysis indicted that the region of MLL containing AT hook motifs was responsible for the nuclear localization of the chimeric protein. ### MLL/GPH Fusion Gene Eguchi et al. (2001) found that the gephyrin gene (GPH; 603930) can partner with MLL in leukemia associated with the translocation t(11;14)(q23;q24). The child in whom this translocation was discovered showed signs of acute undifferentiated leukemia 3 years after intensive chemotherapy that included the topoisomerase II inhibitor VP16. The AT hook motifs and a DNA methyltransferase homology domain of the MLL gene were fused to the C-terminal half of GPH, including a presumed tubulin-binding site and a domain homologous to the E. coli molybdenum cofactor biosynthesis protein. Eguchi et al. (2001) suggested that MLL-GPHN may have been generated by the chemotherapeutic agent, followed by error-prone DNA repair via nonhomologous end-joining. ### MLL/GMPS Fusion Gene In a patient with treatment-related acute myeloid leukemia and the karyotype t(3;11)(q25;q23), Pegram et al. (2000) identified GMPS (600358) to be the partner gene of MLL. The authors stated that GMPS was the first partner gene of MLL to be identified on 3q and the first gene of this type to be found in leukemia-associated translocations. ### MLL/FBP17 Fusion Gene Fuchs et al. (2001) reported fusion of the gene encoding formin-binding protein-17 (FBP17; 606191) to MLL in a child with acute myelogeneous leukemia and a complex chromosome rearrangement, ins(11;9)(q23;134)inv(11)(q13q23). The fused mRNA was represented by MLL at the 5-prime end and FBP17 at the 3-prime end. ### MLL/LPP Fusion Gene By FISH and Southern blot analyses, Daheron et al. (2001) identified a rearrangement in the mixed lineage leukemia gene due to a novel t(3;11)(q28;q23) translocation in a patient who developed acute myeloid leukemia of the M5 type 3 years after treatment for a follicular lymphoma. Through inverse PCR, they identified the LPP gene (600700) on 3q28 as the MLL fusion partner. The breakpoint occurred in intron 8 of MLL and LPP. They found that the MLL/LPP and LPP/MLL predicted proteins contain many of the features present in other MLL rearrangements. ### MLL/PNUTL1 Fusion Gene Megonigal et al. (1998) examined the MLL genomic translocation breakpoint in acute myeloid leukemia of infant twins. Southern blot analysis showed 2 identical MLL gene rearrangements indicating chromosomal translocation. The rearrangements were detected in the second twin before signs of clinical disease and the intensity relative to the normal fragment indicated that the translocation was not constitutional. Fluorescence in situ hybridization with an MLL-specific probe and karyotype analyses suggested that a t(11;22)(q23;q11.2) disrupted MLL. Megonigal et al. (1998) used panhandle variant PCR to clone the translocation breakpoint and identified a region of 22q11.2 involved in both leukemia and a constitutional disorder. By ligating a single-stranded oligonucleotide that was homologous to known 5-prime MLL genomic sequence to the 5-prime ends of BamHI-digested DNA through a bridging oligonucleotide, they formed the stem-loop template for panhandle variant PCR, which yielded products of 3.9 kb. The MLL genomic breakpoint was in intron 7. The sequence of the partner DNA from 22q11.2 was identical to the human CDCrel (cell division cycle-related) gene (PNUTL1; 602724) that maps to chromosome 22. Both MLL and PNUTL1 contained homologous CT, TTTGTG, and GAA sequences within a few basepairs of their respective breakpoints, which may have been important in uniting these 2 genes by translocation. RT-PCR amplified an in-frame fusion of MLL exon 7 to PNUTL1 exon 3, indicating that a chimeric mRNA had been transcribed. ### MLL/CDK6 Fusion Gene In an infant diagnosed at the age of 3 weeks with acute lymphoblastic leukemia (ALL; 613065) after presenting with hepatosplenomegaly and marked leukocytosis, Raffini et al. (2002) found a 3-way rearrangement of the MLL, AF4, and CDK6 (603368) genes. By reverse-panhandle PCR, they identified a breakpoint junction of CDK6 from band 7q21-q22 and MLL intron 9. Thus, the patient had an in-frame CDK6-MLL transcript along with an in-frame MLL-AF4 transcript. ### MLL/LASP1 Fusion Gene Strehl et al. (2003) identified a new MLL fusion partner on chromosome 17q in the case of an infant with AML-M4 and a t(11;17)(q23;q21) translocation. FISH and RT-PCR analyses indicated a rearrangement of the MLL gene, but no fusion with previously identified MLL fusion partners at 17q, such as AF17 (600328) or MSF (604061). RACE revealed an in-frame fusion of MLL to LASP1 (602920), a gene that is amplified and overexpressed in breast cancer. The authors stated that retroviral transduction of myeloid progenitors demonstrated that MLL/LASP1 was the fourth known fusion of MLL with a cytoplasmic protein that has no in vitro transformation capability, the others being GRAF (605370), ABI1 (603050), and FBP17. ### MLL/LAF4 Fusion Gene Von Bergh et al. (2002) identified an MLL/LAF4 (601464) fusion gene in an infant with ALL and a t(2;11)(p15;p14) translocation. Bruch et al. (2003) also reported an infant with ALL and an MLL/LAF4 fusion caused by an ins(11;2)(q23;q11.2q11.2) insertion. ### MLL/LARG Fusion Gene In a patient with primary acute myeloid leukemia and a complex karyotype, Kourlas et al. (2000) found that the 5-prime end of MLL at exon 6 was fused in-frame with the 3-prime end of almost the entire open reading frame of the LARG gene (604763), which lies on 11q23. Transcriptional orientation of both genes at 11q23 was found to be from centromere to telomere, consistent with other data that suggested that the MLL/LARG fusion resulted from an interstitial deletion rather than a balanced translocation. ### MLL/CBL Fusion Gene Fu et al. (2003) found that the CBL gene (165360), which lies telomeric to MLL on 11q23, was fused to MLL in an adult patient with de novo acute myeloid leukemia (FAB M1). MLL exon 6 was fused in-frame with CBL exon 8. The genomic junction region involved the fusion of the 3-prime portion of an Alu element in intron 6 of MLL with the 5-prime portion of an Alu element in intron 7 of CBL. The absence of extensive sequence similarity at both breakpoints of MLL and CBL indicated that the recombination was not generated through homologous recombination. The transcriptional orientation of both genes is from centromere to telomere. The results of Southern blot analysis in conjunction with FISH suggested that the MLL/CBL fusion was the result of an interstitial deletion. CBL was the second MLL fusion partner identified on 11q23, the first being the LARG gene. Fu et al. (2003) stated that at least 34 partner genes for MLL had been identified. ### MLL/AF10 Fusion Gene Tanabe et al. (1996) identified an invins(10;11)(p12;q23q12) and other complex chromosomal rearrangements in a 2-year old boy with acute monoblastic leukemia (AML-M5). Cloning of the proximal 10p breakpoint showed that the MLL gene at chromosome 11q23 was fused to the 3-prime portion of AF10 (MLLT10; 602409) at chromosome 10p12. Cloning of the telomeric 10p junction revealed that the 5-prime portion of AF10 was fused with the HEAB gene (608757). The 5-prime AF10/HEAB fusion transcript was out of frame, while the MLL/3-prime AF10 fusion was in frame. ### MLL/AF15q14 Fusion Gene Hayette et al. (2000) described a 48-year-old man with AML-M4 who was cytogenetically characterized as 46,XY,-3,t(11;15)(q23;q1 4),+mar. The bone marrow was hypercellular, with 80% blast cells. The patient was treated by intensive chemotherapy and died 4 month after diagnosis. The translocation resulted in a in-frame fusion between exon 8 of the MLL gene and exon 10 of the AF15q14 gene (609173). The fusion transcript was predicted to encode a 1,503-amino acid protein composed of 1,418 N-terminal amino acids of MLL and 85 C-terminal amino acids of AF15q14, including the bipartite nuclear localization signal. Kuefer et al. (2003) identified a similar t(11;15)(q23;q14) in a 3-year-old boy with de novo T-cell acute lymphoblastic leukemia. In this translocation, exon 9 of the MLL gene was fused in-frame to exon 12 of the AF15q14 gene. The deduced 1,886-amino acid fusion protein, which contains the N terminus of MLL up to lys1362 fused to the entire C terminus of AF15q14 starting from residue ile1819, has a calculated molecular mass of 208 kD. It differs from the fusion protein described by Hayette et al. (2000) in that it has a coiled-coil domain but no nuclear localization signal. ### MLL/CIP29 Fusion Gene In an infant with AML-M4, Hashii et al. (2004) identified a translocation, t(11;12)(q23;q13), in which the coding region of the CIP29 gene (610049) was fused in-frame to exon 9 of the MLL gene. The fusion protein had the N-terminal AT hooks and central DNA methyltransferase homology region of MLL fused to nearly all of the CIP29 protein, including the N-terminal SAP domain and 2 C-terminal nuclear localization signals. RT-PCR confirmed expression of the fusion transcript in patient peripheral blood mononuclear cells. ### MLL/SEPT6 Fusion Gene Kadkol et al. (2006) described an infant with AML who had a rearrangement between chromosomes 11q23 and Xq24. FISH analysis showed a break in MLL, and RT-PCR analysis confirmed expression of an MLL/SEPT6 (300683) fusion transcript. ### MLL/MAML2 Fusion Gene Nemoto et al. (2007) isolated MLL/MAML2 (607537) fusion transcripts from secondary AML and myelodysplastic syndrome (MDS) cells with inv(11)(q21q23). RT-PCR revealed that exon 7 of MLL was fused to exon 2 of MAML2 in the AML and MDS cells. The inv(11)(q21q23) resulted in a chimeric RNA encoding a putative fusion protein containing 1,408 amino acids from the N-terminal part of MLL and 952 amino acids from the C-terminal part of MAML2. The N-terminal part of MAML2, a basic domain that includes a binding site for the NOTCH (see NOTCH1; 190198) intracellular domain, was deleted in MLL/MAML2. The MLL/MAML2 fusion protein in secondary AML and MDS and the MECT1/MAML2 fusion protein in mucoepithelioid carcinoma, benign Warthin tumor, and clear cell hidradenoma contained the same C-terminal part of MAML2. Reporter gene assays revealed that MLL/MAML2 suppressed HES1 (139605) promoter activation by the NOTCH1 intracellular domain. ### MLL/GRAF Fusion Gene Borkhardt et al. (2000) found that the GRAF gene (605370) was fused with MLL in a unique t(5;11)(q31;q23) that occurred in an infant with juvenile myelomonocytic leukemia. ### MLL/ABI1 Fusion Gene Taki et al. (1998) analyzed a patient with AML and t(10;11)(p11.2;q23) and identified, as a fusion partner with MLL, the gene ABI1 (603050) on 10p11.2. The ABI1 gene bore no homology with partner genes of MLL previously described, but the ABI1 protein exhibited sequence similarity to protein of homeotic genes, contained several polyproline stretches, and included a Src homology-3 (SH3) domain at the C terminus. The MLL-ABI1 fusion transcript in this patient was formed by an alternatively spliced ABI1. In-frame MLL-ABI1 fusion transcripts combined the MLL AT-hook motifs and DNA methyltransferase homology region with the homeodomain homologous region, polyproline stretches, and SH3 domain of the alternatively spliced transcript of ABI1. ### MLL/KIAA1524 Fusion Gene Coenen et al. (2011) identified the karyotype 46,XX,t(3;11)(q12-13;q23) in bone marrow of a 4-month-old Caucasian girl who presented with the M5 subtype of AML and central nervous system involvement. The patient died 9 weeks after diagnosis. The translocation resulted in fusion of intron 10 of the MLL gene on chromosome 11 to intron 16 of the KIAA1524 gene (610643) on chromosome 3. The 2 genes are transcribed in opposite orientations, suggesting that the translocation also required a microinversion. RT-PCR analysis confirmed expression of the fusion transcript, which was predicted to encode a 1,673-amino acid protein containing the N-terminal AT-hook domain, subnuclear localization sites, and methyltransferase domain of MLL fused to the C-terminal coiled-coil domain of KIAA1524. ### MLL Duplication In a study of patients with acute leukemia but no microscopically visible change at 11q23, Schichman et al. (1994) found molecular evidence of partial duplication of the ALL1 gene. The direct tandem duplication involved a region spanning exons 2 to 6, and a partially duplicated protein gene product was demonstrated. Thus, the ALL1 gene is leukemogenic when it fuses with itself as well as when it fuses with one of the genes on other chromosomes. In addition to the translocations involving fusion of the ALL1 gene with genes on other chromosomes producing acute lymphoblastic and myelogenous leukemia, the ALL1 gene undergoes self-fusion in acute myeloid leukemias with normal karyotype or trisomy 11. In addition, Baffa et al. (1995) reported rearrangement of the ALL1 gene in a gastric carcinoma cell line. A complex, 3-way translocation involving chromosomes 1 and 11 and resulting in partial duplication of the ALL1 gene was found. Sequencing of RT-PCR products and Northern blot analysis show that only the partially duplicated ALL1 gene was transcribed, producing an mRNA with exon 8 fused to exon 2. Thus, ALL1 gene rearrangement may play a role in the pathogenesis of some solid malignancies. The absence of the normal transcript in this cell line, in association with loss of heterozygosity on 11q23 seen in solid tumors, suggests that ALL1 is involved in tumorigenesis by a loss-of-function mechanism. Approximately 90% of adult patients with de novo AML and trisomy 11 (+11) as a sole abnormality and 11% of adult patients with de novo AML and normal cytogenetics carry a molecular rearrangement of the ALL1 gene. The rearranged ALL1 gene results from the direct tandem duplication of a portion of ALL1 itself. Caligiuri et al. (1997) showed that in cytogenetically normal cases of AML and cases with +11 as the sole cytogenetic abnormality, only 1 chromosome contains the mutated ALL1 allele. Thus, a single mutated ALL1 allele with the partial tandem duplication is sufficient for ALL1-associated leukemogenesis, irrespective of the number of normal genes present. The frequently occurring specific association of +11 and ALL1 gene mutation in the leukemic clone remained unexplained. ### Detection of MLL Rearrangements Thirman et al. (1993) demonstrated that MLL gene rearrangements can be detected with a single probe and a single restriction-enzyme digest. The ability to detect an MLL gene rearrangement rapidly and reliably, especially in patients with limited material for cytogenetic analysis, should make it possible to identify patients who have a poor prognosis and therefore require aggressive chemotherapy or marrow transplantation. Phenotype The MLL gene spans the breakpoint in translocations involving 11q23, which are responsible for approximately 70% of AML and ALL in infants and are also observed in treatment-related leukemias, especially in patients previously treated with drugs inhibiting topoisomerase II (Gibbons et al., 1990; Thirman et al., 1993). In 15 of 26 AML cases in infants, Sorensen et al. (1994) found rearrangement of the MLL gene at the molecular level. These rearrangements were clustered within an 11-kb region containing 9 exons of the gene. In 14 of the 15 cases with rearrangements, the leukemia was associated with myelomonocytic or monocytic phenotypes (M4 or M5 FAB subtypes, respectively), both of which are associated with a poor prognosis in childhood AML. In contrast, only 1 of 11 nonrearranged cases had an M4 or M5 phenotype. Rearrangement also correlated significantly with hyperleukocytosis, another clinical parameter associated with poor outcome. Kobayashi et al. (1993) described a case of acute lymphoblastic leukemia in a 44-year-old woman after adjuvant chemotherapy of breast cancer; they demonstrated rearrangement of the HRX gene. Acute lymphoblastic leukemias carrying a chromosomal translocation involving the MLL gene have a particularly poor prognosis. Armstrong et al. (2002) showed that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms showed that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias. Armstrong et al. (2002) proposed that they constitute a distinct disease, denoted as MLL, and showed that the differences in gene expression are robust enough to classify leukemias correctly as MLL versus acute lymphoblastic leukemia or acute myelogenous leukemia. Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets. Pathogenesis Chromosomal translocations involving the MLL gene occur in about 80% of infant leukemias. Epidemiologic studies have suggested that maternal exposure to various substances such as pesticides, marijuana, or an excess of flavonoids (naturally occurring inhibitors of topoisomerase II) might be associated with acute leukemia in infants (Ross et al., 1994). In search of possible agents inducing infant leukemia, Strick et al. (2000) investigated bioflavonoids, natural substances in food as well as in dietary supplements, that cause site-specific DNA cleavage in the MLL breakpoint cluster region (BCR) in vivo. The MLL BCR DNA cleavage was shown in primary progenitor hematopoietic cells from healthy newborns and adults as well as in cell lines; it colocalized with the MLL BCR cleavage site induced by chemotherapeutic agents, such as etoposide (VP16) and doxorubicin (Dox). Both in vivo and additional in vitro experiments demonstrated topoisomerase II (TOP2A; 126430) as the target of bioflavonoids similar to the 2 chemotherapeutic agents. Based on 20 bioflavonoids tested, Strick et al. (2000) identified a common structure essential for topoisomerase II cleavage. The authors' observations supported a 2-stage model of cellular processing of topoisomerase II inhibitors: the first and reversible stage of this cleavage resulted in DNA repair, but also rarely in chromosome translocations; whereas the second, nonreversible stage led to cell death because of an accumulation of DNA damage. These results suggested that maternal ingestion of bioflavonoids may induce MLL breaks and potentially translocations in utero leading to infant and early childhood leukemia. Strick et al. (2000) concluded that although bioflavonoids may be beneficial in certain circumstances, a potential counterbalancing disadvantage is their possible role in causing chromosome translocations leading to leukemia in all age groups, analogous to the translocation forms of AML and ALL after cancer chemotherapy. Ross (2000) commented on the observations of Strick et al. (2000) in the context of clinical and epidemiologic findings on childhood leukemia. Wang et al. (2008) reported pharmacologic, physiologic, and genetic studies that demonstrated an oncogenic requirement for glycogen synthase kinase-3 (GSK3; see 606784) in the maintenance of a specific subtype of poor prognosis human leukemia, genetically defined by mutations of the MLL protooncogene. In contrast to its previously characterized roles in suppression of neoplasia-associated signaling pathways, GSK3 paradoxically supports MLL leukemia cell proliferation and transformation by a mechanism that ultimately involves destabilization of the cyclin-dependent kinase inhibitor p27(KIP1) (600778). Inhibition of GSK3 in a preclinical murine model of MLL leukemia provided promising evidence of efficacy and earmarked GSK3 as a candidate cancer drug target. Molecular Genetics By whole-exome sequencing in 4 patients with Wiedemann-Steiner syndrome (605130), Jones et al. (2012) identified 3 different heterozygous de novo truncating mutations, all within exon 27 of the MLL gene (159555.0001-159555.0003) in 3 of the 4 patients. Analysis of MLL in 2 additional patients with a similar phenotype revealed heterozygosity for 2 more de novo truncating mutations (159555.0004 and 159555.0005). The variants were confirmed by Sanger sequencing, and none were found in the dbSNP or 1000 Genomes Project databases, in 600 unrelated control exome profiles, or in DNA from the unaffected parents. In 6 unrelated children with WDSTS, Miyake et al. (2016) identified 6 different heterozygous mutations in the KMT2A gene (see, e.g., 159555.0006-159555.0008). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were demonstrated to have occurred de novo in 4 of the patients; complete parental DNA was not available for 2 patients. Four of the mutations resulted in nonsense or frameshift mutations, whereas 2 were missense mutations affecting highly conserved residues. Functional studies of the variants and studies of patient cells were not performed. Animal Model Yu et al. (1995) reported that Mll deletion in mice was embryonic lethal. Mll +/- mice had retarded growth, hemopoietic abnormalities, and bidirectional homeotic transformation of the axial skeleton, as well as sternal malformations. Yamashita et al. (2006) examined the role of MLL in the immune system using Mll +/- mice. Mll +/- Cd4-positive T cells differentiated normally into antigen-specific effector Th1 and Th2 cells in vitro, but the ability of memory Th2 cells to produce Th2 cytokines was dramatically decreased. Histone methylation and acetylation at Th2 cytokine gene loci was not maintained in Mll +/- memory Th2 cells. Levels of Gata3 (131320) mRNA were normal in Mll +/- effector Th2 cells, but they were substantially decreased in Mll +/- memory Th2 cells; mRNA levels of other transcription factors were not affected in Mll +/- memory Th2 cells. Histone modifications of Gata3 were also aberrant in Th2 cell lines in which Mll expression had been knocked down by small interfering RNA. Ovalbumin-induced allergic eosinophilic inflammation was reduced in Mll +/- Th2 cell-transferred mice. Yamashita et al. (2006) concluded that MLL plays a crucial role in control of memory Th2 cell responses by maintaining expression of GATA3 and production of Th2 cytokines. Barabe et al. (2007) demonstrated that upon transplantation into immunodeficient mice, primitive human hematopoietic cells expressing a mixed-lineage leukemia (MLL) fusion gene generated myeloid or lymphoid acute leukemias, with features that recapitulated human diseases. Analysis of serially transplanted mice revealed that the disease is sustained by leukemia-initiating cells that have evolved over time from a primitive cell type with a germline immunoglobulin heavy chain (IgH) gene configuration to a cell type containing rearranged IgH genes. The leukemia-initiating cells retained both myeloid and lymphoid lineage potential and remained responsive to microenvironmental cues. Barabe et al. (2007) concluded that the properties of these cells provide a biologic basis for several clinical hallmarks of MLL leukemias. McMahon et al. (2007) found that fetal liver from Mll-knockout mouse embryos showed defects in the hematopoietic stem and progenitor pool, including reductions in long-term and short-term hematopoietic stem cell numbers and a decrease in the quiescent hematopoietic stem cell fraction. Adult mice with conditional Mll knockout had no apparent abnormalities in mature hematopoietic cells in bone marrow, spleen, and thymus. However, conditional Mll-knockout bone marrow cells produced reduced numbers of colony-forming units and showed reduced ability to compete in hematopoietic reconstitution assays. McMahon et al. (2007) concluded that MLL has a critical role in regulating stem cell self-renewal. Inheritance \- Autosomal dominant (11q23) Misc \- Homology to sequences within Drosophila 'trithorax' gene \- MLL protein is homologous to DNA methyltransferase Lab \- Recurring 11q23 chromosomal translocations Heme \- Acute lymphoid leukemia \- Acute myeloid leukemia \- Myeloid/lymphoid leukemia \- Mixed-lineage leukemia \- Acute monoblastic leukemia (AML-M5) \- Acute myelomonocytic leukemia (AMML-M4) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	LYSINE-SPECIFIC METHYLTRANSFERASE 2A	c3888194	6,126	omim	https://www.omim.org/entry/159555	2019-09-22T16:37:50	{"omim": ["159555"], "synonyms": ["Alternative titles", "MYELOID/LYMPHOID OR MIXED LINEAGE LEUKEMIA GENE", "TRITHORAX, DROSOPHILA, HOMOLOG OF", "HRX", "MYELOID/LYMPHOID LEUKEMIA GENE", "MIXED LINEAGE LEUKEMIA GENE", "ALL1 GENE", "CXXC FINGER PROTEIN 7"]}
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (July 2014) (Learn how and when to remove this template message) Benign lymphoepithelial lesion SpecialtyGastroenterology Benign lymphoepithelial lesion is a type of benign enlargement of the parotid and/or lacrimal glands. This pathologic state is sometimes, but not always, associated with Sjögren's syndrome. ## Contents * 1 Presentation * 2 Locations * 3 Histology * 4 Treatment * 5 Eponym * 6 See also * 7 References * 8 Further reading * 9 External links ## Presentation[edit] Benign lymphoepithelial lesion is most likely to occur in adults around 50 years of age. There is a predilection for gender with 60–80% being female. The gland affected has a diffuse swelling. The swelling can be asymptomatic, but mild pain can also be associated. There is a preponderance of this disease in those who suffer from HIV infection. Most cases of benign lymphoepithelial lesions appear in conjunction with Sjögren's syndrome. When Sjögren's syndrome is present, the swelling is usually bilateral. Otherwise, the affected glands are usually only on one side of the body. In many cases, a biopsy is needed to distinguish benign lymphoepithelial lesions from sialadenosis (sialosis). ## Locations[edit] In 80% of cases, the parotid gland is affected. Lacrimal glands are also affected. ## Histology[edit] Section from salivary gland showing dense lymphoid infiltrate around and within ductal epithelium-Lympho epithelial lesion (H&E,100X) There is a marked lymphoplasmacytic infiltration. Lymphoid follicles surround solid epithelial nests, giving rise to the 'epimyoepithelial islands', that are mainly composed of ductal cells with occasional myoepithelial cells. Excess hyaline basement membrane material is deposited between cells, and there is also acinar atrophy and destruction. ## Treatment[edit] Treatment usually consists of observation unless the patient has concern, there is pain, drainage, or other symptoms related to the lesion. Surgical removal of the affected gland would be recommended in those cases. Another treatment option would be aspiration, which can be repeated multiple times. This is commonly performed in those who are debilitated or in those whose benefit from surgery would be outweighed by the risks. Prognosis is usually good; rarely this condition may devolve into lymphoma, or could actually represent 'occult' lymphoma from the outset. ## Eponym[edit] Historically, bilateral parotid and lacrimal gland enlargement was characterized by the term Mikulicz's disease if the enlargement appeared apart from other diseases. If it was secondary to another disease, such as tuberculosis, sarcoidosis, lymphoma, and Sjögren's syndrome, the term used was Mikulicz's syndrome. Both names derive from Jan Mikulicz-Radecki, the Polish surgeon best known for describing these conditions.[1][2] In more recent times, the terms "Mikulicz's disease" and "Mikulicz's syndrome" were viewed as ambiguous and outdated by some sources.[3] Today Mikulicz's disease is considered to be a subtype of IgG4-related disease, usually accompanied by involvement of one or more other organs in the body.[4] ## See also[edit] * Lymphoepithelial lesion ## References[edit] 1. ^ synd/2087 at Who Named It? \- "Mikulicz's disease" 2. ^ synd/2088 at Who Named It? \- "Mikulicz's syndrome" 3. ^ Ihrler S, Harrison J (2005). "Mikulicz's disease and Mikulicz's syndrome: analysis of the original case report of 1892 in the light of current knowledge identifies a MALT lymphoma". Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 100 (3): 334–9. doi:10.1016/j.tripleo.2005.01.016. PMID 16122662. 4. ^ John H. Stone; Arezou Khosroshahi; Vikram Deshpande; John K. C. Chan; J. Godfrey Heathcote; Rob Aalberse; Atsushi Azumi; Donald B. Bloch; William R. Brugge; Mollie N. Carruthers; Wah Cheuk; Lynn Cornell; Carlos Fernandez-Del Castillo; Judith A. Ferry; David Forcione; Günter Klöppe; Daniel L. Hamilos; Terumi Kamisawa; Satomi Kasashima; Shigeyuki Kawa; Mitsuhiro Kawano; Yasufumi Masaki; Kenji Notohara; Kazuichi Okazaki; Ji Kon Ryu; Takako Saeki; Dushyant Sahani; Yasuharu Sato; Thomas Smyrk; James R. Stone; Masayuki Takahira; Hisanori Umehara; George Webster; Motohisa Yamamoto; Eunhee Yi; Tadashi Yoshino; Giuseppe Zamboni; Yoh Zen; Suresh Chari (October 2012). "Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations". Arthritis & Rheumatism. 64 (10): 3061–3067. doi:10.1002/art.34593. PMC 5963880. PMID 22736240. Bibliography * Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001. * Regezi, Joseph A. Oral Pathology: Clinical Pathologic Correlations. 4th ed. 2002. ## Further reading[edit] * Kahn, LB (Jan 1979). "Benign lymphoepithelial lesion (Mikulicz's disease) of the salivary gland: an ultrastructural study". Human Pathology. 10 (1): 99–104. doi:10.1016/S0046-8177(79)80077-5. PMID 428999. * Lee S, Tsirbas A, McCann J, Goldberg R (2006). "Mikulicz's disease: a new perspective and literature review". Eur J Ophthalmol. 16 (2): 199–203. PMID 16703534. * Tsubota, K; Fujita, H; Tsuzaka, K; Takeuchi, T (Jun 2000). "Mikulicz's disease and Sjögren's syndrome". Investigative Ophthalmology & Visual Science. 41 (7): 1666–73. PMID 10845583. * Azzopardi, JG; Evans, DJ (Nov 1971). "Malignant lymphoma of parotid associated with Mikulicz disease (benign lymphoepithelial lesion)" (PDF). J Clin Pathol. 24 (8): 744–752. doi:10.1136/jcp.24.8.744. PMC 477147. PMID 4943296. * Yamamoto, M; Harada, S; Ohara, M; Suzuki, C; Naishiro, Y; Yamamoto, H; Takahashi, H; Imai, K (Feb 2005). "Clinical and pathological differences between Mikulicz's disease and Sjögren's syndrome". Rheumatology (Oxford, England). 44 (2): 227–34. doi:10.1093/rheumatology/keh447. PMID 15509627. * Delaney, William E.; Balogh, Károly (1966). "Carcinoma of the parotid gland associated with benign lymphoepithelial lesion (Mikulicz's disease) in Sjögren's syndrome". Cancer. 19 (6): 853–860. doi:10.1002/1097-0142(196606)19:6<853::AID-CNCR2820190617>3.0.CO;2-N. ## External links[edit] Classification D * ICD-10: K11.8 * ICD-9-CM: 527.1 * MeSH: D008882 * DiseasesDB: 8218 * Mikulicz syndrome on The National Organization for Rare Disorders (NORD) * Benign lymphoepithelial lesions on Radiopedia * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Benign lymphoepithelial lesion	c0026103	6,127	wikipedia	https://en.wikipedia.org/wiki/Benign_lymphoepithelial_lesion	2021-01-18T18:37:00	{"gard": ["7043"], "mesh": ["D008882"], "umls": ["C0026103"], "icd-9": ["527.1"], "orphanet": ["79078"], "wikidata": ["Q516562"]}
In 2 infant sons of first-cousin parents, Beemer and van Ertbruggen (1984) described a lethal syndrome of hydrocephalus, cardiac malformation, dense bones, ambiguous external genitalia and other genital anomalies, thrombocytopenia, and unusual facies, particularly bulbous nose and broad nasal bridge. GU \- Ambiguous external genitalia Neuro \- Hydrocephalus Inheritance \- Autosomal recessive Skeletal \- Dense bones Heme \- Thrombocytopenia Nose \- Bulbous \- Broad nasal bridge Cardiovascular \- Cardiac malformation ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	BEEMER LETHAL MALFORMATION SYNDROME	c1859526	6,128	omim	https://www.omim.org/entry/209970	2019-09-22T16:30:32	{"mesh": ["C537668"], "omim": ["209970"], "orphanet": ["1237"], "synonyms": ["Alternative titles", "HYDROCEPHALUS, CARDIAC MALFORMATION, DENSE BONES, ETC."]}
Edinburgh malformation syndrome is a rare, genetic, lethal, multiple congenital anomalies/dysmorphic syndrome characterized by consistently abnormal facial appearance, true or apparent hydrocephalus, motor and cognitive developmental delay, failure to thrive (feeding difficulties, vomiting, chest infections) and death within a few months of birth. Carp mouth, hairiness of the forehead, neonatal hyperbilirubinemia and advanced bone age may also be associated. There have been no further descriptions in the literature since 1991. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Edinburgh malformation syndrome	c0795933	6,129	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1895	2021-01-23T18:57:33	{"gard": ["2074"], "mesh": ["C563051"], "omim": ["129850"], "umls": ["C0795933"], "icd-10": ["Q95.2"], "synonyms": ["Typus Edinburgensis"]}
A number sign (#) is used with this entry because of evidence that ARVD11 is caused by heterozygous mutation in the desmocollin-2 gene (DSC2; 125645) on chromosome 18q. Homozygous mutation in the DSC2 gene causes arrhythmogenic right ventricular cardiomyopathy associated with mild palmoplantar keratoderma and woolly hair. For a phenotypic description and a discussion of genetic heterogeneity of ARVD, see ARVD1 (107970). Clinical Features Syrris et al. (2006) reported 4 unrelated families with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Disease penetrance was incomplete; consequently, not all of the patients fulfilled the diagnostic criteria for ARVD/C established by an international task force. The authors noted that incomplete penetrance also had been found in patients with ARVD/C caused by mutations in desmoplakin (DSP; 125647), plakophilin-2 (PKP2; 602861), and desmoglein-2 (DSG2; 125671). Thus, the international criteria cannot be effectively applied to relatives of definitely affected probands who have features of cardiomyopathy on clinical evaluation. This issue was specifically addressed by Hamid et al. (2002), who found that the presence of certain abnormalities was, alone, sufficient to make a diagnosis of ARVD/C in a subject with a definitely affected relative. In ARVD/C, the classic presentation is with right ventricular involvement, with an apparent progression to left ventricular involvement. It was striking that 5 of the 7 individuals affected in the 4 families reported by Syrris et al. (2006) had evidence of significant left ventricular involvement that was more obvious than the right ventricular disease in 2 individuals. None of the affected individuals in the 4 families showed evidence of hair or skin abnormalities. Heuser et al. (2006) described a 58-year-old man with ARVD/C and a mutation in the DSC2 gene. Ventricular tachycardia with left bundle branch block morphology was apparent by age 43 and had led to the implantation of a cardiac defibrillator and antiarrhythmic medication. Angiogram revealed a severely dilated, hypokinetic right ventricle with diastolic bulging at the right ventricular inflow tract. Family history was negative for other clinically affected individuals. ### ARVD and Mild Palmoplantar Keratoderma with or without Woolly Hair Simpson et al. (2009) evaluated 2 Pakistani sibs with ARVD with left ventricular (LV) involvement, associated with mild palmoplantar keratoderma (PPK) and woolly hair. The proband was a 31-year-old otherwise healthy man who presented with syncopal episodes, including an apparent cardiac arrest that responded to a precordial thump. Clinical findings were consistent with a diagnosis of ARVD with significant LV involvement. His asymptomatic parents were first cousins, and although there was no family history of cardiomyopathy, a female cousin had died suddenly at 21 years of age, reportedly due to dehydration. The proband had 2 asymptomatic sisters, 29 years and 25 years of age; the younger sister had woolly hair and mild PPK like the proband, and after cardiac evaluation she was diagnosed as affected using clinical criteria as applied to first-degree relatives of an individual with confirmed ARVD. Examination of the parents and the older of the 2 sisters revealed no cardiac, skin, or hair abnormalities except in the father, who had a history of hypertension and stable angina treated with stenting and demonstrated LV hypertrophy on ECG and echocardiography. Gerull et al. (2013) studied 8 patients from 2 Canadian Hutterite kindreds segregating autosomal recessive sudden cardiac death, 1 from the Dariusleut branch (family D) and 1 from the Lehrerleut branch (family L). Autopsies in 2 individuals, 1 from each family, who both died suddenly at 14 years of age while exercising, showed marked dilation of the left ventricle and fibrofatty replacement of myocardial tissue in the right ventricle. The majority of affected individuals were initially diagnosed with dilated cardiomyopathy or congenital aneurysms because of the impressive left ventricular involvement with regional wall thinning and localized aneurysms seen on echocardiography or cardiac MRI; only 1 patient showed predominantly right ventricular involvement. The authors noted that only 3 of 5 living affected individuals fulfilled a major criterion for structural and functional alterations on cardiac MRI, and even 2 severely affected sibs did not fulfill imaging criteria based on the revised Task Force criteria for ARVD (Marcus et al., 2010). ECG consistently showed T-wave inversion in the right precordial leads in all affected individuals; 4 individuals had T-wave inversion in the inferior and lateral leads as well. Epsilon waves were present in 2 individuals, and 5 had late potentials on signal-averaged ECGs. Ventricular arrhythmias with LBBB morphology were documented in 4 of the 5 living patients, leading to implantation of a cardioverter-defibrillator device. Mild palmoplantar hyperkeratosis was observed in only 1 patient, a 21-year-old affected man from family D, who had normal hair; the authors stated that it was unclear whether the palmoplantar changes were primary or secondary to manual farm work. Molecular Genetics ### Familial Arrhythmogenic Right Ventricular Dysplasia 11 In affected members of 4 unrelated families with ARVD/C, Syrris et al. (2006) identified 2 different heterozygous mutations in the DSC2 gene (125645.0001 and 125645.0002). Both mutations resulted in frameshifts and premature termination of the desmocollin-2 protein. In a patient with ARVD/C, Heuser et al. (2006) identified a heterozygous mutation in intron 5 (125645.0003) of the DSC2 gene, which led to the use of a cryptic splice acceptor site and the creation of a downstream premature termination codon. De Bortoli et al. (2010) detected the E896fsX900 variation (125645.0002), which they designated A897KfsX4, in 5 unrelated Italian ARVD probands, all of whom carried mutations or polymorphisms in other known ARVD genes as well. The A897KfsX4 variant was also found in 6 of 400 control chromosomes (allele frequency, 1.5%), and De Bortoli et al. (2010) suggested that A897KfsX4 should be considered to be a rare polymorphism. ### ARVD and Mild Palmoplantar Keratoderma with or without Woolly Hair In 2 Pakistani sibs with ARVD with left ventricular involvement as well as mild palmoplantar keratoderma and woolly hair, in whom homozygosity mapping excluded the involvement of the JUP (173325), DSP (125647), and PKP2 (602861) genes, Simpson et al. (2009) identified homozygosity for a 1-bp deletion in the DSC2 gene (125645.0004). The unaffected first-cousin parents and an unaffected sister were heterozygous carriers of the mutation, which was not found in 300 control chromosomes. Gerull et al. (2013) screened 2 Canadian Hutterite kindreds with ARVD, 1 from the Dariusleut branch and 1 from the Lehrerleut branch, for mutation in 7 ARVD-associated genes and identified homozygosity for a nonsense mutation in the DSC2 gene (Q554X; 125645.0005) that segregated fully with disease in both families. Genotyping of a population-based sample of 1,535 Schmiedeleut Hutterites from South Dakota revealed a carrier frequency of 9.4%, with identification of 6 homozygotes from 4 families, 3 of whom were clinically asymptomatic. All 144 Schmiedeleut carriers could be traced back through a 9-generation pedigree to their most recent common ancestor couple, born in the 1750s, before the establishment of the 3 Hutterite leuts, suggesting that the mutation was introduced by a single individual. Mild palmoplantar hyperkeratosis was observed in only 1 of the Canadian Hutterite patients, who had normal hair. Gerull et al. (2013) suggested that involvement of hair and skin, as observed in a family of Pakistani origin by Simpson et al. (2009), might be dependent on the exact location of the mutation or a modifying genetic/ethnic background. INHERITANCE \- Autosomal dominant \- Autosomal recessive CARDIOVASCULAR Heart \- Ventricular arrhythmia \- Premature sudden cardiac death \- Left ventricular involvement \- Dyspnea \- Syncope \- Palpitations \- Fibrofatty replacement of right ventricular myocardium SKIN, NAILS, & HAIR Skin \- Palmoplantar keratoderma, mild (in homozygous patients) Hair \- Woolly hair (in some homozygous patients) MISCELLANEOUS \- Patients with homozygous mutations display mild palmoplantar keratoderma with or without woolly hair in addition to ARVD MOLECULAR BASIS \- Caused by mutation in the desmocollin 2 gene (DSC2, 125645.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 11	c1862511	6,130	omim	https://www.omim.org/entry/610476	2019-09-22T16:04:28	{"doid": ["0110082"], "mesh": ["C566254"], "omim": ["107970", "610476"], "orphanet": ["217656"], "synonyms": ["Familial isolated ARVD", "Familial isolated ARVC", "ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY 11", "Alternative titles", "Familial isolated arrhythmogenic ventricular dysplasia", "Familial isolated arrhythmogenic ventricular cardiomyopathy", "Familial isolated arrhythmogenic right ventricular cardiomyopathy"], "genereviews": ["NBK1131"]}
Hashimoto-Pritzker disease, also known as congenital self-healing reticulo-histiocytosis, is a very rare disease characterized by single or multiple red-purple or brown pimples (papules) and lumps (nodules) present at birth (congenital) or soon thereafter. Classic signs and symptoms include congenital or early development of painless papules, nodules or plaques with spontaneous regression in 2-3 months, and increase of a type of immune cells known as Langerhans cell histiocytes. Langerhans cells help regulate the immune system, and are normally found throughout the body. An excess of immature Langerhans cells usually form tumors called granulomas. Most patients have multiple lesions, but in about 25% of cases there is only one lesion. Development of lesions in adulthood, recurrence of the disease, as well as lung and eye involvement, are very rare. Because the lesions often cure by themselves, treatment is usually not necessary, although topical corticoids may be used for persistent lesions. It is considered as a benign, self-limited disorder, but long-term follow-up and a thorough evaluation for internal organ abnormalities is recommended. Hashimoto-Pritzker disease is one form (congenital self-healing variant) of Langerhans cell histiocytosis (LCH). The other forms include a severe, acute and disseminate form known as Letterer-Siwe disease, an intermediate chronic form with multiple lesions known as Hand-Schüller-Christian disease (characterized by diabetes insipidus, bulging of the eye and localized lesions in the bone) and a less severe disease known as eosinophilic granuloma, characterized by solitary or few, and chronic lesions of bone or other organs. Because all the variants have many common symptoms it is though that they may be manifestations of Langerhans cell histiocytosis and not separate syndromes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Hashimoto-Pritzker syndrome	c1275336	6,131	gard	https://rarediseases.info.nih.gov/diseases/2604/hashimoto-pritzker-syndrome	2021-01-18T18:00:09	{"mesh": ["C535843"], "umls": ["C1275336"], "orphanet": ["99872"], "synonyms": ["Hashimoto-Pritzker histiocytosis", "Hashimoto-Pritzker disease", "Congenital Langerhans cell histiocytosis", "OBSOLETE: Hashimoto-Pritzker syndrome"]}
Marcano and Richieri-Costa (1998) reported a Brazilian family with 5 individuals, in 3 generations, with malar hypoplasia, cleft lip with or without cleft palate, mild upslanting palpebral fissures, and abnormal ears. The authors suggested that this phenotype may represent a novel mandibulofacial dysostosis syndrome, which they designated 'Bauru type,' inherited in an autosomal dominant manner. Zechi-Ceide and Guion-Almeida (1999) reported a female patient with upslanting palpebral fissures, high nasal bridge, malar hypoplasia, Robin sequence with severe micrognathia, and hypoplastic tragus and ear lobes. No other family members were affected. The authors suggested that this patient may have the same condition with variable expressivity as that reported by Marcano and Richieri-Costa (1998). The absence of clinical findings in the parents of the patient supported the possibility of a novel mutation leading to the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	MANDIBULOFACIAL DYSOSTOSIS SYNDROME, BAURU TYPE	c1858101	6,132	omim	https://www.omim.org/entry/604830	2019-09-22T16:11:43	{"mesh": ["C565744"], "omim": ["604830"]}
## Clinical Features Verloes and Lesenfants (1997) described a 7-year-old girl with severe hypertelorism, huge palpebral fissures, ectropion of the lower lid, broad raised nasal base, a wide nasal tip, long smooth philtrum, macrostomia, irregularly placed teeth, and micrognathia. Her intellectual development was normal; no internal abnormalities were reported. Her parents were young, healthy, and nonconsanguineous. Verloes and Lesenfants (1997) proposed that this child had a hitherto unreported form of mandibulofacial dysostosis. Corona-Rivera et al. (2013) described a girl, born to nonconsanguineous parents, with macroblepharon, ectropion, macrostomia, large fontanels, broad metopic suture, capillary hemangioma, mild synophrys, hypertrichosis of the eyebrows with lateral thickening, increased density of the upper eyelid eyelashes more marked laterally, downslanting palpebral fissures, a broad nasal bridge, hypertelorism, posteriorly rotated ears, long and smooth philtrum, and a thin vermilion border to the upper lip. She initially showed mild motor delay, but mental development was normal at the age of 4 years. Lagophthalmos resulting from macroblepharon and ectropion produced corneal drying, chronic conjunctivitis, keratitis, and corneal clouding, which was apparent from the age of 2 months. Three-dimensional computed tomography scan of the craniofacial region showed large fontanels, broad metopic suture, and osseous hypertelorism. Corona-Rivera et al. (2013) suggested that the phenotype in this patient was the same as that in the patient of Verloes and Lesenfants (1997). INHERITANCE \- Isolated cases HEAD & NECK Head \- Brachycephalic Face \- Round face \- Flat face \- Micrognathia \- Retrognathism \- Long philtrum \- Smooth philtrum Ears \- Otitis media, recurrent \- Small ears \- Posteriorly rotated ears Eyes \- Hypertelorism \- Long palpebral fissures \- Ectropion of the lower lid \- Conjunctivitis, recurrent \- Downslanting palpebral fissures \- Macroblepharon \- Synophrys, mild \- Hypertrichosis of the eyebrows \- Increased density of the upper eyelid eyelashes \- Lagophthalmos \- Corneal drying \- Keratitis \- Corneal clouding Nose \- Broad nasal bridge \- Raised nasal bridge \- Wide nasal tip \- Anteverted nares Mouth \- Thin, hypoplastic vermilion border \- Macrostomia Teeth \- Irregularly placed teeth \- Oligodontia CARDIOVASCULAR Vascular \- Capillary hemangioma on face SKELETAL Skull \- Large fontanels \- Broad metopic suture SKIN, NAILS, & HAIR Hair \- Synophrys, mild \- Hypertrichosis of the eyebrows \- Increased density of the upper eyelid eyelashes MISCELLANEOUS \- Two patients reported (last curated May 2013) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	MANDIBULOFACIAL DYSOSTOSIS WITH MACROBLEPHARON AND MACROSTOMIA	c1865181	6,133	omim	https://www.omim.org/entry/602562	2019-09-22T16:13:33	{"mesh": ["C566520"], "omim": ["602562"], "orphanet": ["357158"], "synonyms": ["Alternative titles", "VERLOES-LESENFANTS SYNDROME", "MACROBLEPHARON, ECTROPION, HYPERTELORISM, AND MACROSTOMIA"]}
Itai-itai disease (イタイイタイ病, itai-itai byō, "it hurts-it hurts disease") was the name given to the mass cadmium poisoning of Toyama Prefecture, Japan, starting around 1912. The term "itai-itai disease" was coined by locals[1] for the severe pains (Japanese: 痛い itai) people with the condition felt in the spine and joints. Cadmium (Cd) poisoning can also cause softening of the bones and kidney failure. Effective treatments involve the use of chelators to promote urinary excretion of Cd.[2] The cadmium was released into rivers by mining companies in the mountains, which were successfully sued for the damage. Remediation efforts in the affected region have been ongoing since 1972 and were mostly complete as of 2012.[3] Monetary costs of the cleanup have been paid for in part by Japan’s national government, Mitsui Mining, and the Gifu and Toyama prefectural governments.[4] Itai-itai disease is known as one of the Four Big Pollution Diseases of Japan.[5] ## Contents * 1 Etymology * 2 Causes * 3 History * 3.1 Cadmium pollution in Jinzū river * 3.2 Cadmium accumulation in a human body * 4 Symptoms * 5 Treatment * 6 Society * 6.1 Legal action * 6.2 Remediation process * 7 See also * 8 References * 9 External links ## Etymology[edit] The term itai-itai disease (in Japanese イタイイタイ病 itai-itai byō, "it hurts-it hurts disease" or "ouch-ouch disease") was coined by the affected locals for the severe pains that people with itai-itai disease felt in the spine and joints.[6] In Japanese 痛い itai is used as an adjective meaning "painful" or as an interjection equivalent to "ouch". ## Causes[edit] Itai-itai disease was caused by cadmium poisoning due to mining in Toyama Prefecture. Regular mining for silver started in 1589, and soon thereafter, mining for lead, copper, and zinc began. The earliest records of mining for gold in the area date back to 1710. Cadmium is a metal byproduct of mining that is toxic to most organisms. Recent animal studies have shown that cadmium poisoning alone is not enough to elicit all of the symptoms of itai-itai disease.[7] These studies are pointing to damage of the mitochondria of kidney cells by cadmium as a key factor of the disease. ## History[edit] Increased demand for raw materials during the Russo-Japanese War and World War I, as well as new mining technologies from Europe, increased the output of the mines, putting the Kamioka Mines in Toyama among the world's top mines. Production increased even more before World War II. Starting in 1910 and continuing through 1945, cadmium was released in significant quantities by mining operations, and the disease first appeared around 1912.[1] In the 1920s, levels of contaminated tailing waste increased after the creation of new froth flotation processes that boosted zinc production. Fine powdered mineral particles formed in the frothing process escaped and drifted downriver. These particles were subsequently oxidized into ions that were absorbed by aquatic plants, rice crops, fish, and subsequently, humans.[6] Sphalerite, the main zinc containing ore in Komioka, is almost always coupled with greenockite, the only major cadmium containing mineral in the world. Because of this, cadmium is a regular by-product of the zinc ore mining process.[6] Up until 1948, cadmium was discarded as waste into the Jinzū River due to it being of no industrial value, exacerbating the levels of the element’s release into the waterbody.[6] Prior to World War II, the mining, controlled by the Mitsui Mining & Smelting Co., Ltd., increased to satisfy wartime demand. This subsequently increased the pollution of the Jinzū River and its tributaries. The river was used mainly for irrigation of rice fields, but also for drinking water, washing, fishing, and other uses by downstream populations.[1] When the population complained to Mitsui Mining & Smelting Co. about this pollution, the company built a basin to store the mining waste water before leading it into the river. This proved ineffective, and many had already been sickened. The causes of the poisoning were not well understood and, up to 1946, it was thought to be simply a regional disease or a type of bacterial infection.[1] Medical tests started in the 1940s and 1950s, searching for the cause of the disease. Initially, it was expected to be lead poisoning due to the lead mining upstream. Only in 1955 did Dr. Hagino and his colleagues suspect cadmium as the cause of the disease.[1] Toyama Prefecture also started an investigation in 1961, determining that the Mitsui Mining and Smelting's Kamioka Mining Station caused the cadmium pollution and that the worst-affected areas were 30 km downstream of the mine. In 1968, the Ministry of Health and Welfare issued a statement about the symptoms of itai-itai disease caused by the cadmium poisoning.[8] The reduction of the levels of cadmium in the water supply reduced the number of new cases; no new case has been recorded since 1946. While the people with the worst symptoms came from Toyama prefecture, the government found patients with itai-itai disease in five other prefectures. After the first reports of Itai-Itai in 1912, it took 55 years for the epidemiological investigation to discover that the disease was due to cadmium poisoning.[9] Delayed bureaucratic response was a common thread in the Four Big Pollution Diseases of Japan.[1] The mines are still in operation and cadmium pollution levels remain high, although improved nutrition and medical care has reduced the occurrence of itai-itai disease.[7] ### Cadmium pollution in Jinzū river[edit] The Jinzū River in Toyama Japan, where cadmium-containing industrial waste was dumped. This began the spread of Itai-itai disease. Over time, the cadmium that was released as industrial waste began to accumulate in the soil, algae and river organisms. This resulted in the local phytoplankton and algal species absorbing it in high quantities. Cadmium was subsequently passed through the food web to fish consumers. Fish also bioaccumulated cadmium through passive transport in the gills.[10] Cadmium adversely affected fish, causing endocrine disruption and inhibited reproduction, and sometimes mortality.[3] Due to the residents being unaware of the cadmium and its dangers, they used the water from the Jinzū to irrigate their rice fields. Cadmium is highly water soluble and the rice paddy’s prolonged exposure led to the rice strains quickly becoming contaminated and toxic.[11] The local resident’s consumption of these strains of rice and drinking water then resulted in elevated cadmium body burdens – leading directly to symptoms characteristic of Itai-Itai disease.[12] Cadmium is now considered one of the most dangerous toxic metal due to its ability to threaten food safety through being easily be absorbed into the rice paddies, then subsequently the rice.[11] ### Cadmium accumulation in a human body[edit] Studies conducted to estimate the amount of cadmium exposure necessary to develop Itai-Itai Disease found permissible lifetime cadmium intake (LCD) levels for humans to be 1.7 to 2.1 g. When Itai-Itai Disease was first being recognized in just 5% of the afflicted population, LCD levels are estimated to have already been at 2.6 g.[13] Cadmium accumulates mainly in the liver and the kidneys, but has more of an effect on the kidneys.[14] The severe symptoms seen in Itai-itai disease are a direct result of prolonged exposure to cadmium. Cadmium enters the kidneys by binding to metallothionein in the blood and traveling to the glomerulus in the kidney.[15] Once the cadmium makes it into the tubular cells in the kidneys, the cadmium is released and accumulates in the renal cortex until it reaches toxic levels.[14] When cadmium reaches dangerous levels in the renal cortex, it can deactivate metal-dependent enzymes or activate calmodulin, which plays a role in smooth muscle contraction by sensing calcium levels.[14] Once the kidneys have experienced extensive damage, those affected begin experiencing musculoskeletal damage, due to the disruption of calcium homeostasis.[14] This musculoskeletal damage is what causes the bone pain and bone deformities that characterizes Itai-itai disease. ## Symptoms[edit] One of the main effects of cadmium poisoning is weak and brittle bones. Spinal and leg pain is common, and a waddling gait often develops due to bone deformities caused by the long-term cadmium exposure. The pain eventually becomes debilitating, with fractures becoming more common as the bone weakens. Permanent deformation in bones can occur. Other complications include coughing, anemia, and kidney failure, leading to death.[4] A marked prevalence in older, postmenopausal women has been observed, however, the cause of the phenomenon is not fully understood, and is currently under investigation. Cadmium poisoning in postmenopausal women may also result in an increased risk for osteoporosis. Current research has pointed to general malnourishment, as well as poor calcium metabolism relating to the women's age.[7] These studies are pointing to damage of the mitochondria of kidney cells by cadmium as a key factor of the disease.[15] ## Treatment[edit] Any person with Cd-Poisoning must seek immediate medical help. Detoxification of Cadmium (Cd) with EDTA (Ethylene Diamine TetraAcetate) and other chelators is possible. Clinically available chelators include EDTA, DMPS, DMSA, and British Anti-Lewisite (BAL). BAL is more toxic than its derivatives, DMPS and DMSA, and is seldom used clinically. EDTA, DMPS, and DMSA increase urinary excretion of Cd. Studies in vitro and in vivo suggest that EDTA is superior to DMSA in mobilizing intracellular Cd.[2] As EDTA is approved by the FDA for lead and other heavy metals, and has a long history of safe use, it is most widely accepted for clinical use. Use of such chelators as has been seen as therapeutically beneficial to humans and animals when done using established protocols. ## Society[edit] ### Legal action[edit] Twenty-nine plaintiffs, consisting of 9 people with itai-itai disease and 20 of their family members, sued the Mitsui Mining and Smelting Co. in 1968 in the Toyama Prefectural court. In June 1971, the court found the Mitsui Mining and Smelting Co. guilty. Subsequently, the company appealed to the Nagoya District Court in Kanazawa, but the appeal was rejected in August 1972. The Mitsui Mining and Smelting Co. agreed to pay for the medical care of the people who had been affected, finance the monitoring of the water quality performed by the residents, and pay reparations to the people with the disease.[1] Out of the four major pollution events, it was only in the case of Itai-itai Disease that victims succeeded in instilling almost complete pollution control through legal action.[6] People who believe that they have itai-itai disease have to contact the Japanese Ministry of Health, Labor, and Welfare to have their claims assessed. Many people with itai-itai disease were not satisfied with government actions and demanded a change in the official procedures. This caused the government to review the criteria for recognizing a patient legally; the government also reassessed the treatment of the disease. A person is considered to have itai-itai disease if he or she lived in the contaminated areas, has kidney dysfunctions and softening of the bones, but not related heart problems. One hundred and eighty-four patients have been legally recognized since 1967, of whom 54 were recognized in the period from 1980 to 2000. An additional 388 people have been identified as potential patients, those who had not been officially examined yet.[1] Fifteen people with itai-itai were still alive as of 1993[update]. ### Remediation process[edit] Following the trial victory of the plaintiffs over the Misui Mining Co in 1972, Mitsui Mining agreed to begin the process of remediation for the mine, as well as the surrounding farmland and river region. This process began with the first on-site inspection conducted by a team of scientists and government officials. These whole site inspections continue to take place yearly, with additional specialty inspections conducted 6-7 times throughout the year.[16] These specialty checks specifically monitor water originating from the mine, as it has high levels of cadmium, which requires it to be separated and diverted to the Kamioka Mine slag dump. The water and solids are separated and processed before leaving the mine to ensure no groundwater contamination to the surrounding area. The treatment facilities exhaust is also monitored to ensure no cadmium in the airborne byproduct of the zinc refining process.[16] Continuous inspections following the lawsuit have documented considerable decreases in cadmium levels. Total amounts of cadmium discarded decreased from 35 kg per month in 1972 to 3.8 kg per month in 2010; the average concentration of cadmium in the mine’s discharge had been reduced to 1.2 ppb in 2010 from 9 ppb in 1972; and in response to improved dust collection methods, the total amount of cadmium discharged in smoke dropped from >5 kg per month in 1972 to 0.17 kg per month in 2010. In 1996, the mean concentration of cadmium in agricultural lands had returned to the background level of 0.1 ppb, signifying trivial cadmium outflow.[6] This is a success in regards to the lawsuit. The cadmium pollution had also contaminated many of the agricultural areas surrounding the mine. As a response to the metal pollution, the Japanese government enacted the Prevention of Soil Contamination in Agricultural Land Law of 1970. It ordered planting to be stopped so that restoration of the soil could be implemented to areas with 1ppm of cadmium or more in the soil. Surveying in Toyama Prefecture began in 1971, and by 1977, 1500 hectares along the Jinzū River were designated for soil restoration. These farmers were compensated for lost crops and for lost production in past years by the Mitsui Mining and Smelting, Toyama Prefecture, and the national government. As of 1992[update], only 400 hectares remained contaminated.[1] In 1992, the average annual health expense compensation was ¥743 million. Agricultural damage was compensated with ¥1.75 billion per year, or a total of annually ¥2.518 billion. Another ¥620 million were invested annually to reduce further pollution of the river.[1] On 17 March 2012, officials concluded the cleanup project of the cadmium-polluted areas in the Jinzū River basin. Eight-hundred and sixty-three hectares of topsoil had been replaced since the cleanup began in 1979 at a total cost of ¥40.7 billion. The project had been financed by the Japanese national government, Mitsui Mining, and the Gifu and Toyama prefectural governments.[4] ## See also[edit] * Heavy metal poisoning * Onsan illness ## References[edit] 1. ^ a b c d e f g h i j ICETT Itai-itai disease (1998) "Archived copy". Archived from the original on 2008-04-15. Retrieved 2008-05-01.CS1 maint: archived copy as title (link) 2. ^ a b Bernhoft RA (2013). "Cadmium toxicity and treatment". TheScientificWorldJournal. 2013: 394652. doi:10.1155/2013/394652. PMC 3686085. PMID 23844395. 3. ^ a b Levit S (November 2010). A Literature Review of Effects of Cadmium on Fish. The Nature Conservancy. 4. ^ a b c Yoshida F, Hata A, Tonegawa H (1999-09-01). "Itai-Itai disease and the countermeasures against cadmium pollution by the Kamioka mine". Environmental Economics and Policy Studies. 2 (3): 215–229. doi:10.1007/BF03353912. hdl:2115/53361. ISSN 1867-383X. S2CID 1902243. 5. ^ Almeida P, Stearns LB (February 1998). "Political Opportunities and Local Grassroots Environmental Movements: The Case of Minamata". Social Problems. 45 (1): 37–60. doi:10.1525/sp.1998.45.1.03x0156z. ISSN 0037-7791. JSTOR 3097142. 6. ^ a b c d e f Kaji M (2012-07-06). "Role of experts and public participation in pollution control: the case of Itai-itai disease in Japan1". Ethics in Science and Environmental Politics. 12 (2): 99–111. doi:10.3354/esep00126. ISSN 1611-8014. 7. ^ a b c Hamilton JW. "What is Itai-Itai disease". Access Science. McGraw-Hill Global Education Holdings, LLC. Archived from the original on 2013-11-13. Retrieved 2013-11-10. 8. ^ "Itai-itai disease". Kanazawa Medical University. 9. ^ Imamura T, Ide H, Yasunaga H (July 2007). "History of public health crises in Japan". Journal of Public Health Policy. 28 (2): 221–37. doi:10.1057/palgrave.jphp.3200131. PMID 17585323. S2CID 33832761. 10. ^ Han TW, Tseng CC, Cai M, Chen K, Cheng SY, Wang J (February 2020). "Sarcodia suiae". International Journal of Environmental Research and Public Health. 17 (4): 1294. doi:10.3390/ijerph17041294. PMC 7068516. PMID 32085376. 11. ^ a b Zhao FJ, Wang P (February 2020). "Arsenic and cadmium accumulation in rice and mitigation strategies". Plant and Soil. 446 (1–2): 1–21. doi:10.1007/s11104-019-04374-6. ISSN 0032-079X. S2CID 208302679. 12. ^ Nishijo M, Nakagawa H, Suwazono Y, Nogawa K, Kido T (July 2017). "Causes of death in patients with Itai-itai disease suffering from severe chronic cadmium poisoning: a nested case-control analysis of a follow-up study in Japan". BMJ Open. 7 (7): e015694. doi:10.1136/bmjopen-2016-015694. PMC 5734474. PMID 28710217. 13. ^ Inaba T, Kobayashi E, Suwazono Y, Uetani M, Oishi M, Nakagawa H, Nogawa K (November 2005). "Estimation of cumulative cadmium intake causing Itai-itai disease". Toxicology Letters. 159 (2): 192–201. doi:10.1016/j.toxlet.2005.05.011. PMID 16006079. 14. ^ a b c d "Toxicological Profile for Cadmium" (PDF). Agency for Toxic Substances and Disease Registry. U.S. Department of Health and Human Services. September 2012. 15. ^ a b Genchi G, Sinicropi MS, Lauria G, Carocci A, Catalano A (May 2020). "The Effects of Cadmium Toxicity". International Journal of Environmental Research and Public Health. 17 (11): 3782. doi:10.3390/ijerph17113782. PMC 7312803. PMID 32466586. 16. ^ a b "The Itai-itai Disease museum 《About the Itai-itai Disease》". www.pref.toyama.jp. Retrieved 2020-12-23. ## External links[edit] * Additional Information on Itai-Itai Disease * What is Itai-itai disease? * Deletion in proximal tubule cell gene causes symptoms of Itai-Itai * v * t * e Four Big Pollution Diseases of Japan * Itai-itai disease * Minamata disease * Niigata Minamata disease * Yokkaichi asthma Authority control * NDL: 00564287 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Itai-itai disease	c4524035	6,134	wikipedia	https://en.wikipedia.org/wiki/Itai-itai_disease	2021-01-18T18:45:28	{"wikidata": ["Q183472"]}
Tongue disease A picture of black hairy tongue. A non serious tongue disease. SpecialtyGastroenterology Tongue diseases can be congenital or acquired, and are multiple in number. Considered according to a surgical sieve, some example conditions which can involve the tongue are discussed below. Glossitis is a general term for tongue inflammation, which can have various etiologies, e.g. infection. ## Contents * 1 Congenital * 2 Acquired * 2.1 Vascular * 2.2 Infective * 2.3 Traumatic * 2.4 Autoimmune * 2.5 Inflammatory * 2.6 Neurological * 2.7 Neoplastic * 2.8 Degenerative * 2.9 Environmental * 2.10 Unknown * 2.11 Iatrogenic * 3 Epidemiology * 4 History * 5 See also * 6 References * 7 External links ## Congenital[edit] Ankyloglossia Examples of congenital disorders which affect the tongue include: * Aglossia \- complete absence of the tongue at birth * Ankyloglossia (tongue tie) - where the lingual frenum tethers the tongue to the floor of the mouth. If it interferes with oral hygiene and feeding, frenectomy may be indicated. * Hypoglossia \- congenitally short tongue * Microglossia * Macroglossia \- an abnormally large tongue, seen in some disorders such as Down syndrome (although macroglossia can be an acquired condition as well). * Hamartomata \- for example Leiomyomatous hamartoma * Glossoptosis * Choristomata \- For example, osseous choristoma of the tongue, a very rare condition characterized by a nodule on the dorsum of the tongue containing mature lamellar bone without osteoblastic or osteoclastic activity.[1]:808 Cartilaginous (chondroid),[2] and glial choristomas may also very rarely occur on the tongue.[3] * Lingual thyroid * Cleft tongue (bifid tongue) - completely cleft tongue is a rare condition caused by a failure of the lateral lingual swellings to merge.[4] More common is an incompletely cleft tongue, appearing as midline fissure. This is normally classed as fissured tongue. ## Acquired[edit] ### Vascular[edit] * Caviar tongue \- the veins underneath the tongue can become dilated and prominent, giving the undersurface of the tongue a caviar like appearance. * Hemangioma ### Infective[edit] Median rhomboid glossitis * Glossitis \- some types of glossitis are caused by infections, e.g. median rhomboid glossitis (Candida species), "strawberry tongue" (seen in scarlet fever), and syphilitic glossitis (seen in tertiary syphilis). * Oral hairy leukoplakia (seen in people with immunosuppression, caused by Epstein–Barr virus) * Oral candidiasis can affect the tongue. Risk factors for oral candidiasis include antibiotic and corticosteroid use, and immunodeficiency (e.g. HIV),[5] or diabetes mellitus). ### Traumatic[edit] * The tongue may traumatized by mechanical, thermal, electrical or chemical means. A common scenario is where the tongue is bitten accidentally whilst a local anesthetic inferior alveolar nerve block is wearing off. The tongue may develop scalloping on the lateral margins, sometimes termed crenated tongue. This appearance is the result of indentations of the teeth where the tongue is habitually pressed against the teeth ("tongue thrusting", and example of oral parafunction). A lesion similar to morsicatio buccarum can occur on the tongue (sometimes called morsicatio linguarum), caused by chronic chewing on the tongue. The ventral surface (under surface) of the tongue may also be traumatized during oral sexual activity such as cunnilingus ("cunnilingus tongue").[6] ### Autoimmune[edit] * Autoimmune conditions such as Sjögren syndrome can cause xerostomia, with resultant glossitis. ### Inflammatory[edit] * Glossitis * Oral lichen planus ### Neurological[edit] * Hypoglossal nerve weakness can cause atrophy and fasciculation of the tongue. * Melkersson–Rosenthal syndrome \- a neurological disorder characterized by fissured tongue, facial palsy and orofacial swelling. ### Neoplastic[edit] Oral cancer on the side of the tongue * The sides (lateral) and undersurface (ventral) of the tongue are high risk sites for the development of oral cancer, most commonly squamous cell carcinoma. ### Degenerative[edit] * Motor neuron disease (Lou Gehrig's disease) can cause impaired control of tongue movement, affecting speech and swallowing. ### Environmental[edit] * Poor diet can cause malnutrition and nutritional deficiencies. Deficiency of iron, B vitamins and folic acid are common causes for atrophic glossitis. * Black hairy tongue \- some factors thought to cause black hairy tongue are environmental, such as eating a soft diet, poor oral hygiene, smoking and antibiotic use. ### Unknown[edit] Geographic tongue (benign migratory glossitis) * Geographic tongue (benign migratory glossitis) - a common disorder which occasionally causes a burning sensation but is usually painless. Irregular patches of depapillation form on the tongue giving the appearance of a map. The cause is unknown. * Leukoplakia \- can affect the tongue * Tongue coating - food debris, desquamated epithelial cells and bacteria often form a visible tongue coating.[7] This coating has been identified as a major contributing factor in bad breath (halitosis),[7] which can be managed by brushing the tongue gently with a toothbrush or using special oral hygiene instruments such as tongue scrapers or mouth brushes.[8] * Burning mouth syndrome \- this chronic pain disorder commonly involves the tongue. In reflection of this, some of the synonyms for the condition include tongue-specific terms such as "glossodynia" or "burning tongue syndrome". Burning mouth syndrome is characterized by chronic burning sensation on the tongue and other oral mucous membranes in the absences of any identifiable signs or causes. ### Iatrogenic[edit] * Paratrichosis tongue[9] \- Real hair implanted on tongue. ## Epidemiology[edit] Tongue lesions are very common. For example, in the United States one estimated point prevalence was 15.5% in adults.[10] Tongue lesions are more common in persons who wear dentures and tobacco users.[10] The most common tongue conditions are geographic tongue, followed by fissured tongue and hairy tongue.[10] ## History[edit] Hippocrates, Galen and others considered the tongue to be a "barometer" of health, and emphasized the diagnostic and prognostic importance of the tongue.[11] Assessment of the tongue has historically been an important part of a medical examination.[12] The shape and color of the tongue is examined and observed diagnostically in traditional Chinese medicine. For example, scalloping of the tongue is said to indicate qi vacuity.[13] Some modern medical sources still describe the tongue as "the mirror of physical health".[14] This is related to the high rate of turnover of the oral mucosa compared to the skin, which means that systemic conditions may manifest sooner in the mouth than the skin. Physical appearances such as cyanosis are also often more readily apparent in the mouth. ## See also[edit] * Tooth pathology * Tongue * Tongue map * Oral and maxillofacial pathology ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 2. ^ Yaqoob, N; Ahmed, Z; Muzaffar, S (Dec 2002). "Chondroid choristoma of tongue--a rare entity". JPMA. The Journal of the Pakistan Medical Association. 52 (12): 584–5. PMID 12627912. 3. ^ Fan, SQ; Ou, YM; Liang, QC (Apr 2008). "Glial choristoma of the tongue: report of a case and review of the literature". Pediatric Surgery International. 24 (4): 515–9. doi:10.1007/s00383-007-2061-0. PMID 17972083. S2CID 29538827. 4. ^ Rajendran R (1 January 2009). Shafer's Textbook Of Oral Pathology (6th ed.). Elsevier India. p. 27. ISBN 978-81-312-1570-8. 5. ^ Hodgson TA, Greenspan D, Greenspan JS (April 2006). "Oral lesions of HIV disease and HAART in industrialized countries". Adv Dent Res. 19 (1): 57–62. doi:10.1177/154407370601900112. PMID 16672551. S2CID 9526698. 6. ^ Ravikiran Ongole; Praveen BN (10 Feb 2014). Textbook of Oral Medicine, Oral Diagnosis and Oral Radiology. Elsevier Health Sciences. p. 1245. ISBN 9788131237991. 7. ^ a b Newman MG, Takei HH, Klokkevold PR, Carranza FA, eds. (2012). Carranza's clinical periodontology (11th ed.). St. Louis, Mo.: Elsevier/Saunders. pp. 84–96. ISBN 978-1-4377-0416-7. 8. ^ Outhouse, TL; Al-Alawi, R; Fedorowicz, Z; Keenan, JV (Apr 19, 2006). Outhouse, Trent L (ed.). "Tongue scraping for treating halitosis". The Cochrane Database of Systematic Reviews (2): CD005519. doi:10.1002/14651858.CD005519.pub2. PMID 16625641. (Retracted, see doi:10.1002/14651858.cd005519.pub3. If this is an intentional citation to a retracted paper, please replace `{{Retracted}}` with `{{Retracted\|intentional=yes}}`.) 9. ^ Segura-Sampedro JJ, Sampedro-Abascal C, Parra-López L, Muñoz-Rodríguez JC (2015). "Intraoral paratrichosis after autograft". Cir y Cir. 83 (4): 309–11. doi:10.1016/j.circir.2015.05.017. PMID 26118782. 10. ^ a b c Reamy, BV; Derby, R; Bunt, CW (Mar 1, 2010). "Common tongue conditions in primary care". American Family Physician. 81 (5): 627–34. PMID 20187599. 11. ^ "Odd Tongues: The Prevalence of Lingual Disease". The Maxillofacial Center for Diagnostics & Research. Retrieved 11 September 2013. 12. ^ Haller JS (September 1982). "The foul tongue: a 19th century index of disease". West. J. Med. 137 (3): 258–64. PMC 1274095. PMID 6755914. 13. ^ Marnae C. Ergil; Kevin V. Ergil, eds. (2009). Pocket Atlas of Chinese Medicine. Thieme. ISBN 9783131416117. 14. ^ Kostka, E; Wittekindt, C; Guntinas-Lichius, O (August 2008). "[Tongue coating, mouth odor, gustatory sense disorder - earlier and new treatment options by means of tongue scraper]". Laryngo- Rhino- Otologie. 87 (8): 546–50. doi:10.1055/s-2007-995614. PMID 18654938. ## External links[edit] Classification D * ICD-10: K14, Q38.1-Q38.3 * ICD-9-CM: 529, 750.0-750.1 * MeSH: D014060 * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease * v * t * e Congenital malformations and deformations of digestive system Upper GI tract Tongue, mouth and pharynx * Cleft lip and palate * Van der Woude syndrome * tongue * Ankyloglossia * Macroglossia * Hypoglossia Esophagus * EA/TEF * Esophageal atresia: types A, B, C, and D * Tracheoesophageal fistula: types B, C, D and E * esophageal rings * Esophageal web (upper) * Schatzki ring (lower) Stomach * Pyloric stenosis * Hiatus hernia Lower GI tract Intestines * Intestinal atresia * Duodenal atresia * Meckel's diverticulum * Hirschsprung's disease * Intestinal malrotation * Dolichocolon * Enteric duplication cyst Rectum/anal canal * Imperforate anus * Rectovestibular fistula * Persistent cloaca * Rectal atresia Accessory Pancreas * Annular pancreas * Accessory pancreas * Johanson–Blizzard syndrome * Pancreas divisum Bile duct * Choledochal cysts * Caroli disease * Biliary atresia Liver * Alagille syndrome * Polycystic liver disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Tongue disease	c0040409	6,135	wikipedia	https://en.wikipedia.org/wiki/Tongue_disease	2021-01-18T18:32:38	{"mesh": ["D014060"], "umls": ["C0426492", "C0025988", "C0040409"], "wikidata": ["Q7107436"]}
STT3B-CDG is a form of congenital disorders of N-linked glycosylation characterized by intrauterine growth retardation, microcephaly, failure to thrive, developmental delay, intellectual disability, hypotonia, seizures, optic nerve atrophy and respiratory difficulties. Genital abnormalities (micropenis, hypoplastic scrotum, undescended testes) have also been reported. STT3B-CDG is caused by mutations in the gene STT3B (3p24.1). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	STT3B-CDG	c2931007	6,136	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=370924	2021-01-23T18:50:08	{"mesh": ["C535751"], "omim": ["615597"], "umls": ["C2931007"], "icd-10": ["E77.8"], "synonyms": ["CDG syndrome type Ix", "CDG-Ix", "CDG1X", "Carbohydrate deficient glycoprotein syndrome type Ix", "Congenital disorder of glycosylation type 1x", "Congenital disorder of glycosylation type Ix"]}
A number sign (#) is used with this entry because a polymorphism of the gene encoding glycoprotein Ib-alpha (GP1BA; 606672) confers susceptibility to nonarteritic anterior ischemic optic neuropathy. Clinical Features Deutsch et al. (1990) described a family in which identical twin sisters in their forties had bilateral nonarteritic anterior ischemic optic neuropathy (NAION) and a younger sister had unilateral papillophlebitis. Berggren et al. (1974) had reported 3 of 7 sibs with anterior ischemic optic neuropathy; in 2, the involvement was bilateral and in 1 unilateral. Mojon et al. (2002) found a high prevalence of sleep apnea syndrome (107650) in patients with NAION, which supported previous case reports suggesting that such an association existed. This association might explain why approximately 75% of all patients with NAION discovered visual loss upon first awakening or when they first used vision critically after sleeping. The authors stated that sleep apnea syndrome may play an important role in the pathogenesis of NAION. Deramo et al. (2003) investigated the relationship between NAION and serum lipid levels in 37 consecutive patients diagnosed with NAION at or below age 50 years and 74 age- and gender-matched controls. They found that hypercholesterolemia (143890) was a risk factor in these patients and suggested that NAION might be the first manifestation of a previously unrecognized lipid disorder. The patients had experienced a focal, microvascular central nervous system ischemic event at a relatively young age. Deramo et al. (2003) suggested that aggressive treatment of lipid abnormalities might be warranted in these patients. Purvin et al. (2004) reviewed medical records of 20 patients who experienced an episode of NAION in an eye with optic disc drusen (ODD). The authors found that their patients were strikingly similar to those with NAION unassociated with drusen with regard to prevalence of vascular risk factors, pattern of visual field loss, and occurrence of a subsequent similar event in the other eye. In contrast, however, patients with ODD and NAION were younger than those with NAION, were more likely to report preceding episodes of transient visual obscuration, and had a more favorable visual outcome. Molecular Genetics Salomon et al. (2004) reported that the presence of the VNTR B allele of the GP1BA gene (606672.0002) confers a significant risk for NAION and predisposed affected patients to second eye involvement. Eyes \- Nonarteritic anterior ischemic optic neuropathy \- Papillophlebitis Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	NONARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY, SUSCEPTIBILITY TO	c1847711	6,137	omim	https://www.omim.org/entry/258660	2019-09-22T16:24:02	{"omim": ["258660"], "synonyms": ["Alternative titles", "NAION, SUSCEPTIBILITY TO", "OPTIC NEUROPATHY, ANTERIOR ISCHEMIC, SUSCEPTIBILITY TO"]}
## Description Familial anonychia/onychodystrophy with hypoplasia or absence of distal phalanges (ODP) is a rare disorder characterized by onychodystrophy, anonychia, brachydactyly of the fifth finger, and digitalization of the thumbs, with absence or hypoplasia of the distal phalanges of the hands and feet. Generally the nails of the first to third digits are progressively deformed with total anonychia in the last 2 digits and in all toes (summary by Genzer-Nir et al., 2010). A syndrome has been described in which affected females display juvenile hypertrophy of the breast (JHB; 113670) in association with ODP, whereas males have only ODP (mammary-digital-nail syndrome; 613689). Clinical Features Santos et al. (1981) described an 8-generation Portuguese family in which 12 members had brachydactyly and nail dysplasia. The disorder was characterized by brachydactyly of all fingers and toes except the thumb and big toe and absence of distal phalanges and nails in all fingers and toes. The affected members of the family also had a peculiar shape of the nose. Santos et al. (1981) suggested that this family had a type B brachydactyly of Bell classification (or 8 of Fitch) and that the transmission was autosomal dominant. Cooks et al. (1985) described a kindred in which 7 individuals in 2 generations with one instance of male-to-male transmission had a disorder characterized by onychodystrophy, anonychia, brachydactyly of the fifth finger, and digitalization of the thumbs, with absence or hypoplasia of the distal phalanges of the hands and feet. Cooks et al. (1985) stated that the disorder differed from autosomal dominant anonychia-onychodystrophy (107000) in which there is progressive nail hypoplasia from the fifth digit to the thumb, with anonychia often present in the second and third digits whereas in their family they observed nail hypoplasia in the thumb progressing to total nail absence in the fourth and fifth digits. Moreover, in dominant anonychia-onychodystrophy, no bone changes had been described. In autosomal dominant brachydactyly with absence of middle phalanges and hypoplastic nails (112900), the changes in the middle phalanges are distinctive. Relatively bizarre, asymmetric digital anomalies, including absence of one or more digits, distinguish anonychia with ectrodactyly (106900). In '20-nail dystrophy' (161050), dystrophy of the nails progresses with age, whereas in the family of Cooks et al. (1985) the nail findings were present from birth. Houlston and Temple (1994) raised the question of a distinctive facial appearance associated with type B brachydactyly in an English family with at least 11 affected members in 4 generations. Affected members showed wide-spaced, downslanting palpebral fissures, a prominent nose with bulbous tip, and a short philtrum. Nevin et al. (1995) described what they considered to be the second reported family with Cooks syndrome. For members in 3 successive generations, with an instance of male-to-male transmission, had bilateral nail hypoplasia of digits 1-3, with absence of nails of digits 4-5 of the hands, and total absence of toenails. In addition, there was absence/hypoplasia of the distal phalanges of the hands and feet. De Ravel et al. (1999) reported a sib pair with a distinct facies, absence/hypoplasia of the distal phalanges of the hands, feet, and nails, and bulbous digit tips, and suggested that these patients had features of both classic type B brachydactyly (BDB; 113000) and Cooks syndrome. Castori et al. (2007) reported a 2-year-old Caucasian girl with Cooks syndrome. She had slightly shortened fingers with hypoplastic distal flexion creases. Nails were absent on fingers 2 and 3, severely hypoplastic on fingers 1 and 4, and moderately shortened on fingers 5. Her feet showed absent or severely hypoplastic nails on 5 digits total. The digits without nails appeared bulbous-ended with tumor-like soft tissue hypertrophy. Cutaneous syndactyly of toes 2 and 3 and toes 2, 3, and 4 was evident on the left and right foot, respectively. Radiographic examination of the hands showed symmetrical shortening of the distal phalanges with clinodactyly of the fifth digit. Metacarpals were grossly normal. Feet radiographs showed only 2 phalanges in the toes and hypoplastic distal phalanges. There were no facial anomalies. Molecular analysis excluded a mutation in the ROR2 gene (602337). A paternal grandfather had cutaneous syndactyly of the fourth and fifth toes of the right foot. Castori et al. (2007) concluded that Cooks syndrome is distinct from classic brachydactyly type B because the former affects dorsoventral patterning and the latter affects early differentiation of skeletal precursor structures. The authors suggested that the large family reported by Kumar and Levick (1986) (106990) may have had Cooks syndrome. Kurth et al. (2009) reported 4 families with symmetric brachydactyly of the hands and feet, along with hyponychia or anonychia. The phenotype was consistent with Cooks syndrome. Radiographs showed missing middle phalanges and elongated terminal and proximal phalanges. There were no other skeletal anomalies, and sexual development was normal. Inheritance The transmission pattern in the families reported by Santos et al. (1981), Cooks et al. (1985), and Nevin et al. (1995) is consistent with autosomal dominant inheritance of this disorder. Molecular Genetics In affected members of 4 unrelated families with a phenotype consistent with Cooks syndrome, Kurth et al. (2009) identified overlapping duplications in a 2-Mb interval on chromosome 17q24.3, with a minimal critical area of 1.2 Mb. The region encompassed a large gene desert between KCNJ2 (600681) and SOX9 (608160). The duplications were confirmed by quantitative PCR and were not detected in more than 400 control DNA samples. The duplications occurred de novo in 2 families. Kurth et al. (2009) suggested that the duplications involved putative regulatory elements of SOX9 and may induce SOX9 misexpression and/or overexpression at specific time points during development, resulting in abnormal digit and nail development. In mouse embryo, Sox9 was strongly expressed in the distal mesenchymal condensations that develop into terminal phalanges. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Downslanting palpebral fissures Nose \- High nasal bridge \- Prominent nose \- Bulbous tip \- Hypoplastic alae nasi Mouth \- Short philtrum \- High-arched palate SKELETAL Hands \- Fifth finger brachydactyly \- Digitalization of thumbs \- Absent/hypoplastic distal phalanges of hands Feet \- Absent/hypoplastic distal phalanges of feet SKIN, NAILS, & HAIR Nails \- Onychodystrophy \- Anonychia ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	ANONYCHIA-ONYCHODYSTROPHY WITH HYPOPLASIA OR ABSENCE OF DISTAL PHALANGES	c1862841	6,138	omim	https://www.omim.org/entry/106995	2019-09-22T16:44:58	{"mesh": ["C537766"], "omim": ["106995"], "orphanet": ["1487"], "synonyms": ["Alternative titles", "COOKS SYNDROME"]}
Neonatal diabetes Neonatal diabetes mellitus (NDM) is a disease that affects an infant and their body's ability to produce or use insulin. NDM is a monogenic (controlled by a single gene) form of diabetes that occurs in the first 6 months of life. Infants do not produce enough insulin, leading to an increase in glucose accumulation. It is a rare disease, occurring in only one in 100,000 to 500,000 live births.[1] NDM can be mistaken for the much more common type 1 diabetes, but type 1 diabetes usually occurs later than the first 6 months of life. There are two types of NDM: permanent neonatal diabetes mellitus (PNDM) is a lifelong condition. Transient neonatal diabetes mellitus (TNDM) is diabetes that disappears during the infant stage but may reappear later in life.[1] Specific genes that can cause NDM have been identified.[2] The onset of NDM can be caused by abnormal pancreatic development, beta cell dysfunction or accelerated beta cell dysfunction.[3] Individuals with monogenic diabetes can pass it on to their children or future generations. Each gene associated with NDM has a different inheritance pattern. ## Contents * 1 Symptoms and signs * 2 Cause * 3 Mechanism * 3.1 Transient Neonatal Diabetes Mellitus (TNDM) * 3.2 Permanent Neonatal Diabetes Mellitus (PNDM) * 4 Diagnosis * 4.1 Diagnosis of TNDM and PNDM * 4.2 TNDM Diagnosis associated with Chromosome 6q24 Mutations * 4.3 Medical Professionals of NDM * 4.4 Diagnostic Test of NDM * 4.5 Genetic Testing of NDM * 5 Treatment * 6 Prognosis * 7 Recent research * 8 See also * 9 References * 10 External links ## Symptoms and signs[edit] Common symptoms of NDM includes: * Thirst and Frequent Urination An excessive thirst (also known as polydipsia) and increased urination (also known as polyuria) are common signs of diabetes. An individual with diabetes, have accumulated blood glucose. Their kidneys are working overtime to filter and uptake excess sugar. However, their kidneys cannot keep up, excess sugar is excreted into their urine, and this drag along fluids from the diabetic's tissues.[4] This may lead to more frequent urination and lead to dehydration. As a diabetic individual drinks more fluids to satisfy their thirst, he or she urinates even more.[4] * Dehydration Effected areas of the body are the eyes, mouth, kidneys, heart, and pancreas. Other symptoms of dehydration includes headache, thirst and dry mouth, dizziness, tiredness, and dark colored urine.[5] In severe cases of dehydration in diabetics, low blood pressure, sunken eyes, a weak pulse or rapid heart beat, feeling confused or fatigue.[5] Dehydration and high blood glucose for extended period of time, the diabetic's kidney would try to filter the blood of access glucose and excrete this as urine. As the kidneys are filtering the blood, water is being removed from the blood and would need to be replaced.[5] This leads to an increased thirst when the blood glucose is elevated in a diabetic individual. Water is needed to re-hydrate the body. Therefore, the body would take available from other parts of the body, such as saliva, tears, and from cells of the body. If access water is not available, the body would not be able to pass excess glucose out of the blood by urine and can lead to further dehydration.[5] Severe symptoms of NDM (Deficiency of insulin): * Ketoacidosis Is a diabetic complication that occurs when the body produces high levels of acid in the blood (ketones).[6] This effects the pancreas, fat cells, and kidneys. This condition occurs when the body cannot produce enough insulin.[6] In the absence or lack of insulin, the body of an diabetic individual will break down fat as fuel. This process produces a buildup of acids in the bloodstream known as ketones, in which leads to ketoacidosis if left untreated. The symptoms of ketoacidosis develop rapidly or within 24 hours.[6] Symptoms of ketoacidosis are excessive thirst, frequent urination, nausea or vomiting, stomach pain, tiredness, shortness or fruity smell on breath and confusion.[6] * Intrauterine Growth Restriction A condition in which the unborn baby is smaller than he or she should be, due to the fact he or she not growing at a normal rate in the womb.[7] Delayed growth puts the baby at risk of certain problems during pregnancy, delivery, and after birth. The problems are as follows: baby's birth weight is 90% less than normal weight, difficulty handling vaginal delivery, decreased oxygen levels, hypoglycemia (low blood glucose), low resistance to infection, low Apgar scores (a test given after birth to test the baby's physical condition and evaluate if special medical care is needed), Meconium aspiration (inhaling of stools passed while in the uterus) which causes breathing issues, irregular body temperature and high red blood cell count.[7] * Hyperglycemia A condition characterized as high blood glucose, which occurs when the body has too little insulin or when the body cannot use insulin properly.[8] Hyperglycemia affects the pancreas, kidneys, and body's tissues. Characterization of hyperglycemia is high blood glucose, high levels of sugar in the urine, frequent urination and increase thirst.[8] * Hypoglycemia A condition characterized an extremely low blood glucose, usually less than 70 mg/dL.[9] Areas of the body that are affected, pancreas, kidneys, and mental state. ## Cause[edit] Causes of NDM PNDM and TNDM are inherited genetically from the mother or father of the infant. Different genetic inheritance or genetic mutations can lead to different diagnosis of NDM (Permanent or Transient Neonatal Diabetes Mellitus). The following are different types of inheritance or mutations: * Autosomal Dominant: Every cell has two copies of each gene-one gen coming from the mother and one coming from the father. Autosomal dominant inheritance pattern is defined as a mutation that occurs in only one copy of the gene.[1] A parent with the mutation can pass on a copy of the gene and a parent with the mutation can pass on a copy of their working gene (or a copy of their damaged gene).[10] In an autosomal dominant inheritance, a child who has a parent with the mutation has a 50% possibility of inheriting the mutation.[10] * Autosomal Recessive -Autosomal recessive-Generally, every cells have two copies of each gene-one gene is inherited from the mother and one gene is inherited from the father.[1] Autosomal recessive inheritance pattern is defined as a mutation present in both copies if the gene in order for a person to be affected and each parent much pass on a mutated gene for a child to be affected.[1] However, if an infant or child has only one copy, he or she are a carrier of the mutation. If both parents are carriers of the recessive gene mutation, each child have a 25% chance of inheriting the gene.[1] * Spontaneous: A new mutation or change occurs within the gene.[1] * X-linked: When a trait or disease happens in a person who has inherited a mutated gene on the X chromosome (one of the sex chromosome).[1] ## Mechanism[edit] Neonatal Diabetes Mellitus (NDM) ### Transient Neonatal Diabetes Mellitus (TNDM)[edit] TNDM occurs within the first several days to weeks of an infant's life. Intrauterine growth restriction (IUGR) is commonly seen in affected individuals and defined as poor growth of an unborn baby while in his or her mother's womb.[11] In comparison, of PNDM, the insulin dose requirement of TNDM is often lower. TNDM resolves on its own at an average age of twelve weeks. Although, individuals will relapse in 50% of cases (usually during childhood or young adulthood).[12] The parts of the body that are mostly affected are the pancreas, central nervous system and various tissues of the body.[13] An average of 70% of TNDM is caused by defects initiating over-expression of the father genes in the imprinted region (genes whose expression is dependent on the parent that contributed them) of chromosome 6q24 (Chromosome meaning a string-like structure made of nucleic acid and protein that carries genetic material).[14] There are three mechanism that can cause 6q24-related TNDM, which includes the father's DNA being defected by uniparental isodisomy (UPD) on chromosome 6 and inherited duplication of 6q24 (inherited duplication is a small chromosomal change in which a very little amount of genetic material is copied in chromosome 6).[15] The last possible cause of TNDM, the mother's genes are affected by DNA methylation (DNA methylation is the process in which methyl groups or CH3- are added to the DNA molecule. When a methyl group is located on a promoter, it stops gene transcription).[12] In previous research, it has been observed the involvement of an imprinted gene within TNDM, is only expressed by the father's genetic material or chromosome, resulting in an increased expression of the imprinted gene by UPD or inherited duplication that leads to the onset of diabetes.[16] Numerous defects within the genome can lead to over-expression of the father's defected genes in the chromosome 6q24 region and result in TNDM.[15] However, there are two genes in this region that can be associated with TNDM: ZAC and HYMAI Genes ZAC is a zinc-finger protein that controls apoptosis (programmed cell death) and cell cycle arrest (cell division and duplication of DNA stops when the cell detects cell damage or defects) in PLAG1 (pleomorphic adenoma gene-like 1). PLAG1 is a transcription regulator of the type 1 receptor for pituitary adenylated cyclase-activating polypeptide (is a polypeptide that activates adenylate cyclase and increases the cyclic adenosine monophosphate or cAMP. cAMP is a second messenger that is used for neighboring cells to perform signal transduction in targeted cells), which is important for insulin secretion regulation.[12] The function of the HYMAI (hydatiform mole-associated and imprinted transcript) is unknown.[12] Second, chromosome 6q24-TNDM is caused by over-expression of imprinted genes at 6q24 (PLAGL1 [ZAC] and HYMAI).[17] It was discovered that a differentially methylated region (DMR) is present within the shared promoter of these genes. Generally the expression of the mother's alleles of PLAGL1 and HYMAI are blocked or not expressed by DMR methylation and only the father's alleles of PLAG1 and HYMA1 are expressed. The previously listed genetic mechanisms result in twice the normal amount of these two genes and cause chromosome 6q24 TNDM. ZFP57 Gene Third, mother's hypomethylation defects (a genetic defect that stops the allele from getting a methyl group, which would inhibit transcription) can occur from an isolated genomic imprinting or occur as a defect called, "hypomethylation imprinted loci" (HIL). HIL is defined as the loss of a methyl group in the 5-methylcytosine nucleotide at a fixed position on a chromosome.[17] Homozygous ( having two of the same alleles) or heterozygous (defined as having one each of two different alleles) ZFP57 pathogenic variant make up almost half of TNDM-HIL, but the other causes of HIL are unknown.[18][17] Moreover, half of TNDM patients that contain chromosome 6q24-related TNDM experiencing re-occurrence of diabetes during their childhood or young adulthood. The onset of insulin resistance and increased insulin requirements are associated with puberty and pregnancy initiating the relapse of diabetes.[12] In the event of remission, individuals do not show symptoms or impairment Beta-cell function in the fasting state. Insulin secretory response to intravenous glucose loading might be abnormal in those destined to have a relapse of diabetes.[12] TNDM caused by 6q24 genomic defects are always associated with IGUR.[12] Other contributing factors are umbilical hernia and enlarged tongue, which are present in 9 and 30% of patients with chromosome 6q24 related TNDM.[12] KCNJ11 and ABCC8 Genes In addition, TNDM initiated by the genes, KCNJ11 or ABCC8 mutations are similar to mutations in chromosome 6q24-related to TNDM. Normally, the birth weight in infants are lower in chromosome 6q24 TNDM patients and diabetes is initiated at an earlier age (similar to readmission).[12] There may be an overlap between chromosome 6q24 and KCNJ11 and ABCC8-related TNDM, making genetic diagnosis necessary for treatment. INS Gene Recessive mutations in the INS gene encoding insulin were discovered to trigger both PNDM and TNDM. Diabetes occurs because there is an decrease insulin biosynthesis as a result of homozygous mutations. Common phenotype is decreased birth weight and average age of diagnosis is one week.[12] Previous studies show relapse of diabetes occurred at an average age of 26 weeks.[12] ### Permanent Neonatal Diabetes Mellitus (PNDM)[edit] PNDM is associated with mutations in the Beta-cell ATP sensitive potassium channel (KATP) initiated by heterozygous leading to mutations in KCNJ11 and ABCC8, which is a result of 31% and 10% of PNDM cases (results based on Exeter experiment series).[12] Twelve percent of mutations in the insulin gene leads to PNDM.[citation needed] KCNJ11 and ABCC8 Genes association with Beta-cell ATP Sensitive Potassium Channel KCNJ11 encodes Kir6.2 (a protein coding gene in the potassium channel) and ABCC8 encodes the gene, SUR1 (the type 1 subunit of the sulfonylurea receptor), a member of the ATP-binding cassette transporter family, the two components of the KATP channel.[12] This channel links glucose metabolism to insulin secretion by closing in response to ATP. Blood glucose storage into Beta-cells lead to glycolysis and cause ATP generation.[12] The elevated ATP/ adenosine diphosphate ratio causes closure of the KATP channel, and inhibit potassium efflux (a lot of potassium flows out of this channel), that leads to depolarization of the Beta-cell membrane.[12] Depolarization is the loss of the difference in charge between the inner and outer parts of the plasma membrane of a muscle. This occurs because of change in permeability and migration of sodium ions inside the cell. The voltage gated channels then open, allowing calcium (Ca+) to flow inside the channel and cause exocytosis (active transport that moves molecules out of a cell by ejecting them in an energy using process) of insulin-containing granules from the Beta-cells. Activation of defects in KCNJ11 or ABCC8 seems to make the KATP channel less sensitive to ATP, leaving more channels in an open state after high levels of glucose occurs.[12] Resulting in the failure of insulin response to high blood glucose and leading to NDM.[12] ## Diagnosis[edit] ### Diagnosis of TNDM and PNDM[edit] The diagnostic evaluations are based upon current literature and research available on NDM. The following evaluation factors are: patients with TNDM are more likely to have intrauterine growth retardation and less likely to develop ketoacidosis than patients with PNDM. TNDM patients are younger at the age of diagnosis of diabetes and have lower insulin requirements, an overlap occurs between the two groups, therefore TNDM cannot be distinguished from PNDM based clinical feature. An early onset of diabetes mellitus is unrelated to autoimmunity in most cases, relapse of diabetes is common with TNDM, and extensive follow ups are important. In addition, molecular analysis of chromosomes 6 defects, KCNJ11 and ABCC8 genes (encoding Kir6.2 and SUR1) provide a way to identify PNDM in the infant stages. Approximately,50% of PNDM are associated with the potassium channel defects which are essential consequences when changing patients from insulin therapy to sulfonylureas.[citation needed] ### TNDM Diagnosis associated with Chromosome 6q24 Mutations[edit] The uniparental disomy of the chromosome can be used as diagnostic method provide proof by the analysis of polymorphic markers is present on Chromosome 6. Meiotic segregation of the chromosome can be distinguished by comparing allele profiles of polymorphic makers in the child to the child's parents' genome. Normally, a total uniparental disomy of the chromosome 6 is evidenced, but partial one can be identified. Therefore, genetic markers that are close to the region of interest in chromosome 6q24 can be selected. Chromosome duplication can found by that technique also. ### Medical Professionals of NDM[edit] * Physician * Endocrinologist * Geneticist Counselor ### Diagnostic Test of NDM[edit] * Fasting plasma glucose test: measures an diabetic's blood glucose after he or she has gone 8 hours without eat. This test is used to detect diabetes or pre-diabetes * Oral glucose tolerance test\- measures an individual's blood glucose after he or she have gone at least 8 hours without eating and two hours after the diabetic individual have drunk a glucose-containing beverage. This test can be used to diagnose diabetes or pre-diabetes * Random plasma glucose test-the doctor checks one's blood glucose without regard to when an individual may have eaten his or her last meal. This test, along with an evaluation of symptoms, are used to diagnose diabetes but not pre-diabetes. ### Genetic Testing of NDM[edit] * Uniparental Disomy Test: Samples from fetus or child and both parents are needed for analysis. Chromosome of interest must be specified on request form. For prenatal samples (only): if the amniotic fluid (non-confluent culture cells) are provided.[19] Amniotic fluid is added and charged separately. Also, if chorionic villus sample is provided, a genetic test will be added and charged separately. Microsatellites markers and polymerase chain reaction are used on the chromosomes of interest to test the DNA of the parent and child to identify the presence of uniparental disomy[19]. * Intrauterine Growth Restriction Apgar score is a test given after birth to test the baby's physical condition and evaluate if special medical care is needed.[20] ## Treatment[edit] In many cases, neonatal diabetes may be treated with oral sulfonylureas such as glyburide. Physicians may order genetic tests to determine whether or not transitioning from insulin to sulfonylurea drugs is appropriate for a patient. The transfer from insulin injections to oral glibenclamide therapy seems highly effective for most patients and safe. This illuminates how the molecular understanding of some monogenic form of diabetes may lead to an unexpected change of the treatment in children. This is a spectacular example of how the pharmacogenomic approach improves in a tremendous way the quality of life of the young diabetic patients. Insulin Therapy * Long Acting Insulin: (Insulin glargine)-is a hormone that works by lowering levels of blood glucose. It starts to work several hours after an injection and keeps working for 24 hours. It is used to manage blood glucose of diabetics. It is used to treat Type 1 and 2 diabetes in adults and Type 1 diabetes in kids as young as 6 years old.[21] * Short Acting Insulin (e.g. Novolin or Velosulin)-It works similarly to natural insulin and takes up to 30 minutes and lasts for about 8 hours depending on the dosage used.[22] * Intermediate Insulin: (e.g. NPH insulin)- Usually taken in combination with a short acting insulin. Intermediate acting insulin starts to activate within the first hour of injecting and enters a period of peak activity lasting for 7 hours.[23] Sulfonylureas * Sulfonylureas: This medication signals the pancreas to release insulin and help the body's cells use insulin better. This medication can lower A1C levels ( AIC is defined as a measurement of the blood glucose after previous 2–3 months) by 1-2%.[24] ## Prognosis[edit] The outcome for infants or adults with NDM have different outcomes among carriers of the disease. Among affected babies, some have PNDM while others have relapse of their diabetes and other patients may experience permanent remission. Diabetes may reoccur in the patient's childhood or adulthood. It was estimated that neonatal diabetes mellitus will be TNDM in about 50% are half of the cases.[25] During the Neonatal stage, the prognosis is determined by the severity of the disease (dehydration and acidosis), also based on how rapidly the disease is diagnosed and treated. Associated abnormalities (e.g. irregular growth in the womb or enlarged tongue) can effect a person's prognosis.[25] The long-term prognosis depends on the person's metabolic control, which effects the presence and complications of diabetes complications.[25] The prognosis can be confirmed with genetic analysis to find the genetic cause of the disease. WIth proper management, the prognosis for overall health and normal brain development is normally good. It is highly advised people living with NDM seek prognosis from their health care provider.[citation needed] ## Recent research[edit] Clinical Trials of NDM * The research article is entitled, "A Successful Transition to sulfonamides treatment in male infant with novel neonatal diabetes mellitus (NDM) caused by the ABBC8 gene mutation and 3 years follow up".[26] It is a case study on the transitioning of treatments from insulin therapy to sulfonamides therapy. NDM is not initiated by an autoimmune mechanism but mutations in KATP-sensitive channel, KCNJ11, ABCC8 and INS genes are successful targets for changing treatments from insulin to sulfonamides therapy.[26] * Introduction: Within this study a two month old male was admitted into the intensive care unit, because he was showing signs of diabetic ketoacidosis. Other symptoms include, respiratory tract infection, sporous, dehydration, reduced subcutaneous fat, Candida mucous infection. The infant's family history was negative for diseases of importance to hereditary and the eldest sibling was healthy.[26] * Experiment: The current treatment plan consist of therapy for ketoacidosis was started upon admissions into the hospital. Also, subcutaneous insulin was given (0.025-0.05 units/kg/h) and adjusted to the glycaemic profiles and the patient was converted to euglycaemic state. After 24 hours, oral intake of insulin started and treatment continued with subcutaneous short acting insulin then intermediate acting insulin plus 2 dosage of short acting insulin. A genetic analysis was conducted for NDM and mutation of KCNJ11, ABCC8 and INS genes have been given. Sequence analysis showed a rare heterogeneous missense mutation, PF577L, in the patient's exon 12 of ABCC8 gene. This confirms diagnosis of NDM caused by heterozygous mutation in the SUR1 subunit of the pancreatic ATP-sensitive potassium channel, because his parents' white blood cells did not show signs of this mutation.[26] * Results: Switching from the insulin therapy to the sulfonamides was a successful treatment. It is the current regimen used to treat NDM.[26] * Discussion/Conclusion: ABCC8 gene produces SUR1 protein subunit that interacts with pancreatic ATP-sensitive potassium channel. When the channel opens a large amount of insulin is released. Mutations that occur in ABCC8 are associated with congential hyperinsulinism and PNDM or TNDM. Patients that have mutations in their potassium channel, improved their glucose levels with sulfonylurea regimen and glibenclamide showed successful results in managing glucose levels as well. * A 2006 study showed that 90% of patients with a KCNJ11 mutation were able to successfully transition to sulfonylurea therapy.[27] ## See also[edit] * Type 1 Diabetes * Type 2 Diabetes ## References[edit] 1. ^ a b c d e f g h "Monogenic Forms of Diabetes \| NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 2017-11-05. 2. ^ Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young at National Diabetes Information Clearinghouse, a service of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NIH Publication No. 07–6141. March 2007. Copyright cite: This publication is not copyrighted. 3. ^ "Neonatal diabetes - Other types of diabetes mellitus - Diapedia, The Living Textbook of Diabetes". www.diapedia.org. Retrieved 2017-11-06. 4. ^ a b "Diabetes symptoms: When diabetes symptoms are a concern". Mayo Clinic. Retrieved 2017-11-07. 5. ^ a b c d "Dehydration & Diabetes - Symptoms, Causes and Treatment". Retrieved 2017-11-07. 6. ^ a b c d "Diabetic ketoacidosis Symptoms - Mayo Clinic". www.mayoclinic.org. Retrieved 2017-11-07. 7. ^ a b "IUGR Causes, Diagnosis, Complications, Treatment, and More". WebMD. Retrieved 2017-11-07. 8. ^ a b "Hyperglycemia (High Blood Glucose)". American Diabetes Association. Retrieved 2017-11-07. 9. ^ "Hypoglycemia (Low Blood Glucose)". American Diabetes Association. Retrieved 2017-11-07. 10. ^ a b "Monogenic Forms of Diabetes \| NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 2017-11-07. 11. ^ "Intrauterine growth restriction: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2017-11-07. 12. ^ a b c d e f g h i j k l m n o p q Naylor, Rochelle N; Greeley, Siri Atma W; Bell, Graeme I; Philipson, Louis H (2011-06-05). "Genetics and pathophysiology of neonatal diabetes mellitus". Journal of Diabetes Investigation. 2 (3): 158–169. doi:10.1111/j.2040-1124.2011.00106.x. ISSN 2040-1116. PMC 4014912. PMID 24843477. 13. ^ "Neonatal diabetes - Other types of diabetes mellitus - Diapedia, The Living Textbook of Diabetes". www.diapedia.org. Retrieved 2017-11-07. 14. ^ "Imprinted Genes". www.biology-pages.info. Retrieved 2017-11-07. 15. ^ a b Reference, Genetics Home. "16p11.2 duplication". Genetics Home Reference. Retrieved 2017-12-10. 16. ^ Das, S.; Lese, C. M.; Song, M.; Jensen, J. L.; Wells, L. A.; Barnoski, B. L.; Roseberry, J. A.; Camacho, J. M.; Ledbetter, D. H. (December 2000). "Partial Paternal Uniparental Disomy of Chromosome 6 in an Infant with Neonatal Diabetes, Macroglossia, and Craniofacial Abnormalities". American Journal of Human Genetics. 67 (6): 1586–1591. doi:10.1086/316897. ISSN 0002-9297. PMC 1287936. PMID 11038325. 17. ^ a b c Temple, Isabel Karen; Mackay, Deborah J.G.; Docherty, Louise Esther (1993). Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E.; Bean, Lora J.H.; Mefford, Heather C.; Stephens, Karen; Amemiya, Anne; Ledbetter, Nikki (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID 20301706. 18. ^ "What is Homozygous? - Definition, Traits & Example - Video & Lesson Transcript \| Study.com". study.com. Retrieved 2017-11-07. 19. ^ a b "UNIPD - Clinical: Uniparental Disomy". www.mayomedicallaboratories.com. Retrieved 2017-11-07. 20. ^ Jovanovic, L.; Ilic, S.; Pettitt, D. J.; Hugo, K.; Gutierrez, M.; Bowsher, R. R.; Bastyr, E. J. (1999-09-01). "Metabolic and immunologic effects of insulin lispro in gestational diabetes". Diabetes Care. 22 (9): 1422–1427. doi:10.2337/diacare.22.9.1422. ISSN 0149-5992. PMID 10480503. 21. ^ "Insulin glargine Uses, Side Effects & Warnings - Drugs.com". Drugs.com. Retrieved 2017-12-13. 22. ^ "Short Acting Insulin - Regular, Neutral Insulin". Retrieved 2017-12-13. 23. ^ "Intermediate Acting Insulin - Isophane, NPH Insulins". Retrieved 2017-12-13. 24. ^ "Diabetes Medicine: Sulfonylureas - Diabetes Self-Management". Diabetes Self-Management. Retrieved 2017-12-13. 25. ^ a b c "Permanent neonatal diabetes mellitus \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-12-13. 26. ^ a b c d e Katanic, Dragan; Vorgučin, Ivana; Hattersley, Andrew; Ellard, Sian; Houghton, Jayne A. L.; Obreht, Dragana; Pogančev, Marija Knežević; Vlaški, Jovan; Pavkov, Danijela (2017-07-01). "A successful transition to sulfonylurea treatment in male infant with neonatal diabetes caused by the novel abcc8 gene mutation and three years follow-up". Diabetes Research and Clinical Practice. 129: 59–61. doi:10.1016/j.diabres.2017.04.021. ISSN 0168-8227. PMC 5612402. PMID 28511139. 27. ^ Pearson ER; Flechtner I; Njolstad PR; et al. (2006). "Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations". New England Journal of Medicine. 355 (5): 467–477. doi:10.1056/nejmoa061759. PMID 16885550. * Yorifuji, T; Kurokawa, K; Mamada, M; Imai, T; Kawai, M; Nishi, Y; Shishido, S; Hasegawa, Y; Nakahata, T (Jun 2004). "Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: Phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1beta gene due to germline mosaicism". The Journal of Clinical Endocrinology and Metabolism. 89 (6): 2905–8. doi:10.1210/jc.2003-031828. PMID 15181075. * Edghill, EL; Bingham, C; Slingerland, AS; Minton, JA; Noordam, C; Ellard, S; Hattersley, AT (Dec 2006). "Hepatocyte nuclear factor-1 beta mutations cause neonatal diabetes and intrauterine growth retardation: support for a critical role of HNF-1beta in human pancreatic development". Diabetic Medicine. 23 (12): 1301–6. doi:10.1111/j.1464-5491.2006.01999.x. PMID 17116179. ## External links[edit] Classification D * ICD-10: P70.2 External resources * Orphanet: 224 * v * t * e Diabetes Types * Type 1 * Type 2 * LADA * Gestational diabetes * Diabetes and pregnancy * Prediabetes * Impaired fasting glucose * Impaired glucose tolerance * Insulin resistance * KPD * MODY * Neonatal * Transient * Permanent * Type 3c (pancreatogenic) * Type 3 Blood tests * Blood sugar level * Glycosylated hemoglobin * Glucose tolerance test * Postprandial glucose test * Fructosamine * Glucose test * C-peptide * Noninvasive glucose monitor * Insulin tolerance test Management * Diabetic diet * Anti-diabetic drugs * Insulin therapy * intensive * conventional * pulsatile * Cure * Embryonic stem cells * Artificial pancreas * Other * Gastric bypass surgery Complications * Diabetic comas * Hypoglycemia * Ketoacidosis * Hyperosmolar hyperglycemic state * Diabetic foot * ulcer * Neuropathic arthropathy * Organs in diabetes * Blood vessels * Muscle * Kidney * Nerves * Retina * Heart * Diabetic skin disease * Diabetic dermopathy * Diabetic bulla * Diabetic cheiroarthropathy * Neuropathic ulcer * Hyperglycemia * Hypoglycemia Other * Glossary of diabetes * History of diabetes * Notable people with type 1 diabetes [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Neonatal diabetes	c0158981	6,139	wikipedia	https://en.wikipedia.org/wiki/Neonatal_diabetes	2021-01-18T18:34:32	{"umls": ["C0158981"], "orphanet": ["224"], "wikidata": ["Q2898645"]}
Antibiotic synergy is one of three responses possible when two or more antibiotics are used simultaneously to treat an infection. In the synergistic response, the applied antibiotics work together to produce an effect more potent than if each antibiotic were applied singly.[1] Compare to the additive effect, where the potency of an antibiotic combination is roughly equal to the combined potencies of each antibiotic singly, and antagonistic effect, where the potency of the combination is less than the combined potencies of each antibiotic.[1] ## Contents * 1 Clinical interest * 2 Desirability * 3 Current research directions * 4 References ## Clinical interest[edit] Clinical interest in synergism dates back to the early 1950s when practitioners noted that patients with enterococcal endocarditis experienced a high relapse rate when penicillin G alone was used for treatment and a demonstrably lower relapse rate when streptomycin was combined with penicillin G to combat the infection.[2] Since that time the research community has conducted numerous studies regarding the effects and possibilities of antibiotic combinations. Today, combination therapy is recognized as providing a broad spectrum of antibiotic coverage, effectively fighting polymicrobial infections, minimizing selection for antibiotic resistant strains, lowering dose toxicity where applicable, and in some cases providing synergistic activity.[2][3] ## Desirability[edit] Antibiotic synergy is desirable in a clinic sense for several reasons. At the patient level, the boosted antimicrobial potency provided by synergy allows the body to more rapidly clear infections, resulting in shorter courses of antibiotic therapy.[3] Shorter courses of therapy in turn reduce the effects of dose-related toxicity, if applicable.[3] Additionally, synergy aids in total bacterial eradication, more completely removing an infection than would be possible without synergy.[2] At a higher level, synergistic effects are useful for combating resistant bacterial strains through increased potency and for stalling the spread of bacterial resistance through the total eradication of infections, preventing the evolutionary selection of resistant cells and strains.[2][3] ## Current research directions[edit] Further information: Antibiotic properties of nanoparticles Current research on antibiotic synergy and potential therapies is moving in three primary directions. Some research is devoted to finding combinations of extant antibiotics which when combined exhibit synergy. A classic example of this effect is the interaction between β-lactams, which damage the bacteria cell membrane, and aminoglycosides, which inhibit protein synthesis.[1] The damage dealt to the cell wall by β-lactams allows more aminoglycoside molecules to be taken up into the cell than would otherwise be possible, enhancing cell damage.[1] In some cases, antibacterial combinations restore potency to ineffective drugs.[4] Other research has been devoted to finding antibiotic resistance breakers (ARB's) which enhance an antibiotic's potency. This effect is mediated through direct antibacterial activity of the ARB, targeting and destroying mechanisms of bacterial resistance thereby allowing the antibiotic to function properly, interacting with the host to trigger defensive mechanisms, or some combination thereof.[4] The third direction of research involves combining traditional antibiotics with unconventional bactericides such as silver nano particles. Silver nano particles have strong non-specific interactions with bacterial cells that result in cell wall deformation and the generation of damaging reactive oxygen species (ROS) in the presence of cellular components. These effects are thought to weaken bacterial cells, making them more susceptible to assault from conventional antibiotics.[5][6][7][8][9] ## References[edit] 1. ^ a b c d Kohanski, Michael A.; Dwyer, Daniel J.; Collins, James J. (2010). "How antibiotics kill bacteria: from targets to networks". Nature Reviews Microbiology. 8 (6): 423–435. doi:10.1038/nrmicro2333. PMC 2896384. PMID 20440275. 2. ^ a b c d Acar, Jacques F. (2000-11-01). "Antibiotic Synergy and Antagonism". Medical Clinics of North America. 84 (6): 1391–1406. doi:10.1016/S0025-7125(05)70294-7. PMID 11155849. 3. ^ a b c d Leekha, Surbhi; Terrell, Christine L.; Edson, Randall S. (2011). "General Principles of Antimicrobial Therapy". Mayo Clinic Proceedings. 86 (2): 156–167. doi:10.4065/mcp.2010.0639. PMC 3031442. PMID 21282489. 4. ^ a b Brown, David (2015). "Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?". Nature Reviews Drug Discovery. 14 (12): 821–832. doi:10.1038/nrd4675. PMID 26493767. S2CID 22378623. 5. ^ Panáček, Aleš; Smékalová, Monika; Večeřová, Renata; Bogdanová, Kateřina; Röderová, Magdaléna; Kolář, Milan; Kilianová, Martina; Hradilová, Šárka; Froning, Jens P. (2016-06-01). "Silver nanoparticles strongly enhance and restore bactericidal activity of inactive antibiotics against multiresistant Enterobacteriaceae". Colloids and Surfaces B: Biointerfaces. 142: 392–399. doi:10.1016/j.colsurfb.2016.03.007. PMID 26970828. 6. ^ Wang, Yao; Ding, Xiali; Chen, Yuan; Guo, Mingquan; Zhang, Yan; Guo, Xiaokui; Gu, Hongchen (2016). "Antibiotic-loaded, silver core-embedded mesoporous silica nanovehicles as a synergistic antibacterial agent for the treatment of drug-resistant infections". Biomaterials. 101: 207–216. doi:10.1016/j.biomaterials.2016.06.004. PMID 27294538. 7. ^ Zheng, Kaiyuan; Setyawati, Magdiel I.; Lim, Tze-Peng; Leong, David Tai; Xie, Jianping (2016-08-23). "Antimicrobial Cluster Bombs: Silver Nanoclusters Packed with Daptomycin". ACS Nano. 10 (8): 7934–7942. doi:10.1021/acsnano.6b03862. ISSN 1936-0851. PMID 27494437. 8. ^ Panáček, Aleš; Smékalová, Monika; Kilianová, Martina; Prucek, Robert; Bogdanová, Kateřina; Večeřová, Renata; Kolář, Milan; Havrdová, Markéta; Płaza, Grażyna Anna (2015-12-28). "Strong and Nonspecific Synergistic Antibacterial Efficiency of Antibiotics Combined with Silver Nanoparticles at Very Low Concentrations Showing No Cytotoxic Effect". Molecules. 21 (1): 26. doi:10.3390/molecules21010026. PMC 6273824. PMID 26729075. 9. ^ Deng, Hua; McShan, Danielle; Zhang, Ying; Sinha, Sudarson S.; Arslan, Zikri; Ray, Paresh C.; Yu, Hongtao (2016-08-16). "Mechanistic Study of the Synergistic Antibacterial Activity of Combined Silver Nanoparticles and Common Antibiotics". Environmental Science & Technology. 50 (16): 8840–8848. doi:10.1021/acs.est.6b00998. ISSN 0013-936X. PMC 5300770. PMID 27390928. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Antibiotic synergy	None	6,140	wikipedia	https://en.wikipedia.org/wiki/Antibiotic_synergy	2021-01-18T19:04:34	{"wikidata": ["Q19903313"]}
15q14 microdeletion syndrome is a recently described syndrome characterized by developmental delay, short stature and facial dysmorphism. ## Epidemiology It has been described in 4 patients so far. ## Clinical description Dysmorphic features include bitemporal narrowing, smooth philtrum, pointed chin and dysmorphic ears. All reported patients had a cleft palate, whereas congenital heart defects or epilepsy are observed in patients with large deletions. ## Etiology Deletions are located within chromosome band 15q14, distal to the Prader-Willi/Angelman region. They were characterized by comparative genomic hybridization (CGH) microarray and fluorescence in situ hybridization (FISH). They have a variable size with the smallest deletion being 1.6 Mb in length. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	15q14 microdeletion syndrome	c4225666	6,141	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261190	2021-01-23T19:10:26	{"omim": ["616898"], "icd-10": ["Q93.5"], "synonyms": ["Del(15)(q14)", "Monosomy 15q14"]}
Spinocerebellar ataxia type 14 (SCA14) is a rare mild subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive ataxia, dysarthria and nystagmus. ## Epidemiology The disease has been reported in more than twenty families from Europe, the United States, and Australia. ## Clinical description Onset is usually in early adulthood while symptomatic disease onset may be from 10 to 70 years (mean = 33.9 years). In addition to cerebellar signs, hyperreflexia and decreased vibration sense are frequently observed. Some patients have cognitive impairment, parkinsonism characterized by rigidity, as well as focal dystonia, axial myoclonus, facial myokymia, choreic movement of hands and epilepsy. ## Etiology SCA14 is caused by missense mutations in the PRKCG gene (19q13.4) encoding protein kinase C gamma (PKC-gamma). ## Prognosis Prognosis is good. Some patients need supportive devices such as a cane or wheelchair for gait impairment. However, several affected patients have lived beyond 80 years of age. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Spinocerebellar ataxia type 14	c1854369	6,142	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98763	2021-01-23T17:31:49	{"gard": ["9867"], "mesh": ["C537196"], "omim": ["605361"], "umls": ["C1854369"], "icd-10": ["G11.2"], "synonyms": ["SCA14"]}
In human milk, a fourth PGM locus is expressed. The products of 4 alleles are demonstrable by electrophoresis (Ibarra and Cantu, 1981). Nonlactating breast tissue does not show PGM4 activity. The frequency of each of the 4 alleles was estimated to be as follows: PGM4(1) = 0.346; PGM4(2) = 0.475; PGM4(3) = 0.114; PGM4(4) = 0.065. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	PHOSPHOGLUCOMUTASE 4	c1868356	6,143	omim	https://www.omim.org/entry/172110	2019-09-22T16:36:17	{"omim": ["172110"], "synonyms": ["Alternative titles", "PGM4", "MILK PGM"]}
Pachydermoperiostosis (PDP) is a form of primary hypertrophic osteoarthropathy (see this term), a rare hereditary disorder, and is characterized by digital clubbing, pachydermia and subperiosteal new bone formation associated with pain, polyarthritis, cutis verticis gyrata, seborrhea and hyperhidrosis. Three forms have been described: a complete form with pachydermia and periostitis, an incomplete form with evidence of bone abnormalities but lacking pachydermia, and a forme frusta with prominent pachydermia and minimal-to-absent skeletal changes. ## Epidemiology The prevalence is unknown. PDP occurs predominantly in men (male to female ratio: 7:1) and the disease is more severe in men than in women. ## Clinical description PDP typically begins during childhood or adolescence and may stabilize after 5-20 years of progression, or progress constantly. However, in the neonatal period, late closure of the fontanels and a patent arterial duct (see this term) may be observed. PDP presents with digital clubbing and dermatological (pachydermia, thickening and furrowing of the facial features, cutis verticis gyrata, seborrhea, edema, hyperhidrosis) and rheumatological symptoms (joint effusion, arthritis, acro-osteolysis, periosteal ossification). Patients may develop severe kyphosis, restricted motion and neurological manifestations. PDP may also be associated with congenital heart disease, particularly patent arterial duct. ## Etiology Mutations in the HPGD gene (4q33-q34) have been identified. The gene encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the main enzyme of prostaglandin degradation. Patients with homozygous mutations have chronically elevated prostaglandin E2 levels. ## Diagnostic methods Diagnosis is based on clinical signs, X-ray exam, magnetic resonance imaging (MRI) and/or radionucleotide bone imaging showing typical bone abnormalities, such as diaphyseal periostosis and acro-osteolysis. ## Differential diagnosis Differential diagnoses include cranio-osteoarthropathy (see this term), secondary hypertrophic osteoarthropathy, chronic recurrent multifocal osteomyelitis, SAPHO and Camurati-Engelman disease (see these terms), thyroid acropachy and syphilitic periostosis. ## Genetic counseling PDP is inherited as an autosomal recessive trait; however, heterozygous carriers can have a mild phenotype. Genetic counseling should be offered to patients and their families. ## Management and treatment Rheumatologic symptoms can be improved by nonsteroidal anti-inflammatory drugs, corticosteroids or colchicine. Clinical improvement of the dermatological symptoms is achieved by retinoids. Plastic surgery may be helpful for facial involvement. Surgical reduction of finger clubbing has been performed with success. ## Prognosis PDP may progress constantly, leaving patients with chronic debilitating complications, such as clubbing and arthritis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Pachydermoperiostosis	c2674695	6,144	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2796	2021-01-23T18:10:42	{"gard": ["7299"], "mesh": ["D010004"], "omim": ["167100", "259100", "614441"], "icd-10": ["M89.4"], "synonyms": ["PDP", "Touraine-Solente-Gole syndrome"]}
Epidermoid brain cysts (also called intracranial epidermoid cysts or tumors) usually form in the very early stages of the development of a baby (embryo). The cysts develop when cells that are meant to become skin, hair, and nails (epithelial cells) are trapped among the cells that form the brain. Less commonly, the cysts may develop later in life (acquired) when an injury or surgery causes epithelial cells to be trapped in brain tissue. An epidermoid brain cyst has a thin outer layer of epithelial cells surrounding fluid, keratin, and cholesterol. Although epidermoid brain cysts are usually benign (not cancerous) and slow growing, the cysts may grow around and encase cranial nerves and arteries. Thus, epidermoid brain cysts are most often diagnosed in middle-aged adults when the cysts have grown large enough to cause symptoms. Symptoms may include hearing loss, ringing in the ears (tinnitus), headaches, involuntary twitching of the face, or chronic, severe face pain (trigeminal neuralgia). Rarely, an epidermoid cyst may leak into surrounding tissue and cause the lining of the brain (meninges) to become inflamed (aseptic meningitis, meaning the meningitis is not caused by a virus or bacteria). Epidermoid brain cysts may be diagnosed by MRI and CT scans. Treatment usually involves surgery. Complete removal may be difficult if the cysts have surrounded or are very close to cranial nerves, arteries, or brain tissue. Regrowth of the cysts may occur, but in most cases, due to slow growth, symptoms may not return for years. If aseptic meningitis develops due to leakage of the cyst, steroids may be used to control the inflammation. There have been some reports of existing cysts or remnants of cysts left behind after surgery developing into cancer (since the cyst is made of skin cells, the cancer is usually a form of skin cancer, most commonly squamous cell carcinoma). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Epidermoid brain cyst	c0854911	6,145	gard	https://rarediseases.info.nih.gov/diseases/13044/epidermoid-brain-cyst	2021-01-18T18:00:41	{"synonyms": ["Central nervous system epidermoid cyst", "Intracranial epidermoid cyst", "Epidermoid brain tumor"]}
Chorangiosis Micrograph of a chorangiosis. H&E stain. SpecialtyPathology Chorangiosis is a placental pathology characterized by an abundance of blood vessels within the chorionic villi. ## Contents * 1 Associations * 2 Diagnosis * 3 See also * 4 Additional images * 5 References * 6 External links ## Associations[edit] It is associated with gestational diabetes,[1] smoking and high altitude. ## Diagnosis[edit] It is diagnosed by a microscopic examination of the placenta. Commonly used criteria from Altshuler[2][3] are: "a minimum of 10 villi, each with 10 or more vascular channels, in 10 or more areas of 3 or more random, non-infarcted placental areas when using a ×10 ocular." The Altshuler criteria are not theoretically rigorous, as they do not define the area. Normal villi have up to five vascular channels.[3] ## See also[edit] * Chorangioma ## Additional images[edit] * Intermed. mag. * Very high mag. ## References[edit] 1. ^ Daskalakis, G.; Marinopoulos, S.; Krielesi, V.; Papapanagiotou, A.; Papantoniou, N.; Mesogitis, S.; Antsaklis, A. (2008). "Placental pathology in women with gestational diabetes". Acta Obstet Gynecol Scand. 87 (4): 403–7. doi:10.1080/00016340801908783. PMID 18382864. S2CID 43058233. 2. ^ Altshuler, G. (Jan 1984). "Chorangiosis. An important placental sign of neonatal morbidity and mortality". Arch Pathol Lab Med. 108 (1): 71–4. PMID 6546343. 3. ^ a b De La Ossa, MM.; Cabello-Inchausti, B.; Robinson, MJ. (Sep 2001). "Placental chorangiosis". Arch Pathol Lab Med. 125 (9): 1258. doi:10.1043/0003-9985(2001)125<1258:PC>2.0.CO;2 (inactive 2021-01-18). PMID 11520290.CS1 maint: DOI inactive as of January 2021 (link) ## External links[edit] Classification D [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Chorangiosis	c0546474	6,146	wikipedia	https://en.wikipedia.org/wiki/Chorangiosis	2021-01-18T18:39:46	{"wikidata": ["Q5104958"]}
A number sign (#) is used with this entry because of evidence that microhydranencephaly (MHAC) is caused by homozygous mutation in the NDE1 gene (609449) on chromosome 16p13. One such family has been reported. Mutation in the NDE1 gene can also cause lissencephaly-4 (LIS4; 614019). Description Microhydranencephaly (MHAC) is a severe neurodevelopmental defect characterized by extreme microcephaly, profound motor and mental retardation, spasticity, and incomplete cerebral formation. Radiologic studies show gross dilation of the ventricles resulting from the absence of cerebral hemispheres or severe delay in their development, as well as hypoplasia of the corpus callosum, cerebellum, and brainstem (summary by Guven et al., 2012). Clinical Features Kavaslar et al. (2000) reported a large consanguineous Anatolian (Turkish) family with children who had the unusual association of microcephaly and hydranencephaly. In addition, the affected children had severe mental and motor retardation, very small body size, and very small occipitofrontal circumference (OFC). The youngest patient, 4.5 years of age at the time of study, had a height corresponding to a sex mean of 7 months, weight to 1 month, and OFC to prenatal. Guven et al. (2012) reported follow-up of 2 surviving affected female cousins from the family reported by Kavaslar et al. (2000). The patients were 17 and 19 years of age, respectively. Both had thin bones, prominent nasal bridges, poor overall growth, and severe microcephaly (-11.1 and -7.8 SD, respectively). They had severe mental and motor retardation, could sit with support, did not have real eye contact, and had poor social interaction. Neurologic examination showed atrophic optic fundi, poor head control, automutilation of hands, tetraparesis, contractures of the knees, and generalized muscle atrophy. Brain MRI showed residues of cerebral cortical regions, but frontal lobes and the corpus callosum could not be distinguished. The cerebellum, vermis, and brainstem were hypoplastic. Pachygyria was also apparent in 1 patient. Both had notable scalp rugae. Alexander et al. (1995) reported 2 female sibs with fetal brain disruption sequence. Clinical findings included large size at birth with a disproportionately small head circumference and scalp rugae. The degree of microcephaly became more marked with time. Cranial CT scan in both infants revealed gross dilation of the ventricles, almost complete absence of the cerebral hemispheres with a well-formed falx, and a small cerebellum. Elevated semiquantitative mucopolysaccharide levels were consistently obtained from both children, and high resolution electrophoresis revealed an unidentified metabolite and a pattern not consistent with any known mucopolysaccharidosis. Alexander et al. (1995) proposed that accumulation of a neurotoxic metabolite might be responsible for the disease phenotype. Schram et al. (2004) reported 2 sibships with fetal brain degeneration resembling fetal brain disruption sequence: 2 brothers in a Hindu family from Suriname, and a Dutch brother and sister. All of the children had low birth weight, microcephaly, overlapping sutures, and scalp rugae. CT scans of their brains showed severely underdeveloped cerebral hemispheres surrounded by a large amount of cerebrospinal fluid. The authors noted that true hydranencephaly was not present in these cases, but questioned whether a strict delineation between hydranencephaly and fetal brain disruption sequence was justified. Schram et al. (2004) also commented that in cases of sib recurrence, the term 'fetal brain disruption sequence' should be avoided since a disruption sequence indicates an exogenous, sporadic cause of the disorder. Inheritance The transmission pattern of MHAC in the family reported by Kavaslar et al. (2000) was consistent with autosomal recessive inheritance. Mapping By use of homozygosity mapping (Lander and Botstein, 1987) in a single large consanguineous Anatolian (Turkish) family segregating for microhydranencephaly, Kavaslar et al. (2000) showed genetic linkage between the disorder and markers on chromosome 16p13.3-p12.1. Molecular Genetics In 2 cousins, born of consanguineous Turkish parents, with microhydranencephaly (Kavaslar et al., 2000), Guven et al. (2012) identified a homozygous intragenic deletion in the NDE1 gene (609449.0004). The mutation was predicted to result in a completely null allele, but functional studies were not performed. Guven et al. (2012) noted that the MHAC phenotype is more severe than that observed in patients with LIS4 (614019), thus expanding the spectrum of clinical features associated with NDE1 mutations. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly, severe (-5+ SD), progressive Face \- Sloping forehead Ears \- Large ears Eyes \- Exophthalmia \- Atrophic optic fundi Nose \- Prominent nasal bridge SKELETAL \- Multiple joint contractures Skull \- Scalp rugae Feet \- Equinovarus MUSCLE, SOFT TISSUES \- Muscle atrophy NEUROLOGIC Central Nervous System \- Hydranencephaly \- Enlarged ventricles \- Psychomotor retardation, profound \- Spastic quadriplegia \- Hyperreflexia \- Myoclonic seizures \- Athetosis \- Agenesis of corpus callosum \- Hypoplastic cerebellum \- Hypoplastic brainstem \- Pachygyria \- Poor delineation of cerebral cortical regions \- Supratentorial structures unformed or regressed Behavioral Psychiatric Manifestations \- Self-mutilation MOLECULAR BASIS \- Caused by mutation in the homolog of the A. Nidulans nude 1 gene (NDE1, 609449.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	MICROHYDRANENCEPHALY	c1857977	6,147	omim	https://www.omim.org/entry/605013	2019-09-22T16:11:47	{"mesh": ["C537555"], "omim": ["605013"], "orphanet": ["443162"], "synonyms": ["MHAC", "Alternative titles", "HYDRANENCEPHALY AND MICROCEPHALY"]}
## Clinical Features Kovacs et al. (1997) described 2 consecutive mid-trimester fetuses of different sexes with identical anomalies of the upper limbs and the kidneys in association with severe dilatation of the lateral cerebral ventricles. On the parents' decision, both pregnancies were terminated. In the first fetus, an ectopic horseshoe kidney fused at the upper poles was found in the pelvis. In the second fetus, no kidney was found on the right side; a normal kidney on the left side had two ureters, one of which coursed to the right, crossed the midline at the level of the upper sacrum, and reached the bladder at the usual site on the right. Microscopy showed that a significant proportion of the glomeruli had a dilated Bowman capsule, and there were also tubuli with cystic dilatation in the cortex and the medulla. There was absence of the left umbilical artery. In both fetuses, autopsies confirmed a marked ventriculomegaly. Both fetuses had anomalies of the upper limbs: the first had forearms that were short and bent anteriorly with only 4 fingers on each hand, and absence of the radius and thumb bilaterally by x-ray. The second had curved forearms with flexing of the hands medially in an acute angle. Radiographs showed bilateral absence of the radius and thumb. See also 219730 for a disorder characterized by ventriculomegaly and cystic kidneys without limb anomalies. Inheritance Kovacs et al. (1997) postulated an autosomal recessive mode in inheritance in the family reported by them. INHERITANCE \- Autosomal recessive GENITOURINARY Kidneys \- Horseshoe kidney \- Ectopic kidney \- Absent kidney \- Dilated Bowman capsules \- Cystic tubular dilatation in the cortex and medulla Ureters \- Double ureter SKELETAL Limbs \- Short, curved forearms \- Absence of the radii Hands \- Medial flexion of the hands \- Absence of the thumbs NEUROLOGIC Central Nervous System \- Hydrocephalus \- Ventriculomegaly \- Dilated ventricles MISCELLANEOUS \- One family with 2 affected fetuses has been reported (as of August 2011) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	VENTRICULOMEGALY WITH DEFECTS OF THE RADIUS AND KIDNEY	c1865780	6,148	omim	https://www.omim.org/entry/602200	2019-09-22T16:13:53	{"mesh": ["C566565"], "omim": ["602200"]}
Abortion in Belgium was fully legalised on 4 April 1990.[1] Abortion is legal until 12 weeks after conception (14 weeks after the last menstrual period)[2][3] it is required for women to receive counselling at least six days prior to the abortion and to check in with her doctor to monitor her health in the weeks after the procedure.[3] Later abortions are permitted if there is a risk to the woman's life or the fetus shows risk of birth defects.[3] As of 2009[update], the abortion rate was 9.2 abortions per 1000 women aged 15–44 years.[4] ## 1990 liberalisation of abortion laws[edit] Prior to 1990, due to the influences of the Catholic Church, Belgium remained one of the few European countries where abortion was illegal. However, abortions were unofficially permitted (and even reimbursed by the mutualities) as long as they were registered as "curettage". It was estimated that 20,000 abortions were performed each year (in comparison to 100,000 births).[5] When the law liberalising abortion was enacted, it was controversial to many Belgians.[6] A bill to partially liberalise abortion was first submitted by Senators Lucienne Herman-Michielsens and Roger Lallemand in early-1990, and despite the opposition of the ruling Christian People's Party, a coalition of the Socialist and Liberal parties in the federal lower house passed a law to partially liberalise abortion in Belgium. The Belgian bishops appealed to the population at large with a public statement that expounded their doctrinal and pastoral opposition to the law. They warned Belgian Catholics that anyone who co-operated "effectively and directly" in the procurement of abortions was "excluding themselves from the ecclesiastical community." Motivated by the strong stance of the Belgian bishops and the fact that he and his wife Queen Fabiola hadn't been able to get children themselves, King Baudouin notified the Prime Minister on 30 March that he could not sign the law without violating his conscience as a Catholic.[7] Since the legislation would not have the force of law without the king's signature, his refusal to sign threatened to precipitate a constitutional crisis.[8] However, the problem was resolved by an agreement between the king and Prime Minister Martens, by which the Belgian government used a constitutional mechanism which declared the king unable to govern, assumed his authority and enacted the law, after which the Federal Parliament then voted to reinstate the king the next day.[5][9][10][11][12][13] The Vatican described the king's action as a "noble and courageous choice" dictated by a "very strong moral conscience."[14] Others have suggested that Baudouin's action was "little more than a gesture", since he was reinstated as king just 44 hours after he was removed from power.[7] ## References[edit] 1. ^ Belgian King, Unable to Sign Abortion Law, Takes Day Off 2. ^ "Archived copy". Archived from the original on 2017-06-29. Retrieved 2016-01-20.CS1 maint: archived copy as title (link) 3. ^ a b c "Termination of Pregnancy/Abortion in Belgium". Angloinfo Brussels. Angloinfo. Archived from the original on 2016-07-01. Retrieved 2016-06-08. 4. ^ "World Abortion Policies 2013". United Nations. 2013. Retrieved 3 March 2014. 5. ^ a b Belien, Paul (2005). A Throne in Brussels: Britain, the Saxe-Coburgs and the Belgianisation of Europe. Devon: Imprint Academic. pp. 292–293. ISBN 1-84540-033-X. 6. ^ Belgium Eases Its Abortion Law 7. ^ a b Hubert, Vivian; Green, Howard (1 March 2000). New History of Christianity. Continuum International Publishing Group. p. 389. ISBN 978-0-8264-1227-0. Retrieved 7 January 2012. 8. ^ Barker, Eileen (15 April 2010). The Centrality of Religion in Social Life. Ashgate Publishing, Ltd. p. 76. ISBN 978-1-4094-0343-2. Retrieved 7 January 2012. 9. ^ Wilsford, David (1995). Political Leaders of Contemporary Western Europe. Greenwood Press. p. 30. ISBN 978-0-313-28623-0. 10. ^ Roberts, Geoffrey K.; Hogwood, Patricia (2003). West European Politics. Manchester University Press. p. 84. ISBN 978-0-7190-5421-1. 11. ^ Witte, Els; Craeybeckx, Jan; Meynen, Alain (2010). Political History of Belgium. VUB University Press. p. 266. ISBN 978-90-5487-517-8. 12. ^ Encyclopedia of World Constitutions. Facts on File. 2006. p. 92. ISBN 978-0-8160-6078-8. 13. ^ Sandro Magister, "Obama's Pick for Vice President Is Catholic. But the Bishops Deny Him Communion" 14. ^ "Pope Prays at Tomb of Abortion Foe". Associated Press. 4 June 1995. * 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 * 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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 [mRNA]: messenger RNA *[kDa]: kilodalton	Abortion in Belgium	None	6,149	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Belgium	2021-01-18T18:37:26	{"wikidata": ["Q4668443"]}
Typical stance of affected lambs, with arched back Nutritional Muscular Dystrophy (Nutritional Myopathy or White Muscle Disease) is a disease caused by a deficiency of selenium and vitamin E in dietary intake.[1] Soils that contains low levels of selenium produce forages and grains that are deficient in selenium. Similarly, if the forage is of low quality or is not stored properly it may be deficient in vitamin E.[1] If an animal consumes this type of diet without additional supplementation they become susceptible to this disease.[1] This condition often affects young ruminants, such as calves and lambs.[2] Selenium and vitamin E are antioxidants therefore, deficiencies of these nutrients leads to oxidative damage to cells within the body. The muscle cells are the most vulnerable to damage in livestock species.[3] ## Contents * 1 Clinical symptoms * 2 Treatment & Prevention * 3 Horses * 4 Sheep (Stiff Lamb Disease) * 5 Cattle * 6 Gallery * 7 External links * 8 References ## Clinical symptoms[edit] The oxidative damage causes degeneration of muscles, in particular those within the skeletal and cardiac systems.[4] If the cardiac muscles are impaired the animal may exhibit signs of respiratory distress.[1] While deterioration of skeletal muscles results in stiffness, weakness, and recumbency.[5] ## Treatment & Prevention[edit] If the diet is deficient supplement with selenium and/or vitamin E. Injections can be given to treat the condition or as a preventative measure.[1] ## Horses[edit] In equids, it is most common in the first twelve months of life. Neonatal foals born to dams that are selenium-deficient often develop the condition. There are two forms: peracute, and subacute. The peracute form is characterized by recumbency, tachypnea, dyspnea, myalgia, cardiac arrhythmias, and rapid death.[6] The subacute form causes weakness, fasciculations, cramping, and stiffness of muscles, which can lead to recumbency, as well as a stilted gait, dysphagia, ptyalism, and a weak suckle.[6] It may be treated with selenium supplementation, but there is a 30–45% mortality rate.[7] Other sequelae include aspiration pneumonia, failure of passive transfer, and stunting of growth. Clinical laboratory changes include evidence of rhabdomyolysis (elevated CK and AST, myoglobinuria) and low blood selenium levels. On necropsy, muscles are pale with areas of necrosis and edema evidenced as white streaks.[6] Horses may also develop a more chronic delayed form of the disease called Neuroaxonal Dystrophy (NAD) or Equine Degenerative Myeloencephalopathy (EDM).[8] EDM is a more severe form of NAD. The diseases are characterized by the damage and degeneration of the central nervous system. This disease process is heritable in certain breed bloodlines, such as Quarter Horse, Appaloosa, Morgan, Lusitano, and Arabian. It is hypothesized that horses develop this disease continuum because they have a defect in the uptake or utilization of Vitamin E and therefore have a higher baseline requirement.[9] ## Sheep (Stiff Lamb Disease)[edit] In lambs, the disease typically occurs between 3 and 8 weeks of age, but may occur in older lambs as well.[10] Progressive paralysis occurs, which is evident through the following symptoms: arched back, difficulty moving and an open shouldered stance. Cardiac failure may occur in two forms: sudden heart failure or gradual cardiac failure characterized by lung anemia that causes death due to suffocation.[10] Ewes may be given an injection of vitamin E/selenium prior to lambing to prevent deficiencies in lambs. In areas, such as Ontario, where lambs are highly susceptible to the condition, management practices should include vitamin E/selenium injections.[11] ## Cattle[edit] In dairy breeds, the disease may occur in calves between birth and 4 months of age. [12] In rustic breeds or beef cattle, heifers and young steers up to 12 months of age can be affected. In calves, muscles in upper portion of the front legs and the hind legs are degraded, causing the animal to have a stiff gait and it may have difficulty standing. The disease may also present in the form of respiratory distress.[13] ## Gallery[edit] * in a heifer * same animal * in a lamb * other lamb ## External links[edit] Wikimedia Commons has media related to White muscle disease. * Description of the disease in Merck Veterinary Manual ## References[edit] 1. ^ a b c d e "Nutritional Myopathies in Ruminants and Pigs - Musculoskeletal System - Veterinary Manual". Veterinary Manual. Retrieved 2017-04-05. 2. ^ Hansen, Hathaway & Oldfield. 1993. White Muscle Disease and Other Selenium-Responsive Diseases of Livestock. Retrieved from http://www.multiminusa.com/sites/www.multiminusa.com/files/pdfs/se_responsive_diseases.pdf 3. ^ "White Muscle Disease \| Veterinarians Esterhazy, Saskatchewan \| Twin Valley Veterinary Health Services". Retrieved 2017-04-06. 4. ^ "NMSU: Sheep Production & Management - White Muscle Disease-Sheep Health". aces.nmsu.edu. Retrieved 2017-04-06. 5. ^ Abutarbush, Sameeh M.; Radostits, Otto M. (2017-04-06). "Congenital nutritional muscular dystrophy in a beef calf". The Canadian Veterinary Journal. 44 (9): 738–739. ISSN 0008-5286. PMC 340271. PMID 14524629. 6. ^ a b c Aleman, M. (2008). "A review of equine muscle disorders". Neuromuscular Disorders. 18 (4): 277–287. doi:10.1016/j.nmd.2008.01.001. PMID 18395447. 7. ^ Löfstedt, J. (April 1997). "White muscle disease of foals". Vet Clin North Am Equine Pract. 13 (1): 169–85. doi:10.1016/S0749-0739(17)30262-6. PMID 9106350. 8. ^ "Degenerative Diseases of the Spinal Column and Cord - Nervous System". Merck Veterinary Manual. Retrieved 2019-09-05. 9. ^ Burns, Erin N; Finno, Carrie J (2018-09-07). "Equine degenerative myeloencephalopathy: prevalence, impact, and management". Veterinary Medicine: Research and Reports. 9: 63–67. doi:10.2147/VMRR.S148542. ISSN 2230-2034. PMC 6135079. PMID 30234005. 10. ^ a b "Sheep Production and Management: sheep health". aces.nmsu.edu. Retrieved 2017-04-06. 11. ^ National Farm Animal Care Council. 2013. Code of Practice for the Caring and Handling of Sheep. Retrieved from http://www.nfacc.ca/pdfs/codes/sheep_code_of_practice.pdf 12. ^ Gustav Rosenberger, Krankheiten des Rindes, Verlag Paul Parey, Berlin, ISBN 3-489-61716-9. p. 912-913 13. ^ "Selenium Deficiency in Adult Dairy Cattle". The Beef Site. Retrieved 2017-04-06. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Nutritional muscular dystrophy	c0043153	6,150	wikipedia	https://en.wikipedia.org/wiki/Nutritional_muscular_dystrophy	2021-01-18T18:45:24	{"mesh": ["D014912"], "wikidata": ["Q4832491"]}
A number sign (#) is used with this entry because lymphangioleiomyomatosis (LAM) can occur in association with tuberous sclerosis complex (TSC; 191100) due to mutations in the TSC1 (605284) or TSC2 (191092) genes. Sporadic LAM typically results from 2 somatic mutations in the TSC2 gene, although a fraction of sporadic LAM is caused by germline mutations in the TSC1 gene. Clinical Features Pulmonary lymphangiomyomatosis, also known as pulmonary lymphangioleiomyomatosis (Urban et al., 1999), is a rare disease that occurs almost exclusively in women. It was first described by Van Stossel (1937). The average age at onset of symptoms, which include shortness of breath (67%), lung collapse (25%), coughing (12%), and chest pain (10%), is 33 years (Taylor et al., 1990; Johnson et al., 1993). Chest x-rays typically show a diffuse interstitial infiltrate, with no predominance in any 1 lung zone. Although most cases of LAM are pulmonary, cases with retroperitoneal, pelvic, or perirenal involvement in lymph nodes and extranodal sites have been reported (Torres et al., 1995). The disorder is usually diagnosed by open lung biopsy. Microscopically, there is cystic distortion of the normal pulmonary architecture by an atypical smooth muscle infiltrate. Most patients have a slowly declining clinical course. Lung transplantation is the only effective therapy for patients with end-stage disease (Boehler et al., 1996). Lymphangiomyomatosis can occur as an isolated disorder or in association with TSC. Among patients with TSC, it is said to be the third most frequent cause of TSC-related death, after renal disease and brain tumors (Castro et al., 1995). Molecular Genetics Renal angiomyolipomas occur in approximately 50% of sporadic LAM patients and in 70% of TSC patients. Loss of heterozygosity (LOH) in the chromosomal region for the TSC2 gene occurs in 60% of TSC-associated angiomyolipomas. Because of the similar pulmonary and renal manifestations of TSC and sporadic LAM, Smolarek et al. (1998) hypothesized that LAM and TSC have a common genetic basis. They analyzed renal angiomyolipomas from 13 women with sporadic LAM for LOH in the region of the TSC1 (9q34) and TSC2 (16p13) genes. TSC2 LOH was detected in 7 (54%) of the angiomyolipomas. They also found TSC2 LOH in 4 lymph nodes from a woman with retroperitoneal LAM. No TSC1 LOH was found. The findings indicated that the TSC2 gene may be involved in the pathogenesis of sporadic LAM. They noted, however, that genetic transmission of LAM had not been reported. Women with LAM may have low penetrance germline TSC2 mutations, or they may be mosaic, with TSC2 mutations in the lung and the kidney but not in other organs. Examination of DNA from peripheral blood lymphocytes or lymphoblastoid cells of 12 LAM patients and culture of lung cells taken at the time of transplantation for LAM in 8 patients did not reveal any TSC2 mutations (Astrinidis et al., 2000). In 69 patients with pulmonary lymphangioleiomyomatosis, all women, Urban et al. (1999) found no familial instance. Carsillo et al. (2000) described mutations in the TSC2 gene as a cause of sporadic pulmonary lymphangioleiomyomatosis. They identified somatic TSC2 mutations in 5 of 7 angiomyolipomas from sporadic LAM patients. In all 4 patients from whom lung tissue was available, the same mutation found in the angiomyolipoma was present in the abnormal pulmonary smooth muscle cells. In no case was the mutation present in normal kidney, morphologically normal lung, or lymphoblastoid cells. TSC2 LOH was present in 4 of the 5 angiomyolipomas in which the authors identified TSC2 mutations. Therefore, these 4 angiomyolipomas had inactivation of both alleles of TSC2, consistent with the Knudson 2-hit hypothesis and the role of TSC2 as a tumor suppressor gene. No mutations in the TSC1 gene were found. Carsillo et al. (2000) recognized that a model to account for the presence of TSC2 mutations in the renal angiomyolipoma and pulmonary LAM cells but not in other tissues was necessary. They proposed 2 potential mechanisms, either of which would represent a novel mechanism for a disease associated with tumor suppressor gene mutations. One model suggests that sporadic LAM results from somatic mosaicism for TSC2 mutations. Sporadic LAM patients could have TSC2 mutations only in selected kidney and lung cells, and not in surrounding cells within the normal kidney or lung. According to this model, one would expect multiple independent tumor foci, whereas most sporadic LAM patients have a single angiomyolipoma. The second model entertained by Carsillo et al. (2000) involves the migration or spread of smooth muscle cells from the angiomyolipoma to the lung. Angiomyolipomas are histologically benign neoplasms; however, in patients with sporadic, solitary renal angiomyolipomas, it is not unusual to find angiomyolipoma cells in perirenal lymph nodes, suggesting that these cells are capable of spreading beyond the primary tumor. This is the 'benign metastasis' hypothesis (Karbowniczek et al., 2003). Sato et al. (2002) studied the TSC1 and TSC2 genes in 6 Japanese patients with pulmonary LAM in association with the TSC complex (TSC-LAM) and 22 patients with sporadic LAM and identified 6 novel mutations. TSC2 germline mutations were detected in 2 (33.3%) of the 6 patients with TSC-LAM, and a TSC1 germline mutation was detected in 1 (4.5%) of the 22 sporadic LAM patients. In accordance with the tumor suppressor model, LOH was detected in LAM cells from 3 of 4 patients with TSC-LAM and from 4 of 8 patients with sporadic LAM. Furthermore, an identical LOH or 2 identical somatic mutations were demonstrated in LAM cells microdissected from several tissues, suggesting that LAM cells can spread from one lesion to another. These results confirmed the prevailing concept of pathogenesis of LAM: TSC-LAM has a germline mutation, but sporadic LAM does not; sporadic LAM is a TSC2 disease with 2 somatic mutations; and a variety of TSC mutations can cause LAM. However, this study indicated that a fraction of sporadic LAM can be a TSC1 disease; therefore, both TSC genes should be examined, even in patients with sporadic LAM. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	LYMPHANGIOLEIOMYOMATOSIS	c0751674	6,151	omim	https://www.omim.org/entry/606690	2019-09-22T16:10:12	{"doid": ["3319"], "mesh": ["D018192"], "omim": ["606690"], "icd-9": ["516.4"], "icd-10": ["J84.81"], "orphanet": ["538"], "synonyms": ["Alternative titles", "LYMPHANGIOMYOMATOSIS"]}
Desmoplastic trichoepithelioma Desmoplastic trichoepithelioma or sclerosing epithelial hamartoma A desmoplastic trichoepithelioma is a cutaneous condition characterized by a solitary, firm skin lesion on the face.[1]:672 ## Contents * 1 Diagnosis * 2 Treatment * 3 See also * 4 References ## Diagnosis[edit] This section is empty. You can help by adding to it. (May 2018) ## Treatment[edit] Desmoplastic trichoepithelioma is benign tumor and can be managed safely with surgical removal, electrodesiccation and curettage. ## See also[edit] * Trichoepithelioma * 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 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 This Epidermal nevi, neoplasms, cysts article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Desmoplastic trichoepithelioma	c0432526	6,152	wikipedia	https://en.wikipedia.org/wiki/Desmoplastic_trichoepithelioma	2021-01-18T18:42:15	{"wikidata": ["Q5264830"]}
Annular pustular psoriasis SpecialtyDermatology Annular pustular psoriasis is a rare variant of pustular psoriasis, having an annular, or circinate, lesion morphology that may appear at the onset of pustular psoriasis, with a tendency to spread and form enlarged rings.[1]:411[2] ## See also[edit] * Psoriasis * List of cutaneous conditions ## References[edit] 1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. ## External links[edit] Classification D * ICD-10: L40.8 (ILDS L40.820) * 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 [mRNA]: messenger RNA *[kDa]: kilodalton	Annular pustular psoriasis	None	6,153	wikipedia	https://en.wikipedia.org/wiki/Annular_pustular_psoriasis	2021-01-18T18:48:52	{"icd-10": ["L40.8"], "wikidata": ["Q4769723"]}
A number sign (#) is used with this entry because of evidence that X-linked cardiac valvular dysplasia is caused by mutation in the FLNA gene (300017) on chromosome Xq28. Description X-linked cardiac valvular dysplasia is a rare form of heart disease characterized by multivalvular dysplasia and regurgitation, which can lead to lethal heart failure in some patients. Heterozygous females are more mildly affected than hemizygous males. Some patients also exhibit features of Ehler-Danlos syndrome (EDS; see 130000), with hyperextensible skin and joint hypermobility, whereas others have stiffening of joints from early childhood (Kyndt et al., 2007; Ritelli et al., 2017; Mercer et al., 2017). Clinical Features Monteleone and Fagan (1969) described 6 definite and 1 probable case of congenital heart disease in males in 4 sibships of 3 generations of a black kindred in a pattern suggesting X-linked recessive inheritance. Four had mitral and aortic regurgitation, of whom 2 also had tricuspid regurgitation. The fifth definite case had only mitral regurgitation. Histologically, changes in the mitral valve of 1 case resembled those seen in the 'floppy valve syndrome' (Read et al., 1965) or in Marfan syndrome (which was suggested by no other feature of the cases). Di Ferrante et al. (1975) reported 2 Italian maternal cousins with congenital heart disease, 'floppy valve syndrome,' hernias, short stature, stretchable skin, and moderate joint hypermobility, which the authors considered to represent an X-linked form of Ehlers-Danlos syndrome (EDS5; see HISTORY). The proband's cousin had an affected younger brother who had died from severe congestive heart failure. Analysis of the proband's fibroblasts showed deficient activity of lysyl oxidase, the enzyme responsible for oxidative deamination of lysine and hydroxylysine in collagen as a first step in cross-linking of collagen. Addition of catechin, a flavonoid, to the proband's cultured fibroblasts decreased the solubility of collagen they produced. Balaji et al. (1991) reported a 3-generation family in which 6 members had Ebstein anomaly (EA) of the tricuspid valve. The index patient presented at age 5 years with an asymptomatic heart murmur that was clinically diagnosed as EA, which was confirmed on cardiac catheterization 3 years later. At age 30 years, she remained asymptomatic, although echocardiography showed a large right atrium, small right ventricle, and moderate tricuspid regurgitation. She had an asymptomatic 7-year-old daughter with mild EA on echocardiography, and a 3-year-old son with severe EA, who experienced cyanosis and heart failure as a neonate, with moderate tricuspid stenosis and regurgitation as well as a dysplastic stenotic mitral valve on echocardiography. The proband's unaffected sister had 3 affected children, including a 5-year-old asymptomatic girl, a male infant who died at 1 day of life with severe EA, and a 1-month old boy who was born with cyanosis and signs of heart failure who had mild EA by echocardiography. The sisters' 67-year-old father had a history of a 'weak heart' and underwent aortic valve replacement at age 62 years for aortic stenosis; preoperative cardiac catheterization did not show any right heart abnormalities. All of the family members had mild skeletal anomalies, including joint contractures and/or proximally placed and externally rotated fifth toes. The authors stated that it was not clear whether the skeletal findings were coincidental in this family or part of an inherited syndrome with EA. Newbury-Ecob et al. (1993) described a British family in which 2 brothers and the son of a daughter of one of them had valvular dysplasia. The grandson died in severe heart failure in the first day of life. All 4 heart valves were abnormal. The tricuspid and mitral valves had edematous and irregular cusps with short and irregular chordae. The aortic and pulmonary valves were bicuspid but also showed thickening and edema of the cusps. The aortic ring was stenotic. The maternal grandfather was asymptomatic until the age of 25 years when he developed progressive breathlessness; at the age of 41 years, he underwent surgical replacement of the aortic mitral and tricuspid valves, which were the site of myxomatous degeneration with secondary calcification and regurgitation. His brother had severe mitral valve prolapse. Kyndt et al. (2007) studied a large French pedigree segregating X-linked cardiac valvular disease, originally reported by Benichou et al. (1997) and Kyndt et al. (1998), and identified a new branch of the family with a common ancestor born in the eighteenth century. The extended family included 14 affected males, all of whom had mitral valve disease and all but 1 of whom also had aortic valve regurgitation. Twelve male patients had progressive mitral valve prolapse, found on the anterior valve in 4 and on both valves in 8. Five male patients underwent valve surgery, 3 for replacement of the aortic valve, 1 for both aortic and mitral valve replacement, and 1 for mitral valvuloplasty. Mild to moderate tricuspid valve regurgitation was found in 11 affected males, and mild pulmonary regurgitation in 4, but none had surgery of the tricuspid or pulmonary valves. In all but 1 of the affected males, valvular disease was associated with mild hemophilia A (306700), with factor VIII (300841) activity between 15% and 50%. Haplotype analysis in the patient with normal coagulation factor activity demonstrated that valvulopathy and hemophilia were transmitted as independent traits (see MAPPING). There were 30 carrier females in the family, all of whom were asymptomatic; upon examination, however, 14 of the carrier females were considered affected, 12 had minor valve disease and were designated 'undetermined,' and only 4 were considered unaffected. Among carrier females, 4 had mitral valve prolapse, involving the anterior valve in 3 cases and the posterior valve in 1 case; mitral valve regurgitation was mild in 19 and moderate in 4; aortic valve regurgitation was mild in 8, moderate in 3, and severe in 1; tricuspid valve regurgitation was mild in 9 and moderate in 1; and pulmonary valve regurgitation was mild in 2 and moderate in 1. None of the carrier females had undergone valvular surgery. Ritelli et al. (2017) restudied the Italian family with multivalvular disease and features consistent with Ehlers-Danlos syndrome that was originally reported by Di Ferrante et al. (1975), and identified 4 more affected individuals over 3 generations, for a total of 1 female and 5 male patients, who had all died of congestive heart failure. Both male cousins exhibited dysmorphic facial features, including bilateral ptosis, hypertelorism, prominent columella, long philtrum, and thick lower lip. Additional findings included joint hypermobility, mild scoliosis, genua valga, flexible flat feet, and soft, doughy, and hyperextensible skin. The index patient (III.1) experienced progressive heart failure due to an intrinsic defect of all valves, and died awaiting transplantation. Mercer et al. (2017) reexamined 6 affected individuals, 2 brother/sister pairs and their respective mothers, from the family with Ebstein anomaly originally reported by Balaji et al. (1991). The 2 male patients were the most severely affected; in addition to EA, both exhibited mitral valve dysplasia with stenosis and regurgitation as well as pulmonary regurgitation, and 1 also had bicuspid aortic valve with regurgitation. Other cardiac abnormalities in the 4 female patients included patent foramen ovale in 1 and pulmonary regurgitation in another. The men also showed facial dysmorphism, including prominent supraorbital ridges, hypertelorism, and proptosis. All 6 patients had joint stiffness that began in childhood and was most severe in the men, who had fixed flexion of the knees and ankles; both men and 2 women also had limited supination of the elbows. In addition, both men and 1 woman had reduced limb musculature. All 6 patients exhibited proximally placed and externally rotated fifth toes, and keloid scarring was noted in all. Mapping Benichou et al. (1997) did linkage studies of a large 5-generation French pedigree in which males were severely affected and carrier females were also affected but to a milder extent, consistent with X-linked inheritance. Using dinucleotide repeat markers, they assigned the gene for CVD to an 8-cM region of Xq28. A 5.91 lod score was obtained for 2 distal markers, including an intronic microsatellite of the factor VIII gene. In the full report of this study, Kyndt et al. (1998) reported a maximum lod score of 6.54 at theta = 0.0 for 2 polymorphic microsatellite markers, INT3 and DXS1008, the first being intronic to the factor VIII gene. Kyndt et al. (1998) referred to X-linked CVD as X-linked myxomatous valvular dystrophy (XMVD). Haplotype analysis of this chromosomal region allowed definition of an 8-cM minimal interval containing the gene for XMVD, between DXS8011 and Xqter. Kyndt et al. (2007) performed additional linkage analysis in the large French pedigree with valvular dysplasia, including a new branch of the family with a common ancestor born in the eighteenth century, and refined the critical region to a 2.5-Mb interval between DXS10049 and the GAB3 gene (300482) that excluded the factor VIII gene (300841). Molecular Genetics Kyndt et al. (2007) analyzed candidate genes in the large French pedigree with X-linked cardiac valvular disease and identified a hemizygous mutation in the FLNA gene (P637Q; 300017.0030) that segregated with disease. In the British family originally studied by Newbury-Ecob et al. (1993) and in 2 additional families with cardiac valvular disease, Kyndt et al. (2007) identified respective mutations in the FLNA gene (300017.0031-300017.0033). The mutations segregated with disease in the families and were not found in control chromosomes. All 4 families presented no clinically apparent extracardiac abnormalities, no dysmorphic features, and no epileptic seizures. Using DNA from 2 affected male cousins from a 3-generation Italian family originally reported by Di Ferrante et al. (1975), in which 5 affected males and 1 female had died of congestive heart failure due to multivalvular disease, Ritelli et al. (2017) performed exome sequencing and identified hemizygosity for a splicing mutation in the FLNA gene (300017.0037). No other family members were available for segregation analysis. In a 3-generation family with multivalvular dysplasia, originally reported by Balaji et al. (1991) and negative for mutation in the MYH7 (160760) and NKX2-5 (600584) genes, Mercer et al. (2017) analyzed exome data and identified a missense mutation in the FLNA gene (G1554R; 300017.0038) that segregated with the disease. History Beighton (1968) described 2 families in which X-linked inheritance of Ehlers-Danlos syndrome, designated EDS5, was probable. The clinical features included hyperextensible skin and bruising tendency. Fragility of skin was unimpressive. In contrast to the findings of Di Ferrante et al. (1975), a study of material from Beighton's original cases by Siegel et al. (1979) demonstrated no deficiency of lysyl oxidase, and Byers (1980) suggested that such a deficiency was unlikely in this condition. Beighton and Curtis (1985) provided follow-up on the 2 families studied by Beighton (1968). In family 1, a sister of 3 affected males had produced an affected son. The authors noted that all affected individuals from both families had red hair. Steinmann et al. (2002) questioned the existence of EDS V as a distinct entity. They considered the phenotype too ill defined, and thought it more likely that the patients originally reported by Di Ferrante et al. (1975) as having EDS5 had cardiac valvular dysplasia. Malfait et al. (2017) stated that the condition designated EDS5 is no longer included in the EDS spectrum. INHERITANCE \- X-linked HEAD & NECK Face \- Prominent supraorbital ridges (in some patients) Eyes \- Ptosis (in some patients) \- Hypertelorism (in some patients) Mouth \- Thick lips (in some patients) CARDIOVASCULAR Heart \- Thickened cardiac valves \- Dysplastic cardiac valves \- Congestive heart failure \- Mitral valve prolapse \- Mitral regurgitation \- Aortic regurgitation \- Bicuspid aortic valve (rare) \- Ebstein anomaly of tricuspid valve (in some patients) \- Tricuspid regurgitation \- Pulmonary regurgitation SKELETAL \- Joint laxity, mild (in some patients) \- Joint stiffness (in some patients) Limbs \- Limited supination of elbows \- Fixed flexion of knees \- Fixed flexion of ankles Feet \- Proximally placed and externally rotated fifth toe (in some patients) SKIN, NAILS, & HAIR Skin \- Skin laxity (in some patients) \- Keloid scarring (in some patients) MUSCLE, SOFT TISSUES \- Reduced limb musculature (in some patients) MISCELLANEOUS \- Male patients more severely affected than female patients \- Phenotypic variability MOLECULAR BASIS \- Caused by mutation in the filamin-A gene (FLNA, 300017.0030 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	CARDIAC VALVULAR DYSPLASIA, X-LINKED	c0262436	6,154	omim	https://www.omim.org/entry/314400	2019-09-22T16:17:05	{"mesh": ["C535576"], "omim": ["314400"], "orphanet": ["555877"], "synonyms": ["Alternative titles", "VALVULAR HEART DISEASE, CONGENITAL", "MYXOMATOUS VALVULAR DYSTROPHY, X-LINKED", "EHLERS-DANLOS SYNDROME, TYPE V, FORMERLY"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive cutis laxa type IIC (ARCL2C) is caused by homozygous mutation in the ATP6V1E1 gene (108746) on chromosome 22q11. Description Autosomal recessive cutis laxa type IIC (ARCL2C) is characterized by generalized skin wrinkling with sparse subcutaneous fat and dysmorphic progeroid facial features. Most patients also exhibit severe hypotonia as well as cardiovascular involvement (summary by Van Damme et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). Clinical Features Alazami et al. (2016) reported a consanguineous Saudi family (10DG0257) with 2 affected brothers with a cutis laxa syndrome. The index case presented at 1 year of age with cutis laxa and multiple congenital anomalies. He had been born at term via spontaneous vaginal delivery but spent 2 months in the NICU requiring mechanical ventilation. He had a dysplastic right kidney, bilateral nephrocalcinosis, and pyloric stenosis. Growth parameters were all low, but over time he experienced some catchup growth. Dysmorphic features included a short forehead, blepharophimosis, strabismus, entropion, infraorbital puffiness, maxillary hypoplasia, crowding of the teeth, prominent jaw, saggy cheeks, an abnormal bulge of the upper third of the nasal spine, saddle nose, anteverted nares, long philtrum, midline cleft palate, wrinkly skin of the neck and abdomen, prominent veins, bilateral undescended testicles, micropenis, mild camptodactyly, and overriding toes. He had asthma and frequent pneumonias, and brain MRI revealed mildly dilated ventricular system. He had muscle weakness with positive Gowers sign on neurologic exam. His younger brother presented at 2 years of age. He had been born at 37 weeks of gestation via emergency cesarean section; pregnancy had been uncomplicated until the 8th month, when oligohydramnios, congenital heart disease, and hydronephrosis were diagnosed on ultrasound. Apgar scores and growth parameters at birth were normal, but he was dysmorphic in a way nearly identical to his older brother. He remained in the NICU for 3 weeks, during which echocardiogram revealed small patent foramen ovale, small patent ductus arteriosus, mild tricuspid regurgitation, and increased pulmonary pressure. The left kidney was low lying with grade I hydronephrosis, while the right kidney was in normal position with no hydronephrosis. Head ultrasound revealed mild dilatation of the lateral ventricles. Repeat echocardiogram at 2 years of age showed no patent ductus arteriosus, but a small patent foramen ovale and trace mitral and tricuspid regurgitation. Kidney ultrasound revealed preserved corticomedullary differentiation without hydronephrosis. At 1 year of age he could stand and walk with support, and say mama and baba. At 2 years growth was normal but cutis laxa was obvious with dysmorphic features including blepharophimosis, entropion, hypertelorism, malar hypoplasia, and severe microstomia. He also had overriding toes. Van Damme et al. (2017) studied 2 Iranian sisters and a Kuwaiti sister and brother with autosomal recessive cutis laxa. All affected individuals exhibited generalized skin wrinkling with sparse subcutaneous fat and had dysmorphic progeroid facial features, including a 'mask-like' triangular face, short forehead, hypertelorism, entropion, low-set ears with misfolded helices, beaked nose with broad nasal base and narrow nostrils, and a short pointed chin. Additional features in the Iranian proband included hypotonia, clenched hands, ulnar deviation of the fingers, congenital hip dysplasia, flexion contractures of the knees, and club feet. Echocardiography revealed severe dilation of the ascending aortic root and moderate biventricular hypertrophy. She died at age 4 months. A second pregnancy in that family was terminated at 21 weeks' gestation due to increased nuchal thickness and cardiac abnormalities on prenatal ultrasound. Autopsy of the female fetus showed right hypoplastic heart syndrome, with a hypoplastic right ventricle, tricuspid valve stenosis, and hypoplastic pulmonary artery. The Kuwaiti sibs both had bilateral pneumothorax shortly after birth, and also exhibited high-arched palate with dental crowding, severe muscle hypoplasia that limited their mobility, scoliosis, and flat feet. Echocardiography at age 10 years in the sister revealed mild dilation of the right ventricle with reduced diastolic compliance, atrial septal defect, mitral valve prolapse, and aortic and tricuspid insufficiency; electrocardiography showed incomplete right bundle branch block. She also had hypermobile joints. Her 9-year-old brother, who had a normal echocardiogram, was born with bilateral cryptorchidism and bilateral inguinal hernias, and also had temporomandibular joint dysfunction with recurrent dislocations. Molecular Genetics In 2 brothers from a Saudi family with a cutis laxa syndrome, Alazami et al. (2016) detected homozygosity for an arg212-to-trp mutation in the ATP6V1E1 gene (R212W; 108746.0002). In affected individuals from an Iranian family and a Kuwaiti family with cutis laxa, Van Damme et al. (2017) performed whole-exome sequencing and identified homozygosity for 2 different missense mutations in the ATP6V1E1 gene: L128P (108746.0001) in the Iranian family, and R212W (108746.0002) in the Kuwaiti family. The mutations segregated with disease in both families, and were not found in in-house exome cohorts or in the ExAC database. Complexome profiling in cultured fibroblasts showed a markedly reduced abundance of the assembled V1 domain and of the complete membrane-bound V1V0 complex, and the mutations were also shown to affect protein glycosylation. Van Damme et al. (2017) proposed including this form of cutis laxa in the current congenital disorder of glycosylation (CDG) classification as 'ATP6V1E1-related CDG.' INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Weight \- Low weight Other \- Marfanoid habitus HEAD & NECK Face \- Progeroid facies \- Mask-like triangular face \- Short forehead \- Long philtrum \- Prominent nasolabial folds \- Short pointed chin Ears \- Low-set ears \- Misfolded helices Eyes \- Hypertelorism \- Entropion \- Nystagmus Nose \- Prominent beaked nose \- High nasal root \- Broad nasal tip \- Broad columella \- Narrow nostrils Mouth \- High-arched palate \- Dental crowding CARDIOVASCULAR Heart \- Severe dilation of ascending aortic root \- Moderate biventricular hypertrophy \- Mild dilation of right ventricle \- Reduced diastolic compliance of right ventricle \- Hypoplastic right ventricle \- Tricuspid valve stenosis \- Tricuspid insufficiency \- Aortic insufficiency \- Mitral valve prolapse \- Hypoplastic pulmonary artery \- Atrial septal defect \- Incomplete right bundle branch block RESPIRATORY Larynx \- Laryngomalacia Lung \- Bilateral pneumothorax (in early infancy) GENITOURINARY External Genitalia (Male) \- Inguinal hernias, bilateral Internal Genitalia (Male) \- Cryptorchidism, bilateral SKELETAL \- Joint laxity Skull \- Recurrent dislocations of temporomandibular joint Spine \- Kyphoscoliosis Pelvis \- Hip dysplasia Limbs \- Flexion contractures of knees Hands \- Clenched hands \- Ulnar deviation of fingers Feet \- Flat feet \- Club feet SKIN, NAILS, & HAIR Skin \- Generalized skin wrinkling Electron Microscopy \- Reduced elastic fibers \- Fragmented elastic fibers \- Loosely packed collagen fibers \- Variable diameters of collagen fibers MUSCLE, SOFT TISSUES \- Sparse subcutaneous fat \- Marked muscular atrophy \- Reduced muscular strength NEUROLOGIC Central Nervous System \- Hypotonia METABOLIC FEATURES \- Abnormal transferrin isoelectric focusing pattern \- Decreased tetrasialotransferrin \- Increased disialotransferrin \- Increased trisialotransferrin MISCELLANEOUS \- One Kuwaiti and one Iranian family with 2 sibs each have been reported (last curated March 2017) \- Variable congenital heart defects MOLECULAR BASIS \- Caused by mutation in the V1 subunit E 31-kd lysosomal H(+)-transporting ATPase isoform 1 gene (ATP6V1E1, 108746.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIC	c4479387	6,155	omim	https://www.omim.org/entry/617402	2019-09-22T15:45:53	{"doid": ["0070140"], "omim": ["617402", "219200", "617403"], "orphanet": ["357074"], "synonyms": ["ARCL2, Debré type", "ARCL2, classic type", "Autosomal recessive cutis laxa type 2, Debré type"]}
Actinic granuloma Other namesO'Brien granuloma SpecialtyDermatology Actinic granuloma is a cutaneous condition characterized histologically by a dermal infiltrate of macrophages.[1]:706 Actinic granuloma is an asymptomatic granulomatous reaction that affects sun-exposed skin, most commonly on the face, neck, and scalp. It is characterized by annular or polycyclic lesions that slowly expand centrifugally and have an erythematous elevated edge and a hypopigmented, atrophic center. Advise to reduce exposure to the sun and to use sunscreen. Treatment with topical halometasone cream, pimecrolimus cream. ## See also[edit] * Annular elastolytic giant cell granuloma * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. ## External links[edit] Classification D * ICD-10: L57.5 * DiseasesDB: 32799 * v * t * e Radiation-related disorders / Photodermatoses Ultraviolet/ionizing * Sunburn * Phytophotodermatitis * Solar urticaria * Polymorphous light eruption * Benign summer light eruption * Juvenile spring eruption * Acne aestivalis * Hydroa vacciniforme * Solar erythema Non-ionizing Actinic rays * Actinic keratosis * Atrophic actinic keratosis * Hyperkeratotic actinic keratosis * Lichenoid actinic keratosis * Pigmented actinic keratosis * Actinic cheilitis * Actinic granuloma * Actinic prurigo * Chronic actinic dermatitis Infrared/heat * Erythema ab igne (Kangri ulcer * Kairo cancer * Kang cancer * Peat fire cancer) * Cutis rhomboidalis nuchae * Poikiloderma of Civatte Other * Radiation dermatitis * Acute * Chronic radiodermatitis) * Favre–Racouchot syndrome * Photoaging * Photosensitivity with HIV infection * Phototoxic tar dermatitis This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Actinic granuloma	c0263608	6,156	wikipedia	https://en.wikipedia.org/wiki/Actinic_granuloma	2021-01-18T19:05:02	{"umls": ["C0263608"], "icd-10": ["L57.5"], "wikidata": ["Q4676884"]}
A number sign (#) is used with this entry because of evidence that combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia (CIMAH) is caused by compound heterozygous mutation in the MTHFD1 gene (172460) on chromosome 14q23. Description Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia is an inborn error of folate metabolism due to deficiency of methylenetetrahydrofolate dehydrogenase-1. Manifestations may include hemolytic uremic syndrome, macrocytosis, epilepsy, hearing loss, retinopathy, mild mental retardation, lymphopenia involving all subsets, and low T-cell receptor excision circles. Folinic acid supplementation is an effective treatment (summary by Ramakrishnan et al., 2016). Clinical Features Watkins et al. (2011) described a female infant, born to healthy nonconsanguineous parents of Ashkenazi Jewish and Russian descent, who presented at 2 months of age with febrile illness and pallor. She had megaloblastic anemia, atypical hemolytic uremic syndrome (HUS), and severe combined immunodeficiency. Serum cobalamin levels were within the reference range, but there was a consistent elevation of total homocysteine levels in blood. Studies on cultured fibroblasts revealed a selective decreased synthesis of methylcobalamin from labeled exogenous cyanocobalamin, suggestive of a disorder of homocysteine remethylation. Keller et al. (2013) provided additional information on this patient. Shortly after treatment for anemia and a urinary tract infection at age 2 months, she was found to have pancytopenia with elevated lactate dehydrogenase. Bronchoalveolar lavage showed evidence of Pneumocystis jiroveci, and she later developed a Candida albicans infection. Immunologic studies at age 3 months showed marked hypogammaglobulinemia and lymphopenia, with few T cells, B cells, or natural killer cells. Bone marrow biopsy showed giant bands and nuclear-cytoplasmic dyssynchrony, and peripheral blood smear showed hypersegmented neutrophils. There was no evidence of malignancy. Serum vitamin B12 and folate levels were normal, but homocysteine levels were elevated and methionine levels slightly low. The patient's neurologic phenotype included mild bilateral sensorineural hearing loss, symptomatic partial epilepsy that was refractory to multiple antiepileptic agents, and mild mental retardation. Brain MRI at age 11 months showed bilateral small hippocampi, which was unchanged on repeat study at 4 years of age. Cerebrospinal fluid amino acid and neurotransmitter profiles were normal at age 11 months. Burda et al. (2015) reported 4 patients from 2 families with combined immunodeficiency and megaloblastic anemia. One patient (Patient 2) was an 18-month-old girl, born to nonconsanguineous French parents, who presented with asthenia, vomiting, and icteric skin. She had anemia characterized by schizocytosis and thrombopenia, indicating atypical hemolytic uremic syndrome, microangiopathy, retinopathy, and severe arterial hypertension. Bone marrow analysis revealed dyserythropoietic and megaloblastic anemia, leukopenia, and low haptoglobin. Serum cobalamin, transcobalamin, and unsaturated cobalamin binding capacity of total serum were normal, as was serum folate. However, both free and total carnitine were slightly decreased, and analysis of amino and organic acids revealed hyperhomocysteinemia, low-normal methionine, and normal methylmalonic acid. The patient responded slowly but completely with continued treatment with hydroxocobalamin, folinic acid, and betaine. At 6 years of age, her psychomotor development and a cerebral MRI were normal, but a previously diagnosed retinopathy had worsened and was unresponsive to treatment. Patient 3 was a 22-year-old woman from a nonconsanguineous family of Swedish origin who had been monitored closely from birth because of the medical history of her 2 older sibs. Hematologic investigations at day 4 of life showed macroblastic bone marrow with a slight megaloblastic appearance, consistent with cobalamin or folate deficiency, and marked anisocytosis. At 9 weeks of age, anemia and high MCV were noted, and she was diagnosed with thiamine-responsive megaloblastic anemia. At the age of 4 months, Hgb and MCV had normalized, and folic acid and cobalamin treatment was terminated. Bone marrow was then almost normalized with normoblastic erythropoiesis and normal myelopoiesis. At 7 months of age, she became anemic and developed a general inflammatory state. Autoantibodies with high titers against DNA and striated muscle appeared, and antinuclear antibodies were positive. Serum transaminases were only marginally elevated. Liver biopsy showed a low grade lymphohistiocytic inflammation in portal areas and in lobuli. Bone marrow showed macromegaloblastic anemia with anisocytosis and disturbed myelopoiesis. She did not show hyperhomocysteinemia. She was treated successfully with blood transfusions, gammaglobulin infusions, corticosteroids, cobalamin, and folic acid, with rapid response. She remained clinically well on folic acid supplementation. Her sibs remained well until age 6 weeks. Her sister (patient 4) developed moniliasis and presented at 9 weeks of age with anemia, vomiting, and labored breathing. Her brother (patient 5) presented with fever, lesions consistent with hand-foot-and-mouth disease, vomiting, and labored breathing. At age 9 weeks, he was found to have anemia, leukopenia, and thrombocytosis with extreme metabolic acidosis. Both died within hours. Ramakrishnan et al. (2016) reported 2 brothers with combined immunodeficiency and megaloblastic anemia. One brother presented at age 4 months with clinical and immunologic features consistent with P. jirovecii pneumonia. Severe combined immunodeficiency was diagnosed on the basis of susceptibility to this pathogen and severe lymphopenia involving all lymphoid subsets. He remained free of significant infections on immunoglobulin replacement, prophylactic cotrimoxazole, and fluconazole. At 4 years of age, he presented with severe macrocytic anemia, which was confirmed to be megaloblastic on bone marrow examination. His younger brother was found to have severe lymphopenia and was treated prophylactically with cotrimoxazole and fluconazole. He responded to protein vaccines but not to conjugated polysaccharide vaccines. He developed septic arthritis at age 9 and subsequently had immunoglobulin replacement. On retrospective analysis, both brothers showed severe macrocytosis from infancy. Treatment with folinic acid completely cleared the anemia without further episodes and improved lymphocyte function and numbers. Inheritance Combined immunodeficiency and megaloblastic anemia is an autosomal recessive disorder (Watkins et al., 2011). Clinical Management The patient with CIMAH originally reported by Watkins et al. (2011) was treated with intramuscular hydroxocobalamin, oral folate, and betaine. Severe infections were treated and prevented with IVIG and prophylactic trimethoprim/sulfamethoxazole. Patients with CIMAH reported by Burda et al. (2015) and Ramakrishnan et al. (2016) were treated similarly and remained clinically well with folinic acid supplementation. Molecular Genetics In a child with combined immunodeficiency and megaloblastic anemia with hyperhomocysteinemia, Watkins et al. (2011) identified compound heterozygous mutations in the MTHFD1 gene (172460.0003-172460.0004). In a French patient and 3 sibs in a Swedish family with CIMAH, Burda et al. (2015) identified compound heterozygous mutations in the MTHFD1 gene (172460.0005-172460.0008). In 2 brothers with CIMAH, Ramakrishnan et al. (2016) identified compound heterozygous mutations in the MTHFD1 gene (172460.0009-172460.0010). INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, mild (in 1 patient) RESPIRATORY \- Recurrent pulmonary infections ABDOMEN Liver \- Liver fibrosis Gastrointestinal \- Vomiting GENITOURINARY External Genitalia (Female) \- Moniliasis Kidneys \- Atypical hemolytic uremic syndrome SKELETAL \- Septic arthritis SKIN, NAILS, & HAIR Skin \- Eczema NEUROLOGIC Central Nervous System \- Seizures (in 1 patient) \- Mental retardation, mild (in 1 patient) Behavioral Psychiatric Manifestations \- Asthenia METABOLIC FEATURES \- Hyperhomocysteinemia (in some patients) HEMATOLOGY \- Lymphopenia \- Pancytopenia \- Macrocytic anemia \- Megaloblastic anemia \- Dyserythropoietic anemia \- Thrombocytosis \- Thrombopenia IMMUNOLOGY \- Recurrent infections \- Hypogammaglobulinemia \- Severe combined immunodeficiency (SCID) \- Low B cells \- Low T cells \- Low NK cells \- Autoimmune disease (in some patients) LABORATORY ABNORMALITIES \- Decreased methylcobalamin \- Normal serum cobalamin MISCELLANEOUS \- Variable clinical presentation \- Patients respond to folinic acid supplementation MOLECULAR BASIS \- Caused by mutation in the methylenetetrahydrofolate dehydrogenase 1 gene (MTHFD1, 172460.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	COMBINED IMMUNODEFICIENCY AND MEGALOBLASTIC ANEMIA WITH OR WITHOUT HYPERHOMOCYSTEINEMIA	c4540434	6,157	omim	https://www.omim.org/entry/617780	2019-09-22T15:44:58	{"omim": ["617780"], "synonyms": ["Alternative titles", "METHYLENETETRAHYDROFOLATE DEHYDROGENASE 1 DEFICIENCY"]}
Deformity involving outward deviation of an extended forearm Cubitus valgus Cubitus varus versus cubitus valgus SpecialtyMedical genetics Cubitus valgus is a medical deformity in which the forearm is angled away from the body to a greater degree than normal when fully extended. A small degree of cubitus valgus (known as the carrying angle) is acceptable and occurs in the general population.{{cn} When present at birth, it can be an indication of Turner syndrome[1] or Noonan syndrome. It can also be acquired through fracture or other trauma. The physiological cubitus valgus varies from 3° to 29°. Women usually have a more pronounced Cubitus valgus than men. The deformity can also occur as a complication of fracture of the lateral condyle of the humerus, which may lead to tardy/delayed ulnar nerve palsy.The opposite condition is cubitus varus (736.02). ## See also[edit] * Valgus deformity * Varus deformity ## References[edit] 1. ^ Chapter on Amenorrhea in: Bradshaw, Karen D.; Schorge, John O.; Schaffer, Joseph; Lisa M. Halvorson; Hoffman, Barbara G. (2008). Williams' Gynecology. McGraw-Hill Professional. ISBN 978-0-07-147257-9. ## External links[edit] * Image (congenital) Classification D * ICD-10: M21.0, Q74.0 * ICD-9-CM: 736.01, 755.59 * DiseasesDB: 29423 * v * t * e Acquired musculoskeletal deformities Upper limb shoulder * Winged scapula * Adhesive capsulitis * Rotator cuff tear * Subacromial bursitis elbow * Cubitus valgus * Cubitus varus hand deformity * Wrist drop * Boutonniere deformity * Swan neck deformity * Mallet finger Lower limb hip * Protrusio acetabuli * Coxa valga * Coxa vara leg * Unequal leg length patella * Luxating patella * Chondromalacia patellae * Patella baja * Patella alta foot deformity * Bunion/hallux valgus * Hallux varus * Hallux rigidus * Hammer toe * Foot drop * Flat feet * Club foot knee * Genu recurvatum Head * Cauliflower ear General terms * Valgus deformity/Varus deformity * Joint stiffness * Ligamentous laxity * 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 This human musculoskeletal system article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Cubitus valgus	c0158465	6,158	wikipedia	https://en.wikipedia.org/wiki/Cubitus_valgus	2021-01-18T18:32:58	{"icd-9": ["736.01", "755.59"], "icd-10": ["Q74.0", "M21.0"], "wikidata": ["Q1142962"]}
This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (June 2020) (Learn how and when to remove this template message) total color blindness Achromatopsia Known as Total color blindness SpecialtyOphthalmology SymptomsDay blindness, involuntary eye movement, lazy eye, photophobia Causes * Acquired malfunction of the retinal phototransduction pathway * Congenital damage to the diencephalon, thalamus, or the cerebral cortex Diagnosis Electroretinography Frequency1/30,000 × 100% = 0.00333333333333% Achromatopsia, also known as total color blindness, is a medical syndrome that exhibits symptoms relating to at least five conditions. The term may refer to acquired conditions such as cerebral achromatopsia, but it typically refers to an autosomal recessive congenital color vision condition, the inability to perceive color and to achieve satisfactory visual acuity at high light levels, typically exterior daylight. The syndrome is also present in an incomplete form which is more properly defined as dyschromatopsia. It is estimated to affect 1 in 30,000 live births worldwide. There is some discussion as to whether achromats can see color or not. As illustrated in The Island of the Colorblind by Oliver Sacks, some achromats cannot see color, only black, white, and shades of grey. With five different genes currently known to cause similar symptoms, it may be that some do see marginal levels of color differentiation due to different gene characteristics. With such small sample sizes and low response rates, it is difficult to accurately diagnose the 'typical achromatic conditions'. If the light level during testing is optimized for them, they may achieve corrected visual acuity of 20/100 to 20/150 at lower light levels, regardless of the absence of color. One common trait is hemeralopia or blindness in full sun. In patients with achromatopsia, the cone system and fibres carrying color information remain intact. This indicates that the mechanism used to construct colors is defective. ## Contents * 1 Signs and symptoms * 1.1 Complete achromatopsia * 1.2 Incomplete achromatopsia * 2 Cause * 2.1 Acquired * 2.2 Congenital * 3 Pathophysiology * 3.1 ACHM2 * 3.2 ACHM3 * 3.3 ACHM4 * 4 Management * 5 Epidemiology * 6 Terminology * 6.1 Related * 7 References * 7.1 Footnotes * 7.2 Sources * 8 External links ## Signs and symptoms[edit] The syndrome is frequently noticed first in children around six months of age by their photophobic activity or their nystagmus. The nystagmus becomes less noticeable with age but the other symptoms of the syndrome become more relevant as school age approaches. Visual acuity and stability of the eye motions generally improve during the first six to seven years of life – but remain near 20/200. The congenital forms of the condition are considered stationary and do not worsen with age.[citation needed] The five symptoms associated with achromatopsia or dyschromatopsia are:[citation needed] 1. Achromatopsia 2. Amblyopia – reduced visual acuity 3. Hemeralopia – with the subject exhibiting photophobia 4. Nystagmus 5. Iris operating abnormalities The syndrome of achromatopsia or dyschromatopsia is poorly described in current medical and neuro-ophthalmological texts. It became a common term following the release of neuroscientist Oliver Sacks' book, The Island of the Colorblind, in 1997. Up to that time most color blind subjects were described as achromats or achromatopes. Those with a lesser degree of color perception abnormality were described as either protanopes, deuteranopes or tetartanopes – historically tritanopes.Achromatopsia has also been called rod monochromacy and total congenital color blindness. Individuals with the congenital form of this condition show complete absence of cone cell activity via electroretinography at high light levels. There are at least four genetic causes of congenital achromatopsia, two of which involve cyclic nucleotide-gated ion channels (ACHM2, ACHM3), a third involves the cone photoreceptor transducin (GNAT2, ACHM4), and the last remains unknown.[citation needed] ### Complete achromatopsia[edit] Aside from a complete inability to see color, individuals with complete achromatopsia have a number of other ophthalmologic aberrations. Included among these optical aberrations are greatly decreased visual acuity (<0.1 or 20 in daylight, hemeralopia, nystagmus, and severe photophobia. The fundus of the eye appears completely normal.[citation needed] ### Incomplete achromatopsia[edit] In general, symptoms of incomplete achromatopsia (dyschromatopsia) are similar to those of complete achromatopsia except in a diminished form. Individuals with incomplete achromatopsia have reduced visual acuity with or without nystagmus or photophobia. Furthermore, these individuals show only partial impairment of cone cell function but again have retained rod cell function.[citation needed] ## Cause[edit] ### Acquired[edit] Acquired achromatopsia or dyschromatopsia is a condition associated with damage to the diencephalon—primarily the thalamus of the mid brain—or the cerebral cortex—the new brain—specifically the fourth visual association area, V4 which receives information from the parvocellular pathway involved in colour processing.[citation needed] Thalamic achromatopsia or dyschromatopsia is caused by damage to the thalamus; it is most frequently caused by tumor growth since the thalamus is well protected from external damage.Cerebral achromatopsia is a form of acquired color blindness that is caused by damage to the cerebral cortex of the brain, rather than abnormalities in the cells of the eye's retina. It is most frequently caused by physical trauma, hemorrhage or tumor tissue growth.[citation needed] ### Congenital[edit] The known causes of the congenital forms of achromatopsia are all due to malfunction of the retinal phototransduction pathway. Specifically, this form of achromatopsia seems to result from the inability of cone cells to properly respond to light input by hyperpolarizing. Known genetic causes of this are mutations in the cone cell cyclic nucleotide-gated ion channels CNGA3 (ACHM2) and CNGB3 (ACHM3) as well as the cone cell transducin, GNAT2 (ACHM4).A fourth genetic cause (ACHM5, OMIM 613093) was discovered in 2009.[1] It is a mutation of gene PDE6C, located on chromosome locus 10, 10q24. It is estimated that less than two percent of achromatopsias are caused by a mutation in this gene.[citation needed] ## Pathophysiology[edit] The hemeralopic aspect of achromatopsia can be diagnosed non-invasively using electroretinography. The response at low (scotopic) and median (mesotopic) light levels will be normal but the response under high light level (photopic) conditions will be absent. The mesotopic level is approximately a hundred times lower than the clinical level used for the typical high level electroretinogram. When as described, the condition is due to a saturation in the neural portion of the retina and not due to the absence of the photoreceptors per se.[citation needed] In general, the molecular pathomechanism of achromatopsia is either the inability to properly control or respond to altered levels of cGMP; particularly important in visual perception as its level controls the opening of cyclic nucleotide-gated ion channels (CNGs). Decreasing the concentration of cGMP results in closure of CNGs and resulting hyperpolarization and cessation of glutamate release.Native retinal CNGs are composed of 2 α- and 2 β-subunits, which are CNGA3 and CNGB3, respectively, in cone cells. When expressed alone, CNGB3 cannot produce functional channels, whereas this is not the case for CNGA3. Coassembly of CNGA3 and CNGB3 produces channels with altered membrane expression, ion permeability (Na+ vs. K+ and Ca2+), relative efficacy of cAMP/cGMP activation, decreased outward rectification, current flickering, and sensitivity to block by L-cis-diltiazem.[citation needed] Mutations tend to result in the loss of CNGB3 function or gain of function—often increased affinity for cGMP—of CNGA3. cGMP levels are controlled by the activity of the cone cell transducin, GNAT2. Mutations in GNAT2 tend to result in a truncated and, presumably, non-functional protein, thereby preventing alteration of cGMP levels by photons. There is a positive correlation between the severity of mutations in these proteins and the completeness of the achromatopsia phenotype.[citation needed] Molecular diagnosis can be established by identification of biallelic variants in the causative genes. Molecular genetic testing approaches used in achromatopsia can include targeted analysis for the common CNGB3 variant c.1148delC (p.Thr383IlefsTer13), use of a multigenerational panel, or comprehensive genomic testing.[citation needed] ### ACHM2[edit] While some mutations in CNGA3 result in truncated and, presumably, non-functional channels this is largely not the case. While few mutations have received in-depth study, at least one mutation does result in functional channels. Curiously, this mutation, T369S, produces profound alterations when expressed without CNGB3. One such alteration is decreased affinity for Cyclic guanosine monophosphate. Others include the introduction of a sub-conductance, altered single-channel gating kinetics, and increased calcium permeability.[citation needed] When mutant T369S channels coassemble with CNGB3, however, the only remaining aberration is increased calcium permeability.[2] While it is not immediately clear how this increase in Ca2+ leads to achromatopsia, one hypothesis is that this increased current decreases the signal-to-noise ratio. Other characterized mutations, such as Y181C and the other S1 region mutations, result in decreased current density due to an inability of the channel to traffic to the surface.[3] Such loss of function will undoubtedly negate the cone cell's ability to respond to visual input and produce achromatopsia. At least one other missense mutation outside of the S1 region, T224R, also leads to loss of function.[2] ### ACHM3[edit] While very few mutations in CNGB3 have been characterized, the vast majority of them result in truncated channels that are presumably non-functional. This will largely result in haploinsufficiency, though in some cases the truncated proteins may be able to coassemble with wild-type channels in a dominant negative fashion. The most prevalent ACHM3 mutation, T383IfsX12, results in a non-functional truncated protein that does not properly traffic to the cell membrane.[4][5] The three missense mutations that have received further study show a number of aberrant properties, with one underlying theme. The R403Q mutation, which lies in the pore region of the channel, results in an increase in outward current rectification, versus the largely linear current-voltage relationship of wild-type channels, concomitant with an increase in cGMP affinity.[5] The other mutations show either increased (S435F) or decreased (F525N) surface expression but also with increased affinity for cAMP and cGMP.[4][5] It is the increased affinity for cGMP and cAMP in these mutants that is likely the disorder-causing change. Such increased affinity will result in channels that are insensitive to the slight concentration changes of cGMP due to light input into the retina.[citation needed] ### ACHM4[edit] Upon activation by light, cone opsin causes the exchange of GDP for GTP in the guanine nucleotide binding protein (G-protein) α-transducing activity polypeptide 2 (GNAT2). This causes the release of the activated α-subunit from the inhibitory β/γ-subunits. This α-subunit then activates a phosphodiesterase that catalyzes the conversion of cGMP to GMP, thereby reducing current through CNG3 channels.As this process is absolutely vital for proper color processing it is not surprising that mutations in GNAT2 lead to achromatopsia. The known mutations in this gene, all result in truncated proteins. Presumably, then, these proteins are non-functional and, consequently, cone opsin that has been activated by light does not lead to altered cGMP levels or photoreceptor membrane hyperpolarization.[citation needed] ## Management[edit] There is generally no treatment to cure achromatopsia. However, dark red or plum colored filters are very helpful in controlling light sensitivity.[6] Since 2003, there is a cybernetic device called eyeborg that allows people to perceive color through sound waves.[7] Achromatopsic artist Neil Harbisson was the first to use such a device in early 2004, the eyeborg allowed him to start painting in color by memorizing the sound of each color.[8] Moreover, there is some research on gene therapy for animals with achromatopsia, with positive results on mice and young dogs, but less effectiveness on older dogs. However, no experiments have been made on humans. There are many challenges to conducting gene therapy for color blindness on humans.[citation needed] ## Epidemiology[edit] Achromatopsia is a relatively uncommon disorder, with a prevalence of 1 in 30,000 people.[9] However, on the small Micronesian atoll of Pingelap, approximately five percent of the atoll's 3,000 inhabitants are afflicted.[10][11] This is the result of a population bottleneck caused by a typhoon and ensuing famine in the 1770s, which killed all but about twenty islanders, including one who was heterozygous for achromatopsia.[citation needed] The people of this region have termed achromatopsia "maskun", which literally means "not see" in Pingelapese.[12] This unusual population drew neurologist Oliver Sacks to the island for which he wrote his 1997 book, The Island of the Colorblind.[citation needed] ## Terminology[edit] Acquired achromatopsia Cerebral achromatopsia Congenital or inherited achromatopsia 1\. Complete typical achromatopsia 2\. Incomplete atypical achromatopsia, or incomplete atypical dyschromatopsia ### Related[edit] Achromatopsia Complete lack of the perception of color in a subject, seeing only in black, white, and shades of grey. This is different from color agnosia, in which a person can perceive color—as measured by a matching task—but cannot recognize different colors. Amblyopia Defined conceptually by Sir Stewart Duke-Elder in 1973 as a monocular acuity deficit which is not due to refractive error or any organic abnormality.[13] Poor spatial performance of the precision optical servomechanism of the eyes at nominal illumination levels without any morphological cause. One form of lazy eye. Hemeralopia Reduced visual capacity in bright light, i.e. day-blindness. Nystagmus Term to describe both normal and pathological conditions related to the oculomotor system. In the current context, it is a pathological condition involving an uncontrolled oscillatory movement of the eyes during which the amplitude of oscillation is quite noticeable and the frequency of the oscillation tends to be quite low. Photophobia Avoidance of bright light by those suffering from hemeralopia. ## References[edit] ### Footnotes[edit] 1. ^ Thiadens 2009, pp. 240–247. 2. ^ a b Tränkner 2004, pp. 138–147. 3. ^ Patel 2005, pp. 2282–2290. 4. ^ a b Peng 2003, pp. 34533–34540. 5. ^ a b c Bright 2005, pp. 1141–1150. 6. ^ Corn 2010, p. 233. 7. ^ Ronchi 2009, p. 319. 8. ^ Pearlman 2015, pp. 84–90. 9. ^ Thiadens 2011, p. 59. 10. ^ Brody 1970, pp. 1253–1257. 11. ^ Hussels 1972, pp. 304–309. 12. ^ Morton 1972, pp. 277–289. 13. ^ Duke-Elder 1976. ### Sources[edit] * Bright, S. R.; et al. (2005). "Disease-associated mutations in CNGB3 produce gain of function alterations in cone cyclic nucleotide-gated channels". Mol. Vis. 11: 1141–1150. PMID 16379026. * Brody, J. A.; et al. (1970). "Hereditary blindness among Pingelapese people of Eastern Caroline Islands". Lancet. 295 (7659): 1253–1257. doi:10.1016/s0140-6736(70)91740-x. PMID 4192495. * Corn, A. N.; et al. (2010). Foundations of low vision: clinical and functional perspectives. Arlington: AFB Press. ISBN 9780891288831. * Duke-Elder, S.; et al. (1976). Ocular motility and strabismus. System of Ophthalmology. 6. London: Kimpton. ISBN 9780853137764. * Hussels, I. E.; et al. (1972). "Pingelap and Mokil Atolls: achromatopsia". Am. J. Hum. Genet. 24 (3): 304–309. PMC 1762260. PMID 4555088. * Morton, N. E.; et al. (1972). "Pingelap and Mokil Atolls: historical genetics". Am. J. Hum. Genet. 24 (3): 277–289. PMC 1762283. PMID 4537352. * Patel, K. A.; et al. (2005). "Transmembrane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of function and impaired cellular trafficking of the cone CNG channel". Investig. Ophthalmol. Vis. Sci. 46 (7): 2282–2290. doi:10.1167/iovs.05-0179. PMID 15980212.CS1 maint: ref=harv (link) * Pearlman, E. (2015). "I, Cyborg". PAJ. 37 (2): 84–90. doi:10.1162/PAJJ_a_00264. S2CID 57562971. * Peng, C.; et al. (2003). "Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels". J. Biol. Chem. 278 (36): 34533–34540. doi:10.1074/jbc.M305102200. PMID 12815043.CS1 maint: ref=harv (link) * Ronchi, A. M. (2009). eCulture: cultural content in the digital age. Berlin: Springer. ISBN 9783540752738. * Thiadens, A. A. H. J.; et al. (2009). "Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders". Am. J. Hum. Genet. 85 (2): 240–247. doi:10.1016/j.ajhg.2009.06.016. PMC 2725240. PMID 19615668. * Thiadens, A. A. H. J. (2011). Genetic etiology and clinical consequences of cone disorders. Erasmus University Rotterdam. ISBN 9789461690579. * Tränkner, D.; et al. (2004). "Molecular basis of an inherited form of incomplete achromatopsia". J. Neurosci. 24 (1): 138–147. doi:10.1523/JNEUROSCI.3883-03.2004. PMC 6729583. PMID 14715947.CS1 maint: ref=harv (link) ## External links[edit] Look up achromatopsia in Wiktionary, the free dictionary. * Achromatopsia at MedicineNet * Achromatopsia at Merriam-Webster * Achromatopsia at NCBI Classification D * ICD-10: H53.5 * ICD-9-CM: 368.54 * OMIM: 216900 * MeSH: D003117 * DiseasesDB: 83 External resources * MedlinePlus: 001002 * GeneReviews: NBK1418 * GARD: ACHM * Orphanet: 49382 Achromatopsia * v * t * e Color topics * Red * Orange * Yellow * Green * Cyan * Blue * Indigo * Violet * Purple * Magenta * Pink * Brown * White * Gray * Black Color science Color physics * Electromagnetic spectrum * Light * Rainbow * Visible * Spectral colors * Chromophore * Structural coloration * Animal coloration * Color of chemicals * Water * On Vision and Colours * Metamerism * Spectral power distribution Color perception * Color vision * Color blindness * Achromatopsia * test * Tetrachromacy * Color constancy * Color term * Color depth * Color photography * Spot color * Color 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prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis Authority control * GND: 4242792-7 * LCCN: sh85028584 * NLI: 000664610 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Achromatopsia	c0152200	6,159	wikipedia	https://en.wikipedia.org/wiki/Achromatopsia	2021-01-18T18:51:55	{"mesh": ["D003117"], "umls": ["C0152200"], "orphanet": ["49382"], "wikidata": ["Q432396"]}
Primary oculocerebral lymphoma is a rare, primary, organ-specific, extranodal non-Hodgkin's lymphoma (typically diffuse large B-cell lymphoma), simultaneously affecting the intraocular compartments (retina, vitreous, optic nerve, uvea and others) and the central nervous system (commonly the cerebellum, spinal cord or pia mater). The presenting symptoms vary depending on the localization of the tumor and may include vitreous floaters or blurred vision, raised intracranial pressure (headache, vomiting, papilledema) and/or focal neurological deficits. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Primary oculocerebral lymphoma	None	6,160	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=279897	2021-01-23T16:57:06	{"synonyms": ["Primary oculocerebral non-Hodgkin lymphoma"]}
Neural tube defect involving absence of much of the brain, skull and scalp Anencephaly Illustration of an anencephalic fetus SpecialtyMedical genetics; pediatrics Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development.[1] It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day following conception.[2] Strictly speaking, the Greek term translates as "without a brain" (or totally lacking the inside part of the head), but it is accepted that children born with this disorder usually only lack a telencephalon,[3] the largest part of the brain consisting mainly of the cerebral hemispheres, including the neocortex, which is responsible for cognition. The remaining structure is usually covered only by a thin layer of membrane—skin, bone, meninges, etc. are all lacking.[4] With very few exceptions,[5] infants with this disorder do not survive longer than a few hours or possibly days after their birth. ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Relation to genetic ciliopathy * 3 Diagnosis * 3.1 Meroanencephaly * 3.2 Holoanencephaly * 3.3 Craniorachischisis * 4 Prognosis * 5 Epidemiology * 6 Ethical issues * 6.1 Organ donation * 6.2 Brain death * 6.3 Pregnancy termination * 6.4 Legal proceedings * 6.4.1 United States uniform acts * 7 Research * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] The National Institute of Neurological Disorders and Stroke (NINDS) describes the presentation of this condition as follows: "A baby born with anencephaly is usually blind, deaf, unaware of its surroundings and unable to feel pain. Although some individuals with anencephaly may be born with a main brain stem, the lack of a functioning cerebrum permanently rules out the possibility of ever gaining awareness of their surroundings. Reflex actions such as breathing and responses to sound or touch may occur."[4] Due to the presence of the brainstem, children with anencephaly have almost all the primitive reflexes of a newborn, responding to auditory, vestibular and painful stimuli.[6] This means that the child can move, smile, suckle and breathe without the aid of devices.[7] A side view of an anencephalic fetus A front view of an anencephalic fetus X-ray of an anencephalic stillborn fetus ## Causes[edit] The cause of anencephaly is disputed by medical professionals and researchers. Folic acid has been shown to be important in neural tube formation since at least 1991,[8][9] and as a subtype of neural tube defect, folic acid may play a role in anencephaly. Studies have shown that the addition of folic acid to the diet of women of child-bearing age may significantly reduce, although not eliminate, the incidence of neural tube defects. Therefore, it is recommended that all women of child-bearing age consume 0.4 mg of folic acid daily,[4] especially those attempting to conceive or who may possibly conceive, as this can reduce the risk to 0.03%.[10] It is not advisable to wait until pregnancy has begun, since, by the time a woman knows she is pregnant, the critical time for the formation of a neural tube defect has usually already passed. A physician may prescribe even higher dosages of folic acid (5 mg/day) for women having had a previous pregnancy with a neural tube defect.[10] In general, neural tube defects do not follow direct patterns of heredity, though there is some indirect evidence of inheritance,[11] and recent animal models indicate a possible association with deficiencies of the transcription factor TEAD2.[12] Studies show that a woman who has had one child with a neural tube defect such as anencephaly has about a 3% risk of having another child with a neural tube defect,[13] as opposed to the background rate of 0.1% occurrence in the population at large.[14] Genetic counseling is usually offered to women at a higher risk of having a child with a neural tube defect to discuss available testing. An infant with anencephaly and acrania It is known that people taking certain anticonvulsants and people with insulin-dependent diabetes have a higher risk of having a child with a neural tube defect.[15] ### Relation to genetic ciliopathy[edit] Until recently, medical literature did not indicate a connection among many genetic disorders, both genetic syndromes and genetic diseases, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause despite the widely varying set of medical symptoms that are clinically visible in the disorders. Anencephaly is one such disease, part of an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell, organelles present in many cellular types throughout the human body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and, thus, offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel–Gruber syndrome, and some forms of retinal degeneration.[16] ## Diagnosis[edit] Ultrasound image of fetus with anencephaly. Anencephaly can often be diagnosed before birth through an ultrasound examination. The maternal serum alpha-fetoprotein (AFP screening)[17] and detailed fetal ultrasound[18] can be useful for screening for neural tube defects such as spina bifida or anencephaly. ### Meroanencephaly[edit] Meroanencephaly is a rare form of anencephaly characterized by malformed cranial bones, a median cranial defect, and a cranial protrusion called area cerebrovasculosa. Area cerebrovasculosa is a section of abnormal, spongy, vascular tissue admixed with glial tissue ranging from simply a membrane to a large mass of connective tissue, hemorrhagic vascular channels, glial nodules, and disorganized choroid plexuses.[19] ### Holoanencephaly[edit] The most common type of anencephaly, where the brain has entirely failed to form, except for the brain stem. Infants rarely survive more than one day after birth with holoanencephaly.[19] ### Craniorachischisis[edit] Main article: Rachischisis The most severe type of anencephaly where area cerebrovasculosa and area medullovasculosa fill both cranial defects and the spinal column. Craniorachischisis is characterized by anencephaly accompanied by bony defects in the spine and the exposure of neural tissue as the vault of the skull fails to form.[19][20] Craniorachischisis occurs in about 1 of every 1000 live births, but various physical and chemical tests can detect neural tube closure during early pregnancy.[21] ## Prognosis[edit] There is no cure or standard treatment for anencephaly. Prognosis is extremely poor, as many anencephalic fetuses do not survive birth and infants that are not stillborn will usually die within a few hours or days after birth from cardiorespiratory arrest.[4] In almost all cases, anencephalic infants are not aggressively resuscitated because there is no chance of the infants ever achieving a conscious existence. Instead, the usual clinical practice is to offer hydration, nutrition, and comfort measures and to "let nature take its course". Artificial ventilation, surgery (to fix any co-existing congenital defects), and drug therapy (such as antibiotics) are usually regarded as futile efforts. Some clinicians and medical ethicists view even the provision of nutrition and hydration as medically futile.[citation needed] ## Epidemiology[edit] In the United States, anencephaly occurs in about 1 out of every 10,000 births.[22] Rates may be higher among Africans with rates in Nigeria estimated at 3 per 10,000 in 1990 while rates in Ghana estimated at 8 per 10,000 in 1992.[23] Rates in China are estimated at 5 per 10,000.[23] Research has suggested that, overall, female babies are more likely to be affected by the disorder.[24] ## Ethical issues[edit] ### Organ donation[edit] One issue concerning anencephalic newborns is organ donation. Initial legal guidance came from the case of Baby Theresa in 1992, in which the boundaries of organ donation were tested for the first time.[25] Infant organs are scarce, and the high demand for pediatric organ transplants poses a major public health issue. In 1999, it was found that among children who die under the age of two, 30–50% do so while awaiting transplant.[25] In order for infant organs to be viable and used for transplant, they must be removed while the infant still has circulation or very soon after circulation has ceased. However, this poses both legal and ethical issues. In the United States, all states have laws that forbid the removal of organs from a donor until after the donor has died, except in the case of altruistic living donations of a kidney or liver segment. The goal of those in support of organ donation is that it will further contribute to the pool of suitable organs for transplants while the need for lifesaving organ transplants is so great. It has been estimated that 400–500 infant hearts and kidneys and 500–1,000 infant livers are needed in the United States each year.[26] Because anencephalic neonates have partially functioning brain stems, they possess some brain stem reflexes such as spontaneous respirations. For this reason, these patients cannot be declared brain dead. Within the medical community, the main ethical issues with organ donation are a misdiagnosis of anencephaly, the slippery slope argument, that anencephalic neonates would rarely be a source of organs, and that it would undermine confidence in organ transplantation.[27] Slippery slope concerns are a major issue in personhood debates, across the board. In regards to anencephaly, those who oppose organ donation argue that it could open the door for involuntary organ donors such as an elderly person with severe dementia. Another point of contention is the number of children who would actually benefit. There are discrepancies in statistics; however, it is known that most anencephalic children are stillborn.[27] Proposals have been made to bypass the legal and ethical issues surrounding organ donation. These include waiting for death to occur before procuring organs, expanding the definition of death, creating a special legal category for anencephalic infants, and defining them as non-persons.[28] In the United Kingdom, a child born with anencephaly was reported as the country's youngest organ donor. Teddy Houlston was diagnosed as anencephalic at 12 weeks of gestation. His parents, Jess Evans and Mike Houlston, decided against abortion and instead proposed organ donation. Teddy was born on 22 April 2014, in Cardiff, Wales, and lived for 100 minutes, after which his heart and kidneys were removed. His kidneys were later transplanted into an adult in Leeds. Teddy's twin, Noah, was born healthy.[29] ### Brain death[edit] There are four different concepts used to determine brain death: failure of heart, failure of lungs, whole brain death, and neocortical death. Neocortical death, similar to a persistent vegetative state (PVS), involves loss of cognitive functioning of the brain. A proposal by law professor David Randolph Smith,[30] in an attempt to prove that neocortical death should legally be treated the same as brain death, involved PET scans to determine the similarities. However, this proposal has been criticized on the basis that confirming neocortical death by PET scan may risk indeterminacy.[31] ### Pregnancy termination[edit] Anencephaly can be diagnosed before delivery with a high degree of accuracy. Although anencephaly is a fatal condition, the option of abortion is dependent on the abortion laws in the state.[26] According to a 2013 report, 26% of the world's population reside in a country where abortion is generally prohibited.[26] [32] In 2012, Brazil extended the right of abortion to mothers with anencephalic fetuses. This decision is, however, receiving much disapproval by several religious groups.[33] ### Legal proceedings[edit] The case of baby Theresa was the beginning of the ethical debate over anencephalic infant organ donation.[25] The story of baby Theresa remains a focus of basic moral philosophy. Baby Theresa was born with anencephaly in 1992. Her parents, knowing that their child was going to die, requested that her organs be given for transplantation. Although her physicians agreed, Florida law prohibited the infant's organs from being removed while she was still alive. By the time she died nine days after birth, her organs had deteriorated past the point of being viable.[34] Baby K was an anencephalic infant that was kept alive for two years and 174 days under intensive care by order of the US Court of Appeals for the Fourth Circuit. #### United States uniform acts[edit] The Uniform Determination of Death Act (UDDA) is a model bill, adopted by many US states, stating that an individual who has sustained either 1) irreversible cessation of circulatory and respiratory functions or 2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead. This bill was a result of much debate over the definition of death and is applicable to the debate over anencephaly. A related bill, the Uniform Anatomical Gift Act (UAGA), grants individuals and, after death, their family members the right to decide whether or not to donate organs. Because it is against the law for any person to pay money for an organ, the person in need of an organ transplant must rely on a volunteer.[26] There have been two state bills that proposed to change current laws regarding death and organ donation. California Senate Bill 2018 proposed to amend the UDDA to define anencephalic infants as already dead, while New Jersey Assembly Bill 3367 proposed to allow anencephalic infants to be organ sources even if they are not dead.[26][35] ## Research[edit] Some genetic research has been conducted to determine the causes of anencephaly. It has been found that cartilage homeoprotein (CART1) is selectively expressed in chondrocytes (cartilage cells). The CART1 gene to chromosome 12q21.3–q22 has been mapped. Also, it has been found that mice homozygous for deficiency in the Cart1 gene manifested acrania and meroanencephaly, and prenatal treatment with folic acid will suppress acrania and meroanencephaly in the Cart1-deficient mutants.[36][37] ## See also[edit] * Acalvaria ## References[edit] 1. ^ "Cephalic disorders – Overview, Anencephaly, Colpocephaly – neurologychannel". September 3, 2015. Archived from the original on May 9, 2008. Retrieved September 19, 2016. 2. ^ O'Rahilly, M; Muller, F (1992). Human Embryology & Teratology. New York: Wiley-Liss, Inc. p. 253. ISBN 978-0471382256. 3. ^ Chervenak, F.A.; Kurjak, A.; Comstock, C.H. (1995). Ultrasound and the Fetal Brain: Progress in Obstetric and Gynecological Sonography Series (1st publ ed.). New York: Parthenon Pub. Group. p. 102. ISBN 978-1850706120. 4. ^ a b c d "Anencephaly Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". Archived from the original on 2 December 2016. Retrieved 2016-12-02. 5. ^ "Baby Without A Brain, Nickolas Coke, Update". Archived from the original on 2012-09-14. 6. ^ DIAMENT, Aron (1996). Neurologia Infantil. 3ª Edição. São Paulo: Atheneu. p. 745. 7. ^ Luyendijk, W; Treffers, PD (1992). "The smile in anencephalic infants". Clinical Neurology and Neurosurgery. 94 Suppl: S113-7. doi:10.1016/0303-8467(92)90042-2. PMID 1320482. 8. ^ Centers for Disease Control (CDC) (1991-08-02). "Use of folic acid for prevention of spina bifida and other neural tube defects--1983-1991". MMWR. Morbidity and Mortality Weekly Report. 40 (30): 513–516. ISSN 0149-2195. PMID 2072886. 9. ^ "Lancet 1991; 338:8760:131-137". www.sjsu.edu. Archived from the original on 2018-04-08. Retrieved 2018-12-10. 10. ^ a b Ratcliffe, Stephen D., ed. (2008). Family medicine obstetrics (3rd ed.). Philadelphia: Mosby Elsevier. ISBN 978-0-323-04306-9.[page needed] 11. ^ Shaffer, Lisa G.; Marazita, Mary L.; Bodurtha, Joann; Newlin, Anna; Nance, Walter E. (1990). "Evidence for a major gene in familial anencephaly". American Journal of Medical Genetics. 36 (1): 97–101. doi:10.1002/ajmg.1320360119. PMID 2333913. 12. ^ Kaneko, Kotaro J.; Kohn, Matthew J.; Liu, Chengyu; Depamphilis, Melvin L. (2007). "Transcription factor TEAD2 is involved in neural tube closure". Genesis. 45 (9): 577–87. doi:10.1002/dvg.20330. PMC 2765819. PMID 17868131. 13. ^ Cowchock, S.; Ainbender, E.; Prescott, G.; Crandall, B.; Lau, L.; Heller, R.; Muir, W. A.; Kloza, E.; et al. (1980). "The recurrence risk for neural tube defects in the United States: A collaborative study". American Journal of Medical Genetics. 5 (3): 309–14. doi:10.1002/ajmg.1320050314. PMID 7405962. 14. ^ "Archived copy". Archived from the original on 2011-03-04. Retrieved 2011-04-01.CS1 maint: archived copy as title (link)[full citation needed] 15. ^ "Anencephaly". Genetics Home Reference. National Institutes of Health. 22 August 2011. Archived from the original on 2011-08-05. Retrieved 28 August 2011. 16. ^ Badano, Jose L.; Mitsuma, Norimasa; Beales, Phil L.; Katsanis, Nicholas (2006). "The Ciliopathies: An Emerging Class of Human Genetic Disorders". Annual Review of Genomics and Human Genetics. 7: 125–48. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. 17. ^ Joó JG, Beke A, Papp C, et al. (2007). "Neural tube defects in the sample of genetic counselling". Prenat. Diagn. 27 (10): 912–21. doi:10.1002/pd.1801. PMID 17602445. 18. ^ Cedergren M, Selbing A (2006). "Detection of fetal structural abnormalities by an 11-14-week ultrasound dating scan in an unselected Swedish population". Acta Obstetricia et Gynecologica Scandinavica. 85 (8): 912–5. doi:10.1080/00016340500448438. PMID 16862467. 19. ^ a b c Isada, Nelson B.; Qureshi, Faisal; Jacques, Suzanne M.; Holzgreve, Wolfgang; Tout, Mary Jo; Johnson, Mark P.; Evans, Mark I. (1993). "Meroanencephaly: Pathology and Prenatal Diagnosis". Fetal Diagnosis and Therapy. 8 (6): 423–8. doi:10.1159/000263862. PMID 8286034. 20. ^ Murlimanju, N; Vishal, K; Maligi, AM; Naveen, NS (2010). "Craniorachischisis totalis". Journal of Neurosciences in Rural Practice. 1 (1): 54–5. doi:10.4103/0976-3147.63108. PMC 3137839. PMID 21799625. 21. ^ Gilbert, Scott F. (2010). Developmental biology (9th ed.). Sunderland, Mass.: Sinauer Associates. p. 338. ISBN 978-0878933846. 22. ^ "Anencephaly". PubMed Health. May 1, 2011. Archived from the original on 2014-03-28. Retrieved 2017-10-31. 23. ^ a b Neural Tube Defects : From Origin to Treatment: From Origin to Treatment. Oxford University Press. 2005. pp. 125–126. ISBN 9780199775149. Archived from the original on 2016-01-31. Retrieved 2015-08-09. 24. ^ Timson, J. (1970). "The sex ratio in anencephaly". Genetica. 41 (3): 457–65. doi:10.1007/BF00958926. PMID 4922971. 25. ^ a b c Bard, Jennifer S. (1999). "The diagnosis is anencephaly and the parents ask about organ donation: Now what? A guide for hospital counsel and ethics committees". Western New England Law Review. 21 (1): 49–95. PMID 12774804. Archived from the original on 2014-03-26. Retrieved 2012-07-20. 26. ^ a b c d e Meinke, Sue (June 1989). "Anencephalic Infants as Potential Organ Sources: Ethical and Legal Issues" (PDF). National Reference Center for Bioethics Literature. Archived (PDF) from the original on 2012-05-22. Retrieved 19 July 2012. Cite journal requires `\|journal=` (help) 27. ^ a b Glasson, John; Plows, Charles W.; Clarke, Oscar W.; Cosgriff, James H.; Kliger, Craig H.; Ruff, Victoria N.; Tenery, Robert M.; Wilkins, George T.; et al. (1995). "The Use of Anencephalic Neonates as Organ Donors". JAMA. 273 (20): 1614–8. doi:10.1001/jama.1995.03520440068039. PMID 7745776. 28. ^ Ahmad, Ferhaan (1992). "Anencephalic infants as organ donors: Beware the slippery slope". CMAJ. 146 (2): 236–241, 244. PMC 1488368. PMID 1735049. 29. ^ [1] Archived 2018-05-28 at the Wayback Machine. BBC News. Retrieved on 2015-04-23. 30. ^ "Archived copy" (PDF). Archived (PDF) from the original on 2013-10-15. Retrieved 2013-10-15.CS1 maint: archived copy as title (link) 31. ^ Beresford, H. Richard (July 1996). "Ethics in Neuroscience: Mind over Matter" (PDF). Indiana University. Archived from the original (PDF) on November 1, 2005. 32. ^ "The World's Abortion Laws Map 2013 Update" (PDF). Archived (PDF) from the original on 2015-12-02. Retrieved 2015-11-30. 33. ^ "Anencephaly in Brazil: A New Decision, Old Issues". Archived from the original on 13 May 2012. Retrieved 19 July 2012. 34. ^ Rachels, James. "What is Morality" (PDF). Archived (PDF) from the original on 2014-12-14. Retrieved 19 July 2012. 35. ^ "Uniform Declaration of Death Act (UDDA)". Archived from the original on 2013-09-06. Retrieved 2013-08-23. 36. ^ Chen, Chih-Ping (2008). "Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (III)". Taiwanese Journal of Obstetrics and Gynecology. 47 (2): 131–40. doi:10.1016/S1028-4559(08)60070-4. PMID 18603496. 37. ^ Zhao, Qi; Behringer, Richard R.; De Crombrugghe, Benoit (1996). "Prenatal folic acid treatment suppresses acrania and meroanencephaly in mice mutant for the Cart1 homeobox gene". Nature Genetics. 13 (3): 275–83. doi:10.1038/ng0796-275. PMID 8673125. ## External links[edit] Classification D * ICD-10: Q00.0 * ICD-9-CM: 740.0 * OMIM: 206500 * MeSH: D000757 * DiseasesDB: 705 External resources * MedlinePlus: 001580 * eMedicine: neuro/639 Wikimedia Commons has media related to Anencephaly. * v * t * e Congenital malformations and deformations of nervous system Brain Neural tube defect * Anencephaly * Acephaly * Acrania * Acalvaria * Iniencephaly * Encephalocele * Chiari malformation Other * Microcephaly * Congenital hydrocephalus * Dandy–Walker syndrome * other reduction deformities * Holoprosencephaly * Lissencephaly * Microlissencephaly * Pachygyria * Hydranencephaly * Septo-optic dysplasia * Megalencephaly * Hemimegalencephaly * CNS cyst * Porencephaly * Schizencephaly * Polymicrogyria * Bilateral frontoparietal polymicrogyria Spinal cord Neural tube defect * Spina bifida * Rachischisis Other * Currarino syndrome * Diastomatomyelia * Syringomyelia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Anencephaly	c0002902	6,161	wikipedia	https://en.wikipedia.org/wiki/Anencephaly	2021-01-18T18:55:47	{"gard": ["5808"], "mesh": ["D000757"], "umls": ["C0002902"], "icd-9": ["740.0"], "orphanet": ["1048"], "wikidata": ["Q529292"]}
A rare chromosomal anomaly characterized by an extremely variable clinical phenotype and may include heart defects, urogenital abnormalities, velopharyngeal insufficiency with or without cleft palate, and ranging from multiple defects to mild learning difficulties with some individuals being essentially normal. ## Epidemiology Up till now more than 50 unrelated cases have been reported with a high frequency of familial duplications. ## Clinical description The age at diagnosis is variable and depends on the clinical manifestations. The clinical presentation of patients shares features with 22q11.2 deletion syndrome (DG/VCFS), including heart defects, velopharyngeal insufficiency with or without cleft palate. The clinical picture is highly variable with incomplete penetrance, ranging from multiple defects with severe intellectual disability to mild learning difficulties with some individuals being essentially normal. Bladder exstrophy, a very rare malformation in the general population, is significantly associated with the duplication. A high rate of autism spectrum disorder is found. Congenital heart defects and urogenital anomalies can be detected in utero, whereas asymptomatic individuals are usually diagnosed after the birth of a severely affected relative. ## Etiology The basis of this clinical variability remains unclear. The low-copy repeats spanning the region 22q11.2 (LCR22) predispose to homologous recombination events, often nonallelic, that result in rearrangements of 22q11.2. The large majority of affected individuals have identical 3Mb microduplications; however, proximal nested 1.5 Mb duplications or larger duplications are also reported. The 3Mb duplication encompasses a region containing 40 genes including the TBX1 gene that has been shown to be the major disease gene responsible for DG/VCFS. Interestingly, TBX1 gain-of-function mutations resulting in the same phenotypic spectrum as haploinsufficiency have been observed, and suggests that TBX1 overexpression might be responsible for the 22q11.2 duplication syndrome. ## Diagnostic methods The 22q11.2 duplication is detected by fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification, array comparative genome hybridization (aCGH) or genome-wide SNP (single nucleotide polymorphism) microarrays. ## Differential diagnosis The main differential diagnosis is DG/VCFS. ## Antenatal diagnosis Detection of the duplication on fetal sample by FISH or a-CGH should be discussed with the parents of an index case during subsequent pregnancies or when a parent carries the microduplication. ## Genetic counseling Transmission is autosomal dominant. Most cases are inherited from a pauci or asymptomatic parent. An affected individual has a 50% risk of transmitting the duplication. ## Management and treatment Symptomatic treatment should be proposed by a multidisciplinary team including pediatricians, child psychiatrists. ## Prognosis Prognosis is variable. Marked inter and intrafamilial variability is observed among patients. Some patients have been reported to have significant cardiovascular malformations leading to early death. * 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 [mRNA]: messenger RNA *[kDa]: kilodalton	22q11.2 duplication syndrome	c2675369	6,162	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1727	2021-01-23T19:09:54	{"gard": ["10557"], "mesh": ["C567224"], "omim": ["608363"], "umls": ["C2675369"], "icd-10": ["Q92.3"], "synonyms": ["22q11.2 microduplication syndrome", "Dup(22)(q11)", "Duplication 22q11.2", "Trisomy 22q11.2"]}
McKusick (1966) reported on a woman with proportionate dwarfism and bilateral dislocated hips. She was the product of a first-cousin marriage; her great-grandmother (through whom her parents were related) was dwarfed also. The patient died following surgery for rheumatic heart disease. Fuhrmann (1972) reported sisters with proportionate dwarfism and dislocation of the hip. The vertebral bodies showed columnization (greater height than AP dimension). Skel \- Dislocated hips \- Vertebral body columnization Growth \- Proportionate dwarfism Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	DWARFISM, PROPORTIONATE, WITH HIP DISLOCATION	c1857196	6,163	omim	https://www.omim.org/entry/223550	2019-09-22T16:28:40	{"mesh": ["C565614"], "omim": ["223550"]}
Recurrent respiratory papillomatosis is a rare respiratory disease characterized by the development of exophytic papillomas, affecting the mucosa of the upper aero-digestive tract (with a strong predilection for the larynx), caused by an infection with human papilloma virus. Symptoms at presentation may include hoarseness, chronic cough, dyspnea, recurrent upper respiratory tract infections, pneumonia, dysphagia, stridor, and/or failure to thrive. ## Epidemiology The prevalence of recurrent respiratory papillomatosis (RRP) is estimated at about 1/70,400 in the United Kingdom. Annual incidence of the disease is about 1/23,300 in children and 1/55,500 in adults in the United States. The adult form affects males more often than females. ## Clinical description A bimodal age distribution is characteristic, with the disease affecting either young children or young adults. Manifestations depend on the extent and progression of the lesions and include hoarseness, cough, wheezing, voice change, chronic dyspnea, choking and syncope. The symptoms tend to be more severe in children because of the rapid growth of the lesions and can lead to potentially life-threatening airway compromise. Coexisting laryngopharyngeal reflux disease worsens the clinical manifestations of RRP. The clinical course is variable ranging from mild disease with spontaneous remission to an aggressive disease or a chronic clinical course. ## Etiology RRP is caused by a human papillomavirus (HPV) infection. HPV-6 and HPV-11 account for most cases of RRP and within HPV subtypes are considered to be ''low-risk'', or generally not associated with malignancy. Nevertheless, HPV-11 infections most commonly present with an aggressive disease course. Rarely, RRP is caused by HPV types 16, 18, 31, and 33. In neonates, vertical transmission from an infected mother with noticeable genital warts at the time of delivery has been documented. Following infection in humans, HPV is able to promote a specific immune system dysfunction, hence favoring the development of papillomatosis. It is theorized that such behavior is related to specific virus capabilities and a possible genetic predisposition. ## Diagnostic methods Endoscopy is the reliable method used to reach a definite diagnosis. Multiple non-necrotic cauliflower-like smooth lesions can be observed on endoscopy. HPV genotyping can be performed by the detection of HPV DNA by polymerase chain reaction with consensus primers and subsequent restriction mapping or hybridization methods. ## Differential diagnosis The differential diagnosis includes acute laryngitis, upper respiratory tract infection, asthma, bronchitis, and other benign or malignant laryngeal tumors. ## Management and treatment The treatment goals when dealing with RRP are to secure airway patency, preserve the underlying laryngeal tissues, and maintain an acceptable quality of voice. Surgery is performed using either a microscope or an endoscope, adopting a variety of lasers or a microdebrider in order to debulk/remove the papilloma lesions. Complications that might follow surgical procedures include laryngeal stenosis and/or synechiae, which are usually less frequent when using a microdebrider. Adjuvant therapy, often offered to patients that require several surgical procedures, usually includes cidofovir and bevacizumab. Interferon, various virostatics (acyclovir, valacyclovir and cidofovir), indole-3-carbinol, office-based photoangiolytic laser surgery/photodynamic therapy, celecoxib, and the HPV vaccine have also been suggested or investigated (either in the past or are currently undergoing research) as possible treatment options. ## Prognosis The prognosis is often good and morbidity low in most cases. Younger children, especially those under the age of 3 years, and adults with HPV-11 infection generally experience a more severe disease course. Malignant degeneration can rarely occur. Resistance to therapy, frequent recurrences, and lower airway involvement are factors associated with a poorer prognosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Recurrent respiratory papillomatosis	c1168198	6,164	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=60032	2021-01-23T17:20:14	{"gard": ["111"], "mesh": ["C535297"], "umls": ["C1168198"]}
## Description Band 3 is the major glycoprotein of the erythrocyte membrane. It mediates exchange of chloride and bicarbonate across the phospholipid bilayer and plays a central role in respiration of carbon dioxide. It is a 93,000-Da protein composed of 2 distinct domains that function independently. The 50,000-Da C-terminal polypeptide codes for the transmembrane domain that is involved in anion transport. The 43,000-Da cytoplasmic domain anchors the membrane cytoskeleton to the membrane through an ankyrin-binding site (band 2.1) and also contains binding sites for hemoglobin and several glycolytic enzymes. Proteins related to red cell band 3 have been identified in several types of nucleated somatic cells (review by Palumbo et al., 1986). Cloning and Expression Lux et al. (1989) cloned human band 3 from a fetal liver cDNA library. The deduced 911-amino acid protein is similar in structure to other anion exchangers and is divided into 3 regions: a hydrophobic, cytoplasmic domain that interacts with a variety of membrane and cytoplasmic proteins (residues 1-403); a hydrophobic, transmembrane domain that forms the anion antiporter (residues 404-882); and an acidic, C-terminal domain (residues 883-911). Lux et al. (1989) presented a model in which the protein crosses the membrane 14 times. Gene Function Langdon and Holman (1988) concluded that band 3 constitutes the major glucose transporter of human erythrocytes. A monoclonal antibody to band 3 specifically removed band 3 and more than 90% of the reconstitutable glucose transport activity from extracts of erythrocyte membranes; nonimmune serum removed neither. Band 3 is probably a multifunctional transport protein responsible for transport of glucose, anions, and water. Senescent cell antigen (SCA), an aging antigen, is a protein that appears on old cells and marks them for removal by the immune system. The aging antigen is generated by the degradation of protein band 3. Besides its role in the removal of senescent and damaged cells, SCA also appears to be involved in the removal of erythrocytes in hemolytic anemias and the removal of malaria-infected erythrocytes. Band 3 is found in diverse cell types and tissues besides erythrocytes, including hepatocytes, squamous epithelial cells, lung alveolar cells, lymphocytes, kidney, neurons, and fibroblasts. It is also present in nuclear, Golgi, and mitochondrial membranes. Kay et al. (1990) used synthetic peptides to identify antigenic sites on band 3 recognized by the IgG that binds to old cells. Tanner (1993) discussed the molecular and cellular biology of the erythrocyte anion exchanger, band 3. It permits the high rate of exchange of chloride ion by bicarbonate ion across the red cell membrane: the efflux of bicarbonate from the cell in exchange for plasma chloride ion in the capillaries of the tissues (the Hamburger shift, or chloride ion shift) and the reverse process in lung capillaries. At least 2 nonerythroid anion exchange genes have been characterized, AE2 (109280) and AE3 (106195), and tentative evidence for a fourth member of the class, AE4 (SLC4A9; 610207), was mentioned. The ability of AE2 and AE3 to mediate anion transport has been confirmed. As outlined by Tanner (1993), it is not strictly accurate to refer to the AE1 gene as being that for the erythroid anion exchanger because the AE1 gene is expressed in some nonerythroid tissues, where it appears to be transcribed from different tissue-specific promoters. Watts et al. (1996) determined that both ZAP70 (176947) and LCK (153390) can phosphorylate the cytoplasmic fragment of BND3. However, these 2 protein tyrosine kinases act on different sites of the BND3 protein. Pawloski et al. (2001) demonstrated that in human erythrocytes hemoglobin-derived S-nitrosothiol (SNO), generated from imported nitric acid (NO), is associated predominantly with the red blood cell membrane, and principally with cysteine residues in the hemoglobin-binding cytoplasmic domain of the anion exchanger AE1. Interaction with AE1 promotes the deoxygenated structure in SNO-hemoglobin, which subserves NO group transfer to the membrane. Furthermore, Pawloski et al. (2001) showed that vasodilatory activity is released from this membrane precinct by deoxygenation. Thus, the oxygen-regulated cellular mechanism that couples the synthesis and export of hemoglobin-derived NO bioactivity operates, at least in part, through formation of AE1-SNO at the membrane-cytosol interface. Goel et al. (2003) identified a sialic acid-independent host-parasite interaction involved in the Plasmodium falciparum malaria parasite invasion of red blood cells. They showed that 2 nonglycosylated extracellular regions of band 3 function as a crucial host receptor. They identified 2 processing products of merozoite surface protein-1 (MSP1) as major parasite ligands binding to the band 3 receptor. Bruce et al. (2004) studied the properties of band 3 in red cells lacking glycophorin A (GPA; 617922) and found that sulfate, iodide, and chloride transport were reduced. Increased flexibility of the membrane domain of band 3 was associated with reduced anion transport activity. Bruce et al. (2004) suggested that band 3 in the red cell can take up 2 different structures: one with high anion transport activity when GPA is present and one with lower anion transport activity when GPA is absent. By yeast 2-hybrid analysis, affinity copurification, coimmunoprecipitation, and fluorescence-based protein fragment complementation, Nuiplot et al. (2015) confirmed direct interaction between TMEM139 and the kidney isoform of AE1 (kAE1). Knockdown of TMEM139 expression in HEK293T cells reduced membrane localization of kAE1. In contrast, overexpression of TMEM139 increased kAE1 surface expression. Gene Structure Schofield et al. (1994) demonstrated that the EPB3 gene extends over 18 kb and consists of 20 exons. The cDNA sequence comprises 4,906 nucleotides, excluding the poly(A) tail. They found extensive similarity between the human and mouse genes, although the latter covers 17 kb. The additional length of the human gene is mainly caused by the presence of 6 Alu repetitive units in the human gene between intron 13 and exon 20. Two potential promoter regions are positioned so that they could give rise to the different transcripts found in erythroid cells and in the kidney. The kidney transcript would lack exons 1 through 3 of the erythroid transcript. The translation initiator downstream to the human kidney promoter would give rise to a protein with a 20-amino acid section at the N-terminus that is not present in the erythroid protein. Sahr et al. (1994) concluded that the AE1 gene spans approximately 20 kb and consists of 20 exons separated by 19 introns. Its structure showed close similarity to that of the mouse AE1 gene. Sahr et al. (1994) described the upstream and internal promoter sequences of the human AE1 gene used in erythroid and kidney cells, respectively. Biochemical Features ### Crystal Structure Arakawa et al. (2015) reported the crystal structure of the band 3 anion exchanger domain (AE1(CTD)) at 3.5 angstroms. The structure is locked in an outward-facing open conformation by an inhibitor. Comparing this structure with a substrate-bound structure of the uracil transporter UraA in an inward-facing conformation allowed Arakawa et al. (2015) to identify the anion-binding position in the AE1(CTD), and to propose a possible transport mechanism that could explain why selected mutations lead to disease. Mapping Showe et al. (1987) localized the gene for BND3 to 17q21-qter by Southern blot analysis of DNA from somatic cell hybrids. Lux et al. (1989) confirmed assignment of the BND3 gene to chromosome 17. According to HGM10, EPB3 is in the same large restriction fragment as RNU2 (180690), which narrows the localization to 17q21-q22. Using RFLPs of both loci, Stewart et al. (1989) showed that EPB3 is closely linked to NGFR (162010) (maximum lod = 11.40 at theta = 0.00, with a confidence limit of 0.00 to 0.04). Gross (2018) mapped the SLC4A1 gene to chromosome 17q21.31 based on an alignment of the SLC4A1 sequence (GenBank BC096106) with the genomic sequence (GRCh38). Molecular Genetics Mueller and Morrison (1977) and Hsu and Morrison (1985) reported variant forms of band 3 with an elongated N terminus. Both variants are hematologically normal with normal red cell morphologic features; the red cells do not appear to be resistant to invasion by malaria parasites in vitro (Ranney et al., 1990; Schulman et al., 1990). Palatnik et al. (1990) described 3 phenotypes based on the polymorphism of band-3 protein from human red cells. Limited proteolysis of intact red cells from most individuals (homozygotes) yields a peptide of 60 kD, but in some persons (heterozygotes), there is also a 63-kD peptide, and rarely only the single peptide of 63 kD is found. This was the first description of the 63-kD homozygote. The frequency of the p63 allele was estimated to be 0.041 +/- 0.0068 in Caucasoids and 0.125 +/- 0.0121 in Negroids. ### Acanthocytosis Kay et al. (1987, 1988) reported 2 sibs with acanthocytosis whose red cells showed markedly increased anion transport activity. The sibs were clinically normal, the abnormality having been detected through the acanthocytosis found on blood studies for unrelated reasons. Kay et al. (1987, 1988) concluded that the 'disorder' was recessive. Bruce et al. (1993) studied the red cells of one of the sibs reported by Kay et al. (1988) and identified band 3 HT (109270.0032). ### Southeast Asian Ovalocytosis Following up on the demonstration by Liu et al. (1990) that a structurally and functionally abnormal band 3 protein shows absolute linkage with the Southeast Asian Ovalocytosis (SAO; 166900) phenotype, Jarolim et al. (1991) demonstrated that the EPB3 gene in these cases contains a 27-bp deletion, resulting in deletion of 9 amino acids (codons 400-408) in the boundary of cytoplasmic and membrane domains of the band 3 protein (109270.0002). The defect was detected in all 30 ovalocytic subjects from Malaysia, the Philippines, and 2 unrelated coastal regions of Papua New Guinea, whereas it was absent in all 30 controls from Southeast Asia and 20 subjects of different ethnic origin from the United States. The lys56-to-glu mutation (109270.0001) was also found in all SAO subjects; however, it was detected in 5 of 50 control subjects as well, suggesting that it represents a linked polymorphism. Kidson et al. (1981) found that ovalocytic erythrocytes from Melanesians are resistant to invasion by malaria parasites, thus providing a plausible explanation for the polymorphism (also see Serjeantson et al., 1977). Baer (1988) suggested that Malaysian elliptocytosis may be a balanced polymorphism, i.e., that individuals homozygous for the elliptocytosis allele, not clearly identifiable by any assay, may be differentially susceptible to mortality, whereas the heterozygote is at an advantage. Hadley et al. (1983) showed that Melanesian elliptocytes are highly resistant to invasion by Plasmodium knowlesi and P. falciparum in vitro. This is the only human red cell variant known to be resistant to both. Coetzer et al. (1996) described a 4-generation South African kindred with dominantly inherited ovalocytosis and hemolytic anemia. All affected subjects exhibited varying degrees of hemolytic anemia. Additionally, there was evidence for independent segregation of the band 3 Memphis I polymorphism (109270.0001) and the 27-bp deletion in BND3 causing SAO. Six SAO subjects and all 3 normal family members were heterozygous for the band 3 Memphis I polymorphism and one SAO subject was homozygous for this mutation. ### Spherocytosis Type 4 In a 28-year-old female with congenital spherocytic hemolytic anemia (SPH4; 612653), Jarolim et al. (1991) identified a missense mutation in the SLC4A1 gene (109270.0003). In a 33-year-old woman with pregnancy-associated hemolytic anemia and spherocytosis, Rybicki et al. (1993) identified a G40K mutation in SLC4A1 (109270.0004). In a 3-generation Czech family in which 5 affected members exhibited compensated hemolytic disease, Jarolim et al. (1994) identified a 10-bp duplication in the SLC4A1 gene (109270.0005) that segregated with disease. In affected members of a large Swiss family with spherocytosis, Maillet et al. (1995) identified heterozygosity for an SLC4A1 G771D mutation (109270.0007). In an 18-year-old French man with moderate hereditary spherocytosis, Alloisio et al. (1996) identified an R150X mutation in SLC4A1 (109270.0009). The proband's mother, who had the same mutation, had a milder clinical presentation. Further investigation revealed a second, paternally inherited SLC4A1 mutation in the proband (109270.0010). Dhermy et al. (1997) studied 8 kindreds with dominant hereditary spherocytosis and band 3 deficiency mutations. The amount of band 3 appeared to be slightly, but significantly, more reduced in HS patients with missense mutations and presence of the mutant transcripts than in HS patients with premature termination of translation and absence of mutant transcripts, suggesting that SLC4A1 missense mutations may have a dominant-negative effect. Alloisio et al. (1997) reported a V488M mutation in band 3 (109270.0022) that was associated with spherocytosis in heterozygous state. Ribeiro et al. (2000) identified the V488M mutation in homozygosity in a female infant with severe anemia and hydrops, in whom renal tubular acidosis was detected by age 3 months. In a 29-year-old Japanese man with compensated hemolytic anemia and spherocytosis, Inoue et al. (1998) identified homozygosity for an SLC4A1 G130R mutation (109270.0018). In a 22-year-old Japanese man who presented with cholelithiasis and hemolysis and had a history of jaundice since early childhood, Iwase et al. (1998) identified a T837A mutation in SLC4A1 (band 3 Tokyo; 109270.0019). Bruce et al. (2005) identified 11 human pedigrees with dominantly inherited hemolytic anemias, 8 in the hereditary stomatocytosis class (see 'Cryohydrocytosis,' below) and 3 in the spherocytosis class. Affected individuals in these families had an increase in membrane permeability to sodium and potassium ion that was particularly marked at zero degree centigrade. They found that disease in these pedigrees was associated with a series of single amino acid substitutions in the intramembrane domain of the band 3 anion exchanger. Anion movements were reduced in the abnormal red cells. The 'leak' cation fluxes were inhibited by chemically diverse inhibitors of band 3. Expression of the mutated genes in Xenopus laevis oocytes induced abnormal NA and K fluxes in the oocytes, and the induced chloride transport was low. These data were considered consistent with the suggestion that the substitutions convert the protein from an anion exchanger into an unregulated cation channel. All affected individuals were heterozygous for missense mutations in exon 17 of the SLC4A1 gene, including 2 families with spherocytosis who carried the R760Q mutation (109270.0028) that had previously been reported in 2 spherocytosis patients by Jarolim et al. (1995). ### Cryohydrocytosis In 8 unrelated families with cryohydrocytosis (CHC; 185020), Bruce et al. (2005) identified 3 different heterozygous missense mutations in the SLC4A1 gene (109270.0033-109270.0035) that segregated fully with disease in each family. ### Choreoacanthocytosis Tanner (1993) reviewed the evidence that mutations in the AE1 gene can cause choreoacanthocytosis (200150; see Kay, 1991). Kay et al. (1989) reported a band 3 alteration in association with anemia as determined by a reticulocyte count of 20%. The erythrocyte defect was reflected in increased IgG binding, increased breakdown products of band 3, and altered anion- and glucose-transport activity in middle-aged cells. IgG eluted from the red cells of the propositus appeared to have a specificity for senescent cell antigen. This and other studies suggested that band 3 was aging prematurely in erythrocytes of the subject, and that the senescent cell antigen appeared on the middle-aged red cells. Two sibs were affected. Both parents were thought to show 'subtle band 3 changes.' Autosomal recessive inheritance was postulated. ### Distal Renal Tubular Acidosis, Autosomal Dominant Bruce et al. (1997) found that all affected members of 4 families with autosomal dominant familial renal tubular acidosis (RTA; 179800) were heterozygous for mutations in the SLC4A1 gene; these mutations were not found in any of the 9 normal family members studied. In 2 families the mutation was arg589 to his (109270.0012); arg589-to-cys (109270.0013) and ser613-to-phe (109270.0014) changes were found in the other families. Linkage studies confirmed the cosegregation of the disease with a genetic marker close to SLC4A1. Affected individuals with the mutations in arg589 had reduced red cell sulfate transport and altered glycosylation of the red cell band 3 N-glycan chain. The red cells of individuals with the ser613-to-phe mutation had markedly increased red cell sulfate transport but almost normal red cell iodide transport. The erythroid and kidney isoforms of the mutant band 3 protein were expressed in Xenopus oocytes and all showed significant chloride transport activity. Bruce et al. (1997) concluded that dominantly inherited RTA is associated with mutations in band 3; however, both the disease and its autosomal dominant inheritance are not related simply to the anion transport activity of the mutant proteins. Arg589 is located in the cytoplasmic loop between transmembrane segments 6 and 7 of band 3. This arginine is conserved in all known vertebrate sequences of AE1, AE2, and AE3, suggesting that it is functionally important. Arg589 is located in a cluster of basic residues which may form part of the cytoplasmic anion binding site of band 3. The mechanism by which the S613F mutation increases the affinity of the protein for sulfate was not clear. One possibility was that the mutation, which is located near the center of membrane span 7 and results in a substitution of serine by a bulky phenylalanine residue, altered the orientation of membrane span 7 relative to span 6. This may distort the conformation of the cytoplasmic loop between spans 6 and 7 which contains the putative anion binding site so that the clustered basic residues bind sulfate more tightly than the wildtype protein. Bruce et al. (1997) were prompted to undertake this study because of a possible association between dominant RTA and hereditary ovalocytosis (Baehner et al., 1968). Mutations in the families with dominant RTA were different from those affecting band 3 in Southeast Asian ovalocytosis. Complete absence of band 3 was found by Inaba et al. (1996) to result in defective renal acid secretion in cattle. Most of the patients in the 4 families studied by Bruce et al. (1997) presented clinically with renal stones, and the majority had nephrocalcinosis. One patient in a family with the arg589-to-his mutation had rickets when initially seen at age 10 years and developed osteomalacia at the age of 31 after she stopped taking alkali therapy, but no other patient had bone disease. Eight patients were not acidotic when first seen, and were diagnosed as 'incomplete' dominant RTA because they were unable to excrete a urine more acid than pH 5.3 after oral acute ammonium chloride challenge. Compared with acidotic cases, these patients tended to be younger, with lower plasma creatinines, better preservation of urinary concentrating ability, and less (or no) nephrocalcinosis; over a 10-year period, 2 of the patients spontaneously developed acidosis. Acidotic patients were treated with oral alkalis, usually 6 gm of sodium bicarbonate daily, and had normal acid-base status at the time of the study; nonacidotic patients were not treated. Karet et al. (1998) screened 26 kindreds with primary distal renal tubular acidosis (dRTA; 179800) for mutations in the AE1 gene. Inheritance was autosomal recessive in 17, autosomal dominant in 1, and uncertain due to unknown parental phenotype or sporadic disease in 8. No mutations in AE1 were detected in any of the autosomal recessive kindreds, and analysis of linkage showed no evidence of linkage of recessive distal RTA to AE1. In contrast, heterozygous mutations in AE1 were identified in the 1 known dominant distal RTA kindred, in 1 sporadic case, and in 1 kindred with 2 affected brothers. In the dominant kindred, an arg589-to-ser mutation (109270.0015) cosegregated with distal RTA in the extended pedigree. In the sporadic case, an arg589-to-his mutation (109270.0012) proved to be a de novo change. In the third kindred, both affected brothers had an intragenic 13-bp duplication resulting in deletion of the last 11 amino acids of AE1 (band 3 Walton; 109270.0025). Parental consanguinity was identified in 14 of the 17 recessive pedigrees. In the recessive kindreds, 19 of 25 patients were diagnosed at 1 year of age or less, and the remainder presented at 6 years or younger. All index cases presented either acutely with vomiting and dehydration, or with failure to thrive or delayed growth. Younger affected sibs were often diagnosed prospectively. All patients with the recessive disease were found to have nephrocalcinosis, nephrolithiasis, or both, and several had rickets. Nine of these patients from 6 families also had bilateral sensorineural deafness confirmed by audiometry; see renal tubular acidosis with progressive nerve deafness (267300). In contrast, in the 1 dominant kindred (with the arg589-to-ser mutation), 2 propositae were diagnosed because of nephrolithiasis at ages 56 and 36 years. Prospective screening identified other affected family members who were all asymptomatic, and most were diagnosed in adulthood. None of the 6 affected members of this family had radiologic evidence of nephrocalcinosis. The chloride-bicarbonate exchanger AE1, which is mutant in autosomal dominant distal renal tubular acidosis, is normally expressed at the basolateral surface of alpha-intercalated cells in the distal nephron. Devonald et al. (2003) demonstrated that AE1 is aberrantly targeted to the apical surface in this disorder, in contrast with many disorders where mutant membrane proteins are retained intracellularly and degraded. ### Distal Renal Tubular Acidosis with Hemolytic Anemia Tanphaichitr et al. (1998) described novel AE1 mutations in a Thai family with a recessive syndrome of dRTA and hemolytic anemia in which red cell anion transport was normal (611590). A brother and sister were triply homozygous for 2 benign mutations, M31T and K56E (109270.0001), and for a loss-of-function mutation, G701D (109270.0016). The AE1 G701D loss-of-function mutation was accompanied by impaired trafficking to the Xenopus oocyte surface. Coexpression of the erythroid AE1 chaperonin, glycophorin A, along with the AE1 G701D mutation, rescued both AE1-mediated chloride ion transport and AE1 surface expression in oocytes. The genetic and functional data suggested that the homozygous AE1 G701D mutation causes recessively transmitted dRTA in this kindred with apparently normal erythroid anion transport. Bruce et al. (2000) studied 3 Malaysian and 6 Papua New Guinean families with dRTA and Southeast Asian ovalocytosis (SAO). The SAO deletion mutation (109270.0002) occurred in many of the families but did not itself result in distal renal tubular acidosis. Compound heterozygotes of each of the 3 dRTA mutations (G701D, 109270.0016; A858D, 109270.0020; delV850 109270.0021) with SAO all had dRTA, evidence of hemolytic anemia, and abnormal red cell properties. The A858D mutation showed dominant inheritance and the recessive delV850 and G701D mutations showed a pseudodominant phenotype when the transport-inactive SAO allele was also present. Red cell and Xenopus oocyte expression studies showed that the delV850 and A858D mutant proteins had greatly decreased anion transport when present as compound heterozygotes with each other or with SAO. Red cells with A858D/SAO had only 3% of the sulfite ion efflux of normal cells, the lowest anion transport activity reported for human red cells to that time. Bruce et al. (2000) confirmed that the G701D mutant protein has an absolute requirement for glycophorin A for movement to the cell surface. In a female infant with severe anemia and hydrops, in whom renal tubular acidosis was detected by age 3 months, Ribeiro et al. (2000) identified homozygosity for a V488M mutation (109270.0022), which had previously been reported in association with spherocytosis in heterozygous state by Alloisio et al. (1997). Sritippayawan et al. (2004) reported 2 Thai families with recessive dRTA due to different compound heterozygous mutations of the SLC4A1 gene. In the first family, the patient with dRTA had compound heterozygous G701D/S773P (109270.0026) mutations. In the second family, the patient and his sister had dRTA and SAO, and were compound heterozygotes for the SAO deletion mutation and an R602H mutation (109270.0027). Sritippayawan et al. (2004) noted that the second patient had a severe form of dRTA whereas his sister had only mild metabolic acidosis, indicating that other modifying factors or genes might play a role in governing the severity of the disease. Kittanakom et al. (2004) transiently transfected human embryonic kidney HEK293 cells with the renal isoform of SLC4A1 containing the S773P mutation, alone or in combination with wildtype SLC4A1 or with the G701D mutant. The S773P mutant was expressed at a 3-fold lower level than wildtype, had a 2-fold decrease in its half-life, and was targeted for degradation by the proteasome. Both S773P and G701D exhibited defective trafficking to the plasma membrane, providing an explanation for the dysfunction found in dRTA. ### Blood Groups Diego blood group (110500) Di(a) is a low-incidence blood group antigen in Caucasians that is antithetical to Di(b). Prevalence of Di(a) is much higher in American Indians, reaching up to 54% in some groups of South American Indians. Bruce et al. (1994) demonstrated that the Diego blood group polymorphism is the result of a single amino acid substitution at position 854 of the AE1 molecule, with proline of the wildtype band 3 corresponding to the Di(b) antigen and leucine to the Di(a) antigen. Subsequently, Bruce et al. (1995) mapped the low-incidence blood group antigen Wr(a) (109270.0011) to the C-terminal end of the fourth ectoplasmic loop and defined a single amino acid substitution in Wr(b) (109270.0006). Jarolim et al. (1998) studied the molecular basis of 7 low-incidence blood group antigens that likewise are due to variation in AE1. McManus et al. (2000) demonstrated that the Froese blood group polymorphism (601551) is the result of change in the SLC4A1 gene (109270.0029). Zelinski et al. (2000) demonstrated that the Swann blood group (601550) is due to molecular changes in the SLC4A1 gene (109270.0030). Animal Model Inaba et al. (1996) studied a moderately uncompensated bovine anemia associated with spherocytosis inherited in an autosomal incompletely dominant mode and retarded growth. Using biochemical methods they showed that the bovine red cells lacked the band 3 protein completely. Sequence analysis of EPB3 cDNA and genomic DNA showed a C-to-T transition resulting in a missense mutation: CGA-to-TGA; arg646-to-ter. The location of the mutation was at the position corresponding to codon 646 in human EPB3 cDNA. The animal red cells were deficient in spectrin, ankyrin, actin (see 102630), and protein 4.2 (177070), resulting in a distorted and disrupted membrane skeletal network with decreased density. Therefore, the animal's red cell membranes were extremely unstable and showed the loss of surface area in several distinct ways such as invagination, vesiculation, and extrusion of microvesicles, leading to the formation of spherocytes. Inaba et al. (1996) also found that total deficiency of bovine band 3 also resulted in defective chloride/bicarbonate exchange, causing mild acidosis with decreases in bicarbonate concentration and total CO(2) in the animal's blood. The results demonstrated to the authors that bovine band 3 contributes to red cell membrane stability, CO(2) transport, and acid-base homeostasis, but is not always essential to the survival of this mammal. Erythroid band 3 (AE1) is one of 3 anion exchanges that are encoded by separate genes. The AE1 gene is transcribed by 2 promoters: the upstream promoter is used for erythroid band 3, whereas the downstream promoter initiates transcription of the band 3 isoform in kidney. To assess the biologic consequences of band 3 deficiency, Southgate et al. (1996) selectively inactivated erythroid but not kidney band 3 by gene targeting in mice. Although no death in utero occurred, most homozygous mice died within 2 weeks after birth. The erythroid band 3-null mice showed retarded growth, spherocytic red blood cell morphology, and severe hemolytic anemia. Remarkably, the band 3 -/- red blood cells assembled normal membrane skeleton, thus challenging the notion that the presence of band 3 is required for stable biogenesis of the membrane skeleton. Similarly, Peters et al. (1996) used targeted mutagenesis in the mouse to assess AE1 function in vivo. RBCs lacking AE1 spontaneously shed membrane vesicles and tubules, leading to severe spherocytosis and hemolysis, but the levels of the major skeleton components, the synthesis of spectrin in mutant erythroblasts, and skeletal architecture were normal or nearly normal. Their results indicated that AE1 does not regulate RBC membrane skeleton assembly in vivo but is essential for membrane stability. Peters et al. (1996) postulated that stabilization is achieved through AE1-lipid interactions and that loss of these interactions is a key pathogenic event in hereditary spherocytosis. Jay (1996) reviewed the role of band 3 in red cell homeostasis and cell shape. Paw et al. (2003) characterized a zebrafish mutant called retsina (ret) that exhibits an erythroid-specific defect in cell division with marked dyserythropoiesis similar to human congenital dyserythropoietic anemia (see 224100). Erythroblasts from ret fish show binuclearity and undergo apoptosis due to a failure in the completion of chromosome segregation and cytokinesis. Through positional cloning, Paw et al. (2003) demonstrated that the ret mutation is in the Slc4a1 gene, encoding the anion exchanger-1 (also called band 3 and AE1), an erythroid-specific cytoskeletal protein. They further showed an association between deficiency in Slc4a1 and mitotic defects in the mouse. Rescue experiments in ret zebrafish embryos expressing transgenic Slc4a1 with a variety of mutations showed that the requirement for band 3 in normal erythroid mitosis is mediated through its protein 4.1R-binding domains. Paw et al. (2003) concluded that their report established an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrated the concept of cell-specific adaptation for mitosis. Skin \- Jaundice Inheritance \- Autosomal dominant (17q21-q22) Lab \- Band 3 erythrocyte membrane glycoprotein \- Senescent cell antigen (SCA), derived from degraded band 3 marks aging and malaria-infected red cells for removal \- Chloride and bicarbonate exchange function \- Binding sites for hemoglobin and several glycolytic enzymes \- Transport for glucose, anions, and water \- Resistance to red cell invasion by malaria parasites \- Hyperbilirubinemia GI \- Splenomegaly Heme \- Hemolytic anemia (e.g. .0004 Band 3 Montefiore) \- Spherocytosis (e.g. .0003 Band 3 Tuscaloosa) \- Acanthocytosis \- Elliptocytosis \- Macrocytosis \- Stomatocytosis \- Reticulocytosis \- Increased red cell osmotic fragility ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	SOLUTE CARRIER FAMILY 4 (ANION EXCHANGER), MEMBER 1	c1862320	6,165	omim	https://www.omim.org/entry/109270	2019-09-22T16:44:32	{"omim": ["109270"], "synonyms": ["Alternative titles", "BAND 3 OF RED CELL MEMBRANE", "ERYTHROCYTE MEMBRANE PROTEIN BAND 3", "ERYTHROID PROTEIN BAND 3", "ANION EXCHANGE PROTEIN 1"]}
Adenosine Deaminase 2 deficiency is an inherited disorder causing inflammation in the body, especially in the tissues that make up the blood vessels (vasculitis). Though the severity and age of onset can vary, most patients begin having symptoms within the first decade of life. Symptoms may include the following: recurrent strokes, fevers, muscle pain, an enlarged liver or spleen, and areas of skin discoloration known as livedo racemosa or livedo reticularis. The strokes can affect physical or cognitive functioning. Other symptoms may include high blood pressure, aneurysms, immune system abnormalities, and necrosis of the fingers/toes. ADA2 deficiency is thought to be caused by mutations in the CECR1 gene and inherited in an autosomal recessive manner. Mutations in the CECR1 gene have also been associated with a familial form of Sneddon syndrome. Individuals with this form of Sneddon syndrome have been reported to have similar findings as those with ADA2 deficiency but with a later onset. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Adenosine Deaminase 2 deficiency	c3887654	6,166	gard	https://rarediseases.info.nih.gov/diseases/12383/adenosine-deaminase-2-deficiency	2021-01-18T18:02:16	{"omim": ["615688"], "orphanet": ["404553"], "synonyms": ["ADA2 deficiency", "Vasculitis due to DADA2", "DADA2", "Vasculitis due to ADA2 deficiency", "Polyarteritis nodosa, childhood-onset", "Childhood-onset polyarteritis nodosa"]}
Acral arteriolar ectasia is characterized by purple serpiginous ectatic arterioles on the back of the fingers, presenting in the fifth decade of life.[1] A distinct vascular malformation, to our knowledge not described before, is reported. The malformation consists of purple serpiginous vessels on the dorsa of the digits, first arising in the fifth decade of life. The vessels are ectatic arterioles and are believed to represent a rare vascular malformation. ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. Page 586. ISBN 0-7216-2921-0. This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Acral arteriolar ectasia	None	6,167	wikipedia	https://en.wikipedia.org/wiki/Acral_arteriolar_ectasia	2021-01-18T18:53:12	{"wikidata": ["Q4675031"]}
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: "Nodular vasculitis" – news · newspapers · books · scholar · JSTOR (April 2019) Nodular vasculitis SpecialtyDermatology Nodular vasculitis is a skin condition characterized by crops of small, tender, erythematous nodules on the legs, mostly on the calves and shins. Miroscopically there are epithelioid granulomas and vasculitis in the subcutaneous tissue, making it a form of panicullitis. Most of these cases are now thought to be manifestation of tuberculosis and indeed they respond well to anti-tuberculous treatment.[citation needed] ## See also[edit] * Panniculitis * List of cutaneous conditions ## References[edit] ## External links[edit] Classification D * ICD-10: L95.8 (ILDS L95.850) External resources * eMedicine: article/1083213 * v * t * e Cutaneous vasculitis and other vascular-related cutaneous conditions Cutaneous vasculitis * Erythema elevatum diutinum * Capillaritis * Urticarial vasculitis * Nodular vasculitis Microvascular occlusion * Calciphylaxis * Cryoglobulinemic purpura/Cryoglobulinemic vasculitis * vascular coagulopathy: Livedoid vasculitis * Livedoid dermatitis * Perinatal gangrene of the buttock * Malignant atrophic papulosis * Sneddon's syndrome Purpura * Nonthrombocytopenic purpura: Cryofibrinogenemic purpura * Drug-induced purpura * Food-induced purpura * IgA vasculitis * Obstructive purpura * Orthostatic purpura * Purpura fulminans * Purpura secondary to clotting disorders * Purpuric agave dermatitis * Pigmentary purpuric eruptions * Solar purpura * Traumatic purpura * Waldenström hyperglobulinemic purpura * Painful bruising syndrome * ungrouped: Paroxysmal hand hematoma * Postcardiotomy syndrome * Deep vein thrombosis * Superficial thrombophlebitis * Mondor's disease * Blueberry muffin baby * Fibrinolysis syndrome Systemic vasculitis * see Template:Systemic vasculitis Vascular malformations * Arteriovenous malformation * Bonnet–Dechaume–Blanc syndrome * Cobb syndrome * Parkes Weber syndrome * Sinusoidal hemangioma * lymphatic malformation * Hennekam syndrome * Aagenaes syndrome * telangiectasia: Generalized essential telangiectasia * Hereditary hemorrhagic telangiectasia * Unilateral nevoid telangiectasia Ulcer * Venous ulcer * Arterial insufficiency ulcer * Hematopoietic ulcer * Neuropathic ulcer * Acroangiodermatitis Lymphedema * see Template:Lymphatic vessel disease Ungrouped vascular-related cutaneous conditions * Raynaud's phenomenon * Thromboangiitis obliterans * Erythromelalgia * Septic thrombophlebitis * Arteriosclerosis obliterans * Bier spots/Marshall–White syndrome * Cholesterol embolus * Reactive angioendotheliomatosis * Trousseau's syndrome * v * t * e Disorders of subcutaneous fat Panniculitis Lobular * without vasculitis * Cold * Cytophagic histiocytic * Factitial * Gouty * Pancreatic * Traumatic * needle-shaped clefts * Subcutaneous fat necrosis of the newborn * Sclerema neonatorum * Post-steroid panniculitis * Lipodermatosclerosis * Weber–Christian disease * Lupus erythematosus panniculitis * Sclerosing lipogranuloma * with vasculitis: Nodular vasculitis/Erythema induratum Septal * without vasculitis: Alpha-1 antitrypsin deficiency panniculitis * Erythema nodosum * Acute * Chronic * with vasculitis: Superficial thrombophlebitis Lipodystrophy Acquired * generalized: Acquired generalized lipodystrophy * partial: Acquired partial lipodystrophy * Centrifugal abdominal lipodystrophy * HIV-associated lipodystrophy * Lipoatrophia annularis * localized: Localized lipodystrophy Congenital * Congenital generalized lipodystrophy * Familial partial lipodystrophy * Marfanoid–progeroid–lipodystrophy syndrome * Poland syndrome This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Nodular vasculitis	c0028258	6,168	wikipedia	https://en.wikipedia.org/wiki/Nodular_vasculitis	2021-01-18T18:37:32	{"umls": ["C0028258"], "icd-10": ["L95.8"], "wikidata": ["Q7046754"]}
A number sign (#) is used with this entry because of evidence that 3-methylglutaconic aciduria type VIII (MGCA8) is caused by homozygous mutation in the HTRA2 gene (606441) on chromosome 2p13. Description MGCA8 is an autosomal recessive metabolic disorder resulting in death in infancy. Features include hypotonia, abnormal movements, respiratory insufficiency with apneic episodes, and lack of developmental progress, often with seizures. Brain imaging is variable, but may show progressive cerebral atrophy. Laboratory studies show increased serum lactate and 3-methylglutaconic aciduria, suggesting a mitochondrial defect (summary by Mandel et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950). Clinical Features Mandel et al. (2016) reported 3 sibs, born of consanguineous parents of Druze origin, who presented shortly after birth with hypertonia and tremor followed by extrapyramidal signs and dystonic posturing. Two patients showed sensorineural deafness. Later, the infants had no spontaneous movements, lack of acquisition of developmental milestones, reduced or absent response to external stimuli, intractable seizures, and apneic episodes. All died in infancy. Brain imaging showed thin corpus callosum, enlarged ventricles, and cerebral atrophy. Laboratory studies showed intermittent neutropenia, without overt infections, increased plasma and CSF lactate, and 3-methylglutaconic aciduria. Muscle biopsy showed normal mitochondrial respiratory chain complex activities, but immature fibers and abnormal mitochondria with distorted cristae. Mandel et al. (2016) also reported an unrelated boy, born of consanguineous parents of Ashkenazi Jewish origin, who presented shortly after birth with hypotonia, bradycardia, poor muscle tone, weak cry, and minimal response to external stimulation. He had recurrent apneic spells requiring mechanical ventilation, lack of developmental progress, microcephaly, and refractory myoclonic seizures confirmed by EEG. He also had intermittent neutropenia and hyperthermia with no evidence of infection. Brain imaging showed progressive cerebral volume loss; he died at age 5 months. Olahova et al. (2017) reported 5 infants from 2 unrelated consanguineous families with MGCA8. One family was of Pakistani origin and the other was of Mexican origin. The patients had poor feeding, recurrent apneas with respiratory failure, and hypotonia. More variable features included neutropenia, bradycardia, seizures, and/or abnormal movements, such as dystonia, tremor, and clonus. Skeletal muscle biopsy of 1 patient showed denervation and atrophy. Laboratory studies showed increased lactate and urinary excretion of MGCA. All patients died within the first weeks or months of life. Inheritance The transmission pattern of MGCA8 in the families reported by Mandel et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 infant sibs, born of consanguineous parents of Druze origin, and in an unrelated male infant of Ashkenazi Jewish descent, with MGCA8, Mandel et al. (2016) identified homozygous mutations in the HTRA2 gene (606441.0004 and 606441.0005). The mutations, which were found by whole-exome sequencing, segregated with the disorder in the family. Western blot analysis of patient cells showed complete absence of the protein. Patient fibroblasts showed increased sensitivity to apoptotic insults which could be restored by expression of the wildtype protein and by expression of a proteolytically inactive variant. The impaired cell growth of patient cells could only be rescued by a proteolytically active protein, suggesting different roles for the chaperone and inherent protease activity of HTRA2. Patient skeletal muscle showed abnormal mitochondrial morphology with disturbed cristae, but fibroblasts showed normal mitochondrial tubular and reticulated networks, suggesting tissue-specific effects of loss of HTRA2. Mitochondrial respiratory function was normal in patient cells. In 3 infants from 2 unrelated consanguineous families with MGCA8, Olahova et al. (2017) identified homozygous mutations in the HTRA2 gene (606441.0006 and 606441.0007). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. In family 1, of Pakistani origin, the proband was homozygous for the mutation and his unaffected parents were heterozygous carriers; the affected sib was not genetically tested. In the second family, of Mexican origin, 2 affected sibs were homozygous for the mutation; DNA from the parents was unavailable. Fibroblasts and/or skeletal muscle samples from the proband in each family showed undetectable levels of HTRA2, but the steady-state levels of mitochondrial oxidative phosphorylation subunits and complexes were not significantly affected compared to controls. Cells from 1 of the patients showed increased proteolytic processing of OPA1 (605290), which is involved in mitochondrial fission and fusion, but overall mitochondrial morphology was basically normal. In addition, patient fibroblasts were more susceptible to apoptotic insults. INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth HEAD & NECK Head \- Microcephaly, postnatal Ears \- Sensorineural deafness (in some patients) Eyes \- Lack of vision \- Cataracts CARDIOVASCULAR Heart \- Bradycardia RESPIRATORY \- Apneic episodes \- Respiratory failure ABDOMEN Gastrointestinal \- Poor suck \- Feeding difficulties MUSCLE, SOFT TISSUES \- Hypotonia \- Abnormal mitochondria seen on muscle biopsy (in some patients) \- Irregular cristae \- Disordered myofilaments \- Immature muscle fibers \- Oxidative respiratory enzyme activities are normal \- Mitochondrial morphology may be normal NEUROLOGIC Central Nervous System \- Lack of development \- Hypertonia \- Dystonia \- Tremor \- Loss of spontaneous movement \- Seizures, intractable \- Cerebral atrophy \- Thin corpus callosum \- Enlarged ventricles IMMUNOLOGY \- Neutropenia LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased CSF lactate \- 3-methylglutaconic aciduria MISCELLANEOUS \- Onset soon after birth \- Death in infancy MOLECULAR BASIS \- Caused by mutation in the HTRA serine peptidase 2 gene (HTRA2, 606441.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	3-METHYLGLUTACONIC ACIDURIA, TYPE VIII	c4310650	6,169	omim	https://www.omim.org/entry/617248	2019-09-22T15:46:21	{"omim": ["617248"]}
## Clinical Features Book (1950) reported 25 persons in 4 generations of a Swedish family with premolar aplasia, hyperhidrosis, and canities prematura. The author designated the disorder PHC syndrome. Salinas et al. (1992) described an 18-year-old Caucasian woman with congenitally missing premolars, narrow palate, severe functional hyperhidrosis of the hands and feet, small hands, and hypoplastic nails. The authors suggested that this may be a new case of Book syndrome. However, the patient lacked premature graying of hair, and had the additional features of disorganized eyebrows, unilateral simian creases, poorly formed dermatoglyphs, and poorly formed bilateral distal digital creases. Salinas et al. (1992) suggested that the lack of other reports of Book syndrome may result from the clinical features being of relatively little consequence to most affected individuals or from symptoms being treated as separate entities by different specialists. Inheritance Inheritance of the disorder in the family reported by Book (1950) was clearly autosomal dominant with high penetrance. INHERITANCE \- Autosomal dominant HEAD & NECK Teeth \- Bicuspid hypodontia SKIN, NAILS, & HAIR Skin \- Hyperhidrosis (palms and soles) Nails \- Normal nails Hair \- Canities prematura (premature whitening of hair, onset 6-23 years) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	BOOK SYNDROME	c0457014	6,170	omim	https://www.omim.org/entry/112300	2019-09-22T16:44:09	{"mesh": ["C562993"], "omim": ["112300"], "orphanet": ["1262"], "synonyms": ["Alternative titles", "PHC SYNDROME"]}
A rare, genetic developmental defect during embryogenesis syndrome characterized by camptodactyly, joint contractures with amyotrophy, and ectodermal anomalies (oligodontia, enamel abnormalities, longitudinally broken nails, hypohidrotic skin with tendency to excessive bruising and scarring after injuries and scratching), as well as growth retardation, kyphoscoliosis, mild facial dysmorphism, and microcephaly. There have been no further descriptions in the literature since 1992. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Arthrogryposis-ectodermal dysplasia syndrome	c1866427	6,171	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3200	2021-01-23T17:16:05	{"gard": ["5029"], "mesh": ["C537441"], "omim": ["601701"], "umls": ["C1866427"], "synonyms": ["Stoll-Alembik-Finck syndrome"]}
Isolated congenital auditory ossicle malformation is a rare, congenital, middle ear anomaly characterized by, usually unilateral and sporadic, variations in the number, size and/or configuration of the ossicles, with no tympanic membrane and external ear abnormalities and no history of trauma or infection. Patients frequently present late, after schooling has started, with non-progressive, conductive hearing loss often associated with speech delay and poor school performance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Isolated congenital auditory ossicle malformation	None	6,172	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=162526	2021-01-23T17:27:22	{"icd-10": ["Q16.3"], "synonyms": ["Congenital auditory ossicle malformation without external ear abnormality"]}
A number sign (#) is used with this entry because Mulchandani-Bhoj-Conlin syndrome (MBCS) is an imprinting disorder involving genes within the imprinted region of chromosome 20. Description The Mulchandani-Bhoj-Conlin syndrome is characterized by prenatal growth restriction, severe short stature with proportional head circumference, and profound feeding difficulty (Mulchandani et al., 2016). Clinical Features Mulchandani et al. (2016) reported 8 patients with intrauterine growth restriction and postnatal failure to thrive. All 8 patients had severe short stature with proportional head circumference and profound feeding difficulties. Age at last evaluation for the 8 patients ranged from 3 months to 12 years. Four patients had mild facial dysmorphism, including one each with epicanthal folds, triangular face with posteriorly rotated ears, and dolichocephaly with retrognathia. Four had hypotonia, which caused motor delay in 2. Five patients had skeletal anomalies: one each with scoliosis, hyperlordosis, or bifid toe, and 2 with clinodactyly of whom 1 also had mild 2-3 toe syndactyly. The patient with the bifid toe also had a horseshoe kidney. Six patients required gastric feeds for some interval in the first 5 years of life. Four were treated with growth hormone with improved linear growth acceleration and no ill effects. Three had pigmentary changes described as 'hyperpigmented spots,' 'irregular pigment,' and 'a cafe-au-lait macule.' Two patients had initially been diagnosed with Silver-Russell syndrome (180860). Maternal age at the patients' birth ranged from 37 to 43 years. Molecular Genetics By SNP array, Mulchandani et al. (2016) demonstrated that 4 of the 8 patients they reported had maternal isodisomy, 2 had maternal heterodisomy, and 2 had evidence of 2 cell lines showing both maternal isodisomy and heterodisomy. This supported a chromosome 20 trisomy rescue occurring after meiosis II, consistent with the advanced maternal age of each proband's mother. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	MULCHANDANI-BHOJ-CONLIN SYNDROME	c4275029	6,173	omim	https://www.omim.org/entry/617352	2019-09-22T15:46:05	{"omim": ["617352"], "orphanet": ["96186"], "synonyms": ["Alternative titles", "UNIPARENTAL DISOMY, MATERNAL, CHROMOSOME 20", "UPD(20)mat", "Maternal UPD(20)"]}
Megarbane et al. (1999) presented a family with 2 children who had myoclonic epilepsy, congenital deafness, a dystrophic pattern of the macular pigment epithelium, incomplete right bundle branch block, and psychiatric disorders appearing after fever episodes. The parents were second cousins. A mitochondrial origin was initially suspected, but mitochondrial DNA analysis did not detect any of the most frequent mutations usually reported in mitochondrial syndromes. Biochemical analysis, including lactate and pyruvate in serum and cerebrospinal fluid, was normal. The authors compared the findings in their patients to those with a similar condition, congenital deafness and familial myoclonic epilepsy (220300), reported by Latham and Munro (1937). They noted that the patients reported by Latham and Munro (1937) were more severely affected and did not have the ophthalmologic findings seen in their patients. Megarbane et al. (1999) concluded that their patients may have a distinct autosomal recessive syndrome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	MYOCLONIC EPILEPSY, CONGENITAL DEAFNESS, MACULAR DYSTROPHY, AND PSYCHIATRIC DISORDERS	c1858478	6,174	omim	https://www.omim.org/entry/604363	2019-09-22T16:12:02	{"mesh": ["C565786"], "omim": ["604363"]}
Nephrogenic diabetes insipidus is a disorder in which a defect in the small tubes (tubules) in the kidneys causes a person to produce a large amount of urine. Nephrogenic diabetes insipidus occurs when the kidney tubules, which allow water to be removed from the body or reabsorbed, do not respond to a chemical in the body called antidiuretic hormone (ADH) or vasopressin. ADH normally tells the kidneys to make the urine more concentrated. As a result of the defect, the kidneys release an excessive amount of water into the urine, producing a large quantity of very dilute urine. The most common symptoms are frequent urination (polyuria), especially during nighttime (nocturia), and drinking too much liquids (polydipsia). It can be either acquired or hereditary. The acquired form is brought on by certain drugs and chronic diseases and can occur at any time during life. About 90% of all cases of hereditary nephrogenic diabetes insipidus result from mutations in the AVPR2 gene, and about 10% of cases are caused by mutations in the AQP2 gene. Treatment consists of plenty of water intake; medication, such as thiazide diuretics and NSAIDs; and a low-salt, low-protein diet. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Nephrogenic diabetes insipidus	c0162283	6,175	gard	https://rarediseases.info.nih.gov/diseases/7178/nephrogenic-diabetes-insipidus	2021-01-18T17:58:46	{"mesh": ["D018500"], "omim": ["304800"], "orphanet": ["223"], "synonyms": ["Diabetes insipidus nephrogenic", "Diabetes insipidus nephrogenic type 1", "Vasopressin-resistant diabetes insipidus", "ADH resistant diabetes insipidus", "Diabetes insipidus nephrogenic X-linked"]}
Primrose syndrome was originally described in 1982 and fewer than a dozen cases have been reported in the literature. The most distinctive clinical feature is a calcification (hardening) of the outer ear. Other findings include characteristic facial features, a large head (macrocephaly), and intellectual disability. A variety of neurological signs such as brain calcifications, autism, and behavioral abnormalities have been reported in some cases. Additional features such as diabetes, sparse body hair, and muscle wasting become apparent in adulthood. Research has found that some cases of Primrose syndrome are caused by a mutation in the ZBTB20 gene . Most cases have been sporadic. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Primrose syndrome	c0796121	6,176	gard	https://rarediseases.info.nih.gov/diseases/4488/primrose-syndrome	2021-01-18T17:58:10	{"mesh": ["C536420"], "omim": ["259050"], "umls": ["C0796121"], "orphanet": ["3042"], "synonyms": ["Intellectual disability-cataracts-calcified pinnae-myopathy syndrome", "Ossified ear cartilages with mental deficiency, muscle wasting, and bony changes"]}
Paraphrenia Other namesParaphrenic syndrome SpecialtyPsychiatry Paraphrenia is a mental disorder characterized by an organized system of paranoid delusions with or without hallucinations (the positive symptoms of schizophrenia) and without deterioration of intellect or personality (its negative symptom).[1][2][3] This disorder is also distinguished from schizophrenia by a lower hereditary occurrence, less premorbid maladjustment, and a slower rate of progression.[4] Onset of symptoms generally occurs later in life, near the age of 60.[2][5] The prevalence of the disorder among the elderly is between 0.1% and 4%.[1] Paraphrenia is not included in the DSM-5; psychiatrists often diagnose patients presenting with paraphrenia as having atypical psychoses, delusional disorder, psychoses not otherwise specified, schizoaffective disorders, and persistent persecutory states of older adults.[4] Recently, mental health professionals have also been classifying paraphrenia as very late-onset schizophrenia-like psychosis.[4] In the Russian psychiatric manuals, paraphrenia (or paraphrenic syndrome) is the last stage of development of paranoid schizophrenia. "Systematized paraphrenia" (with systematized delusions i. e. delusions with complex logical structure) and "expansive-paranoid paraphrenia" (with expansive/grandiose delusions and persecutory delusions) are the variants of paranoid schizophrenia (F20.0).[6] Sometimes systematized paraphrenia can be seen with delusional disorder (F22.0).[6] The word is from Ancient Greek: παρά – beside, near + φρήν – intellect, mind. ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Neurological * 2.2 Predisposing factors * 3 Diagnosis * 4 Management * 5 Prognosis * 6 Epidemiology * 6.1 Sex differences * 6.2 Age * 6.3 Personality type and living situation * 6.4 Physical factors * 7 History * 8 References * 9 External links ## Signs and symptoms[edit] The main symptoms of paraphrenia are paranoid delusions and hallucinations.[1][7] The delusions often involve the individual being the subject of persecution, although they can also be erotic, hypochondriacal, or grandiose in nature. The majority of hallucinations associated with paraphrenia are auditory, with 75% of patients reporting such an experience; however, visual, tactile, and olfactory hallucinations have also been reported.[1][7] The paranoia and hallucinations can combine in the form of “threatening or accusatory voices coming from neighbouring houses [and] are frequently reported by the patients as disturbing and undeserved".[1] Patients also present with a lack of symptoms commonly found in other mental disorders similar to paraphrenia. There is no significant deterioration of intellect, personality, or habits and patients often remain clean and mostly self-sufficient.[7] Patients also remain oriented well in time and space.[1] Paraphrenia is different from schizophrenia because, while both disorders result in delusions and hallucinations, individuals with schizophrenia exhibit changes and deterioration of personality whereas individuals with paraphrenia maintain a well-preserved personality and affective response.[2][7] ## Causes[edit] ### Neurological[edit] Paraphrenia is often associated with a physical change in the brain, such as a tumor, stroke, ventricular enlargement, or neurodegenerative process.[4] Research that reviewed the relationship between organic brain lesions and the development of delusions suggested that "brain lesions which lead to subcortical dysfunction could produce delusions when elaborated by an intact cortex".[8] ### Predisposing factors[edit] Many patients who present with paraphrenia have significant auditory or visual loss, are socially isolated with a lack of social contact, do not have a permanent home, are unmarried and without children, and have maladaptive personality traits.[4][9][10] While these factors do not cause paraphrenia, they do make individuals more likely to develop the disorder later in life. ## Diagnosis[edit] While the diagnosis of paraphrenia is absent from recent revisions of the DSM and the ICD, many studies have recognized the condition as "a viable diagnostic entity that is distinct from schizophrenia, with organic factors playing a role in a significant portion of patients."[4] As such, paraphrenia is seen as being distinct from both schizophrenia and progressive dementia in old age.[2] Ravindran (1999) developed a list of criteria for the diagnosis of paraphrenia, which agrees with much of the research done up to the time it was published. 1\. A delusional disorder of at least six months duration characterized by the following: a. Preoccupation with one or more semisystematized delusions, often accompanied by auditory hallucinations. b. Affect notably well-preserved and appropriate. Ability to maintain rapport with others. c. None of i. Intellectual deterioration ii. Visual hallucinations iii. Incoherence iv. Flat or grossly inappropriate affect v. Grossly disorganized behavior at times other than during the acute episode. d. Disturbance of behavior understandable in relation to the content of the delusions and hallucinations. e. Only partly meets criterion A for schizophrenia. No significant organic brain disorder.[10] ## Management[edit] Research suggests that paraphrenics respond well to antipsychotic drug therapy if doctors can successfully achieve sufficient compliance.[1][10] Herbert found that Stelazine combined with Disipal was an effective treatment. It promoted the discharging of patients and kept discharged patients from being readmitted later.[9] While behavior therapy may help patients reduce their preoccupation with delusions, psychotherapy is not currently of primary value.[10] ## Prognosis[edit] Individuals who develop paraphrenia have a life expectancy similar to the normal population.[1][2][4][11] Recovery from the psychotic symptoms seems to be rare, and in most cases paraphrenia results in in-patient status for the remainder of the life of the patient.[1][2][9] Patients experience a slow deterioration of cognitive functions and the disorder can lead to dementia in some cases, but this development is no greater than the normal population.[2][4][7] ## Epidemiology[edit] Studies suggest that the prevalence of paraphrenia in the elderly population is around 2–4%.[1] ### Sex differences[edit] While paraphrenia can occur in both men and women, it is more common in women, even after the difference has been adjusted for life expectancies.[1] The ratio of women with paraphrenia to men with paraphrenia is anywhere from 3:1 to 45:2.[5] ### Age[edit] It is seen mainly in patients over the age of 60, but has been known to occur in patients in their 40s and 50s.[2][5] ### Personality type and living situation[edit] It is suggested that individuals who develop paraphrenia later in life have premorbid personalities, and can be described as “quarrelsome, religious, suspicious or sensitive, unsociable and cold-hearted.”[1] Many patients were also described as being solitary, eccentric, isolated and difficult individuals; these characteristics were also long-standing rather than introduced by the disorder.[7] Most of the traits recognized prior to the onset of paraphrenia in individuals can be grouped as either paranoid or schizoid.[9] Patients presenting with paraphrenia were most often found to be living by themselves (either single, widowed, or divorced).[9] There have also been reports of low marriage rate among paraphrenics and these individuals also have few or no children (possibly because of this premorbid personality).[1][5][9] ### Physical factors[edit] The development of paranoia and hallucinations in old age have been related to both auditory and visual impairment, and individuals with paraphrenia often present with one or both of these impairments.[1][5][9] Hearing loss in paraphrenics is associated with early age of onset, long duration, and profound auditory loss.[5] ## History[edit] The term paraphrenia was originally popularized by Karl Ludwig Kahlbaum in 1863 to describe the tendency of certain psychiatric disorders to occur during certain transitional periods in life (describing paraphrenia hebetica as the insanity of the adolescence and paraphrenia senilis as the insanity of the elders.[4][12][13] The term was also used by Sigmund Freud for a short time starting in 1911 as an alternative to the terms schizophrenia and dementia praecox, which in his estimation did not correctly identify the underlying condition,[14][15][16] and by Emil Kraepelin in 1912/3,[17][18] who changed its meaning to describe paraphrenia as it is understood today, as a small group of individuals that have many of the symptoms of schizophrenia with a lack of deterioration and thought disorder.[4][13] Kraepelin's study was discredited by Wilhelm Mayer in 1921 when he conducted a follow-up study using Kraepelin's data. His study suggested that there was little to no discrimination between schizophrenia and paraphrenia; given enough time, patients presenting with paraphrenia will merge into the schizophrenic pool.[4][13] However, Meyer's data are open to various interpretations.[12] In 1952, Roth and Morrissey conducted a large study in which they surveyed the mental hospital admissions of older patients. They characterized patients as having "paraphrenic delusions which… occurred in each case in the setting of a well-preserved intellect and personality, were often ‘primary’ in character, and were usually associated with the passivity failings or other volitional disturbances and hallucinations in clear consciousness pathognomonic of schizophrenia".[4][19] In recent medicine, the term paraphrenia has been replaced by the diagnosis of "very late-onset schizophrenia-like psychosis" and has also been called "atypical psychoses, delusional disorder, psychoses not otherwise specified, schizoaffective disorders, and persistent persecutory states of older adults" by psychotherapists.[4] Current studies, however, recognize the condition as "a viable diagnostic entity that is distinct from schizophrenia, with organic factors playing a role in a significant portion of patients."[4] ## References[edit] 1. ^ a b c d e f g h i j k l m n Almeida, O. P., Howard, H. F., & Levy, R. (1992). Late paraphrenia: a review. International Journal of Geriatric Psychiatry, 7, 543-548. 2. ^ a b c d e f g h Roth, M. (1955). The natural history of mental disorder in old age. The British Journal of Psychiatry, 101, 281-301 3. ^ Roth, M. & Kay, D. W. K. (1998). Late paraphrenia: A variant of schizophrenia manifest in late life or an organic clinical syndrome? A review of recent evidence. International Journal of Geriatric Psychiatry, 13, 775-784 4. ^ a b c d e f g h i j k l m n Casanova, M. F. (2010). The pathology of paraphrenia. Current Psychiatry Reports, 12, 196-201. 5. ^ a b c d e f Almeida, O. P., Howard, R. J., Levy, R., & David, A. S. (1995). Psychotic states arising in late life (late paraphrenia): The role of risk factors. British Journal of Psychiatry, 166, 215-228 6. ^ a b Сметанников, П. Г. (2002). Психиатрия: Краткое руководство для врачей [Psychiatry: A Brief Guide for Physicians] (in Russian). Rostov-on-Don: Phoenix (Феникс). pp. 157, 165. ISBN 5-222-02133-5. 7. ^ a b c d e f Kay, D. W., & Roth, M. (1961). Environmental and hereditary factors in schizophrenias of old-age (late paraphrenia) and their bearing on general problem of causation in schizophrenia. Journal of Mental Science, 107, 649. 8. ^ Cummings, J. L. (1985). Organic delusions: Phenomenology, anatomical correlations, and review. British Journal of Psychiatry, 146, 184-197. 9. ^ a b c d e f g Herbert, M. E., & Jacobson, S. (1967). Late paraphrenia. British Journal of Psychiatry, 113, 461. 10. ^ a b c d Ravindran, A. V., Yatham, L. N., & Munro, A. (1999). Paraphrenia redefined. Canadian Journal of Psychiatry-Revue Canadienne De Psychiatrie, 44, 133-137. 11. ^ Roth, M., & Kay, D. W. K. (1998). Late paraphrenia: A variant of schizophrenia manifest in late life or an organic clinical syndrome? A review of recent evidence. International Journal of Geriatric Psychiatry, 13, 775-784 12. ^ a b Berrios G E (2003) A Conceptual History of Paraphrenia. Journal of Nutrition, Health and Aging 7: 394-399 13. ^ a b c McKenna, P.J. (1997). Schizophrenia and related syndromes. Psychology Press. pp. 239–242. ISBN 978-0-86377-790-5. 14. ^ Sigmund Freud. Psychoanalytische Bemerkungen über einen autobiographisch beschriebenen Fall von Paranoia (Dementia paranoides) (in German). 15. ^ Sigmund Freud. Psycho-Analytic Notes on an Autobiographical Account of a Case of Paranoia (Dementia Paranoides). 16. ^ Peter Widmer (2007). Widmer, Peter; Schmid, Michael (eds.). Psychosen: Eine Herausforderung für die Psychoanalyse (in German). Bielefeld: transcript Verlag. p. 75-102 Paraphrenie - ein vergessenes Konzept Freuds 17. ^ Kraepelin, Emil. "Über paranoide Erkrankungen." Zeitschrift für die gesamte Neurologie und Psychiatrie 11 (1912): 617-638, here 623-626. 18. ^ Kraepelin, E. (1913). Psychiatrie: ein Lehrbuch für Studierende und Ärzte. 3 (8. Auflage ed.). Verlag Johann von Ambrosius Barth. pp. 668, 973–974. 19. ^ Roth, M. & Morrissey, J. D. (1952) Problems in the diagnosis and classification of mental disorders in old age. The Journal of Mental Science, 98, 66–80. ## External links[edit] * Harris, M. J.; Jeste, D. V. (1988). "Late-onset schizophrenia: an overview" (PDF). Schizophrenia Bulletin. 14 (1): 39–55. doi:10.1093/schbul/14.1.39. PMID 3291094. * Canadian Journal of Psychiatry, March 1999, Paraphrenia redefined * Dilip V. Jeste; Jane S. Paulsen; M. Jackuelyn Harris. "Late-Onset Schizophrenia and Other Related Psychoses". www.acnp.org. Archived from the original on 2010-03-08. Retrieved 2009-12-26. Classification D * ICD-10: F22.0, F20.0 * ICD-9-CM: 297.2 * SNOMED CT: 26472000 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Paraphrenia	c0030484	6,177	wikipedia	https://en.wikipedia.org/wiki/Paraphrenia	2021-01-18T19:00:51	{"umls": ["C0030484"], "icd-9": ["297.2"], "icd-10": ["F20.0", "F22.0"], "wikidata": ["Q2476251"]}
A form of congenital disorders of N-linked glycosylation characterized by microcephaly, hepatomegaly, edema of the extremities, intractable seizures, recurrent infections and increased bleeding tendency. The disease is caused by mutations in the gene ALG13 (Xq23). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	ALG13-CDG	c4317295	6,178	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=324422	2021-01-23T18:37:08	{"gard": ["12401"], "omim": ["300884"], "icd-10": ["E77.8"], "synonyms": ["CDG syndrome type Is", "CDG-Is", "CDG1S", "Congenital disorder of glycosylation type 1s", "Congenital disorder of glycosylation type Is"]}
Squamous cell carcinoma of stomach is a rare epithelial tumour of stomach, defined histropathologically as keratinizing cell masses with pearl formation, mosaic pattern of cell arrangement, intercellular bridges, and high concentrations of sulphydryl or disulphide bonds, arising directly from gastric mucosa, without esophageal involvement. It is characterized by preferential location in the upper third of the stomach, high probability of lymphovascular and serosal invasion and late onset of clinical symptoms associated with poor prognosis including nonspecific symptoms of abdominal pain, dysphagia, vomiting, melena or hematochezia, haematemesis and weight loss. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Squamous cell carcinoma of the stomach	c1333789	6,179	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=418959	2021-01-23T18:59:11	{"icd-10": ["C16.0", "C16.1", "C16.2", "C16.3", "C16.4", "C16.5", "C16.8"], "synonyms": ["Gastric squamous cell carcinoma"]}
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-42 (EIEE42) is caused by heterozygous mutation in the CACNA1A gene (601011) on chromosome 19p13. For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). Clinical Features The Epi4K Consortium and Epilepsy Phenome/Genome Project (2013) reported a 19-year-old girl (patient EPGP011141) with EIEE42. She had onset of myoclonic seizures soon after birth and thereafter showed severe intellectual disability. EEG showed generalized and poly-spike wave discharges and generalized background slowing. Other features included alternating esotropia, nystagmus, ataxic gait, contractures, hypotonia, and autistic features. The Epi4K Consortium (2016) reported 5 patients, including 2 sibs, with EIEE42. The patients had onset of seizures shortly after birth or in the first weeks of life. Seizure types were variable, including focal myoclonic, tonic-clonic, tonic, and convulsive status epilepticus. The patients had delayed global development with moderate to severe intellectual disability. All had an abnormal EEG, with variable manifestations including multifocal discharges, spike-wave discharges, and generalized background slowing. Other features included hypotonia, limb hypertonia with hyperreflexia, tremor, ataxic gait, athetosis, and abnormal eye movements. Brain imaging was basically normal. Molecular Genetics In 5 patients, including 2 sibs with early infantile epileptic EIEE42, the Epi4K Consortium (2016) identified 4 different heterozygous missense mutations in the CACNA1A gene (see, e.g., 601011.0035-601011.0037). The mutations were found by targeted sequencing of 27 candidate genes in 531 patients with a similar disorder. Functional studies of the variants and studies of patient cells were not performed. The mutations occurred de novo, except in the 2 sibs who inherited the mutation from the unaffected mother who was a mosaic carrier. CACNA1A mutations occurred in 0.8% of the cohort. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Abnormal eye movements \- Strabismus \- Esotropia \- Nystagmus SKELETAL \- Contractures MUSCLE, SOFT TISSUES \- Hypotonia \- Hypertonia NEUROLOGIC Central Nervous System \- Epileptic encephalopathy \- Seizures, multiple types \- Developmental delay \- Intellectual disability, moderate to severe \- Hyperreflexia \- Tremor \- Ataxia \- Athetosis \- EEG abnormalities PRENATAL MANIFESTATIONS Movement \- Abnormal fetal movements MISCELLANEOUS \- Onset at birth or early infancy \- Most mutations occur de novo MOLECULAR BASIS \- Caused by mutation in the calcium channel, voltage-dependent, P/Q type, alpha-1A subunit gene (CACNA1A, 601011.0017 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 42	c4310716	6,180	omim	https://www.omim.org/entry/617106	2019-09-22T15:46:54	{"doid": ["0080454"], "omim": ["617106"], "orphanet": ["442835"], "synonyms": ["Undetermined EOEE"]}
Pulseless electrical activity Other namesElectromechanical dissociation A drawing of what a rhythm strip showing PEA could look like SpecialtyCardiology Pulseless electrical activity (PEA) refers to cardiac arrest in which the electrocardiogram shows a heart rhythm that should produce a pulse, but does not. Pulseless electrical activity is found initially in about 55% of people in cardiac arrest.[1] Under normal circumstances, electrical activation of muscle cells precedes mechanical contraction of the heart (known as electromechanical coupling). In PEA, there is electrical activity, but the heart either does not contract or there are other reasons this results in an insufficient cardiac output to generate a pulse and supply blood to the organs.[2] While PEA is classified as a form of cardiac arrest, significant cardiac output may still be present which may be determined and best visualized by bedside ultrasound. Cardiopulmonary resuscitation (CPR) is the first treatment for PEA, while potential underlying causes are identified and treated. The medication epinephrine may be administered.[2] Survival is about 20%.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] Pulseless electrical activity leads to a loss of cardiac output, and the blood supply to the brain is interrupted. As a result, PEA is usually noticed when a person loses consciousness and stops breathing spontaneously. This is confirmed by examining the airway for obstruction, observing the chest for respiratory movement, and feeling the pulse (usually at the carotid artery) for a period of 10 seconds.[2] ## Causes[edit] These possible causes are remembered as the 6 Hs and the 6 Ts.[3][4][5] See Hs and Ts * Hypovolemia * Hypoxia * Hydrogen ions (Acidosis) * Hyperkalemia or Hypokalemia * Hypoglycemia * Hypothermia * Tablets or Toxins (Drug overdose)[which?] * Cardiac Tamponade * Tension pneumothorax * Thrombosis (e.g., myocardial infarction, pulmonary embolism) * Tachycardia * Trauma (e.g., hypovolemia from blood loss) The possible mechanisms by which the above conditions can cause pulseless in PEA are the same as those recognized as producing circulatory shock states. These are (1) impairment of cardiac filling, (2) impaired pumping effectiveness of the heart, (3) circulatory obstruction and (4) pathological vasodilation causing loss of vascular resistance and excess capacitance. More than one mechanism may be involved in any given case.[citation needed] ## Diagnosis[edit] Pulseless electrical activity, it is possible to observe by invasive blood pressure (red) the transition from a normal mechanical activity of the heart, which progressively changes in rhythm and contractile quality to asystole, even in the presence of normal electrical activity (green), also confirmed by the pulse oximeter detection even if with artifacts (blue) The absence of a pulse confirms a clinical diagnosis of cardiac arrest, but PEA can only be distinguished from other causes of cardiac arrest with a device capable of electrocardiography (ECG/EKG). In PEA, there is organised or semi-organised electrical activity in the heart as opposed to asystole (flatline) or to the disorganised electrical activity of either ventricular fibrillation or ventricular tachycardia.[2] ## Treatment[edit] Cardiac resuscitation guidelines (ACLS/BCLS) advise that cardiopulmonary resuscitation should be initiated promptly to maintain cardiac output until the PEA can be corrected. The approach in treatment of PEA is to treat the underlying cause, if known (e.g. relieving a tension pneumothorax). Where an underlying cause for PEA cannot be determined and/or reversed, the treatment of pulseless electrical activity is similar to that for asystole.[2] There is no evidence that external cardiac compression can increase cardiac output in any of the many scenarios of PEA, such as hemorrhage, in which impairment of cardiac filling is the underlying mechanism producing loss of a detectable pulse.[citation needed] A priority in resuscitation is placement of an intravenous or intraosseous line for administration of medications. The mainstay of drug therapy for PEA is epinephrine (adrenaline) 1 mg every 3–5 minutes. Although previously the use of atropine was recommended in the treatment of PEA/asystole, this recommendation was withdrawn in 2010 by the American Heart Association due to lack of evidence for therapeutic benefit.[2] Epinephrine too has a limited evidence base, and it is recommended on the basis of its mechanism of action. Sodium bicarbonate 1meq per kilogram may be considered in this rhythm as well, although there is little evidence to support this practice. Its routine use is not recommended for patients in this context, except in special situations (e.g. preexisting metabolic acidosis, hyperkalemia, tricyclic antidepressant overdose).[2] All of these drugs should be administered along with appropriate CPR techniques. Defibrillators cannot be used to correct this rhythm, as the problem lies in the response of the myocardial tissue to electrical impulses. ## References[edit] 1. ^ a b Baldzizhar, A; Manuylova, E; Marchenko, R; Kryvalap, Y; Carey, MG (September 2016). "Ventricular Tachycardias: Characteristics and Management". Critical Care Nursing Clinics of North America. 28 (3): 317–29. doi:10.1016/j.cnc.2016.04.004. PMID 27484660. 2. ^ a b c d e f g 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care (November 2010). "Part 8: Adult Advanced Cardiovascular Life Support". Circulation. 122 (18 Suppl): S729–S767. doi:10.1161/CIRCULATIONAHA.110.970988. PMID 20956224. 3. ^ Mazur, Glen (2003). Acls: Principles And Practice. [Dallas, TX]: Amer Heart Assn. pp. 71–87. ISBN 0-87493-341-2. 4. ^ Barnes, Thomas Garden; Cummins, Richard O.; Field, John; Hazinski, Mary Fran (2003). ACLS for experienced providers. [Dallas, TX]: American Heart Association. pp. 3–5. ISBN 0-87493-424-9. 5. ^ 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care (December 2005). "Part 7.2: Management of Cardiac Arrest". Circulation. 112 (24 Suppl): IV 58–66. doi:10.1161/CIRCULATIONAHA.105.166557. ## External links[edit] Classification D * ICD-10: I46.9 * ICD-9-CM: 427.9 * DiseasesDB: 4166 External resources * eMedicine: med/2963 * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Pulseless electrical activity	c0340861	6,181	wikipedia	https://en.wikipedia.org/wiki/Pulseless_electrical_activity	2021-01-18T18:42:12	{"icd-10": ["I46.9"], "wikidata": ["Q1326997"]}
CD30+ cutaneous T-cell lymphoma Other namesRegressive atypical histiocytosis, Primary C-ALCL, primary cutaneous anaplastic large cell lymphoma SpecialtyDermatology CD30+ cutaneous T-cell lymphoma, also known as primary cutaneous anaplastic large cell lymphoma, is a cutaneous (skin) condition characterized by solitary or localized skin lesions that have a tendency to ulcerate.[1]:738 ## See also[edit] * Cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large cell lymphoma * List of cutaneous conditions ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. ## External links[edit] Classification D * ICD-10: C86.6 * MeSH: D054446 External resources * Orphanet: 300865 This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	CD30+ cutaneous T-cell lymphoma	c1301362	6,182	wikipedia	https://en.wikipedia.org/wiki/CD30%2B_cutaneous_T-cell_lymphoma	2021-01-18T19:03:01	{"mesh": ["D054446"], "umls": ["C1698767", "C1301362"], "orphanet": ["300865"], "wikidata": ["Q5009807"]}
Dialysis-related amyloidosis (DRA), is a type of amyloidosis (see this term) affecting patients with chronic kidney disease (CKD), on long term dialysis characterized by the accumulation of amyloid fibrils consisting of beta 2 microglobulin (β2M) deposits in the musculoskeletal system leading to carpal tunnel syndrome (CTS), chronic arthropathy, cystic bone lesions, destructive osteoarthropathy, and pathologic fractures. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Wild type ABeta2M amyloidosis	None	6,183	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85446	2021-01-23T19:00:14	{"icd-10": ["E85.3"], "synonyms": ["ABeta2Mwt amyloidosis", "Dialysis-related amyloidosis", "Dialysis-related arthropathy", "Wild type ABeta2-microglobulinic amyloidosis"]}
A number sign (#) is used with this entry because of evidence that Netherton syndrome (NETH) is caused by homozygous or compound heterozygous mutation in the SPINK5 gene (605010), encoding the serine protease inhibitor LEKTI, on chromosome 5q32. Description Netherton syndrome is a rare and severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Generalized scaly erythroderma is apparent at or soon after birth and usually persists. Scalp hair is sparse and brittle with a characteristic 'bamboo' shape under light microscopic examination due to invagination of the distal part of the hair shaft to its proximal part. Atopic manifestations include eczema-like rashes, atopic dermatitis, pruritus, hay fever, angioedema, urticaria, high levels of IgE in the serum, and hypereosinophilia. Life-threatening complications are frequent during the neonatal period, including hypernatremic dehydration, hypothermia, extreme weight loss, bronchopneumonia, and sepsis. During childhood, failure to thrive is common as a result of malnutrition, metabolic disorders, chronic erythroderma, persistent cutaneous infections, or enteropathy (summary by Bitoun et al., 2002). Clinical Features The features of this disorder, which was first reported by Netherton (1958), are 'bamboo hair' (trichorrhexis nodosa, or, because of the nodes, invaginata), congenital ichthyosiform erythroderma, and atopic diathesis. It has been observed almost only in females. The parents of the patient reported by Wilkinson et al. (1964) were third cousins. The authors suggested that the disorder is an autosomal recessive inborn error of metabolism. Their patient also had hypogammaglobulinemia. Stankler and Cochrane (1967) described affected sisters of Italian extraction. Porter and Starke (1968) reported an affected male. Several males in the family, including the proband, had histologically typical X-linked ichthyosis and the relationship of these males was consistent with X-linkage. Stevanovic (1969) reported 2 cases, and Julius and Keeran (1971) described another. Altman and Stroud (1969) suggested that Netherton disease and ichthyosis linearis circumflexa are manifestations of the same entity. The term psoriasiform ichthyosis was proposed by them for including both diseases under the same denominator based on the report of 7 cases with both disorders. Smith et al. (1995) reviewed 43 previously reported patients and described a 'new' case in a male. They listed the features as greatly elevated IgE levels with atopic manifestations, an ichthyotic skin condition (ichthyosis linearis circumflexa and/or congenital lamellar ichthyosis), and trichorrhexis invaginata. The disorder may be confused with atopic dermatitis but does not respond to topical corticosteroid treatment. Smith et al. (1995) described successful treatment in their patient with 12% ammonium lactate lotion and management of his allergic disease. The patient was born of nonconsanguineous parents and had a generalized erythematous rash at birth. Smith et al. (1995) noted that 20 of the 44 patients were male. Fartasch et al. (1999) noted that the infant with Netherton syndrome typically displays a generalized erythroderma covered by fine, translucent scales, which can be difficult to distinguish clinically from erythrodermic psoriasis, nonbullous congenital ichthyosiform erythroderma, or other infantile erythrodermas. Some infants with Netherton syndrome develop progressive hypernatremic dehydration, failure to thrive, and enteropathy. These complications can be fatal. Typically, diagnosis is delayed until the appearance of a pathognomonic hair shaft anomaly, trichorrhexis invaginata (bamboo hair). To facilitate the early diagnosis of Netherton syndrome, Fartasch et al. (1999) obtained biopsy specimens from 7 patients with erythrodermic Netherton syndrome and compared their morphologic findings to those of 3 patients with erythrodermic psoriasis and 2 with congenital ichthyosiform erythroderma. In Netherton syndrome, and often in the other 2 conditions, the stratum corneum layer was largely replaced by parakeratotic cells. A distinctive feature occurred only in Netherton syndrome: premature secretion of lamellar body contents. Furthermore, lamellar body-derived extracellular lamellae and stratum corneum lipid membranes were separated extensively by foci of electron-dense material. Finally, transformation of the lamellar body-derived lamellae into mature lamellar membrane structures was disturbed in the Netherton syndrome. These ultrastructural features could permit the early diagnosis of NS before the appearance of the hair shaft abnormality. These abnormalities could explain the impaired permeability barrier in NS, and account for hypernatremia and dehydration in infants with NS. Folster-Holst et al. (1999) described a 28-year-old woman with characteristic clinical signs of Netherton syndrome in which human papillomaviruses were identified in papillomatous skin lesions and plane warts. They suggested that the viruses played a cofactor pathogenic role in the development of the verrucous skin lesions in patients with this disorder. A female sib had died due to widespread congenital erythroderma at the age of 6 weeks. The proband showed severe ichthyotic erythroderma at birth and subsequently developed alopecia involving the scalp, eyelashes, and eyebrows. Marked growth retardation was noted at the age of 2 years. Papillomatous skin lesions developed in the groin at the age of 15 years. Stoll et al. (2001) described an infant who succumbed to hypernatremic dehydration, a major neonatal complication of Netherton syndrome. The child died at 11 days of age. The patient was found to be homozygous for a nonsense mutation in exon 3 of the SPINK5 gene. Prenatal diagnosis by chorionic villus sampling of a second pregnancy revealed the same mutation. Because the conceptus was homozygous for the mutation, the parents requested termination of pregnancy. Renner et al. (2009) studied 9 unrelated children from diverse ethnic backgrounds with Comel-Netherton syndrome. All of the children exhibited the classic triad of congenital ichthyosis, bamboo hair, and allergic diathesis, except for 1 patient who lacked bamboo hair. Recurrent or persistent lesion-associated Staphylococcus aureus skin infections occurred in 8 patients, some of whom developed S. aureus-related sepsis. Recurrent upper and lower respiratory tract infections were present in 8 patients, along with recurrent otitis media and/or externa. Overall, S. aureus was the most frequent infectious agent, followed by Pseudomonas aeruginosa and Klebsiella oxytoca. The majority of patients had recurrent acute gastroenteritis associated with failure to thrive and hypernatremic dehydration, requiring repeated hospitalizations. Immunologic evaluation revealed reduced memory B cells and defective responses to vaccination with Pneumovax and bacteriophage phiX174, characterized by impaired antibody amplification and class-switching. Immune dysregulation was suggested by a skewed Th1 phenotype and elevated proinflammatory cytokine levels, whereas serum concentrations of the chemokine (C-C motif) ligand-5 (CCL5; 187011) and natural killer cell cytotoxicity were decreased. Treatment with intravenous immunoglobulin (IVIG) resulted in remarkable clinical improvement and temporarily increased natural killer cell cytotoxicity. Renner et al. (2009) concluded that the immunopathology of Comel-Netherton syndrome is characterized by cognate and innate immunodeficiency that responds favorably to IVIG. : Smigiel et al. (2017) reported an 8-month-old Polish boy with Netherton syndrome, who from birth had generalized erythroderma covered by fine translucent scales all over the body and scalp. Eyebrows and eyelashes were thin and sparse, and he was hypotonic. He had recurrent episodes of hypernatremic dehydration. Skin infections caused by S. aureus and P. aeruginosa were followed by sepsis, meningitis, and respiratory failure requiring ventilatory assistance, as well as chronic diarrhea. Immunologic examination showed a decreased concentration of IgG and C3 components. Echocardiography revealed tricuspid and pulmonary valve insufficiency as well as conduction abnormalities on electrocardiography. At age 7 months, he was diagnosed with bilateral hypoacusis, and at 8 months showed psychomotor developmental delay. The proband's mother reported that she had absence of scalp hair, eyebrows, and eyelashes from early childhood, and also lacked axillary and pubic hair. Her skin was observed to be smooth with no keratinizing changes. Nevet et al. (2017) reported a Muslim Arab female infant with Netherton syndrome, who at the age of 2 days underwent partial resection of the small intestine for 'apple peel' intestinal atresia. By age 9 months, she had severe failure to thrive and had been repeatedly hospitalized for pulmonary and intestinal infections complicated by sepsis, as well as hypernatremia, hypothermia, osteopenia, and fractures. Skin biopsy showed psoriasiform epidermal hyperplasia and parakeratosis, and immunohistochemistry confirmed the absence of LEKTI in the involved epidermis. The proband died of sepsis at 11 months of age. Biochemical Features Chavanas et al. (2000) studied steady-state levels of the mRNA encoding LEKTI, the gene product of the SPINK5 gene, in cultured epidermal keratinocytes from a healthy control and 5 Netherton syndrome patients. These extracts showed a marked reduction of signal on Northern blot analysis, suggesting nonsense-mediated decay of mutated transcripts, as is frequently observed in recessive disorders (Culbertson, 1999). Bitoun et al. (2003) showed that, in contrast to normal skin, LEKTI precursors and proteolytic fragments were not detected in differentiated primary keratinocytes from Netherton syndrome patients. Defective expression of LEKTI in skin sections was a constant feature in Netherton syndrome patients, demonstrating that loss of LEKTI expression in the epidermis is a diagnostic feature of Netherton syndrome. Pathogenesis Sarri et al. (2017) reviewed published reports of 172 patients from 144 families with Netherton syndrome. They noted that the identified SPINK5 loss-of-function mutations cause epidermal protease hyperactivity, resulting in detachment of stratum corneum, skin barrier defect, and overdesquamation. In addition, upregulation of kallikrein-5 (KLK5; 605643) induces skin inflammation and allergy. They suggested that the consistently observed failure to thrive and/or growth retardation might be explained by dysregulation of human growth hormone (hGH; see 139250) through increased kallikrein activity and hGH proteolysis. Inheritance In a review of 44 cases of Netherton syndrome, Smith et al. (1995) found at least 6 reports of affected sibs and 2 reports of parental consanguinity, suggesting autosomal recessive inheritance. Mapping By linkage analysis and homozygosity mapping in 20 families with Netherton syndrome, Chavanas et al. (2000) mapped the disease locus to 5q32. The NETH locus is telomeric to the cytokine gene cluster in 5q31. Five known genes as well as 38 ESTs mapped within the critical region, but the authors concluded that these were not obvious candidates. Magert et al. (1999) mapped the SPINK5 gene (605010) to the same region of 5q, thus making it a candidate gene for Netherton syndrome. There were functional reasons to suspect that this gene might be involved in Netherton syndrome. Molecular Genetics Among 13 families segregating Netherton syndrome, Chavanas et al. (2000) detected 11 different mutations in the SPINK5 gene (see, e.g., 605010.0001-605010.0003), at least 9 of which generated premature termination codons and predicted mRNA instability. Renner et al. (2009) sequenced the SPINK5 gene in 9 unrelated children from diverse ethnic backgrounds with Comel-Netherton syndrome and identified biallelic mutations in 8 patients (see, e.g., 605010.0005 and 605010.0006); in 1 patient, only 1 mutation was detected, and in another patient, no mutations were found. However, in all 9 patients, LEKTI protein expression was absent or present as small immunoreactive foci in fewer than 2% of epithelial cells from skin biopsies and/or buccal mucosa. In an 8-month-old Polish boy with Netherton syndrome, Smigiel et al. (2017) identified compound heterozygosity for mutations in the SPINK5 gene (605010.0005 and 605010.0007). His mother, who had alopecia from early childhood but no skin changes, was heterozygous for 1 of the mutations; DNA was unavailable from the father. In an 8-year-old girl with Netherton syndrome, who had previously been diagnosed with atopic dermatitis or psoriasis and exhibited dry skin with facial scaling erythema, flexural lichenification, and erythematous serpiginous skin lesions on the trunk and lower limbs, as well as bamboo hair, Shi et al. (2017) identified homozygosity for a SPINK5 missense mutation (T808I). The girl was also found to be heterozygous for a nonsense mutation (E2422X) in the filaggrin gene (FLG; 135940); no mutations were found in 10 other ichthyosis-associated genes. Her parents were both heterozygous for the SPINK5 mutation, and the FLG mutation was inherited from her mother, who reported mild skin dryness in the winter. The authors suggested that mutations in additional genes such as FLG might contribute to the pathogenesis of Netherton syndrome or modify its phenotype. In a Muslim Arab girl with Netherton syndrome and intestinal atresia, who died of sepsis at 11 months of age, Nevet et al. (2017) identified homozygosity for a 1-bp deletion in the SPINK5 gene (605010.0008). Her unaffected parents were heterozygous for the mutation. Genotype/Phenotype Correlations Bitoun et al. (2002) studied 21 families of different geographic origin segregating Netherton syndrome and identified 18 mutations, of which 13 were novel and 7 (39%) were recurrent. Five mutations, 1 of which resulted in perinatal lethal disease in 3 families, were associated with certain ethnic groups. No clear correlation between disease and phenotype was seen, suggesting that the degree of severity may be influenced by other factors. Sarri et al. (2017) reviewed published reports of 172 patients from 144 families with Netherton syndrome, who were homozygous or compound heterozygous for 80 different mutations in the SPINK5 gene. Mutations located more upstream in LEKTI correlated with more severe phenotypes than similar mutations located towards the 3-prime region. The authors noted that no variants had been reported downstream of exon 27, suggesting that such changes may remain undetected because they do not have a dramatic effect on LEKTI function. The authors commented that the quality of health care systems in patients' countries may affect whether outcomes are lethal or not, citing several instances in which patients with the same mutations had disparate outcomes. Sarri et al. (2017) stated that if patients survive their first year of life, they will likely achieve milder disease severity or even partial recovery, noting that no deaths had been recorded in patients older than 9 months of age. Animal Model Hewett et al. (2005) created mice with an R820X mutation in the Spink5 gene. Newborn homozygotes developed a severe ichthyosis with a loss of skin barrier function and dehydration, resulting in death within a few hours. Biochemical analysis of skin revealed a substantial increase in the proteolytic processing of profilaggrin (FLG; 135940) into its constituent filaggrin monomers. Hewett et al. (2005) suggested that in the absence of SPINK5 there is an abnormal increase in the processing of profilaggrin, and that this may play a direct role in the observed deficit in the adhesion of the stratum corneum and the severely compromised epidermal barrier function. In a Spink5 -/- mouse model, Sales et al. (2010) demonstrated that the membrane protease matriptase (606797) initiated Netherton syndrome by premature activation of a pro-kallikrein (see 147910) cascade. Autoactivation of proinflammatory pro-kallikrein-related peptidases that are associated with stratum corneum detachment was either low or undetectable, but they were efficiently activated by matriptase. Ablation of matriptase from Spink5 -/- mice dampened inflammation, eliminated aberrant protease activity, prevented detachment of the stratum corneum, and improved the barrier function of the epidermis. Furio et al. (2014) generated a transgenic mouse model expressing human KLK5 (605643), a protease that is overactive in Netherton syndrome, in the granular layer of the epidermis. Transgenic mice had increased proteolytic activity attributable to KLK5 and its downstream targets Klk7 (604438), Klk14 (606135), and Ela2 (ELANE; 130130). The transgenic mice developed exfoliative erythroderma with scaling, growth delay, and hair abnormalities, as well as defective skin barrier and a detached stratum corneum due to desmosomal cleavage. The mice also displayed cutaneous and systemic hallmarks of severe inflammation and allergy with pruritus. Levels of Ccl8 (602283) and Ccl20 (601960), as well as of cytokines associated with inflammation and with recruitment of Th2 and Th17 cells in skin, were increased. Serum IgE and IgG, particularly IgG1, were also increased. Furio et al. (2014) concluded that the transgenic KLK5 model recapitulates the major cutaneous and systemic features of Netherton syndrome and proposed that KLK5 may be a promising treatment target. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Eyes \- Sparse eyebrows RESPIRATORY Airways \- Asthma ABDOMEN Gastrointestinal \- Enteropathy with villous atrophy \- Intestinal atresia (rare) SKIN, NAILS, & HAIR Skin \- Generalized erythroderma \- Ichthyosis linearis circumflexa \- Congenital lamellar ichthyosis \- Urticaria Skin Histology \- Psoriasiform epidermal hyperplasia \- Parakeratosis Hair \- Sparse, brittle scalp hair \- Trichorrhexis invaginata ("bamboo hair") \- Sparse eyebrows MUSCLE, SOFT TISSUES \- Angioedema NEUROLOGIC Central Nervous System \- Developmental delay METABOLIC FEATURES \- Hypernatremic dehydration HEMATOLOGY \- Hypereosinophilia IMMUNOLOGY \- Elevated immunoglobulin E (IgE) \- Hay fever \- Asthma \- Angioedema \- Food allergy \- Recurrent infections \- Innate immunodeficiency \- Cognate immunodeficiency \- Defective responses to vaccination \- Reduced IgG levels \- Reduced C3 components \- Skewed Th1 phenotype \- Elevated proinflammatory cytokine levels \- Reduced chemokine CC-motif ligand-5 levels \- Reduced natural killer cell cytotoxicity MISCELLANEOUS \- Some severely affected infants die in the neonatal period MOLECULAR BASIS \- Caused by mutation in the serine protease inhibitor, Kazal type, 5 gene (SPINK5, 605010.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	NETHERTON SYNDROME	c0265962	6,184	omim	https://www.omim.org/entry/256500	2019-09-22T16:24:24	{"doid": ["0050474"], "mesh": ["D056770"], "omim": ["256500"], "orphanet": ["634"], "synonyms": ["Alternative titles", "ERYTHRODERMA, ICHTHYOSIFORM, WITH HYPOTRICHOSIS AND HYPER-IgE", "NS", "NETHERTON DISEASE", "COMEL-NETHERTON SYNDROME"]}
A number sign (#) is used with this entry because of evidence that parathyroid carcinoma can be caused by mutation in the CDC73 gene (607393) on chromosome 1q. Clinical Features Parathyroid carcinomas are an uncommon and often devastating cause of primary hyperparathyroidism (145000) (Wang and Gaz, 1985; Shane, 2001). Shane (2001) reviewed the clinical features of parathyroid carcinoma and provided a summary of features that might lead one to suspect parathyroid cancer in a patient with hypercalcemia and elevated parathyroid hormone (PTH; 168450) levels. There is no association of gender with parathyroid carcinoma. The average age of the patient with parathyroid carcinoma is in the fifth decade, approximately 10 years younger than typical patients with primary hyperparathyroidism, who most often present in their fifties or sixties. The serum calcium level of most patients with parathyroid carcinoma is much higher than that seen in patients with primary hyperparathyroidism. This more severe hypercalcemia is almost invariably associated with the typical signs and symptoms of hypercalcemia. The most frequent complaints are fatigue, weakness, weight loss, anorexia, nausea, vomiting, polyuria, and polydipsia. Other common presenting symptoms characteristic of a severely hyperparathyroid state include bone pain, fractures, and renal colic. When reported, PTH levels have ranged from 3 to 10 times above the upper limit of normal for the assay employed. Patients with parathyroid carcinoma may have elevated levels of alpha- and beta-subunits of chorionic gonadotropin (see 118860), whereas patients with primary hyperparathyroidism do not. A palpable neck mass, an unusual finding in primary hyperparathyroidism, had been reported in 30 to 76% of patients with parathyroid carcinoma. Shane (2001) stressed that it is of great importance that parathyroid carcinoma be considered in the differential diagnosis of PTH-dependent hypercalcemia, as the morbidity and mortality associated with this diagnosis are substantial, and optimal outcomes are associated with complete resection of the tumor at the time of the initial operation. Molecular Genetics Shattuck et al. (2003) identified somatic and germline mutations in the CDC73 gene (607393) in patients who had no known family history of primary hyperparathyroidism (HPRT1, 145000) or the hyperparathyroidism-jaw tumor syndrome (HPRT2, HPT-JT; 145001), also caused by mutation in the CDC73 gene, at presentation. Weinstein and Simonds (2003) suggested that it is possible that CDC73 is almost always mutated in parathyroid carcinoma. In most of the tumors studied by Shattuck et al. (2003), there was evidence of biallelic inactivation of the gene, although in many cases the second hit was a mutation, rather than loss of heterozygosity. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	PARATHYROID CARCINOMA	c0687150	6,185	omim	https://www.omim.org/entry/608266	2019-09-22T16:08:06	{"doid": ["1540"], "mesh": ["D010282"], "omim": ["608266"], "orphanet": ["143"], "synonyms": ["Alternative titles", "PRTC"], "genereviews": ["NBK3789"]}
A rare vascular tumor characterized by an ill-defined, slowly growing, asymptomatic cutaneous plaque or nodule mostly involving the limbs, in fewer cases the trunk. The tumor is composed of lymphatic-like channels with prominent intraluminal papillary tufts with hyaline cores lined by hobnail endothelial cells. It is locally aggressive, while metastasis is rare. Infants and children are much more often affected than adults. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Primary intralymphatic angioendothelioma	c0346087	6,186	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=458768	2021-01-23T19:03:40	{"icd-10": ["D18.0"], "synonyms": ["Dabska tumor"]}
This article deals with spasticity-based cerebral palsy chiefly affecting the lower extremities, which is the most common. For other types of cerebral-palsy-based spasticity affecting other limbs in varying combinations, see spastic cerebral palsy. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Spastic diplegia" – news · newspapers · books · scholar · JSTOR (June 2009) (Learn how and when to remove this template message) Spastic diplegia Other namesLittle's disease SpecialtyNeurology Spastic diplegia, historically known as Little's disease, is a form of cerebral palsy (CP) that is a chronic neuromuscular condition of hypertonia and spasticity—manifested as an especially high and constant "tightness" or "stiffness"—in the muscles of the lower extremities of the human body, usually those of the legs, hips and pelvis. Doctor William John Little's first recorded encounter with cerebral palsy is reported to have been among children who displayed signs of spastic diplegia. Spastic diplegia accounts for about 22% of all diagnoses of cerebral palsy, and together with spastic quadriplegia and spastic triplegia make up the broad classification spastic cerebral palsy, which accounts for 70% of all cerebral palsy diagnoses.[1] ## Contents * 1 Presentation * 1.1 Social implications * 2 Mechanism * 3 Treatment * 4 Prognosis * 5 Prevalence * 6 See also * 7 References * 8 Further reading * 9 External links ## Presentation[edit] Individuals with spastic diplegia are very tight and stiff and must work very hard to successfully resist and "push through" the extra tightness they perpetually experience. Other than this, however, these individuals are almost always normal in every significant clinical sense. When they are younger, spastic diplegic individuals typically undergo gait analysis so that their clinicians can determine the best assistive devices for them, if any are necessary, such as a walker or crutches. The main difference between spastic diplegia and a normal gait pattern is its signature "scissor gait"[2]—a style that some able-bodied people might tend to confuse with the effects of drunkenness, multiple sclerosis, or another nerve disease. The degree of spasticity in spastic diplegia (and, for that matter, other types of spastic CP) varies widely from person to person. No two people with spastic diplegia are exactly alike. Balance problems and/or stiffness in gait can range from barely noticeable all the way to misalignments so pronounced that the person needs crutches (typically forearm crutches/lofstrand crutches) or a cane / walking stick to assist in ambulation. Less often, spasticity is severe enough to compel the person to use a wheelchair. In general, however, lower-extremity spasticity in spastic diplegia is rarely so great as to totally prevent ambulation—most people with the condition can walk, and can do so with at least a basic amount of overall stability. Regardless, from case to case, steeply varying degrees of imbalance, potential tripping over uneven terrain while walking, or needing to hold on to various surfaces or walls in certain circumstances to keep upright, are typically ever-present potential issues and are much more common occurrences amongst those with spastic diplegia than among those with a normal or near-normal gait pattern. Among some of the people with spastic diplegia who choose to be ambulatory on either an exclusive or predominant basis, one of the seemingly common lifestyle choices is for the person to ambulate within his or her home without an assistive device, and then to use the assistive device, if any, once outdoors. Others may use no assistive device in any indoor situation at all, while always using one when outdoors. Above the hips, persons with spastic diplegia typically retain normal or near-normal muscle tone and range of motion, though some lesser spasticity may also affect the upper body, such as the trunk and arms, depending on the severity of the condition in the individual (the spasticity condition affecting the whole body equally, rather than just the legs, is spastic quadriplegia, a slightly different classification). In addition, because leg tightness often leads to instability in ambulation, extra muscle tension usually develops in the shoulders, chest, and arms due to compensatory stabilisation movements, regardless of the fact that the upper body itself is not directly affected by the condition. ### Social implications[edit] Although the term "spastic" technically describes the attribute of spasticity in spastic cerebral palsy and was originally an acceptable and common term to use in both self-description and in description by others, it has since gained more notoriety as a pejorative, in particular when used in pop culture to insult able-bodied people when they seem overly anxious or unskilled in sports (see also the article spazz). In 1952, a UK charitable organization with a membership mainly of those with spastic CP was formed; this organization called itself The Spastics Society. However, the charity changed its name to Scope in 1994 due to the term spastics having become enough of a pejorative to warrant the name change. Spastic diplegia's social implications tend to vary with the intensity of the condition in the individual. If its effects are severely disabling, resulting in very little physical activity for the person, social elements can also suffer. Workplace environments can also be limited, since most labor-intensive work requires basic physical agility that spastic diplegics may not possess. However, the degree of variability among individuals with spastic diplegia means that no greater or lesser degree of stigma or real-world limitation is standard. Lesser effects usually mean fewer physical limitations, better-quality exercise, and more real-world flexibility, but the person is still in general seen as different from the norm. How such a person chooses to react to outside opinion is of paramount importance when social factors are considered. ## Mechanism[edit] Spastic diplegia's particular type of brain damage inhibits the proper development of upper motor neuron function, impacting the motor cortex, the basal ganglia and the corticospinal tract. Nerve receptors in the spine leading to affected muscles become unable to properly absorb gamma amino butyric acid (GABA), the amino acid that regulates muscle tone in humans. Without GABA absorption to those particular nerve rootlets (usually centred, in this case, around the sectors L1-S1 and L2-S2), affected nerves (here, the ones controlling the legs) perpetually fire the message for their corresponding muscles to permanently, rigidly contract, and the muscles become permanently hypertonic (spastic). The abnormally high muscle tone that results creates lifelong difficulty with all voluntary and passive movement in the legs, and in general creates stress over time—depending on the severity of the condition in the individual, the constant spasticity ultimately produces pain, muscle/joint breakdown including tendinitis and arthritis, premature physical exhaustion (i.e., becoming physically exhausted even when you internally know that you have more energy than you are able to use), contractures, spasms, and progressively worse deformities/mis-alignments of bone structure around areas of the tightened musculature as the person's years progress. Severe arthritis, tendinitis, and similar breakdown can start as early as the spastic diplegic person's mid-20s (as a comparison, typical people with normal muscle tone are not at risk of arthritis, tendinitis, and similar breakdown until well into their 50s or 60s, if even then). No type of CP is officially a progressive condition, and indeed spastic diplegia does not clinically "get worse" given the nerves, damaged permanently at birth, neither recover nor degrade. This aspect is clinically significant because other neuromuscular conditions with similar surface characteristics in their presentations, like most forms of multiple sclerosis, indeed do degrade the body over time and do involve actual progressive worsening of the condition, including the spasticity often seen in MS. However, spastic diplegia is indeed a chronic condition; the symptoms themselves cause compounded effects on the body that are typically just as stressful on the human body as a progressive condition is. Despite this reality and the fact that muscle tightness is the symptom of spastic diplegia and not the cause, symptoms rather than cause are typically seen as the primary area of focus for treatment, especially surgical treatment, except when a selective dorsal rhizotomy is brought into consideration, or when an oral baclofen regimen is attempted. Unlike any other condition that may present with similar effects, spastic diplegia is entirely congenital in origin—that is, it is almost always acquired shortly before or during a baby's birth process. Things like exposure to toxins, traumatic brain injury, encephalitis, meningitis, drowning, or suffocation do not tend to lead to spastic diplegia in particular or even cerebral palsy generally. Overall, the most common cause of spastic diplegia is Periventricular leukomalacia, more commonly known as neonatal asphyxia or infant hypoxia—a sudden in-womb shortage of oxygen-delivery through the umbilical cord. This sudden lack of oxygen is also almost always combined with premature birth, a phenomenon that, even by itself, would inherently risk the infant developing some type of CP. On the other hand, the presence of certain maternal infections during pregnancy such as congenital rubella syndrome can also lead to spastic diplegia, since such infections can have similar end results to infant hypoxia. ## Treatment[edit] Main article: Management of cerebral palsy As a matter of everyday maintenance, muscle stretching, range of motion exercises, yoga, contact improvisation, modern dance, resistance training, and other physical activity regimens are often utilized by those with spastic CP to help prevent contractures and reduce the severity of symptoms. Major clinical treatments for spastic diplegia are: * Baclofen (and its derivatives), a gamma amino butyric acid (GABA) substitute in oral (pill-based) or intrathecal form. Baclofen is essentially chemically identical to the GABA that the damaged, over-firing nerves cannot absorb, except that it has an extra chemical 'marker' on it that makes the damaged nerves 'think' it is a different compound, and thus those nerves will absorb it. Baclofen is noted for being the sole medication available for GABA-deficiency-based spasticity which acts on the actual cause of the spasticity rather than simply reducing symptomatology as muscle relaxants and painkillers do. The intrathecal solution is a liquid injected into the spinal fluid for trial, and if successful in reducing spasticity, thereafter administered via an intrathecal pump, which has variously been proven potentially very dangerous on one or another level with long-term use (see article), including sudden and potentially lethal baclofen overdose, whereas the oral route, which comes in 10- or 20-milligram tablets and the dosage of which can be gently titrated either upward or downward, as well as safely ceased entirely, has not. * Antispasmodic muscle relaxant chemicals such as tizanidine and botulinum toxin (Botox), injected directly into the spastic muscles; Botox wears off every three months. * Phenol and similar chemical 'nerve deadeners', injected selectively into the over-firing nerves in the legs on the muscle end to reduce spasticity in their corresponding muscles by preventing the spasticity signals from reaching the legs; Phenol wears off every six months. * Orthopedic surgery to release the spastic muscles from their hypertonic state, a usually temporary result because the spasticity source is the nerves, not the muscles; spasticity can fully reassert itself as little as one year post-surgery. * Selective dorsal rhizotomy, a neurosurgery directly targeting and eliminating ("cutting" or "lesioning") the over-firing nerve rootlets and leaving the properly firing ones intact, thereby permanently eliminating the spasticity but compelling the person to spend months re-strengthening muscles that will have been severely weakened by the loss of the spasticity, due to the fact of those muscles not really having had actual strength to begin with. ## Prognosis[edit] Unusually, cerebral palsy, including spastic cerebral palsy, is notable for a glaring overall research deficiency—the fact that it is one of the very few major groups of conditions on the planet in human beings for which medical science has not yet (as of 2011) collected wide-ranging empirical data on the development and experiences of young adults, the middle aged and older adults. An especially puzzling aspect of this lies in the fact that cerebral palsy as defined by modern science was first 'discovered' and specifically addressed well over 100 years ago and that it would therefore be reasonable to expect by now that at least some empirical data on the adult populations with these conditions would have long since been collected, especially over the second half of the 20th century when existing treatment technologies rapidly improved and new ones came into being. The vast majority of empirical data on the various forms of cerebral palsy is concerned near-exclusively with children (birth to about 10 years of age) and sometimes pre-teens and early teens (11-13). Some doctors attempt to provide their own personal justifications for keeping their CP specialities purely paediatric, but there is no objectively apparent set of reasons backed by any scientific consensus as to why medical science has made a point of researching adult cases of multiple sclerosis, muscular dystrophy and the various forms of cancer in young and older adults, but has failed to do so with CP. There are a few orthopaedic surgeons and neurosurgeons who claim to be gathering pace with various studies as of the past few years,[citation needed] but these claims do not yet seem to have been matched by real-world actualisation in terms of easily accessible and objectively verifiable resources available to the general public on the internet and in-person, where many, including medical-science researchers and doctors themselves, would more than likely agree such resources would ideally belong. ## Prevalence[edit] In the industrialized world, the incidence of overall cerebral palsy, which includes but is not limited to spastic diplegia, is about 2 per 1000 live births. Thus far, there is no known study recording the incidence of CP in the overall nonindustrialized world. Therefore, it is safe to assume that not all spastic CP individuals are known to science and medicine, especially in areas of the world where healthcare systems are less advanced. Many such individuals may simply live out their lives in their local communities without any medical or orthopedic oversight at all, or with extremely minimal such treatment, so that they are never able to be incorporated into any empirical data that orthopedic surgeons or neurosurgeons might seek to collect. It is shocking to note that—as with people with physical disability overall—some may even find themselves in situations of institutionalization, and thus barely see the outside world at all. From what is known, the incidence of spastic diplegia is higher in males than in females; the Surveillance of Cerebral Palsy in Europe (SCPE), for example, reports a M:F ratio of 1.33:1. Variances in reported rates of incidence across different geographical areas in industrialized countries are thought to be caused primarily by discrepancies in the criteria used for inclusion and exclusion. When such discrepancies are taken into account in comparing two or more registers of patients with cerebral palsy and also the extent to which children with mild cerebral palsy are included, the incidence rates still converge toward the average rate of 2:1000. In the United States, approximately 10,000 infants and babies are born with CP each year, and 1200–1500 are diagnosed at preschool age when symptoms become more obvious. Those with extremely mild spastic CP may not even be aware of their condition until much later in life: Internet chat forums have recorded men and women as old as 30 who were diagnosed only recently with their spastic CP. Overall, advances in care of pregnant mothers and their babies has not resulted in a noticeable decrease in CP; in fact, because medical advances in areas related to the care of premature babies has resulted in a greater survival rate in recent years, it is actually more likely for infants with cerebral palsy to be born into the world now than it would have been in the past. Only the introduction of quality medical care to locations with less-than-adequate medical care has shown any decreases in the incidences of CP; the rest either have shown no change or have actually shown an increase. The incidence of CP increases with premature or very low-weight babies regardless of the quality of care. ## See also[edit] * Inclusion (disability rights) * Cerebral palsy * Spasticity * Gamma amino butyric acid * Rhizotomy * Tizanidine ## References[edit] 1. ^ Prevalence of Cerebral Palsy \| CerebralPalsy.org 2. ^ Spastic diplegic gait on YouTube ## Further reading[edit] * Miller, F.; Bachrach, S.J. (2006). Cerebral Palsy A Complete Guide for Caregiving (2nd ed.). Johns Hopkins University Press. ISBN 978-0801883552. * Miller, Freeman; Bachrach, Steven J. (1998). Cerebral Palsy: A Complete Guide for Caregiving. Johns Hopkins University Press. ISBN 978-0-8018-5949-6. * Kasper, D.L. et al. (2005), Harrison's Principles of Internal Medicine, McGraw-Hill * Collison, L (2020). Spastic Diplegia - Bilateral Cerebral Palsy. Gillette Children's Healthcare Press. ISBN 978-1952181009. ## External links[edit] Classification D * ICD-10: G80.1 * MeSH: D009128 * v * t * e Cerebral palsy Symptoms and signs Spasticity * Upper motor neuron lesion * Spastic cerebral palsy * Scissor gait * Spastic diplegia * Spastic hemiplegia * Spastic quadriplegia Ataxia and others * Ataxic cerebral palsy * Dyskinetic cerebral palsy Diagnosis General movements assessment Measurement scales * Gross Motor Function Classification System - Expanded & Revised (gross motor function) * Manual Ability Classification System (manual dexterity) * Communication Function Classification System (communication) * Modified Ashworth scale (spasticity) Management * Management of cerebral palsy * Selective percutaneous myofascial lengthening * Rhizotomy Other * People with cerebral palsy * Cerebral palsy organizations * Works about cerebral palsy and other paralytic syndromes [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Spastic diplegia	c0023882	6,187	wikipedia	https://en.wikipedia.org/wiki/Spastic_diplegia	2021-01-18T18:50:29	{"mesh": ["D002547", "C537945"], "umls": ["C0023882", "C0154695"], "wikidata": ["Q3029045"]}
Primary familial brain calcification is a condition characterized by abnormal deposits of calcium (calcification) in blood vessels within the brain. These calcium deposits are visible only on medical imaging and typically occur in the basal ganglia, which are structures deep within the brain that help start and control movement of the body. Other brain regions may also be affected. The main signs and symptoms of primary familial brain calcification are movement disorders and psychiatric or behavioral problems. These difficulties usually begin in mid-adulthood, and worsen over time. Most affected individuals have a group of movement abnormalities called parkinsonism, which include unusually slow movement (bradykinesia), muscle rigidity, and tremors. Other movement problems common in people with primary familial brain calcification include involuntary tensing of various muscles (dystonia), uncontrollable movements of the limbs (choreoathetosis), and an unsteady walking style (gait). Psychiatric and behavioral problems occur in 20 to 30 percent of people with primary familial brain calcification. These problems can include difficulty concentrating, memory loss, changes in personality, a distorted view of reality (psychosis), and decline in intellectual function (dementia). Affected individuals may also have difficulty swallowing (dysphagia), impaired speech, headache, episodes of extreme dizziness (vertigo), seizures, or urinary problems. The severity of primary familial brain calcification varies among affected individuals; some people have no symptoms related to the condition, whereas others have significant movement and psychiatric problems. ## Frequency Primary familial brain calcification was thought to be a rare disorder; however, because brain imaging tests are needed to see the calcium deposits, this condition is believed to be underdiagnosed. Recent research has indicated that primary familial brain calcification may occur in 2 to 6 per 1,000 people, with many affected individuals not showing signs and symptoms of the condition. ## Causes Primary familial brain calcification is caused by mutations in one of several genes. The most commonly mutated gene is called SLC20A2, and accounts for an estimated 40 percent of cases, followed by the PDGFRB gene, which is mutated in about 10 percent of cases. Changes in other genes each account for a small percentage of cases. In about half of individuals with primary familial brain calcification the genetic cause is unknown. These individuals are thought to have mutations in genes that have not yet been linked to the condition. The SLC20A2 gene provides instructions for making a protein called sodium-dependent phosphate transporter 2 (PiT-2). This protein is highly active in nerve cells (neurons) in the brain where it plays a major role in regulating phosphate levels (phosphate homeostasis) by transporting phosphate across cell membranes. SLC20A2 gene mutations lead to the production of a PiT-2 protein that cannot effectively transport phosphate into cells. As a result, phosphate levels in the bloodstream rise. In the brain, the excess phosphate combines with calcium and forms deposits within blood vessels in the brain. The PDGFRB gene provides instructions for making a protein that transmits signals from the cell surface into the cell. These signals control a variety of cell processes. PDGFRB gene mutations result in a protein with impaired signaling ability. However, it is unclear how the mutations cause primary familial brain calcification. The altered signaling may result in an abnormally large amount of calcium entering the cells that line blood vessels in the brain, leading to calcification of these blood vessels. Alternatively, changes in PDGFRB signaling could disrupt processes that regulate levels of phosphate and calcium in brain cells, leading to the formation of calcium deposits. Other genes known to be associated with primary familial brain calcification also have roles in cell signaling and phosphate homeostasis. Researchers suggest that calcium deposits lead to the features of primary familial brain calcification by disrupting the connections between the basal ganglia and other areas of the brain, particularly the frontal lobes. These areas at the front of the brain are involved in reasoning, planning, judgment, and problem-solving. The regions of the brain that regulate social behavior, mood, and motivation may also be affected. Research has shown that people with significant calcification tend to have more signs and symptoms of primary familial brain calcification than people with little or no calcification. However, this association does not apply to all people with primary familial brain calcification. ### Learn more about the genes associated with Primary familial brain calcification * PDGFB * PDGFRB * SLC20A2 Additional Information from NCBI Gene: * JAM2 * MYORG * XPR1 ## Inheritance Pattern In most cases, primary familial brain calcification 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 most cases, an affected person has one parent with the condition. Less commonly, primary familial brain calcification is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Primary familial brain calcification	c4551624	6,188	medlineplus	https://medlineplus.gov/genetics/condition/primary-familial-brain-calcification/	2021-01-27T08:25:34	{"gard": ["6406"], "mesh": ["C536275"], "omim": ["213600", "615007", "615483", "616413", "618317"], "synonyms": []}
A number sign (#) is used with this entry because this form of speech and language abnormality (SPCH1) is caused by heterozygous mutation in the FOXP2 gene (605317) on chromosome 7q31. Description Speech-language disorder-1 is an autosomal dominant disorder characterized by severe orofacial dyspraxia resulting in largely incomprehensible speech. Affected individuals were originally thought to have specific defects in the use of grammatical suffixation rules (Gopnik, 1990; Gopnik and Crago, 1991). The phenotype, however, is broader in nature, with virtually every aspect of grammar and language affected (Fisher et al., 1998). Vargha-Khadem et al. (1998) concluded that the disorder is characterized by abnormal development of several brain areas critical for both orofacial movements and sequential articulation, resulting in marked disruption of speech and expressive language. ### Relation to Specific Language Impairment Children who fail to develop expressive and/or receptive language normally, in the absence of explanatory factors such as neurologic disorders, hearing impairment, or lack of adequate opportunity, are clinically described as having specific language impairment (SLI; see 606711) (Bartlett et al., 2002). See also familial developmental dysphasia (600117). Clinical Features Hurst et al. (1990) reported a family, identified as 'KE,' in which 16 members spanning 3 generations had a severe developmental verbal dyspraxia with normal hearing and intelligence. Inheritance was autosomal dominant. Vargha-Khadem et al. (1995) restudied the 'KE' family, and noted that about half of the male and female members of 4 generations suffered from the severe speech and language disorder. Gopnik (1990) and Gopnik and Crago (1991) reported findings suggesting that the affected members suffered from a specific impairment in grammar, namely, a selective inability to generate syntactic rules such as those for tense, number, and gender. Reported selectivity of the impairment led Gopnik (1990) and Gopnik and Crago (1991), as well as Pinker (1991, 1994) and Jackendoff (1994), to conclude that the KE family has an inherited grammar-specific disorder and thus provides evidence for the existence of 'grammar genes.' However, Vargha-Khadem et al. (1995) described investigations of the same family indicating that the affected members' disorder transcends the generation of morphosyntactic rules to include impaired processing and expression of other areas of grammar, grossly defective articulation of speech sounds, and a severe extralinguistic orofacial dyspraxia. The dyspraxia rendered their speech largely incomprehensible to the naive listener. In addition, the affected family members had both verbal and performance IQ scores that were on average 18 to 19 points below those of the unaffected members. This psychologic profile indicated that the inherited disorder does not affect morphosyntax exclusively, or even primarily; rather, it affects intellectual, linguistic, and orofacial praxic functions generally. Fisher et al. (1998) gave preliminary reports on brain imaging studies of affected and unaffected members of the KE pedigree. Findings suggested that the mutation at the SPCH1 locus results in functional abnormalities in motor-related areas of the frontal lobe, and that these are due, in turn, to abnormal anatomical development of several brain areas, with a key cytopathology being located in the neostriatum. Fisher et al. (1998) suggested that analysis of the gene could further understanding of both the structure and the function of the frontoneostriatal system. Extensive studies of the neural basis of the disorder in the KE family were reported by Vargha-Khadem et al. (1998). The core deficit responsible for the verbal dyspraxia involved sequential articulation and orofacial praxis. A positron emission tomography activation study revealed functional abnormalities in both cortical and subcortical motor-related areas of the frontal lobe, while quantitative analyses of magnetic resonance imaging scans revealed structural abnormalities in several of the same areas, particularly the caudate nucleus, which was found to be abnormally small bilaterally. The authors concluded that genetic mutation or deletion of the SPCH1 gene resulted in the abnormal development of several brain areas that appear to be critical for both orofacial movements and sequential articulation, resulting in marked disruption of speech and expressive language. Watkins et al. (1999) reviewed studies of brain morphometry and function in developmental language disorders and described studies of the autosomal dominant trait in the KE family. Studies of brain morphometry were stimulated by the landmark study of Geschwind and Levitsky (1968), which provided evidence of asymmetry in brain structure that correlated with the well-established functional asymmetry and dominance of the left hemisphere for language. By autopsy of 100 normal brains, they found that the planum temporale (which falls within Wernicke's area, known to be associated with language disorders when damaged in adulthood) was longer on the left in 65%, symmetric in 25%, and shorter on the left in 10% of the sample. This pattern has been found not only in adults but also in fetuses and neonates. Galaburda et al. (1978) showed that the gross asymmetry was associated with microscopic cytoarchitectonic differences between the hemispheres. Watkins et al. (1999) stated that half the members of the first 3 generations of the KE family were affected by a severe disorder of speech and language, which often made their speech unintelligible. The fourth-generation children were all born to unaffected parents and did not demonstrate the disorder; the affected family members of the third generation did not have children. Although no instance of male-to-male transmission was noted, the involvement of 9 females and 6 males suggested that the disorder is not X-linked. It was in this family that linkage to 7q31 was demonstrated for the locus, designated SPCH1. On the basis of their findings with imaging methods, Watkins et al. (1999) suggested that the genetic abnormality in the KE family may directly and selectively affect the development of the caudate nucleus or, perhaps, that of the basal ganglia more generally, resulting in both structural and functional abnormalities of the caudate nuclei bilaterally. Liegeois et al. (2003) performed functional MRI (fMRI) language experiments on several members of the KE family. During covert (silent) verb generation and overt (spoken) verb generation and word repetition, unaffected family members showed a typical left-dominant distribution of activation involving Broca's area in the generation tasks and a more bilateral distribution in the repetition task, whereas the affected members showed a more posterior and more extensively bilateral pattern of activation in all tasks. Consistent with previously reported morphologic abnormalities, the affected members showed significant underactivation relative to unaffected members in Broca's area and its right homolog, as well as in other cortical language-related regions and in the putamen. The findings suggested that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language. MacDermot et al. (2005) reported a 4-year-old boy with developmental delay in speech, language, and social skills. He communicated mainly using single words and was unable to repeat multisyllabic words. His 20-month-old sister had a history of motor and oropharyngeal dyspraxia, was unable to speak any words, could not identify objects, and had poor vocalization. Their mother reported a history of speech delay in childhood and showed severe problems in communication, with poor speech clarity and simple grammatical construction. All 3 patients were found to have a heterozygous nonsense mutation in the FOXP2 gene (605317.0002). Cytogenetics Fisher et al. (1998) noted the report of an interstitial deletion involving 7q31 by Sarda et al. (1988). A 7-year-old boy presented with a dysmorphic face and absence of speech, despite language comprehension and psychomotor development equivalent to those of a 5-year-old. The deletion involved 7q31.2-q32.3. Tyson et al. (2004) described a 14-year-old boy with a cryptic interstitial 7q31.3 deletion who presented with bilateral cleft lip and palate, hearing loss, mild mental retardation, and a language processing disorder. Chromosomal comparative genomic hybridization (CGH) studies of the patient proved inconclusive. Array CGH analysis, which was initiated to perform a higher resolution search for gains and losses, revealed deletion of 2 adjacent clones that map to 7q31.3 and are 4.4 Mb apart. The deletion was confirmed by FISH. Zeesman et al. (2006) reported a 5-year-old girl with an interstitial deletion of paternally-derived chromosome 7q31.2-q32.2 encompassing the FOXP2 gene. She had a severe communication disorder with evidence of oromotor dyspraxia and mild developmental delay. She was unable to cough, sneeze, or laugh spontaneously. She also had dysmorphic features, including microcephaly, brachycephaly, small nose, long philtrum, and downturned corners of the mouth. Rice et al. (2012) reported a mother and son with FOXP2 haploinsufficiency due to a 1.57-Mb deletion on chromosome 7q31, which included 2 other genes, MDFIC and PPP1R3A (600917). The boy had severe childhood apraxia of speech, with poor expressive speech, severely delayed speech acquisition, and inability to laugh, sneeze or cough spontaneously. He showed mildly impaired cognition, which may have been due to the speech limitations. He also lacked fine motor control. His 24-year-old mother was similarly, if slightly less, affected. She had a similar early developmental history, with speech apraxia and mild developmental delay. Neither patient had autistic features. Zilina et al. (2012) reported 2 unrelated families with speech and language disorders and other neurologic deficits associated with deletions of chromosome 7q31 involving the FOXP2 gene. A mother and daughter in the first family were affected. Both had problems chewing and swallowing food, showed pronounced drooling, and had delayed onset of the cough reflex in early life, as well as an inability to sneeze. The daughter showed failure to thrive, developmental delay, dysmorphic features, nystagmus, and myopia. Brain MRI showed mild brain atrophy and mild white matter hyperintensities. At age 3 years, she had some autistic features, low vocalization, poor vocabulary, and mild hand tremor. The mother had some autistic features, moderate speech delay, below average intelligence (IQ 88), poor social skills, emotional lability, and developmental verbal dyspraxia with difficulty in speech expression. Microarray analysis identified an 8.3-Mb deletion on chromosome 7q31.1-q31.31 including the FOXP2 gene in both the mother and the daughter. The mother's deletion was on the paternally derived chromosome. In the second family, the proband had developmental delay, mild dysmorphic features, mild ataxia, occasional aggressive behavior, and significant pronunciation difficulties with poor vocabulary. Her mother had intellectual disability, aggressive behavior, and developmental verbal dyspraxia. The maternal aunt of the proband had a phenotype similar to that of the mother. The maternal grandfather completed only 4 grades at school, had a severe speech defect, aggressive behavior, and balance problems. Molecular analysis in this family showed that the proband, the maternal aunt, and the maternal grandfather all carried a 6.5-Mb deletion of 7q31 including the FOXP2 gene; the mother of the proband refused study. The findings suggested no significant phenotypic difference due to parental origin of FOXP2 defects. Mapping By a genomewide linkage search, Fisher et al. (1997, 1998) identified a region on chromosome 7 that cosegregated with the speech and language disorder (maximum lod score = 6.62), confirming autosomal dominant inheritance with full penetrance. Fine mapping with all available microsatellites from the region enabled them to localize the gene (designated SPCH1) to a 5.6-cM interval in 7q31. Lai et al. (2000) used bioinformatic analyses to assemble a detailed BAC/PAC-based sequence map of the interval on 7q31 shown to contain the SPCH1 gene. The region was found to contain 152 STSs, 20 known genes, and more than 7.75 Mb of completed genomic sequence. They screened the affected chromosome 7 from the KE family with 120 of these STSs, but could detect no evidence of microdeletion. Novel polymorphic markers were generated from the sequence and were used to localize critical recombination breakpoints in the KE family. This allowed refinement of the SPCH1 interval to a region between 2 markers containing approximately 6.1 Mb of completed sequence. In addition, Lai et al. (2000) studied 2 unrelated patients with a similar speech and language disorder, who had de novo translocations involving 7q31. Fluorescence in situ hybridization analyses with BACs/PACs from the sequence map localized the t(5;7)(q22;q31.2) breakpoint in the first patient to a single clone within the newly refined SPCH1 interval. This clone contained the CAGH44 gene (605317), which encodes a brain-expressed protein containing a large polyglutamine stretch. However, Lai et al. (2000) found the t(2;7)(q23;q31.3) breakpoint in the second patient resided within a BAC clone mapping more than 3.7 Mb distal to CAGH44, outside of the SPCH1 critical region. Finally, they investigated the CAGH44 gene in affected individuals of the KE family, and found no mutations in the then-known coding sequence. Molecular Genetics Lai et al. (2001) demonstrated that the FOXP2 gene, which encodes a putative transcription factor containing a polyglutamine tract and forkhead DNA-binding domain, is directly disrupted in the translocation breakpoint in patient CS (unrelated to the family KE). This patient, initially reported by Lai et al. (2000), had speech and language impairment associated with the chromosomal translocation involving the SPCH1 interval. Lai et al. (2001) also identified a point mutation affecting members of the KE family that alters an invariant amino acid residue in the forkhead domain (605317.0001). In 1 of 49 probands with a specific diagnosis of verbal dyspraxia, MacDermot et al. (2005) identified a heterozygous mutation in the FOXP2 gene (605317.0002). The proband's sister and mother also had the mutation. Animal Model Shu et al. (2005) found that Foxp2-null mice demonstrated severe motor abnormalities, premature death, and an absence of ultrasonic vocalizations that are usually elicited when pups are removed from their mothers. Foxp2 +/- mice showed modest developmental motor delays but significant decreases in the number of ultrasonic vocalizations. However, the duration, peak frequency, and bandwidth of the vocalizations were indistinguishable from wildtype. Neuropathologic examination showed severely abnormal early development of cerebellar neuronal cell layers in knockout mice, with less severe changes in heterozygous mice. History Folstein and Mankoski (2000) suggested a relationship between autism (see 209850) and SPCH1 or specific language impairment because genetic studies in the disorders pointed to a locus on 7q31 (see AUTS9, 611015). However, Newbury et al. (2002), using association and mutation screening analyses, concluded that the coding region variants in FOXP2 do not underlie the AUTS9 linkage, and that the FOXP2 gene is unlikely to play a role in autism or more common forms of language impairment. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Orofacial dyspraxia, linguistic and nonlinguistic NEUROLOGIC Central Nervous System \- Language development deficit \- Discrepancy between verbal and nonverbal abilities \- Inability to generate syntactic grammar rules (i.e., tense, gender, number) \- Defect in morphosyntactic rules \- Impaired processing of language \- Impaired expression of language \- Articulation defects \- Phonology deficits \- Orofacial dyspraxia, linguistic and nonlinguistic \- Incomprehensible speech \- Brain imaging shows functional defects in the cortical and subcortical motor-related areas of the frontal lobe \- Structural abnormalities in the basal ganglia (especially caudate) \- Decreased nonverbal IQ \- No other neurologic disorder MISCELLANEOUS \- This specific disorder has been described in 1 family (KE) \- Genetic heterogeneity for phenotypically similar disorders with specific language impairment (SLI1 606711 , SLI2 606712 , SLI3 607134 ) \- See also familial developmental dysphasia ( 600117 ) MOLECULAR BASIS \- Caused by mutation in the forkhead box P2 gene (FOXP2, 605317.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	SPEECH-LANGUAGE DISORDER 1	c0750927	6,189	omim	https://www.omim.org/entry/602081	2019-09-22T16:14:07	{"doid": ["0111275"], "mesh": ["D001072"], "omim": ["602081"], "orphanet": ["209908"], "synonyms": ["DEVELOPMENTAL VERBAL DYSPRAXIA", "SPEECH AND LANGUAGE DISORDER WITH OROFACIAL DYSPRAXIA", "Speech and language disorder with orofacial dyspraxia", "CAS", "Alternative titles", "Developmental verbal dyspraxia", "CHILDHOOD APRAXIA OF SPEECH", "Speech-language disorder type 1"], "genereviews": ["NBK368474"]}
Dopa-responsive dystonia is a disorder that involves involuntary muscle contractions, tremors, and other uncontrolled movements (dystonia). The features of this condition range from mild to severe. This form of dystonia is called dopa-responsive dystonia because the signs and symptoms typically improve with sustained use of a medication known as L-Dopa. Signs and symptoms of dopa-responsive dystonia usually appear during childhood, most commonly around age 6. The first signs of the condition are typically the development of inward- and upward-turning feet (clubfeet) and dystonia in the lower limbs. The dystonia spreads to the upper limbs over time; beginning in adolescence, the whole body is typically involved. Affected individuals may have unusual limb positioning and a lack of coordination when walking or running. Some people with this condition have sleep problems or episodes of depression more frequently than would normally be expected. Over time, affected individuals often develop a group of movement abnormalities called parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability). The movement difficulties associated with dopa-responsive dystonia usually worsen with age but stabilize around age 30. A characteristic feature of dopa-responsive dystonia is worsening of movement problems later in the day and an improvement of symptoms in the morning, after sleep (diurnal fluctuation). Rarely, the movement problems associated with dopa-responsive dystonia do not appear until adulthood. In these adult-onset cases, parkinsonism usually develops before dystonia, and movement problems are slow to worsen and do not show diurnal fluctuations. ## Frequency Dopa-responsive dystonia is estimated to affect 1 per million people worldwide. However, the disorder is likely underdiagnosed because the condition may not be identified in people with mild symptoms, or it may be misdiagnosed in people who have symptoms similar to other movement disorders. ## Causes Mutations in the GCH1 gene are the most common cause of dopa-responsive dystonia. Less often, mutations in the TH or SPR gene cause this condition. The GCH1 gene provides instructions for making an enzyme called GTP cyclohydrolase. This enzyme is involved in the first of three steps in the production of a molecule called tetrahydrobiopterin (BH4). The SPR gene, which provides instructions for making the sepiapterin reductase enzyme, is involved in the last step of tetrahydrobiopterin production. Tetrahydrobiopterin helps process several protein building blocks (amino acids), and is involved in the production of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Specifically, tetrahydrobiopterin is involved in the production of two neurotransmitters called dopamine and serotonin. Among their many functions, dopamine transmits signals within the brain to produce smooth physical movements, and serotonin regulates mood, emotion, sleep, and appetite. The protein produced from the TH gene is also involved in dopamine production. The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which helps convert the amino acid tyrosine to dopamine. Mutations in the GCH1 or SPR gene impair the production of tetrahydrobiopterin, which leads to a decrease in the amount of available dopamine. TH gene mutations result in the production of a tyrosine hydroxylase enzyme with reduced function, which leads to a decrease in dopamine production. A reduction in the amount of dopamine interferes with the brain's ability to produce smooth physical movements, resulting in the dystonia, tremor, and other movement problems associated with dopa-responsive dystonia. Sleep and mood disorders also occur in some individuals with GCH1 or SPR gene mutations; these disorders likely result from a disruption in the production of serotonin. Problems with sleep and episodes of depression are not seen in people with dopa-responsive dystonia caused by TH gene mutations, which is sometimes referred to as Segawa syndrome. Some people with dopa-responsive dystonia do not have an identified mutation in the GCH1, TH, or SPR gene. The cause of the condition in these individuals is unknown. ### Learn more about the genes associated with Dopa-responsive dystonia * GCH1 * SPR * TH ## Inheritance Pattern When dopa-responsive dystonia is caused by mutations in the GCH1 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some 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. Some people who inherit the altered GCH1 gene never develop features of dopa-responsive dystonia. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with a mutated gene do not. For unknown reasons, dopa-responsive dystonia caused by mutations in the GCH1 gene affects females two to four times more often than males. When TH gene mutations are responsible for causing dopa-responsive dystonia, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. When dopa-responsive dystonia is caused by mutations in the SPR gene, it can have either an autosomal recessive or, less commonly, 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 [mRNA]: messenger RNA *[kDa]: kilodalton	Dopa-responsive dystonia	c1851920	6,190	medlineplus	https://medlineplus.gov/genetics/condition/dopa-responsive-dystonia/	2021-01-27T08:24:54	{"gard": ["9817"], "mesh": ["C538007"], "omim": ["128230", "612716", "605407"], "synonyms": []}
Deviation from normal walking (gait) Gait abnormality Other namesAbnormalities of gait Play media Quadrupedalism in a Kurdish family SpecialtyNeurology, orthopedics Gait abnormality is a deviation from normal walking (gait). Watching a patient walk is the most important part of the neurological examination. Normal gait requires that many systems, including strength, sensation and coordination, function in an integrated fashion. Many common problems in the nervous system and musculoskeletal system will show up in the way a person walks.[1] ## Contents * 1 Presentation and causes * 2 See also * 3 References * 4 External links ## Presentation and causes[edit] Patients with musculoskeletal pain, weakness or limited range of motion often present conditions such as Trendelenburg's sign, limping, myopathic gait and antalgic gait. Patients suffering from peripheral neuropathy also experience numbness and tingling in their hands and feet. This can cause ambulation impairment, such as trouble climbing stairs or maintaining balance. Gait abnormality is also common in persons with nervous system problems such as cauda equina syndrome, multiple sclerosis, Parkinson's disease, Alzheimer's disease, myasthenia gravis, normal pressure hydrocephalus, and Charcot–Marie–Tooth disease. Research has shown that neurological gait abnormalities are associated with an increased risk of falls in older adults.[2] Orthopedic corrective treatments may also manifest into gait abnormality, such as lower extremity amputation, healed fractures, and arthroplasty (joint replacement). Difficulty in ambulation that results from chemotherapy is generally temporary in nature, though recovery times of six months to a year are common. Likewise, difficulty in walking due to arthritis or joint pains (antalgic gait) sometimes resolves spontaneously once the pain is gone.[3][4] Hemiplegic persons have circumduction gait, where the affected limb moves through an arc away from the body, and those with cerebral palsy often have scissoring gait. ## See also[edit] * Ataxia * Foot drop * Gait Abnormality Rating Scale * Limp ## References[edit] 1. ^ Harrison's Principles of Internal Medicine, 16th ed., Ch. 346, Approach to the Paitent with Neurological Disease 2. ^ Verghese, Joe; Ambrose, Anne F.; Lipton, Richard B.; Wang, Cuiling (2010-03-01). "Neurological gait abnormalities and risk of falls in older adults". Journal of Neurology. 257 (3): 392–398. doi:10.1007/s00415-009-5332-y. ISSN 0340-5354. PMC 2838981. PMID 19784714. 3. ^ "Gait Abnormality Coding Checklist by Jun Mapili, PT, MA13212503469Ed". Selmanholman.com. Archived from the original on 2014-07-14. Retrieved 2014-06-10. 4. ^ ICD-9-cm Chrisenders Archived May 21, 2005, at the Wayback Machine ## External links[edit] Classification D * ICD-10: R26 * ICD-9-CM: 781.2 * MeSH: D020233 * DiseasesDB: 15409 External resources * MedlinePlus: 003199 * eMedicine: pmr/225 * Videos of various abnormal gaits * Foot Abnormality * v * t * e Symptoms and signs relating to movement and gait Gait * Gait abnormality * CNS * Scissor gait * Cerebellar ataxia * Festinating gait * Marche à petit pas * Propulsive gait * Stomping gait * Spastic gait * Magnetic gait * Truncal ataxia * Muscular * Myopathic gait * Trendelenburg gait * Pigeon gait * Steppage gait * Antalgic gait Coordination * Ataxia * Cerebellar ataxia * Dysmetria * Dysdiadochokinesia * Pronator drift * Dyssynergia * Sensory ataxia * Asterixis Abnormal movement * Athetosis * Tremor * Fasciculation * Fibrillation Posturing * Abnormal posturing * Opisthotonus * Spasm * Trismus * Cramp * Tetany * Myokymia * Joint locking Paralysis * Flaccid paralysis * Spastic paraplegia * Spastic diplegia * Spastic paraplegia * Syndromes * Monoplegia * Diplegia / Paraplegia * Hemiplegia * Triplegia * Tetraplegia / Quadruplegia * General causes * Upper motor neuron lesion * Lower motor neuron lesion Weakness * Hemiparesis Other * Rachitic rosary * Hyperreflexia * Clasp-knife response * v * t * e Musculoskeletal examination Leg Hip examination * Galeazzi test * Allis test * Barlow maneuver * Ober's test * Ortolani test * Patrick's test * Thomas test * Trendelenburg's sign Knee examination * Ballottement * Clarke's test * Drawer test * Lachman test * Patellar tap * Pivot-shift test * Valgus stress test * meniscus * Apley grind test * McMurray test * ligament and meniscus * Unhappy triad Foot and ankle * Hubscher's maneuver * Mulder's sign * Simmonds' test * Thompson test * Ankle * Simmonds' test General * Straight leg raise * Lasègue's sign * Gait abnormality * Trendelenburg gait * Unequal leg length Arm Shoulder examination * Apprehension test * Jobe's test * Neer impingement sign * Yergason's test * rotator cuff * Hawkins–Kennedy test * Watson's test Elbow examination * Cozen's test * Elbow extension test Hand and wrist * Durkan's test * Finkelstein's test * Froment's sign * Lunotriquetral shear test * Phalen maneuver * Tinel sign * Watson's test Spine * Gaenslen's test * Low back pain * Waddell's signs * Lower back flexibility * Schober's test * sacroiliitis * Larrey's sign Other * Range of motion * Palpation * Codman triangle [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Gait abnormality	c0231687	6,191	wikipedia	https://en.wikipedia.org/wiki/Gait_abnormality	2021-01-18T18:41:05	{"mesh": ["D020233"], "umls": ["C0231687"], "icd-10": ["R26"], "wikidata": ["Q827017"]}
A number sign (#) is used with this entry because complement component-2 deficiency is caused by homozygous or compound heterozygous mutation in the C2 gene (613927) on chromosome 6p21. Clinical Features Klemperer et al. (1966, 1967) found C2 deficiency in multiple members of a kindred. No gene product was detected in those with the deficiency (homozygotes). In heterozygotes a partial deficiency of C2 was found. Restudy of the family examined by Silverstein (1960) demonstrated identical findings. None of the homozygotes has been unduly sensitive to bacterial infection or had other evident abnormality. By means of monospecific antiserum, Polley (1968) showed that homozygotes have no second component of complement and heterozygotes have an intermediate amount. Thus, the defect is failure of synthesis rather than synthesis of an inactive analog. Einstein et al. (1975) reported affected brother and sister. The sister had Henoch-Schonlein purpura and 2 previously reported patients with C2 deficiency had this disorder. Friend et al. (1975) studied 3 unrelated persons with deficiency of C2 in association with lupus erythematosus, polyarteritis and membranoproliferative glomerulonephritis. Provost et al. (1983) pointed out that heterozygous C2 deficiency has a frequency of 1 to 2%, that it usually segregates with the HLA-A25,B18,Dw2 haplotype, and that in about one-third of reported cases of homozygous C2 deficiency discoid (cutaneous) lupus and/or an SLE-like disorder is present. Cole et al. (1985) stated that about half of the reported patients with C2 deficiency have autoimmune disease, most commonly systemic lupus erythematosus, Henoch-Schonlein purpura, or polymyositis. By molecular genetic studies of cultured blood monocytes, they concluded that C2 deficiency is not caused by a major gene deletion or rearrangement but is the result of a 'specific and selective pretranslational regulatory defect in C2 gene expression.' Serum from patients with C2 deficiency lack functionally and immunologically detectable C2 protein. Johnson et al. (1992) reported 2 families with C2 deficiency. They designated the defect in the first family as type I; no detectable C2 protein was synthesized. In the second family, there appeared to be a selective block in C2 secretion; the cell lysate showed an increase in C2 and there was measurable C2 in the blood. The defect in the second family was designated as type II. Measurement of conventional C2 hemolytic functional activity did not distinguish between the defects in the 2 families. The type I defect was associated with the MHC haplotype that was found to be associated with C2 deficiency in approximately 94% of chromosomes in the series reported by Awdeh et al. (1981), i.e., haplotype A25, B18, Drw2, BFS, C2Q0, C4A4B2. In the family with type II, 2 different MHC haplotypes were associated with C2 deficiency. D'Cruz et al. (1992) described a brother and sister with homozygous C2 deficiency who developed cutaneous vasculitis and sicca syndrome. The mother had seropositive rheumatoid arthritis. D'Cruz et al. (1992) pictured the vasculitic purpuric rash on the legs of the patient. The rash started as small, raised, maculopapular lesions, some of which progressed to necrosis and ulceration followed by healing. Mapping Raum et al. (1976) concluded that the CFB locus (138470) and the C2 deficiency locus are close together (no recombinant was observed) and that the 2 loci are 3 to 5 centimorgans from the HLA-A (142800) and HLA-B (142830) loci on chromosome 6p. Two crossovers out of 57 were observed for C2 versus HLA-B, and 3 out of 72 for CFB versus HLA-B. The order of the genes was taken to be HLA-A, -B, -D, CFB, C2. Population Genetics Cole et al. (1985) stated that C2 deficiency is the most frequent complement deficiency state among western European populations, occurring in about 1 in 10,000 white persons. Molecular Genetics Friend et al. (1975) found that 3 unrelated persons with deficiency of C2 in association with lupus erythematosus, polyarteritis and membranoproliferative glomerulonephritis were homozygous for the mixed lymphocyte reaction determinant, short 7a (7a). Since two were homozygous HLA-A10, Bw18 and the third was a (A10, B11) (A2, B12.2) heterozygote, the authors suggested linkage disequilibrium between C2 deficiency, A10 and BW18. Awdeh et al. (1981) did C4 allotyping of 13 homozygous C2-deficient persons and found that 23 of 25 haplotypes were of the relatively rare type C4A4B2. Simon et al. (1991) described a RFLP fragment that is a unique marker for C2 deficiency and for the uncommon C2B allele which is associated with type I diabetes. By sequencing of the entire C2 cDNA from 2 patients with type I C2 deficiency, Johnson et al. (1991) identified a homozygous 28-bp deletion (613927.0001); the deletion was not present in normal C2 genes or in type II C2-deficient genes. In patients with type II C2 deficiency, Wetsel et al. (1996) identified compound heterozygosity for 2 missense mutations in the C2 gene (613927.0002-613927.0003). Animal Model Although guinea pigs with C2 and C4 deficiency appeared healthy, Bottger et al. (1986) found that they had serologic characteristics of immune complex disease. INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Skin \- Henoch-Schonlein purpura MUSCLE, SOFT TISSUES \- Polymyositis IMMUNOLOGY \- Autoimmune disease \- Systemic lupus erythematosus \- Sjogren syndrome \- C2 deficiency MOLECULAR BASIS \- Caused by mutation in the complement component 2 gene (C2, 613927.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	COMPLEMENT COMPONENT 2 DEFICIENCY	c3150275	6,192	omim	https://www.omim.org/entry/217000	2019-09-22T16:29:29	{"doid": ["0060295"], "omim": ["217000"], "orphanet": ["169147"], "synonyms": ["Immunodeficiency due to C1, C4, or C2 component complement deficiency", "Alternative titles", "C2 DEFICIENCY", "Immunodeficiency due to an early component of complement deficiency"]}
Acute monocytic leukemia SpecialtyHematology, oncology Acute monocytic leukemia (AMoL, or AML-M5)[1] is a type of acute myeloid leukemia. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Causes[edit] M5 is associated with characteristic chromosomal abnormalities, often involving chromosome 11, such as t(9;11), affecting the MLL (KMTA2) locus at 11q23; however MLL translocations are also found in other leukemia subtypes. The t(8;16) translocation in AMoL is associated with hemophagocytosis. Secondary leukaemia, which may include AML-M5, has been associated with exposure to epipodophyllotoxins, such as etoposide.[2] ## Diagnosis[edit] In order to fulfill World Health Organization (WHO) criteria for AML-5, a patient must have greater than 20% blasts in the bone marrow, and of these, greater than 80% must be of the monocytic lineage. A further subclassification (M5a versus M5b) is made depending on whether the monocytic cells are predominantly monoblasts (>80%) (acute monoblastic leukemia) or a mixture of monoblasts and promonocytes (<80% blasts). Monoblasts can be distinguished by having a roughly circular nucleus, delicate lacy chromatin, and abundant, often basophilic cytoplasm. These cells may also have pseudopods. By contrast, promonocytes have a more convoluted nucleus, and their cytoplasm may contain metachromatic granules. Monoblasts are typically MPO-negative and promonocytes are MPO variable. Both monoblasts and promonocytes stain positive for non-specific esterase (NSE), however NSE may often be negative. Immunophenotypically, M5-AML variably express myeloid (CD13, CD33) and monocytic (CD11b, CD11c) markers. Cells may aberrantly express B-cell marker CD20 and the NK marker CD56. Monoblasts may be positive for CD34. ## Treatment[edit] AML-M5 is treated with intensive chemotherapy (such as anthracyclines) or with bone marrow transplantation. ## References[edit] 1. ^ "Acute Myeloid Leukemia - Signs and Symptoms". 2. ^ Kollmannsberger, C.; et al. (Oct 1998). "Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors". J. Clin. Oncol. (16(10)): 3386–91. ## External links[edit] Classification D * ICD-10: C93.0 * ICD-9-CM: 206.0 * MeSH: D007948 * SNOMED CT: 22331004 * Image at hmds.org.uk * v * t * e Myeloid-related hematological malignancy CFU-GM/ and other granulocytes CFU-GM Myelocyte AML: * Acute myeloblastic leukemia * M0 * M1 * M2 * APL/M3 MP * Chronic neutrophilic leukemia Monocyte AML * AMoL/M5 * Myeloid dendritic cell leukemia CML * Philadelphia chromosome * Accelerated phase chronic myelogenous leukemia Myelomonocyte AML * M4 MD-MP * Juvenile myelomonocytic leukemia * Chronic myelomonocytic leukemia Other * Histiocytosis CFU-Baso AML * Acute basophilic CFU-Eos AML * Acute eosinophilic MP * Chronic eosinophilic leukemia/Hypereosinophilic syndrome MEP CFU-Meg MP * Essential thrombocytosis * Acute megakaryoblastic leukemia CFU-E AML * Erythroleukemia/M6 MP * Polycythemia vera MD * Refractory anemia * Refractory anemia with excess of blasts * Chromosome 5q deletion syndrome * Sideroblastic anemia * Paroxysmal nocturnal hemoglobinuria * Refractory cytopenia with multilineage dysplasia CFU-Mast Mastocytoma * Mast cell leukemia * Mast cell sarcoma * Systemic mastocytosis Mastocytosis: * Diffuse cutaneous mastocytosis * Erythrodermic mastocytosis * Adult type of generalized eruption of cutaneous mastocytosis * Urticaria pigmentosa * Mast cell sarcoma * Solitary mastocytoma Systemic mastocytosis * Xanthelasmoidal mastocytosis Multiple/unknown AML * Acute panmyelosis with myelofibrosis * Myeloid sarcoma MP * Myelofibrosis * Acute biphenotypic leukaemia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Acute monocytic leukemia	c0023465	6,193	wikipedia	https://en.wikipedia.org/wiki/Acute_monocytic_leukemia	2021-01-18T18:47:51	{"gard": ["525"], "mesh": ["D007948"], "umls": ["C0023465"], "icd-10": ["C93.0"], "orphanet": ["514"], "wikidata": ["Q4677938"]}
This article needs to be updated. Please update this article to reflect recent events or newly available information. (December 2019) HIV/AIDS in India is an epidemic. The National AIDS Control Organisation (NACO) estimated that 2.14 million people lived with HIV/AIDS in India in 2017.[1] Despite being home to the world's third-largest population of persons with HIV/AIDS (as of 2018, with South Africa and Nigeria having more),[2] the AIDS prevalence rate in India is lower than that of many other countries. In 2016, India's AIDS prevalence rate stood at approximately 0.30%—the 80th highest in the world.[3] Treatment of HIV/AIDS is primarily via a "drug cocktail" of antiretroviral drugs and education programs to help people avoid infection. New HIV infections each year, and AIDS deaths occurring during the year in India ## Contents * 1 Epidemiology * 2 Management * 3 History * 4 Society and culture * 4.1 HIV/AIDS (Prevention and Control) Bill 2014 * 4.2 Litigation for right of access to treatment * 4.3 Orphans * 4.3.1 Stigma * 4.3.2 Mental health * 4.3.3 Education * 4.3.4 Responses * 5 See also * 5.1 Lists of ART centres * 5.2 Non-governmental organisations * 6 References * 7 External links ## Epidemiology[edit] HIV prevalence among women attending prenatal clinics, commercial sex workers, and injecting drug users, in India in 2001 See also: Epidemiology of HIV/AIDS The main factors which have contributed to India's large HIV-infected population are extensive labour migration and low literacy levels in certain rural areas resulting in a lack of awareness and in gender disparities.[4] The Government of India has also raised concerns about the role of intravenous drug use and prostitution in spreading AIDS.[4][5] According to Avert,[6] the statistics for special populations in 2007 are as follows: State Antenatal clinic HIV prevalence 2007 (%)[7] STD clinic HIV prevalence 2007 (%)[6] IDU HIV prevalence 2007 (%)[6] MSM HIV prevalence 2007 (%)[6] Female sex worker HIV prevalence 2007 (%)[6] A & N Islands 0.25 8.00 16.80 6.60 4.68 Andhra Pradesh 1.00 17.20 3.71 17.04 9.74 Arunachal Pradesh 0.00 0.00 0.00 ... ... Assam 0.00 0.50 2.41 2.78 0.44 Bihar 0.25 0.40 0.60 0.00 3.41 Chandigarh 0.25 0.42 8.64 3.60 0.40 Chhattisgarh 0.25 3.33 ... ... 1.43 D & N Haveli 0.50 ... ... ... ... Daman & Diu 0.13 ... ... ... ... Delhi 0.25 5.20 10.10 11.73 3.15 Goa 0.18 5.60 ... 7.93 ... Gujarat 0.25 2.40 ... 8.40 6.53 Haryana 0.13 0.00 0.80 5.39 0.91 Himachal Pradesh 0.00 0.00 ... 5.39 0.87 Jammu & Kashmir 0.00 0.20 ... ... ... Jharkhand 0.00 0.40 ... ... 1.09 Karnataka 0.50 8.40 2.00 17.60 5.30 Kerala 0.38 1.60 7.85 0.96 0.87 Lakshadweep 0.00 0.00 ... ... 0.00 Madhya Pradesh 0.00 1.72 ... ... 0.67 Maharashtra 0.50 11.62 24.40 11.80 17.91 Manipur 0.75 4.08 17.90 16.4 13.07 Meghalaya 0.00 2.21 4.17 ... ... Mizoram 0.75 7.13 7.53 ... 7.20 Nagaland 0.60 3.42 1.91 ... 8.91 Orissa 0.00 1.60 7.33 7.37 0.80 Pondicherry 0.00 3.22 ... 2.00 1.30 Punjab 0.00 1.60 13.79 1.22 0.65 Rajasthan 0.13 2.00 ... ... 4.16 Sikkim 0.09 0.00 0.47 ... 0.00 Tamil Nadu 0.25 1.33 ... ... ... Tripura 0.25 0.40 0.00 ... ... Uttar Pradesh 0.00 0.48 1.29 0.40 0.78 Uttaranchal 0.00 0.00 ... ... ... West Bengal 0.00 0.80 7.76 5.61 5.92 Note: Some areas in the above table report an HIV prevalence rate of zero in antenatal clinics. This does not necessarily mean HIV is absent from the area, as some states report the presence of the virus at STD clinics and among intravenous drug users. In some states and union territories, the average antenatal HIV prevalence is based on reports from only a small number of clinics. In India, populations which are at a higher risk of HIV are female sex workers, men who have sex with men, injecting drug users, and transgenders/hijras.[8] ## Management[edit] See also: Management of HIV/AIDS People, especially women, visiting the Red Ribbon Express on a tour of India promoting AIDS awareness when it arrived in Chennai in 2012 "Know AIDS - No AIDS" sign on a road in India India has been praised for its extensive anti-AIDS campaigning.[9] According to Michel Sidibé, Executive Director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), India's success comes from using an evidence-informed and human rights-based approach that is backed by sustained political leadership and civil society engagement.[10] A 2012 UNAIDS report lauded India for doing "particularly well" in halving the number of adults newly infected between 2000 and 2009 in contrast to some smaller countries in Asia. In India, the number of deaths due to AIDS stood at 170,000 in 2009. It also points out that India provided substantial support to neighbouring countries and other Asian countries – in 2011, it allocated USD 430 million to 68 projects in Bhutan across key socioeconomic sectors, including health, education and capacity building. In 2011 at Addis Ababa, the Government of India further committed to accelerating technology transfer between its pharmaceutical sector and African manufacturers. The National AIDS Control Organisation (NACO) has increased the number of centres providing free Antiretroviral Treatment (ART) from 54 to 91 centres, with 9 more centres to be operational soon.[when?] Medicines for treating 8,500 patients have been made available at these centres. All the 91 centres have trained doctors, counsellors and laboratory technicians to help initiate patients on ART and provide follow up care while protecting confidentiality. Apart from providing free treatment, all the ART centres provide counselling to the infected persons so that they regularly take their medication. Continuity is the most important factor for the long term effectiveness of the ART drugs, as disruption can lead to drug resistance.[citation needed] At present, 40,000 are on ART, which is expected to go up to 85,000 by March.[when?] Responding to a petition made by NGO's, in 2010, the Supreme Court of India directed the Indian government to provide second-line Antiretroviral Therapy (ART) to all AIDS patients in the country, and warned the government against abdicating its constitutional duty of providing treatment to HIV positive patients on grounds of financial constraint, as it was an issue of the right to life guaranteed under Article 21 of the Indian Constitution. Previously, in an affidavit before the Supreme Court, NACO said second-line ART treatment for HIV patients, costing Rs 28,500 each, could not be extended to those who had received "irrational treatment" by private medical practitioners for the first round, which costs around Rs 6,500. The court rejected both the arguments of financial constraints and that only 10 viral load testing centres were needed for testing patients for migrating from the first line of treatment to the second line, as stated by the Solicitor General representing the government. The court further asked the government to give a clear-cut and "workable" solution within a week's time.[11][12] HIV spending increased in India from 2003 to 2007 and fell by 15% in 2008 to 2009. Currently, India spends about 5% of its health budget on HIV/AIDS. Spending on HIV/AIDS may create a burden in the health sector, which faces a variety of other challenges. Thus, it is crucial for India to step up on its prevention efforts to decrease its spending of the health budget on HIV/AIDS in future.[6] Apart from government funding, there are various international foundations like the UNDP, World Bank, Elton John AIDS Foundation, USAID and others who are funding HIV/AIDS treatment in India.[13][14][15] ## History[edit] See also: History of HIV/AIDS In 1986, the first known cases of HIV in India were diagnosed by Dr. Suniti Solomon and her student Dr. Sellappan Nirmala amongst six female sex workers in Chennai, Tamil Nadu.[16][17] In the same year, the Government of India established the National AIDS Committee within the Ministry of Health and Family Welfare.[18] In 1992, on the basis of National AIDS Committee, the government set up the National AIDS Control Organisation (NACO) to oversee policies and prevention and control programmes relating to HIV and AIDS and the National AIDS Control Programme (NACP) for HIV prevention.[19][20] Subsequently, the State AIDS Control Societies (SACS) were set up in states and union territories. SACS implement the NACO programme at a state level, but have functional independence to upscale and innovate.[21] The first phase was implemented from 1992 to 1999 and focused on monitoring HIV infection rates among high-risk populations in selected urban areas.[18] In 1999, the second phase of the National AIDS Control Programme (NACP II) was introduced to decrease the reach of HIV by promoting behaviour change. The prevention of mother-to-child transmission programme (PMTCT) and the provision of antiretroviral treatment were developed.[22][citation needed] A National Council on AIDS was formed during this phase, consisting of 31 ministries and chaired by the Prime Minister.[18] The second phase ran between 1999 and 2006.[18] A 2006 study published in the British medical journal The Lancet reported an approximately 30% decline in HIV infections from 2000 to 2004 among women aged 15 to 24 attending prenatal clinics in selected southern states of India, where the epidemic is thought to be concentrated. Recent studies suggest that many married women in India, despite practicing monogamy and having no risk behaviours, acquire HIV from their husbands and HIV testing of married males can be an effective HIV prevention strategy for the general population.[23] In 2007, the third phase of the National AIDS Control Programme (NACP III) targeted high-risk groups and conducted outreach programmes. It also decentralised the effort to local levels and non-governmental organisations (NGOs) to provide welfare services to the affected.[6] The US$2.5 billion plan received support from UNAIDS.[24] The third stage dramatically increased targeted interventions, aiming to halt and reverse the epidemic by integrating programmes for prevention, care, support and treatment.[18] By the end of 2008, targeted interventions covered almost 932,000 of those most at risk, or 52% of the target groups (49% of female sex workers, 65% of injection drug users and 66% of men who have sex with men).[18] Some efforts have been made to tailor educational literature to those with low literacy levels, mainly through readily accessible local libraries.[25] Increased awareness regarding the disease and citizen's related rights is in line with the Universal Declaration on Human Rights. In 2009, India established a National HIV and AIDS Policy and the World of Work, which sought to end discrimination against workers on the basis of their real or perceived HIV status.[18] Under this policy, all enterprises are encouraged to establish workplace policies and programmes based on the principles of non-discrimination, gender equity, healthy work environment, non-screening for the purpose of employment, confidentiality, prevention and care and support.[18] Researchers at the Overseas Development Institute have called for greater attention to migrant workers, whose concerns about their immigration status may leave them particularly vulnerable.[18] No agency is tasked with enforcing the non-discrimination policy; instead, a multisectoral approach has been developed involving awareness campaigns in the private sector. The AIDS Bhedbhav Virodhi Andolan (AIDS Anti-Discrimination Movement) has prepared many citizen reports challenging discriminatory policies, and filed a petition in the Delhi High Court regarding the proposed segregation of gay men in prisons. A play titled High Fidelity Transmission by Rajesh Talwar[26] focused on discrimination, the importance of using a condom and illegal testing of vaccines.[27] HIV/AIDS-related television shows and movies have appeared in the past few years, mostly in an effort to appeal to the middle class.[28] An important component of these programs has been the depiction of HIV/AIDS affected persons interacting with non-infected persons in everyday life.[29] As per the UNDP's 2010 report, India had 2.395 million people living with HIV at the end of 2009, up from 2.27 million in 2008. Adult prevalence also rose from 0.29% in 2008 to 0.31% in 2009.[30] Setting up HIV screening centres was the first step taken by the government to screen its citizens and the blood bank.[citation needed] Adult HIV prevalence in India declined from an estimated 0.41% in 2000 to 0.31% in 2009. Adult HIV prevalence at a national level has declined notably in many states, but variations still exist across the states. A decreasing trend is also evident in HIV prevalence among people aged 15–24. A 2012 report described a need for youth HIV counseling.[31] According to NACO data, India has had a 57% reduction in estimated annual new adult HIV infections, from 274,000 in 2000 to 116,000 in 2011, and the estimated number of people living with HIV was 2.08 million in 2011.[32][33] According to NACO, the prevalence of AIDS in India in 2015 was 0.26%, down from 0.41% in 2002;[34] in 2016, it had risen to 0.30%.[3] ## Society and culture[edit] ### HIV/AIDS (Prevention and Control) Bill 2014[edit] The HIV/AIDS (Prevention and Control) Bill 2014, which sought to end stigma and discrimination against HIV positive persons in workplaces, hospitals and society while also ensuring patient privacy, was introduced in the Rajya Sabha on 11 February 2014,[35][36] and was passed on 21 March 2017.[37] ### Litigation for right of access to treatment[edit] * Voluntary Health Association of Punjab v. Union of India[38] * Love Life Society v. Union of India & Others[39] * Wahengbam Joykumar v. Union of India & Others[40] * Delhi Network of Positive People & Another v. Union of India & Others[41] ### Orphans[edit] See also: AIDS orphan This section may contain an excessive amount of intricate detail that may interest only a particular audience. Please help by spinning off or relocating any relevant information, and removing excessive detail that may be against Wikipedia's inclusion policy. (February 2020) (Learn how and when to remove this template message) Orphans who have lost a parent to AIDS celebrate World AIDS Day in Hyderabad, India. There are 2 million children in India that have lost one or both parents due to AIDS.[42] There are also millions of vulnerable children living in India, or children "whose survival, well-being, or development is threatened due to the possibility of exposure to HIV/AIDS,"[42] and the number of these AIDS orphans will continue to grow.[43] Due to the negative treatment and lack of resources for these children, AIDS orphans and vulnerable children in India are at risk for health and educational disparities. They are also at higher risk for becoming infected with HIV themselves, child labour, trafficking, and prostitution.[44] #### Stigma[edit] AIDS orphans are usually cared for by extended family members.[45] These extended family members may be vulnerable as well, as they are often elderly or ill themselves. A study from 2004 found that many AIDS orphans felt that "their guardians felt like they could demand anything of them"[46] because no one else could take them in. These children may be forced to look after a sibling or other family members, so they live in their original home even after parents are deceased. The children may be worried about seizure of land by landlords or neighbours.[47] Due to the stigma surrounding HIV in India, children of HIV-infected parents are treated poorly and often do not have access to basic resources. A study done by the Department of Rural Management in Jharkhand showed that 35% of children of HIV-infected adults were denied basic amenities.[42] Things like proper food are often not given to AIDS orphans by their extended families or caretakers.[47] This, combined with the abuse that many orphans face, leads to a higher rate of mortality among AIDS orphans.[48] Higher education rates in caregivers has been shown to decrease this stigma.[49] AIDS orphans are often not allowed in orphanages because of the concern that they could have AIDS themselves.[50] AIDS orphans were more likely to be bullied by friends or relatives due to the stigma against HIV/AIDS in India.[51] People may falsely believe HIV can be contracted by proximity, so these orphans can lose friends.[52] Often, women widowed by HIV/AIDS face blame for the impact on their children,[53] while families face isolation during the time of illness and after. Parents often lose their jobs due to workplace discrimination.[54] The Human Rights Watch has found many cases of sexual abuse among female AIDS orphans, which often result in trafficking and prostitution.[46] Studies have shown that an increase in quality HIV treatment and care can drastically decrease this discrimination.[49] #### Mental health[edit] The emotional and social effects on AIDS orphans are very detrimental to their health and future life. Specifically, the mental health of AIDS orphans in India is shown to be worse than that for children who were orphaned for other reasons.[51] Before becoming orphans, children whose parents suffer from AIDS face many obstacles. There is "tremendous emotional trauma" associated with having a parent ill with HIV, and the child often worries about resource scarcity, being separated from siblings, and grief over the impending death of the parent.[54] While a parent is ill, a child may experience long periods of uncertainty and episodic crises, which decreases the child's sense of security and stability.[55] A study done in orphanages in Hyderabad showed that orphans in India who have lost one or both parents to AIDS are 1.3 times as likely to be clinically depressed as children orphaned due to other reasons.[51] In addition, the study showed greater depression among younger AIDS orphans, while in other orphans it was mostly seen in older children. A distinction was also made between genders; girls orphaned due to AIDS had a higher rate of depression than boys.[44] #### Education[edit] Because orphans and vulnerable children affected by HIV/AIDS often have many deceased or ill family members, they are often forced into taking jobs at a young age to provide for their family, resulting in lower attendance at school or being forced to drop out of school completely. For example, orphans that have lost their father due to AIDS are often forced to take on high-risk field or manual labour jobs. Orphans that have lost their mothers take on housework and childcare. Girls are more often taken out of school to help with domestic work and care for sick parents.[50] Studies show that 17% of children with HIV-infected parents took on a job to assist with household income.[42] The cost of treatment for HIV is so high that many families often do not have the means to pay for the care or education of the child.[48] If a child is forced to drop out of school in order to take on additional responsibility at home due to the illness of his parent, the child is named a "de-facto" orphan.[42] There has been no correlation found between gender and risk of poor educational outcomes or risk of dropping out of school.[56] Because of stigma, many HIV/AIDS affected orphans are expelled from school.[50] In a study on the education of orphans in India, the caretaker's health was found to be very important in determining if the orphan was at a target educational standard.[56] When a primary caregiver was in poor health, the odds of the orphan being in the target grade level decreased by 54%.[56] #### Responses[edit] While much research has gone into community programming for AIDS orphans, only a few efforts focus on saving the lives of the HIV-infected parents themselves.[57] When comparing institution-based care and community-based care, studies have shown that there is less discrimination in the former.[49] However, the government of India has used institutionalizing orphans as the norm, and have not fully explored other options like fostering or community-based care for AIDS orphans.[50] India pledged to provide better resources for AIDS orphans at the UN General Assembly Special Session on HIV/AIDS in 2001.[47] In 2007, India was the first country in South Asia to create a national response to children affected by AIDS.[58] India created the Policy Framework For Children, which has the goal of providing resources for at least 80% of children affected by HIV/AIDS. This policy takes a rights-based approach. However, this policy fails to address many social determinants of care of AIDS orphans, including the social stigma and discrimination, lack of education, and proper nutrition.[42] The Juvenile Justice (Care and Protection of Children) Act of 2015 was created to provide orphans and vulnerable children in India with necessary resources and care. ## See also[edit] ### Lists of ART centres[edit] These centres provide antiretroviral therapy (ART) to the patients. * List of ARTCs * HOSPITALS AND DOCTORS SPECIALISING IN HIV/AIDS ### Non-governmental organisations[edit] These are NGOs working in India for the prevention of HIV/AIDS and accessibility of treatment and medication. These centres also provide psycho-social support through counseling, acting to function as a bridge between hospital and home care. * Aarogya[59] * Ashraya * End Aids India[60] * Humsafar Trust * India HIV/AIDS Alliance * Naz Foundation (India) Trust * SAATHII[61] * Samapathik Trust[62] * Sankalp Rehabilitation Trust * Suraksha Clinic * YRG Care * Udaan Trust ## References[edit] 1. ^ "NACO Annual Report 2018-2019" (PDF). 2. ^ "Country comparison: people living with HIV/AIDS". The World Factbook—Central Intelligence Agency. Retrieved 2 December 2019. 3. ^ a b "Country comparison HIV/AIDS prevalence". The World Factbook—Central Intelligence Agency. Retrieved 2 December 2019. 4. ^ a b Source of Infections in AIDS cases in India, Embassy of India 5. ^ "Report" (PDF). www.nacoonline.org. Retrieved 24 February 2020. 6. ^ a b c d e f g Overview of HIV and AIDS in India Avert.org 7. ^ "HIV and AIDS in India". avert.org. 21 July 2015. Retrieved 6 April 2018. 8. ^ "HIV cases in India drop more than 50% but challenges remain". Hindustan Times. 19 January 2018. Retrieved 28 August 2018. 9. ^ "Clinton lauds India Aids campaign". BBC News. 26 May 2005. Retrieved 6 April 2018. 10. ^ "HIV declining in India; New infections reduced by 50% from 2000–2009; Sustained focus on prevention required" (PDF). Government of India, Ministry of Health & Family Welfare, Department of AIDS Control, National AIDS Control Organisation. Archived from the original (PDF) on 1 January 2011. 11. ^ "SC forces govt to agree to second-line ART to all AIDS patients". The Times of India. 11 December 2010. 12. ^ "SC cautions govt over HIV treatment". Hindustan Times. 11 December 2010. 13. ^ "Grants – Elton John AIDS Foundation". Elton John AIDS Foundation. Retrieved 28 August 2018. 14. ^ "Funds and Expenditures \| National AIDS Control Organization \| MoHFW \| GoI". naco.gov.in. Retrieved 28 August 2018. 15. ^ "USAID, AMCHAM join hands to address India's development challenges – Times of India". The Times of India. Retrieved 28 August 2018. 16. ^ Sternberg, Steve (23 February 2005). "HIV scars India". USA Today. 17. ^ Pandey, Geeta (30 August 2016). "The woman who discovered India's first HIV cases". BBC News. Retrieved 8 December 2016. 18. ^ a b c d e f g h i Fiona Samuels and Sanju Wagle 2011. Population mobility and HIV and AIDS: review of laws, policies and treaties between Bangladesh, Nepal and India. London: Overseas Development Institute 19. ^ "About Us \| National AIDS Control Organization \| MoHFW \| GoI". naco.gov.in. 20. ^ "The next battleground: AIDS in India". 10 October 1993. 21. ^ "SACS \| National AIDS Control Organization \| MoHFW \| GoI". naco.gov.in. 22. ^ Sharma, Deepak. "HIV/AIDS: A Life Threatening Disease" (PDF). The Pharma Innovation. No. 2: 146–161 – via TPI International Journal. 23. ^ Das, Aritra; Babu, Giridhara R.; Ghosh, Puspen; Mahapatra, Tanmay; Malmgren, Roberta; Detels, Roger (1 December 2013). "Epidemiologic correlates of willingness to be tested for HIV and prior testing among married men in India". International Journal of STD & AIDS. 24 (12): 957–968. doi:10.1177/0956462413488568. PMC 5568248. PMID 23970619. Retrieved 6 April 2018. 24. ^ "India: Driving forward an effective AIDS response". unaids.org. Retrieved 6 April 2018. 25. ^ Ghosh, Maitrayee 2007 ICT and AIDS Literacy: A Challenge for Information Professionals in India. Electronic Library & Information Systems 41(2):134–147 26. ^ Needle, Chael. "High Fidelity Transmission: Review – A&U Magazine". 27. ^ "HIV/AIDS: Closing the Legacy". lilainteractions.in. 28 November 2014. Retrieved 6 April 2018. 28. ^ Pathak, Prachee 2005 "Sterling Towers": A Soap Opera for HIV Awareness Among the Middle Class in Urban India. Dissertations and Theses 2005. 29. ^ Bourgault, Louise M. 2009 AIDS Messages in Three AIDS-Themed Indian Movies: Eroding AIDS-Related Stigma in India and Beyond. Critical Arts: A South-North Journal of Cultural & Media Studies 23(2):171–189. 30. ^ "Health care fails to reach migrants". Hindustan Times. 1 December 2010. 31. ^ Mothi, SN; Swamy, VH; Lala, MM; Karpagam, S; Gangakhedkar, RR (December 2012). "Adolescents living with HIV in India - the clock is ticking". Indian Journal of Pediatrics. 79 (12): 1642–7. doi:10.1007/s12098-012-0902-x. PMID 23150229. S2CID 2346814. 32. ^ "World AIDS Day: India records sharp drop in number of cases". ndtv.com. Retrieved 6 April 2018. 33. ^ "India sees 50% decline in new hiv infections: un report". Hindustan Times. Archived from the original on 4 April 2011. Retrieved 2 April 2011. 34. ^ "World AIDS Day: India records sharp drop in number of cases". ndtv.com. Retrieved 6 April 2018. 35. ^ "HIV/Aids bill tabled in Rajya Sabha". Deccan Herald. 12 February 2014. 36. ^ "Bill to end HIV/AIDS discrimination introduced in Rajya Sabha". Zee News. 11 February 2014. 37. ^ Mishra, Nikita (December 2016). "Decoded: The Good and Bad of the HIV Bill Passed by Rajya Sabha". www.thequint.com. The Quint. Retrieved 23 March 2017. 38. ^ Writ Petition (Civil) No. 311 of 2003, Supreme Court of India 39. ^ Writ Petition (Civil) No. 8700 of 2006, High Court of Delhi 40. ^ Writ Petition (Civil) No. 7 of 2005, Gauhati High Court 41. ^ Writ Petition (Civil) No. 2885 of 2007, High Court of Delhi 42. ^ a b c d e f "AIDS Orphans and Vulnerable Children in India: Problems, Prospects, and Concerns". ResearchGate. Retrieved 23 February 2019. 43. ^ Shetty, Avinash (January 2003). "Children orphaned by AIDS: A global perspective". Seminars in Pediatric Infectious Disease. 14 (1): 25–31. doi:10.1053/spid.2003.127214. PMID 12748919. 44. ^ a b "An In-depth Study of Psychological Distress among Orphan Children Living in Institutional Care in New Delhi and their Coping Mechanisms". IUSSP – 2017 International Population Conference. Retrieved 23 February 2019. 45. ^ Gilborn, Laelia Zoe (January 2002). "The effects of HIV infection and AIDS on children in Africa". Western Journal of Medicine. 176 (1): 12–14. doi:10.1136/ewjm.176.1.12. ISSN 0093-0415. PMC 1071640. PMID 11788529. 46. ^ a b Csete, Joanne (1 June 2004). "Missed Opportunities: Human rights and the politics of HIV/AIDS". Development. 47 (2): 83–90. doi:10.1057/palgrave.development.1100033. ISSN 1461-7072. S2CID 86386789. 47. ^ a b c Ghanashyam, Bharathi (30 January 2010). "India failing children orphaned by AIDS". The Lancet. 375 (9712): 363–364. doi:10.1016/S0140-6736(10)60151-1. ISSN 0140-6736. PMID 20135747. S2CID 26411019. 48. ^ a b Mukiza-Gapere, Jackson; Ntozi, James P. M. (1995). "Care for AIDS orphans in Uganda: findings from focus group discussions". Cite journal requires `\|journal=` (help) 49. ^ a b c Messer, Lynne C.; Pence, Brian W.; Whetten, Kathryn; Whetten, Rachel; Thielman, Nathan; O'Donnell, Karen; Ostermann, Jan (19 August 2010). "Prevalence and predictors of HIV-related stigma among institutional- and community-based caregivers of orphans and vulnerable children living in five less-wealthy countries". BMC Public Health. 10 (1): 504. doi:10.1186/1471-2458-10-504. ISSN 1471-2458. PMC 2936424. PMID 20723246. 50. ^ a b c d "Future Forsaken \| Abuses Against Children Affected by HIV/AIDS in India". Human Rights Watch. 28 July 2004. Retrieved 11 April 2019. 51. ^ a b c "Depression among AIDS-orphaned children higher than among other orphaned children in southern India". ResearchGate. Retrieved 18 March 2019. 52. ^ Salaam, Tiaji (11 February 2005). "AIDS Orphans and Vulnerable Children (OVC): Problems, Responses, and Issues for Congress" (PDF). Congressional Research Service. 53. ^ Van Hollen, Cecilia (1 December 2010). "HIV/AIDS and the Gendering of Stigma in Tamil Nadu, South India". Culture, Medicine, and Psychiatry. 34 (4): 633–657. doi:10.1007/s11013-010-9192-9. ISSN 1573-076X. PMID 20842521. S2CID 28534016. 54. ^ a b Todres, Jonathan (December 2007). "Rights Relationships and the Experience of Children Orphaned by AIDS". UC Davis Law Review. 41. 55. ^ Children orphaned by AIDS : front-line responses from eastern and southern Africa. UNICEF. 1999. OCLC 59176094. 56. ^ a b c Sinha, Aakanksha; Lombe, Margaret; Saltzman, Leia Y.; Whetten, Kathryn; Whetten, Rachel (March 2016). "Exploring Factors Associated with Educational Outcomes for Orphan and Abandoned Children in India". Global Social Welfare. 3 (1): 23–32. doi:10.1007/s40609-016-0043-7. ISSN 2196-8799. PMC 4830269. PMID 27088068. 57. ^ Beckerman, Karen Palmore (6 April 2002). "Mothers, orphans, and prevention of paediatric AIDS". The Lancet. 359 (9313): 1168–1169. doi:10.1016/S0140-6736(02)08248-X. PMID 11955530. S2CID 46158295. 58. ^ Ackerman Gulaid, Laurie. "National responses for children affected by AIDS: Review of progress and lessons learned" (PDF). Unicef. 59. ^ "AIDS Support Group". aidssupport.aarogya.com. 60. ^ "NGO for AIDS in India, HIV/AIDS Non Profit Campaign in India \| End AIDS India". www.endaidsindia.org. 61. ^ "Solidarity and Action Against the HIV Infection in India". www.saathii.org. 62. ^ "Samapathik Trust, Pune - Home". ## External links[edit] Scholia has a topic profile for HIV/AIDS in India. 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nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	HIV/AIDS in India	None	6,194	wikipedia	https://en.wikipedia.org/wiki/HIV/AIDS_in_India	2021-01-18T18:48:42	{"wikidata": ["Q5629844"]}
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: "Autistic catatonia" – news · newspapers · books · scholar · JSTOR (August 2019) Autistic catatonia is a rare type of disorder[citation needed] that affects roughly 10 percent of all adults with autism spectrum disorder. Most are not severely affected but a few exhibit stupor and severe excitement, which is the most extreme form of the disorder. Full expression of excitement could be a sign of comorbid bipolar disorder but more research is needed.[1] More than 40 symptoms have been identified to be a result of the disorder, but some of the symptoms overlap with those of autism spectrum disorder, making diagnosing difficult even for a seasoned professional. In a few cases stupor and hyperactivity can continue for weeks or even months.[citation needed] During the excitement phase individuals show combativeness and can have delusions and hallucinations and can also pose a danger to themselves or others and can make marked destruction of property.[citation needed] In the later stages of medium and even more in the severe (and, if left untreated, lethal) state they will also experience autonomic instability.[2] Childhood schizophrenia increases the risk for autistic catatonia later in life dramatically. There seems to be a common font of brain pathology for psychosis, catatonia and autism.[3] ## Contents * 1 Symptoms * 2 Treatment * 3 History * 4 See also * 5 References * 6 External links ## Symptoms[edit] List of symptoms that has been observed in those with autistic catatonia:[4][failed verification] * Stupor * Mutism * Hyperactivity * Agitation * Excitement * Posing * Negativism * Rigidity * Waxy flexibility, mitmachen, mitgehen – tendency to remain in immobile posture, inability to resist external pressure on posture * Automatic obedience * Combativeness (during excitement) * Aggressivity * Stereotypies * Tics * Grimacing * Echolalia * Echopraxia * Perseveration * Verbigeration * Staring, gaze fixation * Withdrawal * Immobility * Challenging behaviour * Tremor * Slowness * Amotivation * Grasp reflex * Choreoathetoid movements of the trunk and extremities * Autonomic instability (during excitement) * Inability to start or stop actions (if during excitement episodes needs acute psychiatric care) * Impulsivity * Psychosis * Sleep problems, reversal of day and night * Urinary or fecal incontinence * Passivity * Eyerolling * Stiff muscles * Catalepsy * Gegenhalten * Ambitendency – contradictory behavior * Rituals – repetitive behaviors ## Treatment[edit] Treatment consists of high-dose lorazepam or in some cases ECT. The response to the treatment is usually good, especially if detected early.[citation needed] ## History[edit] In the 19th century the psychiatrist Karl Ludwig Kahlbaum observed several symptoms of the disorder. Among them were stupor, mutism, excitement, hyperactivity, posing, negativism, rigidity, waxy flexibility and automatic obedience, stereotypies, tics, grimacing, echo-phenomenon, and self-harming.[citation needed] Also marbling of the skin, profuse sweating, deviation of the pupils and odd reaction to light were considered catatonic phenomenons.[5] During most of the 20th century catatonia was regarded as schizophrenic in its nature, but towards the end of the century it was more commonly observed in those with bipolar disorder and autism spectrum disorder. Now only 15 percent of those with catatonia are considered to have schizophrenia.[medical citation needed] ## See also[edit] * Catatonia ## References[edit] 1. ^ WIng, Lorna (1998). "The History of Asperger Syndrome". In Schopler, Eric; Mesibov, Gary B.; Kunce, Linda J. (eds.). Asperger Syndrome or High-Functioning Autism?. Springer. pp. 11–28. ISBN 978-0-306-45746-3. 2. ^ Wilcox, James Allen; Reid Duffy, Pam (2015-12-09). "The Syndrome of Catatonia". Behavioral Sciences. 5 (4): 576–588. doi:10.3390/bs5040576. PMC 4695780. PMID 26690229. 3. ^ Shorter, E.; Wachtel, L. E. (2013). "Childhood catatonia, autism and psychosis past and present: is there an 'iron triangle'?". Acta Psychiatrica Scandinavica. 128 (1): 21–33. doi:10.1111/acps.12082. PMC 3714300. PMID 23350770. 4. ^ Wing, Lorna; Shah, Amitta (2000). "Catatonia in autistic spectrum disorders". The British Journal of Psychiatry. 176 (4): 357–62. doi:10.1192/bjp.176.4.357. PMID 10827884. 5. ^ Brake, Jonathan A.; Abidi, Sabina (2010). "A Case of Adolescent Catatonia". Journal of the Canadian Academy of Child and Adolescent Psychiatry. 19 (2): 138–40. PMC 2868561. PMID 20467550. ## External links[edit] * Catatonia~clinical at eMedicine * Dhossche, Dirk Marcel; Carroll, Brendan T.; Carroll, Tressa D. (2006). "Is There a Common Neuronal Basis for Autism and Catatonia?". In Dhossche, Dirk Marcel; Wing, Lorna; Ohta, Masataka; et al. (eds.). Catatonia in Autism Spectrum Disorders. International Review of Neurobiology. 72. pp. 151–64. doi:10.1016/S0074-7742(05)72009-2. ISBN 978-0-12-366873-8. PMID 16697296. * Dhossche, Dirk M. (2014). "Decalogue of Catatonia in Autism Spectrum Disorders". Frontiers in Psychiatry. 5: 157. doi:10.3389/fpsyt.2014.00157. PMC 4222130. PMID 25414675. * Ghaziuddin, M.; Quinlan, P.; Ghaziuddin, N. (2005). "Catatonia in autism: a distinct subtype?" (PDF). Journal of Intellectual Disability Research. 49 (1): 102–5. doi:10.1111/j.1365-2788.2005.00666.x. hdl:2027.42/71765. PMID 15634317. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Autistic catatonia	None	6,195	wikipedia	https://en.wikipedia.org/wiki/Autistic_catatonia	2021-01-18T19:08:13	{"wikidata": ["Q23808084"]}
Abortion in Suriname is illegal except in case of the threat to life or health of the woman. The punishment for a woman who has an abortion is up to three years in prison, and the punishment for a doctor or other person who performs the procedure is up to four years.[1] In 2007, Health Minister Celsius Waterberg caused a stir when he criticized the legalization of euthanasia while advocating abortion in limited circumstances, namely in the case of rape or danger to the unborn child.[2] ## See also[edit] * Abortion * Abortion by country * Abortion law ## References[edit] 1. ^ "List of countries and their present status on abortion legislation". Choike. Archived from the original on 2006-11-05. Retrieved 2012-10-21. 2. ^ [1][dead link] * v * t * e Abortion in South America Sovereign states * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Dependencies and other territories * Falkland Islands * French Guiana * South Georgia and the South Sandwich Islands * 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 [mRNA]: messenger RNA *[kDa]: kilodalton	Abortion in Suriname	None	6,196	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Suriname	2021-01-18T18:42:37	{"wikidata": ["Q4668495"]}
A rare autosomal recessive primary immunodeficiency characterized by infancy onset of severe inflammatory bowel disease with life-threatening diarrhea and failure to thrive, oral aphthous ulcers, and recurrent severe upper and lower respiratory tract infections with finger clubbing. Laboratory examination reveals increased IgE and decreased IgG levels, as well as reduced numbers of circulating CD19+ B-cells including IgM+ naive and class-switched IgG memory B-cells, with a concomitant increase in transitional B-cells, while T-cell numbers and function are 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 [mRNA]: messenger RNA *[kDa]: kilodalton	IL21-related infantile inflammatory bowel disease	c4014258	6,197	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=477661	2021-01-23T18:04:03	{"omim": ["615767"], "synonyms": ["IL21-related infantile IBD"]}
## Clinical Features Hoffmann (1894) described slowly progressive juvenile amyotrophic lateral sclerosis with concomitantly progressive dementia in 4 sibs. Staal and Went (1968) described 7 sibs (out of 15), offspring of a first-cousin marriage, affected by the same disorder. Three boys and 4 girls were affected. Death had occurred in 5 of 7 sibs at intervals varying from 9 to 21 years after onset of symptoms which started at about age 10 years. McKusick (1986) noted that he had seen 4 cases of ALS-dementia complex in 2 related and inbred Old Order Amish sibships. The disorder is probably distinct from that observed in another Amish group (see 205100), being distinguished mainly by the associated dementia. Misc \- Onset about age 10 Muscle \- Distal muscular atrophy Neuro \- Dementia Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	AMYOTROPHIC LATERAL SCLEROSIS, JUVENILE, WITH DEMENTIA	c1859806	6,198	omim	https://www.omim.org/entry/205200	2019-09-22T16:31:05	{"mesh": ["C565956"], "omim": ["205200"], "synonyms": ["Alternative titles", "ALS-DEMENTIA COMPLEX"]}
The Jonah complex is the fear of success or the fear of being one's best which prevents self-actualization, or the realization of one's own potential.[1][2] It is the fear of one's own greatness, the evasion of one's destiny, or the avoidance of exercising one's talents.[1][3] As the fear of achieving a personal worst may serve to motivate personal growth, likewise the fear of achieving a personal best may hinder achievement.[1] Jonah escapes from the belly of the great fish[4][5] that has held him captive. The Jonah complex is evident in neurotic people.[6] ## Contents * 1 Etymology * 2 Causes * 3 See also * 4 References ## Etymology[edit] Although Abraham Maslow is credited for the term, the name "Jonah complex" was originally suggested by Maslow's friend, Professor Frank_E._Manuel.[1] The name comes from the story of the Biblical prophet Jonah's evasion of the destiny to prophesy the destruction of Nineveh.[7] Maslow states, "So often we run away from the responsibilities dictated (or rather suggested) by nature, by fate, even sometimes by accident, just as Jonah tried—in vain—to run away from his fate".[1] ## Causes[edit] Any dilemma or challenge faced by an individual may trigger reactions related to the "Jonah complex". These challenges may vary in degree and intensity. Such challenges may include career changes, beginning new stages in life, moving to new locations, interviews or auditions, and undertaking new interpersonal commitments such as marriage.[8] Other causes include * Fear of the sense of responsibility that often attends recognizing one's own greatness, talents, potentials * Fear that an extraordinary life would be too much out of the ordinary, and hence not acceptable to others * Fear of seeming arrogant, self-centered, etc.[7] * Difficulty envisioning oneself as a prominent or authoritative figure[9] ## See also[edit] * Impostor syndrome * Metamotivation * Setting up to fail * Tall poppy syndrome ## References[edit] 1. ^ a b c d e Abraham Maslow. "The Jonah Complex". The Farther Reaches of Human Nature. 2. ^ Department of Cognitive Science, Chris VerWys. Rensselaer Polytechnic Institute, Personality Psychology, Abraham Maslow 3. ^ Haronian, Frank (15 December 1967). "The Repression of the sublime" (PDF). Retrieved 5 October 2011. Cite journal requires `\|journal=` (help) 4. ^ Orig. Hebrew (דָּג (גָּדוֹל. 5. ^ "Jonah ch. 2, vv. 1, 2, 11" in many versions (MT (Masoretic Text), LXX (Septuagint), D–R (Douay–Rheims Bible), NAB (New American Bible), NABRE (New American Bible Revised Edition), and others); "Jonah ch. 1, v. 17 and ch. 2, vv. 1, 10" in KJV (King James Version) and many other Protestant translations. 6. ^ Feist, Feist, Gregory, Jess (2009). Theories of personality (7th ed.). New York McGraw-Hill Higher Education. p. 300. ISBN 978-0-07-338270-8. 7. ^ a b Eric Dodson. "Course Notes for Humanistic Psychology (PSYC 2000)". University of Western Georgia. Archived from the original on 20 September 2015. 8. ^ Goud, N. (1994). Jonah Complex: The fear of growth. Journal of Humanistic Education & Development, 32(3), 98–111. 9. ^ Sumerlin, J. R. and Bundrick, C. M. (1996). "Brief index of self-actualization: A measure of Maslow's model". Journal of Social Behavior and Personality. 11 (2): 253–271. doi:10.2466/pms.1998.87.1.115.CS1 maint: uses authors parameter (link) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA *[kDa]: kilodalton	Jonah complex	None	6,199	wikipedia	https://en.wikipedia.org/wiki/Jonah_complex	2021-01-18T18:35:18	{"wikidata": ["Q6013650"]}

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