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A number sign (#) is used with this entry because obesity is predominantly a polygenic and multifactorial trait. Genetic variation in some genes have been associated with susceptibility to obesity as a monogenic trait (see body mass index (BMI), 606641). Autosomal recessive disorders with obesity as a predominant feature include leptin deficiency (614962), leptin receptor deficiency (614963), prohormone convertase-1 deficiency (600955), and proopiomelanocortin deficiency (609734); associated features in these disorders include hypogonadotropic hypogonadism, hypoadrenalism, and short stature. There are also syndromes associated with obesity such as Prader-Willi syndrome (176270), Bardet-Biedl syndrome (BBS; see 209900), and Cohen syndrome (216550), among others. For a review of the molecular basis of obesity, see Barsh et al. (2000). Bell et al. (2005) provided a comprehensive review of the genetics of human obesity. For a review of the molecular understanding of adaptive thermogenesis, see Lowell and Spiegelman (2000). Barness et al. (2007) reviewed the genetic, molecular, and environmental aspects of obesity and discussed the myriad associated complications, including hypertension (145500), dyslipidemia, endothelial dysfunction, type 2 diabetes mellitus (125853) and impaired glucose tolerance, acanthosis nigricans (100600), hepatic steatosis, premature puberty (see 176400), hypogonadism and polycystic ovary syndrome, obstructive sleep disorder, orthopedic complications, cholelithiasis, and pseudotumor cerebri (243200). Pathogenesis Both Roberts et al. (1988) and Ravussin et al. (1988) presented evidence that reduced energy expenditure is a major 'risk factor' in obesity. The study by Roberts et al. (1988), done in infants from birth to 1 year of age, measured total energy expenditure and metabolizable energy intake over a period of 7 days when the infants were 3 months old, and the postprandial metabolic rate when they were 0.1 and 3 months old. The results were related to weight gain in the first year of life. No significant difference was found between infants who became overweight by the age of 1 year (50% of infants born to overweight mothers) and those who did not, with respect to weight, length, skin-fold thicknesses, metabolic rate at 0.1 and 3 months of age, and metabolizable energy intake at 3 months. However, total energy expenditure at 3 months of age was 20.7% lower in infants who became overweight than in the other infants. In a study done in southwestern American Indians, Ravussin et al. (1988) found that energy expenditure correlated with the rate of change in body weight over a 2-year follow-up period and that, among 94 sibs from 36 families, 24-hour energy expenditure aggregated in families. The 2 predominant populations of microbiota in both the mouse and human gut are members of the bacterial groups known as the Firmicutes and the Bacteroidetes. Ley et al. (2006) found that genetically obese mice (ob/ob) had 50% fewer Bacteroidetes and correspondingly more Firmicutes than their lean wildtype sibs. They also showed that the relative proportion of Bacteroidetes was decreased in obese people in comparison with lean people, and that this proportion increased with weight loss on 2 types of low-calorie diet. Ley et al. (2006) concluded that obesity has a microbial component, which might have potential therapeutic implications. Turnbaugh et al. (2006) demonstrated through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Their results indicated that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait was transmissible: colonization of germ-free mice with an 'obese microbiota' resulted in a significantly greater increase in total body fat than colonization with a 'lean microbiota.' Turnbaugh et al. (2006) concluded that their results identified the gut microbiota as an additional contributing factor to the pathophysiology of obesity. Spalding et al. (2008) showed that adipocyte number is a major determinant of fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese individuals, even after marked weight loss, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, the authors measured adipocyte turnover by analyzing genomic DNA for the integration of (14)C derived from above-ground nuclear bomb tests. Findings indicated that approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate was altered in early-onset obesity, suggesting a tight regulation of fat cell number in this condition during adulthood. Inheritance Zonta et al. (1987) studied the genetic factors in obesity in a sample of nuclear families in northern Italy. Sixty-seven families consisted of the parents and sibs of all elementary school children considered to be obese and 112 families consisted of a similar sample of nonobese children and their parents and sibs. Several analyses suggested the presence of a dominant major gene with weak effect. Several other studies were reviewed. In a study of a Hutterite group, Paganini-Hill et al. (1981) found evidence for a major gene in the determination of 'bulk factor.' In a study in the Danish Adoption Register, Stunkard et al. (1986) found a strong relation between the weight class (thin, median weight, overweight, or obese) and the body-mass index of the biologic parents--for the mothers, p less than 0.0001; for the fathers, p less than 0.02. No relation was found between the weight class of the adoptees and the body-mass index of their adoptive parents. Twin studies (Medlund et al., 1976) also indicated an important role of genetic factors. Stunkard et al. (1986) emphasized that the studies should not discourage persons or their physicians from treating obesity but rather that the genetic information should be a guide to the maintenance of a relatively high level of physical activity and appropriate diet. In 774 adults in 59 pedigrees ascertained through cases of cardiovascular disease, Hasstedt et al. (1989) studied the genetics of a relative-fat-pattern index (RFPI), i.e., the ratio of subscapular skinfold thickness to the sum of subscapular and suprailiac skinfold thicknesses. Likelihood analysis supported recessive inheritance of an allele with a frequency of 46%, which elevated mean RFPI from 0.412 to 0.533 when homozygous. The analysis apportioned the variance in RFPI as 42.3% due to the major locus, 9.5% due to polygenic inheritance, and 48.2% due to random environmental effects. Bouchard et al. (1990) subjected 12 pairs of identical male twins to overfeeding by 1000 kcal per day, 6 days a week, for a period of 100 days. The variance among pairs in response to overfeeding was about 3 times greater than that within pairs. With respect to the changes in regional fat distribution and amount of abdominal visceral fat, the differences were particularly striking, there being about 6 times as much variance among pairs as within pairs. Bouchard et al. (1990) suggested that the explanation lay in the involvement of genetic factors that govern the tendency to store energy as either fat or lean tissue and the various determinants of resting expenditure of energy. Moll et al. (1991) investigated the role of genetic and environmental factors in determining variability in ponderosity (body weight relative to height). Ponderosity was measured by body mass index (BMI; kg per sq m) in the mothers, fathers, and sibs of 284 school children in Muscatine, Iowa. Moll et al. (1991) concluded that there was strong support for a single recessive locus with a major effect that accounted for almost 35% of the adjusted variation in BMI. Polygenic loci accounted for an additional 42% of the variation. Approximately 23% of the adjusted variation was not explained by genetic factors. Thus, according to their analysis, more than 75% of the variation was explained by genetic factors that included a single recessive locus. Approximately 6% of persons in the population were predicted to have 2 copies of the recessive gene, while 37% were predicted to have 1 copy of the gene. Mapping ### Obesity On the basis of accumulating evidence that obesity has a substantial genetic component, Norman et al. (1997) performed a genomewide search for linkage of DNA markers to percent body fat in Pima Indians, a population with a very high prevalence of obesity. Single-marker linkages to percent body fat were evaluated by sib pair analysis for quantitative traits. From these analyses, the best evidence of genes influencing body fat came from markers at 11q21-q22 and 3p24.2-p22. Neither linkage achieved a lod score of 3.0, however. To evaluate potential epistatic interactions among 5 regions, on chromosomes 7, 10, and 20, that had been linked to obesity phenotypes, Dong et al. (2003) conducted pairwise correlation analyses based on alleles shared identical by descent (IBD) for independent obese affected sib pairs, and determined family-specific nonparametric linkage (NPL) scores in 244 families. The correlation analyses were also conducted separately, by race, through use of race-specific allele frequencies. Both the affected sib pair-specific IBD-sharing probability and the family-specific NPL score revealed that there were strong positive correlations between 10q (88-97 cM) and 20q (65-83 cM), through single-point and multipoint analyses with 3 obesity thresholds across African American and European American samples. The results from multiple methods and correlated phenotypes were considered consistent with epistatic interactions between loci on chromosomes 20 and 10 playing a role in extreme human obesity. See BMIQ9 (602025) and BMIQ10 (607514) for a discussion of the loci on 20q and 10q, respectively. To detect potentially imprinted, obesity-related genetic loci, Dong et al. (2005) performed genomewide parent-of-origin linkage analyses under an allele-sharing model for discrete traits and under a family regression model for obesity-related quantitative traits. They studied a European American sample of 1,297 individuals from 260 families and also 2 smaller, independent samples for replication. For discrete trait analysis, they found evidence for a maternal effect in 10p12 (see BMIQ8; 603188) across the 3 samples, with lod scores of 5.69 (single point) and 4.52 (multipoint) for the pooled sample. For quantitative trait analysis, they found the strongest evidence for a maternal effect (single-point lod of 2.85; multipoint lod of 4.01 for BMI and 3.69 for waist circumference) in region 12q24 and for a paternal effect (single-point lod of 4.79; multipoint lod of 3.72 for BMI) in region 13q32, in the European American sample. The results suggested that parent-of-origin effects, perhaps including genomic imprinting, may play a role in human obesity. Loos et al. (2008) performed a metaanalysis of data from 4 European population-based studies and 3 disease-case series, involving a total of 16,876 individuals of European descent, and confirmed the previously reported association between the FTO gene and BMI. They also found a significant association between rs17782313, located 188 kb downstream of the MC4R gene, and BMI in adults (p = 2.8 x 10(-15)) and children (p = 1.5 x 10(-8)). In case-control analyses, the odds for severe childhood obesity reached 1.30 (p = 8.0 x 10(-11)), and overtransmission of the risk allele to obese offspring was observed in 660 families. The authors concluded that common variants near the MC4R gene influence fat mass, weight, and obesity risk at the population level. Qi et al. (2008) examined the associations of the MC4R variants rs17782313 (T-C) and rs17700633 (G-A) with dietary intakes, weight change, and diabetes risk in a prospective cohort of 5,724 women, 1,533 of whom had type 2 diabetes. Under an additive inheritance model, rs17782313 was significantly associated with high intake of total energy (p = 0.028), total fat (p = 0.008), and protein (p = 0.003); adjustment for age, BMI, diabetes status, and other covariates did not appreciably change the associations, and the associations between rs17782313 and higher BMI (p = 0.002) were independent of dietary intakes. Carriers of the rs17782313 C allele had 0.2 kg/m(2) greater 10-year increase in BMI from cohort baseline in 1976 to 1986 (p = 0.028) compared to noncarriers, and per C allele of rs17782313 was associated with a 14% increased risk of type 2 diabetes, adjusting for BMI and other covariates. The SNP rs17700633 was not significantly associated with dietary intake or obesity traits. Meyre et al. (2009) analyzed genomewide association data from 1,380 Europeans with early-onset and morbid adult obesity and 1,416 age-matched normal-weight controls and confirmed association at rs17782313, with replication in an additional 14,186 European individuals (combined p = 4.8 x 10(-15)). Renstrom et al. (2009) performed association studies between 9 SNPs from 9 target genes and obesity in 3,885 nondiabetic and 1,038 diabetic Swedish adults. In models with adipose mass traits, BMI or obesity as outcomes, the most strongly associated SNP rs1121980 was in the FTO gene. Five other SNPs, rs7498665 in the SH2B1 gene (608937), rs4752856 in the MTCH2 gene, rs17782313 in the MC4R gene, rs2815752 in the NEGR1 gene, and rs10938397 in the GNPDA2 gene were significantly associated with obesity. ### Other Associations with Obesity SNPs within APOE (107741) and TGF-beta-1 (190180) have been associated with the obesity phenotypes of fat mass, percentage fat mass, and lean mass. A 3-allele haplotype of the ENPP1 gene (see 173335.0006) is associated with childhood and adult obesity and increased risk of glucose intolerance and type II diabetes (125853). Nonsynonymous SNPs in the SDC3 gene (186357) have been associated with obesity in the Korean population. Variation in the PCSK1 gene (162150.0005) influences risk of obesity. Variation in the PYY gene (600781) may influence susceptibility to obesity. ### Leanness In a case-control study of 7,790 individuals, Andersen et al. (2005) found that the pro203 allele of PPARGC1B (608886.0001) was significantly less frequent among obese participants than normal or overweight subjects (p = 0.004). Andersen et al. (2005) concluded that variation of PPARGC1B may contribute to the pathogenesis of obesity, with the widespread ala203 allele being a risk factor for the development of this common disorder. Lavebratt et al. (2005) genotyped 356 overweight or obese and 148 lean Swedish men for 4 SNPs in the AHSG genes (138680) and found that homozygosity for the AHSG2 haplotype (see 138680.0001) conferred an increased risk for leanness (OR, 1.90; p = 0.027). The AHSG2 haplotype had been associated with lower AHSG levels (Osawa et al., 2005). Lavebratt et al. (2005) suggested that a low level of AHSG is protective against fatness. Molecular Genetics Nishigori et al. (2001) identified mutations in the NR0B2 gene (604630) that segregated with mild or moderate early-onset obesity in Japanese subjects. To identify potential genetic contributors to the quantitative trait body weight, Ahituv et al. (2007) resequenced coding exons and splice junctions of 58 genes in 379 obese and 378 lean individuals. This 96-Mb survey included 21 genes associated with monogenic forms of obesity in human or mice, as well as 37 genes that function in body weight-related pathways. They found that the monogenic obesity-associated gene group was enriched for rare nonsynonymous variants unique to the obese population compared with the lean population. In addition, computational analysis predicted a greater fraction of deleterious variants within the obese cohort. Together, these data suggested that multiple rare alleles contribute to obesity in the population and provide a medical sequencing-based approach to detecting them. The accumulation of mildly deleterious missense mutations in individual human genomes is proposed as a genetic basis for complex diseases. The plausibility of this hypothesis depends on quantitative estimates of the prevalence of mildly deleterious de novo mutations and polymorphic variants in humans and on the intensity of selective pressure against them. Kryukov et al. (2007) combined analysis of mutations causing human mendelian diseases as cataloged in the Human Genome Mutation Database (HGMD) (Stenson et al., 2003) with analysis of human-chimpanzee divergence and systematic data on human genetic variation and found that approximately 20% of new missense mutations in humans result in a loss of function, whereas approximately 27% are effectively neutral. Thus the remaining 53% of new missense mutations have mildly deleterious effects. These mutations give rise to many low-frequency deleterious allelic variants in the human population, as is evident from a new dataset of 37 genes sequenced in more than 1,500 individual human chromosomes. Up to 70% of low frequency missense alleles are mildly deleterious and are associated with a heterozygous fitness loss in the range of 0.001-0.003. Thus, the low allele frequency of an amino acid variant can, by itself, serve as a predictor of its functional significance. The observation that the majority of human rare nonsynonymous variants are deleterious, and thus are of significance to function and phenotype, suggests a strategy for candidate gene association studies. Disease populations are expected to have a higher rate of rare amino acid variants in genes involved in disease than are healthy control populations. This difference can be easily detected in a deep resequencing study. Obviously, this strategy would be highly inefficient if the majority of coding variants at low frequency were neutral. Kryukov et al. (2007) concluded that their analysis provides an explanation for the success of studies, such as the one of Ahituv et al. (2007), which demonstrate an excess of rare missense variants in individuals with phenotypes associated with disease risk. A heterozygous missense mutation in the POMC gene (176830.0004) was associated with severe childhood obesity in 2 unrelated children and segregated with obesity in the 3-generation family of 1 of the children. A heterozygous missense mutation in the CART gene (602606.0001) was associated with obesity in a 3-generation Italian family. Willer et al. (2009) performed a metaanalysis of 15 genomewide association studies for BMI comprising 32,387 participants and followed up top signals in 14 additional cohorts comprising 59,082 participants. They strongly confirmed association with FTO and MC4R and identified 6 additional loci (P less than 5 x 10(-8)): TMEM18 (613220), KCTD15 (615240), GNPDA2 (613222), SH2B1 (608937), MTCH2 (613221), and NEGR1 (613173) (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the CNS, emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity. Animal Model The 'diabetes' mouse (db) and the 'obese' mouse (ob) are indistinguishable phenotypically when bred on the same mouse strain. The db gene maps to mouse chromosome 4, however, in a region that shows extensive conservation of synteny and gene order with human 1p32-p31 (Bahary et al., 1990; Bahary et al., 1991). On the basis of syntenic homology, there thus might be a human obesity gene on chromosome 1p near oncogene JUN (165160). Other recessive mouse models of obesity, such as 'tubby' (TUB; 601197) and 'fat' (fat), may also be in conserved regions. The tub gene was found to lie 2.4 cM from the Hbb gene (141900). Jones et al. (1992) suggested that the human homolog of 'tubby' resides in 11p15 and that the Hbb locus in the human could be used as a linkage marker for studies of familial obesity in humans. See leptin (164160) for a discussion of the human homolog of the murine 'obesity' (ob) locus. Aitman (2003) noted that the approach Schadt et al. (2003) used to study the genetics of obesity in mice was useful in understanding of the molecular pathogenesis of complex diseases. They used mice derived from matings of 2 standard inbred strains and performed gene expression profiles with microarrays in second-generation mice to determine the extent to which approximately 24,000 genes were differentially expressed in the liver tissues of fat and lean mice, as measured by the levels of mRNA. The data were used to form expression signatures of high or low adiposity. The analysis excluded many obvious genes that might have previously been considered strong candidates and identified new genes--including those that encode major urinary protein-1, a protein glycosyltransferase, and a cation-transporting ATPase--that may have been primary determinants of obesity in the obese mice. Ozcan et al. (2004) used cell culture and mouse models to show that obesity causes endoplasmic reticulum (ER) stress. This stress in turn leads to suppression of insulin receptor signaling through hyperactivation of c-Jun N-terminal kinase (JNK; see 601158) and subsequent serine phosphorylation of insulin receptor substrate-1 (IRS1; 147545). Mice deficient in X box-binding protein-1 (XBP1; 194355), a transcription factor that modulates the ER stress response, develop insulin resistance. Ozcan et al. (2004) concluded that ER stress is a central feature of peripheral insulin resistance and type II diabetes (125853) at the molecular, cellular, and organismal levels. Bera et al. (2008) generated mice homozygous for partial inactivation of the Ankrd26 gene (610855) and observed the development of extreme obesity, insulin resistance, and a dramatic increase in body size. The obesity was associated with hyperphagia with no reduction in energy expenditure or activity. The authors noted that the human ANKRD26 gene is located on chromosome 10p12, where Dong et al. (2005) had found linkage to obesity in European American individuals. Chen et al. (2008) developed an alternative to the classic forward genetics approach for dissecting complex disease traits where, instead of identifying susceptibility genes directly affected by variations in DNA, they identified gene networks that are perturbed by susceptibility loci and that in turn lead to disease. Application of this method to liver and adipose gene expression data generated from a segregating mouse population resulted in the identification of a macrophage-enriched metabolic network (MEMN) supported as having a causal relationship with disease traits associated with metabolic syndrome (see 605552). Three genes in this network, lipoprotein lipase (LPL; 609708), lactamase beta (LACTB; 608440), and protein phosphatase 1-like (PPM1L; 611931), were validated as previously unknown obesity genes, strengthening the association between this network and metabolic disease traits. Given the prediction that LPL and LACTB have a causal relationship with obesity, Chen et al. (2008) recorded weight, fat mass, and lean mass for Lpl heterozygous null mice, Lactb transgenic mice, and wildtype littermate controls every 2 weeks starting at 11 weeks of age using quantitative nuclear magnetic resonance (NMR). As predicted, the growth curves for the Lpl heterozygous null and Lactb transgenic animals were significantly different from those of controls, with the fat mass/lean mass ratio difference generally increasing over time. At the final quantitative NMR measurement the fat mass/lean mass ratios in the Lpl heterozygous null mouse and the Lactb transgenic mice were increased by 22% and 20%, respectively, over the wildtype controls (p = 1.09 x 10(-5) and p = 4.48 x 10(-5)), respectively. LPL is the principal enzyme responsible for the hydrolysis of circulating triglycerides and is active in differentiated macrophages, consistent with its presence in the MEMN. LACTB is a serine protease with high similarity to bacterial lactamase, which metabolizes peptidoglycan in the bacterial cell wall. LACTB has been detected in mitochondria as part of the mitochondrial ribosomal complex. Interestingly, a strain of rat that exhibits late-onset obesity contains a mutation in the S26 subunit of the mitochondrial ribosome (611988), at least partially explaining the obesity phenotype. Yang et al. (2009) generated knockout or transgenic mouse models for 9 candidate genes for abdominal obesity and observed that perturbation of 8 of the 9 genes, including Lpl (609708), Tgfbr2 (190182), Lactb (608440), Zpf90 (609451), Gas7 (603127), Gpx3 (138321), Me1 (154250), and C3ar1 (605246), resulted in significant changes in obesity-related traits such as fat/muscle ratios, body weight, adiposity, individual fat pad masses, or plasma lipids. Liver expression signatures revealed alterations in common pathways and subnetworks that relate to metabolic pathways, suggesting that obesity is driven by a gene network instead of a single gene. Perry et al. (2008) identified prominent expression of the Girk4 gene (600734) in mouse hypothalamus, with most pronounced expression in the ventromedial, paraventricular, and arcuate nuclei, neuron populations implicated in energy homeostasis. Girk4-null mice were predisposed to late-onset obesity. By 9 months, Girk4-null mice were approximately 25% heavier than wildtype controls due to greater body fat. Before the development of overweight, Girk4-null mice exhibited a tendency toward greater food intake and an increased propensity to work for food in an operant task. Girk4-null mice also exhibited reduced net energy expenditure, despite displaying elevated resting heart rates and core body temperatures. These data implicated GIRK4-containing channels in signaling crucial to energy homeostasis and body weight. INHERITANCE \- Autosomal dominant \- Autosomal recessive \- Multifactorial GROWTH Weight \- Obesity METABOLIC FEATURES \- Obesity \- Reduced energy expenditure MISCELLANEOUS \- Variable phenotypic severity \- See also leptin deficiency ( 614962 ) and summary information in BMIQ1 ( 606641 ) MOLECULAR BASIS \- Caused by mutation in the melanocortin-4 receptor gene (MC4R, 155541.0001 ) \- Caused by mutation in the gamma peroxisome proliferator activated receptor gene (PPARG, 601487.0001 ) \- Caused by mutation in the uncoupling protein-3 gene (UCP3, 602044.0001 ) \- Caused by mutation in the nuclear receptor subfamily 0, group B, member 2 gene (NR0B2, 604630.0001 ) \- Susceptibility conferred by mutation in the ectonucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1, 173335.0001 ) \- Susceptibility conferred by mutation in the ghrelin gene (GHRL, 605353.0001 ) \- Susceptibility conferred by mutation in the beta-2-adrenergic receptor gene (ADRB2, 109690.0002 ) \- Susceptibility conferred by mutation in the beta-3-adrenergic receptor gene (ADRB3, 109691.0001 ) \- Susceptibility conferred by mutation in the uncoupling protein-1 gene (UCP1, 113730.0001 ) \- Susceptibility conferred by mutation in the uncoupling protein-2 gene (UCP2, 601693.0001 ) \- Susceptibility conferred by mutation in the proopiomelanocortin gene (POMC, 176830.0001 ) \- Susceptibility conferred by mutation in the homolog of the mouse agouti gene (AGRP, 602311.0001 ) \- Susceptibility conferred by mutation in the cocaine- and amphetamine-regulated transcript prepropeptide (CARTPT, 602606.0001 ) ▲ 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	OBESITY	c1857854	900	omim	https://www.omim.org/entry/601665	2019-09-22T16:14:27	{"doid": ["9970"], "mesh": ["C565726"], "omim": ["601665"], "icd-9": ["278.00"], "icd-10": ["E66.9"], "orphanet": ["71526", "71529"]}
Inflammatory myofibroblastic tumor is a rare neoplastic lesion of the submucosal stroma, which can develop in any organ, often occurring in the lung, mesentery, omentum and the retroperitoneal region. It is histologically heterogenous, composed of spindle-shaped cells, myofibroblasts and inflammatory cells. It is usually benign, however local invasion, recurrence, malignant transformation with vascular invasion and metastases may occur. The presentation is nonspecific and depends on the organ involved. Some patients may present with paraneoplastic syndrome (fever, malaise, weight loss, anemia, thrombocytosis) or symptoms related to compression of adjacent organs, such as bowel obstruction. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Inflammatory myofibroblastic tumor	c0334121	901	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178342	2021-01-23T17:45:45	{"gard": ["7146"], "mesh": ["D006104"], "umls": ["C0334121"]}
An extremely rare polymalformative syndrome. ## Epidemiology It was described only once, in 1975, in 3 affected males in a sibship of 13, from second-cousin parents. ## Clinical description Patients were all of low birth weight, had microretrognathia, microstomia, and microglossia, hypoplasia of the radius and ulna with radial deviation of the hands, simian creases and hypoplasia of fingers I and V, hypoplasia of the fibula and tibia with talipes and wide space between toes I and II, and severe malformation of the left heart which may have been responsible for death of all 3 in the first week or so of life. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Lethal faciocardiomelic dysplasia	c1856891	902	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1972	2021-01-23T18:02:58	{"mesh": ["C565578"], "omim": ["227270"], "umls": ["C1856891"], "icd-10": ["Q87.8"]}
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: "Iridoplegia" – news · newspapers · books · scholar · JSTOR (August 2018) (Learn how and when to remove this template message) Iridoplegia is the paralysis of the sphincter of the iris. It can occur in due to direct orbital injury, which may result in short lived blurred vision.[1] ## Types[edit] It can be of three types: 1. accommodative iridoplegia\- Noncontraction of pupils during accommodation. 2. complete iridoplegia\- Iris fails to respond to any stimulation. 3. reflex iridoplegia\- The absence of light reflex, with retention of accommodation reflex. Also called Argyll Robertson pupil. ## Etiology[edit] Iridoplegia has been reported in association with Guillain-Barré syndrome.[2] ## References[edit] 1. ^ Harrison's neurology in clinical medicine. Harrison, Tinsley Randolph, 1900-1978., Hauser, Stephen L., Josephson, Scott Andrew. (2nd ed.). New York: McGraw-Hill Medical. 2010. p. 402. ISBN 9780071741033. OCLC 477051832.CS1 maint: others (link) 2. ^ HUNG, J. C C; APPLETON, R. E (1 July 1997). "Iridoplegia in severe Guillain-Barre syndrome". Archives of Disease in Childhood. 77 (1): 91–91. doi:10.1136/adc.77.1.91a. PMC 1717230. PMID 9279166. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Iridoplegia	c0423302	903	wikipedia	https://en.wikipedia.org/wiki/Iridoplegia	2021-01-18T19:05:40	{"mesh": ["D011681"], "umls": ["C0423302"], "wikidata": ["Q6069638"]}
A number sign (#) is used with this entry because of evidence that mesomelia-synostoses syndrome is a contiguous gene deletion syndrome caused by heterozygous microdeletion on chromosome 8q13. Description The Verloes-David-Pfeiffer mesomelia-synostoses syndrome is an autosomal dominant form of mesomelic dysplasia comprising typical acral synostoses combined with ptosis, hypertelorism, palatal abnormality, congenital heart disease, and ureteral anomalies (summary by Isidor et al., 2009). Mesomelia and synostoses are also cardinal features of the Kantaputra type of mesomelic dysplasia (156232). Clinical Features Verloes and David (1995) described a seemingly 'new' dominantly inherited form of mesomelic shortness of stature with severe skeletal changes in the ankles, knees, and elbows. The father and 2 children (a living 4-year-old girl and an aborted 18-week-old fetus) were affected. Skeletal abnormalities included brachymetacarpy and brachymetatarsy of the third to fifth rays, synostoses in these bones, synostoses of metacarpals and metatarsals II to V with the corresponding carpal/tarsal bones, partial fusion in the proximal row of carpal bones, and mild vertebral anomalies. The father and daughter also had downslanting palpebral fissures, beaked nose, hypertelorism, ptosis, microretrognathia, and transverse agenesis of the soft palate. Abnormally short umbilical cord with unusually long skin coverage was present. Mesomelic shortness increased with time, with progressive curvature of the forearm. A possible further sporadic case was reported independently, with similar facial and skeletal anomalies, nasal speech due to short velum, and hydronephrosis (Pfeiffer et al., 1995). Day-Salvatore and McLean (1998) described a female infant with microcephaly, hypoplastic frontal ridges, telecanthus, blepharoptosis, blepharophimosis, cleft palate, mild microstomia, micrognathia, abnormally modeled ears, hypoplastic left heart, hypoplastic radii and ulnae with radial subluxation, pseudoarthrotic distal humeri, fused metacarpals, tibial bowing, unusual feet with long halluces, hydronephrosis, patent urachus, and abnormal electroencephalogram. Other cardiovascular abnormalities included patent ductus arteriosus, ventricular septal defect, single coronary artery, and retroesophageal subclavian artery. The electroencephalogram was consistent with moderate to severe, diffuse or multifocal cerebral dysfunction, although overt clinical seizure manifestations were not observed. Neurodevelopmental evaluation at age 35 months showed global developmental delays in expressive language and problem-solving skills as well as gross motor skills. Leroy et al. (2003) reported a 4-year-old boy with symmetric carpometacarpal and tarsometatarsal synostoses and moderate acromesomelia, resulting in severe impairment of mobility in the upper limbs and gait. Additional features included hypoplastic supraorbital ridges, telecanthus, ptosis, blepharophimosis, beak-like nose, mild retrognathia, hypoplastic soft palate and uvula, atrial septal defect, ventricular septal defect, coarctation of the aorta, and bilateral hydronephrosis due to congenital vesicoureteral junction stenosis. His stature was in the low normal range, and mental development was normal. Leroy et al. (2003) tabulated the similarities to the patients previously reported by Verloes and David (1995) and Pfeiffer et al. (1995), and suggested that the phenotype results from a mutation that disturbs antenatal pattern formation, specifically distal limb segmentation and joint differentiation. Isidor et al. (2009) reviewed the clinical features of 5 reported patients with the mesomelia-synostoses syndrome (Verloes and David, 1995; Pfeiffer et al., 1995; Day-Salvatore and McLean, 1998; Leroy et al., 2003) and provided follow-up on 3 of the patients. In contrast to other mesomelic syndromes, the clinical course of this mesomelic dysplasia is slowly progressive, at least until adulthood, with development of severe limb deformities despite repeated corrective surgical intervention. Isidor et al. (2009) noted that the unknown mutant gene has at least 2 developmental pathogenic effects, generating congenital malformations and multiple synostoses in early prenatal life, and manifesting in postnatal life as a severe osteochondrodysplasia. Molecular Genetics Using whole-genome oligonucleotide array CGH, Isidor et al. (2010) identified a microdeletion on chromosome 8q13 in each of 5 patients with the mesomelia-synostosis syndrome from 4 previously reported families (Verloes and David, 1995; Pfeiffer et al., 1995; Day-Salvatore and McLean, 1998; and Leroy et al., 2003, respectively). The deletions varied from 582 kb to 738 kb, but always encompassed only 2 genes: SULF1 (610012) and SLCO5A1 (613543). Breakpoint sequence analysis in 2 families showed nonrecurrent deletions. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature, mesomelic HEAD & NECK Eyes \- Downslanting palpebral fissures \- Hypertelorism \- Ptosis Nose \- Beaked nose Mouth \- Microretrognathia \- Hypoplasia of the soft palate \- Absent uvula CARDIOVASCULAR Heart \- Complex congenital heart defect (in 2 of 5 patients, unrelated) GENITOURINARY Kidneys \- Hydronephrosis SKELETAL \- Limited range of motion in joints Spine \- Mild vertebral anomalies Limbs \- Short limbs \- Progressive forearm curvature \- Partial fusion of proximal row of carpal bones Hands \- Brachymetacarpy rays 3-5 \- Metacarpal synostosis (2 to 5) \- Ulnar deviation of hands Feet \- Short feet \- Narrow feet \- Dysfunctional ankle joints \- Brachymetatarsy rays 3-5 \- Metatarsal synostoses (2 to 5) VOICE \- Nasal speech PRENATAL MANIFESTATIONS Placenta & Umbilical Cord \- Short umbilical cord with unusually long skin coverage (in 3 of 5 patients) MOLECULAR BASIS \- A contiguous gene deletion syndrome caused by heterozygous deletion (582-738 kb) of 8q13 including the SULF1 ( 610012 ) and SLCO5A1 ( 613543 ) genes ▲ 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	MESOMELIA-SYNOSTOSES SYNDROME	c1838162	904	omim	https://www.omim.org/entry/600383	2019-09-22T16:16:15	{"mesh": ["C537348"], "omim": ["600383"], "orphanet": ["2496"], "synonyms": ["Alternative titles", "CHROMOSOME 8q13 DELETION SYNDROME", "MESOMELIC DYSPLASIA WITH ACRAL SYNOSTOSES, VERLOES-DAVID-PFEIFFER TYPE", "MESOMELIC DYSPLASIA, SYNDROMIC"]}
In psychiatry, thought withdrawal is the delusional belief that thoughts have been 'taken out' of the patient's mind, and the patient has no power over this.[1] It often accompanies thought blocking. The patient may experience a break in the flow of their thoughts, believing that the missing thoughts have been withdrawn from their mind by some outside agency. This delusion is one of Schneider's first rank symptoms for schizophrenia. Because thought withdrawal is characterized as a delusion, according to the DSM-IV TR it represents a positive symptom of schizophrenia.[2] ## See also[edit] * Thought insertion * Thought broadcasting ## References[edit] 1. ^ Videbeck, S (2008). Psychiatric-Mental Health Nursing, 4th ed. Philadelphia: Wolters Kluwers Health, Lippincott Williams & Wilkins. 2. ^ American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders (DSM-IV TR) 4th edition. USA: American Psychiatric Association This abnormal psychology–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	Thought withdrawal	c0233686	905	wikipedia	https://en.wikipedia.org/wiki/Thought_withdrawal	2021-01-18T18:29:17	{"umls": ["C0233686"], "wikidata": ["Q7797002"]}
Cytophagic histiocytic panniculitis (CHP) is a very rare form of panniculitis manifesting as recurrent multiple subcutaneous nodules (which may progressively become ecchymotic and ulcerated), and histologically characterized by lobular panniculitis with lymphocytic and histiocytic infiltration in the subcutaneous adipose tissue. ## Epidemiology The exact prevalence is unknown, but less than 100 cases have been reported (mostly middle-aged and elderly patients). ## Clinical description The histiocytic infiltration often involves lymph nodes, bone marrow and other tissues of the reticuloendothelial system. Severe fever, malaise, pancytopenia, hepatosplenomegaly, and mucosal ulcers are common systemic symptoms. ## Etiology The etiology remains unclear. In more than 50% of cases, the disease occurs in immunocompromised patients (those with immunodeficiency, autoimmune disease or hematological disease) and is triggered by an infection (mainly with a virus from the herpes-virus family). ## Diagnostic methods Diagnosis relies on the histological features of fat infiltration. ## Differential diagnosis Differential diagnosis includes malignant histiocytosis and virus-associated hemophagocytic syndrome, as well as systemic Weber-Christian panniculitis (see these terms). A search for subcutaneous T-cell lymphoma is mandatory. ## Management and treatment Management involves symptomatic treatment and systemic chemotherapy. Combinations of cytotoxic and immunosuppressive drugs have been reported to be efficient. Chemotherapy followed by stem cell rescue should be considered in severe cases. ## Prognosis Although remissions have been reported, the disease tends to follow a chronic course often complicated by terminal hemorrhagic diathesis and organ system failure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Cytophagic histiocytic panniculitis	c0406594	906	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=94087	2021-01-23T17:56:15	{"umls": ["C0406594"], "icd-10": ["M35.8"], "synonyms": ["CHP", "Winkelmann cytophagic panniculitis"]}
Virus associated hemophagocytic syndrome is a very serious complication of a viral infection. Signs and symptoms of virus associated hemophagocytic syndrome, include high fever, liver problems, enlarged liver and spleen, coagulation factor abnormalities, decreased red or white blood cells and platelets (pancytopenia), and a build-up of histiocytes, a type of immune cell, in various tissues in the body resulting in the destruction of blood-producing cells (histiocytic proliferation with prominent hemophagocytosis). Diagnosis is based upon the signs and symptoms of the patient. The cause of the condition is not known. Treatment is challenging and approach will vary depending on the age and medical history of the patient. Complications of this syndrome can become life threatening. Related conditions (conditions with overlapping signs and symptoms), include histiocytic medullary reticulosis (HMR), familial hemophagocytic lymphohistiocytosis (FHL), and X-linked lymphoproliferative 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	Virus associated hemophagocytic syndrome	None	907	gard	https://rarediseases.info.nih.gov/diseases/7857/virus-associated-hemophagocytic-syndrome	2021-01-18T17:57:10	{"synonyms": []}
Emery-Nelson syndrome is a rare congenital limb malformation syndrome characterized by facial dysmorphism (high forehead, depressed nasal bridge, long philtrum, flat malar region, high arched palate), short stature and deformities of the hands and feet (small hands/feet, flexion contractures of the first three metacarpophalangeal joints, extension contractures of the thumbs at the interphalangeal joints, clawed toes, mild pes cavus). Additional features include neonatal hypotonia, thin and shiny skin of the hands/feet, ridged nails, dry and coarse hair, mild weakness of the orbicularis oculi muscles and occasional ventricular extrasystoles. Intellectual disability may be present. There have been no further descriptions in the literature since 1970. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Emery-Nelson syndrome	c1841693	908	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1927	2021-01-23T18:51:05	{"gard": ["2593"], "mesh": ["C535626"], "omim": ["139750"], "umls": ["C1841693"], "icd-10": ["Q87.8"], "synonyms": ["Hand and foot deformity-flat facies syndrome"]}
A number sign (#) is used with this entry because of evidence that selective pituitary resistance to thyroid hormone is caused by mutation in the thyroid hormone receptor gene (THRB; 190160). Generalized resistance to thyroid hormone (GRTH), autosomal dominant (188570) and autosomal recessive (274300), is also caused by mutation in the THRB gene. Clinical Features In 3 generations of a family, Rosler et al. (1982) found 6 females who had hyperthyroidism due to chronic overstimulation of the thyroid by pituitary thyroid-stimulating hormone (TSH). Complete remission was achieved and maintained with continuing therapy with triiodothyronine (T3). The authors suggested that the inappropriate TSH secretion was due to partial unresponsiveness of the thyrotrophic cells of the pituitary to thyroid hormone. Possibly the unresponsiveness was due to deficiency of pituitary T4 monodeiodinase which converts T4 to T3 or the thyrotrophic cells may have a reduced sensitivity to T3 so that they are shut off only when serum T3 is raised to high levels. Gershengorn and Weintraub (1975) described an 18-year-old woman with clinical and laboratory features of hyperthyroidism despite persistently elevated serum levels of immunoreactive TSH. They proposed the designation 'inappropriate secretion of TSH.' Spanheimer et al. (1982) reported 3 cases, the youngest a 4-year-old girl with goiter and symptoms of hyperthyroidism. The syndrome was attributed to selective pituitary insensitivity to thyroid hormone. Hamon et al. (1988) observed the disorder in a 15-month-old boy. Aguilar Diosdado et al. (1991) observed the disorder in mother and sister of a 12-year-old girl who presented with hyperthyroidism. Molecular Genetics Geffner et al. (1993) described an arg311-to-his mutation in the thyroid hormone receptor beta gene (THRB; 190160.0018) in a patient with PRTH, but the mutation did not fully explain the phenotype inasmuch as the father and a half sister who were clinically clinically unaffected had the same mutation. Geffner et al. (1993) indicated that the original patient with PRTH described by Gershengorn and Weintraub (1975) had been found to have a common mutation of the THRB gene (R338W; 190160.0023) (Mixson et al., 1993). Adams et al. (1994) analyzed 20 cases of generalized resistance to thyroid hormone and 9 cases of selective pituitary resistance to thyroid hormone, sporadic or dominantly inherited. All affected individuals were heterozygous for single nucleotide substitutions in the THRB gene, except for one case of a 7-nucleotide insertion. In this series, 9 individuals exhibited a marked preponderance of thyrotoxic signs and symptoms leading to a diagnosis of PRTH. Adams et al. (1994) documented a dominant mode of inheritance in 4 PRTH families with cosegregation of mutations and thyroid dysfunction. Sporadic mutations were recorded with approximately equal frequency in GRTH and PRTH. Both GRTH and PRTH phenotypes were observed in different families harboring the same mutation and could coexist in affected members of a single kindred. Even in a single individual, thyrotoxic symptoms were variable. Although Adams et al. (1994) did not find a clear association between particular mutations and PRTH, it was noteworthy that the R338W mutation was associated with PRTH in 4 out of 5 of their kindreds as well as in 2 other cases reported in the literature (Mixson et al., 1993; Sasaki et al., 1993). Endocrine \- Hyperthyroidism \- Selective pituitary insensitivity to thyroid hormone Lab \- Increased pituitary thyroid-stimulating hormone (TSH) Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY	c1840364	909	omim	https://www.omim.org/entry/145650	2019-09-22T16:39:49	{"mesh": ["C564154"], "omim": ["145650"], "orphanet": ["165994"], "synonyms": ["Alternative titles", "HYPERTHYROIDISM, FAMILIAL, DUE TO INAPPROPRIATE THYROTROPIN SECRETION"]}
Mycotic aneurysm Other namesmycotic aneurysm or microbial arteritis SpecialtyInfectious disease An infected aneurysm[1] is an aneurysm arising from bacterial infection of the arterial wall. It can be a common complication of the hematogenous spread of bacterial infection.[2] William Osler first used the term "mycotic aneurysm" in 1885 to describe a mushroom-shaped aneurysm in a patient with subacute bacterial endocarditis. This may create considerable confusion, since "mycotic" is typically used to define fungal infections. However, mycotic aneurysm is still used for all extracardiac or intracardiac aneurysms caused by infections, except for syphilitic aortitis.[3] The term "infected aneurysm" proposed by Jarrett and associates[4] is more appropriate, since few infections involve fungi.[5] According to some authors, a more accurate term might have been endovascular infection or infective vasculitis, because mycotic aneurysms are not due to a fungal organism.[6] Mycotic aneurysms account for 2.6% of aortic aneurysms.[3] For the clinician, early diagnosis is the cornerstone of effective treatment. Without medical or surgical management, catastrophic hemorrhage or uncontrolled sepsis may occur. However, symptomatology is frequently nonspecific during the early stages, so a high index of suspicion is required to make the diagnosis.[5] Intracranial mycotic aneurysms (ICMAs) complicate about 2% to 3% of infective endocarditis (IE) cases, although as many as 15% to 29% of patients with IE have neurologic symptoms.[6] ## References[edit] 1. ^ Greenfield, Lazar J, and Michael W. Mulholland. Greenfield's Surgery: Scientific Principles and Practice. Philadelphia: Wolters Kluwer Health/Nut Williams & Wilkins, 2011. Print. Page 1563 2. ^ Yang CY, Liu KL, Lee CW, et al. (2005). "Mycotic aortic aneurysm presenting initially as an aortic intramural air pocket". AJR Am J Roentgenol. 185 (2): 463–5. doi:10.2214/ajr.185.2.01850463. 3. ^ a b Bayer AS, Scheld WM. Endocarditis and intravascular infections. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Philadelphia: Churchill Livingstone; 2000:888-892. 4. ^ Jarrett F, Darling RC, Mundth ED, Austen WG. Experience with infected aneurysms of the abdominal aorta. Arch Surg. 1975;110:1281-1286. 5. ^ a b Mycotic (Infected) Aneurysm Caused by Streptococcus pneumoniae. Khosrow Afsari, et al. Infect Med. 2001;18(6) http://www.medscape.com/viewarticle/410168 6. ^ a b "Archived copy" (PDF). Archived from the original (PDF) on 2013-10-14. Retrieved 2013-08-09.CS1 maint: archived copy as title (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	Mycotic aneurysm	c0002950	910	wikipedia	https://en.wikipedia.org/wiki/Mycotic_aneurysm	2021-01-18T18:28:35	{"mesh": ["D000785"], "wikidata": ["Q17130655"]}
Pigeonpox virus Virus classification (unranked): Virus Realm: Varidnaviria Kingdom: Bamfordvirae Phylum: Nucleocytoviricota Class: Pokkesviricetes Order: Chitovirales Family: Poxviridae Genus: Avipoxvirus Species: Pigeonpox virus Pigeon pox is a viral disease to which pigeons are susceptible.[1] There is a live viral vaccine available (ATCvet code: QI01ED01 (WHO)). Pigeon pox is caused by Pigeonpox virus that is spread by mosquitoes and dirty water but not in droppings. The disease causes pox scabs to form around the bird's face, mouth and feet.[2] ## References[edit] 1. ^ "Pigeon Pox". www.pigeon-aid.org.uk. Archived from the original on 2017-07-07. Retrieved 2008-12-23. 2. ^ "Pigeon Pox". www.pigeon-aid.org.uk. Taxon identifiers * Wikidata: Q18975505 * Wikispecies: Pigeonpox virus * EoL: 540241 * IRMNG: 11460535 * NCBI: 10264 This virus-related article is a stub. You can help Wikipedia by expanding it. * v * t * e This veterinary medicine–related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Pigeon pox	None	911	wikipedia	https://en.wikipedia.org/wiki/Pigeon_pox	2021-01-18T18:31:21	{"wikidata": ["Q7193348"]}
Adie syndrome is is a neurological disorder affecting the pupil of the eye and the autonomic nervous system. It is characterized by one eye with a pupil that is larger than normal that constricts slowly in bright light (tonic pupil), along with the absence of deep tendon reflexes, usually in the Achilles tendon. In most cases, the cause of Adie syndrome is unknown. Some cases may result from trauma, surgery, lack of blood flow, or infection. Treatment may not be necessary. Glasses and eye drops may help when treatmend is needed. The term Adie syndrome is used when both the pupil and deep tendon reflexes are affected. When only the pupil is affected, the disorder may be referred to as Adie's pupil. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Adie syndrome	c0001519	912	gard	https://rarediseases.info.nih.gov/diseases/5749/adie-syndrome	2021-01-18T18:02:15	{"mesh": ["D000270"], "omim": ["103100"], "synonyms": ["Tonic, sluggishly reacting pupil and hypoactive or absent tendon reflexes", "Holmes-Adie syndrome", "HAS", "Adie's Pupil"]}
Pancreatic hypoplasia-diabetes-congenital heart disease syndrome is characterized by partial pancreatic agenesis, diabetes mellitus, and heart anomalies (including transposition of the great vessels, ventricular or atrial septal defects, pulmonary stenosis, or patent ductus arteriosis). ## Epidemiology It has been described in one Japanese family, in which the mother and at least two of her four children were affected (another two children died shortly after birth). ## Genetic counseling The syndrome appears to be inherited 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	Pancreatic hypoplasia-diabetes-congenital heart disease syndrome	c2931296	913	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2255	2021-01-23T18:03:56	{"gard": ["347"], "mesh": ["C536714"], "omim": ["600001"], "umls": ["C2931296"], "icd-10": ["Q87.8"], "synonyms": ["Yorifuji-Okuno syndrome"]}
A rare organic aciduria characterized by impaired isoleucine degradation with increased plasma or whole blood C5 acylcarnitine levels (typically observed in newborn screening) and increased urinary excretion of N-methylbutyrylglycine. The condition is usually clinically asymptomatic, although patients with muscular hypotonia, developmental delay, and seizures (among others) have been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	2-methylbutyryl-CoA dehydrogenase deficiency	c1864912	914	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79157	2021-01-23T19:09:41	{"gard": ["10322"], "mesh": ["C566487"], "omim": ["610006"], "umls": ["C1864912"], "icd-10": ["E71.1"], "synonyms": ["2-methylbutyric aciduria", "Developmental delay due to 2-methylbutyryl-CoA dehydrogenase deficiency", "SBCAD deficiency", "Short/branched-chain acyl-coA dehydrogenase deficiency"]}
For a general discussion of hereditary prostate cancer, see 176807. Mapping Gudmundsson et al. (2007) performed a genomewide association scan of 1,501 Icelandic men with prostate cancer and 11,290 controls, followed by 3 case-control replication studies in individuals from the Netherlands, Spain, and Chicago and found an association between prostate cancer and the A allele of rs4430796 in intron 2 of the TCF2 gene (HNF1B; 189907) (p = 1.4 x 10(-11) for the combined studies). The authors noted that the risk conferred by this variant is modest (allele odds ratio, 1.22), but because it is common, the population-attributable risk is substantial. In a large genomewide association study of prostate cancer, Thomas et al. (2008) confirmed the association found by Gudmundsson et al. (2007) with the A allele of the SNP rs4430796 (9.58 x 10(-10)). In a large 2-stage genomewide association study of prostate cancer involving white participants from the United Kingdom and Australia screening 541,129 SNPs, Eeles et al. (2008) found 6 strongly associated SNPs on chromosome 17 (P less than 10(-6)). Four of these were at 17q12, with the strongest association observed for rs7501939 in the HNF1B gene (OR = 0.71, P = 10(-12)). A P value of 8.3 x 10(-12) was observed for the SNP rs4430796. Sun et al. (2008) carried out a fine mapping study of the HNF1B gene at 17q12 in 2 study populations and identified a second locus associated with prostate cancer risk, approximately 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hotspot. Sun et al. (2008) confirmed the association with a SNP in the second locus (rs11649743) in 5 additional populations, with P = 1.7 x 10(-9) for an allelic test of the 7 studies combined. The association at each SNP remained significant after adjustment for the other. By targeted SNP analysis of 542 non-Hispanic men with prostate cancer from 403 families and 473 unaffected men, Levin et al. (2008) found that the A allele of rs4430796 in the HNF1B gene on 17q12 was significantly associated with prostate cancer, particularly among men diagnosed before age 50 years (p = 0.006 with an odds ratio of 1.92), but not later age (p = 0.118). Homozygous carriers of the A allele had a 3.70-fold increased risk of developing prostate cancer at an early age compared to noncarriers. The results confirmed the prostate cancer association with SNPs on chromosome 17q12, and indicated that this locus may also play a role in hereditary prostate cancer with early onset. Berndt et al. (2011) genotyped 79 SNPs in the 17q12 region harboring HNF1B in 10,272 patients with prostate cancer and 9,123 controls of European descent. The most significant association was with rs4430796 (p = 1.62 x 10(-24)). Risk was also associated with rs7405696 (p = 9.35 x 10(-23)), even after adjustment for rs4430796 (p = 0.007). At the second locus in this region, prostate cancer risk was associated with rs11649743 (p = 3.54 x 10(-8)), but an even stronger association was found for rs4794758 (p = 4.95 x 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (p = 0.32 for rs11649743; p = 0.002 for rs4794758). Sequential conditional analyses indicated that 5 SNPs (rs4430796, rs7405696, rs4794758, rs1016990, and rs3094509) together comprised the best model for risk in this region. The study demonstrated a complex relationship between variants in the HNF1B region and prostate cancer risk. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	PROSTATE CANCER, HEREDITARY, 11	c2931456	915	omim	https://www.omim.org/entry/611955	2019-09-22T16:02:35	{"doid": ["10283"], "mesh": ["C537243"], "omim": ["611955"], "orphanet": ["1331"]}
A number sign (#) is used with this entry because of evidence that X-linked mental retardation-101 (MRX101) is caused by mutation in the MID2 gene (300204) on chromosome Xq22. One such family has been reported. Clinical Features Geetha et al. (2014) reported a large family from northern India in which 11 males spanning 3 generations had mental retardation. All 6 patients evaluated had global developmental delay. Facial dysmorphism was not prominent, but several patients had long face, prominent ears, and squint or strabismus. Two had seizures. Most also had hyperactivity, often with aggressive outbursts. Inheritance The transmission pattern in the family with MRX101 reported by Geetha et al. (2014) was consistent with X-linked recessive inheritance. Molecular Genetics In affected members of a family with MRX101, Geetha et al. (2014) identified a hemizygous missense mutation in the MID2 gene (R347Q; 300204.0001). The mutation was found using a combination of linkage analysis and targeted next-generation sequencing. Carrier females in the family were unaffected. Transfection of the mutation in HEK293T cells showed abnormal localization of the mutant protein, which was found in aggregate form or enclosed in vesicles in the cytoplasm rather than being bound to microtubules. By direct sequencing of the coding exons of the MID2 gene among 480 patients with intellectual disability, Geetha et al. (2014) identified an individual with a missense mutation (N343S); however, functional assays indicated that this mutation may not be disease causing. INHERITANCE \- X-linked recessive HEAD & NECK Face \- Long face (in some patients) Ears \- Large ears (in some patients) Eyes \- Squint \- Strabismus NEUROLOGIC Central Nervous System \- Global developmental delay \- Impaired cognition \- Mental retardation \- Poor speech \- Lack of speech \- Seizures (in some patients) Behavioral Psychiatric Manifestations \- Hyperactivity \- Aggressive outbursts MISCELLANEOUS \- Onset at birth \- One family from Punjab, India has been reported (last curated August 2014) MOLECULAR BASIS \- Caused by mutation in the midline 2 gene (MID2, 300204.0001 ) ▲ 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	MENTAL RETARDATION, X-LINKED 101	c2931498	916	omim	https://www.omim.org/entry/300928	2019-09-22T16:19:09	{"mesh": ["C567906"], "omim": ["300928"], "orphanet": ["777"]}
Sexual attraction to individuals of particular age ranges The term chronophilia was used by John Money to describe a form of paraphilia in which an individual experiences sexual attraction limited to individuals of particular age ranges.[1][2] The term has not been widely adopted by sexologists, who instead use terms that refer to the specific age range in question.[3] An arguable historical precursor was Richard von Krafft-Ebing's concept of "age fetishism".[4] ## Sexual preferences based on age[edit] * Pedohebephilia refers to an expansion and reclassification of pedophilia and hebephilia with subgroups, proposed during the development of the DSM-5.[5] It refers more broadly to sexual attractions. Under the proposed revisions, people who are dysfunctional as a result of it would be diagnosed with pedohebephilic disorder. People would be broken down into types based on the idea of being attracted to one, the other or both of the subgroups. The proposed revision was not ratified for inclusion in the final published version of DSM-5. * Infantophilia (sometimes called nepiophilia) is a subtype of pedophilia describing a sexual preference for children less than 5 years old (including toddlers and infants).[6] * Pedophilia is a psychological disorder in which an adult or older adolescent experiences a sexual preference for prepubescent children.[7][8] According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), pedophilia is a paraphilia in which a person has intense sexual urges towards children, and experiences recurrent sexual urges towards and fantasies about children. Pedophilic disorder is further defined as psychological disorder in which a person meets the criteria for pedophilia above, and also either acts upon those urges, or else experiences distress or interpersonal difficulty as a consequence.[9][10] The diagnosis can be made under the DSM or ICD criteria for persons age 16 and older.[11] Not all pedophiles commit child sexual abuse, and not all child molesters are pedophiles.[12] * Attraction to adolescents * Hebephilia and ephebophilia are sexual preferences for pubescent and post-pubescent youths, respectively.[13] The term hebephilia was introduced by Bernard Glueck in 1955.[14] * Attraction to adults * Teleiophilia (from Greek téleios, "full grown") is a sexual preference for adults.[15] The term was coined by Ray Blanchard in 2000.[16] * Mesophilia (derived from the Greek "mesos", "intermediate") is a sexual preference for middle-aged adults. The term was coined by Michael Seto in 2016.[17] * Gerontophilia is a sexual preference for the elderly.[18] ## See also[edit] * Age disparity in sexual relationships * List of paraphilias * MILF (slang) ## References[edit] 1. ^ Money, John (1986). Lovemaps: clinical concepts of sexual/erotic health and pathology, paraphilia, and gender transposition of childhood, adolescence, and maturity. pp. 70, 260. ISBN 978-0-8290-1589-8. 2. ^ Money, John (1990). Gay, Straight, and In-Between: The Sexology of Erotic Orientation. pp. 137, 183. ISBN 978-0-19-505407-1. 3. ^ Janssen, D.F. (2017). "John Money's 'Chronophilia': Untimely Sex between Philias and Phylisms". Sexual Offender Treatment. 12 (1). ISSN 1862-2941. 4. ^ Janssen, D.F. (2015). ""Chronophilia": Entries of Erotic Age Preference into Descriptive Psychopathology". Medical History. 59 (4): 575–598. doi:10.1017/mdh.2015.47. ISSN 0025-7273. PMC 4595948. PMID 26352305. 5. ^ DSM-5 U 03 Archived 2011-11-13 at the Wayback Machine 6. ^ Greenberg DM, Bradford J, Curry S (1995). "Infantophilia--a new subcategory of pedophilia?: a preliminary study". Bull Am Acad Psychiatry Law. 23 (1): 63–71. PMID 7599373.. 7. ^ World Health Organization, International Statistical Classification of Diseases and Related Health Problems: ICD-10 Section F65.4: Pedophilia (online access via ICD-10 site map table of contents) 8. ^ Blanchard, R.; Kolla, N. J.; Cantor, J. M.; Klassen, P. E.; Dickey, R.; Kuban, M. E.; Blak, T. (2007). "IQ, handedness, and pedophilia in adult male patients stratified by referral source". Sexual Abuse: A Journal of Research and Treatment. 19 (3): 285–309. doi:10.1177/107906320701900307. PMID 17634757. S2CID 220359453. 9. ^ American Psychiatric Association, Highlights of Changes from DSM-IV-TR to DSM-5 Archived October 19, 2013, at the Wayback Machine Paraphilic disorders (page 18) 10. ^ American Psychiatric Association (June 2000). Diagnostic and Statistical Manual of Mental Disorders DSM-IV TR (Text Revision). 1. Arlington, VA, USA: American Psychiatric Publishing, Inc. p. 943. doi:10.1176/appi.books.9780890423349. ISBN 978-0-89042-024-9. Archived from the original on 2011-10-25. Retrieved 2010-05-14. 11. ^ "The ICD-10 Classification of Mental and Behavioral Disorders – Diagnostic criteria for research" (PDF). (715 KB) (see F65.4, pp. 166–167) 12. ^ Fagan PJ, Wise TN, Schmidt CW, Berlin FS (November 2002). "Pedophilia". JAMA. 288 (19): 2458–65. doi:10.1001/jama.288.19.2458. PMID 12435259. 13. ^ Blanchard, R. Blanchard, R., Lykins, A. D., Wherrett, D., Kuban, M. E., Cantor, J. M., Blak, T., Dickey, R., & Klassen, P. E. (2008). Pedophilia, hebephilia, and the DSM–V. Archives of Sexual Behavior. doi:10.1007/s10508-008-9399-9. 14. ^ Glueck, B. C. Jr. (1955). Final report: Research project for the study and treatment of persons convicted of crimes involving sexual aberrations. June 1952 to June 1955. New York: New York State Department of Mental Hygiene. 15. ^ Blanchard, R.; Barbaree, H. E.; Bogaert, A. F.; Dickey, R.; Klassen, P.; Kuban, M. E.; Zucker, KJ; et al. (2000). "Fraternal birth order and sexual orientation in pedophiles". Archives of Sexual Behavior. 29 (5): 463–478. doi:10.1023/A:1001943719964. PMID 10983250. S2CID 19755751. 16. ^ Blanchard, R. & Barbaree, H. E. (2005). "The strength of sexual arousal as a function of the age of the sex offender: Comparisons among pedophiles, hebephiles, and teleiophiles". Sexual Abuse: A Journal of Research and Treatment. 17 (4): 441–456. doi:10.1177/107906320501700407. PMID 16341604. S2CID 220355347. 17. ^ Seto,M (2016). "The Puzzle of Male Chronophilias". Archives of Sexual Behavior. 46 (1): 3–22. doi:10.1007/s10508-016-0799-y. PMID 27549306. S2CID 1555795. 18. ^ Kaul, A.; Duffy, S. (1991). "Gerontophilia: A case report". Medicine, Science and the Law. 31 (2): 110–114. doi:10.1177/002580249103100204. PMID 2062191. S2CID 6455643. * v * t * e Paraphilias List * Abasiophilia * Acrotomophilia * Agalmatophilia * Algolagnia * Apotemnophilia * Autassassinophilia * Biastophilia * Capnolagnia * Chremastistophilia * Chronophilia * Coprophagia * Coprophilia * Crurophilia * Crush fetish * Dacryphilia * Dendrophilia * Emetophilia * Eproctophilia * Erotic asphyxiation * Erotic hypnosis * Erotophonophilia * Exhibitionism * Formicophilia * Frotteurism * Gerontophilia * Homeovestism * Hybristophilia * Infantophilia * Kleptolagnia * Klismaphilia * Lactaphilia * Macrophilia * Masochism * Mechanophilia * Microphilia * Narratophilia * Nasophilia * Necrophilia * Object sexuality * Odaxelagnia * Olfactophilia * Omorashi * Paraphilic infantilism * Partialism * Pedophilia * Podophilia * Plushophilia * Pyrophilia * Sadism * Salirophilia * Scopophilia * Somnophilia * Sthenolagnia * Tamakeri * Telephone scatologia * Transvestic fetishism * Trichophilia * Troilism * Urolagnia * Urophagia * Vorarephilia * Voyeurism * Zoophilia * Zoosadism See also * Other specified paraphilic disorder * Erotic target location error * Courtship disorder * Polymorphous perversity * Sexual fetishism * Human sexual activity * Perversion * Sexology * Book * Category * v * t * e Pedophilia and child sexual abuse Associated chronophilias * Hebephilia * Ephebophilia Behavior and legal aspects * Age of consent reform * Child pornography * Hurtcore * Child erotica * Simulated * Legality * Legal status of drawn pornography depicting minors * Child grooming * Causes of clerical child abuse * Commercial sexual exploitation of children * Child prostitution * Child sex tourism * Child trafficking * Cybersex trafficking * Child marriage * Marriageable age * Pederasty By country * Afghanistan * Australia * Egypt * Nigeria * United Kingdom Treatment methods * Chemical castration * Castration * Cognitive behavioral therapy Research and support groups * Association for the Treatment of Sexual Abusers * Circles of Support and Accountability * Silentlambs * Survivors Network of those Abused by Priests * Virtuous Pedophiles Prevention organizations * Association for the Treatment of Sexual Abusers * Child Exploitation and Online Protection Command * Jewish Community Watch * Prevention Project Dunkelfeld * Special Rapporteur on the sale of children, child prostitution and child pornography * The Awareness Center * Tzedek Social views * Anti-pedophile activism * Creep Catchers * Dark Justice * Perverted-Justice * Sweetie (internet avatar) * Pedophile advocacy groups Related * Anglican Communion sexual abuse cases * Catholic Church sexual abuse cases * by country * debate * media coverage * Society of Jesus * Child sexual abuse in New York City religious institutions * Jehovah's Witnesses' handling of child sexual abuse cases * Mormon sexual abuse cases * Royal Commission into Institutional Responses to Child Sexual Abuse * Scouting sexual abuse cases * Sexual abuse cases in Haredi Judaism * Adass Israel School * Brooklyn's Haredi community * Jewish Care controversy * Manny Waks case * Sotadic Zone Psychology portal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Chronophilia	None	917	wikipedia	https://en.wikipedia.org/wiki/Chronophilia	2021-01-18T18:42:26	{"wikidata": ["Q1088341"]}
For other uses, see Spoilage. This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article possibly contains original research. Please improve it by verifying the claims made and adding inline citations. Statements consisting only of original research should be removed. (August 2018) (Learn how and when to remove this template message) This article is written like a personal reflection, personal essay, or argumentative essay that states a Wikipedia editor's personal feelings or presents an original argument about a topic. Please help improve it by rewriting it in an encyclopedic style. (August 2018) (Learn how and when to remove this template message) (Learn how and when to remove this template message) A spoiled child or spoiled brat is a derogatory term aimed at children who exhibit behavioral problems from being overindulged by their parents or other caregivers. Children and teens who are perceived as spoiled may be described as "overindulged", "grandiose", "narcissistic" or "egocentric-regressed". When the child has a neurological condition such as autism, ADHD or intellectual disability, observers may see them as "spoiled”. There is no specific scientific definition of what "spoiled" means, and professionals are often unwilling to use the label because it is considered vague and derogatory.[1][2] Being spoiled is not recognized as a mental disorder in any of the medical manuals, such as the ICD-10[3] or the DSM-IV,[4] or its successor, the DSM-5.[5] ## Contents * 1 As syndrome * 1.1 Potential causes * 1.2 Differential diagnosis * 1.3 Prevention * 1.4 Treatment * 2 Infants * 3 Only children * 4 Later life * 5 See also * 6 References * 7 Further reading ## As syndrome Richard Weaver, in his work Ideas Have Consequences, introduced the term “spoiled child psychology” in 1948. In 1989, Bruce McIntosh coined the term the "spoiled child syndrome".[1] The syndrome is characterized by "excessive, self-centered, and immature behavior". It includes lack of consideration for other people, recurrent temper tantrums, an inability to handle the delay of gratification, demands for having one's own way, obstructiveness, and manipulation to get their way.[6] McIntosh attributed the syndrome to "the failure of parents to enforce consistent, age-appropriate limits", but others, such as Aylward, note that temperament is probably a contributory factor.[7] Temper tantrums are recurrent. McIntosh observes that "many of the problem behaviors that cause parental concern are unrelated to spoiling as properly understood". Children may have occasional temper tantrums without them falling under the umbrella of "spoiled". Extreme cases of spoiled child syndrome will involve frequent temper tantrums, physical aggression, defiance, destructive behavior, and refusal to comply with even the simple demands of daily tasks.[7] This can be similar to the profile of children diagnosed with Pathological Demand Avoidance, which is part of the autism spectrum.[8] ### Potential causes * Failure of parents to enforce consistent, age-appropriate limits.[6] * Parents shielding the child from normal everyday frustrations.[6] * Provision of excessive material gifts, even when the child has not behaved appropriately.[6] * Improper role models provided by parents.[6] ### Differential diagnosis Children with underlying medical or mental health problems may exhibit some of the symptoms. Speech or hearing disorders, and attention deficit disorder, may lead to children's failing to understand the limits set by parents. Children who have recently experienced a stressful event, such as the separation of the parents (divorce) or the birth or death of a close family relative, may also exhibit some or all of the symptoms. Children of parents who themselves have psychiatric disorders may manifest some of the symptoms, because the parents behave erratically, sometimes failing to perceive their children's behavior correctly, and thus fail to properly or consistently define limits of normal behavior for them.[6] ### Prevention Parents can seek advice, support, and encouragement to empower them in parenthood from diverse sources. ### Treatment Treatment by a physician involves assessing parental competence, and whether the parents set limits correctly and consistently. Physicians will rule out dysfunction in the family, referring dysfunctional families for family therapy and dysfunctional parents for parenting skills training, and counsel parents in methods for modifying their child's behavior.[6] ## Infants In early infancy, a baby signals desire for food, contact, and comfort by crying. This behavior can be viewed as a distress signal indicating that some biological need is not being met. Parents sometimes worry about spoiling their children by giving them too much attention, specialists in child development maintain that babies cannot be spoiled in the first six months of life.[9] During the first year, children are developing a sense of basic trust and attachment. ## Only children Main article: Only child Alfred Adler (1870–1937) believed that "only children" were likely to experience a variety of problems from their situation. Adler theorized that because only children have no rivals for their parents' affection, they will become pampered and spoiled, particularly by their mother. He suggested that this could later cause interpersonal difficulties if the person is not universally liked and admired.[10] A 1987 quantitative review of 141 studies on 16 different personality traits contradicted Adler's theory. This research found no evidence of any "spoilage" or other pattern of maladjustment in only children. The major finding was that only children are not very different from children with siblings. The main exception to this was the finding that only children are generally higher in achievement motivation.[11] A second analysis revealed that only children, first-borns, and children with only one sibling score higher on tests of verbal ability than later-borns and children with multiple siblings.[12] ## Later life Spoiling in early childhood tends to create characteristic reactions that persist, fixed, into later life. These can cause significant social problems. Spoiled children may have difficulty coping with situations such as teachers scolding them or refusing to grant extensions on homework assignments, playmates refusing to allow them to play with their toys and playmates refusing playdates with them, a loss in friends, failure in employment, and failure with personal relationships. As adults, spoiled children may experience problems with anger management, professionalism, and personal relationships; a link with adult psychopathy has been observed.[13][14] ## See also * Child discipline * Freaky Friday * Little Emperor Syndrome * Oppositional defiant disorder * Parenting * Tantrum * Grounding (punishment) ## References 1. ^ a b Bruce J. McIntosh (January 1989). "Spoiled Child Syndrome". Pediatrics. 83 (1): 108–115. PMID 2642617. 2. ^ Alder, Alfred (1992). "Individual Psychology". Journal of Individual Psychology. University of Texas Press, 1992. 23–24: 355. 3. ^ "ICD 10". Priory.com. Retrieved 2013-05-05. 4. ^ "APA Diagnostic Classification DSM-IV-TR". BehaveNet. Archived from the original on 2011-10-26. Retrieved 2013-05-05. 5. ^ "DSM-5". DSM-5. 2016-10-01. Retrieved 2017-03-22. 6. ^ a b c d e f g Vidya Bhushan Gupta (1999). "Spoiled Child Syndrome". Manual of Developmental and Behavioral Problems in Children. Inform Health Care. pp. 198–199. ISBN 978-0-8247-1938-8. 7. ^ a b Glen P. Aylward (2003). Practitioner's Guide to Behavioral Problems in Children. Springer. p. 35. ISBN 978-0-306-47740-9. 8. ^ "What is pathological demand avoidance? - NAS". Autism.org.uk. Retrieved 22 June 2016. 9. ^ "Archived copy". Archived from the original on 2008-12-25. Retrieved 2009-05-21.CS1 maint: archived copy as title (link) 10. ^ Adler, A. (1964). Problems of neurosis. New York: Harper and Row. 11. ^ Polit, D. F. & Falbo, T. (1987). "Only children and personality development: A quantitative review". Journal of Marriage and the Family. 49 (2): 309–325. doi:10.2307/352302. JSTOR 352302. 12. ^ Polit, D. F. & Falbo, T. (1988). "The intellectual achievement of only children". Journal of Biosocial Science. 20 (3): 275–285. doi:10.1017/S0021932000006611. PMID 3063715. 13. ^ Leslie D. Weatherhead (2007). Psychology Religion and Healing. READ BOOKS. p. 272. ISBN 978-1-4067-4769-0. 14. ^ Michael Osit (2008). Generation Text. AMACOM Div American Mgmt Assn. p. 59. ISBN 978-0-8144-0932-9. ## Further reading * Bruce J. McIntosh (January 1989). "Spoiled Child Syndrome". Pediatrics. 83 (1): 108–115. PMID 2642617. * Ricktober (October 2004). "Spoiled". * Eileen Gallo; Jon J. Gallo & Kevin J. Gallo (2001). Silver Spoon Kids: How to Raise a Responsible Child in an Age of Affluence. McGraw-Hill Professional. ISBN 978-0-8092-9437-4. * Alfie Kohn (2016). The Myth of the Spoiled Child: Coddled Kids, Helicopter Parents, and Other Phony Crises. Beacon Press. ISBN 978-0807073889. * v * t * e Narcissism Types * Collective * Egomania * Flying monkeys * Healthy * Malignant * Narcissistic personality disorder * Spiritual * Workplace Characteristics * Betrayal * Boasting * Egocentrism * Egotism * Empathy (lack of) * Envy * Entitlement (exaggerated sense of) * Fantasy * Grandiosity * Hubris * Magical thinking * Manipulative * Narcissistic abuse * Narcissistic elation * Narcissistic rage and narcissistic injury * Narcissistic mortification * Narcissistic supply * Narcissistic withdrawal * Perfectionism * Self-esteem * Self-righteousness * Shamelessness * Superficial charm * Superiority complex * True self and false self * Vanity Defences * Denial * Idealization and devaluation * Distortion * Projection * Splitting Cultural phenomena * Control freak * Don Juanism * Dorian Gray syndrome * My way or the highway * Selfie Related articles * Codependency * Counterdependency * Dark triad * Ego ideal * "Egomania" (film) * Egotheism * Empire-building * God complex * History of narcissism * Messiah complex * Micromanagement * Narcissism of small differences * Narcissistic leadership * Narcissistic parent * Narcissistic Personality Inventory * Narcissus (mythology) * On Narcissism * Sam Vaknin * Self-love * Self-serving bias * Spoiled child * The Culture of Narcissism * Workplace bullying * v * t * e Parenting Kinship terminology * Adoptive * Alloparenting * Coparenting * Extended family * Foster care * Kommune 1 * Noncustodial * Nuclear family * Orphaned * Shared parenting * Single parent * Blended family * Surrogacy * In loco parentis Theories · Areas * Attachment theory * Applied behavior analysis * Behaviorism * Child development * Cognitive development * Developmental psychology * Human development * Love * Maternal bond * Nature versus nurture * Parental investment * Paternal bond * Pediatrics * Social psychology Styles * Attachment parenting * Baby talk * Concerted cultivation * Gatekeeper parent * Helicopter parent * Nurturant parenting * Slow parenting * Soccer mom * Strict father model * Taking children seriously * Tiger parenting * Work at home parent Techniques * After-school activity * Allowance * Bedtime * Child care * Co-sleeping * Homeschooling * Latchkey kid * Parent management training * Play (date) * Role model * Spoiled child * Television * The talk * Toy (educational) Child discipline * Blanket training * Corporal punishment in the home * Curfew * Grounding * Positive discipline * Tactical ignoring * Time-out Abuse * Child abandonment * Child abuse * Child labour * Child neglect * Cinderella effect * Incest * Narcissistic parent * Parental abuse by children Legal and social aspects * Child custody * Child support * Cost of raising a child * Deadbeat parent * Disownment * Marriage * Parental alienation * Parental responsibility * Paternity * Shared parenting Experts * T. Berry Brazelton * Rudolf Dreikurs * David Elkind * Jo Frost * Haim Ginott * Thomas Gordon * Alan E. Kazdin * Truby King * Annette Lareau * Penelope Leach * William Sears * B. F. Skinner * Benjamin Spock Organizations * Families Need Fathers * Mothers Apart from Their Children * Mothers' Union * National Childbirth Trust * National Parents Organization * Parent–teacher association * Parents Against Child Sexual Exploitation [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Spoiled child	None	918	wikipedia	https://en.wikipedia.org/wiki/Spoiled_child	2021-01-18T18:34:09	{"wikidata": ["Q3054155"]}
Familial amyloid cardiomyopathy SpecialtyCardiology Familial amyloid cardiomyopathy (FAC), or transthyretin amyloid cardiomyopathy (ATTR-CM) results from the aggregation and deposition of mutant and wild-type transthyretin (TTR) protein in the heart.[1] TTR amyloid fibrils infiltrate the myocardium, leading to diastolic dysfunction from restrictive cardiomyopathy, and eventual heart failure.[2] Both mutant and wild-type transthyretin comprise the aggregates because the TTR blood protein is a tetramer composed of mutant and wild-type TTR subunits in heterozygotes. Several mutations in TTR are associated with FAC, including V122I, V20I, P24S, A45T, Gly47Val, Glu51Gly, I68L, Gln92Lys, and L111M. One common mutation (V122I), which is a substitution of isoleucine for valine at position 122, occurs with high frequency in African-Americans, with a prevalence of approximately 3.5%. FAC is clinically similar to senile systemic amyloidosis,[3] in which cardiomyopathy results from the aggregation of wild-type transthyretin exclusively.[4][5] ## Contents * 1 Presentation * 2 Diagnosis * 3 Management * 4 See also * 5 References ## Presentation[edit] The onset of FAC caused by aggregation of the V122I mutation and wild-type TTR, and senile systemic amyloidosis caused by the exclusive aggregation of wild-type TTR, typically occur after age 60. Greater than 40% of these patients present with carpal tunnel syndrome before developing ATTR-CM. Cardiac involvement is often identified with the presence of conduction system disease (sinus node or atrioventricular node dysfunction) and/or congestive heart failure, including shortness of breath, peripheral edema, syncope, exertional dyspnea, generalized fatigue, or heart block.[6][7] Unfortunately, echocardiographic findings are indistinguishable from those seen in AL amyloidosis, and include thickened ventricular walls (concentric hypertrophy, both right and left) with a normal-to-small left ventricular cavity, increased myocardial echogenicity, normal or mildly reduced ejection fraction (often with evidence of diastolic dysfunction and severe impairment of contraction along the longitudinal axis), and bi-atrial dilation with impaired atrial contraction. Unlike the situation in AL amyloidosis, the ECG voltage is often normal, although low voltage may be seen (despite increased wall thickness on echocardiography). Marked axis deviation, bundle branch block, and AV block are common, as is atrial fibrillation. ## Diagnosis[edit] This section is empty. You can help by adding to it. (August 2018) ## Management[edit] Although not based on a human clinical trial, the only currently accepted disease-modifying therapeutic strategy available for familial amyloid cardiomyopathy is a combined liver and heart transplant. Treatments aimed at symptom relief are available, and include diuretics, pacemakers, and arrhythmia management. Thus, Senile systemic amyloidosis and familial amyloid polyneuropathy are often treatable diseases that are misdiagnosed.[8][9][10] ## See also[edit] * Amyloid * Transthyretin * Senile systemic amyloidosis * Restrictive cardiomyopathy ## References[edit] 1. ^ Jacobson, D. R., Pastore, R. D., Yaghoubian, R., Kane, I., Gallo, G., Buck, F. S. & Buxbaum, J. N. (1997). Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis that occurs in black Americans. The New England Journal of Medicine 336, 466-73. 2. ^ "Familial". Amyloidosis Foundation. Archived from the original on 31 July 2013. Retrieved 23 August 2013. 3. ^ Westermark, P., Sletten, K., Johansson, B. & Cornwell, G. G., 3rd. (1990). Fibril in Senile Systemic Amyloidosis is derived from normal transthyretin. Proceedings of the National Academy of Sciences of the United States of America 87, 2843-5. 4. ^ Ng, B., Connors, L. H., Davidoff, R., Skinner, M. & Falk, R. H. (2005). Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis. Arch Intern Med 165, 1425-9. 5. ^ Westermark, P., Bergstrom, J., Solomon, A., Murphy, C. & Sletten, K. (2003). Transthyretin-derived senile systemic amyloidosis: clinicopathologic and structural considerations. Amyloid 10 Suppl 1, 48-54. 6. ^ Falk, R. H. & Elkayam, U. (2010). Cardiomyopathy: the importance of recognizing the uncommon diagnosis. Prog Cardiovasc Dis 52, 262-3. 7. ^ Snyder, M. E., Haidar, G. R., Spencer, B. & Maurer, M. S. (2011). Transthyretin cardiac amyloidosis diagnosed by analyzing a prostatic tissue sample: a case report. J Am Geriatr Soc 59, 1745-7. 8. ^ Falk, R. H. (2011). Cardiac amyloidosis: a treatable disease, often overlooked. Circulation 124, 1079-85. 9. ^ Bhuiyan, T., Helmke, S., Patel, A. R., Ruberg, F. L., Packman, J., Cheung, K., Grogan, D. & Maurer, M. S. (2011). Pressure-volume relationships in patients with transthyretin (ATTR) cardiac amyloidosis secondary to V122I mutations and wild-type transthyretin. Transthyretin cardiac amyloid study (TRACS). Circ.: Heart Failure 4, 121-128. 10. ^ Miller, A. L., Falk, R. H., Levy, B. D. & Loscalzo, J. (2010). A heavy heart. N. Engl. J. Med. 363, 1464-1470. * v * t * e Amyloidosis Common amyloid forming proteins * AA * ATTR * Aβ2M * AL * Aβ/APP * AIAPP * ACal * APro * AANF * ACys * ABri Systemic amyloidosis * AL amyloidosis * AA amyloidosis * Aβ2M/Haemodialysis-associated * AGel/Finnish type * AA/Familial Mediterranean fever * ATTR/Transthyretin-related hereditary Organ-limited amyloidosis Heart AANF/Isolated atrial Brain * Familial amyloid neuropathy * ACys+ABri/Cerebral amyloid angiopathy * Aβ/Alzheimer's disease Kidney * AApoA1+AFib+ALys/Familial renal Skin * Primary cutaneous amyloidosis * Amyloid purpura Endocrine Thyroid ACal/Medullary thyroid cancer Pituitary APro/Prolactinoma Pancreas AIAPP/Insulinoma AIAPP/Diabetes mellitus type 2 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Familial amyloid cardiomyopathy	c0342613	919	wikipedia	https://en.wikipedia.org/wiki/Familial_amyloid_cardiomyopathy	2021-01-18T18:56:24	{"orphanet": ["85451"], "synonyms": ["ATTR cardiomyopathy", "ATTRV122I-related amyloidosis", "TTR-related amyloid cardiomyopathy", "TTR-related cardiac amyloidosis", "Transthyretin amyloid cardiopathy", "Transthyretin-related familial amyloid cardiomyopathy"], "wikidata": ["Q5432929"]}
This article relies largely or entirely on a single source. Relevant discussion may be found on the talk page. Please help improve this article by introducing citations to additional sources. Find sources: "Peritoneal carcinomatosis" – news · newspapers · books · scholar · JSTOR (November 2018) Peritoneal carcinomatosis Intestines with peritoneal carcinomatosis from gastric cancer, appearing as a grainy serosal surface.[1] SpecialtyOncology Peritoneal carcinomatosis (PC) is intraperitoneal dissemination (carcinosis) of any form of cancer that does not originate from the peritoneum itself. PC is most commonly seen in abdominopelvic malignancies. Computed tomography (CT) is particularly important for detailed preoperative assessment and evaluation of the radiological Peritoneal Cancer Index (PCI). ## References[edit] 1. ^ Turaga, Kiran K.; Gamblin, T. Clark; Pappas, Sam (2012). "Surgical Treatment of Peritoneal Carcinomatosis from Gastric Cancer". International Journal of Surgical Oncology. 2012: 1–4. doi:10.1155/2012/405652. ISSN 2090-1402. This medical 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	Peritoneal carcinomatosis	c0346990	920	wikipedia	https://en.wikipedia.org/wiki/Peritoneal_carcinomatosis	2021-01-18T18:41:22	{"umls": ["C0346990"], "wikidata": ["Q2071182"]}
A rare arthrogryposis syndrome characterized by the association of multiple congenital joint contractures (of the large joints, fingers and toes) and hyperkeratosis (i.e. thick, scaling and fissured skin), with death occurring in early infancy. There have been no further reports in the literature since 1993. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Arthrogryposis-hyperkeratosis syndrome, lethal form	c1859710	921	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1485	2021-01-23T18:29:06	{"gard": ["3053"], "mesh": ["C535883"], "omim": ["208158"], "umls": ["C1859710"], "synonyms": ["Johnston-Aarons-Schelley syndrome"]}
A rare, life-threatening, congenital, non-syndromic, conotruncal heart malformation disease characterized by absent or severely undeveloped pulmonary valve leaflets (with a restrictive ring of thickened tissue at the place of the pulmonary valve annulus), associated with an intact ventricular septum and a patent ductus arteriosus, manifesting with marked respiratory insufficiency. Additional features include dilated main pulmonary artery (with or without dilatation of pulmonary artery branches), to-and-fro flow at site of the dysplastic pulmonary valve, and systolic pressure gradient across narrowed pulmonary valve. Tricuspid atresia and variable extra-cardiac anomalies (e.g. diaphragmatic hernia or cleft lip/palate), may be present. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Pulmonary valve agenesis-intact ventricular septum-persistent ductus arteriosus syndrome	None	922	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99048	2021-01-23T17:23:08	{"icd-10": ["Q22.2"], "synonyms": ["APV/PDA, non-Fallot type"]}
A number sign (#) is used with this entry because of evidence that xeroderma pigmentosum complementation group G (XPG) and XPG/Cockayne syndrome are caused by homozygous or compound heterozygous mutation in the ERCC5 gene (133530) on chromosome 13q33. Homozygous mutation in the ERCC5 gene can also cause cerebrooculofacioskeletal syndrome-3 (COFS3; 616570). Description For a general description of xeroderma pigmentosum, see XPA (278700), and of Cockayne syndrome, see CSA (216400). Complementation group G has one of the smallest series of cases (Arlett et al., 1980). Clinical Features Cheesbrough and Kinmont (1978) and Keijzer et al. (1979) reported the first individual with XP complementation group G. She was noted to have facial photosensitive erythema at age 3 months and blistering on exposed skin at 5 months. She was normal until age 11 years, when she showed unstable gait and began to show mental deterioration. She reached age 17 years with no keratoses or skin tumors. Physical examination showed microcephaly with mental retardation, intention tremor of the arms, ataxia, moderate spasticity, wide-based gait, and bilateral pes cavus. Cells derived from the patient exhibited a low level of excision repair (2%) and impaired post-replication repair characteristic of XP. Arlett et al. (1980) reported a second individual with XPG who was over 7 years old. These patients were reported before the relationship between xeroderma pigmentosum group G and Cockayne syndrome was appreciated (Lalle et al., 2002). Norris et al. (1987) described a brother and sister, aged 14 and 12 years, respectively, with XP group G. Both patients manifested only mild cutaneous changes, with no UV-induced skin tumors, although abnormal sensitivity to UVB wavelengths was demonstrated by radiation monochromator skin testing. Physical and neurologic development was normal. Vermeulen et al. (1993) reported genetic studies of 2 unrelated, severely affected patients with clinical characteristics of Cockayne syndrome but with a biochemical defect typical of xeroderma pigmentosum. By complementation analysis, using somatic cell fusion and nuclear microinjection of cloned repair genes, they assigned these 2 patients to XP complementation group G. Zafeiriou et al. (2001) described a premature, small for gestational age infant girl with microphthalmia, bilateral congenital cataracts, hearing impairment, progressive somatic and neurodevelopmental arrest, and infantile spasms. She presented a massive photosensitive reaction with erythema and blistering after minimal sun exposure, which slowly gave rise to small skin cancers. Her skin fibroblasts were 10-fold more sensitive than normal to UV exposure due to a severe deficiency in nucleotide excision repair. By complementation analysis, the patient was assigned to the XPG group. Molecular Genetics Lalle et al. (2002) found that the first 2 patients reported with XPG (Cheesbrough and Kinmont, 1978; Keijzer et al., 1979; Arlett et al., 1980) produced XPG proteins with severely impaired endonuclease activity. Both patients were compound heterozygous for truncating mutations in the ERCC5 gene (133530.0009, 133530.0010) and another mutation (133530.0008 and 133530.0011, respectively). The mutant cells, unlike those from xeroderma pigmentosum group G/Cockayne syndrome patients, were capable of limited transcription-coupled repair of oxidative lesions. Lalle et al. (2002) suggested that the residual ERCC5 activity in these patients was responsible for the absence of severe early-onset Cockayne syndrome symptoms. In a patient with XPG/CS, Zafeiriou et al. (2001) identified compound heterozygosity for 2 mutations in the ERCC5 gene (133530.0006; 133530.0007). Genotype/Phenotype Correlations Some patients with a combined phenotype of xeroderma pigmentosum and Cockayne syndrome fall into complementation group G. Nouspikel et al. (1997) demonstrated that patients with the combined phenotype XPG/CS have mutations that would produce severely truncated XPG proteins. In contrast, 2 sib XPG patients without CS were able to make full-length XPG, but had a missense mutation that inactivated its function in nucleotide excision repair (133530.0002). These results suggested that XPG/CS mutations abolish interactions required for a second important XPG protein function and that it is the loss of the second function that leads to the Cockayne syndrome clinical phenotype. Although Figure 6 of the report of Nouspikel et al. (1997) was retracted by Leadon, the remaining authors asserted that the validity of the conclusion was not challenged (Snyder, 2006). Soltys et al. (2013) reported 2 Brazilian sibs, born of unrelated parents, with a mild form of XPG due to compound heterozygosity for 2 missense mutations in the ERCC5 gene (133530.0014 and 133530.0015). Both patients developed photosensitivity with mild skin lesions first apparent in infancy, but had no history of skin cancer or skin cancer precursor lesions up to ages 22 and 17 years, respectively. Patient cells showed a strong DNA repair defect in response to UV light, but not in response to oxidative stress. In vitro functional expression studies showed that both mutant proteins were able to partially restore activity in cells lacking ERCC5 in response to UV light, but not as well as the wildtype protein. In contrast, both mutant proteins showed activity comparable to wildtype in response to oxidative stress. Soltys et al. (2013) suggested that more severe ERCC5 defects that also impair the response to oxidative stress-induced injury, usually truncating mutations (see, e.g., 133530.0003), are associated with the more severe phenotype observed in Cockayne syndrome. History Complementation tests by cell fusion demonstrated that the NER syndromes are genetically heterogeneous and comprise 10 or more complementation groups: 7 in xeroderma pigmentosum, 2 in Cockayne syndrome, and 2 in TTD (Hoeijmakers, 1994). The finding of additional patients combining features of xeroderma pigmentosum and Cockayne syndrome within complementation groups XPB (610651), XPD (278730), and XPG indicated that there is considerable clinical heterogeneity with phenotypic overlap within the subsets of complementation groups. INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth (in some patients) HEAD & NECK Head \- Microcephaly (in some patients) Eyes \- Cataracts (in some patients) \- Microphthalmia (in some patients) SKELETAL Feet \- Pes cavus (in some patients) SKIN, NAILS, & HAIR Skin \- Photosensitivity \- Abnormal sensitivity to UVB wavelengths by radiation monochromator skin testing NEUROLOGIC Central Nervous System \- Developmental deterioration (in some patients) \- Tremor (in some patients) \- Ataxia (in some patients) \- Spasticity (in some patients) LABORATORY ABNORMALITIES \- Defective DNA repair after ultraviolet radiation damage MISCELLANEOUS \- Variable severity \- Some patients have no neurologic abnormalities MOLECULAR BASIS \- Caused by mutation in the excision-repair, complementing defective, in Chinese hamster, number 5 gene (ERCC5, 133530.0001 ) ▲ 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	XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP G	c0009207	923	omim	https://www.omim.org/entry/278780	2019-09-22T16:21:04	{"doid": ["0110849"], "mesh": ["D003057"], "omim": ["278780"], "orphanet": ["191", "1466", "220295", "910"], "synonyms": ["Alternative titles", "XP, GROUP G", "XERODERMA PIGMENTOSUM VII"], "genereviews": ["NBK1397"]}
Facial femoral syndrome Other namesFemoral Hyperplasia-Unusual Facies syndrome Facial femoral syndrome is a rare congenital disorder.[1] It is also known as femoral dysgenesis, bilateral femoral dysgenesis, bilateral-Robin anomaly and femoral hypoplasia-unusual facies syndrome. The main features of this disorder are underdeveloped thigh bones (femurs) and unusual facial features. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] * Facial[citation needed] * Lips - Cleft palate and/or thin lips. Prominent philtrum * Jaw - Small and/or retracted jaw (micrognathia/retrognathia) * Ears - Small or virtually absent ears (microtia/anotia) * Eyes - Upwardly slanting eyelids * Skeleton[citation needed] * Short limbs (micromelia) * Femurs - absent/abnormal * Fused bones of the spine (sacrum and coccyx) * Deformation of the foot that may be turned outward or inward ((talipes)-varus/valgus) * Extra fingers or toes (polydactyly) * Abnormal vertebral size or shape * Short stature (dwarfism) * Others[citation needed] * Genitourinary abnormalities * Underdeveloped lungs * Patent ductus arteriosus Of note intellectual development typically is normal. ## Cause[edit] The cause of this condition is not known. A genetic basis is suspected. More than one case have been reported in three families.[citation needed] ## Diagnosis[edit] The diagnosis is based on the combination of unusual facial features and the dysplastic or absent femurs.[citation needed] Diagnosis may be made antenatally.[2] ## Treatment[edit] There is no known specific treatment for this condition. Management is supportive.[citation needed] ## Epidemiology[edit] This is a rare disorder with 92 cases reported up to 2017.[1] ## History[edit] This condition was first described in 1975.[3] ## References[edit] 1. ^ a b Luisin M, Chevreau J, Klein C, Naepels P, Demeer B, Mathieu-Dramard M, Jedraszak G, Gondry-Jouet C, Gondry J, Dieux-Coeslier A, Morin G (2017) Prenatal diagnosis of femoral facial syndrome: Three case reports and literature review. Am J Med Genet A 2. ^ Castro S, Peraza E, Zapata M (2014) Prenatal diagnosis of femoral-facial syndrome: case report. J Clin Ultrasound 42(1):49-52 3. ^ Daentl DL, Smith DW, Scott CI, Hall BD, Gooding CA (1975) Femoral hypoplasia--unusual facies syndrome. J. Pediat. 86: 107-111 ## External links[edit] Classification D * OMIM: 134780 * MeSH: C537916 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Facial femoral syndrome	c0265263	924	wikipedia	https://en.wikipedia.org/wiki/Facial_femoral_syndrome	2021-01-18T19:10:06	{"gard": ["61"], "mesh": ["C537916"], "umls": ["C0265263"], "orphanet": ["1988"], "wikidata": ["Q18020133"]}
Barth syndrome is a rare condition characterized by an enlarged and weakened heart (dilated cardiomyopathy), weakness in muscles used for movement (skeletal myopathy), recurrent infections due to small numbers of white blood cells (neutropenia), and short stature. Barth syndrome occurs almost exclusively in males. In males with Barth syndrome, dilated cardiomyopathy is often present at birth or develops within the first months of life. Over time, the heart muscle becomes increasingly weakened and is less able to pump blood. Individuals with Barth syndrome may have elastic fibers in place of muscle fibers in some areas of the heart muscle, which contributes to the cardiomyopathy. This condition is called endocardial fibroelastosis; it results in thickening of the muscle and impairs its ability to pump blood. In people with Barth syndrome, the heart problems can lead to heart failure. In rare cases, the cardiomyopathy gets better over time and affected individuals eventually have no symptoms of heart disease. In Barth syndrome, skeletal myopathy, particularly of the muscles closest to the center of the body (proximal muscles), is usually noticeable from birth and causes low muscle tone (hypotonia). The muscle weakness often causes delay of motor skills such as crawling and walking. Additionally, affected individuals tend to experience extreme tiredness (fatigue) during strenuous physical activity. Most males with Barth syndrome have neutropenia. The levels of white blood cells can be consistently low (persistent), can vary from normal to low (intermittent), or can cycle between regular episodes of normal and low (cyclical). Neutropenia makes it more difficult for the body to fight off foreign invaders such as bacteria and viruses, so affected individuals have an increased risk of recurrent infections. Newborns with Barth syndrome are often smaller than normal, and their growth continues to be slow throughout life. Some boys with this condition experience a growth spurt in puberty and are of average height as adults, but many men with Barth syndrome continue to have short stature in adulthood. Males with Barth syndrome often have distinctive facial features including prominent cheeks. Affected individuals typically have normal intelligence but often have difficulty performing tasks involving math or visual-spatial skills such as puzzles. Males with Barth syndrome have increased levels of a substance called 3-methylglutaconic acid in their blood and urine. The amount of the acid does not appear to influence the signs and symptoms of the condition. Barth syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). Even though most features of Barth syndrome are present at birth or in infancy, affected individuals may not experience health problems until later in life. The age at which individuals with Barth syndrome display symptoms or are diagnosed varies greatly. The severity of signs and symptoms among affected individuals is also highly variable. Males with Barth syndrome have a reduced life expectancy. Many affected children die of heart failure or infection in infancy or early childhood, but those who live into adulthood can survive into their late forties. ## Frequency Barth syndrome is estimated to affect 1 in 300,000 to 400,000 individuals worldwide. More than 150 cases have been described in the scientific literature. ## Causes Mutations in the TAZ gene cause Barth syndrome. The TAZ gene provides instructions for making a protein called tafazzin. Tafazzin is located in structures called mitochondria, which are the energy-producing centers of cells. Tafazzin is involved in altering a fat (lipid) called cardiolipin, which plays critical roles in the mitochondrial inner membrane. Once altered by tafazzin, cardiolipin is key in maintaining mitochondrial shape, energy production, and protein transport within cells. TAZ gene mutations result in the production of tafazzin proteins with little or no function. As a result, tafazzin cannot alter cardiolipin. A lack of functional cardiolipin impairs normal mitochondrial shape and functions. Tissues with high energy demands, such as the heart and skeletal muscles, are most susceptible to cell death due to reduced energy production in mitochondria. Additionally, abnormally shaped mitochondria are found in affected white blood cells, which could affect their ability to grow (proliferate) and mature (differentiate), leading to neutropenia. Dysfunctional mitochondria likely lead to other signs and symptoms of Barth syndrome. ### Learn more about the gene associated with Barth syndrome * TAZ ## Inheritance Pattern This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Barth syndrome	c0574083	925	medlineplus	https://medlineplus.gov/genetics/condition/barth-syndrome/	2021-01-27T08:25:48	{"gard": ["5890"], "mesh": ["D056889"], "omim": ["302060"], "synonyms": []}
Primary unilateral adrenal hyperplasia (PUAH) is a surgically-correctable form of primary (hyper) aldosteronism (PA; see this term) characterized by renin suppression, unilateral aldosterone hypersecretion, and moderate to severe hypertension secondary to hyperplasia of the adrenal gland. ## Epidemiology The prevalence of primary unilateral adrenal hyperplasia is unknown. ## Clinical description PUAH may be associated with hypokalemia, which, when present, may be symptomatic with muscular weakness, cramps, paresthesia or palpitations with or without atrial fibrillation. ## Etiology The etiology of PUAH is not known. Unilateral adrenalectomy abolishes aldosterone hypersecretion and hypokalemia in most patients with PUAH. ## Diagnostic methods Diagnostic methods include peripheral aldosterone and renin determinations, adrenal venous sampling which makes it possible to differentiate unilateral from bilateral aldosterone hypersecretion, and CT scan showing normal adrenals or unilateral adrenal hyperplasia. ## Management and treatment Blood pressure is significantly improved in the majority of the patients, but hypertension is cured in only 50% of cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Primary unilateral adrenal hyperplasia	c4274967	926	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231580	2021-01-23T16:56:19	{"icd-10": ["E26.0"], "synonyms": ["PUAH"]}
Palindromic rheumatism SpecialtyRheumatology Palindromic rheumatism (PR) is a syndrome characterised by recurrent, self-resolving inflammatory attacks in and around the joints, consists of arthritis or periarticular soft tissue inflammation.[1] The course is often acute onset, with sudden and rapidly developing attacks or flares. There is pain, redness, swelling, and disability of one or multiple joints. The interval between recurrent palindromic attacks and the length of an attack is extremely variable from few hours to days. Attacks may become more frequent with time but there is no joint damage after attacks. It is thought to be an autoimmune disease, possibly an abortive form of rheumatoid arthritis. ## Contents * 1 Presentation * 2 Causes * 3 Diagnosis * 4 Management * 5 Etymology * 6 References * 7 External links ## Presentation[edit] The exact prevalence of palindromic rheumatism in general population is unknown, and this condition is often considered a rare disease by nonrheumatologists.[2] However, recent Canadian study showed that the incidence of PR in a cohort of incident arthritis was one case of PR for every 1.8 cases of rheumatoid arthritis (RA).[3] The incidence of PR is less than that of RA but is not as rare as that was thought to be. Palindromic rheumatism is a syndrome presented with inflammatory para-arthritis (soft tissue rheumatism) and inflammatory arthritis both of which cause sudden inflammation in one or several joints or soft tissue around joints. The flares usually present with mono- or oligo-articular involvement,[4] which have onset over hours and last a few hours to a few days, and then go away completely. However episodes of recurrence form a pattern, with symptom-free periods between attacks lasting for weeks to months. The most commonly involved joints were knees, metacarpophalangeals and proximal interphalangeals.[4] Constitutionally, there may or may not be a fever, and swelling of the joints. The soft tissues are involved with swelling of the periarticular tissues, especially heel pads and finger pads. Nodules may be found in the subcutaneous tissues.[1] The frequency of attacks may be variable over the course but there is no joint damage after attacks.[1] It typically affects people between the ages of 20 and 50. One study showed an average age of onset of 49.[3] A population cohort study in Taiwan suggested that patients with PR had an increased risk of developing rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, and polymyositis.[5] ## Causes[edit] Palindromic rheumatism is a disease of unknown cause. It has been suggested that it is an abortive form of rheumatoid arthritis (RA), since anti-cyclic citrullinated peptide antibodies (anti-CCP) and antikeratin antibodies (AKA) are present in a high proportion of patients, as is the case in rheumatoid arthritis.[6] Unlike RA and some other forms of arthritis, palindromic rheumatism affects men and women equally.[3] Palindromic rheumatism is frequently the presentation for Whipple disease which is caused by the infectious agent Tropheryma whipplei (formerly T. whippelii).[7] ## Diagnosis[edit] Due to the symptoms of palindromic arthritis and the nature of the attacks, diagnosis can be difficult or take a long time. The symptoms can be similar to many other forms of arthritis or other autoimmune diseases. It is often a case of eliminating the other conditions before getting the correct diagnosis due to there being no specific test for PR diagnosis. No single test can confirm a diagnosis. A doctor may make a diagnosis based on medical history and signs and symptoms. Palindromic rheumatism must be distinguished from acute gouty arthritis and an atypical, acute onset of rheumatoid arthritis (RA). Without specific tests (such as analysis of joint fluid), it may be difficult to distinguish palindromic rheumatism from other episodic joint problems. It is important to note that a person may experience more than one autoimmune disorder at the same time, as overlap syndrome. Laboratory findings are usually normal. Blood tests may show an elevation of the ESR and CRP, but are otherwise unremarkable. Rheumatoid factor may be present especially in the group that is likely to develop rheumatoid arthritis. Proposed classification by Guerne and Weismann in 1992:[8] * A 6-month history of brief sudden-onset and recurrent episodes of monoarthritis or rarely polyarthritis or of soft tissue inflammation. * Direct observation of one attack by a physician. * Three or more joints involved in different attacks. * No radiologic evidence of bone or joint erosion. * Exclusion of other arthritides, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or gout ## Management[edit] Treatment may include nonsteroidal anti-inflammatory drugs (NSAIDs) for acute attacks. Antimalarials, such as hydroxychloroquine, have been helpful in reducing the frequency and duration of attacks and may reduce the likelihood that palindromic rheumatism will progress to rheumatoid arthritis.[9] ## Etymology[edit] Palindromic rheumatism derives its name from the Greek palindromos meaning to take the same road once again (palin, again + dromos, pathway) emphasizing how the illness begins and ends in a similar way. The term "palindrome" means a word that is spelled the same forward as backward (examples include "kayak" and "mum"). ## References[edit] 1. ^ a b c Mankia, Kulveer; Emery, Paul (February 2017). "What can palindromic rheumatism tell us?". Best Practice & Research. Clinical Rheumatology. 31 (1): 90–98. doi:10.1016/j.berh.2017.09.014. ISSN 1532-1770. PMID 29221602. 2. ^ Cabrera-Villalba, Sonia; Sanmartí, Raimon (October 2013). "Palindromic rheumatism: a reappraisal". International Journal of Clinical Rheumatology. 8 (5): 569–577. doi:10.2217/ijr.13.51. ISSN 1758-4272. S2CID 29844854. 3. ^ a b c Powell, Anne; Davis, Paul; Jones, Niall; Russell, Anthony S. (June 2008). "Palindromic rheumatism is a common disease: comparison of new-onset palindromic rheumatism compared to new-onset rheumatoid arthritis in a 2-year cohort of patients". The Journal of Rheumatology. 35 (6): 992–994. ISSN 0315-162X. PMID 18412310. 4. ^ a b Khabbazi, Alireza; Hajialiloo, Mehrzad; Kolahi, Sousan; Soroosh, Mohsen; Esalatmanesh, Kamal; Sharif, Sakinehkhatoon (August 2012). "A multicenter study of clinical and laboratory findings of palindromic rheumatism in Iran". International Journal of Rheumatic Diseases. 15 (4): 427–430. doi:10.1111/j.1756-185X.2012.01739.x. ISSN 1756-185X. PMID 22898224. S2CID 22199026. 5. ^ Chen, Hsin-Hua; Chao, Wen-Cheng; Liao, Tsai-Ling; Lin, Ching-Heng; Chen, Der-Yuan (2018). "Risk of autoimmune rheumatic diseases in patients with palindromic rheumatism: A nationwide, population-based, cohort study". PLOS ONE. 13 (7): e0201340. Bibcode:2018PLoSO..1301340C. doi:10.1371/journal.pone.0201340. ISSN 1932-6203. PMC 6062130. PMID 30048527. 6. ^ Salvador G; Gomez A; Vinas O; et al. (August 2003). "Prevalence and clinical significance of anti-cyclic citrullinated peptide and antikeratin antibodies in palindromic rheumatism. An abortive form of rheumatoid arthritis?". Rheumatology (Oxford). 42 (8): 972–5. doi:10.1093/rheumatology/keg268. PMID 12730510. 7. ^ Krol, Charlotte G.; de Meijer, Paul H. E. M. (August 2013). "Palindromic rheumatism: consider Whipple's disease". International Journal of Rheumatic Diseases. 16 (4): 475–476. doi:10.1111/1756-185X.12084. ISSN 1756-185X. PMID 23992271. S2CID 26363391. 8. ^ Guerne, P. A.; Weisman, M. H. (October 1992). "Palindromic rheumatism: part of or apart from the spectrum of rheumatoid arthritis". The American Journal of Medicine. 93 (4): 451–460. doi:10.1016/0002-9343(92)90177-d. ISSN 0002-9343. PMID 1341421. 9. ^ Arthritis Foundation [1] ## External links[edit] Classification D * ICD-10: M12.3 * ICD-9-CM: 719.3 * MeSH: C538103 C538103, C538103 * DiseasesDB: 9508 * v * t * e Diseases of joints General * Arthritis * Monoarthritis * Oligoarthritis * Polyarthritis Symptoms * Joint pain * Joint stiffness Inflammatory Infectious * Septic arthritis * Tuberculosis arthritis Crystal * Chondrocalcinosis * CPPD (Psudogout) * Gout Seronegative * Reactive arthritis * Psoriatic arthritis * Ankylosing spondylitis Other * Juvenile idiopathic arthritis * Rheumatoid arthritis * Felty's syndrome * Palindromic rheumatism * Adult-onset Still's disease Noninflammatory * Hemarthrosis * Osteoarthritis * Heberden's node * Bouchard's nodes * Osteophyte [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Palindromic rheumatism	c0085574	927	wikipedia	https://en.wikipedia.org/wiki/Palindromic_rheumatism	2021-01-18T18:57:45	{"gard": ["7304"], "mesh": ["C538103"], "umls": ["C0085574", "C0158178"], "wikidata": ["Q3495854"]}
A rare variant of cutaneous lichen planus characterized by both annular and atrophic LP features in the same lesion. ## Epidemiology Fewer than ten cases have been reported in the literature. ## Clinical description Small violaceous papules develop on the trunk and extremities and are characterized by an atrophic centre and a raised hyperpigmented border. Patients are generally middle-aged and have no past history of cutaneous lesions. Histopathologically, the peripheral border has the typical features of lichen planus, while the centre of the lesion shows loss of rete ridges. There is loss of elastic fibres within the papillary dermis, both centrally and peripherally. ## Etiology Etiology is unknown. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Annular atrophic lichen planus	c4304037	928	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254411	2021-01-23T17:32:55	{"gard": ["12676"], "icd-10": ["L43.8"], "synonyms": ["Annular atrophic LP"]}
Cholesteryl ester storage disease is is a type of lysosomal acid lipase deficiency. It is an inherited disease that causes a buildup of fats (lipids) in the tissues and organs of the body and calcium deposits in the adrenal glands. The liver is most severely affected in most cases. Some people with cholesteryl ester storage disease may develop liver cirrhosis that progresses to liver failure. People with cholesteryl ester storage disease may also build up fatty deposits on the artery walls (atherosclerosis). This buildup can narrow the arteries and increase the risk for heart attack or stroke. Cholesteryl ester storage disease is caused by mutations in the LIPA gene. It is inherited in an autosomal recessive manner. Enzyme replacement therapy is available for the treatment of lysosomal acid lipase deficiencies, including cholesteryl ester storage disease, in the United States, the European Union, and Japan. A low cholesterol diet may also be helpful. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Cholesteryl ester storage disease	c0008384	929	gard	https://rarediseases.info.nih.gov/diseases/12099/cholesteryl-ester-storage-disease	2021-01-18T18:01:28	{"mesh": ["D015217"], "omim": ["278000"], "orphanet": ["75234"], "synonyms": ["CESD", "Cholesterol ester hydrolase deficiency", "Cholesterol ester storage disease"]}
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: "Otofacial syndrome" – news · newspapers · books · scholar · JSTOR (July 2018) Otofacial syndrome SpecialtyOral and maxillofacial surgeon Otofacial syndrome is an extraordinarily rare congenital deformity in which a person is born without a mandible, and, consequently, without a chin. In nearly all cases, the child does not survive because it is unable to breathe and eat properly. Even with reconstructive surgery, the tongue is extremely underdeveloped, making unaided breathing and swallowing impossible. ## Cause[edit] This section is empty. You can help by adding to it. (September 2017) ## Treatment[edit] The first challenge to survival is assisted breathing and tubal feeding. This is a lifelong affair, generally requiring the patient to spend nearly all of the time under direct hospital care. American surgeons successfully used bone from the hip of an Irish teenager named Alan Doherty to rebuild a jaw and chin. Surgeons began the procedures in June 2007 and completed the final of seven surgeries on 25 August 2008. Doherty is now able to smile, but is still unable to breathe, eat, or speak on his own.[1][2] ## References[edit] 1. ^ "Surgeons give teenager a new chin". BBC News. 2008-12-19. Retrieved 2008-12-19. 2. ^ "A New Face for Teenager Born Without Jaw". Fox News. 2008-08-27. Retrieved 2008-12-19. * v * t * e Congenital malformations and deformations of face and neck Face * jaw: Otocephaly * mouth: Macrostomia * Microstomia * lip: Macrocheilia * Microcheilia * chin: Microgenia * multiple/other: Hallermann–Streiff syndrome * Branchial cleft cyst Neck * Webbed neck Ungrouped * Preauricular sinus and cyst This article about a congenital malformation is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Otofacial syndrome	None	930	wikipedia	https://en.wikipedia.org/wiki/Otofacial_syndrome	2021-01-18T18:37:05	{"wikidata": ["Q7108929"]}
Hornova and Dlurosova (1968) described a brother and sister, aged 7 and 12 years, with presumed primary amyloidosis of the gingiva and conjunctiva and mental retardation. At 7 months of age in the boy and 5 months in the girl, the eyelids became swollen and leukoma with blindness ensued. The nature of the disorder is unclear. Eye \- Eyelids swollen \- Leukoma \- Blindness Mouth \- Primary amyloidosis of gingiva Neuro \- Mental retardation 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	AMYLOIDOSIS OF GINGIVA AND CONJUNCTIVA, WITH MENTAL RETARDATION	c1859815	931	omim	https://www.omim.org/entry/204850	2019-09-22T16:31:07	{"mesh": ["C565958"], "omim": ["204850"]}
Genetic mutation affecting cats A Munchkin with legs extended A dwarf cat is any domestic cat which has the condition of dwarfism due to a genetic mutation. Unlike undersized cats of normal proportions, dwarf cats display symptoms of osteochondrodysplasia—genetic disorders of bone and cartilage, typically manifested as noticeably short legs.[1] Since the mid-twentieth century, cat breeds with embedded dwarfism have been developed for sale. The ethics of their selective breeding is hotly debated, and many countries prohibit it as cruelty to animals. ## Contents * 1 Characteristics * 2 Breeds * 3 Recognition and controversy * 4 See also * 5 References * 6 External links ## Characteristics[edit] The term "dwarf cat" is incorrectly applied to cats such as Toy and Teacup Persians which, though small, are breeds of normal feline proportions.[2] True dwarf cats are chondrodysplastic and have much shorter and thicker legs. Typically, half of a dwarf cat litter are non-dwarves born with normal leg length. ## Breeds[edit] The Munchkin is the original breed of dwarf cats. The International Cat Association (TICA) gave recognition to the Munchkin as a breed in 1994,[3] along with a Persian–Munchkin hybrid, the Minuet.[4] Other proposed breeds like the Skookum and Bambino have not been given recognition, although a Sphynx–Munchkin hybrid, the Minskin, is under study.[5] Four other breeds include the Lambkin and the Kinkalow, the Genetta and the Scottish Kilt ## Recognition and controversy[edit] Unlike TICA, most cat registries and pet associations do not recognize any dwarf cat as a legitimate breed. The animals are excluded from most major pet shows and contests. Largely an American phenomenon, they are not widely accepted outside of the United States. In its registration rules, the Fédération Internationale Féline prohibits breeds based on dwarfism, and specifically mentions the Munchkin as an example of unacceptable manipulation of "genetic disease".[6] They are effectively banned under the European Convention for the Protection of Pet Animals and have been strongly condemned in the British magazine Cat World. In the US itself, the ASPCA admonishes its supporters to "stay vigilant" against the small but spreading market.[7] ## See also[edit] * Grumpy Cat * Lil Bub ## References[edit] 1. ^ Khuly, P. "Why I Can't Stand the Hype Over Dwarf Cats". vetstreet.com. Vetstreet. Retrieved 3 March 2014. 2. ^ "DWARF, MIDGET AND MINIATURE CATS (TEACUP CATS)". Retrieved 30 October 2014. 3. ^ "Munchkin breed introduction". Tica.org. TICA, Inc. 2013. Archived from the original on 13 December 2013. Retrieved 12 December 2013. 4. ^ "Napoleon breed introduction". Tica.org. TICA, Inc. 2013. Archived from the original on 13 December 2013. Retrieved 12 December 2013. 5. ^ "Minskin breed introduction". Tica.org. TICA, Inc. 2013. Archived from the original on 13 December 2013. Retrieved 12 December 2013. 6. ^ Breeding and Registration Rules: 2.7.3 Genetic Diseases. Fédération Internationale Feline 7. ^ "Cat History". Aspca.org. ASPCA. 2013. Retrieved 13 December 2013. ## External links[edit] * Short-Legged Cat Breeds * v * t * e Domestic cats Felinology * Anatomy * Genetics * Dwarf cat * Kitten * Odd-eyed cat * Squitten Coat genetics Bicolor cat Black cat Calico cat Tabby cat Tortoiseshell cat Health * Aging * Declawing * Diet * dental health * senior * Neutering * Spaying * Vaccination Behavior * Body language * Catfight * Catnip * valerian * Communication * Meow * Purr * Kneading * Intelligence * Play and toys * Righting reflex * Senses Human–cat interaction * Ailurophobia * Animal-assisted therapy * Bodega cat * Cat cafés * Cat massage * Cat meat * Cat-scratch disease * Cat show * Cats in ancient Egypt * Cultural depictions * Internet * Farm cat * Feral cat * Cats and Islam * Lolcat * National Cat Day * Puppy cat * Ship's cat * Zoonosis Registries * American Cat Fanciers Association * Associazione Nazionale Felina Italiana * Canadian Cat Association * Cat Aficionado Association * Cat Fanciers' Association * Fédération Internationale Féline * Governing Council of the Cat Fancy * Southern Africa Cat Council * The International Cat Association * World Cat Congress * World Cat Federation Breeds (full list) (experimental) Fully domestic Abyssinian American Curl American Shorthair Balinese Brazilian Shorthair British Shorthair Birman Bombay Burmese Burmilla California Spangled Chartreux Chinese Li Hua Colorpoint Shorthair Cornish Rex Cymric Devon Rex Donskoy Egyptian Mau European Shorthair Exotic Shorthair German Rex Himalayan Japanese Bobtail Javanese Khao Manee Korat Kurilian Bobtail Lykoi Maine Coon Manx Munchkin Norwegian Forest Ocicat Ojos Azules Oriental Shorthair Persian Peterbald Pixie-bob Raas Ragdoll Ragamuffin Russian Blue Scottish Fold Selkirk Rex Siamese Siberian Singapura Snowshoe Somali Sphynx Thai Traditional Persian Tonkinese Toyger Turkish Angora Turkish Van Hybrid Bengal Chausie Highlander Savannah Serengeti Landraces * Aegean * Cyprus * Domestic long-haired * Domestic short-haired * Kellas * Sokoke * Van Diseases and disorders * Acne * Asthma * Calicivirus * Congenital sensorineural deafness * Feline corneal sequestrum * Flea * Heartworm * Hepatic lipidosis * Hypertrophic cardiomyopathy * Immunodeficiency virus * Infectious peritonitis * Leukemia virus * Lower urinary tract disease * Panleukopenia * Polydactyly * Rabies * Ringworm * Roundworm * Skin disorders * Tick * Toxoplasmosis * Viral rhinotracheitis * Book * 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	Dwarf cat	None	932	wikipedia	https://en.wikipedia.org/wiki/Dwarf_cat	2021-01-18T18:52:47	{"wikidata": ["Q5317900"]}
A rare breast malformation disorder characterized by unilateral or bilateral, symmetrical or asymmetrical, uncontrolled, rapid and massive enlargement of the breast(s) in peripubertal females, occurring in various members of a family. Additional associated manifestations may include skin hyperemia, dilated subcutaneous veins, skin necrosis, kyphosis, lordosis and anonychia. Growth and development are otherwise 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	Familial juvenile hypertrophy of the breast	c0405471	933	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=180176	2021-01-23T18:48:49	{"mesh": ["C536821"], "omim": ["113670"], "icd-10": ["N62"], "synonyms": ["Familial juvenile gigantomastia", "Virginal breast hypertrophy"]}
A number sign (#) is used with this entry because otopalatodigital syndrome type I (OPD1) is caused by gain-of-function mutations in the gene encoding filamin A (FLNA; 300017) on chromosome Xq28. Description Otopalatodigital syndrome-1 is 1 of 4 otopalatodigital syndromes caused by mutations in the FLNA gene. The disorders, which include frontometaphyseal dysplasia (FMD1; 305620), otopalatodigital syndrome-2 (OPD2; 304120), and Melnick-Needles syndrome (MNS; 309350), constitute a phenotypic spectrum. At the mild end of the spectrum, males with OPD1 have cleft palate and mild skeletal anomalies with conductive deafness caused by ossicular anomalies. FMD is characterized by a generalized skeletal dysplasia, deafness and urogenital defects. Males with OPD2 have disabling skeletal anomalies in addition to variable malformations in the hindbrain, heart, intestines, and kidneys that frequently lead to perinatal death. The most severe phenotype, MNS, is characterized by a skeletal dysplasia in the heterozygote. Affected males exhibit severe malformations similar to those observed in individuals with OPD2, resulting in prenatal lethality or death in the first few months of life (review by Robertson, 2005). Verloes et al. (2000) suggested that these disorders constitute a single entity, which they termed 'frontootopalatodigital osteodysplasia.' Clinical Features Dudding et al. (1967) described 3 male sibs with conduction deafness, cleft palate, characteristic facies, and a generalized bone dysplasia. A broad nasal root gives the patient a pugilistic appearance. Wide-spacing of the toes creates a resemblance to the foot of a tree frog. X-linkage and autosomal inheritance could not be distinguished. Roentgenologic features were reviewed in the same patients by Langer (1967). (The male patient reported by Taybi (1962) may have had this condition.) Conductive hearing loss, somewhat broad thumbs and great toes, short fingernails, fifth finger clinodactyly, dislocation of the head of the radius, pectus excavatum, and mild dwarfism were also features. A secondary ossification center at the base of the second metacarpal and metatarsal is characteristic. Turner (1970) observed affected half brothers who had different fathers, thus supporting X-linked inheritance. Weinstein and Cohen (1966) suggested that an X-linked form of cleft palate exists. Affected males and carrier females showed hypertelorism and median frontal prominence. Four males in 3 sibships connected through 5 presumably heterozygous females were affected. Gorlin (1967) suggested that the condition in this family was the OPD syndrome. The x-ray changes in the hands and feet were consistent (Gorlin, 1971). Gall et al. (1972) and Poznanski et al. (1974) demonstrated heterozygote changes in radiographs of the hands and feet. Pazzaglia and Beluffi (1986) described a family with affected persons in 4 generations. Severe scoliosis was present in 1 patient, a feature that apparently had not previously been reported in the OPD syndrome. Also in this family, there was no deafness or cleft palate. On the other hand, many of the skeletal findings were thought to be characteristic. The pedigree was consistent with X-linked inheritance with variable and intermediate expression in the female. Rosenbaum et al. (1986) described a family with affected mother, son, and daughter; in only the male was the expression complete. The mother was related to her husband as a first cousin. Another couple, both of whom were related to this man and his wife as first cousins, had 3 children thought to have Larsen syndrome (245600), manifest by congenital dislocation of the hips and knees associated with flattened facies. Le Marec et al. (1988) described a family with affected persons in 5 generations. They suggested that the disorder called OPD II (304120) by Fitch et al. (1983) might be allelic. Kozlowski (1993) pointed out that long second metacarpal and fifth metatarsal are typical in OPD I. Extracarpal bones occur as in Larsen syndrome, particularly typical changes at the elbow and especially a deepened fossa at the proximal ulna. Kozlowski (1993) emphasized that OPD I, a relatively common bone dysplasia, can have very subtle clinical and radiologic expression that may go unnoticed until the disorder is recognized in a more severely affected member of the family. OPD II, on the other hand, is a severe disorder. Gorlin (1993) indicated that mental retardation is not a feature of OPD I. Verloes et al. (2000) reported a mild case of OPD2, a severe case of OPD2 with anomalies of the central nervous system and some manifestations of frontometaphyseal dysplasia, a lethal case of OPD2 with similarities to Melnick-Needles syndrome, and 3 unrelated boys born to mothers with MNS (1 with a severe form, 1 with a lethal form, and an aborted fetus). They reviewed the features in these disorders and in OPD1 and suggested that these disorders constitute a single entity, which they called 'fronto-otopalatodigital osteodysplasia.' Verloes et al. (2000) also discussed the relationship to similar syndromes, such as Yunis-Varon syndrome (216340), type III atelosteogenesis (108721), and boomerang dysplasia (112310). Morava et al. (2003) described 2 families in which both males and females showed the facial and skeletal characteristics of FMD in association with severe progressive scoliosis. Some also had hearing loss and urogenital anomalies, leading Morava et al. (2003) to suggest that these were examples of frontootopalatodigital osteodysplasia as described by Verloes et al. (2000). Mapping In studies of a 3-generation family with OPD1, Hoo et al. (1991) and Hoar et al. (1992) found a suggestion of linkage to DNA markers on the distal long arm of the X chromosome. Studies of another family by Biancalana et al. (1991) excluded linkage to the Xq26 region and provided further support for mapping of the OPD1 gene to Xq28. A combined lod score of 3.19 was reported. Robertson et al. (2001) found linkage of the more severe, frequently lethal phenotype, termed OPD2, to the same region of distal Xq28 to which the OPD1 locus had been mapped. This provided support for allelism between OPD1 and OPD2. Furthermore, it was possible to reduce the size of the disease interval to 1.8 to 2.1 Mb. They demonstrated that female carriers of OPD2 exhibited skewed inactivation that segregated with the high-risk haplotype and may be inversely related to the severity with which they manifest features of the disorder. Molecular Genetics Robertson et al. (2003) demonstrated that OPD1 is caused by gain-of-function mutations in the gene encoding filamin A (FLNA; 300017). They also demonstrated FLNA mutations in OPD2. In a 26-year-old Mexican female with OPD1, Hidalgo-Bravo et al. (2005) identified a heterozygous missense mutation in the FLNA gene (300017.0020). The patient had prominent features of OPD1, including cleft palate; an extremely skewed pattern of X inactivation toward the maternal allele was noted. Robertson et al. (2006) identified a mutation in the FLNA gene (300017.0009) in 2 brothers with OPD1. The mutation was not identified in leukocytes of the mother, suggesting germline mosaicism. The authors emphasized the importance of the finding for genetic counseling. In 6 females with cranial hyperostosis and various skeletal abnormalities from a 4-generation pedigree, Stefanova et al. (2005) identified heterozygosity for a deletion in the FLNA gene (300017.0016). The phenotype of affected females resembled FMD with some overlap to OPD1 and OPD2, but no signs specific for MNS. However, males had severe extraskeletal malformations and died early, thus constituting an overlap with OPD2 and MNS. Stefanova et al. (2005) concluded that the disorder in this family is best described as an intermediate OPD-spectrum phenotype that bridges the FMD and OPD2 phenotypes. Zenker et al. (2006) described a de novo mutation in the FLNA gene (300017.0022) in a girl with manifestations of FMD and OPD1. INHERITANCE \- X-linked dominant GROWTH Height \- Short stature (<10th percentile for age) HEAD & NECK Head \- Prominent occiput \- Prominent supraorbital ridges Face \- Frontal bossing \- Flat face Ears \- Conductive hearing loss Eyes \- Hypertelorism \- Downslanting palpebral fissures Nose \- Small nose \- Broad nasal root Mouth \- Microstomia \- Cleft palate Teeth \- Selective tooth agenesis \- Impacted teeth CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum ABDOMEN External Features \- Omphalocele SKELETAL Skull \- Absent frontal sinuses \- Absent sphenoid sinuses \- Thick frontal bone \- Thick skull base \- Delayed closure of anterior fontanel \- Steep clivus \- Dense middle-ear ossicles Spine \- Scoliosis \- Small pedicles Pelvis \- Small iliac crests \- Hip dislocation \- Flat acetabulum \- Coxa valga Limbs \- Limited elbow extension \- Limited knee flexion \- Radial head dislocation \- Mild, lateral femoral bowing Hands \- Short, broad distal phalanges, especially thumbs \- Short square nails \- Short third, fourth, fifth metacarpals \- Supernumerary carpal bones \- Fusion of hamate and capitate Feet \- Short, broad halluces \- Toe syndactyly \- Anomalous fifth metatarsal \- Extra calcaneal ossification center \- Gap between first and second toes \- 'Tree-frog' feet SKIN, NAILS, & HAIR Nails \- Nail dystrophy \- Short square fingernails NEUROLOGIC Central Nervous System \- Mild mental retardation MISCELLANEOUS \- Intermediate expression in females \- Complete manifestation in males \- Otopalatodigital syndrome type II (OPD2, 304120 ) is an allelic disorder with a more severe, frequently lethal phenotype \- Frontometaphyseal dysplasia (FMD, 305620 ) is an allelic disorder \- Melnick-Needles syndrome (MNS, 309350 ) is an allelic disorder \- Periventricular heterotopia ( 300049 ) is an allelic disorder MOLECULAR BASIS \- Caused by mutation in the filamin A gene ( 300017.0009 ) ▲ 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	OTOPALATODIGITAL SYNDROME, TYPE I	c0265251	934	omim	https://www.omim.org/entry/311300	2019-09-22T16:17:32	{"mesh": ["C536065"], "omim": ["311300"], "orphanet": ["90650"], "synonyms": ["Alternative titles", "OPD I SYNDROME", "OPD SYNDROME 1"], "genereviews": ["NBK1393"]}
Brachydactyly-syndactyly, Zhao type is a recently described syndrome associating a brachydactyly type A4 (short middle phalanges of the 2nd and 5th fingers and absence of middle phalanges of the 2nd to 5th toes) and a syndactyly of the 2nd and 3rd toes. Metacarpals and metatarsals anomalies are common. ## Epidemiology This syndrome has been described in two families. ## Etiology It is caused by HOXD13 mutations in 2q31-q32 ## Genetic counseling Brachydactyly-syndactyly, Zhao type is inherited 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	Brachydactyly-syndactyly, Zhao type	c1853137	935	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93409	2021-01-23T18:40:09	{"mesh": ["C565193"], "omim": ["610713"], "icd-10": ["Q73.8"]}
For the monotypic bird genus, see Bornean bristlehead. Pityriasis SpecialtyDermatology Pityriasis commonly refers to flaking (or scaling)[1] of the skin. The word comes from the Greek πίτυρον "bran". ## Contents * 1 Classification * 2 See also * 3 References * 4 External links ## Classification[edit] Types include: * Pityriasis alba * Pityriasis lichenoides chronica * Pityriasis lichenoides et varioliformis acuta * Pityriasis rosea * Pityriasis circinata * Pityriasis rubra pilaris * Pityriasis versicolor * Dandruff, historically called Pityriasis capitis * Pityriasis amiantacea ## See also[edit] * Desquamation * List of cutaneous conditions ## References[edit] 1. ^ "pityriasis" at Dorland's Medical Dictionary ## External links[edit] Classification D * ICD-9-CM: 696.5 * MeSH: D010915 * 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	Pityriasis	c0032024	936	wikipedia	https://en.wikipedia.org/wiki/Pityriasis	2021-01-18T18:41:51	{"mesh": ["D010915"], "icd-9": ["696.5"], "wikidata": ["Q2097389"]}
A rare renal tubulopathy secondary to urinary tract infection (UTI) and/or urinary tract malformation (UTM) characterized by renal tubular resistance to aldosterone, characterized by hyponatremia, metabolic acidosis, hyperkalemia and inappropriately high serum aldosterone concentration and clinically manifesting as dehydration, vomiting, and poor oral intake. ## Epidemiology So far, less than 100 cases have been reported worldwide. Because of its association with underlying UTMs, there is a strong male preponderance with more than 80% of affected infants being males. Due to the non-specific manifestations, the true prevalence of transient pseudohypoaldosteronism (TPHA1) is possibly underestimated. ## Clinical description TPHA1 occurs exclusively during the neonatal or early infantile period (90 % during the first six months of life). The clinical course is transient, typically resolving with treatment of the UTI, and may range from asymptomatic to life-threatening. The clinical features are non-specific and include nausea, vomiting, poor activity and low oral intake. As a consequence, life-threating salt loss, hyperkalemia and hemodynamic compromise may occur. ## Etiology Risk factors for TPHA1 in infants with UTI include male sex, young age and urinary tract malformation. Young age may contribute to the development of TPHA1 through low renal mineralocorticoid receptor expression and physiological partial aldosterone resistance. Urinary tract malformation has been found to be associated with decreased expression of mineralocorticoid receptor and increase in mineralocorticoid receptor resistance. In addition, bacterial factors including bacterial endotoxins and host factors such as TGF-beta, INF-alpha, IL-1 and -6 have also been speculated to involve the pathogenesis of TPHA1 in infants with UTI. ## Diagnostic methods The diagnosis can be confirmed by the findings of inappropriately elevated serum aldosterone in the setting of hyponatremia with renal sodium wasting, hyperkalemia with impaired renal potassium excretion, and non-anion gap metabolic acidosis. Infants should be screened for UTI and UTMs. ## Differential diagnosis The differential diagnoses include patients with impaired renal function (chronic kidney disease stage III to V), pre-existing electrolyte imbalance, medications (Na channel blockers, mineralocorticoid receptor blockers, calcineurin inhibitors, angiotensin converting enzyme inhibitors) which may cause pseudohypoaldosteronism. In cases of recurrent or persistent pseudohypoaldosteronism, the differential diagnosis should include pseudohypoaldosteronism type 1. ## Genetic counseling TPHA1 is not an inherited condition; however, in the cases of recurrent or persistent pseudohypoaldosteronism after treatment, the genetic analysis for the genes responsible for PHA1 may be considered. ## Management and treatment Early recognition and prompt treatment is crucial for affected infants with life-threatening hyperkalemia, salt wasting, and acidosis. The mainstays of treatment include antibiotics for UTI, volume repletion with salt supplementation for hyponatremia and in some cases bicarbonate for correction of metabolic acidosis. The need for additional therapeutic measures, such as loop diuretics, beta2 agonist, ion exchange resins, and calcium gluconate are determined by the severity of hyperkalemia. ## Prognosis The outcome is typically favorable as TPHA1 resolves with treatment of dehydration and urinary tract infection; however, the prognosis for affected infants with life-threatening hyperkalemia, salt wasting, and acidosis depends on early recognition and prompt treatment. * 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	Transient pseudohypoaldosteronism	c4273962	937	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93164	2021-01-23T17:29:03	{"icd-10": ["N15.8"], "synonyms": ["Secondary pseudohypoaldosteronism", "TPHA"]}
A number sign (#) is used with this entry because of evidence that familial candidiasis-6 (CANDF6) is caused by heterozygous mutation in the IL17F gene (606496) on chromosome 6p12. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of familial candidiasis, see CANDF1 (114580). Molecular Genetics Puel et al. (2011) investigated a multiplex family from Argentina with autosomal dominant inheritance of chronic cutaneous candidiasis. No mutations were identified in the IL22 (605330), IL22RA (605457), IL10RB (123889), IL17RA (605461), IL17RC (610925), or IL17A (603149) genes. However, Puel et al. (2011) detected a heterozygous ser65-to-leu mutation in the IL17F gene in the index case (606496.0001). Serine-65 is conserved across mammalian species. This mutation was found in all affected individuals but also in 2 apparently healthy female members, aged 9 months and 21 years, which suggested incomplete penetrance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	CANDIDIASIS, FAMILIAL, 6	c0006845	938	omim	https://www.omim.org/entry/613956	2019-09-22T15:56:58	{"doid": ["2058"], "mesh": ["D002178"], "omim": ["613956"], "orphanet": ["1334"], "synonyms": ["Alternative titles", "CANDIDIASIS, FAMILIAL CHRONIC MUCOCUTANEOUS, AUTOSOMAL DOMINANT"]}
Imperforate anus - Anorectal malformations Other namesAnorectal malformations An X-ray showing imperforate anus SpecialtyMedical genetics An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies.[1] The cause of ARMs is unknown; the genetic basis of these anomalies is very complex because of their anatomical variability. In 8% of patients, genetic factors are clearly associated with ARMs.[2] Anorectal malformation in Currarino syndrome represents the only association for which the gene HLXB9 has been identified.[1][3] ## Contents * 1 Types * 2 Presentation * 2.1 Associated anomalies * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 History * 8 References * 9 External links ## Types[edit] There are other forms of anorectal malformations though imperforate anus is most common. Other variants include anterior ectopic anus.[4] This form is more commonly seen in females and presents with constipation.[5] ## Presentation[edit] There are several forms of imperforate anus and anorectal malformations. The new classification is in relation of the type of associated fistula.[6] The classical Wingspread classification was in low and high anomalies:[citation needed] * A low lesion, in which the colon remains close to the skin. In this case, there may be a stenosis (narrowing) of the anus, or the anus may be missing altogether, with the rectum ending in a blind pouch. * A high lesion, in which the colon is higher up in the pelvis and there is a fistula connecting the rectum and the bladder, urethra or the vagina. * A persistent cloaca (from the term cloaca, an analogous orifice in reptiles and amphibians), in which the rectum, vagina and urinary tract are joined into a single channel. Imperforate anus is usually present along with other birth defects—spinal problems, heart problems, tracheoesophageal fistula, esophageal atresia, renal anomalies and limb anomalies are among the possibilities, collectively being called the VACTERL association.[7] ### Associated anomalies[edit] Imperforate anus is associated with an increased incidence of some other specific anomalies as well, together being called the VACTERL association.[citation needed] Other entities associated with an imperforate anus are trisomies 18 and 21, the cat-eye syndrome (partial trisomy or tetrasomy of a maternally derived chromosome 22), Baller–Gerold syndrome, Currarino syndrome, caudal regression syndrome, FG syndrome, Johanson–Blizzard syndrome, McKusick–Kaufman syndrome, Pallister–Hall syndrome, short rib–polydactyly syndrome type 1, Townes–Brocks syndrome, 13q deletion syndrome, urorectal septum malformation sequence and the OEIS complex (omphalocele, exstrophy of the cloaca, imperforate anus, spinal defects).[citation needed] ## Diagnosis[edit] When an infant is born with an anorectal malformation, it is usually detected quickly as it is a very obvious defect. Doctors will then determine the type of birth defect the child was born with and whether or not there are any associated malformations. It is important to determine the presence of any associated defects during the newborn period in order to treat them early and avoid further sequelae. There are two main categories of anorectal malformations: those that require a protective colostomy and those that do not. The decision to open a colostomy is usually taken within the first 24 hours of birth.[citation needed] Sonography can be used to determine the type of imperforate anus.[8] ## Treatment[edit] Imperforate anus usually requires immediate surgery to open a passage for feces unless a fistula can be relied on until corrective surgery takes place. Depending on the severity of the imperforate, it is treated either with a perineal anoplasty[9] or with a colostomy. While many surgical techniques to definitively repair anorectal malformations have been described, the posterior sagittal approach (PSARP) has become the most popular. It involves dissection of the perineum without entry into the abdomen and 90% of defects in boys can be repaired this way.[citation needed] ## Prognosis[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (February 2010) (Learn how and when to remove this template message) With a high lesion, many children have problems controlling bowel function and most also become constipated. With a low lesion, children generally have good bowel control, but they may still become constipated. For children who have a poor outcome for continence and constipation from the initial surgery, further surgery to better establish the angle between the anus and the rectum may improve continence and, for those with a large rectum, surgery to remove that dilated segment may significantly improve the bowel control for the patient. An antegrade enema mechanism can be established by joining the appendix to the skin (Malone stoma); however, establishing more normal anatomy is the priority. ## Epidemiology[edit] Imperforate anus has an estimated incidence of 1 in 5000 births.[10][11] It affects boys and girls with similar frequency.[12] However, imperforate anus will present as the low version 90% of the time in females and 50% of the time in males. Imperforate anus is an occasional complication of sacrococcygeal teratoma.[13] ## History[edit] 7th-century Byzantine physician Paulus Aegineta described a surgical treatment for imperforate anus for the first time.[14] 10th-century Persian physician Haly Abbas was the first to highlight preserving the sphincter muscles throughout the surgery and the prevention of strictures with a stent.[14] He has reported the use of wine for wound care in this surgery. Some reports of children surviving this surgery are available from the early medieval Islamic era.[15] ## References[edit] 1. ^ a b Nixon, H. H. (14 November 2006). Holschneider, Alexander Matthias; Hutson, John M. (eds.). Anorectal Malformations in Children: Embryology, Diagnosis, Surgical Treatment, Follow-up. Proceedings of the Royal Society of Medicine. 65. Springer. p. 819. doi:10.1007/978-3-540-31751-7. ISBN 978-3-540-31750-0. PMC 1644586. Retrieved 15 September 2013. 2. ^ Moore, Samuel W (14 November 2006). "Genetics, Pathogenesis and Epidemiology of Anorectal Malformations and Caudal Regression Syndrome". In Holschneider, Alexander Matthias; Hutson, John M. (eds.). Anorectal Malformations in Children: Embryology, Diagnosis, Surgical Treatment, Follow-up. Springer. pp. 31–48. doi:10.1007/978-3-540-31751-7_3. ISBN 978-3-540-31750-0. 3. ^ Belloni, E; Martucciello, G; Verderio, D; Ponti, E; Seri, M; Jasonni, V; Torre, M; Ferrari, M; Tsui, LC; Scherer, SW (January 2000). "Involvement of the HLXB9 homeobox gene in Currarino syndrome". American Journal of Human Genetics. 66 (1): 312–9. doi:10.1086/302723. PMC 1288336. PMID 10631160. 4. ^ Bill AH, Jr; Johnson, RJ; Foster, RA (February 1958). "Anteriorly placed rectal opening in the perineum ectopic anus; a report of 30 cases". Annals of Surgery. 147 (2): 173–9. doi:10.1097/00000658-195802000-00005. PMC 1450565. PMID 13498637. 5. ^ Leape, LL; Ramenofsky, ML (December 1978). "Anterior ectopic anus: a common cause of constipation in children". Journal of Pediatric Surgery. 13 (6D): 627–30. doi:10.1016/S0022-3468(78)80105-5. PMID 731362. 6. ^ Pena A, Levitt MA. (2006) "Anorectal Malformations" in: Grosfeld et al. Ed. "Pediatric Surgery", Mosly 7. ^ Colorectal Center, Cincinnati Children's Hospital Medical Center. "Anorectal Malformations / Imperforate Anus." Retrieved July, 2005. 8. ^ Haber HP, Seitz G, Warmann SW, Fuchs J (2007). "Transperineal sonography for determination of the type of imperforate anus". AJR. American Journal of Roentgenology. 189 (6): 1525–9. doi:10.2214/AJR.07.2468. PMID 18029895. 9. ^ Becmeur F, Hofmann-Zango I, Jouin H, Moog R, Kauffmann I, Sauvage P (2001). "Three-flap anoplasty for imperforate anus: results for primary procedure or for redoes". European Journal of Pediatric Surgery. 11 (5): 311–4. doi:10.1055/s-2001-18555. PMID 11719868. 10. ^ Texas Pediatric Associates. "Imperforate anus." Retrieved 13 July 2005. 11. ^ MedLine Plus. "Imperforate anus." Retrieved 13 July 2005. 12. ^ Adotey JM, Jebbin NJ (2004). "Anorectal disorders requiring surgical treatment in the University of Port Harcourt Teaching Hospital, Port Harcourt". Nigerian Journal of Medicine: Journal of the National Association of Resident Doctors of Nigeria. 13 (4): 350–4. PMID 15523860. 13. ^ Bhat NA, Mathur M, Bhatnagar V (2003). "Sacrococcygeal teratoma with anorectal malformation". Indian Journal of Gastroenterology. 22 (1): 27. PMID 12617452. 14. ^ a b Iranikhah, A.; Heydari, M.; Hakimelahi, J.; Gharehbeglou, M.; Ghadir, M. R. (2016). "Surgical Repair of Imperforate Anus: A Report from Haly Abbas (949-982AD)". J. Pediatr. Surg. 51 (1): 192–3. doi:10.1016/j.jpedsurg.2015.11.001. PMID 26651280. 15. ^ Raffensperger, John G (2012). Children's Surgery: A Worldwide History. McFarland. p. 148. ## External links[edit] * Medline Plus Medical Encyclopedia: Imperforate anus Classification D * ICD-10: Q42.3 * ICD-9-CM: 751.2 * OMIM: 301800 207500 * MeSH: D001006 * DiseasesDB: 34522 External resources * MedlinePlus: 001147 * eMedicine: ped/1171 ped/2923 * 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	Imperforate anus	c0003466	939	wikipedia	https://en.wikipedia.org/wiki/Imperforate_anus	2021-01-18T18:54:49	{"gard": ["6769"], "mesh": ["D001006"], "umls": ["C0003466"], "icd-9": ["751.2"], "orphanet": ["557"], "wikidata": ["Q484631"]}
A number sign (#) is used with this entry because of evidence that cone-rod dystrophy-2 (CORD2) is caused by heterozygous mutation in the CRX gene (602225) on chromosome 19q13. Description Cone-rod dystrophy (CORD) characteristically leads to early impairment of vision. An initial loss of color vision and of visual acuity is followed by nyctalopia (night blindness) and loss of peripheral visual fields. In extreme cases, these progressive symptoms are accompanied by widespread, advancing retinal pigmentation and chorioretinal atrophy of the central and peripheral retina (Moore, 1992). In many families, perhaps a majority, central and peripheral chorioretinal atrophy is not found (Tzekov, 1998). ### Genetic Heterogeneity of Autosomal Cone-Rod Dystrophy There are several other autosomal forms of CORD for which the molecular basis is known. CORD3 (604116) is caused by mutation in the ABCA4 gene (601691) on chromosome 1p22. CORD5 (600977) is caused by mutation in the PITPNM3 gene (608921) on chromosome 17p13. CORD6 (601777) is caused by mutation in the GUCY2D gene (600179) on chromosome 17p13.1. CORD7 (603649) is caused by mutation in the RIMS1 gene (606629) on chromosome 6q13. CORD9 (612775) is caused by mutation in the ADAM9 gene (602713) on chromosome 8p11. CORD10 (610283) is caused by mutation in the SEMA4A gene (607292) on chromosome 1q22. CORD11 (610381) is caused by mutation in the RAXL1 gene (610362) on chromosome 19p13. CORD12 (612657) is caused by mutation in the PROM1 gene (604365) on chromosome 4p15. CORD13 (608194) is caused by mutation in the RPGRIP1 gene (605446) on chromosome 14q11. CORD14 (see 602093) is caused by mutation in the GUCA1A gene (600364) on chromosome 6p21. CORD15 (613660) is caused by mutation in the CDHR1 gene (609502) on chromosome 10q23. CORD16 (614500) is caused by mutation in the C8ORF37 gene (614477) on chromosome 8q22. CORD18 (615374) is caused by mutation in the RAB28 gene (612994) on chromosome 4p15. CORD19 (615860) is caused by mutation in the TTLL5 gene (612268) on chromosome 14q24. CORD20 (615973) is caused by mutation in the POC1B gene (614784) on chromosome 12q21. CORD21 (616502) is caused by mutation in the DRAM2 gene (613360) on chromosome 1p13. A diagnosis of CORD was made in an individual with a mutation in the AIPL1 gene (604392.0004) on chromosome 17p13.1, as well as in an individual with a mutation in the UNC119 gene (604011.0001) on chromosome 17q11.2. Other mapped loci for autosomal CORD include CORD1 (600624) on chromosome 18q21.1-q21.3; CORD8 (605549) on chromosome 1q12-q24; and CORD17 (615163) on chromosome 10q26. For a discussion of X-linked forms of cone-rod dystrophy, see CORDX1 (304020). Clinical Features Hittner et al. (1975) described an extensively affected kindred with an autosomal dominant dystrophy of the retinal photoreceptors and pigment epithelium that is characterized by simultaneous abiotrophic degeneration of rods and cones. The onset of decreased central vision with concurrent progressive constriction of peripheral visual fields occurs prior to age 10. Unlike previously described cone dystrophies, there is an inexorable progression to no light perception. Ferrell et al. (1981) provided follow-up on the family reported by Hittner et al. (1975). In all, 25 affected persons had been identified. Evans et al. (1995) reported the clinical features of 34 affected members in 4 generations. Loss of visual acuity occurred in the first decade of life, onset of night blindness occurred after 20 years of age, and little visual function remained after the age of 50 years. Central and, later, peripheral retinal fundus changes were associated with central scotoma, pseudoaltitudinal field defects, and finally, global loss of function. Psychophysical and electrophysiologic testing before the age of 26 years showed more marked loss of cone than of rod function. Evans et al. (1995) found complete blindness (no light perception) in only 3 of the 34 patients studied, and these 3 were all over 65 years of age. Serious effects on visual acuity (light perception only) were present in 10 other patients; however, their mean age was 60.3 years. All other patients retained some visual acuity. Papaioannou et al. (1998) reported a 4-generation family of Greek origin with clinical features similar to those described in the British family by Evans et al. (1994). Itabashi et al. (2004) characterized the clinical features of a Japanese family with CORD. The ophthalmic findings included CORD with negative-type electroretinograms (ERGs) and a rapid progression after age 40 years. The authors concluded that genotype-phenotype correlation in the CRX gene in their patient and others reported in the literature suggested that the negative-type ERG might be indicative of a mutation in the CRX gene. Inheritance In the large kindred with autosomal dominant cone-rod dystrophy studied by Evans et al. (1994), it appeared that inheritance was influenced by meiotic drive, resulting in segregation distortion. Affected fathers (N = 25) produced 71 children of whom 31 (44%) were affected, a value approximating the expected 1:1 ratio; however, 63 of 101 children (63%) born to 26 affected mothers inherited the CORD gene. The cumulative binomial distribution calculation for this finding in the progeny of affected mothers gave p = 0.008. Mapping In a large British family segregating cone-rod dystrophy, Evans et al. (1994) found linkage of the disorder to chromosome 19q13.1-q32.1 (maximum lod of 10.08 distal to D19S47). In a family reported by Papaioannou et al. (1998) who had clinical features similar to those described in the British family by Evans et al. (1994), linkage analysis gave a maximum lod score of 2.7 at theta = 0.0 with marker D19S412. ### Additional Heterogeneity Kylstra and Aylsworth (1993) reported a case of cone-rod retinal dystrophy in association with neurofibromatosis type I (NF1; 162200) and suggested a localization for CORD (CORD4) close to the NF1 gene (613113) on 17q. ### Exclusion Mapping In the family originally reported by Hittner et al. (1975), Ferrell et al. (1981) found no linkage with 17 marker loci. Specifically, a large negative lod score with Rh argued against location of the CORD gene on 1p, a large negative lod score with acid phosphatase-1 argued against its location on 2p, and a large negative lod score with ABO and transcobalamin II argued against its location on 9q. Molecular Genetics In affected members of 2 pedigrees with CORD2, Freund et al. (1997) identified a missense and a frameshift mutation in the CRX gene, an OTX-like homeobox gene. The authors showed that the missense mutation (602225.0001) was not a polymorphic variant and concluded that mutation in the CRX gene is responsible for the CORD2 phenotype. In a Japanese family with CORD, Itabashi et al. (2004) found a 1-bp deletion in exon 1 of the CRX gene (602225.0009). By whole-exome sequencing in a group of 50 patients with CORD who were negative for mutations in known retinal disease genes, Dharmat et al. (2017) identified compound heterozygosity for a nonsense mutation (R405X) and a missense mutation (L614P) in the IFT81 gene (605489) in a 22-year-old woman. Her unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in internal controls or public variant databases. The L614P variant was not able to rescue ciliogenesis defects in IFT81 -/- hTERT-RPE1 cells or zebrafish. The proband had progressively decreasing vision with photophobia from age 12 years, and examination revealed impaired color vision and decreased visual acuity, characteristic pigmented lesions in the fundus, reduced responses on ERG that were more severe in cones than in rods, and thinning of the retinal layers in the macular area on ocular coherence tomography. She had no extraocular anomalies. The authors concluded that IFT81 was a candidate gene for inherited nonsyndromic retinal dystrophy. Eyes \- Cone-rod retinal dystrophy \- Initial color vision and visual acuity loss \- Night blindness \- Peripheral visual field loss \- Widespread retinal pigmentation \- Chorioretinal atrophy \- Early blindness Inheritance \- Autosomal dominant (19q13.1-q13.2) ▲ 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	CONE-ROD DYSTROPHY 2	c3489532	940	omim	https://www.omim.org/entry/120970	2019-09-22T16:43:04	{"doid": ["0111005"], "mesh": ["D000071700"], "omim": ["120970"], "orphanet": ["1872"], "synonyms": ["Alternative titles", "CONE-ROD RETINAL DYSTROPHY", "CONE-ROD DYSTROPHY", "RETINAL CONE-ROD DYSTROPHY"]}
A rare, multiple congenital anomalies/dysmorphic syndrome characterized by microcephaly, intellectual disability, seizures, and congenital heart defects (e.g. atrial/ventricular septal defect, hypoplastic aortic arch with persistent ductus arteriosus). Additional manifestations include mild hypothyroidism, skeletal abnormalities, micropenis, delayed psychomotor development, dysmorphic facial features (including epicanthus, depressed nasal bridge, prominent antitragus), and pulmonary vascular occlusive disease. There have been no further descriptions in the literature since 1989. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Microcephaly-seizures-intellectual disability-heart disease syndrome	c2931529	941	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2519	2021-01-23T17:30:37	{"mesh": ["C537544"], "umls": ["C2931529"], "icd-10": ["Q87.8"]}
Paroxysmal nocturnal hemoglobinuria Other namesParoxysmal nocturnal haemoglobinuria, Marchiafava–Micheli syndrome Intravascular hemolytic anemia SpecialtyHematology Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired,[1] life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to the presence of defective surface protein DAF on the red blood cell, which normally functions to inhibit such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. Other key features of the disease, such as the high incidence of blood clot formation, are incompletely understood.[2] PNH is the only hemolytic anemia caused by an acquired (rather than inherited) intrinsic defect in the cell membrane (deficiency of glycophosphatidylinositol leading to the absence of protective proteins on the membrane).[3] It may develop on its own ("primary PNH") or in the context of other bone marrow disorders such as aplastic anemia ("secondary PNH"). Only a minority of affected people have the telltale red urine in the morning that originally gave the condition its name.[4] Allogeneic bone marrow transplantation is the only cure, but has significant rates of additional medical problems and death.[5] The monoclonal antibody eculizumab reduces the need for blood transfusions and improves quality of life for those affected by PNH.[5] Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to the extent that it may be equivalent to that of the general population.[6] Eculizumab costs at least $440,000 for a single year of treatment and has been reported as one of the world's most expensive drugs.[7][8][9] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 3.1 Classification * 4 Screening * 5 Treatment * 5.1 Acute attacks * 5.2 Long-term * 5.3 Eculizumab * 6 Epidemiology * 7 History * 8 References * 9 External links ## Signs and symptoms[edit] The classic sign of PNH is red discoloration of the urine due to the presence of hemoglobin and hemosiderin from the breakdown of red blood cells.[10] As the urine is more concentrated in the morning, this is when the color is most pronounced. This phenomenon mainly occurs in those who have the primary form of PNH, who will notice this at some point in their disease course. The remainder mainly experience the symptoms of anemia, such as tiredness, shortness of breath, and palpitations.[4] A small proportion of patients report attacks of abdominal pain, difficulty swallowing and pain during swallowing, as well as erectile dysfunction in men; this occurs mainly when the breakdown of red blood cells is rapid, and is attributable to spasm of smooth muscle due to depletion of nitric oxide by red cell breakdown products.[11] Forty percent of people with PNH develop thrombosis (a blood clot) at some point in their illness. This is the main cause of severe complications and death in PNH. These may develop in common sites (deep vein thrombosis of the leg and resultant pulmonary embolism when these clots break off and enter the lungs), but in PNH blood clots may also form in more unusual sites: the hepatic vein (causing Budd-Chiari syndrome), the portal vein of the liver (causing portal vein thrombosis), the superior or inferior mesenteric vein (causing mesenteric ischemia) and veins of the skin. Cerebral venous thrombosis, an uncommon form of stroke, is more common in those with PNH.[4] ## Pathophysiology[edit] CD55 protein/Decay Accelerating Factor structure CD59 protein/Protectin structure All cells have proteins attached to their membranes, often serving as a mode of communication or signaling between the cell and the surrounding environment. These signaling proteins are physically attached to the cell membrane in various ways, commonly anchored by glycolipids such as glycosyl phosphatidylinositols (GPI). PNH occurs as a result of a defect in the assembling of these glycolipid-protein structures on the surface of blood cells.[4] The most common defective enzyme in PNH is phosphatidylinositol glycan A (PIGA), one of several enzymes needed to make GPI. The gene that codes for PIGA is located on the X chromosome, which means that only one active copy of the gene for PIGA is present in each cell (initially, females have two copies, but one is silenced through X-inactivation).[1] A mutation in the PIGA gene can lead to the absence of GPI anchors expressed on the cell membrane. When this mutation occurs in a hematopoietic stem cell in the bone marrow, all of the cells it produces will also have the defect.[4] Several of the proteins that anchor to GPI on the cell membrane are used to protect the cell from destruction by the complement system, and, without these anchors, the cells are more easily targeted by the complement proteins.[3] Although red blood cells, white blood cells, and platelets are targeted by complement, red blood cells are particularly vulnerable to lysis.[citation needed] The complement system is part of the innate immune system and has a variety of functions, from destroying invading microorganisms by opsonization to direct destabilization by the membrane attack complex. The main proteins that protect blood cells from destruction are decay-accelerating factor (DAF/CD55), which disrupts formation of C3-convertase, and protectin (CD59/MIRL/MAC-IP), which binds the membrane attack complex and prevents C9 from binding to the cell.[4] The symptoms of esophageal spasm, erectile dysfunction, and abdominal pain are attributed to the fact that hemoglobin released during hemolysis binds with circulating nitric oxide, a substance that is needed to relax smooth muscle. This theory is supported by the fact that these symptoms improve on administration of nitrates or sildenafil (Viagra), which improves the effect of nitric oxide on muscle cells.[4] There is a suspicion that chronic hemolysis causing chronically depleted nitric oxide may lead to the development of pulmonary hypertension (increased pressure in the blood vessels supplying the lung), which in turn puts strain on the heart and causes heart failure.[12] Historically, the role of the sleep and night in this disease (the "nocturnal" component of the name) has been attributed to acidification of the blood at night due to relative hypoventilation and accumulation of carbon dioxide in the blood during sleep. This hypothesis has been questioned by researchers who note that not all those with PNH have increased hemolysis during sleep, so it is uncertain how important a role sleep actually plays in this disease.[13] ## Diagnosis[edit] Blood tests in PNH show changes consistent with intravascular hemolytic anemia: low hemoglobin, raised lactate dehydrogenase, raised bilirubin (a breakdown product of hemoglobin), and decreased levels of haptoglobin; there can be raised reticulocytes (immature red cells released by the bone marrow to replace the destroyed cells) if there is no iron deficiency present. The direct antiglobulin test (DAT, or direct Coombs' test) is negative, as the hemolysis of PNH is not caused by antibodies.[4] If the PNH occurs in the setting of known (or suspected) aplastic anemia, abnormal white blood cell counts and decreased platelet counts may be seen at this. In this case, anemia may be caused by insufficient red blood cell production in addition to the hemolysis.[4] Historically, the sucrose lysis test, in which a patient's red blood cells are placed in low-ionic-strength solution and observed for hemolysis, was used for screening. If this was positive, the Ham's acid hemolysis test (after Dr Thomas Ham, who described the test in 1937) was performed for confirmation.[5][14] The Ham test involves placing red blood cells in mild acid; a positive result (increased RBC fragility) indicates PNH or Congenital dyserythropoietic anemia. This is now an obsolete test for diagnosing PNH due to its low sensitivity and specificity. Today, the gold standard is flow cytometry for CD55 and CD59 on white and red blood cells. Based on the levels of these cell proteins, erythrocytes may be classified as type I, II, or III PNH cells. Type I cells have normal levels of CD55 and CD59; type II have reduced levels; and type III have absent levels.[4] The fluorescein-labeled proaerolysin (FLAER) test is being used more frequently to diagnose PNH. FLAER binds selectively to the glycophosphatidylinositol anchor and is more accurate in demonstrating a deficit than simply for CD59 or CD55.[5] ### Classification[edit] PNH is classified by the context under which it is diagnosed:[4] * Classic PNH. Evidence of PNH in the absence of another bone marrow disorder. * PNH in the setting of another specified bone marrow disorder such as aplastic anemia and myelodysplastic syndrome (MDS). * Subclinical PNH. PNH abnormalities on flow cytometry without signs of hemolysis. ## Screening[edit] There are several groups where screening for PNH should be undertaken. These include patients with unexplained thrombosis who are young, have thrombosis in an unusual site (e.g. intra-abdominal veins, cerebral veins, dermal veins), have any evidence of hemolysis (e.g. a raised LDH), or have a low red blood cell, white blood cell, or platelet count.[15] Those who have a diagnosis of aplastic anemia should be screened annually.[4] ## Treatment[edit] ### Acute attacks[edit] There is disagreement as to whether steroids (such as prednisolone) can decrease the severity of hemolytic crises. Transfusion therapy may be needed; in addition to correcting significant anemia, this suppresses the production of PNH cells by the bone marrow, and indirectly the severity of the hemolysis. Iron deficiency develops with time, due to losses in urine, and may have to be treated if present. Iron therapy can result in more hemolysis as more PNH cells are produced.[4] ### Long-term[edit] PNH is a chronic condition. In patients with only a small clone and few problems, monitoring of the flow cytometry every six months gives information on the severity and risk of potential complications. Given the high risk of thrombosis in PNH, preventive treatment with warfarin decreases the risk of thrombosis in those with a large clone (50% of white blood cells type III).[4][16] Episodes of thrombosis are treated as they would in other patients, but, given that PNH is a persisting underlying cause, it is likely that treatment with warfarin or similar drugs needs to be continued long-term after an episode of thrombosis.[4] ### Eculizumab[edit] In 2007, the drug eculizumab was approved for the treatment of PNH. Prior to eculizumab the median life expectancy of an individual with PNH was approximately 10 years. Since that time, short and mid term studies of patients on eculizumab demonstrate that the drug returns the patient to a normal life expectancy, improves quality of life, and decreases the need for blood transfusions.[6][9] Eculizumab is controversial due to its high cost, as it is among the most expensive pharmaceuticals in the world, with a price of US$440,000 per person per year.[8] Eculizumab is a humanized monoclonal antibody that acts as a terminal complement inhibitor. The U.S. Food and Drug Administration (FDA) has issued a black-box warning as those who take the medication have a 1,000 to 2,000-fold greater risk of invasive meningococcal disease. People on eculizumab are strongly advised to receive meningococcal vaccination at least two weeks prior to starting therapy and to consider preventative antibiotics for the duration of treatment.[17] ## Epidemiology[edit] PNH is rare, with an annual rate of 1-2 cases per million.[4] The prognosis without disease-modifying treatment is 10–20 years.[18] Many cases develop in people who have previously been diagnosed with aplastic anemia or myelodysplastic syndrome. The fact that PNH develops in MDS also explains why there appears to be a higher rate of leukemia in PNH, as MDS can sometimes transform into leukemia.[4] 25% of female cases of PNH are discovered during pregnancy. This group has a high rate of thrombosis, and the risk of death of both mother and child are significantly increased (20% and 8% respectively).[4] ## History[edit] The first description of paroxysmal hemoglobinuria was by the German physician Paul Strübing (Greifswald, 1852–1915) during a lecture in 1881, later published in 1882.[19] Later comprehensive descriptions were made by Ettore Marchiafava and Alessio Nazari in 1911,[20] with further elaborations by Marchiafava in 1928[21] and Ferdinando Micheli in 1931.[22][23] The Dutch physician Enneking coined the term "paroxysmal nocturnal hemoglobinuria" (or haemoglobinuria paroxysmalis nocturna in Latin) in 1928, which has since become the default description.[24] ## References[edit] 1. ^ a b Luzzatto, L. (15 August 2013). "PNH from mutations of another PIG gene". Blood. 122 (7): 1099–1100. doi:10.1182/blood-2013-06-508556. PMID 23950173. 2. ^ Parker, Charles (2012). "Paroxysmal nocturnal hemoglobinuria". Curr Opin Hematol. 19 (3): 141–148. doi:10.1097/MOH.0b013e328351c348. PMID 22395662. S2CID 21266914. 3. ^ a b Kumar Vinay; Abbas AK; Fausto N; Mitchell RN (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. p. 652. ISBN 978-1-4160-2973-1. 4. ^ a b c d e f g h i j k l m n o p q r Parker C, Omine M, Richards S, et al. (2005). "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood. 106 (12): 3699–709. doi:10.1182/blood-2005-04-1717. PMC 1895106. PMID 16051736. 5. ^ a b c d Brodsky, RA (2009). "How I treat paroxysmal nocturnal hemoglobinuria". Blood. 113 (26): 6522–7. doi:10.1182/blood-2009-03-195966. PMC 2710914. PMID 19372253. 6. ^ a b Wong, EKS; Kavanagh, D (January 2018). "Diseases of complement dysregulation-an overview". Seminars in Immunopathology. 40 (1): 49–64. doi:10.1007/s00281-017-0663-8. PMC 5794843. PMID 29327071. 7. ^ "Alexion Pharmaceuticals ordered to lower price of $500K a year drug in Canada \| CBC News". CBC. Retrieved 2018-11-29. 8. ^ a b "British watchdog wants U.S. biotech Alexion to justify cost of drug". Reuters. March 3, 2014. Retrieved June 6, 2014. 9. ^ a b Martí-Carvajal, AJ; Anand, V; Cardona, AF; Solà, I (30 October 2014). "Eculizumab for treating patients with paroxysmal nocturnal hemoglobinuria". The Cochrane Database of Systematic Reviews. 10 (10): CD010340. doi:10.1002/14651858.CD010340.pub2. PMID 25356860. 10. ^ "Paroxysmal Nocturnal Hemoglobinuria - NORD (National Organization for Rare Disorders)". NORD. 2016. Retrieved 3 July 2017. 11. ^ Rother, RP; Bell, L; Hillmen, P; Gladwin, MT (6 April 2005). "The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease". JAMA. 293 (13): 1653–62. doi:10.1001/jama.293.13.1653. PMID 15811985. 12. ^ Rother RP, Bell L, Hillmen P, Gladwin MT (April 2005). "The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease". JAMA. 293 (13): 1653–62. doi:10.1001/jama.293.13.1653. PMID 15811985. 13. ^ Parker, CJ (Apr 2002). "Historical aspects of paroxysmal nocturnal haemoglobinuria: 'defining the disease'". British Journal of Haematology. 117 (1): 3–22. doi:10.1046/j.1365-2141.2002.03374.x. PMID 11918528. 14. ^ Ham TH (1937). "Chronic haemolytic anaemia with paroxysmal nocturnal haemoglobinuria: study of the mechanism of haemolysis in relation to acid-base equilibrium". N Engl J Med. 217 (23): 915–918. doi:10.1056/NEJM193712022172307. 15. ^ Hill A, Kelly RJ, Hillmen P (2013). "Thrombosis in paroxysmal nocturnal hemoglobinuria". Blood. 121 (25): 4985–4996. doi:10.1182/blood-2012-09-311381. PMID 23610373. 16. ^ Hall C, Richards S, Hillmen P (November 2003). "Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH)". Blood. 102 (10): 3587–91. doi:10.1182/blood-2003-01-0009. PMID 12893760. 17. ^ "Patients Receiving Eculizumab (Soliris) at High Risk for Invasive Meningococcal Disease Despite Vaccination". Centers for Disease Control and Prevention Health Alert Network. 7 July 2017. 18. ^ Pu, JJ; Brodsky, RA (June 2011). "Paroxysmal nocturnal hemoglobinuria from bench to bedside". Clinical and Translational Science. 4 (3): 219–24. doi:10.1111/j.1752-8062.2011.00262.x. PMC 3128433. PMID 21707954. 19. ^ Strübing P (1882). "Paroxysmale Hämoglobinurie". Dtsch Med Wochenschr (in German). 8: 1–3 and 17–21. doi:10.1055/s-0029-1196307. 20. ^ Marchiafava E, Nazari A (1911). "Nuovo contributo allo studio degli itteri cronici emolitici". Policlinico [Med] (in Italian). 18: 241–254. 21. ^ Marchiafava E (1928). "Anemia emolitica con emosiderinuria perpetua". Policlinico [Med] (in Italian). 35: 105–117. 22. ^ Micheli F (1931). "Uno caso di anemia emolitica con emosiderinuria perpetua". G Accad Med Torino (in Italian). 13: 148. 23. ^ Strübing-Marchiafava-Micheli syndrome at Who Named It? 24. ^ Enneking J (1928). "Eine neue form intermittierender haemoglobinurie (Haemoglobinuria paroxysmalis nocturia)". Klin Wochenschr (in German). 7 (43): 2045–2047. doi:10.1007/BF01846778. S2CID 30149910. ## External links[edit] Classification D * ICD-10: D59.5 * ICD-9-CM: 283.2 * OMIM: 300818 * MeSH: D006457 * DiseasesDB: 9688 External resources * MedlinePlus: 000534 * eMedicine: article/207468 * v * t * e Diseases of red blood cells ↑ Polycythemia * Polycythemia vera ↓ Anemia Nutritional * Micro-: Iron-deficiency anemia * Plummer–Vinson syndrome * Macro-: Megaloblastic anemia * Pernicious anemia Hemolytic (mostly normo-) Hereditary * enzymopathy: Glucose-6-phosphate dehydrogenase deficiency * glycolysis * pyruvate kinase deficiency * triosephosphate isomerase deficiency * hexokinase deficiency * hemoglobinopathy: Thalassemia * alpha * beta * delta * Sickle cell disease/trait * Hereditary persistence of fetal hemoglobin * membrane: Hereditary spherocytosis * Minkowski–Chauffard syndrome * Hereditary elliptocytosis * Southeast Asian ovalocytosis * Hereditary stomatocytosis Acquired AIHA * Warm antibody autoimmune hemolytic anemia * Cold agglutinin disease * Donath–Landsteiner hemolytic anemia * Paroxysmal cold hemoglobinuria * Mixed autoimmune hemolytic anemia * membrane * paroxysmal nocturnal hemoglobinuria * Microangiopathic hemolytic anemia * Thrombotic microangiopathy * Hemolytic–uremic syndrome * Drug-induced autoimmune * Drug-induced nonautoimmune * Hemolytic disease of the newborn Aplastic (mostly normo-) * Hereditary: Fanconi anemia * Diamond–Blackfan anemia * Acquired: Pure red cell aplasia * Sideroblastic anemia * Myelophthisic Blood tests * Mean corpuscular volume * normocytic * microcytic * macrocytic * Mean corpuscular hemoglobin concentration * normochromic * hypochromic Other * Methemoglobinemia * Sulfhemoglobinemia * Reticulocytopenia * v * t * e Lymphoid and complement disorders causing immunodeficiency Primary Antibody/humoral (B) Hypogammaglobulinemia * X-linked agammaglobulinemia * Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia * IgA deficiency * IgG deficiency * IgM deficiency * Hyper IgM syndrome (1 * 2 * 3 * 4 * 5) * Wiskott–Aldrich syndrome * Hyper-IgE syndrome Other * Common variable immunodeficiency * ICF syndrome T cell deficiency (T) * thymic hypoplasia: hypoparathyroid (Di George's syndrome) * euparathyroid (Nezelof syndrome * Ataxia–telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency * Hyper IgM syndrome (1) Severe combined (B+T) * x-linked: X-SCID autosomal: Adenosine deaminase deficiency * Omenn syndrome * ZAP70 deficiency * Bare lymphocyte syndrome Acquired * HIV/AIDS Leukopenia: Lymphocytopenia * Idiopathic CD4+ lymphocytopenia Complement deficiency * C1-inhibitor (Angioedema/Hereditary angioedema) * Complement 2 deficiency/Complement 4 deficiency * MBL deficiency * Properdin deficiency * Complement 3 deficiency * Terminal complement pathway deficiency * Paroxysmal nocturnal hemoglobinuria * Complement receptor deficiency * v * t * e Inborn error of lipid metabolism: Phospholipid metabolism disorders Tafazzin * 3-Methylglutaconic aciduria 2 (Barth syndrome) * CMD3A Other * Paroxysmal nocturnal hemoglobinuria * Hyperphosphatasia with mental retardation 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	Paroxysmal nocturnal hemoglobinuria	c0024790	942	wikipedia	https://en.wikipedia.org/wiki/Paroxysmal_nocturnal_hemoglobinuria	2021-01-18T18:47:55	{"gard": ["7337"], "mesh": ["D006457"], "umls": ["C0024790"], "orphanet": ["447"], "wikidata": ["Q1479494"]}
A number sign (#) is used with this entry because autosomal dominant isolated ectopia lentis-1 (ECTOL1) is caused by heterozygous mutation in the FBN1 gene (134797) on chromosome 15q21. Mutation in the same gene causes Marfan syndrome (154700), of which ectopia lentis is a feature. Description Ectopia lentis is defined as an abnormal stretching of the zonular fibers that leads to lens dislocation, resulting in acute or chronic visual impairment (Greene et al., 2010). Citing the revised Ghent criteria for Marfan syndrome, Loeys et al. (2010) proposed the designation 'ectopia lentis syndrome' (ELS) for patients with ectopia lentis and a mutation in the FBN1 gene who lack aortic involvement, to highlight the systemic nature of the condition and to emphasize the need for assessment of features outside the ocular system (see DIAGNOSIS). ### Genetic Heterogeneity of Isolated Ectopia Lentis An autosomal recessive form of isolated ectopia lentis (ECTOL2; 225100) is caused by mutation in the ADAMTSL4 gene (610113). Clinical Features McKusick (1972) restudied the family reported by McGavic (1966) as having Weill-Marchesani syndrome (608328) and concluded that they probably suffered from an autosomal dominant form of 'simple' ectopia lentis. Eleven members were affected; all members with or without ectopia lentis were short. Stevenson et al. (1982) reported 2 families, 1 black and 1 white, in which congenital dislocation of the lenses was associated with joint stiffness and dolichostenomelia but no arachnodactyly or cardiovascular complications typical of Marfan syndrome. In 1 family, 11 persons in 4 generations were affected. By echocardiography, the aortic root measured 3.8 cm in a 55-year-old woman and 4.0 cm in a 52-year-old man, both with ectopia lentis. Molecular genetic studies are necessary in families of this type. Further uncertainty as to whether families with seemingly isolated ectopia lentis represent an entity separate from the Marfan syndrome arose from the findings of Tsipouras et al. (1992): in 2 families, the isolated ectopia lentis was linked to the fibrillin gene (FBN1; 134797) on chromosome 15, the same gene to which Marfan syndrome is linked. The experience with a variety of phenotypes produced by mutations in different parts of the collagen genes and indeed in many other genes suggests that isolated ectopia lentis could be caused by mutation in the FBN1 gene of a different nature or at a different site than those which cause the full-blown Marfan syndrome. Already a considerable range of phenotypes has been observed with FBN1 mutations. Diagnosis Loeys et al. (2010) reported the establishment of a revised Ghent nosology for the diagnosis of Marfan syndrome (MFS), which emphasizes the cardiovascular manifestations and in which aortic root aneurysm and ectopia lentis are considered cardinal clinical features that together prove sufficient for an unequivocal diagnosis of MFS. Noting that patients with familial ectopia lentis typically have some skeletal features of MFS and an FBN1 mutation, the authors proposed the designation 'ectopia lentis syndrome' (ELS) to better highlight the systemic nature of the condition and the need for assessment of features outside the ocular system. Loeys et al. (2010) stated that the presence of a personal or family history of aortic aneurysm, or the identification of an FBN1 mutation previously associated with aortic aneurysm, would be sufficient to transition a patient's diagnosis to Marfan syndrome. They also suggested that to ensure vigilance of other organ systems, the diagnosis of ectopia lentis syndrome should not be formally invoked before 20 years of age. Chandra et al. (2015) reviewed all published cases of FBN1-associated isolated ectopia lentis and found that 57 (46.3%) of 123 such probands were subsequently reclassified as MFS, and that 37 (38.5%) of 96 mutations reported to cause isolated ectopia lentis had also been found in patients with aortic dilation/dissection. The authors suggested that ectopia lentis caused by mutation in the FBN1 gene is actually part of a spectrum of fibrillinopathies with MFS, and that the term 'isolated ectopia lentis' should be avoided in such cases. Inheritance Falls and Cotterman (1943) described a family with a large number of affected persons in 5 generations, and Chace (1945) observed affected persons in 3 generations. Autosomal dominant inheritance was suggested. Jaureguy and Hall (1979) reported isolated congenital ectopia lentis in 6 persons in 3 generations of a family. Mapping Edwards et al. (1994) described a kindred in which ectopia lentis appeared to occur in the absence of clear indications of Marfan syndrome in other systems. Linkage studies demonstrated linkage to FBN1 on chromosome 15q21. Molecular Genetics Ades et al. (2004) used denaturing high performance liquid chromatography (DHPLC) to facilitate the characterization of the previously elusive FBN1 mutation in the large autosomal dominant ectopia lentis kindred described by Edwards et al. (1994). They presented a 9-year update of the clinical status of the family. They found an arg240-to-cys (R240C) mutation in the FBN1 gene (134797.0042), which had been reported 3 times before: once in a family with classic Marfan syndrome (Loeys et al., 2001), once in 1 member of a multigeneration ectopia lentis kindred (Korkko et al., 2002), and once in an adult from a familial ectopia lentis kindred who had ectopia lentis and involvement of the skin, without cardiovascular involvement (Comeglio et al., 2002). The report of Ades et al. (2004) was the second finding of the R240C mutation in association with isolated ectopia lentis, and supported the previous evidence that the R240C mutation can result in 2 quite distinct, yet related, phenotypes. Presumably modification by the genetic background is involved in the phenotypic differences. Comeglio et al. (2007) analyzed the FBN1 gene in 38 patients with isolated ectopia lentis and identified mutations in 19 (50%). Faivre et al. (2009) analyzed the clinical and molecular characteristics of 146 adult probands with known FBN1 mutations who did not fulfill the Ghent criteria for Marfan syndrome. The authors noted that in the 12 patients with isolated ectopia lentis, missense mutations involving a cysteine were predominant, mutations in exons 24-32 were underrepresented, and no mutations leading to a premature termination were found. They stated that analysis of recurrent mutations and of affected family members of probands with only 1 major clinical criterion argued for a clinical continuum between such phenotypes and classic Marfan syndrome. Aragon-Martin et al. (2010) analyzed the FBN1 gene in 36 UK patients with ectopia lentis who did not fulfill the Ghent criteria for Marfan syndrome and identified causative mutations in 23 (64%). The authors noted that this represented an improved mutation detection rate over their previous study (Comeglio et al., 2007), due to rescreening of patients who were negative for mutation by SSCA with the more sensitive dHPLC detection method. Yang et al. (2012) studied a 5-generation Chinese family in which 16 members were affected with isolated ectopia lentis and identified a heterozygous missense mutation in the FBN1 gene (R974C; 134797.0063) that segregated with the disease. Yang et al. (2012) reviewed published reports and stated that 18 FBN1 mutations associated with isolated ectopia lentis had been found, 3 of which had also been found in association with Marfan syndrome in different families; they also noted that 15 of the mutations were cysteine substitutions. Genotype/Phenotype Correlations Chandra et al. (2012) studied 16 patients with isolated ectopia lentis and identified homozygous or compound heterozygous mutations in the ADAMTSL4 gene (610113) in 8 patients (see, e.g., 610113.0003) and heterozygous mutations in the FBN1 gene in 4 patients. No mutations were identified in the remaining 4 patients. The median age of diagnosis of ectopia lentis was 35 years in patients with FBN1 mutations versus 2 years in patients with ADAMTSL4 mutations (p less than 0.01). Mean axial length was 22.74 mm in FBN1 patients compared to 27.54 mm in ADAMTSL4 patients (p less than 0.01). Other ophthalmic features, including corneal thickness and power, foveal thickness, visual acuity, and direction of lens displacement, were similar for both groups. Chandra et al. (2012) concluded that ADAMTSL4 mutations appear to cause earlier manifestation of ectopia lentis and are associated with increased axial length compared to mutations in FBN1. History Horner (1876) reported persons with ectopia lentis in 3 generations, and Usher (1924) reported 7 affected persons in 3 successive generations. In these early reports one cannot be certain that Marfan syndrome was not present. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Ectopia lentis, isolated (congenital lens dislocation) MOLECULAR BASIS \- Caused by mutation in the fibrillin-1 gene (FBN1, 134797.0015 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	ECTOPIA LENTIS 1, ISOLATED, AUTOSOMAL DOMINANT	c0013581	943	omim	https://www.omim.org/entry/129600	2019-09-22T16:41:51	{"doid": ["0111150"], "mesh": ["D004479"], "omim": ["129600"], "orphanet": ["1885"]}
For a phenotypic description and a discussion of genetic heterogeneity of psoriasis, see PSORS1 (177900). Mapping In a single large multiplex psoriasis family, Matthews et al. (1996) found evidence of linkage to 4q, using parametric linkage analyses. The maximum total pairwise lod score obtained was 3.03 with the microsatellite marker D4S1535 at theta = 0.08. Nonparametric multipoint analysis demonstrated significant excess allele sharing, with a P value of 0.0026, at the same locus. Matthews et al. (1996) as well as the workers reporting linkage to 17q urged caution in the assessment of linkage to psoriasis susceptibility loci as a number of factors complicate the analyses. These include incomplete penetrance, phenocopies, misdiagnosis, and the lack of a robust genetic model that accurately accounts for the observed familial aggregation. In a 12.5-cM genomewide scan for psoriasis susceptibility loci by recombination-based tests, Nair et al. (1997) found linkage to the HLA region (maximum lod = 3.52), as well as suggestive linkage to 16q (maximum lod = 2.50) and 20p (maximum lod = 2.62). However, Nair et al. (1997) could not confirm the previously reported locus on distal 4q. Enlund et al. (1999) performed complete multipoint parametric and nonparametric linkage analysis in 104 Swedish families (153 sib pairs) between the reported major psoriasis susceptibility loci on chromosomes 4q, 6p and 17q and polymorphic microsatellite markers in their vicinity. They confirmed a significant linkage to the HLA region on 6p but only a suggestive linkage to 17q and no linkage to 4q. In a genomewide association study of 223 U.S. patients with psoriasis, including 91 with psoriatic arthritis, and 519 European controls, followed by replication in a U.K. cohort of 576 patients with psoriatic arthritis and 480 controls, Liu et al. (2008) found evidence for a locus on chromosome 4q27, which harbors the IL2 (147680) and IL21 (605384) genes. The most significant association in the discovery set was with rs13151961 (p = 4 x 10(-5)); rs13151961, rs7684187, and rs6822844 showed association with psoriatic arthritis in the replication cohort (p values from 0.001 to 0.008). Liu et al. (2008) noted that this region overlaps with the PSORS3 locus (601454) and the CELIAC6 locus. Pathogenesis Caruso et al. (2009) observed high IL21 protein and mRNA levels in skin lesions from patients with psoriasis compared to skin samples from nonlesional skin and from controls. IL21 was mostly produced by CD4+ T cells. IL21 transcript levels and IL21-expressing circulating T cells were also found in peripheral blood of individuals with psoriasis. Lesional skin, T cells, B cells, and natural killer cells expressed the IL21 receptor. Treatment of keratinocytes from nonlesional skin caused epidermal hyperplasia and infiltration of the epidermis and dermis with inflammatory cells. In a human psoriasis xenograft mouse model, IL21 converted uninvolved skin into psoriatic plaques, and blockade of IL21 resolved inflammation and reduced keratinocyte proliferation. The findings indicated a role for IL21 gene, which maps to chromosome 4q26-q27, in the epidermal hyperplasia of psoriasis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	PSORIASIS 3, SUSCEPTIBILITY TO	c1832345	944	omim	https://www.omim.org/entry/601454	2019-09-22T16:14:43	{"omim": ["601454"]}
Paternal uniparental disomy of chromosome 6 is an uniparental disomy of paternal origin characterized by intrauterine growth retardation, transient neonatal diabetes mellitus, and macroglossia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Paternal uniparental disomy of chromosome 6	None	945	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96191	2021-01-23T17:38:00	{"icd-10": ["Q99.8"], "synonyms": ["UPD(6)pat"]}
Progressive external ophthalmoplegia-myopathy-emaciation syndrome is a rare mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies characterized by progressive external ophthalmoplegia without diplopia, cerebellar atrophy, proximal skeletal muscle weakness with generalized muscle wasting, profound emaciation, respiratory failure, spinal deformity and facial muscle weakness (manifesting with ptosis, dysphonia, dysphagia and nasal speech). Intellectual disability, gastrointestinal symptoms (e.g. nausea, abdominal fullness, and loss of appetite), dilated cardiomyopathy and renal colic have also been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Progressive external ophthalmoplegia-myopathy-emaciation syndrome	c3554462	946	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=352447	2021-01-23T17:18:55	{"omim": ["615084"], "icd-10": ["G71.3"], "synonyms": ["Mitochondrial DNA maintenance syndrome due to MGME1 deficiency", "PEO-myopathy-emaciation syndrome", "mtDNA maintenance syndrome due to MGME1 deficiency"]}
Saebo (1948) described 3 persons in 3 successive generations: grandfather, mother, and daughter. The tumor is distinct from the conjunctival lipodermoid of the Goldenhar syndrome (164210). Eyes \- Conjunctival lipoma Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	LIPOMA OF THE CONJUNCTIVA	c1835373	947	omim	https://www.omim.org/entry/151700	2019-09-22T16:38:51	{"mesh": ["C563620"], "omim": ["151700"]}
Dysgammaglobulinemia SpecialtyHematology Dysgammaglobulinemia is a type of immune disorder characterized by a reduction in some types of gamma globulins, resulting in heightened susceptibility to some infectious diseases where primary immunity is antibody based.[1][2] It is distinguished from hypogammaglobulinemia, which is a reduction in all types of gamma globulins.[3] Hyper IgM syndrome can be considered a form of dysgammaglobulinemia, because it results from a failure of transformation from IgM production to production of other antibodies, and so the condition can be interpreted as a reduction of the other types. ## Contents * 1 See also * 2 References * 3 Further reading * 4 External links ## See also[edit] * Immunodeficiency ## References[edit] 1. ^ "Dysgammaglobulinemia" at Dorland's Medical Dictionary 2. ^ Dysgammaglobulinemia at eMedicine Dictionary 3. ^ "hypogammaglobulinemia" at Dorland's Medical Dictionary ## Further reading[edit] * Raif S. Geha et al.: "Hyper Immunoglobulin M Immunodeficiency (Dysgammaglobulinemia)", Journal of Clinical Investigation, 1979 August; 64(2): 385–391, doi:10.1172/JCI109473. Accessed 2009-07-17. * Andre Cruchaud et al.: "The site of synthesis of the 19S T-globulins in dysgammaglobulinemia" (1962). Accessed 2009-07-17. ## External links[edit] Classification D * ICD-10: D80.2-D80.4 * ICD-9-CM: 279.06 * MeSH: D004406 * v * t * e Lymphoid and complement disorders causing immunodeficiency Primary Antibody/humoral (B) Hypogammaglobulinemia * X-linked agammaglobulinemia * Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia * IgA deficiency * IgG deficiency * IgM deficiency * Hyper IgM syndrome (1 * 2 * 3 * 4 * 5) * Wiskott–Aldrich syndrome * Hyper-IgE syndrome Other * Common variable immunodeficiency * ICF syndrome T cell deficiency (T) * thymic hypoplasia: hypoparathyroid (Di George's syndrome) * euparathyroid (Nezelof syndrome * Ataxia–telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency * Hyper IgM syndrome (1) Severe combined (B+T) * x-linked: X-SCID autosomal: Adenosine deaminase deficiency * Omenn syndrome * ZAP70 deficiency * Bare lymphocyte syndrome Acquired * HIV/AIDS Leukopenia: Lymphocytopenia * Idiopathic CD4+ lymphocytopenia Complement deficiency * C1-inhibitor (Angioedema/Hereditary angioedema) * Complement 2 deficiency/Complement 4 deficiency * MBL deficiency * Properdin deficiency * Complement 3 deficiency * Terminal complement pathway deficiency * Paroxysmal nocturnal hemoglobinuria * Complement receptor deficiency This article about a disease of the blood or immune system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Dysgammaglobulinemia	c0013374	948	wikipedia	https://en.wikipedia.org/wiki/Dysgammaglobulinemia	2021-01-18T19:10:52	{"mesh": ["D004406"], "umls": ["C0013374"], "icd-9": ["279.06"], "icd-10": ["D80.4", "D80.2"], "wikidata": ["Q3042106"]}
Chronic solvent-induced encephalopathy (CSE) is a condition induced by long-term exposure to organic solvents, often but not always in the workplace, that lead to a wide variety of persisting sensorimotor polyneuropathies and neurobehavioral deficits even after solvent exposure has been removed.[1][2][3] This syndrome can also be referred to as "psycho-organic syndrome", "organic solvent syndrome", "chronic painter's syndrome", "occupational solvent encephalopathy", "solvent intoxication", "toxic solvent syndrome", "painters disease", "psycho-organic syndrome", "chronic toxic encephalopathy", and "neurasthenic syndrome".[1][2][3][4][5] The multiple names of solvent-induced syndromes combined with inconsistency in research methods makes referencing this disease difficult and its catalog of symptoms vague.[1][3][6][7] ## Contents * 1 Symptoms * 1.1 Neurological * 1.2 Sensory alterations * 1.3 Psychological * 2 Causes * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 History * 6 References ## Symptoms[edit] Two characteristic symptoms of CSE are deterioration of memory (particularly short-term memory), and attention impairments. There are, however, numerous other symptoms that accompany to varying degrees. Variability in the research methods studying CSE makes characterizing these symptoms difficult, and some may be questionable regarding whether they are actual symptoms of solvent-induced syndromes, simply because of how infrequently they appear.[7] Characterizing of CSE symptoms is more difficult because CSE is currently poorly defined, and the mechanism behind it is not understood yet. ### Neurological[edit] Reported neurological symptoms include difficulty sleeping, decrease in intellectual capacity, dizziness, altered visual perceptive abilities, affected psychomotor skills, forgetfulness, and disorientation.[6][8] The mechanism behind these symptoms beyond solvent molecules crossing the blood-brain barrier is currently unknown. Neurological signs include impaired vibratory sensation at extremities and an inability to maintain steady motion, a possible effect from psychomotor damage in the brain. Other symptoms that have been seen include fatigue, decreased strength, and unusual gait.[9] One study found that there was a correlation between decreased red blood cell count and level of solvent exposure, but not enough data has been found to support any blood tests to screen for CSE. ### Sensory alterations[edit] A 1988 study indicated that some solvent-exposed workers suffered from loss of smell or damage to color vision; however this may or may not have been actually caused by exposure to organic solvents.[8] There is other evidence for subtle impairment of color vision (especially impairment of Titian color or "blue-yellow" color discernment), synergistic exacerbation of hearing loss, and loss of the sense of smell (anosmia).[7] ### Psychological[edit] Psychological symptoms of CSE that have been reported include mood swings, increased irritability, depression, a lack of initiative, uncontrollable and intense displays of emotion such as spontaneous laughing or crying, and a severe lack of interest in sex.[1][2][6][8] Some psychological symptoms are believed to be linked to frustration with other symptoms, neurological, or pathophysiological symptoms of CSE. A case study of a painter diagnosed with CSE reported that the patient frequently felt defensive, irritable, and depressed because of his memory deficiencies.[4] ## Causes[edit] Organic solvents that cause CSE are characterized as volatile, blood soluble, lipophilic compounds that are typically liquids at normal temperature.[2][10] These can be compounds or mixtures used to extract, dissolve, or suspend non-water-soluble materials such as fats, oils, lipids, cellulose derivatives, waxes, plastics, and polymers. These solvents are often used industrially in the production of paints, glues, coatings, degreasing agents, dyes, polymers, pharmaceuticals, and printing inks. Exposure to solvents can occur by inhalation, ingestion, or direct absorption through the skin. Of the three, inhalation is the most common form of exposure, with the solvent able to rapidly pass through lung membranes and then into fatty tissue or cell membranes. Once in the bloodstream, organic solvents easily cross the blood-brain barrier, due to their lipophilic properties.[4] However, the sequence of effects that these solvents have on the brain is not yet fully understood.[5] Some common organic solvents known to cause CSE include formaldehyde, acetates, and alcohols.[citation needed] ## Diagnosis[edit] Due to its non-specific nature, diagnosing CSE requires a multidisciplinary "Solvent Team" typically consisting of a neurologist, occupational physician, occupational hygienist, neuropsychologist, and sometimes a psychiatrist or toxicologist. Together, the team of specialists assess the patient's history of exposure, symptoms, and course of symptom development relative to the amount and duration of exposure, presence of neurological signs, and any existing neuropsychological impairment.[1] Furthermore, CSE must be diagnosed "by exclusion". This means that all other possible causes of the patient's symptoms must first be ruled out beforehand. Because screening and assessing for CSE is a complex and time-consuming procedure requiring several specialists of multiple fields, few cases of CSE are formally diagnosed in the medical field. This may, in part, be a reason for the syndrome's lack of widespread recognition. The solvents responsible for neurological effects dissipate quickly after an exposure, leaving only indirect evidence of their presence, in the form of temporary or permanent impairments. Brain imaging techniques which have been explored in research have shown little promise as alternative methods to diagnose CSE. Neuroradiology and functional imaging have shown mild cortical atrophy,[4] and effects in dopamine-mediated frontostriatal circuits in some cases.[1] Examinations of regional cerebral blood flow in some imaging techniques have also shown some cerebrovascular abnormalities in patients with CSE, but the data were not different enough from healthy patients to be considered significant.[6] The most promising brain imaging technique being studied currently is functional magnetic resonance imaging (fMRI) but as of now, no specific brain imaging techniques are available to reliably diagnose CSE.[1][5] ### Classification[edit] Introduced by a working group from the World Health Organization (WHO) in 1985, WHO diagnostic criteria states that CSE can occur in three stages, organic affective syndrome (type I), mild chronic toxic encephalopathy (type II), and severe chronic toxic encephalopathy (type III). Shortly after, a workshop in Raleigh-Durham, NC (United States) released a second diagnostic criterion which recognizes four stages as symptoms only (type 1), sustained personality or mood swings (type 2A), impairment of intellectual function (type 2B), and dementia (type 3). Though not identical, the WHO and Raleigh criteria are relatively comparable. WHO type I and Raleigh types 1 and 2A are believed to encompass the same stages of CSE, and WHO type II and Raleigh type 2B both involve deficiencies in memory and attention. No other international classifications for CSE have been proposed, and neither the WHO nor Raleigh criteria have been uniformly accepted for epidemiological studies.[1][2][10] ## Treatment[edit] Like diagnosis, treating CSE is difficult because it is vaguely defined and data on the mechanism of CSE effects on neural tissue are lacking. There is no existing treatment that is effective at completely recovering any neurological or physical function lost due to CSE. This is believed to be because of the limited regeneration capabilities in the central nervous system. Furthermore, existing symptoms of CSE can potentially worsen with age. Some symptoms of CSE, such as depression and sleep issues, can be treated separately, and therapy is available to help patients adjust to any untreatable disabilities. Current treatment for CSE involves treating accompanying psychopathology, symptoms, and preventing further deterioration.[3][5] ## History[edit] Cases of CSE have been studied predominantly in northern Europe, though documented cases have been found in other countries such as the United States, France, and China. The first documented evidence for CSE was in the early 1960s from a paper published by Helena Hanninen, a Finnish neuropsychologist. Her paper described a case of workers suffering from carbon disulfide intoxication at a rubber manufacturing company and coined the term "psycho-organic syndrome".[citation needed] Studies of solvent effects on intellectual functioning, memory, and concentration were carried out in the Nordic countries, with Denmark spearheading the research. Growing awareness of the syndrome in the Nordic countries occurred in the 1970s. To reduce cases of CSE in the workforce, a diagnostic criterion for CSE appeared on information notices in occupational disease records in the European Commission. Following, from 1998 to 2004, was a health surveillance program for CSE cases among construction painters in the Netherlands. By 2000, a ban was put into action against using solvent-based paints indoors, which resulted in a considerable reduction of solvent exposure to painters. As a result, the number of CSE cases dropped substantially after 2002. In 2005–2007, no new CSE cases were diagnosed among construction painters in the Netherlands, and no occupational CSE has been encountered in workers under thirty years of age in Finland since 1995.[1][11] Though movements to reduce CSE have been successful, CSE still poses an issue to many workers that are at occupational risk. Statistics published in 2012 by Nicole Cherry et al. claim that at least 20% of employees in Finland still encounter organic solvents at the workplace, and 10% of them experience some form of disadvantage from the exposure. In Norway, 11% of the male population of workers and 7% of female workers are still exposed to solvents daily and as of 2006, the country has the highest rate of diagnosed CSE in Europe.[2][11] Furthermore, due to the complexity of screening for CSE, there is still a high likelihood of a population of undiagnosed cases.[1] Occupations that have been found to have higher risk of causing CSE are painter, printer, industrial cleaner, and paint or glue manufacturer.[5] Of them, painters have been found to have the highest recorded incidence of CSE. Spray painters in particular have higher exposure intensities than other painters.[3] Studies of instances of CSE have specifically been carried out in naval dockyards, mineral fiber manufacturing companies, and rayon viscose plants.[12] ## References[edit] 1. ^ a b c d e f g h i j van der Laan, Gert; Markku Sainio (2012). "Chronic Solvent induced Encephalopathy: A step Forward". NeuroToxicology. 33 (4): 897–901. doi:10.1016/j.neuro.2012.04.012. PMID 22560998. 2. ^ a b c d e f Bast-Pettersen, Rita (November 2009). "The neuropsychological diagnosis of chronic solvent induced encephalopathy (CSE)—A reanalysis of neuropsychological test results in a group of CSE patients diagnosed 20 years ago, based on comparisons with matched controls". NeuroToxicology. 30 (6): 1195–1201. doi:10.1016/j.neuro.2009.04.008. PMID 19422849. 3. ^ a b c d e Baker, EL; Letz, RE; Eisen, EA; Pothier, LJ; Plantamura, DL; Larson, M; Wolford, R (February 1988). "Neurobehavioral effects of solvents in construction painters". Journal of Occupational Medicine. 30 (2): 116–23. PMID 3351646. 4. ^ a b c d Feldman, Robert G.; Ratner, Marcia Hillary; Ptak, Thomas (1999). "Chronic Toxic Encephalopathy in a Painter Exposed to Mixed Solvents". Environmental Health Perspectives. National Institute of Environmental Health Sciences. 107 (5): 417–22. doi:10.1289/ehp.99107417. ISSN 0091-6765. JSTOR 3434546. PMC 1566426. PMID 10210698. 5. ^ a b c d e van Valen, Evelien; Wekking, Ellie; van der Laan, Gert; Sprangers, Mirjam; van Dijk, Frank (November 2009). "The course of chronic solvent induced encephalopathy: A systematic review". NeuroToxicology. 30 (6): 1172–1186. doi:10.1016/j.neuro.2009.06.002. PMID 19538991. 6. ^ a b c d Krstev, Srmena; Bogoljub Perunicic; Boris Farkic; Radmila Banicevic (March 1, 2003). "Neuropsychiatric Effects in Workers with Occupational Exposure to Carbon Disulfide". Journal of Occupational Health. 45 (2): 81–87. doi:10.1539/joh.45.81. PMID 14646298.CS1 maint: date and year (link) 7. ^ a b c Dick, F D (1 March 2006). "Solvent neurotoxicity". Occupational and Environmental Medicine. 63 (3): 221–226. doi:10.1136/oem.2005.022400. PMC 2078137. PMID 16497867. 8. ^ a b c Baker, Edward L. (October 1, 1994). "A Review of Recent Research on Health Effects of Human Occupational Exposure to Organic Solvents: A Critical Review". Journal of Occupational Medicine. 36 (10): 1079–1092. doi:10.1097/00043764-199410000-00010. PMID 7830166.CS1 maint: date and year (link) 9. ^ Maizlish, N A; L J Fine; J W Albers; L Whitehead; G D Langold (January 1, 1987). "A neurological evaluation of workers exposed to mixtures of organic solvents". British Journal of Industrial Medicine. 44 (1): 14–25. doi:10.1136/oem.44.1.14. PMC 1007773. PMID 3814530.CS1 maint: date and year (link) 10. ^ a b van der Hoek, Joffrey; Maarten M. Verberk; Gerard Hageman (December 27, 1999). "Criteria for solvent-induced chronic toxic encephalopathy: a systematic review". International Archives of Occupational and Environmental Health. 73 (6): 362–368. doi:10.1007/s004200000119. PMID 11007338. S2CID 39903241. 11. ^ a b Furu, Heidi; Markku Sainio; Hanna Kaisa Hyvarinen; Ritva Akila; Beatrice Back; Sanni Uuksulainen; Ari Kaukiainen (2012). "Detecting chronic solvent encephalopathy in occupations at risk". NeuroToxicology. 33 (4): 734–741. doi:10.1016/j.neuro.2012.04.018. PMID 22560996. 12. ^ Cherry, Nicola; Helen Hutchins; T Pace; H A Waldron (May 1, 1985). "Neurobehavioral effects of repeated occupational exposure to toluene and paint solvents". British Journal of Industrial Medicine. 42 (5): 291–300. doi:10.1136/oem.42.5.291. PMC 1007475. PMID 3872680.CS1 maint: date and year (link) * v * t * e Occupational safety and health Occupational diseases and injuries * Acrodynia * Asbestosis * Asthma * Barotrauma * Berylliosis * Brucellosis * Byssinosis ("brown lung") * Chalicosis * Chimney sweeps' carcinoma * Chronic solvent-induced encephalopathy * Coalworker's pneumoconiosis ("black lung") * Concussions in sport * Decompression sickness * De Quervain syndrome * Erethism * Exposure to human nail dust * Farmer's lung * Fiddler's neck * Flock worker's lung * Glassblower's cataract * Golfer's elbow * Hearing loss * Hospital-acquired infection * Indium lung * Laboratory animal allergy * Lead poisoning * Mesothelioma * Metal fume fever * Mule spinners' cancer * Noise-induced hearing loss * Phossy jaw * Pneumoconiosis * Radium jaw * Repetitive strain injury * Silicosis * Silo-filler's disease * Sports injury * Surfer's ear * Tennis elbow * Tinnitus * Writer's cramp Occupational hygiene * Occupational hazard * Biological hazard * Chemical hazard * Physical hazard * Psychosocial hazard * Hierarchy of hazard controls * Prevention through design * Exposure assessment * Occupational exposure limit * Occupational epidemiology * Workplace health surveillance Professions * Environmental health * Industrial engineering * Occupational health nursing * Occupational health psychology * Occupational medicine * Occupational therapist * Safety engineering Agencies and organizations * Canadian Centre for Occupational Health and Safety * European Agency for Safety and Health at Work * UK Health and Safety Executive * International Labour Organization * US National Institute for Occupational Safety and Health * US Occupational Safety and Health Administration * National Institute for Safety and Health at Work (Spain) * World Health Organization Standards * Bangladesh Accord * ISO 45001 * Occupational Safety and Health Convention, 1981 * Worker Protection Standard (US) * Working Environment Convention, 1977 Safety * Checklist * Code of practice * Contingency plan * Diving safety * Emergency procedure * Emergency evacuation * Hazard * Hierarchy of hazard controls * Hazard elimination * Administrative controls * Engineering controls * Hazard substitution * Personal protective equipment * Job safety analysis * Lockout-tagout * Permit To Work * Operations manual * Redundancy (engineering) * Risk assessment * Safety culture * Standard operating procedure Legislation * Diving regulations * Occupational Safety and Health Act (United States) See also * Environment, health and safety * Environmental toxicology * Ergonomics * Health physics * Indoor air quality * International Chemical Safety Card * National Day of Mourning (Canadian observance) * Process safety management * Public health * Risk management * Safety data sheet * Toxic tort * Workers' compensation * Category * Occupational diseases * Journals * Organizations * Commons * Glossary [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Chronic solvent-induced encephalopathy	None	949	wikipedia	https://en.wikipedia.org/wiki/Chronic_solvent-induced_encephalopathy	2021-01-18T19:07:57	{"wikidata": ["Q5114000"]}
Epidermoid cysts are keratinous cysts which may be impossible to distinguish clinically from sebaceous cysts (184500). Epidermoid cysts occur with Gardner syndrome (175100). Inheritance \- Autosomal dominant Skin \- Epidermoid cysts ▲ 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	EPIDERMOID CYSTS	c0014511	950	omim	https://www.omim.org/entry/131600	2019-09-22T16:41:33	{"mesh": ["D004814"], "omim": ["131600"], "icd-9": ["706.2"], "icd-10": ["L72.0", "L72.3", "K09.8"]}
A rare common cystic lymphatic malformation characterized by a benign cystic lesion composed of dilated lymphatic channels. Mixed cystic lesions consist of cysts both larger (macrocystic) and smaller (microcystic) than 1 cm in diameter. They usually present at birth or during the first years of life and most often occur in the head and neck region but may affect any site. Symptoms depend on the location and extent of the lesion. Infection, trauma, or intracystic hemorrhage can lead to lesional expansion. Malignant transformation does not occur. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Mixed cystic lymphatic malformation	None	951	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=458792	2021-01-23T17:17:03	{"icd-10": ["D18.1"], "synonyms": ["Mixed cystic lymphangioma"]}
Lower respiratory tract infection Conducting passages SpecialtyPulmonology Frequency291 million (2015)[1] Deaths2.74 million (2015)[2] Lower respiratory tract infection (LRTI) is a term often used as a synonym for pneumonia but can also be applied to other types of infection including lung abscess and acute bronchitis. Symptoms include shortness of breath, weakness, fever, coughing and fatigue.[3] A routine chest X-ray is not always necessary for people who have symptoms of a lower respiratory tract infection.[4] Influenza affects both the upper and lower respiratory tracts.[citation needed] Antibiotics are the first line treatment for pneumonia; however, they are neither effective nor indicated for parasitic or viral infections. Acute bronchitis typically resolves on its own with time. In 2015 there were about 291 million cases.[1] These resulted in 2.74 million deaths down from 3.4 million deaths in 1990.[5][2] This was 4.8% of all deaths in 2013.[5] ## Contents * 1 Bronchitis * 2 Pneumonia * 3 Causes * 4 Prevention * 5 Treatment * 6 Epidemiology * 7 Society and culture * 8 References * 9 External links ## Bronchitis[edit] Main article: Bronchitis Bronchitis describes the swelling or inflammation of the[6] bronchial tubes. Additionally, bronchitis is described as either acute or chronic depending on its presentation and is also further described by the causative agent. Acute bronchitis can be defined as acute bacterial or viral infection of the larger airways in healthy patients with no history of recurrent disease.[7] It affects over 40 adults per 1000 each year and consists of transient inflammation of the major bronchi and trachea.[8] Most often it is caused by viral infection and hence antibiotic therapy is not indicated in immunocompetent individuals.[9][6] Viral bronchitis can sometimes be treated using antiviral medications depending on the virus causing the infection, and medications such as anti-inflammatory drugs and expectorants can help mitigate the symptoms.[10][6] Treatment of acute bronchitis with antibiotics is common but controversial as their use has only moderate benefit weighted against potential side effects (nausea and vomiting), increased resistance, and cost of treatment in a self-limiting condition.[8][11] Beta2 agonists are sometimes used to relieve the cough associated with acute bronchitis. In a recent systematic review it was found there was no evidence to support their use.[6] Acute exacerbations of chronic bronchitis (AECB) are frequently due to non-infective causes along with viral ones. 50% of patients are colonised with Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis.[7] Antibiotics have only been shown to be effective if all three of the following symptoms are present: increased dyspnea, increased sputum volume, and purulence. In these cases, 500 mg of amoxicillin orally, every 8 hours for 5 days or 100 mg doxycycline orally for 5 days should be used.[7] ## Pneumonia[edit] Main article: Pneumonia Pneumonia occurs in a variety of situations and treatment must vary according to the situation.[10] It is classified as either community or hospital acquired depending on where the patient contracted the infection. It is life-threatening in the elderly or those who are immunocompromised.[12][13] The most common treatment is antibiotics and these vary in their adverse effects and their effectiveness.[12][14] Pneumonia is also the leading cause of death in children less than five years of age in low income countries.[14] The most common cause of pneumonia is pneumococcal bacteria, Streptococcus pneumoniae accounts for 2/3 of bacteremic pneumonias.[15] This is a dangerous type of lung infection with a mortality rate of around 25%.[13] For optimal management of a pneumonia patient, the following must be assessed: pneumonia severity (including treatment location, e.g., home, hospital or intensive care), identification of causative organism, analgesia of chest pain, the need for supplemental oxygen, physiotherapy, hydration, bronchodilators and possible complications of emphysema or lung abscess.[16] ## Causes[edit] Deaths from lower respiratory infections per million persons in 2012 24-120 121-151 152-200 201-241 242-345 346-436 437-673 674-864 865-1,209 1,210-2,085 Disability-adjusted life year for lower respiratory infections per 100,000 inhabitants in 2004.[17] no data less than 100 100–700 700–1,400 1,400–2,100 2,100–2,800 2,800–3,500 3,500–4,200 4,200–4,900 4,900–5,600 5,600–6,300 6,300–7,000 more than 7,000 Typical bacterial Infections: * Haemophilus influenzae * Staphylococcus aureus * Klebsiella pneumoniae Atypical bacterial Infections: * Legionella pneumophila * Mycoplasma pneumoniae * Chlamydophila pneumoniae * Chlamydia psittaci This list is incomplete; you can help by adding missing items with reliable sources. Parasitic infections: * Respiratory cryptosporidiosis Viral infections: * Adenovirus * Influenza A virus * Influenza B virus * Human parainfluenza viruses * Human respiratory syncytial virus * Severe acute respiratory syndrome coronavirus (SARS-CoV) * Middle East respiratory syndrome coronavirus (MERS-CoV) * Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Aspiration pneumonia ## Prevention[edit] Vaccination helps prevent bronchopneumonia, mostly against influenza viruses, adenoviruses, measles, rubella, streptococcus pneumoniae, haemophilus influenzae, diphtheria, bacillus anthracis, chickenpox, and bordetella pertussis.[18] Specifically for the children with low serum retinol or who are suffering from malnutrition, vitamin A supplements are recommended as a preventive measure against acute LRTI.[19] ## Treatment[edit] Antibiotics do not help the many lower respiratory infections which are caused by parasites or viruses. While acute bronchitis often does not require antibiotic therapy, antibiotics can be given to patients with acute exacerbations of chronic bronchitis.[20] The indications for treatment are increased dyspnoea, and an increase in the volume or purulence of the sputum.[21] The treatment of bacterial pneumonia is selected by considering the age of the patient, the severity of the illness and the presence of underlying disease. A systematic review of 32 randomised controlled trials with 6,078 participants with acute respiratory infections compared procalcitonin (a blood marker for bacterial infections) to guide the initiation and duration of antibiotic treatment, against no use of procalcitonin. Among 3,336 people receiving procalcitonin-guided antibiotic therapy, there were 236 deaths, compared to 336 deaths out 3,372 participants who did not. Procalcitonin-guided antibiotic therapy also reduced the antibiotic use duration by 2.4 days, and there were fewer antibiotic side effects. This means that procalcitonin is useful for guiding whether to use antibiotics for acute respiratory infections and the duration of the antibiotic.[22] Amoxicillin and doxycycline are suitable for many of the lower respiratory tract infections seen in general practice.[20] Another cochrane review suggests that new studies are needed to confirm that azithromycin may lead to less treatment failure and lower side effects than amoxycillin.[23] In the other hand, there is no sufficient evidence to consider the antibiotics as a prophlaxis for the high risk children under 12 years.[24] Oxygen supplementation is often recommended for people with severe lower respiratory tract infections.[25] Oxygen can be provided in a non-invasive manner using nasal prongs, face masks, a head box or hood, a nasal catheter, or a nasopharyngeal catheter.[25] For children younger than 15 years old, nasopharyngel catheters or nasal prongs are recommended over a face mask or head box.[25] A Cochrane review in 2014 presented a summary to identify children complaining of severe LRTI, however; further research is required to determine the effectiveness of supplemental oxygen and the best delivery method.[25] ## Epidemiology[edit] Lower respiratory infectious disease is the fifth-leading cause of death and the combined leading infectious cause of death, being responsible for 2.74 million deaths worldwide.[26] This is generally similar to estimates in the 2010 Global Burden of Disease study.[27] This total only accounts for Streptococcus pneumoniae and Haemophilus Influenzae infections and does not account for atypical or nosocomial causes of lower respiratory disease, therefore underestimating total disease burden. ## Society and culture[edit] Lower respiratory tract infections place a considerable strain on the health budget and are generally more serious than upper respiratory infections. Workplace burdens arise from the acquisition of a lower respiratory tract infection, with factors such as total per person expenditures and total medical service utilisation demonstrated as greater among individuals experiencing a lower respiratory tract infection.[28] Pan-national data collection indicates that childhood nutrition plays a significant role in determining the acquisition of a lower respiratory tract infection, with the promotion of the implementation of nutrition program, and policy guidelines in affected countries.[26] ## References[edit] 1. ^ a b GBD 2015 Disease Injury Incidence Prevalence Collaborators (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282. 2. ^ a b GBD 2015 Mortality Causes of Death Collaborators (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/s0140-6736(16)31012-1. PMC 5388903. PMID 27733281. 3. ^ Antibiotic Expert Group (2014). Therapeutic Guidelines: Antibiotic (15th ed.). Therapeutic Guidelines Limited. ISBN 9780992527211. 4. ^ Cao, Amy Millicent Y.; Choy, Joleen P.; Mohanakrishnan, Lakshmi Narayana; Bain, Roger F.; van Driel, Mieke L. (2013-12-26). "Chest radiographs for acute lower respiratory tract infections". The Cochrane Database of Systematic Reviews (12): CD009119. doi:10.1002/14651858.CD009119.pub2. ISSN 1469-493X. PMC 6464822. PMID 24369343. 5. ^ a b GBD 2013 Mortality Causes of Death Collaborators (January 2015). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013" (PDF). Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442. 6. ^ a b c d Becker LA, Hom J, Villasis-Keever M, van der Wouden JC (September 2015). "Beta2-agonists for acute cough or a clinical diagnosis of acute bronchitis". The Cochrane Database of Systematic Reviews (9): CD001726. doi:10.1002/14651858.CD001726.pub5. PMC 7078572. PMID 26333656. 7. ^ a b c Antibiotic Expert Group. Therapeutic guidelines: Antibiotic. 13th ed. North Melbourne: Therapeutic Guidelines; 2006. 8. ^ a b Wark P (July 2015). "Bronchitis (acute)". BMJ Clinical Evidence. 2015. PMC 4505629. PMID 26186368. 9. ^ Therapeutic guidelines : respiratory. 2nd ed: North Melbourne : Therapeutic Guidelines Limited, 2000.[page needed] 10. ^ a b Integrated pharmacology / Clive Page ... [et al.]. 2nd ed: Edinburgh : Mosby, 2002.[page needed] 11. ^ Smith, SM; Fahey, T; Smucny, J; Becker, LA (1 March 2014). Smith, Susan M (ed.). "Antibiotics for acute bronchitis". The Cochrane Database of Systematic Reviews (3): CD000245. doi:10.1002/14651858.CD000245.pub3. PMID 24585130. 12. ^ a b Pakhale S, Mulpuru S, Verheij TJ, Kochen MM, Rohde GG, Bjerre LM (October 2014). "Antibiotics for community-acquired pneumonia in adult outpatients". The Cochrane Database of Systematic Reviews (10): CD002109. doi:10.1002/14651858.CD002109.pub4. PMC 7078574. PMID 25300166. 13. ^ a b Moberley S, Holden J, Tatham DP, Andrews RM (January 2013). "Vaccines for preventing pneumococcal infection in adults". The Cochrane Database of Systematic Reviews (1): CD000422. doi:10.1002/14651858.CD000422.pub3. PMC 7045867. PMID 23440780. 14. ^ a b Lodha R, Kabra SK, Pandey RM (June 2013). "Antibiotics for community-acquired pneumonia in children". The Cochrane Database of Systematic Reviews (6): CD004874. doi:10.1002/14651858.CD004874.pub4. PMC 7017636. PMID 23733365. 15. ^ The Merck manual of diagnosis and therapy. 17th ed / Mark H. Beers and Robert Berkow ed: Whitehouse Station, N.J. : Merck Research Laboratories, 1999.[page needed] 16. ^ Kumar Pius, Prince Sree; Alexis, Anitha; P, Suresh Kumar; Ganesan, Manivel (2017). "Diagnosis of Sputum Culture Positive Organisms and Their Antimicrobial Sensitivity Profile in a Tertiary Care Centre- Kanyakumari". Journal of Evidence Based Medicine and Healthcare. 4 (4): 168–171. doi:10.18410/jebmh/2017/33. 17. ^ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002. 18. ^ Woodhead M, Blasi F, Ewig S, Garau J, Huchon G, Ieven M, Ortqvist A, Schaberg T, Torres A, van der Heijden G, Read R, Verheij TJ (November 2011). "Guidelines for the management of adult lower respiratory tract infections--full version". Clinical Microbiology and Infection. 17 Suppl 6: E1–59. doi:10.1111/j.1469-0691.2011.03672.x. PMC 7128977. PMID 21951385. 19. ^ Chen, Hengxi; Zhuo, Qi; Yuan, Wei; Wang, Juan; Wu, Taixiang (23 January 2008). "Vitamin A for preventing acute lower respiratory tract infections in children up to seven years of age". Cochrane Database of Systematic Reviews (1): CD006090. doi:10.1002/14651858.CD006090.pub2. PMID 18254093. 20. ^ a b Ball P, Baquero F, Cars O, File T, Garau J, Klugman K, Low DE, Rubinstein E, Wise R (January 2002). "Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence". The Journal of Antimicrobial Chemotherapy. 49 (1): 31–40. doi:10.1093/jac/49.1.31. PMID 11751764. 21. ^ Woodhead M, Blasi F, Ewig S, Huchon G, Ieven M, Leven M, Ortqvist A, Schaberg T, Torres A, van der Heijden G, Verheij TJ (December 2005). "Guidelines for the management of adult lower respiratory tract infections". The European Respiratory Journal. 26 (6): 1138–80. doi:10.1183/09031936.05.00055705. PMID 16319346. 22. ^ Schuetz, Philipp; Wirz, Yannick; Sager, Ramon; Christ-Crain, Mirjam; Stolz, Daiana; Tamm, Michael; Bouadma, Lila; Luyt, Charles E; Wolff, Michel; Chastre, Jean; Tubach, Florence; Kristoffersen, Kristina B; Burkhardt, Olaf; Welte, Tobias; Schroeder, Stefan; Nobre, Vandack; Wei, Long; Bucher, Heiner C C; Bhatnagar, Neera; Annane, Djillali; Reinhart, Konrad; Branche, Angela; Damas, Pierre; Nijsten, Maarten; de Lange, Dylan W; Deliberato, Rodrigo O; Lima, Stella SS; Maravić-Stojković, Vera; Verduri, Alessia; Cao, Bin; Shehabi, Yahya; Beishuizen, Albertus; Jensen, Jens-Ulrik S; Corti, Caspar; Van Oers, Jos A; Falsey, Ann R; de Jong, Evelien; Oliveira, Carolina F; Beghe, Bianca; Briel, Matthias; Mueller, Beat (12 October 2017). "Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections". Cochrane Database of Systematic Reviews. 10: CD007498. doi:10.1002/14651858.CD007498.pub3. PMC 6485408. PMID 29025194. 23. ^ Laopaiboon, Malinee; Panpanich, Ratana; Swa Mya, Kyaw (8 March 2015). "Azithromycin for acute lower respiratory tract infections". Cochrane Database of Systematic Reviews (3): CD001954. doi:10.1002/14651858.CD001954.pub4. PMC 6956663. PMID 25749735. 24. ^ Onakpoya, Igho J; Hayward, Gail; Heneghan, Carl J (26 September 2015). "Antibiotics for preventing lower respiratory tract infections in high-risk children aged 12 years and under". Cochrane Database of Systematic Reviews (9): CD011530. doi:10.1002/14651858.CD011530.pub2. PMID 26408070. 25. ^ a b c d Rojas-Reyes, Maria Ximena; Granados Rugeles, Claudia; Charry-Anzola, Laura Patricia (10 December 2014). "Oxygen therapy for lower respiratory tract infections in children between 3 months and 15 years of age". Cochrane Database of Systematic Reviews (12): CD005975. doi:10.1002/14651858.CD005975.pub3. PMC 6464960. PMID 25493690. 26. ^ a b GBD 2015 LRI Collaborators (November 2017). "Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of Disease Study 2015". The Lancet. Infectious Diseases. 17 (11): 1133–1161. doi:10.1016/S1473-3099(17)30396-1. PMC 5666185. PMID 28843578. 27. ^ Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, et al. (December 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. hdl:10536/DRO/DU:30050819. PMID 23245604. 28. ^ Chen Y, Shan X, Zhao J, Han X, Tian S, Chen F, Su X, Sun Y, Huang L, Grundmann H, Wang H, Han L (November 2017). "Predicting nosocomial lower respiratory tract infections by a risk index based system". Scientific Reports. 7 (1): 15933. Bibcode:2017NatSR...715933C. doi:10.1038/s41598-017-15765-z. PMC 5698311. PMID 29162852. ## External links[edit] Classification D * ICD-10: J10-J22, J40-J47 * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Lower respiratory tract infection	c0149725	952	wikipedia	https://en.wikipedia.org/wiki/Lower_respiratory_tract_infection	2021-01-18T18:34:04	{"icd-10": ["J10"], "wikidata": ["Q3631290"]}
A number sign (#) is used with this entry because hyperekplexia-3 (HKPX3) is caused by homozygous or compound heterozygous mutation in the GLYT2 gene (SLC6A5; 604159) on chromosome 11p15. There is also evidence that a heterozygous mutation in the SLC6A5 gene can result in HKPX3. For a general description and a discussion of genetic heterogeneity of hyperekplexia, see HKPX1 (149400). Clinical Features Rees et al. (2006) reported 7 patients, including 2 sibs, with hyperekplexia. Affected individuals presented with neonatal hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. Notably, in some cases, symptoms resolved in the first year of life. Inheritance In 5 families with HKPX3 reported by Rees et al. (2006), the transmission pattern was consistent with autosomal recessive inheritance. The mother of 1 patient, who was heterozygous for a truncating SLC6A5 mutation (604159.0002) had nocturnal myoclonus and a nervous disposition, suggesting a partial phenotype. Another patient had a heterozygous mutation, consistent with autosomal dominant inheritance. Molecular Genetics In 6 patients, including 2 brothers, with hyperekplexia-3, Rees et al. (2006) identified homozygous or compound heterozygous mutations in the SLC6A5 gene (see, e.g., 604159.0001-604159.0007). An additional patient with the disorder was found to carry a heterozygous mutation (604159.0008), consistent with autosomal dominant inheritance. INHERITANCE \- Autosomal dominant \- Autosomal recessive RESPIRATORY \- Apneic episodes, neonatal \- Breath-holding episodes, infancy MUSCLE, SOFT TISSUES \- Hypertonia, neonatal \- Muscle stiffness NEUROLOGIC Central Nervous System \- Exaggerated startle response to tactile or acoustic stimuli \- Hypertonicity MISCELLANEOUS \- Onset in infancy \- Some patients have resolution of symptoms in first year of life MOLECULAR BASIS \- Caused by mutation in the presynaptic glycine transporter-2 gene (SLC6A5, {604159.0001) ▲ 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	HYPEREKPLEXIA 3	c1835614	953	omim	https://www.omim.org/entry/614618	2019-09-22T15:54:46	{"doid": ["0060698"], "mesh": ["C538136"], "omim": ["614618"], "orphanet": ["3197"], "genereviews": ["NBK1260"]}
Myringomycosis is a fungal infection of the tympanic membrane. It is caused by the presence of the fungus Aspergillus nigricans or flavescens.[1] ## References[edit] 1. ^ Lilienthal, S. (2004). A Treatise on Diseases of the Skin. B. Jain Publishers. p. 184. ISBN 978-81-8056-076-7. ## Further reading[edit] * Archives of Ophthalmology and Otology. William Wood. 1874. * Burnett, C. H. (1884). The ear. Рипол Классик. ISBN 9785879321241. This article about a disease of the ear and mastoid process 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	Myringomycosis	None	954	wikipedia	https://en.wikipedia.org/wiki/Myringomycosis	2021-01-18T18:56:26	{"wikidata": ["Q6948241"]}
Hypoplasia of the right ventricle and tricuspid valve was observed in brother and sister by Davachi et al. (1967), who pointed out that at least 2 families with multiple affected sibs had been reported (Medd et al., 1961; Sackner et al., 1961). Chessa et al. (2000) described a 1-day-old male child and his 34-year-old father who were found to have isolated right ventricular hypoplasia (IRVH) with atrial septal defect. Isolated right ventricular hypoplasia is usually associated with a communication between the atria in the form of a patent foramen ovale or secondum atrial septal defect; the right ventricular outflow tract is normal. Although affected sibs had been reported by Medd et al. (1961) and by Becker et al. (1971), this appeared to be the first report of familial IRVH in successive generations. Cardiac \- Hypoplasia of right ventricle \- Hypoplasia of tricuspid valve 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	RIGHT VENTRICULAR HYPOPLASIA, ISOLATED	c1848587	955	omim	https://www.omim.org/entry/277200	2019-09-22T16:21:22	{"mesh": ["C535682"], "omim": ["277200"], "orphanet": ["439"], "synonyms": ["Alternative titles", "IRVH"]}
"MPS II" redirects here. For the Chinese romanization system, see Mandarin Phonetic Symbols II. Hunter syndrome Structure of heparan sulfate, one of the GAGs that builds up in the tissues of people with Hunter syndrome SpecialtyEndocrinology SymptomsSkeletal abnormalities, hearing loss, retinal degeneration, enlarged liver and spleen ComplicationsUpper airway disease; cardiovascular failure CausesDefiency of the enzyme iduronate-2-sulfatase Differential diagnosisMucopolysaccharidosis type I; other mucopolysaccharidoses PrognosisIn severe cases, death usually occurs by age 15. In attenuated cases, patients may survive into their 50s Frequency1 in 100,000 to 150,000 male births[1] Hunter syndrome, or mucopolysaccharidosis type II (MPS II), is a rare genetic disorder in which large sugar molecules called glycosaminoglycans (or GAGs or mucopolysaccharides) build up in body tissues. It is a form of lysosomal storage disease. Hunter syndrome is caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S).[2][3] The lack of this enzyme causes heparan sulfate and dermatan sulfate to accumulate in all body tissues.[4] Hunter syndrome is the only MPS syndrome to exhibit X-linked recessive inheritance.[4] The symptoms of Hunter syndrome are comparable to those of MPS I. It causes abnormalities in many organs, including the skeleton, heart, and respiratory system. In severe cases, this leads to death during the teenaged years. Unlike MPS I, corneal clouding is not associated with this disease.[1] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 5.1 Enzyme replacement therapy * 5.2 Bone-marrow and stem-cell transplantation * 5.3 Gene editing therapy * 6 Prognosis * 7 Epidemiology * 8 History * 9 Research * 10 Society * 11 See also * 12 References * 13 External links ## Signs and symptoms[edit] Hunter syndrome may present with a wide variety of phenotypes. It has traditionally been categorized as either "mild" or "severe" depending on the presence of central nervous system symptoms, but this is an oversimplification. Patients with "attenuated" or "mild" forms of the disease may still suffer from significant health issues. For severely affected patients, the clinical course is relatively predictable; patients will normally die at an early age. For those with milder forms of the disease, a wider variety of outcomes exist. Many live into their 20s and 30s, but some may have near-normal life expectancies and may even have children. Cardiac and respiratory abnormalities are the usual cause of death for patients with milder forms of the disease.[2] The symptoms of Hunter syndrome (MPS II) are generally not apparent at birth. Often, the first symptoms may include abdominal hernias, ear infections, runny noses, and colds. As the buildup of GAGs continues throughout the cells of the body, signs of MPS II become more visible. Physical appearances of many children with the syndrome include a distinctive coarseness in their facial features, including a prominent forehead, a nose with a flattened bridge, and an enlarged tongue. They may also have a large head, as well as an enlarged abdomen. For severe cases of MPS II, a diagnosis is often made between the ages of 18 and 36 months. In milder cases, patients present similarly to children with Hurler–Scheie syndrome, and a diagnosis is usually made between the ages of 4 and 8 years.[2] The continued storage of GAGs leads to abnormalities in multiple organ systems. After 18 months, children with severe MPS II may suffer from developmental decline and progressive loss of skills.[1] The thickening of the heart valves and walls of the heart can result in progressive decline in cardiac function. The walls of the airway may become thickened, as well, leading to obstructive airway disease. As the liver and spleen grow larger with time, the abdomen may become distended, making hernias more noticeable. All major joints may be affected by MPS II, leading to joint stiffness and limited motion. Progressive involvement of the finger and thumb joints results in decreased ability to pick up small objects. The effects on other joints, such as hips and knees, can make walking normally increasingly difficult. If carpal tunnel syndrome develops, a further decrease in hand function can occur. The bones themselves may be affected, resulting in short stature. In addition, pebbly, ivory-colored skin lesions may be found on the upper arms, legs, and upper back of some people with it. These skin lesions are considered pathognomic for the disease. Finally, the storage of GAGs in the brain can lead to delayed development with subsequent intellectual disability and progressive loss of function. The age at onset of symptoms and the presence or absence of behavioral disturbances are predictive factors of ultimate disease severity in very young patients. Behavioral disturbances can often mimic combinations of symptoms of attention deficit hyperactivity disorder, autism, obsessive compulsive disorder, and/or sensory processing disorder, although the existence and level of symptoms differ in each affected child. They often also include a lack of an appropriate sense of danger, and aggression. The behavioral symptoms of MPS II generally precede neurodegeneration and often increase in severity until the mental handicaps become more pronounced.[5] By the time of death, most children with severe MPS II have severe mental disabilities and are completely dependent on their caretakers.[2] ## Genetics[edit] MPS II has an X-linked recessive pattern of inheritance. Since Hunter syndrome is an X-linked recessive disorder, it preferentially affects male patients. The IDS gene is located on the X chromosome. The IDS gene encodes for an enzyme called iduronate-2-sulfatase (I2S). A lack of this enzyme leads to a buildup of GAGs, which cause the symptoms of MPS II.[6] Females generally have two X chromosomes, whereas males generally have one X chromosome that they inherit from their mother and one Y chromosome that they inherit from their father. If a female inherits one copy of the mutant allele for MPS II, she will usually have a normal copy of the IDS gene which can compensate for the mutant allele. This is known as being a genetic carrier. A male who inherits a defective X chromosome, though, usually does not have another X chromosome to compensate for the mutant gene. Thus, a female would need to inherit two mutant genes to develop MPS II, while a male patient only needs to inherit one mutant gene. A female carrier can be affected due to X-inactivation, which is a random process.[citation needed] ## Pathophysiology[edit] Dermatan sulfate is one of the GAGs that build up in the tissues of people with MPS II. The human body depends on a vast array of biochemical reactions to support critical functions. One of these functions is the breakdown of large biomolecules. The failure of this process is the underlying problem in Hunter syndrome and related storage disorders. The biochemistry of Hunter syndrome is related to a problem in a part of the connective tissue known as the extracellular matrix, which is made up of a variety of sugars and proteins. It helps to form the architectural framework of the body. The matrix surrounds the cells of the body in an organized meshwork and functions as the glue that holds the cells of the body together. One of the parts of the extracellular matrix is a molecule called a proteoglycan. Like many components of the body, proteoglycans need to be broken down and replaced. When the body breaks down proteoglycans, one of the resulting products is mucopolysaccharides (GAGs).[citation needed] In MPS II, the problem concerns the breakdown of two GAGs: dermatan sulfate and heparan sulfate. The first step in the breakdown of dermatan sulfate and heparan sulfate requires the lysosomal enzyme iduronate-2-sulfatase, or I2S. In people with MPS II, this enzyme is either partially or completely inactive. As a result, GAGs build up in cells throughout the body, particularly in tissues that contain large amounts of dermatan sulfate and heparan sulfate. The rate of GAGs buildup is not the same for all people with MPS II, resulting in a wide spectrum of medical problems.[citation needed] ## Diagnosis[edit] The first laboratory screening test for an MPS disorder is a urine test for GAGs. Abnormal values indicate that an MPS disorder is likely. The urine test can occasionally be normal even if the child actually has an MPS disorder. A definitive diagnosis of MPS II is made by measuring I2S activity in serum, white blood cells, or fibroblasts from skin biopsy. In some people with MPS II, analysis of the I2S gene can determine clinical severity. Prenatal diagnosis is routinely available by measuring I2S enzymatic activity in amniotic fluid or in chorionic villus tissue. If a specific mutation is known to run in the family, prenatal molecular genetic testing can be performed. DNA sequencing can reveal if someone is a carrier for the disease.[2] ## Treatment[edit] Because of the wide variety of phenotypes, the treatment for this disorder is specifically determined for each patient. Until recently, no effective therapy for MPS II was available, so palliative care was used. Recent advances, though, have led to medications that can improve survival and well-being in people with MPS II. ### Enzyme replacement therapy[edit] Idursulfase, a purified form of the missing lysosomal enzyme, underwent clinical trial in 2006[6] and was subsequently approved by the United States Food and Drug Administration as an enzyme replacement treatment for MPS II. Idursulfase beta, another enzyme replacement treatment, was approved in Korea by the Ministry of Food and Drug Safety. Recent advances in enzyme replacement therapy (ERT) with idursulfase have been proven to improve many signs and symptoms of MPS II, especially if started early in the disease. After administration, it can be transported into cells to break down GAGs, but as the medication cannot cross the blood–brain barrier, it is not expected to lead to cognitive improvement in patients with severe central nervous system symptoms. Even with ERT, treatment of various organ problems from a wide variety of medical specialists is necessary.[2] ### Bone-marrow and stem-cell transplantation[edit] Bone-marrow transplantation and hematopoietic stem-cell transplantation (HSCT) have been used as treatments in some studies.[7][8] While transplantation has provided benefits for many organ systems, it has not been shown to improve the neurological symptoms of the disease. Although HSCT has shown promise in the treatment of other MPS disorders, its results have been unsatisfactory so far in the treatment of MPS II. ERT has been shown to lead to better outcomes in MPS II patients.[2] ### Gene editing therapy[edit] In February 2019, medical scientists working with Sangamo Therapeutics, headquartered in Richmond, California, announced the first "in body" human gene editing therapy to permanently alter DNA \- in a patient with MPS II.[9] Clinical trials by Sangamo involving gene editing using zinc finger nuclease are ongoing as of February 2019.[10] ## Prognosis[edit] Earlier onset of symptoms is linked to a worse prognosis. For children who exhibit symptoms between the ages of 2 and 4, death usually occurs by the age of 15 to 20 years. The cause of death is usually due to neurological complications, obstructive airway disease, and cardiac failure. If patients have minimal neurologic involvement, they may survive into their 50s or beyond.[1][6] ## Epidemiology[edit] An estimated 2,000 people are afflicted with MPS II worldwide, 500 of whom live in the United States.[11] A study in the United Kingdom indicated an incidence among males around one in 130,000 male live births.[12] ## History[edit] The syndrome is named after physician Charles A. Hunter (1873–1955), who first described it in 1917.[13][14] ## Research[edit] Beginning in 2010, a phase I/II clinical trial evaluated intrathecal injections of a more concentrated dose of idursulfase than the intravenous formulation used in enzyme replacement therapy infusions, in hopes of preventing the cognitive decline associated with the severe form of the condition.[15] Results were reported in October 2013.[16] A phase II/III clinical trial began in 2014.[17] In 2017, a 44-year-old[18] patient with MPS II was treated with gene therapy in an attempt to prevent further damage by the disease. This is the first case of gene therapy being used in vivo in humans.[19] The study was extended to six patients in 2018.[20] ## Society[edit] On 24 July 2004, Andrew Wragg, 38, of Worthing, West Sussex, England, suffocated his 10-year-old son Jacob with a pillow, because of the boy's disabilities related to MPS II. A military security specialist, Wragg also claimed that he was under stress after returning from the war in Iraq. He denied murdering Jacob, but pleaded guilty to manslaughter by reason of diminished capacity. Mrs. Justice Anne Rafferty, called the case "exceptional", gave Wragg a two-year prison sentence for manslaughter, then suspended his sentence for two years. Rafferty said "nothing [was] to be gained" from sending Wragg to prison for the crime.[21][22][23] ## See also[edit] * Hurler syndrome (MPS I) * Sanfilippo syndrome (MPS III) * Morquio syndrome (MPS IV) * Prenatal testing * Genetic counseling ## References[edit] 1. ^ a b c d "Mucopolysaccharidoses Fact Sheet". National Institute of Neurological Disorders and Stroke. 15 November 2017. Retrieved 11 May 2018. 2. ^ a b c d e f g Wraith JE, Scarpa M, Beck M, et al. (March 2008). "Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy". Eur. J. Pediatr. 167 (3): 267–77. doi:10.1007/s00431-007-0635-4. PMC 2234442. PMID 18038146. 3. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. p. 544. ISBN 978-0-7216-2921-6. 4. ^ a b Le, Tao; Bhushan, Vikas; Hofmann, Jeffrey (2012). First Aid for the USMLE Step 1. McGraw-Hill. p. 117. 5. ^ Schwartz, Ida VD (2007). "A clinical study of 77 patients with mucopolysaccharidosis type II". Acta Paediatrica. 96 (455): 63–70. doi:10.1111/j.1651-2227.2007.00212.x. PMID 17391446. 6. ^ a b c Muenzer, J; Wraith, JE; Beck, M; Giugliani, R; Harmatz, P; Eng, CM; Vellodi, A; Martin, R; Ramaswami, U; Gucsavas-Calikoglu, M; Vijayaraghavan, S; Wendt, S; Puga, AC; Ulbrich, B; Shinawi, M; Cleary, M; Piper, D; Conway, AM; Kimura, A (August 2006). "A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)". Genetics in Medicine. 8 (8): 465–73. doi:10.1097/01.gim.0000232477.37660.fb. PMID 16912578. 7. ^ Guffon, N (May 2009). "Bone marrow transplantation in children with Hunter syndrome: outcome after 7 to 17 years". 154 (5). Journal of Pediatrics. pp. 733–737. doi:10.1016/j.jpeds.2008.11.041. PMID 19167723. 8. ^ Annibali, R (October 2013). "Hunter syndrome (Mucopolysaccharidosis type II), severe phenotype: long term follow-up on patients undergone to hematopoietic stem cell transplantation". 65 (5). Minerva Pediatrica. pp. 487–496. PMID 24056375. 9. ^ Marchione, Marilyn (7 February 2019). "Tests suggest scientists achieved 1st 'in body' gene editing". AP News. Retrieved 7 February 2019. 10. ^ Staff (2 February 2019). "Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II". ClinicalTrials.gov. U.S. National Library of Medicine. Retrieved 7 February 2019. 11. ^ LaTercera.com (in Spanish)[permanent dead link] 12. ^ Young ID, Harper PS (1982). "Incidence of Hunter's syndrome". Hum. Genet. 60 (4): 391–2. doi:10.1007/BF00569230. PMID 6809596. 13. ^ Hunter's syndrome (Charles A. Hunter) at Who Named It? 14. ^ Hunter, C. A. (1917). "A Rare Disease in Two Brothers". Proceedings of the Royal Society of Medicine. London. 10 (Sect Study Dis Child): 104–116. PMC 2018097. PMID 19979883. 15. ^ "A Phase I/II, Randomized, Safety and Ascending Dose Ranging Study of Intrathecal Idursulfase-IT Administered in Conjunction With Intravenous Elaprase in Pediatric Patients With Hunter Syndrome and Cognitive Impairment". Clinicaltrials.gov. U.S. National Institutes of Health. 15 June 2009. Retrieved 22 July 2018. 16. ^ "A Safety and Dose Ranging Study of Idursulfase (Intrathecal) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Hunter Syndrome Who Have Central Nervous System Involvement and Are Receiving Treatment With Elaprase® - Results". Clinicaltrials.gov. U.S. National Institutes of Health. 31 October 2013. Retrieved 20 July 2014. 17. ^ "Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment (AIM-IT)". Clinicaltrials.gov. U.S. National Institutes of Health. July 2014. Retrieved 20 July 2014. 18. ^ Marchione, Marilynn (15 November 2017). "US scientists try 1st gene editing in the body". Associated Press. Retrieved 16 November 2017. 19. ^ Marchione, Marilynne (14 November 2017). "Scientists Attempt First Gene Editing Inside a Patient". Time. Retrieved 15 November 2017. 20. ^ Marchione, Mailynn (5 September 2018). "Early results boost hopes for historic gene editing attempt". AP News. Retrieved 6 September 2018. 21. ^ NEWS.BBC.co.uk, "Father cleared of murdering son", BBC News 22. ^ Guardian.co.uk, "Former SAS soldier who smothered terminally ill son walks free" The Guardian 23. ^ NEWS.BBC.co.uk, "Review 'will clarify murder laws'" BBC News ## External links[edit] * Media related to Hunter syndrome at Wikimedia Commons * GeneReview/NIH/UW entry on Mucopolysaccharidosis Type II Classification D * ICD-10: E76.1 * ICD-9-CM: 277.5 * OMIM: 309900 * MeSH: D016532 * DiseasesDB: 6050 External resources * MedlinePlus: 001203 * eMedicine: ped/1029 * Patient UK: Hunter syndrome * GeneReviews: Mucopolysaccharidosis Type II * v * t * e Lysosomal storage diseases: Inborn errors of carbohydrate metabolism (Mucopolysaccharidoses) Catabolism * MPS I * Hurler Syndrome, Hurler-Scheie Syndrome, Scheie Syndrome * MPS II: Hunter Syndrome * MPS III: Sanfilippo Syndrome * MPS IV: Morquio Syndrome * MPS VI: Maroteaux-Lamy Syndrome * MPS VII: Sly Syndrome * MPS IX: Hyaluronidase deficiency * v * t * e X-linked disorders X-linked recessive Immune * Chronic granulomatous disease (CYBB) * Wiskott–Aldrich syndrome * X-linked severe combined immunodeficiency * X-linked agammaglobulinemia * Hyper-IgM syndrome type 1 * IPEX * X-linked lymphoproliferative disease * Properdin deficiency Hematologic * Haemophilia A * Haemophilia B * X-linked sideroblastic anemia Endocrine * Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy * KAL1 Kallmann syndrome * X-linked adrenal hypoplasia congenita Metabolic * Amino acid: Ornithine transcarbamylase deficiency * Oculocerebrorenal syndrome * Dyslipidemia: Adrenoleukodystrophy * Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency * Pyruvate dehydrogenase deficiency * Danon disease/glycogen storage disease Type IIb * Lipid storage disorder: Fabry's disease * Mucopolysaccharidosis: Hunter syndrome * Purine–pyrimidine metabolism: Lesch–Nyhan syndrome * Mineral: Menkes disease/Occipital horn syndrome Nervous system * X-linked intellectual disability: Coffin–Lowry syndrome * MASA syndrome * Alpha-thalassemia mental retardation syndrome * Siderius X-linked mental retardation syndrome * Eye disorders: Color blindness (red and green, but not blue) * Ocular albinism (1) * Norrie disease * Choroideremia * Other: Charcot–Marie–Tooth disease (CMTX2-3) * Pelizaeus–Merzbacher disease * SMAX2 Skin and related tissue * Dyskeratosis congenita * Hypohidrotic ectodermal dysplasia (EDA) * X-linked ichthyosis * X-linked endothelial corneal dystrophy Neuromuscular * Becker's muscular dystrophy/Duchenne * Centronuclear myopathy (MTM1) * Conradi–Hünermann syndrome * Emery–Dreifuss muscular dystrophy 1 Urologic * Alport syndrome * Dent's disease * X-linked nephrogenic diabetes insipidus Bone/tooth * AMELX Amelogenesis imperfecta No primary system * Barth syndrome * McLeod syndrome * Smith–Fineman–Myers syndrome * Simpson–Golabi–Behmel syndrome * Mohr–Tranebjærg syndrome * Nasodigitoacoustic syndrome X-linked dominant * X-linked hypophosphatemia * Focal dermal hypoplasia * Fragile X syndrome * Aicardi syndrome * Incontinentia pigmenti * Rett syndrome * CHILD syndrome * Lujan–Fryns syndrome * Orofaciodigital syndrome 1 * Craniofrontonasal dysplasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Hunter syndrome	c2718304	956	wikipedia	https://en.wikipedia.org/wiki/Hunter_syndrome	2021-01-18T18:36:08	{"gard": ["6675"], "mesh": ["D016532"], "umls": ["C2718304"], "icd-9": ["277.5"], "orphanet": ["580"], "wikidata": ["Q1529983"]}
Post-maturity syndrome develops in about 20% of human pregnancies continuing past the expected dates.[1] Ten years ago it was generally held that the postmature fetus ran some risk of dying in the uterus before the onset of labour because of degeneration and calcification of the placenta.[2]Features of post-maturity syndrome include oligohydramnios, meconium aspiration, macrosomia and fetal problems such as dry peeling skin, overgrown nails, abundant scalp hair, visible creases on palms and soles, minimal fat deposition and skin colour become green or yellow due to meconeum staining. Post-maturity refers to any baby born after 42 weeks gestation or 294 days past the first day of the mother's last menstrual period. Less than 6 percent of all babies are born at 42 weeks or later.[3] In most cases, continued fetal growth between 39 and 43 wk gestation results in a macrosomic infant. However, sometimes the placenta involutes, and multiple infarcts and villous degeneration cause placental insufficiency syndrome. In this syndrome, the fetus receives inadequate nutrients and oxygen from the mother, resulting in a thin (due to soft-tissue wasting), small-for-gestational-age, undernourished infant with depleted glycogen stores. Post term, the amniotic fluid volume eventually decreases, leading to oligohydramnios.[4]Although pregnancy is said to last nine months, health care providers track pregnancy by weeks and days. The estimated delivery date, also called the estimated due date or EDD, is calculated as 40 weeks or 280 days from the first day of the last menstrual period. Only 4 percent (1 in 20) women will deliver on their due date.[5] The terms Post-maturity or "Post-term" are both words used to describe babies born after 42 weeks.The terms "post-maturity" and "post-term" are interchangeable.[6]As there are many definitions for prolonged pregnancy the incidence varies from 2 to 10%.When incidence is taken as delivery beyond 42 weeks it is 10%, if it is taken according to the delivered baby's weight and length it is 2%.[7]The baby may have birth weight of 4kg and length of 54 cm but these findings are variable, even the baby may have underweight[7].Post-maturity is more likely to happen when a mother has had a post-term pregnancy before. After one post-term pregnancy, the risk of a second post-term birth increases by 2 to 3 times.[8]Other, minor risk factors include an older or obese mother, a white mother, male baby, or a family history of post-maturity.[9]Maternal risks include obstructed labor, perennial damage, instrumental vaginal delivery, a Cesarean section, infection, and post postpartum hemorrhage.[10]Accurate pregnancy due dates can help identify babies at risk for post-maturity. Ultrasound examinations early in pregnancy help establish more accurate dating by measurements taken of the fetus.[6]Pregnancies complicated by gestational diabetes, hypertension, or other high-risk conditions should be managed according to guidelines for those conditions.[11] If there are no maternal or fetal complications, labor can be induced after assessing the favorability of the cervix and excluding cephalo-pelvic disproportions. Otherwise emergency lower segment Caesarean section (LSCS) should be made. The syndrome was first described by Stewart H. Clifford in 1954.[12] ## References[edit] 1. ^ Mohd, Jasmine; K. H. Tan; George S. H. Yeo (May–June 2008). "Induction of labour and Perinatal outcome in Post-term Pregnancy" (PDF). Journal of Paediatrics, Obstetric & Gynaecology. CMPMedica: 107–114. Archived from the original (PDF) on 2010-05-09. Retrieved 2010-01-02. 2. ^ S. G. CLAYTON, M.S., F.R.C.O.G., s.\\. "Foetal Distress in Post-maturity". doi:10.1177/003591575304600207. Cite journal requires `\|journal=` (help)CS1 maint: multiple names: authors list (link) 3. ^ "default - Stanford Children's Health". www.stanfordchildrens.org. Retrieved 2019-04-15. 4. ^ "Postmature (Postterm) Infant - Pediatrics". Merck Manuals Professional Edition. Retrieved 2019-05-09. 5. ^ "UpToDate". www.uptodate.com. Retrieved 2019-05-08. 6. ^ a b Philadelphia, The Children's Hospital of (2014-08-23). "Postmaturity". www.chop.edu. Retrieved 2019-04-15. 7. ^ a b "Postdated or prolonged pregnancy: definition,incidence,causes, diagnosis, risks and management". srsree.blogspot.com. Retrieved 2019-05-08. 8. ^ "Definition of Postmaturity". MedicineNet. Retrieved 2019-04-15. 9. ^ "Postmaturity in the Newborn - Health Encyclopedia - University of Rochester Medical Center". www.urmc.rochester.edu. Retrieved 2019-04-15. 10. ^ "Post-term Pregnancy (Prolonged Pregnancy). Postmaturity". patient.info. Retrieved 2019-04-15. 11. ^ Kalb, Daniel B.; Mencer, Melanie; Gautam, Neeta; Nguyen, Hayley; Briscoe, Donald (2005-05-15). "Management of Pregnancy Beyond 40 Weeks' Gestation". American Family Physician. 71 (10): 1935–1941. ISSN 0002-838X. 12. ^ Clifford, Stewart H. (January 1954). "Postmaturity—With placental dysfunction: Clinical syndrome and pathologic findings". The Journal of Pediatrics. Elsevier. 44 (1): 1–13. doi:10.1016/S0022-3476(54)80085-0. ISSN 0022-3476. PMID 13131191. This 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	Post-maturity syndrome	c0221007	957	wikipedia	https://en.wikipedia.org/wiki/Post-maturity_syndrome	2021-01-18T19:07:03	{"umls": ["C0221007"], "icd-10": ["P08.2"], "wikidata": ["Q7233555"]}
This article is about lobar pneumonia. For the disease in general, see Pneumonia. For classification, see Classification of pneumonia. Lobar pneumonia Figure A shows the location of the lungs and airways in the body. This figure also shows pneumonia affecting the lower lobe of the left lung. Figure B shows normal alveoli. Figure C shows infected alveoli. SpecialtyPulmonology Lobular pneumonia is a form of pneumonia characterized by inflammatory exudate within the intra-alveolar space resulting in consolidation that affects a large and continuous area of the lobe of a lung.[1][2] It is one of three anatomic classifications of pneumonia (the other being bronchopneumonia and atypical pneumonia). In children round pneumonia develops instead because the pores of Kohn which allow the lobar spread of infection are underdeveloped.[3] ## Contents * 1 Mechanism * 2 Stages * 3 In children * 4 Diagnosis * 5 References * 6 External links ## Mechanism[edit] The invading organism starts multiplying, thereby releasing toxins that cause inflammation and edema of the lung parenchyma. This leads to the accumulation of cellular debris within the lungs. This leads to consolidation or solidification, which is a term that is used for macroscopic or radiologic appearance of the lungs affected by pneumonia. Bacterial pneumonia is mainly classified into lobar and diffuse[citation needed] ## Stages[edit] Micrograph of lobar pneumonia, H&E stain. Lobar pneumonia usually has an acute progression. Classically, the disease has four stages:[1] * Congestion in the first 24 hours: This stage is characterized histologically by vascular engorgement, intra-alveolar fluid, small numbers of neutrophils, often numerous bacteria. Grossly, the lung is heavy and hyperemic. * Red hepatization or consolidation: Vascular congestion persists, with extravasation of red cells into alveolar spaces, along with increased numbers of neutrophils and fibrin. The filling of airspaces by the exudate leads to a gross appearance of solidification, or consolidation, of the alveolar parenchyma. This appearance has been likened to that of the liver, hence the term "hepatization". * Grey hepatization: Red cells disintegrate, with persistence of the neutrophils and fibrin. The alveoli still appear consolidated, but grossly the color is paler and the cut surface is drier. * Resolution (complete recovery): The exudate is digested by enzymatic activity, and cleared by macrophages or by cough mechanism. Enzymes produced by neutrophils will liquify exudates, and this will either be coughed up in sputum or be drained via lymph. ## In children[edit] The openings between the alveoli known as the pores of Kohn, and the collateral airways of the canals of Lambert, are undeveloped in children. Spread of infection that would otherwise occur is prevented and can result in round pneumonia, most commonly caused by S. pneumoniae. This clinically presents with an initial mild respiratory infection, followed by fever. On imaging it presents an opaque pulmonary consolidation which is unusually round, and can resemble a lung mass. However it quickly resolves with antibiotics.[4] ## Diagnosis[edit] The most common organisms which cause lobar pneumonia are Streptococcus pneumoniae, also called pneumococcus, Haemophilus influenzae and Moraxella catarrhalis. Mycobacterium tuberculosis, the tubercle bacillus, may also cause lobar pneumonia if pulmonary tuberculosis is not treated promptly. Other organisms that cause lobar pneumonia are Legionella pneumophila and Klebsiella pneumoniae.[2] Like other types of pneumonia, lobar pneumonia can present as community acquired, in immune suppressed patients or as nosocomial infection. However, most causative organisms are of the community acquired type. Pathological specimens to be obtained for investigations include: 1. Sputum for culture, AAFBS and gram stain 2. Blood for full hemogram/complete blood count, ESR and other acute phase reactants 3. Procalcitonin test, more specific On a posterioanterior and lateral chest radiograph, an entire lobe will be radiopaque, which is indicative of lobar pneumonia.[5] * Chest radiograph of a lobar pneumonia, affecting the right middle lobe. * CT scan of the same case. The identification of the infectious organism (or other cause) is an important part of modern treatment of pneumonia. The anatomical patterns of distribution can be associated with certain organisms,[6] and can help in selection of an antibiotic while waiting for the pathogen to be cultured. ## References[edit] 1. ^ a b Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 749. ISBN 0-7216-0187-1. 2. ^ a b Le, Tao (2017). First Aid for the USMLE Step 1 2018. New York: McGraw-Hill Education. p. 664. 3. ^ Weerakkody, Yuranga. "Round pneumonia \| Radiology Reference Article \| Radiopaedia.org". Radiopaedia. 4. ^ https://radiopaedia.org/articles/round-pneumonia-1?lang=us 5. ^ E., Weinberger, Steven. Principles of pulmonary medicine. Cockrill, Barbara A.,, Mandel, Jess,, Preceded by : Weinberger, Steven E. (Seventh ed.). Philadelphia, PA. ISBN 9780323523738. OCLC 1020498796. 6. ^ "Lobar Pneumonia". Retrieved 2008-11-16. ## External links[edit] * Media related to Lobar pneumonia at Wikimedia Commons Classification D * ICD-10: J18.1 * ICD-9-CM: 481 * MeSH: D011018 * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Lobar pneumonia	c0032300	958	wikipedia	https://en.wikipedia.org/wiki/Lobar_pneumonia	2021-01-18T19:09:14	{"mesh": ["D011014"], "icd-9": ["481"], "icd-10": ["J18.1"], "wikidata": ["Q6663548"]}
Neonatal onset multisystem inflammatory disease (NOMID) is an inflammatory disorder present from birth (congenital) characterized by tissue damage of the nervous system, skin, and joints. Individuals with NOMID have a skin rash that is present from birth and persists throughout life. Other symptoms may include: headaches, seizures, and vomiting resulting from chronic meningitis (inflammation of the tissue that covers and protects the brain and spinal cord); intellectual disability; episodes of mild fever; and hearing and vision problems. NOMID is the most severe form of the cryopyrin associated periodic syndromes (CAPS) caused by mutations in the NLRP3 (CIAS1) gene. About 50% of affected individuals with NOMID are found to have mutations in this gene. This condition is inherited in an autosomal dominant manner. Treatment may include the use of medications to suppress the process of inflammation, such as anti-inflammatories, corticosteroids, and interleukin-1 beta receptors. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Neonatal Onset Multisystem Inflammatory disease	c0409818	959	gard	https://rarediseases.info.nih.gov/diseases/1356/neonatal-onset-multisystem-inflammatory-disease	2021-01-18T17:58:47	{"mesh": ["D056587"], "omim": ["607115"], "umls": ["C0409818"], "orphanet": ["1451"], "synonyms": ["Chronic Infantile Neurological Cutaneous Articular syndrome", "CINCA syndrome", "CINCA", "Infantile Onset Multisystem Inflammatory Disease", "IOMID", "NOMID", "Multisystem inflammatory disease, neonatal-onset", "Prieur Griscelli syndrome"]}
A rare, congenital renal tract malformation characterized by the complete absence of development of one or both kidneys (unilateral or bilateral renal agenesis respectively), accompanied by absent ureter(s). ## Epidemiology The birth prevalence of unilateral renal agenesis (RA) is estimated at around 1/2,000. Fetal prevalence of bilateral renal agenesis in Europe has been estimated at 1/8,500. ## Clinical description Most patients with unilateral RA are asymptomatic early in life if the other kidney is fully functional in which case the condition is commonly detected as an incidental finding later in life. However, hypertension, proteinuria and renal failure may develop in the long run (20-50% of cases at the age of 30). Unilateral RA is occasionally associated with additional urogenital tract anomalies on the same side (e.g. seminal vesicle hypoplasia and absence of the vas deferens), cardiac anomalies (such as atrial or ventricular septal defects) and/or gastrointestinal anomalies (such as anal atresia). Bilateral RA is characterized by complete absence of kidney development, absent ureters and subsequent absence of fetal renal function resulting in Potter sequence with pulmonary hypoplasia related to oligohydramnios, which left untreated is fatal shortly after birth. ## Etiology Renal agenesis results from a developmental failure of the ureteric bud and the metanephric mesenchyme. Unilateral renal agenesis can be caused by mutations in many genes, such as RET (10q11.2), BMP4 (14q22-q23), FRAS1 (4q21.21), FREM1 (9p22.3), or UPK3A (22q13.31). A few cases of bilateral renal agenesis have been found to be caused by mutations in the RET, FGF20 (8p22) or ITGA8 (10p13) genes. Maternal diabetes mellitus or use of specific drugs during pregnancy may also causerenal agenesis. ## Diagnostic methods Diagnosis is based on ultrasonography, showing an empty renal fossa and no ectopic kidney. Additional radiological examinations like MRI (magnetic resonance imaging) and/or DMSA (dimercaptosuccinic acid) scintigraphy may confirm the diagnosis. The contra-lateral kidney may be compensatory hypertrophied. ## Differential diagnosis Differential diagnoses of an empty renal fossa include kidney ectopia and involution of multi-cystic dysplastic kidneys (MCDK). ## Antenatal diagnosis Prenatal diagnosis may be made by prenatal ultrasonography. ## Genetic counseling In familial cases, unilateral RA is typically inherited in an autosomal dominant manner with incomplete penetrance. Bilateral RA is inherited autosomal recessively. ## Management and treatment Clinical management of unilateral renal agenesis with fully functioning contra-lateral kidney included routine evaluations of blood-pressure and screening for proteinuria as individuals with RA have an elevated risk of chronic kidney disease. ## Prognosis The prognosis of RA with fully functioning contra-lateral kidney is generally good. Without intensive care, bilateral RA is fatal shortly after birth. * 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	Renal agenesis	c1609433	960	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=411709	2021-01-23T17:18:03	{"gard": ["9228"], "mesh": ["C536482"], "omim": ["191830", "615721"], "umls": ["C0542519", "C1609433", "C1619700"], "icd-10": ["Q60.0", "Q60.1", "Q60.2"]}
Pfeiffer et al. (1987) described 2 sibs from healthy parents with this combination of manifestations. Curiously, no mention was made of the sex of the sibs. Stratton and Parsons (1989) described a sporadic case. In addition to craniosynostosis involving the sagittal suture, micrognathia with limited mouth opening, tracheobronchial anomalies, congenital heart defects, microphallus, cryptorchidism, and growth and mental retardation were features. Williamson-Kruse and Biesecker (1995) reported a fourth case. Although most of the features were similar to those described in the earlier patient, a heart defect was missing, suggesting that congenital heart defect is not an obligatory feature of the cardiocranial syndrome! The patient was male; one of the original sibs of Pfeiffer et al. (1987) was female. Autosomal recessive inheritance was supported by the finding of Pfeiffer cardiocranial syndrome in a brother and sister by Digilio et al. (1997). Craniosynostosis was present in only 1 of the sibs, suggesting intrafamilial variability. Further, the clinical spectrum of the disorder was expanded by inclusion of renal, joint, and palpebral abnormalities. GU \- Microphallus \- Cryptorchidism Respiratory \- Tracheobronchial anomalies Neuro \- Mental retardation Inheritance \- Autosomal recessive Growth \- Retardation Cardiac \- Congenital heart defects HEENT \- Craniosynostosis, sagittal \- Micrognathia \- Limited mouth opening ▲ 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	CRANIOSTENOSIS, SAGITTAL, WITH CONGENITAL HEART DISEASE, MENTAL DEFICIENCY, AND MANDIBULAR ANKYLOSIS	c1857495	961	omim	https://www.omim.org/entry/218450	2019-09-22T16:29:15	{"mesh": ["C535578"], "omim": ["218450"], "orphanet": ["2872"], "synonyms": ["PFEIFFER CARDIOCRANIAL SYNDROME", "Craniosynostosis-congenital heart disease-intellectual disability syndrome", "Alternative titles", "Sagittal craniostenosis with congenital heart disease, mental deficiency and mandibular ankylosis", "Pfeiffer-Singer-Zschiesche syndrome"]}
A rare, genetic, primary combined T and B cell immunodeficiency characterized by recurrent, severe viral and bacterial infections. Immunologic findings include decreased immunoglobulin levels, decreased numbers of B and NK cells, reduced relative CD19+ B cells in peripheral blood, impaired memory responses to viral infections and defective antigen-specific T-cell proliferation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	NIK deficiency	None	962	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=447731	2021-01-23T17:52:45	{"icd-10": ["D81.8"], "synonyms": ["Primary immunodeficiency with multifaceted aberrant lymphoid immunity"]}
Autosomal spastic paraplegia type 72 is a rare, genetic, pure hereditary spastic paraplegia disorder characterized by early childhood onset of slowly progressive crural spastic paraparesis presenting with spastic gait, mild stiffness at rest, hyperreflexia (in lower limbs), extensor plantar responses and, in some, mild postural tremor, pes cavus, sphincter disturbances and sensory loss at ankles. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Autosomal spastic paraplegia type 72	c3810160	963	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=401849	2021-01-23T17:00:50	{"omim": ["615625"], "icd-10": ["G11.4"], "synonyms": ["SPG72"]}
Rozycki et al. (1971) described a syndrome of deafness associated with short stature, vitiligo, muscle wasting, and achalasia. See 606579 for the association of vitiligo and congenital deafness, and 142623 and 193500 for a description of congenital deafness with Hirschsprung disease, another aganglionic state. Reference to an association of achalasia and leukoderma was given by McKusick (1973). Rozycki et al. (1971) observed affected brother and sister with first-cousin parents. Inheritance \- Autosomal recessive Growth \- Short stature Skin \- Vitiligo Muscle \- Muscle wasting GI \- Achalasia Ears \- Congenital hearing loss ▲ 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	DEAFNESS, CONGENITAL, WITH VITILIGO AND ACHALASIA	c1857339	964	omim	https://www.omim.org/entry/221350	2019-09-22T16:28:57	{"mesh": ["C565642"], "omim": ["221350"], "orphanet": ["3239"]}
A number sign (#) is used with this entry because Kelley-Seegmiller syndrome is caused by mutation in the HPRT gene (308000) that results in partial deficiency of hypoxanthine guanine phosphoribosyltransferase. Description Virtually complete deficiency of HPRT residual activity is associated with the Lesch-Nyhan syndrome (LNS; 300322), whereas partial deficiency (at least 8%) is associated with the Kelley-Seegmiller syndrome. LNS is characterized by abnormal metabolic and neurologic manifestations. In contrast, Kelley-Seegmiller syndrome is usually associated only with the clinical manifestations of excessive purine production. Renal stones, uric acid nephropathy, and renal obstruction are often the presenting symptoms of Kelley-Seegmiller syndrome, but rarely of LNS. After puberty, the hyperuricemia in Kelley-Seegmiller syndrome may cause gout (summary by Zoref-Shani et al., 2000). Clinical Features In 5 male patients with gout, Kelley et al. (1967) found a partial deficiency of hypoxanthine-guanine phosphoribosyltransferase. Two brothers in 1 family were 24 and 11 years old; three brothers in another family were 42, 49, and 55 years old. In the first family, nephrolithiasis began at age 6 or 7, followed in one by gouty arthritis at age 13. In the 3 brothers, acute gouty arthritis began between ages 20 and 31 and 2 had had recurrent nephrolithiasis. The 2 brothers of the first family had spinocerebellar derangement distinct from the neurologic disorder of the Lesch-Nyhan syndrome. The characteristics of the enzyme were the same in each family but different between families. The differences concerned relative activities for guanine and hypoxanthine and heat stability. McDonald and Kelley (1971) presented evidence of genetic heterogeneity in the Lesch-Nyhan syndrome. In the patient they reported, HPRT showed altered kinetics. Among 425 cases of hyperuricemia with gout or uric acid stone or both, Yu et al. (1972) found 7 with partial HPRT deficiency and 5 of these were members of one family. Andres et al. (1987) reported the case of a 12-year-old boy who presented with acute renal failure accompanied by a disproportionate increase of serum uric acid level and massive uric acid crystalluria. After alkalinization and allopurinol therapy, serum uric acid and renal function returned to normal. HPRT deficiency was found as the basis of the abnormality. Zoref-Shani et al. (2000) reported a 4.5-year-old boy who was admitted to the hospital at the age of 3.5 years with acute renal failure due to uric acid nephropathy. A streptococcal throat infection and fever were present at the same time and may have been precipitating or contributing factors. The precise nature of the DNA change was not described. The authors stated that the underlying HPRT mutation was unique in that the specific activity in HPRT and erythrocyte and fibroblast lysates was normal, but the rate of uptake of hypoxanthine into nucleotides of intact cultured fibroblasts was markedly reduced (23% of normal). Other metabolic features of the mutation were described as well. With allopurinol treatment, the patient had had no further problems and was developing normally at 5 years of age. Srivastava et al. (2002) reported the case of a 12-year-old boy who presented with recurrent acute renal failure from hyperuricemia and had no phenotypic features of Lesch-Nyhan syndrome. Acute infectious mononucleosis may have triggered the acute renal failure, and treatment with allopurinol prevented further episodes. Unlike the cells from patients with Lesch-Nyhan syndrome, the in vitro cultures of this patient's T lymphocytes did not proliferate in the presence of purine analog 6-thioguanine. Molecular Genetics In a patient with recurrent acute renal failure from hyperuricemia, Srivastava et al. (2002) identified a novel HPRT missense mutation (308000.0059). INHERITANCE \- X-linked recessive GENITOURINARY Kidneys \- Nephrolithiasis \- Renal failure SKELETAL Feet \- Gout LABORATORY ABNORMALITIES \- Hyperuricemia \- Hyperuricosuria MISCELLANEOUS \- Partial deficiency of hypoxanthine phosphoribosyltransferase (HPRT, 78% activity) MOLECULAR BASIS \- Caused by mutation in the hypoxanthine phosphoribosyltransferase gene (HPRT1, 308000.0001 ) ▲ 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	KELLEY-SEEGMILLER SYNDROME	c0268117	965	omim	https://www.omim.org/entry/300323	2019-09-22T16:20:26	{"mesh": ["C562583"], "omim": ["300323"], "orphanet": ["79233"], "synonyms": ["Alternative titles", "GOUT, HPRT-RELATED", "HYPOXANTHINE GUANINE PHOSPHORIBOSYLTRANSFERASE 1 DEFICIENCY, PARTIAL", "HPRT DEFICIENCY, PARTIAL", "HPRT1 DEFICIENCY, PARTIAL"]}
5q minus (5q-) syndrome is a type of bone marrow disorder called myelodysplastic syndrome (MDS). MDS comprises a group of conditions in which immature blood cells fail to develop normally, resulting in too many immature cells and too few normal mature blood cells. In 5q- syndrome, development of red blood cells is particularly affected, leading to a shortage of these cells (anemia). In addition, the red blood cells that are present are unusually large (macrocytic). Although many people with 5q- syndrome have no symptoms related to anemia, especially in the early stages of the condition, some affected individuals develop extreme tiredness (fatigue), weakness, and an abnormally pale appearance (pallor) as the condition worsens. Individuals with 5q- syndrome also have abnormal development of bone marrow cells called megakaryocytes, which produce platelets, the cells involved in blood clotting. A common finding in people with 5q- syndrome is abnormal cells described as hypolobated megakaryocytes. In addition, some individuals with 5q- syndrome have an excess of platelets, while others have normal numbers of platelets. MDS is considered a slow-growing (chronic) blood cancer. It can progress to a fast-growing blood cancer called acute myeloid leukemia (AML). Progression to AML occurs less commonly in people with 5q- syndrome than in those with other forms of MDS. ## Frequency MDS affects nearly 1 in 20,000 people in the United States. It is thought that 5q- syndrome accounts for 15 percent of MDS cases. Unlike other forms of MDS, which occur more frequently in men than women, 5q- syndrome is more than twice as common in women. ## Causes 5q- syndrome is caused by deletion of a region of DNA from the long (q) arm of chromosome 5. Most people with 5q- syndrome are missing a sequence of about 1.5 million DNA building blocks (base pairs), also written as 1.5 megabases (Mb). However, the size of the deleted region varies. This deletion occurs in immature blood cells during a person's lifetime and affects one of the two copies of chromosome 5 in each cell. The commonly deleted region of DNA contains 40 genes, many of which play a critical role in normal blood cell development. Research suggests that loss of multiple genes in this region contributes to the features of 5q- syndrome. Loss of the RPS14 gene leads to the problems with red blood cell development characteristic of 5q- syndrome, and loss of MIR145 or MIR146A contributes to the megakaryocyte and platelet abnormalities and may promote the overgrowth of immature cells. Scientists are still determining how the loss of other genes in the deleted region might be involved in the features of 5q- syndrome. ### Learn more about the genes and chromosome associated with 5q minus syndrome * MIR145 * MIR146A * RPS14 * chromosome 5 ## Inheritance Pattern This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception. This alteration is called a somatic mutation. Affected people typically have no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	5q minus syndrome	c0740302	966	medlineplus	https://medlineplus.gov/genetics/condition/5q-minus-syndrome/	2021-01-27T08:25:13	{"gard": ["8723"], "mesh": ["C535323"], "omim": ["153550"], "synonyms": []}
Davis et al. (1981) reported a family in which 9 men in 3 generations presented with a slowly progressive spastic quadriparesis and varying degrees of psychomotor retardation. Both features of the syndrome were evident from early in life. None of the affected males had children. None of the carrier females showed abnormalities. The authors found no report of the same disorder. Neuro \- Slowly progressive spastic quadriparesis \- Mental retardation Inheritance \- ? X-linked ▲ 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	MENTAL RETARDATION WITH SPASTIC PARAPLEGIA	c1839727	967	omim	https://www.omim.org/entry/309640	2019-09-22T16:17:39	{"mesh": ["C564099"], "omim": ["309640"], "orphanet": ["163982"], "synonyms": []}
Ectopic crossed fused kidney in a fetus approx. 34 weeks Crossed dystopia (syn.unilateral fusion cross fused renal ectopia) is a rare form of renal ectopia where both kidneys are on the same side of the spine. In many cases, the two kidneys are fused together, yet retain their own vessels and ureters.[1] The ureter of the lower kidney crosses the midline to enter the bladder on the contralateral side. Both renal pelves can lie one above each other medial to the renal parenchyma (unilateral long kidney) or the pelvis of the crossed kidney faces laterally (unilateral "S" shaped kidney). Urogram is diagnostic. The anomaly can be diagnosed through ultrasound or urography, but surgical intervention is only necessary if there are other complications, such as tumors or pyelonephritis.[citation needed] ## References[edit] 1. ^ "Anomalies of renal position". europdoctor. Retrieved 22 June 2013. This article related to the genitourinary system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Crossed renal ectopia	c0221353	968	wikipedia	https://en.wikipedia.org/wiki/Crossed_renal_ectopia	2021-01-18T19:03:54	{"mesh": ["D000069337"], "umls": ["C0221353", "C0266302"], "wikidata": ["Q16948277"]}
## Summary ### Clinical characteristics. Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues distributed along the paravertebral axis from the base of the skull to the pelvis) and pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas cause catecholamine excess; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base and neck (referred to as head and neck PGL [HNPGL]) and sometimes in the upper mediastinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically lead to catecholamine excess. Symptoms of PGL/PCC result from either mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for developing metastatic disease is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas. ### Diagnosis/testing. The diagnosis of a hereditary PGL/PCC syndrome should be suspected in any individual with a diagnosis of paraganglioma or pheochromocytoma. A diagnosis of hereditary PGL/PCC is strongly suspected in an individual with multiple, multifocal, recurrent, or early-onset paraganglioma or pheochromocytoma and/or a family history of paraganglioma or pheochromocytoma. The diagnosis is established in a proband by identification of a germline heterozygous pathogenic variant in MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, or TMEM127 on molecular genetic testing. ### Management. Treatment of manifestations: For secretory PGL/PCC, treatment requires using medications for alpha adrenergic receptor blockade followed by surgery. For nonsecretory HNPGLs, surgical resection should be considered only after a detailed analysis of benefits and risks of a surgical procedure. All individuals with HNPGL should be evaluated for catecholamine excess before surgical resection, which, if present, can suggest an additional primary PGL/PCC. Watchful waiting or radiation therapy are options for HNPGLs. PGL/PCCs identified in individuals known to have SDHB pathogenic variants may benefit from resection over radiation or watchful waiting because of the higher risk for metastatic disease. Prevention of secondary complications: Early detection through surveillance and removal of tumors may prevent or minimize complications related to mass effects, unregulated catecholamine secretion, and metastatic disease. Surveillance: Beginning between ages six and eight years, individuals at risk for hereditary PGL/PCC syndromes should have annual biochemical and clinical surveillance for signs and symptoms of PGL/PCC and biennial full-body MRI examination. Consider endoscopic evaluation for gastrointestinal stromal tumors in individuals with unexplained gastrointestinal symptoms. Agents/circumstances to avoid: Hypoxic conditions (e.g., living at high altitude, cigarette smoking) may increase tumor incidence and promote tumor growth, although data are extremely limited. Evaluation of relatives at risk: First-degree relatives of an individual with a known MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, or TMEM127 pathogenic variant should be offered molecular genetic testing to clarify their genetic status to improve diagnostic certainty and reduce the need for costly screening procedures in those who have not inherited the pathogenic variant. ### Genetic counseling. The hereditary PGL/PCC syndromes are inherited in an autosomal dominant manner. Pathogenic variants in SDHD demonstrate parent-of-origin effects and generally cause disease only when the pathogenic variant is inherited from the father. Pathogenic variants in SDHAF2 and possibly MAX exhibit parent-of-origin effects similar to those of pathogenic variants in SDHD. A proband with a hereditary PGL/PCC syndrome may have inherited the pathogenic variant from a parent or, rarely, have a de novo pathogenic variant; the proportion of individuals with a de novo pathogenic variant is unknown. Each child of an individual with a hereditary PGL/PCC syndrome-causing pathogenic variant has a 50% chance of inheriting the pathogenic variant. An individual who inherits an SDHD pathogenic variant from his/her mother is at a very low but not negligible risk of developing disease. An individual who inherits an SDHD pathogenic variant from his/her father is at high risk of manifesting PGL/PCC. If the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis The Endocrine Society guidelines for pheochromocytoma and paraganglioma [Lenders et al 2014] and American College of Medical Genetics guidelines for cancer predisposition [Hampel et al 2015] recommend that all individuals with paraganglioma or pheochromocytoma (PGL/PCC) be referred for clinical genetic testing for pathogenic variants in susceptibility genes. ### Suggestive Findings Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes should be suspected in any individual with a paraganglioma or pheochromocytoma, particularly individuals with the following findings [Young 2011, Lenders et al 2014]: * Tumors that are: * Multiple (i.e., >1 paraganglioma or pheochromocytoma), including bilateral adrenal pheochromocytoma * Multifocal with multiple synchronous or metachronous tumors * Recurrent * Early onset (i.e., age <45 years) * Extra-adrenal * Metastatic * A family history of paraganglioma or pheochromocytoma, or relatives with unexplained or incompletely explained sudden death Note: Many individuals with hereditary PGL/PCC syndrome may present with a solitary tumor of the skull base or neck, thorax, abdomen, adrenal, or pelvis and no family history of paraganglioma or pheochromocytoma. The following clinical and laboratory features suggest a paraganglioma or pheochromocytoma. Clinical features * Signs and symptoms of catecholamine excess (e.g., classic signs and symptoms of sustained or paroxysmal elevations in blood pressure, headache, palpitations, arrhythmia, profuse sweating, apprehension or anxiety, and non-classic signs and symptoms of pallor, nausea/vomiting, and sudden change in glycemic control) * Symptoms may be triggered by changes in body position, increases in intra-abdominal pressure, medications (e.g., metoclopramide), anesthesia induction, exercise, or micturition. * Palpable abdominal mass * Enlarging mass of the skull base or neck * Compromise of cranial nerves (VII, IX, X, XI) and sympathetic nerves in the head and neck area (e.g., hoarseness, dysphagia, soft palate paresis, Horner syndrome) * Tinnitus Laboratory findings. Elevated fractionated metanephrines and/or catecholamines in plasma and/or a 24-hour urine sample can include any of the following: * Epinephrine (adrenaline) and its major metabolite metanephrine * Norepinephrine (noradrenaline) and its major metabolite normetanephrine * Dopamine and its major metabolite 3-methyoxytyramine Note: (1) Measurement of fractionated metanephrine concentrations in plasma or urine is preferred, as it is more sensitive than measurement of catecholamine concentrations [Young 2011]. (2) False positive results may be reduced by follow-up testing for 24-hour urine fractionated metanephrines when plasma normetanephrine concentrations are less than fourfold above the reference range [Algeciras-Schimnich et al 2008]. (3) The secretion of epinephrine with little norepinephrine excess suggests an adrenal pheochromocytoma, which may be associated with multiple endocrine neoplasia type 2 [Young 2011]. ### Establishing the Diagnosis The diagnosis of hereditary PGL/PCC should be strongly suspected in an individual with multiple, multifocal, recurrent, or early-onset paraganglioma or pheochromocytoma and/or a family history of paraganglioma or pheochromocytoma. The diagnosis of hereditary PGL/PCC syndromes is established in a proband with a germline heterozygous pathogenic variant in one of the genes listed in Table 1. #### Molecular Genetic Testing Approaches for hereditary PGL/PCC syndromes include use of a multigene panel and single-gene testing (in certain circumstances). A multigene panel that includes MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, and TMEM127 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder, a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. Single-gene testing. Given the cost-effectiveness of multigene panel testing and overlap of phenotype in hereditary PGL/PCC syndromes, single-gene testing is not commonly used. However, in certain situations, it may be more cost effective to use single-gene testing. Prioritized genetic testing may be pursued as single-gene testing based on clinical features: * SDHB in simplex cases, with extra-adrenal tumors [Amar et al 2007]; or in an individual with a malignant tumor * SDHD in individuals with nonsecretory (parasympathetic) or secretory (sympathetic) head and neck paragangliomas (HNPGLs) * Targeted testing for a known familial pathogenic variant ### Table 1. Molecular Genetic Testing Used in Hereditary Paraganglioma-Pheochromocytoma Syndromes View in own window Gene 1, 2Proportion of Hereditary PGL/PCC Syndromes Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detectable by Method Sequence analysis 4Gene-targeted deletion/duplication analysis 5 MAX~1% 6>95% 72 probands 8 SDHA0.6%-3% 6, 9~100% 10None reported SDHAF2<0.1% 6~100% 11None reported SDHB10%-25% 12 12%-20% of HNPGL 13 24%-44% of chest, abdomen, pelvic PGL/PCC 14~85%-95% 12, 13, 14~5%-15% 15 SDHC2%-8% 12, 14~85% 12, 16~15% 17, 18 SDHD~8%-9% 12 ~40%-50% of HNPGL 13 ~15% of chest, abdomen, pelvic PGL/PCC 14~95% 12, 13, 14~5% 17 TMEM127~2% 6~100% 19None reported Unknown 20 1\. Genes are listed in alphabetic order. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. See Molecular Genetics for information on allelic variants detected in this gene. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Due to pseudogenes, many labs do not perform SDHA deletion/duplication analysis. 6\. Bausch et al [2017] 7\. Comino-Méndez et al [2011], Burnichon et al [2012], Rattenberry et al [2013] 8\. Whole-gene deletion reported by Burnichon et al [2012]; complex rearrangement reported by Korpershoek et al [2016] 9\. Burnichon et al [2009], Korpershoek et al [2011], Buffet et al [2012] 10\. Welander et al [2013], Casey et al [2017], van der Tuin et al [2018] 11\. Hao et al [2009], Kunst et al [2011], Piccini et al [2012], Currás-Freixes et al [2015], Zhu et al [2015], Bausch et al [2017] 12\. Andrews et al [2018] 13\. Baysal et al [2002], Burnichon et al [2009] 14\. Amar et al [2005], Burnichon et al [2009] 15\. Single-exon (most commonly exon 1), multiexon, and whole-gene deletions have been reported [Cascón et al 2006, Burnichon et al 2009, Neumann et al 2009, Solis et al 2009, Buffet et al 2012, Rattenberry et al 2013] 16\. Schiavi et al [2005], Peczkowska et al [2008], Neumann et al [2009], Else et al [2014] 17\. Baysal et al [2004], Burnichon et al [2009], Neumann et al [2009], Hoekstra et al [2017] 19\. Qin et al [2010], Yao et al [2010], Neumann et al [2011], Qin et al [2014] 20\. KIF1B, EGLN1 (formerly known as PHD2), MDH2, EPAS1, and FH have been reported to be associated with hereditary PGL/PCC; their clinical significance is as yet unclear. #### Tumor Immunohistochemistry If germline molecular genetic testing for hereditary PGL/PCC syndromes is not readily available, the results of immunohistochemical tumor analysis may suggest the presence of an underlying germline pathogenic variant. When any component of the mitochondrial respiratory chain complex 2 is completely inactivated, it appears that the entire complex becomes unstable, resulting in degradation of the SDHB subunit. Therefore, immunohistochemistry for SDHB is negative if there is complete inactivation of SDHA, SDHB, SDHC, or SDHD. As a result, negative staining for SDHB in tumor tissue appears to occur when a germline pathogenic variant in SDHA, SDHB, SDHC, or SDHD is accompanied by inactivation of the normal allele; thus, negative staining for SDHB may suggest the presence of a germline pathogenic variant of one of the SDH subunits [van Nederveen et al 2009, Gill et al 2010, Pai et al 2014, Udager et al 2018]. Germline pathogenic variants in SDHA show loss of staining for SDHA, in addition to loss of staining for SDHB [Korpershoek et al 2011, Papathomas et al 2015]. For these reasons, some recommend SDHB immunohistochemistry in individuals with familial and apparently sporadic PGL/PCC to guide molecular genetic testing; however, evidence is currently insufficient to advocate for the routine use of immunohistochemistry to guide molecular testing as several nonconcordant cases have been reported. Pathogenic variants in VHL also appear to contribute to difficulty in interpreting SDHB immunohistochemistry results. Therefore, since there are still some challenges in interpreting SDHB immunohistochemistry, and the procedure is not widely available, it is unclear whether it should be routinely performed on PGL/PCC tumor tissue. ## Clinical Characteristics ### Clinical Description In individuals with hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes, tumors arise within the paraganglia – collections of neural crest cells distributed along the paravertebral axis from the base of the skull to the pelvis – as well as in some visceral locations. The 2017 World Health Organization (WHO) Classification of Endocrine Tumours classifies paragangliomas/pheochromocytomas by location and (directly or indirectly) secretory status [Lloyd et al 2017]. Paragangliomas (paraganglion tumors) arise from neuroendocrine tissues (paraganglia) distributed along the paravertebral axis from their predominant location at the skull base to the pelvis. Head and neck paragangliomas (HNPGLs) and those in the upper mediastinum are primarily associated with the parasympathetic nervous system and typically do not secrete catecholamines or other hormones. Approximately 5% of HNPGLs secrete catecholamines. The rare secretory tumors in the head and neck area are either a subset of carotid body tumors or arise from the cervical sympathetic chain. Most HNPGLs do not metastasize, although there are many exceptions. Clinical complications of HNPGLs are typically the result of mass effect: * Carotid body paragangliomas often present as asymptomatic, enlarging lateral neck masses. (The carotid bodies are located at or near the bifurcations of the carotid arteries, in the lateral upper neck at approximately the level of the fourth cervical vertebra.) Affected individuals may experience mass effects, including cranial nerve and sympathetic chain compression, with resulting neuropathies. On physical examination masses are vertically (but not horizontally) fixed; bruits and/or thrills may be present. * Vagal paragangliomas present in a manner similar to carotid body paragangliomas. Signs and symptoms include neck masses, hoarseness, pharyngeal fullness, dysphagia, dysphonia (impaired use of the voice), pain, cough, and aspiration. Dysphonia may be caused by mass effects within the throat or by pressure on nerves supplying the vocal cords or tongue. * Jugulotympanic paragangliomas may present with pulsatile tinnitus, hearing loss, and other lower cranial nerve abnormalities. Blue-colored, pulsatile masses may be visualized behind the tympanic membrane on otoscopic examination [Gujrathi & Donald 2005]. Paragangliomas in the lower mediastinum, abdomen, and pelvis are typically associated with the sympathetic nervous system and usually secrete catecholamines. Sympathetic paragangliomas located along the paravertebral axis (and not in the adrenal gland) are called "extra-adrenal sympathetic paragangliomas." Extra-adrenal sympathetic paragangliomas have an increased likelihood of malignant transformation [Ayala-Ramirez et al 2011]. Pheochromocytomas are catecholamine-secreting paragangliomas confined to the adrenal medulla. Malignancy is less likely in pheochromocytomas but certainly does occur (see Genotype-Phenotype Correlations). Pheochromocytomas are also known as adrenal chromaffin tumors. Note: "Chromaffin cells/tumors" is another term for any sympathetic (catecholamine-secreting) neuroendocrine cells/tumors regardless of location. "Chromaffin" refers to the brown-black color that results from oxidization and polymerization of catecholamines contained in the cells/tumors by chromium salts (e.g., potassium dichromate). Signs and symptoms of paraganglioma and pheochromocytoma are similar in individuals with hereditary PGL/PCC syndromes and individuals with sporadic (i.e., not inherited) tumors, most often coming to medical attention in the following four clinical settings: * Signs and symptoms of catecholamine excess, including episodic or sustained elevations in blood pressure and pulse, headaches, palpitations (perceived episodic, forceful, often rapid heartbeat), arrhythmias, excessive sweating, pallor, apprehension, and anxiety. Nausea, emesis, fatigue, sudden alteration in glycemic control, and weight loss can also be seen. Paroxysmal symptoms may be triggered by changes in body position, increases in intra-abdominal pressure, medications (e.g., metoclopramide), anesthesia induction, exercise, or micturition in individuals with urinary bladder paragangliomas. Urinary bladder paragangliomas may also be accompanied by painless hematuria. * Signs and symptoms related to mass effects from the neoplasm (particularly HNPGLs) which can compromise cranial nerves (e.g., VII, IX, X, XI) and sympathetic nerves in the head and neck area leading to hoarseness, dysphagia, soft palate paresis, Horner syndrome, and/or tinnitus * Incidentally discovered mass on MRI/CT performed for other reasons * Screening of at-risk relatives Biochemical features of PGL/PCC. Catecholamines and metanephrines secreted by PGL/PCC can be any of the following: * Epinephrine (adrenaline) and its major metabolite metanephrine * Norepinephrine (noradrenaline) and its major metabolite normetanephrine * Dopamine and its major metabolite 3-methoxytyramine Plasma chromogranin A, not a catecholamine but another substance often secreted by PGL/PCC, can sometimes be useful for diagnosis. Its specificity is not great, however, as many other medical conditions (e.g., liver and kidney disease; gastrointestinal conditions such as IBS and colon cancer; other malignancies) and medications (e.g., proton pump inhibitors) can elevate plasma chromogranin A levels. Radiographic features of PGL/PCC. Individuals with hereditary PGL/PCC syndromes should be evaluated by imaging for tumor localization. CT rather than MRI is often the imaging modality of choice, given its excellent spatial resolution of the thorax, abdomen, and pelvis [Lenders et al 2014]. MRI is a better option in individuals for whom radiation exposure must be limited, such as pregnant women, and for lifelong screening for biochemically silent PGL/PCC and other manifestations in those asymptomatic individuals with known germline pathogenic variants. * Paragangliomas can be identified anywhere along the paravertebral axis from the skull base to the pelvis, including the para-aortic sympathetic chain, as well as some other visceral locations. Common sites of neoplasia are near the renal vessels and in the organ of Zuckerkandl (chromaffin tissues near the origin of the inferior mesenteric artery and the aortic bifurcation). A less common site is within the urinary bladder wall. * PGL/PCC tumors usually exhibit high signal intensity on T2-weighted MRI and have no loss of signal intensity on in- and out-of-phase imaging, which helps distinguish pheochromocytomas from benign adrenal cortical adenomas. On CT examination these tumors are characterized by heterogeneous appearance with cystic areas, high unenhanced CT attenuation (density, Hounsfield units >10), increased vascularity on contrast-enhanced CT, and slow contrast washout. * Multiple tumors can be present. * Whole-body MRI with targeted MRI for positive tumors may be a reasonable approach for both diagnosis and monitoring of individuals with hereditary PGL/PCC syndromes. This strategy minimizes radiation exposure associated with CT scanning, while taking advantage of the high sensitivity of T2-weighted MRI. * Digital subtraction angiography (DSA) is sensitive for the detection of small paragangliomas and can be diagnostically definitive. DSA is essential if preoperative embolization or carotid artery occlusion is to be performed. Distinguishing benign and malignant PGL/PCCs. No reliable pathology studies are available to distinguish a primary benign PGL/PCC from a primary malignant PGL/PCC. Furthermore, biopsy of PGL/PCC is contraindicated because this invasive procedure carries the risk of precipitating a hypertensive crisis, hemorrhage, and tumor cell seeding [Vanderveen et al 2009], and regardless, the pathology of the primary tumor cannot reliably predict the development of metastatic disease [Wu et al 2009]. Malignancy is defined as the presence of PGL/PCC metastases to other sites, the most common of which are bone, lung, liver, and lymph nodes. In fact, the 2017 WHO replaced the term "malignant pheochromocytoma" with "metastatic pheochromocytoma" to avoid confusion in the definition. Having to wait for evidence of metastasis to establish the malignant nature of a tumor may have introduced bias into the present understanding of the natural history of these tumors. For PGL/PCCs that have not metastasized, operative treatment can be curative. However, once metastases have occurred there is no cure, with a five-year survival rate of 50%-69% [Hescot et al 2013, Asai et al 2017, Fishbein et al 2017, Hamidi et al 2017]. To detect metastases, the following radiographic studies can be used: * 68-Ga-DOTATATE PET CT is a more sensitive modality to detect somatostatin receptor positive disease, especially in individuals with metastatic disease [Janssen et al 2015, Chang et al 2016, Janssen et al 2016]. * 123I-metaiodobenzylguanidine (MIBG) scintigraphy is a technique that measures tumor uptake of a catecholamine analog radioisotope. MIBG has greater specificity for localization than CT and MRI, but lower sensitivity. It may be used to further characterize masses detected by CT or MRI and to look for additional sites of disease, and it is used in individuals with metastatic disease where treatment with I-131 MIBG is a consideration. * Octreotide scintigraphy, a technique that measures tumor uptake of a somatostatin analog radioisotope, may be used in addition to MIBG scintigraphy as some MIBG-negative tumors are positive with octreotide scintigraphy. The sensitivity is fairly low, however. Octreotide scintigraphy has been largely replaced by 68-Ga-DOTATATE PET CT, where available, because of the significantly higher sensitivity. * 2- deoxy-2-(18F)-fluoro--D-glucose position emission tomography (FDG-PET), or PET using other imaging compounds, can also assist in detecting metastatic disease. A decisional algorithm for the use of functional imaging in hereditary PGL/PCC syndromes has recently been proposed in the Endocrine Society's Clinical Practice Guideline. See Lenders et al [2014], Figure 2 (full text). Other tumors * Gastrointestinal stromal tumors (GISTs). The majority of GISTs associated with PGL (Carney Stratakis syndrome; OMIM 606864) occur in individuals with a germline pathogenic variant in SDHA or SDHC. Children with GISTs are more likely to have a germline pathogenic variant in a PGL/PCC susceptibility gene than an adult with a GIST. Most GISTs associated with hereditary PGL/PCC syndromes occur in the stomach and are often multifocal (>40%). * Pulmonary chondromas can occur together with GIST and paraganglioma (Carney triad; OMIM 604287). This is an extremely rare disorder that primarily affects young women. Adrenal cortical adenoma and esophageal leiomyoma were later shown to be associated with the syndrome [Stratakis 2009]. Carney found that 78% of affected individuals had two of the three classic tumors and 22% had all three neoplasms [Carney 1999]. Although Carney triad is most often not inherited, at least a subset of individuals (~10%) has a germline pathogenic variant in an SDHx gene [Boikos et al 2016]. In some individuals without an identified germline pathogenic variant, somatic alterations in methylation patterns of SDHx genes can be found in the GIST tumors [Boikos et al 2016]. * Renal clear cell carcinoma is part of the tumor spectrum of hereditary PCC/PGL syndromes, particularly in individuals with pathogenic variants in SDHB and SDHD [Ricketts et al 2010]. The lifetime risk of developing a renal tumor for individuals with an SDHB pathogenic variant is 4.7%, compared to 1.7% in the general population [Andrews et al 2018]. * Other tumors including papillary thyroid carcinoma, pituitary adenomas, and neuroendocrine tumors have been described in individuals with SDHx germline pathogenic variants. However, whether there is an increased risk of developing these other tumors has not been established. Longevity. With staged tumor-targeted treatment modalities some affected individuals have lived with metastatic disease for 20 or more years [Fishbein et al 2017, Hamidi et al 2017]. ### Phenotype Correlations by Gene Although persons with MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, and TMEM127 pathogenic variants can develop pheochromocytomas and/or paragangliomas within any paraganglial tissue, the following correlations between the gene involved and tumor location are used to guide testing, surveillance, and, in some instances, recommended treatment (also see Table 2): MAX. Germline MAX pathogenic variants have most commonly been reported in association with PCCs. Some affected individuals had additional PGLs; all those who have done so presented with PCCs initially [Comino-Méndez et al 2011, Burnichon et al 2012, Bausch et al 2017]. SDHA. Germline SDHA pathogenic variants have been identified in individuals with PCCs and PGLs (sympathetic and parasympathetic) [Burnichon et al 2010, Korpershoek et al 2011, Bausch et al 2017]. SDHAF2. Germline pathogenic variants in SDHAF2 have only been seen in association with HNPGLs [Hao et al 2009, Bayley et al 2010, Kunst et al 2011, Piccini et al 2012, Currás-Freixes et al 2015, Zhu et al 2015, Bausch et al 2017]. SDHB. Germline pathogenic variants in SDHB are generally associated with higher morbidity and mortality than pathogenic variants in the other SDHx genes [Ricketts et al 2010, Andrews et al 2018]. They are strongly associated with extra-adrenal sympathetic paragangliomas with an increased risk of metastatic disease, and, less frequently, with PCCs and parasympathetic PGLs [Andrews et al 2018]. Up to 50% of persons with metastatic extra-adrenal paragangliomas have a germline SDHB pathogenic variant [Fishbein et al 2013]. SDHC. Germline SDHC pathogenic variants appear to be primarily (but not exclusively) associated with HNPGL. However, up to 10% of SDHC-related tumors are observed in the thoracic cavity [Peczkowska et al 2008, Else et al 2014]. SDHD. SDHD pathogenic variants are mainly associated with HNPGL, although extra-adrenal PGL and PCC certainly occur [Ricketts et al 2010, Andrews et al 2018]. Persons with a germline SDHD pathogenic variant are more likely to have multifocal disease than persons with sporadic tumors or those with a germline SDHB pathogenic variant [Boedeker et al 2005]. TMEM127. Germline TMEM127 pathogenic variants are associated with adrenal PCC but can also be associated with HNPGL and extra-adrenal PGL [Neumann et al 2011]. Renal cell carcinoma has also been associated [Qin et al 2014]. ### Table 2. Distinguishing Clinical Features of PGL/PCC by Genetic Etiology View in own window GeneDistinguishing Clinical Features 1 PGL vs PCCBilateral PCC or multiple PGLBiochemical phenotypeMalignancy riskMOI MAXPCC~60% bilateralMixed25%Possibly paternal 2 SDHAPGL, PCCSingleMixedLowAD SDHAF2 3PGL (skull base & neck)~90% multipleUnclearLowPaternal 2 SDHBPGL~20% multipleNorepinephrine/ normetanephrine34%-97%AD SDHCPGL~20% multipleNorepinephrine/ normetanephrineLowAD SDHDPGL (skull base & neck)~50% multipleNorepinephrine/ normetanephrine, often silent<5%Paternal 4 TMEM127PCC, rarely PGL~25% bilateralMixedLowAD AD = autosomal dominant ; MOI = mode of inheritance 1\. General rules of thumb; exceptions exist. 2\. Mode of inheritance is likely paternal; only a few pedigrees have been described. 3\. Phenotype is not well described as only a few families have been reported. 4\. Maternal transmission has been rarely reported. ### Genotype-Phenotype Correlations No consistent genotype-phenotype correlations have been identified. ### Penetrance Age-related penetrance. Penetrance estimates vary (see Table 3). Penetrance was initially believed to be quite high, but larger studies with less bias from probands suggest a much lower penetrance. No reliable penetrance data are currently available for MAX, SDHAF2, or TMEM127 pathogenic variants. ### Table 3. Estimated Penetrance for SDHB and SDHD Pathogenic Variants View in own window GeneAge in YearsPenetrance of PGL/PCC in Non-ProbandsPenetrance of PGL/PCC in Probands and Non-ProbandsReferences SDHA7010%50%van der Tuin et al [2018] SDHB6021.8%-26.4%23.9%-57.6%Jochmanova et al [2017], Andrews et al [2018] SDHC6025% 1NRAndrews et al [2018] SDHD6043.2%NRAndrews et al [2018] NR = not reported 1\. This estimate is higher than expected based on clinical experience. ### Nomenclature The hereditary PGL/PCC syndromes were initially referred to as the hereditary paraganglioma syndromes prior to the discovery of their association with pheochromocytomas. Hereditary paragangliomas of the head and neck have also been referred to as familial glomus tumors and familial nonchromaffin paragangliomas. Initially these syndromes were numbered PGL1-5. However, now that the genetic basis has been determined, it makes most sense to refer to the associated affected gene; e.g., SDHB-associated hereditary PGL/PCC syndrome. Carney-Stratakis syndrome (OMIM 606864) and Carney triad (OMIM 604287) are largely historic terms predating the use of a molecular-driven nomenclature and are best reserved for individuals with the clinical features but without SDHx germline pathogenic variants. Pheochromocytomas are tumors of the adrenal medulla, which is a specialized paraganglion. Paragangliomas arise from paraganglial tissue anywhere in the body, usually as head and neck paragangliomas (HNPGLs; e.g., carotid body tumor, glomus jugulare tumor, glomus tympanicum tumor, glomus vagale tumor), as thoracic paragangliomas either arising from paraganglia associated with the large arteries or the paraspinal sympathetic chain, or as abdominal paragangliomas (e.g., organ of Zuckerkandl, para-adrenal, bladder wall). The term "chromaffin" tumor is largely historic and refers to positive staining by chromium salts, which react with catecholamines. Therefore, usually only catecholamine-secreting tumors, such as pheochromocytomas and sympathetic paragangliomas, are truly chromaffin – while most parasympathetic tumors are silent. ### Prevalence The incidence of hereditary PGL/PCC syndromes is not precisely known. The incidence of pheochromocytoma is approximately 0.6:100,000/year [Berends et al 2018]. About 25% of all pheochromocytomas arise in individuals with a hereditary predisposition. The incidence of paragangliomas is lower, but these tumors are more often associated with hereditary predisposition. Altogether, about 35%-40% of all PGL/PCC are associated with a hereditary predisposition. ## Differential Diagnosis The differential diagnosis of hereditary PGL/PCC syndromes includes sporadic PCC and PGL or other syndromes that predispose to PCC or PGL development. Sporadic pheochromocytoma. The incidence of all PCC is ~0.6/100,000, and 75% are thought to be sporadic (not associated with hereditary predisposition). Sporadic paraganglioma. The incidence of sporadic PGL is not known. It is believed to be less common than sporadic PCC; but the association with hereditary predisposition is higher than for PCC. Several genetic disorders (see Table 4) associated with an increased risk of pheochromocytomas (PCC) and/or paragangliomas (PGL) have additional clinical features that are not seen in individuals with hereditary PGL/PCC syndromes. ### Table 4. Disorders to Consider in the Differential Diagnosis of Hereditary PGL/PCC View in own window DisorderGeneMOIClinical Features of the Differential Diagnosis Disorder 1 Overlapping w/hereditary PGL/PCCDistinguishing from hereditary PGL/PCC Neurofibromatosis type INF1AD * PCC that secrete epinephrine &/or norepinephrine * PGL are rare. * Café au lait macules * Axillary & inguinal freckling * Neurofibromas Von Hippel-Lindau diseaseVHLAD * PCC that secrete norepinephrine/ normetanephrine * PGL are infrequent. * Hemangioblastomas * Renal, pancreatic, epididymal, & broad ligament cysts * Renal cell carcinoma * Pancreatic neuroendocrine tumors Multiple endocrine neoplasia type 2RETAD * PCC that secrete epinephrine/metanephrine &/or norepinephrine/normetanephrine * PGL are rare. MEN2A: * Medullary thyroid carcinoma * Hyperparathyroidism MEN2B: * Mucocutaneous neuromas * Ganglioneuromatosis * Slender body habitus * Joint laxity * Skeletal malformations Polycythemia-paraganglioma-somatostatinoma syndromeEPAS1See footnote 2.PGL * Mainly in females * Polycythemia * Somatostatinoma AD = autosomal dominant; MOI = mode of inheritance; PCC = pheochromocytoma; PGL = paraganglioma 1\. General rules of thumb; exceptions exist. 2\. To date, all reported individuals with polycythemia-paraganglioma-somatostatinoma syndrome have the disorder as the result of a somatic mosaic pathogenic variant (i.e., a pathogenic variant not inherited from a parent). ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndrome, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended. Refer the individual to an expert on PGL/PCC (often an endocrinologist, oncologist, and/or clinical geneticist). Involvement of other subspecialties and multidisciplinary care (e.g., ENT, cardiology, gastroenterology) should be included when appropriate. The specialist with expertise in PGL/PCC (often an endocrinologist or oncologist) should then complete the evaluation (see following). Note: Evaluate for and treat hypertension and tachycardia, as they need to be controlled prior to initiation of therapy. For individuals with suspected PGL/PCC (based on symptoms or biochemical findings) * Cross-sectional imaging (MRI/CT) is the preferred method to define tumor extent. CT or MRI may be preferable based on suspected tumor location. HNPGL are often best characterized by MRI examination, thoracic PGL are best characterized by CT examination, and abdominal tumors by either MRI or CT examination. * Functional studies, such as somatostatin-receptor-based imaging (e.g., 68-Ga- DOTATATEPET CT) or less commonly other functional studies (e.g., FDG-PET, 123I-MIBG) can aid in defining cross-sectional imaging findings as functional tumors. For individuals with a suspected gastrointestinal stromal tumor (GIST) (based on symptoms). Clinical (including endoscopic) evaluation for GIST in children, adolescents, or young adults who are heterozygous for a hereditary PGL/PCC-related pathogenic variant and who have unexplained gastrointestinal symptoms (e.g., abdominal pain, upper gastrointestinal bleeding, nausea, vomiting, difficulty swallowing) or who experience unexplained intestinal obstruction or anemia [Pasini et al 2008, Rednam et al 2017] For at-risk asymptomatic individuals * Tumor screening for secreting and nonsecreting PGL/PCC and other associated tumors (e.g., renal cell carcinoma, GIST) utilizing non-radiating imaging (e.g., whole-body MRI every 2 years) * Biochemical evaluation, including plasma-free fractionated metanephrines or 24-hour urine fractionated metanephrines (optional dopamine or 3-methoxytyramine) to screen for functional PGL/PCC Other. Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Clinical practice guidelines for the management of individuals with PGL/PCC have been published [Lenders et al 2014] (full text). The management of tumors in individuals with hereditary PGL/PCC syndromes resembles management of sporadic tumors; however, persons with hereditary PGL/PCC syndromes are more likely to have multiple tumors and multifocal and/or metastatic disease than are those with sporadic tumors. For catecholamine-secreting tumors, treatment is directed toward containing the effect of catecholamines through antagonism of catecholamine excess with pharmacologic adrenergic blockade prior to surgical removal [Lenders et al 2014]. For nonsecretory HNPGL, early detection allows for a timely decision regarding treatment (or surveillance). Early detection is believed to reduce operative morbidity and improve prognosis [Rinaldo et al 2004, Gujrathi & Donald 2005]. However, watchful waiting and radiation therapy are often equally beneficial or better approaches. Because most HNPGL are nonsecretory, all individuals with HNPGL should be evaluated for catecholamine excess before surgical resection, which, if present, can suggest an additional primary PGL/PCC. * For carotid body, glomus tympanicum, and vagal paragangliomas, approaches may include observation, surgical resection, and radiation. The decision should be based on the extent of the tumor (e.g., Shamblin I and II carotid body tumors are good candidates for surgery), treatment-associated risks (e.g., resection of glomus vagal tumors almost invariably leads to loss of the ipsilateral vagal and recurrent laryngeal nerve), and presumed malignant potential (e.g., SDHB-associated tumors could be considered for more aggressive therapy). Radiation therapy is an option, and there is currently no evidence for an increased incidence of secondary malignancies in this population due to the underlying genetic condition [Taïeb et al 2014]. * For jugular paragangliomas, small tumors may potentially be removed without complications or permanent nerve injuries. However, resection of larger tumors is often associated with CSF leak, meningitis, stroke, hearing loss, cranial nerve palsy, or even death. Therefore, close observation with symptomatically guided surgery may be prudent. Radiation therapy can also be considered [Taïeb et al 2014]. In selected individuals, stereotactic radiosurgery may also be performed [Taïeb et al 2014]. For pheochromocytomas, surgery, preferably laparoscopic, is the treatment of choice [Lenders et al 2014]. * Preoperative. The chronic and acute effects of catecholamine excess from adrenal chromaffin tumors must be treated preoperatively. Alpha-adrenergic blockade is required to control blood pressure and prevent intraoperative hypertensive crises. The Endocrine Society guidelines have an algorithm for medication titration [Lenders et al 2014]: * Alpha-adrenergic blockade (with phenoxybenzamine or prazosin/doxazosin) starting at least seven to ten days preoperatively is indicated to allow for normalization of blood pressure and volume expansion. The dose of the α-blocker is adjusted for a low normal systolic blood pressure for age. * Second-line treatment includes blood pressure control with calcium channel blockers (e.g., amlodipine, nicardipine) [Lenders et al 2014]. * A liberal sodium diet and fluid intake are indicated to allow for plasma volume expansion. * Once adequate α-adrenergic blockade or blood pressure control with calcium channel blockers is achieved, initiation of β-adrenergic blockade may be required to control reflex tachycardia. The dose of the β-adrenergic blocker is adjusted for a target heart rate of 80 beats per minute. * Postoperative. Approximately two to eight weeks after surgery, 24-hour urine fractionated metanephrines and/or plasma-free metanephrines should be measured. * If the levels are normal, resection of the biochemically active pheochromocytoma or paraganglioma should be considered complete. * If the levels are increased, an unresected second tumor and/or occult metastases should be suspected. Metastatic paraganglioma or pheochromocytoma. Treatment options include blood pressure control with alpha blockade to reduce symptoms from high catecholamine levels in individuals with sympathetic tumors, surgical debulking to reduce tumor burden due to mass effect or catecholamine secretion, radiation therapy especially for bony lesions, liver-directed therapy, systemic therapy with chemotherapy (e.g., cyclophosphamide, vincristine, dacarbazine), or I-131 MIBG therapy. In August 2018, one form of MIBG, AZEDRA® (ultratrace iobenguane I-131), was the first FDA-approved systemic therapy for inoperable and metastatic PGL/PCC [Noto et al 2018] (see www.fda.gov). In individuals with SDHB pathogenic variants and paragangliomas or pheochromocytomas, preference is given for surgical resection over watchful waiting due to the risk for metastases. Prompt resection is particularly important for extra-adrenal sympathetic paragangliomas because of their tendency to metastasize. ### Prevention of Secondary Complications Early detection through surveillance and removal of tumors may prevent or minimize complications related to mass effects, catecholamine excess, and development of metastatic disease. ### Surveillance Individuals known to have a hereditary PGL/PCC syndrome and relatives at risk based on family history who have not undergone DNA-based testing need regular clinical monitoring by a physician or medical team with expertise in treatment of hereditary PGL/PCC syndromes. Surveillance is based on physical exam, review of systems, biochemistry, and cross-sectional imaging. Although no clear consensus has been developed regarding when, how, and how often biochemical studies and imaging should be done in at-risk individuals, it is reasonable to consider lifelong annual biochemical and clinical surveillance. In addition, cross-sectional imaging should be recommended for all at-risk individuals, usually including imaging from skull base to pelvis. However, decision making for frequency and intensity of screening should consider the underlying genetic alteration and associated penetrance. Expert working groups recently recommended starting surveillance at age six to eight years [Rednam et al 2017]. Benn et al [2006] estimated that if lifelong screening were to begin at age ten years, disease would be detected in all persons with SDHD pathogenic variants and 96% of persons with SDHB pathogenic variants. Monitoring includes the following: * Annual measurement of plasma-free metanephrines to detect active catecholamine-secreting tumors or 24-hour urine for fractionated metanephrines. Dopamine (and/or 3-methyoxytyramine) can be measured as well to detect dopamine-only-secreting tumors, but measurement of dopamine is part of catecholamine testing and catecholamines are prone to a higher rate of false positives. * Every two years, cross-sectional imaging of skull base to pelvis [Fishbein & Nathanson 2012, Eijkelenkamp et al 2017, Rednam et al 2017]. This is recommended to detect nonsecreting PGL/PCC as well as other associated tumors, such as renal cell carcinoma. Whole-body MRI has become a good option at expert centers [Jasperson et al 2014]. Whenever possible the preference should be given to non-radiation-containing imaging procedures (e.g., MRI) to avoid unnecessary radiation exposure in this population that requires lifetime surveillance. Cross-sectional imaging will detect most PCC and PGL as well as renal cell cancers. Functional scans, such as 68-Ga-DOTATATE PET CT, 123I-MIBG, or FDG-PET, are helpful in identifying metastatic disease and the functional nature of tumors observed on cross-sectional imaging, but should remain reserved for selected individuals (e.g., those with concern for metastatic tumors). Imaging surveillance should be considered starting at age six to eight years. However, discussion with the family regarding risks (e.g., anesthesia necessary for MRI in children) vs benefits (tumor detection) is important. * In individuals (especially children, adolescents, or young adults) who have unexplained gastrointestinal symptoms (e.g., abdominal pain, upper gastrointestinal bleeding, nausea, vomiting, difficulty swallowing) or who experience unexplained intestinal obstruction or anemia, endoscopic evaluation for GISTs should be considered (e.g., esophagogastroduodenoscopy) as the majority of tumors will be in the stomach [Pasini et al 2008, Rednam et al 2017]. ### Agents/Circumstances to Avoid There is some limited evidence that the penetrance of hereditary PGL/PCC syndromes may be increased in those who live in high altitudes or are chronically exposed to hypoxic conditions [Astrom et al 2003]. However, no recommendation can be based on this very limited evidence. Activities such as cigarette smoking that predispose to chronic lung disease should be discouraged. ### Evaluation of Relatives at Risk Evaluation of apparently asymptomatic older and younger at-risk relatives of an affected individual is recommended. Identification of at-risk family members improves diagnostic certainty and reduces the need for costly screening procedures in those at-risk family members who have not inherited a pathogenic variant. Early detection of tumors can facilitate surgical removal, decrease related morbidity, and potentially result in removal prior to malignant transformation or metastasis. Evaluations can include the following: * Molecular genetic testing. If the pathogenic variant in the family is known, molecular testing of the family members of the proband should be offered by age six to eight years. Note: Pathogenic variants in SDHD and SDHAF2 (and possibly MAX) demonstrate parent-of-origin effects and cause disease almost exclusively when they are paternally inherited. However, a thorough family history and risk assessment should be used in determining surveillance strategies in these families regardless of suspected parent-of-origin effects. * Screening. If the pathogenic variant in the family is not known, screening for PGL/PCC can be considered in families with more than one individual with PGL/PCC. Of note, there are only very rare families with more than one individual with PGL/PCC in which no germline pathogenic variant was found. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management There are no published consensus management guidelines for the diagnosis and management of hereditary PGL/PCC syndromes during pregnancy. A high index of suspicion for these tumors in pregnant women is indicated, since there are other more common causes of hypertension during pregnancy (e.g., preeclampsia). Secretory PGLs/PCCs are more likely to present at any time during pregnancy (whereas preeclampsia is more common in the 2nd or 3rd trimester) and are typically not associated with weight gain, edema, proteinuria, or thrombocytopenia. Individuals with PGLs/PCCs are more likely to present with palpitations, sweating pallor, orthostatic hypotension, and glucosuria, and the hypertension may be episodic. Every individual with hereditary PGL/PCC syndrome should be evaluated for an active catecholamine-secreting tumor prior to planned pregnancy or as soon as pregnancy is known. This evaluation can be done by measurement of fractionated metanephrines and catecholamines in a 24-hour urine sample or measurement of plasma-free metanephrines. There is no consensus regarding the frequency of follow-up biochemical evaluation during pregnancy, but obtaining levels during the second trimester (preferred window for surgery) and prior to delivery should be considered. MRI without gadolinium administration should be the first-line test used to localize a tumor, since CT examination will expose the fetus to radiation. Radioisotope imaging studies should be deferred until after pregnancy in nonlactating mothers for similar reasons. Surgery is the definitive treatment for these tumors, with appropriate α-adrenergic and (if needed) subsequent β-adrenergic blockade to prevent a hypertensive crisis. Phenoxybenzamine is the α-blocker of choice in pregnant individuals [Reisch et al 2006]. For intra-abdominal PGL/PCC, a laparoscopic surgical approach is ideal if the tumor size allows. After 24 weeks' gestation, surgery may need to be delayed until fetal maturity is reached (~34 weeks) because of problems with tumor accessibility. An open surgical approach combined with elective C-section may be necessary in these situations. A good outcome with vaginal delivery has only been described in a few individuals [Junglee et al 2007]. See MotherToBaby for further information on medication use during pregnancy. ### Therapies Under Investigation For metastatic PGL/PCC, several therapies are under investigation. Preliminary studies with peptide receptor radionuclide therapy (PRRT) have shown clinical and biochemical responses that suggest increased survival in PGL/PCC [Kong et al 2017]. Furthermore, tyrosine kinase inhibitors such as cabozantinib are under investigation (see clinicaltrials.gov), and sunitinib showed a modest increase in progression-free survival [Ayala-Ramirez et al 2012]. There are a number of open studies in North America and Europe. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Hereditary Paraganglioma-Pheochromocytoma Syndromes	None	969	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1548/	2021-01-18T21:20:38	{"synonyms": []}
Medullary sponge kidney (MSK) is a birth defect of the tubules - tiny tubes inside the kidneys. In MSK, tiny sacs called cysts form in the inner part of the kidney (the medulla), creating a sponge-like appearance. The cysts keep urine from flowing freely through the tubules. MSK is present at birth but symptoms typically do not occur until adolescence or adulthood. Many people with MSK have no symptoms, but others may have blood in the urine, kidney stones, and urinary tract infections. Rarely, MSK leads to more serious problems, such as chronic pain and kidney failure. The cause for MSK is unknown but some cases may run in families. Treatment is aimed at preventing and removing kidney stones and treating urinary tract infections with antibiotics. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Medullary sponge kidney	c0022681	970	gard	https://rarediseases.info.nih.gov/diseases/232/medullary-sponge-kidney	2021-01-18T17:59:11	{"mesh": ["D007691"], "orphanet": ["1309"], "synonyms": ["Cacchi Ricci disease", "Precalyceal canalicular ectasia", "Cacchi-Ricci syndrome", "Sponge kidney", "Cystic dilatation of renal collecting tubes", "Cacchi-Ricci disease", "MSK", "Precalicial canalicular ectasia"]}
Atopic dermatitis Other namesAtopic eczema, infantile eczema, prurigo Besnier, allergic eczema, neurodermatitis[1] Atopic dermatitis of the inside crease of the elbow SpecialtyDermatology SymptomsItchy, red, swollen, cracked skin[2] ComplicationsSkin infections, hay fever, asthma[2] Usual onsetChildhood[2][3] CausesUnknown[2][3] Risk factorsFamily history, living in a city, dry climate[2] Diagnostic methodBased on symptoms after ruling out other possible causes[2][3] Differential diagnosisContact dermatitis, psoriasis, seborrheic dermatitis[3] TreatmentAvoiding things that worsen the condition, daily bathing followed by moisturising cream, steroid creams for flares[3] Frequency~20% at some time[2][4] Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis).[2] It results in itchy, red, swollen, and cracked skin.[2] Clear fluid may come from the affected areas, which often thickens over time.[2] While the condition may occur at any age, it typically starts in childhood, with changing severity over the years.[2][3] In children under one year of age, much of the body may be affected.[3] As children get older, the areas on the insides of the knees and elbows are most commonly affected.[3] In adults, the hands and feet are most commonly affected.[3] Scratching the affected areas worsens the symptoms, and those affected have an increased risk of skin infections.[2] Many people with atopic dermatitis develop hay fever or asthma.[2] The cause is unknown but believed to involve genetics, immune system dysfunction, environmental exposures, and difficulties with the permeability of the skin.[2][3] If one identical twin is affected, there is an 85% chance the other also has the condition.[5] Those who live in cities and dry climates are more commonly affected.[2] Exposure to certain chemicals or frequent hand washing makes symptoms worse.[2] While emotional stress may make the symptoms worse, it is not a cause.[2] The disorder is not contagious.[2] The diagnosis is typically based on the signs and symptoms.[3] Other diseases that must be excluded before making a diagnosis include contact dermatitis, psoriasis, and seborrheic dermatitis.[3] Treatment involves avoiding things that make the condition worse, daily bathing with application of a moisturising cream afterwards, applying steroid creams when flares occur, and medications to help with itchiness.[3] Things that commonly make it worse include wool clothing, soaps, perfumes, chlorine, dust, and cigarette smoke.[2] Phototherapy may be useful in some people.[2] Steroid pills or creams based on calcineurin inhibitors may occasionally be used if other measures are not effective.[2][6] Antibiotics (either by mouth or topically) may be needed if a bacterial infection develops.[3] Dietary changes are only needed if food allergies are suspected.[2] Atopic dermatitis affects about 20% of people at some point in their lives.[2][4] It is more common in younger children.[3] Males and females are equally affected.[2] Many people outgrow the condition.[3] Atopic dermatitis is sometimes called eczema, a term that also refers to a larger group of skin conditions.[2] Other names include "infantile eczema", "flexural eczema", "prurigo Besnier", "allergic eczema", and "neurodermatitis".[1] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Genetics * 2.2 Hygiene hypothesis * 2.3 Allergens * 2.4 Role of Staphylococcus aureus * 2.5 Hard water * 3 Pathophysiology * 4 Diagnosis * 5 Treatments * 5.1 Lifestyle * 5.2 Diet * 5.3 Medication * 5.4 Light * 5.5 Alternative medicine * 6 Epidemiology * 7 Research * 8 References * 9 External links ## Signs and symptoms[edit] The pattern of atopic eczema varies with age. People with AD often have dry and scaly skin that spans the entire body, except perhaps the diaper area, and intensely itchy red, splotchy, raised lesions to form in the bends of the arms or legs, face, and neck.[7][8][9][10][11] AD commonly affects the eyelids where signs such as Dennie-Morgan infraorbital fold, infra-auricular fissure, and periorbital pigmentation can be seen.[12] Post-inflammatory hyperpigmentation on the neck gives the classic 'dirty neck' appearance. Lichenification, excoriation and erosion or crusting on the trunk may indicate secondary infection. Flexural distribution with ill-defined edges with or without hyperlinearity on the wrist, finger knuckles, ankle, feet and hand are also commonly seen.[13] ## Causes[edit] The cause of AD is not known, although there is some evidence of genetic, environmental, and immunologic factors.[14] ### Genetics[edit] Many people with AD have a family history of atopy. Atopy is an immediate-onset allergic reaction (type 1 hypersensitivity reaction) that manifests as asthma, food allergies, AD or hay fever.[7][8] About 30% of people with atopic dermatitis have mutations in the gene for the production of filaggrin (FLG), which increase the risk for early onset of atopic dermatitis and developing asthma.[15][16] ### Hygiene hypothesis[edit] According to the hygiene hypothesis, early childhood exposure to certain microorganisms (such as gut flora and helminth parasites) protects against allergic diseases by contributing to the development of the immune system.[17] This exposure is limited in a modern "sanitary" environment, and the incorrectly-developed immune system is prone to develop allergies to harmless substances. There is some support for this hypothesis with respect to AD.[18] Those exposed to dogs while growing up have a lower risk of atopic dermatitis.[19] There is also support from epidemiological studies for a protective role for helminths against AD.[20] Likewise children with poor hygiene are at a lower risk for developing AD, as are children who drink unpasteurised milk.[20] ### Allergens[edit] In a small percentage of cases, atopic dermatitis is caused by sensitization to foods.[21] Also, exposure to allergens, either from food or the environment, can exacerbate existing atopic dermatitis.[22] Exposure to dust mites, for example, is believed to contribute to one's risk of developing AD.[23] A diet high in fruits seems to have a protective effect against AD, whereas the opposite seems true for fast foods.[20] Atopic dermatitis sometimes appears associated with celiac disease and non-celiac gluten sensitivity, and the improvement with a gluten-free diet indicates that gluten is a causative agent in these cases.[24][25] ### Role of Staphylococcus aureus[edit] Colonization of the skin by the bacterium S. aureus is extremely prevalent in those with atopic dermatitis.[26] Studies have found that abnormalities in the skin barrier of persons with AD are exploited by S. aureus to trigger cytokine expression, thus aggravating the condition.[27] ### Hard water[edit] Atopic dermatitis in children may be linked to the level of calcium carbonate or "hardness" of household water, when used to drink.[28] So far these findings have been supported in children from the United Kingdom, Spain, and Japan.[28] ## Pathophysiology[edit] The pathophysiology may involve a mixture of type I and type IV-like hypersensitivity reactions.[29] ## Diagnosis[edit] Atopic dermatitis is typically diagnosed clinically, meaning it is diagnosed based on signs and symptoms alone, without special testing.[30] Several different forms of criteria developed for research have also been validated to aid in diagnosis.[31] Of these, the UK Diagnostic Criteria, based on the work of Hanifin and Rajka, has been the most widely validated.[31][32] UK diagnostic criteria[32] People must have itchy skin, or evidence of rubbing or scratching, plus three or more of the following: Skin creases are involved: flexural dermatitis of fronts of ankles, antecubital fossae, popliteal fossae, skin around eyes, or neck, (or cheeks for children under 10) History of asthma or allergic rhinitis (or family history of these conditions if patient is a child ≤4 years old) Symptoms began before age 2 (can only be applied to patients ≥4 years old) History of dry skin (within the past year) Dermatitis is visible on flexural surfaces (patients ≥age 4) or on the cheeks, forehead, and extensor surfaces (patients<age 4) ## Treatments[edit] There is no known cure for AD, although treatments may reduce the severity and frequency of flares.[7] ### Lifestyle[edit] Applying moisturisers may prevent the skin from drying out and decrease the need for other medications.[33] Affected persons often report that improvement of skin hydration parallels with improvement in AD symptoms.[7] Health professionals often recommend that persons with AD bathe regularly in lukewarm baths, especially in salt water, to moisten their skin.[8][34] Avoiding woollen clothing is usually good for those with AD. Likewise silk, silver-coated clothing may help.[34] Dilute bleach baths have also been reported effective at managing AD.[34] ### Diet[edit] The role of vitamin D on atopic dermatitis is not clear, but there is some evidence that vitamin D supplementation may improve its symptoms.[35][36] Studies have investigated the role of long chain polyunsaturated fatty acids (LCPUFA) supplementation and LCPUFA status in the prevention and treatment of atopic diseases, but the results are controversial. It remains unclear if the nutritional intake of n-3 fatty acids has a clear preventive or therapeutic role, or if n-6 fatty acids consumption promotes atopic diseases.[37] Several probiotics seem to have a positive effect with a roughly 20% reduction in the rate of atopic dermatitis.[38][39] The best evidence is for multiple strains of bacteria.[40] In people with celiac disease or non-celiac gluten sensitivity, a gluten free diet improves their symptoms and prevents the occurrence of new outbreaks.[24][25] ### Medication[edit] Topical corticosteroids, such as hydrocortisone, have proven effective in managing AD.[7][8] If topical corticosteroids and moisturisers fail, short-term treatment with topical calcineurin inhibitors like tacrolimus or pimecrolimus may be tried, although their use is controversial as some studies indicate that they increase the risk of developing skin cancer or lymphoma.[7][41] A 2007 meta-analysis showed that topical pimecrolimus is not as effective as corticosteroids and tacrolimus.[42] However a 2015 meta-analysis indicated that topical tacrolimus and pimecrolimus are more effective than low dose topical corticosteroids, and found no evidence for increased risk of malignancy or skin atrophy.[43] In 2016, crisaborole, an inhibitor of PDE-4, was approved as a topical treatment for mild-to-moderate eczema.[44][45] Other medications used for AD include systemic immunosuppressants such as ciclosporin, methotrexate, interferon gamma-1b, mycophenolate mofetil and azathioprine.[7][46] Antidepressants and naltrexone may be used to control pruritus (itchiness).[47] In 2017, the biologic agent dupilumab was approved to treat moderate-to-severe eczema.[48] Leukotriene inhibitors such as monteleukast are of unclear benefit as of 2018.[49] There is tentative evidence that allergy immunotherapy is effective in atopic dermatitis, but the quality of the evidence is low.[50] This treatment consists of a series of injections or drops under the tongue of a solution containing the allergen.[50] Antibiotics, either by mouth or applied topically, is commonly used to target overgrowth of Staphylococcus aureus in the skin of people with atopic dermatitis. However, a 2019 meta-analysis found no clear evidence of benefit.[51] ### Light[edit] A more novel form of treatment involves exposure to broad or narrow-band ultraviolet (UV) light. UV radiation exposure has been found to have a localized immunomodulatory effect on affected tissues and may be used to decrease the severity and frequency of flares.[52][53] In particular, the usage of UVA1 is more effective in treating acute flares, whereas narrow-band UVB is more effective in long-term management scenarios.[54] However, UV radiation has also been implicated in various types of skin cancer, and thus UV treatment is not without risk.[55] ### Alternative medicine[edit] While there are several Chinese herbal medicines intended for treating atopic eczema, there is no conclusive evidence that these treatments, taken by mouth or applied topically, reduce the severity of eczema in children or adults.[56] ## Epidemiology[edit] Since the beginning of the twentieth century, many inflammatory skin disorders have become more common; atopic dermatitis (AD) is a classic example of such a disease. It now affects 15–30% of children and 2–10% of adults in developed countries and in the United States has nearly tripled in the past thirty to forty years.[8][57] Over 15 million American adults and children have atopic dermatitis.[58] ## Research[edit] Evidence suggests that IL-4 is central in the pathogenesis of AD.[59] Therefore, there is a rationale for targeting IL-4 with anti-IL-4 inhibitors.[60] People with atopic dermatitis are more likely to have Staphylococcus aureus living on them.[61] The role this plays in pathogenesis is yet to be determined. Medications in Phase III trials as treatments include tralokinumab[62] and abrocitinib.[63] ## References[edit] 1. ^ a b Williams, Hywel C. (2000). The epidemiology of atopic dermatitis. Clinical and Experimental Dermatology. 25. New York: Cambridge University Press. pp. 522–9. doi:10.1046/j.1365-2230.2000.00698.x. ISBN 9780521570756. PMID 11122223. S2CID 31546363. Archived from the original on 2015-06-19. 2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y "Handout on Health: Atopic Dermatitis (A type of eczema)". National Institute of Arthritis and Musculoskeletal and Skin Diseases. May 2013. Archived from the original on 30 May 2015. Retrieved 19 June 2015. 3. ^ a b c d e f g h i j k l m n o p Tollefson MM, Bruckner AL (December 2014). "Atopic dermatitis: skin-directed management". Pediatrics. 134 (6): e1735–44. doi:10.1542/peds.2014-2812. PMID 25422009. 4. ^ a b Thomsen SF (2014). "Atopic dermatitis: natural history, diagnosis, and treatment". ISRN Allergy. 2014: 354250. doi:10.1155/2014/354250. PMC 4004110. PMID 25006501. 5. ^ Williams, Hywel (2009). Evidence-Based Dermatology. John Wiley & Sons. p. 128. ISBN 9781444300178. Archived from the original on 2017-09-08. 6. ^ Carr WW (August 2013). "Topical calcineurin inhibitors for atopic dermatitis: review and treatment recommendations". Paediatric Drugs. 15 (4): 303–10. doi:10.1007/s40272-013-0013-9. PMC 3715696. PMID 23549982. 7. ^ a b c d e f g Berke R, Singh A, Guralnick M (July 2012). "Atopic dermatitis: an overview" (PDF). American Family Physician. 86 (1): 35–42. PMID 22962911. Archived (PDF) from the original on 2015-09-06. 8. ^ a b c d e Kim, BS (21 January 2014). Fritsch, P; Vinson, RP; Perry, V; Quirk, CM; James, WD (eds.). "Atopic Dermatitis". Medscape Reference. WebMD. Archived from the original on 10 February 2014. Retrieved 3 March 2014. 9. ^ Brehler, R (2009). "Atopic Dermatitis". In Lang, F (ed.). Encyclopedia of molecular mechanisms of diseases. Berlin: Springer. ISBN 978-3-540-67136-7. 10. ^ Baron SE, Cohen SN, Archer CB (May 2012). "Guidance on the diagnosis and clinical management of atopic eczema". Clinical and Experimental Dermatology. 37 Suppl 1: 7–12. doi:10.1111/j.1365-2230.2012.04336.x. PMID 22486763. S2CID 28538214. 11. ^ Schmitt J, Langan S, Deckert S, Svensson A, von Kobyletzki L, Thomas K, Spuls P (December 2013). "Assessment of clinical signs of atopic dermatitis: a systematic review and recommendation". The Journal of Allergy and Clinical Immunology. 132 (6): 1337–47. doi:10.1016/j.jaci.2013.07.008. PMID 24035157. 12. ^ Kwatra SG, Tey HL, Ali SM, Dabade T, Chan YH, Yosipovitch G (June 2012). "The infra-auricular fissure: a bedside marker of disease severity in patients with atopic dermatitis". Journal of the American Academy of Dermatology. 66 (6): 1009–10. doi:10.1016/j.jaad.2011.10.031. PMID 22583715. Retrieved 2016-03-20. 13. ^ Lau, Chu-Pak (2006-01-01). Problem-Based Medical Case Management. Hong Kong University Press. ISBN 9789622097759. Archived from the original on 2016-04-01. 14. ^ Grey K, Maguiness S (August 2016). "Atopic Dermatitis: Update for Pediatricians". Pediatric Annals (Review). 45 (8): e280–6. doi:10.3928/19382359-20160720-05. PMID 27517355. 15. ^ Park KD, Pak SC, Park KK (December 2016). "The Pathogenetic Effect of Natural and Bacterial Toxins on Atopic Dermatitis". Toxins (Review). 9 (1): 3. doi:10.3390/toxins9010003. PMC 5299398. PMID 28025545. 16. ^ Irvine AD, McLean WH, Leung DY (October 2011). "Filaggrin mutations associated with skin and allergic diseases". The New England Journal of Medicine (Review). 365 (14): 1315–27. doi:10.1056/NEJMra1011040. PMID 21991953. 17. ^ Scudellari, Megan (2017). "News Feature: Cleaning up the hygiene hypothesis". Proceedings of the National Academy of Sciences. 114 (7): 1433–1436. Bibcode:2017PNAS..114.1433S. doi:10.1073/pnas.1700688114. PMC 5320962. PMID 28196925. 18. ^ Bieber T (April 2008). "Atopic dermatitis". The New England Journal of Medicine. 358 (14): 1483–94. doi:10.1056/NEJMra074081. PMID 18385500. 19. ^ Pelucchi C, Galeone C, Bach JF, La Vecchia C, Chatenoud L (September 2013). "Pet exposure and risk of atopic dermatitis at the pediatric age: a meta-analysis of birth cohort studies". The Journal of Allergy and Clinical Immunology. 132 (3): 616–622.e7. doi:10.1016/j.jaci.2013.04.009. hdl:2434/239729. PMID 23711545. 20. ^ a b c Flohr C, Mann J (January 2014). "New insights into the epidemiology of childhood atopic dermatitis". Allergy. 69 (1): 3–16. doi:10.1111/all.12270. PMID 24417229. S2CID 32645590. 21. ^ di Mauro G, Bernardini R, Barberi S, Capuano A, Correra A, De' Angelis GL, Iacono ID, de Martino M, Ghiglioni D, Di Mauro D, Giovannini M, Landi M, Marseglia GL, Martelli A, Miniello VL, Peroni D, Sullo LR, Terracciano L, Vascone C, Verduci E, Verga MC, Chiappini E (2016). "Prevention of food and airway allergy: consensus of the Italian Society of Preventive and Social Paediatrics, the Italian Society of Paediatric Allergy and Immunology, and Italian Society of Pediatrics". The World Allergy Organization Journal (Review). 9: 28. doi:10.1186/s40413-016-0111-6. PMC 4989298. PMID 27583103. 22. ^ Williams H, Flohr C (July 2006). "How epidemiology has challenged 3 prevailing concepts about atopic dermatitis" (PDF). The Journal of Allergy and Clinical Immunology. 118 (1): 209–13. doi:10.1016/j.jaci.2006.04.043. PMID 16815157. 23. ^ Fuiano N, Incorvaia C (June 2012). "Dissecting the causes of atopic dermatitis in children: less foods, more mites". Allergology International. 61 (2): 231–43. doi:10.2332/allergolint.11-RA-0371. PMID 22361514. 24. ^ a b Fasano A, Sapone A, Zevallos V, Schuppan D (May 2015). "Nonceliac gluten sensitivity". Gastroenterology (Review). 148 (6): 1195–204. doi:10.1053/j.gastro.2014.12.049. PMID 25583468. "Many patients with celiac disease also have atopic disorders. Thirty percent of patients’ allergies with GI symptoms and mucosal lesions, but negative results from serologic (TG2 antibodies) or genetic tests (DQ2 or DQ8 genotype) for celiac disease, had reduced GI and atopic symptoms when they were placed on GFDs. These findings indicated that their symptoms were related to gluten ingestion. GFDs = Gluten free diet" 25. ^ a b Mansueto P, Seidita A, D'Alcamo A, Carroccio A (2014). "Non-celiac gluten sensitivity: literature review" (PDF). Journal of the American College of Nutrition (Review). 33 (1): 39–54. doi:10.1080/07315724.2014.869996. hdl:10447/90208. PMID 24533607. S2CID 22521576. 26. ^ Goh CL, Wong JS, Giam YC (September 1997). "Skin colonization of Staphylococcus aureus in atopic dermatitis patients seen at the National Skin Centre, Singapore". International Journal of Dermatology. 36 (9): 653–7. doi:10.1046/j.1365-4362.1997.00290.x. PMID 9352404. S2CID 3112669. 27. ^ Nakatsuji T, Chen TH, Two AM, Chun KA, Narala S, Geha RS, Hata TR, Gallo RL (November 2016). "Staphylococcus aureus Exploits Epidermal Barrier Defects in Atopic Dermatitis to Trigger Cytokine Expression". The Journal of Investigative Dermatology. 136 (11): 2192–2200. doi:10.1016/j.jid.2016.05.127. PMC 5103312. PMID 27381887. 28. ^ a b Sengupta P (August 2013). "Potential health impacts of hard water". International Journal of Preventive Medicine (Review). 4 (8): 866–75. PMC 3775162. PMID 24049611. 29. ^ Mittermann, Irene; Aichberger, Karl J.; Bünder, Robert; Mothes, Nadine; Renz, Harald; Valenta, Rudolf (2004). "Autoimmunity and Atopic Dermatitis". Current Opinion in Allergy and Clinical Immunology. 4 (5): 367–71. doi:10.1097/00130832-200410000-00007. PMID 15349035. S2CID 32865828. Archived from the original on 2016-08-29. Retrieved 2017-04-16. 30. ^ Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, Berger TG, Bergman JN, Cohen DE, Cooper KD, Cordoro KM, Davis DM, Krol A, Margolis DJ, Paller AS, Schwarzenberger K, Silverman RA, Williams HC, Elmets CA, Block J, Harrod CG, Smith Begolka W, Sidbury R (February 2014). "Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis". Journal of the American Academy of Dermatology. 70 (2): 338–51. doi:10.1016/j.jaad.2013.10.010. PMC 4410183. PMID 24290431. 31. ^ a b Brenninkmeijer EE, Schram ME, Leeflang MM, Bos JD, Spuls PI (April 2008). "Diagnostic criteria for atopic dermatitis: a systematic review". The British Journal of Dermatology. 158 (4): 754–65. doi:10.1111/j.1365-2133.2007.08412.x. PMID 18241277. S2CID 453564. 32. ^ a b Williams HC, Burney PG, Pembroke AC, Hay RJ (September 1994). "The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. III. Independent hospital validation". The British Journal of Dermatology. 131 (3): 406–16. doi:10.1111/j.1365-2133.1994.tb08532.x. PMID 7918017. S2CID 37406163. 33. ^ Varothai S, Nitayavardhana S, Kulthanan K (June 2013). "Moisturizers for patients with atopic dermatitis". Asian Pacific Journal of Allergy and Immunology. 31 (2): 91–8. PMID 23859407. Archived from the original (PDF) on 2015-04-02. Retrieved 2014-03-03. 34. ^ a b c Lio PA (October 2013). "Non-pharmacologic therapies for atopic dermatitis". Current Allergy and Asthma Reports. 13 (5): 528–38. doi:10.1007/s11882-013-0371-y. PMID 23881511. S2CID 40875822. 35. ^ Dębińska A, Sikorska-Szaflik H, Urbanik M, Boznański A (2015). "The role of vitamin D in atopic dermatitis". Dermatitis (Review). 26 (4): 155–61. doi:10.1097/DER.0000000000000128. PMID 26172483. S2CID 35345939. 36. ^ Kim G, Bae JH (September 2016). "Vitamin D and atopic dermatitis: A systematic review and meta-analysis". Nutrition (Systematic Review and Meta-Analysis). 32 (9): 913–20. doi:10.1016/j.nut.2016.01.023. PMID 27061361. 37. ^ Lohner S, Decsi T. Role of Long-Chain Polyunsaturated Fatty Acids in the Prevention and Treatment of Atopic Diseases. In: Polyunsaturated Fatty Acids: Sources, Antioxidant Properties and Health Benefits (edited by: Angel Catalá). NOVA Publishers. 2013. Chapter 11, pp. 1-24. (ISBN 978-1-62948-151-7) 38. ^ Makrgeorgou A, Leonardi-Bee J, Bath-Hextall FJ, Murrell DF, Tang ML, Roberts A, Boyle RJ (November 2018). "Probiotics for treating eczema". The Cochrane Database of Systematic Reviews. 11: CD006135. doi:10.1002/14651858.CD006135.pub3. PMC 6517242. PMID 30480774. 39. ^ Pelucchi C, Chatenoud L, Turati F, Galeone C, Moja L, Bach JF, La Vecchia C (May 2012). "Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis: a meta-analysis". Epidemiology. 23 (3): 402–14. doi:10.1097/EDE.0b013e31824d5da2. PMID 22441545. S2CID 40634979. 40. ^ Chang YS, Trivedi MK, Jha A, Lin YF, Dimaano L, García-Romero MT (March 2016). "Synbiotics for Prevention and Treatment of Atopic Dermatitis: A Meta-analysis of Randomized Clinical Trials". JAMA Pediatrics. 170 (3): 236–42. doi:10.1001/jamapediatrics.2015.3943. PMID 26810481. 41. ^ "Archived copy". Archived from the original on 2015-03-29. Retrieved 2015-03-23.CS1 maint: archived copy as title (link) 42. ^ Ashcroft DM, Chen LC, Garside R, Stein K, Williams HC (October 2007). "Topical pimecrolimus for eczema". The Cochrane Database of Systematic Reviews (4): CD005500. doi:10.1002/14651858.CD005500.pub2. PMID 17943859. 43. ^ Cury Martins J, Martins C, Aoki V, Gois AF, Ishii HA, da Silva EM (July 2015). "Topical tacrolimus for atopic dermatitis". The Cochrane Database of Systematic Reviews (7): CD009864. doi:10.1002/14651858.CD009864.pub2. PMC 6461158. PMID 26132597. 44. ^ "FDA Approves Eucrisa for Eczema". U.S. Food and Drug Administration. 14 December 2016. 45. ^ "Eucrisa (crisaborole) Ointment, 2%, for Topical Use. Full Prescribing Information". Anacor Pharmaceuticals, Inc. Palo Alto, CA 94303 USA. Retrieved 17 December 2016. 46. ^ Yarbrough KB, Neuhaus KJ, Simpson EL (March–April 2013). "The effects of treatment on itch in atopic dermatitis". Dermatologic Therapy. 26 (2): 110–9. doi:10.1111/dth.12032. PMC 4524501. PMID 23551368. 47. ^ Kim K (November 2012). "Neuroimmunological mechanism of pruritus in atopic dermatitis focused on the role of serotonin". Biomolecules & Therapeutics. 20 (6): 506–12. doi:10.4062/biomolther.2012.20.6.506. PMC 3762292. PMID 24009842. 48. ^ "FDA approves new eczema drug Dupixent". US Food & Drug Administration. 28 March 2017. Archived from the original on 28 March 2017. Retrieved 29 March 2017. 49. ^ Ferguson L, Futamura M, Vakirlis E, Kojima R, Sasaki H, Roberts A, Mori R (October 2018). "Leukotriene receptor antagonists for eczema". The Cochrane Database of Systematic Reviews. 10: CD011224. doi:10.1002/14651858.cd011224.pub2. PMC 6517006. PMID 30343498. 50. ^ a b Tam H, Calderon MA, Manikam L, Nankervis H, García Núñez I, Williams HC, Durham S, Boyle RJ (February 2016). "Specific allergen immunotherapy for the treatment of atopic eczema" (PDF). The Cochrane Database of Systematic Reviews. 2: CD008774. doi:10.1002/14651858.CD008774.pub2. hdl:10044/1/31818. PMID 26871981. 51. ^ George, Susannah Mc; Karanovic, Sanja; Harrison, David A.; Rani, Anjna; Birnie, Andrew J.; Bath-Hextall, Fiona J.; Ravenscroft, Jane C.; Williams, Hywel C. (29 October 2019). "Interventions to reduce Staphylococcus aureus in the management of eczema". The Cochrane Database of Systematic Reviews. 2019 (10). doi:10.1002/14651858.CD003871.pub3. ISSN 1469-493X. PMC 6818407. PMID 31684694. 52. ^ Tintle S, Shemer A, Suárez-Fariñas M, Fujita H, Gilleaudeau P, Sullivan-Whalen M, Johnson-Huang L, Chiricozzi A, Cardinale I, Duan S, Bowcock A, Krueger JG, Guttman-Yassky E (September 2011). "Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response". The Journal of Allergy and Clinical Immunology. 128 (3): 583–93.e1–4. doi:10.1016/j.jaci.2011.05.042. PMC 3448950. PMID 21762976. 53. ^ Beattie PE, Finlan LE, Kernohan NM, Thomson G, Hupp TR, Ibbotson SH (May 2005). "The effect of ultraviolet (UV) A1, UVB and solar-simulated radiation on p53 activation and p21". The British Journal of Dermatology. 152 (5): 1001–8. doi:10.1111/j.1365-2133.2005.06557.x. PMID 15888160. S2CID 22191753. 54. ^ Meduri NB, Vandergriff T, Rasmussen H, Jacobe H (August 2007). "Phototherapy in the management of atopic dermatitis: a systematic review". Photodermatology, Photoimmunology & Photomedicine. 23 (4): 106–12. doi:10.1111/j.1600-0781.2007.00291.x. PMID 17598862. 55. ^ Jans J, Garinis GA, Schul W, van Oudenaren A, Moorhouse M, Smid M, Sert YG, van der Velde A, Rijksen Y, de Gruijl FR, van der Spek PJ, Yasui A, Hoeijmakers JH, Leenen PJ, van der Horst GT (November 2006). "Differential role of basal keratinocytes in UV-induced immunosuppression and skin cancer". Molecular and Cellular Biology. 26 (22): 8515–26. doi:10.1128/MCB.00807-06. PMC 1636796. PMID 16966369. 56. ^ Gu S, Yang AW, Xue CC, Li CG, Pang C, Zhang W, Williams HC (September 2013). "Chinese herbal medicine for atopic eczema". The Cochrane Database of Systematic Reviews (9): CD008642. doi:10.1002/14651858.CD008642.pub2. PMID 24018636. 57. ^ Saito H (August 2005). "Much atopy about the skin: genome-wide molecular analysis of atopic dermatitis". International Archives of Allergy and Immunology. 137 (4): 319–25. doi:10.1159/000086464. PMID 15970641. S2CID 20040720. 58. ^ "Atopic Dermatitis". www.uchospitals.edu. 1 January 2015. Archived from the original on 2015-04-08. Retrieved 2 April 2015. 59. ^ Bao L, Shi VY, Chan LS (February 2013). "IL-4 up-regulates epidermal chemotactic, angiogenic, and pro-inflammatory genes and down-regulates antimicrobial genes in vivo and in vitro: relevant in the pathogenesis of atopic dermatitis". Cytokine. 61 (2): 419–25. doi:10.1016/j.cyto.2012.10.031. PMID 23207180. 60. ^ Di Lernia V (January 2015). "Therapeutic strategies in extrinsic atopic dermatitis: focus on inhibition of IL-4 as a new pharmacological approach". Expert Opinion on Therapeutic Targets. 19 (1): 87–96. doi:10.1517/14728222.2014.965682. PMID 25283256. 61. ^ Totté JE, van der Feltz WT, Hennekam M, van Belkum A, van Zuuren EJ, Pasmans SG (October 2016). "Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis". The British Journal of Dermatology. 175 (4): 687–95. doi:10.1111/bjd.14566. PMID 26994362. S2CID 23617550. 62. ^ "Tralokinumab in Combination With Topical Corticosteroids for Moderate to Severe Atopic Dermatitis - ECZTRA 3 (ECZema TRAlokinumab Trial no. 3)". ClinicalTrials.gov. Retrieved November 27, 2019. 63. ^ "Study to Evaluate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis (JADE Mono-1)". ClinicalTrials.gov. Retrieved November 27, 2019. ## External links[edit] Classification D * ICD-10: L20 * ICD-9-CM: 691.8 * OMIM: 603165 * MeSH: D003876 * DiseasesDB: 4113 External resources * MedlinePlus: 000853 * eMedicine: emerg/130 derm/38 ped/2567 oph/479 Wikimedia Commons has media related to Atopic dermatitis. * NIH Handout on Health: Atopic Dermatitis * DermAtlas 9 * "Atopic Dermatitis". Genetics Home Reference. U.S. National Library of Medicine. * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Allergic conditions Respiratory system * Allergic rhinitis (hay fever) * Asthma * Hypersensitivity pneumonitis * Eosinophilic pneumonia * Eosinophilic granulomatosis with polyangiitis * Allergic bronchopulmonary aspergillosis * Farmer's lung * Laboratory animal allergy Skin * Angioedema * Urticaria * Atopic dermatitis * Allergic contact dermatitis * Hypersensitivity vasculitis Blood and immune system * Serum sickness Circulatory system * Anaphylaxis Digestive system * Coeliac disease * Eosinophilic gastroenteritis * Eosinophilic esophagitis * Food allergy * Egg allergy * Milk intolerance Nervous system * Eosinophilic meningitis Genitourinary system * Acute interstitial nephritis Other conditions * Drug allergy * Allergic conjunctivitis * Latex allergy * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji * v * t * e Hypersensitivity and autoimmune diseases Type I/allergy/atopy (IgE) Foreign * Atopic eczema * Allergic urticaria * Allergic rhinitis (Hay fever) * Allergic asthma * Anaphylaxis * Food allergy * common allergies include: Milk * Egg * Peanut * Tree nut * Seafood * Soy * Wheat * Penicillin allergy Autoimmune * Eosinophilic esophagitis Type II/ADCC * * IgM * IgG Foreign * Hemolytic disease of the newborn Autoimmune Cytotoxic * Autoimmune hemolytic anemia * Immune thrombocytopenic purpura * Bullous pemphigoid * Pemphigus vulgaris * Rheumatic fever * Goodpasture syndrome * Guillain–Barré syndrome "Type V"/receptor * Graves' disease * Myasthenia gravis * Pernicious anemia Type III (Immune complex) Foreign * Henoch–Schönlein purpura * Hypersensitivity vasculitis * Reactive arthritis * Farmer's lung * Post-streptococcal glomerulonephritis * Serum sickness * Arthus reaction Autoimmune * Systemic lupus erythematosus * Subacute bacterial endocarditis * Rheumatoid arthritis Type IV/cell-mediated (T cells) Foreign * Allergic contact dermatitis * Mantoux test Autoimmune * Diabetes mellitus type 1 * Hashimoto's thyroiditis * Multiple sclerosis * Coeliac disease * Giant-cell arteritis * Postorgasmic illness syndrome * Reactive arthritis GVHD * Transfusion-associated graft versus host disease Unknown/ multiple Foreign * Hypersensitivity pneumonitis * Allergic bronchopulmonary aspergillosis * Transplant rejection * Latex allergy (I+IV) Autoimmune * Sjögren syndrome * Autoimmune hepatitis * Autoimmune polyendocrine syndrome * APS1 * APS2 * Autoimmune adrenalitis * Systemic autoimmune disease Authority control * GND: 4223208-9 * NDL: 00560319 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Atopic dermatitis	c0011615	971	wikipedia	https://en.wikipedia.org/wiki/Atopic_dermatitis	2021-01-18T19:10:41	{"mesh": ["D003876"], "umls": ["C0011615", "C4280605"], "wikidata": ["Q268667"]}
Mycetoma is a chronic infection that is caused by fungi or actinomycetes (bacteria that produce filaments, like fungi). The first symptom of the condition is generally painless swelling beneath the skin, which progresses to a nodule (lump) over several years. Eventually, affected people experience massive swelling and hardening of the affected area; skin rupture; and formation of sinus tracts (holes) that discharge pus and grains filled with organisms. Some affected people have no discomfort while others report itching and/or pain. Mycetoma is rare in the United States, but is commonly diagnosed in Africa, Mexico and India. In these countries, it occurs most frequently in farmers, shepherds, and people living in rural areas. Frequent exposure to penetrating wounds by thorns or splinters is a risk factor. Treatment varies based on the cause of the condition and may include antibiotics or antifungal medications. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Mycetoma	c0024449	972	gard	https://rarediseases.info.nih.gov/diseases/3862/mycetoma	2021-01-18T17:58:52	{"mesh": ["D008271"], "orphanet": ["2583"], "synonyms": ["Madura foot"]}
Neutrophil immunodeficiency syndrome is a primary immunodeficiency characterized by neutrophilia with severe neutrophil dysfunction, leukocytosis, a predisposition to bacterial infections and poor wound healing, including an absence of pus in infected areas. ## Epidemiology Prevalence is unknown but, to date, two cases have been reported. ## Clinical description Neutrophil immunodeficiency syndrome presents as similar to leukocyte-adhesion deficiency (LAD; see this term), however there is no evidence of deficiency in the CD11b/CD18 complex. ## Etiology The disease is due to a point dominant negative mutation in the RAC2 gene causing decreased Rac2 protein expression and a defect in a signaling pathway controlling shape change/motility of neutrophils as well as assembly and activation of NADPH oxidase. ## Genetic counseling The mode of transmission is unknown. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Neutrophil immunodeficiency syndrome	c1842398	973	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=183707	2021-01-23T18:01:55	{"mesh": ["C564275"], "omim": ["608203"], "umls": ["C1842398"], "icd-10": ["D71"]}
Natal teeth are teeth present at birth and neonatal teeth are teeth that erupt within a month after delivery. Sibert and Porteous (1974) observed natal teeth in 6 members of a kindred. Limrick (1893) first observed natal teeth in a mother, her son and her sister's daughter. Bodenhoff and Gorlin (1963) reported a frequency of about 1 in 3,000 live births for natal teeth. Alaluusua et al. (2002) reported a prevalence of 1 in 1,000 for natal and neonatal teeth in Finland. Ribnik and Hoyme (1989) found an increased frequency of natal teeth in native Americans, particularly in those of Athabascan origin. Alaluusua et al. (2002) found no association between median levels of environmental toxicants in breast milk and early tooth eruption. Natal teeth occur with Ellis-van Creveld syndrome (225500), pachyonychia congenita (see 167200), and Hallermann-Streiff syndrome (234100). King Louis XIV of France was born with teeth, 'a considerable vexation to his wet-nurses' (McKusick, 1955). According to Bodenhoff and Gorlin (1963), the illustrious company also includes Richard III, Zoroaster, Hannibal, Mirabeau, Richelieu, Mazarin, and Broca. Inheritance \- Autosomal dominant Teeth \- Natal teeth ▲ 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	TEETH PRESENT AT BIRTH	c0027443	974	omim	https://www.omim.org/entry/187050	2019-09-22T16:32:50	{"mesh": ["D009306"], "omim": ["187050"], "icd-10": ["K00.6"], "synonyms": ["Alternative titles", "NATAL TEETH"]}
A number sign (#) is used with this entry because Fazio-Londe disease is caused by homozygous mutation in the C20ORF54 gene (SLC52A3; 613350) on chromosome 20p13. One such family has been reported. Mutations in the SLC52A3 gene also cause Brown-Vialetto-Van Laere syndrome (BVVLS; 211530), a similar disorder with the additional feature of sensorineural hearing loss. Description Fazio-Londe disease is a progressive bulbar palsy with onset in childhood that presents with hypotonia and respiratory insufficiency (summary by Bosch et al., 2011). Clinical Features Londe (1894) reported affected 5- and 6-year-old brothers whose parents were first cousins. Marinesco (1915) described it in a 12-year-old girl and her 8-year-old brother. Pyramidal tracts were not involved. Fazio's cases are said (Gomez et al., 1962) to have been a mother and her 4.5-year-old son. Benjamins (1980) described an identically affected sib of the child reported by Gomez et al. (1962). The boy had been seen at age 29 months because of progressive inspiratory stridor. He showed mild bilateral ptosis and almost immobile vocal cords. At 32 months he had difficulty swallowing, ptosis, bilateral facial weakness, absent gag reflex, generalized hyperreflexia and diminished diaphragmatic motion. He died at 36 months of age; the sib had died at 44 months. The disorder showed phenotypic overlap with amyotrophic lateral sclerosis (ALS; 105400). Bosch et al. (2011) reported 2 sibs from a consanguineous family. The first child, a boy, presented at 6 months of age with a short history of progressive muscle weakness followed by life-threatening apneic spells requiring ventilation. He had generalized muscle weakness, severe head lag, and diaphragmatic paralysis. His sister presented at 3 months of age with failure to thrive and generalized axial muscle weakness. Sensorineural hearing loss was excluded by brainstem-evoked response audiometry. Biochemical Features The proband of the consanguineous family with Fazio-Londe disease reported by Bosch et al. (2011) had an acylcarnitine profile suggestive of multiple acyl-CoA dehydrogenase deficiency (MADD; 231680), with an abnormal concentration of short- and medium-chain moieties. Clinical Management Because of the possibility of riboflavin responsiveness, the first patient of Bosch et al. (2011) was treated with high-dose riboflavin (vitamin B2, 10 mg/kg per day). The MADD-associated metabolic abnormalities disappeared within days and the patient's muscle tone slowly improved over the next month. He was able to walk independently at age 22 months. The diaphragmatic paralysis persisted and he required nightly ventilation until 41 months of age. At 46 months of age his cognitive development was normal, and he demonstrated no further cranial nerve palsy. Based on these results, the patient's sister was also treated with riboflavin. She experienced normalization of muscle tone within 7 days and rapid catch-up growth. After 3 months of riboflavin supplementation, her growth and development were normal. Molecular Genetics Bosch et al. (2011) identified a consanguineous family with 2 affected children who were found to be homozygous for a splice site mutation in the C20ORF54 gene (613350.0008). Spinal muscular atrophy (SMA; 253300) had been excluded by genetic testing. Eyes \- Ptosis Respiratory \- Progressive inspiratory stridor \- Diminished diaphragmatic motion Neuro \- Bulbar palsy \- Swallowing difficulty \- Bilateral facial weakness \- Absent gag reflex \- Generalized hyperreflexia \- Pyramidal tracts uninvolved 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	FAZIO-LONDE DISEASE	c0015708	975	omim	https://www.omim.org/entry/211500	2019-09-22T16:30:18	{"mesh": ["D010244"], "omim": ["211500"], "icd-10": ["G12.1"], "orphanet": ["56965", "97229"], "synonyms": ["Alternative titles", "BULBAR PALSY, PROGRESSIVE, OF CHILDHOOD"], "genereviews": ["NBK299312"]}
Monilethrix Other namesMoniliform hair syndrome Beaded hair (60x magnification). SpecialtyMedical genetics Monilethrix (also referred to as beaded hair)[1] is a rare autosomal dominant hair disease that results in short, fragile, broken hair that appears beaded.[2][3] It comes from the Latin word for necklace (monile) and the Greek word for hair (thrix).[4] ## Contents * 1 Presentation * 2 Cause * 3 Diagnosis * 4 Management * 5 See also * 6 References * 7 External links ## Presentation[edit] The presentation may be of alopecia (baldness). Individuals vary in severity of symptoms. Nail deformities may also be present as well as hair follicle keratosis and follicular hyperkeratosis. ## Cause[edit] Monilethrix has an autosomal dominant pattern of inheritance. Monilethrix is caused by mutations affecting the genes KRTHB1 (KRT81), KRTHB3 (KRT83), or KRTHB6 (KRT86) which code for type II hair cortex keratins.[5] The disorder is inherited in an autosomal dominant manner.[2] This means that the defective gene(s) responsible for the disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. ## Diagnosis[edit] Monilethrix may be diagnosed with trichoscopy.[6][7] ## Management[edit] This section is empty. You can help by adding to it. (April 2017) ## See also[edit] * List of cutaneous conditions * List of conditions caused by problems with junctional proteins * List of cutaneous conditions caused by mutations in keratins ## References[edit] 1. ^ James W, Berger T, Elston D (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. ISBN 978-0-7216-2921-6. 2. ^ a b Celep, F.; Uzumcu, A.; Sonmez, F.; Uyguner, O.; Balci, Y.; Bahadir, S.; Karaguzel, A. (2009). "Pitfalls of mapping a large Turkish consanguineous family with vertical monilethrix inheritance". Genetic Counseling (Geneva, Switzerland). 20 (1): 1–8. PMID 19400537. 3. ^ Freedberg; et al. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. p. 639. ISBN 978-0-07-138076-8. 4. ^ Genetic and Rare Diseases Information Center (2008-09-09). "Monilethrix". NIH Office of Rare Diseases Research. Retrieved 2011-01-15. 5. ^ Schweizer J (2006). "More than one gene involved in monilethrix: intracellular but also extracellular players". J. Invest. Dermatol. 126 (6): 1216–9. doi:10.1038/sj.jid.5700266. PMID 16702971. 6. ^ Rudnicka L, Olszewska M, Rakowska A, Kowalska-Oledzka E, Slowinska M (2008). "Trichoscopy: a new method for diagnosing hair loss". J Drugs Dermatol. 7 (7): 651–654. PMID 18664157. 7. ^ Rakowska A, Slowinska M, Kowalska-Oledzka E, Rudnicka L (2008). "Trichoscopy in genetic hair shaft abnormalities". J Dermatol Case Rep. 2 (2): 14–20. doi:10.3315/jdcr.2008.1009. PMC 3157768. PMID 21886705. ## External links[edit] Classification D * ICD-10: Q84.1 (ILDS Q84.140) * ICD-9-CM: 757.4 * OMIM: 158000 * MeSH: D056734 * DiseasesDB: 29592 External resources * eMedicine: derm/763 * Orphanet: 573 * v * t * e Congenital malformations and deformations of skin appendages Nail disease * Anonychia * Leukonychia * Pachyonychia congenita/Onychauxis * Koilonychia Hair disease * hypotrichosis/abnormalities: keratin disease * Monilethrix * IBIDS syndrome * Sabinas brittle hair syndrome * Pili annulati * Pili torti * Uncombable hair syndrome * Björnstad syndrome * Giant axonal neuropathy with curly hair * hypertrichosis: Zimmermann–Laband syndrome * 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 genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e This condition of the skin appendages 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	Monilethrix	c0546966	976	wikipedia	https://en.wikipedia.org/wiki/Monilethrix	2021-01-18T19:01:40	{"gard": ["93"], "mesh": ["D056734"], "umls": ["C0546966"], "icd-9": ["757.4"], "orphanet": ["573"], "wikidata": ["Q1363508"]}
For other uses, see Caul (disambiguation). A caul or cowl (Latin: Caput galeatum, literally, "helmeted head") is a piece of membrane that can cover a newborn's head and face.[1] Birth with a caul is rare, occurring in fewer than 1 in 80,000 births.[citation needed] The caul is harmless and is immediately removed by the physician or midwife upon delivery of the child. The "en-caul" birth, not to be confused with the "caul" birth, occurs when the infant is born inside the entire amniotic sac. The sac balloons out at birth, with the amniotic fluid and child remaining inside the unbroken or partially broken membrane. ## Contents * 1 Types * 2 Removal * 3 Epidemiology * 4 History * 5 In literature * 6 Notable people born "in the caul" * 7 References * 8 External links ## Types[edit] The amniotic sac from an en-caul birth A child "born with the caul" has a portion of a birth membrane remaining on the head. There are two types of caul membranes, and there are four ways such cauls can appear. The most common caul type is a piece of the thin, translucent inner lining of the amnion which breaks away and forms tightly against the head during the birthing process.[2][self-published source?] Such a caul typically clings to the head and face, but on rarer occasions drapes over the head and partly down the torso. In Germany, this would be called a "helmet" (Galea) for boys; in the Netherlands it is also called a "helmet", both for boys and girls (Helm) and in Italy a "fillet" (vitta) or "shirt" (camicia). In Poland, it is called a "bonnet" (czepek), for both sexes. ## Removal[edit] The caul is harmless and is immediately removed by the physician or midwife upon delivery of the child. If the membrane is of the amniotic tissue, it is removed by easily slipping it away from the child's skin. The removal of the thicker membrane is more complex. If done correctly, the attending practitioner will place a small incision in the membrane across the nostrils so that the child can breathe. The loops are then carefully un-looped from behind the ears. Then, the remainder of the caul can be either peeled back very carefully from the skin, or gently rubbed with a sheet of paper, which is then peeled away. If removed too quickly, the caul can leave wounds on the infant's flesh at the attachment points, which may leave permanent scars.[2] ## Epidemiology[edit] Birth with a caul is rare, occurring in fewer than 1 in 80,000 births. This statistic includes en-caul births, which occur more frequently than authentic caul births; therefore authentic caul births are rarer than the statistic indicates.[3] Most "en-caul" births are premature. ## History[edit] According to Aelius Lampridius, the boy-emperor Diadumenian (208–218) was so named because he was born with a diadem formed by a rolled caul.[citation needed] In medieval times the appearance of a caul on a newborn baby was seen as a sign of good luck.[4] It was considered an omen that the child was destined for greatness. Gathering the caul onto paper was considered an important tradition of childbirth: the midwife would rub a sheet of paper across the baby's head and face, pressing the material of the caul onto the paper. The caul would then be presented to the mother, to be kept as an heirloom. Some Early Modern European traditions linked caul birth to the ability to defend fertility and the harvest against the forces of evil, particularly witches and sorcerers.[5] Folklore developed suggesting that possession of a baby's caul would give its bearer good luck and protect that person from death by drowning. Cauls were therefore highly prized by sailors. Medieval women often sold these cauls to sailors for large sums of money; a caul was regarded as a valuable talisman.[6] In the Polish language, the idiom w czepku urodzony/a ('born in a bonnet'), and, in Italian, nato/a con la camicia/a ('born with a shirt'), they both mean a person who is always very lucky. The Russian phrase родился в рубашке (rodilsya v rubashke, literally, "born in a shirt") refers to caul birth and figuratively means "born lucky". It is often applied to someone who is oblivious to a pending disaster that is avoided only through luck as if the birth caul persists as supernatural armor, and in this sense commonly appears in titles or descriptions of Russian dashcam videos.[citation needed] Not all cultural beliefs about cauls are positive. In Romanian folklore, babies born with a caul are said to become strigois upon death.[citation needed] ## In literature[edit] Charles Dickens, David Copperfield, published London 1850: > I was born with a caul, which was advertised for sale, in the newspapers, at the low price of fifteen guineas. Whether sea-going people were short of money about that time, or were short of faith and preferred cork jackets, I don't know; all I know is, that there was but one solitary bidding, and that was from an attorney connected with the bill-broking business, who offered two pounds in cash, and the balance in sherry, but declined to be guaranteed from drowning on any higher bargain. Consequently the advertisement was withdrawn at a dead loss ... and ten years afterwards, the caul was put up in a raffle down in our part of the country, to fifty members at half-a-crown a head, the winner to spend five shillings. I was present myself, and I remember to have felt quite uncomfortable and confused, at a part of myself being disposed of in that way. The caul was won, I recollect, by an old lady with a hand-basket.... It is a fact which will be long remembered as remarkable down there, that she was never drowned, but died triumphantly in bed, at ninety-two. In The Legend of Thyl Ulenspiegel and Lamme Goedzak by Charles De Coster (published 1867), Thyl was born with a caul. In Betty Smith's novel A Tree Grows in Brooklyn, Francie Nolan is born with a caul. The midwife who officiated the birth stole the caul and later sold it for $2 to a sailor from the Brooklyn Navy Yard. It was believed that whoever wore a caul could not drown. A prophecy given to an infant born with the caul is the basis of the Grimm fairy tale The Devil with the Three Golden Hairs. In The Shipping News, the Pulitzer Prize winning book by Annie Proulx, Quoyle's friend Partridge had been born with a caul and "was sure of his own good fortune". In the film Oscar and Lucinda, Oscar's father gives him the caul that was upon his head at birth. Oscar has a phobia of the ocean and of water in general, linked to the death of his mother when he was a child. He carries this caul with him until he dies by drowning. In the play Gypsy: A Musical Fable, Mama Rose tells Louise (Gypsy Rose Lee): "You were born with a caul. That means you got powers to read palms and tell fortunes – and wonderful things are gonna happen to you." Toni Morrison's Song of Solomon stages a scene where observers describe Milkman as "mysterious" and "deep", while asking if he was born with a caul. Another myth associated with a caul is featured in the short story "The Scarlet Ibis". When the main character's brother, Doodle, is born in a caul, his aunt states that cauls are made of Jesus' nightgown and everyone must respect Doodle as he may become a saint someday. In Stephen King's The Shining, the 5-year-old son of the main character, Danny "Doc" Torrance, is born with a caul that made him appear as if he had "no face" at the time of his birth. Although his mother and father do not believe that Danny has "second sight", Danny does have precognitive abilities throughout the story. In the sequel Doctor Sleep, the character Abra is also born with a caul and has paranormal abilities. In the romance book "The Amityville Horror" by Jay Anson (1977), Francine, a medium that tried to help the Lutz family by making a "reading" in their house, stated that she was born with the "Venetian veil" (a caul). Later, George Lutz found out that this meant she was "very sensitive to the energies". In Majgull Axelsson's April Witch, both of the central characters Hubertsson and Desirée are "born to the caul". In Guillermo del Toro's and Chuck Hogan's The Fall, the second installment of The Strain trilogy, Dr. Ephraim Goodweather's son, Zack, is described as being "born in the caul". In Ami McKay's The Birth House, the main character, Dora Rare, is born with a caul over her eyes. Because the character is born in a sailing town, the caul is considered valuable, and the mother gives it to the midwife for safe keeping. When the caul is presented to Dora as an adult, she does not allow her husband to take it and he drowns that very night. Dean Koontz talks about cauls in his novel Whispers. Twins were born, both with a caul. "She was fascinated. You know, some people think that a child born with a caul has the gift of second sight." However, the mother believes it's the mark of a demon. Tina McElroy Ansa's novel Baby of the Family features a lead character born with the caul. She struggles to deal with the ability to see spirits due to her family's inability to believe in the phenomenon and properly prepare her to deal with her gift. In Orson Scott Card's novel Seventh Son, the first part of the series The Tales of Alvin Maker, Alvin Miller (the seventh son of a seventh son) is born with a caul, a sign of his extraordinarily strong magical gifts. In Ole Edvart Rølvaag's Giants in the Earth, Beret and Per Hansa's son, Peder Seier (or Peder Victorious), is born with the caul. Per Hansa was a fisherman in Norway before coming to the plains of South Dakota, and the symbolism of the caul is important to these particular immigrants. In an attempt to stay true to the original Norwegian text, the translation refers to the caul as "the helmet". In Brian McGreevy's Hemlock Grove, Roman and Shelley Godfrey are both born with a caul, indicating their "supernatural" nature to their mother. In Louise Penny's mystery novel The Cruelest Month (also spelled The Cruellest Month), Inspector Jean Guy Beauvoir was born with a caul. In Guy Gavriel Kay's historical fantasy novel Tigana, those born with the caul are marked as Night Walkers, people capable of entering a dream world to fight an unknown struggle for the land known as the Ember War. This may be based on a 16th-century Italian fertility cult, the Benandanti. In Deborah Harkness' historical fiction novel A Discovery of Witches, Diana Bishop is born with a caul. Her parents believe that is a sign that Diana's destiny is to "remain between worlds". In Truman Capote's Jug of Silver, Appleseed, a main character who correctly guesses the amount of change in a jar, is said to have been born with a caul on his head. In the strange underground work (a mix of avant-garde black militancy and pornography) by Steven Cannon, Groove, Bang and Jive Around (1969, rptd. Therion, 1998), protagonist Annette "was born with a caul over her face" (p. 111). Though it remains open to interpretation in the story, there is a suggestion that this birth may have ties to her privileged status in a New Orleans voodoo lineage (she's a blood relation of Doctor John and Marie Laveau): "...you were born with a caul over your face. But lots of 'um is born that way, don't make 'um any better than the rest. But you been blessed. I saw to that myself... Blessed you are with the power to see behind the mask, the invisibles, into the future..." (215). In Diana Gabaldon's historical romance novel Drums of Autumn, it is remarked that Claire's daughter, Brianna, was born with a caul. ## Notable people born "in the caul"[edit] * Barbara Barondess[7] * Edwin Booth[8] * Lord Byron[9] * Gabriele d'Annunzio[10] * J. G. Farrell, novelist[9][11] * George Formby, English comedian * Sigmund Freud[12] * Johnny Giles[13] * Lillian Gish[9] * Liberace[9] * Edna St. Vincent Millay[14] * Kim Woodburn[15] * Jonas Salk[16] * Abraham Ribicoff[17] * Nancy Wake[18][19] * Jason Tunney * Heather McColl * Charles XII of Sweden ## References[edit] 1. ^ caul. Thefreedictionary.com. Retrieved on 2011-10-15. 2. ^ a b http://caulbearersunited.webs.com/-%20New%20Folder/EarliestCaulBearer.pdf[full citation needed][permanent dead link][self-published source] 3. ^ Caul, or Face Veil, Occasionally Present at Birth. Archived from the original at Medical College of Wisconsin Archived 2006-04-24 at the Wayback Machine on 21 April 2008. Retrieved 22 August 2015[failed verification][citation needed] 4. ^ Vikki Campion. (2008-12-31) Dolores Pancaldi's birth in protective membrane. The Daily Telegraph via News.com.au. Retrieved on 2011-10-15. 5. ^ The story of these so-called benandanti is recounted in Carlo Ginzburg's study The Night Battles: Witchcraft and Agrarian Cults in the Sixteenth and Seventeenth Centuries, Baltimore: Johns Hopkins University Press, 1983. 6. ^ Oliver, Harry (2006). "12". Black Cats & Four-Leaf Clovers. New York: Penguin Books. ISBN 978-0-399-53609-0.[page needed] 7. ^ Barondess MacLean, Barbara. One Life is Not Enough. Hippocrene Books: New York, 1986. 8. ^ Giblin, James (2005). Good brother, bad brother: the story of Edwin Booth and John Wilkes Booth. New York: Clarion Books. p. 7. ISBN 0-618-09642-6. 9. ^ a b c d "Notable Caul Bearers - Arts". Caul Bearers United - Lifting the Veil. 10. ^ Lucy Hughes-Hallett. The Pike: Gabriele d'Annunzio – poet, seducer and preacher of war. Fourth Estate, 2013, p. 90. ISBN 978-0-00-721395-5. 11. ^ The Siege of Krishnapur[permanent dead link] New York Review Books 12. ^ D.P. Morgalis, Freud and his Mother. Pep-web.org. Retrieved on 2011-10-15. 13. ^ Giles, John (2010). A Football Man: The Autobiography. Hodder & Soughton. p. 13. ISBN 978-1-444-72096-9. 14. ^ Nancy Milford. Savage Beauty: The Life of Edna St. Vincent Millay. Random House, 2002, p. 18. ISBN 0-375-76081-4. 15. ^ Woodburn, Kim (7 September 2006). Unbeaten: The Story of My Brutal Childhood. Hodder & Stoughton Ltd. ISBN 0-340-92221-4. 16. ^ "Dr. Jonas Salk, the Knight in a White Lab Coat: An Interview with Charlotte DeCroes Jacobs \| History News Network". historynewsnetwork.org. 17. ^ Tolchin, Martin (July 30, 1974). "Ribicoff's Charmed Life: From Poverty to Power". The New York Times. 18. ^ "Nancy Wake dead, aged 98. Extract by Peter Fitzsimons". Mamamia. August 8, 2011. 19. ^ Fitzsimons, Peter (2002). Nancy Wake: A Biography of Our Greatest War Heroine. ISBN 0732274567. ## External links[edit] Look up caul in Wiktionary, the free dictionary. * "Caul, or Face Veil, Occasionally Present at Birth" * Folklore of the Isle of Man, Ch. 8 * Caul Bearers United: Authentic Caul History, includes references from The Social History of the Caul by Dr. Thomas R. Forbes [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Caul	None	977	wikipedia	https://en.wikipedia.org/wiki/Caul	2021-01-18T18:31:49	{"wikidata": ["Q603476"]}
A number sign (#) is used with this entry because multiple endocrine neoplasia type IIA (MEN2A) is caused by heterozygous mutation in the RET oncogene (164761) on chromosome 10q11. Description Multiple endocrine neoplasia type IIA is an autosomal dominant syndrome of multiple endocrine neoplasms, including medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid adenomas. MEN2B (162300), characterized by MTC with or without pheochromocytoma and with characteristic clinical abnormalities such as ganglioneuromas of the lips, tongue and colon, but without hyperparathyroidism, is also caused by mutation in the RET gene (summary by Lore et al., 2001). For a discussion of genetic heterogeneity of multiple endocrine neoplasia, see MEN1 (131100). Clinical Features Schimke and Hartmann (1965) described a syndrome of pheochromocytoma and medullary thyroid carcinoma with abundant amyloid stroma. A similar but distinct condition is described under neuromata, mucosal, with endocrine tumors (MEN2B; 162300). Steiner et al. (1968) described a family with 11 cases in successive generations. The pheochromocytomas were bilateral, parathyroid adenoma was present in several, and one patient had Cushing syndrome. Steiner et al. (1968) referred to this disorder as 'multiple endocrine neoplasia, type II' to distinguish it from the multiple endocrine adenomatosis described by Wermer (MEN1; 131100) and called type I by Steiner et al. (1968). Urbanski (1967) found parathyroid adenoma to be part of the syndrome also. Meyer and Abdel-Bari (1968) presented observations consistent with the view that medullary carcinoma is a thyrocalcitonin-producing neoplasm of parafollicular cells of the thyroid. Parathyroid hyperplasia or adenomas in some of these patients may be secondary to hypocalcemic effects of thyrocalcitonin. Johnston et al. (1970), as well as others, have shown calcitonin-secretion by medullary thyroid carcinoma. Kaplan et al. (1970) showed that the adrenal medulla produces a calcitonin-like material indistinguishable from that of the thyroid by bio- and radioimmunoassay. They suggested that the parafollicular cells of the thyroid are of neural crest origin. The finding that medullary carcinoma of the thyroid arises from parafollicular cells and that, like the cell of origin, it sometimes produces thyrocalcitonin may account for the association of parathyroid hyperplasia and perhaps parathyroid adenoma. Poloyan et al. (1970) was impressed with the histologic similarity between the medullary thyroid cancer and pheochromocytoma metastases. Keiser et al. (1973) pointed out that histaminase is useful in the identification of metastases of medullary carcinoma. In their opinion parathyroid adenomas are a primary feature of the disorder. Pearson et al. (1973) studied 21 members of a kindred with surgically confirmed multiple endocrine neoplasms. All 21 had medullary carcinoma of the thyroid. Adrenal pheochromocytomas were present in 10 and were bilateral in 6. Three had one or more parathyroid glands showing adenomatous hyperplasia and 10 showed chief cell hyperplasia. The thyroid cancer metastasized to other areas including the liver, lungs, and bone in several of the patients. All patients had elevated peripheral thyrocalcitonin. Peripheral parathyroid hormone was elevated in only 2; however, parathyroid hormone was elevated in the inferior thyroid vein of all patients examined. Hamilton et al. (1978) suggested that an increased urinary epinephrine fraction is a sensitive and reliable screening test for pheochromocytoma in MEN II, comparable to the calcitonin radioimmunoassay for medullary carcinoma of the thyroid. Carney et al. (1975) found bilateral adrenal medullary hyperplasia in an asymptomatic 12-year-old girl. She had bilateral thyroid carcinoma and hyperparathyroidism. The adrenals were explored because of elevated urinary levels of vanillylmandelic acid. Migrating neural crest cells are able to decarboxylate and store precursors of aromatic amines that fluoresce after exposure to formaldehyde vapor. The last is a method for identifying neural crest origin of enterochromaffin, argyrophil cells of the bronchi, islets of Langerhans, and parafollicular cells of the thyroid, among others. These are collectively termed the amine precursor uptake and decarboxylase (APUD) system (Pearse, 1969). Tischler et al. (1976) extended the evidence of neural origin by demonstrating that cultured cells from medullary carcinoma of the thyroid, bronchial carcinoid, and pheochromocytoma display all-or-nothing action potentials of short duration. Easton et al. (1989) estimated on the basis of clinical history that 41% of gene carriers are asymptomatic at age 70. Screening by the standard tests for detecting the earliest manifestations of the syndrome increased the penetrance to an estimated 93% by age 31. There was some suggestion of an earlier onset of medullary thyroid cancer in female gene carriers, and of a tendency for pheochromocytoma to cluster in families. Other Features Le Marec et al. (1980) reported congenital megacolon with plexus hyperplasia in a family with Sipple syndrome. Megacolon of this type seems to be more usual in MEN III than in MEN II. Cameron et al. (1978) described the Zollinger-Ellison syndrome with type II MEA, a first. These families represent an overlap of phenotypic features in the 3 forms of MEN. Gagel et al. (1989), Nunziata et al. (1989), and Kousseff et al. (1991) observed primary localized cutaneous amyloidosis (PLCA) in association with MEN2A. Gagel et al. (1989) and Kousseff et al. (1991) referred to it as cutaneous lichen amyloidosis. In a family with 6 affected members in 5 generations, a mother and her daughter had interscapular cutaneous pruritic lesions (Kousseff et al., 1991). Kousseff (1992) provided a pedigree and photographs of the skin lesions. Cutaneous lichen amyloidosis as an apparently independent autosomal dominant trait has also been described (105250). The skin deposits of amyloid associated with pruritus in the interscapular region represents a form of 'friction amyloidosis' (Wong and Lin, 1988). It is related to notalgia paresthetica, an inherited neuropathy of the posterior dorsal nerve rami. ('Notalgia' means 'back pain.') The neuropathy hypothesis was supported by the finding of mutations in the RET protooncogene which is expressed in the peripheral and central nervous system. Ceccherini et al. (1994) demonstrated a specific cys634-to-tyr missense mutation (164761.0004) in affected members of a pedigree in which MEN2A was combined with localized cutaneous lichen amyloidosis. Skinner et al. (2008) identified 10 different heterozygous mutations in the RET gene (see, e.g., 164761.0053 and 164761.0054) in paraffin-embedded tissue from 7 (37%) of 19 stillborn fetuses with bilateral renal agenesis and in 2 (20%) of 10 stillborn fetuses with unilateral renal agenesis. Two fetuses had 2 RET mutations. Parental DNA was not studied. In vitro functional expression studies showed that the mutations resulted in either constitutive RET phosphorylation or absent phosphorylation. Skinner et al. (2008) postulated a loss-of-function effect. The fetuses did not have evidence of Hirschsprung disease (HSCR; 142623), MEN2A, MEN2B (162300), or familial medullary thyroid carcinoma (155240). However, Skinner et al. (2008) noted that these conditions generally present with clinical findings later in childhood; they may have been present in the fetuses and not detected by standard autopsy. Jeanpierre et al. (2011) identified heterozygous variations in the RET gene in 7 (6.6%) of 105 fetuses with severe kidney developmental defects leading to death or termination in utero. Four of the variants were also present in unaffected fathers. In vitro functional studies of most the variants were not performed, but at least 1 was likely a neutral polymorphism. Analysis of 171 additional cases with renal developmental defects showed that the frequency of RET variants was significantly higher in cases compared to controls, suggesting that variants may confer predisposition to a spectrum of renal developmental defects. However, Jeanpierre et al. (2011) concluded that genetic alteration of RET is not a major mechanism leading to renal agenesis or kidney developmental defects. Hibi et al. (2014) reported a family with MEN2A associated with a heterozygous RET mutation (C618R; 164761.0025). The female proband had MTC and pheochromocytoma, and her brother died of MTC at age 45 years. The proband had 3 asymptomatic sons, all of whom carried the C618R mutation. Two of the sons were found to have unilateral renal agenesis, and 1 also had Hirschsprung disease. Hibi et al. (2014) noted that knockout of Ret in mice results in loss of enteric neurons as well as renal agenesis or severe dysgenesis (Schuchardt et al., 1994). The findings in the family reported by Hibi et al. (2014) supported the hypothesis that a constitutively active RET mutation might partially impair RET function and thereby cause loss of function phenotypes, such as renal agenesis or HSCR. However, Hibi et al. (2014) concluded that renal agenesis/dysgenesis is probably extremely rare in patients with RET mutations. Hwang et al. (2014) identified 3 different heterozygous RET missense mutations in 3 of 650 different families with various congenital anomalies of the kidney and urinary tract (CAKUT) who were screened for mutations in the coding regions of 12 known dominant renal disease-causing genes. Although clinical details were sparse, the renal phenotype of these patients included renal hypodysplasia, unilateral renal agenesis, vesicoureteral reflux, ureteropelvic junction obstruction, duplex collecting system, and ureterocele. Biochemical Features Eisenhofer et al. (2001) examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in MEN2 and von Hippel-Lindau syndrome to underlying differences in the expression of tyrosine hydroxylase (TH; 191290), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT; 171190), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN2 patients and 30 von Hippel-Lindau patients with adrenal pheochromocytomas. MEN2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than von Hippel-Lindau patients. MEN2 patients all had elevated plasma concentrations of the epinephrine metabolite metanephrine, whereas von Hippel-Lindau patients showed specific increases in the norepinephrine metabolite normetanephrine. The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from von Hippel-Lindau than from MEN2 patients. Cytogenetics In affected members of 7 families, Van Dyke et al. (1982) found a small deletion of chromosome 20p12.2 segregating with MEN II. Van Dyke et al. (1981) demonstrated the 20p deletion in 16 cases of MEN II in 7 families, and in 1 case of MEN III. Hsu et al. (1981) found a higher frequency of metaphases with chromosome and chromatid abnormalities (average, 11.0%) in cases of Sipple syndrome than in controls (average, 3.8%). In one pair of sibs, they failed to find the same deletion in chromosome 20. Jackson (1982) stated that his group had correctly identified 18 persons in blinded studies. A small deletion was found in 18 members of 8 families with Sipple syndrome and also in 2 unrelated patients with MEN III. See Babu et al. (1982). Although, as they pointed out, their experience is not proof of the absence of deletion, Gustavson et al. (1983) could not demonstrate such by high resolution banding in either MEN I or MEN II. High resolution cytogenetics in 5 persons studied by Emmertsen et al. (1983) showed no deletion in band 20p12.2. In both MEN2A and MEN2B, Babu et al. (1984) reported the finding of an interstitial deletion in band 20p12.2. In a double-blind study, 2 of 13 controls were thought to have the deletion; all 9 blood samples from 8 affected members of 4 MEN2A families were found to have the deletion; from 3 MEN2B families, 5 blood samples from 4 affected members showed the deletion, whereas 3 did not. The authors suggested that these 2 entities are genetically closely related; that the dominant expression of the mutation at 20p12.2 is hyperplasia of thyroid C cells and adrenal medullary cells; that in accordance with Knudson's 2-mutation-event theory and in analogy to retinoblastoma, thyroid cancer and pheochromocytoma are recessive manifestations. Zatterale et al. (1984) could not detect a 20p12.2 deletion in prometaphase banding studies. Babu et al. (1987) reported on an expanded double-blind study of chromosome 20 deletion in MEN2A and MEN2B. A deletion in 20p12.2 was found in 15 of 21 MEN2A patients and in 4 of 8 MEN2B patients. These findings await explanation since the locus for these disorders maps elsewhere. Mapping Jackson et al. (1976) found a suggestion of linkage to P blood group (111400) but not to HLA. Simpson et al. (1979) found 23.1% recombination between MEN II and HLA, but this linkage was rendered highly unlikely by further studies by Simpson and Falk (1982). Jackson et al. (1979) concluded that medullary thyroid cancer fits a 2-mutation theory. They suggested that C-cell hyperplasia is the gene-determined first mutational event and cancer the second. Emmertsen et al. (1983) found no significantly positive lod scores between MEN II and 25 different genetic markers. Simpson et al. (1984) assigned the calcitonin gene to chromosome 11 by use of a cDNA clone isolated from medullary thyroid carcinoma and a somatic cell hybrid panel. With a TaqI RFLP detected by this probe, they studied linkage of the calcitonin locus and MEN2; negative lod scores were found at all recombination values. Goodfellow et al. (1984) studied linkage between MEN2 and DNA probes assigned to 20p12.2 by in situ hybridization. Negative lod scores were obtained. In 2 large MEN2A pedigrees, Goodfellow et al. (1985) studied linkage with 2 RFLPs found in an anonymous DNA segment D20S5, which had been isolated from a chromosome 19/20 flow-sorted library and shown by in situ hybridization to be located at 20p12. Linkage was excluded at theta equal to or less than 0.13. In studies of a single large kindred, Kruger et al. (1986) excluded close linkage with several markers and found no statistically significant linkage with any marker. Low positive lod scores were obtained with GC (139200), GPT (138200) and HP (140100). Perrier et al. (1987) found no linkage of MEN2 and HLA. By multipoint linkage analysis, Farrer et al. (1987) excluded a large portion of chromosome 13 as the site of the MEN2A locus. Farrer et al. (1987) could find no linkage of MEN2A to 3 DNA markers that mapped to chromosome 20. Simpson et al. (1987) performed linkage studies in 5 families, each with at least 1 member found to have a deletion at 20p12.2. In these families, the MEN2 locus was found to be linked to a DNA marker on chromosome 10, D10S5, which by in situ hybridization maps to 10q21.1. The maximal lod score was 3.58 for a recombination fraction of 0.19. With 2 RFLPs recognized by an RBP3 probe (180290), Simpson et al. (1987) found a maximal lod score of 8.0 at theta = 0.11. In studies of 5 Japanese families, Yamamoto et al. (1989) found that MEN2A is closely linked to RBP3; the maximum lod score was 5.19 at a recombination fraction of 0.00. In 2 kindreds, Mathew et al. (1987) found a maximal lod score of 3.88 at theta = 0.04 for linkage with RBP3, which has been positioned at 10p11.2-q11.2. Sobol et al. (1989) reported on linkage studies in 35 families with medullary carcinoma of the thyroid, with or without pheochromocytoma. Their results suggest that a susceptibility gene for hereditary medullary carcinoma of the thyroid may be located at the same locus on chromosome 10 as that of MEN2A. Narod et al. (1989) did linkage studies in 18 families, 9 with MEN2A and 9 with medullary carcinoma of the thyroid without pheochromocytoma, with probes specific for the pericentromeric region of chromosome 10 and concluded that the mutations for the 2 presentations are closely situated. Genetic heterogeneity of the susceptibility locus was not seen among these 18 families. The genetic mutation for medullary carcinoma was in disequilibrium with alleles at 2 closely linked markers. Using a panel of markers from the pericentric region of chromosome 10, Lairmore et al. (1991) performed linkage studies in 2 large families with medullary thyroid carcinoma (MTC1) and 6 families with MEN2B. The maximum lod score between MTC1 and marker D10Z1 was 5.88 with 0% recombination. MEN2B showed similarly tight linkage to D10Z1, with a maximum lod score of 3.58 at 0% recombination. The multipoint lod score for MEN2B at D10Z1 was 4.08. Linkage studies in a single large MEN2A kindred showed tight linkage to D10Z1 in this condition as well, with a maximum multipoint lod score of 7.04 at a recombination fraction of 0. The highest lod score obtained was between MEN2A and the haplotyped locus RBP3 with a lod score of 11.33 at a recombination fraction of 0. Linkage data between MEN2A and 3 additional markers on 10q, as well as between MEN2A and the FNRB locus (135630) on 10p11.2, were also presented. Lairmore et al. (1991) found no evidence for genetic heterogeneity among families with MEN2A, MEN2B, and MTC. In 2 families with medullary thyroid carcinoma with parathyroid tumors alone, Carson et al. (1990) demonstrated that the disorder was closely linked to 2 markers in the vicinity of the centromere of chromosome 10, namely, RBP3 and D10Z1. Using a centromeric marker at the D10Z1 locus in 30 families with MEN2A, Narod et al. (1991) demonstrated tight linkage with the centromere. Brooks-Wilson et al. (1992) characterized a dense cluster of CpG islands at D10S94 in proximal 10q11.2. No recombinants between D10S94 and MEN2A had been identified. They generated a 570-kb restriction map by pulsed field gel electrophoresis. Six CpG islands were clustered within a 180-kb region. They suggested that these CpG islands may represent the 5-prime ends of candidate genes for MEN2A, MEN2B, and/or MTC1. McDonald et al. (1992) further identified an MEN2A candidate gene by use of an evolutionarily conserved sequence from D10S94. The gene spanned 11 kb and had an unmethylated CpG island at its 5-prime end. It encoded a putative 415-amino acid polypeptide similar in sequence to nucleolin (164035), an abundant nucleolar protein. In a patient with MEN2A, they found no difference in the candidate gene, termed mcs94-1, from the MEN2A chromosome or its wildtype homolog. By genetic linkage analysis, Gardner et al. (1993) demonstrated that the MEN2A gene is located in a small region of 10q11.2 flanked by D10S141 proximally and D10S94 distally, these 2 markers being separated by a sex-average genetic distance of 0.55 cM. Mole et al. (1993) constructed a YAC contig spanning 1.1 Mb of band 10q11.2 which must include MEN2A because it encompassed 3 markers, D10S141, RET, and D10S94. A 480-kb region separated D10S141 and D10S94. Janson et al. (1991) constructed a physical map of the MEN2 region by combining data from pulsed field gel electrophoresis (PFGE) with those generated from a panel of radiation-reduced somatic cell hybrids. Comparison of the physical map with the linkage map showed a recombination rate higher than expected: thus, for the closest pair of linked markers on the centromeric side of MEN2, 1 centimorgan corresponded to approximately 300 kb, and for markers on the telomeric side, 1 centimorgan corresponded to approximately 350 to 600 kb. There is evidence from other sources that the 11q12-q13 region is unusual in having a high G-C content, suggesting a high concentration of genes and other characteristics including increased meiotic recombination usually associated with telomeric regions (Saccone et al., 1992). Molecular Genetics Mathew et al. (1987) found deletion of a hypervariable region of DNA on 1p in 7 of 14 tumors (pheochromocytomas and medullary carcinomas) developing in patients with MEN2. In 1 of 2 families examined, the deleted chromosome was that inherited from the affected parent. Thus, the site of deletion presumably does not represent the location of the inherited gene. The deleted region was distal to the breakpoint commonly detected in neuroblastomas (256700), which share with the tumors of MEN2 embryologic origin from neuroectoderm. The most frequent breakpoint involved in neuroblastomas is 1p32, whereas the genes deleted in the tumors studied by Mathew et al. (1987) were located at 1p35-p33. In an analysis of tumor DNA from 42 patients with MEN2A, Landsvater et al. (1989) showed that markers on chromosome 10 were lost in only 1 tumor, a result that contrasts with studies in other tumors for which both familial and sporadic cases are known. That MEN2A is genetically heterogeneous is suggested by the linkage in some families to markers at the 10q11.2 region and the lack of linkage in other families. The basis of the above subclassification, whether different mutations in one gene or mutations in adjacent genes in the 10q11.2 region, is not clear (Simpson, 1992). The subclasses do seem to 'breed true' in different families. In a panel of 34 families with MEN2A, Narod et al. (1992) found no evidence of genetic heterogeneity. No recombination was observed between MEN2A and any of 4 DNA marker loci. Narod et al. (1992) constructed haplotypes for 11 polymorphisms in the MEN2A region for mutation-bearing chromosomes in 24 French families and for 100 spouse controls. One haplotype was present in 4 MEN2A families but was not observed in any control (P = less than 0.01). Two additional families shared a core segment of this haplotype near the MEN2A gene. Narod et al. (1992) suggested that these 6 families had a common affected ancestor. Because the incidence of pheochromocytoma among carriers varied from 0.0 to 74% in these 6 families, they suggested that additional factors modify the expression of the gene. Curiously, the most consistent molecular genetic abnormality that has been found in pheochromocytomas and medullary thyroid cancers, either sporadic or part of MEN2, is loss of heterozygosity (LOH) on 1p. Using RFLP analysis, Moley et al. (1992) identified loss of all or a portion of 1p in 12 of 18 pheochromocytomas. LOH of 1p was found in all 9 pheochromocytomas in MEN2A and MEN2B patients, compared with only 2 of 7 sporadic pheochromocytomas. They also found 1p LOH in the pheochromocytoma of 1 of 2 von Hippel-Lindau patients (193300). LOH on 1p was noted in only 3 of 24 informative medullary thyroid carcinomas, and these were from patients with MEN2A. Mulligan et al. (1993) identified missense mutations in the RET protooncogene in 20 of 23 apparently distinct MEN2A families, but not in 23 normal controls. Of these 20 mutations, 19 affected the same conserved cysteine residue at the boundary of the RET extracellular and intracellular domains. Quadro et al. (2001) reported a patient affected by MEN2A bearing a heterozygous cys634-to-arg (164761.0011) germline mutation in exon 11 and an additional somatic mutation (164761.0012) of the RET protooncogene. A large intragenic deletion spanning exon 4 to exon 16 affected the normal allele and was detected by quantitative PCR, Southern blot analysis, and screening of several polymorphic markers. This deletion causes RET loss of heterozygosity exclusively in the metastasis and not in the primary tumor, thus suggesting a role for this second mutational event in tumor progression. No additional mutations were found in the other exons analyzed. The authors concluded that this unusual genetic profile may be related to the clinical course and very poor outcome. Huang et al. (2000) and Koch et al. (2001) identified 2 second-hit mechanisms involved in the development of MEN2-associated tumors: trisomy 10 with duplication of the mutant RET allele and loss of the wildtype RET allele. However, some of the MEN2-associated tumors investigated did not demonstrate either mechanism. Huang et al. (2003) studied the TT cell line, derived from MEN2-associated medullary thyroid carcinoma with a RET germline mutation in codon 634, for alternative mechanisms of tumorigenesis. Although they observed a 2-to-1 ratio between mutant and wildtype RET at the genomic DNA level in this cell line, FISH analysis revealed neither trisomy 10 nor loss of the normal chromosome 10. Instead, a tandem duplication event was responsible for amplification of mutant RET. In further studies Huang et al. (2003) demonstrated for the first time that the genomic chromosome 10 abnormalities in this cell line cause an increased production of mutant RET mRNA. The authors concluded that these findings provided evidence for a third second-hit mechanism resulting in overrepresentation and overexpression of mutant RET in MEN2-associated tumors. Abu-Amero et al. (2006) identified nonsynonymous germline mitochondrial DNA (mtDNA) mutations in both normal and tumor tissue from 20 (76.9%) of 26 cases of medullary thyroid carcinoma, including 9 (69.2%) of 13 sporadic cases and 11 (84.6%) of 13 familial cases; 10 of 13 familial cases were patients with MEN2. The familial cases tended to have transversion mtDNA mutations rather than transition mutations. All 13 familial cases also had germline RET mutations. Abu-Amero et al. (2006) suggested that mtDNA mutations may be involved in medullary thyroid carcinoma tumorigenesis and/or progression. Diagnosis In the Netherlands, Vasen et al. (1987) demonstrated the usefulness of screening and a central registry for the long-term follow-up of cases. In an 18-year study of a large kindred, Gagel et al. (1988) found that prospective screening and early treatment of manifestations of multiple endocrine neoplasia can prevent metastasis of medullary thyroid carcinoma and the morbidity and mortality of pheochromocytoma. Medullary carcinoma of the thyroid is the most consistent single manifestation of this disorder and occurs in almost all cases by age 40. Before age 40 in particular, it is necessary to use a provocative test of the combined calcitonin secretagogues enterogastrone and calcium in order to detect the disorder since the basal levels are not elevated (Baylin, 1989). As part of a French national program, Sobol et al. (1989) used DNA probes in a genetic linkage study of 130 members of 11 families of European and North African origin who were ascertained through members with MEN2A. No recombination was found between the mutation causing MEN2A and 2 of 3 markers used. All 11 families were informative for at least 1 of the markers and linkage information was adequate to permit genetic counseling in 8 families. Sobol et al. (1989) concluded that RFLP analysis is more useful in predicting the carrier state than conventional endocrine challenge, especially in younger persons, but accuracy is maximal when both methods are used. Mathew et al. (1991), including 23 members of the MEN2A International Collaborative Group, described 4 markers from the pericentric region of chromosome 10 that are tightly linked to MEN2A and are useful for testing for carrier status in individuals genetically at risk but showing a negative biochemical screening test for thyroid C-cell hyperplasia. The tests were also accurate for prenatal diagnosis. Calmettes et al. (1992) reported the consensus on biochemical and genetic screening formulated by the European Community Concerted Action on the subject of medullary thyroid carcinoma. For biochemical screening, measurement of the basal and pentagastrin- and/or calcium-stimulated serum levels of calcitonin by radioimmunoassay was considered essential starting at the age of 3 and continuing annually until the age of 35. Furthermore, annual screening for pheochromocytoma by measurement of urinary excretion of catecholamines and for hyperparathyroidism by serum calcium determination was considered indicated. Biochemical screening can be reserved for gene carriers in some families; genetic screening using genetic markers can be done with 95% accuracy in informative families whenever DNA is available from at least 2 family members proven to be affected. Total thyroidectomy at an early stage usually cures the patient with medullary thyroid carcinoma. On the basis of studies in a very large kindred, Landsvater et al. (1993) found 7 individuals with abnormal calcitonin test results. Five of these people were thyroidectomized, and C-cell hyperplasia was diagnosed. Four were the offspring of a mother at risk for the development of MEN2A who showed, however, normal calcitonin test results throughout the years, whereas the father, who was not at risk, had abnormal test results over a period of 10 years, without evidence of progressive elevation. None of the 7 individuals developed other manifestations of MEN2A. DNA analysis using markers linked to the MEN2A gene demonstrated, with more than 99% likelihood, that none of the persons who could be genotyped was a gene carrier. Thus, C-cell hyperplasia due to some mechanism other than the presence of the MEN2A gene may occur in MEN2A kindreds. Schuffenecker et al. (1997) reported that 5.6% to 9% of cases of MEN2A/MTC are de novo cases with no family history. They reported further that new mutations in the RET oncogene in these cases were demonstrated exclusively on the paternal allele. Retrospective analysis on 274 MEN2A cases revealed that in 40.2% of patients pheochromocytoma occurred 2 to 11 years subsequent to MTC. Schuffenecker et al. (1997) concluded that all apparently sporadic MTC patients should be examined for de novo RET mutations. Sporadic medullary thyroid carcinoma has usually been found to result from a mutational event occurring at the single-cell level, indicating that they are monoclonal. By clonality assay of medullary carcinoma of the thyroid in MEN type 2, Ferraris et al. (1997) showed the carcinomas they studied to be polyclonal in most instances. They used a polymorphic trinucleotide repeat of the X-linked human androgen receptor gene (313700) to demonstrate that 10 out of 11 MTCs expressed a polyclonal pattern of X inactivation; furthermore, a significant percentage of cases clinically defined as sporadic showed a polyclonal pattern. Brandi et al. (2001) authored a consensus statement covering the diagnosis and management of MEN1 (131100) and MEN2, including important contrasts between them. The most common tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial MTC. They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy. Gourgiotis et al. (2003) reported the case of a 42-year-old woman with MEN2A in whom biopsy-proven recurrent MTC was detected by 6-[18F]fluorodopamine PET scanning. The study showed a focus of radionuclide accumulation corresponding to the parapharyngeal mass. After resection of the latter, pathology confirmed metastatic MTC. Clinical Management Medullary thyroid carcinoma is the most common cause of death in patients with MEN2A. Skinner et al. (2005) sought to determine whether total thyroidectomy in asymptomatic young members of kindreds with this genetic disorder who had a mutated allele in the RET protooncogene (164761) could prevent or cure medullary thyroid carcinoma. In a total of 50 patients of 19 years of age or younger who were consecutively identified through a genetic screening program as carriers of a RET mutations characteristic of MEN2A underwent total thyroidectomy. Five to 10 years after surgery, each patient was evaluated by physical examination and by determination of plasma calcitonin levels after stimulation with provocative agents, mainly combined calcium and pentagastrin. In 44 of the 50 patients, basal and stimulated plasma calcitonin levels were at or below the limits of detection of the assay. The data suggested that there was a lower incidence of persistent or recurrent disease in children who underwent total thyroidectomy before 8 years of age and in children in whom there were no metastases to cervical lymph nodes. Skinner et al. (2005) concluded that a longer period of evaluation would be necessary to confirm that the subjects are cured. Moore and Dluhy (2005) reviewed considerations that led to several conclusions. First, this complex pediatric endocrine surgery should be conducted at centers with expert teams of surgeons, endocrinologists, anesthesiologists, geneticists, and pediatricians. An integral member of such a team at most centers should be a genetic counselor who constructs family pedigrees, arranges for screening of persons at risk, and provides information and emotional support to the patient and the family. Second, surgery should occur at the earliest stage at which the team can perform it safely. In the absence of completely definitive data linking genotype to phenotype, the age at which surgery is safe is likely to be 3 years or younger. History See 171300 for a review of the original description of classic pheochromocytoma (Frankel, 1886) and follow-up of the patient's living relatives, which revealed the presence of MEN2A in the family. INHERITANCE \- Autosomal dominant ABDOMEN Gastrointestinal \- Hirschsprung disease SKIN, NAILS, & HAIR Skin \- Cutaneous lichen amyloidosis ENDOCRINE FEATURES \- Cushing syndrome \- Hypertension \- C-cell hyperplasia \- Hyperparathyroidism NEOPLASIA \- Pheochromocytoma \- Medullary thyroid carcinoma \- Parathyroid adenoma LABORATORY ABNORMALITIES \- Increased urinary epinephrine \- Elevated calcitonin \- Pentagastrin stimulation test MOLECULAR BASIS \- Caused by mutations in the RET protoncogene (RET, {1645761.0001}) ▲ 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	MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIA	c0025268	978	omim	https://www.omim.org/entry/171400	2019-09-22T16:36:20	{"doid": ["0050430"], "mesh": ["D018813"], "omim": ["171400"], "icd-9": ["258.02"], "icd-10": ["E31.22"], "orphanet": ["653", "247698"], "synonyms": ["Alternative titles", "PHEOCHROMOCYTOMA AND AMYLOID-PRODUCING MEDULLARY THYROID CARCINOMA", "PTC SYNDROME", "SIPPLE SYNDROME"], "genereviews": ["NBK1257"]}
Spondylospinal thoracic dysostosis is an extremely rare skeletal disorder characterized by a short, curved spine and fusion of the spinous processes, short thorax with 'crab-like' configuration of the ribs, underdevelopment of the lungs (pulmonary hypoplasia), severe arthrogryposis and multiple pterygia (webbing of the skin across joints), and underdevelopment of the bones of the mouth. This condition is believed to be inherited in an autosomal recessive manner. It does not appear to be compatible with life. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Spondylospinal thoracic dysostosis	c1866184	979	gard	https://rarediseases.info.nih.gov/diseases/10571/spondylospinal-thoracic-dysostosis	2021-01-18T17:57:31	{"mesh": ["C566622"], "omim": ["601809"], "umls": ["C1866184"], "synonyms": []}
Chondrodysplasia punctata 1, X-linked recessive (CDPX1) is a genetic disorder present from birth that affects bone and cartilage development. On x-ray, infants with CDPX1 have characteristic spots at the ends of their bones. These spots are called chondrodysplasia punctata or stippled epiphyses and typically disappear between ages 2 and 3. Additional common features of CDPX1 are shortened fingers and a flattened nose. Some people with this condition have breathing abnormalities, hearing loss, abnormalities of the spinal bones in the neck, and intellectual delays. CDPX1 is caused by mutations in the ARSE gene, which is located on the X chromosome. This condition is inherited in an X-linked recessive manner and occurs almost exclusively in males. Most affected individuals have a normal lifespan, although some individuals experience complications that can be life-threatening. Although there is no specific treatment or cure for CDPX1, there are ways to manage symptoms. A team of doctors or specialists is often needed to figure out the treatment options for each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Chondrodysplasia punctata 1, X-linked recessive	c1844853	980	gard	https://rarediseases.info.nih.gov/diseases/1296/chondrodysplasia-punctata-1-x-linked-recessive	2021-01-18T18:01:28	{"mesh": ["C535941"], "omim": ["302950"], "orphanet": ["79345"], "synonyms": ["Chondrodysplasia punctata 1 X-linked recessive", "CDPX1", "CPXR", "Arylsulfatase E deficiency", "Chondrodysplasia punctata, brachytelephalangic", "Chondrodysplasia punctata brachytelephalangic"]}
Panic disorder Someone with a panic attack, being reassured by another person. SpecialtyPsychiatry, Clinical psychology SymptomsSudden periods of intense fear, palpitations, sweating, shaking, shortness of breath, numbness[1][2] Usual onsetSudden and recurrent[1] CausesUnknown[3] Risk factorsFamily history, smoking, psychological stress, history of child abuse[2] Diagnostic methodBased on symptoms after ruling out other potential causes[2][3] Differential diagnosisHeart disease, hyperthyroidism, drug use[2][3] TreatmentCounselling, medications[3] MedicationAntidepressants, benzodiazepines, beta blockers[1][3] Frequency2.5% of people at some point[4] Panic disorder is an anxiety disorder characterized by reoccurring unexpected panic attacks.[1] Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath, numbness, or a feeling that something terrible is going to happen.[1][2] The maximum degree of symptoms occurs within minutes.[2] There may be ongoing worries about having further attacks and avoidance of places where attacks have occurred in the past.[1] The cause of panic disorder is unknown.[3] Panic disorder often runs in families.[3] Risk factors include smoking, psychological stress, and a history of child abuse.[2] Diagnosis involves ruling out other potential causes of anxiety including other mental disorders, medical conditions such as heart disease or hyperthyroidism, and drug use.[2][3] Screening for the condition may be done using a questionnaire.[5] Panic disorder is usually treated with counselling and medications.[3] The type of counselling used is typically cognitive behavioral therapy (CBT) which is effective in more than half of people.[3][4] Medications used include antidepressants and occasionally benzodiazepines or beta blockers.[1][3] Following stopping treatment up to 30% of people have a recurrence.[4] Panic disorder affects about 2.5% of people at some point in their life.[4] It usually begins during adolescence or early adulthood but any age can be affected.[3] It is less common in children and older people.[2] Women are more often affected than men.[3] ## Contents * 1 Signs and symptoms * 1.1 Interoceptive * 2 Causes * 2.1 Psychological models * 2.2 Substance misuse * 2.2.1 Smoking * 2.2.2 Stimulants * 2.2.3 Alcohol and sedatives * 3 Mechanism * 4 Diagnosis * 5 Treatment * 5.1 Psychotherapy * 5.1.1 Cognitive behavioral therapy * 5.1.2 Interoceptive techniques * 5.2 Medication * 5.3 Other treatments * 6 Epidemiology * 7 Children * 8 References * 9 External links ## Signs and symptoms[edit] Panic disorder sufferers usually have a series of intense episodes of extreme anxiety during panic attacks. These attacks typically last about ten minutes, and can be as short-lived as 1–5 minutes, but can last twenty minutes to more than an hour, or until helpful intervention is made. Panic attacks can wax and wane for a period of hours (panic attacks rolling into one another), and the intensity and specific symptoms of panic may vary over the duration.[citation needed] In some cases, the attack may continue at unabated high intensity or seem to be increasing in severity. Common symptoms of an attack include rapid heartbeat, perspiration, dizziness, dyspnea, trembling, uncontrollable fear such as: the fear of losing control and going crazy,[6] the fear of dying[7] and hyperventilation. Other symptoms are a sensation of choking, paralysis, chest pain, nausea, numbness or tingling, chills or hot flashes, faintness, crying[8] and some sense of altered reality.[9] In addition, the person usually has thoughts of impending doom.[10] Individuals suffering from an episode have often a strong wish of escaping from the situation that provoked the attack. The anxiety of panic disorder is particularly severe and noticeably episodic compared to that from generalized anxiety disorder. Panic attacks may be provoked by exposure to certain stimuli (e.g., seeing a mouse) or settings (e.g., the dentist's office).[9] Nocturnal panic attacks are common in people with panic disorder.[11] Other attacks may appear unprovoked. Some individuals deal with these events on a regular basis, sometimes daily or weekly. Limited symptom attacks are similar to panic attacks but have fewer symptoms. Most people with PD experience both panic attacks and limited symptom attacks. ### Interoceptive[edit] Studies investigating the relationship between interoception and panic disorder have shown that people with panic disorder feel heartbeat sensations more intensely when stimulated by pharmacological agents, suggesting that they experience heightened interoceptive awareness compared to subjects without PD.[12] ## Causes[edit] ### Psychological models[edit] While there is not just one explanation for the cause of panic disorder, there are certain perspectives researchers use to explain the disorder. The first one is the biological perspective. Past research concluded that there is irregular norepinephrine activity in people who have panic attacks.[13] Current research also supports this perspective as it has been found that those with panic disorder also have a brain circuit that performs improperly. This circuit consists of the amygdala, central gray matter, ventromedial nucleus of the hypothalamus, and the locus ceruleus.[14] There is also a cognitive perspective. Theorists believe that people with panic disorder may experience panic reactions because they mistake their bodily sensations for life-threatening situations.[15] These bodily sensations cause some people to feel as though are out of control which may lead to feelings of panic. This misconception of bodily sensations is referred to as anxiety sensitivity, and studies suggest that people who score higher on anxiety sensitivity surveys are fives times more likely to be diagnosed with panic disorder.[16] Panic disorder has been found to run in families, which suggests that inheritance plays a strong role in determining who will get it.[17] Psychological factors, stressful life events, life transitions, and environment as well as often thinking in a way that exaggerates relatively normal bodily reactions are also believed to play a role in the onset of panic disorder. Often the first attacks are triggered by physical illnesses, major stress, or certain medications. People who tend to take on excessive responsibilities may develop a tendency to suffer panic attacks. Post-traumatic stress disorder (PTSD) patients also show a much higher rate of panic disorder than the general population. Prepulse inhibition has been found to be reduced in patients with panic disorder.[18] ### Substance misuse[edit] Substance abuse is often correlated with panic attacks. In a study, 39% of people with panic disorder had abused substances. Of those who used alcohol, 63% reported that the alcohol use began prior to the onset of panic, and 59% of those abusing illicit drugs reported that drug use began first. The study that was conducted documented the panic-substance abuse relationship. Substance abuse began prior to the onset of panic and substances were used to self-medicate for panic attacks by only a few subjects.[19] In another study, 100 methamphetamine-dependent individuals were analyzed for co-morbid psychiatric disorders; of the 100 individuals, 36% were categorized as having co-morbid psychiatric disorders. Mood and Psychotic disorders were more prevalent than anxiety disorders, which accounted for 7% of the 100 sampled individuals.[20] #### Smoking[edit] Tobacco smoking increases the risk of developing panic disorder with or without agoraphobia[21][22] and panic attacks; smoking started in adolescence or early adulthood particularly increases this risk of developing panic disorder.[23][24][25] While the mechanism of how smoking increases panic attacks is not fully understood, a few hypotheses have been derived. Smoking cigarettes may lead to panic attacks by causing changes in respiratory function (e.g. feeling short of breath). These respiratory changes in turn can lead to the formation of panic attacks, as respiratory symptoms are a prominent feature of panic.[23][26] Respiratory abnormalities have been found in children with high levels of anxiety, which suggests that a person with these difficulties may be susceptible to panic attacks, and thus more likely to subsequently develop panic disorder. Nicotine, a stimulant, could contribute to panic attacks.[27][28] However, nicotine withdrawal may also cause significant anxiety which could contribute to panic attacks.[29] It is also possible that panic disorder patients smoke cigarettes as a form of self-medication to lessen anxiety. Nicotine and other psychoactive compounds with antidepressant properties in tobacco smoke which act as monoamine oxidase inhibitors in the brain can alter mood and have a calming effect, depending on dose. #### Stimulants[edit] A number of clinical studies have shown a positive association between caffeine ingestion and panic disorder and/or anxiogenic effects.[30][31] People who have panic disorder are more sensitive to the anxiety-provoking effects of caffeine. One of the major anxiety-provoking effects of caffeine is an increase in heart rate.[32][33][34][35] Certain cold and flu medications containing decongestants may also contain pseudoephedrine, ephedrine, phenylephrine, naphazoline and oxymetazoline. These may be avoided by the use of decongestants formulated to prevent causing high blood pressure.[36] #### Alcohol and sedatives[edit] About 30% of people with panic disorder use alcohol and 17% use other psychoactive drugs.[37] This is in comparison with 61% (alcohol)[38] and 7.9% (other psychoactive drugs)[39] of the general population who use alcohol and psychoactive drugs, respectively. Utilization of recreational drugs or alcohol generally make symptoms worse.[40] Most stimulant drugs (caffeine, nicotine, cocaine) would be expected to worsen the condition, since they directly increase the symptoms of panic, such as heart rate. Deacon and Valentiner (2000)[41] conducted a study that examined co-morbid panic attacks and substance use in a non-clinical sample of young adults who experienced regular panic attacks. The authors found that compared to healthy controls, sedative use was greater for non-clinical participants who experienced panic attacks. These findings are consistent with the suggestion made by Cox, Norton, Dorward, and Fergusson (1989)[42] that panic disorder patients self-medicate if they believe that certain substances will be successful in alleviating their symptoms. If panic disorder patients are indeed self-medicating, there may be a portion of the population with undiagnosed panic disorder who will not seek professional help as a result of their own self-medication. In fact, for some patients panic disorder is only diagnosed after they seek treatment for their self-medication habit.[43] While alcohol initially helps ease panic disorder symptoms, medium- or long-term alcohol abuse can cause panic disorder to develop or worsen during alcohol intoxication, especially during alcohol withdrawal syndrome.[44] This effect is not unique to alcohol but can also occur with long-term use of drugs which have a similar mechanism of action to alcohol such as the benzodiazepines which are sometimes prescribed as tranquilizers to people with alcohol problems.[44] The reason chronic alcohol misuse worsens panic disorder is due to distortion of the brain chemistry and function.[45][46][47] Approximately 10% of patients will experience notable protracted withdrawal symptoms, which can include panic disorder, after discontinuation of benzodiazepines. Protracted withdrawal symptoms tend to resemble those seen during the first couple of months of withdrawal but usually are of a subacute level of severity compared to the symptoms seen during the first 2 or 3 months of withdrawal. It is not known definitively whether such symptoms persisting long after withdrawal are related to true pharmacological withdrawal or whether they are due to structural neuronal damage as a result of chronic use of benzodiazepines or withdrawal. Nevertheless, such symptoms do typically lessen as the months and years go by eventually disappearing altogether.[48] A significant proportion of patients attending mental health services for conditions including anxiety disorders such as panic disorder or social phobia have developed these conditions as a result of alcohol or sedative abuse. Anxiety may pre-exist alcohol or sedative dependence, which then acts to perpetuate or worsen the underlying anxiety disorder. Someone suffering the toxic effects of alcohol abuse or chronic sedative use or abuse will not benefit from other therapies or medications for underlying psychiatric conditions as they do not address the root cause of the symptoms. Recovery from sedative symptoms may temporarily worsen during alcohol withdrawal or benzodiazepine withdrawal.[49][50][51][52] ## Mechanism[edit] The neuroanatomy of panic disorder largely overlaps with that of most anxiety disorders. Neuropsychological, neurosurgical, and neuroimaging studies implicate the insula, amygdala, hippocampus, anterior cingulate cortex (ACC), lateral prefrontal cortex, and periaqueductal grey. During acute panic attacks, viewing emotionally charged words, and rest, most studies find elevated blood flow or metabolism. However, the observation of amygdala hyperactivity is not entirely consistent, especially in studies that evoke panic attacks chemically. Hippocampus hyperactivity has been observed during rest and viewing emotionally charged pictures, which has been hypothesized to be related to memory retrieval bias towards anxious memories. Insula hyperactivity during the onset of and over the course of acute panic episodes is thought to be related to abnormal introceptive processes; the perception that bodily sensations are "wrong" is a transdiagnostic finding(i.e. found across multiple anxiety disorders), and may be related to insula dysfunction. Rodent and human studies heavily implicate the periaqueductal grey in generating fear responses, and abnormalities related to the structure and metabolism in the PAG have been reported in panic disorder. The frontal cortex is implicated in panic disorder by multiple lines of evidence. Damage to the dorsal ACC has been reported to lead to panic disorder. Elevated ventral ACC and dorsolateral prefrontal cortex during symptom provocation and viewing emotional stimuli have also been reported, although findings are not consistent.[53] Researchers studying some individuals with panic disorder propose they may have a chemical imbalance within the limbic system and one of its regulatory chemicals GABA-A. The reduced production of GABA-A sends false information to the amygdala which regulates the body's "fight or flight" response mechanism and, in return, produces the physiological symptoms that lead to the disorder. Clonazepam, an anticonvulsant benzodiazepine with a long half-life, has been successful in keeping the condition under control.[54] Recently, researchers have begun to identify mediators and moderators of aspects of panic disorder. One such mediator is the partial pressure of carbon dioxide, which mediates the relationship between panic disorder patients receiving breathing training and anxiety sensitivity; thus, breathing training affects the partial pressure of carbon dioxide in a patient's arterial blood, which in turn lowers anxiety sensitivity.[55] Another mediator is hypochondriacal concerns, which mediate the relationship between anxiety sensitivity and panic symptomatology; thus, anxiety sensitivity affects hypochondriacal concerns which, in turn, affect panic symptomatology.[56] Perceived threat control has been identified as a moderator within panic disorder, moderating the relationship between anxiety sensitivity and agoraphobia; thus, the level of perceived threat control dictates the degree to which anxiety sensitivity results in agoraphobia.[57] Another recently identified moderator of panic disorder is genetic variations in the gene coding for galanin; these genetic variations moderate the relationship between females suffering from panic disorder and the level of severity of panic disorder symptomatology.[58] ## Diagnosis[edit] The DSM-IV-TR diagnostic criteria for panic disorder require unexpected, recurrent panic attacks, followed in at least one instance by at least a month of a significant and related behavior change, a persistent concern of more attacks, or a worry about the attack's consequences. There are two types, one with and one without agoraphobia. Diagnosis is excluded by attacks due to a drug or medical condition, or by panic attacks that are better accounted for by other mental disorders.[59] The ICD-10 diagnostic criteria: The essential feature is recurrent attacks of severe anxiety (panic), which are not restricted to any particular situation or set of circumstances and are therefore unpredictable. The dominant symptoms include: * sudden onset of palpitations * chest pain * choking sensations * dizziness * feelings of unreality (depersonalization or derealization) * secondary fear of dying, losing control, or going mad Panic disorder should not be given as the main diagnosis if the person has a depressive disorder at the time the attacks start; in these circumstances, the panic attacks are probably secondary to depression.[60] The Panic Disorder Severity Scale (PDSS) is a questionnaire for measuring the severity of panic disorder.[61] ## Treatment[edit] Panic disorder is a serious health problem that in many cases can be successfully treated, although there is no known cure. Identification of treatments that engender as full a response as possible, and can minimize relapse, is imperative.[62] Cognitive behavioral therapy and positive self-talk specific for panic[63] are the treatments of choice for panic disorder. Several studies show that 85 to 90 percent of panic disorder patients treated with CBT recover completely from their panic attacks within 12 weeks.[64] When cognitive behavioral therapy is not an option, pharmacotherapy can be used. SSRIs are considered a first-line pharmacotherapeutic option.[65][66][67] ### Psychotherapy[edit] Panic disorder is not the same as phobic symptoms, although phobias commonly result from panic disorder.[68] CBT and one tested form of psychodynamic psychotherapy have been shown efficacious in treating panic disorder with and without agoraphobia.[69][70][71] A number of randomized clinical trials have shown that CBT achieves reported panic-free status in 70–90% of patients about 2 years after treatment.[64] A 2009 Cochrane review found little evidence concerning the efficacy of psychotherapy in combination with benzodiazepines such that recommendations could not be made.[72] Symptom inductions generally occur for one minute and may include: * Intentional hyperventilation – creates lightheadedness, derealization, blurred vision, dizziness * Spinning in a chair – creates dizziness, disorientation * Straw breathing – creates dyspnea, airway constriction * Breath holding – creates sensation of being out of breath * Running in place – creates increased heart rate, respiration, perspiration * Body tensing – creates feelings of being tense and vigilant Another form of psychotherapy that has shown effectiveness in controlled clinical trials is panic-focused psychodynamic psychotherapy, which focuses on the role of dependency, separation anxiety, and anger in causing panic disorder. The underlying theory posits that due to biochemical vulnerability, traumatic early experiences, or both, people with panic disorder have a fearful dependence on others for their sense of security, which leads to separation anxiety and defensive anger. Therapy involves first exploring the stressors that lead to panic episodes, then probing the psychodynamics of the conflicts underlying panic disorder and the defense mechanisms that contribute to the attacks, with attention to transference and separation anxiety issues implicated in the therapist-patient relationship.[73] Comparative clinical studies suggest that muscle relaxation techniques and breathing exercises are not efficacious in reducing panic attacks. In fact, breathing exercises may actually increase the risk of relapse.[74] Appropriate treatment by an experienced professional can prevent panic attacks or at least substantially reduce their severity and frequency—bringing significant relief to 70 to 90 percent of people with panic disorder.[75] Relapses may occur, but they can often be effectively treated just like the initial episode. vanApeldoorn, F.J. et al. (2011) demonstrated the additive value of a combined treatment incorporating an SSRI treatment intervention with cognitive behavior therapy (CBT).[76] Gloster et al. (2011) went on to examine the role of the therapist in CBT. They randomized patients into two groups: one being treated with CBT in a therapist guided environment, and the second receiving CBT through instruction only, with no therapist guided sessions. The findings indicated that the first group had a somewhat better response rate, but that both groups demonstrated a significant improvement in reduction of panic symptomatology. These findings lend credibility to the application of CBT programs to patients who are unable to access therapeutic services due to financial, or geographic inaccessibility.[77] Koszycky et al. (2011) discuss the efficacy of self-administered cognitive behavioural therapy (SCBT) in situations where patients are unable to retain the services of a therapist. Their study demonstrates that it is possible for SCBT in combination with an SSRI to be as effective as therapist-guided CBT with SSRI. Each of these studies contributes to a new avenue of research that allows effective treatment interventions to be made more easily accessible to the population.[78] #### Cognitive behavioral therapy[edit] Cognitive behavioral therapy encourages patients to confront the triggers that induce their anxiety. By facing the very cause of the anxiety, it is thought to help diminish the irrational fears that are causing the issues to begin with. The therapy begins with calming breathing exercises, followed by noting the changes in physical sensations felt as soon as anxiety begins to enter the body. Many clients are encouraged to keep journals. In other cases, therapists may try and induce feelings of anxiety so that the root of the fear can be identified.[79] Comorbid clinical depression, personality disorders and alcohol abuse are known risk factors for treatment failure.[80] As with many disorders, having a support structure of family and friends who understand the condition can help increase the rate of recovery. During an attack, it is not uncommon for the sufferer to develop irrational, immediate fear, which can often be dispelled by a supporter who is familiar with the condition. For more serious or active treatment, there are support groups for anxiety sufferers which can help people understand and deal with the disorder. Current treatment guidelines American Psychiatric Association and the American Medical Association primarily recommend either cognitive-behavioral therapy or one of a variety of psychopharmacological interventions. Some evidence exists supporting the superiority of combined treatment approaches.[69][81][82] Another option is self-help based on principles of cognitive-behavioral therapy.[83] Using a book or a website, a person does the kinds of exercises that would be used in therapy, but they do it on their own, perhaps with some email or phone support from a therapist.[84] A systematic analysis of trials testing this kind of self-help found that websites, books, and other materials based on cognitive-behavioral therapy could help some people.[83] The best-studied conditions are panic disorder and social phobia.[83] #### Interoceptive techniques[edit] Interoceptive exposure is sometimes used for panic disorder. People's interoceptive triggers of anxiety are evaluated one-by-one before conducting interoceptive exposures, such as addressing palpitation sensitivity via light exercise.[12] Despite evidence of its clinical efficacy, this practice is reportedly used by only 12–20% of psychotherapists. Potential reasons for this underutilization include "lack of training sites, logistical hurdles (e.g., occasional need for exposure durations longer than a standard therapy session), policies against conducting exposures outside of the workplace setting, and perhaps most tellingly, negative therapist beliefs (e.g., that interoceptive exposures are unethical, intolerable, or even harmful)."[12] ### Medication[edit] Appropriate medications are effective for panic disorder. Selective serotonin reuptake inhibitors are first line treatments rather than benzodiazapines due to concerns with the latter regarding tolerance, dependence and abuse.[85] Although there is little evidence that pharmacological interventions can directly alter phobias, few studies have been performed, and medication treatment of panic makes phobia treatment far easier (an example in Europe where only 8% of patients receive appropriate treatment).[86] Medications can include: * Antidepressants (SSRIs, MAOIs, tricyclic antidepressants and norepinephrine reuptake inhibitors) * Antianxiety agents (benzodiazepines): Use of benzodiazepines for panic disorder is controversial. The American Psychiatric Association states that benzodiazepines can be effective for the treatment of panic disorder and recommends that the choice of whether to use benzodiazepines, antidepressants with anti-panic properties or psychotherapy should be based on the individual patient's history and characteristics.[87] Other experts believe that benzodiazepines are best avoided due to the risks of the development of tolerance and physical dependence.[88] The World Federation of Societies of Biological Psychiatry, say that benzodiazepines should not be used as a first-line treatment option but are an option for treatment-resistant cases of panic disorder.[89] Despite increasing focus on the use of antidepressants and other agents for the treatment of anxiety as recommended best practice, benzodiazepines have remained a commonly used medication for panic disorder.[90][91] They reported that in their view there is insufficient evidence to recommend one treatment over another for panic disorder. The APA noted that while benzodiazepines have the advantage of a rapid onset of action, that this is offset by the risk of developing a benzodiazepine dependence.[92] The National Institute of Clinical Excellence came to a different conclusion, they pointed out the problems of using uncontrolled clinical trials to assess the effectiveness of pharmacotherapy and based on placebo-controlled research they concluded that benzodiazepines were not effective in the long-term for panic disorder and recommended that benzodiazepines not be used for longer than 4 weeks for panic disorder. Instead NICE clinical guidelines recommend alternative pharmacotherapeutic or psychotherapeutic interventions.[93] When compared to placebos, benzodiazepines demonstrate possible superiority in the short term but the evidence is low quality with limited applicability to clinical practice.[94] ### Other treatments[edit] For some people, anxiety can be greatly reduced by discontinuing the use of caffeine.[95] Anxiety can temporarily increase during caffeine withdrawal.[96][97][98] ## Epidemiology[edit] Age-standardized disability-adjusted life year rates for panic disorder per 100,000 inhabitants in 2004. no data less than 95 95–96.5 96.5–98 98–99.5 99.5–101 101–102.5 102.5–104 104–105.5 105.5–107 107–108.5 108.5–110 more than 110 Panic disorder typically begins during early adulthood; roughly half of all people who have panic disorder develop the condition between the ages of 17 and 24, especially those subjected to traumatic experiences. However, some studies suggest that the majority of young people affected for the first time are between the ages of 25 and 30. Women are twice as likely as men to develop panic disorder and it occurs far more often in people with above average intelligence.[99] Panic disorder can continue for months or years, depending on how and when treatment is sought. If left untreated, it may worsen to the point where one's life is seriously affected by panic attacks and by attempts to avoid or conceal the condition. In fact, many people have had problems with personal relationships, education and employment while struggling to cope with panic disorder. Some people with panic disorder may conceal their condition because of the stigma of mental illness. In some individuals, symptoms may occur frequently for a period of months or years, then many years may pass with little or no symptoms. In some cases, the symptoms persist at the same level indefinitely. There is also some evidence that many individuals (especially those who develop symptoms at an early age) may experience symptom cessation later in life (e.g., past age 50).[citation needed] In 2000, the World Health Organization found prevalence and incidence rates for panic disorder to be very similar across the globe. Age-standardized prevalence per 100,000 ranged from 309 in Africa to 330 in East Asia for men and from 613 in Africa to 649 in North America, Oceania, and Europe for women.[100] ## Children[edit] A retrospective study has shown that 40% of adult panic disorder patients reported that their disorder began before the age of 20.[101] In an article examining the phenomenon of panic disorder in youth, Diler et al. (2004)[102] found that only a few past studies have examined the occurrence of juvenile panic disorder. They report that these studies have found that the symptoms of juvenile panic disorder almost replicate those found in adults (e.g. heart palpitations, sweating, trembling, hot flashes, nausea, abdominal distress, and chills).[103][104][105][106][107] The anxiety disorders co-exist with staggeringly high numbers of other mental disorders in adults.[108] The same comorbid disorders that are seen in adults are also reported in children with juvenile panic disorder. Last and Strauss (1989)[109] examined a sample of 17 adolescents with panic disorder and found high rates of comorbid anxiety disorders, major depressive disorder, and conduct disorders. Eassau et al. (1999)[105] also found a high number of comorbid disorders in a community-based sample of adolescents with panic attacks or juvenile panic disorder. Within the sample, adolescents were found to have the following comorbid disorders: major depressive disorder (80%), dysthymic disorder (40%), generalized anxiety disorder (40%), somatoform disorders (40%), substance abuse (40%), and specific phobia (20%). Consistent with this previous work, Diler et al. (2004) found similar results in their study in which 42 youths with juvenile panic disorder were examined. Compared to non-panic anxiety disordered youths, children with panic disorder had higher rates of comorbid major depressive disorder and bipolar disorder. Children differ from adolescents and adults in their interpretation and ability to express their experience. Like adults, children experience physical symptoms including accelerated heart rate, sweating, trembling or shaking, shortness of breath, nausea or stomach pain, dizziness or light-headedness. In addition, children also experience cognitive symptoms like fear of dying, feelings of being detached from oneself, feelings of losing control or going crazy, but they are unable to vocalize these higher-order manifestations of fear. They simply know that something is going wrong and that they are very afraid. Children can only describe physical symptoms. They have not yet developed the constructs to put these symptoms together and label them as fear. Parents often feel helpless when they watch a child suffer. They can help children give a name to their experience, and empower them to overcome the fear they are experiencing[110] The role of the parent in treatment and intervention for children diagnosed with panic disorder is discussed by McKay & Starch (2011). They point out that there are several levels at which parental involvement should be considered. The first involves the initial assessment. Parents, as well as the child, should be screened for attitudes and treatment goals, as well as for levels of anxiety or conflict in the home. The second involves the treatment process in which the therapist should meet with the family as a unit as frequently as possible. Ideally, all family members should be aware and trained in the process of cognitive behavior therapy (CBT) in order to encourage the child to rationalize and face fears rather than employ avoidant safety behaviors. McKay & Storch (2011) suggest training/modeling of therapeutic techniques and in-session involvement of the parents in the treatment of children to enhance treatment efficacy.[111] Despite the evidence pointing to the existence of early-onset panic disorder, the DSM-IV-TR currently only recognizes six anxiety disorders in children: separation anxiety disorder, generalized anxiety disorder, specific phobia, obsessive-compulsive disorder, social anxiety disorder (a.k.a. social phobia), and post-traumatic stress disorder. Panic disorder is notably excluded from this list. ## References[edit] 1. ^ a b c d e f g "Anxiety Disorders". NIMH. March 2016. Archived from the original on 29 September 2016. Retrieved 1 October 2016. 2. ^ a b c d e f g h i American Psychiatric Association (2013), Diagnostic and Statistical Manual of Mental Disorders (5th ed.), Arlington: American Psychiatric Publishing, pp. 208–217, 938, ISBN 978-0890425558 3. ^ a b c d e f g h i j k l m "Panic Disorder: When Fear Overwhelms". NIMH. 2013. Archived from the original on 4 October 2016. Retrieved 1 October 2016. 4. ^ a b c d Craske MG, Stein MB (December 2016). "Anxiety". Lancet. 388 (10063): 3048–3059. doi:10.1016/S0140-6736(16)30381-6. PMID 27349358. S2CID 208789585. 5. ^ Herr NR, Williams JW, Benjamin S, McDuffie J (July 2014). "Does this patient have generalized anxiety or panic disorder?: The Rational Clinical Examination systematic review". JAMA. 312 (1): 78–84. doi:10.1001/jama.2014.5950. PMID 25058220. 6. ^ Craske, Michelle G.; Kircanski, Katharina; Epstein, Alyssa; Wittchen, Hans-Ulrich; Pine, Danny S.; Lewis-Fernández, Roberto; Hinton, Devon (February 2010). "Panic disorder: a review of DSM-IV panic disorder and proposals for DSM-V". Depression and Anxiety. 27 (2): 93–112. doi:10.1002/da.20654. PMID 20099270. S2CID 17789728. 7. ^ Freire, Rafael C.; Perna, Giampaolo; Nardi, Antonio E. (July 2010). "Panic Disorder Respiratory Subtype: Psychopathology, Laboratory Challenge Tests, and Response to Treatment". Harvard Review of Psychiatry. 18 (4): 220–229. doi:10.3109/10673229.2010.493744. PMID 20597592. S2CID 13567414. 8. ^ Diler, Rasim Somer; Birmaher, Boris; Brent, David A.; Axelson, David A.; Firinciogullari, Sekip; Chiapetta, Laurel; Bridge, Jeff (2004). "Phenomenology of panic disorder in youth". Depression and Anxiety. 20 (1): 39–43. doi:10.1002/da.20018. PMID 15368595. S2CID 23612310. 9. ^ a b Frisch, N. and Frisch, L. 2006. Psychiatric Mental Health Nursing. 3rd ed. Canada: Thomson Delmar Learning.[page needed] 10. ^ Healy (2009) Psychiatric Drugs Explained 11. ^ O’Mahony, J.F; Ward, B.G (2003). "Differences between those who panic by day and those who also panic by night". Journal of Behavior Therapy and Experimental Psychiatry. 34 (3–4): 239–249. doi:10.1016/j.jbtep.2003.10.001. 12. ^ a b c Khalsa, Sahib S.; Lapidus, Rachel C. (2016). "Can Interoception Improve the Pragmatic Search for Biomarkers in Psychiatry?". Frontiers in Psychiatry. 7: 121. doi:10.3389/fpsyt.2016.00121. PMC 4958623. PMID 27504098. 13. ^ Comer, Ronald (2014). Fundamentals of Abnormal Psychology (7th ed.). New York: Worth Publishers. p. 122. ISBN 978-1-4292-9563-5. 14. ^ Etkin A (2010). "Functional neuroanatomy of anxiety: a neural circuit perspective". In Stein MB, Steckler T (eds.). Behavioral Neurobiology of Anxiety and Its Treatment. Current Topics in Behavioral Neurosciences. 2. pp. 251–77. doi:10.1007/7854_2009_5. ISBN 978-3-642-02911-0. PMID 21309113. 15. ^ Clark DA, Beck AT (2012). The Anxiety and Worry Workbook: The Cognitive Behavioral Solution. New York: Guilford Press. 16. ^ Hawks E, Blumenthal H, Feldner MT, Leen-Feldner EW, Jones R (September 2011). "An examination of the relation between traumatic event exposure and panic-relevant biological challenge responding among adolescents". Behavior Therapy. Elsevier Ltd. 42 (3): 427–38. doi:10.1016/j.beth.2010.11.002. PMID 21658525. 17. ^ "Panic Disorder and Pharmacological Treatment Options". Archived from the original on 15 April 2012. Retrieved 12 May 2012. 18. ^ Ludewig S, Geyer MA, Ramseier M, Vollenweider FX, Rechsteiner E, Cattapan-Ludewig K (January 2005). "Information-processing deficits and cognitive dysfunction in panic disorder". Journal of Psychiatry & Neuroscience. 30 (1): 37–43. PMC 543839. PMID 15644996. 19. ^ Katerndahl DA, Realini JP (1999). "Relationship between substance abuse and panic attacks". Addictive Behaviors. 24 (5): 731–6. doi:10.1016/s0306-4603(98)00078-1. PMID 10574314. 20. ^ Akindipe T, Wilson D, Stein DJ (June 2014). "Psychiatric disorders in individuals with methamphetamine dependence: prevalence and risk factors". Metabolic Brain Disease. 29 (2): 351–7. doi:10.1007/s11011-014-9496-5. PMID 24532047. S2CID 14880172. 21. ^ Roy-Byrne PP, Craske MG, Stein MB (September 2006). "Panic disorder". Lancet. 368 (9540): 1023–32. doi:10.1016/S0140-6736(06)69418-X. PMID 16980119. S2CID 43357552. 22. ^ Cosci F, Knuts IJ, Abrams K, Griez EJ, Schruers KR (May 2010). "Cigarette smoking and panic: a critical review of the literature". The Journal of Clinical Psychiatry. 71 (5): 606–15. doi:10.4088/JCP.08r04523blu. PMID 19961810. 23. ^ a b Johnson JG, Cohen P, Pine DS, Klein DF, Kasen S, Brook JS (November 2000). "Association between cigarette smoking and anxiety disorders during adolescence and early adulthood". JAMA. 284 (18): 2348–51. doi:10.1001/jama.284.18.2348. PMID 11066185. 24. ^ Isensee B, Wittchen HU, Stein MB, Höfler M, Lieb R (July 2003). "Smoking increases the risk of panic: findings from a prospective community study". Archives of General Psychiatry. 60 (7): 692–700. doi:10.1001/archpsyc.60.7.692. PMID 12860773. 25. ^ Goodwin RD, Lewinsohn PM, Seeley JR (November 2005). "Cigarette smoking and panic attacks among young adults in the community: the role of parental smoking and anxiety disorders". Biological Psychiatry. 58 (9): 686–93. doi:10.1016/j.biopsych.2005.04.042. PMID 16018987. S2CID 33807953. 26. ^ Breslau N, Klein DF (December 1999). "Smoking and panic attacks: an epidemiologic investigation". Archives of General Psychiatry. 56 (12): 1141–7. doi:10.1001/archpsyc.56.12.1141. PMID 10591292. 27. ^ Pine DS, Klein RG, Coplan JD, Papp LA, Hoven CW, Martinez J, et al. (October 2000). "Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill comparison group". Archives of General Psychiatry. 57 (10): 960–7. doi:10.1001/archpsyc.57.10.960. PMID 11015814. 28. ^ Gorman JM, Kent J, Martinez J, Browne S, Coplan J, Papp LA (February 2001). "Physiological changes during carbon dioxide inhalation in patients with panic disorder, major depression, and premenstrual dysphoric disorder: evidence for a central fear mechanism". Archives of General Psychiatry. 58 (2): 125–31. doi:10.1001/archpsyc.58.2.125. PMID 11177114. 29. ^ Leyro TM, Zvolensky MJ (March 2013). "The Interaction of Nicotine Withdrawal and Panic Disorder in the Prediction of Panic-relevant Responding to a Biological Challenge". Psychology of Addictive Behaviors. 27 (1): 90–101. doi:10.1037/a0029423. PMC 3663295. PMID 22867297. Retrieved 10 May 2020. 30. ^ Hughes RN (June 1996). "Drugs which Induce Anxiety: Caffeine" (PDF). New Zealand Journal of Psychology. 25 (1): 36–42. Archived (PDF) from the original on 25 January 2016. 31. ^ Vilarim MM, Rocha Araujo DM, Nardi AE (August 2011). "Caffeine challenge test and panic disorder: a systematic literature review". Expert Review of Neurotherapeutics. 11 (8): 1185–95. doi:10.1586/ern.11.83. PMID 21797659. S2CID 5364016. 32. ^ Halter MJ (2008). Varcarolis' Foundations of Psychiatric Mental Health Nursing: A Clinical Approach. ISBN 978-1455753581. 33. ^ Lara DR (2010). "Caffeine, mental health, and psychiatric disorders". Journal of Alzheimer's Disease. 20 Suppl 1 (Suppl 1): S239-48. doi:10.3233/JAD-2010-1378. PMID 20164571. 34. ^ Lee MA, Flegel P, Greden JF, Cameron OG (May 1988). "Anxiogenic effects of caffeine on panic and depressed patients". The American Journal of Psychiatry. 145 (5): 632–5. doi:10.1176/ajp.145.5.632. PMID 3358468. 35. ^ Nardi AE, Lopes FL, Valença AM, Freire RC, Veras AB, de-Melo-Neto VL, et al. (May–June 2007). "Caffeine challenge test in panic disorder and depression with panic attacks". Comprehensive Psychiatry. 48 (3): 257–63. doi:10.1016/j.comppsych.2006.12.001. PMID 17445520. 36. ^ "High blood pressure and cold remedies: Which are safe?". Archived from the original on 31 January 2017. Retrieved 21 January 2017. 37. ^ "Panic Disorder". Mental Health America. Archived from the original on 6 February 2014. Retrieved 2 July 2007. 38. ^ "FASTSTATS — Alcohol Use". Centers for Disease Control and Prevention. Archived from the original on 8 July 2013. Retrieved 28 June 2013. 39. ^ "FASTSTATS — Illegal Drug Use". Centers for Disease Control and Prevention. 30 May 2013. Archived from the original on 5 July 2013. Retrieved 28 June 2013. 40. ^ Practice guideline for the treatment of patients with panic disorder (PDF). American Psychiatric Association. 2010. p. 41. "Despite the anxiolytic effects perceived by some patients, use of many substances can trigger or worsen panic symptoms." 41. ^ Deacon BJ, Valentiner DP (2000). "Substance use and non-clinical panic attacks in a young adult sample". Journal of Substance Abuse. 11 (1): 7–15. doi:10.1016/S0899-3289(99)00017-6. PMID 10756510. 42. ^ Cox BJ, Norton GR, Dorward J, Fergusson PA (1989). "The relationship between panic attacks and chemical dependencies". Addictive Behaviors. 14 (1): 53–60. doi:10.1016/0306-4603(89)90016-6. PMID 2718824. 43. ^ Cox BJ, Norton GR, Swinson RP, Endler NS (1990). "Substance abuse and panic-related anxiety: a critical review". Behaviour Research and Therapy. 28 (5): 385–93. doi:10.1016/0005-7967(90)90157-E. PMID 2256896. 44. ^ a b Terra MB, Figueira I, Barros HM (August 2004). "Impact of alcohol intoxication and withdrawal syndrome on social phobia and panic disorder in alcoholic inpatients". Revista do Hospital das Clinicas. 59 (4): 187–92. doi:10.1590/S0041-87812004000400006. PMID 15361983. 45. ^ Wetterling T, Junghanns K (December 2000). "Psychopathology of alcoholics during withdrawal and early abstinence". European Psychiatry. 15 (8): 483–8. doi:10.1016/S0924-9338(00)00519-8. PMID 11175926. 46. ^ Cowley DS (January 1992). "Alcohol abuse, substance abuse, and panic disorder". The American Journal of Medicine. 92 (1A): 41S–48S. doi:10.1016/0002-9343(92)90136-Y. PMID 1346485. 47. ^ Cosci F, Schruers KR, Abrams K, Griez EJ (June 2007). "Alcohol use disorders and panic disorder: a review of the evidence of a direct relationship". The Journal of Clinical Psychiatry. 68 (6): 874–80. doi:10.4088/JCP.v68n0608. PMID 17592911. 48. ^ Ashton H (1991). "Protracted withdrawal syndromes from benzodiazepines". Journal of Substance Abuse Treatment. 8 (1–2): 19–28. doi:10.1016/0740-5472(91)90023-4. PMID 1675688. 49. ^ Cohen SI (February 1995). "Alcohol and benzodiazepines generate anxiety, panic and phobias". Journal of the Royal Society of Medicine. 88 (2): 73–7. PMC 1295099. PMID 7769598. 50. ^ Belleville G, Morin CM (March 2008). "Hypnotic discontinuation in chronic insomnia: impact of psychological distress, readiness to change, and self-efficacy". Health Psychology. 27 (2): 239–48. doi:10.1037/0278-6133.27.2.239. PMID 18377143. 51. ^ Ashton CH (1987). "Benzodiazepine Withdrawal: Outcome in 50 Patients". British Journal of Addiction. 82 (6): 655–671. doi:10.1111/j.1360-0443.1987.tb01529.x. PMID 2886145. 52. ^ Onyett SR (April 1989). "The benzodiazepine withdrawal syndrome and its management". The Journal of the Royal College of General Practitioners. 39 (321): 160–3. PMC 1711840. PMID 2576073. 53. ^ Goodkind, Madeleine S.; Etkin, Amit (2017). "Functional Neurocircuitry and Neuroimaging Studies of Anxiety Disorders". In Charney, Dennis S; Nestler, Eric J; Sklar, Pamela; Buxbaum, Joseph D (eds.). Charney & Nestler's Neurobiology of Mental Illness. pp. 435–450. doi:10.1093/med/9780190681425.003.0034. ISBN 978-0-19-068142-5. 54. ^ Cameron, Oliver G.; Huang, Grace C.; Nichols, Thomas; Koeppe, Robert A.; Minoshima, Satoshi; Rose, David; Frey, Kirk A. (1 July 2007). "Reduced γ-Aminobutyric AcidA–Benzodiazepine Binding Sites in Insular Cortex of Individuals With Panic Disorder". Archives of General Psychiatry. 64 (7): 793–800. doi:10.1001/archpsyc.64.7.793. PMID 17606813. 55. ^ Meuret AE, Rosenfield D, Hofmann SG, Suvak MK, Roth WT (March 2009). "Changes in respiration mediate changes in fear of bodily sensations in panic disorder". Journal of Psychiatric Research. 43 (6): 634–41. doi:10.1016/j.jpsychires.2008.08.003. PMC 3327292. PMID 18835608. 56. ^ Berrocal C, Moreno FR, Cano J (May 2007). "Anxiety sensitivity and panic symptomatology: the mediator role of hypochondriacal concerns". The Spanish Journal of Psychology. 10 (1): 159–66. doi:10.1017/s1138741600006429. PMID 17549889. 57. ^ White KS, Brown TA, Somers TJ, Barlow DH (January 2006). "Avoidance behavior in panic disorder: the moderating influence of perceived control". Behaviour Research and Therapy. 44 (1): 147–57. doi:10.1016/j.brat.2005.07.009. PMID 16300725. 58. ^ Unschuld PG, Ising M, Erhardt A, Lucae S, Kohli M, Kloiber S, et al. (January 2008). "Polymorphisms in the galanin gene are associated with symptom-severity in female patients suffering from panic disorder". Journal of Affective Disorders. 105 (1–3): 177–84. doi:10.1016/j.jad.2007.05.006. PMID 17573119. 59. ^ American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th, text revision (DSM-IV-TR) ed. 2000. ISBN 0-89042-025-4. Panic Disorder without Agoraphobia. Panic Disorder with Agoraphobia. 60. ^ http://apps.who.int/classifications/icd10/browse/2015/en#/F41.0 Archived 2 November 2015 at the Wayback Machine 61. ^ Shear, M. Katherine; Clark, Duncan; Feske, and Ulrika (1 February 1998). "The Road to Recovery in Panic Disorder: Response, Remission, and Relapse". The Journal of Clinical Psychiatry. 59 (suppl 8): 4–8. PMID 9707156. 62. ^ Salvador-Carulla L, Seguí J, Fernández-Cano P, Canet J (April 1995). "Costs and offset effect in panic disorders". The British Journal of Psychiatry. Supplement. 166 (27): 23–8. doi:10.1192/S0007125000293367. PMID 7794590. 63. ^ Ellis R, Ryan JA (2005). "Emotional Intelligence and Positive Psychology: Therapist Tools for Training/Coaching Clients to Move Beyond Emotional Relief". Annals of the American Psychotherapy Assn. 8 (3): 42–43. 64. ^ a b Nolen-Hoeksema S (2 December 2013). Abnormal Psychology. McGraw-Hill. p. 132. ISBN 978-0078035388. 65. ^ Cloos JM (January 2005). "The treatment of panic disorder". Current Opinion in Psychiatry. 18 (1): 45–50. PMID 16639183. Archived from the original on 4 April 2011. 66. ^ Foldes-Busque G, Marchand A, Landry P (October 2007). "[Early detection and treatment of panic disorder with or without agoraphobia: update]". Canadian Family Physician. 53 (10): 1686–93. PMC 2231433. PMID 17934032. 67. ^ Rathgeb-Fuetsch M, Kempter G, Feil A, Pollmächer T, Schuld A (September 2011). "Short- and long- term efficacy of cognitive behavioral therapy for DSM-IV panic disorder in patients with and without severe psychiatric comorbidity". Journal of Psychiatric Research. 45 (9): 1264–8. doi:10.1016/j.jpsychires.2011.03.018. PMID 21536308. 68. ^ American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th, text revision (DSM-IV-TR) ed. 2000. ISBN 0-89042-025-4. 69. ^ a b Marks, Isaac M.; Swinson, Richard P.; Başoǧlu, Metin; Kuch, Klaus; Noshirvani, Homa; O'Sullivan, Geraldine; Lelliott, Paul T.; Kirby, Marlene; McNamee, Gary; Sengun, Seda; Wickwire, Kim (June 1993). "Alprazolam and Exposure Alone and Combined in Panic Disorder with Agoraphobia: A Controlled Study in London and Toronto". British Journal of Psychiatry. 162 (6): 776–787. doi:10.1192/bjp.162.6.776. PMID 8101126. S2CID 25233822. 70. ^ Milrod BL, Leon AC, Barber JP, Markowitz JC, Graf E (June 2007). "Do comorbid personality disorders moderate panic-focused psychotherapy? An exploratory examination of the American Psychiatric Association practice guideline". The Journal of Clinical Psychiatry. 68 (6): 885–91. doi:10.4088/JCP.v68n0610. PMID 17592913. 71. ^ Barlow DH, Gorman JM, Shear MK, Woods SW (May 2000). "Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial". JAMA. 283 (19): 2529–36. doi:10.1001/jama.283.19.2529. PMID 10815116. 72. ^ Watanabe, Norio; Churchill, Rachel; Furukawa, Toshi A (21 January 2009). "Combined psychotherapy plus benzodiazepines for panic disorder". Cochrane Database of Systematic Reviews (1): CD005335. doi:10.1002/14651858.CD005335.pub2. PMID 19160253. 73. ^ Busch, Fredric N.; Milrod, Barbara L. (1 February 2008). "Panic-Focused Psychodynamic Psychotherapy". Psychiatric Times. 25 (2). 74. ^ Schmidt, Norman B.; Woolaway-Bickel, Kelly; Trakowski, Jack; Santiago, Helen; Storey, Julie; Koselka, Margaret; Cook, Jeff (2000). "Dismantling cognitive–behavioral treatment for panic disorder: Questioning the utility of breathing retraining". Journal of Consulting and Clinical Psychology. 68 (3): 417–424. CiteSeerX 10.1.1.561.9948. doi:10.1037//0022-006x.68.3.417. PMID 10883558. 75. ^ "Panic Disorder". National Institute of Mental Health. Archived from the original on 28 April 2006. Retrieved 12 May 2006. 76. ^ van Apeldoorn, F. J.; van Hout, W. J. P. J.; Mersch, P. P. A.; Huisman, M.; Slaap, B. R.; Hale, W. W.; Visser, S.; van Dyck, R.; den Boer, J. A. (April 2008). "Is a combined therapy more effective than either CBT or SSRI alone? Results of a multicenter trial on panic disorder with or without agoraphobia". Acta Psychiatrica Scandinavica. 117 (4): 260–270. doi:10.1111/j.1600-0447.2008.01157.x. hdl:1874/385414. PMID 18307586. S2CID 23376651. 77. ^ Gloster, Andrew T.; Wittchen, Hans-Ulrich; Einsle, Franziska; Lang, Thomas; Helbig-Lang, Sylvia; Fydrich, Thomas; Fehm, Lydia; Hamm, Alfons O.; Richter, Jan; Alpers, Georg W.; Gerlach, Alexander L.; Ströhle, Andreas; Kircher, Tilo; Deckert, Jürgen; Zwanzger, Peter; Höfler, Michael; Arolt, Volker (2011). "Psychological treatment for panic disorder with agoraphobia: A randomized controlled trial to examine the role of therapist-guided exposure in situ in CBT". Journal of Consulting and Clinical Psychology. 79 (3): 406–420. doi:10.1037/a0023584. PMID 21534651. 78. ^ Koszycki, D.; Taljaard, M.; Segal, Z.; Bradwejn, J. (February 2011). "A randomized trial of sertraline, self-administered cognitive behavior therapy, and their combination for panic disorder". Psychological Medicine. 41 (2): 373–383. doi:10.1017/S0033291710000930. PMID 20462466. 79. ^ Nolen-Hoeksema S (1 January 2014). Abnormal Psychology. McGraw-Hill Education – Europe. ISBN 978-1-259-06072-4.[page needed] 80. ^ Seguí J, Márquez M, Canet J, García L (1999). "Causas de fracaso en el tratamiento psicofarmacologico del trastorno por angustia" [Causes of failure in psychopharmacological treatment of anxiety disorder]. Actas Espanolas de Psiquiatria (in Spanish). 27 (4): 250–258. PMID 10469946. 81. ^ Barlow, David H.; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott W. (17 May 2000). "Cognitive-Behavioral Therapy, Imipramine, or Their Combination for Panic Disorder: A Randomized Controlled Trial". JAMA. 283 (19): 2529. doi:10.1001/jama.283.19.2529. PMID 10815116. 82. ^ Wiborg, Ida M.; Dahl, AA (1 August 1996). "Does Brief Dynamic Psychotherapy Reduce the Relapse Rate of Panic Disorder?". Archives of General Psychiatry. 53 (8): 689–94. doi:10.1001/archpsyc.1996.01830080041008. PMID 8694682. 83. ^ a b c Lewis, Catrin; Pearce, Jennifer; Bisson, Jonathan I. (January 2012). "Efficacy, cost-effectiveness and acceptability of self-help interventions for anxiety disorders: systematic review". British Journal of Psychiatry. 200 (1): 15–21. doi:10.1192/bjp.bp.110.084756. PMID 22215865. 84. ^ Lewis, Catrin; Pearce, Jennifer; Bisson, Jonathan I. (January 2012). "Efficacy, cost-effectiveness and acceptability of self-help interventions for anxiety disorders: systematic review". British Journal of Psychiatry. 200 (1): 15–21. doi:10.1192/bjp.bp.110.084756. PMID 22215865. 85. ^ Moylan, Steven; Giorlando, Francesco; Nordfjærn, Trond; Berk, Michael (March 2012). "The role of alprazolam for the treatment of panic disorder in Australia". Australian & New Zealand Journal of Psychiatry. 46 (3): 212–224. doi:10.1177/0004867411432074. PMID 22391278. S2CID 11006795. 86. ^ Goodwin, R.D.; Faravelli, C.; Rosi, S.; Cosci, F.; Truglia, E.; de Graaf, R.; Wittchen, H.U. (August 2005). "The epidemiology of panic disorder and agoraphobia in Europe". European Neuropsychopharmacology. 15 (4): 435–443. doi:10.1016/j.euroneuro.2005.04.006. PMID 15925492. S2CID 14905286. 87. ^ "Clinical guidelines and evidence review for panic disorder and generalised anxiety disorder" (PDF). National Collaborating Centre for Primary Care. 2004. Archived (PDF) from the original on 19 February 2009. Retrieved 16 June 2009. 88. ^ Damsa, Cristian; Lazignac, Coralie; Iancu, Ruxandra; Niquille, Marc; Miller, Nick; Mihai, Adriana; Virgillito, Salvatore; Adam, Eric (2008). "Troubles paniques : du diagnostic différentiel vers une prise en charge urgente" [Panic disorders: differential diagnosis and care in emergencies]. Revue Médicale Suisse (in French). 4 (144): 404–409. PMID 18320769. 89. ^ Bandelow B, Zohar J, Hollander E, Kasper S, Möller HJ (October 2002). "World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders". The World Journal of Biological Psychiatry. 3 (4): 171–99. doi:10.3109/15622970209150621. PMID 12516310. 90. ^ Bruce SE, Vasile RG, Goisman RM, Salzman C, Spencer M, Machan JT, Keller MB (August 2003). "Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia?". The American Journal of Psychiatry. 160 (8): 1432–8. doi:10.1176/appi.ajp.160.8.1432. PMID 12900305. 91. ^ Stevens JC, Pollack MH (2005). "Benzodiazepines in clinical practice: consideration of their long-term use and alternative agents". The Journal of Clinical Psychiatry. 66. 66 Suppl 2: 21–7. PMID 15762816. 92. ^ Work Group on Panic Disorder (January 2009). "APA Practice Guideline for the Treatment of Patients With Panic Disorder, Second Edition" (PDF). Retrieved 12 July 2009. 93. ^ School Of Health Related Research (Scharr), University of Sheffield (2004). Clinical Guidelines for the Management of Anxiety: Management of Anxiety. National Collaborating Centre for Primary Care. OCLC 708544131. PMID 20945576.[page needed] 94. ^ Breilmann J, Girlanda F, Guaiana G, Barbui C, Cipriani A, Castellazzi M, et al. (March 2019). "Benzodiazepines versus placebo for panic disorder in adults". The Cochrane Database of Systematic Reviews. 3: CD010677. doi:10.1002/14651858.CD010677.pub2. PMC 6438660. PMID 30921478. 95. ^ Bruce MS, Lader M (February 1989). "Caffeine abstention in the management of anxiety disorders". Psychological Medicine. 19 (1): 211–4. doi:10.1017/S003329170001117X. PMID 2727208. 96. ^ Prasad, Chandan (2005). Nutritional Neuroscience. CRC Press. p. 351. ISBN 978-0415315999. Retrieved 7 October 2012. 97. ^ Nehlig A (2004). Coffee, Tea, Chocolate, and the Brain. CRC Press. p. 136. ISBN 978-0415306911. Retrieved 7 October 2012. 98. ^ Juliano, Laura M.; Griffiths, Roland R. (1 October 2004). "A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features". Psychopharmacology. 176 (1): 1–29. doi:10.1007/s00213-004-2000-x. PMID 15448977. S2CID 5572188. 99. ^ "Facts about Panic Disorder". National Institute of Mental Health. Archived from the original on 7 September 2006. Retrieved 30 September 2006. 100. ^ Ayuso-Mateos JL. "Global burden of panic disorder in the year 2000" (PDF). World Health Organization. Archived (PDF) from the original on 28 October 2013. Retrieved 27 February 2013. 101. ^ Moreau DL, Follet C (1993). "Panic disorder in children and adolescents". Child Adolesc Psychiatr Clin N Am. 2 (4): 581–602. doi:10.1016/S1056-4993(18)30527-3. PMID 1530067. 102. ^ Diler RS, Birmaher B, Brent DA, Axelson DA, Firinciogullari S, Chiapetta L, Bridge J (2004). "Phenomenology of panic disorder in youth". Depression and Anxiety. 20 (1): 39–43. doi:10.1002/da.20018. PMID 15368595. S2CID 23612310. 103. ^ Alessi NE, Magen J (November 1988). "Panic disorder in psychiatrically hospitalized children". The American Journal of Psychiatry. 145 (11): 1450–2. doi:10.1176/ajp.145.11.1450. PMID 3189608. 104. ^ Biederman J, Faraone SV, Marrs A, Moore P, Garcia J, Ablon S, et al. (February 1997). "Panic disorder and agoraphobia in consecutively referred children and adolescents". Journal of the American Academy of Child and Adolescent Psychiatry. 36 (2): 214–23. doi:10.1097/00004583-199702000-00012. PMID 9031574. 105. ^ a b Essau CA, Conradt J, Petermann F (1999). "Frequency of panic attacks and panic disorder in adolescents". Depression and Anxiety. 9 (1): 19–26. doi:10.1002/(SICI)1520-6394(1999)9:1<19::AID-DA3>3.0.CO;2-#. PMID 9989346. 106. ^ King NJ, Gullone E, Tonge BJ, Ollendick TH (January 1993). "Self-reports of panic attacks and manifest anxiety in adolescents". Behaviour Research and Therapy. 31 (1): 111–6. doi:10.1016/0005-7967(93)90049-Z. PMID 8417721. 107. ^ Macauly JL, Kleinknecht RA (1989). "Panic and panic attacks in adolescents". J Anxiety Disord. 3 (4): 221–41. doi:10.1016/0887-6185(89)90016-9. 108. ^ de Reiter C, Rifkin H, Garssen B, Van Schawk A (1989). "Comorbidity among the anxiety disorders". J Anxiety Disord. 3 (2): 57–68. doi:10.1016/0887-6185(89)90001-7. 109. ^ Last CG, Strauss CC (1989). "Panic disorder in children and adolescents". J Anxiety Disord. 3 (2): 87–95. doi:10.1016/0887-6185(89)90003-0. 110. ^ Beidel DC, Alfano CA (2011). Child Anxiety Disorders: A Guide to Research and Treatment (2nd ed.). New York, U.S.A.: Routledge Taylor & Frances Group. 111. ^ Lewin, Adam B. (2011). "Parent Training for Childhood Anxiety". Handbook of Child and Adolescent Anxiety Disorders. pp. 405–417. doi:10.1007/978-1-4419-7784-7_27. ISBN 978-1-4419-7782-3. ## External links[edit] * Panic disorder at Curlie Classification D * ICD-10: F41.0 * ICD-9-CM: 300.01, 300.21 * OMIM: 167870 * MeSH: D016584 * DiseasesDB: 30913 External resources * MedlinePlus: 000924 * eMedicine: article/287913 * Patient UK: Panic disorder * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy * v * t * e Symptoms and signs relating to perception, emotion and behaviour Cognition * Confusion * Delirium * Psychosis * Delusion * Amnesia * Anterograde amnesia * Retrograde amnesia * Convulsion * Dizziness * Disequilibrium * Presyncope/Lightheadedness * Vertigo Emotion * Anger * Anxiety * Depression * Fear * Paranoia * Hostility * Irritability * Suicidal ideation Behavior * Verbosity * Russell's sign Perception * Sensory processing disorder * Hallucination (Auditory hallucination) * Smell * Anosmia * Hyposmia * Dysosmia * Parosmia * Phantosmia * Hyperosmia * Synesthesia * Taste * Ageusia * Hypogeusia * Dysgeusia * Hypergeusia * v * t * e Emotions (list) Emotions * Acceptance * Adoration * Aesthetic emotions * Affection * Agitation * Agony * Amusement * Anger * Angst * Anguish * Annoyance * Anticipation * Anxiety * Apathy * Arousal * Attraction * Awe * Boredom * Calmness * Compassion * Confidence * Contempt * Contentment * Courage * Cruelty * Curiosity * Defeat * Depression * Desire * Despair * Disappointment * Disgust * Distrust * Ecstasy * Embarrassment * Vicarious * Empathy * Enthrallment * Enthusiasm * Envy * Euphoria * Excitement * Fear * Flow (psychology) * Frustration * Gratification * Gratitude * Greed * Grief * Guilt * Happiness * Hatred * Hiraeth * Homesickness * Hope * Horror * Hostility * Humiliation * Hygge * Hysteria * Indulgence * Infatuation * Insecurity * Inspiration * Interest * Irritation * Isolation * Jealousy * Joy * Kindness * Loneliness * Longing * Love * Limerence * Lust * Mono no aware * Neglect * Nostalgia * Outrage * Panic * Passion * Pity * Self-pity * Pleasure * Pride * Grandiosity * Hubris * Insult * Vanity * Rage * Regret * Social connection * Rejection * Remorse * Resentment * Sadness * Melancholy * Saudade * Schadenfreude * Sehnsucht * Self-confidence * Sentimentality * Shame * Shock * Shyness * Sorrow * Spite * Stress * Suffering * Surprise * Sympathy * Tenseness * Trust * Wonder * Worry World views * Cynicism * Defeatism * Nihilism * Optimism * Pessimism * Reclusion * Weltschmerz Related * Affect * consciousness * in education * measures * in psychology * Affective * computing * forecasting * neuroscience * science * spectrum * Affectivity * positive * negative * Appeal to emotion * Emotion * and art * and memory * and music * and sex * classification * evolution * expressed * functional accounts * group * homeostatic * perception * recognition * in conversation * in animals * regulation * interpersonal * work * Emotional * aperture * bias * blackmail * competence * conflict * contagion * detachment * dysregulation * eating * exhaustion * expression * intelligence * and bullying * intimacy * isolation * lability * labor * lateralization * literacy * prosody * reasoning * responsivity * security * selection * symbiosis * well-being * Emotionality * bounded * Emotions * and culture * in decision-making * in the workplace * in virtual communication * history * moral * self-conscious * social * social sharing * sociology * Feeling * Gender and emotional expression * Group affective tone * Interactions between the emotional and executive brain systems * Meta-emotion * Pathognomy * Pathos * Social emotional development * Stoic passions * Theory * affect * appraisal * discrete emotion * somatic marker * constructed emotion Authority control * GND: 4400193-9 * NDL: 00920346 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Panic disorder	c0030319	981	wikipedia	https://en.wikipedia.org/wiki/Panic_disorder	2021-01-18T18:57:10	{"mesh": ["D016584"], "umls": ["C0030319"], "icd-9": ["300.01", "300.21"], "icd-10": ["F41.0"], "wikidata": ["Q741713"]}
A number sign (#) is used with this entry because of evidence that facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome (FHEIG) is caused by heterozygous mutation in the KCNK4 gene (605720) on chromosome 11q13. Clinical Features Bauer et al. (2018) reported 3 unrelated children, aged 11 months, 5 years, and 8 years, with a similar neurodevelopmental syndrome identified through genetic research programs and GeneMatcher. Two patients were of Italian descent and 1 was European. Overall developmental progress was highly variable: patient 1 met essentially no developmental milestones at age 11 months, patient 2 met major milestones by age 5, but had a delay in motor skills and language, and patient 3 had mildly delayed milestones with walking at 3 years and single words at age 8. All had significant generalized hypertrichosis and a similar facial gestalt, including hypotonic facies, bitemporal narrowing, micrognathia, deep-set eyes, bushy eyebrows and long eyelashes, low-set ears, short deep philtrum, gingival overgrowth, prominent upper and lower vermilion, and everted upper lip. Other more variable features included nystagmus with optic hypoplasia, hypotonia, and hyperreflexia. Patients 2 and 3 had early-onset focal and generalized seizures that could be controlled with medication. Patient 1 did not have overt seizures, but he had an abnormal EEG with a disorganized pattern, some high voltage activity, and diffuse slow wave activity. Brain imaging in this patient showed a thin corpus callosum and enlarged ventricles. Patient 2 had a developmental index of 85 on the Griffiths scale. Patient 3 also had brachydactyly and congenital hip dysplasia. Molecular Genetics In 3 unrelated children with FHEIG, Bauer et al. (2018) identified de novo heterozygous missense mutations in the KCNK4 gene (A172E, 605720.0001 and A244P, 605720.0002). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were not present in the gnomAD database. In vitro functional expression studies using patch-clamp recording in CHO cells showed that the mutations caused a significant increase in basal K+ membrane conductance compared to wildtype. The mutant channels were insensitive to voltage, mechanical, and lipid stimulation, likely reflecting their maximum activation basally. Coexpression experiments indicated a dominant gain-of-function behavior of the mutations. Molecular modeling predicted that the lateral fenestrations of the channel were significantly less open in the mutant channels compared to wildtype, suggesting that the gating of the channel is affected, favoring channel opening and thus resulting in increased basal activation in the mutants. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Bitemporal narrowing \- Micrognathia \- Hypotonic facies \- Smooth philtrum \- Short philtrum \- Deep philtrum Ears \- Low-set ears Eyes \- Poor visual contact \- Optic hypoplasia \- Nystagmus \- Deep-set eyes \- Thick eyebrows \- Straight eyebrows \- Synophrys \- Long eyelashes Mouth \- Large mouth \- Everted upper lip \- Prominent upper and lower vermilion \- Gingival hyperplasia SKELETAL Pelvis \- Hip dysplasia (1 patient) Hands \- Fifth finger clinodactyly \- Brachydactyly SKIN, NAILS, & HAIR Hair \- Hypertrichosis, generalized MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Impaired intellectual development, variable \- Delayed motor development, variable \- Poor speech \- Seizures \- Hyperreflexia \- Thin corpus callosum (in some patients) \- Enlarged ventricles (in some patients) MISCELLANEOUS \- Three unrelated patients have been reported (last curated April 2019) \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the potassium channel, subfamily K, member 4 gene (KCNK4, 605720.0001 ) ▲ 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	FACIAL DYSMORPHISM, HYPERTRICHOSIS, EPILEPSY, INTELLECTUAL/DEVELOPMENTAL DELAY, AND GINGIVAL OVERGROWTH SYNDROME	None	982	omim	https://www.omim.org/entry/618381	2019-09-22T15:42:12	{"omim": ["618381"]}
Combined immunodeficiency due to OX40 deficiency is a rare combined T and B cell immunodeficiency characterized by susceptibility to develop an aggressive, childhood-onset, disseminated, cutaneous and systemic Kaposi sarcoma. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Combined immunodeficiency due to OX40 deficiency	c3810053	983	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=431149	2021-01-23T17:18:38	{"omim": ["615593"], "icd-10": ["D81.8"], "synonyms": ["Combined immunodeficiency with childhood-onset Kaposi sarcoma", "Combined immunodeficiency with impaired immunity to HHV-8", "Combined immunodeficiency with impaired immunity to human herpes virus 8"]}
Peripartum cardiomyopathy (PPCM) is an idiopathic, potentially fatal form of dilated cardiomyopathy that develops during the final month of pregnancy or within five months after delivery. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Peripartum cardiomyopathy	c0877208	984	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=563	2021-01-23T17:15:35	{"gard": ["220"], "umls": ["C0269972", "C0877208"], "icd-10": ["O90.3"], "synonyms": ["Postpartum cardiomyopathy"]}
Congenital cardiac diverticulum (CCD) is a very rare congenital malformation characterized by a muscular appendix emerging from the left ventricular apex, rarely from the right ventricle or from both chambers, with clinical manifestations ranging from asymptomatic to life-threatening hemodynamic collapse. ## Epidemiology CCD is a very rare malformation. Exact prevalence and incidence data are not available. About 0.4% or 1 of 250 cardiac necropsy cases showed this malformation. In the literature, the combined number of aneurysm/diverticle reports is 418 cases. Incidence of 1/2700 on echocardiographic studies (0.04% of the population) has been reported. A very slightly higher incidence has been reported in males compared to females (1.05:1.0). ## Clinical description Congenital cardiac diverticulum is often associated with other cardiac abnormalities (midline defects) but is mostly an isolated anomaly. It is mostly found in infants and children and occasionally as an incidental finding in adults. The left ventricular apex is the most common location, but right ventricular diverticula are also reported. Two types of CCD are described: fibrous CCD which may be asymptomatic or associated with thromboembolic events, and muscular CCD with normal myocardial contraction which is frequently associated with other congenital anomalies and may cause rupture, aortic insufficiency, endocarditis, heart failure and tachyarrhythmia. Other clinical manifestations may include dyspnea, palpitation, and chest pain. Fetal death has also been described because of intrauterine diverticulum rupture. Congenital aneurysms are composed of collagenous or connective tissue and are associated with akinesis or dyskinesis. Acquired forms of cardiac diverticulum/aneurysm are common, particularly after myocardial infarction. ## Etiology The etiology of congenital cardiac diverticulum is not known. Hemodynamic factors may play a role. In the 4th embryonic life there are outpouchings in the early wall of the left ventricle which later enlarge ventriclular cavity volume. Failure during this process could be responsible for the development of aneurysms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Cardiac diverticulum	c4020965	985	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1686	2021-01-23T18:49:47	{"gard": ["1094"], "icd-10": ["Q24.8"]}
Dyggve-Melchior-Clausen (DMC) syndrome is a rare, progressive genetic condition characterized by abnormal skeletal development, microcephaly, and intellectual disability. Only about 100 cases have been reported to date. Skeletal abnormalities may include a barrel-shaped chest with a short trunk, partial dislocation of the hips, knock knees, bowlegs, and decreased joint mobility. A small number of affected individuals experience instability in the upper neck vertebrae that can lead to spinal cord compression, weakness and paralysis. Normally, there is growth deficiency resulting in short stature. DMC is caused by mutations in the DYM gene and is inherited in an autosomal recessive manner. Some researchers have described an X-linked pattern of inheritance, which has not been confirmed to date. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Dyggve-Melchior-Clausen syndrome	c0265286	986	gard	https://rarediseases.info.nih.gov/diseases/6295/dyggve-melchior-clausen-syndrome	2021-01-18T18:00:48	{"mesh": ["C535726"], "omim": ["223800", "304950"], "orphanet": ["239"], "synonyms": ["Dyggve-Melchior-Clausen disease", "DMC syndrome"]}
For a clinical description of atopic dermatitis and an overview of linkage studies, see 603165. Mapping Beyer et al. (2000) tested for the association and linkage between atopic dermatitis and 5 chromosomal regions: 5q31-q33, 6p21.3, 12q15-q24.1, 13q12-q31, and 14q11.2/14q32.1-q32.3. Marker analysis was performed in 2 Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 nonatopic children, all from a German birth cohort study; parental DNA was tested in 77 of 192 children with atopic dermatitis; (ii) 40 Swedish families with at least 1 family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. In both populations, they found a significant association between atopic dermatitis and marker D13S218 on chromosome 13q12-q14 (ATOD5). In the German population, parental transmission of marker alleles showed significant evidence for linkage to the same marker. Beyer et al. (2000) also found evidence for linkage to markers on 5q31-q33 (ATOD6; 605845) in the German population. Bradley et al. (2002) conducted a genomewide linkage analysis with 367 microsatellite markers, using a nonparametric affected relative-pair method in 109 atopic dermatitis pedigrees. For the semiquantitative phenotype severity score of atopic dermatitis, suggestive linkage was found to chromosome regions 13q14 (at D13S325, Z = 3.21, P less than 0.001), 3q14 (at D3S2459, Z = 2.55, P less than 0.001), 15q14-q15 (at D15S118, Z = 3.07, P less than .001), and 17q21 (at D17S1290, Z = 3.08, P less than 0.001). Polymorphic markers at 13q14 have also been linked to asthma, suggesting that more than one phenotype of atopic hypersensitivity may be influenced by genes in this region. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	DERMATITIS, ATOPIC, 5	c1853900	987	omim	https://www.omim.org/entry/605844	2019-09-22T16:10:52	{"mesh": ["C565280"], "omim": ["605844"]}
This article is about congenital disorders in humans. For animals, see Teratology. Condition present at birth regardless of cause; human disease or disorder developed prior to birth Birth defect Other namesCongenital disorder, congenital disease, congenital deformity, congenital anomaly[1] A boy with Down syndrome, one of the most common birth defects[2] SpecialtyMedical genetics, pediatrics SymptomsPhysical disability, intellectual disability, developmental disability[3] Usual onsetPresent at birth[3] TypesStructural, functional[4] CausesGenetics, exposure to certain medications or chemicals, certain infections during pregnancy[5] Risk factorsInsufficient folic acid, drinking alcohol or smoking, poorly controlled diabetes, mother over the age of 35[6][7] TreatmentTherapy, medication, surgery, assistive technology[8] Frequency3% of newborns (US)[2] Deaths628,000 (2015)[9] A birth defect, also known as a congenital disorder, is a condition present at birth regardless of its cause.[3] Birth defects may result in disabilities that may be physical, intellectual, or developmental.[3] The disabilities can range from mild to severe.[7] Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part and functional disorders in which problems exist with how a body part works.[4] Functional disorders include metabolic and degenerative disorders.[4] Some birth defects include both structural and functional disorders.[4] Birth defects may result from genetic or chromosomal disorders, exposure to certain medications or chemicals, or certain infections during pregnancy.[5] Risk factors include folate deficiency, drinking alcohol or smoking during pregnancy, poorly controlled diabetes, and a mother over the age of 35 years old.[6][7] Many are believed to involve multiple factors.[7] Birth defects may be visible at birth or diagnosed by screening tests.[10] A number of defects can be detected before birth by different prenatal tests.[10] Treatment varies depending on the defect in question.[8] This may include therapy, medication, surgery, or assistive technology.[8] Birth defects affected about 96 million people as of 2015.[11] In the United States, they occur in about 3% of newborns.[2] They resulted in about 628,000 deaths in 2015, down from 751,000 in 1990.[12][9] The types with the greatest numbers of deaths are congenital heart disease (303,000), followed by neural tube defects (65,000).[9] ## Contents * 1 Classification * 1.1 Primarily structural * 1.1.1 Terminology * 1.1.2 Examples of primarily structural congenital disorders * 1.2 Primarily metabolic * 1.3 Other * 2 Causes * 2.1 Alcohol exposure * 2.2 Toxic substances * 2.2.1 Medications and supplements * 2.2.2 Toxic substances * 2.3 Smoking * 2.4 Infections * 2.5 Lack of nutrients * 2.6 Physical restraint * 2.7 Genetics * 2.8 Socioeconomics * 2.9 Radiation * 2.10 Parent's age * 2.11 Unknown * 3 Prevention * 4 Screening * 5 Epidemiology * 5.1 United States * 6 See also * 7 References * 8 External links ## Classification[edit] Much of the language used for describing congenital conditions antedates genome mapping, and structural conditions are often considered separately from other congenital conditions. Many metabolic conditions are now known to have subtle structural expression, and structural conditions often have genetic links. Still, congenital conditions are often classified in a structural basis, organized when possible by primary organ system affected.[citation needed] ### Primarily structural[edit] Several terms are used to describe congenital abnormalities. (Some of these are also used to describe noncongenital conditions, and more than one term may apply in an individual condition.) #### Terminology[edit] * A congenital physical anomaly is an abnormality of the structure of a body part. It may or may not be perceived as a problem condition. Many, if not most, people have one or more minor physical anomalies if examined carefully. Examples of minor anomalies can include curvature of the fifth finger (clinodactyly), a third nipple, tiny indentations of the skin near the ears (preauricular pits), shortness of the fourth metacarpal or metatarsal bones, or dimples over the lower spine (sacral dimples). Some minor anomalies may be clues to more significant internal abnormalities. * Birth defect is a widely used term for a congenital malformation, i.e. a congenital, physical anomaly that is recognizable at birth, and which is significant enough to be considered a problem. According to the Centers for Disease Control and Prevention (CDC), most birth defects are believed to be caused by a complex mix of factors including genetics, environment, and behaviors,[13] though many birth defects have no known cause. An example of a birth defect is cleft palate, which occurs during the fourth through seventh weeks of gestation.[14] Body tissue and special cells from each side of the head grow toward the center of the face. They join together to make the face.[14] A cleft means a split or separation; the "roof" of the mouth is called the palate.[15] * A congenital malformation is a physical anomaly that is deleterious, i.e. a structural defect perceived as a problem. A typical combination of malformations affecting more than one body part is referred to as a malformation syndrome. * Some conditions are due to abnormal tissue development: * A malformation is associated with a disorder of tissue development.[16] Malformations often occur in the first trimester. * A dysplasia is a disorder at the organ level that is due to problems with tissue development.[16] * Conditions also can arise after tissue is formed: * A deformation is a condition arising from mechanical stress to normal tissue.[16] Deformations often occur in the second or third trimester, and can be due to oligohydramnios. * A disruption involves breakdown of normal tissues.[16] * When multiple effects occur in a specified order, they are known as a sequence. When the order is not known, it is a syndrome. #### Examples of primarily structural congenital disorders[edit] A limb anomaly is called a dysmelia. These include all forms of limbs anomalies, such as amelia, ectrodactyly, phocomelia, polymelia, polydactyly, syndactyly, polysyndactyly, oligodactyly, brachydactyly, achondroplasia, congenital aplasia or hypoplasia, amniotic band syndrome, and cleidocranial dysostosis. Congenital heart defects include patent ductus arteriosus, atrial septal defect, ventricular septal defect, and tetralogy of Fallot. Congenital anomalies of the nervous system include neural tube defects such as spina bifida, encephalocele, and anencephaly. Other congenital anomalies of the nervous system include the Arnold–Chiari malformation, the Dandy–Walker malformation, hydrocephalus, microencephaly, megalencephaly, lissencephaly, polymicrogyria, holoprosencephaly, and agenesis of the corpus callosum. Congenital anomalies of the gastrointestinal system include numerous forms of stenosis and atresia, and perforation, such as gastroschisis. Congenital anomalies of the kidney and urinary tract include renal parenchyma, kidneys, and urinary collecting system.[17] Defects can be bilateral or unilateral, and different defects often coexist in an individual child. ### Primarily metabolic[edit] Main article: Inborn error of metabolism A congenital metabolic disease is also referred to as an inborn error of metabolism. Most of these are single-gene defects, usually heritable. Many affect the structure of body parts, but some simply affect the function. ### Other[edit] Other well-defined genetic conditions may affect the production of hormones, receptors, structural proteins, and ion channels. ## Causes[edit] ### Alcohol exposure[edit] Main articles: Fetal alcohol spectrum disorder and Fetal alcohol syndrome The mother's consumption of alcohol during pregnancy can cause a continuum of various permanent birth defects: cranofacial abnormalities,[18] brain damage,[19] intellectual disability,[20] heart disease, kidney abnormality, skeletal anomalies, ocular abnormalities.[21] The prevalence of children affected is estimated at least 1% in U.S.[22] as well in Canada. Very few studies have investigated the links between paternal alcohol use and offspring health.[23] However, recent animal research has shown a correlation between paternal alcohol exposure and decreased offspring birth weight. Behavioral and cognitive disorders, including difficulties with learning and memory, hyperactivity, and lowered stress tolerance have been linked to paternal alcohol ingestion. The compromised stress management skills of animals whose male parent was exposed to alcohol are similar to the exaggerated responses to stress that children with fetal alcohol syndrome display because of maternal alcohol use. These birth defects and behavioral disorders were found in cases of both long- and short-term paternal alcohol ingestion.[24][25] In the same animal study, paternal alcohol exposure was correlated with a significant difference in organ size and the increased risk of the offspring displaying ventricular septal defects at birth.[25] ### Toxic substances[edit] Further information: Developmental toxicity, Drugs in pregnancy, and Environmental toxins and fetal development Substances whose toxicity can cause congenital disorders are called teratogens, and include certain pharmaceutical and recreational drugs in pregnancy, as well as many environmental toxins in pregnancy.[26] A review published in 2010 identified six main teratogenic mechanisms associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption, and specific receptor- or enzyme-mediated teratogenesis.[27] An estimated 10% of all birth defects are caused by prenatal exposure to a teratogenic agent.[28] These exposures include medication or drug exposures, maternal infections and diseases, and environmental and occupational exposures. Paternal smoking use has also been linked to an increased risk of birth defects and childhood cancer for the offspring, where the paternal germline undergoes oxidative damage due to cigarette use.[29][30] Teratogen-caused birth defects are potentially preventable. Nearly 50% of pregnant women have been exposed to at least one medication during gestation.[31] During pregnancy, a woman can also be exposed to teratogens from the contaminated clothing or toxins within the seminal fluid of a partner.[32][24][33] An additional study found that of 200 individuals referred for genetic counseling for a teratogenic exposure, 52% were exposed to more than one potential teratogen.[34] The United States Environmental Protection Agency studied 1,065 chemical and drug substances in their ToxCast program (part of the CompTox Chemicals Dashboard) using in silica modeling and a human pluripotent stem cell-based assay to predict in vivo developmental intoxicants based on changes in cellular metabolism following chemical exposure. Findings of the study published in 2020 were that 19% of the 1065 chemicals yielded a prediction of developmental toxicity.[35] #### Medications and supplements[edit] Probably, the most well-known teratogenic drug is thalidomide. It was developed near the end of the 1950s by Chemie Grünenthal as a sleep-inducing aid and antiemetic. Because of its ability to prevent nausea, it was prescribed for pregnant women in almost 50 countries worldwide between 1956 and 1962.[36] Until William McBride published the study leading to its withdrawal from the market at 1961, about 8,000 to 10,000 severely malformed children were born. The most typical disorder induced by thalidomide were reductional deformities of the long bones of the extremities. Phocomelia, otherwise a rare deformity, therefore helped to recognise the teratogenic effect of the new drug. Among other malformations caused by thalidomide were those of ears, eyes, brain, kidney, heart, and digestive and respiratory tracts; 40% of the prenatally affected children died soon after birth.[36] As thalidomide is used today as a treatment for multiple myeloma and leprosy, several births of affected children were described in spite of the strictly required use of contraception among female patients treated by it. Vitamin A is the sole vitamin that is embryotoxic even in a therapeutic dose, for example in multivitamins, because its metabolite, retinoic acid, plays an important role as a signal molecule in the development of several tissues and organs. Its natural precursor, β-carotene, is considered safe, whereas the consumption of animal liver can lead to malformation, as the liver stores lipophilic vitamins, including retinol.[36] Isotretinoin (13-cis-retinoic-acid; brand name Roaccutane), vitamin A analog, which is often used to treat severe acne, is such a strong teratogen that just a single dose taken by a pregnant woman (even transdermally) may result in serious birth defects. Because of this effect, most countries have systems in place to ensure that it is not given to pregnant women, and that the patient is aware of how important it is to prevent pregnancy during and at least one month after treatment. Medical guidelines also suggest that pregnant women should limit vitamin A intake to about 700 μg/day, as it has teratogenic potential when consumed in excess.[37][38] Vitamin A and similar substances can induce spontaneous abortions, premature births, defects of eyes (microphthalmia), ears, thymus, face deformities, and neurological (hydrocephalus, microcephalia) and cardiovascular defects, as well as mental retardation.[36] Tetracycline, an antibiotic, should never be prescribed to women of reproductive age or to children, because of its negative impact on bone mineralization and teeth mineralization. The "tetracycline teeth" have brown or grey colour as a result of a defective development of both the dentine and the enamel of teeth.[36] Several anticonvulsants are known to be highly teratogenic. Phenytoin, also known as diphenylhydantoin, along with carbamazepine, is responsible for the fetal hydantoin syndrome, which may typically include broad nose base, cleft lip and/or palate, microcephalia, nails and fingers hypoplasia, intrauterine growth restriction, and mental retardation. Trimethadione taken during pregnancy is responsible for the fetal trimethadione syndrome, characterized by craniofacial, cardiovascular, renal, and spine malformations, along with a delay in mental and physical development. Valproate has antifolate effects, leading to neural tube closure-related defects such as spina bifida. Lower IQ and autism have recently also been reported as a result of intrauterine valproate exposure.[36] Hormonal contraception is considered as harmless for the embryo. Peterka and Novotná[36] do, however, state that synthetic progestins used to prevent miscarriage in the past frequently caused masculinization of the outer reproductive organs of female newborns due to their androgenic activity. Diethylstilbestrol is a synthetic estrogen used from the 1940s to 1971, when the prenatal exposition has been linked to the clear-cell adenocarcinoma of the vagina. Following studies showed elevated risks for other tumors and congenital malformations of the sex organs for both sexes. All cytostatics are strong teratogens; abortion is usually recommended when pregnancy is discovered during or before chemotherapy. Aminopterin, a cytostatic drug with antifolate effect, was used during the 1950s and 1960s to induce therapeutic abortions. In some cases, the abortion did not happen, but the newborns suffered a fetal aminopterin syndrome consisting of growth retardation, craniosynostosis, hydrocephalus, facial dismorphities, mental retardation, and/or leg deformities[36][39] #### Toxic substances[edit] Drinking water is often a medium through which harmful toxins travel. Heavy metals, elements, nitrates, nitrites, and fluoride can be carried through water and cause congenital disorders. Nitrate, which is found mostly in drinking water from ground sources, is a powerful teratogen. A case-control study in rural Australia that was conducted following frequent reports of prenatal mortality and congenital malformations found that those who drank the nitrate-containing groundwater, as opposed to rain water, ran the risk of giving birth to children with central nervous system disorders, muscoskeletal defects, and cardiac defects.[40] Chlorinated and aromatic solvents such as benzene and trichloroethylene sometimes enter the water supply due to oversights in waste disposal. A case-control study on the area found that by 1986, leukemia was occurring in the children of Woburn, Massachusetts, at a rate that was four times the expected rate of incidence. Further investigation revealed a connection between the high occurrence of leukemia and an error in water distribution that delivered water to the town with significant contamination with manufacturing waste containing trichloroethylene.[41] As an endocrine disruptor, DDT was shown to induce miscarriages, interfere with the development of the female reproductive system, cause the congenital hypothyroidism, and suspectibly childhood obesity.[36] Fluoride, when transmitted through water at high levels, can also act as a teratogen. Two reports on fluoride exposure from China, which were controlled to account for the education level of parents, found that children born to parents who were exposed to 4.12 ppm fluoride grew to have IQs that were, on average, seven points lower than their counterparts whose parents consumed water that contained 0.91 ppm fluoride. In studies conducted on rats, higher fluoride in drinking water led to increased acetylcholinesterase levels, which can alter prenatal brain development. The most significant effects were noted at a level of 5 ppm.[42] The fetus is even more susceptible to damage from carbon monoxide intake, which can be harmful when inhaled during pregnancy, usually through first- or second-hand tobacco smoke. The concentration of carbon monoxide in the infant born to a nonsmoking mother is around 2%, and this concentration drastically increases to a range of 6%–9% if the mother smokes tobacco. Other possible sources of prenatal carbon monoxide intoxication are exhaust gas from combustion motors, use of dichloromethane (paint thinner, varnish removers) in enclosed areas, defective gas water heaters, indoor barbeques, open flames in poorly ventilated areas, and atmospheric exposure in highly polluted areas. Exposure to carbon monoxide at toxic levels during the first two trimesters of pregnancy can lead to intrauterine growth restriction, leading to a baby who has stunted growth and is born smaller than 90% of other babies at the same gestational age. The effect of chronic exposure to carbon monoxide can depend on the stage of pregnancy in which the mother is exposed. Exposure during the embryonic stage can have neurological consequences, such as telencephalic dysgenesis, behavioral difficulties during infancy, and reduction of cerebellum volume. Also, possible skeletal defects could result from exposure to carbon monoxide during the embryonic stage, such as hand and foot malformations, hip dysplasia, hip subluxation, agenesis of a limb, and inferior maxillary atresia with glossoptosis. Also, carbon monoxide exposure between days 35 and 40 of embryonic development can lead to an increased risk of the child developing a cleft palate. Exposure to carbon monoxide or polluted ozone exposure can also lead to cardiac defects of the ventrical septal, pulmonary artery, and heart valves.[43] The effects of carbon monoxide exposure are decreased later in fetal development during the fetal stage, but they may still lead to anoxic encephalopathy.[44] Industrial pollution can also lead to congenital defects. Over a period of 37 years, the Chisso Corporation, a petrochemical and plastics company, contaminated the waters of Minamata Bay with an estimated 27 tons of methylmercury, contaminating the local water supply. This led to many people in the area to develop what became known as the "Minamata disease". Because methylmercury is a teratogen, the mercury poisoning of those residing by the bay resulted in neurological defects in the offspring. Infants exposed to mercury poisoning in utero showed predispositions to cerebral palsy, ataxia, inhibited psychomotor development, and mental retardation.[45] Landfill sites have been shown to have adverse effects on fetal development. Extensive research has shown that landfills have several negative effects on babies born to mothers living near landfill sites: low birth weight, birth defects, spontaneous abortion, and fetal and infant mortality. Studies done around the Love Canal site near Niagara Falls and the Lipari Landfill in New Jersey have shown a higher proportion of low birth-weight babies than communities farther away from landfills. A study done in California showed a positive correlation between time and quantity of dumping and low birth weights and neonatal deaths. A study in the United Kingdom showed a correlation between pregnant women living near landfill sites and an increased risk of congenital disorders, such as neural tube defects, hypospadias, epispadia, and abdominal wall defects, such as gastroschisis and exomphalos. A study conducted on a Welsh community also showed an increase incidence of gastroschisis. Another study on 21 European hazardous-waste sites showed that those living within 3 km had an increased risk of giving birth to infants with birth defects and that as distance from the land increased, the risk decreased. These birth defects included neural tube defects, malformations of the cardiac septa, anomalies of arteries and veins, and chromosomal anomalies.[46] Looking at communities that live near landfill sites brings up environmental justice. A vast majority of sites are located near poor, mostly black, communities. For example, between the early 1920s and 1978, about 25% of Houston's population was black. However, over 80% of landfills and incinerators during this time were located in these black communities.[47] Another issue regarding environmental justice is lead poisoning. A fetus exposed to lead during the pregnancy can result in learning difficulties and slowed growth. Some paints (before 1978) and pipes contain lead. Therefore, pregnant women who live in homes with lead paint inhale the dust containing lead, leading to lead exposure in the fetus. When lead pipes are used for drinking water and cooking water, this water is ingested, along with the lead, exposing the fetus to this toxin. This issue is more prevalent in poorer communities because more well-off families are able to afford to have their homes repainted and pipes renovated.[48] ### Smoking[edit] Paternal smoking prior to conception has been linked with the increased risk of congenital abnormalities in offspring.[23] Smoking causes DNA mutations in the germline of the father, which can be inherited by the offspring. Cigarette smoke acts as a chemical mutagen on germ cell DNA. The germ cells suffer oxidative damage, and the effects can be seen in altered mRNA production, infertility issues, and side effects in the embryonic and fetal stages of development. This oxidative damage may result in epigenetic or genetic modifications of the father's germline. Fetal lymphocytes have been damaged as a result of a father's smoking habits prior to conception.[32][30] Correlations between paternal smoking and the increased risk of offspring developing childhood cancers (including acute leukemia, brain tumors, and lymphoma) before age five have been established. Little is currently known about how paternal smoking damages the fetus, and what window of time in which the father smokes is most harmful to offspring.[30] ### Infections[edit] Main article: Vertically transmitted infection A vertically transmitted infection is an infection caused by bacteria, viruses, or in rare cases, parasites transmitted directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. Congenital disorders were initially believed to be the result of only hereditary factors. However, in the early 1940s, Australian pediatric ophthalmologist Norman Gregg began recognizing a pattern in which the infants arriving at his surgery were developing congenital cataracts at a higher rate than those who developed it from hereditary factors. On October 15, 1941, Gregg delivered a paper that explained his findings-68 out of the 78 children who were afflicted with congenital cataracts had been exposed in utero to rubella due to an outbreak in Australian army camps. These findings confirmed, to Gregg, that, in fact, environmental causes for congenital disorders could exist. Rubella is known to cause abnormalities of the eye, internal ear, heart, and sometimes the teeth. More specifically, fetal exposure to rubella during weeks five to ten of development (the sixth week particularly) can cause cataracts and microphthalmia in the eyes. If the mother is infected with rubella during the ninth week, a crucial week for internal ear development, destruction of the organ of Corti can occur, causing deafness. In the heart, the ductus arteriosus can remain after birth, leading to hypertension. Rubella can also lead to atrial and ventricular septal defects in the heart. If exposed to rubella in the second trimester, the fetus can develop central nervous system malformations. However, because infections of rubella may remain undetected, misdiagnosed, or unrecognized in the mother, and/or some abnormalities are not evident until later in the child's life, precise incidence of birth defects due to rubella are not entirely known. The timing of the mother's infection during fetal development determines the risk and type of birth defect. As the embryo develops, the risk of abnormalities decreases. If exposed to the rubella virus during the first four weeks, the risk of malformations is 47%. Exposure during weeks five through eight creates a 22% chance, while weeks 9-12, a 7% chance exists, followed by 6% if the exposure is during the 13th-16th weeks. Exposure during the first eight weeks of development can also lead to premature birth and fetal death. These numbers are calculated from immediate inspection of the infant after birth. Therefore, mental defects are not accounted for in the percentages because they are not evident until later in the child's life. If they were to be included, these numbers would be much higher.[49] Other infectious agents include cytomegalovirus, the herpes simplex virus, hyperthermia, toxoplasmosis, and syphilis. Maternal exposure to cytomegalovirus can cause microcephaly, cerebral calcifications, blindness, chorioretinitis (which can cause blindness), hepatosplenomegaly, and meningoencephalitis in fetuses.[49] Microcephaly is a disorder in which the fetus has an atypically small head,[50] cerebral calcifications means certain areas of the brain have atypical calcium deposits,[51] and meningoencephalitis is the enlargement of the brain. All three disorders cause abnormal brain function or mental retardation. Hepatosplenomegaly is the enlargement of the liver and spleen which causes digestive problems.[52] It can also cause some kernicterus and petechiae. Kernicterus causes yellow pigmentation of the skin, brain damage, and deafness.[53] Petechaie is when the capillaries bleed resulting in red/purple spots on the skin.[54] However, cytomegalovirus is often fatal in the embryo. The herpes simplex virus can cause microcephaly, microphthalmus (abnormally small eyeballs),[55] retinal dysplasia, hepatosplenomegaly, and mental retardation.[49] Both microphthalmus and retinal dysplasia can cause blindness. However, the most common symptom in infants is an inflammatory response that develops during the first three weeks of life.[49] Hyperthermia causes anencephaly, which is when part of the brain and skull are absent in the infant.[49][56] Mother exposure to toxoplasmosis can cause cerebral calcification, hydrocephalus (causes mental disabilities),[57] and mental retardation in infants. Other birth abnormalities have been reported as well, such as chorioretinitis, microphthalmus, and ocular defects. Syphilis causes congenital deafness, mental retardation, and diffuse fibrosis in organs, such as the liver and lungs, if the embryo is exposed.[49] ### Lack of nutrients[edit] Further information: Nutrition in pregnancy and Folate deficiency For example, a lack of folic acid, a B vitamin, in the diet of a mother can cause cellular neural tube deformities that result in spina bifida. Congenital disorders such as a neural tube deformity can be prevented by 72% if the mother consumes 4 mg of folic acid before the conception and after 12 weeks of pregnancy.[58] Folic acid, or vitamin B9, aids the development of the foetal nervous system.[58] Studies with mice have found that food deprivation of the male mouse prior to conception leads to the offspring displaying significantly lower blood glucose levels.[59] ### Physical restraint[edit] External physical shocks or constraint due to growth in a restricted space may result in unintended deformation or separation of cellular structures resulting in an abnormal final shape or damaged structures unable to function as expected. An example is Potter syndrome due to oligohydramnios. This finding is important for future understanding of how genetics may predispose individuals for diseases such as obesity, diabetes, and cancer. For multicellular organisms that develop in a womb, the physical interference or presence of other similarly developing organisms such as twins can result in the two cellular masses being integrated into a larger whole, with the combined cells attempting to continue to develop in a manner that satisfies the intended growth patterns of both cell masses. The two cellular masses can compete with each other, and may either duplicate or merge various structures. This results in conditions such as conjoined twins, and the resulting merged organism may die at birth when it must leave the life-sustaining environment of the womb and must attempt to sustain its biological processes independently. ### Genetics[edit] Main article: Genetic disorder See also: List of genetic disorders Genetic causes of birth defects include inheritance of abnormal genes from the mother or the father, as well as new mutations in one of the germ cells that gave rise to the fetus. Male germ cells mutate at a much faster rate than female germ cells, and as the father ages, the DNA of the germ cells mutates quickly.[60][29] If an egg is fertilized with sperm that has damaged DNA, a possibility exists that the fetus could develop abnormally.[60][61] Genetic disorders are all congenital (present at birth), though they may not be expressed or recognized until later in life. Genetic disorders may be grouped into single-gene defects, multiple-gene disorders, or chromosomal defects. Single-gene defects may arise from abnormalities of both copies of an autosomal gene (a recessive disorder) or of only one of the two copies (a dominant disorder). Some conditions result from deletions or abnormalities of a few genes located contiguously on a chromosome. Chromosomal disorders involve the loss or duplication of larger portions of a chromosome (or an entire chromosome) containing hundreds of genes. Large chromosomal abnormalities always produce effects on many different body parts and organ systems. ### Socioeconomics[edit] A low socioeconomic status in a deprived neighborhood may include exposure to "environmental stressors and risk factors".[62] Socioeconomic inequalities are commonly measured by the Cartairs-Morris score, Index of Multiple Deprivation, Townsend deprivation index, and the Jarman score.[63] The Jarman score, for example, considers "unemployment, overcrowding, single parents, under-fives, elderly living alone, ethnicity, low social class and residential mobility".[63] In Vos’ meta-analysis these indices are used to view the effect of low SES neighborhoods on maternal health. In the meta-analysis, data from individual studies were collected from 1985 up until 2008.[63] Vos concludes that a correlation exists between prenatal adversities and deprived neighborhoods.[63] Other studies have shown that low SES is closely associated with the development of the fetus in utero and growth retardation.[64] Studies also suggest that children born in low SES families are "likely to be born prematurely, at low birth weight, or with asphyxia, a birth defect, a disability, fetal alcohol syndrome, or AIDS".[64] Bradley and Corwyn also suggest that congenital disorders arise from the mother's lack of nutrition, a poor lifestyle, maternal substance abuse and "living in a neighborhood that contains hazards affecting fetal development (toxic waste dumps)".[64] In a meta-analysis that viewed how inequalities influenced maternal health, it was suggested that deprived neighborhoods often promoted behaviors such as smoking, drug and alcohol use.[62] After controlling for socioeconomic factors and ethnicity, several individual studies demonstrated an association with outcomes such as perinatal mortality and preterm birth.[62] ### Radiation[edit] For the survivors of the atomic bombing of Hiroshima and Nagasaki, who are known as the Hibakusha, no statistically demonstrable increase of birth defects/congenital malformations was found among their later conceived children, or found in the later conceived children of cancer survivors who had previously received radiotherapy.[65][66][67][68] The surviving women of Hiroshima and Nagasaki who were able to conceive, though exposed to substantial amounts of radiation, later had children with no higher incidence of abnormalities/birth defects than in the Japanese population as a whole.[69][70] Relatively few studies have researched the effects of paternal radiation exposure on offspring. Following the Chernobyl disaster, it was assumed in the 1990s that the germ line of irradiated fathers suffered minisatellite mutations in the DNA, which was inherited by descendants.[24][71] More recently, however, the World Health Organization states, "children conceived before or after their father's exposure showed no statistically significant differences in mutation frequencies".[72] This statistically insignificant increase was also seen by independent researchers analyzing the children of the liquidators.[73] Animal studies have shown that incomparably massive doses of X-ray irradiation of male mice resulted in birth defects of the offspring.[32] In the 1980s, a relatively high prevalence of pediatric leukemia cases in children living near a nuclear processing plant in West Cumbria, UK, led researchers to investigate whether the cancer was a result of paternal radiation exposure. A significant association between paternal irradiation and offspring cancer was found, but further research areas close to other nuclear processing plants did not produce the same results.[32][24] Later this was determined to be the Seascale cluster in which the leading hypothesis is the influx of foreign workers, who have a different rate of leukemia within their race than the British average, resulted in the observed cluster of 6 children more than expected around Cumbria.[74] ### Parent's age[edit] Main articles: Advanced maternal age and Paternal age effect Certain birth complications can occur more often in advanced maternal age (greater than 35 years). Complications include fetal growth restriction, preeclampsia, placental abruption, pre-mature births, and stillbirth. These complications not only may put the child at risk, but also the mother.[75] The effects of the father's age on offspring are not yet well understood and are studied far less extensively than the effects of the mother's age.[76] Fathers contribute proportionally more DNA mutations to their offspring via their germ cells than the mother, with the paternal age governing how many mutations are passed on. This is because, as humans age, male germ cells acquire mutations at a much faster rate than female germ cells.[29][32][60] Around a 5% increase in the incidence of ventricular septal defects, atrial septal defects, and patent ductus arteriosus in offspring has been found to be correlated with advanced paternal age. Advanced paternal age has also been linked to increased risk of achondroplasia and Apert syndrome. Offspring born to fathers under the age of 20 show increased risk of being affected by patent ductus arteriosus, ventricular septal defects, and the tetralogy of Fallot. It is hypothesized that this may be due to environmental exposures or lifestyle choices.[76] Research has found that there is a correlation between advanced paternal age and risk of birth defects such as limb anomalies, syndromes involving multiple systems, and Down syndrome.[60][29][77] Recent studies have concluded that 5-9% of Down syndrome cases are due to paternal effects, but these findings are controversial.[60][61][29][78] There is concrete evidence that advanced paternal age is associated with the increased likelihood that a mother will have a miscarriage or that fetal death will occur.[60] ### Unknown[edit] Although significant progress has been made in identifying the etiology of some birth defects, approximately 65% have no known or identifiable cause.[28] These are referred to as sporadic, a term that implies an unknown cause, random occurrence regardless of maternal living conditions,[79] and a low recurrence risk for future children. For 20-25% of anomalies there seems to be a "multifactorial" cause, meaning a complex interaction of multiple minor genetic anomalies with environmental risk factors. Another 10–13% of anomalies have a purely environmental cause (e.g. infections, illness, or drug abuse in the mother). Only 12–25% of anomalies have a purely genetic cause. Of these, the majority are chromosomal anomalies.[80] ## Prevention[edit] Folate supplements decrease the risk of neural tube defects. Tentative evidence supports the role of L-arginine in decreasing the risk of intrauterine growth restriction.[81] ## Screening[edit] Main article: Newborn screening Newborn screening tests were introduced in the early 1960s and initially dealt with just two disorders. Since then tandem mass spectrometry, gas chromatography–mass spectrometry, and DNA analysis has made it possible for a much larger range of disorders to be screened. Newborn screening mostly measures metabolite and enzyme activity using a dried blood spot sample.[82] Screening tests are carried out in order to detect serious disorders that may be treatable to some extent.[83] Early diagnosis makes possible the readiness of therapeutic dietary information, enzyme replacement therapy and organ transplants.[84] Different countries support the screening for a number of metabolic disorders (inborn errors of metabolism (IEM)), and genetic disorders including cystic fibrosis and Duchenne muscular dystrophy.[83][85] Tandem mass spectroscopy can also be used for IEM, and investigation of sudden infant death, and shaken baby syndrome.[83] Screening can also be carried out prenatally and can include obstetric ultrasonography to give scans such as the nuchal scan. 3D ultrasound scans can give detailed information of structural anomalies. ## Epidemiology[edit] Congenital anomalies deaths per million persons in 2012 0–26 27–34 35–46 47–72 73–91 92–111 112–134 135–155 156–176 177–396 Disability-adjusted life year for congenital anomalies per 100,000 inhabitants in 2004.[86] no data less than 160 160–240 240–320 320–400 400–480 480–560 560–640 640–720 720–800 800–900 900–950 more than 950 Congenital anomalies resulted in about 632,000 deaths per year in 2013 down from 751,000 in 1990.[12] The types with the greatest death are congenital heart defects (323,000), followed by neural tube defects (69,000).[12] Many studies have found that the frequency of occurrence of certain congenital malformations depends on the sex of the child (table).[87][88][89][90][91] For example, pyloric stenosis occurs more often in males while congenital hip dislocation is four to five times more likely to occur in females. Among children with one kidney, there are approximately twice as many males, whereas among children with three kidneys there are approximately 2.5 times more females. The same pattern is observed among infants with excessive number of ribs, vertebrae, teeth and other organs which in a process of evolution have undergone reduction—among them there are more females. Contrarily, among the infants with their scarcity, there are more males. Anencephaly is shown to occur approximately twice as frequently in females.[92] The number of boys born with 6 fingers is two times higher than the number of girls.[93] Now various techniques are available to detect congenital anomalies in fetus before birth.[94] About 3% of newborns have a "major physical anomaly", meaning a physical anomaly that has cosmetic or functional significance.[95] Physical congenital abnormalities are the leading cause of infant mortality in the United States, accounting for more than 20% of all infant deaths. Seven to ten percent of all children[clarification needed] will require extensive medical care to diagnose or treat a birth defect.[96] The sex ratio of patients with congenital malformations Congenital anomaly Sex ratio, ♂♂:♀♀ Defects with female predominance Congenital hip dislocation 1 : 5.2;[97] 1 : 5;[98] 1 : 8;[91] 1 : 3.7[99] Cleft palate 1 : 3[98] Anencephaly 1 : 1.9;[97] 1 : 2[92] Craniocele 1 : 1.8[97] Aplasia of lung 1 : 1.51[97] Spinal herniation 1 : 1.4[97] Diverticulum of the esophagus 1 : 1.4[97] Stomach 1 : 1.4[97] Neutral defects Hypoplasia of the tibia and femur 1 : 1.2[97] Spina bifida 1 : 1.2[99] Atresia of small intestine 1 : 1[97] Microcephaly 1.2 : 1[99] Esophageal atresia 1.3 : 1;[97] 1.5 : 1[99] Hydrocephalus 1.3 : 1[99] Defects with male predominance Diverticula of the colon 1.5 : 1[97] Atresia of the rectum 1.5 : 1;[97] 2 : 1[99] Unilateral renal agenesis 2 : 1;[97] 2.1 : 1[99] Schistocystis 2 : 1[97] Cleft lip and palate 2 : 1;[98] 1.47 : 1[99] Bilateral renal agenesis 2.6 : 1[97] Congenital anomalies of the genitourinary system 2.7 : 1[91] Pyloric stenosis, congenital 5 : 1;[98] 5.4 : 1[91] Meckel's diverticulum More common in boys[97] Congenital megacolon More common in boys[97] All defects 1.22 : 1;[100] 1.29 : 1[91] * Data[91] obtained on opposite-sex twins. ** — Data[99] were obtained in the period 1983–1994. P. M. Rajewski and A. L. Sherman (1976) have analyzed the frequency of congenital anomalies in relation to the system of the organism. Prevalence of men was recorded for the anomalies of phylogenetically younger organs and systems.[97] In respect of an etiology, sexual distinctions can be divided on appearing before and after differentiation of male's gonads during embryonic development, which begins from eighteenth week. The testosterone level in male embryos thus raises considerably.[101] The subsequent hormonal and physiological distinctions of male and female embryos can explain some sexual differences in frequency of congenital defects. It is difficult to explain the observed differences in the frequency of birth defects between the sexes by the details of the reproductive functions or the influence of environmental and social factors. ### United States[edit] The CDC and National Birth Defect Project studied the incidence of birth defects in the US. Key findings include: * Down syndrome was the most common condition with an estimated prevalence of 14.47 per 10,000 live births, implying about 6,000 diagnoses each year. * About 7,000 babies are born with a cleft palate, cleft lip or both. * Adjusted National Prevalence Estimates and Estimated Number of Cases in the United States, 2004–2006[102] Birth Defects Cases per Births Estimated Annual Number of Cases Estimated National Prevalence per 10,000 Live Births (Adjusted for maternal race/ethnicity) Central nervous system defects Anencephaly 1 in 4,859 859 2.06 Spina bifida without anencephaly 1 in 2,858 1460 3.50 Encephalocele 1 in 12,235 341 0.82 Eye defects Anophthalmia/ microphthalmia 1 in 5,349 780 1.87 Cardiovascular defects Common truncus 1 in 13,876 301 0.72 Transposition of great arteries 1 in 3,333 1252 3.00 Tetralogy of Fallot 1 in 2,518 1657 3.97 Atrioventricular septal defect 1 in 2,122 1966 4.71 Hypoplastic left heart syndrome 1 in 4,344 960 2.30 Orofacial defects Cleft palate without cleft lip 1 in 1,574 2651 6.35 Cleft lip with and without cleft palate 1 in 940 4437 10.63 Gastrointestinal defects Esophageal atresia/tracheoeophageal fistula 1 in 4,608 905 2.17 Rectal and large intestinalatresia/stenosis 1 in 2,138 1952 4.68 Musculoskeletal defects Reduction deformity, upper limbs 1 in 2,869 1454 3.49 Reduction deformity, lower limbs 1 in 5,949 701 1.68 Gastroschisis 1 in 2,229 1871 4.49 Omphalocele 1 in 5,386 775 1.86 Diaphragmatic hernia 1 in 3,836 1088 2.61 Chromosomal anomalies Trisomy 13 1 in 7,906 528 1.26 Trisomy 21 (Down syndrome) 1 in 691 6037 14.47 Trisomy 18 1 in 3,762 1109 2.66 ## See also[edit] * Malformative syndrome * ICD-10 Chapter Q: Congenital malformations, deformations and chromosomal abnormalities * Idiopathic * List of congenital disorders * List of ICD-9 codes 740-759: Congenital anomalies * March of Dimes * Mitochondrial disease * Supernumerary body part ## References[edit] 1. ^ Ruth A. Hannon (2010). Porth pathophysiology : concepts of altered health states (1st Canadian ed.). Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 128. ISBN 978-1-60547-781-7. 2. ^ a b c "Birth Defects". Dec 15, 2015. Retrieved 17 Jan 2016. 3. ^ a b c d "Birth Defects: Condition Information". www.nichd.nih.gov. Retrieved 8 December 2017. 4. ^ a b c d "What are the types of birth defects?". www.nichd.nih.gov. Retrieved 8 December 2017. 5. ^ a b "What causes birth defects?". www.nichd.nih.gov. Retrieved 8 December 2017. 6. ^ a b "How many people are affected by/at risk for birth defects?". www.nichd.nih.gov. Retrieved 8 December 2017. 7. ^ a b c d "Facts Birth Defects". Centers for Disease Control and Prevention. 7 September 2017. Retrieved 8 December 2017. 8. ^ a b c "What are the treatments for birth defects?". www.nichd.nih.gov. Retrieved 8 December 2017. 9. ^ a b c GBD 2015 Mortality and Causes of Death, Collaborators. (8 October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/s0140-6736(16)31012-1. PMC 5388903. PMID 27733281. 10. ^ a b "How do health care providers diagnose birth defects?". www.nichd.nih.gov. Retrieved 8 December 2017. 11. ^ GBD 2015 Disease and Injury Incidence and Prevalence, Collaborators. (8 October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282. 12. ^ a b c GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442. 13. ^ Birth Defects Research Archived 2015-09-24 at the Wayback Machine. Centers for Disease Control and Prevention. 14. ^ a b "Facts about Cleft Lip and Cleft Palate \| Birth Defects \| NCBDDD \| CDC". www.cdc.gov. Retrieved 2016-03-16. 15. ^ communications. "Cleft Lip and Cleft Palate". American Academy of Otolaryngology–Head and Neck Surgery. Retrieved 2016-03-16. 16. ^ a b c d Graham, John Whichello (2007). Smith's Recognizable Patterns of Human Deformation, 3rd Edition. Philadelphia: Saunders. p. 3. ISBN 978-0-7216-1489-2. 17. ^ "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)". UpToDate – Wolters Kluer Health. Retrieved 29 October 2012. 18. ^ Jones K, Smith D (1975). "The fetal alcohol syndrome". Teratology. 12 (1): 1–10. doi:10.1002/tera.1420120102. PMID 1162620. 19. ^ Clarren S, Alvord E, Sumi S, Streissguth A, Smith D (1978). "Brain malformations related to prenatal exposure to ethanol". J Pediatr. 92 (1): 64–7. doi:10.1016/S0022-3476(78)80072-9. PMID 619080. 20. ^ Abel EL, Sokol RJ (November 1986). "Fetal alcohol syndrome is now leading cause of mental retardation". Lancet. 2 (8517): 1222. doi:10.1016/s0140-6736(86)92234-8. PMID 2877359. S2CID 42708464. 21. ^ Strömland K, Pinazo-Durán M (2002). "Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies". Alcohol Alcohol. 37 (1): 2–8. doi:10.1093/alcalc/37.1.2. PMID 11825849. 22. ^ May PA.; Gossage JP. (2001). "Estimating the prevalence of fetal alcohol syndrome. A summary". Alcohol Res Health. 25 (3): 159–67. PMC 6707173. PMID 11810953. 23. ^ a b De Santis, Marco; Cesari, Elena; Cavaliere, Annafranca; Ligato, Maria Serena; Nobili, Elena; Visconti, Daniela; Caruso, Alessandro (September 2008). "Paternal exposure and counselling: Experience of a Teratology Information Service". Reproductive Toxicology. 26 (1): 42–46. doi:10.1016/j.reprotox.2008.06.003. PMID 18598753. 24. ^ a b c d Trasler, Jacquetta M.; Doerksen, Tonia (September 1999). "Teratogen update: paternal exposures—reproductive risks". Teratology. 60 (3): 161–172. doi:10.1002/(SICI)1096-9926(199909)60:3<161::AID-TERA12>3.0.CO;2-A. PMID 10471901. 25. ^ a b Abel, E. L. (2004). "Paternal contribution to fetal alcohol syndrome". Addiction Biology. 9 (2): 127–133. doi:10.1080/13556210410001716980. PMID 15223537. S2CID 22202776. 26. ^ Alliance, Genetic; Health, District of Columbia Department of (2010-02-17). Teratogens/Prenatal Substance Abuse. Genetic Alliance. 27. ^ van Gelder MM, van Rooij IA, Miller RK, Zielhuis GA, de Jong-van den Berg LT, Roeleveld N (January 2010). "Teratogenic mechanisms of medical drugs". Hum Reprod Update. 16 (4): 378–94. doi:10.1093/humupd/dmp052. PMID 20061329. 28. ^ a b Ronan O'Rahilly; Fabiola Müller (2001). Human embryology & teratology. New York: Wiley-Liss. ISBN 978-0-471-38225-6. 29. ^ a b c d e Zhu, J. L.; Madsen, K. M.; Vestergaard, M; Olesen, A. V.; Basso, O; Olsen, J (15 July 2005). "Paternal age and congenital malformations". Human Reproduction. 20 (11): 3173–3177. doi:10.1093/humrep/dei186. PMID 16006461. 30. ^ a b c Ji, B.-T.; Shu, X.-O.; Zheng, W.; Ying, D.-M.; Linet, M. S.; Wacholder, S.; Gao, Y.-T.; Jin, F. (5 February 1997). "Paternal Cigarette Smoking and the Risk of Childhood Cancer Among Offspring of Nonsmoking Mothers". JNCI Journal of the National Cancer Institute. 89 (3): 238–243. doi:10.1093/jnci/89.3.238. PMID 9017004. 31. ^ Bracken MB, Holford TR; Holford (1981). "Exposure to prescribed drugs in pregnancy and association with congenital malformations". Obstetrics and Gynecology. 58 (3): 336–44. PMID 7266953. 32. ^ a b c d e Anderson, Diana; Schmid, ThomasE; Baumgartner, Adolf (2014). "Male-mediated developmental toxicity". Asian Journal of Andrology. 16 (1): 81–8. doi:10.4103/1008-682X.122342. PMC 3901885. PMID 24369136. 33. ^ Chia, S-E; Shi, L. M. (1 March 2002). "Review of recent epidemiological studies on paternal occupations and birth defects". Occupational and Environmental Medicine. 59 (3): 149–155. doi:10.1136/oem.59.3.149. PMC 1763633. PMID 11886946. 34. ^ King CR (1986). "Genetic counseling for teratogen exposure". Obstetrics and Gynecology. 67 (6): 843–6. doi:10.1097/00006250-198606000-00020. PMID 3703408. 35. ^ Zurlinden, TJ; Saili, KS; Rush, N; Kothiya, P; Judson, RS; Houck, KA; Hunter, ES; Baker, NC; Palmer, JA; Thomas, RS; Knudson, TB (2020). "Profiling the ToxCast Library With a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity". Toxicological Sciences. 174 (2): 189–209. doi:10.1093/toxsci/kfaa014. PMID 32073639. 36. ^ a b c d e f g h i Novotná, Miroslav Peterka, Božena (2010). Úvod do teratologie: příčiny a mechanizmy vzniku vrozených vad (1. vyd. ed.). Praha: Karolinum Press. ISBN 978-80-246-1780-0. 37. ^ Hunt JR (1996). "Teratogenicity of high vitamin A intake". N. Engl. J. Med. 334 (18): 1197–1200. doi:10.1056/NEJM199605023341814. PMID 8602195. 38. ^ Hartmann S, Brørs O, Bock J, et al. (2005). "Exposure to retinoic acids in non-pregnant women following high vitamin A intake with a liver meal". International Journal for Vitamin and Nutrition Research. 75 (3): 187–94. doi:10.1024/0300-9831.75.3.187. PMID 16028634. 39. ^ "Search Jablonski's Syndromes Database". United States National Library of Medicine. 40. ^ Croen, Lisa; Todoroff, Karen; Shaw, Gary (2001). "Maternal Exposure to Nitrate from Drinking Water and Diet and Risk for Neural Tube Defects". American Journal of Epidemiology. 153 (4): 325–31. doi:10.1093/aje/153.4.325. PMID 11207149. 41. ^ Costas, K.; Knorr, R.S.; Condon, S.K. (2002). "A case-control study of childhood leukemia in Woburn, Massachusetts: the relationship between leukemia incidence and exposure to public drinking water". Science of the Total Environment. 300 (1–3): 23–35. Bibcode:2002ScTEn.300...23C. doi:10.1016/s0048-9697(02)00169-9. PMID 12685468. 42. ^ "In Harm's Way: Toxic Threats to Child Development". May 2000: 90–2. Retrieved 7 December 2014. Cite journal requires `\|journal=` (help) 43. ^ Ritz, B.; Yu, F.; Fruin, S.; Chapa, G.; Shaw, G.; Harris, J. (2002). "Ambient Air Pollution and Risk of Birth Defects in Southern California" (PDF). American Journal of Epidemiology. 155 (1): 17–25. doi:10.1093/aje/155.1.17. PMID 11772780. Retrieved 7 December 2014. 44. ^ Aubard, Yves; Magne, Isabelle (12 Aug 2005). "Carbon monoxide poisoning in pregnancy". British Journal of Obstetrics and Gynaecology. 107 (7): 833–8. doi:10.1111/j.1471-0528.2000.tb11078.x. PMC 2146365. PMID 10901551. 45. ^ Griesbauer, Laura. "Methylmercury Contamination in Fish and Shellfish". CSA. CSA 2007. Retrieved 7 December 2014. 46. ^ Rushton, Lesley (2003). "Health hazards and waste management". British Medical Bulletin. 68 (1): 183–97. doi:10.1093/bmb/ldg034. PMID 14757717. S2CID 1500545. 47. ^ Bullard, Robert. "Environmental Justice for All". National Humanities Center. Retrieved 9 December 2014. 48. ^ "Lead Poisoning". Mayo Clinic. Retrieved 9 December 2014. 49. ^ a b c d e f Sadler, T.W. (1985). Langman's Medical Embryology (5th ed.). Baltimore: William & Wilkins. pp. 109–12. 50. ^ "Microcephaly". Mayo Clinic. Retrieved 7 December 2014. 51. ^ "Cerebral calcification, nonarteriosclerotic". MedicineNet.com. Retrieved 7 December 2014. 52. ^ "Hepatosplenomegaly-Symptoms, Causes, Treatment". Symptoms and Treatment RSS. Retrieved 7 December 2014. 53. ^ "Kernicterus". MedlinePlus Medical Encyclopedia. Retrieved 7 December 2014. 54. ^ "Petechiae". Mayo Clinic. Retrieved 7 December 2014. 55. ^ "Microphthalmus". Texas School for the Blind and Visually Impaired. Retrieved 7 December 2014. 56. ^ "Facts about Anencephaly". Centers for Disease Control and Prevention. Retrieved 7 December 2014. 57. ^ "Hydrocephalus". Mayo Clinic. Retrieved 7 December 2014. 58. ^ a b Raats, Monique (1998). Changing Preconceptions. London: Health Education Authority. p. 11. ISBN 978-0-7521-1231-2. 59. ^ Anderson, Lucy M.; Riffle, Lisa; Wilson, Ralph; Travlos, Gregory S.; Lubomirski, Mariusz S.; Alvord, W. Gregory (March 2006). "Preconceptional fasting of fathers alters serum glucose in offspring of mice". Nutrition. 22 (3): 327–331. doi:10.1016/j.nut.2005.09.006. PMID 16500559. 60. ^ a b c d e f Sartorius, G. A.; Nieschlag, E. (20 August 2009). "Paternal age and reproduction". Human Reproduction Update. 16 (1): 65–79. doi:10.1093/humupd/dmp027. PMID 19696093. 61. ^ a b Savitz, David A.; Schwingl, Pamela J.; Keels, Martha Ann (October 1991). "Influence of paternal age, smoking, and alcohol consumption on congenital anomalies". Teratology. 44 (4): 429–440. doi:10.1002/tera.1420440409. PMID 1962288. 62. ^ a b c de Graaf, Johanna P.; Steegers, Eric A.P.; Bonsel, Gouke J. (April 2013). "Inequalities in perinatal and maternal health". Current Opinion in Obstetrics and Gynecology. 25 (2): 98–108. doi:10.1097/GCO.0b013e32835ec9b0. PMID 23425665. S2CID 41767750. 63. ^ a b c d Vos, Amber A.; Posthumus, Anke G.; Bonsel, Gouke J.; Steegers, Eric A.P.; Denktaş, Semiha (August 2014). "Deprived neighborhoods and adverse perinatal outcome: a systematic review and meta-analysis". Acta Obstetricia et Gynecologica Scandinavica. 93 (8): 727–740. doi:10.1111/aogs.12430. PMID 24834960. S2CID 39860659. 64. ^ a b c Bradley, Robert H.; Corwyn, Robert F. (February 2002). "S S C D". Annual Review of Psychology. 53 (1): 371–399. doi:10.1146/annurev.psych.53.100901.135233. PMID 11752490. S2CID 43766257. 65. ^ Health risk assessment from the nuclear accident after the 2011 Great East Japan Earthquake and Tsunami based on a preliminary dose estimation (PDF). World Health Organization. 2013. p. 23–24. ISBN 978-92-4-150513-0. 66. ^ Heath, Clark W. (1992). "The Children of Atomic Bomb Survivors: A Genetic Study". JAMA: The Journal of the American Medical Association. 268 (5): 633–634. Bibcode:1992RadR..131..229A. doi:10.1001/jama.1992.03490050109039. PMC 1682172. "No differences were found (in frequencies of birth defects, stillbirths, etc), thus allaying the immediate public concern that atomic radiation might spawn an epidemic of malformed children" 67. ^ Kalter, Harold (2010). Teratology in the Twentieth Century Plus Ten. Springer Netherlands. p. 21. ISBN 978-90-481-8820-8. Retrieved 28 October 2014. 68. ^ Winther, J F; Boice, J D; Thomsen, B L; Schull, W J; Stovall, M; j h Olsen (2003). "Sex ratio among offspring of childhood cancer survivors treated with radiotherapy". British Journal of Cancer. 88 (3): 382–7. doi:10.1038/sj.bjc.6600748. PMC 2747537. PMID 12569380. 69. ^ "Birth defects among the children of atomic-bomb survivors (1948–1954)". RERF.jp. Radiation Effects Research Foundation. Retrieved 2013-11-21. 70. ^ Voosen, Paul (11 April 2011). "Nuclear crisis: Hiroshima and Nagasaki cast long shadows over radiation science". E&E News. Retrieved 28 October 2014. 71. ^ Dubrova, Yuri E.; Nesterov, Valeri N.; Krouchinsky, Nicolay G.; Ostapenko, Valdislav A.; Neumann, Rita; Neil, David L.; Jeffreys, Alec J. (25 April 1996). "Human minisatellite mutation rate after the Chernobyl accident". Nature. 380 (6576): 683–686. Bibcode:1996Natur.380..683D. doi:10.1038/380683a0. PMID 8614461. S2CID 4303433. 72. ^ Bennett, Burton; Repacholi, Michael; Carr, Zhanat, eds. (2006). Health Effects of the Chernobyl Accident and Special Health Care Programmes: Report of the UN Chernobyl Forum, Expert Group "Health" (PDF). Geneva: World Health Organization (WHO). p. 79. ISBN 978-92-4-159417-2. Retrieved 20 August 2011. 73. ^ Furitsu Katsumi (2005). "Microsatellite mutations show no increases in the children of the Chernobyl liquidators". Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 581 (1–2): 69–82. doi:10.1016/j.mrgentox.2004.11.002. PMID 15725606. 74. ^ Dickinson HO, Parker L (1999). "Quantifying the effect of population mixing on childhood leukaemia risk: the Seascale cluster". British Journal of Cancer. 81 (1): 144–151 [146, 149]. doi:10.1038/sj.bjc.6690664. PMC 2374359. PMID 10487626. 75. ^ Lean, Samantha C.; Derricott, Hayley; Jones, Rebecca L.; Heazell, Alexander E. P. (2017-10-17). "Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis". PLOS ONE. 12 (10): e0186287. Bibcode:2017PLoSO..1286287L. doi:10.1371/journal.pone.0186287. ISSN 1932-6203. PMC 5645107. PMID 29040334. 76. ^ a b Olshan, Andrew F.; Schnitzer, Patricia G.; Baird, Patricia A. (July 1994). "Paternal age and the risk of congenital heart defects". Teratology. 50 (1): 80–84. doi:10.1002/tera.1420500111. PMID 7974258. 77. ^ Yang, Q.; Wen, S.W.; Leader, A.; Chen, X.K.; Lipson, J.; Walker, M. (7 December 2006). "Paternal age and birth defects: how strong is the association?". Human Reproduction. 22 (3): 696–701. doi:10.1093/humrep/del453. PMID 17164268. 78. ^ Wiener-Megnazi, Zofnat; Auslender, Ron; Dirnfeld, Martha (12 December 2011). "Advanced paternal age and reproductive outcome". Asian Journal of Andrology. 14 (1): 69–76. doi:10.1038/aja.2011.69. PMC 3735149. PMID 22157982. 79. ^ Bezerra Guimarães MJ, Marques NM, Melo Filho DA (2000). "Taux de mortalité infantile et disparités sociales à Recife, métropole du Nord-Est du Brésil" [Infant mortality rate and social disparity at Recife, the metropolis of the North-East of Brazil]. Santé (in French). 10 (2): 117–21. PMID 10960809. 80. ^ Kumar, Abbas and Fausto, eds., Robbins and Cotran's Pathologic Basis of Disease, 7th edition, p.473. 81. ^ Chen, J; Gong, X; Chen, P; Luo, K; Zhang, X (16 August 2016). "Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis". BMC Pregnancy and Childbirth. 16: 225. doi:10.1186/s12884-016-1009-6. PMC 4986189. PMID 27528012. 82. ^ Simonsen, H (25 November 2002). "[Screening of newborns for inborn errors of metabolism by tandem mass spectrometry]". Ugeskrift for Laeger. 164 (48): 5607–12. PMID 12523003. 83. ^ a b c Wilcken, B; Wiley, V (February 2008). "Newborn screening". Pathology. 40 (2): 104–15. doi:10.1080/00313020701813743. PMID 18203033. 84. ^ Ezgu, F (2016). Inborn Errors of Metabolism. Advances in Clinical Chemistry. 73. pp. 195–250. doi:10.1016/bs.acc.2015.12.001. ISBN 9780128046906. PMID 26975974. 85. ^ "Newborn screening for DMD shows promise as an international model". Nationwide Children's Hospital. 2012-03-19. Retrieved 2018-04-02. 86. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved Nov 11, 2009. 87. ^ Gittelsohn, A; Milham, S (1964). "Statistical Study of Twins—Methods". American Journal of Public Health and the Nations Health. 54 (2): 286–294. doi:10.2105/ajph.54.2.286. PMC 1254713. PMID 14115496. 88. ^ Fernando, J; Arena, P; Smith, D. W. (1978). "Sex liability to single structural defects". American Journal of Diseases of Children. 132 (10): 970–972. doi:10.1001/archpedi.1978.02120350034004. PMID 717306. 89. ^ Lubinsky, M. S. (1997). "Classifying sex biased congenital anomalies". American Journal of Medical Genetics. 69 (3): 225–228. doi:10.1002/(SICI)1096-8628(19970331)69:3<225::AID-AJMG1>3.0.CO;2-K. PMID 9096746. 90. ^ Lary, J. M.; Paulozzi, L. J. (2001). "Sex differences in the prevalence of human birth defects: A population-based study". Teratology. 64 (5): 237–251. doi:10.1002/tera.1070. PMID 11745830. 91. ^ a b c d e f Cui, W; Ma, C. X.; Tang, Y; Chang, V; Rao, P. V.; Ariet, M; Resnick, M. B.; Roth, J (2005). "Sex differences in birth defects: A study of opposite-sex twins". Birth Defects Research Part A: Clinical and Molecular Teratology. 73 (11): 876–880. doi:10.1002/bdra.20196. PMID 16265641. 92. ^ a b World Health Organization reports). "Congenital malformations", Geneve, 1966, p. 128. 93. ^ Darwin C. (1871) The descent of man and selection in relation to sex. London, John Murray, 1st ed. 94. ^ "Diagnosis \| Birth Defects \| NCBDDD \| CDC". Centers for Disease Control and Prevention. 2017-12-04. Retrieved 2018-11-07. 95. ^ Kumar, Abbas and Fausto, eds., Robbins and Cotran's Pathologic Basis of Disease, 7th edition, p.470. 96. ^ Dicke JM (1989). "Teratology: principles and practice". Med. Clin. North Am. 73 (3): 567–82. doi:10.1016/S0025-7125(16)30658-7. PMID 2468064. 97. ^ a b c d e f g h i j k l m n o p q r Rajewski P. M., Sherman A. L. (1976) The importance of gender in the epidemiology of malignant tumors (systemic-evolutionary approach). In: Mathematical treatment of medical-biological information. M., Nauka, p. 170–181. 98. ^ a b c d Montagu A. (1968) Natural Superiority of Women, The, Altamira Press, 1999. 99. ^ a b c d e f g h i Riley M., Halliday J. (2002) Birth Defects in Victoria 1999–2000, Melbourne. 100. ^ Shaw, G. M.; Carmichael, S. L.; Kaidarova, Z; Harris, J. A. (2003). "Differential risks to males and females for congenital malformations among 2.5 million California births, 1989–1997". Birth Defects Research Part A: Clinical and Molecular Teratology. 67 (12): 953–958. doi:10.1002/bdra.10129. PMID 14745913. 101. ^ Reyes, F. I.; Boroditsky, R. S.; Winter, J. S.; Faiman, C (1974). "Studies on human sexual development. II. Fetal and maternal serum gonadotropin and sex steroid concentrations". The Journal of Clinical Endocrinology & Metabolism. 38 (4): 612–617. doi:10.1210/jcem-38-4-612. PMID 4856555. 102. ^ "Key Findings: Updated National Birth Prevalence Estimates for Selected Birth Defects in the United States, 2004–2006". CDC. Centers for Disease Control and Prevention (CDC) and the National Birth Defects Prevention Network. Retrieved October 1, 2014. ## External links[edit] Classification D * MeSH: D009358 * DiseasesDB: 28811 * CDC’s National Center on Birth Defects and Developmental Disabilities * v * t * e Chromosome abnormalities Autosomal Trisomies/Tetrasomies * Down syndrome * 21 * Edwards syndrome * 18 * Patau syndrome * 13 * Trisomy 9 * Tetrasomy 9p * Warkany syndrome 2 * 8 * Cat eye syndrome/Trisomy 22 * 22 * Trisomy 16 Monosomies/deletions * (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome) * 1 * Wolf–Hirschhorn syndrome * 4 * Cri du chat syndrome/Chromosome 5q deletion syndrome * 5 * Williams syndrome * 7 * Jacobsen syndrome * 11 * Miller–Dieker syndrome/Smith–Magenis syndrome * 17 * DiGeorge syndrome * 22 * 22q11.2 distal deletion syndrome * 22 * 22q13 deletion syndrome * 22 * genomic imprinting * Angelman syndrome/Prader–Willi syndrome (15) * Distal 18q-/Proximal 18q- X/Y linked Monosomy * Turner syndrome (45,X) Trisomy/tetrasomy, other karyotypes/mosaics * Klinefelter syndrome (47,XXY) * XXYY syndrome (48,XXYY) * XXXY syndrome (48,XXXY) * 49,XXXYY * 49,XXXXY * Triple X syndrome (47,XXX) * Tetrasomy X (48,XXXX) * 49,XXXXX * Jacobs syndrome (47,XYY) * 48,XYYY * 49,XYYYY * 45,X/46,XY * 46,XX/46,XY Translocations Leukemia/lymphoma Lymphoid * Burkitt's lymphoma t(8 MYC;14 IGH) * Follicular lymphoma t(14 IGH;18 BCL2) * Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH) * Anaplastic large-cell lymphoma t(2 ALK;5 NPM1) * Acute lymphoblastic leukemia Myeloid * Philadelphia chromosome t(9 ABL; 22 BCR) * Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) * Acute promyelocytic leukemia t(15 PML,17 RARA) * Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1) Other * Ewing's sarcoma t(11 FLI1; 22 EWS) * Synovial sarcoma t(x SYT;18 SSX) * Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB) * Myxoid liposarcoma t(12 DDIT3; 16 FUS) * Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS) * Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1) Other * Fragile X syndrome * Uniparental disomy * XX male syndrome/46,XX testicular disorders of sex development * Marker chromosome * Ring chromosome * 6; 9; 14; 15; 18; 20; 21, 22 * v * t * e Disability Main topics * Disability * Disability studies * Medical model * Social model * Society for Disability Studies Approaches * Freak show * IEP * Inclusion * Learning disability * Mainstreaming * Physical therapy * driver rehabilitation * Special needs * school * education Rights, law, support Rights * Ableism/disablism * Disability rights * Pejorative terms Law * AODA * ADA * Convention on the Rights of Persons with Disabilities * Declaration on the Rights of Disabled Persons * International Classification of Functioning, Disability and Health Services * Services for mental disorders * Services for the disabled Support * DLA * ODSP * Rail * SSDI * SSI * Students * CNIB Activist groups * CCD * DPI * MINDS * Reach Canada * Visitability Structural and assistive * Activities of daily living * Assistive technology * Independent living * Mobility aid * Orthotics and braces * Personal Care Assistant * Physical accessibility * Prosthetics * Universal design * Web accessibility Social issues * Augmentative and alternative communication * Emotional or behavioral disability * Invisible disability * Disability and religion * Disability and poverty * Disability and sexuality Arts, media, culture, sport * Disability culture * Disability art * Disability in the arts * Disability in the media * Disabled sports * Deaflympics * Paralympics * Special Olympics * Category * Lists [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Birth defect	c0242354	988	wikipedia	https://en.wikipedia.org/wiki/Birth_defect	2021-01-18T18:51:43	{"mesh": ["D009358"], "wikidata": ["Q727096"]}
Bullous pemphigoid is a skin disorder characterized by large blisters. The blisters are usually located on the arms, legs, or middle of the body. In some people, the mouth or genitals are also affected. The blisters may break open and form ulcers or open sores. Bullous pemphigoid usually occurs in older persons and is rare in young people. Symptoms may come and go. In most patients, the condition goes away after several years. Bullous pemphigoid is an autoimmune disorder which occurs when the body's immune system attacks and destroys healthy body tissue by mistake. Treatment may include corticosteroids taken by mouth or applied to the skin. Medicines that suppress the immune system may also be prescribed. For some, antibiotics in the tetracycline family are useful. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Bullous pemphigoid	c0030805	989	gard	https://rarediseases.info.nih.gov/diseases/5972/bullous-pemphigoid	2021-01-18T18:01:41	{"mesh": ["D010391"], "synonyms": ["Senile Dermatitis Herpetiformis", "Pemphigoid", "Parapemphigus", "Old Age Pemphigus", "Benign Pemphigus"]}
This article provides insufficient context for those unfamiliar with the subject. Please help improve the article by providing more context for the reader. (October 2009) (Learn how and when to remove this template message) D-bifunctional protein deficiency Other names17β-hydroxysteroid dehydrogenase IV deficiency SpecialtyMedical genetics D-Bifunctional protein deficiency is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder,[1] often resembling Zellweger syndrome.[2] Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment.[3] Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life. ## Contents * 1 Classification * 2 D-BP Protein * 3 Genetic * 4 Chemistry * 5 Diagnosis * 6 References * 7 External links ## Classification[edit] DBP deficiency can be divided into three types:[4] * type I, characterized by a deficiency in both the hydratase and dehydrogenase units of D-BP * type II, in which only the hydratase unit is non-functional * type III, with only a deficiency in the dehydrogenase unit Type I deficient patients showed a large structural modification to the D-BP as a whole. Most of these individuals showed either a deletion or an insertion resulting in a frameshift mutation. Type II and III patients showed small scale changes in the overall structure of D-BP[6]. Amino acid changes in the catalytic domains or those in contact with substrate or cofactors were the main cause of these variations of D-BP deficiency. Other amino acid changes were seen to alter the dimerization of the protein, leading to improper folding. Many mutations have been found in the gene coding for D-BP (HSD17B4) on the q arm two of chromosome five (5q23.1) in Homo sapiens, most notably individuals homozygous for a missense mutation (616S).[4] ## D-BP Protein[edit] The D-bifunctional protein is composed of three enzymatic domains: the N-terminal short chain alcohol dehydrogenase reductase (SDR), central hydratase domain, and the C-terminal sterol carrier protein 2 (SDR).[1] The DBP protein (79kDa) also known as "multifunctional protein 2", "multifunctional enzyme 2", or "D-peroxisomal bifunctional"enzyme", catalyzes the second and third steps of peroxisomal β-oxidation of fatty acids and their derivatives . A non-functional D-BP protein results in the abnormal accumulation of long chain fatty acids and bile acid intermediates. The D-BP protein contains a peroxisomal targeting signal 1 (PTS1) unit at the C-terminus allowing for its transport into peroxisomes by the PTS1 receptor. Inside the peroxisomes, the D-BP protein is partially cleaved exclusively between the SDR and hydratase"domains.[1] DBP is a stereospecific enzyme; hydratase domain forms only (R)-hydroxy-acyl-CoA intermediates from trans-2-enoyl-CoAs.[4] D-BP is expressed throughout the entire human body, with the highest mRNA levels in the liver and brain. The hydrogenase and hydratase units of DBP exist as dimers, necessary for correct folding and therefore function of the enzyme. ## Genetic[edit] The D-BP gene (HSD17B4), found on the long arm of chromosome 5, consists of 24 exons and 23 introns and is over 100kb in size. Exons 1-12 code for the SDR domain, 12-21 for the hydratase domain, and 21-24 for the SCP2 domain. Transcription is regulated at 400 basepairs upstream of the transcription start site.[1] The missense mutation G16S is the most common mutation that leads to D-BP deficiency. In a 2006 study in which 110 patients were tested, 28 suffered from this frameshift mutation. The second most frequent mutation was the missense mutation N457Y which was seen in 13 of the 110 patients. Type I patients showed only deletions, insertions, and nonsense mutations were identified, most leading to shortened polypeptides. Most type II patients show missense mutations in D-BP hydratase unit as well as some in-frame deletions. Type III"individuals commonly show missense mutations in the coding region of the dehydrogenase domain.[4] ## Chemistry[edit] Enzymatic activity of D-BP fails if the protein cannot effectively bind the cofactor NAD+, as shown in the G16S mutation. Glycine 16 forms a short loop and creates a hole for the adenine ring of NAD+ to enter. Other amino acid side chains alter the shape of this loop due to steric hindrance, and prevent proper NAD+ binding. Other mutations that exist are due to incorrect polypeptide folding. L405 (leucine located at residue 405) located in the substrate binding domain of the hydratase 2 unit, plays an important role in binding CoA ester moiety. One mutation seen in D-BP deficiency patients is caused by a leucine to proline substitution. This breaks the hydrophobic interactions necessary for proper substrate binding with CoA esters.[4] ## Diagnosis[edit] The most common clinical observations of patients suffering from D-bifunctional protein deficiency include hypotonia, facial and skull dysmorphism, neonatal seizures, and neuronal demyelination.[5] High levels of branched fatty acids, such as pristinic acid, bile acid intermediates, and other D-BP substrates are seen to exist. Reduced pristinic acid β-oxidation is a common indicator of D-BP deficiency.[1] D-BP can be distinguished from Zellweger Syndrome by normal plasmalogen synthesis. Recent studies in D-BP knockout mice show compensatory upregulation of other peroxisomal enzymes in absence of D-BP such as palmitoyl-CoA oxidase, peroxisomal thiolase, and branched chain acyl-CoA oxidase.[1] ## References[edit] 1. ^ a b c d e f Möller G, van Grunsven EG, Wanders RJ, Adamski J (January 2001). "Molecular basis of D-bifunctional protein deficiency". Mol. Cell. Endocrinol. 171 (1–2): 61–70. doi:10.1016/s0303-7207(00)00388-9. PMID 11165012. 2. ^ Itoh M, Suzuki Y, Akaboshi S, Zhang Z, Miyabara S, Takashima S (March 2000). "Developmental and pathological expression of peroxisomal enzymes: their relationship of D-bifunctional protein deficiency and Zellweger syndrome". Brain Res. 858 (1): 40–7. doi:10.1016/S0006-8993(99)02423-3. PMID 10700594. 3. ^ Buoni S, Zannolli R, Waterham H, Wanders R, Fois A (January 2007). "D-bifunctional protein deficiency associated with drug resistant infantile spasms". Brain Dev. 29 (1): 51–4. doi:10.1016/j.braindev.2006.06.004. PMID 16919904. 4. ^ a b c d e Ferdinandusse S, Ylianttila MS, Gloerich J, Koski MK, Oostheim W, Waterham HR, Hiltunen JK, Wanders RJ, Glumoff T (January 2006). "Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis". Am. J. Hum. Genet. 78 (1): 112–24. doi:10.1086/498880. PMC 1380208. PMID 16385454. 5. ^ van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ (August 1999). "Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency". Hum. Mol. Genet. 8 (8): 1509–16. doi:10.1093/hmg/8.8.1509. PMID 10400999. ## External links[edit] Classification D * ICD-10: E80.3 * OMIM: 261515 * MeSH: C536663 * DiseasesDB: 33358 * v * t * e Genetic disorder, organelle: Peroxisomal disorders and lysosomal structural disorders Peroxisome biogenesis disorder * Zellweger syndrome * Neonatal adrenoleukodystrophy * Infantile Refsum disease * Adult Refsum disease-2 * RCP 1 Enzyme-related * Acatalasia * RCP 2&3 * Mevalonate kinase deficiency * D-bifunctional protein deficiency * Adult Refsum disease-1 Transporter-related * X-linked adrenoleukodystrophy Lysosomal * Danon disease See also: proteins, intermediates [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	D-bifunctional protein deficiency	c0342870	990	wikipedia	https://en.wikipedia.org/wiki/D-bifunctional_protein_deficiency	2021-01-18T18:35:48	{"gard": ["4539"], "mesh": ["C536663", "C537286"], "umls": ["C0342870"], "orphanet": ["300", "2981"], "wikidata": ["Q5203306"]}
Juel-Jensen (1987) referred to a family he had seen in which 4 brothers had many attacks of varicella. He observed a 15-year-old brother in his second attack at the age of 15. A 19-year-old brother had also had 2 attacks; an 18-year-old brother had had 8 attacks, and a brother aged 16.5 had had 3 attacks, all of increasing severity. The parents and 2 sisters had had only a single attack of standard severity. In other respects the boys were entirely normal. Extensive investigations failed to reveal genetic or lymphocyte functional abnormalities. Immunology \- Severe recurrent varicella 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	VARICELLA, SEVERE RECURRENT	c1833487	991	omim	https://www.omim.org/entry/600670	2019-09-22T16:15:58	{"mesh": ["C563458"], "omim": ["600670"]}
Inability to move the eyes up and down Not to be confused with Parinaud's oculoglandular syndrome. 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: "Parinaud's syndrome" – news · newspapers · books · scholar · JSTOR (February 2015) (Learn how and when to remove this template message) Parinaud's syndrome Other namesDorsal midbrain syndrome, vertical gaze palsy, upward gaze palzy, sunset sign,[1] setting-sun sign,[2] sun-setting sign,[3] sunsetting sign,[4] sunset eye sign,[5] setting-sun phenomenon[5] SpecialtyNeurology Parinaud's syndrome is an inability to move the eyes up and down. It is caused by compression of the vertical gaze center at the rostral interstitial nucleus of medial longitudinal fasciculus (riMLF). The eyes lose the ability to move upward and down. It is a group of abnormalities of eye movement and pupil dysfunction. It is caused by lesions of the upper brain stem and is named for Henri Parinaud[6][7] (1844–1905), considered to be the father of French ophthalmology. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 References * 7 Further reading * 8 External links ## Signs and symptoms[edit] Parinaud's syndrome is a cluster of abnormalities of eye movement and pupil dysfunction, characterized by: * Paralysis of upwards gaze: Downward gaze is usually preserved. This vertical palsy is supranuclear, so doll's head maneuver should elevate the eyes, but eventually all upward gaze mechanisms fail.[8] * Pseudo-Argyll Robertson pupils: Accommodative paresis ensues, and pupils become mid-dilated and show light-near dissociation. * Convergence-retraction nystagmus: Attempts at upward gaze often produce this phenomenon. On fast up-gaze, the eyes pull in and the globes retract. The easiest way to bring out this reaction is to ask the patient to follow down-going stripes on an optokinetic drum.[9] * Eyelid retraction (Collier's sign) * Conjugate down gaze in the primary position: "setting-sun sign". Neurosurgeons see this sign most commonly in patients with failed hydrocephalus shunts. It is also commonly associated with bilateral papilledema. It has less commonly been associated with spasm of accommodation on attempted upward gaze, pseudoabducens palsy (also known as thalamic esotropia) or slower movements of the abducting eye than the adducting eye during horizontal saccades, see-saw nystagmus and associated ocular motility deficits including skew deviation, oculomotor nerve palsy, trochlear nerve palsy and internuclear ophthalmoplegia. ## Causes[edit] cross section of midbrain showing lesion Parinaud's syndrome results from injury, either direct or compressive, to the dorsal midbrain. Specifically, compression or ischemic damage of the mesencephalic tectum, including the superior colliculus adjacent oculomotor (origin of cranial nerve III) and Edinger-Westphal nuclei, causing dysfunction to the motor function of the eye. Classically, it has been associated with three major groups: * Young patients with brain tumors in the pineal gland or midbrain: pinealoma (intracranial germinomas) are the most common lesion producing this syndrome. * Women in their 20s-30s with multiple sclerosis * Older patients following stroke of the upper brainstem However, any other compression, ischemia or damage to this region can produce these phenomena: obstructive hydrocephalus, midbrain hemorrhage, cerebral arteriovenous malformation, trauma and brainstem toxoplasmosis infection. Neoplasms and giant aneurysms of the posterior fossa have also been associated with the midbrain syndrome. Vertical supranuclear ophthalmoplegia has also been associated with metabolic disorders, such as Niemann-Pick disease, Wilson's disease, kernicterus, and barbiturate overdose. ## Diagnosis[edit] This section is empty. You can help by adding to it. (September 2017) Diagnosis can be made via combination of physical exam, particularly deficits of the relevant cranial nerves. Confirmation can be made via imaging, such as CT scan or MRI. ## Treatment[edit] Treatment is primarily directed towards etiology of the dorsal midbrain syndrome. A thorough workup, including neuroimaging is essential to rule out anatomic lesions or other causes of this syndrome. Visually significant upgaze palsy can be relieved with bilateral inferior rectus recessions. Retraction nystagmus and convergence movement are usually improved with this procedure as well. ## Prognosis[edit] The eye findings of Parinaud's syndrome generally improve slowly over months, especially with resolution of the causative factor; continued resolution after the first 3–6 months of onset is uncommon. However, rapid resolution after normalization of intracranial pressure following placement of a ventriculoperitoneal shunt has been reported. ## References[edit] 1. ^ Larner, A. J. (2001). A Dictionary of Neurological Signs: Clinical Neurosemiology. Springer Science & Business Media. p. 202. ISBN 978-1-4020-0042-3. 2. ^ Biglan, Albert W. (1984-01-01). "Setting Sun Sign in Infants". American Orthoptic Journal. 34 (1): 114–116. doi:10.1080/0065955X.1984.11981637. ISSN 0065-955X. 3. ^ MPH, Eudocia Quant Lee, MD; MD, David Schiff; MD, Patrick Y. Wen (2011-09-28). Neurologic Complications of Cancer Therapy. Demos Medical Publishing. p. 383. ISBN 978-1-61705-019-0. 4. ^ Waterston, Tony; Helms, Peter; Ward-Platt, Martin (2016-07-06). Paediatrics: A Core Text on Child Health, Second Edition. CRC Press. p. 149. ISBN 978-1-138-03131-9. 5. ^ a b Gaillard, Frank. "Sunset eye sign \| Radiology Reference Article \| Radiopaedia.org". Radiopaedia. Retrieved 2020-01-05. 6. ^ synd/1906 at Who Named It? 7. ^ H. Parinaud. Paralysie des mouvements associés des yeux. Archives de neurologie, Paris, 1883, 5: 145-172. 8. ^ Neuro-Ophthalmic Examination 9. ^ "Convergence-retraction nystagmus". www.aao.org. Archived from the original on 14 September 2016. Retrieved 17 March 2020. ## Further reading[edit] * Aguilar-Rebolledo F, Zárate-Moysén A, Quintana-Roldán G (1998). "Parinaud's syndrome in children". Rev. Invest. Clin. (in Spanish). 50 (3): 217–20. PMID 9763886. * Waga S, Okada M, Yamamoto Y (1979). "Reversibility of Parinaud syndrome in thalamic hemorrhage". Neurology. 29 (3): 407–9. doi:10.1212/wnl.29.3.407. PMID 571990. S2CID 42247406. ## External links[edit] Classification D * ICD-10: G46.3 * ICD-9-CM: 378.81 * MeSH: D015835 * DiseasesDB: 32982 * v * t * e Symptoms, signs and syndromes associated with lesions of the brain and brainstem Brainstem Medulla (CN 8, 9, 10, 12) * Lateral medullary syndrome/Wallenberg * PICA * Medial medullary syndrome/Dejerine * ASA Pons (CN 5, 6, 7, 8) * Upper dorsal pontine syndrome/Raymond-Céstan syndrome * Lateral pontine syndrome (AICA) (lateral) * Medial pontine syndrome/Millard–Gubler syndrome/Foville's syndrome (basilar) * Locked-in syndrome * Internuclear ophthalmoplegia * One and a half syndrome Midbrain (CN 3, 4) * Weber's syndrome * ventral peduncle, PCA * Benedikt syndrome * ventral tegmentum, PCA * Parinaud's syndrome * dorsal, tumor * Claude's syndrome Other * Alternating hemiplegia Cerebellum * Latearl * Dysmetria * Dysdiadochokinesia * Intention tremor) * Medial * Cerebellar ataxia Basal ganglia * Chorea * Dystonia * Parkinson's disease Cortex * ACA syndrome * MCA syndrome * PCA syndrome * Frontal lobe * Expressive aphasia * Abulia * Parietal lobe * Receptive aphasia * Hemispatial neglect * Gerstmann syndrome * Astereognosis * Occipital lobe * Bálint's syndrome * Cortical blindness * Pure alexia * Temporal lobe * Cortical deafness * Prosopagnosia Thalamus * Thalamic syndrome Other * Upper motor neuron lesion * Aphasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Parinaud's syndrome	c0152222	992	wikipedia	https://en.wikipedia.org/wiki/Parinaud%27s_syndrome	2021-01-18T19:08:59	{"mesh": ["D015835"], "icd-9": ["378.81"], "icd-10": ["G46.3"], "wikidata": ["Q1503804"]}
A number sign (#) is used with this entry because neuronal ceroid lipofuscinosis-7 (CLN7) is caused by homozygous or compound heterozygous mutation in the MFSD8 gene (611124), which encodes a putative lysosomal transporter, on chromosome 4q28. Description The neuronal ceroid lipofuscinoses (NCL, or CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally (summary by Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730). Clinical Features Topcu et al. (2004) reported the so-called Turkish variant of late-infantile CLN in 17 of 28 Turkish patients. Most of the families were consanguineous. The mean age at disease onset was 5.1 years (range, 2 to 7 years), with seizures or motor impairment as the most common presenting symptom. As the disease progressed, mental regression, myoclonus, speech impairment, loss of vision, and personality disorders developed, and most of the patients became nonambulatory within 2 years after onset. The features distinguishing the Turkish variant from CLN2 and CLN3 included a more severe course regarding seizures, the presence of condensed fingerprint profiles on electron microscopic examination of lymphocytes, and lack of vacuolated lymphocytes. Mole et al. (2005) stated that the clinical phenotype of CLN7 is considered to be the same as Turkish patients with CLN8 (600143). Stogmann et al. (2009) reported a consanguineous Egyptian family in which 5 members had late-infantile CLN. The average age at onset was 5 years, and all patients presented with seizures, including complex partial, secondary generalized tonic-clonic, and myoclonic jerks. All showed gradual deterioration and loss of psychomotor skills about 1 year after the seizures started. Three patients showed aggressive behavior, memory impairment, and language abnormalities with substantial loss of speech function. The disorder was progressive, with motor impairment ultimately resulting in disability of sitting and walking and eventual bedridden status. Two patients died at age 13 years. One patients developed extrapyramidal signs, including axial rigidity, hesitation in initiation of movement, and coarse postural tremor, and also showed frontal manifestations including bilateral positive grasp, paratonia, and positive snout reflexes. None of the patients had visual impairment. Skin biopsies were not informative, likely due to lack of proper sampling. Aldahmesh et al. (2009) reported a consanguineous Saudi family in which 3 individuals had variant late infantile-onset NCL. The proband developed poor vision at age 6 years and had onset of focal seizures with secondary generalization 1 year later. His vision deteriorated to blindness by age 7.5, and he had declining cognitive function. By age 10, he had minimal verbal communication and retinitis pigmentosa. There was no evidence of ultrastructural deposits of NCL on conjunctival biopsy. Brain MRI showed atrophic changes which were more in the occipital lobe. A 14-year-old brother and an 18-year-old half-sister had a similar presentation, with onset of poor vision around age 7 years, progression to blindness, seizures, and cognitive decline. The 14-year-old brother had a rapidly progressive course and has been in a vegetative state since age 11. The 18-year-old half-sister has significant impairment of cognitive functions comparable to the index case and intractable seizures. Her EEG showed diffuse slowing with frequent, multifocal sharp waves. Aldahmesh et al. (2009) commented that the phenotype in this family was similar to that reported in other patients with this form of CLN. ### Clinical Variability Kousi et al. (2009) reported a Dutch patient with a protracted course of CLN7. The patient presented at age 11 years with visual failure. He had motor impairment and seizures in his mid-twenties, followed by mental and speech regression in his thirties, and loss of independent ambulation at age 39. Genetic analysis identified a homozygous mutation in the MFSD8 gene (A157P; 611124.0007) that resulted in the substitution of a neutral nonpolar alanine with a neutral nonpolar proline. Kousi et al. (2009) postulated that the mild impact of the mutation on amino acid substitution may have contributed to the later onset and milder course of the disorder in this patient. Importantly, patients with later onset of CLN should still be considered to have mutations in the MFSD8 gene. Mapping Wheeler et al. (1999) referred to a group of patients with the so-called Turkish variant of late-onset infantile CLN as having CLN7. Although some of these patients have been found to carry mutations in the CLN8 (607837) or CLN6 (606725) genes, the underlying molecular defect in other Turkish patients had not been determined. Ranta et al. (2004) and Siintola et al. (2005) excluded 7 Turkish families with late-onset infantile CLN from all known CLN loci, including CLN8; these patients had previously been reported by Topcu et al. (2004). Siintola et al. (2005) concluded that these Turkish families may still represent a distinct genetic entity, CLN7. Siintola et al. (2007) performed a genomewide scan with SNP markers and homozygosity mapping in 9 Turkish families, including the families reported by Topcu et al. (2004) and 1 Indian family who were not linked to any known NCL locus, and mapped a variant late infantile-onset NCL (vLINCL) locus to chromosome 4q28.1-q28.2 in 5 families. Molecular Genetics In 6 families with vLINCL, 5 of them Turkish families reported by Topcu et al. (2004), Siintola et al. (2007) identified 6 different mutations in the MFSD8 gene (see, e.g., 611124.0001-611124.0003 and 611124.0010). MFSD8 belongs to the major facilitator superfamily of transporter proteins and is expressed ubiquitously, with several alternatively spliced variants. Like the majority of the previously reported NCL proteins, MFSD8 localizes mainly to the lysosomal compartment. Analysis of the genome-scan data suggested the existence of at least 3 more genes in the remaining 5 families, further corroborating the great genetic heterogeneity of LINCLs. In affected individuals of a consanguineous Egyptian family with CLN7, Stogmann et al. (2009) identified a homozygous mutation in the MFSD8 gene (611124.0004). In 3 affected individuals of a consanguineous Saudi family with CLN7, Aldahmesh et al. (2009) identified a homozygous mutation in the MFSD8 gene (P412L; 611124.0005). In 32 of 80 patients from 75 families with late-infantile onset CLN, Kousi et al. (2009) identified 10 mutations in the MFSD8 gene, including 8 novel mutations (see, e.g., 611124.0006-611124.0007). Although most of the patients were of Turkish origin, many were from other regions, including India, the Netherlands, Italy, and Czech Republic. The phenotype was mostly homogeneous, with onset between 1.5 and 5 years, developmental regression, seizures, mental and motor regression, speech impairments, ataxia, visual failure, and myoclonus. Most of the mutations were private, found only in a single family. However, all known CLN loci were excluded in Turkish patients from 35 families with late-infantile onset of CLN, indicating genetic heterogeneity. In 9 (39%) of 23 children with late infantile-onset CLN, 22 of Italian origin and 1 from the southeast of France, who were negative for mutation in known CLN-associated genes, Aiello et al. (2009) identified homozygosity or compound heterozygosity for pathogenic mutations in MFSD8 (see, e.g., 611124.0001, 611124.0009, and 611124.0011-611124.0012). Mutation-positive patients were characterized by early psychomotor regression and seizures, with 7 of 9 developing mental regression, personality disorders, and speech impairment within 3 to 4 years after onset, and 4 becoming unable to walk unaided within 2 years. In 14 of the patients, Aiello et al. (2009) found no mutations in any of the known CLN-causing genes, suggesting further genetic heterogeneity of vLINCL. Population Genetics Kousi et al. (2009) identified a homozygous mutation in the MFSD8 gene (T294K; 611124.0006) in 14 Roma patients from 12 families with CLN7 from the former Czechoslovakia. The phenotype was characterized by late-infantile onset, developmental regression, seizures, visual failure, and ataxia. Haplotype analysis was consistent with a founder effect. Animal Model Ashwini et al. (2016) performed neurologic evaluations on 4 unrelated client-owned Chihuahua dogs from Japan, Italy, and England that exhibited progressive neurologic signs consistent with a diagnosis of NCL. Brain and in some cases also retinal and heart tissues were examined postmortem for the presence of lysosomal storage bodies characteristic of NCL. The affected dogs exhibited massive accumulation of autofluorescent lysosomal storage bodies in the brain, retina, and heart accompanied by brain atrophy and retinal degeneration. The dogs were screened for known canine NCL mutations that had been reported in a variety of dog breeds. All 4 dogs were homozygous for the MFSD8 single-basepair deletion (c.843delT) previously associated with NCL in a Chinese Crested dog and in 2 affected littermate Chihuahuas from Scotland. The dogs were all homozygous for the normal alleles at the other genetic loci known to cause different forms of canine NCL. The MFSD8 c.843delT mutation was not present in 57 Chihuahuas that were either clinically normal or suffered from unrelated diseases or in 1761 unaffected dogs representing 186 other breeds. Based on these data Ashwini et al. (2016) considered it almost certain that the MFSD8 c.843delT mutation is the cause of NCL in Chihuahuas. Because the disorder occurred in widely separated geographic locations or in unrelated dogs from the same country, it is likely that the mutant allele is widespread among Chihuahuas. Ashwini et al. (2016) suggested that genetic testing for this mutation in other Chihuahuas is therefore likely to identify intact dogs with the mutant allele that could be used to establish a research colony that could be used to test potential therapeutic interventions for the corresponding human disease. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Optic atrophy \- Retinopathy \- Loss of vision, progressive \- Blindness NEUROLOGIC Central Nervous System \- Neurodegeneration \- Delayed psychomotor development \- Delayed speech development \- Cognitive decline, rapid \- Ataxia \- Seizures, refractory \- Myoclonic seizures \- EEG abnormalities \- Sleep disorders \- Cerebral atrophy \- Cerebellar atrophy \- Intracellular accumulation of material resulting in curvilinear profiles on ultrastructural analysis \- Intracellular accumulation of material resulting in fingerprint profiles on ultrastructural analysis \- Intracellular accumulation of material resulting in rectilinear profiles on ultrastructural analysis MISCELLANEOUS \- Onset in childhood (ages 1.5 to 7 years) \- Some patients show normal development until onset of disorder \- Rapidly progressive disorder \- Patients often become wheelchair-bound \- Intracellular accumulation of material can occur in neuronal and nonneuronal cells \- Intracellular accumulation of material may not always be apparent MOLECULAR BASIS \- Caused by mutation in the major facilitator superfamily domain-containing protein-8 gene (MFSD8, 611124.0001 ) ▲ 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	CEROID LIPOFUSCINOSIS, NEURONAL, 7	c0022340	993	omim	https://www.omim.org/entry/610951	2019-09-22T16:03:53	{"doid": ["0110722"], "mesh": ["D009472"], "omim": ["610951"], "orphanet": ["168491", "228366"]}
Hyperesthesia Other namesHyperaesthesia SpecialtyNeurology, psychiatry Hyperesthesia is a condition that involves an abnormal increase in sensitivity to stimuli of the sense. Stimuli of the senses can include sound that one hears, foods that one tastes, textures that one feels, and so forth. Increased touch sensitivity is referred to as "tactile hyperesthesia", and increased sound sensitivity is called "auditory hyperesthesia". In the context of pain hyperaesthesia can refer to an increase in sensitivity where there is both allodynia and hyperalgesia.[1] In psychology, Jeanne Siaud-Facchin uses the term by defining it as an "exacerbation des sens"[2]:37 that characterizes gifted children (and adults): for them, the sensory information reaches the brain much faster than the average, and the information is processed in a significantly shorter time. ## Other animals[edit] Feline hyperesthesia syndrome is an uncommon but recognized condition in cats, particularly Siamese, Burmese, Himalayan, and Abyssinian cats. It can affect cats of all ages, though it is most prevalent in mature animals. The disease can be somewhat difficult to detect as it is characterized by brief bursts of abnormal behavior, lasting around a minute or two.[3] One of its symptoms is also found in dogs that have canine distemper disease (CD) caused by canine distemper virus (CDV).[citation needed] ## References[edit] 1. ^ "IASP Terminology - IASP". www.iasp-pain.org. Retrieved 2020-06-19. 2. ^ Siaud-Facchin, Jeanne (2002). Odile Jacob (ed.). L'enfant surdoué (in French). Paris. p. 338. 3. ^ "Hyperesthesia Syndrome". Cornell Feline Health Center. Retrieved April 11, 2014. ## External links[edit] Classification D * ICD-10: R20.3 * ICD-9-CM: 782.0 * MeSH: D006941 * DiseasesDB: 30788 * v * t * e Symptoms and signs relating to skin and subcutaneous tissue Disturbances of skin sensation * Hypoesthesia * Paresthesia * Formication * Hyperesthesia * Hypoalgesia * Hyperalgesia Circulation * Cyanosis * Pallor * Livedo * Livedo reticularis * Flushing * Petechia * Blanching Edema * Peripheral edema * Anasarca Other * Rash * Desquamation * Induration * Diaphoresis * Mass * Neck mass Skin * Asboe-Hansen sign * Auspitz's sign * Borsari's sign * Braverman's sign * Crowe sign * Dennie–Morgan fold * Darier's sign * Fitzpatrick's sign * Florid cutaneous papillomatosis * Gottron's sign * Hutchinson's sign * Janeway lesion * Kerr's sign * Koebner's phenomenon * Koplik's spots * Leser-Trelat sign * Nikolsky's sign * Pastia's sign * Russell's sign * Wickham striae * Wolf's isotopic response * Munro's microabscess Nails * Aldrich-Mees' lines * Beau's lines * Muehrcke's lines * Terry's nails This medical symptom 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	Hyperesthesia	c0020453	994	wikipedia	https://en.wikipedia.org/wiki/Hyperesthesia	2021-01-18T18:32:02	{"mesh": ["D006941"], "umls": ["C0020453"], "icd-9": ["782.0"], "icd-10": ["R20.3"], "wikidata": ["Q1638131"]}
Functioning gonadotropic adenoma is a very rare pituitary tumor, macroscopically characterized by a soft, well vascularized, variable sized adenoma, with occasional areas of hemorrage or necrosis, that secretes biologically active gonadotropins. In addition to common neurological signs due to mass effect (headache and/or visual field deterioration), additional clinical manifestations include menstrual irregularities (secondary amenorrhea, oligomenorhea or severe menorrhagia), galactorrhea, infertility or ovarian hyperstimulation syndrome (in premenopausal women), testicular enlargement and, occasionally, hypogonadism (in men) and isosexual precocious puberty (in children). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Functioning gonadotropic adenoma	c0346304	995	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91348	2021-01-23T18:04:32	{"umls": ["C0346304"], "icd-10": ["D35.2"], "synonyms": ["Functioning pituitary gonadotropic adenoma", "Gonadotroph adenoma"]}
Linsk et al. (1975) described a sibship, offspring of Sicilian first cousins, in which 4 of 6 sibs in early adulthood developed a clinical disorder in the hematopoietic and immunoglobulin-producing systems. A female sib died at age 21 years with myeloid aplasia. A male sib presented at age 17 with erythroid and plasma cell aplasia with hypogammaglobulinemia. Two other female sibs, aged 21 and 35, had a lymphoproliferative disorder associated with hypogammaglobulinemia. Two affected sibs had absence of leukocyte alkaline phosphatase. Electron microscopy of the peripheral leukocytes from 2 of the affected sibs and 1 of the asymptomatic sibs showed curious intranuclear and intracytoplasmic linear 'crystalloid' structures. Inheritance \- Autosomal recessive Immunology \- Hypogammaglobulinemia Lab \- Absent leukocyte alkaline phosphatase \- Leukocyte intranuclear and intracytoplasmic linear 'crystalloid' structures by electron microscopy Heme \- Myeloid aplasia \- Erythroid aplasia \- Plasma cell aplasia \- Lymphoproliferative disorder ▲ 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	IMMUNOERYTHROMYELOID HYPOPLASIA	c0272167	996	omim	https://www.omim.org/entry/242880	2019-09-22T16:26:20	{"mesh": ["C538361"], "omim": ["242880"]}
## Clinical Features Govrin-Yehudain et al. (2004) reported a 3-generation Druze pedigree in which 4 females presented with juvenile hypertrophy of the breast (JHB; see 113670) and congenital anonychia. They developed rapid and massive breast enlargement at ages 13 to 14 years, before menarche, and underwent breast reduction surgery. Three required subsequent surgery after recurrence of breast enlargement. All were related through their fathers, who had congenital anonychia of the hands and feet, but no other abnormalities. The mothers and sisters of the 4 patients had normal breasts and normal nails. Genzer-Nir et al. (2010) examined 11 affected members, 6 males and 5 females, from the 3-generation Druze pedigree with JHB and congenital anonychia originally reported by Govrin-Yehudain et al. (2004), and proposed the designation 'mammary-digital-nail syndrome.' All affected individuals presented with congenital onychodystrophy and/or anonychia and abnormalities of the distal phalanges (see Cooks syndrome, 106995), involving digitalization of thumbs, hypoplasia of the distal phalanges of the second to fourth digits, total absence of distal phalanx of the fifth digit, bilateral absence of all distal creases of the second to fifth digits, and hypoplasia and complete absence of distal phalanges and nails of the great toes. The JHB phenotype presented only in females, and in the 4 affected postpubertal females, the breasts enlarged dramatically during a 3-month period before and shortly after menarche, reaching enormous proportions. The 4 females had regular menses, normal laboratory evaluation, and no exposure to drug or hormonal therapy. An additional 40 members of the family were examined, including secondary sex characteristics, but no further abnormalities were found. Mapping Genzer-Nir et al. (2010) performed linkage analysis under an assumption of autosomal dominant inheritance with full penetrance in the 3-generation Druze pedigree with mammary-digital-nail syndrome and obtained a maximum lod score of 4.27 at 3 continuous loci, D22S1154, D22S277, and D22S283, within a 30-cM (19.3-Mb) interval on chromosome 22q12.3-q13.1. Haplotype analysis narrowed the critical interval to 12.5 cM (4.3 Mb). Noting that 9 of 30 unaffected family members examined carried the same haplotype as affected individuals, including 3 unaffected offspring of the founding father, Genzer-Nir et al. (2010) suggested that the founder was a germline mosaic for a dominant mutation. Reanalysis of the genotypes under a germline-mosaic model generated a maximum lod score of 4.87 (theta = 0.0) for 4 continuous markers (D22S277, D22S1142, D22S683, and D22S283) in the 12.5-cM critical interval. Molecular Genetics In a 3-generation Druze pedigree with mammary-digital-nail syndrome mapping to chromosome 22q12.3-q13.1, originally reported by Govrin-Yehudain et al. (2004), Genzer-Nir et al. (2010) found no mutations in any of 38 candidate genes selected for sequence analysis. INHERITANCE \- Autosomal dominant CHEST Breasts \- Breast hypertrophy, in females SKELETAL Hands \- Thumbs, digitalized \- Hypoplasia of distal phalanges of second to fourth digits \- Absence of distal phalanx of fifth digit Feet \- Hypoplasia or absence of distal phalanges of great toes SKIN, NAILS, & HAIR Skin \- Absence of all distal creases of second to fifth digits 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	MAMMARY-DIGITAL-NAIL SYNDROME	c3150946	997	omim	https://www.omim.org/entry/613689	2019-09-22T15:57:50	{"omim": ["613689"], "orphanet": ["238744"], "synonyms": ["MDN syndrome", "Onycho-digito-mammary syndrome"]}
"PICA syndrome" redirects here. For the appetite for non-nutritive substances, see Pica (disorder). Lateral medullary syndrome Other namesWallenberg syndrome, posterior inferior cerebellar artery syndrome Medulla oblongata, shown by a transverse section passing through the middle of the olive. (Lateral medullary syndrome can affect structures in upper left: #9=vagus nerve, #10=acoustic nucleus, #12=nucleus gracilis, #13=nucleus cuneatus, #14=head of posterior column and lower sensory root of trigeminal nerve and #19=Ligula.) SpecialtyNeurology Lateral medullary syndrome is a neurological disorder causing a range of symptoms due to ischemia in the lateral part of the medulla oblongata in the brainstem. The ischemia is a result of a blockage most commonly in the vertebral artery or the posterior inferior cerebellar artery.[1] Lateral medullary syndrome is also called Wallenberg's syndrome, posterior inferior cerebellar artery (PICA) syndrome and vertebral artery syndrome.[2] ## Contents * 1 Signs and symptoms * 1.1 Based on location * 2 Cause * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 History * 7.1 Adolf Wallenberg * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] This syndrome is characterized by sensory deficits that affect the trunk and extremities contralaterally (opposite to the lesion), and sensory deficits of the face and cranial nerves ipsilaterally (same side as the lesion). Specifically a loss of pain and temperature sensation if the lateral spinothalamic tract is involved. The cross body finding is the chief symptom from which a diagnosis can be made.[citation needed] Patients often have difficulty walking or maintaining balance (ataxia), or difference in temperature of an object based on which side of the body the object of varying temperature is touching.[2] Some patients may walk with a slant or suffer from skew deviation and illusions of room tilt. The nystagmus is commonly associated with vertigo spells. These vertigo spells can result in falling, caused from the involvement of the region of Deiters’ nucleus.[citation needed] Common symptoms with lateral medullary syndrome may include difficulty swallowing, or dysphagia. This can be caused by the involvement of the nucleus ambiguus, as it supplies the vagus and glossopharyngeal nerves. Slurred speech (dysarthria), and disordered vocal quality (dysphonia) are also common. The damage to the cerebellum or the inferior cerebellar peduncle can cause ataxia. Damage to the hypothalamospinal fibers disrupts sympathetic nervous system relay and gives symptoms that are similar to the symptoms caused by Horner syndrome – such as miosis, anhidrosis and partial ptosis.[citation needed] Palatal myoclonus, the twitching of the muscles of the mouth, may be observed due to disruption of the central tegmental tract. Other symptoms include: hoarseness, nausea, vomiting, a decrease in sweating, problems with body temperature sensation, dizziness, difficulty walking, and difficulty maintaining balance. Lateral medullary syndrome can also cause bradycardia, a slow heart rate, and increases or decreases in the patients average blood pressure.[2] Clinical B1000 diffusion weighted MRI image showing an acute left sided dorsal lateral medullary infarct ### Based on location[edit] Features of lateral medullary syndrome Dysfunction Effects Vestibular nuclei Vestibular system: Vomiting, vertigo, nystagmus Inferior cerebellar peduncle Ipsilateral cerebellar signs including ataxia, dysmetria (past pointing), dysdiadochokinesia Central tegmental tract Palatal myoclonus Lateral spinothalamic tract Contralateral deficits in pain and temperature sensation from body (limbs and torso) Spinal trigeminal nucleus & tract Ipsilateral deficits in pain and temperature sensation from face Nucleus ambiguus \- (which affects vagus nerve and glossopharyngeal nerve) - localizing lesion (all other deficits are present in lateral pontine syndrome as well) Ipsilateral laryngeal, pharyngeal, and palatal hemiparalysis: dysphagia, hoarseness, absent gag reflex (efferent limb—CN X) Descending sympathetic fibers Ipsilateral Horner's syndrome (ptosis, miosis, & anhidrosis) ## Cause[edit] The three major arteries of the cerebellum: the SCA, AICA, and PICA. (Posterior inferior cerebellar artery is PICA.) Human brainstem blood supply description. PICA is#12. It is the clinical manifestation resulting from occlusion of the posterior inferior cerebellar artery (PICA) or one of its branches or of the vertebral artery, in which the lateral part of the medulla oblongata infarcts, resulting in a typical pattern. The most commonly affected artery is the vertebral artery, followed by the PICA, superior middle and inferior medullary arteries.[citation needed] ## Diagnosis[edit] Since lateral medullary syndrome is often caused by a stroke, diagnosis is time dependent. Diagnosis is usually done by assessing vestibular-related symptoms in order to determine where in the medulla that the infarction has occurred. Head Impulsive Nystagmus Test of Skew (HINTS) examination of oculomotor function is often performed, along with computed tomography (CT) or magnetic resonance imaging (MRI) to assist in stroke detection. Standard stroke assessment must be done to rule out a concussion or other head trauma.[2] ## Treatment[edit] Treatment for lateral medullary syndrome is dependent on how quickly it is identified.[2] Treatment for lateral medullary syndrome involves focusing on relief of symptoms and active rehabilitation to help patients return to their daily activities. Many patients undergo speech therapy. Depressed mood and withdrawal from society can be seen in patients following the initial onslaught of symptoms. In more severe cases, a feeding tube may need to be inserted through the mouth or a gastrostomy may be necessary if swallowing is impaired. In some cases, medication may be used to reduce or eliminate residual pain. Some studies have reported success in mitigating the chronic neuropathic pain associated with the syndrome with anti-epileptics such as gabapentin. Long term treatment generally involves the use of antiplatelets like aspirin or clopidogrel and statin regimen for the rest of their lives in order to minimize the risk of another stroke.[2] Warfarin is used if atrial fibrillation is present. Other medications may be necessary in order to suppress high blood pressure and risk factors associated with strokes. A blood thinner may be prescribed to a patient in order to break up the infarction and reestablish blood flow and to try to prevent future infarctions.[3] One of the most unusual and difficult to treat symptoms that occur due to Wallenberg syndrome are interminable, violent hiccups. The hiccups can be so severe that patients often struggle to eat, sleep and carry on conversations. Depending on the severity of the blockage caused by the stroke, the hiccups can last for weeks. Unfortunately there are very few successful medications available to mediate the inconvenience of constant hiccups.[citation needed] For dysphagia symptoms, repetitive transcranial magnetic stimulation has been shown to assist in rehabilitation. Overall, traditional stroke assessment and outcomes are used to treat patients, since lateral medullary syndrome is often caused by a stroke in the lateral medulla.[3] Treatment for this disorder can be disconcerting because some individuals will always have residual symptoms due to the severity of the blockage as well as the location of the infarction. Two patients may present with the same initial symptoms right after the stroke has occurred, but after several months one patient may fully recover while the other is still severely handicapped. This variation in outcome may be due to but not limited to the size of the infarction, the location of the infarction, and how much damage resulted from it.[4] ## Prognosis[edit] The outlook for someone with lateral medullary syndrome depends upon the size and location of the area of the brain stem damaged by the stroke.[2] Some individuals may see a decrease in their symptoms within weeks or months. Others may be left with significant neurological disabilities for years after the initial symptoms appeared.[5] However, more than 85% of patients have seen minimal symptoms present at six months from the time of the original stroke, and have been able to independently accomplish average daily within a year.[6] ## Epidemiology[edit] The lateral medullary syndrome is the most common form of posterior ischemic stroke syndrome. It is estimated that there are around 600,000 new cases of this syndrome in the United States alone.[7] Those at the overall highest risk for lateral medullary syndrome are men at an average age of 55.06. Having a history of hypertension, diabetes and smoking all increase the risk of large artery atherosclerosis.[8] Large artery atherosclerosis is thought to be the greatest risk factor for lateral medullary syndrome due to the deposits of cholesterol, fatty substances, cellular waste products, calcium and fibrin. Otherwise known as plaque build up in the arteries.[9] ## History[edit] The earliest description of lateral medullary syndrome was first written by Gaspard Vieusseux at the Medical and Chirurgical Society of London describing the symptoms observed at the time. Adolf Wallenberg further reinforced these signs after completing his first case report in 1895. He was able to make an accurate localization of the lesion and soon after proved it following a postmortem examination. Wallenberg accomplished three more published articles about lateral medullary syndrome.[10] ### Adolf Wallenberg[edit] Adolf Wallenberg was a renowned neurologist and neuroanatomist most widely known for his clinical descriptions of Lateral Medullary Syndrome. He completed his doctorate at University of Leipzig in 1886. By 1928 he had spent 2 years (1886-1888) as an assistant at the city hospital in Danzig, 21 years (1907-1928) as the director of internal and psychiatric departments and 18 years (1910-1928) as a titular professor. In 1929, Wallenberg received the Erb Commemorative Medal for his work in the field of anatomy, physiology and pathology of the nervous system.[11] Wallenberg's first patient in 1885 was a 38-year-old male suffering from symptoms of vertigo, hypoesthesia, loss of pain and temperature sensitivity, paralysis of multiple locations, ataxia and more. His background in neuroanatomy helped him in correctly locating the patient's lesion to the lateral medulla and connected it to a blockage of the ipsilateral posterior inferior cerebral artery. After the death of his patient in 1899, he was able to prove his findings after a postmortem examination. He continued his work with many patients and by 1922 he had reported his 15th patient with clinicopathological correlations. In 1938, Adolf Wallenberg was forced to end his career as a physician by the German occupation.[11] When the Nazis came to power, he was stripped of his research laboratory and forced to stop working because he was Jewish. He emigrated to Great Britain in 1938, then relocated to the United States in 1943.[citation needed] ## See also[edit] * Alternating hemiplegia of childhood * Benedikt syndrome * Lateral pontine syndrome * Medial medullary syndrome * Weber's syndrome ## References[edit] 1. ^ Lui, Forshing; Anilkumar, Arayamparambil C. (2018), "Wallenberg Syndrome", StatPearls, StatPearls Publishing, PMID 29262144, retrieved 2019-03-11 2. ^ a b c d e f g "Wallenberg syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17. 3. ^ a b "Wallenberg Syndrome". Physiopedia. Retrieved 7 November 2017. 4. ^ http://www.healthline.com/galecontent/wallenberg-syndrome 5. ^ wallenbergs at NINDS 6. ^ "Wallenberg Syndrome". Physiopedia. Retrieved 7 November 2017. 7. ^ DeMyer, William (1998). Neuroanatomy. Williams & Wilkins. ISBN 9780683300758. 8. ^ "Wallenberg Syndrome". Physiopedia. Retrieved 7 November 2017. 9. ^ "Atherosclerosis". American Heart Association. The American Heart Association. Retrieved 29 November 2017. 10. ^ synd/1778 at Who Named It? 11. ^ a b Aminoff, Michael (29 April 2014). Encyclopedia of the Neurological Sciences (Second ed.). Tomah, WI: Academic Press. p. 744. ISBN 9780123851581. Retrieved 30 November 2017. ## External links[edit] Classification D * ICD-10: I66.3 * MeSH: D014854 * DiseasesDB: 10449 External resources * eMedicine: emerg/834 * MRI of Lateral Medullary Infarction (Wallenberg) MedPix Images * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar insufficiency * Subclavian steal syndrome Classification * Brain ischemia * Cerebral infarction * Classification * Transient ischemic attack * Total anterior circulation infarct * Partial anterior circulation infarct Other * CADASIL * Binswanger's disease * Transient global amnesia Haemorrhagic stroke Extra-axial * Epidural * Subdural * Subarachnoid Cerebral/Intra-axial * Intraventricular Brainstem * Duret haemorrhages General * Intracranial hemorrhage Aneurysm * Intracranial aneurysm * Charcot–Bouchard aneurysm Other * Cerebral vasculitis * Cerebral venous sinus thrombosis * v * t * e Symptoms, signs and syndromes associated with lesions of the brain and brainstem Brainstem Medulla (CN 8, 9, 10, 12) * Lateral medullary syndrome/Wallenberg * PICA * Medial medullary syndrome/Dejerine * ASA Pons (CN 5, 6, 7, 8) * Upper dorsal pontine syndrome/Raymond-Céstan syndrome * Lateral pontine syndrome (AICA) (lateral) * Medial pontine syndrome/Millard–Gubler syndrome/Foville's syndrome (basilar) * Locked-in syndrome * Internuclear ophthalmoplegia * One and a half syndrome Midbrain (CN 3, 4) * Weber's syndrome * ventral peduncle, PCA * Benedikt syndrome * ventral tegmentum, PCA * Parinaud's syndrome * dorsal, tumor * Claude's syndrome Other * Alternating hemiplegia Cerebellum * Latearl * Dysmetria * Dysdiadochokinesia * Intention tremor) * Medial * Cerebellar ataxia Basal ganglia * Chorea * Dystonia * Parkinson's disease Cortex * ACA syndrome * MCA syndrome * PCA syndrome * Frontal lobe * Expressive aphasia * Abulia * Parietal lobe * Receptive aphasia * Hemispatial neglect * Gerstmann syndrome * Astereognosis * Occipital lobe * Bálint's syndrome * Cortical blindness * Pure alexia * Temporal lobe * Cortical deafness * Prosopagnosia Thalamus * Thalamic syndrome Other * Upper motor neuron lesion * Aphasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Lateral medullary syndrome	c0043019	998	wikipedia	https://en.wikipedia.org/wiki/Lateral_medullary_syndrome	2021-01-18T18:50:47	{"gard": ["9263"], "mesh": ["D014854"], "umls": ["C0043019"], "wikidata": ["Q2140130"]}
HyHyperinsulism due to UCP2 deficiency (HIUCP2) is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI, see this term) characterized by hypoglycemic episodes from the neonatal period, a good clinical response to diazoxide and a probable transient nature of the disease with spontaneous resolution. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor *[BMI]: body mass index	Hyperinsulinism due to UCP2 deficiency	c4303082	999	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276556	2021-01-23T17:19:21	{"icd-10": ["E16.1"], "synonyms": ["Hyperinsulinemic hypoglycemia due to UCP2 deficiency"]}

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