17q12 duplication occurs when a person has an extra copy of a portion of chromosome 17 . Our genetic information is organized in structures called chromosomes. People with 17q12 duplication have an extra piece of genetic information from chromosome 17. Some people with this duplication do not have any signs or symptoms. Other people may have symptoms including intellectual disability, developmental delay, and behavioral challenges. Some people with 17q12 duplication may also have vision problems. Rarely, people with 17q12 duplication may also have other health problems, such as problems with the heart or kidneys. 17q12 duplication occurs when a portion of chromosome 17 is duplicated.

17q12 duplication is a chromosomal change in which a small piece of chromosome 17 is copied (duplicated ) abnormally in each cell. The duplication occurs on the long (q) arm of the chromosome at a position designated q12. Signs and symptoms related to 17q12 duplications vary significantly, even among members of the same family. Some individuals with the duplication have no apparent signs or symptoms, or the features are very mild. Other individuals can have intellectual disability, delayed development, and a wide range of physical abnormalities.

17q12 microduplication syndrome is a rare chromosomal anomaly with variable phenotypic expression and reduced penetrance associated with developmental delay, mild to severe intellectual disability, speech delay, seizures, microcephaly, behavioral abnormalities, autism spectrum disorder, eye or vision defects (such as strabismus, astigmatism, amblyopia, cataract, coloboma, and microphthalmia), non-specific dysmorphic features, hypotonia, cardiac and renal anomalies, schizophrenia.

Tubulointerstitial nephritis and uveitis Other names Acute tubulointerstitial nephritis and uveitis syndrome Specialty Ophthalmology Tubulointerstitial nephritis and uveitis ( TINU ) is a rare medical condition in which there is uveitis (inflammation of the uvea in the eye) together with tubulointerstitial nephritis (inflammation of the tubules inside the kidney). Contents 1 Symptoms and signs 2 Diagnosis 3 Management 4 Prevalence 5 History 6 References 7 External links Symptoms and signs [ edit ] Uveitis may cause pain of the affected eye together with changes in vision. It may be accompanied by nonspecific systemic symptoms such as fever, involuntary weight loss, fatigue, loss of appetite, abdominal pain, and joint pains. [1] Diagnosis [ edit ] This section is empty. You can help by adding to it . ( August 2017 ) Management [ edit ] This section is empty. You can help by adding to it . ( August 2017 ) Prevalence [ edit ] It is a very rare disease.

A rare renal tubular disease characterized by early-onset tubulointerstitial nephritis associated with anterior uveitis. Epidemiology Approximately 200 cases have been reported in the literature to date. It comprises up to a third of bilateral acute onset acute uveitis in patients younger than 20 years old. Females are predominantly affected with a female:male ratio of 2.5-5:1. Clinical description Presentation is typically in children and adolescents (median age of onset of 15 years old) with either uveitis or tubulointerstitial nephritis.

Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis is a type 2 collagen-related bone disorder characterized by precocious, generalized osteoarthritis (with onset as early as childhood) and mild, dysplastic spinal changes (flattening of vertebrae, irregular endplates and wedge-shaped deformities) resulting in a mildly short trunk.

Wass, John A. H.; Stewart, Paul M. (2011-07-28). Oxford Textbook of Endocrinology and Diabetes .

A rare, endocrine disease characterized by autoimmune Addison disease associated with autoimmune thyroid disease or type I diabetes mellitus, or both, and without chronic candidiasis. Additional endocrine (hypogonadism, hypoparathyroidism) and non-endocrine diseases (vitiligo, autoimmune hepatitis, autoimmune gastritis, pernicious anemia, and myasthenia gravies) may be present.

Autoimmune polyglandular syndrome type 2 is an autoimmune disorder that affects many hormone-producing ( endocrine ) glands. It is characterized by the presence of Addison's disease along with autoimmune thyroid disease and/or type 1 diabetes . Affected individuals may also have problems with other endocrine glands and other common features include primary hypogonadism , myasthenia gravis , and celiac disease . Autoimmune polyglandular syndrome type 2 is diagnosed in adulthood, typically around age 30. The cause of autoimmune polyglandular syndrome type 2 is unknown, although it may involve a combination of genetic and environmental factors.

Pulmonary alveolar microlithiasis Pulmonary alveolar microlithiasis is inherited in an autosomal recessive manner Specialty Pulmonology Pulmonary alveolar microlithiasis (PAM) is a rare, inherited disorder of lung phosphate balance that is associated with small stone formation in the airspaces of the lung . Mutations in the gene SLC34A2 [1] [2] result in loss of a key sodium, phosphate co-transporter (called Npt2b ), known to be expressed in distal alveolar type II cells , as well as in the mammary gland, and to a lesser extent in intestine, kidney, skin, prostate and testes. As the disease progresses, the lung fields become progressively more dense (white) on the chest xray, and low oxygen level, lung inflammation and fibrosis, elevated pressures in the lung blood vessels, and respiratory failure ensue, usually in middle age. The clinical course of PAM can be highly variable, with some patients remaining asymptomatic for decades, and others progressing more rapidly. There is no effective treatment, and the mechanisms of stone formation, inflammation and scarring are not known.

Pulmonary alveolar microlithiasis is a disorder in which many tiny fragments (microliths) of a compound called calcium phosphate gradually accumulate in the small air sacs (alveoli) located throughout the lungs. These deposits eventually cause widespread damage to the alveoli and surrounding lung tissue (interstitial lung disease) that leads to breathing problems. People with this disorder can develop a persistent cough and difficulty breathing (dyspnea), especially during physical exertion. Affected individuals may also experience chest pain that worsens when coughing, sneezing, or taking deep breaths. Pulmonary alveolar microlithiasis is usually diagnosed before age 40.

A rare genetic respiratory disease characterized by widespread intra-alveolar accumulation of minute calcium phosphate microliths, leading to pulmonary fibrosis, pulmonary hypertension, and chronic respiratory failure. Age of onset is highly variable, and most patients are asymptomatic for years or decades, before signs and symptoms like dyspnea on exertion, dry cough, chest pain, hemoptysis, or finger clubbing develop. The disease takes a long-term progressive course. Routine chest radiographs typically show a fine, ''sandstorm-like'' micronodular pattern that is more pronounced in the bases than in the apices.

Pulmonary alveolar microlithiasis is a disorder in which tiny fragments (microliths) of calcium phosphate gradually accumulate in the small air sacs (alveoli) of the lungs. These deposits eventually cause widespread damage to the alveoli and surrounding lung tissue (interstitial lung disease). People with this disorder may also develop a persistent cough and difficulty breathing (dyspnea), especially during physical exertion. Chest pain that worsens when coughing, sneezing, or taking deep breaths is another common feature. People with pulmonary alveolar microlithiasis may also develop calcium phosphate deposits in other organs and tissue of the body.

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-63 can be caused by mutation in the ACSL4 (300157) gene. Clinical Features Raynaud et al. (2000) reported a 4-generation family with nonspecific nonsyndromic X-linked mental retardation. Affected males showed nonprogressive mental retardation ranging from severe to moderate, without seizures, whereas carrier females showed highly variable cognitive capacities, ranging from moderate mental retardation to normal intelligence. Mapping Raynaud et al. (2000) reported a 4-generation family with nonspecific nonsyndromic X-linked mental retardation mapped between DXS990 and DXS1227 (Xq21.33-q27.1) with a maximum lod at theta = 0.0 of 2.14 at DXS1001. Molecular Genetics In the proband of the family reported by Raynaud et al. (2000) as MRX63, Meloni et al. (2002) identified a mutation in the ACSL4 gene (300157.0001).

Clinical Features Martinez et al. (2001) reported a 4-generation family in which 5 males had mild to moderate nonspecific mental retardation. Brain CT scan performed in 1 patient was normal. Inheritance The pedigree pattern in the family with mental retardation reported by Martinez et al. (2001) was consistent with X-linked inheritance. Mapping By typing of markers throughout the X chromosome in a 4-generation family with nonsyndromic mental retardation, Martinez et al. (2001) mapped the phenotype locus to a 2-cM interval between markers DXS8019 and DXS365 on chromosome Xp22.2. Molecular Genetics Exclusion Studies In a family with nonsyndromic mental retardation mapping to Xp22.2, Martinez et al. (2001) performed direct sequencing of the RSK2 gene (300075) but found no causal mutation. They concluded that another unidentified gene for X-linked mental retardation is located near RSK2.

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-104 (MRX104) is caused by mutation in the FRMPD4 gene (300838) on chromosome Xp22. Clinical Features Hu et al. (2016) reported a large family (P58) in which 5 males had mild to severe intellectual disability with variable seizures, poor or absent speech, and behavioral problems. They also reported an unrelated patient (L87) who presented at age 17 years with significant developmental delay, absence of speech, and autism spectrum disorder. Piard et al. (2018) reported follow-up of the patients reported by Hu et al. (2016) and identified 4 additional male patients from 2 additional unrelated families. Including the previous report, there were 10 affected males from 4 unrelated families with patients ranging from 4 to 66 years of age.

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-99 (MRX99) is caused by mutation in the USP9X gene (300072) on chromosome Xp11. Heterozygous mutation in the USP9X gene can also cause female-restricted X-linked syndromic mental retardation-99 (MRXS99F; 300968). Clinical Features Homan et al. (2014) reported 4 patients from 3 unrelated families with X-linked recessive mental retardation. The families were previously ascertained by Tarpey et al. (2009) in a large-scale study that resequenced coding exons of the X chromosome in patients with mental retardation. The patients showed developmental delay, hypotonia, and some behavioral abnormalities, such as aggression.

A number sign (#) is used with this entry because X-linked mental retardation-90 (MRX90) is caused by mutation in the DLG3 (300189) gene on chromosome Xq13. Clinical Features Tarpey et al. (2004) reported 4 families in each of which at least 2 males had moderate to severe nonsyndromic X-linked mental retardation. Philips et al. (2014) reported 2 unrelated Finnish families with MRX90. Three affected males in 1 family (D172) had delayed psychomotor development with speech delay, mild to moderate intellectual disability, narrow thorax, molar hypoplasia, short and upslanting palpebral fissures, high-arched palate, and hypotonia. Five males in the second family (D301) had delayed motor and language development with moderate to severe mental retardation.

A number sign (#) is used with this entry because this form of X-linked mental retardation, referred to as MRX41 or MRX48, is caused by mutation in the GDI1 gene (300104) on chromosome Xq28. Clinical Features Hamel et al. (1996) reported a family segregating mild to moderate mental retardation as an X-linked trait (MRX41). Des Portes et al. (1997) reported a large 3-generation family segregating nonspecific X-linked mental retardation (MRX48). The pedigree suggested X-linked semidominant inheritance: moderate to severe mental retardation was found in 7 males and milder intellectual impairment in 2 females, without any specific clinical, radiologic, or biologic features. Bienvenu et al. (1998) reported a large French family (family R) in which all affected males showed moderate to severe mental retardation.

A number sign (#) is used with this entry because X-linked mental retardation-21 (MRX21) is caused by mutation in the IL1RAPL1 gene (300206) on chromosome Xp21. Description This form of nonsyndromic X-linked mental retardation is characterized by a spectrum of cognitive neurologic impairments or disabilities ranging from moderate mental retardation to high-functioning autism. Males are typically severely affected, but some carrier females may manifest milder deficits (summary by Piton et al., 2008). Clinical Features Kozak et al. (1993) reported a 3-generation Italian family in which 4 male patients had moderate mental retardation without any specific or consistent phenotypic abnormalities. One obligate female carrier had mild retardation and another 2 had normal intelligence, suggesting incomplete penetrance in females.

Clinical Features Golla et al. (2002) reported a family in which 4 males had mild to moderate nonspecific X-linked mental retardation, with no intellectual impairment in their obligate carrier mothers. Mapping By linkage analysis in a family in which 4 affected males had nonsyndromic mental retardation, Golla et al. (2002) obtained the same multipoint lod score of 2.08 for 2 intervals on the X chromosome: one in the pericentromeric region and the other at Xq26. Since the responsible gene was not characterized, haplotyping was the only means available for carrier and prenatal testing for this form of MRX, which they designated MRX42. Carrier risk estimation using pedigree and haplotype data for 5 females at risk was presented, and the difficulties of prenatal diagnosis given linkage to 2 different regions was discussed.

In the first family, designated MRX49, 5 male patients in 2 generations showed mild to moderate mental retardation. By 2-point linkage analysis with 28 polymorphic markers, dispersed over the X chromosome, a maximum lod score of 2.107 was found with markers DXS7107 and DXS8051 at theta = 0.0, localizing the MRX49 locus at Xp22.3-p22.2.

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-1 (MRX1) is caused by hemizygous or heterozygous mutation in the IQSEC2 gene (300522) on chromosome Xp11. Clinical Features Suthers et al. (1988) reported a large family in which multiple males spanning several generations had nonsyndromic X-linked mental retardation. Two developed psychiatric problems and 1 had infrequent seizures. Carrier females were 'less academically able compared to their non-carrier sibs' (Shoubridge et al., 2010). Shoubridge et al. (2010) provided follow-up of a family with X-linked mental retardation reported by Gedeon et al. (1994) as MRX18. Affected males had moderate to severe intellectual disability, and some had seizures.

A number sign (#) is used with this entry because this form of nonspecific X-linked mental retardation is caused by mutation in the FTSJ1 gene (300499). Clinical Features Nonspecific X-linked mental retardation (MRX) includes several distinct entities with mental retardation but without additional distinguishing features. Hamel et al. (1999) described a 4-generation family segregating X-linked mental retardation. Affected members had nonprogressive mental retardation noted during childhood, and several demonstrated aggressive behavior. The mental retardation in tested members of the family was moderate to severe; none of the patients was able to read, write, or solve simple arithmetic problems.

A number sign (#) is used with this entry because of evidence that Tonne-Kalscheuer syndrome (TOKAS) is caused by hemizygous mutation in the RLIM gene (300379) on chromosome Xq13. Description Tonne-Kalscheuer syndrome (TOKAS) is an X-linked recessive multiple congenital anomaly disorder with 2 main presentations. Most patients exhibit global developmental delay apparent from early infancy, impaired intellectual development, speech delay, behavioral abnormalities, and abnormal gait. Affected individuals also have dysmorphic facial features that evolve with age, anomalies of the hands, feet, and nails, and urogenital abnormalities with hypogenitalism. A subset of more severely affected males develop congenital diaphragmatic hernia in utero, which may result in perinatal or premature death.

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-105 (MRX105) is caused by mutation in the USP27X gene (300975) on chromosome Xp11. Clinical Features Hu et al. (2016) reported 2 unrelated families (D177 and L75) in which a total of 7 males had borderline to moderate intellectual disability, variable poor or absent speech, and behavioral problems. No additional clinical details were provided. Inheritance The transmission pattern of MRX105 in the families reported by Hu et al. (2016) was consistent with X-linked recessive inheritance. Molecular Genetics In 3 affected males from a family (D177) with MRX105, Hu et al. (2016) identified a hemizygous truncating mutation in the USP27X gene (300975.0001). An unrelated male patient (family L75) with MRX105 was found to carry a hemizygous missense mutation in the USP27X gene (Y381H; 300975.0002); 3 others males in this family were affected, but genetic studies were not performed.

Clinical Features Vervoort et al. (2002) reported 9 male patients with a mutation in the AGTR2 gene who had moderate to severe mental retardation. Five of the patients had seizures and, with the exception of 1 patient, they were not hypertensive. Two patients also showed autistic behavior. Cytogenetics Vervoort et al. (2002) analyzed a de novo balanced translocation 46,X,t(X;7)(q24;q22) in a female patient with moderate mental retardation. This patient had completely skewed X inactivation. They mapped the X-chromosome breakpoint and demonstrated by RT-PCR that the AGTR2 gene was silenced in this patient. History Vervoort et al. (2002) screened affected males from 33 families with possible X-linked MR but no definitive linkage data, and a large cohort of 552 unrelated male patients with MR of unknown cause but negative for the FMR1 expansion.

A number sign (#) is used with this entry because this form of X-linked mental retardation (MRX19) is caused by mutation in the RPS6KA3 gene (300075). Description X-linked mental retardation-19 (MRX19) is a nonsyndromic form of mild to moderate mental retardation. Carrier females may be mildly affected. Mutation in the RPS6KA3 gene also causes Coffin-Lowry syndrome (CLS; 303600), a mental retardation syndrome with dysmorphic facial features and skeletal anomalies. Some patients with RPS6KA3 mutations have an intermediate phenotype with mental retardation and only mild anomalies reminiscent of CLS. These individuals have mutations resulting in some residual protein function, which likely explains the milder phenotype (summary by Field et al., 2006).

Clinical Features Shoichet et al. (2003) reported a 7-year-old girl with severe developmental delay who had a de novo balanced chromosome rearrangement, t(X;7)(p11.3;q11.21). At age 2 years, she did not yet walk or speak, and she exhibited clearly delayed psychomotor development. At age 3 years 9 months, occasional convulsions, predominantly localized to the shoulders and upper back, were reported, which led to the diagnosis of myoclonic epilepsy. At age 5 years 6 months, her physical development was in the normal range. She had no dysmorphic features. Screening for inborn errors of metabolism resulted in no indication of amino acidopathies or organic acidurias.

Clinical Features Molinari et al. (2008) reported an Australian family with nonsyndromic X-linked mental retardation. Of 5 sibs, there was 1 healthy girl, 2 girls with mild mental retardation, and 2 boys with severe mental retardation. The 2 affected males had a similar phenotype with the same degree of handicap. Both were in educational classes for the moderately handicapped and were able to hold a limited conversation; however, neither learned to read or write. Both were on disability pensions as adults. Their mother was described as slow and was found to carry the mutation.

Clinical Features Annunziata et al. (2003) reported an Italian family in which 9 males in 2 generations had nonspecific moderate to severe mental retardation. Mapping In an Italian family in which 9 males in 2 generations had nonspecific mental retardation, Annunziata et al. (2003) found linkage of the disorder to the pericentromeric region of the X chromosome. Haplotype construction delineated an 8-cM critical region for the locus, which they designated MRX81, at Xp11.2-q12 between DXS1039 and DXS1216. Molecular Genetics Exclusion Studies Annunziata et al. (2003) excluded 2 candidate genes for MRX81: oligophrenin-1 (300127) and ephrin-B1 (300035). INHERITANCE - X-linked recessive NEUROLOGIC Central Nervous System - Mental retardation, moderate to severe MISCELLANEOUS - Based on a report of 9 affected males from one Italian family - No consistent features other than mental retardation - Obligate carrier females have normal intelligence ▲ Close

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-96 (MRX96) is caused by mutation in the SYP gene (313475). Clinical Features Tarpey et al. (2009) identified 4 families with X-linked mental retardation who had mutations in the SYP gene. In 3 families, all with truncating mutations, mental retardation was mild to moderate and there were no consistent additional features, although epilepsy was noted in some individuals. Female carriers had no manifestations. Molecular Genetics The SYP mutations found by Tarpey et al. (2009) in 4 unrelated families with mental retardation included 3 truncating mutations and a missense mutation (313475.0001-313475.0002). INHERITANCE - X-linked recessive NEUROLOGIC Central Nervous System - Mental retardation, mild to moderate - Epilepsy (in some patients) MOLECULAR BASIS - Caused by mutation in the synaptophysin gene (SYP, 313475.0001 ) ▲ Close

A number sign (#) is used with this entry because of evidence that the phenotype is caused by microduplications within a region of chromosome Xp11.22 (chrX:53.0-54.3 Mb) that involve the HSD17B10 (300256) and HUWE1 (300697) genes. Increased dosage of HUWE1 is believed to be responsible for the phenotype (Froyen et al., 2012). Point mutations in the HSD17B10 and HUWE1 genes have been found to cause syndromic forms of mental retardation, MRXS10 (see 300438) and MRXST (309590), respectively. Clinical Features Gedeon et al. (1994) reported a family in which 6 males spanning 3 generations had moderate mental retardation with slow speech development inherited in an X-linked pattern. No significant common dysmorphic features were noted. Donnelly et al. (1996) reported a 4-generation family with multiple males affected with global retardation that became apparent between ages 2 and 4 years.

Clinical Features Hamel et al. (1999) described a 6-generation family segregating X-linked mental retardation. Affected members demonstrated nonprogressive mental retardation during childhood and had large, simple ears, relatively large hands, and normal behavior. The propositus also had clinodactyly of the fifth fingers and flat feet; findings in other affected individuals included short stature, high-arched palate, high nasal bridge, full lips, and large testes. The mental retardation in family MRX45 ranged from mild to severe: most affected members showed higher adaptive than intellectual functioning, and most could read, write, and solve simple arithmetic problems. Cytogenetics In a female patient with severe mental retardation and a de novo translocation t(X;9)(p11.23;q34.3), Kleefstra et al. (2004) characterized the breakpoints and found that the translocation disrupted the ZNF81 gene.

Clinical Features Sismani et al. (2003) reported a Greek family with apparently nonsyndromic X-linked mental retardation. The affected males had moderate to severe mental retardation, severe speech problems, and aggressive behavior. Mapping Sismani et al. (2003) performed linkage analysis on a Greek family with apparently nonsyndromic X-linked mental retardation. Two-point linkage analysis with 26 polymorphic markers spanning the entire X chromosome allowed assignment of the causative gene to a 27-Mb interval in Xq12-q21.3. Molecular Genetics Exclusion Studies In affected members of a family segregating X-linked mental retardation, Sismani et al. (2003) performed DNA analysis of 3 known or candidate MRX genes from the Xq12-q21 region, OPHN1 (300127), ATRX (300032), and RSK4 (300303), and found no mutations.

Clinical Features Yntema et al. (1998) reported a large Dutch family in which 12 males in 3 generations were affected with nonspecific X-linked mental retardation. Of 9 examined patients, 6 showed moderate mental retardation, and 1 each showed mild, severe, and profound mental retardation. Obligate female carriers were all normal. Mapping Linkage analysis of the family reported by Yntema et al. (1998) yielded a maximum lod score of 5.12 at HPRT between DXS8072 and DXS294 at Xq25-q26. Cytogenetics Kutsche et al. (2000) studied a male patient with severe mental retardation, mildly dysmorphic features, and sensorineural hearing loss who carried an apparently balanced X;21 translocation with breakpoints in Xq26 and 21p11. His unaffected mother carried the same translocation (von Ballestrem et al., 1996).

Clinical Features Lehrke (1974) described a nonspecific form of X-linked mental retardation in a large kindred designated family 1. The pedigree was updated by Howard-Peebles and Roberts (1984). Affected males had lower verbal IQs than performance IQs. Several of the affected males had performance IQs above 80; however, because of the lower (12.3 points on average) verbal IQs, they were considered retarded. Mapping Gregg et al. (1996) mapped the gene for this form of X-linked mental retardation, designated MRX23, to Xq23-q24 by linkage studies in the large kindred (family 1) of Lehrke (1974). Multipoint linkage analysis gave a maximum lod score of 6.7 between markers DXS1220 and DXS424.

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-72 (MRX72) is caused by hemizygous mutation in the RAB39B gene (300774) on chromosome Xq28. Mutation in the RAB39B gene can also cause X-linked recessive mental retardation with early-onset Parkinson disease, known as Waisman syndrome (WSMN; 311510). Clinical Features Russo et al. (2000) reported a 3-generation Sardinian family segregating X-linked mental retardation. Three affected individuals had seizures and 1 had features of autism (see 209850). Giannandrea et al. (2010) reported a large family with X-linked mental retardation spanning 2 generations.

A number sign (#) is used with this entry because nonsyndromic X-linked mental retardation-58 is caused by mutation in the TM4SF2 gene (TSPAN7; 300096) on chromosome Xp11. Clinical Features Holinski-Feder et al. (1999) described an Austrian family with nonsyndromic X-linked mental retardation. The 5 affected males in the family had mild to moderate mental retardation and no consistent dysmorphic features, while obligatory carrier females were normal. Mapping By linkage analysis in an Austrian family with nonsyndromic X-linked mental retardation, Holinski-Feder et al. (1999) mapped the disorder locus to an X pericentromeric location, with flanking markers DXS989 and DXS1111, with a maximum multipoint lod score of 2.09. Molecular Genetics In the affected family reported by Holinski-Feder et al. (1999), Abidi et al. (2002) identified a 2-bp deletion (300096.0003) in the TM4SF2 gene, resulting in a premature stop codon and truncated protein.

Clinical Features Gendrot et al. (1994) reported a French family in which 9 persons had moderate mental deficiency and poor speech in 3 generations. Some of the patients had facial dysmorphism, epilepsy, and macroorchidism. Mapping By linkage analysis in a family segregating mental retardation, Gendrot et al. (1994) found no recombination between the disease locus, designated MRX14, and 2 loci: DXS255 at Xp11.22 (maximum lod = 3.31 at theta = 0) and PGKP1 at Xq11.2-q12 (maximum lod = 3.08 at theta = 0). In a note added in proof, Gendrot et al. (1994) stated that they had found a recombination with MAOB (309860) at Xp11.3, reducing the linkage interval to Xp11.3-q13.3. GU - Macroorchidism Neuro - Moderate mental deficiency - Poor speech - Epilepsy Facies - Facial dysmorphism Inheritance - X-linked ▲ Close

IQSEC2 is a genetic condition that causes intellectual disability and sometimes other physical, neurological, or psychiatric symptoms. People with this condition can have seizures that are often difficult to control with medications. Other symptoms may include motor and language development delay, regression of learning abilities, autistic-like behavior, characteristic hand movements, and behavioral problems. Physical features may include abnormal head shape (plagiocephaly), very small head (microcephaly), reduced muscle tone (hypotonia), and crossed eyes (strabismus). This condition is caused by mutations in the IQSEC2 gene, which is located on chromosome X .

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.

A number sign (#) is used with this entry because of evidence that X-linked mental retardation-107 (MRX107) is caused by hemi- or heterozygous mutation in the CXORF56 gene (301012) on chromosome Xq24. One such family has been reported. Clinical Features Verkerk et al. (2018) reported a large 3-generation Dutch family in which 5 males and 1 female had mild to moderate intellectual disability. The patients had delayed development but were able to attend special schools, and some were able to work in a sheltered environment. Two males had significant behavioral problems, such as pervasive developmental disorder, attention disorder, hyperactivity, and transgressive behavior. The patients had variable dysmorphic facial features, including long, narrow face, prominent chin, upward slanting palpebral fissures, flat philtrum, narrow upper lip, and large ears with prominent cruxes.

Clinical Features Lugtenberg et al. (2006) studied a family in which 6 males in 3 generations had moderate to severe nonsyndromic mental retardation in an X-linked pattern of inheritance (XLMR). The 17-year-old proband had an IQ of 45. His mother had normal intelligence. He was the second son of unrelated parents and had 1 affected brother, 3 healthy sisters, and 1 carrier sister with borderline intelligence. Mapping The family reported by Lugtenberg et al. (2006) segregating X-linked mental retardation had previously been studied (family T40) by Raynaud et al. (2000), who found evidence of linkage of mental retardation to Xp11.3. History In a family in which 6 males in 3 generations had moderate to severe nonsyndromic mental retardation in a pattern consistent with X-linked recessive inheritance, Lugtenberg et al. (2006) identified a 352G-T transversion in exon 6 of ZNF674 cDNA, predicted to result in a glu118-to-ter (E118X; 300573.0001) truncated protein containing the Kruppel-associated box domains but lacking the zinc finger domains, which are crucial for DNA binding.

A number sign (#) is used with this entry because of evidence that this form of nonsyndromic X-linked mental retardation (MRX97) is caused by hemizygous mutation in the ZNF711 gene (314990) on chromosome Xq21. Clinical Features Yntema et al. (1999) reported a family (MRX65) in which 6 males in 3 generations had mild to moderate intellectual disability with speech delay. Four patients were obese. Van der Werf et al. (2017) provided follow-up of this family, noting that dysmorphic features included a broad face and prominent forehead. Van der Werf et al. (2017) reported another 4-generation family in which 5 males had mild to moderate intellectual disability, most often with motor delay and poor speech. Two had autistic features. Variable dysmorphic features included long face, synophrys, and relatively large ears.

Clinical Features Martinez et al. (2004) described a Basque family in which 5 males in 4 sibships in 2 generations had nonsyndromic mental retardation. Mapping In a Basque family with nonsyndromic mental retardation, Martinez et al. (2004) found linkage to Xq24-q25 with a maximum lod score of 2.4. Haplotype studies and multipoint linkage analysis suggested a localization of the MRX82 locus to an interval of 7.6 Mb defined by markers DXS6805 and DXS7346, in Xq24 and Xq25, respectively. The linked interval contained the gene encoding glutamate receptor-3 (GRIA3; 305915), but mutation analysis showed no pathologic changes. INHERITANCE - X-linked recessive SKELETAL Spine - Kyphosis - Scoliosis NEUROLOGIC Central Nervous System - Mental retardation, mild to profound - Seizures (patient A) - Abnormal EEG (patient B) - Postnatal hypotonia (patient A) - Normal cerebral CT scan (patient A) Behavioral Psychiatric Manifestations - Autistic behavior (patient A) MISCELLANEOUS - Based on a report of an extended ethnically Basque family ▲ Close

Clinical Features Zhang et al. (2004) reported a Chinese family in which 3 males in 3 generations had nonspecific X-linked mental retardation. The obligate carrier females were not affected. Mapping By 2-point linkage analysis, Zhang et al. (2004) demonstrated linkage of nonspecific mental retardation in a Chinese family to several markers located at Xq22.2, with a maximum lod score of 2.41 at theta = 0.0 for 2 adjacent markers (DXS1191 and DXS1230). Recombination events were observed with flanking markers DXS8080 and DXS456, located at Xp11.3 and Xq22.3, respectively, and a region of approximately 22.3 cM was defined. The localized region observed in this family overlapped with 29 other MRX loci previously reported in Xp11.3-q22.3. INHERITANCE - X-linked recessive GROWTH Height - Short stature HEAD & NECK Face - Broad forehead NEUROLOGIC Central Nervous System - Mental retardation, mild to moderate MISCELLANEOUS - No characteristic pattern of anomalies ▲ Close

Clinical Features Proops et al. (1983) reported a Japanese family (family F) living in Hawaii with mental retardation in 3 generations. Affected males were mildly or moderately retarded, while a number of heterozygous females were mildly retarded. The affected males were relatively short with a large head, highly arched palate, square face, prominent ears, and large testicular volumes. Their speech was limited and characterized by repetitive phrases or inflections. Affected males and females were described as having a pleasant demeanor.

A number sign (#) is used with this entry because this form of nonspecific X-linked mental retardation is caused by mutation in the ARX gene (300382) on chromosome Xp21. Description ARX-related mental retardation is a form of nonsyndromic X-linked mental retardation. It is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1; 308350) to Partington syndrome (309510) (Kato et al., 2004; Wallerstein et al., 2008). Clinical Features Hamel et al. (1999) described a two 4-generation families (MRX43 and MRX52) segregating X-linked mental retardation. Affected members in family MRX43 had moderate to profound nonprogressive mental retardation recognized in early childhood.

Clinical Features Ahmad et al. (2001) described a large Pakistani family with X-linked nonspecific mental retardation. Mapping By linkage analysis in a Pakistani family segregating nonsyndromic mental retardation, Ahmad et al. (2001) identified a novel disease locus, MRX53, located in a critical region spanning approximately 15 cM between DXS1210 and DXS1047 on Xq22.2-q26. A lod score of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081. INHERITANCE - X-linked recessive NEUROLOGIC Central Nervous System - Mental retardation (IQ between 45-50) - Normal gross motor development MISCELLANEOUS - Based on a report of 8 affected males in one Pakistani family ▲ Close

Clinical Features Claes et al. (1997) added 2 families to the growing list of nonspecific X-linked mental retardation (XLMR) families in which the disease gene could be mapped to a specific site on the X chromosome. The first family reported was designated MRX49 (300114). The second of these families, designated MRX50, contained 4 males in 2 generations showing moderate mental retardation. Mapping Linkage analysis in the MRX50 family by Claes et al. (1997) showed location of the locus at Xp11.3-p11.21 in the pericentromeric part of the short arm of the X chromosome, overlapping with a large number of other MRX gene regions: MRX1 (309530), MRX5, MRX7, MRX8, MRX9 (309549), MRX10, MRX11, MRX12 (300957), MRX13, MRX14 (300062), MRX15, MRX18, MRX22, MRX26, MRX31, and MRX38 (see 300419). Gedeon et al. (1996) hypothesized that all of the MRX assignments clustered on the pericentromeric part of Xp could be accounted for by 2 gene locations, namely the MRX1 and the MRX10 locations. Some of these families with pericentromeric gene locations show additional characteristic abnormalities and some of them show manifestations of disease in heterozygous carriers.

Description Impaired mental functioning occurs as an isolated feature or as part of many syndromes listed in the X-linked catalog. Mental retardation that is not associated with other distinguishing features is referred to as 'nonspecific.' The Human Gene Mapping Nomenclature Committee (Mulley et al., 1992) proposed to designate each newly reported apparently unique X-linked mental retardation (MRX) family with gene symbols (e.g., MRX1, MRX2) if a minimal lod score of 2.0 was demonstrated between the MR locus and 1 or more X chromosome markers. Mapping Lazzarini et al. (1995) reported a family with MRX20. Fragile X syndrome was excluded cytogenetically and by absence of linkage to the Xq27.3 region. On the other hand, linkage studies using short tandem repeat polymorphism (STRP) markers indicated that the mutation is at a locus in the centromeric region of the X chromosome.

Overview Ebstein anomaly is a rare heart problem that's present at birth. That means it's a congenital heart defect. In this condition, the valve that separates the top and bottom right heart chambers does not form correctly. This valve is called the tricuspid valve. As a result, the valve does not close as it should. Blood moves backward from the bottom to top chamber, making it harder for the heart to work. In people with Ebstein anomaly, the heart can grow larger. The condition can lead to heart failure.

Ebstein's malformation is a rare congenital cardiac anomaly characterized by rotational displacement of the septal and inferior leaflets of the tricuspid valve such that they are hinged within the right ventricle, rather than as expected at the atrioventricular junction. Epidemiology Prevalence is estimated at 1/50,000-1/200,000. Both sexes are equally affected. Clinical description Clinical presentation is heterogeneous and depends on the severity of the lesion (extent of tethering of the antero-superior leaflet across the normal valvar orifice), and the degree of dysfunction of the right ventricle. Patients with minor forms of the disease remain asymptomatic or may present with an incidental murmur, exertional dyspnea, fatigue, or palpitations. Those with severe forms can present at various ages with arrhythmias, cyanosis, and sometimes cardiac failure.

Tricuspid valve disease that is a congenital heart defect in which the septal leaflet of the tricuspid valve is displaced towards the apex of the right ventricle of the heart Ebstein's anomaly Pathological specimen and ultrasound image of a heart with Ebstein's anomaly: Abbreviations: RA: right atrium; ARV: atrialized right ventricle; FRV: functional right ventricle; AL: anterior leaflet; SL: septal leaflet; LA: left atrium; LV: left ventricle; asterisk: grade II tethering of the tricuspid septal leaflet Specialty Cardiology Ebstein's anomaly is a congenital heart defect in which the septal and posterior leaflets of the tricuspid valve are displaced towards the apex of the right ventricle of the heart . It is classified as a critical congenital heart defect [1] accounting for <1% of all congenital heart defects presenting in ≈1 per 200,000 live births. [2] Contents 1 Signs and symptoms 1.1 Related abnormalities 1.1.1 Anatomic abnormalities 1.1.2 Electrophysiologic abnormalities 2 Risk factors 3 Treatment 3.1 Medication 3.2 Surgery 4 History 5 References 6 External links Signs and symptoms [ edit ] The annulus of the valve is still in the normal position. The valve leaflets, however, are to a varying degree, attached to the walls and septum of the right ventricle. A subsequent "atrialization" of a portion of the morphologic right ventricle (which is then contiguous with the right atrium) is seen. This causes the right atrium to be large and the anatomic right ventricle to be small in size.

Ebstein's anomaly is a rare heart defect in which parts of the tricuspid valve (which separates the right ventricle from the right atrium) are abnormal. The abnormality causes the tricuspid valve to leak blood backwards into the right atrium. The backup of blood flow can lead to heart swelling and fluid buildup in the lungs or liver. Sometimes, not enough blood gets out of the heart into the lungs and the person may appear blue. Symptoms range from mild to very severe. Treatment depends on the severity of the defect and may include medications, oxygen therapy, or surgery.

A number sign (#) is used with this entry because of evidence that Carpenter syndrome-2 (CRPT2) is caused by homozygous or compound heterozygous mutation in the MEGF8 gene (604267) on chromosome 19q13. Description Carpenter syndrome-2 is an autosomal recessive multiple congenital malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet, in association with abnormal left-right patterning and other features, most commonly obesity, umbilical hernia, cryptorchidism, and congenital heart disease (summary by Twigg et al., 2012). For a discussion of genetic heterogeneity of Carpenter syndrome, see 201000. Clinical Features Altunhan et al. (2011) described a Turkish boy who was born with acrocephaly and a peculiar facies characterized by frontal bossing. Digital abnormalities included clinodactyly of the fifth fingers, membranous syndactyly of fingers 3 and 4, syndactyly of toes 1 and 2, and preaxial polydactyly of the big toes bilaterally.

A rare syndromic craniosynostosis with variable phenotypic expression characterized by craniosynostosis, intellectual disability, distinctive facies, abnormalities of the fingers and toes (brachydactyly, polydactyly and syndactyly), short stature, congenital heart disease, skeletal defects, obesity, genital abnormalities and umbilical hernia. Epidemiology Over 70 cases have been described in the literature. Clinical description Presentation at birth is with macrosomia, umbilical hernia and craniosynostosis which ranges from cloverleaf configuration to predominant involvement of the metopic ridge to craniofacial asymmetry. Cranial anomalies may lead to raised intercranial pressure, difficulty in articulation, frequent otitis media and resultant hearing loss. Typical abnormalities of the digits include brachydactyly, cutaneous syndactyly, preaxial polydactyly in the toes and postaxial polydactlyly in the hands with broad thumbs and absent middle phalanges. Characteristic facial features may include flat nasal bridge with epicanthal folds, down-slanting palpebral fissures, corneal anomalies, low-set, posteriorly rotated malformed ears, and an underdeveloped maxilla and mandible.

Carpenter syndrome Other names Acrocephalopolysyndactyly type II Specialty Medical genetics Carpenter syndrome , also called acrocephalopolysyndactyly type II , [1] is an extremely rare autosomal recessive [2] congenital disorder characterized by craniofacial malformations, obesity , and syndactyly . [2] It was first characterized in 1909, and is named for George Alfred Carpenter . [3] [4] Contents 1 Presentation 1.1 Description 2 Genetics 3 Diagnosis 3.1 Types 4 Treatment 5 Occurrence 6 See also 7 References 8 External links Presentation [ edit ] Carpenter syndrome presents several features: [ citation needed ] Tower-shaped skull ( craniosynostosis ) Additional or fused digits (fingers and toes) Obesity Reduced height Intellectual disability is also common with the disorder, although some patients may have average intellectual capacity. [5] Description [ edit ] Carpenter Syndrome belongs to a group of rare genetic disorders known as acrocephalopolysyndactyly, abbreviated ACPS (RN, 2007). There were originally five types of ACPS, but this number has been decreased because they have been found to be closely related to one another or to other disorders (Paul A. Johnson, 2002). The most common physical manifestation of Carpenter Syndrome is early fusing of the fibrous cranial sutures which results in an abnormally pointed head. The fusion of the skull bones is evident from birth (National Organization for Rare Disorders, Inc., 2008). Babies’ mobile cranial bones form a cone shape as they pass through the birth canal and soon thereafter return to a normal shape; however, a baby affected by carpenter syndrome maintains a cone shaped head.

Carpenter syndrome is a condition characterized by premature fusion of skull bones (craniosynostosis); finger and toe abnormalities; and other developmental problems. The features in affected people vary. Craniosynostosis can give the head a pointed appearance; cause asymmetry of the head and face; affect the development of the brain; and cause characteristic facial features. Other signs and symptoms may include dental abnormalities; vision problems; hearing loss; heart defects; genital abnormalities; obesity; various skeletal abnormalities; and a range of intellectual disability. Carpenter syndrome can be caused by mutations in the RAB23 or MEGF8 gene and is inherited in an autosomal recessive manner. Treatment focuses on the specific features in each affected person. Life expectancy is shortened but very variable.

Geniospasm is movement disorder of the mentalis muscle. Geniospasm Other names Hereditary geniospasm Mentalis muscle Specialty Neurology It is a benign genetic disorder linked to chromosome 9q13-q21 [1] where there are episodic involuntary up and down movements of the chin and lower lip . The movements consist of rapid fluttering or trembling at about 8 Hz superimposed onto a once per three seconds movement of higher amplitude and occur symmetrically in the V shaped muscle. The tongue and buccal floor muscles may also be affected but to a much lesser degree. The movements are always present but extreme episodes may be precipitated by stress, concentration or emotion and commence in early childhood. The condition is extremely rare and in a study in 1999 only 23 families in the world were known to be affected, [ citation needed ] although it may be under-reported.

Hereditary geniospasm is a movement disorder that causes episodes of involuntary tremors of the chin and lower lip. The episodes may last anywhere from a few seconds to hours and may occur spontaneously or be brought on by stress. The episodes usually first appear in infancy or childhood and tend to lessen in frequency with age. Hereditary geniospasm is believed to be inherited in an autosomal dominant pattern . Although the exact gene that causes the condition is unknown, it has been suggested that mutations in a gene on chromosome 9 may be responsible in some families.

Hereditary geniospasm is a movement disorder characterized by episodes of involuntary tremor of the chin and lower lip. Epidemiology The disorder has been described in less than 25 families from Europe and the USA, with a slight male preponderance (male-to-female ratio of 1.3:1). Clinical description Onset usually occurs in childhood and may be precipitated by stress and emotion. Episodes may occur during sleep. There are no associated neurological abnormalities, although abnormal EEG, sleep disorders and involvement of other facial muscles have occasionally been described. Spontaneous improvement with age is possible. Etiology A locus has been identified at 9q13-q21 in a single four-generation British family.

Complement 2 deficiency Specialty Hematology Complement 2 deficiency is a type of complement deficiency caused by any one of several different alterations in the structure of complement component 2 . It has been associated with an increase in infections . [1] [2] It can present similarly to systemic lupus erythematosus (SLE). [3] References [ edit ] ^ Alper CA, Xu J, Cosmopoulos K, et al. (July 2003). "Immunoglobulin deficiencies and susceptibility to infection among homozygotes and heterozygotes for C2 deficiency" (PDF) . J. Clin. Immunol . 23 (4): 297–305. doi : 10.1023/A:1024540917593 . PMID 12959222 . ^ Sherwood L. Gorbach; John G. Bartlett; Neil R. Blacklow (2004). Infectious diseases .

Complement component 2 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and viruses. People with complement component 2 deficiency have a significantly increased risk of recurrent bacterial infections, specifically of the lungs (pneumonia), the membrane covering the brain and spinal cord (meningitis), and the blood (sepsis ), which may be life-threatening. These infections most commonly occur in infancy and childhood and become less frequent in adolescence and adulthood. Complement component 2 deficiency is also associated with an increased risk of developing autoimmune disorders such as systemic lupus erythematosus (SLE) or vasculitis.

Complement component 2 deficiency (C2D) is a genetic condition that affects the immune system. Signs and symptoms include recurrent bacterial infections and risk for a variety of autoimmune conditions . Infections can be very serious and are common in early life. They become less frequent during the teen and adult years. The most frequent autoimmune conditions associated with C2D are lupus (10-20%) and vasculitis. C2D is caused by mutations in the C2 gene and is inherited in an autosomal recessive fashion.

A rare low-grade astrocytoma characterized by a benign, slowly growing lesion typically arising in the wall of the lateral ventricles, composed of large ganglioid astrocytes. The tumor corresponds to WHO grade I and typically occurs during the first two decades of life in patients with tuberous sclerosis complex. Most patients present with worsening of epilepsy or symptoms of increased intracranial pressure.

A number sign (#) is used with this entry because of evidence that autosomal recessive hypohidrotic ectodermal dysplasia-11B (ECTD11B) can be caused by homozygous mutation in the EDAR (604095)-associated death domain gene (EDARADD; 606603) on chromosome 1q42-q43. Description Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Hypohidrotic, or anhidrotic, ectodermal dysplasia (HED/EDA) is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis). Typical clinical manifestations also include dryness of the skin, eyes, airways, and mucous membranes presumably due to the defective development of several exocrine glands. Hypohidrotic ectodermal dysplasia can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose, and prominent lips) and occasionally with absent nipples (summary by Cluzeau et al., 2011).

A number sign (#) is used with this entry because autosomal dominant ectodermal dysplasia-11A (ECTD11A) is caused by heterozygous mutation in the EDAR (604095)-associated death domain gene (EDARADD; 606603) on chromosome 1q42-q43. Description Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Hypohidrotic, or anhidrotic, ectodermal dysplasia (HED/EDA) is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis). Typical clinical manifestations also include dryness of the skin, eyes, airways, and mucous membranes presumably due to the defective development of several exocrine glands. Hypohidrotic ectodermal dysplasia can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose, and prominent lips) and occasionally with absent nipples (summary by Cluzeau et al., 2011).

A number sign (#) is used with this entry because X-linked hypohidrotic ectodermal dysplasia-1 (ECTD1) is caused by mutation in the gene encoding ectodysplasin-A (EDA; 300451) on chromosome Xq13. Description Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Hypohidrotic, or anhidrotic, ectodermal dysplasia (HED/EDA) is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis). Typical clinical manifestations also include dryness of the skin, eyes, airways, and mucous membranes presumably due to the defective development of several exocrine glands. Hypohidrotic ectodermal dysplasia can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose, and prominent lips) and occasionally with absent nipples.

Genotype/Phenotype Correlations Van der Hout et al. (2008) identified mutations in the EDAR gene in 5 (28%) of 18 EDA-negative probands with hypohidrotic ectodermal dysplasia.

Keratoderma hereditarium mutilans is a rare, diffuse, mutilating, hereditary palmoplantar keratoderma disorder characterized by severe, honeycomb-pattern palmoplantar keratosis and pseudoainhum of the digits leading to autoamputation, associated with mild to moderate congenital sensorineural hearing loss. Additional features include stellate keratosis on the extensor surfaces of the fingers, feet, elbows and knees. Alopecia, onychogryphosis, nail dystrophy or clubbing, spastic paraplegia and myopathy may also be associated.

Vohwinkel syndrome is a disorder with classic and variant forms, both of which affect the skin. In the classic form of Vohwinkel syndrome, affected individuals have thick, honeycomb-like calluses on the palms of the hands and soles of the feet (palmoplantar keratoses) beginning in infancy or early childhood. Affected children also typically have distinctive starfish-shaped patches of thickened skin on the tops of the fingers and toes or on the knees. Within a few years they develop tight bands of abnormal fibrous tissue around their fingers and toes (pseudoainhum); the bands may cut off the circulation to the digits and result in spontaneous amputation. People with the classic form of the disorder also have hearing loss. The variant form of Vohwinkel syndrome does not involve hearing loss, and the skin features also include widespread dry, scaly skin (ichthyosis), especially on the limbs.

Vohwinkel syndrome is an inherited condition that affects the skin. People with the "classic form" generally have honeycomb-patterned calluses on the palms of the hands and the soles of the feet (palmoplantar keratoses); constricting bands of tissue on the fingers and toes which can cause amputation; starfish-shaped, thickened skin on the tops of the fingers and knees; and hearing loss. A "variant form" of Vohwinkel syndrome has also been identified which is characterized by ichthyosis in addition to the classic skin abnormalities and is not associated with hearing loss. Classic Vohwinkel syndrome is caused by changes (mutations) in the GJB2 gene and the variant form is caused by mutations in the LOR gene. Both are inherited in an autosomal dominant manner. Although there is currently no cure for the condition, treatments are available to alleviate symptoms.

Overview A molar pregnancy is a rare complication of pregnancy. It involves unusual growth of cells called trophoblasts. These cells typically become the organ that feeds a growing fetus. That organ also is known as the placenta. There are two types of molar pregnancy — complete molar pregnancy and partial molar pregnancy. In a complete molar pregnancy, the placental tissue swells and appears to form fluid-filled cysts. There is no fetus. In a partial molar pregnancy, the placenta might have both regular and irregular tissue.

Recurrent hydatidiform mole is a condition that affects women and is characterized by the occurrence of at least two abnormal pregnancies that result in the formation of hydatidiform moles. A hydatidiform mole is a mass that forms early in pregnancy and is made up of cells from an abnormally developed embryo and placenta. Normally, the embryo would develop into a fetus and the placenta would grow to provide nutrients to the growing fetus. When a hydatidiform mole occurs once, it is known as sporadic hydatidiform mole; if it happens again, the condition is known as recurrent hydatidiform mole. The first symptom of a hydatidiform mole is often vaginal bleeding in the first trimester of pregnancy.

A number sign (#) is used with this entry because of evidence that recurrent hydatidiform mole-1 (HYDM1) is caused by homozygous or compound heterozygous mutation in the NLRP7 gene (609661) on chromosome 19q13. Description A hydatidiform mole is an abnormal pregnancy characterized by hydropic placental villi, trophoblastic hyperplasia, and poor fetal development. Familial recurrent hydatidiform mole is an autosomal recessive condition in which women experience recurrent pregnancy losses, predominantly complete hydatidiform mole (CHM). However, unlike sporadic CHMs, which are androgenetic with 2 paternal chromosome complements, CHMs associated with familial recurrence are genetically biparental in origin with both a maternal and a paternal contribution to the genome. Other pregnancy losses in this condition include partial hydatidiform mole, stillbirths, ectopic pregnancies, early neonatal deaths, and miscarriages, some of which may be undiagnosed molar pregnancies.

A hydatidiform mole is a benign gestational trophoblastic disease developing during pregnancy. Resulting from an abnormal fertilization characterized by trophoblastic proliferation, normal embryo development is rendered impossible. Hydatidiform moles can be either complete or partial. Epidemiology The condition appears to occur in approximately 1/1,000 pregnancies and in 1/41 miscarriages in Europe. Clinical description Complete moles are asymptomatic in 40% of cases. Most often, a mole is detected upon suspicion of miscarriage in the first trimester, with bleeding and pelvic pain.

Molar pregnancy is a condition in which the placenta does not develop properly. The symptoms of molar pregnancy, which may include vaginal bleeding, severe morning sickness, stomach cramps, and high blood pressure, typically begin around the 10th week of pregnancy. Because the embryo does not form or is malformed in molar pregnancies, and because there is a small risk of developing a cancer called choriocarcinoma , a D&C is usually performed.

Wild-type transthyretin amyloid ( WTTA ), also known as senile systemic amyloidosis ( SSA ) and abbreviated as ATTR , [1] is a disease that typically affects the heart and tendons of elderly people. It is caused by accumulation of a wild-type (that is to say a normal ) protein called transthyretin . This is in contrast to a related condition called transthyretin-related hereditary amyloidosis where a genetically mutated transthyretin protein tends to deposit at a much earlier age than in WTTA, due to abnormal conformation and bioprocessing. It belongs to a group of diseases called amyloidosis , chronic progressive conditions linked to abnormal deposition of normal or abnormal proteins, because these proteins are misshapen and cannot be properly degraded and eliminated by the cell metabolism. Contents 1 Signs and symptoms 2 Natural course 3 Diagnosis 4 Treatment 4.1 Orphan drug status for transthyretin (TTR) amyloidosis 5 See also 6 References 7 External links Signs and symptoms [ edit ] Wild-type transthyretin amyloid accumulates mainly in the heart , where it causes stiffness and often thickening of its walls, leading consequently to shortness of breath and intolerance to exercise, called diastolic dysfunction .

Wandering spleen is a rare condition that occurs when the spleen lacks one or more of the ligments that hold the spleen in its normal position in the upper left abdomen. If a person is born with this condition it is referred to as congenital wandering spleen. The condition is not hereditary. Acquired wandering spleen may occur during adulthood due to injuries or other underlying conditions that may weaken the ligaments that hold the spleen. Symptoms of wandering spleen may include englargement of the spleen ( splenomegaly ), abdominal pain, intestinal obstruction, nausea, vomiting, fever, and a lump in the abdomen or the pelvis. Some individuals with this condition do not have symptoms. Treatment for this condition involes removal of the spleen ( splenectomy ).