Fluorescence in situ hybridization (FISH) with specific probes is needed to detect a low level mosaicism. The diagnosis, suspected on the basis of clinical manifestations, is based on cytogenetic testing showing the presence of extra material derived from chromosome 22q11. Other cytogenetic anomalies have been rarely reported, including partial trisomy of chromosome 22 and intrachromosomal triplication of the 22q11 region. In one third of cases, this extra chromosome is present in a mosaic state. Most patients harbor a small supernumerary bisatellited marker chromosome (sSMC) that results in partial tetrasomy of 22pter-22q11. Short stature with growth hormone deficiency is possible in some cases. Most patients have mild intellectual disability (although some moderate to severe) but a few have normal cognitive development. Rarer malformations may affect almost every organ. Other variable features include hernias, cryptorchidism and hypospadias in males. Possible gastrointestinal malformations are biliary atresia, intestinal malrotation and/or Hirschsprung disease (see this term). Skeletal abnormalities include spinal defects and limb malformations. Congenital kidney abnormalities include absence of one or both kidneys, hydronephrosis, supernumerary kidneys, and/or renal hypoplasia. The most frequently reported congenital heart defect is congenital total pulmonary venous return anomaly and, less frequently, tetralogy of Fallot (see these terms). In some individuals, the anal canal is narrow or absent with a fistula from the rectum into an abnormal location (the bladder, vagina or perineum). Cleft lip/palate (see this term) is sometimes observed. Characteristic facial features are down-slanting palpebral fissures, inner epicanthic folds, hypertelorism, flat nasal bridge, and small mandible. In addition to preauricular tags and/or pits, the external ears may be low-set and severely reduced with possible atresia of the external ear canal. Less frequently, unilateral microphtalmia, aniridia, cornea clouding, cataract and/or Duane anomaly are observed. Eye coloboma may involve the iris, the choroid and/or the retina. The typical eye anomaly is absent in up to 50% of patients. Preauricular skin tags and/or pits are the most consistent feature. The 3 main visible characteristics are preauricular anomalies, anal atresia, and iris coloboma but none are found consistently. Clinical descriptionĬES covers a very wide clinical spectrum in terms of features and severity, ranging from a normal phenotype to severe multisystemic disease. Males and females appear to be affected equally. CES has an estimated prevalence of 1/50,000 to 1/150,000 live births.
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