Cat-eye syndrome (ORPHA:195)
Cat eye syndrome (CES) is a rare chromosomal disorder with a highly variable clinical presentation. Most patients have multiple malformations affecting the eyes (iris coloboma), ears (preauricular pits and/or tags), anal region (anal atresia), heart and kidneys. Intellectual disability is usually mild or borderline normal.
Epidemiology
CES has an estimated prevalence of 1/50,000 to 1/150,000 live births. Males and females appear to be affected equally.
Clinical description
CES covers a very wide clinical spectrum in terms of features and severity, ranging from a normal phenotype to severe multisystemic disease. The 3 main visible characteristics are preauricular anomalies, anal atresia, and iris coloboma but none are found consistently. Preauricular skin tags and/or pits are the most consistent feature. The typical eye anomaly is absent in up to 50% of patients. Eye coloboma may involve the iris, the choroid and/or the retina. Less frequently, unilateral microphtalmia, aniridia, cornea clouding, cataract and/or Duane anomaly are observed. 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. Characteristic facial features are down-slanting palpebral fissures, inner epicanthic folds, hypertelorism, flat nasal bridge, and small mandible. Cleft lip/palate (see this term) is sometimes observed. 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). The most frequently reported congenital heart defect is congenital total pulmonary venous return anomaly and, less frequently, tetralogy of Fallot (see these terms). Congenital kidney abnormalities include absence of one or both kidneys, hydronephrosis, supernumerary kidneys, and/or renal hypoplasia. Skeletal abnormalities include spinal defects and limb malformations. Possible gastrointestinal malformations are biliary atresia, intestinal malrotation and/or Hirschsprung disease (see this term). Other variable features include hernias, cryptorchidism and hypospadias in males. Rarer malformations may affect almost every organ. Most patients have mild intellectual disability (although some moderate to severe) but a few have normal cognitive development. Short stature with growth hormone deficiency is possible in some cases.
Etiology
Most patients harbor a small supernumerary bisatellited marker chromosome (sSMC) that results in partial tetrasomy of 22pter-22q11. In one third of cases, this extra chromosome is present in a mosaic state. Other cytogenetic anomalies have been rarely reported, including partial trisomy of chromosome 22 and intrachromosomal triplication of the 22q11 region.
Diagnostic methods
The diagnosis, suspected on the basis of clinical manifestations, is based on cytogenetic testing showing the presence of extra material derived from chromosome 22q11. Fluorescence in situ hybridization (FISH) with specific probes is needed to detect a low level mosaicism.
Differential diagnosis
Differential diagnosis includes other chromosomal disorders with overlapping phenotypes such as CHARGE syndrome and VACTERL/VATER association (see these terms).
Antenatal diagnosis
Prenatal diagnosis is possible through karyotyping and FISH analysis of prenatal samples.
Genetic counseling
The extra chromosome usually arises de novo.
Management and treatment
Multidisciplinary management is necessary and depends on the specific symptoms that are apparent in each patient. Surgical correction is necessary for anal atresia and severe cardiac malformations. Bacterial infections should be anticipated and treated vigorously. Patients should be screened for visual and hearing impairment. Early intervention with educational support can be beneficial.
Prognosis
Some patients die from severe malformations in early infancy. Otherwise, life expectancy is generally not significantly reduced.

                            Last update: 
                            January 2016


                            - Expert reviewer(s): 
                            Dr Catherine TURLEAU