FISH approach to determine cat eye syndrome chromosome breakpoints of a patient with cat eye syndrome type II

We report a 19-year-old man with craniofacial dysmorphic features, anorectal malformations, eye colobomas, orthopaedic anomalies, and mild neurodevelopmental delay. Cat eye syndrome (CES) was suspected, and confirmed by cytogenetic analysis which showed the presence of a supernumerary bisatellited chromosome, identified by fluorescence in situ hybridization (FISH) as invdup(22). The marker was further analyzed with six BAC clones located at the 22q11.1 and 22q11.2 regions; this analysis allowed correct assignment at low copy repeat 4 on chromosome 22 (LCR22-4) of the two breakpoints, confirming the presence of a CES chromosome type II. The patient's phenotype is considered in the light of the cytogenetic, and FISH investigations results and other patients reported in literature. Molecular definition of the breakpoints at the LCR22-4 copy confirms the role of different chromosome 22-specific LCRs in CES chromosomes generation, as well as in other chromosome 22 germ line rearrangements. Our report confirms that, unlike other conditions, i.e. the invdup(15) bisatellited dicentric marker, the CES phenotype does not appear to correlate with the size of the marker chromosome. Additional cases are necessary to be able to draw more specific genotype-phenotype correlations and to determine the outcome of patients with CES, especially when this rare condition is diagnosed in prenatal age.