Background Velo-cardio-facial syndrome (VCFS) is associatedwith interstitial deletions of chromosome 22q11.About 30% of patientswithVCFS

Declaration of interest Funding fromthe PPPHealthcare Medical Trust, London,UK.Collection of probands in Bulgaria fundedby the Janssen Research Foundation and inthe UK by the Medical Research Council. Velo-cardio-facial syndrome (VCFS) is a genetic disorder associated with characteristic dysmorphology, cleft palate, cardiac anomalies and major psychiatric disorders, including schizophrenia (Shprintzen et al, 1978; Murphy et al, 1999). The frequencies of the disorder have been reported to be 1/ 4000 (Wilson et al, 1994) and 1/9700 live births (du Montcel et al, 1996), but both of these frequencies were only minimum estimates. The disorder is associated with interstitial deletions of chromosome 22q11; 87% of cases share a 3 Mb deletion, 8% have a smaller nested 1.5 Mb deletion, 4% have one of two other nested deletions and the remainder have unique deletions (Shaikh et al, 2000) (Fig. 1). It has been proposed that deletions in this region are facilitated by the presence of low copy repeats (LCR22) at the boundaries of the various deletions (Carlson et al, 1997). Most cases occur sporadically in the population, indicating that the 22q11 region is highly prone to rearrangement.