Description of the smallest critical region for Dandy-Walker malformation in chromosome 13 in a girl with a cryptic deletion related to t(6;13)(q23;q32)

Abstract

We report on a girl with mild dysmorphic facial features, Dandy-Walker malformation (DWM), iris coloboma, profound hearing loss, and hyperlaxity of skin and joints, whose karyotype is 46,XX,t(6;13)(q23;q32)dn and who has a cryptic imbalance at the 13q32 translocation breakpoint assessed by array-CGH. Our patient has many clinical manifestations in common with those of the previously reported cases of 13q32 deletions, which suggests that at least part of the abnormal phenotype is probably due to the imbalance. The recurrent finding of DWM among patients with 13q deletions has led to the suggestions that candidate gene/s for its development are on chromosome 13. We describe the smallest 13q deletion associated to DWM, which allows further narrowing of the previously established critical region for this brain malformation to 13q32.2-32.3. Among the few genes of the deleted region, ZIC2 and ZIC5 seem the most plausible candidates, which is in keeping with some previous reports. This work also illustrates the usefulness of array-CGH platforms in the identification of cryptic imbalances in carriers of apparently balanced rearrangements with abnormal phenotypes.