Velo-cardio-facial syndrome. Intrafamilial variability of the phenotype

We describe a mother and son with velo-cardio-facial syndrome (VCFS) in whom cytogenetic and DNA molecular studies demonstrate an interstitial deletion of the long arm of chromosome 22. Although these two individuals manifest the typical facial and cognitive features of VCFS, they are discordant for the cardiovascular and palatal anomalies, which are seminal manifestations of the disorder. Previously, this degree of phenotypic variability had not been well appreciated within a single family segregating the VCFS deletion. A review of other familial cases of VCFS suggests that the family described in this article is not atypical. Because a microdeletion would be expected to be inherited without alteration within individual families, the phenotypic variability observed in these families appears to be an intrinsic quality of the syndrome and not wholly due to genetic heterogeneity.