Introduction

It has been known for over a decade that the majority of cases of DiGeorge Syndrome (DGS) and velo-cardio-facial syndrome (VCFS) are caused by an interstitial deletion of chromosome 22q11 (Carey et al., 1992). Rarely, terminal deletions and balanced translocations involving chromosome 22q11 may also cause the syndrome, and some cases appear to have a robust diagnosis but no deletion. Estimates of the frequency with which the deletions occur have been made from populations where ascertainment is thought to be particularly high and generally suggest an incidence of 1: 4000 live births (Wilson et al., 1994; Du Montcel et al., 1996); 5–10% of deletions are inherited (Ryan et al., 1997). Molecular studies have shown that most patients have a 3Mb interstitial deletion – the typically deleted region, or TDR – a minority having somewhat smaller (1.5–2 Mb) deletions (Emanuel et al., 1998). As will be evident from other chapters in this volume there is a great deal of variation in severity and type of malformation between patients. However, there is no evidence that the size or the precise endpoints of the deletion have any influence on phenotype. Variation of phenotype extends to individuals within the same family and, as molecular studies have shown that deletion size is stable in different members of the same family, this cannot be ascribed to subtle differences in the extent or position of the deletion. Moreover, phenotypic discordance between monozygotic twins has been described (Goodship et al., 1995).