Overview

Velo-cardio-facial syndrome (VCFS) is one of a number of syndromes which are associated with monosomic deletions of chromosome 22q11.2 (Kelley et al., 1982, Kelley et al., 1993, Driscoll et al., 1992). It is estimated that 80–100% of patients with the clinical features of VCFS have a chromosome 22q11.2 deletion and 90% of those with the deletion carry an identical 2.5–3 megabase deletion (Motzkin et al., 1993). DiGeorge syndrome, conotruncal anomaly face syndrome, and occasional patients with Opitz GBBB, CHARGE association, and Noonan's syndrome are also associated with chromosome 22q11.2 deletions. Although the immunodeficiency was generally believed to be associated with DiGeorge syndrome, most patients with the deletion will have compromise of T-cell production regardless of their other phenotypic features. The clinical findings are generally not related to the specific genes encompassed by the breakpoints and family studies confirm that twins and siblings with the same deletion may have very discordant clinical features (Kasprzak et al., 1998; Yamagishi et al., 1998; Vincent et al., 1999). The deletion is mediated by homologous recombination between low copy number repeats (Edelmann et al., 1999) and includes several genes implicated in development. Some patients with VCFS have been identified as having monosomic deletions of chromosome 10 p (Schuffenhauer et al., 1998; Daw et al., 1996). The more proximal region appears to mediate immunodeficiency while the distal region mediates hypocalcemia.