Velo-cardio-facial syndrome (VCFS) is the most common contiguous gene deletion syndrome in humans, caused by a microdeletion from chromosome 22 at the q11.2 locus. Moreover, it is one of the most common multiple anomaly syndromes associated with congenital heart disease and is certainly the most common syndrome causing conotruncal heart anomalies. The population prevalence of this syndrome is probably increasing because of the advances in the diagnosis and treatment of congenital heart malformations. Presenting symptoms are highly variable because VCFS is often the trigger for a number of developmental malformation sequences, including DiGeorge sequence, Robin sequence, and Potter sequence. Because of the variability of the phenotypic expression of VCFS, the disorder has been delineated in several sets of literature from different areas of specialization, and from publications in the U.S., Eastern Europe, and Japan. The result has been nosologic differences with various names for the same disorder caused by a 22q11.2 deletion, including VCFS, Shprintzen syndrome, DiGeorge syndrome, Sedlačková syndrome, Cayler syndrome, and conotruncal anomalies face syndrome. All of these labels represent exactly the same syndrome. Understanding the cause of the various phenotypes associated with VCFS is dependent on careful studies of genotype to phenoype matching. The deleted region in most cases of VCFS encompasses 3 million base pairs of DNA and 30 genes. The challenge is therefore to determine if the broad spectrum of anomalies are caused by one major gene, most or all of the deleted genes, or the interaction between the genes in the deleted region and other genes elsewhere in the genome. There is some evidence for each of these hypotheses. The ability to complete phenotype to genotype matching is enhanced by the recognition of more cases and the careful study of phenotypic expression. Towards this end, screening of cases with congenital heart disease is imperative and guidelines for screening are discussed.
Shprintzen, Robert J. "Velo-Cardio-Facial Syndrome." Progress in Pediatric Cardiology 20.2 (2005): 187-193.