An autosomal dominant condition (OMIM:192430), most commonly arising as a spontaneous mutation, which is characterised by cleft palate, cardiac defects–especially ventricular septal defect, typical facies–i.e., prominent tubular nose, narrow palpebral fissures, and slightly retruded mandible, and learning disabilities. Less common features included microcephaly, mental retardation, short stature, slender hands and digits, minor auricular anomalies, inguinal hernia and Pierre Robin syndrome.
Molecular pathology Defects, in particular, haploinsufficiency of TBX1, which encodes a DNA-binding domain known as the T-box that regulates embryonic development, cause velocardiofacial syndrome and DiGeorge syndrome, the chromosome region for which—DGCR—also maps to 22q11, are thought to represent different clinical manifestations of the same defective gene and that DiGeorge syndrome is due to reduced gene dosage. Defects of CLDN5, which encodes claudin 5, have also been linked to velocardiofacial syndrome. Other genes lost in chromosome 22q11.2 deletion include that for the putative transcription factor TUPLE1. A collective acronym such as CATCH22 may reduce the confusion relating to the differing presentations of chromosomal losses in this region, which manifest themselves as velocardiofacial (aka Shprintzen) syndrome, conotruncal anomaly face (aka Takao) syndrome, and isolated outflow tract defects of the heart including tetralogy of Fallot and truncus arteriosus.
Synonyms Chromosome 22q11.2 deletion syndrome, VCF syndrome, VCFS, Shprintzen VCF syndrome