Molecular and Genetic Aspects of DiGeorge/Velocardiofacial Syndrome
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Cytogenetic, molecular, and clinical genetic studies have contributed to our understanding of the etiology, pathogenesis, and natural history of DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). Submicroscopic deletions of chromosome 22q11.2 are the leading cause of both of these disorders. The 22q11.2 deletion syndrome is recognized as one of the most common microdeletion syndromes. The clinical features are highly variable and include a variety of congenital anomalies, medical problems, and cognitive and neuropsychological difficulties.
Infrequently, other chromosomal rearrangements are found in patients with DGS/VCFS, and, rarely, point mutations in the gene TBX1 , a transcription factor, that maps to the deleted region. The most sensitive and widely used diagnostic test for detecting the 22q11.2 deletion is fluorescence in situ hybridization using probes from the commonly deleted region. Alternatively, polymerase chain reaction can be performed to confirm failure to inherit a parental allele in the region or to determine copy number. Prenatal diagnosis is also available, particularly when a conotruncal cardiac defect is identified during a pregnancy or when a parent carries a deletion. Genetic counseling is recommended before testing to review the natural history of the disorder, testing options, and test sensitivity and limitations.
