Today, congenital cardiovascular disease is virtually always amenable to corrective or palliative surgical interventions. However, the mechanisms causing developmental anomalies of the heart and vessels have remained obscure until recently. This review presents genetic defects causing the pediatric vasculopathies; Marfan's syndrome, inherited supravalvar aortic stenosis, and Williams' syndrome. A synopsis of known mutations causing human cardiomyopathies in nuclear genes encoding contractile proteins, cardiomyocyte structural proteins, and mitochondrial proteins essential for cardiac energy production is provided. The molecular genetic evidence implicating single gene mutations in the pathogenesis of conotruncal anomalies (the 22q11 monosomy or "cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcemia with deletions on chromosome 22" [CATCH-22] syndrome), heterotaxy syndromes, trisomies and atrioventricular canal defects, and secundum atrial septal defects is presented. The consequences of these genetic causes for diagnostic evaluation and perioperative care are emphasized. Single gene defects are a common cause of congenital cardiac disease. Copyright 1998 by W.B. Saunders Company