Congenital cardiovascular malformations: an intersection of human genetics and developmental biology

Abstract

The practice of pediatric cardiology is poised to benefit from dramatic developments in human genetics and developmental biology. While clinicians have long known that congenital cardiovascular malformations arise as a result of disruption of the developmental process, it has taken decades to define the mechanisms. The combination of epidemiology, models of cardiovascular development in vertebrates, and the unprecedented understanding of the human genome has lead to new insights into ideology and pathogenesis. Expanded knowledge of Down's syndrome, cono-truncal defects, abnormalities of situs and looping, and Marfan syndrome, William's syndrome, and supravalvar aortic stenosis, Holt–Oram syndrome and Alagille syndrome, will allow clinical cardiologists to answer more precisely the three questions posed by parents: (1) will our child be all right; (2) what caused our child's heart defect; and (3) what about our other children and our grandchildren? This is the promise of the intersection of human genetics, developmental biology, and clinical pediatric cardiology.