Development Gone Awry: Congenital Heart Disease

ABSTRACT—Significant advances in the understanding of the molecular and genetic basis of congenital heart disease have emerged from gene inactivation studies in mice and from human genetic investigations. However, the ability to utilize information gleaned from animal models to inform clinical care of patients depends on an accurate anatomic analysis and presentation in terms that are meaningful to the clinical pediatric cardiologist. Likewise, the enormous depth and breadth of accumulated clinical experience can inform the developmental biologist and can highlight the importance and interrelationships of particular phenotypes. The explosion of potentially informative genetic tools demands that basic scientists and clinicians concerned with congenital cardiac disease enhance the ongoing bidirectional dialogue. In some cases, categories of congenital disease familiar to clinicians are not recognized by developmental biologists, and mechanisms accepted by the biologist seem inconsistent with clinical experience. In this review, we summarize some of the more clinically significant forms of congenital heart disease, and we highlight relevant genetic and developmental pathways.