Heart Malformation

Abstract

Congenital heart disease (CHD) is the most common human birth defect worldwide,1 taking a tremendous toll on affected families, caregivers, and healthcare systems. Approximately 40 000 children are born each year in the United States with a heart malformation, and at least another 40 000 are born annually with subclinical malformations that result in heart disease later in adulthood. Significant advances in cardiac care and surgery have lowered mortality, and there are now >1 million survivors of CHD in the United States. As a result, the economic effects of CHD are substantial, particularly when lifetime costs of management are considered. Article see p 295 As an increasing proportion of the CHD population reaches reproductive age, questions of the genetic contribution to disease and risk of transmission have become paramount. Such individuals also often suffer age-dependent complications in heart function that may be related to the initial developmental and/or genetic insult that resulted in the CHD. Although their causes remain generally unknown, most CHDs are thought to have a multifactorial origin with an interplay of genetic and environmental effects.2 However, the relative contributions of genes and the environment have been difficult to discern. In this issue of Circulation , Oyen et al3 use a uniquely sized and annotated population to estimate recurrence risk for specific CHDs in families and thereby indirectly assess the role of genetic inheritance in CHD. A number of studies have attempted to quantify the risks conferred by a family history of CHD, demographic qualities, or environmental exposures.4,5 Gestational insults such as rubella infection and gestational diabetes can predispose to CHD, as can exposure to ethanol and other teratogens like retinoic acid.4,6 Although the incidence of CHD is higher in the setting of these exposures, most fetuses remain unaffected, suggesting that only a …