Genetic insights into normal and abnormal heart development

Congenital heart defects (CHDs) affect 1–2% of newborn children and are the leading cause of death in infants under 1 year of age. CHDs represent the single largest class of birth defects and account for 25% of all human congenital abnormalities. Numerous epidemiologic studies have established the heritable nature of CHDs. However, despite the remarkable progress of the past decade, very few CHD-causing genes have been identified so far. Molecular and genetic analysis of heart development—which requires the execution of specific genetic programs—has led to the identification of essential cardiac regulators and mutations that are linked to human CHD. Elucidation of the mechanisms of action of these transcription factors has also provided a molecular framework that will continue to help furthering our understanding of the molecular basis of normal and abnormal heart growth. This review will summarize present knowledge of cardiac development and illustrate how analysis of heart development has helped understand the genetic basis of some CHDs and how these advances could translate into better prevention, diagnosis, and care of congenital heart disease.