Molecular Basis of Cardiac Development and Congenital Heart Disease

Abstract

Cardiovascular malformations are the most common type of birth defect and result in significant mortality worldwide. The etiology for the majority of these anomalies remains unknown. The heart is the first organ to form, and the process of cardiac development has been well described in multiple species. More recently, advances in the characterization of the molecular pathways critical for normal cardiac development has led to the identification of numerous genes necessary for this complex morphogenetic process. This work has aided the discovery of an increasing number of genetic contributors being implicated as the cause of human cardiovascular malformations. This chapter summarizes normal cardiac development and outlines the discoveries of the genetic causes of congenital heart disease. We begin by summarizing the stages of cardiac development from early cardiomyocyte specification to the later stages of chamber and septa formation, valvulogenesis, and development of the outflow tracts. Next, we discuss the roles of the multiple cellular contributors that are necessary for normal heart formation. We finish this chapter by highlighting the intricacies of the molecular pathways regulating cardiac embryogenesis that are now beginning to be elucidated and how they have impacted human disease.KeywordsCongenital Heart DiseaseCopy Number VariationArray Comparative Genome HybridizationNoonan SyndromePharyngeal ArchThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.