Genetics of Conotruncal Anomalies

Abstract

Conotruncal (or outflow tract) defects are among the most common congenital heart diseases found at birth, and are the leading cause of mortality and morbidity in the first year of life. In the last 20 years, the progenitor cells that contribute to cardiac outflow tract development have received much attention. Thus, the role of neural crest and second heart field derivatives has been established during outflow tract development. Particularly, second heart field cells contribute to growth of the outflow tract by addition of cells from the splanchnic pharyngeal mesoderm, whereas neural crest cells populate the endocardial cushions within the outflow tract. It is now well accepted that defective neural crest or second heart field deployment results in a spectrum of conotruncal anomalies ranging from outflow tract alignment to septation defects. In addition, recent studies have improved our understanding of signaling pathways and transcriptional networks required for outflow tract development. In this chapter, we present an overview of cardiac development, with emphasis on the genetic causes of outflow tract anomalies and highlight relevant genetic data for cardiac development in humans as well as animal models.