Genetics of Congenital Heart Malformations: Clinical and Molecular Studies

Abstract

Congenital heart malformations (CHM) are among the most common congenital defects, occurring in 8 out of 1000 live-births. In the past decade significant progress has been made in the identification of genes implicated in the signaling pathways involved in cardiovascular development. A major contribution has come from the study of model systems from fruit fly to mouse. Additionally, multiple disease genes implicated in genetic forms of human CHM have been identified, mainly through positional genetics in multiplex families. Especially human syndromes with CHM ("syndromic" CHM) have been instrumental in the elucidation of these disease genes, but recently also a number of disease genes implicated in "non-syndromic" CHM have been identified. In this chapter the most important forms of syndromic CHM with the different signaling pathways involved, and the genetic and environmental factors contributing to non-syndromic CHM are summarized. Several recent reviews have addressed the progress in the identification of these genes and pathways.