The genetics of congenital heart disease: a review of recent developments

As our understanding of the molecular regulation of cardiac development has progressed, an increasing number of genes that cause congenital heart disease when mutated are being identified. This review focuses on the progress made during the past year.

After PTPN11 was identified as a Noonan syndrome disease gene, additional discoveries have made clear that mutations in other genes along the RAS signaling pathway can cause a spectrum of syndromes and possibly isolated congenital heart disease. Similarly, alterations of genes in other signaling and transcriptional pathways may contribute to the development of atrial septal defects and bicuspid aortic valves. Recently identified disease genes for syndromes associated with congenital heart disease are also reviewed. Finally, the possibility that somatic mosaicism may contribute to the development of congenital heart disease is discussed.

The recent knowledge about the molecular genetic causes of congenital heart disease is reviewed. In many instances, these gene discoveries are being rapidly translated into meaningful genetic testing, which is improving the diagnosis and prognostication for congenital heart disease in isolation or in the context of a syndrome. Ultimately, genetic information will be necessary for planning care as well as clinical research.