Cardiology in review 2017 10 17() doi 10.1097/CRD.0000000000000170
Due to improved survival and clinical outcomes, congenital heart disease is an area of growing importance within the medical community. As these patients reach adulthood and have children, there has been a growing appreciation for the increased risk of CHD among their offspring, strongly implying a genetic element. Given the growing wealth of genetic data available and these clinical implications, this review serves to re-examine the role of genetics within CHD, using Tetralogy of Fallot as a model pathology. TOF is one of the oldest documented CHDs, with a growing prevalence of adult patients, and thus serves as an excellent model for this review. Given the complex nature of cardiac development, it is not surprising that multiple transcription factors and signaling molecules responsible for cardiogenesis have been implicated in TOF, with additional, previously non-implicated genes being routinely reported within the literature. This review focuses on the well characterized genes gata4, nkx2.5, jag1, foxc2, tbx5 and tbx1, which have been previously implicated in TOF. Furthermore, this paper will attempt to summarize the specific clinical implications associated with the affected genes, such as right- sided aortic arches, associated syndromic presentations, and parental carrier states.