Genetic insights into the Tetralogy of Fallot

Abstract

Tetralogy of Fallot (TOF), (OMIM #187500) one of the first known congenital heart disease (CHDs) with a rising frequency of adult patients, is a suitable paradigm for our analysis given the expanding abundance of genetic data available and these clinical consequences. Given the complexity of cardiac development, it has been associated with untreated maternal diabetes, maternal intake of retinoic acid, phenylketonuria, chromosomal anomalies (trisomies 21, 18, 13), microdeletions of chromosome 22q11.2, and it is not unexpected that a variety of transcription factors and signaling molecules involved in 9 cardiogenesis have been linked to TOF, with the literature consistently reporting the existence of new, previously unrecognized genes. The well studied genes GATA4, NKX2.5, JAG1, FOXC2, TBX5, and TBX1, which have previously been linked to TOF, are the focus of this review.