Genetics of Transposition of Great Arteries: Between Laterality Abnormality and Outflow Tract Defect

Transposition of great arteries (TGA) is a complex congenital heart disease whose etiology is still unknown. This defect has been associated, at least in part, with genetic abnormalities involved in laterality establishment and heart outflow tract development, which suggest a genetic heterogeneity. In animal models, the evidence of association with certain genes is strong but, surprisingly, genetic anomalies of its human orthologues are found only in a low proportion of patients and in nonaffected subjects, so that the underlying causes remain as an unexplored field. Evidence related to TGA suggests different pathogenic mechanisms involved between patients with normal organ disposition and isomerism. This article reviews the most important genetic abnormalities related to TGA and contextualizes them into the mechanism of embryonic development, comparing them between humans and mice, to comprehend the evidence that could be relevant for genetic counseling.

Automated summary

Transposition of great arteries (TGA) is a complex congenital heart disease with unknown etiology, associated with genetic abnormalities in laterality establishment and heart outflow tract development. Strong evidence of association with certain genes is found in animal models, but genetic anomalies of human orthologues are low, leaving underlying causes unexplored. Pathogenic mechanisms differ between patients with normal organ disposition and isomerism, highlighting the need for further research in this area.