Genes Associated with Thoracic Aortic Aneurysm and Dissection: An Update and Clinical Implications

Abstract

Thoracic aortic aneurysm (TAA) is a lethal disease, with a natural history of enlarging progressively until dissection or rupture occurs. Since the discovery almost 20 years ago that ascending TAAs are highly familial, our understanding of the genetics of thoracic aortic aneurysm and dissection (TAAD) has increased exponentially. At least 29 genes have been shown to be associated with the development of TAAD, the majority of which encode proteins involved in the extracellular matrix, smooth muscle cell contraction or metabolism, or the transforming growth factor-β signaling pathway. Almost one-quarter of TAAD patients have a mutation in one of these genes. In this review, we provide a summary of TAAD-associated genes, associated clinical features of the vasculature, and implications for surgical treatment of TAAD. With the widespread use of next-generation sequencing and development of novel functional assays, the future of the genetics of TAAD is bright, as both novel TAAD genes and variants within the genes will continue to be identified.

Keywords: Aortic aneurysm; Genetics; Thoracic aortic aneurysm and dissection (TAAD).

Figure 1.

Simplified schematic illustration of ascending aorta dimensions for prophylactic surgical intervention divided by gene category: ECM genes, SMC contractile unit and metabolism genes, and TGF-β signaling pathway genes (data derived from Table 1). ECM, extracellular matrix; LDS, Loeys-Dietz syndrome; MFS, Marfan syndrome; SMC, smooth muscle cell; EDS, Ehlers-Danlos syndrome.