Update on the genetic risk for thoracic aortic aneurysms and acute aortic dissections: implications for clinical care

Abstract

Genetic variation plays a significant role in predisposing individuals to thoracic aortic aneurysms and dissections. Advances in genomic research have led to the discovery of 11 genes validated to cause heritable thoracic aortic disease (HTAD). Identifying the pathogenic variants responsible for aortic disease in affected patients confers substantial clinical utility by establishing a definitive diagnosis to inform tailored treatment and management, and enables identification of at-risk relatives to prevent downstream morbidity and mortality. The availability and access to clinical genetic testing has improved dramatically such that genetic testing is considered an integral part of the clinical evaluation for patients with thoracic aortic disease. This review provides an update on our current understanding of the genetic basis of thoracic aortic disease, practical recommendations for genetic testing, and clinical implications.

Figure 1.—

Evaluation and genetic testing process for patients with thoracic aortic disease. Genetic testing is recommended for individuals with syndromic features, family history of TAAD and/or early age of disease onset. Thoracic aortic imaging is recommended for first-degree relatives of all individuals with TAAD regardless of age of onset to detect asymptomatic aneurysms. Genetic testing can lead to a positive result, triggering gene-based management and cascade testing of at-risk relatives. Individuals with negative or VUS results should be managed according to standards of care, which includes the recommendation for imaging in first-degree relatives. LDS: Loeys-Dietz syndrome; MFS: Marfan syndrome; TAAD: thoracic aneurysms and acute dissections; VUS: variant of unknown significance. *May be asymptomatic aneurysm.