Genetics of Thoracic and Abdominal Aortic Diseases: Aneurysms, Dissections, and Ruptures

This review summarizes the current understanding of the inherited basis for aortic aneurysmal disease and clearly highlights the need to differentiate between thoracic and abdominal aortic manifestations. Approximately 20% of thoracic aortic aneurysms are associated with an autosomal pattern of inheritance from a mutation in a single gene, whereas abdominal aortic aneurysms (AAAs) do not typically demonstrate such inheritance but rather seem to present as a polygenic disorder involving variants of weaker effect. This notwithstanding, there are some distinct biological pathway similarities between thoracic aortic disease (TAD) and AAA; these include the TGF-β and low-density lipoprotein receptor-related protein (LRP1) pathways, as well as other aspects of vascular smooth muscle cell function.

Currently, over a dozen causative genes have been validated for heritable TAD. Each confers a high risk for disease, and genetic testing for these genes is now offered clinically. The situation is far less advanced for AAA, and although polygenic AAA risk scores are being developed, using genetic variants to predict AAAs has not progressed to the extent that it can be used to identify at-risk individuals.