The genetic basis of thoracic aortic disease: The future of aneurysm classification?

Abstract

The expansion in the repertoire of genes linked to thoracic aortic aneurysms (TAA) has revolutionised our understanding of the disease process. The clinical benefits of such progress are numerous, particularly helping our understanding of non-syndromic hereditary causes of TAA (HTAAD) and further refinement in the subclassification of disease. Furthermore, the understanding of aortic biomechanics and mechanical homeostasis has been significantly informed by the discovery of deleterious mutations and their effect on aortic phenotype. The drawbacks in genetic testing in TAA lie with the inability to translate genotype to accurate prognostication in the risk of thoracic aortic dissection (TAD), which is a life-threatening condition. Under current guidelines, there are no metrics by which those at risk for dissection with normal aortic diameters may undergo preventive surgery. Future research lies with more advanced genetic diagnosis of HTAAD and investigation of the diverse pathways involved in its pathophysiology, which will i) serve to improve our understanding of the underlying mechanisms, ii) improve guidelines for treatment and iii) prevent complications for HTAAD and sporadic aortopathies.

Keywords: Thoracic aortic aneurysms (TAA); aortic dissection; genotype; hereditary aortic aneurysms and dissection; polymorphisms; syndromic.