2020 Volume 60 Issue 3 Pages 25-34
Thoracic aortic aneurysms increase the risk of aortic dissection or rupture, and hereditary thoracic aortic aneurysms and dissections (TAADs) can be life-threatening in young adulthood, even if patients receive optimal medical care. There is currently no genotype-specific medical treatment due to the lack of comprehensive understanding of governing molecular mechanisms. Hereditary TAADs can be divided into two categories: syndromic (associated with abnormalities of other organ systems) and non-syndromic (with manifestations restricted to the aorta). Recent advances in DNA sequencing technology have identified several causative genes for hereditary TAADs, including Marfan syndrome, Loeys–Dietz syndrome, vascular Ehlers–Danlos syndrome, and familial non-syndromic TAADs. Syndromic TAADs are typically caused by pathogenic variants in the transforming growth factor-β signal and extracellular matrix-related genes, such as FBN1, TGFBR1, TGFBR2, SMAD3, TGFB2, COL3A1, while approximately 20% of the non-syndromic hereditary TAADs result from altered components of the contractile apparatus of vascular smooth muscle cells, encoded by ACTA2, MYH11, MYLK, and PRKG1 genes. The genotype–phenotype relationship of hereditary TAADs has been extensively investigated to improve the methods for risk stratification and personalized treatment strategies. In this review, we present the current understanding of genotype–phenotype relationship and molecular mechanisms responsible for aortopathies of hereditary TAADs.
