Cardiogenetics: genetic testing in the diagnosis and management of patients with aortic disease

Thoracic aortic aneurysm and aortic dissection have a potent genetic underpinning with 20% of individuals having an affected relative. Heritable thoracic aortic diseases (HTAD) may be classified as syndromic (including Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome and others) or non-syndromic (without recognisable phenotypes) and relate to pathogenic variants in multiple genes affecting extracellular matrix proteins, transforming growth factor-beta (TGF-β) signalling and smooth muscle contractile function. Clinical and imaging characteristics may heighten likelihood of an underlying HTAD. HTAD should be investigated in individuals with thoracic aortic aneurysm or aortic dissection, especially when occurring in younger individuals, in those with phenotypic features and in those with a family history of aneurysm disease. Screening family members for aneurysm disease is important. Consultation with a medical geneticist and genetic testing of individuals at increased risk for HTAD is recommended. Medical management and prophylactic aortic surgical thresholds are informed by an accurate clinical and molecular diagnosis.