Testing patterns for genetically triggered aortic and arterial aneurysms and dissections at an academic center

Objective: The contemporary practice of testing for genetically triggered aortic and arterial aneurysms and dissections is not well described. This study aimed to describe this practice at a tertiary care academic center and to ascertain the yield of testing in establishing the diagnosis in patients referred on the basis of clinical suspicion.

Methods: This is a retrospective cohort study of patients referred for vascular genetic testing at an academic medical center between 2010 and 2015. Patients were identified by Current Procedural Terminology diagnostic codes 81405, 81408, and 81479 for genetic testing (Marfan syndrome, Loeys-Dietz syndrome, aneurysms-osteoarthritis syndrome, COL3A1, and familial thoracic aortic aneurysm panel [ACTA2, COL3A1, TGFBR1, TGFBR2, SMAD3, TGFB2, MYLK, MYH11, and PRKG1 genes]) and by review of the collagen vascular laboratory database for genetic testing results. Data abstracted included demographics, clinical history, reason for referral, family history, referring provider type, and outcomes of genetic testing.

Results: Ninety-six patients (44.3% male; median age, 40.8 years) were referred for suspected genetic vascular disease. Genetic testing was performed in 75 cases thought to have heritable mutations related to aortic or arterial aneurysms and dissections. The most common reason for genetic testing was a personal history of aortic or arterial aneurysms and dissections (62.3%; mean age, 45.8 ± 11.1 years), followed by a family history of aortic or arterial aneurysms and dissections without a personal history (26.6%; age, 28.8 ± 17.9 years). The most common genetic testing performed was a familial thoracic aortic aneurysm gene panel (44%), followed by single gene testing for vascular Ehlers-Danlos syndrome (33.3%). Genetic testing identified a pathogenic mutation in 36% of the cases. The highest likelihood of identifying a pathogenic mutation was in those who had a family history with an already diagnosed mutation (57.1%), followed by patients with aortic root and ascending aortic aneurysm or dissection (42.3%).

Conclusions: In patients with suspected genetically triggered vascular disease, the yield of clinical vascular genetic testing is reasonable when selective genetic testing is performed on the basis of personal or family history. These tests should be obtained with appropriate expertise in genetic counseling and interpretation of genetic testing results. Negative genetic test results in the setting of a positive family history demonstrate the limits of testing and known mutations leading to genetically triggered aortic and arterial aneurysms and dissections and support the need for novel gene discovery.