Testing Patterns for Genetically Triggered Vascular Disease at an Academic Center
Kelli Hicks, BS1, Melanie Pepin, MS CGC2, Peter Byers, MD2, Sherene Shalhub, MPH MD3.
1University of Washington, Seattle, WA, USA, 2Medical Genetics, Department of Pathology, University of Washington, Seattle, WA, USA, 3Division of Vascular Surgery, Department of Surgery, University of Washington, Seattle, WA, USA.
OBJECTIVES: The contemporary practice of testing for genetically triggered aortic and arterial aneurysms/dissections is not well described. This study aims to (1) describe this practice at a tertiary care academic center, and (2) ascertain the yield of testing in establishing the diagnosis in patients referred based on clinical suspicion.
METHODS: This is a retrospective cohort study of patients referred for vascular genetic testing at an academic medical center. Patients were identified using (1) CPT codes: 81405, 81408, and 81479 (Marfan Syndrome, Loeys-Dietz Syndrome, Aneurysms-Osteoarthritis Syndrome, COL3A1, Familial Thoracic Aortic Aneurysm panel [ACTA2, COL3A1, TGFBR1, TGFBR2, SMAD3, TGFB2, MYLK, MYH11, PRKG1 genes]) and (2) the collagen vascular laboratory (CDL) database for genetic testing. Data abstracted included demographics, clinical history and reason for referral, family history, referring clinic, and outcomes of genetic testing.
RESULTS: Records of 96 patients (44.3% male) referred between 2010 and 2016 for suspected genetic nature of their aortic/arterial dissections were reviewed. The median age at referral was 40.8 (range 0.1-70) years. The most common reasons for referral diagnosis was vascular Ehlers-Danlos syndrome (41.7%) and Familial Arterial Aneurysm (25%). A positive family history (i.e. aneurysms, dissections, sudden death, or premature vascular disease [stroke and myocardial infarction]) was ascertained in 46.9%. Family history alone was the reason for referral in 12.1% of cases. Testing was performed for mutations in a single gene, panel testing, and targeted single mutation testing in 46.9%, 34.4%, and 13.5% respectively. Testing was recommended but not obtained due to a decline by the insurance carrier in 4 of 21 (19%) patients where these data were available. Testing yielded positive results for a pathogenic mutation in 25% of cases and variants of unknown significance in 12.5%. Patients with a family history were more likely to have positive testing results (48.8% vs. 30.4%) though not significant (p=0.075). Negative testing results were obtained in 33.3% of the patients with a family history but who did not have a known mutation.
CONCLUSIONS: In patients with suspected genetically triggered vascular disease, the yield of a positive test is reasonable. These tests should be obtained with expertise in testing results interpretation. Negative test in the setting of a positive family history demonstrate the limits of testing and known mutations leading to genetically triggered aortic and arterial aneurysms/dissections.
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