Real-world uptake and outcomes of family screening in adults with thoracic aortopathy: a retrospective cohort study.

Background: Thoracic aortopathy is a disorder with genetic influence usually presenting in adulthood for which family screening is potentially desirable. Family screening is recommended, but the predictors of a positive screen and real-world pickup rates are unknown. Methods: This was a retrospective cohort of 1022 probands (first affected family member identified) with thoracic aortopathy and one or more features suggestive of a genetic etiology, and their presenting family members, assessed in a cardiac clinic (2009?2024). Imaging and genetic testing were employed in family screening. The prespecified outcomes were uptake and pickup rate of family screening, and proband and family member specific characteristics that predicted a positive family screen. Results: Among probands, 43.5% had one or more family member screened, with an average of 3 relatives per successful proband. 27.6% of family members screened positive. A pre-existing family history of aortopathy was the only variable predicting a higher incidence rate for positive family screen (p = 0.0003). Age of presentation < 60 was not predictive. For family members, extravascular features (p < 0.0001), closer relation to the proband (p < 0.02), male sex (p < 0.0001) and older age (p< 0.0001) all predicted a positive screen. Family members were eight times more likely to screen positive through imaging as compared to genetic testing. Probands with a genetic diagnosis of Marfan and Loeys Dietz syndromes accounted for only 4% of the total. Conclusions: Proband-initiated family screening for thoracic aortopathy has a high yield of affected individuals, even among older probands.