Utility of familial screening in non-syndromic thoracic aortic disease

Abstract

Abstract Background Non-syndromic heritable thoracic aortic disease (nsHTAD) is an autosomal dominant disorder with high mortality rate if undetected. Familial evaluation could be useful to identify high-risk patients early. Purpose To assess the yield of clinical and genetic screening in a cohort of patients with suspected nsHTAD. Methods We collected clinical and genetic data about patients with suspected nsHTAD treated in a specialized clinic. Bicuspid aortic valve cases were excluded. Genetic study was performed with next-generation-sequencing, including at least 30 related genes. All first degree relatives were offered evaluation according to current guidelines. Results Twenty-five index cases were analysed (mean age: 48.3 years, male: 64%). Sixteen patients (64%) presented with acute aortic dissection (postmortem diagnosis was performed in 6 cases with sudden cardiac death). Hypertension was reported in 13 cases (52%) and 8 patients (32%) had smoking history. Family history of aortic aneurysm or dissection was identified in 13 cases (52%). Eighty-three first-degree relatives were evaluated. Clinically affected family members were detected in 10 families (40%). Genetic cause of the disease was identified in 6 families (24%). Table 1 describes main characteristics of index cases with pathogenic variants. Combined clinical and genetic screening was positive in 12 families (48%) and identified 24 relatives (29%) with aortic dilatation or carrier status for the disease. Conclusions The combination of clinical and genetic screening in suspected nsHTAD is a useful tool for early detection of the disease in family members at risk and for the prevention of future complications. Funding Acknowledgement Type of funding sources: None. Table 1