Clinical and genetic characterization of adult patients presenting with non-syndromic vascular aneurysms and dissections.

BACKGROUND: Genetic disorders affecting the arterial tree in the form of aneurysms and dissections are highly morbid conditions that strike younger persons leading to bleeding, infarction, or even death. Although clinically recognizable syndromes, notably Marfan, Ehlers Danlos, and Loeys-Dietz syndromes encompass the principal diagnosable phenotypes along the genetic vascular disorder spectrum, a substantial subset of patients cannot be adequately classified under a known diagnosis through clinical or molecular diagnostic methods. Here we describe patients presenting with multiple-aneurysms and/or pseudoaneurysm syndromes (MAPS), and clinically characterize this novel phenotype, present data on natural history and prognosis, and propose management guidelines.

METHODS: Thirty-two patients with MAPS were identified from February 2006 to October 2015 through the University of Colorado Adult Medical Genetics Clinic. A subset of patients underwent clinical genetic testing utilizing the Marfan/TAAD/Related disorders panel, and another subset was enrolled for research-based exome-sequencing.

RESULTS: Thirty-two patients (10 men, 22 women) were classified as MAPS patients with an average age of diagnosis at 39.5 (±13.3) and 35.4 (±12.8) years, respectively. Symptom presentation and progression are presented based on vascular territory, notably of the heart, head, and neck, which could manifest with fatal complications. Secondary arterial events occurred at an average of 6.7±6.0 years after the initial MAPS episode. Genetic analysis revealed 9 gene variants that are likely pathogenic and implicated in MAPS.

CONCLUSIONS: These data more broadly illuminate a phenotype of aneurysms, dissections, and/or pseudoaneurysms that do not classify under a recognizable genetic vascular diagnosis. Our data should provide useful clinical information for providers managing patients with MAPS.