Characteristic Morphologies of the Bicuspid Aortic Valve in Patients with Genetic Syndromes

Background: In patients with bicuspid aortic valve (BAV), complications including progressive aortic stenosis and aortic dilatation develop over time. The morphology of cusp fusion is one of the determinants of the type and severity of these complications. We present the association of morphology of cusp fusion in BAV patients with distinctive genetic syndromes. Methods: The Mayo Clinic echocardiography database was retrospectively reviewed to identify patients (age ≤ 22 years) diagnosed with BAV from 1990 to 2016. Cusp fusion morphology was determined from the echocardiographic studies, while coexisting cardiac defects and genetic syndromes were determined from chart review. Results: A total of 1,037 patients with BAV were identified: 550 (53%) had an isolated BAV, 299 (29%) had BAV and a coexisting congenital heart defect, and 188 (18%) had BAV and a coexisting genetic syndrome or disorder. There were no differences in distribution of morphology across the three groups. However, right-noncoronary (RN) cusp fusion was the predominant morphology associated with Down syndrome (P =.002) and right-left (RL) cusp fusion was the predominant morphology associated with Turner syndrome (P =.02), DiGeorge syndrome (P =.02), and Shone syndrome (P =.0007), when compared with valve morphology in patients with isolated BAV. Isolated BAV patients with RN cusp fusion had larger ascending aorta diameter (P =.001) and higher number of patients with ≥ moderate aortic regurgitation (P =.02), while those with RL cusp fusion had larger sinus of Valsalva diameter (P =.0006). Conclusions: Morphological subtypes of BAV are associated with different genetic syndromes, suggesting distinct perturbations of developmental pathways in aortic valve malformation.