Abstract 9122: Polyvalvular Heart Disease in Children Associated With FilaminA Mutations

Introduction: FilaminA ( FLNA ), an X-linked gene encoding an actin binding protein, is one of the only known causative genes for periventricular nodular heterotopia (PVNH) and mitral valve (MV) prolapse. FLNA mutations have been well associated with familial MV prolapse and polyvalvular disease in adults. There is limited data, however, on the type and distribution of valve disease in children with FLNA mutations. We aim to assess the frequency of polyvalvular disease in a predominantly pediatric cohort. Methods: We retrospectively enrolled subjects from a large registry at Boston Children’s Hospital of patients and families with PVNH and FLNA mutations with at least one transthoracic echo and clinical phenotyping of their cardiovascular and neurologic status. Additionally, data from published subjects with FLNA mutations and PVNH were included in the cohort. Imaging data about valvular heart disease were extracted for all subjects. Results: 165 patients with FLNA mutations formed our cohort (128 F, median age 9 yrs, range 0-71 yrs), with 53% ≤ 21 yrs. Valve disease was the most common type of isolated structural disease, presenting in 58% (62/110) of FLNA patients with congenital heart disease. Of these patients, 45% (28/62, 10 M) had polyvalvular disease and 36% (22/62, 8 M) underwent cardiac surgery. MV prolapse or dysplasia was present in 60% (37/62) of patients. Aortic valve abnormalities were equally common, also occurring in 60% (37/62) of patients (e.g. bicuspid aortic valves and aortic valve prolapse). Notably, tricuspid valve dysplasia did not occur independently (n=0), and always presented with involvement of other cardiac valves. In patients with polyvalvular disease, mitral and aortic valves were most commonly involved together, occurring in 23% (14/62) of patients. Males with FLNA mutations were more likely to have polyvalvular disease with more severe clinical phenotypes. Conclusions: In this largest cohort of predominantly children with FLNA mutations, FLNA patients frequently have polyvalvular disease on echocardiography. When polyvalvular disease is detected especially involving the tricuspid valve, pediatric cardiologists should consider genetic testing for FLNA mutations as a potential contributor of disease.