FLNA Mutations in Multisystem Disease: A Diagnostic Key for Unexplained Valvular and Connective Tissue Disorder

Keloid formation, multivalvular cardiac disease, and pulmonary and skeletal abnormalities rarely present together, suggesting a potential genetic syndrome. Mutations in FLNA have been implicated in such cases, expanding the known phenotypic spectrum.

A 35-year-old male with a history of bicuspid aortic valve, Wolff- Parkinson-White syndrome, asthma, and spondylolisthesis presented with dyspnea. Examination revealed spontaneous keloid formation and echocardiography confirmed severe aortic regurgitation and mitral stenosis. Genetic testing identified an X-linked FLNA mutation (c.4726G>A, p.G1576R). He underwent successful mechanical aortic and mitral valve replacement.

This case expands the clinical spectrum of FLNA mutations, emphasizing their role in connective tissue, cardiovascular, pulmonary, and skeletal disorders. It magnifies the diagnostic challenge of overlapping syndromes and the importance of genetic testing in unexplained multivalvular disease.

Genetic testing is essential in patients with unexplained valvular disease and connective tissue abnormalities, aiding diagnosis and management of FLNA-related syndromes.