FBN1 and Marfan syndrome: In MFS, secondary to mutated structural fibrillin-1, excessive activation of TGF-β in the lungs, heart valves, and aorta causes the pathological features.400,403 LDS is caused by inactivating mutations in genes encoding TβRI and TβRII.404 Physical manifestations of LDS include arterial aneurysms, hypertelorism, bifid uvula/cleft palate and bone overgrowth resulting in arachnodactyly, joint laxity, and scoliosis.