Fibrillinopathies: Skeletal manifestations of marfan syndrome and marfan-related conditions

The fibrillinopathies are connective tissue disorders that share a constellation of features and differ by specific clinical and molecular findings. This chapter discusses the phenotype, molecular basis, pathogenesis, and treatment of the most prevalent types while emphasizing their skeletal manifestations. Marfan syndrome (MFS) affects at least 1 in 5000 people and is an autosomal dominant (AD) disorder caused by defects in fibrillin-1 leading to pleiotropic complications primarily involving the cardiovascular, musculoskeletal, integumentary, and visual systems. Congenital contractural arachnodactyly is a rare AD disorder delineated from MFS by crumpled ear helices, multiple congenital flexion contractures, and typically absence of dolichocephaly, myopia, ectopia lentis, and aortic enlargement. Homocystinuria is an inborn error of metabolism that deserves mention because of phenotypic similarities with MFS. The pleiotropic nature of MFS and the MFS-related disorders necessitates multidisciplinary management including regular surveillance.