GDF5 (CDMP1) and Chondrodysplasia (Grebe, Hunter–Thompson, and Du Pan Types), and Brachydactyly, Type C

Abstract

Abstract The human osteochondrodysplasias comprise a large and heterogeneous group of inherited disorders affecting skeletal morphogenesis. Grebe-type chondrodysplasia (OMIM 200700) is characterized by a normal axial skeleton and severely shortened and deformed extremities exhibiting a proximo-distal gradient of severity. This condition is classi%ed as a form of acromesomelic dysplasia. Two other phenotypically similar conditions are the Hunter–Thompson (OMIM 201250) and Du Pan (OMIM 228900) types of chondrodysplasia. Brachydactyly type C (BTC) (OMIM 113100) is characterized primarily by shortening and hypersegmentation of phalangeal and metacarpal bones, and occasionally polydactyly and other skeletal abnormalities. In contrast to the autosomal recessive Grebe, Hunter– Thompson, and Du Pan types of chondrodysplasia, BTC is inherited as autosomal dominant. These conditions are caused by mutations in the gene encoding growth differentiation factor 5 (GDF5), otherwise known as cartilage-derived morphogenetic protein-1 (CDMP1) (OMIM 601146), and they together comprise the spectrum of CDMP1 morphopathies. CDMP1 encodes a signaling molecule, which is a member of the transforming growth factor-β (TGF-β) superfamily.