GDF5-missense mutations at position N445 are associated with multiple synostosis syndrome.

Pedigrees are shown on left. Clinical phenotypes associated with GDF5 mutations N445T (I) or N445K (II, III, IV) are shown in (A–E). Pictures in each horizontal line belong to one patient. (I) N445T mutation in a 5 year old boy; (II), (III) N445K mutation in affected sibs, both adults; (IV) 9 year old girl with the N445K mutation. (A) Hand radiographs show fusion and abnormal configuration of carpal bones as well as proximal symphalangism of fingers II to V in all affected. Short first metacarpal bones are present in patient I and II, shortened first proximal phalanges are visible in patient II. (B) Clinical pictures display the brachydactyly of fingers II to V and missing flexion creases (see II, III). Some distal phalanges are hypoplastic to variable degree (I). (C, D) Feet are similarly affected with fusion of tarsal bones, proximal symphalangism, shortened toes or hypoplastic toenails. (E) Synostosis of humerus and radius leading to a stiffened elbow joint.