Symphalangism, Proximal, 1b

A number sign (#) is used with this entry because this form of proximal symphalangism (SYM1B) is caused by heterozygous mutation in the GDF5 gene (601146) on chromosome 20q11.

For a discussion of genetic heterogeneity of proximal symphalangism (SYM1), see SYM1A (185800).

Clinical Features

Seemann et al. (2005) described a family diagnosed with SYM1 on the basis of the affected members' inability to bend the fourth and fifth fingers at the interphalangeal joints and the loss of flexion creases at the corresponding sites. X-rays of the hands showed a complete bony fusion between the proximal and middle phalanges of the fifth digit and, to a lesser extent, the fourth.

Wang et al. (2006) described 2 large 5-generation Chinese families in which 17 members were diagnosed with SYM1. The patients exhibited some unique clinical features, including absence of the cuboid bone and lack of shortness of the first and fifth metacarpal bones, and the presence of distal interphalangeal joint fusions and flat feet. The fusions and malformations were noted to be more severe with increasing age.

Molecular Genetics

In affected members of a family with proximal symphalangism in whom mutations in the NOG gene (135100) had been excluded, Seemann et al. (2005) identified a heterozygous missense mutation in the GDF5 gene (R438L; 601146.0011).

In affected members of 2 large 5-generation Chinese families with SYM1 in whom linkage to NOG had been excluded, Wang et al. (2006) identified heterozygosity for a missense mutation in the GDF5 gene (E491K; 601146.0014).

Yang et al. (2008) identified heterozygosity for a missense mutation (L373R; 601146.0017) in the GDF5 gene in a Han Chinese family with proximal symphalangism.