Syndactyly, Type V

A number sign (#) is used with this entry because of evidence that syndactyly type V (SDTY5) is caused by heterozygous mutation in the HOXD13 gene (142989) on chromosome 2q31.

Clinical Features

The characteristic finding in this rare type of syndactyly is the presence of an associated metacarpal and metatarsal fusion. The metacarpals and metatarsals most commonly fused are the 4th and 5th or the 3rd and 4th. Soft tissue syndactyly usually affects the 3rd and 4th fingers and the 2nd and 3rd toes. Syndactyly is usually more extensive and complete. Kemp and Ravn (1932) described this anomaly in 5 generations of a family from the island of Seeland.

Robinow et al. (1982) reported syndactyly type V in a mother and 3 of her 4 children. All had fusion of metacarpals 4 and 5. None had metatarsal fusion although other anomalies of the feet were present.

The difficulties of categorizing the several forms of syndactyly and polysyndactyly are evident (Malik et al., 2005).

In the Han Chinese family described by Zhao et al. (2007), there were 23 affected individuals in 6 generations. In 9 affected individuals, bilateral or unilateral fusion of metacarpals 4 and 5 were demonstrated. The fusion was variable in extent. The proband had a complete fusion in his right hand and 8 other affected individuals had bilateral complete fusion. None of the affected individuals had metatarsal fusion. The most constant foot deformities were varus deviation of the first metatarsals; valgus deviation of toes 1 through 4; hyperplasia of the first ray; hypoplasia and shortness of metatarsals 2 through 5; and shortened and tucked fifth toes. Zhao et al. (2007) was of the opinion that the disorder in this family most resembled that described by Robinow et al. (1982).

Molecular Genetics

In the family reported by Kemp and Ravn (1932), Kjaer et al. (2005) found a polyalanine expansion in the HOXD13 gene (142989.0008), a duplication of 21 basepairs that expanded the polyalanine repeat from 15 to 22 alanine residues.

In a Han Chinese family with syndactyly type V, Zhao et al. (2007) detected a missense mutation in the HOXD13 gene (Q317R; 142989.0009).