A number sign (#) is used with this entry because of evidence that brachydactyly-syndactyly syndrome is caused by heterozygous mutation in the HOXD13 gene (142989) on chromosome 2q31. One such family has been reported.

Heterozygous mutation in HOXD13 can also cause brachydactyly and syndactyly in association with oligodactyly. One such patient has been reported.

Zhao et al. (2007) described a Han Chinese family in which 23 affected individuals in 6 generations exhibited a complex brachydactyly-syndactyly syndrome. Digital photographs and radiographs were taken for 16 and 13 of them, respectively. Most of the patients exhibited generalized shortening of the hands and feet, 11 displayed broad and short distal phalanges of the thumbs, and 14 had mild cutaneous syndactyly of toes 2 and 3. Radiographs revealed a constant feature in all 13 patients: absence of middle phalanges of toes 2 through 5 and very marked short middle phalanges of the fifth finger. Combined shortening of the middle phalanges was noted, with the effect that the second and fifth fingers were most severely affected. In many cases the shortened middle phalanges were fused with the distal ones. Shortening of metacarpal 5, either alone or in combination with metatarsal 5 and/or other metacarpals/metatarsals, and short proximal phalanges of toes 1, 3, and 4 were noted in several patients. Other common limb anomalies included broad first metatarsals and hallux phalanges, often associated with hallux valgus. The proband also had small spurs of bone between the first and second metatarsals. These limb phenotypes overlapped those of brachydactyly types A4 (BDA4; 112800), D (113200), and E (113300), and syndactyly type I (185900).

Brachydactyly/Syndactyly/Oligodactyly Syndrome

Ibrahim et al. (2013) studied a girl with a complex brachydactyly-syndactyly-oligodactyly phenotype, who was born with normal measurements and had normal psychomotor development. Her hands had only 4 fingers each, as well as severe shortening of the digits and camptodactyly. The terminal phalanges and nails of the thumbs were absent. The left foot had only 3 shortened toes, and the nail of the great toe was absent. Partial cutaneous webbing (syndactyly) was present between the other toes, and the fibular toe was deviated to the tibial side. The right foot had only 4 shortened toes, with partial syndactyly of 2 toes, and the nail of the great toe was absent. X-rays showed missing and deformed metacarpals, metatarsals, and rudimentary phalangeal bones. There was no family history of congenital malformations.

In a large Han Chinese family segregating brachydactyly-syndactyly syndrome, Zhao et al. (2007) found deletion of 21 basepairs in the HOXD13 gene (142989.0010) in affected members. The deletion was located in the imperfect GCN (where N denotes A-C, G, or T) triplet-containing exon 1 of HOXD13, and resulted in a polyalanine contraction of 7 residues. The site and length of the polyalanine tract in HOXD13, like that in the paralogous HOXA13 (142959), are highly conserved among mammals.

In a girl exhibiting brachydactyly, syndactyly, and oligodactyly, who was negative for mutation in the ROR2 gene (602337), Ibrahim et al. (2013) identified heterozygosity for a de novo missense mutation in the HOXD13 gene (Q317K; 142989.0018) that was not found in the dbSNP database.