Figure 1.

Split-foot malformation with mesoaxial polydactyly (SFMMP) in two families. (A) Pedigree of family F1. Black symbols indicate individuals with a split-foot phenotype and/or hearing loss. (+) c.1103T reference allele of ZAK; (−) c.1103T > G (p.Phe368Cys) mutation of ZAK. Autozygosity mapping was performed with DNA from individuals designated with an asterisk; and exome sequencing was performed with DNA from individual VI:3, designated with an arrowhead. (B) Pedigree of family F2. IV:2 is affected by the split-foot phenotype. (+) Reference allele; (−) genomic deletion of exons 12–16 of ZAK. (C) Pictures of the feet of affected individuals from family F1 showing no split foot in V:2, bilateral split-foot malformation in VI:3 and VI:4, and unilateral split-foot malformation in VI:1. (D) Hands and feet of the affected child in family F2. The nail anomaly is boxed. (E) Radiographs of the feet of individual VI:4 in family 1 showing bilateral split-foot malformation, syndactyly between the first and rudimentary second toes, duplication of the left proximal phalanx of the second toe corresponding to mesoaxial polydactyly (arrowhead), Y-shaped appearance of the right metatarsal bone II due to synostosis between the horizontally placed remnant of the proximal phalanx II and the hypoplastic metatarsal II, and hypoplastic and misshaped phalangeal bones of toes III to V with fusions of some interphalangeal joints. In addition to split-foot malformation with missing third toe, the radiograph of the left foot of individual F2-IV:2 shows cutaneous syndactyly between the first and second toes and hypoplasia of the distal phalanx of the first ray and of the middle and distal phalanges of the second toe. A second rudimentary phalangeal bone of toe II is present (arrowhead). There is hypoplasia of middle and distal phalanges of toes IV and V, as well as syndactyly between these toes. (F) Clinical pictures of individual F1-IV:4 and individual F2-IV:2 showing a duplication of the nail bed on digit IV of both hands.