Split-hand/split-foot malformation

A genetic malformation syndrome of the limbs with syndactyly, median clefts of the hands and feet, and aplasia (failure of development) and/or hypoplasia (underdevelopment) of the phalanges (the digits), the metacarpals (the bones leading up to the fingers), and the metatarsals (the bones leading up to the toes).

The split-hand/split-foot malformation (SHFM) involves ectrodactyly (the absence of all or part of a finger or toes) It has also been called the lobster-claw deformity.

SHFM is inherited as an autosomal dominant trait with variable expressivity and incomplete penetrance.

The gene for SHFM is on chromosome 7 in the region of bands q21.2-q21.3. SHFM has been found to be due to a mutation in the p63 gene required for the development and maintenance of what is called the apical ectodermal ridge, a critical signaling center in the developing limbs.

This ridge is crucial for the development of the thumb-pinky axis, proper differentiation of cells in the developing limb, and linear growth of the limb.

Mutations in the p63 protein are also responsible for the EEC (ectrodactyly, ectodermal dysplasia, and facial cleft) syndrome.

The location of the mutation in the p63 protein determines whether it leads to SHFM or EEC.