Split-Hand/Foot Malformation (SHFM)

Split-hand/foot malformation (SHFM) is a congenital limb defect affecting the central rays of the autopod that consists of hypoplasia of digits (phalanges, metacarpals, and metatarsals), a deep cleft down the center of the hand or foot, and fusion of remaining digits (Gane and Natarajan 2016), with the incidence varying between 0.64 and 1.00 per 10,000 births (Dai et al. 2010). In severe cases, a lobster claw-like appearance is noted in the extremities, in contrast with mild cases showing limited syndactyly and several instances of non-penetrance. SHFM may represent itself as an isolated entity (non-syndromic) or as part of a syndrome (syndromic) such as long bone deficiency. Both are associated with chromosomal rearrangements, including deletions or translocations (Duijf et al. 2003). Due to the genetic heterogeneity of SHFM, miscellaneous classifications have been proposed; the one containing six types of SHFM is the most prominent. SHFM 1, 2, 3, 4, 5, and 6 are respectively mapped to chromosomes 7q21.3q22 (Scherer et al. 1994), Xq24q26 (Faiyaz-Ul-Haque et al. 2005), 10q24 (de Mollerat et al. 2003), p63 gene on 3q27 (Ianakiev et al. 2000), 2q31 (Boles et al. 1995), and WNT10B (Ugur and Tolun 2008). However, a more extensive classification involving 12 types can be seen in Table 1 as well as the phenotypes of the above-listed SHFM types.