Congenital Ectrodactyly and Its Genetic Linkage

Congenital ectrodactyly is usually clinically characterized with phalangeal dysplasia. Severe cases may be manifested with median split of hand and foot and/or combined with fusion of the rest fingers and toes, named a syndrome of split hand/foot malformation (SHFM). Some severe patients may be accompanied by ectodermal and craniofacial dysplasia, mental retardation and orofacial fissure. Till now there were seven types of SHFM reported. Among them, SHFM1, SHFM3, SHFM4, and SHFM5 are autosomal dominant, SHFM6 is autosomal recessive, SHFM2 is X-linked inheritance, and SHFLD manifested as autosomal incomplete dominant inheritance. The related genes are DSSI, DLX5, and DLX6 at 7q21.3-q22.1 (SHFM1), FGF3 and TDU at Xq26 (SHFM2), HUG1、TLX1、LBX1、BTRC、POLL、FBXW4 at 10q24 (SHFM3), TP63 at 3q27 (SHFM4), DLX1, DLX2 at 2q31 (SHFM5), WNT10B at 12q13.11-q13 (SHFM6), and BHLHA9 at 17p13.3 or l19p13.11. Gene diagnosis is the key to locate the mutation and the effective methods for healthy reproduction. Genetic diagnostic steps should be based on genetic frequency and the healthy reproductive strategy may be based on pre-implantation genetic diagnosis (PGD) and prenatal genetic diagnosis.