Split-hand/foot malformation with long-bone deficiency and BHLHA9 duplication: Two cases and expansion of the phenotype to radial agenesis

Split-hand/foot malformation (SHFM) with long-bone deficiency (SHFLD, MIM#119100) is a rare condition characterised by SHFM associated with long-bone malformation usually involving the tibia. Previous published data reported several unrelated patients with 17p13.3 duplication and SHFLD. Recently, BHLHA9 has been proposed to be the major candidate gene responsible for this limb malformation. Here we report two new patients affected with ectrodactyly harbouring a 17p13.3 duplication detected by array-CGH. Both duplications contain 3 genes including BHLHA9 and are inherited from an unaffected parent. One of the patients presents a complete radial agenesis, expanding the phenotype of SHFLD3.

► Two further cases of split-hand/foot malformation with long-bone deficiency (SHFLD3).
► SHFLD3 is associated with 17p13.3 duplication encompassing BHLHA9.
► Expansion of the phenotype of SHFLD3 to radial agenesis.