Novel Homozygous DLX5 and WNT10B Variants Expand the Genetic and Phenotypic Spectrum of Autosomal Recessive Split-Hand/Foot Malformations (SHFM1D and SHFM6).

This study expands both the genetic and phenotypic spectra of autosomal recessive SHFM. We report the second documented case of SHFM1D worldwide. It is the first case to link the recessive SHFM1D with hypospadias, thereby expanding its clinical spectrum. Our findings also distinguish the distinct pathogenic mechanisms of DLX5 and WNT10B-related malformations. Further research into the DLX5/WNT10B pathways may provide insights into human development and differentiation in the context of SHFM and associated anomalies.