A classification system for split-hand/ foot malformation (SHFM): A proposal based on 3 pedigrees with WNT10B...

Area of Science:

• Genetics
• Developmental Biology
• Medical Research

Background:

• Split hand/foot malformation type 6 (SHFM6) is a rare congenital disorder.
• SHFM6 is caused by pathogenic variants in the WNT10B gene.
• Specific phenotypic characteristics of SHFM6 have not been well-defined.

Observation:

• This study presents three unrelated families with SHFM6.
• Three novel WNT10B pathogenic variants were identified: two nonsense, one splice, and one compound heterozygous.
• The first compound heterozygous pathogenic variant for SHFM6 is reported.

Findings:

• SHFM6 exhibits distinct phenotypic features, including more severe foot defects, polydactyly, flexion contractures, and phalangeal dysplasia.
• A classification system for hand/foot defects in SHFM6 was developed.
• WNT10B pathogenic variants are confirmed as the cause of SHFM6 with specific associated phenotypes.

Implications:

• This research expands the understanding of WNT10B gene function in limb development.
• The findings provide a basis for improved diagnosis and genetic counseling for SHFM6.
• Further research into WNT10B-related disorders can elucidate developmental pathways.