| Affiliation: | 1. Clinique de Génétique Guy Fontaine, H?pital Jeanne de Flandre, CHU Lille, Lille, France;2. Laboratoire de Biochimie et Biologie Moléculaire, Centre de Biologie Pathologie, CHU Lille, Lille, France;3. EA7364‐RADEME, Université de Lille, Lille, France;4. Unité de Foetopathologie, AP‐HP, H?pital Antoine Béclère, Clamart, France;5. INSERM U1169, Kremlin Bicêtre, France;6. Servi?o de Genética Departamento da Crian?a e da Família, Hospital de Santa Maria, Lisbon, Portugal;7. Service de Génétique Clinique, Département de Génétique, AP‐HM CHU Timone Enfants, Marseille, France;8. https://orcid.org/0000-0002-1368-1023;9. Florence Petit, Clinique de Génétique Guy Fontaine, H?pital Jeanne de Flandre, CHU Lille, F‐59000 Lille, France. |
| Abstract: | Split‐hand/foot malformation (SHFM) is a genetically heterogeneous congenital limb malformation typically limited to a defect of the central rays of the autopod, presenting as a median cleft of hands and feet. It can be associated with long bone deficiency or included in more complex syndromes. Among the numerous genetic causes, WNT10B homozygous variants have been recently identified in consanguineous families, but remain still rarely described (SHFM6; MIM225300). We report on three novel SHFM families harboring WNT10B variants and review the literature, allowing us to highlight some clinical findings. The feet are more severely affected than the hands and there is a frequent asymmetry without obvious side‐bias. Syndactyly of third–fourth fingers was a frequent finding (62%). Polydactyly, which was classically described in SHFM6, was only present in 27% of patients. No genotype–phenotype correlation is delineated but heterozygous individuals might have mild features of SHFM, suggesting a dose‐effect of the WNT10B loss‐of‐function. |
