Limb disorders

Gene: SCNM1

Green List (high evidence)

Comment on list classification: There are 7 unrelated families reported in literature where individuals harbouring biallelic SCNM1 variants presented with polydactyly, sometimes together with syndactyly and brachydactyly. Hence, this gene should be promoted to Green at the next update.

Created: 10 Apr 2026, 3:56 p.m. | Last Modified: 10 Apr 2026, 3:56 p.m.

Panel Version: 7.29

PMID: 36084634 Iturrate et al., 2022
4 individuals from 3 unrelated families with orofaciodigital syndrome. All 4 presented with tongue nodules, hypodontia / microdontia, facial dysmorphism, polydactyly, syndactyly of the toes, type A brachydactyly. 1 individual had a cleft palate. Skeletal features (mesomelic leg/arm shortening, short tibia) were present in 4/4 individuals. No ID/GDD. SCNM1 homozygous variants detected: c.187delC, p.Arg63Valfs∗33; c.152C>A, p.Pro51Gln; and c.301_302insAluYc1 insertion.

Functional evidence: Primary fibroblasts containing SCNM1 mutations, as well as SCNM1 knockout and SCNM1 knockdown RPE-1 cells, were also found with abnormally elongated cilia.

PMID: 41291844 Iturrate et al., 2025
Report of five new patients from four unrelated families with bi-allelic variants in SCNM1. Phenotype: bilateral postaxial polydactyly of hands and feet (5/5), dysmorphic features, ID/GDD (3 unrelated individuals), mesomelic leg shortening (2/4), cleft palate (1/4), hypodontia / microdontia (1/3). Molar tooth sign absent on MRI.
Sources: Literature

Created: 10 Apr 2026, 3:53 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Orofaciodigital syndrome XIX, OMIM:620107; orofaciodigital syndrome 19, MONDO:0859310

Publications

• 36084634
• 41291844