Skeletal dysplasia

Gene: SCNM1

Green List (high evidence)

Comment on list classification: There are 3 unrelated families reported in literature where individuals harbouring biallelic SCNM1 variants presented skeletal dysplasia features, such as mesomelic arm and / or leg shortening. Hence, this gene should be promoted to Green at the next update.

Created: 10 Apr 2026, 3:58 p.m. | Last Modified: 10 Apr 2026, 3:58 p.m.

Panel Version: 8.46

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