Distinct mutations of the SMCHD1 gene are responsible for a form of facioscapulohumeral myopathy (FSH type 2) but also for an ultra-rare syndrome comprising abnormalities of the olfactory system such as arhinia, nasal hypoplasia or anosmia. American researchers collected clinical and genetic data from eleven patients with the latter syndrome:
- only three had a genotype compatible with FSH2 (shortening of D4Z4 repeats, hypomethylation and presence of a permissive 4qA allele),
- the production of the DUX4 protein was well de-repressed in the fibroblasts of these patients, as in FSH, however,
- no neuromuscular phenotype could be objectified, proof of the complexity of the mechanisms involved in explaining the phenotypic variations of the SMCHD1 gene.
Cross-sectional, Neuromuscular Phenotyping Study of Arhinia Patients With SMCHD1 Variants. Mohassel P, Chang N, Inoue K, et al. Neurology. 2022 Feb 4:10.1212/WNL.0000000000200032.
