-related congenital myopathy: expansion of the clinical and genetic spectrum.

BACKGROUND

Biallelic pathogenic variants in have recently been associated with two congenital myopathy phenotypes: a severe form associated with hypotonia, long bone fractures, respiratory insufficiency and infantile death, and a milder form characterised by proximal muscle weakness with survival into adulthood.

OBJECTIVE

We report eight patients from four unrelated families with biallelic pathogenic variants in exon 15 of .

METHODS

Whole exome sequencing was used to detect variants in .

RESULTS

Common clinical features were noted for all patients, which included proximal myopathy, normal serum creatine kinase levels and diffuse muscle atrophy with relative preservation of the quadriceps femoris muscle on muscle imaging. Additionally, some patients with -related myopathy had respiratory involvement and required bilevel positive airway pressure support. Muscle biopsy showed multi-minicores and type I fibre predominance with internalised nuclei.

CONCLUSION

-related congenital myopathy is an emerging entity that is clinically recognisable. Phenotypic variability associated with variants in can result from differences in variant location and type and is also observed between patients homozygous for the same variant, rendering specific genotype-phenotype correlations difficult. Our work broadens the phenotypic spectrum of -related congenital myopathy.