X-Linked Myotubular Myopathy: A Novel Mutation Expanding the Genotypic Spectrum of a Phenotypically Heterogeneous Myopathy

X-linked myotubular myopathy (XLMTM), a centronuclear congenital myopathy secondary to pathogenic variants in the MTM1 gene encoding myotubularin. is typically recognized for its classic and severe phenotype which includes neonatal hypotonia, severe muscle weakness, long-term ventilator dependence, markedly delayed gross motor milestones with inability to independently ambulate, and a high neonatal and childhood mortality. However, milder congenital forms of the condition and other phenotypes are recognized. We describe a 6-year-old boy with a mild XLMTM phenotype with independent gait and no respiratory insufficiency even in the neonatal period. The child has a hemizygous novel splice site variant in the MTM1 gene (c.232-25A >T) whose pathogenicity was confirmed by cDNA studies (exon 5 skipping) and muscle biopsy findings. We also compared the phenotype of our patient with the few reported cases that presented a mild XLMTM phenotype and no respiratory distress at birth, and discussed the potential mechanisms underlying this phenotype such as the presence of residual expression of the normal myotubularin transcript.

Automated summary

We describe a case of mild XLMTM phenotype with independent gait and no respiratory insufficiency in the neonatal period. The patient carries a novel pathogenic variant in the MTM1 gene, confirmed by genetic testing and muscle biopsy findings. Comparison with similar cases suggests that residual expression of the normal myotubularin transcript may underlie this phenotype.