Background: MTM1-related myopathy is an inherited skeletal-muscle disorder caused by pathogenic variants in MTM1, which encodes myotubularin. Although classically associated with severe neonatal disease in males, its clinical spectrum includes milder male phenotypes and symptomatic heterozygous females. 

Objective: To review the molecular pathogenesis, clinical spectrum, diagnosis, management, prognosis, and emerging therapies, with emphasis on manifesting females and the possible contribution of skewed X-chromosome inactivation. Methods: This narrative review synthesizes clinical, genetic, pathological, and translational literature identified through PubMed/MEDLINE, Web of Science, and Google Scholar for January 1995 through October 2026. It is not a systematic review or meta-analysis. 

Results: Pathogenic MTM1 variants disrupt myotubularin function, phosphoinositide regulation, membrane organization, and skeletal-muscle architecture. Presentations range from neonatal respiratory failure to childhood- or adult-recognized weakness. Heterozygous females may develop progressive or asymmetric weakness, ocular manifestations, and respiratory dysfunction. Molecular testing is central to diagnosis, with imaging, electrophysiology, and biopsy providing complementary evidence. Supportive multidisciplinary care remains essential while gene replacement and other disease-modifying approaches are investigated. 

Conclusion: Recognition of the full clinical spectrum, including affected females, is important for timely diagnosis and appropriate surveillance. Skewed X-chromosome inactivation is a possible contributor to female disease expression but should not be assumed without direct evidence. Further natural-history and therapeutic research is needed.