X-linked myotubular myopathy
| X-linked myotubular myopathy | |
|---|---|
| Other names | XLMTM |
 | |
| This condition is inherited in an X-linked recessive manner. | |
X-linked myotubular myopathy (MTM) is a form of centronuclear myopathy (CNM) associated with mutations in the myotubularin 1 gene. It is predominantly found in male infants. It is one of the most severe forms of congenital muscle disease, characterized by marked muscle weakness, hypotonia, and difficulty with feeding and breathing.[1] Abbreviations such as XL-MTM, XLMTM or X-MTM are sometimes used to emphasize that the mutation occurs on the X chromosome.
Genetics
MTM is caused by mutations in the myotubularin gene (MTM1), located on the long arm of the X chromosome (Xq28). Because males have only one X chromosome, they are at greater risk for diseases stemming from mutations encoded in it; this is why X-linked MTM is most commonly observed in males.[2] Females can be "carriers" for an X-linked genetic abnormality, but often will not be clinically affected themselves, as they have a second wildtype copy of MTM1.
There are, however, two scenarios where a female with an X-linked recessive abnormality would display clinical symptoms: manifesting carrier, and X-inactivation. A manifesting carrier usually has no noticeable problems at birth, with symptoms showing up later in life. With X-inactivation, one of the female's X chromosome copies is silenced, preventing the wildtype gene from expressing and forcing symptomatic expression of the mutated MTM1. Thus, she congenitally presents (is born with) MTM.[3] Girls with myopathy and a muscle biopsy showing a centronuclear pattern should be tested for MTM1 mutations.[3]
Research
Astellas Gene Therapies (earlier called Audentes Therapeutics) is developing an experimental gene therapy to treat the condition. A clinical trial was halted in 2020 after two boys participating in the trial died of liver inflammation and sepsis.[4]
References
- ↑ "X-linked myotubular myopathy: MedlinePlus Genetics". medlineplus.gov. Retrieved 2026-04-17.
- ↑ Frost, Dr Amy. "X-linked inheritance — Knowledge Hub". GeNotes. Retrieved 2026-04-17.
- 1 2 Jungbluth H, Sewry C, Buj-Bello A, Kristiansen M, Ørstavik K, Kelsey A, Manzur A, Mercuri E, Wallgren-Pettersson C, Muntoni F (2003). "Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation". Neuromuscul Disord. 13 (1): 55–9. doi:10.1016/S0960-8966(02)00194-3. PMID 12467733. S2CID 11161762.
- ↑ Kaiser, Jocelyn (29 Jun 2020). "Two deaths in gene therapy trial for rare muscle disease". Science. Retrieved 2026-04-17.