What Is XLMTM?

X-linked myotubular myopathy (XLMTM), commonly known as MTM, is a rare genetic muscle disease (“myopathy”) that causes muscle weakness and low muscle tone. It is present from birth and most common in boys, though girls can be affected too. The condition is estimated to occur in about 1 in 40,000 to 1 in 50,000 newborn males.1-3



XLMTM is part of a larger group of conditions called centronuclear myopathies, which are sometimes also called myotubular myopathies. These conditions get their name from a unique feature seen when doctors look at muscle cells under a microscope. Inside healthy muscle cells, there are tiny "control centers" called nuclei, usually found along the edges of the muscle fibers. But with centronuclear myopathies, these nuclei are found right in the middle of the muscle fibers. There are different forms of centronuclear myopathy.

 

XLMTM may also be referred to as:2

 

  • Myotubular myopathy (MTM)
  • X-linked centronuclear myopathy (XLCNM)
  • XL-MTM
  • X-MTM

Understanding the Causes of XLMTM

The cause of XLMTM is a change in a specific gene called MTM1, which is supposed to tell the body how to make a protein called myotubularin. This protein is vital for strong, healthy muscles. With XLMTM, individuals do not make enough of this protein, leading to very weak muscles and low muscle tone.1,2,4

XLMTM Is an Inherited Muscle Condition

XLMTM is an inherited genetic condition, meaning it's passed down in families through a defective gene. People are born with XLMTM, or symptoms appear soon after birth.

Understanding the Causes of XLMTM

Because the MTM1 gene is on the X chromosome, XLMTM has a specific way of being passed down in families called an X-linked recessive inheritance pattern. This means that XLMTM usually affects more males than females, and females are more often carriers of the gene. However, as the understanding of X-linked conditions evolves, researchers are learning that female carriers can be affected to varying degrees.1,2,5

Recognizing Signs and Symptoms

Here are some common signs and how they often impact daily life and care for individuals with XLMTM:

Muscle Weakness and Breathing Challenges:

Individuals with XLMTM are often born with generalized muscle weakness (myopathy) and low muscle tone (hypotonia). Symptoms are present at birth or shortly thereafter. Many affected individuals may fail to breathe spontaneously and require mechanical ventilation and the use of a tracheostomy tube and ventilator.

Feeding Difficulties:

Most people living with XLMTM have difficulties with feeding and swallowing (dysphagia). This often means tube feeding is required (e.g., with a gastrostomy tube).

Frequent Infections:

Affected individuals are prone to developing respiratory infections, which can be life-threatening and require additional care.

Motor Skill Development:

Individuals often have limited spontaneous movement and poor head control. They may not be able to sit, walk, or stand without support and often require the use of a wheelchair.

Physical Complications:

Additional symptoms may also include facial weakness, skeletal abnormalities such as scoliosis, and joint contractures, requiring the use of splints, braces, and other assistive technology.

Communication:

Speech and communication difficulties may also occur, especially for those dependent on mechanical ventilation. Many individuals will use alternative forms of communication, such as sign language, speaking valves with tracheostomy, and assistive technology communication devices.

Other Signs:

Affected boys often have undescended testes (cryptorchidism) and long, thin fingers and toes.

Cognitive Function:

Cognitive function is not thought to be affected. However, many individuals will require specialized education services and assistance with neurodevelopmental needs.

Though XLMTM is not a progressive disease, symptoms and individual needs may change as a person grows. Maintaining open communication with your healthcare providers is important to adapt care as needed.

Diagnosing XLMTM

A healthcare provider may recommend a muscle biopsy or genetic test to confirm a diagnosis of XLMTM.

Muscle Biopsy

A muscle biopsy is when a very small piece of muscle tissue is carefully removed so doctors can examine it. This is done to help diagnose muscle conditions. The tissue is looked at closely under a microscope, and it can also be used for other special studies. The biopsy can be done using a needle or through a small cut in the skin.

Genetic Test

A genetic test is a blood test that looks for mutations in a person’s genes that cause conditions like XLMTM. It can take about 4 weeks to get the results of this test. A doctor might suggest speaking with a genetic counselor or other specialists to help understand the results and figure out what steps to take next.

It’s a good idea to talk to a healthcare provider about how to check if these tests are covered by insurance.

References

 

1. Lawlor MW, Dowling JJ. X-linked myotubular myopathy. Neuromuscul Disord. 2021;31(10):1004-1012. doi:10.1016/j.nmd.2021.08.003 2. Dowling JJ, Lawlor MW, Das S. X-linked myotubular myopathy. In: Adam MP, Bick S, Mirzaa GM, et al., eds. GeneReviews® [Internet]. Updated August 23, 2018. Accessed November 17, 2025. https://www.ncbi.nlm.nih.gov/books/NBK1432 3. Vandersmissen I, Biancalana V, Servais L, et al. An integrated modelling methodology for estimating the prevalence of centronuclear myopathy. Neuromuscul Disord. 2018;28(9):766-777. doi:10.1016/j.nmd.2018.06.012 4. Lawlor MW, Beggs AH, Buj-Bello A, et al. Skeletal muscle pathology in X-linked myotubular myopathy: review with cross-species comparisons. J Neuropathol Exp Neurol. 2016;75(2):102-110. doi:10.1093/jnen/nlv020 5. X-linked myotubular myopathy. National Organization for Rare Disorders (NORD). Updated April 13, 2016. Accessed November 17, 2025. https://rarediseases.org/rare-diseases/x-linked-myotubular-myopathy/ 6. Graham RJ, Muntoni F, Hughes I, et al. Mortality and respiratory support in X-linked myotubular myopathy: a RECENSUS retrospective analysis. Arch Dis Child. 2020;105(4):332-338. doi:10.1136/archdischild-2019-317910 7. Annoussamy M, Lilien C. Gidaro T, et al. X-linked myotubular myopathy: A prospective international natural history study. Neurology. 2019;92(16):e1852-e1867. doi:10.1212/WNL.0000000000007319 8. Amburgey K, Tsuchiya E, de Chastonay S, et al. A natural history study of X-linked myotubular myopathy. Neurology. 2017;89(13):1355-1364. doi:10.1212/WNL.0000000000004415 9. Dowling JJ, Müller-Felber W, Smith BK, et al. INCEPTUS natural history, run-in study for gene replacement clinical trial in X-linked myotubular myopathy. J Neuromuscul Dis. 2022;9(4):503-516. doi:10.3233/JND-210781 10. Woo H, Lee S, Han JY, et al. Clinical characteristics and neurologic outcomes of X-linked myotubular myopathy. Ann Child Neurol. 2022;30(3):127-133. doi: 10.26815/acn.2022.00171 11. Cumbo F, Tosi M, Mizzoni I, et al. Cognitive, adaptive and perseverative aspects characterization of children with XLMTM: An explorative study. Eur J Paediatr Neurol. 2024;51:58-61. doi: 10.1016/j.ejpn.2024.05.013