Women with X-Linked Myotubular Myopathy (MTM1)
X-linked myotubular myopathy (XLMTM) is often seen as a condition that affects males, but females carrying the altered MTM1 gene should also be seen, heard, and supported. This page is here to provide clear information on what it means to be a woman with the altered MTM1 gene, the rare cases where symptoms occur, and how research and advocacy is helping to improve understanding and support.
Cause of XLMTM
X-Linked myotubular myopathy (XLMTM) is caused by a change in the MTM1 gene on the X chromosome, one of the sex chromosomes. Males have one X chromosome and one Y chromosome; females have two X chromosomes. Since males only have one copy of the MTM1 gene, they are much more likely to be affected by XLMTM.
Females who have a confirmed alteration on the MTM1 gene are often referred to as ‘carriers’ of the condition, meaning they can pass on the altered gene but often do not experience signs and symptoms. However, sometimes, a female carrier may have symptoms of XLMTM, such as, but not limited to, muscle weakness, fatigue (tiredness), difficulty exercising, muscle pain and muscle cramps. These symptoms are often mild but can be severe in rare cases. Clinicians may refer to female carriers experiencing symptoms as ‘manifesting carriers’, but there is a growing view that affected women should not be referred to merely as ‘carriers’ as this may underplay any symptoms they are experiencing. It is now thought that women who are experiencing symptoms, even if mild, should be referred to as ‘women with XLMTM’.
You can scroll further down this page to read the more simplistic, lay explanation which gives an analogy on the patterns of inheritance based from new findings in a 2025 study paper.
Why can women with an XLMTM mutation have symptoms?
As females don’t need both of their X chromosomes, one of them is turned off in every single cell of the body. This process usually occurs randomly as the female embryo develops.
But sometimes this process becomes skewed, when one X chromosome is switched off more than the other (skewed X-inactivation). This is thought to be what happens in females with symptoms of XLMTM; the healthy X chromosome is inactivated and the X carrying the altered MTM1 gene is active. The reasons for skewed X-inactivation are not well understood.
Why do symptoms vary between women, even in the same family?
As X-inactivation is usually random, and this randomness is not inherited, it is not the same from female to female. This is why symptoms of XLMTM can vary considerably between women with an alteration in the MTM 1 gene, even within the same family.
Research about women with an alteration in the MTM1 gene
Researchers are working hard to learn more about the symptoms that some women with XLMTM experience. More knowledge will help to improve care and support for these women and potentially allow them to participate in clinical trials testing new treatments for XLMTM.
A European study (2020, Voermans, et al) which was supported by the Myotubular Trust found that symptoms in women with an alteration in the MTM1 gene are more common than previously assumed. Mapping out the variation of symptoms is an important step towards greater recognition of females affected by XLMTM.
A new study is being planned to take place in the UK in 2026
As XLMTM is often thought of as only affecting males, women with XLMTM who are experiencing symptoms may feel forgotten. By funding research and working closely with clinicians and families, the Myotubular Trust is helping to raise awareness, and support for females affected by XLMTM too.
Explained simply
Imagine every cell has two copies of an instruction manual for running a particular part of the body—one copy on each X chromosome. (In women each cell has two X chromosomes)
Early in development, each cell puts one of the two manuals away and uses the other. Which manual is put away is largely random.
Now imagine that one manual contains a printing error (the genetic variant), while the other is correct.
- Some cells will use the correct manual.
- Other cells will use the manual with the error.
Different people can end up with very different proportions of cells using each manual. How our cells choose which manual to use is not inherited. It is a random choice in every person.
Sometimes the balance is fairly even; sometimes many more cells use one manual than the other. This is skewed X-inactivation.
This means that having the same genetic change does not necessarily mean having the same outcome. If most of the cells in an important tissue are using the correct manual, the person may have few effects. If more of those cells are using the manual with the error, the effects may be greater.
In short: X-inactivation is like each cell choosing which of two instruction manuals to follow. The proportion and distribution of cells following each version can help explain why an X-linked genetic change can affect different people in different ways. Even the balance of those choices can vary between family members, ie they can inherit the same genetic change but have different symptoms because each person develops their own unique pattern of X-inactivation.
Useful Resources
Remember The Girls is an organisation aiming to break stigma facing females impacted by X-linked conditions by providing them with tools to seek support, engage with research, and access family planning options. It also advocates for increased attention of clinicians to the physical, emotional, and reproductive needs of females impacted by X-linked conditions.
Useful Publications
XLMTM Female Carriers : a review of patient reported data collected by the MTM & CNM Global Patient Registry J Bohill, et al (2025)
Neuromuscular Features in XL-MTM Carriers : A Cross-sectional Study in an Unselected Cohort Franken, Bouman, Reumers, et al (2022)
(Lay Report) Outcomes of a Questionnaire Study on Symptoms of Female Carriers, Voermans et al (2020)
Spectrum of clinical features in x-linked myotubular myopathy female carriers Reumers, Braun, et al (2021)
Adult MTM1-related myopathy Carriers Foley, et al (2019)
Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues, Biancalana et al (2017)
X inactivation patterns in carriers of X linked myotubular myopathy Kristiansen et al (2003)
Patterns of X-linked inheritance:A new approach for the genome era Basava, et al (2025)
Care Guidelines
You can also visit our ‘Factsheets’ page for standards of care and other useful management references.
If you are concerned about your respiratory health or experience frequent chest infections please contact your GP for a referral to a local NHS respiratory care team who can test your lung function and advise you accordingly. A good source for practical information on breathing well can be found on the Asthma and Lung UK website. Two further resources about airways clearance and mouthpiece ventilation can be found here:
Developing Best Practice Guidelines for Management of Mouthpiece Ventilation in Neuromuscular Disorders Chatwin, et al (2020)
Airways clearance techniques in neuromuscular disorders: a state of the art review Chatwin et al (2018)
If you don’t have a genetic diagnosis, ask your GP for a referral to your Regional Genetics Service for advice and guidance. You can ask for this referral at any point – whether your immediate or extended family has had a genetic diagnosis of myotubular myopathy / centronuclear myopathy recently, or in the past. You are always welcome to email the Myotubular Trust at contact@myotubulartrust.org if you need any support to obtain a genetics referral. To find out more about a genetics please read ‘Getting A Diagnosis’.
MDUK provide a good resource about exercise if you have a neuromuscular weakness, which can be found here : https://www.musculardystrophyuk.org/support/information/your-condition/exercise-for-adults/
