Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

X-linked myotubular myopathy

Reviewed July 2014

What is X-linked myotubular myopathy?

X-linked myotubular myopathy is a condition that primarily affects muscles used for movement (skeletal muscles) and occurs almost exclusively in males. People with this condition have muscle weakness (myopathy) and decreased muscle tone (hypotonia) that are usually evident at birth.

The muscle problems in X-linked myotubular myopathy impair the development of motor skills such as sitting, standing, and walking. Affected infants may also have difficulties with feeding due to muscle weakness. Individuals with this condition often do not have the muscle strength to breathe on their own and must be supported with a machine to help them breathe (mechanical ventilation). Some affected individuals need breathing assistance only periodically, typically during sleep, while others require it continuously. People with X-linked myotubular myopathy may also have weakness in the muscles that control eye movement (ophthalmoplegia), weakness in other muscles of the face, and absent reflexes (areflexia).

In X-linked myotubular myopathy, muscle weakness often disrupts normal bone development and can lead to fragile bones, an abnormal curvature of the spine (scoliosis), and joint deformities (contractures) of the hips and knees. People with X-linked myotubular myopathy may have a large head with a narrow and elongated face and a high, arched roof of the mouth (palate). They may also have liver disease, recurrent ear and respiratory infections, or seizures.

Because of their severe breathing problems, individuals with X-linked myotubular myopathy usually survive only into early childhood; however, some people with this condition have lived into adulthood.

X-linked myotubular myopathy is a member of a group of disorders called centronuclear myopathies. In centronuclear myopathies, the nucleus is found at the center of many rod-shaped muscle cells instead of at either end, where it is normally located.

How common is X-linked myotubular myopathy?

The incidence of X-linked myotubular myopathy is estimated to be 1 in 50,000 newborn males worldwide.

What genes are related to X-linked myotubular myopathy?

Mutations in the MTM1 gene cause X-linked myotubular myopathy. The MTM1 gene provides instructions for producing an enzyme called myotubularin. Myotubularin is thought to be involved in the development and maintenance of muscle cells.

MTM1 gene mutations probably disrupt myotubularin's role in muscle cell development and maintenance, causing muscle weakness and other signs and symptoms of X-linked myotubular myopathy.

Related Gene(s)

Changes in this gene are associated with X-linked myotubular myopathy.

  • MTM1

How do people inherit X-linked myotubular myopathy?

X-linked myotubular myopathy is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked myotubular myopathy, the affected male inherits one altered copy from his mother in 80 to 90 percent of cases. In the remaining 10 to 20 percent of cases, the disorder results from a new mutation in the gene that occurs during the formation of a parent's reproductive cells (eggs or sperm) or in early embryonic development. Females with one altered copy of the MTM1 gene generally do not experience signs and symptoms of the disorder. In rare cases, however, females who have one altered copy of the MTM1 gene experience some mild muscle weakness.

Where can I find information about diagnosis or management of X-linked myotubular myopathy?

These resources address the diagnosis or management of X-linked myotubular myopathy and may include treatment providers.

  • Gene Review: X-Linked Centronuclear Myopathy (http://www.ncbi.nlm.nih.gov/books/NBK1432)
  • Genetic Testing Registry: Severe X-linked myotubular myopathy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0410203)

You might also find information on the diagnosis or management of X-linked myotubular myopathy in Educational resources (http://www.ghr.nlm.nih.gov/condition/x-linked-myotubular-myopathy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/x-linked-myotubular-myopathy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about X-linked myotubular myopathy?

You may find the following resources about X-linked myotubular myopathy helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for X-linked myotubular myopathy?

  • CNM
  • MTMX
  • X-linked centronuclear myopathy
  • XLMTM
  • XMTM

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about X-linked myotubular myopathy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding X-linked myotubular myopathy?

cell ; chromosome ; decreased muscle tone ; embryonic ; enzyme ; gene ; His ; hypotonia ; incidence ; inheritance ; inherited ; joint ; motor ; muscle cell ; muscle cells ; muscle tone ; mutation ; new mutation ; nucleus ; ophthalmoplegia ; palate ; recessive ; reproductive cells ; respiratory ; scoliosis ; sex chromosomes ; sperm ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Biancalana V, Caron O, Gallati S, Baas F, Kress W, Novelli G, D'Apice MR, Lagier-Tourenne C, Buj-Bello A, Romero NB, Mandel JL. Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype. Hum Genet. 2003 Feb;112(2):135-42. Epub 2002 Nov 28. (http://www.ncbi.nlm.nih.gov/pubmed/12522554?dopt=Abstract)
  • Bijarnia S, Puri RD, Jain M, Kler N, Roy S, Urtizberea JA, Biancalana V, Verma IC. Mutation studies in X-linked myotubular myopathy in three Indian families. Indian J Pediatr. 2010 Apr;77(4):431-3. doi: 10.1007/s12098-010-0057-6. Epub 2010 Mar 31. (http://www.ncbi.nlm.nih.gov/pubmed/20358311?dopt=Abstract)
  • Cahill PJ, Rinella AS, Bielski RJ. Orthopaedic complications of myotubular myopathy. J Pediatr Orthop. 2007 Jan-Feb;27(1):98-103. (http://www.ncbi.nlm.nih.gov/pubmed/17195806?dopt=Abstract)
  • Echaniz-Laguna A, Biancalana V, Böhm J, Tranchant C, Mandel JL, Laporte J. Adult centronuclear myopathies: A hospital-based study. Rev Neurol (Paris). 2013 Aug-Sep;169(8-9):625-31. doi: 10.1016/j.neurol.2012.12.006. Epub 2013 Aug 9. (http://www.ncbi.nlm.nih.gov/pubmed/23938035?dopt=Abstract)
  • Gene Review: X-Linked Centronuclear Myopathy (http://www.ncbi.nlm.nih.gov/books/NBK1432)
  • Hoffjan S, Thiels C, Vorgerd M, Neuen-Jacob E, Epplen JT, Kress W. Extreme phenotypic variability in a German family with X-linked myotubular myopathy associated with E404K mutation in MTM1. Neuromuscul Disord. 2006 Nov;16(11):749-53. Epub 2006 Sep 26. (http://www.ncbi.nlm.nih.gov/pubmed/17005396?dopt=Abstract)
  • Lawlor MW, Alexander MS, Viola MG, Meng H, Joubert R, Gupta V, Motohashi N, Manfready RA, Hsu CP, Huang P, Buj-Bello A, Kunkel LM, Beggs AH, Gussoni E. Myotubularin-deficient myoblasts display increased apoptosis, delayed proliferation, and poor cell engraftment. Am J Pathol. 2012 Sep;181(3):961-8. doi: 10.1016/j.ajpath.2012.05.016. Epub 2012 Jul 27. (http://www.ncbi.nlm.nih.gov/pubmed/22841819?dopt=Abstract)
  • McEntagart M, Parsons G, Buj-Bello A, Biancalana V, Fenton I, Little M, Krawczak M, Thomas N, Herman G, Clarke A, Wallgren-Pettersson C. Genotype-phenotype correlations in X-linked myotubular myopathy. Neuromuscul Disord. 2002 Dec;12(10):939-46. (http://www.ncbi.nlm.nih.gov/pubmed/12467749?dopt=Abstract)
  • Pierson CR, Tomczak K, Agrawal P, Moghadaszadeh B, Beggs AH. X-linked myotubular and centronuclear myopathies. J Neuropathol Exp Neurol. 2005 Jul;64(7):555-64. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16042307?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2014
Published: December 22, 2014