x-linked Myotubular Myopathy

What is Myotubular Myopathy?

X-linked Myotubular Myopathy (XLMTM) is the most common and usually most severe centronuclear myopathy. Due to the position of the MTM1-gene usually only boys are affected. Probably, 1 in 50000 newborn baby boys is affected.

Before birth most  parents report much amniotic fluid and little movements of the child. After birth severe hypertonia (floppy infant syndrome) and breathing difficulties (respiratory sufficiency) are common.

Symptoms of  Myotubular Myopathy vary in extent and combination. Usually the hypertonia causes problems with the respiration as well as with swallowing and thus the ability to eat. Therefore, most affected patients  need a respiration aids (from breathing masks to ventilation machines), feeding tubes and (electric) wheelchairs.

Many boys with myotubular myopathy have one or more of the following symptoms: long, slim head, high palate (roof of the mouth), little eye movement (Ophthalmoparesis), hanging eye lids (Ptosis), undescended testicles (Maldescensus testis), body height more than 90% of  boys of the same agee.

Often connected with myotubular myopathy seem the following symptoms: problems with the kidneys (kidney stones and calcification), the liver (bleeding,  internal anomalies), scoliosis, high frequency of bone fractures

How is Myotubular Myopathy inherited?

IMG_1051Quelle: Wikipedia

Myotubular Myopathy is inherited via a mutation in the MTM1 – gene. This gene is on one of the X chromosomes of the mother, more exactly on the long arm  of an X chromosome in position Xq28.

In 10 – 20 %  the boy did not inherit the mutated MTM1 gene from his mother. Instead, it was a spontaneous (“de novo”) mutation. In these cases, the mother is not a carrier of the mutation or the related condition.

How is Myotubular Myopathy diagnosed?

Usually the symptoms of the affected child would lead to a variety of muscle conditions. Mutations in a lot of genes could be responsible  for the condition. Therefore, in most cases a muscle biopsy is conducted.  The result of the muscle biopsy is a thin section of muscle fibers that will show in the case of centronuclear myopathies a very characteristic pattern with centralized nuclei. In normal muscle cells the nuclei are at the border of the cells. Thus, by the muscle biopsy, a lot of possible other conditions / mutations in other genes can be excluded. Now, only 3 to 4 possible genes (the genes responsible for centronuclear myopathies, MTM1, DNM2, …) have to be tested. If the condition is severe and the affected person is a boy, the probability of a mutation in the MTM1 gene is higher than for any other gene. Thus this gene is tested first.

What are the molecular causes of myotubular Myopathy?

German and French researchers (among them Volker Haucke and Jocelyn Laporte) published in January 2016 an article in nature  that contributes to a better understanding of the molecular causes of myotubular myopathy.

Are there therapeutic approaches for a cure for myotubular myopathy?

Yes, there are some promising approaches.
The most advanced approach is gene therapy. In fall 2017 the first clinical test with human patients started. Probably in 2018 the study will be extended to study sites in Europe (London and Munich).
In addition, there are some other therapies.


Artikel zum Weiterlesen:


  • http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=DE&data_id=364&Disease_Disease_Search_diseaseGroup=myotubulare-myopathie&Disease_Disease_Search_diseaseType=Pat&Krankheite(n)/Krankheitsgruppe=Myopathie–zentronukleare–X-chromosomale–Myotubulare-Myopathie-&title=Myopathie–zentronukleare–X-chromosomale–Myotubulare-Myopathie-&search=Disease_Search_Simple (Zugriff vom 18.09.2015)
  • http://rarediseases.org/rare-diseases/x-linked-myotubular-myopathy/ (Zugriff vom 18.09.2015)
  • Cahill, Patrick J.; Rinella, Anthony S.; Bielski, Robert J. (2007): Orthopaedic complications of myotubular myopathy. In Journal of pediatric orthopedics 27 (1), pp. 98–103. DOI: 10.1097/BPO.0b013e31802b6c73.
  • Jungbluth, Heinz; Wallgren-Pettersson, Carina; Laporte, Jocelyn (2008): Centronuclear (myotubular) myopathy. In Orphanet journal of rare diseases 3, p. 26. DOI: 10.1186/1750-1172-3-26.
  • Das S, Dowling J, Pierson CR.(2002):X-linked Centronuklear Myopathy.In Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K, editors. (http://www.ncbi.nlm.nih.gov/books/NBK1432/) GeneReviews®[Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. 2002 Feb 25 [updated 2011 Oct 06].