Myotubular Myopathy

Also known as: Centronuclear Myopathy

Background

The myotubular or centronuclear myopathies (CNMs) are a group of rare inherited neuromuscular diseases. There are three forms, each with distinct inheritance patterns:

  • X-linked myotubular myopathy (XLMTM)
  • autosomal recessive centronuclear myopathy (ar-CNM)
  • autosomal dominant centronuclear myopathy (ad-CNM)

The CNMs are a subgroup of the congenital myopathies – which means there is muscle weakness and wasting usually present at birth. In addition to weakness of the voluntary muscles, in most forms of CNM there is also weakness of the muscles controlling eye movements, and variable involvement of the muscles involved in swallowing and breathing. Contractures (stiffness) of the joints and deformities of the spine are also relatively common.

Credits

Last updated June 2015 by Dr H Jungbluth, Consultant Paediatric Neurologist, Evelina Children’s Hospital, London, UK.

What are the symptoms?

X-linked myotubular myopathy (XLMTM)

This is one of the more common types of CNM and the most severe. Due to its specific inheritance pattern the condition almost always affects boys. At birth, the symptoms include hypotonia (floppiness), breathing and swallowing difficulties. Motor skills are the most affected, causing difficulties with sitting, standing and walking. The muscles controlling eye movements are almost always affected, but problems with eye movement may not begin until later in life. Some people may need to use a ventilator to breathe. Difficulties with feeding often result in the need for a feeding tube inserted into the stomach. Sadly this condition may mean a reduced life-expectancy for the child, mainly depending on the degree of breathing difficulties.

Autosomal recessive CMN (ar-CNM)

ar-CNM usually occurs in infancy or early childhood. Symptoms include hypotonia, breathing and swallowing difficulties. There is usually weakness of the muscles closest to the trunk of the body, known as the proximal muscles. Weakness of the face muscles may occur, including droopiness of the eyelids and abnormalities of eye movements. Some children may have problems with feeding, and may require breathing support.

Autosomal dominant CNM (ad-CNM)

ad-CNM is generally not as severe as the X-linked or the autosomal-recessive forms. Symptoms develop slowly from birth until well into adulthood. Many affected people are able to walk well into adulthood, but may find themselves in a wheelchair in later life.

What are the causes?

Genes causing all forms of the condition have now been identified:

  • X-linked myotubular myopathy (XLMTM) – myotubularin (MTM1) gene
  • Autosomal-recessive CNM – skeletal muscle ryanodine receptor (RYR1) gene, amphysin II (BIN1)gene and titin (TTN) gene
  • Autosomal-dominant CNM – dynamin 2 (DNM2) gene and, rarely, amphysin II (BIN1) gene.

It is thought that further genes that cause CNM will be identified in time, as not everyone affected by the condition has a change in one of the known genes.

How is it diagnosed?

A diagnosis of CNMs can be made by taking a piece of muscle (a muscle biopsy) and looking at this under a microscope. Genetic testing may be undertaken to look for a mutation in the MTM1, RYR1, BIN1, DNM2 and TTN genes.

How is it treated?

There are supportive measures which can improve the quality of life. In particular, regular physiotherapy and non-strenuous exercise may help maintaining joint range and mobility. Nasogastric or feeding gastrostomy tubes are advised if normal feeding is difficult. Individuals who have problems with their breathing may have to use non-invasive ventilation, particularly at night. The use of antibiotics to treat chest infections and prophylactic immunisations (for example, against flu) are advised. There is no cure for CNMs at the moment, but research is currently ongoing to identify potential therapies.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
CNMs can be inherited in an X-linked recessive, autosomal-recessive and autosomal dominant manner. Affected families should be referred to a genetics centre for information and support.

Prenatal diagnosis
Prenatal diagnosis is possible if the mutation causing the CNM in an affected family has been identified.

Is there support?

The Myotubular Trust

Email: via website
Website: https://myotubulartrust.org/

The trust is a Registered Charity in England Wales no. 1137177. They provide information and support to anyone affected by centronuclear and myotubular myopathy. They also raise awareness and fund and promote research.

Group details added June 2021.

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