About centronuclear and myotubular myopathy

The centronuclear myopathies belong to a group of conditions known as congenital myopathies which are inherited muscle disorders from birth. The characteristic feature of the centronuclear myopathies is the presence of the nucleus in the centre of the muscle fibre instead of the usual position at the edge.

Manifesting as a defect in the cell structure of voluntary muscles and causing low muscle tone the conditions affect both children and adults. The term myotubular myopathy is currently used to describe the x linked form of the condition while centronuclear myopathy is used to refer to the autosomal forms. Collectively, the three forms are known by the umbrella term of the ‘centronuclear myopathies’ as illustrated below.*

Image showing the centronuclear myopathies

* Note

Mutations in other genes, namely SPEG and CACNA1S have recently been identified as

leading to a CNM like phenotype in some patients.

The centronuclear myopathies are so rare that there are no good estimates of their incidence, a guess-timate would be somewhere between 1/50,000 and 1/100,000 for each form and perhaps slightly greater when the forms are combined. To put this into perspective, Duchenne Muscular Dystrophy affects about 1/3500 male births or 1 in 7,000 children born (Source: The Beggs Laboratory).

X Linked myotubular myopathy

Although all forms of centronuclear myopathy are considered rare, the most commonly known is x-linked myotubular myopathy which it is estimated affects 1 in 50,000 males from birth. There are also incidences of female x-linked manifesting carriers. Those affected by x-linked myotubular myopathy often have diminished respiratory capacity and are often partially or totally ventilator dependent. Parents are frequently told their children will not live past their first birthday but this is untrue. Many of the children with this condition are trached, meaning that a tube is inserted into the individuals neck to help them breath and this may result in them being behind with their language skills but a speaking valve can help with this.

Dominant centronuclear myopathy

The autosomal dominant form of centronuclear myopathy is generally not as severe as the x-linked or recessive forms of the condition and follows a mild course. It has been noted that the condition can affect individuals differently with onset ranging from birth to 50 years. Many are often able to walk well into adulthood but do find themselves in a wheelchair in later life, however the age that this occurs is not consistent among those affected. Those with the condition often report deterioration in their ability to carry out everyday tasks such as walking up stairs, rising from a sitting position unaided, lifting and carrying and with tasks such as opening bottles.

Recessive centronuclear myopathy

The autosomal recessive form of centronuclear myopathy usually occurs in infancy or early childhood. Weakness of the muscles in the face may occur, as may droopiness of the eyelids. Some people may have problems with feeding. There is usually weakness of the muscles closest to the trunk of the body, known as the proximal muscles.

Genes causing all three forms of the condition have now been identified, these are:

The function of the genes is currently unknown and it is thought that further genes that cause centronuclear myopathy will be identified in time, as not everyone affected by the condition has a change in one of the three genes that have been identified so far. In 2006 two people affected by centronuclear myopathy were found to have alterations in the hJUMPY gene. One of these patients also had an alteration in the DNM2 gene which causes the autosomal dominant form of the condition. Then in 2007 an alteration was found in the RYR1 gene that is known to cause a congenital myopathy known called central core disease. More research will be required to understand the significance of these findings.

Further information

Further information about centronuclear and myotubular myopathy can be found in the resources area of this website.

Further information about myopathies can be found below.