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Myotubular myopathy
Sunday, 14 August 2005
Sunday, 14 August 2005
Centronuclear Myopathy


Myotubular myopathy (MTM) is a disease that affects the muscles. Most children inherit this condition in an X-linked manner (XLMTM). However, there are forms of the disease that are inherited in an autosomal dominant or autosomal recessive form. This disease is characterized by muscle weakness that ranges from mild to severe.


The X-linked form of the disease affects males almost exclusively. The prevalence is roughly estimated at 1 in 50,000 newborn males. The autosomal forms show no sex preference, and there is no prevalence data since these forms are even more rare than the X-linked form.

Signs and Symptoms

In its most severe form the baby is born with very low muscle tone and has difficulty breathing. The infant is placed on a ventilator to facilitate breathing. These babies have distinct facial features: drooping eyelids, protruding lips, high forehead, long face with a small midface, and high-arched palate. They are often very long with low weight, have long fingers and/or toes, sometimes with club-foot. They frequently have no reflexes and have undescended testes. Their movement milestones are delayed and often they fail to walk. Those that survive depend on a ventilator for the rest of their lives and are severely disabled. About 40% of children with more mild forms of XLMTM require intermittent ventilation or no ventilation at all. Some may only require ventilation as newborns. These children achieve their movement milestones more quickly than those with severe forms and are able to walk. Usually, they do not have the facial features of the severe form. Female carriers of XLMTM do not typically have symptoms, although some female carriers may have mild symptoms, such as easy fatigue or gait problems. Additional medical complications can occur due to the myopathy: loss of movement of the eyes, drooping eyelids, short-sightedness, abnormal position of the teeth, and scoliosis (abnormal spinal curvature). Other medical complications occasionally associated with XLMTM include: constriction of the opening between the stomach and small intestine, gallstones, kidney stones, and liver problems. Children with the autosomal dominant form of MTM begin having symptoms between the first and third decades. Muscle weakness progresses slowly appearing as clumsiness, easy fatigability, and/or a sleepy facial expression. An initial pattern of weakness is apparent in this form of MTM. The muscles of the limbs that are closer to the body are affected, but sometimes the facial muscles are affected. However, the muscles that move the eyes and those of the airway are not affected. However, as the disease progresses all the muscles become weak and atrophied. Children with the autosomal recessive form of MTM present with symptoms in early childhood to early adulthood. The symptoms are like those in the autosomal dominant form. However, the facial muscles are more frequently affected, as well as the muscles that move the eye. Reflexes can be absent.

Possible Causes

In X-linked myotubular myopathy the affected gene is MTM1. This gene codes for the protein myotubularin. Myotubularin is a lipid phosphatase that acts on one of the biochemical pathways that regulate the trafficking of important molecules into the cell. This change in the gene results in a non-functional protein or no protein at all. Current theories propose that myotubularin is necessary for proper muscle cell maturation, and in its absence maturation does not occur properly. The exact mechanism of how this occurs is not yet understood. In the autosomal dominant form of the disease a change in the myogenic factor-6 gene (MYF6) on chromosome 12 is affected. Its exact mechanism and role is not understood, but it is believe that it is an important factor involved in the maturation of muscle cells. The malfunctioning protein appears to cause muscle cells to stop developing. In the autosomal recessive form of the disease no abnormal genes have been found. Although the cause of the disease is yet unknown, it is believed that this form of the disease occurs from degeneration of the muscle cells rather than from their inability to mature.


A muscle biopsy is obtained for examination. This can often be done using a needle, and is a relatively minor procedure. The biopsy of children with XLMTM shows abnormal muscle cells with the typical abnormalities caused by the disease. In particular, the muscle cells have centrally located nuclei. Normally nuclei are located around the periphery of the muscle cell. Muscle biopsy does not significantly differ between the three forms of the disease. However, sometimes special cell stains can differentiate between X-linked and autosomal form. Genetic tests and familial pedigree must be considered to determine if the disease is X-linked or autosomal. If this cannot be determined, it is harder to give information about what a person’s outcome may be. Many times there is a family history of this disease. Genetic testing of the MTM1 gene detects mutations in about 80-85% of affected individuals. The test is used to confirm diagnosis, screen the parents for carrier status and to make a prenatal diagnosis. A test to detect the presence of myotubularin may be useful for diagnosis in individuals for whom no mutation is found.


Currently there is no cure for the disease. Treatments are supportive and aim to alleviate the symptoms. For those patients who have trouble breathing, ventilators are used to breath for them. People with MTM are susceptible to respiratory infections for which they receive treatment. Feeding through a tube inserted into the stomach is often needed in the severe cases of MTM. A team of health specialists, therapists, and nurses as well as medical and other supportive equipment are often necessary. The autosomal forms of the disease tend to be less severe than the X-linked form. However, these forms are progressive. Eventually, supportive treatments such as those above are required for many with the disease.


Children with the most severe forms of MTM, particularly XLMTM, usually do not live past their first year. However, there are children who have survived and live with the aid of ventilators and other medical support. Children with mild and moderate forms can develop normally and live to adulthood. The muscle disease of XLMTM is not progressive and children with mild and moderate forms can improve their muscle strength slowly over time. However, the symptoms begin to worsen as they become elderly. Intelligence is usually not affected by the disease. The autosomal forms of the disease are progressive. Although the severity of the progressive symptoms can vary, the most severe cases result in disability and can be fatal.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


Myotubular Myopathy Resource Group This website provides information about myotubular myopathy as well as support and other resources for people who have or have had a child with this disease. Muscular Dystrophy Association This website has a variety of information about myotubular myopathy. There is a chat page that parents can go to and an “Ask the Expert” page. The Joshua Frase Foundation: A foundation passionate about supporting families affected by Myotubular Myopathy and Centronuclear Myopathy. A terrific website filled with a huge amount of useful information.

Google Search for Myotubular myopathy

References and Sources