X-linked myotubular myopathy

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What is X-Linked Myotubular Myopathy?

X-linked myotubular myopathy (MTMX), caused by harmful genetic changes (mutations) in the MTM1 gene located on the X-chromosome, is a rare disorder belonging to a group of diseases known as centronuclear myopathies. Males have one copy of the X-chromosome and, therefore, one copy of the MTM1 gene, while females have two. Because of this, MTMX primarily affects males. Presentation of the condition can vary (as described below), but MTMX almost always affects the strength of the muscles used for movement (skeletal muscles) and results in low muscle tone (hypotonia).

Severe X-Linked Myotubular Myopathy

Most affected individuals have the severe (classic) form of the disease. Signs of this condition may present before birth with decreased fetal movement or too much amniotic fluid (polyhydramnios). At birth, babies typically have low muscle tone and develop multiple problems due to this muscle weakness, including feeding problems, delayed motor development, and respiratory failure requiring mechanical ventilator support. Some affected individuals cannot move on their own and may have absent reflexes. Many affected individuals also have weakness in the muscles that control eye movement (ophthalmoplegia) and have characteristic facial features such as large heads, narrow faces, and high, arched roofs of their mouths. Features seen less frequently may include curvature of the spine (scoliosis); liver disease; recurrent infections; seizures; or stiffening of the muscles resulting in tight joints (contractures). Affected individuals typically have some sort of intellectual disability, although this may be due to lack of oxygen in the neonatal period.

Moderate and Mild X-Linked Myotubular Myopathy

The mild and moderate forms of MTMX are less common than the classic form. In the moderate form of the disease, developmental delay may be milder and individuals may be able to to breathe on their own or with minimal mechanical support. In the mild form of disease, individuals have less-severe muscle weakness, have near-normal motor development, and are generally able to walk. Additionally, in the mild form, ventilator support becomes unnecessary with age and affected individuals tend not to develop the characteristic facial features. It is important to note that it is usually not possible to predict the form of the disease based on the harmful genetic change carried.

Most female carriers do not have symptoms, but there are rare reports of carrier females developing mild or moderate symptoms associated with this condition.

How common is X-Linked Myotubular Myopathy?

The estimated incidence of MTMX is 1 in 40,000 male births, though this is based on limited data. Approximately 10-20% of affected males do not inherit a mutation from a carrier mother (a de novo, or new, mutation).

How is X-Linked Myotubular Myopathy treated?

Currently, there is no cure for MTMX. Management focuses on maximizing functional abilities and minimizing complications, using a team of specialists with expertise in the long-term care of children with neuromuscular disorders. For example, a physical therapist and/or rehabilitation medicine specialist may manage movement issues, a neurologist may assist with motor delays and seizures, a pulmonologist may manage the need for mechanical ventilation, and a surgeon may determine the need for a breathing tube (tracheostomy) and/or feeding tube. Other specialties may be involved, as needed.

What is the prognosis for an individual with X-Linked Myotubular Myopathy?

Because of severe breathing problems, 25% of male infants affected with MTMX do not survive the first year of life. Most young children who live longer than one year will need extensive support, including a breathing tube, a feeding tube, and/or a wheelchair. Individuals with the mild or moderate forms may live into childhood or adolescence, but survival into adulthood is uncommon.