X-linked myotubular myopathy
What is X-Linked Myotubular Myopathy?
X-linked myotubular myopathy (MTMX) is a rare disorder that belongs to a larger group of disorders known as centronuclear myopathies. This condition almost exclusively occurs in 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 or 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 show low muscle tone and they develop multiple problems due to this muscle weakness including feeding problems, delayed motor development, and respiratory failure requiring mechanical ventilator support. Some individuals can not move on their own. Many also have weakness in the muscles that control eye movement (ophthalmoplegia), characteristic facial features such as large head, narrow face, high and arched roof of the mouth, and absent reflexes. Less common features that may occur include stiffening of the muscles resulting in tight joints (contractures), curvature of the spine (scoliosis), liver disease, recurrent infections, and seizures. Intellectual disability is also common in affected individuals, though some may develop difficulties as a result of seizures or lack of oxygen (related to mismanaged respiratory failure).
Moderate and Mild X-Linked Myotubular Myopathy
In the moderate form of the disease, individuals may have less severely delayed milestones, and they are more likely to be able to breathe on their own or with minimal support from mechanical ventilation. In the mild form of the disease, muscle weakness may improve. Individuals are more likely to have near-normal motor development and are generally able to walk, ventilator support becomes unnecessary with age, and they tend to not 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 mutations carried, but the moderate and mild forms are less common.
Most female carriers do not have symptoms, however there are reports of carrier females developing mild/moderate symptoms associated with this condition. However, this seems to be a rare occurrence.
How common is X-Linked Myotubular Myopathy?
The worldwide incidence for MTMX is unknown. It has been reported that MTMX affects approximately 1 in 50,000 male newborns, though this is only based on a single estimate from a French registry. Approximately 10-20% of males affected do not inherit a mutation from a carrier mother (de novo mutation).
How is X-Linked Myotubular Myopathy treated?
Currently there is no cure for MTMX. Treatment focuses on trying to maximize functional abilities and minimize complications with a team of specialists, generally those that have expertise in long-term care of children with neuromuscular disorders. For example, a physical therapist and/or rehabilitation medicine specialist will manage movement issues. A neurologist may assist with motor delays and seizures. A pulmonologist will likely manage the need for mechanical ventilation, and a surgeon will determine the need for a tracheostomy and feeding tube. Other specialties are involved as needed.
What is the prognosis for a person with X-Linked Myotubular Myopathy?
Because of their severe breathing problems, the vast majority of individuals affected with X-linked myotubular myopathy do not survive infancy. Some individuals, especially with the milder forms, may live into childhood or adolescence, but survival into adulthood is generally uncommon. Individuals who have survived long-term have developed other medical problems.