The specific symptoms and severity of XLMTM can vary greatly from one person to another, though the majority of individuals with MTM have a severe presentation. While the disorder may be fatal during infancy or childhood, some affected individuals will only develop mild to moderate symptoms. Because of the variable nature of XLMTM, parents should talk to their child’s physician and medical team about their specific case, associated symptoms and overall prognosis.
One classification subdivides XLMTM into a severe (classic) form, a moderate form and a mild form. Most affected individuals have the severe (classic) form of XLMTM. Moderate and mild forms of XLMTM are far less common. In the severe form, affected male infants exhibit extreme Muscle Weakness and Hypotonia (floppiness) at or shortly after birth. Weakness of the muscles used to breathe and swallow can cause respiratory distress and feeding difficulties during infancy often noticeable within the first few days or weeks of life. Respiratory distress can be present at birth and can cause affected infants to require constant, prolonged ventilation during infancy. Affected infants may be unable to suck, swallow or breathe on their own. In the U.S., the initial hospital stay for surviving infants is approximately 90 days.
Some children with XLMTM will die during the first few months or years of life. Other individuals will survive this initial period but require 24 hour ventilator, feeding, and wheelchair support. However, other individuals will become independent of a ventilator or only require periodic assisted ventilation such as during sleep. A proportion of affected individuals will survive into the teenage years and beyond. Of note, long-term ventilation during infancy carries risks including recurrent infection, inadequate shallow breathing (hypoventilation), and lack of oxygen in the blood (hypoxia).
Muscle Weakness and poor muscle development can also cause delays in the attainment of motor milestones. Most affected individuals are unable to walk (non-ambulatory). Muscle Weakness associated with XLMTM is not believed to be progressive, but this has not been definitely confirmed. Individuals with XLMTM often grow tired more easily than their peers.
Affected infants often have Distinctive facial features including a high forehead, underdevelopment of the middle of the face (midface hypoplasia), Weakness of facial muscles, and a disproportionately long and narrow head (dolichocephaly) with a long face. Some infants have a narrow, high-arched roof of the mouth (palate) and later on develop severe misalignment of the teeth (malocclusion). Partial or complete Paralysis of one or more of the muscles that control the movements of the eye (ophthalmoparesis) is also common. Drooping of the upper eyelids (ptosis) and nearsightedness (myopia) may also occur.
In some individuals, growth parameters may be abnormal. In general, head circumference is larger than would be expected based on age and gender (macrocephaly). Affected infants may be in the 90th percentile for length at birth. Weakness of the facial muscles is often very obvious.
Additional symptoms may occur including abnormally long fingers and toes, Absence of reflexes (areflexia), and shortening or hardening of tissue that causes deformity and restricts movements of affected areas, especially the joints (contractures). Failure of the testes to descend into the scrotum (cryptorchidism) may also occur. As affected individuals grow older, more symptoms can occur including fractures of the long bones, malformation of the hip (hip dysplasia) and abnormal side-to-side curvature of the spine (scoliosis). Scoliosis can worsen respiratory problems and cause individuals who no longer require assisted ventilation to go back onto ventilator support. In some cases, advanced bone age and premature production of sex hormones called androgens (premature adrenarche) has also been reported.
Many long-term survivors with severe XLMTM require a wheelchair and need assistance for normal daily activities. A variety of additional low incidence complications have been reported in long-term survivors. Such complications include narrowing of the outlet that connects the stomach to the small intestine (pyloric stenosis), gallstones, kidney stones, mild Anemia due to the formation of abnormal red blood cells (spherocytosis), bleeding abnormalities, and liver dysfunction. Some individuals develop peliosis hepatitis, a liver condition characterized by randomly located, multiple blood-filled cavities throughout the liver. This condition can cause life-threatening bleeding (hemorrhaging) episodes.
Cognitive development and intelligence are usually unaffected, except in extremely rare cases or in individuals who suffer a significant hypoxic episode, in which the brain is deprived of oxygen.
Mild and Moderate Myotubular Myopathy Some individuals may have milder forms of the disorder. The moderate form of XLMTM is generally characterized by similar signs and symptoms to the severe form. However, individuals will have longer periods of time where the need for ventilator support is decreased. In addition, affected individuals will attain motor milestones faster than individuals with the severe form.
Individuals with the mild form of XLMTM only experience slight delays in attaining motor milestones and most achieve the ability to walk. These individuals may only require ventilator support in the newborn period. Some individuals with the mild form do not have the characteristic facial features that are seen in the severe form of XLMTM, and often also have eye movement paralysis.
Individuals with mild or moderate XLMTM are at risk for breathing problems including especially nocturnal hypoventilation and sleep apnea. In addition, respiratory decompensation can develop when dealing with an unrelated illness. This may require a return to or an increase in ventilator support.
At least three multigenerational families have been described in the medical literature with male family members who developed mild cases of XLMTM, sometimes not developing symptoms until adulthood.