It is a congenital muscle disease characterized by generalized hypotonia, muscle weakness, and central nuclei on muscle biopsy (myotube-like aspect). The onset of the disease is at birth or early childhood. However, it can also appear during adolescence or adulthood, but rarely. It is potentially associated with respiratory failure and death.
XMTM; X-Linked Myotubular Myopathy; XLMTM; Centronuclear Myopathy.
A clinical classification for this broader phenotype (termed MTM1) was described by Herman et al (1999). Neonates were classified as severe, moderate, or mild as follows:
Severe (Classic): Clinical features include characteristic facies, chronic ventilator dependence, grossly delayed motor milestones, nonambulatory, or death in infancy.
Moderate: More rapid achievement of motor milestones than patients with the severe form; prolonged periods of decreased ventilatory support.
Mild: Ambulatory with minimally delayed motor milestones, lack of chronic ventilatory support beyond the newborn period, lack of typical myopathic facies.
The exact incidence remains unknown, but it is estimated at 1:50,000 male births in the general population. The disorder predominantly affects males, but female carriers, while typically asymptomatic, can develop a range of symptoms. It has been reported that females, very rarely, can also develop a severe form similar to what is observed in males.
Three types of myotubular myopathy are recognized based on the mode of inheritance: X-linked, autosomal recessive, and autosomal dominant pattern. For the neonatal form, the gene has been localized on chromosome Xq28.
The myotubular or centronuclear myopathies are a group of inherited myopathies defined by the presence of central nuclei in affected skeletal muscle. Males with XLMTM with identifiable mutations in MTM1 can be said to have MTM1. Typically, X-linked myotubular myopathy is the most severe form, presenting with hypotonia and respiratory distress in affected newborn males. It is associated with high neonatal mortality. Surviving patients typically have prolonged ventilator dependence and grossly delayed motor milestones. Female carriers of XLMTM are generally asymptomatic, although rare manifesting heterozygotes have been described. The autosomal dominant (or adult) form has a later onset and a milder course. The course and severity of the autosomal recessive (or infantile) form is intermediate between the X-linked and the autosomal dominant form. Intelligence is usually within the normal range.
Creatine kinase level is normal or slightly increased. The diagnosis of XLMTM has traditionally relied upon the presence of characteristic pathology in muscle samples: atrophy predominantly of type I muscle fibers, which have centrally placed myofiber nuclei. The central areas of muscle fibers are devoid of myofibrils, with aggregation of mitochondria. Resemblance to fetal myotubes is thought to reflect an arrest in morphogenesis of the muscle fibers. The diagnosis of XLMTM should be considered in any male with ...