Medical complications in long-term survivors with X-linked myotubular myopathy

J Pediatr. 1999 Feb;134(2):206-14. doi: 10.1016/s0022-3476(99)70417-8.


Objectives: X-linked myotubular myopathy (MTM1) is a rare developmental disorder of skeletal muscle characterized by the presence of central nuclei in biopsy specimens from affected male subjects. Until recently, the disorder was usually fatal within the first year of life. This study was undertaken to determine the outcome in long-term survivors (>1 year of age) with MTM1.

Methods: Clinical data were obtained on 55 male subjects from 49 independent North American families for which a mutation was identified in the X-linked myotubularin gene by direct genomic sequencing. Medical records were reviewed and families were interviewed to ascertain features at birth, length of survival, developmental milestones, and medical complications.

Results: Seventy-four percent (26 of 35) of the affected male subjects over the age of 1 year are living (range, 1 to 27 years); 80% remain completely or partially ventilator-dependent. In the absence of significant hypoxia, cognitive development is normal, and the muscle disorder appears nonprogressive. Several patients have had other medical problems not previously reported to be associated with MTM1. These include pyloric stenosis (4 male subjects from 3 families), spherocytosis (2 patients), gallstones (4 patients), kidney stones or nephrocalcinosis (2 patients), a vitamin K responsive bleeding diathesis (2 patients), and height >/=90% for age (40% of the patients). Six patients have had biochemical evidence of liver dysfunction, and 2 patients died after significant liver hemorrhage.

Conclusions: These data suggest that the prognosis for X-linked MTM may not be as poor as previously reported. However, at least some long-term survivors appear at risk for medical complications involving other organ systems, and patients should be carefully monitored for these potentially life-threatening complications. The pleiotropic symptoms demonstrated in these patients strongly suggest that the function of the MTM1 protein is not limited to developing muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cognition
  • Gastrointestinal Diseases / etiology
  • Genetic Linkage*
  • Growth
  • Hematologic Diseases / etiology
  • Humans
  • Infant
  • Male
  • Muscle, Skeletal / ultrastructure
  • Muscular Diseases / complications
  • Muscular Diseases / genetics*
  • Muscular Diseases / physiopathology
  • Mutation
  • Prognosis
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Psychomotor Performance
  • Respiratory Tract Diseases / etiology
  • Survivors
  • X Chromosome*


  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatases, Non-Receptor
  • myotubularin