X-linked myotubular myopathy is a form of centronuclear myopathy associated with myotubularin 1. Genetically inherited traits and conditions are often referred to based upon whether they are located on the "sex chromosomes" versus whether they are located on "autosomal" chromosomes. Thus, genetically inherited conditions are categorized as being sex-linked or autosomal. Females have two X-chromosomes, while males only have a single X chromosome, and a genetic abnormality located on the X chromosome is much more likely to cause clinical disease in a male than in a female. The X-linked form of MTM is the most commonly diagnosed type. Almost all cases of X-linked MTM occurs in males. Females can be "carriers" for an X-linked genetic abnormality, but usually they will not be clinically affected themselves. Two exceptions for a female with a X-linked recessive abnormality to have clinical symptoms: one is a manifesting carrier and the other is X-inactivation. A manifesting carrier usually has no noticeable problems at birth; symptoms show up later in life. In X-inactivation, the female, actually presents with full-blown X-linked MTM. Thus, she congenitally presents MTM. Thus, although MTM1mutations most commonly cause problems in boys, these mutations can also cause clinical myopathy in girls, for the reasons noted above. Girls with myopathy and a muscle biopsy showing a centronuclear pattern should be tested for MTM1 mutations.
This condition is caused by mutations in the myotubularin gene which is located on the long arm of the X chromosome. Many clinicians and researchers use the abbreviations XL-MTM, XLMTM or X-MTM to emphasize that the genetic abnormality for myotubular myopathy is X-linked, having been identified as occurring on the X chromosome. The specific gene on the X chromosome is referred to as MTM-1. In theory, some cases of CNM may be caused by an abnormality on the X chromosome, but located at a different site from the gene MTM1, but currently MTM1 is the only X-linked genetic mutation site identified for myotubular or centronuclear myopathy. Clinical suspicion for X-linked inheritance would be a disease affecting multiple boys and a pedigree chart showing inheritance only through the maternal side of each generation.
