Myotubular Myopathy Genetic Testing Study

Study Summary

Myotubular myopathy (XLMTM) is an X-linked disorder caused by mutations in the myotubularin gene (MTM1). The clinical spectrum is variable and ranges from individuals who require a wheelchair and full time breathing support to those who are able to walk and breathe on their own. Symptoms of myotubular myopathy include long faces, facial weakness with eye muscle weakness, breathing support with a muscle biopsy demonstrating central nucleated fibers. These symptoms may be caused by mutations or changes in the MTM1, BIN1 (bridging integrator 1), DNM2 (dynamin 2) and RYR1 (ryanodine receptor 1) genes. However, the majority are caused by mutations in the MTM1 gene. Some patients with symptoms consistent with myotubular myopathy who initially have negative testing of the MTM1 gene were later found to have a unique type of change in the MTM1 gene. This unique change, called a deletion or duplication, can be found with a different type of genetic test called a CGH (comparative genomic hybridization) array. Investigators do not know how frequent deletions and duplications are in patients with X-linked myotubular myopathy. Recently, there have been advances in identifying potential treatments for XLMTM. The next step will be to proceed with clinical trials of potential treatments. In order to be ready for clinical trials, it is important that investigators find the specific genetic change that is causing XLMTM in people with this diagnosis. This study will attempt to find changes in the MTM1 gene in individuals who have clinical symptoms consistent with a diagnosis of XLMTM. Participants will be asked to enroll in the CMDIR (Congenital Muscle Disease International Registry), complete a brief clinical survey, provide access to medical records, and provide a saliva or blood sample for genetic testing. Results of genetic testing will be communicated to participants by the physician specified in the consent by the signing person. Study Hypothesis: Not all individuals with a cl

Primary Outcome

To confirm presence, locations and frequencies of mutations in the MTM1 gene in study participants presenting with symptoms as listed in the Brief Summary and muscle biopsy and/or family history typical for myotubular myopathy or prior confirmation of a mutation in the MTM1 gene by research sequencing.

Interventions

• OTHER Genetic Testing