Myotubular Myopathy Event Study

Study Overview
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Brief Summary
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X-Linked myotubular myopathy (XLMTM), a form of centronuclear myopathy (CNM) is the result of a mutation in the MTM1 (myotubularin) gene which leads to altered myotubularin. Myotubularin is essential for optimum muscle function. To date, over 100 mutations have been described resulting in a range of disease onset and symptom severity. The early onset form presents with neonatal hypotonia, muscle weakness, respiratory distress and an ongoing requirement for continuous ventilatory support with the inability to maintain a sitting position once placed. Males with both later onset and milder symptoms usually do not require ongoing ventilatory support, achieve a higher maximal motor function with ability to sit when placed and even walk, and have improved survival rates. Males with XLMTM may experience complications (events) at birth and throughout their lifetime. The goal of the study is to identify the number of events over twelve months in males with genetically confirmed XLMTM. Parents or affected individuals over the age of 18 years who are able to access telephone will provide answers to an established event survey to evaluate the frequency and types of events. Emergency department, hospital admissions and mortality will be confirmed by obtaining medical reports. The investigators hypothesize that there will be no association between the frequency of events and markers of clinical severity including the need for ventilatory support at birth, current level of ventilatory support (no support, support less than 12 hours, support more than 12 hours) and current motor function (walking, sitting without support, inability to sit without support).

Official Title
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Prospective Study of Adverse Event Rates in Males With X-Linked Myotubular Myopathy

Conditions
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X-linked Myotubular Myopathy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males with a confirmed MTM1 mutation OR males with a muscle biopsy consistent with myotubular myopathy AND family history consistent with X-linked inheritance AND English-speaking parent/guardian of a living male child or a decisionally impaired adult OR English-speaking affected male over 18 years of age who can access telephone signed study consent enrolled in the Congenital Muscle Disease International Registry (CMDIR) Exclusion Criteria: males with only a clinical diagnosis of XLMTM but without family history of XLMTM an affected male who has a genetically confirmed form of centronuclear myopathy (CNM) that is not caused by a mutation in the MTM1 gene females with MTM1 due to the limited number of females affected and the variability of clinical presentation
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survey of a defined set of events | Changes in care needed, breathing support, motor ability, medications and medical care, nutrition/weight management, communication/vision/learning/behavior, and frequency of outpatient/hospital/ER visits are recorded by a monthly telephone survey. | 12 months | 
| Frequency of a predefined set of events related to ventilatory status | To analyze the strength of the association between the frequency of events surveyed and 1) duration of ventilatory support directly after birth and 2) current need for ventilatory support. | 12 months | 
| Frequency of a predefined set of events related to current motor function | To analyze the strength of the association between the frequency of events surveyed and current motor function | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between event frequency and genotype | To determine the strength of the association between the frequency of the events surveyed and the affected individual's genotype. | 12 months | 
| Association between event rate and season | To analyze event rates with respect to two seasonal clusters, October through March and April through September. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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respiratory function, natural history study, CMDIR (Congenital Muscle Disease International Registry), X-linked myotubular myopathy, centronuclear myopathy, myotubularin, MTM1 gene, mutation, survival, adverse event, disease complication, hospital admission, emergency room visit, motor function