MRI on Persons With Mutations in POMT2 Gene (LGMD2N)

Study Overview
=================
Brief Summary
-----------------
POMT2 mutation is known to cause Walker Warburg Syndrome and Muscle-Brain-Eye syndrome. Recently it has been connected to limb girdle muscular dystrophy (LGMD), a disorder characterized by muscle weakness and atrophy of the proximal muscles of the shoulder and pelvic girdles. LGMD is classified based on its inheritance pattern and genetic cause into more than 31 different types. LGMD with POMT2 mutations is a new phenotype - type 2N. Very few patients with the LGMD2N phenotype has been reported. In this study, the investigators examine five new cases with the LGMD phenotype. The primary aim is to examine the muscle involvement using MRI.

Official Title
-----------------
MRI on Persons With Mutations in POMT2 Gene (LGMD2N)

Conditions
-----------------
Limb-girdle Muscular Dystrophy

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Persons with genetically verified mutations in POMT2 Exclusion Criteria: All contraindications for undergoing an MRI scan

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with LGMD2N<br>Five patients over 18 years old with genetically verified LGMD2N | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI scan for qualitative analysis of muscle involvement | The MRI protocol include T1-weighted brain and whole body examination. Four cross-sectional slices at shoulder, lumbar back, thigh and calf are chosen for qualitative analysis using the grading scale from 1 to 4 developed by Mercuri et al. (2007) to evaluate the involvement of muscles by looking at the fat infiltration. | One MRI scan per subject (exam lasts approximately 60 min.) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Biopsy | One muscle biopsy from each patient from the tibialis anterior muscle or the deltoid muscle will be analyzed for glycosylated α-dystroglycan, merosin and POMT2. (Concentration determined by standard biochemical analysis). | One muscle biopsy per subject (last approximately 15 min.) | 
| 10 meter walk test | Measurement of the time it takes to walk 10 meters. | Exam last approximately 5 min | 
| Neurological examination and test of muscle strength | Muscle strength (in arms and legs) will be examined by the principal investigator based on the Medical Research Council (MRC) scale with values spanning from 5(=normal strength) to 1(=No contraction). | Exam last approximately 15 min. | 
| Questionnaires | Data will be collected using Minimal mental examination (MMSE) | Data will be collected once for patients with LGMD2N (exam last approximately 45 min.) | 
| Heart examination | Echocardiography and Electrocardiogram (ECG). | Exam last approximately 45 min | 
| Forced Vital Capacity (FVC) | FVC is measured as the best of three attempts using a hand-held spirometer. | Exam last approximately 15 min | 
| Electromyography (EMG) | EMG is used for measuring nerve conducting velocity and neuromuscular activity with repetitive stimulation (3Hz). | Exam last approximately 30 min | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MRI, LGMD, POMT2