MRI on Persons With Mutations in POMT2 Gene (LGMD2N)

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.

Study Overview

• Status: Completed
• Conditions: Limb-girdle Muscular Dystrophy

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, DK-2100
    • Copenhagen Neuromuscular Center, Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Persons diagnosed with LGMD2N in Denmark and France are invited to the study.

Description

Inclusion Criteria:

• Persons with genetically verified mutations in POMT2

Exclusion Criteria:

• All contraindications for undergoing an MRI scan

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with LGMD2N; 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
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
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.)
Electromyography (EMG)	EMG is used for measuring nerve conducting velocity and neuromuscular activity with repetitive stimulation (3Hz).	Exam last approximately 30 min

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Sofie T. Østergaard, Bsc., Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, Copenhagen University

Publications and helpful links

General Publications

• Ostergaard ST, Johnson K, Stojkovic T, Krag T, De Ridder W, De Jonghe P, Baets J, Claeys KG, Fernandez-Torron R, Phillips L, Topf A, Colomer J, Nafissi S, Jamal-Omidi S, Bouchet-Seraphin C, Leturcq F, MacArthur DG, Lek M, Xu L, Nelson I, Straub V, Vissing J. Limb girdle muscular dystrophy due to mutations in POMT2. J Neurol Neurosurg Psychiatry. 2018 May;89(5):506-512. doi: 10.1136/jnnp-2017-317018. Epub 2017 Nov 24.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: April 27, 2016
• First Submitted That Met QC Criteria: April 29, 2016
• First Posted (Estimate): May 3, 2016

Study Record Updates

• Last Update Posted (Actual): April 11, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: MRI; LGMD; POMT2
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle
• Other Study ID Numbers: STO-POMT2