European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A)

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Limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A) is a progressive myopathy caused by deficiency of calpain 3, a calcium-dependent cysteine protease of skeletal muscle, and it represents the most frequent type of LGMD worldwide. In the last few years, muscle magnetic resonance imaging (MRI) has been proposed as a tool for identifying patterns of muscular involvement in genetic disorders and as a biomarker of disease progression in muscle diseases. In this study, 57 molecularly confirmed LGMDR1 patients from a European cohort (age range 7–78 years) underwent muscle MRI and a global evaluation of functional status (Gardner-Medwin and Walton score and ability to raise the arms).


We confirmed a specific pattern of fatty substitution involving predominantly the hip adductors and hamstrings in lower limbs. Spine extensors were more severely affected than spine rotators, in agreement with higher incidence of lordosis than scoliosis in LGMDR1. Hierarchical clustering of lower limb MRI scores showed that involvement of anterior thigh muscles discriminates between classes of disease progression. Severity of muscle fatty substitution was significantly correlated with CAPN3 mutations: in particular, patients with no or one “null” alleles showed a milder involvement, compared to patients with two null alleles (i.e., predicting absence of calpain-3 protein). Expectedly, fat infiltration scores strongly correlated with functional measures. The “pseudocollagen” sign (central areas of sparing in some muscle) was associated with longer and more severe disease course.


We conclude that skeletal muscle MRI represents a useful tool in the diagnostic workup and clinical management of LGMDR1.

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We would like to thank all participating patients and their families.

Author information

Correspondence to Andrea Barp.

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Conflicts of interest

The authors have non-competing interests with regard to the present work. The authors declare no financial support for the conduct of the study. Dr. Scheidegger reports other from Sanofy Genzyme, outside the submitted work; Dr. Bello reports personal fees from PTC Therapeutics, grants from Santhera Pharmaceuticals to his Institution, personal fees from Sarepta Therapeutics, personal fees from Reveragen Biopharma, outside the submitted work; Dr. Pegoraro reports non-financial support from Genzyme, grants and non-financial support from Santhera, personal fees from Sarepta, personal fees and non-financial support from PTC Therapeuticals, personal fees and non-financial support from Roche, outside the submitted work; Maggie C. Walter has served on advisory boards for Avexis, Biogen, Novartis, Roche, Santhera, Sarepta, PTC Therapeutics, Ultragenyx, Wave Sciences, received funding for Travel or Speaker Honoraria from Novartis, Biogen, Ultragenyx, Santhera, PTC Therapeutics, and worked as an ad-hoc consultant for AskBio, Audentes Therapeutics, Biogen Pharma GmbH, Fulcrum Therapeutics, GLG Consult, Guidepoint Global, Gruenenthal Pharma, Novartis, Pharnext, PTC Therapeutics, and Roche. The remaining authors have nothing to disclose.

Ethical standards

The study has been approved by ethics committees of all the involved institutions. All data were gathered after informed consent was obtained from each participant, in accordance with specific national laws and the ethics standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Boxplots of Gardner-Medwin & Walton (GMW) score by T1w Mercuri score in 29 lower limb muscles. The boxplots illustrate the correlation between T1w MRI findings in each muscle and functional score (GMW) outcome measures evaluated within ± 12 month before or after performing the MRI. The thirty hand panels correspond to GMW correlations. The muscles are ordered from proximal to distal (hip/abdomen, thigh, leg) starting from the top and left. Red dashed lines indicate correlations, and their thickness is proportional to the strength of the correlation (PDF 2507 kb)

Supplementary Material 2 (PNG 181 kb)

Boxplots illustrating correlations between the presence of a “pseudocollagen sign” and disease duration and severity in our CAPN3 cohort. The presence/absence of “pseudocollagen sign” is indicated on the horizontal axis of the graphs, while disease duration and Gardner-Medwin & Walton score are indicated in the vertical axis (PDF 142 kb)

Supplementary file4 (DOCX 22 kb)

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Barp, A., Laforet, P., Bello, L. et al. European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A). J Neurol 267, 45–56 (2020) doi:10.1007/s00415-019-09539-y

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  • Muscle MRI
  • Mercuri score
  • CAPN3 mutations