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Diagnostic interest of whole-body MRI in early- and late-onset LAMA2 muscular dystrophies: a large international cohort

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Abstract

Background

LAMA2-related muscular dystrophy (LAMA2-RD) encompasses a group of recessive muscular dystrophies caused by mutations in the LAMA2 gene, which codes for the alpha-2 chain of laminin-211 (merosin). Diagnosis is straightforward in the classic congenital presentation with no ambulation and complete merosin deficiency in muscle biopsy, but is far more difficult in milder ambulant individuals with partial merosin deficiency.

Objective

To investigate the diagnostic utility of muscle imaging in LAMA2-RD using whole-body magnetic resonance imaging (WBMRI).

Results

27 patients (2–62 years, 21–80% with acquisition of walking ability and 6 never ambulant) were included in an international collaborative study. All carried two pathogenic mutations, mostly private missense changes. An intronic variant (c.909 + 7A > G) was identified in all the Chilean cases. Three patients (two ambulant) showed intellectual disability, epilepsy, and brain structural abnormalities. WBMRI T1w sequences or T2 fat-saturated images (Dixon) revealed abnormal muscle fat replacement predominantly in subscapularis, lumbar paraspinals, gluteus minimus and medius, posterior thigh (adductor magnus, biceps femoris, hamstrings) and soleus. This involvement pattern was consistent for both ambulant and non-ambulant patients. The degree of replacement was predominantly correlated to the disease duration, rather than to the onset or the clinical severity. A “COL6-like sandwich sign” was observed in several muscles in ambulant adults, but different involvement of subscapularis, gluteus minimus, and medius changes allowed distinguishing LAMA2-RD from collagenopathies. The thigh muscles seem to be the best ones to assess disease progression.

Conclusion

WBMRI in LAMA2-RD shows a homogeneous pattern of brain and muscle imaging, representing a supportive diagnostic tool.

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Fig. 1

adapted from Oliveira et al. Hum Mut 2018)

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Availability of data and material (data transparency)

Complete data are shown in the manuscript or in supplementary material. Images are available for other researchers upon reasonable request.

Code availability (software application or custom code)

R code is available upon reasonable request.

Abbreviations

IHC:

Immunohistochemical

MDC1A:

Merosin-deficient congenital muscular dystrophy type 1A

LGMD-R23:

Limb girdle muscular dystrophy R23

LHBF:

Long head of biceps femoris

WBMRI:

Whole-body magnetic resonance imaging

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Acknowledgements

We thank patients and families for their generous collaboration. We thank all MRI technical teams involved in the muscle imaging acquisition for their technical excellence and continuous support for performing neuromuscular imaging. This work is generated within the European Reference Network for Neuromuscular Diseases, FILNEMUS (French Neuromuscular Network) and the MYO-MRI COST-Action BM1304. We thank ISCIII for the financial support for studying LAMA2-RD in Spain.

Funding

No direct funding supported this study. Indirect contributions are recognized in acknowledgement section.

Author information

Authors and Affiliations

  1. APHP, GH Université Paris-Saclay, Neuromuscular Center, Child Neurology and ICU Department, Raymond Poincare Hospital, Garches, France

    Susana Quijano-Roy, Marta Gómez García de la Banda, Audrey Benezit, Helge Amthor, Ivana Dabaj & Eliana Cavassa

  2. Université de Versailles, U1179 INSERM-UVSQ, Versailles, France

    Susana Quijano-Roy & Helge Amthor

  3. Department of Paediatric Neurology, Motol University Hospital, Prague, Czech Republic

    Jana Haberlova

  4. Pediatric Neurology Department, Clinica Las Condes, Santiago de Chile, Chile

    Claudia Castiglioni

  5. Instituto Nacional de Rehabilitación Pedro Aguirre Cerda, Santiago de Chile, Chile

    Claudia Castiglioni

  6. Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    John Vissing & Nicoline Løkken

  7. Pediatric Neurology, Vall d’Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, Passeig de la Vall d’Hebron 119-129, 08035

    Francina Munell, Laura Costa Comellas & David Gómez-Andrés

  8. Department of Pediatric Neurology and Reference Center for Neuromuscular Diseases AOC, CHU Montpellier, Montpellier, France

    François Rivier

  9. PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France

    François Rivier

  10. APHP, Neuromuscular Reference Center, Pitié-Salpêtrière Hospital, Institute of Myology, Paris, France

    Tanya Stojkovic

  11. Univ Paris Est UPE, INSERM, U955 IMRB, APHP, Centre de Référence de Pathologie Neuromusculaire Nord-Est-Ile-de-France, Hôpital Henri Mondor, Créteil, France

    Edoardo Malfatti

  12. Unità Operativa Complessa Di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia

    Giorgio Tasca

  13. CHU de Rouen, Service de Néonatologie, Réanimation pédiatrique, Neuropédiatrie et Éducation Fonctionnelle de L’enfant, INSERM U 1245, ED497, 76000, Rouen, France

    Ivana Dabaj

  14. Department of Neurology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

    Clara Gontijo Camelo

  15. Nord/Est/Ile de France Neuromuscular Reference Center, PHENIX FHU, Hôpital Raymond-Poincaré, AP-HP. INSERM U1179, Garches, France

    Pascal Laforêt

  16. Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, GIN, Grenoble, France

    John Rendu

  17. Sorbonne Université, Myology Institute, Neuromuscular Morphology Unit, Center for Research in Myology, GH Pitié-Salpêtrière, Paris, France

    Norma B. Romero

  18. Centre de Référence de Pathologie Neuromusculaire Paris-Est, GHU Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France

    Norma B. Romero

  19. Unit for Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children’s Hospital, Rome, Italy

    Fabiana Fattori

  20. APHM, Laboratoire de Génétique Moléculaire, Hôpital TIMONE Enfants; Aix Marseille University, INSERM, MMG, Marseille, France

    Christophe Beroud

  21. Centre of Molecular Biology and Genetics, University Hospital Brno, Brno, Czech Republic

    Jana Zídková

  22. Radiology Department, CHU Montpellier, Montpellier, France

    Nicolas Leboucq

  23. Pediatric Neuroradiology, Radiology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Ángel Sanchez-Montañez

  24. Diagnostic Imaging Service, Clinica Las Condes, Santiago de Chile, Chile

    Ximena Ortega

  25. Department of Radiology, Motol University Hospital, Prague, Czech Republic

    Martin Kynčl

  26. AP-HP, UF Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Centre de Génétique Moléculaire et Chromosomique, GH Pitié Salpêtrière, Paris, France

    Corinne Metay

  27. Sorbonne Université - Inserm UMRS974, Centre de Recherche en Myologie, GH Pitié-Salpêtrière, Paris, France

    Corinne Metay

  28. APHP, GH Université Paris-Saclay, DMU Smart Imaging, Medical Imaging Department, Raymond Poincaré Teaching Hospital, Garches, France

    Robert Y. Carlier

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  1. Susana Quijano-Roy
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Correspondence to David Gómez-Andrés.

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Quijano-Roy, S., Haberlova, J., Castiglioni, C. et al. Diagnostic interest of whole-body MRI in early- and late-onset LAMA2 muscular dystrophies: a large international cohort. J Neurol 269, 2414–2429 (2022). https://doi.org/10.1007/s00415-021-10806-0

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