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

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

  • Susana Quijano-Roy
  • Jana Haberlova
  • Claudia Castiglioni
  • Francina Munell
  • François Rivier
  • Tanya Stojkovic
  • Edoardo Malfatti
  • Marta Gómez García de la Banda
  • Giorgio Tasca
  • Laura Costa Comellas
  • Audrey Benezit
  • Helge Amthor
  • Ivana Dabaj
  • Clara Gontijo Camelo
  • Pascal Laforêt
  • John Rendu
  • Norma B. Romero
  • Eliana Cavassa
  • Fabiana Fattori
  • Christophe Beroud
  • Jana Zídková
  • Nicolas Leboucq
  • Nicoline Løkken
  • Ángel Sanchez-Montañez
  • Ximena Ortega
  • Martin Kynčl
  • Corinne Metay
  • David Gómez-Andrés
  • Robert Y. Carlier

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.

TidsskriftJournal of Neurology
Sider (fra-til)2414–2429
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
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.

Publisher Copyright:
© 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

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