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

Susana Quijano-Roy (1, 2, 3) , Jana Haberlova (4) , Claudia Castiglioni , John Vissing (5) , Francina Munell (6) , Francois Rivier (7, 8) , Tanya Stojkovic (9, 10) , Edoardo Malfatti (11, 12) , Marta Gómez García de La Banda (1, 2) , Giorgio Tasca (13) , Laura Costa Comellas (6) , Audrey Benezit (1, 2) , Helge Amthor (1, 2, 3) , Ivana Dabaj (1, 2, 14, 15, 16) , Clara Gontijo Camelo , Pascal Laforêt (3, 2) , John Rendu (17, 18, 19) , Norma Romero (10, 20, 10) , Eliana Cavassa (1, 2) , Fabiana Fattori (21) , Christophe Béroud (22, 23) , Jana Zídková (24) , Nicolas Leboucq (25) , Nicoline Løkken (5) , Ángel Sanchez-Montañez (6) , Ximena Ortega , Martin Kynčl (4) , Corinne Metay (9, 26) , David Gómez-Andrés (6) , Robert Carlier (1, 27)

1 AP-HP. Université Paris Saclay
2 Hôpital Raymond Poincaré [AP-HP]
3 END-ICAP - Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées
4 University Hospital Motol [Prague]
5 UCPH - University of Copenhagen = Københavns Universitet
6 Vall d'Hebron University Hospital [Barcelona]
7 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
8 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
9 CHU Pitié-Salpêtrière [AP-HP]
10 Institut de Myologie
11 IMRB - Institut Mondor de Recherche Biomédicale
12 CHU Henri Mondor [Créteil]
13 Fondazione Policlinico Universitario Agostino Gemelli IRCCS
14 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
15 CHU Rouen
16 CBG - Cancer and Brain Genomics
17 Dynamique et Structure du Cytosquelette Neuronal
18 UGA - Université Grenoble Alpes
19 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
20 SU - Sorbonne Université
21 IRCCS Ospedale Pediatrico Bambino Gesù = Bambino Gesù Children’s Hospital
22 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
23 Département de génétique médicale [Hôpital de la Timone - APHM]
24 University Hospital Brno
25 CHU Montpellier
26 Centre de recherche en Myologie – U974 SU-INSERM
27 Service d'Imagerie Médicale [Raymond-Poincaré]

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 defciency in muscle biopsy, but is far more difcult in milder ambulant individuals with partial merosin defciency. 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 identifed 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 diferent 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.

Mots clés: Congenital muscular dystrophy; Heatmap; Merosin; Muscle MRI; Myopathy

Domaines: Sciences du Vivant [q-bio]

Susana Quijano-Roy, Jana Haberlova, Claudia Castiglioni, John Vissing, Francina Munell, et al.. Diagnostic interest of whole-body MRI in early- and late-onset LAMA2 muscular dystrophies: a large international cohort. Journal of Neurology, 2022, 269, pp.2414-2429. ⟨10.1007/s00415-021-10806-0⟩. ⟨hal-03359688⟩