TY - JOUR
T1 - Diagnostic interest of whole-body MRI in early- and late-onset LAMA2 muscular dystrophies
T2 - a large international cohort
AU - Quijano-Roy, Susana
AU - Haberlova, Jana
AU - Castiglioni, Claudia
AU - Vissing, John
AU - Munell, Francina
AU - Rivier, François
AU - Stojkovic, Tanya
AU - Malfatti, Edoardo
AU - Gómez García de la Banda, Marta
AU - Tasca, Giorgio
AU - Costa Comellas, Laura
AU - Benezit, Audrey
AU - Amthor, Helge
AU - Dabaj, Ivana
AU - Gontijo Camelo, Clara
AU - Laforêt, Pascal
AU - Rendu, John
AU - Romero, Norma B
AU - Cavassa, Eliana
AU - Fattori, Fabiana
AU - Beroud, Christophe
AU - Zídková, Jana
AU - Leboucq, Nicolas
AU - Løkken, Nicoline
AU - Sanchez-Montañez, Ángel
AU - Ortega, Ximena
AU - Kynčl, Martin
AU - Metay, Corinne
AU - Gómez-Andrés, David
AU - Carlier, Robert Y
N1 - © 2021. Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - Congenital muscular dystrophy
KW - Heatmap
KW - Merosin
KW - Muscle MRI
KW - Myopathy
UR - http://www.scopus.com/inward/record.url?scp=85115623953&partnerID=8YFLogxK
U2 - 10.1007/s00415-021-10806-0
DO - 10.1007/s00415-021-10806-0
M3 - Journal article
C2 - 34559299
SN - 0340-5354
VL - 269
SP - 2414
EP - 2429
JO - Journal of Neurology
JF - Journal of Neurology
IS - 5
ER -