Quijano-Roy Susana, Haberlova Jana, Castiglioni Claudia, Vissing John, Munell Francina, Rivier François, Stojkovic Tanya, Malfatti Edoardo, Gómez García de la Banda Marta, Tasca Giorgio, Costa Comellas Laura, Benezit Audrey, Amthor Helge, Dabaj Ivana, Gontijo Camelo Clara, Laforêt Pascal, Rendu John, Romero Norma B, Cavassa Eliana, Fattori Fabiana, Beroud Christophe, Zídková Jana, Leboucq Nicolas, Løkken Nicoline, Sanchez-Montañez Ángel, Ortega Ximena, Kynčl Martin, Metay Corinne, Gómez-Andrés David, Carlier Robert Y
APHP, GH Université Paris-Saclay, Neuromuscular Center, Child Neurology and ICU Department, Raymond Poincare Hospital, Garches, France.
Université de Versailles, U1179 INSERM-UVSQ, Versailles, France.
J Neurol. 2022 May;269(5):2414-2429. doi: 10.1007/s00415-021-10806-0. Epub 2021 Sep 24.
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.
To investigate the diagnostic utility of muscle imaging in LAMA2-RD using whole-body magnetic resonance imaging (WBMRI).
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.
WBMRI in LAMA2-RD shows a homogeneous pattern of brain and muscle imaging, representing a supportive diagnostic tool.
层粘连蛋白α2相关型肌营养不良症（LAMA2-RD）是一组由LAMA2基因突变引起的隐性肌营养不良症，该基因编码层粘连蛋白-211（巢蛋白）的α-2链。在典型的先天性病例中，诊断较为简单，患者无法行走，肌肉活检显示完全缺乏巢蛋白，但在症状较轻、仍可行走且巢蛋白部分缺乏的个体中，诊断则困难得多。
利用全身磁共振成像（WBMRI）研究肌肉成像在LAMA2-RD诊断中的应用价值。
一项国际合作研究纳入了27例患者（年龄2至62岁，21%至80%的患者获得了行走能力，6例从未行走）。所有患者均携带两个致病突变，大多为私人错义突变。在所有智利病例中均鉴定出一个内含子变异（c.909 + 7A > G）。3例患者（2例可行走）出现智力残疾、癫痫和脑结构异常。WBMRI的T1加权序列或T2脂肪抑制图像（狄克逊法）显示，肩胛下肌、腰背部椎旁肌、臀小肌和臀中肌、大腿后部（大收肌、股二头肌、腘绳肌）和比目鱼肌主要出现异常肌肉脂肪替代。这种受累模式在可行走和不可行走的患者中均一致。替代程度主要与疾病持续时间相关，而非与发病或临床严重程度相关。在可行走的成年人中，在几块肌肉中观察到了“COL6样夹心征”，但肩胛下肌、臀小肌和臀中肌不同的受累变化有助于将LAMA2-RD与胶原病区分开来。大腿肌肉似乎是评估疾病进展的最佳部位。
LAMA2-RD患者的WBMRI显示出脑和肌肉成像的均匀模式，是一种辅助诊断工具。
