Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland.
Division of Neuropediatrics, Children's Hospital, Cantonal Hospital Aarau (KSA), Aarau, Switzerland.
J Neuromuscul Dis. 2024;11(5):1021-1033. doi: 10.3233/JND-240023.
LAMA2-related muscular dystrophy (LAMA2-RD) is an autosomal-recessive disorder and one of the most common congenital muscular dystrophies. Due to promising therapies in preclinical development, there is an increasing effort to better define the epidemiology and natural history of this disease.
The present study aimed to describe a well-characterized baseline cohort of patients with LAMA2-RD in Switzerland.
The study used data collected by the Swiss Registry for Neuromuscular Disorders (Swiss-Reg-NMD). Diagnostic findings were derived from genetics, muscle biopsy, creatine kinase-level and electrophysiological testing, as well as from brain MRIs. Further clinical information included motor assessments (CHOP INTEND, MFM20/32), joint contractures, scoliosis, ophthalmoplegia, weight gain, feeding difficulties, respiratory function, cardiac investigations, EEG findings, IQ and schooling.
Eighteen patients with LAMA-RD were included in the Swiss-Reg-NMD as of May 2023 (age at inclusion into the registry: median age 8.7 years, range 1 month - 31 years F = 8, M = 10). Fourteen patients presented with the severe form of LAMA2-RD (were never able to walk; CMD), whereas four patients presented with the milder form (present or lost walking capability; LGMD). All patients classified as CMD had symptoms before 12 months of age and 11/14 before the age of six months. 15 carried homozygous or compound heterozygous pathogenic or likely pathogenic variants in LAMA2 and two were homozygous for a variant of unknown significance (one patient unknown). Brain MRI was available for 14 patients, 13 had white matter changes and 11 had additional structural abnormalities, including cobblestone malformations, pontine hypoplasia and an enlarged tegmento-vermial angle not reported before.
This study describes the Swiss cohort of patients with LAMA2-RD and gives insights into measuring disease severity and disease progression, which is important for future clinical trials, as well as for a better clinical understanding and management of patients with LAMA2-RD.
层粘连蛋白 2 相关肌营养不良症（LAMA2-RD）是一种常染色体隐性遗传病，也是最常见的先天性肌营养不良症之一。由于临床前开发中具有前景的治疗方法，人们越来越努力地更好地定义这种疾病的流行病学和自然史。
本研究旨在描述瑞士具有良好特征的 LAMA2-RD 患者基线队列。
本研究使用瑞士神经肌肉疾病登记处（Swiss-Reg-NMD）收集的数据。诊断发现源自遗传学、肌肉活检、肌酸激酶水平和电生理学检查以及脑 MRI。进一步的临床信息包括运动评估（CHOP INTEND、MFM20/32）、关节挛缩、脊柱侧凸、眼肌麻痹、体重增加、喂养困难、呼吸功能、心脏检查、脑电图发现、智商和学校教育。
截至 2023 年 5 月，18 名 LAMA-RD 患者被纳入 Swiss-Reg-NMD（登记时的年龄中位数为 8.7 岁，范围为 1 个月至 31 岁 F=8，M=10）。14 名患者表现出 LAMA2-RD 的严重形式（从未能够行走；CMD），而 4 名患者表现出较轻的形式（出现或丧失行走能力；LGMD）。所有被归类为 CMD 的患者在 12 个月之前出现症状，11/14 名患者在 6 个月之前出现症状。15 名患者携带 LAMA2 的纯合或复合杂合致病性或可能致病性变异，2 名患者携带不明意义变异的纯合子（一名患者情况不明）。14 名患者可提供脑部 MRI，13 名患者有白质变化，11 名患者有额外的结构异常，包括鹅卵石样畸形、桥脑发育不良和以前未报道的增大的脑桥小脑角。
本研究描述了瑞士 LAMA2-RD 患者队列，并深入了解了测量疾病严重程度和疾病进展的方法，这对于未来的临床试验以及更好地了解和管理 LAMA2-RD 患者的临床具有重要意义。
