A Multicenter Cross-Sectional Study of the Swiss Cohort of LAMA2-Related Muscular Dystrophy.

Autor:	Enzmann C; 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., Steiner L; Department of Paediatrics, Division of Neuropaediatrics, Development and Rehabilitation, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland., Pospieszny K; University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland., Zweier C; Department of Human Genetics, Inselspital Bern University Hospital, and University of Bern, Bern, Switzerland., Plattner K; Department of Human Genetics, Inselspital Bern University Hospital, and University of Bern, Bern, Switzerland., Baumann D; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland., Henzi B; Department of Paediatrics, Division of Neuropaediatrics, Development and Rehabilitation, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland., Galiart E; Neuromuscular Center Zurich and Department of Pediatric Neurology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland., Fink M; Department of Paediatrics, Division of Neuropaediatrics, Development and Rehabilitation, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland., Jacquier D; Pediatric Neurology and Neurorehabilitation Unit, Lausanne University Hospital, Lausanne, Switzerland., Stettner GM; Neuromuscular Center Zurich and Department of Pediatric Neurology, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland., Ripellino P; Department of Neurology, Neurocenter of Southern Switzerland EOC, Lugano, Switzerland.; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland., Fluss J; Neuropediatric Unit, Children's Hospital, University Hospital of Geneva, Geneva, Switzerland., Klein A; Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland.; Department of Paediatrics, Division of Neuropaediatrics, Development and Rehabilitation, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.
Jazyk:	angličtina
Zdroj:	Journal of neuromuscular diseases [J Neuromuscul Dis] 2024; Vol. 11 (5), pp. 1021-1033.
DOI:	10.3233/JND-240023
Abstrakt:	Background: 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. Objective: The present study aimed to describe a well-characterized baseline cohort of patients with LAMA2-RD in Switzerland. Methods: 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. Results: 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. Conclusion: 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.
Databáze:	MEDLINE
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