{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:16:56Z","timestamp":1791998216356,"version":"4.4.0"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2024,8,22]]},"abstract":"<jats:p>Background: LAMA2-related dystrophies (LAMA2-RDs) represent one of the most common forms of congenital muscular dystrophy and have historically been classified into two subtypes: complete or partial deficiency of laminin-211 (merosin). Patients with LAMA2-RD with the typical congenital phenotype manifest severe muscle weakness, delayed motor milestones, joint contractures, failure to thrive, and progressive respiratory insufficiency. Objective: While a comprehensive prospective natural history study has been performed in LAMA2-RD patients over 5 years of age, the early natural history of patients with LAMA2-RD 5 years and younger has not been comprehensively characterized. Methods: We extracted retrospective data for patients with LAMA2-RD ages birth through 5 years via the Congenital Muscle Disease International Registry (CMDIR). We analyzed the data using a phenotypic classification based on maximal motor milestones to divide patients into two phenotypic groups: \u201cSit\u201d for those patients who attained that ability to remain seated and \u201cWalk\u201d for those patients who attained the ability to walk independently by 3.5 years of age. Results: Sixty patients with LAMA2-RD from 10 countries fulfilled the inclusion criteria. Twenty-four patients had initiated non-invasive ventilation by age 5 years. Hospitalizations during the first years of life were often related to respiratory insufficiency. Feeding\/nutritional difficulties and orthopedic issues were commonly reported. Significant elevations of creatine kinase (CK) observed during the neonatal period declined rapidly within the first few months of life. Conclusions: This is the largest international retrospective early natural history study of LAMA2-RD to date, contributing essential data for understanding early clinical findings in LAMA2-RD which, along with the data being collected in international, prospective early natural history studies, will help to establish clinical trial readiness. Our proposed nomenclature of LAMA2-RD1 for patients who attain the ability to sit (remain seated) and LAMA2-RD2 for patients who attain the ability to walk independently is aimed at further improving LAMA2-RD classification.<\/jats:p>","DOI":"10.3233\/jnd-240048","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T11:30:12Z","timestamp":1724412612000},"page":"1-11","source":"Crossref","is-referenced-by-count":3,"title":["An International Retrospective Early Natural History Study of LAMA2-Related Dystrophies"],"prefix":"10.1177","author":[{"given":"Lauren","family":"Hinkley","sequence":"first","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rotem","family":"Orbach","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Park","sequence":"additional","affiliation":[{"name":"Cure CMD, Congenital Muscle Disease International Registry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Cure CMD, Congenital Muscle Disease International Registry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Dziewczapolski","sequence":"additional","affiliation":[{"name":"Cure CMD, Congenital Muscle Disease International Registry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten G.","family":"B\u00f6nnemann","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Reghan","family":"Foley","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JND-240048_ref1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/cge.13560","article-title":"Congenital muscular dystrophies in China","volume":"96","author":"Ge","year":"2019","journal-title":"Clin Genet"},{"key":"10.3233\/JND-240048_ref2","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.nmd.2017.06.008","article-title":"Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period","volume":"27","author":"Sframeli","year":"2017","journal-title":"Neuromuscular Disorders"},{"key":"10.3233\/JND-240048_ref3","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.nmd.2004.06.009","article-title":"The congenital muscular dystrophies in A century of exciting progress","volume":"14","author":"Muntoni","year":"2004","journal-title":"Neuromuscular Disorders"},{"issue":"9","key":"10.3233\/JND-240048_ref4","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1073\/pnas.87.9.3264","article-title":"Merosin, a tissue-specific basement membrane protein, is a laminin-like protein","volume":"87","author":"Ehrig","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"10.3233\/JND-240048_ref5","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1083\/jcb.124.3.381","article-title":"Human laminin M chain (merosin): complete primary structure, chromosomal assignment, and expression of the M and A chain in human fetal tissues","volume":"124","author":"Vuolteenaho","year":"1994","journal-title":"J Cell Biol"},{"key":"10.3233\/JND-240048_ref6","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.nmd.2005.04.009","article-title":"Prenatal diagnosis in laminin \u03b12 chain (merosin)-deficient congenital muscular dystrophy: A collective experience of five international centers","volume":"15","author":"Vainzof","year":"2005","journal-title":"Neuromuscular Disorders"},{"issue":"2","key":"10.3233\/JND-240048_ref7","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S0960-8966(98)00112-6","article-title":"Merosin-deficient congenital muscular dystrophy associated with abnormal cerebral cortical gyration: an autopsy study","volume":"9","author":"Taratuto","year":"1999","journal-title":"Neuromuscul Disord"},{"key":"10.3233\/JND-240048_ref8","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/(SICI)1097-0177(200006)218:2<213::AID-DVDY1>3.0.CO;2-R","article-title":"Form and function: The laminin family of heterotrimers","volume":"218","author":"Colognato","year":"2000","journal-title":"Developmental Dynamics"},{"issue":"4","key":"10.3233\/JND-240048_ref9","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1083\/jcb.122.4.809","article-title":"A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin","volume":"122","author":"Ervasti","year":"1993","journal-title":"J Cell Biol"},{"key":"10.3233\/JND-240048_ref10","doi-asserted-by":"crossref","first-page":"21437","DOI":"10.1074\/jbc.M702963200","article-title":"Role of laminin terminal globular domains in basement membrane assembly","volume":"282","author":"McKee","year":"2007","journal-title":"Journal of Biological Chemistry"},{"key":"10.3233\/JND-240048_ref11","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.matbio.2017.11.009","article-title":"Laminin-deficient muscular dystrophy: Molecular pathogenesis and structural repair strategies","volume":"71\u201372","author":"Yurchenco","year":"2018","journal-title":"Matrix Biology"},{"issue":"2","key":"10.3233\/JND-240048_ref12","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/ng1095-216","article-title":"Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy","volume":"11","author":"Helbling-Leclerc","year":"1995","journal-title":"Nat Genet"},{"key":"10.3233\/JND-240048_ref13","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fnmol.2020.00123","article-title":"LAMA2-Related Dystrophies: Clinical Phenotypes, Disease Biomarkers, and Clinical Trial Readiness","volume":"13","author":"Sarkozy","year":"2020","journal-title":"Front Mol Neurosci"},{"issue":"7","key":"10.3233\/JND-240048_ref14","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0960-8966(98)00065-0","article-title":"Laminin alpha 2-chain gene mutations in two siblings presenting with limb-girdle muscular dystrophy","volume":"8","author":"Naom","year":"1998","journal-title":"Neuromuscul Disord"},{"key":"10.3233\/JND-240048_ref15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1212\/WNL.51.1.101","article-title":"Laminin \u03b12 muscular dystrophy: Genotype\/phenotype studies of 22 patients","volume":"51","author":"Pegoraro","year":"1998","journal-title":"Neurology"},{"issue":"3-4","key":"10.3233\/JND-240048_ref16","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0960-8966(98)00013-3","article-title":"Merosin-deficient congenital muscular dystrophy with severe mental retardation and normal cranial MRI: a report of two siblings","volume":"8","author":"Topalo\u011flu","year":"1998","journal-title":"Neuromuscul Disord"},{"key":"10.3233\/JND-240048_ref17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/humu.10157","article-title":"Clinical and molecular study in congenital muscular dystrophy with partial laminin \u03b12 (LAMA2) deficiency","volume":"21","author":"Tezak","year":"2003","journal-title":"Hum Mutat"},{"key":"10.3233\/JND-240048_ref18","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/j.1399-0004.2008.01068.x","article-title":"LAMA2 gene analysis in a cohort of 26 congenital muscular dystrophy patients","volume":"74","author":"Oliveira","year":"2008","journal-title":"Clin Genet"},{"key":"10.3233\/JND-240048_ref19","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.nmd.2010.02.001","article-title":"Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations","volume":"20","author":"Geranmayeh","year":"2010","journal-title":"Neuromuscular Disorders"},{"key":"10.3233\/JND-240048_ref20","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/cge.12366","article-title":"Genotype\/phenotype analysis in Chinese laminin-\u03b12 deficient congenital muscular dystrophy patients","volume":"87","author":"Xiong","year":"2015","journal-title":"Clin Genet"},{"key":"10.3233\/JND-240048_ref21","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1212\/01.WNL.0000138498.66940.7F","article-title":"LAMA2 loss-of-function mutation in a girl with a mild congenital muscular dystrophy","volume":"63","author":"Prandini","year":"2004","journal-title":"Neurology"},{"key":"10.3233\/JND-240048_ref22","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1002\/acn3.51172","article-title":"LAMA2-related muscular dystrophy: Natural history of a large pediatric cohort","volume":"7","author":"Zambon","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"issue":"1","key":"10.3233\/JND-240048_ref23","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/s13023-021-01950-x","article-title":"Natural history and genetic study of LAMA2-related muscular dystrophy in a large Chinese cohort","volume":"16","author":"Tan","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"10.3233\/JND-240048_ref24","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1212\/01.WNL.0000138498.66940.7F","article-title":"LAMA2 loss-of-function mutation in a girl with a mild congenital muscular dystrophy","volume":"63","author":"Prandini","year":"2004","journal-title":"Neurology"},{"issue":"2","key":"10.3233\/JND-240048_ref25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0960-8966(98)00110-2","article-title":"Merosin-deficient congenital muscular dystrophy: the spectrum of brain involvement on magnetic resonance imaging","volume":"9","author":"Philpot","year":"1999","journal-title":"Neuromuscul Disord"},{"key":"10.3233\/JND-240048_ref26","doi-asserted-by":"crossref","first-page":"483","DOI":"10.3233\/JND-221638","article-title":"Brain MRI abnormalities, epilepsy and intellectual disability in LAMA2 related dystrophy - a genotype\/phenotype correlation","volume":"10","author":"Camelo","year":"2023","journal-title":"J Neuromuscul Dis"},{"key":"10.3233\/JND-240048_ref27","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/s00247-004-1398-y","article-title":"Merosin-deficient congenital muscular dystrophy (CMD): A study of 25 Brazilian patients using MRI","volume":"35","author":"Leite","year":"2005","journal-title":"Pediatr Radiol"},{"key":"10.3233\/JND-240048_ref28","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/epi.16493","article-title":"Epilepsy in LAMA2-related muscular dystrophy: An electro-clinico-radiological characterization","volume":"61","author":"Natera-de Benito","year":"2020","journal-title":"Epilepsia"},{"issue":"396","key":"10.3233\/JND-240048_ref29","doi-asserted-by":"crossref","first-page":"eaal4649","DOI":"10.1126\/scitranslmed.aal4649","article-title":"Linker proteins restore basement membrane and correct LAMA2-related muscular dystrophy in mice","volume":"9","author":"Reinhard","year":"2017","journal-title":"Sci Transl Med"},{"key":"10.3233\/JND-240048_ref30","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1016\/j.ajpath.2011.12.019","article-title":"Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy","volume":"180","author":"Rooney","year":"2012","journal-title":"American Journal of Pathology"},{"key":"10.3233\/JND-240048_ref31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41586-019-1430-x","article-title":"A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene","volume":"572","author":"Kemaladewi","year":"2019","journal-title":"Nature"},{"issue":"5","key":"10.3233\/JND-240048_ref32","doi-asserted-by":"crossref","first-page":"e200089","DOI":"10.1212\/NXG.0000000000200089","article-title":"LAMA2-Related Muscular Dystrophy Across the Life Span: A Cross-sectional Study","volume":"9","author":"Bouman","year":"2023","journal-title":"Neurol Genet"},{"key":"10.3233\/JND-240048_ref33","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.nmd.2020.03.009","article-title":"Clinical and genomic characteristics of LAMA2 related congenital muscular dystrophy in a patients\u2019 cohort from Qatar","volume":"30","author":"Abdel Aleem","year":"2020","journal-title":"A population specific founder variant. Neuromuscular Disorders"},{"key":"10.3233\/JND-240048_ref34","doi-asserted-by":"crossref","first-page":"E1932","DOI":"10.1212\/WNL.0000000000008517","article-title":"Longitudinal changes in clinical outcome measures in COL6-related dystrophies and LAMA2-related dystrophies","volume":"93","author":"Jain","year":"2019","journal-title":"Neurology"},{"issue":"11","key":"10.3233\/JND-240048_ref35","doi-asserted-by":"crossref","first-page":"e1387","DOI":"10.1002\/mgg3.1387","article-title":"Novel mutation identification and copy number variant detection via exome sequencing in congenital muscular dystrophy","volume":"8","author":"Cauley","year":"2020","journal-title":"Mol Genet Genomic Med"},{"issue":"1","key":"10.3233\/JND-240048_ref36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12887-020-1909-5","article-title":"Hypoglycemia in patients with congenital muscle disease","volume":"20","author":"Hayes","year":"2020","journal-title":"BMC Pediatr"},{"key":"10.3233\/JND-240048_ref37","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1002\/acn3.51829","article-title":"Newborn screening for Duchenne muscular dystrophy: A two-year pilot study","volume":"10","author":"Tavakoli","year":"2023","journal-title":"Ann Clin Transl Neurol"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JND-240048","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:52:50Z","timestamp":1777506770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.medra.org\/servlet\/aliasResolver?alias=iospress&doi=10.3233\/JND-240048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,22]]},"references-count":37,"URL":"https:\/\/doi.org\/10.3233\/jnd-240048","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,22]]}}}