{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T02:10:55Z","timestamp":1785636655995,"version":"3.56.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize natural history of Laminin\u2010\u03b12 related muscular dystrophies (LAMA2\u2010RD) to help anticipating complications and identifying reliable outcome measures for clinical trial design and powering.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective, single\u2010center, cross\u2010sectional and longitudinal study on 46 LAMA2\u2010RD pediatric patients (37 families). Patients were seen at the Dubowitz Neuromuscular Centre, London between 1985 and 2019. Data were collected by case note reviews. Time\u2010to\u2010event analysis was performed to estimate median age at complications occurrence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty two patients had complete deficiency of Laminin\u2010\u03b12 (CD) and four had partial deficiency (PD). Median age at first and last assessment was 2\u00a0years and 12.1\u00a0years, respectively. Median follow\u2010up length was 7.8\u00a0years (range 0\u201018\u00a0years). Seven CD patients died at median age 12\u00a0years. One CD and two PD subjects achieved independent ambulation. We observed a linear increase in elbow flexor contractures in CD subjects. Thirty\u2010two CD and one PD patient developed scoliosis, nine underwent spinal surgery. Twenty\u2010two CD required nocturnal noninvasive ventilation (median age 11.7\u00a0years). CD subjects showed a 2.9% linear annual decline in forced vital capacity % predicted. Nineteen CD and one PD patient required gastrostomy insertion for failure to thrive and\/or unsafe swallow (median age 10.9\u00a0years). Four CD patients had partial seizures. Mild left cardiac ventricular dysfunction and rhythm disturbances were identified in seven CD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This retrospective longitudinal study provides long\u2010term natural history of LAMA2\u2010RD. This will help management and identification of key milestones of disease progression that could be considered for future therapeutic intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51172","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T07:20:43Z","timestamp":1601018443000},"page":"1870-1882","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["LAMA2\u2010related muscular dystrophy: Natural history of a large pediatric cohort"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6539-5360","authenticated-orcid":false,"given":"Alberto A.","family":"Zambon","sequence":"first","affiliation":[{"name":"Dubowitz Neuromuscular Centre UCL Great Ormond Street Institute of Child Health &amp; Great Ormond Street Hospital London UK"},{"name":"Neurology Department IRCCS San Raffaele Scientific Institute Milan 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