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LAMA2-related muscular dystrophy: Natural history of a large pediatric cohort

Zambon, AA; Ridout, D; Main, M; Mein, R; Phadke, R; Muntoni, F; Sarkozy, A; (2020) LAMA2-related muscular dystrophy: Natural history of a large pediatric cohort. Annals of Clinical and Translational Neurology , 7 (10) pp. 18870-1882. 10.1002/acn3.51172. Green open access

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Abstract

OBJECTIVE: To characterize natural history of Laminin-α2 related muscular dystrophies (LAMA2-RD) to help anticipating complications and identifying reliable outcome measures for clinical trial design and powering. METHODS: We conducted a retrospective, single-center, cross-sectional and longitudinal study on 46 LAMA2-RD 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-to-event analysis was performed to estimate median age at complications occurrence. RESULTS: Forty two patients had complete deficiency of Laminin-α2 (CD) and four had partial deficiency (PD). Median age at first and last assessment was 2 years and 12.1 years, respectively. Median follow-up length was 7.8 years (range 0-18 years). Seven CD patients died at median age 12 years. One CD and two PD subjects achieved independent ambulation. We observed a linear increase in elbow flexor contractures in CD subjects. Thirty-two CD and one PD patient developed scoliosis, nine underwent spinal surgery. Twenty-two CD required nocturnal noninvasive ventilation (median age 11.7 years). 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 years). Four CD patients had partial seizures. Mild left cardiac ventricular dysfunction and rhythm disturbances were identified in seven CD patients. INTERPRETATION: This retrospective longitudinal study provides long-term natural history of LAMA2-RD. This will help management and identification of key milestones of disease progression that could be considered for future therapeutic intervention.

Type: Article
Title: LAMA2-related muscular dystrophy: Natural history of a large pediatric cohort
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/acn3.51172
Publisher version: https://doi.org/10.1002/acn3.51172
Language: English
Additional information: ª 2020 The Authors. An nals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neur ological Association.This is an open access article under the terms of the Cr eative Commons Attribution-NonCommerc ial-NoDerivs License, which permits use anddistribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10110159
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