Pediatrics, Perinatology and Child Health; Developmental Neuroscience; Neurology (clinical)
Abstract :
[en] [en] AIM: To investigate the associations between mutations expected to differentially affect Dp140 expression and long-term trajectories of respiratory and upper-limb motor outcomes in Duchenne muscular dystrophy (DMD).
METHOD: In a retrospective analysis of population-based longitudinal data from three real-world and natural history data sources, individuals with DMD aged 5 years to 18 years were subdivided according to the predicted effects of the participants' DMD mutation on dystrophin isoform expression (group 1, Dp427 absent, Dp140/Dp71 present; group 2, Dp427/Dp140 absent, Dp71 present).
RESULTS: A total of 459 participants were studied, with upper-limb outcomes assessed in 71 (27 in group 1 and 44 in group 2) and forced vital capacity percentage predicted (%pred) assessed in 434 (224 in group 1 and 210 in group 2). Mean grip strength %pred was on average 7.1 percentage points lower in group 2 than in group 1 (p = 0.03). Mean pinch strength %pred was on average 9.2 percentage points lower in group 2 than in group 1 (p = 0.04). Mean forced vital capacity %pred was on average 4.3 percentage points lower in group 2 than in group 1 (p = 0.01).
INTERPRETATION: In individuals with DMD, DMD mutations predicted to affect Dp140 expression were associated with more severe trajectories of respiratory and upper-limb motor outcomes.
Disciplines :
Pediatrics
Author, co-author :
Chesshyre, Mary ; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK
Ridout, Deborah; Population, Policy and Practice Research and Teaching Department, UCL GOS Institute of Child Health, London, UK
Stimpson, Georgia; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK
Ricotti, Valeria; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK ; NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, UCL, London, UK ; Great Ormond Street Hospital NHS Foundation Trust, London, UK
De Lucia, Silvana; AP-HP, Sorbonne University, Institute of Myology, AFM-Telethon, I-Motion Pediatric Clinical Trials Platform, Armand Trousseau Hospital, Paris, France
Niks, Erik H; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
Straub, Volker; The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK ; NIHR Newcastle Biomedical Research Centre, University of Newcastle, Newcastle upon Tyne, UK
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques ; Department of Paediatrics, MDUK Oxford Neuromuscular Centre, Oxford, UK ; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
Hogrel, Jean-Yves ; Institute of Myology, Paris, France
Baranello, Giovanni ; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK
Manzur, Adnan; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK
UK NorthStar Clinical Network
Muntoni, Francesco; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK ; NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, UCL, London, UK ; Great Ormond Street Hospital NHS Foundation Trust, London, UK
The Upper Limb Evaluation in Non Ambulatory Patients With Neuromuscular Disorder study was partly funded by Advanced Diagnostics for New Therapeutic Approaches, a programme dedicated to personalized medicine, coordinated by Institut M\u00E9rieux and supported by research and innovation aid from the French public agency OSEO.The support of the National Institute for Health and Care Research to the Great Ormond Street Hospital Biomedical Research Centre (FM); the Great Ormond Street Institute of Child Health (FM); and UCL and Great Ormond Street Hospital Trust (FM) are also gratefully acknowledged. Dr. Baranello and Georgia Stimpson are supported by a grant from the Great Ormond Street Hospital Children's Charity and Muscular Dystrophy UK.The financial support of L'Association Fran\u00E7aise Contre les Myopathies for the Outcome measures in Duchenne Muscular Dystrophy: A Natural History Study (NCT02780492) is gratefully acknowledged.We acknowledge the work of the UK NorthStar Clinical Network in the collection of data used in this publication. The UK NorthStar Clinical Network is funded by Muscular Dystrophy UK (grant no. 22GRO\u2010PG24\u20100598). Prof. Francesco Muntoni (UCL) is the Principal Investigator of the UK NorthStar Clinical Network. We thank Certus Technology Associates Limited for hosting the database for the UK NorthStar Clinical Network.
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