Natural history of Charcot-Marie-Tooth disease during childhood

Kayla M D Cornett; Manoj P Menezes; Rosemary R Shy; Isabella Moroni; Emanuela Pagliano; Davide Pareyson; Timothy Estilow; Sabrina W Yum; Trupti Bhandari; Francesco Muntoni; Matilde Laura; Mary M Reilly; Richard S Finkel; Kate J Eichinger; David N Herrmann; Paula Bray; Mark Halaki; Michael E Shy; Joshua Burns

doi:10.1002/ana.25009

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Natural history of Charcot-Marie-Tooth disease during childhood

Journal article

Peer reviewed

Natural history of Charcot-Marie-Tooth disease during childhood

Kayla M D Cornett, Manoj P Menezes, Rosemary R Shy, Isabella Moroni, Emanuela Pagliano, Davide Pareyson, Timothy Estilow, Sabrina W Yum, Trupti Bhandari, Francesco Muntoni, …

Annals of neurology, Vol.82(3), pp.353-359

09/2017

DOI: 10.1002/ana.25009

PMCID: PMC8294172

PMID: 28796392

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https://www.ncbi.nlm.nih.gov/pmc/articles/8294172View

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Abstract

To determine the rate of disease progression in a longitudinal natural history study of children with Charcot-Marie-Tooth (CMT) disease.\nTwo hundred six (103 female) participants aged 3 to 20 years enrolled in the Inherited Neuropathies Consortium were assessed at baseline and 2 years. Demographic, anthropometric, and diagnostic information were collected. Disease progression was assessed with the CMT Pediatric Scale (CMTPedS), a reliable Rasch-built linearly weighted disability scale evaluating fine and gross motor function, strength, sensation, and balance.\nOn average, CMTPedS Total scores progressed at a rate of 2.4 ± 4.9 over 2 years (14% change from baseline; p < 0.001). There was no difference between males and females (mean difference, 0.5; 95% confidence interval [CI], -0.9 to 1.9; p = 0.49). The most responsive CMTPedS items were dorsiflexion strength (z-score change, -0.3; 95% CI, -0.6 to -0.05; p = 0.02), balance (z-score change, -1.0; 95% CI, -1.9 to -0.09; p = 0.03), and long jump (z-score change, -0.4; 95% CI, -0.7 to -0.02; p = 0.04). Of the most common genetic subtypes, 111 participants with CMT1A/PMP22 duplication progressed by 1.8 ± 4.2 (12% change from baseline; p < 0.001), 9 participants with CMT1B/MPZ mutation progressed by 2.2 ± 5.1 (11% change), 6 participants with CMT2A/MFN2 mutation progressed by 6.2 ± 7.9 (23% change), and 7 participants with CMT4C/SH3TC2 mutations progressed by 3.0 ± 4.5 (12% change). Participants with CMT2A progressed faster than CMT1A (mean difference, -4.4; 95% CI, -8.1 to -0.8; p = 0.02). Children with CMT1A progressed consistently through early childhood (3-10 years) and adolescence (11-20 years; mean difference, 1.1; 95% CI, -0.6 to 2.7; p = 0.19), whereas CMT2A appeared to progress faster during early childhood than adolescence (mean difference, 10.0; 95% CI, -2.2 to 22.2; p = 0.08).\nUsing the CMTPedS as an outcome measure of disease severity, children with CMT progress at a significant rate over 2 years. Understanding the rate at which children with CMT deteriorate is essential for adequately powering trials of disease-modifying interventions. Ann Neurol 2017;82:353-359.

Humans

Child, Preschool

Male

Charcot-Marie-Tooth Disease - pathology

Myelin Proteins - genetics

Disease Progression

Charcot-Marie-Tooth Disease - genetics

Young Adult

Adolescent

Female

Mutation

Child

Longitudinal Studies

Details

Title: Subtitle: Natural history of Charcot-Marie-Tooth disease during childhood
Creators: Kayla M D Cornett - The University of Sydney, Sydney Children's Hospitals Network (Randwick and Westmead, Sydney, New South Wales, Australia
Manoj P Menezes - Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
Rosemary R Shy - Carver College of Medicine, Department of Pediatrics, University of Iowa, Iowa City, IA
Isabella Moroni - IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy
Emanuela Pagliano - IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy
Davide Pareyson - IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy
Timothy Estilow - Neuromuscular Program, The Children's Hospital of Philadelphia, Philadelphia, PA
Sabrina W Yum - Division of Neurology, The Children's Hospital of Philadelphia, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Trupti Bhandari - UCL Institute of Child Health & Great Ormond Street Hospital, London, United Kingdom
Francesco Muntoni - UCL Institute of Child Health & Great Ormond Street Hospital, London, United Kingdom
Matilde Laura - MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, United Kingdom
Mary M Reilly - MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, United Kingdom
Richard S Finkel - Neuromuscular Program, Division of Neurology, Nemours Children's Hospital, Orlando, FL
Kate J Eichinger - Department of Neurology, University of Rochester, Rochester, NY
David N Herrmann - Department of Neurology, University of Rochester, Rochester, NY
Paula Bray - The University of Sydney, Sydney Children's Hospitals Network (Randwick and Westmead, Sydney, New South Wales, Australia
Mark Halaki - Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
Michael E Shy - Carver College of Medicine, Department of Neurology, University of Iowa, Iowa City, IA
Joshua Burns - Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
Resource Type: Journal article
Publication Details: Annals of neurology, Vol.82(3), pp.353-359
DOI: 10.1002/ana.25009
PMID: 28796392
PMCID: PMC8294172
NLM abbreviation: Ann Neurol
ISSN: 0364-5134
eISSN: 1531-8249
Publisher: United States
Grant note: G0601943 / Medical Research Council\nU54 NS065712 / NINDS NIH HHS
Language: English
Date published: 09/2017
Academic Unit: Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984070850602771

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