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, Kayla M.D. CornettManoj P. Menezes, Robert Ouvrier, Gyula Acsadi, Rosemary R. Shy, Daniela Calabrese, Maria Foscan, Roberta Sala, 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, Kristy Rose, Mark Halaki, Julie Pallant, Monkol Lek, Michael E. Shy, Joshua Burns, for the CMTPedS Study Group

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To determine the rate of disease progression in a longitudinal natural history study of children with Charcot-Marie-Tooth (CMT) disease. Methods: Two 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. Results: On 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). Interpretation: Using 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.

Original languageEnglish
Pages (from-to)353-359
Number of pages7
JournalAnnals of Neurology
Volume82
Issue number3
DOIs
Publication statusPublished - Sep 1 2017

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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