TY - JOUR
T1 - Natural history of Charcot-Marie-Tooth disease during childhood
AU - Cornett, Kayla M.D.
AU - Menezes, Manoj P.
AU - Shy, Rosemary R.
AU - Moroni, Isabella
AU - Pagliano, Emanuela
AU - Pareyson, Davide
AU - Estilow, Timothy
AU - Yum, Sabrina W.
AU - Bhandari, Trupti
AU - Muntoni, Francesco
AU - Laura, Matilde
AU - Reilly, Mary M.
AU - Finkel, Richard S.
AU - Eichinger, Kate J.
AU - Herrmann, David N.
AU - Bray, Paula
AU - Halaki, Mark
AU - Shy, Michael E.
AU - Burns, Joshua
AU - Cornett, Kayla M.D.
AU - Menezes, Manoj P.
AU - Ouvrier, Robert
AU - Acsadi, Gyula
AU - Shy, Rosemary R.
AU - Calabrese, Daniela
AU - Foscan, Maria
AU - Sala, Roberta
AU - Moroni, Isabella
AU - Pagliano, Emanuela
AU - Pareyson, Davide
AU - Estilow, Timothy
AU - Yum, Sabrina W.
AU - Bhandari, Trupti
AU - Muntoni, Francesco
AU - Laura, Matilde
AU - Reilly, Mary M.
AU - Finkel, Richard S.
AU - Eichinger, Kate J.
AU - Herrmann, David N.
AU - Bray, Paula
AU - Rose, Kristy
AU - Halaki, Mark
AU - Pallant, Julie
AU - Lek, Monkol
AU - Shy, Michael E.
AU - Burns, Joshua
AU - for the CMTPedS Study Group
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ana.25009
DO - 10.1002/ana.25009
M3 - Article
C2 - 28796392
AN - SCOPUS:85029785877
VL - 82
SP - 353
EP - 359
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 3
ER -