Premium
Natural history of Charcot‐Marie‐Tooth disease during childhood
Author(s) -
Cornett Kayla M.D.,
Menezes Manoj P.,
Shy Rosemary R.,
Moroni Isabella,
Pagliano Emanuela,
Pareyson Davide,
Estilow Timothy,
Yum Sabrina W.,
Bhandari Trupti,
Muntoni Francesco,
Laura Matilde,
Reilly Mary M.,
Finkel Richard S.,
Eichinger Kate J.,
Herrmann David N.,
Bray Paula,
Halaki Mark,
Shy Michael E.,
Burns Joshua
Publication year - 2017
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25009
Subject(s) - confidence interval , medicine , natural history study , natural history , balance (ability) , anthropometry , demography , physical therapy , sociology
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