Axonal-demyelinating differences in functional change in pediatric Charcot–Marie–Tooth and related neuropathies

Charcot–Marie–Tooth disease and related neuropathies (CMTR) are heterogeneous inherited neuropathies with variable progression, yet data on pediatric disease progression by neurophysiological subtype are limited. We evaluated 1-year clinical and functional changes in children with CMTR and compared axonal versus demyelinating trajectories. We conducted a prospective cohort study of 20 Thai children with CMTR who were aged 3–20 years. Participants were assessed at baseline and after 1 year using the Rasch-modified Charcot–Marie–Tooth Examination Score (CMTES-R), Charcot–Marie–Tooth Pediatric Scale (CMTPedS), manual muscle testing (MMT), Foot Posture Index, and muscle length testing. Within-subject changes in clinical outcomes over time were assessed using appropriate paired statistical tests. Thirteen patients had axonal forms and seven had demyelinating forms; the patients’ mean age was 13.0 ± 4.9 years. The axonal variants involved MFN2 (n = 3), GDAP1 (n = 2), and GAN, GJB1, IGHMBP2, KIF1A, PRDM12 (n = 1 each); 3 axonal variants were genetically undiagnosed. The demyelinating variants comprised MPZ (n = 2), PMP22 duplication (n = 2), EGR2 (n = 1), NEFL (n = 1), and PMP22 deletion (n = 1). At both time points, 85% of the patients were ambulatory, 15% used a wheelchair, and 65% used an ankle-foot orthosis. CMTPedS increased by 1.0 ± 3.4 points over 1 year (p = 0.271), with a larger change in axonal versus demyelinating cases (+ 1.1 ± 3.2 vs. + 0.7 ± 4.0). CMTES-R changed minimally (median + 0.5), and MMT showed stable strength. The clinical progression in pediatric CMTR was heterogeneous and differed by neurophysiological subtype, with more pronounced 1-year functional decline in axonal disease. These findings support vigilant longitudinal monitoring of pediatric CMTR, particularly where genetic testing access is limited.