, et al
Natural history of Charcot-Marie-Tooth disease during childhood
Ann Neurol
; doi:

Investigators from multiple international institutions conducted a prospective study to evaluate the natural history of disease progression in children with Charcot-Marie-Tooth (CMT) disease. Study participants were children 3–20 years old with CMT who were enrolled at 1 of 8 sites of the Inherited Neuropathies Consortium. Participating institutions were in the United States, Australia, and Europe. At enrollment (baseline), demographic information was collected on study children. In addition, CMT genotype was determined. At baseline and 2 years (±6 months) later, participants completed the CMT Pediatric Scale (CMTPedS), a validated 11-item performance-based measure assessing fine and gross motor function, strength, sensation, and balance. Possible CMTPedS scores range from 0–44, with higher scores indicative of more severe disease. Children with CMTPedS scores 0–14 are considered mildly affected, 15–29 moderately affected, and 30–44 severely affected. Paired t-tests were used to assess change in CMTPedS scored from baseline to follow-up, and t-tests were used to compare scores among children with different CMT genetic subtypes.

A total of 206 children with a mean age of 9.8 ± 3.9 years at baseline were enrolled, including 103 females. The most common CMT genetic subtypes were CMT1A (58% of participants), CMT1B (5%), CMT2A (4%), and CMT4C (4%). Baseline and follow-up CMTPedS tests were completed by 187 study participants. Children with subtype CMT1A had significantly lower (better) CMTPedS scores at baseline than those with the other 3 common subtypes (mean baseline scores 14.6, 19.4, 26.7, and 26.1, respectively,). Compared to baseline, mean CMTPedS scores progressed by 2.4 ± 4.9 over the 2-year study period (P < .001, compared to baseline), with no difference in rates of progression between males and females. Among 111 children with subtype CMT1A, scores increased by 12% (P <.001). CMTPedS scores increased by 11% in 9 children with subtype CMT1B, 23% in 6 participants with subtype CMT2A, and 12% in 7 participants with subtype CMT4C (all changes from baseline were statistically non-significant, likely due to the small number of children in each subtype). Compared to those with subtype CMT1A, children with subtype CMT2A had significantly greater increases in CMTPedS scores from baseline to follow-up (P = .02).

The authors conclude that over a 2-year period, CMTPedS scores increased significantly in children with CMT, suggesting an increase in disease severity.

Dr Urion has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

CMT disease is an eponym for a group of inherited peripheral neuropathies that can be sensory, motor, or sensorimotor in their presentation. They may be autosomal dominant, autosomal recessive, or X-linked. CMT is the most commonly encountered inherited neurologic condition, with a prevalence of 1:2,500.

This report provides important information regarding the natural history and progression of the various forms...

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