Natural history of Charcot‐Marie‐Tooth disease during childhood

Abstract

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.

Balance impairment in pediatric charcot–marie–tooth disease

“…An understanding of genotype–phenotype relationships, sex differences, and the interrelationship of age and disease related balance impairment would provide the ability to anticipate and describe more accurately the progression of balance and the factors that drive its progression. A better understanding of the development of balance and factors that influence balance in children with CMT has begun to emerge with an understanding of expectations for change over 2 years in various genetic subtypes of CMT . This, along with greater understanding of the relationships between balance and related impairments, can be the basis for a thoughtful approach to impairment‐targeted treatment trials.…”

Fifteen‐year longitudinal follow‐up of a patient with severe early‐onset Charcot‐Marie‐Tooth disease type 2A

“…Prior clinical trials in CMT have been undermined by an inability to detect changes in measures of disease severity over the trial duration, underscoring the need to define quantifiable and robust readouts of disease burden. Recent studies have suggested that longitudinal measures of ankle dorsiflexion and grip strength may provide a means to track disease progression . However, in severe disease, measures of ankle dorsiflexion strength are subject to a floor effect as demonstrated in this study.…”

“…An understanding of the natural history of CMT is essential for individual prognostication and for the design of clinical trials. Although many cross‐sectional studies have characterized age of onset and severity of CMT2A, and a recent study described the progression of six pediatric patients with CMT2A over a period of 2 years, there have been no long‐term natural history studies. Here, we report a quantitative 15‐year study of a patient with severe early‐onset axonal neuropathy caused by MFN2 mutation.…”

“…Notably, our results also suggest that comparison of strength measures to normative data is imperative, as stable measures of strength during a period of expected growth and development may reflect nascent deterioration. With attention to the contributions of age, we propose that a combination of clinical measures including quantitative proximal lower extremity strength, CMT neuropathy scores incorporating distal upper and lower extremity strength, and recently validated measures such as quantitative muscle MRI may provide a sensitive readout of disease progression in CMT2A that could be used to assess efficacy of interventions in future clinical trials.…”

Functional outcome measures for infantile Charcot‐Marie‐Tooth disease: a systematic review

“…CMT comparatively affects higher order motor skills such as balance and endurance, poor hand function/hand weakness, gait abnormalities, and distal muscle weakness (Cornett et al, ) . Further, CMT progresses more slowly compared to conditions such as SMA, over years rather than months (Cornett et al, ) . Therefore, ceiling effects are likely to be observed in infants with CMT for outcome measures, such as the CHOP INTEND, which are specifically developed for very weak children with neuromuscular disease.…”