Novel outcome measures for Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) is the most frequent neuromuscular hereditary disorder. CMT is a clinically heterogeneous neuropathy, characterised by the cardinal clinical features of distal wasting, weakness and sensory loss with reduced tendon reflexes and variable foot deformity. CMT1A is the most frequent subtype, and is due to the excessive expression of the peripheral myelin protein PMP22. X-linked CMT is the second most common form and is associated with mutations in the gap-junction protein beta 1 gene on chromosome Xq13.1 encoding for connexin 32 protein.CMT1B is associated with mutations in the myelin protein zero. At least 200 patients will be recruited in this study. The aim of this project is to evaluate the reliability and validity of two clinical tools, 6-minute walk test (6MWT) and StepWatchTM Activity Monitor (SAM), in CMT disease. These measures, that have never been used in CMT patients, most likely well reflect patient's activities of daily living and appear to be promising to detect clinically meaningful changes in future therapeutic trials. We also wish to examine the relationship among 6MWT and SAM and other four measures already validated in CMT1A population (10 meter walking test, CMTNeuropathy score, the MVIC of upper and lower limb muscle groups by hand-held myometry and SF-36). The study will allow to compare the sensitivity of all these tools, to select the most appropriate outcome measures in this disorder and to collect longitudinal data over a 1-year period in a relatively large cohort of ambulant CMT patients, including three different genetic subtypes.