Charcot Marie Tooth 1A (CMT1A) is a genetic neuropathy characterized by demyelination of peripheral nerves that weakens muscles and disperses afferent sensory feedback. Since fatigue is a common symptom claimed by CMT1A patients, this study aimed at assessing central and peripheral mechanisms of fatigue in 6 patients and 6 matched healthy volunteers during a fatiguing voluntary task. We simultaneously recorded surface electromyography (sEMG) of vastus lateralis and electroencephalography (EEG) during 4 blocks of isometric knee extensions at 40% of maximal voluntary contraction (MVC) for a total of 240 2-s contractions. At the beginning of the session and after each block, we measured MVC, single twitch (ST) and rating of perceived effort (RPE). The movement related cortical potentials (MRCPs) were extracted from EEG records, segmented in 2-s epochs (1500 ms before and 500 ms after each contraction) and averaged in two main blocks, referred to as early (blocks 1-2) and late (blocks 3-4) stages of fatigue. Torque, sEMG patterns of fatigue described by MVC and ST slopes and RPE did not differ between groups, while MRCP components showed lower amplitude over sensorimotor areas and higher prefrontal activity in CMT1A patients than controls in the late stage (-6.3±2.7 vs -12.8±6.4 mV and 4.5±3.8 vs 0.1±2.6 mV, respectively; p<0.05). CMT1A patients, therefore, show dysregulation in both limb representation and in the awareness of movement complexity in relation to a fatiguing task.