Charcot-Marie-Tooth disease type 1A is the most common form of inherited neuropathy that causes peripheral nerve damage in all four limbs. In addition to the well-known distal motor and sensory symptoms, fatigue is one of the most common symptoms reported by patients. However, there is very little scientific data on this topic. Fatigue is associated with changes in mobility and quality of life. This study investigates the magnitude and impact of fatigue on patients' sensory-motor function and mobility (standing and walking). Fatigue is a complex phenomenon. It is therefore essential to assess all the factors that may be at the origin of this symptom (perceived fatigue and fatigability) using innovative and robust assessment methods.

These methods are based on quantitative non-invasive neurophysiologic measures (electromyography and transcranial magnetic stimulation). The patients can quantify and identify more precisely the origin of fatigability (peripheral and central). This objective approach needs to be combined with the usual methods of measuring fatigue using valid and reliable patient-reported outcome measures. A quantitative measure of movement during walking must also be included to assess changes in fatigue during functional movement.

To quantify the proportion of fatigue associated with CMT1A, the investigators chose to compare data from patients with those of healthy subjects matched for age, height and lean body mass.

A better understanding of the role of fatigue in limiting walking and balance capacities in these patients will allow the investigators to refine the inpatient and outpatient management.

Inclusion criteria for patients:

• Age ≥ 18 years and < 75 years
• Patient with mCMT1A confirmed by genetic analysis (based on data recorded in the patient file)
• Patient able to walk a minimum of 200 metres without a break, with or without equipment and/or technical aids (collected during questioning)
• Patient able to get on and off a cycloergometer safely without assistance or with minimal assistance
• Patient who has had a cardiological check-up before the stress test (ECG and cardiac ultrasound less than 6 months old) or for whom a check-up is scheduled before the inclusion
• Patient affiliated to a health insurance scheme or beneficiary of such a scheme

Inclusion criteria for Healthy volunteers:

• Age ≥ 18 years and < 75 years
• Subject affiliated to or benefiting from a health insurance scheme
• Subject who has had a cardiological work-up prior to stress testing (ECG and cardiac ultrasound less than 6 months old) or for whom a work-up is scheduled prior to the procedure.

Exclusion criteria for patients:

• Patients with all other forms of neuropathy (HNPP, other types of CMT, secondary neuropathies)

• Patients with any of the following

  • An associated neurological disease other than mCMT1A
  • Severe joint disease of the lower limbs
  • Contraindication to isokinetic testing
  • Contraindication to an exercise stress test and exercise reconditioning program
  • A contraindication to Transcranial Magnetic Stimulation (TMS) : epilepsy, intracranial metallic foreign body, hearing aid or cochlear implant, unstable skull bone fracture, deafness, etc.

• Patients who have undergone lower limb surgery in the 12 months prior to inclusion or for whom lower limb surgery is scheduled during the participation period.

• Pregnant or breastfeeding or planning to become pregnant within the next 4 months

• BMI > 35 kg/m2

• Patient unable to give informed consent, unable to understand informed information

• Subject under court protection

• Subject under guardianship or curatorship

• Subject in a period of exclusion (determined by a previous or current study)

Exclusion criteria for healthy volunteers:

• History of neurological disease

• Severe joint damage in the lower limbs

• Any of the following

  • Contraindication to isokinetic testing
  • A contraindication to an exercise stress test and an exercise reconditioning program
  • A contraindication to TMS: epilepsy, intracranial metallic foreign body, hearing aid or cochlear implant, unstable skull bone fracture, deafness, etc.

• Any person who has undergone surgery on the lower limbs in the 12 months prior to inclusion, or for whom surgery on the lower limbs is scheduled during the participation period.

• Pregnant or breastfeeding, or planning to become pregnant within the next 4 months

• Person unable to give informed consent, unable to understand informed information

• BMI > 35 kg/m2

• Person under legal protection

• Person under guardianship or curatorship

• Person in a period of exclusion (determined by a previous or current study)