Charcot–Marie–Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body.

[5][6] It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940),[7] and the Briton Howard Henry Tooth (1856–1925).

[11] Loss of touch sensation in the feet, ankles, and legs as well as in the hands, wrists, and arms occurs with various types of the disease.

Early- and late-onset forms occur with 'on and off' painful spasmodic muscular contractions that can be disabling when the disease activates.

Overuse of an affected hand or limb can activate symptoms including numbness, spasm, and painful cramping.

Gastrointestinal problems can be part of CMT,[12][13] as can difficulty chewing, swallowing, and speaking (due to atrophy of vocal cords).

[15] Pain due to postural changes, skeletal deformations, muscle fatigue, and cramping is fairly common in people with CMT.

Mutated MFN2 causes the mitochondria to form large clusters, or clots, which are unable to travel down the axon towards the synapses.

However, it is thought that mutant glycyl-tRNA synthetase (GlyRS) interferes with transmembrane receptors, causing motor disease,[36][37] and that mutations in the gene could disrupt the ability of GlyRS to interact with its cognate RNA, disrupting protein production.

The GARS1 mutations present in CMT2D cause a deficient amount of glycyl-tRNA in cells, preventing the elongation phase of protein synthesis.

GARS1 mutations also stall initiation of translation due to a stress response that is induced by glycine addition failure.

Mutant GlysRS interferes with neuronal transmembrane receptors, including neuropilin 1 (Nrp1) and vascular endothelial growth factor (VEGF), causing neuropathy.

In CMTX, mutated connexons create nonfunctional gap junctions that interrupt molecular exchange and signal transport.

To see signs of muscle weakness, the neurologist may ask patients to walk on their heels or to move part of their leg against an opposing force.

To identify sensory loss, the neurologist tests for deep-tendon reflexes, such as the knee jerk, which are reduced or absent in CMT.

[26] The constant cycle of demyelination and remyelination, which occurs in CMT, can lead to the formation of layers of myelin around some nerves, termed an "onion bulb".

[47] Muscles show fiber type grouping, a similarly nonspecific finding that indicates a cycle of denervation/reinnervation.

[10] Appropriate footwear is also very important for people with CMT, but they often have difficulty finding well-fitting shoes because of their high-arched feet and hammertoes.

These procedures include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability.

[15] CMT patients must take extra care to avoid falling as fractures take longer to heal in someone with an underlying disease process.

[51] In most cases, ankle-foot orthoses that have functional elements for the foot lifting and adjustable control of the lowering of the forefoot make sense.

If the calf muscles are weak, an orthosis should therefore be equipped with functional elements to activate the forefoot lever.

An orthotic joint with an adjustable dynamic dorsiflexion stop with a strong spring in combination with a lower leg shell in front of the shin is recommended for this.

Studies confirm the positive effect of orthoses with adjustable functional elements in patients with paralysis of these muscle groups.

[52][53][54][55] It is of great advantage if the resistances of the two functional elements can be set separately from one another in the two directions of movement, dorsiflexion and plantar flexion.

"[58] The disease is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940),[7] and the Briton Howard Henry Tooth (1856–1925).