Charcot–Marie–Tooth disease
Other names Charcot–Marie–Tooth neuropathy, peroneal muscular atrophy, Dejerine-Sottas syndrome

The foot of a person with Charcot–Marie–Tooth disease: The lack of muscle, a high arch, and claw toes are signs of this genetic disease.
Pronunciation
[ʃaʁko maʁi tuːθ]
Specialty Neurology, podiatry, orthopedics, physical medicine and rehabilitation
Symptoms Foot drop, hammertoe, peripheral muscle wasting of lower legs and lower arm/hands
Usual onset Childhood – early adulthood
Duration Lifelong
Causes Family history (genetics)
Risk factors Family history (genetics), high-arched feet, flat-arched feet
Diagnostic method Genetic testing, nerve conduction study or electromyogram (EMG)
Differential diagnosis Muscular dystrophy
Treatment Management to maintain function
Prognosis Progressive
Frequency Prevalence: 1 in 2,500[1][2]
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. This disease is the most commonly inherited neurological disorder, affecting about one in 2,500 people.[3][4] It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940),[5] and the Briton Howard Henry Tooth (1856–1925).[6][7]

There is no known cure. Care focuses on maintaining function. CMT was previously classified as a subtype of muscular dystrophy.[3]

Signs and symptoms
Symptoms of CMT usually begin in early childhood or early adulthood but can begin later. Some people do not experience symptoms until their early 30s or 40s. Usually, the initial symptom is foot drop or high arches early in the course of the disease. This can be accompanied by hammertoe, where the toes are always curled. Wasting atrophy of muscle tissue of the lower parts of the legs may give rise to a "stork leg" or "inverted champagne bottle" appearance. Weakness in the hands and forearms occurs in many people as the disease progresses.[8]

High-arched feet (pes cavus) or flat-arched feet (pes planus) are classically associated with the disorder.[9] 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. Sensory and proprioceptive nerves in the hands and feet are often damaged, while unmyelinated pain nerves are left intact. Overuse of an affected hand or limb can activate symptoms including numbness, spasm, and painful cramping.[8]

Symptoms and progression of the disease can vary. Involuntary grinding of teeth and squinting are prevalent and often go unnoticed by the person affected. Breathing can be affected in some, as can hearing, vision, and neck and shoulder muscles. Scoliosis is common, causing hunching and loss of height. Hip sockets can be malformed. Gastrointestinal problems can be part of CMT,[10][11] as can difficulty chewing, swallowing, and speaking (due to atrophy of vocal cords).[12] A tremor can develop as muscles waste. Pregnancy has been known to exacerbate CMT, as well as severe emotional stress. Patients with CMT must avoid periods of prolonged immobility such as when recovering from a secondary injury, as prolonged periods of limited mobility can drastically accelerate symptoms of CMT.[13]

Pain due to postural changes, skeletal deformations, muscle fatigue, and cramping is fairly common in people with CMT. It can be mitigated or treated by physical therapies, surgeries, and corrective or assistive devices. Analgesic medications may also be needed if other therapies do not provide relief from pain.[14] Neuropathic pain is often a symptom of CMT, though, like other symptoms of CMT, its presence and severity vary from case to case. For some people, pain can be significant to severe and interfere with daily life activities. However, pain is not experienced by all people with CMT. When neuropathic pain is present as a symptom of CMT, it is comparable to that seen in other peripheral neuropathies, as well as postherpetic neuralgia and complex regional pain syndrome, among other diseases.[15]

Atypical presentations of CMT can also lead to leg muscles, specifically the calves, enlarging.[16] This hypertrophic type of CMT is not caused by the muscles enlarging directly, but by pseudohypertrophy of the legs as fatty tissue enters the leg muscles.[17][18][19]

Causes

Chromosome 17
Charcot–Marie–Tooth disease is caused by genetic mutations that cause defects in neuronal proteins. Nerve signals are conducted by an axon with a myelin sheath wrapped around it. Most mutations in CMT affect the myelin sheath, but some affect the axon.[20]