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. It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925).There is no known cure. Care focuses on maintaining function. CMT was previously classified as a subtype of muscular dystrophy. 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 early in the course of the disease. This can also cause hammertoe, where the toes are always curled. Wasting 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.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. High-arched feet (pes cavus) or flat-arched feet (pes planus) are classically associated with the disorder.
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. Causes
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. Classification
CMT is a heterogeneous disease and the mutations linked to it may occur in a number of different genes. Based on the affected gene, CMT is categorized into several types and subtypes. Chromosome 17
The most common cause of CMT (70–80% of the cases) is the duplication of a large region on the short arm of chromosome 17 that includes the gene PMP22.Some mutations affect the gene MFN2, on chromosome 1, which codes for a mitochondrial protein. Mutated MFN2 causes the mitochondria to form large clusters, or clots, which are unable to travel down the axon towards the synapses. This prevents the synapses from functioning. X-linked CMT and Schwann cells
CMT can also be produced by X-linked mutations and is named X-linked CMT (CMTX). In CMTX, mutated connexons create nonfunctional gap junctions that interrupt molecular exchange and signal transport.The mutation can appear in GJB1 coding for connexin 32, a gap junction protein expressed in Schwann cells.