CMT stands for Charcot-Marie-Tooth disease, the most common inherited neurological disorder in the world. It affects roughly 1 in 2,500 people and causes progressive weakness in the feet, legs, hands, and forearms due to damage to the peripheral nerves. The condition is named after three physicians, Jean-Marie Charcot, Pierre Marie, and Howard Henry Tooth, who first described it in 1886.
CMT is not a single disease but a group of genetic conditions that all target the peripheral nerves connecting the brain and spinal cord to the rest of the body. Symptoms typically appear during adolescence or early adulthood, and while the disease progresses slowly over a lifetime, life expectancy is usually normal.
How CMT Affects the Nerves
Peripheral nerves have two key components: the axon (the long fiber that carries electrical signals) and the myelin sheath (a fatty coating that insulates the axon and speeds up signal transmission). CMT damages one or both of these structures, depending on the type.
In demyelinating forms, the myelin sheath breaks down. Without that insulation, nerve signals slow dramatically. In axonal forms, the nerve fiber itself deteriorates, which weakens the strength of the signal even though the speed stays relatively normal. Some intermediate types affect both. The majority of CMT cases are demyelinating, though up to one third are primarily axonal.
The Major Types of CMT
CMT is classified into several types based on which part of the nerve is affected and how the condition is inherited.
CMT1 is the most common form. It’s demyelinating, meaning the myelin sheath is the primary target. Between 70 and 80 percent of people with CMT1 have an extra copy of a gene called PMP22 on chromosome 17. That duplication causes a specific subtype called CMT1A. Another 10 to 12 percent of CMT1 cases involve a different gene, MPZ.
CMT2 is the axonal form, where the nerve fiber itself is damaged. The most frequently identified cause is mutations in the MFN2 gene, accounting for about 20 percent of CMT2 cases.
CMTX is an X-linked form, meaning the gene mutation sits on the X chromosome. About 90 percent of CMTX cases involve mutations in the GJB1 gene. Because males have only one X chromosome, they tend to be more severely affected than females, who have a second X that can partially compensate.
CMT4 follows an autosomal recessive inheritance pattern, meaning a child needs to inherit a defective copy of the gene from both parents to develop the disease. This form is rarer and often more severe.
What CMT Feels Like
The earliest signs usually show up in the feet and lower legs. Weakness in the ankles makes it difficult to lift the front of the foot, a problem called foot drop. Walking becomes clumsy, and tripping or falling happens frequently. Running may become impossible.
Over time, the muscles in the lower legs shrink. This atrophy can give the calves a distinctive shape, sometimes described as looking like an upside-down champagne bottle, where the thigh stays normal-sized but the calf narrows dramatically. High foot arches (pes cavus) and curled toes (hammertoes) are common structural changes that develop as certain muscles weaken while others tighten.
The hands and forearms are typically affected later. Fine motor tasks like buttoning a shirt or writing can become difficult. Sensory loss in the limbs, fingers, and toes is also common, though it tends to be mild compared to the muscle weakness. The progression is slow, unfolding over years and decades rather than months.
How CMT Is Diagnosed
Diagnosis usually starts with a neurological exam and a detailed family history, since CMT runs in families. The next step is a nerve conduction study, which measures how fast electrical signals travel through your peripheral nerves.
This test is critical for distinguishing between the major types. A nerve conduction velocity below 38 meters per second points toward a demyelinating form like CMT1, while a velocity above that threshold suggests an axonal form like CMT2. In axonal cases, the speed is preserved, but the strength of the electrical signal (its amplitude) is noticeably reduced.
Genetic testing then confirms the specific subtype. Testing typically begins with the most common culprit: the PMP22 duplication that causes CMT1A. In one large study, 80 percent of patients tested for PMP22 abnormalities received a positive result, making it the highest-yield genetic test in CMT diagnosis. If that comes back negative, testing moves to other genes in a stepwise fashion based on the inheritance pattern and nerve conduction findings. Nerve biopsies, once a standard part of the workup, are now reserved for cases where genetic testing doesn’t provide a clear answer.
Inheriting CMT
The inheritance pattern depends on the type. CMT1 and CMT2 are most often autosomal dominant, meaning you only need one copy of the mutated gene (from one parent) to develop the disease. If one of your parents has an autosomal dominant form, each of your children has a 50 percent chance of inheriting it.
CMT4 is autosomal recessive. Both parents must carry a copy of the mutation, and even then, each child has only a 25 percent chance of being affected. CMTX follows X-linked inheritance, so affected fathers pass the mutation to all daughters (who become carriers and may have milder symptoms) but none of their sons.
Managing Symptoms Day to Day
There is no cure for CMT yet, so treatment focuses on maintaining function and quality of life. Physical therapy and exercise are the most consistently supported interventions. Strength and endurance training improve daily function and help slow the loss of mobility.
Orthotics play a significant role for many people. Custom shoe inserts can help with high arches and foot pain, while ankle-foot orthoses (AFOs) provide more substantial support for foot drop, muscle weakness, and balance problems. Research suggests that customizing these devices to the individual, rather than using off-the-shelf products, produces better results. For children with CMT, orthotics are often introduced early to manage foot deformities and balance issues as they grow.
When foot deformities become severe enough that bracing alone isn’t sufficient, surgery is an option. Tendon transfer procedures can reroute working tendons to compensate for weakened muscles. Transferring the long toe extensor tendons to bones in the midfoot, for instance, significantly improves the ability to lift the foot and reduces claw toe deformity. These transfers require only about 25 percent of the tendons’ maximum force to bring the foot to a neutral position, making them an effective solution for foot drop regardless of whether clawed toes are present.
Treatments in Development
The research pipeline for CMT has expanded significantly. As of mid-2025, one drug is in a Phase 3 clinical trial: an aldose reductase inhibitor being tested for a specific form of CMT caused by mutations in both copies of the SORD gene. Several other compounds are in Phase 1 or Phase 2 trials targeting CMT1A and broader CMT subtypes.
Gene therapy represents the most ambitious frontier. More than a dozen programs are in preclinical development, exploring strategies like replacing defective genes, silencing overactive ones (particularly the extra PMP22 copy in CMT1A), and even using CRISPR gene editing. These approaches are still years from reaching patients, but the sheer number of programs reflects growing investment in the space. For a disease that has had no approved treatments for over a century, the current pipeline is the most active it has ever been.