Charcot-Marie-Tooth disease (CMT) is an inherited condition that damages the peripheral nerves, the long cables that carry signals between the brain, spinal cord, and the rest of the body. It primarily causes progressive weakness and loss of sensation in the feet, legs, and hands. CMT affects roughly 1 in 6,400 people, making it one of the most common inherited neurological disorders, though it is still classified as rare.
Despite its name, CMT has nothing to do with teeth. It’s named after the three physicians who first described it in 1886. The condition is lifelong, but life expectancy is typically normal, and many people manage it effectively with the right support.
How CMT Damages the Nerves
Your peripheral nerves work like electrical cables. Each nerve cell has a long, thin fiber called an axon that carries signals, and that axon is wrapped in a fatty insulating layer called myelin. Myelin speeds up signal transmission the same way rubber insulation keeps an electrical wire working efficiently.
CMT is caused by genetic defects that damage either the axon, the myelin, or both. When the myelin breaks down, nerve signals slow dramatically. When the axon itself is damaged, the signals weaken or fail entirely. Either way, the result is the same: the brain’s instructions don’t reach the muscles properly, and sensory information from the limbs doesn’t make it back to the brain. Over time, muscles that no longer receive strong nerve signals begin to shrink and weaken, a process called atrophy.
The Main Types of CMT
CMT is not a single disease but a group of related conditions, each tied to different genes and inheritance patterns. The most clinically important distinction is which part of the nerve is affected.
- CMT1 targets the myelin sheath. It’s the most common form, and most cases follow an autosomal dominant inheritance pattern, meaning you only need one copy of the faulty gene (from one parent) to develop the disease. A duplication of the PMP22 gene causes the most frequent subtype, CMT1A, which accounts for roughly 20% to 65% of all CMT cases depending on the population studied.
- CMT2 targets the axon itself rather than the myelin. It’s less common than CMT1 and is also usually autosomal dominant, though a few subtypes require two copies of the faulty gene (autosomal recessive).
- CMT4 can affect either the axon or the myelin, but it is distinguished by its recessive inheritance pattern. Both parents must carry the gene for a child to be affected.
- CMTX is caused by mutations on the X chromosome. 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.
Doctors can distinguish demyelinating from axonal forms using nerve conduction studies. A motor nerve conduction velocity below 38 meters per second in the upper limbs points toward a myelin problem (CMT1), while velocities above that threshold suggest an axonal form (CMT2).
What CMT Feels Like and How It Progresses
CMT usually starts in the feet and lower legs, then gradually moves to the hands and forearms. Symptoms most often appear in adolescence or early adulthood, though some people notice them in childhood and others not until middle age. The pace varies widely, even among family members who carry the same mutation.
Early signs typically include difficulty walking, frequent tripping, and a sense that your ankles feel unstable. As the muscles in the lower legs weaken and shrink, the legs can develop a characteristic narrowing below the knee, sometimes compared to an inverted champagne bottle shape. The feet often develop a high arch (pes cavus) and curled toes (hammertoes) because the muscles pulling the foot into different positions lose their balance of strength. Reflexes at the ankle and knee tend to diminish or disappear.
Hand involvement usually comes later. You might notice difficulty with buttons, zippers, or writing. Grip strength decreases, and fine motor tasks become harder. Sensory loss can reduce your ability to feel temperature, touch, or pain in the affected areas, which raises the risk of unnoticed injuries, particularly to the feet.
Pain is more common than many people expect from a condition traditionally described as a motor and sensory neuropathy. Cramping, aching in the legs, and neuropathic pain (burning or tingling sensations) are frequently reported.
Scoliosis and Other Complications
About one-third of people with CMT develop scoliosis, a sideways curvature of the spine. It’s typically diagnosed around age 13, with an average curve of about 28 degrees at the time it’s found. Nearly half of those with CMT-related scoliosis also develop increased forward rounding of the upper back (thoracic kyphosis). These spinal changes happen because the muscles supporting the trunk are affected by the same nerve damage that weakens the limbs.
Hip dysplasia can occur in more severe cases, and some people with advanced CMT experience mild respiratory muscle involvement, though this is uncommon in the typical forms of the disease. Because sensation in the feet is reduced, skin breakdown and foot ulcers are a real concern, especially if shoes don’t fit well over a high-arched foot.
How CMT Is Diagnosed
Diagnosis usually begins when a neurologist notices the combination of distal weakness, foot deformities, reduced reflexes, and a family history of similar symptoms. Nerve conduction studies measure how fast and how strongly electrical signals travel through the peripheral nerves, and they remain the key initial test. These studies help determine whether the problem is primarily in the myelin or the axon.
Genetic testing confirms the specific type. Because so many genes can cause CMT (over 100 have been identified), testing often starts with the most common culprit, the PMP22 duplication, and expands from there if needed. Genetic confirmation matters not just for the person affected but for family planning, since different types carry different inheritance risks.
Managing CMT Day to Day
There is no cure for CMT yet, so treatment focuses on maintaining function, preventing complications, and adapting to changes as they happen.
Ankle-foot orthoses (AFOs) are one of the most widely used tools. These braces fit inside your shoes and compensate for the weakness in the muscles that lift the front of the foot, helping prevent tripping and improving balance. Traditional plastic AFOs work well but can be bulky. Custom carbon-fiber braces are gaining popularity because they’re lighter and thinner, though they cost more and require specialized fitting. 3D-printed AFOs are an emerging option that offers good dimensional accuracy and performance comparable to hand-crafted braces.
Physical therapy plays a central role. The goals are to maintain range of motion, preserve the strength you have, improve balance, and reduce fatigue. Stretching is particularly important for preventing the tendons in the ankles and feet from tightening permanently. Low-impact exercise like swimming or cycling helps maintain cardiovascular fitness without overstressing weakened muscles.
Occupational therapy addresses hand weakness with adaptive tools for daily tasks. When foot and ankle deformities become severe enough to cause pain or make bracing ineffective, surgery to realign bones or transfer tendons can improve foot positioning and function.
Treatment Research for CMT
The most promising drug candidate for CMT1A is PXT3003, an oral medication designed to reduce the overproduction of the PMP22 protein that damages myelin in the most common form of the disease. A Phase II trial in 80 adults showed it was safe and improved neuropathy scores at the highest dose. A larger Phase III trial involving 350 adults completed its 15-month treatment phase in October 2023, and results from that study will determine whether it becomes the first approved drug specifically targeting CMT.
Another approach, VM202, uses a non-viral gene therapy to promote nerve regeneration through a growth factor that stimulates repair in the cells that produce myelin. It received orphan drug and fast-track designations from the FDA, though early results in other conditions suggest its benefits may be temporary. Vitamin C (ascorbic acid) was once a popular hope based on animal studies, but a comprehensive analysis of 34 randomized controlled trials found no therapeutic benefit in humans with CMT1A.