Charcot-Marie-Tooth disease type 1 (CMT1) is an inherited nerve disorder that damages the protective coating around peripheral nerves, gradually weakening the muscles in your feet, legs, and hands. It affects roughly 1 in 5,000 to 1 in 7,000 people, making it one of the most common inherited neurological conditions. CMT1 does not typically shorten life expectancy, but it is progressive, and understanding how it works helps explain both what to expect and how to manage it.
How CMT1 Damages Nerves
Peripheral nerves carry signals between your brain and your limbs. Each nerve fiber is wrapped in a fatty insulating layer called myelin, which helps electrical signals travel quickly. In CMT1, the genes responsible for building and maintaining that myelin layer are faulty, so the insulation gradually breaks down. Without healthy myelin, nerve signals slow dramatically. In a healthy person, motor nerve signals in the upper limbs travel well above 50 meters per second. In CMT1, those speeds typically drop to between 15 and 30 meters per second. A reading below 38 m/s on a nerve conduction test is the accepted cutoff that points toward a demyelinating form like CMT1, rather than a type that damages the nerve fiber itself.
Over time, the repeated cycles of myelin loss and incomplete repair cause the nerve fibers underneath to degenerate as well. This secondary damage to the nerve fibers themselves is what ultimately drives most of the muscle weakness and sensory loss people experience.
Genetic Subtypes of CMT1
CMT1 is not a single genetic condition. It has several subtypes, each linked to a different gene.
CMT1A is by far the most common, accounting for about 70% of all CMT1 cases and more than half of all CMT cases worldwide. It is caused by a duplication of the PMP22 gene on chromosome 17. That extra copy means cells produce too much of a protein that is a key structural component of myelin. The excess protein disrupts the normal composition of the myelin sheath, destabilizes it, and eventually kills the cells responsible for producing it. Think of it like a recipe that calls for a precise ratio of ingredients: doubling one ingredient throws off the whole product.
CMT1B accounts for roughly 10 to 12% of CMT1 cases. It results from mutations in the MPZ gene, which codes for a different myelin protein. Symptoms are similar to CMT1A, though the age of onset and severity can vary more widely.
Other rarer subtypes exist (CMT1C, CMT1D, CMT1E), each tied to different genes involved in myelin production or maintenance. Together, they make up a small fraction of cases.
What CMT1 Feels Like
CMT1 is a length-dependent disorder, meaning the longest nerves in your body are affected first. Because the nerves running to your feet and lower legs are the longest, that is where symptoms start. Most people notice problems in childhood or adolescence, though the exact timing varies. Early signs often include tripping, difficulty running, or an awkward gait that parents or teachers notice before the child does.
The hallmark physical changes are high arches (pes cavus) and curled toes (hammer toes). These foot deformities develop because the muscles controlling foot shape weaken unevenly, with some tightening while others waste away. The calves may look noticeably thin compared to the thighs. Walking becomes unstable due to a combination of muscle weakness, loss of position sense in the feet, and the skeletal changes in the feet themselves. Foot deformities are one of the biggest sources of disability in CMT.
As the disease progresses over years or decades, weakness spreads upward into the hands and forearms. People often describe difficulty with fine motor tasks: buttoning a shirt, pulling a zipper, or writing. Physical examination may reveal subtle wasting of the small muscles at the base of the thumb and pinky finger. Sensory loss in the fingers and toes is common, and deep tendon reflexes (the knee-jerk response, for example) are reduced or absent.
Pain is a more variable symptom. Some people experience significant muscle cramps or neuropathic discomfort, while others have relatively little pain. The progression is slow, typically unfolding over decades rather than months, and severity ranges widely even among family members carrying the same genetic mutation.
How CMT1 Is Diagnosed
Diagnosis usually begins with a physical exam and a detailed family history. Because CMT1 is inherited in an autosomal dominant pattern, a parent with the condition has a 50% chance of passing it to each child. A clear family pattern of foot deformities and weakness often raises suspicion before any tests are ordered.
Nerve conduction studies are the next step. These tests measure how fast electrical signals travel along your nerves. A reading below 38 m/s in the upper limb motor nerves is the key marker that distinguishes CMT1 from axonal types of CMT, where nerve conduction speeds remain closer to normal. Electromyography (EMG), which measures electrical activity in muscles, can show signs of nerve damage and help rule out other conditions.
Genetic testing confirms the diagnosis and identifies the specific subtype. For suspected CMT1, labs typically test for PMP22 gene duplication first, since it accounts for the vast majority of cases. If that test comes back normal, sequencing of other hereditary neuropathy genes follows. Knowing the exact genetic cause matters for family planning, prognosis, and eligibility for clinical trials.
Managing Symptoms Day to Day
There is currently no treatment that reverses or halts the underlying nerve damage in CMT1. Management focuses on preserving function, preventing complications, and adapting to the changes the disease brings.
Ankle-foot orthoses (AFOs) are one of the most commonly prescribed tools. These are lightweight braces that fit around the foot and lower leg, holding the ankle in a neutral position. They compensate for foot drop, reduce tripping, and help slow the progression of foot contractures by keeping muscles and tendons in a better position. Some people manage well with high-top shoes or boots alone, especially early in the disease.
Physical therapy plays a central role. A regular program of low-impact exercise and stretching helps maintain range of motion, prevent muscles from tightening into fixed positions, and preserve strength in muscles that are still functional. The goal is not to reverse weakness but to maximize what your body can still do and prevent secondary problems like joint stiffness.
Occupational therapy addresses the hand and fine motor challenges. Therapists can recommend assistive devices and adaptive techniques for tasks like writing, cooking, or getting dressed. Splints for the fingers or hands can help prevent toe and finger contractures.
When conservative measures are not enough, surgery is an option. Procedures can release tight tendons, correct bone deformities in the feet, or realign joints. These surgeries do not treat the underlying nerve disease, but they can meaningfully improve mobility and reduce pain from severe foot deformities.
Long-Term Outlook
CMT1 does not reduce life expectancy. Most people live full lifespans, though the degree of disability varies considerably. Some individuals walk independently throughout their lives with only minor accommodations. Others eventually need a wheelchair for longer distances, particularly in later decades. The rate of progression is generally slow enough that people have time to adapt, both physically and practically.
A phase 3 clinical trial (called PREMIER) has been testing a combination drug called PXT3003 specifically in CMT1A, with 350 participants enrolled. Results from that trial may clarify whether a pharmacological treatment can slow disease progression. For now, though, the foundation of care remains physical management: bracing, therapy, surgery when needed, and staying as active as the disease allows.