Charcot-Marie-Tooth disease (CMT)

What is Charcot-Marie-Tooth disease, and how common is it?

Charcot-Marie-Tooth disease (CMT) is a group of inherited conditions that damage the peripheral nerves, the nerves outside your brain and spinal cord¹. You may also see it called hereditary motor and sensory neuropathy. It's the most common inherited neuropathy². It's progressive: symptoms slowly get worse and everyday tasks become harder¹.

Estimates of how common it is vary. About 1 in 2,500 people is one estimate³, and other counts come out differently⁴.

There are several main types. In CMT1, the most common, the insulating layer around the nerves (the myelin sheath) slowly breaks down. CMT2 is less common and usually less severe, with the damage in the nerve fibre itself (the axon). CMT3 is rare and severe, with symptoms starting in early childhood⁵. Most people first show signs by the age of 20⁶.

What causes it, and who gets it?

CMT is caused by faults in genes that damage the peripheral nerves⁵. No single gene is responsible: dozens have been linked to it⁷³, and the faulty genes can be passed on in several different ways⁵. The most common cause is an extra copy (a duplication) of a gene called PMP22, behind more than half of all cases⁷. In some types the faulty genes make the myelin sheath break down. In others the axons are damaged and don't carry signals as strongly⁵.

Nearly all cases are inherited⁷, so a family history of CMT is the main known risk. The pattern of inheritance can differ between types.

What does it feel like, how is it diagnosed, and what can make it serious?

CMT usually starts in the feet and lower legs, because the longest nerves are affected first. Weakness often becomes noticeable in the teens or early adulthood, but it can start at any age⁷. Common early signs are weak muscles that make it hard to lift the foot (foot drop), a high-stepped walk with frequent tripping or falls, and balance problems⁷. The feet can change shape, with high arches, flat feet or curled toes (hammer toes)⁷⁸, and foot deformities are common⁹. Feeling in the feet and lower legs is often dulled for touch, heat and cold, and some people have aching or burning sensations⁸. Nerve pain can range from mild to severe⁷. Foot drop and a high-stepped walk raise the risk of tripping, falls and ankle injury⁸⁹. Later, weakness and numbness can spread to the hands and arms¹⁰, and some people develop tremor or scoliosis (a curved spine)¹⁰.

CMT is diagnosed from your symptoms, family history and an examination, followed by a nerve conduction test (a test of how well your nerves carry signals)¹¹. High arches with wasting of the lower leg muscles are a prompt to look for a nerve problem, and family history is always explored¹². Genetic testing is then done step by step, starting with the PMP22 duplication¹¹.

Some features can mean a more serious form of CMT, though they're rare. Trouble swallowing, vocal cord problems that affect the voice, and difficulty breathing are linked to certain types. Some CMT2 types may involve the vocal cords or the nerve to the diaphragm, which can cause speech or breathing problems⁷. Breathing problems are a leading cause of serious illness in neuromuscular conditions¹³. A severe, early-onset form called CMT4D has also been reported with deafness, a curved spine and cognitive delay¹³. Most types have normal hearing, though CMT4C can bring mild hearing loss¹⁴.

Some medicines can make CMT worse. The cancer drug vincristine, and possibly paclitaxel, can occasionally cause a harsher form of nerve damage in people with CMT, so care is advised and nerve function should be closely monitored¹⁵¹⁶. People with CMT shouldn't be denied effective treatments, such as cancer treatment, that may prolong life or improve health¹⁶. Whether nitrous oxide (a gas sometimes used for pain relief) can worsen CMT isn't settled¹⁷.

CMT can also sit alongside other nerve conditions. A chronic inflammatory nerve condition (CIDP) has been reported with one common type, and an unusual pattern on a nerve conduction test can point to another or an extra neuropathy¹².

What helps first?

There's no cure for CMT, and no medicine that changes its course¹¹². Care focuses on managing symptoms with a team of health professionals, ideally starting early, with personalised exercise advice, adapted orthoses (braces and supports) and assessment for conservative surgery¹¹. The aim is to keep your mobility, flexibility and muscle strength as much as possible, using physical and occupational therapy, braces and other devices².

Exercise has the most support. Strengthening the muscles that lift the ankle can limit how much weakness progresses in children with CMT1A¹⁸. Strength or endurance training may improve function and daily activities in people with CMT, though the role of orthoses isn't completely clear yet, and an agreed exercise programme can't yet be set¹⁹. For other outcomes the evidence is weak¹⁸.

People with CMT usually can't train at the intensities recommended for healthy people, and high-intensity training is linked with reduced performance and more injuries in neuromuscular disease³. Overexertion, or not following exercise instructions, can make symptoms worse¹⁶. It helps to keep exercise planned and personalised, and to follow the instructions you're given.

What helps if that isn't enough?

Nothing beyond first-line care has been shown to change the condition itself. Management stays focused on symptoms, with orthotic adaptation and assessment for conservative surgery such as tendon transfer (where a tendon is moved)¹¹. Braces, other orthopaedic devices and orthopaedic surgery are among the treatments that can help with symptoms². Some people rely on foot or leg braces to keep walking, and medicines to relieve nerve pain may be prescribed when it is severe⁷.

Vitamin C (ascorbic acid) gives little worthwhile improvement in fatigue for people with CMT1A, though it seemed safe and well tolerated²⁰.

What is the outlook with CMT?

CMT is slowly progressive, and for most people it doesn't affect life expectancy⁸. Lower-leg muscles usually weaken further, and hand weakness can make writing, doing up buttons and turning doorknobs harder⁸. Symptoms vary from person to person, even within a family. It isn't possible to predict when they will start, how fast they'll progress or how severe they'll be¹⁰.

Foot drop is the most prominent walking pattern in CMT, and people with CMT fall often⁹. Taking steps to lower the chance of falls and ankle injury makes sense.

Because CMT is inherited and progressive rather than something that clears and returns, there's no coming back to guard against. Rehabilitation aims to keep you moving and manage symptoms, and no evidence-based rehabilitation protocol can yet be set¹⁹.