Living with Charcot–Marie–Tooth disease

Charcot-Marie-Tooth disease: understanding, living with, and anticipating the future

What is Charcot-Marie-Tooth disease (CMT)?

A rare and progressive hereditary neuropathy

When we hear about “Charcot’s disease,” we often think of Stephen Hawking. The famous astrophysicist lived with amyotrophic lateral sclerosis (ALS), a serious disease that affects motor neurons and causes progressive paralysis. But what many ignore is that there is another pathology with a very similar name: Charcot-Marie-Tooth disease. And yet, these two diseases have nothing to do with each other.

The confusion mainly comes from the name. ALS, sometimes simply called “Charcot’s disease,” attacks the central nervous system, progresses rapidly, and affects overall motor skills. Charcot-Marie-Tooth (CMT), on the other hand, is a rare genetic neuropathy that affects the peripheral nerves. It evolves much more slowly and mainly manifests through motor and sensory disorders in the feet, legs, and hands. So no, Stephen Hawking did not have Charcot-Marie-Tooth disease, despite his impressive longevity, even if the names can be confusing. And that is precisely why it is important to better understand this neuropathy, still too little known to the general public.

Photographie du célèbre astrophysicien Stephen Hawkings

Stephen Hawking at his office in the Department of Applied Mathematics and Theoretical Physics at the University of Cambridge in 2005. Photograph by Murdo Macleod, The Guardian.

Charcot-Marie-Tooth diseases (often abbreviated CMT) are hereditary peripheral neuropathies. They owe their name to the three doctors who described them in 1886: Jean-Martin Charcot, Pierre Marie, and Howard Henry Tooth. In short, this means they are transmitted by genes and affect the nerves responsible for transmitting information between the brain, the spinal cord, and the muscles. It affects between 30,000 and 50,000 people in France, or about 1 in 2,500.

The different types of CMT

To date, 80 genes have been identified as responsible for Charcot-Marie-Tooth disease, each leading to a specific form of the disease. To classify this large number of variants, doctors and researchers have developed a classification based on 3 criteria:

  • The nature of the peripheral nerve damage
  • The mode of genetic transmission
  • The genetic anomaly involved

According to these criteria, there are 6 main categories of Charcot-Marie-Tooth: CMT1, CMT2, CMT4, CMTX, DI-CMT, and RI-CMT.

These genetic anomalies affect the peripheral nerves such as those in the legs and arms, making it difficult to move without a wheelchair or upper-limb technical assistance

. This mainly results in lack of muscle strength, sensory disturbances in the extremities, and balance problems.

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🐙 The octopus vocab: simplifying the terms

  • The myelin sheath is the insulating layer around the nerve, similar to plastic around an electrical wire
  • The axon is the extension of the nerve, which carries the signal to the extremities of the human body.
  • When a gene is said to be X-linked, it means it is located on the X chromosome. Each parent passes on one sex chromosome to their child:
    • The father (XY) passes either an X (if it’s a girl) or a Y (if it’s a boy)
    • The mother (XX) always passes one of her two X chromosomes

This has different consequences depending on whether the child is a girl (XX) or a boy (XY), because boys only have one X.

CMT vs. Charcot’s disease: two different diseases

As said before, Charcot-Marie-Tooth disease and Charcot’s disease (amyotrophic lateral sclerosis) are two different pathologies.

Name

Charcot-Marie-Toothe disease (CMT)

Amyotrophic lateral sclerosis – Charcot’s disease

Type
Hereditary genetic disease

Neurodegenerative motor neuron

disease (non-hereditary)

Severity

Chronic, slow, and not fatal

Rapid, severe, and fatal

Cause

Genetic mutations affecting peripheral nerves

(those controlling muscles and sensations with the brain)

Central and peripheral motor neurons such as the cortex or spinal cord die gradually

Age of onset

Childhood or adolescence (sometimes later)
Adulthood

Symptoms

  • Progressive muscle weakness
  • Foot deformities
  • Loss of sensation in extremities
  • Balance disorders
  • Progressive muscle paralysis
  • Small involuntary muscle movements (fasciculations)

Treatment

No curative treatment, but: rehabilitation and orthoses possible, adaptable life to remain autonomous
No curative treatment, but: promising clinical trials, possible slowing of the disease
  • Type: hereditary genetic disease
  • Severity: chronic, slow-progressing, and non-fatal
  • Cause: genetic mutations affecting the peripheral nerves (the ones that control muscles and communicate sensations with the brain)
  • Age of onset: childhood or adolescence (sometimes later)
  • Symptoms: progressive muscle weakness, foot deformities, loss of sensation in the extremities, balance problems
  • Treatment: no curative treatment, but: physical therapy and orthoses are possible, adaptable lifestyle to maintain autonomy
  • Type: neurodegenerative disease of the motor neurons (non-hereditary)
  • Severity: rapid, severe, and fatal
  • Cause: central and peripheral motor neurons, such as the cortex or spinal cord, gradually die
  • Age of onset: adulthood
  • Symptoms: progressive muscle paralysis, small involuntary muscle movements (fasciculations)
  • Treatment: no curative treatment, but: promising clinical trials, disease progression can sometimes be slowed


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🐙 The octopus vocab: motor neurons, what’s that?

A motor neuron is a particular nerve cell that makes muscles move. It acts as a messenger between the brain and the muscles to trigger movement or contraction. If it is damaged, as in Charcot’s disease (ALS), the muscle no longer receives the command to contract, thus weakens and becomes paralyzed.

What are the symptoms and how do they progress?

Early signs and progressive disorders

Charcot-Marie-Tooth disease is the most common hereditary neuropathy (nerve disorder). The early symptoms, which usually appear during childhood or adolescence, are fairly well known:

  • Inability to flex the ankle to lift the front part of the foot.
  • Atrophy of the calf muscles, followed by the hand muscles.
  • Sensory disturbances in the hands and feet.
  • Balance problems.
  • Foot deformities (high arches) and hammer toes
    ➡️ Only in certain types of CMT.

CMT is a broad spectrum of variants. In some types, women may be asymptomatic, while in others, foot deformities are the only early sign of the disease. Each type has its own specific characteristics.

Functional impact on daily life

Charcot-Marie-Tooth disease leads daily to physical limitations that can complicate simple gestures like walking or handling small objects. People affected are often fatigued due to the extra effort they make to compensate for the muscle weakness that gradually sets in. To maintain mobility, limit potential falls, and conserve strength, they often use motorized or non-motorized technical aids such as splints, canes, wheelchairs, etc. Even though the disease is slow, it remains disabling and has a real impact on comfort and quality of life.

Diagnosis and screening: putting a name to the disease

Diagnostic process: from symptom to genetics

When a case of Charcot-Marie-Tooth is suspected, the first step is to consult a general practitioner who will order a series of tests. It begins with a neurological clinical examination, where the health professional assesses muscle strength, reflexes, and sensitivity. Then follow complementary tests such as electromyogram (EMG), which measures the electrical activity of nerves and muscles to detect neuropathic involvement.

 

Genetic tests play an essential role in confirming the type of CMT involved and guiding management. However, it is still common for patients to go through a long diagnostic wandering before finally putting a name to their symptoms. This is why it is recommended to go to a rare disease expert center, where teams are trained in this type of pathology and have the necessary tools to provide a reliable and rapid diagnosis.

Genetic transmission and family counseling

Charcot-Marie-Tooth disease (CMT) is a hereditary neuropathy, meaning it is passed down through genes. There are several modes of genetic transmission:

  • Autosomal dominant: only one parent carrying the gene can pass the disease to the child, with a 50% chance.
  • Autosomal recessive: both parents must carry the gene for a child to inherit it.
  • X-linked: the gene responsible is located on the X chromosome, which usually affects boys more severely.

In some cases, the mutation is “de novo,” meaning it appears spontaneously without being inherited from the parents. This can make diagnosis more challenging and may surprise families.

To help relatives understand the risks of transmission and plan for parenthood, genetic counseling is essential. It allows for the analysis of family history using a medical family tree and helps assess the probabilities for each family member.

Management: living with Charcot-Marie-Tooth disease

Essential non-drug approaches

Although there is no curative treatment yet for Charcot-Marie-Tooth disease, many non-drug approaches help preserve mobility and improve quality of life. Functional rehabilitation care is central:

  • Physiotherapy: helps maintain muscle strength, prevent stiffness, and reduce fall risk.
  • Occupational therapy: promotes adaptation of daily gestures and improves autonomy at home or at work.
  • Ankle or hand orthoses: stabilize movements and facilitate walking.
  • Podiatric orthoses: correct foot disorders (such as high-arched foot) for better comfort and balance.
  • Orthopedic surgery: in some cases, considered to correct severe deformities.

Medical follow-up and psychological support

Managing CMT relies on a multidisciplinary approach: effective coordination between several health professionals to meet the various needs of those affected:

  • Neurologist: ensures general follow-up of disease progression.
  • Rehabilitation doctor: coordinates physiotherapy, occupational therapy, and technical aids.
  • Pain specialist: intervenes in cases of associated chronic pain.
  • Psychologist/psychiatrist: supports the person and their relatives emotionally.

Psychological support is essential to foster acceptance of the diagnosis, maintain self-esteem, and avoid isolation. Support groups or individual consultations may be offered.

Research and innovation: hopes for the future

Current therapeutic advances

Scientific research is progressing rapidly in the field of hereditary neuropathies such as Charcot-Marie-Tooth disease (CMT). Between new therapeutic strategies and technological innovations, several avenues offer real hope. Currently, researchers are working on promising approaches:

  • Gene therapies: aim to correct the defective gene responsible for the disease. This approach is already being tested for certain rare forms of CMT, notably via AAV vectors – small harmless viruses used to deliver genetic material into cells.
  • Therapeutic RNA therapies: in 2023, French CNRS researchers created a special RNA molecule attached to a small drop of fat called squalene. Since RNA is a messenger molecule using DNA instructions to make proteins needed by the human body, this particularly helped mice with CMT. The treatment helped nerves better transmit signals and restore their natural protection, myelin.
  • Cellular and animal models: essential for testing treatments, they make it possible to observe the effects of molecules on human cells or genetically modified mice.

Technological innovation serving autonomy

Beyond treatments, technological advances offer concrete solutions to improve the quality of life of people living with CMT:

  • Smart orthoses: adaptive devices that assist walking in real time, depending on foot position or muscle fatigue.
  • Partial and mechatronic exoskeletons: designed to stabilize the hands or lower limbs, they facilitate gripping or posture while reducing fatigue.
  • Connected grasping aids: motorized clamps, ergonomic handles, or mobile applications to remotely assist daily gestures.

These technologies are integrated into individualized care programs, in connection with rehabilitation centers and technological platforms.

Adapting daily life: concrete advice for patients and caregivers

Adapting the living environment

Adapting one’s environment is essential to improve the autonomy and well-being of people living with neuromuscular diseases such as CMT. Whether at home, school, or work, concrete adjustments help improve comfort and safety.

  • Housing adaptation: ergonomic furniture, simplified movement with home automation, and secured access for better mobility.
  • School and professional accessibility: adaptation of tools, workstations, and educational pathways according to specific needs. An occupational therapist can help design an optimal environment.

CMT disease: all your questions

What are the first symptoms?

The first signs of Charcot-Marie-Tooth disease (CMT) often appear in childhood or adolescence. They generally include:

  • Muscle weakness in the legs
  • Difficulty lifting the front of the foot (foot drop)
  • Sensory disturbances in hands and feet
  • Calf muscle atrophy
  • Loss of balance
  • Sometimes deformities such as high-arched foot or hammer toes

Each person does not present all of these signs, and the intensity varies depending on the type of CMT.

The different types of CMT?

The disease includes several forms, classified according to: the affected part of the nerve (myelin or axon), the mode of genetic transmission, and the gene involved.

The main forms are:

  • CMT1: myelin is affected, dominant transmission
  • CMT2: axon is affected, dominant transmission
  • CMT4: myelin is affected, recessive transmission (both parents are carriers)
  • CMTX: X-linked, often transmitted by the mother
  • DI-CMT & RI-CMT: intermediate forms

Is the disease progressive?

Yes, Charcot-Marie-Tooth disease is a progressive condition, but it evolves slowly. Symptoms worsen over years, often over several decades. Some people maintain good autonomy all their lives, while others will need technical aids to move or perform daily gestures.

Can it be cured?

Currently, there is no curative treatment. However, many types of care help slow progression and improve quality of life:

  • Physiotherapy
  • Occupational therapy
  • Use of orthoses or surgery
  • Psychological support

Research is ongoing, particularly in gene therapy and therapeutic RNA, with promising results in animal models.

Is CMT hereditary?

Yes, it is a genetic neuropathy. It can be transmitted according to several modes:

  • Dominant: only one carrier parent is enough
  • Recessive: both parents must be carriers
  • X-linked: transmitted by the mother, often more severe in boys

“De novo” cases (without family history) are also possible.

What is the life expectancy?

Life expectancy is generally normal. Although Charcot-Marie-Tooth disease can be disabling, it does not affect vital functions such as breathing or cognition.

What daily adaptations?

Many solutions promote daily adaptation:

  • At home: ergonomic furniture, home automation, technical aids
  • At school or work: specific adjustments with an occupational therapist

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