Charcot Marie Tooth Disease

Written By: Chloe Wilson BSc(Hons) Physiotherapy
Reviewed By: FPE Medical Review Board

Charcot Marie Tooth Disease is the most common inherited neurological disorder. Learn about the causes, symptoms, diagnosis and treatment

Charcot Marie Tooth Disease (CMT), aka peroneal muscular atrophy, causes weakness and loss of sensation in the feet, legs and hands. 

CMT is the most common inherited neurological disorder and affects approximately 1 in every 2,500 people.

Charcot Marie Tooth Disease was first identified in 1886 by three doctors, Jean-Marie Charcot, Pierre Marie and Howard Henry Tooth. 

CMT develops gradually, starting with symptoms of weakness and decreased sensation in the feet which can spread progressively over time up the legs, sometimes also affecting the hands and arms.  It often results in abnormalities in the shape of the foot such as high foot arches. 

Whilst there is no cure for Charcot Marie Tooth Disease, there are a number of treatment options available to reduce symptoms.  

Charcot Marie Tooth Symptoms

The symptoms of Charcot Marie Tooth disease varying depending on the type of disease, but there are many shared characteristics including:  

Classic presentation of Charcot Marie Tooth Disease. Note the high foot arch and curled toes.
  • Changes in Foot Position: CMT typically results in very high foot arches but CMT can also cause flat foot arches

  • Curled Toes: The position of the toes can change into a flexed position, known as hammertoe

  • Pain: may be experienced, usually associated with postural changes, weakness and cramp
  • Muscle Weakness: Wasting of the muscles results in weakness.  This starts in the feet and ankles and can gradually spread up the legs, resulting in what is referred to as an upside-down champagne bottle appearance of the legs due to muscle wasting.  Weakness may also develop in the hands and forearms, making fine motor control activities  like writing difficult

  • Altered Sensation: Decreased or absent sensation (ability to feel touch or temperature) in the feet and hands

  • Cramp: Muscle cramp commonly occurs with CMT disease
Almost half of all Charcot Marie Tooth Disease sufferers develop scoliosis (curvature of the spine)
  • Spinal Deformity: Curvature of the spine (known as scoliosis) affects up to half of CMT disease sufferers

  • Difficulty Walking: Muscle weakness often leads to difficulty walking and can result in frequent trips, falls and ankle sprains due to an inability to pick the foot up effectively, known as a foot drop.  Clumsiness is often one of the first signs of Charcot Marie Tooth disease in children

  • Altered Reflexes: Reflexes such as the knee and ankle jerk may be decreased or absent

  • CMT 3: presents during infancy, usually by the age of two resulting in floppy baby syndrome and delayed motor skills.  

Symptoms of Charcot Marie Tooth develop gradually, usually starting during childhood and get progressively worse over time.  CMT symptoms usually appear between the ages of 5 and 15 years.

Whilst CMT symptoms progress over time, in most cases, Charcot Marie Tooth Disease does not affect life expectancy.  Occasionally however, it can cause breathing problems. 

What Causes Charcot Marie Tooth Disease?

Charcot Marie Tooth Disease is a type of peripheral neuropathy.  Let me explain. Our bodies are made up of two nervous systems:

Charcot Marie Foot Disease is caused by a problem in the peripheral nervous system

Central Nervous System: brain and spinal cord
Peripheral Nervous System: nerve fibres that travel round the body. 

In CMT disease, there is a problem with the peripheral nervous system. 

There are two types of nerve in the peripheral nervous system:

Motor nerves: which control movement
Sensory nerves: which interpret touch such as heat, cold and pressure

Our nerves work by sending messages in the form of electrical signals from the central nervous system to the rest of the body through the peripheral nervous system. 

Think of them like a telephone cable.  The wires inside, known as the axon, transmit the electrical signals from one place to another. 

Diagram of a neuron. In Charcot Marie Tooth disease, there can be problems with the myelin sheath or the axon affecting how nerve impulses transmit

The protective outer covering, known as the myelin sheath, protects and insulates the wires from damage so the signals can transmit without interruption.   It also allows signals to transmit quicker.

In Charcot Marie Tooth Disease, there may be a problem with:

The Myelin Sheath: This breaks down, exposing the axon to damage, which affects the transmission of signals down the nerve
The Axon: which reduces the strength of the electrical signals

Genetics and CMT Disease

Charcot Marie Tooth disease is caused by a problem with genes. We are made up of around 30,000 pairs of genes.  For each pair, we inherit one copy from our mother and one from our father to make a pair, so we have two copies of every gene.  

Charcot Marie Tooth disease can be caused by a mutation of a number of different genes.  The mutation affects the production of the proteins that form the axon and myelin sheaths in the peripheral nerves.  Gradually over time, the nerves degenerate, reducing their ability to transmit signals.

There are three ways that we can inherit the genetic mutations that cause Charcot Marie tooth disease:

Autosomal Dominant Inheritance
This is the most common cause of peroneal muscular atrophy and affects people where one parent has CMT.

Mutation of one of the inherited genes in the pair is sufficient to cause the disease.  If one parent carries the mutated gene, there is a 50% chance of the disease being passed on

Autosomal recessive inheritance for charcot marie tooth disease

Autosomal Recessive Inheritance
This affects people who's parents are carriers of CMT gene mutations but do not have the disease themselves.

It requires a mutation of both of the copies of the gene in a pair, i.e. both parents would have to pass on affected genes. 

If both parents are carriers of mutated CMT genes, there is a 50% chance of their child being a carrier (carrying one CMT gene but not displaying any symptoms), 25% chance of having CMT disease and 25% chance of inheriting two normal genes. 

If only one parent had a recessive CMT gene, their child would not develop peroneal muscular atrophy but would have a 50% chance of being a carrier

X-Linked Inheritance
The mutated gene is linked to the X chromosome (female), not the Y chromosome (male). Males are made up of XY chromosomes and females have XX chromosomes.  

When CMT disease is linked with an X chromosome, there is a 50% chance of a mother passing the disease on.  If she passes the gene on to a son, he will be symptomatic.  If she passes the gene on to a daughter, she is likely to only have mild symptoms as the unaffected X chromosome tends to override the condition.

Very rarely a gene may mutate spontaneously causing peroneal muscular atrophy, rather than being passed down genetically.

Types of CMT Disease

There are five main types of Charcot Marie Tooth Disease:

  • CMT Type 1: This is the most common type of Charcot Marie Tooth Disease accounting for 30% of cases.   Gene duplication causes the myelin sheath to break down, known as demyelination.  The body responds with a proliferation of Schwann cells which wrap around the axon resulting in remyelination.  The cycle keeps repeating producing what is known as the onion bulb effect

  • CMT Type 2: Results from abnormalities in the axon itself.  It accounts for 20-40% of cases

  • CMT Type 3: develops in infancy and results in severe demyelination and thinning of the myelin sheath.  It is the most severe form of Charcot Marie Tooth Disease causing severe muscle wasting and weakness as well as sensory problems.  It is also known as Dejerine-Sottas disease and is extremely rare

  • CMT Type 4: this is a rare type of Charcot Marie tooth disease that affects the myelin sheath

  • CMT Type X: this is another demyelinating neuropathy caused by a mutation in the X chromosome, more commonly affecting men.  It accounts for 10-20% of cases

How Is Charcot Marie Tooth Disease Diagnosed?

Diagnosing Charcot Marie Tooth Disease starts with your doctor asking you about your symptoms and any family history of the disease.  Examination will start with observation of your foot position, testing muscle strength, reflexes and sensory testing.  They will also look for signs of enlarged nerves that can be seen or felt through the skin. 

If your doctor suspects Charcot Marie Tooth Disease, you will be referred to a neurologist (a specialist doctor of the nervous system).  They will carry out further tests which may include:

Nerve conduction tests are often used to diagnose Charcot Marie Tooth Disease
  • Nerve Conduction Tests
    This is where they look at the speed and strength of the signals transmitted through the peripheral nerves.  This is done using electrodes placed on the skin which produce small electric shocks to stimulate the nerves.  Slow or weak signals may indicate CMT disease

  • Electromyogram (EMG)
    This tests the electrical activity at your muscles at rest and when contracting.  Small needles connected to a machine are placed in your muscles.  They measure the muscles electrical activity at rest and then when you try and contract the muscle.  Specific patterns of activity can be seen in some types of CMT disease
  • Nerve Biopsy
    If nerve conduction and EMG tests have been inconclusive, a nerve biopsy may be performed.  This is when a small section of a peripheral nerve is removed under local anaesthetic and examined under a microscope for signs of Charcot Marie Tooth disease

  • Gene Testing
    Genetic testing from a blood sample can be used to diagnose most types of peroneal muscular atrophy, but not all genes that cause the disease have been identified yet

Charcot Marie Tooth Treatment

There is currently no cure for Charcot Marie Tooth disease, but a combination of therapy, orthotics, surgery and medication can help to reduce symptoms.  Treatment for CMT Disease may include:

Physiotherapy

Daily calf stretches are really important with Charcot Marie Tooth disease to prevent tightness developing

Rehab programmes are a vital part of peroneal muscular atrophy treatment.  

Strengthening exercises: help combat the weakness associated with the disease.  They are most effective when started early, before the muscles have a chance to waste

Stretches: particularly for the calf muscles and Achilles tendon should be done daily to prevent muscle contractures

General fitness programmes also help to reduce fatigue from the extra effort required for movement.  Low impact activities such as cycling and swimming are recommended to limit the force put through the joints.  

It can also help to work on balance and posture to prevent injuries or associated problems.

Occupation Therapy

This looks at ways to make your activities of daily living such as washing and dressing easier, through practical methods and using adaptive aids.

Orthotics

There's a huge variety of orthotics that be helpful with Charcot Marie Tooth disease, depending on your symptoms.

Orthotics can be really useful for correcting foot position and supporting the ankle with charcot marie tooth disease

Shoe Inserts: help to correct foot position such as fallen arches

AFO: an ankle foot orthosis is particularly useful if you have a foot drop as it holds your foot in a neutral position so you aren't tripping over your toes when you walk

Braces: ankle and knee braces can be useful for providing support and stability of the foot and leg and make activities such as walking easier

Each of these can help reduce the risk of injury for people suffering from Charcot Marie Tooth disease.  

Painkillers

Analgesics may be prescribed to reduce pain associated with the disease.  Neurotoxic drugs such as vincristine should be avoided as they can make the condition worse.

Surgery

Sometimes surgery is necessary to combat structural deformities of the foot and ankle.  Bone surgery such as an osteotomy or arthrodesis helps correct the shape of the foot such as realigning hammertoes, correcting severely fallen foot arches or fusing the ankle joint for stability. 

Soft tissue release is done if muscles and tendons have become too type such as plantar fascia release.  Spinal surgery may be required if a scoliosis has developed. 

What Else Can Help?

Exercises can make a big difference for people suffering from Charcot Marie Tooth disease.  Exercise programmes should be carried out under the guidance of a physiotherapist, but visit the strengthening exercises and ankle stretches for some suggestions of things that might help treat peroneal muscular atrophy.

If Charcot Marie Tooth Disease is not sounding quite like your problem, visit the foot pain diagnosis section for help working out what is wrong, or the common foot problems section.

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Page Last Updated: 11/05/20
Next Review Due: 11/05/22

References

1. Gait & Posture Journal: Evaluation of muscle strength, balance and functionality of individuals with type 2 Charcot-Marie-Tooth Disease. de França Costa IMP, Nunes PS, de Aquino Neves EL, Lima Santos Barreto LC, Garcez CA, Souza CC, Pereira Oliveira PM, Sales Ferreira LA, Brandão Lima VN, de Souza Araújo AA. 2018

2. American Journal of Human Genetics: Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2.Lassuthova P1, Rebelo AP2, Ravenscroft G, Lamont PJ et al. American Journal of Human Genetics 2018

3. British Medical Journal Best Practice: Charcot Marie Tooth Disease.  May 2018