Charcot Marie Tooth Disease

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Introduction

Introduction

Charcot-Marie-Tooth disease (CMT) is a group of inherited conditions that damage the peripheral nerves.

It's also known as hereditary motor and sensory neuropathy (HMSN).

The peripheral nerves are found outside the main central nervous system (brain and spinal cord). They control the muscles and relay sensory information, such as the sense of touch, from the limbs to the brain.

People with CMT may have:

  • muscle weakness in the feet, ankles, legs and hands
  • an awkward way of walking (gait)
  • highly arched or very flat feet
  • numbness in the feet, arms and hands

The symptoms of CMT usually start to appear between the ages of five and 15, although they sometimes don't develop until well into middle age or later.

CMT is a progressive condition. This means the symptoms slowly get worse, making everyday tasks increasingly difficult.

Read more about the symptoms of CMT

What causes CMT?

CMT is caused by an inherited fault in one of the many genes responsible for the development of the peripheral nerves. This fault means the nerves become damaged over time.

A child with CMT may have inherited the genetic fault responsible for the disease from one or both of their parents.

There's no single faulty gene that causes CMT. There are many varieties of CMT that are caused by different genetic faults and these can be inherited in several different ways.

The chances of passing CMT to your child depend on the specific genetic faults you and your partner carry.

Read more about the causes of CMT.

Testing for CMT

See your GP if you think you may be developing symptoms of CMT. If your GP suspects CMT, they'll refer you to a neurologist (a doctor who specialises in treating conditions of the nervous system) for further tests to confirm the diagnosis.

You should also see your GP if you or your partner have a family history of CMT and are considering having a baby. Your GP can refer you for genetic counselling, where you can discuss your concerns and the options available with a genetics specialist.

Read more about diagnosing CMT.

How CMT is treated

There's currently no cure for CMT. However treatments can help relieve symptoms, aid mobility and increase the independence and quality of life for people with the condition.

These treatments may include:

In some cases, surgery may be needed to correct problems such as flat feet and muscle contractures (where muscles shorten and lose their normal range of movement).

Read more about treating CMT.

Living with CMT

CMT isn't life-threatening and most people with the condition have the same life expectancy as a person without the condition.

However, it can make everyday activities very difficult. Living with a long-term, progressive condition can also have a significant emotional impact.

Some people find it helpful to speak to others with the condition through support groups. You may also benefit from a talking therapy, such as cognitive behavioural therapy (CBT).

You can find more information, support and practical advice about living with CMT on the CMT UK website. CMT UK is the main charity and support group for people with CMT in the UK.

Information about you

If you have CMT, your clinical team will pass information about you on to the National Congenital Anomaly and Rare Diseases Registration Service (NCARDRS).

This helps scientists look for better ways to prevent and treat this condition. You can opt out of the register at any time.

Find out more about the register.


Symptoms of Charcot-Marie-Tooth disease

Symptoms of Charcot-Marie-Tooth disease

The symptoms of Charcot-Marie-Tooth disease (CMT) can differ from person to person, even among relatives with the condition.

Symptoms can vary depending on the type of CMT and even people with the same type can experience it differently.

For example, it's not possible to predict the age at which symptoms will first appear, how quickly the disease will progress, or its severity.

Read about the causes of CMT for more information on the different types.

Early symptoms of CMT

CMT is a progressive condition, which means the symptoms gradually get worse over time. Therefore, it may be difficult to spot any symptoms in young children who have CMT.

Signs that a young child may have CMT include:

  • appearing unusually clumsy and accident-prone for their age
  • finding it difficult to walk because they may have problems lifting their feet from the ground
  • their toes dropping forward as they lift their feet (known as 'foot drop')

Main symptoms of CMT

The main symptoms of CMT usually appear between the ages of five and 15, although they sometimes don't develop until well into middle age or later.

Some of the main symptoms of CMT include:

  • muscle weakness in the feet, ankles and legs at first
  • having feet that are very highly arched, which can make the ankle unstable, or having very flat feet
  • curled toes ('hammer toes')
  • an awkward or high step and difficulty using the ankle muscles to lift the foot, which makes walking more difficult
  • a lack of sensation in the arms and feet
  • very cold hands and feet, caused by poor circulation
  • wasting of the muscles in the lower legs, causing legs to have a distinctive 'upside-down champagne bottle' shape
  • feeling tired a lot of the time, as a result of the extra effort it takes to move around

Some people also develop additional problems such as:

  • tremor (uncontrollable shaking)
  • scoliosis (abnormal curvature of the spine)
  • problems speaking, breathing or swallowing (dysphagia) - but these symptoms are rare in CMT

Later symptoms of CMT

As CMT progresses, the muscle weakness and lack of sensation worsens and starts to affect your hands and arms more. This can lead to problems with both manual dexterity and hand strength, making tasks such as doing up the buttons of a shirt very difficult.

Persistent problems with walking and posture can put excessive strain on your body, which often leads to muscle and joint pain. Less commonly, damaged nerves may also cause pain, known as neuropathic pain.

Problems with mobility and walking tend to get worse with age. It's uncommon to lose the ability to walk completely, but older people with CMT often need a walking aid to get around.


Causes of Charcot-Marie-Tooth disease

Causes of Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) is caused by mutations (faults) in genes that cause the peripheral nerves to become damaged.

The peripheral nerves are a network of nerves that run from the brain and spinal cord (the central nervous system). They carry impulses to and from the rest of the body, such as the limbs and organs, and are responsible for the body's senses and movements.

A peripheral nerve is similar to an electrical cable, and is made up of two parts:

  • the axon - which transmits electrical information between your brain and limbs, similar to the wiring in an electrical cable
  • the myelin sheath - which is wrapped around the axon to protect it and ensure the electrical signal isn't broken, similar to the insulation around electrical cable

In some types of CMT, faulty genes cause the myelin sheath to disintegrate. The axons become damaged without this protection, which affects the transmission of messages between the brain and the muscles and senses. This leads to muscle weakness and numbness.

In other types of CMT, the axons are directly affected and don't transmit electrical signals at the normal strength. This means muscles and senses are understimulated, leading to symptoms of muscle weakness and numbness.

How CMT is inherited

A child with CMT may have inherited the genetic fault responsible for the disease from just one or both of their parents.

There's no single faulty gene that causes CMT. The many varieties of CMT are caused by different genetic mutations and the faulty genes can be inherited in several different ways.

Autosomal dominant

Autosomal dominant inheritance of CMT occurs when one copy of a mutated gene is enough to cause the condition. If either parent carries a faulty gene, there's a 50% chance the condition will be passed on to each child they have.

Autosomal recessive

Autosomal recessive inheritance of CMT occurs when two copies of the defective gene are needed to cause the condition. You inherit one copy from each parent. As your parents only have one copy of the gene, they don't develop CMT themselves.

If both you and your partner are carriers of the autosomal recessive CMT gene, there's a:

  • 25% chance each child you have will develop CMT
  • 50% chance each child you have will inherit one of the defective genes and be able to pass the condition to any children they have (known as being a 'carrier') - although they won't have any of the symptoms of CMT themselves
  • 25% chance each child you have will receive a pair of healthy genes and won't develop CMT

If only one parent has the autosomal recessive gene, your children won't develop CMT. However, there's a 50% chance each child will be a carrier.

X-linked inheritance

In X-linked inheritance, the mutated gene is located on the X chromosome and passed from mother to son. Chromosomes are the parts of cells that carry your genes.

Men have XY sex chromosomes. They receive the X chromosome from their mother and the Y chromosome from their father. Women have XX chromosomes. They receive one X chromosome from their mother and the other X chromosome from their father.

A woman with the defective X chromosome will usually have no or very mild symptoms because the other healthy X chromosome counters the effect of the defective one. However, there's a 50% chance she'll pass on the defective gene to her son and that he'll develop CMT.

If a woman with the defective X chromosome only has daughters, CMT can skip a generation until one of her grandsons inherits it.

Types of CMT

There are many different types of CMT that are all caused by different mutations (changes) in your genes.

The main types of CMT are:

  • CMT 1 - the most common type, caused by defective genes that cause the myelin sheath to slowly break down
  • CMT 2 - a less common and usually less severe type than CMT 1, caused by defects in the axon
  • CMT 3 (Dejerine-Sottas syndrome) - a rare and severe type of CMT that affects the myelin sheath, causing severe muscle weakness and sensory problems to begin developing in early childhood
  • CMT 4 - another rare and severe type of CMT that affects the myelin sheath, which begins developing in early childhood and causes many people to eventually lose the ability to walk
  • CMT X - caused by a mutation in the 'X' chromosome and more common in men than women

You can read more about the classification of CMT on CMT UK.


Diagnosing Charcot-Marie-Tooth disease

Diagnosing Charcot-Marie-Tooth disease

If you have early symptoms of Charcot-Marie-Tooth disease (CMT), your GP will ask about your symptoms and may carry out a physical examination.

Your GP may want to know:

  • when your symptoms started
  • how severe your symptoms are
  • if anyone in your family has CMT

During a physical examination, your GP will be looking for evidence of the condition, such as muscle weakness, poor or absent reflexes, and foot deformities, such as high arches or flat feet.

Further tests

If CMT is suspected, you may be referred to a neurologist (a doctor who specialises in treating conditions of the nervous system) for further testing. Tests you may have are described below.

Nerve conduction test

A nerve conduction test measures the strength and speed of signals transmitted through your peripheral nerves (network of nerves that run from the brain and spinal cord to and from the rest of the body, such as the limbs and organs).

Electrodes (small metal discs) are placed on your skin, which release a small electric shock that stimulates the nerves. The speed and strength of the nerve signal is then measured. An unusually slow or weak signal could indicate CMT.

Electromyography (EMG)

Electromyography (EMG) uses a small needle-shaped electrode placed in your skin to measure the electrical activity of your muscles. Some types of CMT cause a distinctive change in the pattern of electrical activity that can be detected by an EMG.

Genetic testing

Genetic testing involves taking your blood sample and testing it for defective genes known to cause CMT. So far, many of these genes have been found, but there may be more not yet identified.

Most people with CMT should be able to have their diagnosis confirmed by genetic testing and find out exactly which type of CMT they have. For others, genetic testing may prove inconclusive because an unidentified gene may be involved in their CMT.

Nerve biopsy

In a small number of cases where other tests have been inconclusive, a test called a nerve biopsy may be carried out.

This is a minor surgical procedure where a sample of a peripheral nerve is removed from your leg for testing. CMT can cause physical changes to the shape of the nerve, which can be seen under a microscope. The biopsy is carried out under a local anaesthetic, so you'll be awake, but unable to feel pain.

Being diagnosed with CMT

Everyone reacts differently when told they have CMT. You may experience feelings of shock, denial, confusion or fear. Some people are relieved that there's finally an explanation for their symptoms.

You may find the following advice useful if you've recently been diagnosed with CMT:

  • take all the time you need - don't rush into making important decisions about your health
  • find the support you need - talk to your family and friends when you feel ready; you may also find it helpful to contact other people with CMT through the charity CMT UK
  • find out what you can about CMT - both from your healthcare team and reliable online resources, such as CMT UK
  • get involved in your care - work closely with your healthcare team to come up with a treatment plan that best suits you

Tests before and during pregnancy

Couples with a family history of CMT who are thinking of having a baby can be referred to a genetics specialist for advice.

A genetic counsellor can help couples work through the decision-making process and explain possible tests that can be carried out and any alternatives you may want to consider, such as adoption.

Read more about genetic testing and counselling.

The main tests that can be carried out during pregnancy to check if a baby will develop certain types of CMT are:

  • chorionic villus sampling (CVS) - where a small sample of placenta is removed from the womb and tested for known CMT genes, usually during weeks 11 to 14 of pregnancy
  • amniocentesis - where a sample of amniotic fluid is taken for testing, usually during weeks 15 to 20 of pregnancy

If these tests show that your child is likely to have CMT, you can discuss with your genetic counsellor whether you want to continue the pregnancy or have a termination (abortion).

However, it's important to be aware that the results of these tests won't indicate how serious your child's CMT will be. This is because the symptoms and progression of the condition can vary widely, even among family members with the same type of CMT.

It's also important to bear in mind that both these tests can slightly increase your chances of having a miscarriage.

Pre-implantation genetic diagnosis

For some couples at risk of having a child with CMT, pre-implantation genetic diagnosis (PGD) may be an option.

PGD involves using in vitro fertilisation (IVF), where eggs are removed from a woman's ovaries before being fertilised with sperm in a laboratory. After a few days, the resulting embryos can be tested for certain types of CMT and a maximum of two unaffected embryos are transferred into the womb.

Funding for PGD is decided on an individual basis. For example, you may be considered ineligible for PGD on the NHS if you already have unaffected children or if the chances of having a successful pregnancy are thought to be low. In these cases, you can choose to fund PGD yourself, although each attempt is likely to cost at least £9,000 (including drug costs).


Treating Charcot-Marie-Tooth disease

Treating Charcot-Marie-Tooth disease

There's no cure for Charcot-Marie-Tooth disease (CMT), but therapies are available to help reduce your symptoms and enable you to live as independently as possible.

As CMT gets worse over time, you'll need to be assessed regularly to check for any new developments in your condition. How often you're assessed depends on the type of CMT you have and the severity of your symptoms.

Your treatment programme may involve a number of healthcare professionals working together in a multidisciplinary team (MDT). You'll usually have a doctor who co-ordinates your treatment programme and makes sure every aspect of your condition is closely monitored and treated if necessary.

Physiotherapy

Physiotherapy is one of the most important therapies for improving the symptoms of CMT and reducing the risk of muscle contractures (where muscles shorten and lose their normal range of movement).

Physiotherapy uses physical methods, such as massage and manipulation, to promote healing and wellbeing. It usually involves low-impact exercises such as stretching, swimming and moderate weight-training.

There's a lack of good quality medical research into the benefits of exercise for people with CMT. However, it's possible that some types of exercise are beneficial. For example:

  • strengthening exercises that focus on improving muscle strength, such lifting weights, may help improve overall strength and reduce 'foot drop'
  • aerobic exercise, such as walking or swimming, which raises your heart rate and makes you breathe harder, may improve your fitness and your ability to function on a day-to-day basis
  • posture and balance exercises, such as yoga, may also have benefits

Any exercise needs to be carefully planned as part of a personalised exercise programme. A certain level of exercise may be safe, but you risk making symptoms worse if you don't follow proper instructions or if you over-exert yourself.

Speak to your GP or physiotherapist about arranging a suitable exercise programme that will allow you to pace yourself. Read more information about the benefits of exercise.

Occupational therapy

Occupational therapy involves identifying problem areas in your everyday life, such as dressing yourself, then working out practical solutions.

Occupational therapy will be useful if muscle weakness in your arms and hands makes it difficult for you to do day-to-day tasks, such as dressing or writing.

An occupational therapist will teach you how to use adaptive aids to compensate for your difficulties, such as clothing with clasps instead of buttons, and magnetic tubes that allow you to pick up objects.

Orthoses and walking aids

Orthoses are devices worn inside your shoes or on your legs to improve the strength and functionality of your limbs, or to correct your gait (the way you walk).

There are several different types of orthoses, including:

  • insoles in your shoes
  • custom-made shoes that support your ankles
  • ankle or leg braces
  • thumb splints that can improve your hand strength

It's unusual to completely lose the ability to walk, but you may benefit from using a wheelchair occasionally. Moving around can be difficult if you have CMT and using a wheelchair every now and again can give you a chance to rest.

Taking care of yourself

In addition to the treatment you receive, there are some general precautions you can take to avoid further problems. These may include:

  • try to maintain a healthy weight - being overweight can make moving around more difficult and put more strain on your body
  • take good care of your feet - make sure you check and clean your feet regularly, as there's a risk of injury and infection if you have reduced sensation in your feet
  • avoid drinking too much alcohol - as this has many health risks, which may be worse if you have CMT
  • avoid caffeine (found in tea, coffee, cola and energy drinks) and nicotine (found in tobacco) if you have tremors (shaking), as they can make this worse
  • avoid medicines that can cause nerve damage - CMT UK has a list of medications to avoid or use with caution if you have CMT

Ask your MDT if they have specific lifestyle advice for you, as risks may vary from person to person.

Controlling pain

There are two types of pain associated with CMT:

  • joint and muscle pain - caused by the stresses that CMT places on your body
  • neuropathic pain - caused by damage to your nerves (this is less common)

Joint and muscle pain can usually be controlled by taking non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen.

Neuropathic pain may be treated with tricyclic antidepressants (TCAs) or an anti-convulsant medication (a medicine often used to prevent seizures). These medications weren't originally designed to be painkillers, but there's evidence to suggest they're effective in treating long-term nerve pain in some people.

Surgery

If CMT causes significant deformities, surgery may be needed to correct them. Some of the types of surgery that may be carried out are described below. 

Osteotomy

An osteotomy is a surgical procedure used to correct severe flatness of the feet. An incision (cut) is made in your foot and the surgeon removes or repositions the bones in your foot to correct its shape.

After surgery, your foot (or feet) will need to be kept in plaster for several weeks until the bones have healed.

Arthrodesis

Arthrodesis can also be used to correct flat feet, as well as relieve joint pain and correct heel deformities. It involves fusing the three main joints in the back of your feet to strengthen your feet, correct their shape and relieve pain.

After surgery, your foot (or feet) will be placed in plaster, and you won't be able to place any weight on them for six weeks. During this time, you'll need to use crutches or a wheelchair.

Once you can put weight on your feet, you'll need to wear the cast for another six weeks (12 weeks in total). However, it may take up to 10 months for you to fully recover from the operation.

Plantar fascia release

Plantar fascia release is a surgical procedure used to relieve persistent heel pain caused by inflamed tendons. Tendons are the fibrous cords that join bones to muscle.

During the procedure, part of the tendon is removed and the remaining tendon repositioned and allowed to heal. Afterwards, you'll need to wear a cast for three weeks and won't be able to put any weight on your feet during this time.

Spinal surgery

Although abnormal curvature of the spine (scoliosis) can often be treated using a back brace, corrective surgery may be required.

Read more about treating scoliosis.

Research into treatments

There's some promising research that may provide new ways of treating people with CMT. This research includes:

  • using stem cells (cells at an early stage of development) to repair nerve damage
  • using hormones (powerful chemicals) and gene therapy to slow progression of the condition

Research looking into whether ascorbic acid (vitamin C) could help people with CMT has recently been carried out, but unfortunately no evidence of a benefit was found.

Speak to your care team if you're interested in taking part in a clinical research trial. You can also search for CMT clinical trials to see what research is currently being carried out.