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 get slowly worse, making everyday tasks increasingly difficult.
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 is 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.
Testing for CMT
See your GP if you think you may be developing symptoms of CMT. If your GP suspects you may have the condition, they will 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.
How CMT is treated
There is 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 physiotherapy, exercise, occupational therapy and walking aids. 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).
Living with CMT
CMT is not life-threatening, and most people with the condition have the same life expectancy as a person who does not have CMT.
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.
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.
You can't predict the age at which symptoms will first appear, how quickly the disease will progress and its severity, for example.
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) or problems speaking, breathing or swallowing (dysphagia).
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 is uncommon to lose the ability to walk completely, but older people with CMT will often need a walking aid to get around.
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) and carry impulses to and from the rest of the body, such as the limbs and organs. Peripheral nerves 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 is like the wiring in an electrical cable. It is the part of the nerve that transmits the electrical information between your brain and limbs.
The myelin sheath acts like the insulation of an electrical cable. It is wrapped around the axon to protect it and ensure the electrical signal is not broken.
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 do not transmit electrical signals at the normal strength, which means muscles and senses are understimulated. Again, this leads 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 is no single faulty gene that causes CMT. The many varieties of CMT (see below) are caused by different genetic mutations.
CMT is an unusual genetic disorder because the faulty genes can be inherited in several different ways. These ways are described below.
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 is a 50% chance the condition will be passed on to each child they have.
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 do not develop CMT themselves.
If both you and your partner are carriers of the autosomal recessive CMT gene:
there is a 25% chance each child you have will develop CMT
there is a 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 will not have any of the symptoms of CMT themselves
there is a 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 will not develop CMT. However, there is a 50% chance each child will be a carrier.
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 is a 50% chance she will pass on the defective gene to her son and that he will 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 – caused by defective genes that cause the myelin sheath to slowly break down. The most common type.
CMT 2 – caused by defects in the axon. Less common and usually less severe than CMT 1.
CMT 3 – also known as Dejerine-Sottas disease, a rare and severe type of CMT that affects the myelin sheath. Characterised by severe muscle weakness and sensory problems. Unlike other types of CMT, symptoms usually begin in early childhood.
CMT 4 – another rare type of CMT that affects the myelin sheath. The exact genes that cause it have not yet been identified. As with CMT 3, symptoms usually begin in childhood and many people with the condition are eventually unable to walk.
CMT X – caused by a mutation in the 'X' chromosome. More common in men than women.
Diagnosing Charcot-Marie-Tooth disease
If you have early symptoms of Charcot-Marie-Tooth disease (CMT), your GP will ask about your symptoms and whether there is a family history of it.
Your GP may want to know when your symptoms started, how severe your symptoms are and if anyone in your family has CMT. They may then carry out a physical examination.
During the 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.
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) 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 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.
It is estimated that most people with CMT will 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.
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 will 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 is finally an explanation for their symptoms.
You may find the following advice useful if you have recently been diagnosed with CMT:
take all the time you need – don't rush into making important decisions about your health
find any 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.
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 between 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 your child is likely to have CMT, you can discuss with your genetic counsellor whether you want to continue the pregnancy or have an abortion.
However, it's important to be aware that the results of these tests will not 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.
However, funding for PGD is decided on an individual basis. For example, you may be considered ineligible for PGD 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 £8,000.
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 will need to be assessed regularly to check for any new developments in your condition. How often you are assessed will depend 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 will 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 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 is a lack of good quality medical research into the benefits of exercise for people with CMT. However, it is 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' (the inability to lift the foot and toes properly when walking)
aerobic exercise, which raises your heart rate and makes you breathe harder, such as walking or swimming, 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.
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 that has 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 is 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 because 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 is 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 and cola) 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.
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 were not originally designed to be painkillers, but there is evidence to suggest they are effective in treating long-term nerve pain in some people.
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.
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 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 will not be able to place any weight on them for six weeks. During this time, you will need to use crutches or a wheelchair.
Once you can put weight on your feet, you will 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 will need to wear a cast for three weeks and will not be able to put any weight on your feet during this time.
Although abnormal curvature of the spine (scoliosis) can often be treated using a back brace, corrective surgery may be required.
Research into treatments
There is some promising research that may provide new ways of treating people with CMT. This research includes:
using stem cells (cells that are 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 are 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.