Charcot Marie Tooth disease

Charcot-Marie-Tooth disease (CMT) is an inherited condition that affects nerves or myelin, a protective covering around nerves. In individuals born with the defective genes, nerves gradually shrivel up and die, a process called axonal degeneration. As muscles require input from nerves to survive, the death of these nerves causes the secondary degeneration of their associated muscles. This leads to weakness then muscle wasting and deformity, and eventually arthritis. In addition, sensory nerves are often affected, so that numbness is common. Conditions like CMT are called by the general term ‘neuromuscular’ disorders, which means simply disease affected nerves then muscles.

Although all nerves to muscles are affected, the nerves travelling to your arms and legs are the longest and most likely to degenerate. For this reason, many people first experience symptoms in their feet. This gradually travels up their legs and into their thighs, as well as beginning in their hands and moving up the arms. Different forms of CMT begin at different ages depending on severity, however many appear in adolescence or early adulthood. The types vary widely in severity, even among family members, but tend to slowly worsen over time. It is important to remember that the disease begins long before symptoms are present, so genetic testing is highly recommended for family members.

Charcot-Marie-Tooth disease affects about one person in 2,500 and is the most common inherited neuromuscular disorder. It is usually managed by a rheumatologist, physiotherapist, podiatrist and other specialists.

Different types of Charcot-Marie-Tooth – Classification and Significance

There are many different genes involved in Charcot-Marie-Tooth, however the many different types are broadly grouped into

  • CMT1 – disorders of the protective ‘myelin’ casing around the nerves
  • CMT2 – the nerve shrivels up (‘axonal degeneration’)
  • Purely motor CMT (dHMN)

There are, however, sub-types and mixed patterns of CMT that do not fit easily into this division.

CMT1 – Myelin is a special coating on nerves that helps the signals from the brain to travel quickly (‘conduction’). De-myelinating diseases, like CMT and the more commonly known MS (multiple sclerosis), have slow nerve conduction, secondary degeneration of the underlying nerve, and abnormal formations of myelin clumps (‘onion-bulb formations’).The most common form of CMT is the moderately severe CMT1A. The most severe form of CMT also fits into this group and is called Dejerine-Sottas neuropathy, a rapidly worsening form that may involve the eyes in addition to the arms and legs.

CMT2 – The axon is the long string-like section of nerve that travels through the body (as opposed to the ‘nerve body’ which sits in the spinal cord or brain). Axonal degeneration is a process where the axon breaks down then is regrown, only to break down again. With each regrowth, the axon is progressively more abnormal. In this form of CMT, the speed of nerve conduction is relatively normal.

Differential Diagnosis

Though CMT is usually quite easily identifiable to the doctor, there are a number of other rare conditions that appear similar, including acquired neuropathies, motor neuron diseases and distal myopathies.

Symptoms

  • Numbness – this can involve loss of the ability to sense painful things, and many people with Charcot-Marie-Tooth develop ulcers from not realising they were touching something hot. Unfortunately, most people do not realise they are gradually losing sensation in their feet, so this needs to be identified by the doctor then meticulously cared for by the patient (see below).
  • Nerve (neuropathic) pain, arthritis pain associated with deformed joints
  • Wasting of the many small muscles in the feet leads to deformities including high arches (pes cavus) and hammer toes
  • Difficulty running and walking, abnormal gait, tendency to trip over, tendency to ankle sprains, difficulty fitting shoes
  • Foot drop

Causes

Charcot-Marie-Tooth disease is a group of related conditions all caused by inherited mutations in the genes involved with the structure and function of the nerves that serve your feet, legs, hands and arms.

In some cases, these genetic mutations result in damage to the nerve itself. Other mutations damage the myelin sheath, the protective coating that surrounds the nerve. The end result, however, is the same — weaker messages traveling between your extremities and your brain.

That means some of the muscles in your feet may not receive your brain’s signal to contract, so you’re more likely to trip and fall. And your brain may not receive pain messages from your feet, so if you’ve rubbed a blister on your toe, for example, it may get infected without your realizing it.

Risk Factors

  • Family history – this is the most important risk factor. There are different types of inheritance, for example some types of CMT are more common in males (X-linked), while others are passed from parent-child (autosomal dominant).
  • Chemotherapy – some drugs used in chemo can accelerate the destruction of nerves.

Investigations

Your doctor may recommend the following tests, which can help provide information about the extent of your nerve damage and what may be causing it.

  • Nerve conduction studies
  • DNA testing
  • Genetic testing

Complications

The most devastating complication of CMT is perhaps the loss of walking capacity. Though this is fairly rare in the most common type of CMT (CMT1A), it occurs in other types. Aside from this, some people suffer from twisting of the spine (scoliosis) and hand deformities in addition to their leg deformities.

Treatment

Unfortunately there is no cure for CMT. Despite this, sufferers can be assisted through rehabilitation and physical therapies. Particular exercises assist in maintaining normal gait and strength in the lower muscles, though weightlifting and similar resistance-type exercise should generally be avoided. Aerobic exercise is also recommended to maintain cardiovascular fitness, though this can be difficult if movements are too painful.

Shoe modifications are strongly recommended for sufferers of CMT. Not only do devices like orthotics help maintain the arch of the foot and thus maintain normal walking patterns, they also prevent the formation of ulcers and calluses over areas where the deformed foot rubs against the shoe. Some modified shoes prevent twisted ankles and are recommended in people who frequently suffer sprains.

Surgery may be helpful in correcting deformities and/or facillitating painless, stable walking. Generally, surgical therapies for CMT fall into two categories:

  • Soft-tissue – this includes tendon transfers, tendon release, fasciotomy. The purpose of these procedures is to ‘re-balance’ the way the muscles pull on the deforming foot. 
  • Bone modifying – osteotomies (trimming of bony lumps to correct deformity), arthrodesis (fusion of bones). These procedures help to correct the alignment of bones, as well as reducing pain. However, this may mean that a degree of mobility in the foot and ankle is lost.

Unfortunately, CMT is a progressive disease. This means that though surgery may initially fix the deformity, the continued destruction of nerves and muscles may cause the deformity to come back. Furthermore, procedures like arthrodesis have a high risk of arthritis developing later in life. For this and many other reasons, it is not always easy to know when surgery is appropriate in CMT. In general, surgery will only be offered in severe cases or when the surgeon is confident of a clear benefit. It is very important to understand that longterm benefits from surgery can be hard to predict, and the expectations from surgery must be discussed with the surgeon.

CMT sufferers may need painkillers relatively frequently. Pain may be associated with deformed joints (secondary arthritis) or may be related to the destruction of the nerves. Arthritic pain can usually be managed with panadol, while nerve pain may require the intervention of a pain specialist and treatment with special pain medications.

Future Treatments for CMT

Drugs currently being tested include

  • progesterone blockers (antagonists) – there is evidence that the hormone progesterone increases the action of certain genes that cause nerve destruction. For this reason, drugs that block this hormone are being developed for use in humans.
  • ‘neurotropic’ factors – this term refers to molecules that encourage the regrowth of damaged nerves. Early tests have shown that these help numbness.
  • Vitamin C – simple vitamin C is believed to have a protective effect on myelin and hence there are many trials currently running that involve giving CMT patient high doses.
  • curcumin – this molecule protects both axons and myelin from destruction and is still being trialled.

The above mentioned agents are still in early stages of clinical testing. Many of them cause significant side effects in humans and consequently require further development before they can be prescribed.

More Information

Please note that the accuracy of any information provided by external sites is not guaranteed by Orthoanswer. Always discuss your condition with your doctor/health specialist.

References

D. Pareyson, et al., ‘Diagnosis, natural history, and management of Charcot-Marie-Tooth disease’, Lancet Neurology, Vol 8, 2009, pp 654–667.
N. E. Strauss, et al., ‘Foot conditions related to neuromuscular disorders in adults’, Physical Medicine and Rehabilitation, Vol 15, Is. 15, Oct 2001, pg. 489.

Seeking Advice

Your Family Doctor (GP)

Your Family Doctor will be able to diagnose and help treat your problem. He or she will be able to

  • tell you about your problem
  • advise you of the best treatment methods
  • prescribe you medications
  • and if necessary, refer you to Specialists (Consultants) for further treatment

While you might first discuss your symptoms with your family doctor, he or she will probably refer you to a neurologist for further evaluation.

Prevention

As Charcot Marie Tooth is an inherited disease, there is currently no way to prevent it.

F.A.Q. | Frequently Asked Questions