The foot of a person with Charcot-Marie-Tooth. The lack of muscle, high arch, and hammer toes are signs of the genetic disease.
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Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease, also known as Hereditary Motor and Sensory Neuropathy (HMSN) or Peroneal Muscular Atrophy, is an inherited disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages of disease. The disease is presently incurable. more...

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The disorder is caused by the absence of molecules that are essential for normal function of the nerves due to deficiencies in the structure of the genes coding these molecules. The absence of these chemical substances gives rise to dysfunction either in the axon or the myelin sheath of the nerve cell.

The disease is named for those who classically described it: Jean-Martin Charcot (1825-1893) and his pupil Pierre Marie (1853-1940) ("Sur une forme particulière d'atrophie musculaire progressive, souvent familiale débutant par les pieds et les jambes et atteignant plus tard les mains", Revue médicale, Paris, 1886; 6: 97-138.), and Howard Henry Tooth (1856-1925) ("The peroneal type of progressive muscular atrophy", dissertation, London, 1886.)


Symptoms usually begin in late-childhood or early adulthood. Usually, the initial symptom is foot drop due to involvement of the peroneal nerve, which is responsible for raising the feet, early in the course of the disease. This can also cause hammer toe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to "stork leg" appearance. Symptoms and progression of the disease can vary. Extreme emotional stress is thought to hasten the progression.


The diagnosis is established by electromyography examination (which shows that the velocity of nerve impulse conduction is decreased and the time required to charge the nerve is increased) and nerve biopsy. Genetic markers have been identified for some, but not all forms of the disease.

Types of the disease

CMT Type 1 (CMT1)

Type 1 affects approximately 80% of CMT patients and is the most common type of CMT. The subtypes share clinical symptoms. Autosomal dominant. Causes demyelination, which can be detected by measuring nerve conduction velocities.

  • CMT type 1A - CMT1A (OMIM 118220) - The most common form of the disease, caused by mutations in the PMP22 gene (locus 17p11.2). 70-80% of Type 1 patients. Average NCV: 15-20m/s
  • CMT type 1B - CMT1B (OMIM 118200) - Caused by mutations in the MPZ gene (1q22) producing protein zero (P0). 5-10% of Type 1 patients. Average NCV: <20m/s
  • CMT type 1C - CMT1C - Sometimes called Dejerine-Sottas disease - Causes severe demyelination, which can be detected by measuring nerve conduction velocities. Autosomal dominant. Usually shows up in infancy. LITAF Gene (16p13.1-p12.3) Average NCV: 26-42m/s. Identical symptoms to CMT-1A.
  • CMT type 1D - CMD1D - EGR2 Gene (10q21.1-q22.1) - Average NCV: 15-20m/s


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Numbness and tingling
From Gale Encyclopedia of Medicine, 4/6/01 by Richard Robinson


Numbness and tingling are decreased or abnormal sensations caused by altered sensory nerve function.


The feeling of having a foot "fall asleep" is a familiar one. This same combination of numbness and tingling can occur in any region of the body and may be caused by a wide variety of disorders. Sensations such as these, which occur without any associated stimulus, are called paresthesias. Other types of paresthesias include feelings of cold, warmth, burning, itching, and skin crawling.

Causes & symptoms


Sensation is carried to the brain by neurons (nerve cells) running from the outer parts of the body to the spinal cord in bundles called nerves. In the spinal cord, these neurons make connections with other neurons that run up to the brain. Paresthesias are caused by disturbances in the function of neurons in the sensory pathway. This disturbance can occur in the central nervous system (the brain and spinal cord), the nerve roots that are attached to the spinal cord, or the peripheral nervous system (nerves outside the brain and spinal cord).

Peripheral disturbances are the most common cause of paresthesias. "Falling asleep" occurs when the blood supply to a nerve is cut off--a condition called ischemia. Ischemia usually occurs when an artery is compressed as it passes through a tightly flexed joint. Sleeping with the arms above the head or sitting with the legs tightly crossed frequently cause numbness and tingling.

Direct compression of the nerve also causes paresthesias. Compression can be short-lived, as when a heavy backpack compresses the nerves passing across the shoulders. Compression may also be chronic. Chronic nerve compression occurs in entrapment syndromes. The most common example is carpal tunnel syndrome. Carpal tunnel syndrome occurs when the median nerve is compressed as it passes through a narrow channel in the wrist. Repetitive motion or prolonged vibration can cause the lining of the channel to swell and press on the nerve. Chronic nerve root compression, or radiculopathy, can occur in disk disease or spinal arthritis.

Other causes of paresthesias related to disorders of the peripheral nerves include:

  • Metabolic or nutritional disturbances. These disturbances include diabetes, hypothyroidism (a condition caused by too little activity of the thyroid gland), alcoholism, malnutrition, and vitamin B12 deficiency.
  • Trauma. Trauma includes injuries that crush, sever, or pull on nerves.
  • Inflammation.
  • Connective tissue disease. These diseases include arthritis, systemic lupus erythematosus (a chronic inflammatory disease that affects many systems of the body, including the nervous system), polyarteritis nodosa (a vascular disease that causes widespread inflammation and ischemia of small and medium-size arteries), and Sjögren's syndrome (a disorder marked by insufficient moisture in the tear ducts, salivary glands, and other glands).
  • Toxins. Toxins include heavy metals (metallic elements such as arsenic, lead, and mercury which can, in large amounts, cause poisoning), certain antibiotics and chemotherapy agents, solvents, and overdose of pyridoxine (vitamin B6).
  • Malignancy.
  • Infections. Infections include Lyme disease, human immunodeficiency virus (HIV), and leprosy.
  • Hereditary disease. These diseases include Charcot-Marie-Tooth disease (a hereditary disorder that causes wasting of the leg muscles, resulting in malformation of the foot), porphyria (a group of inherited disorders in which there is abnormally increased production of substances called porphyrins), and Denny-Brown's syndrome (a hereditary disorder of the nerve root).

Paresthesias can also be caused by central nervous system disturbances, including stroke, TIA (transient ischemic attack), tumor, trauma, multiple sclerosis, or infection.


Sensory nerves supply or innervate particular regions of the body. Determining the distribution of symptoms is an important way to identify the nerves involved. For instance, the median nerve innervates the thumb, the first two fingers, half of the ring finger, and the part of the hand to which they connect. The ulnar nerve innervates the other half of the ring finger, the little finger, and the remainder of the hand. Distribution of symptoms may also aid diagnosis of the underlying disease. Diabetes usually causes a symmetrical "glove and stocking" distribution in the hands and feet. Multiple sclerosis may cause symptoms in several, widely separated areas.

Other symptoms may accompany paresthesias, depending on the type and severity of the nerve disturbance. For instance, weakness may accompany damage to nerves that carry both sensory and motor neurons. (Motor neurons are those that carry messages outward from the brain.)


A careful history of the patient is needed for a diagnosis of paresthesias. The medical history should focus on the onset, duration, and location of symptoms. The history may also reveal current related medical problems and recent or past exposure to drugs, toxins, infection, or trauma. The family medical history may suggest a familial disorder. A work history may reveal repetitive motion, chronic vibration, or industrial chemical exposure.

The physical and neurological examination tests for distribution of symptoms and alterations in reflexes, sensation, or strength. The distribution of symptoms may be mapped by successive stimulation over the affected area of the body.

Lab tests for paresthesia may include blood tests and urinalysis to detect metabolic or nutritional abnormalities. Other tests are used to look for specific suspected causes. Nerve conduction velocity tests, electromyography, and imaging studies of the affected area may be employed. Nerve biopsy may be indicated in selected cases.


Treatment of paresthesias depends on the underlying cause. For limbs that have "fallen asleep," restoring circulation by stretching, exercising, or massaging the affected limb can quickly dissipate the numbness and tingling. If the paresthesia is caused by a chronic disease such as diabetes or occurs as a complication of treatments such as chemotherapy, most treatments are aimed at relieving symptoms. Anti-inflammatory drugs such as aspirin or ibuprofen are recommended if symptoms are mild. In more difficult cases, antidepressant drugs such as amitriptyline (Elavil) are sometimes prescribed. These drugs are given at a much lower dosage for this purpose than for relief of depression. They are thought to help because they alter the body's perception of pain. In severe cases, opium derivatives such as codeine can be prescribed. As of 1998, trials are being done to determine whether treatment with human nerve growth factor will be effective in regenerating the damaged nerves.

Alternative treatment

Several alternative treatments are available to help relieve symptoms of paresthesia. Nutritional therapy includes supplementation with B complex vitamins, especially vitamin B12 (intramuscular injection of vitamin B12 is most effective). Vitamin supplements should be used cautiously however. Overdose of Vitamin B6 is one of the causes of paresthesias. People experiencing paresthesia should also avoid alcohol. Acupuncture and massage are said to relieve symptoms. Self-massage with aromatic oils is sometimes helpful. The application of topical ointments containing capsaicin, the substance that makes hot peppers hot, provides relief for some. It may also be helpful to wear loosely fitting shoes and clothing. None of these alternatives should be used in place of traditional therapy for the underlying condition.


Treating the underlying disorder may reduce the occurrence of paresthesias. Paresthesias resulting from damaged nerves may persist throughout or even beyond the recovery period. The overall prognosis depends on the cause.


Preventing the underlying disorder may reduce the incidence of paresthesias. For those with frequent paresthesias caused by ischemia, changes in posture may help.

Key Terms

A test that uses electrodes to record the electrical activity of muscle. The information gathered is used to diagnose neuromuscular disorders.
Motor nerve
Motor or efferent nerve cells carry impulses from the brain to muscle or organ tissue.
Nerve conduction velocity test
A test that measures the time it takes a nerve impulse to travel a specific distance over the nerve after electronic stimulation.
Nerve growth factor
A protein resembling insulin that affects growth and maintenance of nerve cells
Peripheral nervous system
The part of the nervous system that is outside the brain and spinal cord. Sensory, motor, and autonomic nerves are included.
Sensory nerves
Sensory or afferent nerves carry impulses of sensation from the periphery or outward parts of the body to the brain. Sensations include feelings, impressions, and awareness of the state of the body.

Further Reading

For Your Information


  • Bradley, Walter G., et al., eds. Neurology in Clinical Practice. 2nd ed. Boston: Butterworth-Heinemann, 1996.


  • McKnight, Jerry T. and Bobbi B. Adcock. "Paresthesias: A Practical Diagnostic Approach." American Family Physician 56(December 1997): 2253-2260.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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