Madisons Foundation - Moms And Dads In Search Of Needed Support
Monday, 19 July 2004
Sunday, 28 November 2004
Charcot Marie Tooth Disorder, Hereditary Sensory Motor Neuropathy, Dejerine-Sottas Disease
Charcot Marie Tooth Disease (CMT) is an inherited disease of the peripheral nerves, the nerves that run from the spinal cord to tissues.. The nerves of the legs and feet are most commonly affected, while the hands and face are rarely involved. CMT is also known as Hereditary Sensory and Motor Neuropathy (HSMN) and is divided into three major types: CMT type 1, CMT type 2, and CMT type 3 (also known as Dejerine-Sottas disease). The less common types of CMT include CMT type 4 and X-linked CMT.
Charcot Marie Tooth Disease is the most common inherited disorder of the peripheral nervous system, which consists of all the nerves outside of the brain and the spinal cord. Of the different types, CMT type 1A is the most common form, found in 50% of patients with CMT. Type 2 is the second most common form, found in 20-40% of CMT patients. X-linked CMT makes up the remaining 10-20% of patients with CMT.
CMT types 1, 2, and 3 are transmitted in an autosomal dominant fashion, meaning that if one parent has the disease or the gene for the disease, his or her child has a 50% chance of having the disease as well. Other forms of CMT may be transmitted in either an autosomal recessive fashion (CMT type 4), or in an X-linked fashion. In autosomal recessive inheritance, parents are not usually affected, but both parents carry the gene. If the child inherits a copy from each parent, the child will have the disease. There is about a 25% chance of this happening with every pregnancy. In X-linked CMT, the mother has the gene on one of her X chromosomes, and about 50% of her children will be affected, though boys are more severely affected than girls.
CMT affects 1 in 2500 individuals, with males exhibiting the disorder three times more frequently than females. All ethnic groups are affected, though some types of CMT type 4 have been described in certain ethnic groups. Ten to twenty percent of the people who have inherited the abnormal gene or genes from their parents will not have any symptoms. Those people who develop symptoms usually display them by age thirty, though occasionally people do not have symptoms until even later. People with CMT type 3 (formerly known as Dejerine-Sottas disease) usually develop symptoms in early infancy and have more severe disease than those with CMT type 1.
Signs and Symptoms
In CMT, the signs and symptoms develop gradually and may be very subtle at first. The progression of disease lasts many years, often with long periods of stability.
• Difficulty with running, jumping, and participating in organized sports
• Frequent ankle sprains, frequent trips or falls
• Cramps or muscle twitching (fasciculations) after exercise
• Muscle weakness in the legs and feet
• Numbness of the lower extremities, and occasionally the hands and forearms
• Loss of sensation in the lower extremities
• Shrinking (atrophy) of the muscles in the feet and legs. Wasting of the muscles lead to the excessive elevation of the knees when walking because the muscles are too weak to lift the foot off the ground. This action is termed steppage gait. After lifting the foot via lifting the knees, the toes hit the ground first instead of the heel and this phenomenon is named foot drop.
• Bumps along the nerves in 25% of patients with CMT type 1 and 3. These bumps can also be found in patients with type 4 or X-linked disease. The bumps are caused by increased growth, or hypertrophy, of the nerves when the body attempts to repair the damaged nerves. They are often felt where the nerves are close to the skin, such as the sides of the knees and elbows, and behind the ear. Foot deformities can be high arches (pes cavus), and flexed toes (“hammer toes”) in two thirds of patients. Some patients develop flat feet (pes planus)
• Scoliosis, i.e. abnormal curvature of the spine
• Kyphosis, i.e. abnormal curvature of the spine leading to too much forward arch in the upper back.
Less common signs:
• Paralysis of the vocal cords, which may lead to hoarseness of voice or trouble breathing
• Deafness (CMT type 1 and X-linked)
• Involvement of the hand muscles leading to abnormally clenched hands and difficulty with tasks like writing, buttoning, opening doors, etc.
• Blindness (in X-linked CMT)
• Heart block – the electrical signals synchronize the heart to beat properly, and those signals can be blocked. As a result, the heart rate may decline, in which case the patient may require placement of a pacemaker, a machine that regulates the heart rate.
The peripheral nerves of the body consist of sensory, motor, and autonomic nerves, all of which may be damaged in CMT. Sensory nerves carry signals of touch, temperature, pain, texture, etc. to the spinal cord, which then transmits the signals to the brain. Motor nerves receive commands from the brain via the spinal cord to control muscle movements. Autonomic nerves receive commands from the brain via the spinal cord to regulate the smooth muscles, which can be found in the blood vessels, intestines, and urinary bladder, etc. These nerves also control the sweat glands. Charcot Marie Tooth Disease types 1 and 3 are caused by demyelination, o r the loss of the protective sheaths that surround the peripheral nerves. In CMT type 1A and 3A, the abnormal gene produces a defective protein called peripheral myelin protein 22 (PMP22) that normally helps fold the protective myelin sheath. Without the myelin sheath, the nerves cannot conduct electrical signals properly, which leads to the lack of sensation or motor function. The other subtypes of type 1 and 3 lead to the same problem but through slightly different proteins.
Charcot Marie Tooth Disease type 2 is caused by the destruction or degeneration of the nerve endings, also known as axonopathy. Type 2 CMT does not have overgrowth of the Schwann cells and the myelin sheaths are normal. Several of the protein products of the abnormal genes have been characterized, but most are still under research and tests are not yet available.
The rare forms of Charcot Marie Tooth Disease, type 4 and X-linked, often have combined demyelination or axonopathy. X-linked CMT also has a variable presentation and may resemble types 1 or 2, with boys more severely affected than girls. Boys often will demonstrate disease similar to type 1 CMT, and girls will often be asymptomatic or be very mildly affected.
Charcot Marie Tooth can be diagnosed by the history and physical examination conducted by your doctor. Usually patients will present with symptoms of weakness of the lower extremities, a history of difficulty with coordination in physical activities (trips, falls, sprains), or loss of sensation in the feet. A family history may reveal other members of multiple generations with neurological deficits, perhaps some who require physical therapy, crutches, or braces.
A diagnosis can be made with a combination of a nerve conduction velocity (NCV) study and a nerve biopsy. The NCV test assesses the speed with which the nerves transmit signals. Types 1, 3, and often type 4 also, have malformed myelin sheaths, which slows down the nerve’s signal conduction speed. The NCV is not affected in CMT type 2 because the myelin sheath is normal and allows for rapid signal conduction down the nerves. Electromyography (EMG) can test the muscles to determine the cause of the weakness of the muscle. Nerve biopsy consists of taking a sample of a peripheral nerve, usually the sural nerve located in the calf. The biopsy will help identify whether the myelin or the axon is affected, and so help classify the disease.
Genetic testing (obtained by a blood sample) exists for CMT type 1A, 1B, and X-linked CMT. The testing for other CMT types is sometimes available from research laboratories.
Treatment is mainly supportive. Patients are referred to physical and occupational therapy to facilitate muscle strengthening and endurance. Exercise is very important to preserve function, mobility, and promote weight maintenance or weight loss. Bracing of the affected extremities is important to minimize deformities of the limbs, improve mobility, and prevent accidental trauma. Those with mild disease should wear shoes with good ankle support. Patients with more significant disease may need orthotic braces. Orthopedic surgery consultations can help with bracing (orthotics: knee, leg, ankle, and foot braces, shoe inserts, etc.) and surgical correction of deformities to improve mobility. Crutches and wheelchairs may be necessary for some patients. Genetic counseling and disease education are vital in the management of Charcot Marie Tooth Disease. Pain medications can support patients with neuropathic pain, which results from damaged nerves. All CMT patients should also avoid drugs that may further injure the peripheral nerves. For example, isoniazid for tuberculosis, and nitrofuratoin for urinary infections are some drugs that may be harmful to peripheral nerves. Although there is no cure for patients with Charcot Marie Tooth disease currently, most patients maintain an active and relatively healthy lifestyle with minor disabilities.
The prognosis varies depending on the type of CMT. CMT does not affect a person’s intelligence, memory, or life expectancy. People with Charcot Marie Tooth become or remain fully functioning adults. A person affected by CMT type 1 has minimal to mild disabilities. Most people only require physical therapy, occupational therapy, and braces to help them move around. Approximately 5% of the people affected by CMT type 1 become dependent on a wheelchair. Type 2 disease is in general much milder than type 1. Dejerine Sottas disease is the most severe form of CMT and symptoms generally present in infancy. These children may not be able to develop the muscle strength to walk, thus may become wheelchair bound and require a high level of care.
Connect with other parents
In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.
Hereditary Neuropathy Foundation
Good source of updates on research, support groups, frequently asked questions, and links to fundraising events and activities.
Charcot Marie Tooth Association (CMTA)
Great website for parents, has basic information on CMT, great support reference site, link to the North American Database operated out of Wayne State University, and news updates on research and medical alerts
Jack Miller Center for Peripheral Neuropathy
Comprehensive site about all peripheral neuropathies, has newsletter, glossary, and list of treatment modalities.
National Institute of Neurological Disorders and Stroke
Comprehensive site about CMT, with other links to web sites to provide updated information and research.
De Girolami U, Anthony DC, Frosch MP (1999). Peripheral nerve and skeletal muscle. In Cotran RS, Kumar V, Collins T, Robbins, SL. (eds) Robbins Pathologic Basis of Disease, 6th ed. WB Saunders and Co, p 1277-1278.
Griffin JW (2000). Hereditary neuropathies. In Cecil RL, Goldman L, Bennett JC (eds) Cecil Textbook of Medicine, 21st ed. WB Saunders and Co, p 2196-2197.
Mercier, LR (2004). Charcot-marie-Tooth disease (PTG), Ferri’s Clinical Advisor: Instant diagnosis and treatment, Mosby, p 202.
Siddique N, Sufit R, Siddique T. (2003). Degenerative neuropathies: hereditary sensory and motor neuropathies. In Goetz CG, Pappert EJ, Schmitt B (eds) Textbook of Clinical Neurology, 2nd ed. Elsevier, p 777-779.