Genetic testing

Genetic testing involves taking a sample of your blood and testing it for the defective genes that are known to cause CMT. As not all of the genes involved in CMT have been identified, there is a chance that the test will be inconclusive.

X-linked

In X-linked inheritance, the mutated gene is located on the 'x' chromosome, and is passed from a mother to her son.

Men have 'x-y' sex chromosomes, and they receive the 'x' chromosome from their mother, and the 'y' chromosome from their father. Women have 'x-x' sex chromosomes, and they receive one 'x' chromosome from their mother and the other 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 affect of the defective one. However, there is a 50% chance that 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 the condition.

How the periphery nerves work

In order to understand the causes of Charcot-Marie-Tooth disease (CMT) it is useful to first understand how the periphery nerves work.

A periphery nerve is much like an electrical cable which is made of two parts - the axon and the myelin sheath.

* The axon - is like the wiring in an electrical cable. It is the part of the nerve that transmits the electrical information between the brain and your limbs.
* The myelin sheath - acts like the insulation of an electrical cable. It is wrapped around the axon, protecting it, and it also ensures that the electrical signal does not get broken up.

Different types of CMT (see below) can damage both of these functions. In some types of CMT, faulty genes cause the myelin sheath to disintegrate. Without the protection of the myelin sheath, the axons become damaged and the muscles and senses no longer receive the proper messages from the brain. This leads to the symptoms of muscle weakness and numbness.

In other types of CMT, it is the axons which are directly affected. Due to faulty genes, the axons do not transmit the electrical signals at the proper strength, so that the muscles and senses are under-stimulated. Again, this leads to symptoms of muscle weakness and numbness.

Types of CMT

CMT 1

CMT 1 is caused by defective genes that are involved in the production of the myelin sheath. The defects cause the myelin sheath to slowly break down. CMT 1 is the most common type of CMT, accounting for around 35% of cases.

CMT 2

CMT 2 is caused be defects in the axon. It is less common than CMT 1, accounting for around 17% of cases.

CMT 3

CMT 3, also known as Dejerine-Sottas disease, is a rare and severe type of CMT that affects the myelin sheath. It is characterised by extreme muscle weakness and sensory problems. Unlike many other types of CMT, the symptoms normally begin in early childhood.

CMT 4

CMT 4 is another rare type of CMT that also affects the myelin sheath. The exact genes that cause CMT 4 have not yet been identified, but it is thought that several different genetic processes may be involved. As with CMT 3, the symptoms of CMT 4 usually begin in childhood, and many people with the condition are unable to walk.

CMT X

CMT X is a type of CMT that is caused by a mutation in the 'x' chromosome, which is one of the chromosomes that determine what sex you are. CMT X is more common in men than women, and it is estimated to account for around 10% of CMT cases.

Plantar fascia release

Plantar fascia release is a surgical procedure that is used to relieve persistent heel pain that is caused by inflamed tendons. Part of the tendon is removed and the remaining tendon is repositioned and allowed to heal.

You will need to wear a cast for three weeks and will not be able to place any weight on your feet during this time.

Arthrodesis

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

After surgery, your foot (or feet) will be placed in a cast and you will not be able to place any weight on them for six weeks. You will need to use crutches, or a wheelchair.

Once you are able to place weight on your feet, the cast will need to be kept on for another six weeks (12 weeks in total). Full recovery from the operation may take up to 10 months.

Osteotomy

An osteotomy is a surgical procedure that is used to correct severe flatness of the feet. A cut is made in your foot and the surgeon then removes, or repositions, the bones in your foot in order to correct its shape.

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

Surgery

If CMT causes significant deformities in your feet, which cause you pain, surgery may be required to correct them. There are three main surgical techniques that are used to correct deformities. They are:

* osteotomy,
* arthodesis, and
* plantar fascia release.

Charcot-Marie-Tooth disease and sleep apnoea syndrome: a family study.

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a genetically heterogeneous group of hereditary motor and sensory polyneuropathies in which sleep apnoea has rarely been reported and no causal relation shown. We looked for an association between the most common subtype of CMT disease (CMT1A) and sleep apnoea syndrome. METHODS: Having diagnosed sleep apnoea and CMT in one family member (index case), we prospectively investigated 13 further members not previously suspected of having neuropathy or apnoeas. All had a neurological examination, electroneuromyography, polysomnography, and genetic testing for CMT disease. FINDINGS: 11 of the 14 family members had the autosomal dominant demyelinating form of CMT disease with PMP22 gene duplication on chromosome 17. Whatever their neurological disability, all 11 individuals had sleep apnoea syndrome with a mean (SD) apnoea-hypopnoea index of 46.6/h (28.5) of sleep (normal value <15/h). The remaining three family members were free from neuropathy and sleep apnoea syndrome. Sleep apnoea and neuropathy severity were highly correlated; the compound muscle action potential (CMAP) amplitude of the median nerve was inversely correlated with the apnoea-hypopnoea index (r=-0.69, p=0.029). The severity of neuropathy and sleep apnoea were higher in male CMT individuals and were correlated with age and body mass index. No wake or sleep diaphragmatic dysfunction was shown. INTERPRETATION: We think that sleep apnoea syndrome is related to a pharyngeal neuropathy. Upper airway dysfunction, previously described in the CMT2C subtype, might be a clinical expression of the CMT1A subtype, to which familial susceptibility could predispose.

A New Variant of Charcot-Marie-Tooth Disease Type 2

Charcot-Marie-Tooth (CMT) disease is the most common inherited motor and sensory neuropathy. The axonal form of the disease is designated as “CMT type 2” (CMT2). Although four loci known to be implicated in autosomal dominant CMT2 have been mapped thus far (on 1p35-p36, 3q13.1, 3q13-q22, and 7p14), no one causative gene is yet known. A large Russian family with CMT2 was found in the Mordovian Republic (Russia). Affected members had the typical CMT2 phenotype. Additionally, several patients suffered from hyperkeratosis, although the association, if any, between the two disorders is not clear. Linkage with the CMT loci already known (CMT1A, CMT1B, CMT2A, CMT2B, CMT2D, and a number of other CMT-related loci) was excluded. Genomewide screening pinpointed the disease locus in this family to chromosome 8p21, within a 16-cM interval between markers D8S136 and D8S1769. A maximum two-point LOD score of 5.93 was yielded by a microsatellite from the 5′ region of the neurofilament-light gene (NF-L). Neurofilament proteins play an important role in axonal structure and are implicated in several neuronal disorders. Screening of affected family members for mutations in the NF-L gene and in the tightly linked neurofilament-medium gene (NF-M) revealed the only DNA alteration linked with the disease: a A998C transversion in the first exon of NF-L, which converts a conserved Gln333 amino acid to proline. This alteration was not found in 180 normal chromosomes. Twenty unrelated CMT2 patients, as well as 26 others with an undetermined form of CMT, also were screened for mutations in NF-L, but no additional mutations were found. It is suggested that Gln333Pro represents a rare disease-causing mutation, which results in the CMT2 phenotype.

Gene Discovery Opens Door to Further Research In Inherited Neurological Disorders

BETHESDA, MD., April 28, 2003 - Scientists at the National Human Genome Research Institute (NHGRI) and at the National Institute of Neurological Disorders and Stroke (NINDS) have identified the gene responsible for two related, inherited neurological disorders, and have, for the first time, directly implicated this gene and its enzyme product in a human genetic disease.

The discovery supports further investigation of this gene family for additional neurological disease genes, research that may shed light on a range of disorders, including carpal tunnel syndrome, which affects the hands and the wrists, and the fatal degenerative disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.

NHGRI and NINDS scientists, working together at the National Institutes of Health (NIH), found the gene responsible for Charcot-Marie-Tooth (CMT) disease type 2D and distal spinal muscular atrophy (dSMA) type V. The gene, called GARS-the glycyl tRNA synthetase gene-is located on chromosome 7 and encodes, or provides the instructions to make, one of the aminoacyl tRNA synthetases, a family of enzymes vital to the cell's ability to build proteins.

"The identification of the defective gene on chromosome 7 responsible for a type of Charcot-Marie-Tooth disease provides another vivid example of how the recently completed human genome sequence is accelerating studies in human genetics," said Francis S. Collins, M.D., Ph.D., director of NHGRI. "With this discovery, we now know that the GARS gene-whose function is so fundamental to biological processes-can be mutated in a fashion that results in a highly discrete neurological disease."

The study, a collaboration between the laboratories of Eric Green, M.D., Ph.D., at NHGRI, Kenneth Fischbeck, M.D., at NINDS, and Lev Goldfarb, M.D., also at NINDS, will be available online [ncbi.nlm.nih.gov] in April and published in the May issue of the American Journal of Human Genetics. Lead author Anthony Antonellis, a graduate student in Dr. Green's laboratory, directed the project.

The scientists identified four disease-related mutations and speculate that a mutated copy of GARS leads to a reduction in the activity of the gene's enzyme product. More research into why this disruption produces the specific symptoms of CMT type 2D and dSMA type V will be necessary.

"Identifying this chromosome 7 disease gene at this particular time was especially gratifying in light of the recent completion of a finished sequence of this chromosome," said Dr. Green, who is the Scientific Director of NHGRI and chief of its Genome Technology Branch. Dr. Green also directs the NIH Intramural Sequencing Center. His laboratory has been involved in mapping and sequencing chromosome 7 as part of the Human Genome Project.

"This discovery is another piece of a jigsaw puzzle picture of how peripheral nerve diseases and motor neuron diseases happen," said Dr. Fischbeck, chief of the Neurogenetics Branch at NINDS. Dr. Fischbeck's laboratory studies hereditary motor neuron diseases and peripheral neuropathies. "It provides a more complete view of the mechanism of these diseases. This will hopefully lead to new treatment approaches. The more complete the picture, the more we know how to intervene."

Charcot-Marie-Tooth disease, named after the three physicians who first reported it in 1886, is a group of genetic diseases that causes muscle weakness and wasting, or atrophy, in the feet, legs, hands, and forearms, as well as diminished sensation in the limbs. CMT disease affects the peripheral nerves-the nerves that travel to the muscles of the limbs-and is therefore known as a peripheral neuropathy. Estimated to affect one in 2,500 individuals, it is the most common inherited neurological disorder.

Some forms of CMT disease are autosomal dominant, meaning that a person needs to inherit only one defective copy of the responsible gene to acquire the disease. Other forms are autosomal recessive, meaning both copies of the gene must be defective to result in illness. There is also a form of CMT that is X-linked, meaning that the responsible gene is located on the X chromosome, one of the two sex chromosomes.

In most cases, CMT disease begins with mild symptoms, typically foot and ankle weakness and fatigue. As atrophy progresses, the patient develops a distinct walk, a consequence of muscle weakness in the front of the leg: the feet slap with each step and the body may sway from side to side. Eventually the toes and the fingers curl due to weakness and atrophy in the small muscles of the feet and the hands. Writing and other functions of the hands become difficult. The sensory loss that accompanies the atrophy diminishes the patient's ability to distinguish between hot and cold and affects the patient's sense of touch.

People with CMT disease usually begin to experience symptoms in adolescence or early adulthood. There is no cure for the disease, but there are treatment options, including physical therapy and bracing. Life expectancy is usually normal.

CMT disease can be divided into two classes, depending on where the dysfunction occurs in the peripheral nerves. In CMT type 1, the peripheral nerves' axons-the part of the nerve cell that transmits electrical signals to the muscles-lose their protective outer coverings, their myelin sheaths. This disrupts the axons' function. In CMT type 2, the axons' responses are diminished due to a defect within the axons themselves.

CMT type 2, the less common of the two classes, can be further separated into at least six subtypes, caused by defects in different genes. The GARS gene is implicated in CMT type 2D, a form of CMT that primarily affects the hands and the forearms. CMT type 2D is inherited in an autosomal dominant fashion.

Spinal muscular atrophy (SMA) refers to a group of genetic diseases more diverse than those of CMT. SMA is characterized by weakness and wasting of the muscles of the limbs, but the types vary greatly in severity. Most common are autosomal recessive childhood-onset forms that may be fatal. Other types of SMA are inherited in an autosomal dominant fashion. All types of SMA are due to the degeneration of nerve cells within the spinal cord, as opposed to degeneration of the peripheral nerves.

Distal spinal muscular atrophy (dSMA) disease is a type of SMA that affects the hands and the feet. The GARS gene is implicated in dSMA type V. Its symptoms of muscle weakness and atrophy in the hands and the forearms mirror those of CMT type 2D, except that people with dSMA type V do not experience sensory loss. dSMA type V is also an autosomal dominant genetic disorder, like CMT type 2D.

Even though the GARS gene is implicated in only two specific types of CMT and SMA, this discovery will guide researchers in studying other forms of these diseases, as well as other neurological disorders. Because carpal tunnel syndrome affects the hands and the forearms, scientists may now investigate whether the GARS gene plays some role in this disorder. And two defective forms of the gene implicated in Lou Gehrig's disease are known to interact with a GARS family member.

Ultimately, the GARS gene and its family may provide a rich new resource for scientists investigating inherited and non-inherited neurological diseases.

"The next step is to explore what it is about motor nerve cells that make them particularly vulnerable to mutations in these genes," said Dr. Fischbeck.

NHGRI is one of the 27 institutes and centers at the National Institutes of Health, which is an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information about NHGRI can be found at its Web site: www.genome.gov.

What do we know about Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) is an inherited neurological disease characterized by a slowly progressive degeneration of the muscles in the foot, lower leg, hand, and forearm, and a mild loss of sensation in the limbs, fingers, and toes. The first sign of CMT is generally a high arched foot or gait disturbances.

Other symptoms of the disorder may include foot-bone abnormalities such as high arches and hammer toes, problems with hand function and balance, occasional lower leg and forearm muscle cramping, loss of some normal reflexes, occasional partial sight and/or hearing loss, and, in some individuals, scoliosis (curvature of the spine).

People with CMT disease usually begin to experience symptoms in adolescence or early adulthood. There is no cure for the disease, but there are treatment options, including physical therapy and bracing. Life expectancy is usually normal.

CMT disease can be divided into two classes, depending on where the dysfunction occurs in the peripheral nerves:

* In CMT type 1, the peripheral nerves' axons - the part of the nerve cell that transmits electrical signals to the muscles - lose their protective outer coverings, their myelin sheaths. This disrupts the axons' function.

* In CMT type 2, the axons' responses are diminished due to a defect within the axons themselves. CMT type 2, the less common of the two classes, can be further separated into at least six subtypes, caused by defects in different genes.

The NINDS supports research on CMT and other peripheral neuropathies in an effort to learn how to better treat, prevent, and even cure these disorders. Ongoing research includes efforts to identify more of the mutant genes and proteins that cause the various disease subtypes, efforts to discover the mechanisms of nerve degeneration and muscle atrophy with the hope of developing interventions to stop or slow down these debilitating processes, and efforts to find therapies to reverse nerve degeneration and muscle atrophy.

One promising area of research involves gene therapy experiments. Research with cell cultures and animal models has shown that it is possible to deliver genes to Schwann cells and muscle. Another area of research involves the use of trophic factors or nerve growth factors, such as the hormone androgen, to prevent nerve degeneration.

How is Charcot-Marie-Tooth disease treated

There is no cure for CMT, but physical therapy, occupational therapy, braces and other orthopedic devices, and even orthopedic surgery can help patients cope with the disabling symptoms of the disease. In addition, pain-killing drugs can be prescribed for patients who have severe pain.

Physical and occupational therapy, the preferred treatment for CMT, involves muscle strength training, muscle and ligament stretching, stamina training, and moderate aerobic exercise. Most therapists recommend a specialized treatment program designed with the approval of the patient's physician to fit individual abilities and needs. Therapists also suggest entering into a treatment program early; muscle strengthening may delay or reduce muscle atrophy, so strength training is most useful if it begins before nerve degeneration and muscle weakness progress to the point of disability.

Stretching may prevent or reduce joint deformities that result from uneven muscle pull on bones. Exercises to help build stamina or increase endurance will help prevent the fatigue that results from performing everyday activities that require strength and mobility. Moderate aerobic activity can help to maintain cardiovascular fitness and overall health. Most therapists recommend low-impact or no-impact exercises, such as biking or swimming, rather than activities such as walking or jogging, which may put stress on fragile muscles and joints.

Many CMT patients require ankle braces and other orthopedic devices to maintain everyday mobility and prevent injury. Ankle braces can help prevent ankle sprains by providing support and stability during activities such as walking or climbing stairs. High-top shoes or boots can also give the patient support for weak ankles. Thumb splints can help with hand weakness and loss of fine motor skills. Assistive devices should be used before disability sets in because the devices may prevent muscle strain and reduce muscle weakening. Some CMT patients may decide to have orthopedic surgery to reverse foot and joint deformities.

How is Charcot-Marie-Tooth disease diagnosed

Diagnosis of CMT begins with a standard patient history, family history, and neurological examination. Patients will be asked about the nature and duration of their symptoms and whether other family members have the disease. During the neurological examination a physician will look for evidence of muscle weakness in the arms, legs, hands, and feet, decreased muscle bulk, reduced tendon reflexes, and sensory loss. Doctors look for evidence of foot deformities, such as high arches, hammertoes, inverted heel, or flat feet. Other orthopedic problems, such as mild scoliosis or hip dysplasia, may also be present. A specific sign that may be found in patients with CMT1 is nerve enlargement that may be felt or even seen through the skin. These enlarged nerves, called hypertrophic nerves, are caused by abnormally thickened myelin sheaths.

If CMT is suspected, the physician may order electrodiagnostic tests for the patient. This testing consists of two parts: nerve conduction studies and electromyography (EMG). During nerve conduction studies, electrodes are placed on the skin over a peripheral motor or sensory nerve. These electrodes produce a small electric shock that may cause mild discomfort. This electrical impulse stimulates sensory and motor nerves and provides quantifiable information that the doctor can use to arrive at a diagnosis. EMG involves inserting a needle electrode through the skin to measure the bioelectrical activity of muscles. Specific abnormalities in the readings signify axon degeneration. EMG may be useful in further characterizing the distribution and severity of peripheral nerve involvement.

If all other tests seem to suggest that a patient has CMT, a neurologist may perform a nerve biopsy to confirm the diagnosis. A nerve biopsy involves removing a small piece of peripheral nerve through an incision in the skin. This is most often done by removing a piece of the nerve that runs down the calf of the leg. The nerve is then examined under a microscope. Patients with CMT1 typically show signs of abnormal myelination. Specifically, "onion bulb" formations may be seen which represent axons surrounded by layers of demyelinating and remyelinating Schwann cells. Patients with CMT2 usually show signs of axon degeneration.

Genetic testing is available for some types of CMT and may soon be available for other types; such testing can be used to confirm a diagnosis. In addition, genetic counseling is available to parents who fear that they may pass mutant genes to their children.

What causes Charcot-Marie-Tooth disease

A nerve cell communicates information to distant targets by sending electrical signals down a long, thin part of the cell called the axon. In order to increase the speed at which these electrical signals travel, the axon is insulated by myelin, which is produced by another type of cell called the Schwann cell. Myelin twists around the axon like a jelly-roll cake and prevents dissipation of the electrical signals. Without an intact axon and myelin sheath, peripheral nerve cells are unable to activate target muscles or relay sensory information from the limbs back to the brain.

CMT is caused by mutations in genes that produce proteins involved in the structure and function of either the peripheral nerve axon or the myelin sheath. Although different proteins are abnormal in different forms of CMT disease, all of the mutations affect the normal function of the peripheral nerves. Consequently, these nerves slowly degenerate and lose the ability to communicate with their distant targets. The degeneration of motor nerves results in muscle weakness and atrophy in the extremities (arms, legs, hands, or feet), and in some cases the degeneration of sensory nerves results in a reduced ability to feel heat, cold, and pain.

The gene mutations in CMT disease are usually inherited. Each of us normally possesses two copies of every gene, one inherited from each parent. Some forms of CMT are inherited in an autosomal dominant fashion, which means that only one copy of the abnormal gene is needed to cause the disease. Other forms of CMT are inherited in an autosomal recessive fashion, which means that both copies of the abnormal gene must be present to cause the disease. Still other forms of CMT are inherited in an X-linked fashion, which means that the abnormal gene is located on the X chromosome. The X and Y chromosomes determine an individual's sex. Individuals with two X chromosomes are female and individuals with one X and one Y chromosome are male. In rare cases the gene mutation causing CMT disease is a new mutation which occurs spontaneously in the patient's genetic material and has not been passed down through the family.

What are the types of Charcot-Marie-Tooth disease

There are many forms of CMT disease, including CMT1, CMT2, CMT3, CMT4, and CMTX. CMT1, caused by abnormalities in the myelin sheath, has three main types. CMT1A is an autosomal dominant disease resulting from a duplication of the gene on chromosome 17 that carries the instructions for producing the peripheral myelin protein-22 (PMP-22). The PMP-22 protein is a critical component of the myelin sheath. An overabundance of this gene causes the structure and function of the myelin sheath to be abnormal. Patients experience weakness and atrophy of the muscles of the lower legs beginning in adolescence; later they experience hand weakness and sensory loss. Interestingly, a different neuropathy distinct from CMT1A called hereditary neuropathy with predisposition to pressure palsy (HNPP) is caused by a deletion of one of the PMP-22 genes. In this case, abnormally low levels of the PMP-22 gene result in episodic, recurrent demyelinating neuropathy. CMT1B is an autosomal dominant disease caused by mutations in the gene that carries the instructions for manufacturing the myelin protein zero (P0), which is another critical component of the myelin sheath. Most of these mutations are point mutations, meaning a mistake occurs in only one letter of the DNA genetic code. To date, scientists have identified more than 30 different point mutations in the P0 gene. As a result of abnormalities in P0, CMT1B produces symptoms similar to those found in CMT1A. The gene defect that causes CMT1C, which also has symptoms similar to those found in CMT1A, has not yet been identified.

CMT2 results from abnormalities in the axon of the peripheral nerve cell rather than the myelin sheath. There are many subtypes of CMT2, designated by the letters from A-L. Each subtype is characterized by the mode of inheritance and associated clinical features. The genetic loci have been identified for some subtypes. Recently, a mutation was identified in the gene that codes for the kinesin family member 1B-beta protein in families with CMT2A. Kinesins are proteins that act as motors to help power the transport of materials along the train tracks (microtubules) of the cell. Another recent finding is a mutation in the neurofilament-light gene, identified in a Russian family with CMT2E. Neurofilaments are structural proteins that help maintain the normal shape of a cell.

CMT3 or Dejerine-Sottas disease is a severe demyelinating neuropathy that begins in infancy. Infants have severe muscle atrophy, weakness, and sensory problems. This rare disorder can be caused by a specific point mutation in the P0 gene or a point mutation in the PMP-22 gene.

CMT4 comprises several different subtypes of autosomal recessive demyelinating motor and sensory neuropathies. Each neuropathy subtype is caused by a different genetic mutation, may affect a particular ethnic population, and produces distinct physiologic or clinical characteristics. Patients with CMT4 generally develop symptoms of leg weakness in childhood and by adolescence they may not be able to walk. The gene abnormalities responsible for CMT4 have yet to be identified.

CMTX is an X-linked dominant disease and is caused by a point mutation in the connexin-32 gene on the X chromosome. The connexin-32 protein is expressed in Schwann cells-cells that wrap around nerve axons, making up a single segment of the myelin sheath. This protein may be involved in Schwann cell communication with the axon. Males who inherit one mutated gene from their mothers show moderate to severe symptoms of the disease beginning in late childhood or adolescence (the Y chromosome that males inherit from their fathers does not have the connexin-32 gene). Females who inherit one mutated gene from one parent and one normal gene from the other parent may develop mild symptoms in adolescence or later or may not develop symptoms of the disease at all.

What are the symptoms of Charcot-Marie-Tooth disease

The neuropathy of CMT affects both motor and sensory nerves. A typical feature includes weakness of the foot and lower leg muscles, which may result in foot drop and a high-stepped gait with frequent tripping or falls. Foot deformities, such as high arches and hammertoes (a condition in which the middle joint of a toe bends upwards) are also characteristic due to weakness of the small muscles in the feet. In addition, the lower legs may take on an "inverted champagne bottle" appearance due to the loss of muscle bulk. Later in the disease, weakness and muscle atrophy may occur in the hands, resulting in difficulty with fine motor skills.

Onset of symptoms is most often in adolescence or early adulthood, however presentation may be delayed until mid-adulthood. The severity of symptoms is quite variable in different patients and even among family members with the disease. Progression of symptoms is gradual. Pain can range from mild to severe, and some patients may need to rely on foot or leg braces or other orthopedic devices to maintain mobility. Although in rare cases patients may have respiratory muscle weakness, CMT is not considered a fatal disease and people with most forms of CMT have a normal life expectancy.

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their life style,the way the people treat them and many more.

WHAT IS CHARCOT MARIE TOOTH DISEASE

This inherited neurolomuscular syndrome was discovered by three European doctors, Jean Charcot, Pierre Marie and Howard Tooth in the late eighteen hundreds. Their surnames are represented in the disease name, and this often misleads and confuses the general public because it does not reflect or explain the nature of the disease itself. CMT is considered to be the most commonly inherited form of peripheral neuropathy affecting approximately one in 2,500 adults.
CMT is diagnosed by clinical features of muscle atrophy, age of onset, electromyography (EMG), nerve biopsy and through genetic testing.

Charcot-Marie-Tooth disease (CMT) is a hereditary motor-sensory neuropathy (HMSN). HMSNs are a group of progressive neurological disorders that affect the motor and sensory units of the peripheral nervous system. CMT causes weakness because the nerve signals are impaired (demyelinated) before they reach the muscle. Over time this causes atrophy (a loss of muscle strength) in various areas of the body such as the feet, legs, hands, and diaphragm.

Although considered a "family disease", people are commonly affected differently. To date there is no known cure or treatment to arrest levels or rates of progression.