Charcot-Marie-Tooth disease ( CMT ) is one of the hereditary motor and sensory neuropathies, a group of congenital disorders derived from the peripheral nervous system characterized by progressive muscle loss. tissue and touch sensation in various parts of the body. Currently incurable, it is the most commonly inherited neurological disorder, affecting about one in 2,500 people. CMT was previously classified as a subtype of muscular dystrophy.
Video Charcot-Marie-Tooth disease
Signs and symptoms
CMT symptoms usually begin in early childhood or early adulthood, but may begin later. Some people do not experience symptoms until the early 30s or 40s. Usually, the initial symptoms are the fall of the foot at the beginning of the course of the disease. This can also cause a hammer leg, where the toes always roll up. Wasting muscle tissue on the bottom of the foot can cause the appearance of "stork legs" or "bottles of reverse champagne". Weakness in the hands and forearms occur in many people as the disease develops.
The loss of touch sensation in the feet, ankles, and feet, as well as in the hands, wrists, and arms occurs with various types of diseases. Early and late forms appear with painful 'on and off' spasmodic contractions that can be paralyzing when the disease is active. Tall curved legs (pes cavus) or flat curved legs (pes planus) are classically associated with the disorder. The sensory and proprioceptive nerves in the hands and feet are often damaged, while the unelorinable nerve pain is left intact. Overuse of affected hands or limbs may activate symptoms including numbness, seizures, and painful cramps.
The symptoms and progression of the disease may vary. Grinding teeth and squinting are common, and often undetectable by affected people. Breathing can be affected in some people, such as hearing, sight, and neck and shoulder muscles. Scoliosis often occurs, causing a blow and loss of height. The hip socket may be incorrectly formatted. Gastrointestinal problems can be part of the CMT, such as difficulty chewing, swallowing, and talking (due to atrophy of the vocal cords). Tremors can develop as a waste of muscles. Pregnancy has been known to aggravate CMT, as well as severe emotional stress. Patients with CMT should avoid prolonged periods of immobility such as when recovering from secondary injury, as prolonged periods of limited mobility can drastically accelerate CMT symptoms.
Pain due to postural changes, bone deformation, muscle fatigue, and cramps are quite common in people with CMT. These can be reduced or treated with physical therapy, surgery, and corrective devices or assistive devices. Analgesic drugs may also be needed if other therapies do not provide relief from pain. Neuropathic pain is often a symptom of CMT, although, like other CMT symptoms, its presence and severity vary from case to case. For some people, the pain can be significant to severe and disrupt the activities of everyday life. However, the pain is not experienced by everyone with CMT. When neuropathic pain is present as a symptom of CMT, it is comparable to that seen in other peripheral neuropathies, as well as postherpetic neuralgia and complex regional pain syndromes, among other diseases.
Maps Charcot-Marie-Tooth disease
Cause
Charcot-Marie-Tooth disease is caused by mutations that cause defects in neuronal proteins. The nerve signals are performed by the axon with the sheath of the enveloping myelin. Most mutations in CMT affect the myelin sheath, but some affect the axon.
The most common cause of CMT (70-80% of cases) is duplication of large areas of the short arm of chromosome 17 which includes the PMP22 genes. Some mutations affect the MFN2 gene, which encodes the mitochondrial protein. Cells contain separate sets of genes in nuclei and mitochondria. In nerve cells, mitochondria walk down long axons. In some forms of CMT, mutated MFN2 causes mitochondria to form large groups, or clumps, which can not travel to axons toward synapses. It prevents synapses from functioning.
CMT is divided into primary demyelinating neuropathy (CMT1, CMT3, and CMT4) and primary axonal neuropathy (CMT2), with frequent overlap. Another cell involved in CMT is the Schwann cell, which creates the myelin sheath, by wrapping the plasma membrane around the axon.
Neurons, Schwann cells, and fibroblasts work together to create functional nerves. Schwann cells and neurons exchange molecular signals that regulate survival and differentiation. These signals are disturbed in the CMT.
Schwann's demyelinating cells cause abnormal structures and functional axons. They can cause axon degeneration, or they may cause the axons to not function properly.
The myelin sheath allows the nerve cells to signal faster. When the myelin sheath is damaged, the nerve signals are slower, and this can be measured by a general neurological test, electromyography. When the axon is damaged, though, this results in reduced muscle action potential of the compound.
Diagnosis
CMT can be diagnosed by symptoms, by measuring the speed of nerve impulses (nerve conduction studies), through nerve biopsy, and by DNA testing. DNA testing can provide a definitive diagnosis, but not all genetic markers for CMT are known. CMT is first noticed when a person develops weakness of the lower leg, such as foot drop, or foot deformity, including hammertoes and high curvature, but the signs alone do not lead to diagnosis. The patient should be referred to a neurologist or rehabilitation medication. To see signs of muscle weakness, neurologists ask patients to walk on their heels or to move their legs against opposing forces. To identify sensory loss, neurologist tests for deep tendon reflexes, such as knee jerks, are reduced or absent in CMT. Doctors also ask about family history, because the CMT is hereditary. A lack of family history does not rule out CMT, but it helps to exclude other causes of neuropathy, such as diabetes or exposure to certain chemicals or drugs.
In 2010, CMT was one of the first diseases in which the genetic cause of certain patient diseases was precisely determined by sequencing the entire genome of the affected individual. This was done by scientists employed by the Charcot Marie Tooth Association (CMTA). Two mutations identified in the gene, SH3TC2 , are known to cause CMT. The researchers then compared the genomes of affected patients with the patient's maternal genome, father, and seven siblings with and without the disease. Mothers and fathers each have one copy of a normal gene and one mutant, and have mild or no symptoms. The offspring that inherit two mutant genes are presented completely with this disease.
Histology
The constant cycle of demyelination and remielination, which occurs in CMT, can lead to the formation of myelin layers around some nerves, called "bulb bulbs". This is also seen in chronic inflammatory demyelinating polyneuropathy. Muscles show a grouping of fiber types, similar nonspecific findings that denote the denervation/re-conservation cycle. Typically, type I and type II muscle fibers show random distributions such as boxes. However, when reinnervation occurs, the fiber groups associated with one nerve have the same type. The standard for indicating the type of fiber is histoenzymatic adenosine triphosphatase (ATPase at pH 9.4).
Classification
CMT is the result of genetic mutations in a number of genes. Based on the affected genes, CMT can be categorized into types and subtypes.
Management
Often, the most important goal for patients with CMT is to maintain movement, muscle strength, and flexibility. Therefore, an interprofessional team approach with occupational therapy, physical therapy, orthotist, podiatrist, and or orthopedic surgeon is recommended. PT usually focuses on muscle strength training, muscle stretching, and aerobic exercise, while OT can provide education on energy conservation strategies and daily life activities. Physical therapy should be involved in designing an exercise program that suits one's personal strength and flexibility. Bracing can also be used to fix problems caused by CMT. An orthotist can cope with gait abnormalities by prescribing the use of foot orthoses. These orthoses help control foot drop and ankle instability and often provide a better sense of balance for the patient. Appropriate footwear is also very important for people with CMT, but they often have trouble finding the right shoes because of the high arched legs and hammer legs. Due to a lack of good sensory acceptance in the legs, CMT patients may also need to see a podiatrist to help cut the nail or remove calluses that develop on the foot pads. The final decision a patient can take is to have surgery. Using a podiatrist or orthopedic surgeon, patients may choose to stabilize their feet or correct progressive problems. This procedure includes straightening and pinning the toes, lowering the arch, and occasionally, combining the ankle joint to provide stability. CMT patients should be careful to avoid falling because fractures take longer to heal in someone with an underlying disease process. In addition, the resulting inactivity may cause the CMT to worsen.
The Charcot-Marie-Tooth Association classifies vincristine chemotherapy drugs as "definite high risk" and states, "vincristine has proven dangerous and should be avoided by all CMT patients, including those without symptoms."
Also, some corrective surgical procedures can be performed to improve the physical condition.
Prognosis
The severity of symptoms varies greatly even for the same type of CMT. Cases of monozygotic twins with varying severity of disease have been reported, suggesting that identical genotypes are associated with varying degrees of severity (see penetration). Some patients can live a normal life and are almost or completely asymptomatic. The 2007 review states that "Life expectancy is not known to be changed in most cases".
History
The disease is named-The classic They Described it: Jean-Martin Charcot (1825-1893), his disciple Pierre Marie (1853-1940) ( See also
References
external links
- Charcot-Marie-Tooth's disease in Curlie (based on DMOZ)
Source of the article : Wikipedia
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