Charcot-Marie-Tooth disease
Encyclopedia
Charcot–Marie–Tooth disease- (CMT), known also as Morbus Charcot-Marie-Tooth, Charcot-Marie-Tooth neuropathy, hereditary motor and sensory neuropathy (HMSN), hereditary sensorimotor neuropathy (HSMN), or peroneal muscular atrophy, is an inherited disorder of nerve
s (neuropathy) that takes different forms. It 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. Currently incurable, this disease is one of the most common inherited neurological disorders.
Estimates of incidence vary widely from 1 in 380,000 people affected
to 1 in 2,500 people affected http://emedicine.medscape.com/article/315260-overview. This larger figure might equate to approximately 23,000 people in the UK and 125,000 people in the USA.
with a myelin
sheath wrapped around it. Most mutations in CMT affect the myelin sheath. Some affect the axon.
The most common cause of CMT (70-80% of the cases) is the duplication of a large region in chromosome 17p12 that includes the gene PMP22. Some mutations affect the gene MFN2
, which codes for a mitochondrial protein. Cells contain separate sets of genes in their nucleus
and in their mitochondria. In nerve cells, the mitochondria travel down the long axons. In some forms of CMT, mutated MFN2
causes the mitochondria to form large clusters, or clots, which are unable to travel down the axon towards the synapses. This prevents the synapses from functioning.
CMT is divided into the primary demyelinating neuropathies (CMT1, CMT3, and CMT4) and the primary axonal neuropathies (CMT2), with frequent overlap. Another cell involved in CMT is the Schwann cell
, which creates the myelin sheath, by wrapping its plasma membrane around the axon in a structure that is sometimes compared to a Swiss roll
.
Neurons, Schwann cells, and fibroblast
s work together to create a working nerve. Schwann cells and neurons exchange molecular signals that regulate survival and differentiation. These signals are disrupted in CMT.
Demyelinating Schwann cells causes abnormal axon structure and function. They may cause axon degeneration. Or they may simply cause axons to malfunction.
The myelin sheath allows nerve cells to conduct signals faster. When the myelin sheath is damaged, nerve signals are slower, and this can be measured by a common neurological test, electromyography
.
When the axon is damaged, on the other hand, this results in a reduced compound muscle action potential
(CMAP).
early in the course of the disease. This can also cause claw toe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to "stork leg" or "inverted bottle" appearance. Weakness in the hands and forearms occurs in many people later in life as the disease progresses.
Symptoms and progression of the disease can vary. Breathing can be affected in some; so can hearing, vision, as well as the neck and shoulder muscles. Scoliosis
is common. Hip sockets
can be malformed. Gastrointestinal problems can be part of CMT, as can chewing, swallowing, and speaking (as vocal cords atrophy). A tremor
can develop as muscles waste. Pregnancy
has been known to exacerbate CMT, as well as extreme emotional stress. Patients with CMT must avoid periods of prolonged immobility such as when recovering from a secondary injury as prolonged periods of limited mobility can drastically accelerate symptoms of CMT.
Neuropathic pain
is often a symptom of CMT, though, like other symptoms of CMT, its presence and severity varies from case to case. For some people, pain can be significant to severe and interfere with daily life activities. However, pain is not experienced by all people with CMT. When 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 syndrome
, among other diseases.
), through biopsy
of the nerve, and through DNA testing. DNA testing can give a definitive diagnosis, but not all the genetic marker
s for CMT are known.CMT is first noticed when someone develops lower leg weakness and foot deformities such as foot drop, hammertoes and high arches. But signs alone do not lead to diagnosis. Patients must be referred to a neurologist or a physical medicine and rehabilitation physician (physiatrist). To see signs of muscle weakness the neurologist will ask patients to walk on their heels or to move part of their leg against an opposing force. In order to identify sensory loss the neurologist will test for deep tendon reflexes, such as the knee jerk, which are reduced or absent in CMT. The doctor will also ask about family history because CMT is hereditary. The lack of family history does not rule out CMT, but it will allow the doctor to rule out other causes of neuropathy such as diabetes or exposure to certain chemicals or drugs.
In 2010, CMT was one of the first diseases where the genetic cause of a particular patient's disease was precisely determined by sequencing the whole genome of an affected individual. Two mutations were identified in a gene, SH3TC2, known to cause CMT. Researchers then compared the affected patient's genome to the genomes of the patient's mother, father, and seven siblings with and without the disease. The mother and father each had one normal and one mutant copy of this gene, and had mild or no symptoms. The offspring that inherited two mutant genes presented fully with the disease. Sequencing the initial patient's whole genome cost $50,000, but researchers estimated that it would soon cost $5,000 and become common.
Clinical categories
Genetic subtypes
has been proposed, and has shown some benefit in animal models. A clinical trial to determine the effectiveness of high doses of ascorbic acid (vitamin C) in treating humans with CMT type 1A has been conducted. The results of the trial upon children have shown that a high dosage intake of ascorbic acid is safe but the efficacy endpoints expected were not met. In 2010, a study published in the Journal Science indicated that scientists had identified those proteins that control the thickness of myelin sheath. This discovery is expected to open the avenue to new treatments in the coming years.
The most important activity for patients with CMT is to maintain what movement, muscle strength and flexibility they have. Therefore, physical therapy and moderate activity are recommended but overexertion should be avoided. A physiotherapist should be involved in designing a exercise program that fits a patient’s personal strengths and flexibility. Bracing can also be used to correct problems caused by CMT. Gait abnormalities can be corrected by the use of either articulated (hinged) or unarticulated, braces called AFOs (ankle-foot orthoses). These braces help control foot drop and ankle instability and often provide a better sense of balance for patients. Appropriate footwear is also very important for people with CMT, but they often have difficulty finding well-fitting shoes because of their high arched feet and hammer toes. Due to the lack of good sensory reception in the feet, CMT patients may also need to see a podiatrist for help in trimming nails or removing calluses that develop on the pads of the feet. A final decision a patient can make is to have surgery. Using a podiatrist or an orthopedic surgeon, patients can choose to stabilize their feet or correct progressive problems. These procedures include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability.
The Charcot-Marie-Tooth Association classifies the chemotherapy
drug vincristine
as a "definite high risk" and states that "vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms."
There are also several corrective surgical procedures that can be done to improve physical condition.
Genetic testing is available for many of the different types of Charcot-Marie-Tooth and may help guide treatment.
(1825–1893), 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.)
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
s (neuropathy) that takes different forms. It 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. Currently incurable, this disease is one of the most common inherited neurological disorders.
Estimates of incidence vary widely from 1 in 380,000 people affected
to 1 in 2,500 people affected http://emedicine.medscape.com/article/315260-overview. This larger figure might equate to approximately 23,000 people in the UK and 125,000 people in the USA.
Molecular causes
Charcot–Marie–Tooth disease is caused by mutations that cause defects in neuronal proteins. Nerve signals are conducted by an axonAxon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
with a myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
sheath wrapped around it. Most mutations in CMT affect the myelin sheath. Some affect the axon.
The most common cause of CMT (70-80% of the cases) is the duplication of a large region in chromosome 17p12 that includes the gene PMP22. Some mutations affect the gene MFN2
MFN2
Mitofusin-2 is a protein that in humans is encoded by the MFN2 gene.- Function :Mitofusin-2 is a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network...
, which codes for a mitochondrial protein. Cells contain separate sets of genes in their nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
and in their mitochondria. In nerve cells, the mitochondria travel down the long axons. In some forms of CMT, mutated MFN2
MFN2
Mitofusin-2 is a protein that in humans is encoded by the MFN2 gene.- Function :Mitofusin-2 is a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network...
causes the mitochondria to form large clusters, or clots, which are unable to travel down the axon towards the synapses. This prevents the synapses from functioning.
CMT is divided into the primary demyelinating neuropathies (CMT1, CMT3, and CMT4) and the primary axonal neuropathies (CMT2), with frequent overlap. Another cell involved in CMT is the Schwann cell
Schwann cell
Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system . Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle...
, which creates the myelin sheath, by wrapping its plasma membrane around the axon in a structure that is sometimes compared to a Swiss roll
Swiss roll
A Swiss roll or jelly roll is a type of sponge cake roll. The thin cake is made of eggs, flour and sugar and baked in a very shallow rectangular baking tray, called a sheet pan. The cake is removed from the pan and spread with jam or buttercream, rolled up, and served in circular slices.The...
.
Neurons, Schwann cells, and fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s work together to create a working nerve. Schwann cells and neurons exchange molecular signals that regulate survival and differentiation. These signals are disrupted in CMT.
Demyelinating Schwann cells causes abnormal axon structure and function. They may cause axon degeneration. Or they may simply cause axons to malfunction.
The myelin sheath allows nerve cells to conduct signals faster. When the myelin sheath is damaged, nerve signals are slower, and this can be measured by a common neurological test, electromyography
Electromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
.
When the axon is damaged, on the other hand, this results in a reduced compound muscle action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
(CMAP).
Symptoms
Symptoms of CMT usually begin in late childhood or early adulthood. Some people don't experience symptoms until their early thirties or forties. Usually, the initial symptom is foot dropFoot drop
Foot drop is the dropping of the forefoot due to weakness, damage to the peroneal nerve or paralysis of the muscles in the anterior portion of the lower leg. It is usually a symptom of a greater problem, not a disease in itself. It is characterized by the inability or difficulty in moving the ankle...
early in the course of the disease. This can also cause claw toe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to "stork leg" or "inverted bottle" appearance. Weakness in the hands and forearms occurs in many people later in life as the disease progresses.
Symptoms and progression of the disease can vary. Breathing can be affected in some; so can hearing, vision, as well as the neck and shoulder muscles. Scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
is common. Hip sockets
Acetabulum
The acetabulum is a concave surface of the pelvis. The head of the femur meets with the pelvis at the acetabulum, forming the hip joint.-Structure:...
can be malformed. Gastrointestinal problems can be part of CMT, as can chewing, swallowing, and speaking (as vocal cords atrophy). A tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
can develop as muscles waste. Pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
has been known to exacerbate CMT, as well as extreme emotional stress. Patients with CMT must avoid periods of prolonged immobility such as when recovering from a secondary injury as prolonged periods of limited mobility can drastically accelerate symptoms of CMT.
Neuropathic pain
Neuropathic pain
Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...
is often a symptom of CMT, though, like other symptoms of CMT, its presence and severity varies from case to case. For some people, pain can be significant to severe and interfere with daily life activities. However, pain is not experienced by all people with CMT. When pain is present as a symptom of CMT, it is comparable to that seen in other peripheral neuropathies, as well as Postherpetic neuralgia
Postherpetic neuralgia
Postherpetic neuralgia is a neuralgia caused by the varicella zoster virus. Typically, the neuralgia is confined to a dermatomic area of the skin and follows an outbreak of herpes zoster in that same dermatomic area...
and Complex regional pain syndrome
Complex regional pain syndrome
Complex regional pain syndrome is a chronic progressive disease characterized by severe pain, swelling and changes in the skin. It often affects an arm or a leg and may spread to another part of the body.Though treatment is often unsatisfactory, early multimodal therapy can cause dramatic...
, among other diseases.
Diagnosis
CMT can be diagnosed through symptoms, through measurement of the speed of nerve impulses (electromyographyElectromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
), through biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
of the nerve, and through DNA testing. DNA testing can give a definitive diagnosis, but not all the genetic marker
Genetic marker
A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify cells, individuals or species. It can be described as a variation that can be observed...
s for CMT are known.CMT is first noticed when someone develops lower leg weakness and foot deformities such as foot drop, hammertoes and high arches. But signs alone do not lead to diagnosis. Patients must be referred to a neurologist or a physical medicine and rehabilitation physician (physiatrist). To see signs of muscle weakness the neurologist will ask patients to walk on their heels or to move part of their leg against an opposing force. In order to identify sensory loss the neurologist will test for deep tendon reflexes, such as the knee jerk, which are reduced or absent in CMT. The doctor will also ask about family history because CMT is hereditary. The lack of family history does not rule out CMT, but it will allow the doctor to rule out other causes of neuropathy such as diabetes or exposure to certain chemicals or drugs.
In 2010, CMT was one of the first diseases where the genetic cause of a particular patient's disease was precisely determined by sequencing the whole genome of an affected individual. Two mutations were identified in a gene, SH3TC2, known to cause CMT. Researchers then compared the affected patient's genome to the genomes of the patient's mother, father, and seven siblings with and without the disease. The mother and father each had one normal and one mutant copy of this gene, and had mild or no symptoms. The offspring that inherited two mutant genes presented fully with the disease. Sequencing the initial patient's whole genome cost $50,000, but researchers estimated that it would soon cost $5,000 and become common.
Types
As of early 2010, mutations in 39 genes have been identified as causes of CMT. CMT can be categorized first into major clinical categories, and then into subtypes according to those mutations. Type 1 primarily affects the myelin sheath, and is either dominant, recessive or X-linked. Type 2 primarily affects the axon, and is either dominant or recessive. Other types are mixed.Clinical categories
| Name | Inheritance | Frequency | Notes |
|---|---|---|---|
| CMT Type 1 (CMT1) | Autosomal dominant | Type 1 affects approximately one-third of CMT patients and is the most common type of CMT. The subtypes share clinical symptoms. | Causes demyelination, which can be detected by measuring nerve conduction velocities. (anatomic changes directly affect the myelin sheath, with secondary axonal changes. In areas of focal demyelination, impulse conduction is slowed. The prolongation slows conduction velocity along the nerve segment.) |
| CMT Type 2 (CMT2) | Autosomal dominant (except CMT2B1) |
Type 2 affects approximately 20-40% of CMT patients. | Main effect is on the axon. The average nerve conduction velocity Nerve conduction velocity Nerve conduction velocity is the speed at which an electrochemical signal propagates down a neural pathway. Many things can affect this, including axon diameter, myelination, the internal resistance of the axon, and temperature. Nerve conduction velocity differs from species to species, and to a... is slightly below normal, but generally above 38m/s Metre per second Metre per second is an SI derived unit of both speed and velocity , defined by distance in metres divided by time in seconds.... The type-2 form of Charcot-Marie-Tooth disease (CMT2) tends to affect the lower extremities more than the upper extremities. CMT2 is often a clinically less severe disease than CMT1. |
| CMT Type 3 (CMT3) | Autosomal recessive | Type 3 affects very few CMT patients. | |
| CMT Type 4 (CMT4) | Autosomal recessive | Type 4 affects very few CMT patients. | |
| CMT X-Linked (CMTX) | X-linked dominant (only CMTX1) |
CMTX affects approximately 10-20% of CMT patients. | Approx 10% of X-linked CMT patients have some other form than CMTX. However a study published in 1997 indicates that a connexin 32 gene mutation is associated with this form which may be more common than previously thought. |
Genetic subtypes
| Type | OMIM | Gene | Locus Locus (genetics) In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map... |
Description >- | CMT1A |
PMP22 | 17p11.2 | NCV Nerve conduction velocity Nerve conduction velocity is the speed at which an electrochemical signal propagates down a neural pathway. Many things can affect this, including axon diameter, myelination, the internal resistance of the axon, and temperature. Nerve conduction velocity differs from species to species, and to a... : 20-25m/s Metre per second Metre per second is an SI derived unit of both speed and velocity , defined by distance in metres divided by time in seconds.... when associated with essential tremor and ataxia, called Roussy-Levy Syndrome >- | CMT1B |
MPZ | 1q22 | NCV Nerve conduction velocity Nerve conduction velocity is the speed at which an electrochemical signal propagates down a neural pathway. Many things can affect this, including axon diameter, myelination, the internal resistance of the axon, and temperature. Nerve conduction velocity differs from species to species, and to a... : <15m/s Metre per second Metre per second is an SI derived unit of both speed and velocity , defined by distance in metres divided by time in seconds.... >- | CMT1C |
LITAF LITAF Lipopolysaccharide-induced tumor necrosis factor-alpha factor is a protein that in humans is encoded by the LITAF gene.It is associated with Charcot–Marie–Tooth disease 1C.-External Links:* -Further reading:... |
16p13.1-p12.3 | demyelination Myelin Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination... , which can be detected by measuring nerve conduction velocities. Usually shows up in infancy. Average NCV Nerve conduction velocity Nerve conduction velocity is the speed at which an electrochemical signal propagates down a neural pathway. Many things can affect this, including axon diameter, myelination, the internal resistance of the axon, and temperature. Nerve conduction velocity differs from species to species, and to a... : 26-42m/s Metre per second Metre per second is an SI derived unit of both speed and velocity , defined by distance in metres divided by time in seconds.... . Identical symptoms to CMT-1A. >- | CMT1D |
EGR2 EGR2 Early growth response protein 2 is a protein that in humans is encoded by the EGR2 gene.-Further reading:-External links:* *... |
10q21.1-q22.1 | NCV Nerve conduction velocity Nerve conduction velocity is the speed at which an electrochemical signal propagates down a neural pathway. Many things can affect this, including axon diameter, myelination, the internal resistance of the axon, and temperature. Nerve conduction velocity differs from species to species, and to a... : 15-20m/s >- | CMT1E |
PMP22 | 17p11.2 | >- | NEFL NEFL Neurofilament light polypeptide is a protein that in humans is encoded by the NEFL gene.It is associated with Charcot–Marie–Tooth disease 1F and 2E.-Interactions:NEFL has been shown to interact with MAP2, Protein kinase N1 and TSC1.... |
8p21 | >- | MFN2 MFN2 Mitofusin-2 is a protein that in humans is encoded by the MFN2 gene.- Function :Mitofusin-2 is a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network... or KIF1B KIF1B Kinesin-like protein KIF1B is a protein that in humans is encoded by the KIF1B gene.-External links:*... |
1p36 | >- | RAB7 (RAB7A RAB7A Ras-related protein Rab-7a is a protein that in humans is encoded by the RAB7A gene.Various mutations of RAB7A are associated with Hereditary sensory neuropathy type 1C , also known as Charcot-Marie-Tooth syndrome type 2B .... , RAB7B RAB7B Ras-related protein Rab-7b is a protein that in humans is encoded by the RAB7B gene.- Function :Rab7 is a small GTPase that plays a role in the transport and degradation of proteins in endosomes and lysosomes in mammalian cells. Rab7b, is localized to lysosome-associated compartments and is... ) |
3q21. | >- | LMNA LMNA Lamin A/C also known as LMNA is a protein that in humans is encoded by the LMNA gene. Lamin A/C belongs to the lamin family of proteins.-Function:... |
1q22 | >- | MED25 MED25 Mediator of RNA polymerase II transcription subunit 25 is an enzyme that in humans is encoded by the MED25 gene.-External links:*... |
19q13.3 | >- | 'TRPV4 TRPV4 Transient receptor potential cation channel subfamily V member 4 is a protein that in humans is encoded by the TRPV4 gene.This gene encodes TRPV4, a member of the OSM9-like transient receptor potential channel subfamily in the transient receptor potential superfamily of ion channels... |
12q23-q24 | >- | GARS GARS Glycyl-tRNA synthetase is an enzyme that in humans is encoded by the GARS gene.-Interactions:Glycyl-tRNA synthetase has been shown to interact with EEF1D.-External links:* *... |
7p15 | >- | NEFL NEFL Neurofilament light polypeptide is a protein that in humans is encoded by the NEFL gene.It is associated with Charcot–Marie–Tooth disease 1F and 2E.-Interactions:NEFL has been shown to interact with MAP2, Protein kinase N1 and TSC1.... |
8p21 | >- | HSPB1 | 7q11-q21 | >- | 12q12-13 | >- | GDAP1 GDAP1 Ganglioside-induced differentiation-associated protein 1 is a protein that in humans is encoded by the GDAP1 gene.-External links:* * *... |
8q13-q21.1 | >- | MPZ | 1q22 | >- | GDAP1 GDAP1 Ganglioside-induced differentiation-associated protein 1 is a protein that in humans is encoded by the GDAP1 gene.-External links:* * *... |
8q13-q21.1 | >- | HSPB8 HSPB8 Heat shock protein beta-8 is a protein that in humans is encoded by the HSPB8 gene.-Interactions:HSPB8 has been shown to interact with Hsp27 and HSPB2.-External links:*... |
12q24 | >- | varies | varies | NCV Nerve conduction velocity Nerve conduction velocity is the speed at which an electrochemical signal propagates down a neural pathway. Many things can affect this, including axon diameter, myelination, the internal resistance of the axon, and temperature. Nerve conduction velocity differs from species to species, and to a... : Normal (50–60 m/s). This is an old classification. Currently this is referred to as CMT4F. >- | CMT4A |
GDAP1 GDAP1 Ganglioside-induced differentiation-associated protein 1 is a protein that in humans is encoded by the GDAP1 gene.-External links:* * *... |
8q13-q21.1 | >- | MTMR2 MTMR2 Myotubularin-related protein 2 is a protein that in humans is encoded by the MTMR2 gene.-External links:*... |
11q22 | >- | CMT4B2 (SBF2 SBF2 Myotubularin-related protein 13 is a protein that in humans is encoded by the SBF2 gene.-External links:*... ) |
11p15 | >- | KIAA1985 (SH3TC2 SH3TC2 SH3 domain and tetratricopeptide repeats-containing protein 2 is a protein that in humans is encoded by the SH3TC2 gene. It is expressed in in the Schwann cells that wrap the myelin sheath around nerves.- Function :... ) |
5q32 | >- | NDRG1 NDRG1 Protein NDRG1 is a protein that in humans is encoded by the NDRG1 gene.It has been reported that NDRG1 localizes to the endosomes and is a Rab4a effector involved in vesicular recycling.-External links:*... |
8q24.3 | >- | EGR2 EGR2 Early growth response protein 2 is a protein that in humans is encoded by the EGR2 gene.-Further reading:-External links:* *... |
10q21.1-10q22.1 | >- | PRX PRX (gene) Periaxin is a protein that in humans is encoded by the PRX gene.-External links:*... |
19q13.1-19q13.2 | >- | FGD4 FGD4 FYVE, RhoGEF and PH domain-containing protein 4 is a protein that in humans is encoded by the FGD4 gene.-External links:*... |
12p11.21 | >- | KIAA0274 (FIG4 Fig4 Polyphosphoinositide phosphatase also known as phosphatidylinositol 3,5-bisphosphate 5-phosphatase or SAC domain-containing protein 3 is an enzyme that in humans is encoded by the FIG4 gene.- Function :... ) |
6q21 | >- | GJB1 GJB1 Gap junction beta-1 protein is a protein that in humans is encoded by the GJB1 gene.- Function :Connexins are membrane-spanning proteins that assemble to form gap junction channels that facilitate the transfer of ions and small molecules between cells... |
Xq13.1 | NCV Nerve conduction velocity Nerve conduction velocity is the speed at which an electrochemical signal propagates down a neural pathway. Many things can affect this, including axon diameter, myelination, the internal resistance of the axon, and temperature. Nerve conduction velocity differs from species to species, and to a... : 25-40m/s Metre per second Metre per second is an SI derived unit of both speed and velocity , defined by distance in metres divided by time in seconds.... >- | CMTX2 |
Xq22.2 | >- | Unknown, but 11 of 15 eliminated | Xq26 | >- | Xq24-q26.1 | >- | Xq22-q24 | Known as Rosenberg-Chutorian syndrome. Signs include optic atrophy, polyneuropathy and deafness |
Management and treatment
Although there is no current standard treatment, the use of ascorbic acidAscorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
has been proposed, and has shown some benefit in animal models. A clinical trial to determine the effectiveness of high doses of ascorbic acid (vitamin C) in treating humans with CMT type 1A has been conducted. The results of the trial upon children have shown that a high dosage intake of ascorbic acid is safe but the efficacy endpoints expected were not met. In 2010, a study published in the Journal Science indicated that scientists had identified those proteins that control the thickness of myelin sheath. This discovery is expected to open the avenue to new treatments in the coming years.
The most important activity for patients with CMT is to maintain what movement, muscle strength and flexibility they have. Therefore, physical therapy and moderate activity are recommended but overexertion should be avoided. A physiotherapist should be involved in designing a exercise program that fits a patient’s personal strengths and flexibility. Bracing can also be used to correct problems caused by CMT. Gait abnormalities can be corrected by the use of either articulated (hinged) or unarticulated, braces called AFOs (ankle-foot orthoses). These braces help control foot drop and ankle instability and often provide a better sense of balance for patients. Appropriate footwear is also very important for people with CMT, but they often have difficulty finding well-fitting shoes because of their high arched feet and hammer toes. Due to the lack of good sensory reception in the feet, CMT patients may also need to see a podiatrist for help in trimming nails or removing calluses that develop on the pads of the feet. A final decision a patient can make is to have surgery. Using a podiatrist or an orthopedic surgeon, patients can choose to stabilize their feet or correct progressive problems. These procedures include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability.
The Charcot-Marie-Tooth Association classifies the chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
drug vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
as a "definite high risk" and states that "vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms."
There are also several corrective surgical procedures that can be done to improve physical condition.
Genetic testing is available for many of the different types of Charcot-Marie-Tooth and may help guide treatment.
History
The disease is named after those who classically described it: Jean-Martin CharcotJean-Martin Charcot
Jean-Martin Charcot was a French neurologist and professor of anatomical pathology. He is known as "the founder of modern neurology" and is "associated with at least 15 medical eponyms", including Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis...
(1825–1893), 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
Howard Henry Tooth
Howard Henry Tooth, CMG, CB was a British neurologist and one of the discoverers of Charcot-Marie-Tooth disease.-Early life and education:...
(1856–1925) ("The peroneal type of progressive muscular atrophy", dissertation, London, 1886.)
External Links
- GeneReviews/NIH/NCBI/UW entry on Charcot-Marie-Tooth Hereditary Neuropathy Overview
- GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy Type 1
- GeneReviews/NIH/NCBI/UW entry on Charcot-Marie-Tooth Neuropathy X Type 5
- OMIM entries on on Charcot-Marie-Tooth Neuropathy X Type 5
- GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy X Type 1
- OMIM entries on Charcot-Marie-Tooth Neuropathy X Type 1
- GeneReviews/NCBI/NIH/UW entry on GARS-Associated Axonal Neuropathy, Charcot-Marie-Tooth Neuropathy Type 2D, Distal Spinal Muscular Atrophy V
- CMT United Kingdom www.cmt.org.uk
- CMT Central - An Insight into CMT - www.charcotmarietooth.webs.com