The disease Charcot-Marie-Tooth is a sensory-motor polyneuropathy, that is, a medical condition that causes damage or degeneration of the nerves peripherals (National Institutes of Health, 2014). It is one of the most frequent neurological pathologies of hereditary origin (National Institute of Neurological Disorders and Stroke, 2016).
It gets its name from the three doctors who first described it, Jean-Martin Charcot, Pierre de Marie, and Howard Henry Thooth, in 1886 (Muscular Dystrophy Association, 2010).
It is characterized by a clinical course in which sensory and motor symptoms appear, some of them include muscle deformity or weakness in the upper and lower extremities and especially in the feet (Cleveland Clinic, 2016).
In addition, it is a genetic disease, caused by the existence of various mutations in the genes that are responsible for production of proteins related to the function and structure of peripheral nerves (National Institute of Neurological Disorders and Stroke,
Generally, the characteristic symptoms of Charcot-Marie-Tooth disease begin to appear in adolescence or early adulthood and their progression is usually gradual (National Institute of Neurological Disorders and Stroke, 2016).
Although this pathology does not generally endanger the life of the affected person (Muscular Dystrophy Association, 2010), a cure has not yet been discovered.
The treatment used in Charcot-Marie-Tooth disease usually includes physical therapy, the use of surgery and orthopedic devices, occupational therapy, and the prescription of drugs for symptom control (Cleveland Clinic, 2016).
Characteristics of Charcot-Marie-Tooth disease
Charcot-Marie-Tooth (CMT) disease is a motor-sensory polyneuropathy, caused by a genetic mutation that affects the peripheral nerves and produces a wide variety of symptoms among which are: arched feet, inability to hold the body in a horizontal position, muscle weakness, joint pain, among others (Charcot-Marie-Tooth Association, 2016).
The term polyneuropathy is used to refer to the existence of a lesion in multiple nerves, regardless of the type of injury and the affected anatomical area (Colmer Oferil, 2008).
Specifically, Charcot-Marie-Tooth disease affects the peripheral nerves, which are those outside the brain and the spinal cord (Clinica Dam, 2016) and are responsible for innervating the muscles and sensory organs of the extremities (Cleveland Clinic, 2016).
Therefore, the peripheral nerves, through their different fibers, are responsible for transmitting motor and sensory information (Charcot-Marie-Tooth Association, 2016.
Thus, the pathologies that affect the peripheral nerves are called peripheral neuropathies and will be called motor, sensory or sensory-motor depending on the nerve fibers affected.
Charcot-Marie-Tooth disease therefore encompasses the development of various motor and sensory disorders (National Institute of Neurological Disorders and Stroke, 2016).
Charcot-Marie-Tooh disease is the most prevalent type of hereditary peripheral neuropathy (Errando, 2014).
Normally, it is a childhood or juvenile onset pathology (Bereciano et al., 2011), whose average age of presentation is around 16 years old (Errando, 2014).
This pathology can affect anyone, regardless of their race, place of origin or ethnic group and approximately 2.8 have been recorded million cases worldwide (Charcot-Marie-Tooth Association, 2016).
In the United States, Charcot-Marie-Tooth disease affects approximately 1 in 2,500 people in the general population (National Institute of Neurological Disorders and Stroke, 2016).
On the other hand, in Spain it has a prevalence of 28.5 cases per 100 inhabitants (Bereciano et al., 2011).
Characteristic symptoms and signs
Depending on the involvement of the nerve fibers, the characteristic signs and symptoms of Charcot-Marie-Tooth disease will present in Progressive form.
Normally, the clinic of Charcto-Maria-Tooth disease is characterized by the progressive development of weakness and muscular atrophy of the extremities.
The nerve fibers that innervate the legs and arms are the most extensive, so they will be the first affected areas (Charcot-Marie-Tooth Association, 2016).
Generally, the clinical course of Charcot-Marie-Tooth disease usually begins in the feet causing muscle weakness and numbness (Charcot-Marie-Tooth Association, 2016).
Although there are various forms of Charcot-Marie-Tooth disease, the most characteristic symptoms may include (Charcot-Marie-Tooth Association, 2016; National Institute of Neurological Disorders and Stroke, 2016):
- Bone and muscle deformity in the feet: presence of cavus or arched feet or hammer toes.
- Difficulty or inability to keep the feet in a horizontal position.
- Significant loss of muscle mass, especially in the lower extremities.
- Alterations and balance problems.
In addition, various sensory symptoms may also appear such as numbness of the lower limbs, muscle pain, decreased or loss of sensation in the legs and feet, among others (Mayo Clinic, 2016).
As a consequence, affected people often stumble when walking, falling, or presenting an altered gait, frequently.
In addition, as the involvement of the peripheral nerve fibers progresses, similar symptoms may develop in the upper extremities, arms, and hands (Charcot-Marie-Tooth Association, 2016).
Despite the fact that this is the most common symptomatology, the clinical presentation is highly variable. Some affected may have a severe muscle atrophy in the hands and feet, in addition to various deformities, whereas in other people only mild muscle weakness may be seen or pes cavus (OMIN, 2016; Pareyson, 1999; Murakami et al., 1996).
The characteristic clinical course of Charcot-Marie-Tooth disease is due to the presence of an alteration in the motor and sensory fibers of the peripheral nerves (Charcot-Marie-Tooth Association, 2016).
All these fibers are made up of a multitude of nerve cells through which the flow of information circulates. To improve the efficiency and speed of transmission, the axons of these cells are covered by myelin (National Institute of Neurological Disorders and Stroke, 2016).
If the axons and their covers are not intact, the information will not be able to circulate efficiently and therefore, a multitude of sensory and motor symptomatology (National Institute of Neurological Disorders and Stroke, 2016).
The presence of genetic mutations, on many occasions can lead to the development of alterations in normal or habitual function peripheral nerves, as is the case with Charcot-Marie-Tooth disease (Mayo Clinic, 2016).
Experimental studies have indicated that genetic mutations in Charcot-Marie-Tooth disease are generally inherited.
In addition, more than 80 different genes related to the occurrence of this pathology have been identified (Charcot-Marie-Tooth Association, 2016).
Types of Charcot-Marie-Tooth disease
There are different types of Charcot-Marie-Tooth disease (National Institute of Neurological Disorders and Stroke, 2016), which are usually classified as function of various criteria such as the hereditary pattern, the moment of clinical presentation or the severity of the pathology (Muscular Association, 2010).
However, the main types include CMT1, CMT2, CMT3, CMT4, and CMTX (National Institute of Neurological Disorders and Stroke, 2016)
Next, we will describe the main characteristics of the most common types (Muscular Dystrophy Association, 2010):
Charcot-Marie-Tooth type I and type II (CMT1 and CMT2)
Types I and II of this pathology have a typical onset during childhood or adolescence and are the most frequent types.
Type I presents an autosomal dominant inheritance, while type II can present an autosomal dominant or recessive inheritance.
In addition, some subtypes can also be distinguished, such as the case of CMT1A, which develops as a consequence of a mutation in the PMP22 gene located on chromosome 17. This type of genetic disorder is responsible for approximately 60% of diagnosed cases of kidney disease. Charcot-Marie-Tooth.
Charcot-Marie-Tooth Type X (CMTX)
In this type of Charcot-Marie-Tooth disease, the typical onset of the clinical course is also associated with childhood and adolescence.
It has an X- linked genetic inheritance . This type of pathology presents clinical characteristics similar to types I and II, and, in addition, it usually affects the male sex in a majority.
Charcot-Marie-Tooth type III (CMT3)
Type III Charcto-Marie-Tooth disease is commonly known as Dejerine Sottas disease or syndrome (DS). (Charcot-Marie-Tooth Association, 2016).
In this pathology, the first symptoms usually appear in the first stages of life, typically before 3 years of age.
At the genetic level, it can present an autosomal dominant or recessive inheritance.
Furthermore, it is one of the most severe forms of Charcto-Marie-Tooh disease. Those affected have a severe neuropathy with weakness generalized, loss of sensation, bone deformities and in many cases, they present a significant or slight loss of hearing.
Charcot-Marie-Tooth type IV (CMT4)
In type IV Charcot-Marie-Tooth disease, the typical onset of symptoms occurs during childhood or adolescence and also at the genetic, it is an autosomal recessive disorder.
Specifically, Type IV is the demyelinating form of Charcot-Marie-Tooth disease. Some of the symptoms include muscle weakness in distal and proximal areas, or sensory dysfunction.
Affected people in childhood, usually present a generalized delay in motor development, in addition to a deficient muscle tone.
The first phase of the identification of Charcot-Marie-Tooh disease is related both to the elaboration of the family history and to the observation of the symptoms.
It is essential to determine if the affected person has a hereditary neuropathy. Various family surveys are generally carried out to determine the presence of other cases of this pathology (Bereciano et al., 2012).
Therefore, some of the questions that will be asked to the patient will be related to the appearance and duration of their symptoms, and with the presence of other family members affected by Charcot-Marie-Tooth disease (National Institute of Neurological Disorders and Stroke, 2016).
On the other hand, the physical and neurological examination is also essential to determine the presence of symptoms. compatible with this pathology.
During the physical and neurological examination, the different specialists try to observe the presence of muscle weakness in the extremities, reduction significant muscle mass, decreased reflexes or loss of sensitivity (National Institute of Neurological Disorders and Stroke, 2016).
In addition, it is also about determining the presence of other types of alterations such as deformities in the feet and hands (pes cavus, hammer toes, pee flat or inverted heel), scoliosis , hip dysplasia , among others (National Institute of Neurological Disorders and Stroke, 2016).
However, since many of those affected are asymptomatic or have very subtle clinical signs, it will also be necessary to use some clinical tests or tests (Bereciano et al., 2012).
Thus, a neurophysiological examination is frequently performed (Bereciano et al., 2012):
- Nerve conduction study : in this type of test, the objective is to measure the speed and efficiency of the electrical signals that are transmitted through nerve fibers. Small electrical pulses are usually used to stimulate the nerve, and responses are recorded. When the electrical transmission is weak or slow, it offers us an indicator of possible nerve involvement (Mayo Clinic, 2016).
- Electromyography (EMG) : in this case, muscle electrical activity is recorded, offering us information about the ability of the muscle to respond to nerve stimulation (Mayo Clinic, 2016).
In addition, other types of tests are also carried out such as:
- Nerve biopsy : In this type of test , a small piece of peripheral nerve tissue is removed to determine the presence of histological abnormalities. Normally, patients with the CMT1 type have abnormal myelination, while those with the CMT1 type CMT2, usually present axonal degeneration (National Institute of Neurological Disorders and Stroke, 2016).
- Genetic test: these tests are used to determine the presence of genetic defects or alterations compatible with the disease.
Chacot-Marie-Tooth disease has a progressive course, therefore symptoms tend to slowly worsen over time.
Muscle weakness and numbness, difficulty walking, loss of balance, or orthopedic problems often progress to causing a severe state of functional disability (Charcot-Marie-Tooth Association, 2016).
Currently, there is no treatment that will cure or stop Charcot-Marie-Tooth disease.
The most commonly used therapeutic stockings usually include (Charcot-Marie-Tooth Association, 2016).
- Physical and occupational therapy : they are used to maintain and improve muscular capacities and control the functional independence of the affected person.
- Orthopedic devices : this type of equipment is used to compensate for physical alterations.
- Surgery : there are some types of bone and muscle deformities that can be treated through orthopedic surgery. The objective fundamental is to maintain or restore the ability to walk.
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