The disease Charcot-Marie-Tooth is a sensorimotor polyneuropathy, ie a medical condition that causes damage or degeneration of 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 receives its name from the three doctors who described it for the first time, 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 deformity or muscle 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 genes that are responsible for the 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 in the early stages of adulthood and their progression is usually gradual (National Institute of Neurological Disorders and Stroke, 2016).
Although this pathology usually does not 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 disease (CMT) is a motor-senile 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 maintain 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 anatomic area (Colmer Oferil, 2008).
Specifically, Charcot-Marie-Tooth disease affects the peripheral nerves, which are those that are outside the brain and the spinal cord (Clinica Dam, 2016) and are responsible for innervate the muscles and sensory organs in the limbs (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, pathologies that affect the peripheral nerves are called peripheral neuropathies and are called motor, sensory or sensory-motor depending on the nerve fibers affected.
Charcot-Marie-Tooth disease thus 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 peripheral hereditary 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 of age (Errando, 2014).
This pathology can affect anyone, regardless of race, place of origin or ethnic group and approximately 2.8 million cases have been registered worldwide (Charcot-Marie-Tooth Association, 2016).
In the United States, Charcot-Marie-Tooth disease affects approximately 1 in every 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.habitants (Bereciano et al., 2011).
Symptoms and characteristic signs
Depending on the involvement of the nerve fibers, the signs and symptoms characteristic of Charcot-Marie-Tooth disease will be presented progressively.
Normally, the clinical symptoms of Charcto-Maria-Tooth disease are characterized by the progressive development of weakness and muscular atrophy of the extremities.
The nerve fibers that innervate the legs and arms are the largest, so they will be the first affected areas (Charcot-Marie-Tooth Association, 2016).
Generally, the clinical course of Charcot-Marie-Tooth disease usually begins with the feet causing muscle weakness and numbness (Charcot-Marie-Tooth Association, 2016).
Although there are several 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 muscular deformity in the feet: presence of cavus or arched foot or hammertoes.
- 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 extremities, muscle pain, decreased or loss of sensation in the legs and feet, among others (Mayo Clinic, 2016).
As a result, affected people often stumble when they walk, fall, or present an altered gait, frequently.
In addition, as the involvement of peripheral nerve fibers progresses, similar symptoms may develop in the upper extremities, arms and hands (Charcot-Marie-Tooth Association, 2016).
Although this is the most common symptomatology, the clinical presentation is very variable. Some sufferers may have severe muscle atrophy in the hands and feet, as well as various deformities, while in others only mild muscle weakness or cavus foot can be observed (OMIN, 2016, Pareyson, 1999, Murakami et al., 1996). .
The clinical course characteristic 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 formed by 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 coated with 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 symptoms will develop (National Institute of Neurological Disorders and Stroke, 2016).
The presence of genetic mutations can, in many cases, lead to the development of alterations in the normal or habitual function of the peripheral nerves, as is the case of Charcot-Marie-Tooth disease (Mayo Clinic, 2016).
Experimental studies have indicated that genetic mutations of Charcot-Marie-Tooth disease are usually hereditary.
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 several types of Charcot-Marie-Tooth disease (National Institute of Neurological Disorders and Stroke, 2016), which are usually classified according to various criteria such as the hereditary pattern, the time of clinical presentation or the severity of the pathology (Muscular Dystrophy 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 has an autosomal dominant inheritance, while type II can present an autosomal dominant or recessive inheritance.
In addition, some subtypes can also be distinguished, as in the case of CMT1A, which develops as a consequence of a mutation in the PMP22 gene located on chromosome 17. This type of genetic involvement is responsible for approximately 60% of diagnosed cases of Charcot-Marie-Tooth disease.
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 a genetic inheritance linked to the X chromosome. This type of pathology presents clinical characteristics similar to types I and II, and, in addition, usually affects the male sex.
Charcot-Marie-Tooth type III (CMT3)
Type III of the Charcto-Marie-Tooth enferemdad is usually known as the disease or Dejerine Sottas syndrome (DS) (Charcot-Marie-Tooth Association, 2016).
In this pathology, the first symptoms usually appear in the first stage of life, typically before 3 years of age.
At the genetic level, it can present an autosomal dominant or recessive inheritance.
In addition, it is one of the most severe forms of the Charcto-Marie-Tooh enferemdad. Those affected have a severe neuropathy with generalized weakness , loss of sensibility, bone deformities and in many cases, they present a significant or slight loss of hearing.
Charcot-Marie-Tooth type IV (CMT4)
In type IV of Charcot-Marie-Tooth disease, the typical onset of symptoms occurs during childhood or adolescence and, in addition, at the genetic level , it is an autosomal recessive affectation.
Specifically, Type IV is the demyelinating form of Charcot-Marie-Tooth disease. Some of the symptoms include muscle weakness in the distal and proximal areas, or sensory dysfunction.
People affected in childhood tend to have a generalized delay of motor development, in addition to a deficient muscular volume.
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 symptomatology.
It is essential to determine if the affected person has a hereditary neuropathy. Generally, several family surveys are 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 of the patient will be related to the appearance and duration of their symptoms, and to the presence of other members of the family 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 fundamental for the determination of the presence of a symptomatology compatible with this pathology.
During the physical and neurological examination, different specialists try to observe the presence of muscle weakness in the extremities, significant reduction of muscle mass, decreased reflexes or loss of sensitivity (National Institute of Neurological Disorders and Stroke, 2016).
In addition, it is also to determine the presence of other types of alterations such as deformities in the feet and hands (dig foot, hammertoes, flat pee or inverted heel), scoliosis, dysplasia in the hip, among others (National Institute of Neurological Disorders and Stroke, 2016).
However, since many of those affected are asymptomatic or present very subtle clinical signs, it will also be necessary to use some tests or clinical tests (Bereciano et al., 2012).
Thus, a neurophysiological examination is frequently performed (Bereciano et al., 2012):
- Nerve conduction study : in this type of tests, the objective is to mediate the speed and efficiency of electrical signals that are transmitted through nerve fibers. Generally, small electrical pulses are used to stimulate the nerve and responses are recorded. When the electrical transmission is weak or slow, it offers an indicator of possible nervous affectation (Mayo Clinic, 2016).
- Electromyography (EMG) : in this case, the muscle electrical activity is recorded, offering information about the muscle’s ability 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 tests , a small portion 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 CMT2 type usually present with axonal degeneration (National Institute of Neurological Disorders and Stroke, 2016).
- Genetic test: these tests are used to determine the presence of defects or genetic alterations compatible with the disease.
Chacot-Marie-Tooth disease presents a progressive course, therefore, symptoms usually get worse slowly over time.
Muscle weakness and numbness, difficulty walking, loss of balance or orthopedic problems usually progress to cause a serious state of functional disability (Charcot-Marie-Tooth Association, 2016).
Also Read: Bell’s palsy: Symptoms, Causes and Treatment
Currently, there is no treatment that cures or stops Charcot-Marie-Tooth disease.
The most commonly used therapeutic measures usually include (Charcot-Marie-Tooth Association, 2016).