The Charcot-Marie-Tooth disease is A sensory-motor polyneuropathy, that is, a medical pathology that causes nerve damage or degeneration (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 limbs and especially in the feet (Cleveland Clinic, 2016).
In addition, it is a genetic disease, caused by the existence of several mutations in genes that are responsible for the Production of proteins related to the function and structure of the peripheral nerves (National Institute of Neurological Disorders and Stroke,
2016).
Typically, 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 generally does not endanger the person's life (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, the Occupational therapy And drug prescriptions for symptom control (Cleveland Clinic, 2016).
Characteristics of Charcot-Marie-Tooth disease
Charcot-Marie-Tooth disease (CMT) 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 keep the body in a horizontal position, muscle weakness, joint pain, between 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 of the affected anatomical area (Colmer Oferil, 2008).
Specifically, Charcot-Marie-Tooth disease affects the peripheral nerves, which are those outside the brain Y the spinal cord (Clinica Dam, 2016) and are responsible for innervating the muscles and sensory organs of 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 will be called motor, sensory or sensorimotor as a function of the affected nerve fibers.
Charcot-Marie-Tooth disease therefore encompasses the development of various motor and sensory disorders (National Institute of Neurological Disorders and Stroke, 2016).
About us
Charcot-Marie-Tooth disease is the most prevalent type of hereditary peripheral neuropathy (Errando, 2014).
Usually, it is a pathology of childhood or juvenile onset (Bereciano et al., 2011), whose average age of presentation is around the 16 years old (Errando, 2014).
This pathology can affect any person, regardless of race, place of origin or ethnic group and has been recorded approximately 2.8 Millions of cases around the world (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 presents a prevalence of 28.5 cases per 100 inhabitants (Bereciano et al., 2011).
Symptoms and characteristic signs
Depending on the involvement of nerve fibers, the characteristic signs and symptoms of Charcot-Marie-Tooth disease will be Progressive form.
Typically, the Charcot-Marie-Tooth disease clinic is characterized by the progressive development of weakness and muscle atrophy of the extremities.
The nerve fibers that innervate the legs and arms are the most extensive, making them 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 muscle deformity in the feet: presence of a cavus or arched foot or hammer toes.
- Difficulty or inability to hold the feet in a horizontal position.
- Significant loss of muscle mass, especially in the lower limbs.
- Alterations and problems of balance.
In addition, various sensory symptoms may also appear, such as numbness of the lower extremities, muscle pain, Decrease or loss of sensation of legs and feet, among others (Mayo Clinic, 2016).
As a consequence, affected people often stumble upon walking, falling, or having an altered gait, frequently.
In addition, as the involvement of peripheral nerve fibers progresses, similar symptoms may develop in the upper limbs, arms and hands (Charcot-Marie-Tooth Association, 2016).
Although this is the most common symptomatology, the clinical presentation is highly variable. Some affected Severe muscle atrophy in the hands and feet, as well as various deformities, while in others only mild muscle weakness or the Foot cavo (OMIN, 2016, Pareyson, 1999, Murakami et al., 1996).
Causes
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 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 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, in many cases can lead to the development of alterations in 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 the genetic mutations of Charcot-Marie-Tooth disease are generally 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 disease Charcot-Marie-Tooth
There are several types of Charcot-Marie-Tooth disease (National Institute of Neurological Disorders and Stroke, 2016), which are often categorized into Function of 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)
We will now 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 present a typical onset during childhood or adolescence and are the most frequent types.
Type I has an autosomal dominant inheritance, whereas 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 gene PMP22 located On chromosome 17. This type of genetic involvement is responsible for approximately 60% of the diagnosed cases of Charcot-Marie-Tooth.
Charcot-Marie-Tooth Type X (CMTX)
In this type of Charcot-Marie-Tooth disease, the typical onset of 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, it usually affects the majority of men.
Charcot-Marie-Tooth type III (CMT3)
Type III of Charcot-Marie-Tooth disease is commonly known as Dejerine Sottas (DS) (Charcot-Marie-Tooth Association, 2016).
In this pathology, the first symptoms usually appear in the early stages of life, typically before 3 years of age.
At the genetic level, it may present an autosomal dominant or recessive inheritance.
In addition, it is one of the most severe forms of the disease of Charco-Marie-Tooh. Those affected have severe neuropathy with weakness Generalized, loss of sensitivity, 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 infancy or adolescence and, at the same 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.
People affected in childhood, usually have a generalized delay of motor development, in addition to a poor muscle tone.
Diagnosis
The first phase of identification of Charcot-Marie-Tooh disease is related both to the development of family history and to the observation of symptomatology.
It is critical to determine if the person has hereditary neuropathy. Generally, several family surveys are carried out to 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 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, the different specialists try to observe the presence of muscular weakness in the extremities, reduction Significant muscle mass, decreased reflexes or loss of sensation (National Institute of Neurological Disorders and Stroke, 2016).
In addition, it is also a question of determining the presence of other alterations such as deformities in the feet and hands (foot cavus, hammer toe, pee Flat 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 have 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 the electrical signals that are Transmit through the nerve fibers. Generally, small electrical pulses are used to stimulate the nerve and the responses are recorded. When the electrical transmission is weak or slow, it gives us an indication of possible nerve involvement (Mayo Clinic, 2016).
- Electromyography (EMG) : In this case, the muscular electrical activity is recorded, offering us information about The ability of the muscle to respond to nerve stimulation (Mayo Clinic, 2016).
In addition, other tests are also performed, 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. Typically, patients with CMT1 type present abnormal myelination, while those with type CMT2, 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.
Treatment
Charcot-Marie-Tooth disease presents a progressive course, therefore, the symptoms usually worsen slowly with the passage of time.
Muscle weakness and numbness, difficulty walking, loss of balance or orthopedic problems often progress to cause A serious condition of functional disability (Charcot-Marie-Tooth Association, 2016).
There is currently no treatment to cure or stop Charcot-Marie-Tooth disease.
The most commonly used therapeutic means include (Charcot-Marie-Tooth Association, 2016).
- Physical and occupational therapy : They are used to maintain and improve the muscular capacities and to control the functional independence of the Affected person.
- Orthopedic devices : These types of equipment are 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.
References
- Association, D.M. (2010). Facts about Charcot-Marie-Tooth disease and related illnesses.
- Berciano, J., Sevilla, T., Casasnovas, C., Sivera, R., Vilchez, J., Infante, J.,. . . Pelayo-Negro, A. (2012). Diagnostic guide in the patient with Charcot-Marie-Tooth disease. Neurology, 27 (3), 169-178.
- Bereciano, J., Gallardo, E., García, A., Pelayo-Negro, A., Infante, J., & Combarros, O. (2011). Charcot-Marie-Tooth Disease: Review with Emphasis In the pathophysiology of the cavus foot. Rev es cir ortop traumatol., 55 (2), 140-150.
- Clinic, C. (s.f.). Charcot-Marie-Tooth Disease (CMT). Obtained from Cleveland Clinic.
- CMTA. (2016). What is Charcot's disease? Marieâ??? Tooth (CMT)? Obtained from Charcot-Marie-Tooth Association.
- Colomer Oferil, J. (2008). Sensory-motor polyneuropathies. Spanish Association of Pediatrics .
- Errando, C. (2014). Charcot-Marie-Tooth disease.
- Mayo Clinic. (S.f.). Charcot-Marie-Tooth disease . Obtained from Mayo Clinic.
- NIH. (2013). Charcot-Marie-Tooth disease . Obtained from MedlinePlus.
- NIH. (2016). Charcot-Marie-Tooth Disease Fact Sheet . Retrieved from the National Institute of Neurological Disorders and Stroke.