- Characteristics of Charcot-Marie-Tooth disease
- Statistics
- Characteristic symptoms and signs
- Causes
- Types of Charcot-Marie-Tooth disease
- Charcot-Marie-Tooth type I and type II (CMT1 and CMT2)
- Charcot-Marie-Tooth Type X (CMTX)
- Charcot-Marie-Tooth type III (CMT3)
- Charcot-Marie-Tooth type IV (CMT4)
- Diagnosis
- Treatment
- References
The disease Charcot-Marie-Tooth is a sensorimotor polyneuropathy, ie a medical condition that causes damage or degeneration of the peripheral nerves (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 is named after the three physicians 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 the production of proteins related to the function and structure of peripheral nerves (National Institute of Neurological Disorders and Stroke,
2016).
Generally, the characteristic symptoms of Charcot-Marie-Tooth disease begin to appear in adolescence or early adulthood and its 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 disease (CMT) is a motor-sensory polyneuropathy, caused by a genetic mutation that affects the peripheral nerves and produces a wide variety of symptoms, including: 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 lesion and the affected anatomical area (Colmer Oferil, 2008).
Specifically, Charcot-Marie-Tooth disease affects the peripheral nerves, which are those outside the brain and 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, pathologies that affect 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).
Statistics
Charcot-Marie-Tooh disease is the most prevalent type of inherited 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 of age (Errando, 2014).
This pathology can affect any person, regardless of their 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 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 appear progressively.
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 in the lower extremities, 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 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 patients may have severe muscle atrophy in the hands and feet, in addition to various deformities, while in other people only mild muscle weakness or pes cavus may be observed (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 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 symptoms will develop (National Institute of Neurological Disorders and Stroke, 2016).
The presence of genetic mutations, on many occasions, can lead to the development of alterations in the normal or usual function of the peripheral nerves, as is the case of 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 based on 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 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 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 presents a genetic inheritance linked to the X chromosome. This type of pathology has clinical characteristics similar to types I and II, and, in addition, it usually affects the majority of males.
Charcot-Marie-Tooth type III (CMT3)
Type III of Charcto-Marie-Tooth disease is commonly known as Dejerine Sottas (DS) disease or syndrome (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 present a severe neuropathy with generalized weakness, 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, furthermore, at the genetic level, 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.
Diagnosis
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. Generally, various 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 to the patient will be related to the appearance and duration of their symptoms, and 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 for determining the presence of a symptomatology compatible with this pathology.
During the physical and neurological examination, the different specialists try to observe the presence of muscle weakness in the extremities, a significant reduction in muscle mass, decreased reflexes or loss of sensitivity (National Institute of Neurological Disorders and Stroke, 2016).
In addition, it also tries to determine the presence of other types of alterations such as deformities in the feet and hands (pes cavus, hammer toes, flat feet 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 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 the 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 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 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 CMT2 type tend to have 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.
Treatment
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 severe 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 ultimate goal is to maintain or restore the ability to walk.
References
- Association, DM (2010). Facts about Charcot-Marie-Tooth disease and related diseases.
- Berciano, J., Sevilla, T., Casasnovas, C., Sivera, R., Vilchez, J., Infante, J.,… Pelayo-Negro, A. (2012). Diagnostic guide in patients 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: a review with emphasis on the pathophysiology of pes cavus. Rev es cir ortop traumatol., 55 (2), 140-150.
- Clinic, C. (sf). Charcot-Marie-Tooth Disease (CMT). Obtained from Cleveland Clinic.
- CMTA. (2016). What is Charcot – Marie – Tooth disease (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. (sf). Charcot-Marie-Tooth disease. Obtained from Mayo Clinic.
- NIH. (2013). Charcot-Marie-Tooth disease. Retrieved from MedlinePlus.
- NIH. (2016). Charcot-Marie-Tooth Disease Fact Sheet. Obtained from National Institute of Neurological Disorders and Stroke.