Duchenne muscular dystrophy: symptoms and treatment

Duchenne's muscular dystrophy is a genetic disorder associated with a disorder in the structure of the muscle fibers. Muscle fibers in this disease, in the end, break up, and the ability to move is lost. Duchenne's muscular dystrophy is transmitted adherent to the sex, men are ill. It manifests itself already in childhood. In addition to muscle disorders, the disease leads to skeletal deformities, can be accompanied by respiratory and heart failure, mental and endocrine disorders. A radical method of treatment, which allows to eradicate the disease, is not yet available. All existing measures are only symptomatic. Quite often, patients manage to survive the threshold of 30 years. This article is devoted to the causes, symptoms, diagnosis and treatment of Duchenne muscular dystrophy.

The disease was first described in 1861 (according to other sources - 1868) by a French neurologist and bears his name. It is not so rare: 1 case for , 00 newborns. Of all the known medicines, muscular dystrophy is the most common.

Cause of disease

At the heart of Duchenne muscular dystrophy is a genetic defect of the sex X chromosome.

One of the sites of the X chromosome contains a gene that codes for the production in the body of a special muscle protein called dystrophin. Protein dystrophin forms the basis of muscle fibers (myofibrils) at a microscopic level. The function of dystrophin is to maintain the cellular skeleton, to ensure the ability of myofibrils to multiple acts of contraction and relaxation. With Duchenne muscular dystrophy, this protein is either absent altogether or synthesized by a defective one. The level of normal dystrophin does not exceed 3%. This leads to the destruction of muscle fibers. Muscles are reborn and replaced with fat and connective tissue. Naturally, at the same time, the motor component of human activity is lost.

The disease is inherited by a recessive type linked to the X chromosome. What does this mean? Since all the human genes are paired, that is, they duplicate each other, in order for pathological changes in the body to appear with hereditary disease, it is necessary that the genetic defect originated in one chromosome or similar parts of both chromosomes. If the disease occurs only with mutations in both chromosomes, then this type of inheritance is called recessive. When a genetic anomaly is detected only in one chromosome, but the disease still develops, this type of inheritance is called dominant. Recessive type is possible only with simultaneous damage to identical chromosomes. If the second chromosome is "healthy then the disease does not arise. That is why Duchenne's muscular dystrophy is the lot of males, because they have one X chromosome in the genetic set, and the other (pair) - U. If the boy gets a "broken" X chromosome, then he must have a disease, because he does not have a healthy chromosome. In order for Duchenne's muscular dystrophy to arise in the girl, it is necessary to coincide in her genotype of two pathological X chromosomes that it is almost unlikely (in this case, the girl's daddy must be sick, and the mother in the genetic set must have a defective X chromosome). Girls act only as carriers of the disease and pass it on to their sons. Of course, some cases of the disease are not the result of inheritance, but arise sporadically. This means the appearance of a mutation in the genetic set of the child spontaneously. A new mutation can be inherited (provided that the ability to reproduce is preserved).

Symptoms of the disease

Duchenne's muscular dystrophy always manifests itself before the age of five. Most often, the first symptoms occur even before 3 years. All pathological manifestations of the disease can be divided into several groups (depending on the nature of the changes):

• defeat of skeletal musculature;
• deformations of the skeleton;
• defeat of the heart muscle;
• mental disorders;
• endocrine disorders.

Skeletal muscle damage

The defeat of muscle tissue is the main manifestation of the disease. It causes a generalized muscle weakness. The initial symptoms creep unnoticed.

Children are born without any deviations. However, their motor development lags behind in the pace compared with peers. Such children are less active and motile. While the child is very small, it is often associated with the characteristics of temperament and do not pay attention to the initial changes.

Obvious signs arise with the onset of walking. Children often fall and move on their toes (on socks). It should be noted that these violations are not interpreted at the first steps of the child, because uprightness at first for all children is associated with falls and awkwardness. When most of the peers are already quite confidently moving, boys with Duchenne muscular dystrophy persistently continue to fall.

When the child learns to talk, he begins to complain of weakness and rapid fatigue, intolerance to physical activity. Running, climbing, jumping and other favorite activities of children for a child with Duchenne muscular dystrophy are not attractive.

The gait of such children resembles a duck: they seem to fall from one foot to the other.

A peculiar manifestation of the disease is a symptom of Hovers. It consists in the following: when a child tries to rise from his knees, squat, from the floor he uses his hands to help the weak muscles of his legs. For this he rests his hands on himself, "climbing the ladder, on himself."

Duchenne muscular dystrophy has an ascending type of muscle weakness. This means that at first weakness manifests itself in the legs, then spreads to the pelvis and trunk, then to the shoulders, neck and, finally, to the hands, respiratory muscles and head.

Despite the fact that with this disease, the muscle fibers undergo destruction and development of atrophy, some muscles may look quite normal or even inflated outwardly. The so-called pseudohypertrophy of muscles develops. Most often this process is noticeable in the gastrocnemius, gluteal and deltoid muscles, muscles of the tongue. The place of broken muscle fibers occupies fatty tissue, which is why the effect of good muscular development is created, which is not the case for testing.

The atrophic process in muscles is always symmetrical. The ascending direction of the process leads to the appearance of an "aspen" of the waist, "pterygoid" blades (the scapulae lag behind the torso, like wings), the symptom of "free shoulder-straps" (when the head seems to fall into the shoulders when trying to lift the child under mouse). The face is hypomimetic, the lips can thicken (muscle replacement with fat and connective tissue). Pseudohypertrophy of the tongue becomes the cause of speech disorders.

The destruction of muscles is accompanied by the development of muscle contractures and shortening of the tendons (it is clearly seen in the example of the Achilles tendon).

Tendon reflexes (knee, Achilles, biceps, triceps and so on) are gradually decreasing. Muscles feel dense, but painless. Muscle tone usually decreases.

The gradual progression of muscle weakness leads to the fact that by the age of 10-12 many children lose the ability to move independently and need a wheelchair. The ability to stand remains, on average, up to 16 years.

Separately, we should mention the involvement of respiratory muscles in the pathological process. This is observed after the adolescent period. The weakness of the diaphragm and other muscles involved in the act of breathing leads to a gradual decrease in the vital capacity of the lungs and the volume of ventilation. At night, it is especially noticeable (there are attacks of suffocation), so children may have fears of going to sleep. Forms respiratory failure, which aggravates the course of intercurrent infections.

Deformations of the skeleton

This is associated with muscle changes symptoms. Children gradually develop lumbar flexure (lordosis), curvature of the thoracic spine to the side (scoliosis) and stoop (kyphosis), the shape of the foot changes. Over time, diffuse osteoporosis develops. These symptoms further contribute to impairment of motor disorders.

Defeat of the heart muscle

It is a mandatory symptom of Duchenne muscular dystrophy. Patients develop cardiomyopathy (hypertrophic or dilated). Clinically, it manifests itself as heart rhythm disturbances, blood pressure changes. The boundaries of the heart are increasing, but such a large heart has small functionalities. In the end, heart failure is formed. The combination of severe heart failure with respiratory disorders against the background of an infection can cause death in patients with Duchenne muscular dystrophy.

Mental disorders

This is not an obligatory, but possible sign of the disease. It is associated with a deficiency of a particular form of dystrophin - apodystrophin, contained in the brain. Intellectual disabilities range from insignificant to idiocy. In this case, the severity of mental disorders is in no way related to the degree of muscle disorders. Social disadaptation due to the inability to move around freely and visit children's institutions (kindergartens, schools) contributes to the aggravation of cognitive disorders.

Endocrine Disorders

Occur in 30-50% of patients. Can be quite diverse, but more often this obesity with the predominant deposition of fat in areas of the mammary glands, thighs, buttocks, shoulder girdle, underdevelopment (or disruption of function) of sexual bodies. Patients often have low growth.

Duchenne's muscular dystrophy is steadily progressing. By 15-20 years, almost all patients are not able to service themselves because of immobility. In the end, bacterial infections (respiratory and urinary organs, infected decubitus with insufficient care), which, on the background of cardiac and respiratory insufficiency, lead to a fatal outcome. Few of the patients survive the age of 30 years.

Diagnostics

Diagnosis of Duchenne muscular dystrophy is based on several types of research, the main one of which is a genetic test (DNA diagnosis).

Only the detection of a chromosome X defect in the site that is responsible for the synthesis of dystrophin, reliably confirms the diagnosis. Before carrying out such an analysis, the diagnosis is preliminary.

From other methods of research can be used:

• determination of activity of creatine phosphokinase (CK). This enzyme reflects the death of muscle fibers. Its concentration in muscular dystrophy Duchenne exceeds the norm in tens and hundreds of times to 5 years of age. Later, the level of the enzyme gradually decreases, because some of the muscle fibers are irreversibly destroyed;
• electromyography. This method allows us to confirm the fact that the disease is based on the primary changes in the muscles, while the nerve wires are completely intact;
• muscle biopsy. With its help determine the protein content of dystrophin in the muscle. However, in connection with the improvement of genetic diagnostics in recent decades, this traumatic procedure has receded into the background;
• respiratory tests (examination of the vital capacity of the lungs), ECG, ultrasound of the heart. These methods are not used to establish a diagnosis, but are necessary to identify pathological changes in the respiratory and cardiovascular systems in order to correct the available violations.

Detection of a sick child in the family means that the pathogen X chromosome is present in the mother's genotype. In rare cases, the mother can be healthy if the mutation occurred in the child by accident. The presence of a defective X chromosome carries a risk for subsequent pregnancies. Therefore, such families should be advised by a geneticist. In the event of repeated pregnancies, parents are offered prenatal diagnostics, that is, a study genotype of an unborn child with the aim of excluding hereditary diseases, including muscular dystrophy Duchenne.

For the study, fetal cells will be needed, which are obtained by various procedures at different periods of pregnancy (for example, chorionic biopsy, amniocentesis and others). And although these medical manipulations carry a certain risk for pregnancy, they allow you to accurately answer the question: does the fetus have a genetic disease.

Treatment

Duchenne's muscular dystrophy is currently an incurable disease. It is possible to help a child (an adult) to prolong the time of motor activity, using various ways of supporting muscular strength, compensating for changes in the cardiovascular and respiratory systems.

Despite this, the scientists' forecasts regarding the complete cure for this disease are quite optimistic, since the first steps have already been taken in this direction.

Currently, for the treatment of Duchenne muscular dystrophy from medications use:

• Steroids (with regular application they can reduce muscle weakness);
• β-2-adrenomimetics (also temporarily give strength to the muscles, but do not slow the progression of the disease).

The use of β-2-adrenomimetics (Albuterol, Formotherol) has no statistically significant recognition, since there is little experience with their use in this pathology. The control of changes in the state of health in a group of patients who used these drugs was carried out for one year. Therefore, to assert that they work for a longer time, there is no possibility.

The basis of treatment today are steroids. It is believed that their use allows for some time to maintain muscle strength, that is, they can slow the progression of the disease. In addition, it has been proven that steroids reduce the risk of scoliosis in Duchenne muscular dystrophy. Nevertheless, the possibilities of these drugs are limited, and the disease will progress steadily.

When do they start treatment with hormones? It is believed that the optimal time for the initiation of therapy is a phase of the disease, when the motor skills do not improve, but do not deteriorate yet. Usually it happens at the age of 4-6 years. The most commonly used drugs are Prednisolone and Deflazacort. Doses are assigned individually. The drugs are used as long as there is a visible clinical effect. When the phase of disease progression comes, the necessity of using steroids disappears, and they are gradually (!) Canceled.

From medicamentous preparations also at muscular dystrophy Duchenne apply heart means (antiarrhythmic, metabolic, inhibitors of an angiotensin-converting enzyme). They allow you to deal with the cardiological aspects of the disease.

Of non-drug treatment methods, a significant role is played by physiotherapy and orthopedic care. Physiotherapy techniques allow longer, without their application, to maintain flexibility and mobility of joints, support muscular strength. It is proved that moderate physical activity favorably influences the course of the disease, but inaction and bed rest, on the contrary, contribute to an even faster progression of the disease. Therefore it is necessary to support as much as possible physical activity, even after the patient has "moved" to a wheelchair. Regular courses of massage are shown. The well-being of the patient is positively influenced by swimming.

Orthopedic adaptations can greatly facilitate the life of the patient. Their list is quite wide and diverse: it's various kinds of verticals (help to keep standing), and devices for self-standing, and wheelchairs with wheelchairs electric drive, and special tires to eliminate contractures in the lower leg (used even at night), and corsets for the spine, and long tires for the legs (knee-ankle orthoses), and much other.

When the disease affects both the respiratory muscles and independent breathing becomes ineffective, it is possible to use artificial ventilation devices of various modifications.

And yet, even the use of all these measures in a complex does not allow one to overcome the disease. To date, there are a number of promising areas of research, which, perhaps, will be a breakthrough in the treatment of Duchenne muscular dystrophy. Among the most common among them are:

• gene therapy (the introduction of the "right" gene with the help of virus particles, the delivery of genetic constructs in the composition of liposomes, oligopeptides, polymeric carriers and others);
• regeneration of muscle fibers with the help of stem cells;
• transplantation of myogenic cells that are capable of synthesizing normal dystrophin;
• skipping exons (using antisense oligoribonucleotides) as an attempt to slow the progression of the disease and soften its course;
• replacement of dystrophin with another protein, atrophine, the gene of which is deciphered. The technique was tested on mice and gave positive results.

Each of the new developments carries a hope for patients with Duchenne muscular dystrophy for complete recovery.

Thus, Duchenne's muscular dystrophy is the genetic problem of males. The disease is characterized by progressive muscular weakness due to the destruction of muscle fibers. Currently, it is an incurable disease, but many scientists around the world are working to create a radical way to deal with it.

Animated film "Muscular Dystrophy of Duchenne Eng. voice, subtitles in Russian: