Myopathy Duzhenna Becker Genetics. Becker Dystrophy

The progressive muscular becker dystrophy (G71.0) is a hereditary progressive disease of the nervous system due to degenerative changes in muscle fibers in the absence of primary pathology of peripheral motioneron.

The reason is the mutation in 21 locus of the short shoulder of the X-chromosome - in the gene encoding the dystrophin protein. The inheritance is recessive, adhesive with the X-chromosome. Men sick.

Symptoms of progressive muscular dystrophy of becker

Debit the disease is observed aged 10-15 years. Originally appear weakness, fatigue with intensive physical exertion; Then gradually increasing weakness in the muscles of the legs, starting with the hips with a less intense load for several years. The ability to independently moves to 30-40 years.

With objective inspection, symmetric proximal muscle weakness in the legs (3-4 points on early and up to 0-1 points in the late stages of the disease) (up to 100%) are detected. Atrophy muscles in the area of \u200b\u200bthe pelvic belt, hips (90%), pseudogiperrophy of calf muscles (80%) are growing atrophy. It is characteristic of the patient with the patient of compensatory myopathic techniques when rising - the symptom of Goras (the patient "climbs"). There is an early reduction in knee tendon reflexes (70%). Pronounced Malgia in the legs, Krampi (35%). Changes in the type "duck" (50%). Difficulty when walking on the stairs - the patient helps themselves with the help of hands - 90%. In 30-50% of cases, the lumbar hyperlordosis, the "hollow stop", walking on the fingers due to the contracture of the Achillov tendons.

With an additional survey, cardiomyopathy (cardiivalgia, blockade of the feet legs of the beam), neuroendocrine disorders (hypogenitalism, testicular atrophy, gynecomastia) can be detected.

Pseudogiperrophy ion muscles	Application by the patient of compensatory myopathic techniques when rising - the symptom of Govers (patient "climbs in itself")

Diagnostics

• DNA diagnostics.
• Research of blood serum (increase in KFK 5-20 times, LDH).
• EMG (primary muscular nature of change).
• Biopsy of skeletal muscles (signs of primary muscle dystrophy and denervation).
• ECG / EHOCG (violation of atrioventricular and / or intraventricular conductivity, myocardial hypertrophy, dilatation of ventricles, stagnant heart failure, cardiomyopathy).

Differential diagnosis:

• Erba muscular dystrophy.
• Spinal Amiotrophy Kugelberg-Vanderder.
• Polymizit, dermatomyomyomy.
• Metabolic myopathy.
• Hereditary polyneuropathy.

Treatment of progressive muscular dystrophy of Becker

• Symptomatic therapy.
• Dosage leaf.
• Glucocorticosteroids.
• Surgical treatment of contractures.

Treatment is assigned only after confirming the diagnosis by a specialist doctor.

Basic drugs

There are contraindications. Consultation of a specialist is necessary.

• (Systemic glucocorticosteroid). Dosing mode: inside, at a dose of 20-80 mg / day. on 3-4 reception. Supporting dose 5-10 mg / day.
• Metlandrindiol (anabolic steroid). Dosing mode: sublingual, adults in a dose of 0.025-0.050 g / day, children at a dose of 1.0-1.5 mg / kg / day. on 3-4 reception.
• ATP (means that improves muscle trophy). Dosing mode: V / m, at a dose of 1 ml of 1% solution 1-2 times a day. The course of treatment is 30-40 injections. Repeated course - after 1-2 months.

Below to the group of heavy pathologies, the treatment of which today is difficult. Among such chromosomal anomalies there are various violations. Many of them have neurological symptoms. Examples are Miodistrophia Duzhenna, Becker. These diseases are developing in childhood and have a progressive course. Despite the achievements of neurology, such pathologies are poorly treatable. This is due to chromosomal changes that are laid during the formation of the body.

Description of Miodistrophi Dusenna

Duchend Miodistrophia is a genetic disease that exhibits the progressive impaired muscular apparatus. Pathology is rare. The prevalence of the anomaly is approximately 3 people per 10,000 male persons. The disease almost in all cases amazes boys. Nevertheless, the development of miodastrophia among girls is not excluded. This pathology manifests itself in early childhood.

Another disease that has the same causes and symptoms is Miodistrophia Becker. It has a more favorable flow. The lesion of muscle tissue occurs significantly later - in adolescence. At the same time, the symptoms are developing gradually, and the patient maintains ability to work for several years. Like Miodistrophia Duzhenna, this pathology is distributed to the male population. The frequency of occurrence is 1 person for 20 thousand boys.

Miodistrophy Duzhenna: Neuroimmunology of the disease

The reason for both pathologies lies in the violation of the X-chromosome. Genetic changes occurring at Miodystrophy of Becker and Dunene, studied in the 30s of the last century. Nevertheless, etiological therapy has not yet been found. The inheritance type of anomaly is recessive. This means that if the pathological gene is present at one of the parents, the probability of the birth of a patient child is 25%. X-chromosome is the longest in the body. At both, the violation occurs in the same locus (P21). This damage leads to a decrease in protein synthesis, which is included in the cell membrane of muscle tissue. With miodistrophiy dushenna, it is completely absent. Therefore, the violations are manifested much earlier. In case of bicker, protein synthesis is synthesized in small quantities or is pathological.

Clinical picture of Miodistrophi

Duchend Miodistrophy is characterized by the damage to the neuromuscular apparatus. The disease can be suspected at the age of 2-3 years. During this period it becomes noticeable that the child lags behind in physical development from its peers, it goes badly, runs and jumps. So the kids are hard to climb the steps, it often falls. Muscle defeat begins with lower limbs. Later it applies to all proximal muscles departments. Degeneration occurs in the upper shoulder belt, in these places there is a thinning of muscles. Over the years, Miodistrophia progresses. The lesion of the muscles and the constant load on them lead to contractures - resistant curvature of the limbs. In addition, heart diseases are observed in patients with Miodistrophia Durane, which periodically make themselves felt. Also for this pathology is characterized by a decrease in intellectual abilities (not very pronounced).

Becker Miodistrophia has the same symptoms, but develops later. The first manifestations are observed in 10-15 years. There is a gradual change in the gait, sharpness appears, later develop contractures. Violations from the cardiovascular system are weakly expressed. Intellect with this disease is usually not reduced.

How to diagnose Miodistrophi?

Diaran Miodistrophia (or Becker) diagnosis can put an experienced neurologist. First of all, it is based on the clinical picture of these diseases. There are attention to such symptoms as the thinning of the muscles of the proximal departments, false hypertrophy of the icy muscles (arises due to fibrosis and deposits of adipose tissue). These manifestations are almost always combined with cardiovascular pathologies. On ECG, you can notice a rhythm violation,

Also patients with Miodistracy Duzhenna are a little behind their peers in mental development. To determine this, a psychologist is working with children. If this disease is suspected, the miography (definition of the electric potential of muscles) and Ehox is the study of the heart chambers. To accurately determine the presence of pathology, genetic diagnosis is performed. In case of bicker and dunes, patients should be observed in several specialists. Among them is a neurologist, a psychologist and a cardiologist.

Treatment

Unfortunately, the etiological treatment of Miodesfia of Duzhenna and Becker is not developed. Nevertheless, symptomatic and supportive therapy is shown. In the early stages of the disease, medical physical education courses are carried out, massage. With a significant disability, passive movements of the limbs must be performed. To slow down the progression of the development of extensible contractures, resort to the fixation of the legs during sleep. Supporting therapy allows you to extend the life of patients and weaken the symptoms of the disease. Use calcium preparations, Galanamin and Preveyor medicines. In some cases, hormonal agents are prescribed, mainly "prednisone". With progressive violations from the heart, cardioprotectors are prescribed.

Miodistrophia Duzhenna and Becker: Forecast

The forecast of Miodistracy Duzhenna is disappointing. Early development of symptoms and rapid progression of the disease lead to disabilities in childhood. Patients with this pathology require constant care. On average, the life expectancy of patients is about 20 years. Becker Miodistrophy is characterized by a favorable course. With constant observation of doctors and performing their instructions, the performance of patients is preserved up to 30-35 years.

Etiology and Muscular Dystrophy Momentity. Durane muscular dystrophy (MIM №310200) is a Phaternic X-clutch progressive myopathy caused by mutations in the DMD gene. The occurrence is approximately 1 3,500 newborn boys.

Pathogenesis of muscle dystrophy Duzhenna. The DMD gene encodes dystrophy, intracellular protein, expressing mainly in smooth, skeletal and heart muscle, as well as in some neurons of the brain. The skeletal muscles of the dystrophy is part of a large complex associated with the sarchatma proteins that ensure the stability of the sarchatrol.

Mutations B. gene DMDDurane Miodyatrophy, include major deletions (60-65%), large duplications (5-10%) and small deletions, insertion or nucleotide replacement (25-30%). The largest deletions occur in one of the two hot spots. Nucleotide substitutions are found throughout the gene, mainly in dinucleotides CPG.

De Novo. mutations arise with a comparable frequency in the course of ovogenesis and spermatogenesis; The largest deny de novo deletions occur in ovogenesis, while the majority of de novo nucleotide substitutions occur during spermatogenesis.

MutationsCaused by the phenotypic absence of dystrophin leads to a more severe muscle damage than mutant DMD alleles expressing partially functional dystrophy. The correlations between the genotype and the phenotype for the intellectual decrease is not detected.

Phenotype and development of muscle dystrophy Duzhenna

Men with Durane Muscular Dystrophy. Miodistrophia is a progressive myopathy, leading to the degeneration and weakness of muscles. Starting with the muscles of the hip belt and neck flexors, the muscular weakness progressively captures the shoulder belt and the distal muscles of the limbs and the body. Although occasionally and detect randomly patients during the neonatal period due to hypotension or development delays, usually sick boys are diagnosed between the ages of 3 and 5, when the gait anomalies appear.

By 5 years most affected children Using the receptions of Goras and have pseudo-boilers of the muscles of the towers, i.e. An increase in the legs due to the replacement of muscles with fatty and connective tissue. By age, 12 years old, the main part of the patients are immobilized in a wheelchair and have contractures and scoliosis. Most patients die from violation of pulmonary function and pneumonia; The average age of death is 18 years old.

Nearly 95% of patients miodistrophia Dushenna These or other cardiological deviations (dilatation cardiomyopathy or electrocardiographic anomalies) have, and 84% have visible lesions of the muscles of the heart when opening. Chronic heart impairments are almost 50% of patients, occasionally heart failure causes them complaints. Although dystrophy is also present in smooth muscles, smooth muscle complications are rare and include the expansion of the stomach, the vibration of the intestine and the bladder hypotension.

Sick miodistrophia Dushenna They have IQ about 1 rms deviation below normal, and almost a third has one or another degree of mental backwardness. The reasons for this are not established.

Women with Durane Muscular Dystrophy

The age of the beginning and severity miodistrophi Duzhenna Women depend on the degree of displacement of the inactivation of the X-chromosome. If the X-chromosome, carrying a mutant DMD allele, is active in most cells, a woman develops signs of Miodistracy Duzhenna; If a predominantly active X chromosome, carrying a normal DMD allele, women have only a few or do not have any symptoms of this disease.

No matter if they have clinical symptoms skeletal muscular weaknessWomen carrier have deviations in the function of the heart muscle, such as dilatation cardiomyopathy, dilatation of the left ventricle and electrocardiographic changes.

Features of the phenotypic manifestations of dystrophy Duzhenna:
Age of Begin: Childhood
Muscle weakness
Hypertrophy of the heads
Small intellectual insufficiency
High level of serum creatineinase

Treatment of Muscular Dystrophy Duzhenna

Digger Durane Muscular Dystrophy Based on family history and DNA analysis or muscle biopsy with immunohistochemical definition of dystrophin.

Currently treatment of Muscular Dystrophy Duzhenna It is impossible, although improving symptomatic treatment has increased the average life of life from the end of childhood to early maturity. Objectives of therapy - slow down the development of the disease, to ensure mobility, prevent or fix contractures and scoliosis, control the body weight and improve the functions of the lungs and hearts.

Glucocorticoid therapy It may slow down the development of the disease for several years. Explore several types of experimental treatment, including genlin transmission. Most patients also need expanded counseling, as they deal with the psychological effects of chronic fatal disease.

The risk of inheritance of muscle dystrophy

The third part of mothers who gave birth to a sole sick son, ourselves are carriers of mutations in the DMD gene. Nevertheless, the definition of carriage remains a difficult task, since currently affordable molecular methods do not detect small mutations of the single-deactive substitution. The determination of the risk of carriage in families without found deletion or duplication is based on the clutch analysis, series of analyzes of the level of blood serum and the mosaic expression of dystrophin in muscle biopsy samples (due to accidental inactivation of the X-chromosome). When consulting in connection with the risk assessment of the repetition, it is necessary to take into account the high frequency of mosaicism in the genital cells (approximately 14%).

If the mother is a carrier, each son It has a 50% risk of dried muscle dystrophy, and each daughter - 50% risk to inherit DMD mutation. Reflecting the random nature of the inactivation of the X-chromosome, the daughter who inherited mutation in the DMD gene has a low risk of dysenne muscular dystrophy; Nevertheless, for reasons, completely incomprehensible, the risk of cardiac anomalies can reach 50-60%. If the mother is not a carrier according to the results of DNA testing, it remains approximately 7% of the risk of having a boy with muscle dystrophy of Durane due to sexual mosaicism. For these mothers show genetic counseling and possibly prenatal diagnostics.

Example of Durane Muscular Dystrophy. A.I., 7-year-old boy, is a survey due to a slight developmental delay. He has difficulty lifting on the steps, running, a decrease in strength and endurance with intensive physical exertion. His parents, two brothers and sisters are completely healthy; Other family members have no similar complaints. During the inspection, it was revealed by bouncing, admission of the shit (sequence of movements facilitating the flooring from the floor), the weakness of the proximal muscles, which is dying ("duck") gait, sealing the achille tendons and noticeably hypertrophied muscles of the legs. The level of blood creatinase was 50 times higher than the norm.

Insofar as anamnesis And the data of the medical examination, including an increased level of creatineinase, made it possible to assume myopathy, the child for further surveys is sent to the neurogenetic clinic. The results of muscle biopsy showed a pronounced change in the size of muscle fibers, fiber necrosis, the growing of fat and connective tissue and the absence of dystrophy. Based on these results, the child has a preliminary diagnosis of Duzhenna muscle dystrophy, and it is tested for deletions in the dystrophin gene; It turned out that he had to deletion from 45 to 48 exon.

Durane and Becker Miodistrophy are diseases with a X-linked recessive type of inheritance, which are characterized by progressive proximal muscle weakness due to the degeneration of muscle fibers. Becker Miodesfia is distinguished by later early and less severe manifestations.

The diagnosis is suggested clinically and confirm when the protein (dystrophin) is determined, which is a product of a mutated gene. Treatment is concentrated on maintaining a function with the help of physiotherapy and the application of clamps and orthopedic devices; Some patients with a pronounced decrease in the function are prescribed prednisolone.

What is caused by Miodistrophia Duzhenna and Becker?

Dystrophy Duzhenna and Becker are caused by mutations in XP21 locus. During dystrophy Duzhenna, the mutation leads to the absence of dystrophin, the cell wall membrane protein. In the becker dystrophy, an anomalous dystrophy or its insufficient amount is synthesized as a result of mutation. Miodistrophia Duzhenna is found in 1/3000 liveborn boys; Becker dystrophy - 1/30,000 liveborn boys.

Symptoms of Miodistrophi Dushenne and Becker

Duchend Miodistrophia is usually manifested between two and three years. The weakness of the proximal muscles is developing, as a rule, starting from the lower limbs. In children there is a gait for the turnout, gait with a support for socks and lordosis. Such children often fall, it is difficult for them to run, jump, climb the stairs and from the floor. Durane Miodistrophia disease is steadily progressing, bending contractures of joints and scoliosis arise. It develops dense pseudogiperrophy (fat and fibrous substitution of individual enlarged muscle groups, especially the icy muscles). Most patients are chained to a wheelchair for 12 years and die from respiratory complications by 20 years. The defeat of the heart is usually asymptomatic, despite the fact that 90% of patients identify changes to the ECG. In a third of patients, there is a slight unpressing reduction in intelligence, to a greater extent with a violation of verbal, rather than non-verbal tests.

Becker Miodistrophi is manifested clinically much later, and its symptoms are less pronounced. Patients are usually able to walk at least up to 15 years, and many remain walking and adult age. Most of the affected patients live more than 30-40 years.

Diajunction of Miodistrophiya Duzhenna and Becker

The diagnosis is suspected of characteristic clinical manifestations, age of the occurrence, a family history, indicating a hspet type of inheritance. Signs of myopathy are found in electromyography (rapidly caused, short low-amplitude motor potentials) and muscle biopsy (necrosis and pronounced differences in muscle fibers). The level of creatineinase can increase to 100 times compared with normal.

The diagnosis is confirmed by the analysis of the dystrophin in immune staining. Dystrophy is not determined in patients with dystrophy of Duzhenna; In patients with dystrophy of dystrophy becker, as a rule, anomalous (with lower molecular weight) or is detected in low concentrations. DNA analysis in peripheral blood leukocytes to identify mutations can also confirm the diagnosis in the detection of anomalies of the dystrophin gene (deletion and duplication of approximately 65% \u200b\u200band point mutations about 25% of patients).

Identification of carriage and prenatal diagnosis are possible using conventional methods (analysis of pedigree, determination of creatineinase, fetus determination) in combination with DNA analysis and immune painting of muscle tissue with antibodies to dystrophin.

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