Duchenne's Dystrophy

The disease, which is called Duchenne's dystrophy, is associated with damage to the gene structures responsible for the production of large muscle protein dystrophin. Such a pathology is transmitted by a hereditary path, an autosomal recessive type of inheritance: that is, this pathology hides, as it were, or manifests itself through a generation. This type is linked to the X chromosome.

Causes of the duchenne Dystrophy

Pathology appears due to the gene mutation that occurs in the region xp21. More than a quarter of such pathologies are associated with a persistent change in the genotype in the maternal ovum. The remaining cases are explained by the heterozygosity of the patient's mother by pathology of mutagenesis in the dystrophin gene.

It is generally accepted that about 7% of all recurring cases are due to the formation of several cellular generations in the female ovary with mutated and normal alleles of dystrophin. The most common type of mutation (about 65%) is the significant loss of chromosome regions. In 5% of patients, the chromosome segment is doubled, and in the remaining cases, pathology is point mutation, when one or more nucleotides are involved, whereas the mutations are longer gene defects.

Pathology is transmitted by an autosomal recessive type, with a linkage to the X chromosome (affects male individuals). More than half of these pathologies occur spontaneously, due to gene mutation.

In genetic examination, an important role is played by the determination in the sisters of the patient of the latent signs of the disease. From such carrier of the mutated gene, the transmission of pathology of 50% of its male children can occur, and 50% of its daughters will become carriers of the mutated gene.

Women who have a damaged gene share it with their child, although they do not suffer from myopathy themselves. Mostly, the disease affects boys. Girls can also get sick, but this happens very rarely: this can happen only if the chromosome structure is defective.

Symptoms of the duchenne Dystrophy

The initial symptoms of Duchenne's dystrophy can be seen already at the age of 1 to 5 years. A sick child is characterized by inhibition of early motor activity. When trying to walk alone (in children older than 1 year), you can observe constant falls, entanglement of legs, rapid fatigue. If the baby still begins to walk, then he is shifting from foot to foot (duck walk), it is difficult for him to climb the steps and get up from his knees.

Gradually, in small patients, there is an increase in the volume of different muscle groups, which is similar in appearance to heavily inflated muscles. With the further course and the aggravation of pathology, such an increase passes, on the contrary, to a decrease in muscles.

The disease spreads through the body in an ascending way: from the muscles of the legs and small pelvis to the back, shoulders and hands.

Even at the initial stages of the disease, a decrease in tendon reflexes can be observed. Further, the curvature of the spine develops, the thorax becomes saddle or keel, the feet are deformed. There are problems with the heart muscle: there are signs of cardiac arrhythmias and left ventricular hypertrophy. A quarter of patients show symptoms of mental retardation: most often this is manifested as signs of oligophrenia.

Approximately 12 years of age, patients stop walking, after 2-3 years completely lose the ability to make movements. At the age of 20-30 more of these patients die. At later stages of the disease, muscle weakness passes to the respiratory and swallowing system. Lethal outcome comes from joining bacterial infections or from a lack of respiratory and cardiac activity.

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Forms

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Duchenne muscular dystrophy

Duchenne muscular dystrophy, fortunately, is relatively rare and manifests itself in muscle weakness. According to statistics, this pathology occurs in about one baby from 3,000 newborns. In addition, there are several fairly rare forms of myopathy, differing in less pronounced manifestations.

The development of muscular dystrophy is associated with the slow destruction of the connections between the nervous and muscle fibers.

Girls born from a mother with a damaged gene can also become carriers of such damage, although the disease is almost never manifested.

In addition to Duchenne's dystrophy, medicine also distinguishes other types of myopathies, which are extremely rare:

• Becker's syndrome (also affects boys, has an innate type, but manifests itself only to the period of puberty and retreats to around 45 years);
• congenital form of myopathy (affects children regardless of sex, but can occur, we can say, only in isolated cases);
• shoulder-shoulder-facial form of myopathy - is not immediately apparent, but for about 10 years. In pathology, weakness of facial muscles is noted, sluggish reaction of the face musculature when trying to express certain emotions;
• pathology of Emery-Dreyfus (a similar kind of myopathy with negative consequences for the myocardium).

[8], [9], [10], [11],

Progressive Dystrophy of Duchesne

Duchenne's progressive dystrophy is a serious, most common form of myopathy. It develops in infancy, usually in children under 3 years old, occasionally at an older age. Practically in all patients (with a few exceptions) there is an increase in the size of gastrocnemius muscles (sometimes in conjunction with deltoid and quadriceps). This increase is often associated with fatty infiltration of the muscles, but in some cases it actually increases muscles.

The decrease in the volume of muscle mass is observed mainly in the back and pelvic region. Along with atrophic disorders, it is often possible to note the presence of mental retardation.

It is not uncommon to violate the integrity and shape of bones, even due to minor loads and injuries. After 5-10 years from the first manifestations of pathology, it is possible to detect damage to the heart muscle, which is expressed by tachycardia and ECG disorders. A characteristic feature is the increased activity of serum creatine kinase.

In general, the disease is more severe than with other forms of myopathy. Atrophic changes spread rapidly throughout the body. Most patients by the age of 10 are practically unable to move. Such patients are extremely rarely able to live up to 30 years, dying from concomitant diseases.

Diagnostics of the duchenne Dystrophy

The diagnosis of Duchenne's dystrophy should be confirmed by genetic testing, but in some cases, the appointment of other studies.

1. The genetic test is carried out unequivocally, even if the doctor is sure that the patient has muscular dystrophy. With the help of this method, you can determine the precise characteristics of pathological disorders in DNA. In addition to the diagnosis, this study will help parents decide on future pregnancies. Also, the results of the genetic test will be useful to the relatives of the carrier mother of the mutated gene.
2. The doctor can advise you to undergo a biopsy of muscle fibers. Such research will show whether the protein produces dystrophin, and if produced, then in what quantity. Using biopsy specialists determine the exact amount of protein in myocytes. But biopsy can not be a substitute for genetic analysis!
3. The method of electromyography (determination of the conductivity of nerve impulses) was relevant a few years ago, but now it is not necessary.
4. Blood test for creatine kinase: in Duchenne's dystrophy, the amount of this enzyme is much higher than normal.
5. Evaluation of cardiac activity, respiratory system, muscle capabilities, ECG, determination of cardiac biological markers and bone tissue density.

It is very important to determine the exact diagnosis, if experts suspect a child of myopathy. And it is necessary to do this in the very near future. The doctor will appoint the qualified treatment on the basis of these researches, having preliminary spent conversation with parents and having explained to them all features of disease.

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Treatment of the duchenne Dystrophy

Currently, Duchenne's dystrophy medications have not been invented yet. Although scientific research on this topic is conducted quite intensively: scientists of Great Britain, Israel and the United States are working on it. The newest methods that are under development:

• skipping exons is a procedure that helps slow the rate of myopathy. This method softens the course of the disease, greatly alleviates the symptoms, but does not eliminate the mutation;
• introduction of the dystrophin gene with the use of viral vectors or plasmids - allows patients to maintain their ability to move and walk longer, which greatly improves their quality of life;
• transplantation of myogenic cells is the introduction of fibroblasts, which contributes to the synthesis of a new unmutated dystrophin. This method has several advantages: it is a long-lasting positive result, the ability to combine the procedure with other therapeutic methods, the ability to use at almost any age, and the controlled production of a new dystrophin;
• restoration of muscle fibers using embryonic stem cells, muscle stem cells - these methods improve muscle regeneration, allow dystrophin to be produced in large quantities, strengthen muscle structure and significantly restore muscle function;
• regulation of atrophine for the replacement of dystrophin is a method based on an experiment that proves that when there is a deficiency of atrophine, the same symptoms are observed as in the case of a deficiency of dystrophin. These proteins are similar in structure and function. Through long-term scientific research, scientists came to the conclusion that the regulation of the atrophin gene can be used as a treatment for Duchesne's dystrophy;
• blocking of myostatin. Myostatin is an inactive protein that has the ability to trigger biochemical processes that inhibit the formation of muscles. Accordingly, blocking of this protein should promote the growth of muscle tissue;
• blocking the transforming growth factor of β - protein inhibiting the function of myosatellite cells (myogenic stem cells). This method will help to reduce the degree of fibrosis;
• increase in the regulation of insulin-like growth factor-1 - a protein similar in structure to insulin. The growth factor-1 improves the quality of muscle tissue, activates development and increases muscle strength.

At the moment, the specialists offer the following treatment for Duchenne's dystrophy:

• taking corticosteroid drugs to increase muscle strength and ease the patient's condition;
• use of β-2-agonists for temporary muscle strength;
• physiotherapeutic procedures, myostimulation;
• orthopedic assistance (strollers, walkers, shin restraints, etc.).

"Elixir of healing" from Duchenne's dystrophy, unfortunately, does not exist, so when looking for effective treatment with extreme caution, treat the drugs and procedures that can be presented to your attention as a "panacea."

Do not buy an unknown medicine if there is no reliable evidence of its effectiveness. Remember that you can spend a large financial sum, and, besides, not only not to help, but also to hurt your baby.

Prevention

Of course, talking about the prevention of hereditary disease associated with a gene mutation is difficult. Undoubtedly, in families where there are cases of birth of children with muscular dystrophy of Duchesne, it is mandatory to conduct consultations of the geneticist, preferably before the beginning of pregnancy planning by a young couple.

If a child with a muscle pathology has already appeared, then every effort should be made to prevent the loss of muscle tissue and to maintain the motor activity of the child as long as possible. In such situations, it is unacceptable to drop your hands and allow the muscles to atrophy. It is necessary to be engaged with the kid special gymnastics to keep amplitude of movements in joints. To prevent contractures it is recommended to use supporting corsets and fixatives.

Children who have a little, but can walk, should do this as often as possible. Do not force the child into bed: let it be active, this will allow the muscles to slow down the regression. Such children should be given maximum attention and care, they should not feel deprived or offended.

A good effect is provided by swimming, which you can do and even need. Remember: doing nothing (constant bed rest) will only accelerate the progression of the disease. It is necessary to allow the patient, at least, to satisfy his own needs.

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Forecast

Dystrophic processes in the disease affect the entire muscular system: the muscles of the respiratory system, the heart, the skeleton. Patients with Duchene dystrophy often survive to 15, maximum to 30 years. Studies conducted by world scientists in this direction give hope for an improvement in the quality and longevity of such patients.

And now there are cases when patients could live up to 40 or even 50 years. This result was due to the presence of special and constant care: equipment to support the respiratory system, adequate drug therapy.

Detection of the gene, which is the main factor in the development of the disease, has given a tremendous impetus to the continuation of scientific experiments in the therapy of gene mutations. However, at the moment, unfortunately, there is no treatment that would completely cure myopathy. The methods used only provide an opportunity to improve and prolong the life of the patient.

It remains to be believed that in a short time science will find a way to correct the hereditary pathology, and Duchenne's dystrophy will finally be defeated.

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