Duchenne's dystrophy

The disease, which is called Duchenne dystrophy, is associated with damage to the gene structures responsible for the production of a large muscle protein, dystrophin. This pathology is transmitted hereditarily, by an autosomal recessive type of inheritance: that is, this pathology either hides or manifests itself after a generation. This type is linked to the X chromosome.

Causes Duchenne dystrophy

The pathology appears as a result of a gene mutation occurring in the xp21 region. More than a quarter of such pathologies are associated with a persistent change in the genotype in the mother's egg. The remaining cases are explained by the heterozygosity of the patient's mother for the pathology of mutagenesis in the dystrophin gene.

It is generally accepted that approximately 7% of all periodically occurring cases of the disease are a consequence of the formation of several cell generations with mutated and normal dystrophin alleys in the female ovary. The most common type of mutation (about 65%) is significant loss of chromosome sections. In 5% of patients, a doubling of a chromosome section is detected, and in the remaining cases of pathology, a point mutation is detected, when one or more nucleotides are affected, while mutation refers to more extensive gene defects.

The pathology is transmitted in an autosomal recessive manner, linked to the X chromosome (affects males). More than half of such pathologies occur spontaneously, due to gene mutation.

In genetic testing, it is important to identify hidden signs of the disease in the patient's sisters. Such a carrier of a mutated gene can transmit the pathology to 50% of her male children, and 50% of her daughters will also become carriers of the mutated gene.

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

Symptoms Duchenne dystrophy

Initial symptoms of Duchenne dystrophy can be noticed already at the age of 1 to 5 years. A sick child is characterized by inhibition of early motor activity. When trying to walk independently (in children over 1 year old), one can observe constant falls, tangling of legs, rapid fatigue. If the baby does start walking, then he waddles from foot to foot (duck gait), it is difficult for him to climb stairs and get up from his knees.

Little by little, small patients experience an increase in the volume of various muscle groups, which outwardly resembles heavily pumped muscles. With further progression and aggravation of the pathology, such an increase, on the contrary, turns into a decrease in muscles.

The disease spreads throughout the body in an ascending manner: from the muscles of the legs and pelvis to the back, shoulders and arms.

Already at the initial stages of the disease, a decrease in tendon reflexes can be observed. Then, curvature of the spine develops, the chest becomes saddle- or keel-shaped, and the feet are deformed. Problems with the heart muscle arise: signs of heart rhythm disturbances and left ventricular hypertrophy appear. A quarter of patients show symptoms of mental retardation: most often, this is manifested by signs of oligophrenia.

Around the age of 12, patients stop walking, and after 2-3 years they completely lose the ability to move. At 20-30 years of age, most of these patients die. In the later stages of the disease, muscle weakness spreads to the respiratory and swallowing systems. Death occurs from accompanying bacterial infections or from insufficient respiratory and cardiac activity.

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Forms

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Duchenne muscular dystrophy

Duchenne muscular dystrophy is fortunately relatively rare and manifests itself in muscle weakness. According to statistics, this pathology occurs in approximately one baby out of 3,000 newborns. In addition, several rather rare forms of myopathy are known, which are distinguished by less pronounced manifestations.

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

Girls born to a mother with a damaged gene can also become carriers of such damage, although the disease almost never manifests itself in them.

In addition to Duchenne dystrophy, medicine also identifies other types of myopathies that are extremely rare:

• Becker syndrome (also affects boys, has a congenital type, but manifests itself only during puberty and subsides at approximately 45 years of age);
• congenital form of myopathy (affects babies regardless of gender, but can occur, one might say, only in isolated cases);
• scapulohumeral-facial myopathy - does not manifest itself immediately, but over the course of about 10 years. With this pathology, weakness of the facial muscles and a sluggish reaction of the facial muscles when trying to express certain emotions are noted;
• Emery-Dreifuss pathology (a similar type of myopathy with negative consequences for the myocardium).

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Progressive Duchenne muscular dystrophy

Progressive Duchenne muscular dystrophy is a serious, most common form of myopathy. It develops in infancy, usually in children under 3 years of age, and occasionally at an older age. Almost all patients (with a few exceptions) have enlarged calf muscles (sometimes in combination with deltoids and quadriceps). This enlargement is often associated with fatty infiltration of the muscles, but in some cases it is the muscles that actually enlarge.

A decrease in muscle mass is observed mainly in the back and pelvic girdle. Along with atrophic disorders, mental retardation can often be noted.

It is not uncommon for the integrity and shape of bones to be compromised even as a result of minor loads and injuries. After 5-10 years from the first manifestations of the pathology, damage to the heart muscle can be detected, which is expressed by tachycardia and ECG abnormalities. A characteristic sign is increased activity of serum creatine kinase.

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

Diagnostics Duchenne dystrophy

The diagnosis of Duchenne muscular dystrophy should be confirmed by genetic testing, but in some cases other tests may be ordered.

1. A genetic test is performed unambiguously, even if the doctor is sure that the patient has muscular dystrophy. With the help of this method, it is possible to determine the precise characteristics of pathological disorders in DNA. In addition to making a diagnosis, this study will help parents decide on future pregnancies. The results of the genetic test will also be useful to relatives of the mother who is a carrier of the mutated gene.
2. The doctor may recommend a muscle fiber biopsy. This test will show whether the body produces the protein dystrophin, and if so, in what quantities. With the help of a biopsy, specialists determine the exact amount of protein in myocytes. But a biopsy cannot replace genetic analysis!
3. The electromyography method (determination of the conductivity of nerve impulses) was relevant several years ago, but now it is not necessary.
4. Blood test for creatine kinase: in Duchenne muscular dystrophy, the amount of this enzyme significantly exceeds the norm.
5. Assessment of cardiac activity, respiratory system, muscular capabilities, ECG, determination of cardiac biological markers and bone density.

It is very important to determine the exact diagnosis if specialists suspect myopathy in a child. Moreover, this must be done as soon as possible. The doctor will prescribe qualified treatment based on these studies, having previously talked to the parents and explained to them all the features of the disease.

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Treatment Duchenne dystrophy

At present, no cure for Duchenne muscular dystrophy has been invented yet. Although scientific research on this topic is being conducted quite intensively: scientists from Great Britain, Israel and the USA are working on it. The latest methods currently under development are:

• Exon skipping is a procedure that helps slow down the rate of progression of myopathy. This method softens the course of the disease, significantly alleviates symptoms, but does not eliminate the mutation;
• the introduction of the dystrophin gene using viral gene carriers or plasmids allows patients to maintain the ability to move and walk for a longer period of time, which greatly improves their quality of life;
• myogenic cell transplantation is the introduction of fibroblasts, which promotes the enhancement of the synthesis of new unmutated dystrophin. This method has a number of advantages: it is a long-term positive result, the possibility of combining the procedure with other treatment methods, the possibility of use at almost any age and controlled production of new dystrophin;
• muscle fiber restoration 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;
• utrophin regulation to replace dystrophin is a method based on an experiment proving that utrophin deficiency causes the same symptoms as dystrophin deficiency. These proteins are similar in structure and function. Through long-term scientific research, scientists have come to the conclusion that utrophin gene regulation can be used as a treatment for Duchenne dystrophy;
• blocking myostatin. Myostatin is an inactive protein that has the ability to trigger biochemical processes that inhibit muscle formation. Accordingly, blocking this protein should promote muscle tissue growth;
• blocking transforming growth factor β, a protein that inhibits the function of myosatellite cells (myogenic stem cells). This method will help reduce the degree of fibrosis;
• upregulation of insulin-like growth factor-1, a protein similar in structure to insulin. Growth factor-1 improves the quality of muscle tissue, activates development and increases muscle strength.

At present, specialists offer the following treatment for Duchenne muscular dystrophy:

• taking corticosteroid drugs to increase muscle strength and alleviate the patient's condition;
• use of β-2-agonists to temporarily increase muscle strength;
• physiotherapy procedures, myostimulation;
• orthopedic care (wheelchairs, walkers, ankle braces, etc.).

Unfortunately, there is no “cure” for Duchenne muscular dystrophy, so when looking for effective treatment, be extremely cautious about medications and procedures that may be presented to you as a “cure-all.”

Do not buy an unknown medicine if there is no reliable evidence of its effectiveness. Remember that you can spend a large amount of money, and, in addition, not only not help, but also harm your baby.

Prevention

Of course, it is difficult to talk about the prevention of a hereditary disease associated with a gene mutation. Of course, in families where there are cases of children born with Duchenne muscular dystrophy, it is imperative to consult a geneticist, preferably before the young couple starts planning a pregnancy.

If a child with a muscle pathology has already been born, then it is necessary to make every effort to prevent the loss of muscle tissue and to maintain the child's motor activity for as long as possible. In such situations, it is unacceptable to give up and allow the muscles to atrophy. It is necessary to do special gymnastics with the baby to maintain the range of motion in the joints. To prevent contractures, it is recommended to use supporting corsets and fixators.

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

Swimming has a good effect, and you can and should do it. Remember: doing nothing (constant bed rest) will only speed up the progression of the disease. It is necessary to allow the patient to at least 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, heart, skeleton. Patients with Duchenne dystrophy most often live to 15, maximum 30 years. Research conducted by world scientists in this area gives hope for improving the quality and duration of life of such patients.

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

The discovery of the gene that is the main factor in the development of the disease gave a huge boost to the continuation of scientific experiments in the therapy of gene mutations. However, at the moment, unfortunately, there is no treatment that would help to completely cure myopathy. The methods used only make it possible to improve and prolong the life of the patient.

It remains to be believed that science will soon find a way to correct the hereditary pathology, and Duchenne muscular dystrophy will finally be defeated.

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