Congenital muscle weakness, which progresses with the development of the body, is called “Duchenne muscular dystrophy” in medicine. This disease occurs exclusively in males. Understanding the nature of the pathology makes it possible to ease its course and help children cope with the initial manifestations.
Characteristics of the disease
Duchenne muscular dystrophy is a genetic pathology caused by a disorder in the structure of muscle fibers. Gradually they disintegrate, and the person loses the ability to move. The disease manifests itself already in infancy. First, muscle disorders occur, then skeletal deformities occur. The clinical picture is complemented by endocrine and mental disorders.
Myodystrophy was first described in 1861 by a French neurologist, after whom it was later named. It is diagnosed quite often: 1 case in 3,500 newborns. There is no radical treatment. The therapy offered by doctors is exclusively symptomatic. Patients with this diagnosis rarely survive the age of 30.
Main reasons
Muscular dystrophy is a consequence of abnormalities in the genetic code of DNA. The mutation occurs in a gene located on the X chromosome. One of its sections is responsible for the production of a special protein - dystrophin. This substance at the microscopic level forms the basis of muscle fibers and performs several functions:
- maintenance of the cell skeleton;
- ensuring the ability of muscle fibers to contract and relax.
In this disease, dystrophin is absent or poorly synthesized. The level of “normal” protein does not exceed 3%. This mutation leads to the destruction of fibers in the muscles. They gradually degenerate and are replaced by fatty and connective tissue. As a result, the person loses the ability to move.
What type of inheritance does Duchenne muscular dystrophy have? The disease is transmitted according to a recessive trait. In the human body, all genes are paired. In order for pathological disorders to appear with a hereditary disease, the genetic defect must occur in one chromosome or in similar areas of both. In the second case, we are talking about a recessive type of inheritance.
If a genetic defect is diagnosed in only one chromosome, but the disease progresses, they speak of a dominant transmission trait. The recessive type is possible with simultaneous damage to identical DNA structures. When the second chromosome is absolutely “healthy”, pathology does not develop. Therefore, dystrophy is diagnosed only in males. They have one X chromosome in their genetic set, and the second (Y) is a pair.
What does science say about the fair sex? Duchenne muscular dystrophy is rarely diagnosed in girls. To do this, two pathological X chromosomes must match in the genotype, which is unlikely. Girls can only act as carriers of the disease and pass it on to their sons.
General clinical picture
The disease leaves its mark on the neuromuscular system. Its manifestations can be observed in children aged 2-3 years. Parents begin to notice that the baby lags behind his peers in physical development. The pathological process progresses quickly and spreads to the lower extremities. Then it moves to other areas of the muscles.
Damage to the muscle corset and excessive loads lead to curvature of the limbs. Sick children also experience changes in the functioning of the heart and mental retardation.
All pathological manifestations of the disease can be divided into several groups:
- damage to skeletal muscles;
- heart failure;
- skeletal deformity;
- mental disorders;
- endocrine disorders.
Let us consider the clinical manifestations of each group in more detail.
Skeletal muscle damage
Children are born without serious health problems. However, after just a few months, their motor development begins to lag. These kids are less active. Doctors and parents do not yet notice obvious deviations, attributing everything to temperamental characteristics.
The initial symptoms of the disease appear after the first steps. Children with Duchenne dystrophy constantly fall and walk on their toes. While most of their peers are already confidently standing on their feet, they stubbornly continue to experience difficulty moving.
The next stage in the manifestation of the disease is the period when babies acquire the ability to speak. They begin to complain to their parents about weakness and fatigue. Jumping on the playground, running, climbing horizontal bars - all these types of activities do not bring them pleasure.
What other symptoms does Duchenne muscular dystrophy have? Govers' disorder is considered a unique manifestation of the disease. Every time the child tries to get up from the floor, he uses his hands to help the weak leg muscles. To this end, he leans his limbs on himself, moving them all over his body.
The gradual progression of the disease leads to the fact that sick children by the age of 10-12 lose the ability to move independently. Most of them need a wheelchair. The ability to hold the body in an upright position lasts only until the age of 16.
Skeletal deformities
This group includes symptoms associated with muscle disorders. Duchenne muscular dystrophy is manifested by increased lumbar curvature, which is complemented by curvature of the thoracic spine and stoop. Many babies' feet change shape. Over time, severe osteoporosis develops. The listed symptoms further aggravate the clinical picture and contribute to the worsening of motor disorders.
Heart failure
Progressive muscular dystrophy is necessarily accompanied by damage to the heart muscle. As a rule, cardiomyopathy develops. Clinically, it manifests itself as pressure changes and heart rhythm disturbances. The boundaries of the main muscle of the body increase, but at the same time its functionality is sharply reduced. The result is heart failure.
The combination of these defects with respiratory dysfunction often causes death.
Mental disorders
This symptom is considered optional, but possible. Its appearance may be due to a deficiency of one of the types of dystrophin - apodystrophin, which is found in the brain. At the same time, weak muscles and the severity of mental disorders are not interrelated. A child’s inability to attend kindergarten and school only increases cognitive impairment.
Endocrine disorders
Various types of endocrine disorders are diagnosed in 30-50% of patients. They can be expressed in the form of obesity or underdevelopment of the genital organs. Excess deposits are most often observed in the area of the mammary glands, shoulder girdle and buttocks. Patients with Duchenne dystrophy are usually short in stature.
Medical examination
Diagnosis of Duchenne muscular dystrophy is based on several types of studies, the main one of which is a DNA test. Detection of a defect in the X chromosome in the area responsible for the synthesis of dystrophin is considered the final confirmation of the diagnosis.
Other diagnostic methods used today include:
- CPK (determination of creatine phosphokinase activity). This enzyme is a direct reflection of the death of muscle fibers. In children with Duchenne dystrophy, its level exceeds the norm hundreds of times.
- Electromyography.
- Breathing tests, ECG, ultrasound of the heart. Allows you to identify abnormalities in the functioning of other organ systems.
- Muscle biopsy. Using this method, the content of dystrophin in the body is determined.
Progressive muscular dystrophy in a child means that a pathological X chromosome is present in the mother’s genotype. Only in isolated cases does a woman turn out to be completely healthy. The presence of a defective gene poses a threat to subsequent pregnancies. Therefore, such families are recommended to visit a geneticist.
When a second pregnancy occurs, the couple is offered so-called prenatal diagnostics. It involves the study of the child’s genotype while still in the womb. This study eliminates the risk of hereditary diseases, which include Duchenne muscular dystrophy.
Prenatal diagnosis is based on the use of cellular material. It is obtained through various procedures: chorionic villus biopsy, amniocentesis, etc. The listed manipulations carry a certain risk for the fetus, but with their help it is possible to diagnose a genetic disease with a 100% guarantee.
Drug treatment
Duchenne muscular dystrophy is an incurable disease. But patients with this diagnosis should not remain bedridden. To help a child prolong the period of physical activity, modern medicine offers several ways.
Among the medications for this purpose, patients are prescribed steroids and beta-agonists. The use of the latter (“Albuterol”, “Formoterol”) is not reliably recognized. Therefore, there is no need to talk about their effectiveness today. Such drugs are used exclusively as experimental treatments.
The mainstay of therapy is steroids. Their regular use allows you to replenish muscle strength for a while. Doctors suggest that such drugs can slow down the progression of the disease, as well as prevent the occurrence of scoliosis. However, the capabilities of steroids are limited. Duchenne muscular dystrophy will continue to develop in any case.
Additionally, patients are prescribed cardiac medications. These are primarily ATP inhibitors, antiarrhythmic and metabolic medications. They allow you to resist the cardiac aspects of the disease.
Physiotherapy and orthopedic care
Non-drug therapy involves the appointment of physiotherapy and orthopedic care. In the first case we are talking about various massage techniques and swimming. Physiotherapeutic effects help maintain mobility and flexibility of joints longer. Moderate activity has a beneficial effect on the course of the disease. On the other hand, inaction and bed rest can only worsen the clinical picture. Therefore, doctors recommend maintaining physical activity for as long as possible.
Orthopedic care is an important component of therapy for patients diagnosed with Duchenne muscular dystrophy. Treatment with medications coupled with special devices can significantly make their life easier. Their list is very diverse: various verticalizers, devices for independently adopting a comfortable position, electric wheelchairs, spinal corsets, leg splints and much more.
Prognosis for patients
Duchenne muscular dystrophy is a serious genetic disease, the first signs of which are found in children in the first months of life. At first, the boys experience difficulty walking, then they cannot even get up from the floor. Drug treatment with steroids significantly changes the course of the pathological process. The drugs help restore muscle strength for a while.
It is quite difficult to predict exactly when a patient will start using a wheelchair. Typically, the need for this device appears at the age of 8-11 years. With further development of muscle weakness, it becomes difficult for the patient to maintain body position, and complications may arise.
What prognosis do doctors give when diagnosed with Duchenne muscular dystrophy? The disease can significantly reduce life expectancy. However, currently, the majority of young men reach adulthood, but under the condition of high-quality medical and physiotherapeutic care.
However, women are carriers of a defective gene that causes symptoms to develop. The first manifestations of the disease can be noticed between the ages of 2 and 5 years, but manifestations of the disorder may not appear until 10 years of age. Children who have myopathy fall more often and have a harder time getting up compared to healthy peers. When trying to stand up, the child first rises on all fours, then leans on his hands and. By the age of 8-10 years, the patient may begin to have problems with gait. The disease begins to progress and by about 10-12 years the boy may lose the ability to move.
As a result of a genetic disorder, scoliosis is formed and damage to the cardiac myocardium is observed, which becomes noticeable on the ECG. On average, patients with Duchenne myopathy die at the age of 20 years, but there are cases where patients live up to 25-30 years. The cause of death is heart and pulmonary failure as a result of muscle atrophy.
Treatment
The disease is diagnosed by DNA analysis. Myopathy can also be detected by examining the composition of the patient's muscle tissue for the presence of dystrophin. The second method is more often used to confirm the diagnosis, and the first makes it possible to establish the presence of a specific form of the disease.
There are no medications to treat Duchenne myopathy. Today, medications are being developed to reduce the rate of development of the disease. Conservative treatment is aimed at controlling the symptoms that appear during the process in order to improve the quality of life. Typically, standard therapy involves prescribing corticosteroid medications (Prednisolone or Deflazacort), which can increase the patient's energy and strength and reduce the intensity of symptoms.
Some studies have shown that muscle strength in patients can be increased with the help of beta-2 agonists (Salmeterol, Formoterol), but these drugs do not slow the progression of the disease. Physical activity (for example, swimming) makes the progression of the disease smoother, while bed rest, on the contrary, worsens the patient’s condition.
Exercise therapy helps maintain muscle function, and orthopedic devices (such as splints, canes, or wheelchairs) help improve quality of life and enable the patient to care for himself. In the final stages of the disease, respiratory support for the patient in a hospital setting with the help of special auxiliary devices is important.
Muscular dystrophy, or Duchenne myopathy, is a severe hereditary pathology that is constantly progressing. It is almost impossible to slow down muscle breakdown.
This is due to congenital changes. People first started talking about Duchenne myopathy in the middle of the 19th century. This pathology was discovered by a French neurologist. At that moment, one type of course of the disease was known, after some time several more ways of developing the condition were identified.
This type of disease is very similar to Becker's muscular dystrophy, but at the same time differs from it in complexity and external features.
Duchenne muscular dystrophy affects 1 child out of 4000. This type of pathology is one of the most common muscular dystrophies and is a congenital disease.
One of the genes in the structure of the human genome was given the name of a neurologist, after whom the deviation was named. Duchenne muscular dystrophy can be influenced by various factors:
- incest;
- genetic predisposition, for example, if a relative has Duchenne myopathy;
- improper synthesis of muscle fibers, accelerated spread and replacement by fatty tissue, connective fibers;
- hereditary forms of Duchenne syndrome, most often transmitted from the mother;
- genome mutation during formation during pregnancy;
- abnormalities in chromosomal structures of unknown origin;
- severe disturbances in the development of dystrophin;
- pathological changes in biochemistry in the blood.
Duchenne myopathy also develops in connective tissue diseases that are not directly related to genetic abnormalities.
Characteristics of hereditary pathology
The genetic nature of the disease was immediately proven after the discovery of the syndrome in 1868. This pathology is almost identical to Becker’s myodystrophy, that is, it has the same genetic prerequisites for its formation.
However, Becker muscular dystrophy has other symptoms. The disease is characterized by the following features:
- diagnosed in boys under 5 years of age;
- progresses rapidly;
- never detected in girls;
- muscle atrophy has a stepwise development - first the pelvic girdle suffers;
- then the leg muscles are involved;
- after this, Duchenne myopathy affects the muscles of the back and shoulders;
- progressive Duchenne muscular dystrophy ends with damage to the hands;
- a specific sign of a disorder is spinal deformity, most often found in the form of kyphosis or lordosis;
- Duchenne muscular dystrophy is almost always accompanied by damage to the sternum and feet, they become irregular in shape and greatly change the human body;
- in pathology, in contrast to Becker muscular dystrophy, damage to the left cardiac ventricle, arrhythmia and cardiopathy appears;
- approximately 30% of patients develop mental retardation.
Duchenne muscular dystrophy is never mild, always has an extremely unfavorable prognosis. It develops quickly, the patient loses the ability to walk by the age of 12. In Duchenne muscular dystrophy, death occurs due to infection of the bronchi or lungs, after cardiac arrest.
Symptoms of the disorder
The first signs of Duchenne myopathy occur already at the age of 1.5 years. In rare cases, they cannot be noticed until 5 years of age. Signs of Duchenne disease appear mild at first. Their combination depends on your overall health:
- the child develops severe instability, there is clumsiness in movement, he often falls and is very slow;
- Duchenne myopathy is accompanied by the fact that while walking the child wobbles and constantly stumbles, as a result of which the child is afraid to get up on his feet, and severe motor passivity occurs;
- over time, with Duchenne muscular dystrophy, a “duck” gait with the chest protruded forward and shoulder blades retracted becomes visible;
- if the child is sitting or lying down, then it becomes difficult to take a standing position with Duchenne muscular dystrophy;
- when trying to take a standing position, the baby seems to stand on a ladder and rises up with his backside;
- muscle hypertrophy occurs, they are filled with adipose tissue;
- Duchenne muscular dystrophy also affects the functioning of the heart, resulting in pathologies and failure;
- Duchenne muscular dystrophy is often accompanied by another symptom - abnormalities appear in skeletal biopsies;
- the position of large joints gradually changes, deformation of the feet begins;
- Duchenne myopathy in 100% of cases leads to complete disability of the patient; he requires a chair;
- at the age of 15, with Duchenne muscular dystrophy, deep disability occurs, dangerous cardiac arrest and chronic or constantly recurrent disorders in the lungs.
Against the background of Duchenne muscular dystrophy, a young patient develops acute depression, which children find difficult to tolerate. Often the cause of death in Becker and Duchenne muscular dystrophy is suicide.
Diagnosis of the disease
Duchenne muscular dystrophy is extremely difficult to diagnose. To do this, a set of methods is used. The first thing you should do if you suspect Duchenne myopathy is an ECG. To confirm the diagnosis, it is necessary that the analysis shows abnormalities in the wall of the left ventricle.
The next stage is to determine the level of dystrophin, which does not change towards normal dystrophy. It is also necessary to donate blood for biochemical analysis. If you have Becker's muscular dystrophy or the disease named after the French neurologist, high levels of CPK are noted.
Additionally, you need to undergo EMG, gene diagnostics, and muscle biopsy. It is the latter analysis that allows us to identify the disease with fairly high accuracy. Electromyography is not inferior in effectiveness in terms of diagnosing Duchenne muscular dystrophy.
Treatment tactics
For Duchenne muscular dystrophy treatment to be effective, you need to strictly follow the plan after diagnosis. The disease can never be completely cured, but it can make the patient’s life much easier. Modern medicine can slow down Duchenne myopathy using the following methods:
- Tactics for detecting the disease before 5 years of age. Radical treatment for Duchenne muscular dystrophy is not required. Genetic consultation and constant support of the parents of a sick child are needed.
- Treatment of Duchenne myopathy up to 8 years of age. In this case, muscle tissue support is needed. Doctors prescribe glucocorticosteroids to slow the progression of the disease: Prednisolone or Deflazacort.
- Therapy from 8 to 20 years. In this case, the muscles are significantly weakened, Duchenne muscular dystrophy leads the child to a wheelchair.
- Therapy from 20 years. In this case, the drugs partially stop working, and respiratory diseases progress.
Duchenne myopathy requires constant use of certain vitamin groups (B, E), as well as calcium, anabolic hormones, potassium and some types of amino acids. For Duchenne muscular dystrophy, injections of ATP, Retabolil, and glutamic acid are required.
Important! You can maintain health with Duchenne muscular dystrophy using other methods - exercise therapy and electrophoresis.
Exercise therapy is carried out in small courses with the obligatory participation of a therapist. Doctors also recommend massage. For electrophoresis in Duchenne myopathy, it is necessary to use substances such as lipase, calcium chloride, and Proserin.
In severe cases, all treatment is carried out at home, if there are medical capabilities to organize complex therapy with special devices.
A prerequisite for the treatment of Duchenne myopathy is constant monitoring by a cardiologist. It is also necessary to create a competent menu. When sick, you need to eat a lot of steamed vegetables, fruits, vegetable fats and lean meat. The consumption of alcohol, caffeine and strong tea is prohibited.
Consequences and complications
In 100% of cases, Duchenne myopathy is accompanied by severe consequences for the body and greatly shortens life. The patient always dies from complications of the disease - cardiac arrest or pulmonary infection.
If Duchenne muscular dystrophy is detected at an early age, there is a chance that the person will live to be 30 years old. But only subject to adequate therapy and an integrated approach. Complications of Duchenne myopathy often include osteoporosis, lesions of the spine and joints, as well as pathologies of the digestive system.
Duchenne muscular dystrophy is a severe genetic disorder, the treatment of which is not able to protect a person from one outcome - death. In some cases, patients manage to live more than 20 years after diagnosis. In other cases, infants die within the first year of life.
Duchenne muscular dystrophy is a severe X-linked disease for which there is still no effective treatment. In one of the last issues Science Three articles have been published about the successful testing of CRISPR/Cas9 technology in mouse models for the treatment of this disease. Maybe this approach has a chance to reach clinics?
Dystrophin is located on the intracellular surface of the sarcolemma along the entire length of muscle fibers and is part of the dystrophin-associated glycoprotein complex (DAGC). It binds at one end to the cytoskeletal F-actin and at the other to β-dystroglycan, which stabilizes the fibers during contraction. The dystrophin gene is one of the longest in humans.
Figure 1. Mutations in dystrophin are the cause of Duchenne muscular dystrophy. A - Dystrophin binds to actin filaments (part of the cytoskeleton) through the N-ABD and ABD2 domains) and to DAHA through the CR and CT domains. b - Crystal structure of N-ABD dystrophin. Actin binding zones are shown yellow, the four well-studied disease-causing mutations are red.
There is no cure for Duchenne muscular dystrophy yet, but today's therapy is aimed at slowing the progression of the disease and treating complications. The “gold standard” is corticosteroids, which were proposed as a treatment several decades ago. However, their use causes many side effects.
It is not surprising that many genetic and molecular research groups are developing pre- and postnatal treatments for Duchenne muscular dystrophy. The disease is mainly studied in various strains of mice. In one of the last issues Science published three independent works on methods of treating Duchenne muscular dystrophy. The research teams were led by Eric Olson ( Eric Olson) from the University of Texas, Amy Wadgers ( Amy Wagers) from Harvard University and Charles Gersbach ( Charles Gersbach) from Duke University. All groups used an exon skipping technique, in which one or more exons are removed from the mRNA, to restore muscle function (Figure 2). In this case, the protein turns out to be shorter, but can still perform its supporting and anchoring functions in the muscle fiber, and the “annoying circumstance” - an extra stop codon - also turns out to be “missed”.
Figure 2. Exon skipping in the dystrophin gene in Duchenne muscular dystrophy. A - In patients with DMD in the gene DMD there are mutations that disrupt the reading frame during protein synthesis. For example, when exon 50 is deleted, “out-of-frame” mRNA appears, which leads to the synthesis of truncated, nonfunctional or unstable dystrophin (left). In one therapeutic approach, an antisense oligonucleotide "masks" exon 51 so that it is "skipped" by splicing and the reading frame is restored. The result is a shorter but partially functional dystrophin (on right). In new works, “extra” exons are simply cut out from the genome using CRISPR/Cas9. b - Multiexon skipping in DMD therapy. If exons 45–55 are skipped, mutations of which occur in approximately 63% of patients, the resulting short dystrophin will lead to the transformation of the standard DMD phenotype into an asymptomatic or milder DMD phenotype.
The exon deletion strategy even has advantages over recreating the full length of the gene: it is easier to design than reconstructing each patient's individual deletions.
To cut out “extra” nucleotide sequences, the researchers used the genome editing technology CRISPR (clustered regularly interspaced short palindromic repeats) / Cas9 (CRISPR-associated protein 9), which, by the way, was just allowed to be used in experiments on embryos by a London institute.
You can read more about this technique, borrowed from bacteria, in the articles: “ CRISPR systems: immunization of prokaryotes», « Mutagenic chain reaction: genome editing on the verge of science fiction" And " Shouldn't we try... changing the genome?» .
Competing laboratories: who will be the first to translate technology into therapy for humans?
Scientists from three laboratories have successfully applied exon skipping technology in vivo on a standard object - mice - and showed that their method helps restore the reading frame and partially restore the synthesis of dystrophin. Since even its low level (3–15% of normal) brings therapeutic benefits, the results of the work can be called successful.
This is not the first time Eric Olson's group has used the CRISPR/Cas9 method in their work on Duchenne muscular dystrophy. In 2014, scientists corrected a mutation in the mouse germline and prevented the disease from developing. However, since prenatal genome editing on human embryos is (yet?) prohibited, researchers had to come up with a way to apply the technology postnatally.
Their latest work used adeno-associated virus-9 (AAV9) to deliver the components needed for editing into tissue. The researchers tested several methods of administering AAV9 at different days after the pups were born. In all cases, dystrophin gene expression was restored in cardiac and skeletal muscle, but to varying degrees. Moreover, protein production increased from 3 to 12 weeks post-injection, and skeletal muscle function improved at 4 weeks post-injection. “The challenge now for the Wellstone researchers is to translate the discoveries from the mouse model to patients with muscular dystrophy.”, says Pradeep Mammen, co-director of the Wellstone Center.
Amy Wagers' group conducted a largely similar experiment. After many preparatory stages of work on genome editing and exon skipping in cells and animals, their experiment was also crowned with success: programmable CRISPR complexes within adeno-associated virus (AAV) were delivered through local and systemic administration to differentiated skeletal fibers, cardiomyocytes and satellite muscle cells newborn and adult mice. If editing is aimed only at muscle fibers, the effect may fade over time. However, as Wagers notes, gene editing in satellite cells can provide much longer-lasting results. It can lead to the creation of a pool of regenerative cells carrying the edited dystrophin gene, and as a result of normal muscle repair, the edited gene will also end up in the muscle fibers.
Finally, as everyone has already guessed, scientists led by Charles Gersbach also discovered the therapeutic effect of using AAV-CRISPR/Cas9 in a mouse model. Intraperitoneal injection of the viral vector into newborn mice resulted in restoration of dystrophin synthesis in the abdominal muscles (abdominal muscles), diaphragm and heart seven weeks after injection. As the authors note, therapy of the cardiac and pulmonary muscles is extremely important, since it is their failure that often leads to the death of patients with Duchenne disease. Intravenous administration of AAV vectors to six-week-old mice also led to a significant restoration of dystrophin production in the heart muscle. “There is still a lot of work remaining to translate [the technology] into a therapy for humans and confirm its safety, says Gersbach. - But the results of our first experiments are already very encouraging.". The team intends to optimize the delivery system and evaluate the effectiveness and safety of the strategy in larger animals (Figure 3). Which of the three laboratories will overtake the others and be the first to conduct tests on humans?
Therapy for Duchenne muscular dystrophy: old and new approaches
Other studies show that restoration of normal levels of nitric oxide (NO) synthesis, which is reduced in patients due to impaired NO synthase (nNOS) activity, reduces inflammation, increases the activity of intrinsic stem cells and reconstructs the morphology and function of skeletal muscles.
The drug Givinostat is already in phase II clinical trials - histone deacetylase inhibitor, which slows disease progression in a mouse model.
This massive experimental attack on Duchenne muscular dystrophy gives us hope. Will CRISPR/Cas9 technology lead the way in developing therapies that can be adopted by clinicians? Perhaps the publication of similar works on other diseases is not far off, where it is necessary to get rid of mutations in a single gene? We will find out in the upcoming issues Science(as well as other honorary magazines).
Literature
- van Putten M., Hulsker M., Nadarajah V.D., van Heiningen S.H., van Huizen E., van Iterson M. et al. (2012). The effects of low levels of dystrophin on mouse muscle function and pathology. PLoS One. 7 , e31937;
- Russo F.B., Cugola F.R., Fernandes I.R., Pignatari G.C., Beltrão-Braga P.C. (2015). Induced pluripotent stem cells for modeling neurological disorders. World J. Transplant. 5 , 209–221;
- Falzarano M. S., Scotton C., Passarelli C., Ferlini A. (2015). Duchenne muscular dystrophy: from diagnosis to therapy. Molecules. 20 , 18168–18184;
- Bushby K., Finkel R., Birnkrant D.J., Case L.E., Clemens P.R., Cripe L. et al. (2010).
The disease, called Duchenne muscular dystrophy, is genetic, inherited only by boys and is characterized by changes in the structure of muscle fibers.
The breakdown of muscle fibers, over time, leads to loss of the ability to move.
Muscular dystrophy appears in children after one year of age. In addition to muscle pathologies, patients experience processes of skeletal deformation, heart failure and respiratory failure, possible disturbances in the endocrine system and mental deviations.
This disease is provoked by a gene mutation; in most cases, disorders occur in the mother’s egg and are inherited by the son.
When and how do symptoms begin to appear in Duchenne muscular dystrophy?
The first manifestations of dystrophy become noticeable in children after a year, when the baby makes his first attempts to walk independently. In such cases, there is some inhibition of motor activity: when trying to get up, the child begins to fall, the legs begin to get tangled, and the baby quickly gets tired.
If a child with muscular dystrophy is able to move independently, his gait will resemble that of a duck, and it will be problematic to get up from his knees and walk up the steps.
In childhood, muscles increase in size; this condition is very similar in appearance to pumped up muscles. As the disease progresses, muscle mass begins to decrease.
As a rule, muscular dystrophy begins in the lower extremities, spreading to the pelvis, muscles of the back and arms.
At first, limited activity is accompanied by a decrease in tendon reflexes. Over time, the process of deformation of the spinal column, chest and feet begins. The work of the heart is disrupted, left ventricular hypertrophy appears. Some patients may have mental deviations, which manifest themselves in the form of mental retardation. At the age of 12–14 years, due to Duchenne muscular dystrophy, patients are unable to stand on their feet and therefore stop moving independently. After a few years, complete loss of motor activity begins. Most patients survive only until they are thirty years old.
In the later period of the disease, muscle weakness begins to affect the respiratory system and swallowing functions. The death of such patients occurs due to bacteria entering the body or due to insufficient functioning of the heart and lungs.
Methods for diagnosing the disease
The main research method in diagnosing Duchenne muscular dystrophy is DNA diagnostics. The final diagnosis is based on the results of a genetic test (if a defect is detected in the X chromosome in the area responsible for the synthesis of dystrophin).
Additional diagnostic methods include:
- Determination of the level of activity of the CPK enzyme: in childhood, the levels of this enzyme greatly exceed the norm; after five years, the level of CPK decreases slightly. Creatine phosphokinase (CPK) reflects the breakdown of muscle fibers;
- Electromyography: using this method, the primary processes of muscle changes are confirmed;
- A biopsy can be performed to determine the amount of dystrophin in the muscles, however, this procedure is rarely used.
In order to identify disorders of the heart and lungs, ECG, ultrasound and breathing tests are prescribed.
Help with muscular dystrophy
Progressive muscular dystrophy cannot be treated; the only help for this disease is to make the person’s condition and life easier.
From childhood, after a final diagnosis is made, psychotherapy sessions are prescribed, which will significantly contribute to the duration of an active life. Physical exercise is of great importance; with its help, joints can remain mobile for a long period of time. In some cases, the doctor may prescribe a corset or splints, this will protect the child from contractures.
Also, for muscular dystrophy, medications are used, which include steroids (with constant use there is a decrease in muscle weakness) and β-2-adrenergic agonists (strength increases in the muscles, but such drugs are not able to inhibit this disease).
To maintain the functions of the cardiovascular system, drugs are prescribed that act accordingly, for example, anti-arrhythmia and metabolic drugs.
Patients with Duchenne muscular dystrophy require constant monitoring by specialists, since early diagnosis of various changes in internal organs will help increase life expectancy.
The prognosis for the disease is not encouraging, however, in the world of modern medicine, scientists are successfully advancing in the study of the disease, and perhaps soon the life of such patients will become easier and its duration will increase.
