Duchenne muscular dystrophy is an inherited pathology of the muscular system linked to the X chromosome, manifested in the first 3-5 years of life and characterized by rapidly spreading and worsening muscle weakness. Initially, the muscles of the pelvic girdle and thighs are affected, then the shoulders and back, gradually immobility occurs. Myodystrophy is accompanied by skeletal deformities and heart damage. Diagnosis of Duchenne muscular dystrophy includes neurological and cardiological examination, determination of the level of CPK, electromyography, consultation of a geneticist, DNA analysis, muscle biopsy. Treatment is symptomatic. Due to the weakness of the respiratory muscles, a ventilator is required at the final stage of the disease.
General information
Duchenne muscular dystrophy is a severe form of myodystrophy, characterized by early onset, rapid aggravation of muscle weakness, pronounced skeletal deformities and damage to the heart muscle. It was first described by the French neurologist Duchenne in 1853. Its prevalence is 1 case per 4 thousand newborn boys. Pathology is transmitted recessively linked to the X chromosome. Boys get sick. There are cases of the disease among girls, which is associated with the XO karyotype, gonadotropic mosaicism or the presence of abnormalities in the structure of chromosomes. Duchenne myodystrophy is characterized by the onset in the first 3-5 years of a child’s life, a severe course leading to complete immobility and death of patients on average by the age of 15-25 years.
Causes
The development of Duchenne muscular dystrophy is associated with the presence of a mutation in the 21st locus of the short arm of the X chromosome in the gene encoding the protein dystrophin. About 70% of cases of the disease are caused by a defective dystrophin gene obtained from a mother carrier of a pathological mutation. The remaining 30% are associated with the appearance of fresh mutations in the mother’s eggs. Unlike Becker’s myodystrophy, with Duchenne muscular dystrophy, genetic aberrations lead to a shift in the DNA reading frame and a complete cessation of dystrophin synthesis, which causes a more severe course of pathology.
Normally, dystrophin, which is included in the sarcolemma of myocytes, ensures its integrity and resistance to stretching that occurs during contractile activity of muscle fibers. The absence of dystrophin entails a violation of the integrity of the sarcolemma, the destruction of myocytes and their replacement with adipose and connective tissue. Clinically, this process is expressed by a progressive decrease in the ability of muscles to contract, loss of muscle strength and tone, muscle atrophy.
Symptoms
The debut of Duchenne myodystrophy occurs in the period from 1 to 5 years. As a rule, already at the 1st year of life, some lag in the child’s motor development is noticeable. There is a delay in the timing of the start of sitting, getting up and walking independently. When a child begins to walk, he is clumsy and more unstable than his peers; he often stumbles.
Muscle weakness occurs in the 3-4 years of life. Initially, it is expressed in pathologically increased fatigue when walking up stairs or over long distances. Over time, the duck gait typical of myodystrophy becomes noticeable. Attention is drawn to the peculiarities of the child’s behavior — every time he rises from a squatting position, he actively leans his hands on his own body, as if climbing it like a ladder (a symptom of Govers).
Muscle atrophy begins with the muscles of the hips and pelvic girdle. Duchenne muscular dystrophy is characterized by their rapid upward spread to the shoulder girdle, the musculature of the back and the proximal parts of the arms. Due to muscular atrophy, a “wasp” waist and “wing-shaped” shoulder blades separated from the back are formed. A typical symptom is pseudohypertrophy of the calf muscles. There is a loss of tendon reflexes: first, knee reflexes, then reflexes from the triceps and biceps of the shoulder. Achilles and carporadial reflexes can be preserved for a long time. Tendon retractions and muscle contractures develop over time.
Duchenne muscular dystrophy is accompanied by disorders in the musculoskeletal system. Curvature of the spine (kyphosis, enhanced lordosis, scoliosis), deformities of the chest (keeled or saddle-shaped), deformities of the feet are characteristic. Cardiovascular disorders are caused by the development of cardiomyopathy and include arrhythmia, lability of blood pressure, deafness of heart tones. 50% of patients have neuroendocrine disorders — adiposogenital dystrophy, Itsenko-Cushing syndrome, etc. About 30% of patients suffer from oligophrenia, usually limited by the degree of debility. There may be ADHD, autism-type disorders, dyslexia, short-term memory disorders.
Complications
By the age of 7-10, Duchenne muscular dystrophy leads to pronounced motor limitations. By the age of 12, patients, as a rule, lose the ability to walk, and by the age of 15, most patients completely lose the ability to move independently. The spread of the dystrophic process to the respiratory musculature leads to a progressive drop in the vital capacity of the lungs and, ultimately, the inability to perform respiratory movements.
Diagnostics
The diagnosis of Duchenne myodystrophy is helped by anamnesis, neurological examination, results of electrophysiological testing, determination of creatine phosphokinase (CPK) in biochemical blood analysis, morphological and immunochemical examination of muscle tissue samples, genetic counseling and DNA analysis:
- EFI. Electroneurography and electromyography determine the safety of impulses along nerve fibers, a reduced amplitude of the M-response, which indicates a primary muscular type of lesion. A 30-50-fold increase in the level of creatine phosphokinase is characteristic.
- Genetic diagnostics. A genealogical study is conducted at the geneticist’s consultation, which allows to identify the presence of cases of Duchenne myodystrophy in the patient’s family and to identify women who are carriers of the mutant dystrophin gene. DNA diagnostics can reveal anomalies in the dystrophin gene. It should be borne in mind that the non-detection of a mutation in DNA analysis does not indicate its absence, since the search for point mutations is usually not included in the tasks of analysis due to its long duration and complexity.
- Biopsy. In cases where there is a clinical picture of myodystrophy, and DNA analysis has not revealed the presence of a mutation, a muscle biopsy is indicated. Morphological examination of the biopsy determines the heterogeneity and necrosis of myocytes, their replacement by connective tissue elements. Immunochemical analysis indicates the complete absence of dystrophin in the studied muscle fibers.
- Other studies. Additionally, the examination of the musculoskeletal and cardiovascular systems is carried out – an orthopedist’s consultation, spine x-ray, chest x-ray, cardiologist consultation, ECG, echocardiography. According to the indications, it is recommended to consult an endocrinologist, a pulmonologist, and other specialists.
At the same time, differential diagnosis should be carried out with other myopathies — metabolic, inflammatory, Becker myodystrophy, Dreyfus muscular dystrophy, Erba-Roth dystrophy, as well as with polyneuropathy, polymyositis, ALS.
Treatment
Therapy used in clinical practice includes symptomatic and pathogenetic directions. Within the framework of these directions, drug therapy, physical rehabilitation, respiratory support are used:
- Corticosteroids. The main role in the treatment of Duchenne muscular dystrophy today is assigned to glucocorticosteroids, which are prescribed to both capable and incapable of independent movement of patients. GCS help slow down the progression of muscle weakness, have a moderate pulmoprotective and cardioprotective effect, reduce the risk of orthopedic complications. Due to the large number of side effects of glucocorticosteroid therapy, careful monitoring of the child’s condition, timely correction of the dose and regimen of the drug is necessary.
- Metabolic therapy. It is aimed at improving metabolic processes in skeletal muscles, bones, heart muscle, liver, reducing side effects from taking GCS. It includes the appointment of B vitamins, levocarnitine, Ca preparations, vitamin D.
- Physical therapy. In order to minimize the formation of contractures and prolong the motor activity of patients, physical therapy, massage, physiotherapy, passive and active stretching are performed. It is recommended to use orthoses, a verticalizer, special tires, and therapeutic swimming classes.
- Respiratory support. It is important to control the respiratory function and the gas composition of the blood. With a drop of up to 40%, artificial ventilation of the lungs during sleep is recommended. In the future, the ventilator time increases in proportion to the decrease in VEL. At the beginning, ventilation can be carried out with the help of a mask device. Then a tracheostomy is necessary, and a ventilator is performed by attaching the device to the tracheostomy tube. Modern portable ventilators run on batteries and can be fixed on a wheelchair.
Prognosis and prevention
Of all forms of myodystrophy, Duchenne muscular dystrophy has the most unfavorable prognosis. The manifestation of the disease at an early age leads to the fact that by the age of 15, patients become completely immobilized. A fatal outcome is inevitable. Often patients do not reach the age of 25. Usually, the fatal outcome is caused by intercurrent infections, congestive pneumonia, heart or respiratory failure.
Preventive measures are aimed at identifying women carriers of the abnormal dystrophin gene and preventing the birth of a sick child in them. As part of preventive measures, genetics consultations for couples planning pregnancy, pregnancy consultations and prenatal DNA diagnostics are carried out.
