Duchenne Muscular Dystrophy
Duchenne muscular dystrophy is the most common muscular dystrophy with onset in children, affecting 1 in 3,300 male newborns, with a prevalence of 63 cases per 1 million.
The disease is genetically transmitted, recessive, X-linked, thus the disease is transmitted to male newborns by mothers who do not develop clinical signs of disease. A third of patients do not have positive family history of disease, suggesting that the disease also occurs by spontaneous mutations. Duchenne disease and Becker phenotype affects almost exclusively males.
Duchenne Muscular Dystrophy Diagnosis
Duchenne muscular dystrophy was first described by Charles Bell in 1830, but Duchenne in 1868 is the one who established diagnostic criteria that are valid today:
- Weakness with onset in the legs;
- Hyperlordosis with wide-based gait;
- Hypertrophy of weak muscles;
- Progressive course over time;
- Reduced muscle contractility on electrical stimulation in advanced stages of the disease;
- Absence of bladder or bowel dysfunction, sensory disturbance, or febrile illness.
Serum creatine phosphokinase(CPK) is dramatically increased in this disease, 50-100 times the normal amount. This value is very high from childhood, probably from birth, when the disease is not clinically apparent. Normal or slightly elevated creatine phosphokinase values do not match the diagnosis. Creatine phosphokinase may be elevated in amniotic fluid. The enzyme decreases when the muscle is atrophied.
Electrocardiogram is abnormal in 80% of patients. Most often appear arrhythmias. Dystrophic cardiomyopathy occurs by affecting the cardiac dystrophin. Echocardiography reveals small ventricles and prolonged diastolic relaxation.
DNA and immunoassay analysis of dystrophin in Duchenne muscular dystrophy, ease the diagnosis. Only one third of male patients do not present detectable deletions in DNA testing. Gene amplification by PCR (polymerase chain reaction) detects dystrophin gene deletions in two thirds of patients with Duchenne disease. PCR allows diagnosis of asymptomatic carriers and antenatal diagnosis in the eighth week of gestation. In cases where dystrophin gene mutations or duplications are absent, muscle biopsy is required.
Electromyography (EMG) narrows the diagnostic area, excluding diseases of neurogenic origin. EMG should be performed on more muscle, obvious changes are present especially in the proximal muscle of lumbo-pelvic belt. Usually, EMG reveals no spontaneous activity, early positive waves, moderate and high fibrillation potentials. Motor unit potentials are of short duration and variable amplitude, either normal and low. Typically occur polyphasic waves due to variability in size of muscle fibers.
Nerve conduction velocity is normal.
Muscle biopsy is characteristic for muscle diseases with excessive variations in the diameter of muscle fibers, muscle fibers are hypertrophied, central nuclei, excessive interstitial fibrosis and necrotic muscle fibers undergoing regeneration. However muscle biopsy should be correlated with clinical data.
In Duchenne muscular dystrophy to describe these aspects of muscle biopsy:
- Necrosis and degeneration of muscular fibers with phagocytosis and small regenerating basophilic fibers;
- Cellular infiltration with lymphocytes and macrophages in the necrotic fibers;
- Variations in size of muscle fibers, atrophies alternating with hypertrophies;
- Increased number of nuclei, with a central disposition.
In female carriers, muscular biopsy shows changes in 30% of cases, even if serum creatine phosphokinase is normal.
A minority of female carriers are symptomatic, but for the detection of this cases other tests are needed. Serum creatine phosphokinase is increased in two thirds of female carriers. Imunoflorescent assay for dystrophin is necessary and does not establish with certainty the diagnosis of carrier. Muscle biopsy is necessary to quantify the level of dystrophin.
Duchenne Muscular Dystrophy Treatment
Family support is essential for these children. Prophylaxis of immobilization effects is required because installation of vicious contractures andcifoscoliosis should be delayed as much as possible. Are required lung function monitoring, forced vital capacity and use of spirometry to prevent atelectasis and pneumonia. In the terminal stages of illness may be required tracheostomy and assisted ventilation. Surgery can prolong mobilization. Also, patients with Duchenne muscular dystrophy should avoid obesity. It was observed that administration of prednisone can produce a slight delay in disease progression.
Genetic counseling is the most effective prevention. Genetic testing can determine if the mother is a carrier, in which case there is a 50% risk of having a child with Duchenne muscular dystrophy. Analysis of chorionic villi and amniotic cells allow prenatal diagnosis.
Trying to transfer myoblasts in dystrophic muscle proved to be ineffective.