About Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration and weakness. It is caused by mutations in the dystrophin gene, which is crucial for muscle function. This condition primarily affects boys and typically presents symptoms in early childhood. As the disease progresses, it leads to the loss of ambulatory ability, respiratory complications, and cardiac issues. Without effective treatment, most individuals with DMD face a significantly shortened lifespan.

The DMD gene is located on the Xp21.2 locus (location) of the X chromosome.

Because women have two X chromosomes, even if they inherit the defective chromosome, the disease is rarely expressed in girls with the same intensity as in boys.

The symptoms of female carriers are most often so minor that the carrier is revealed only during the diagnosis of a male child.

The DMD gene has 79 protein coding sections (exons).

This 79 exons code the dystrophin protein found in muscle cells.

The dystrophin protein is an important member of the dystrophin-associated protein complex (DAPC), a protein complex found in the membrane that borders the striated muscle fiber. The task of DAPC is to provide a connection between the components of the extracellular matrix and the actin-based citoskeleton.

One end of dystrophin is specialized for binding to the interior of the muscle cell and the other end to various proteins on the cell membrane. By ensuring and stabilizing the structure of the DAPC, it plays an important role in maintaining the mechanical stability and elasticity of the cell.

In the absence of functional dystrophin, the stability of the cell membrane decreases and it is easily damaged during contraction. This leads to the initiation of inflammatory processes and, as a final result, the destruction of the muscle cell. Necrosis of muscle fibers results in phagocytosis and further inflammation. Dystrophin deficiency leads to continuous muscle damage, muscle fibers are replaced by scar and fat tissues, which causes progressive muscle weakness.

Early expression, diagnosis and symptoms

Between the ages of 3 and 5:

Delay in early developmental milestones (sitting, walking, speaking) often contributes to early diagnosis.

A classic symptom is difficulty standing up from a lying or sitting position. When the child tries to get up from lying on his stomach, he compensates for the weakness of the pelvic muscles by using the upper limbs: he first leans on his arms and knees, then "walks" his hands to his legs to fully straighten.

In the early years, a waddling gait, a more pronounced curvature of the lumbar spine and enlarged calf muscles can also be characteristic symptoms, but unfortunately the latter is often ignored or misinterpreted.

The diagnosis can be clearly demonstrated by immunohistochemistry. In the case of typical clinical symptoms, genetic diagnosis can prevent a muscle biopsy, and only in the case of its negativity, a myopathological examination of the muscle is recommended. Genetic testing of the dystrophin gene is important in all cases.

5-7 years old:

In the early ambulatory phase, several symptoms appear (e.g. difficulty climbing stairs), mainly in the form of motor delays and difficulty standing up.

Adolescence and young adulthood:

Motor delays are followed by functional decline.

Joint movement restriction (contracture) can develop due to the shortening of the muscles and tendons around the joint, which further increases the limitation of movement. The decline gradually results in the loss of mobility and wheelchair dependence in the teenage years.

Limb and spine deformities appear rapidly after being in a wheelchair. Due to the weakness of the muscles near the spine, a large degree of scoliosis can develop, which can only be corrected to a limited extent by surgical intervention.

The deformities negatively affect the respiratory function, so the child may need mechanical ventilation by the end of his teenage years, the beginning of his 20s. By young adulthood, the inability to perform everyday activities (e.g. self-feeding) may appear.

If the muscles of the esophagus are affected, swallowing difficulties may develop. As a result, nutritional disorders and aspiration pneumonia may develop, so artificial feeding may be necessary.

Loss of diaphragmatic muscle function causes increasing respiratory impairment and cardiac dysfunction in teens and twenties.

Eventually, disease progression leads to cardiomyopathy, respiratory failure, and early death.

Life expectancy:

Average life expectancy is 18 to 25 years. Most people with DMD die of respiratory and heart failure.