Which are the causes of Becker muscular dystrophy?

Becker muscular dystrophy (BMD) is a genetic disorder that primarily affects the muscles, leading to progressive muscle weakness and wasting over time. It is caused by mutations in the dystrophin gene, which provides instructions for producing a protein called dystrophin. Dystrophin is crucial for maintaining the structural integrity of muscle fibers.

BMD is inherited in an X-linked recessive pattern, meaning it primarily affects males. Females can also be carriers of the mutated gene but are typically asymptomatic or have milder symptoms due to the presence of a second X chromosome. The severity of BMD can vary widely among affected individuals, even within the same family.

Genetic mutations in the dystrophin gene are the underlying cause of BMD. These mutations can result in the production of an abnormal or truncated dystrophin protein or lead to a complete absence of dystrophin. The dystrophin protein plays a crucial role in stabilizing the muscle cell membrane and protecting it from damage during muscle contraction and relaxation.

Without functional dystrophin, muscle fibers become more susceptible to damage, leading to a cascade of events that ultimately result in muscle degeneration. The exact mechanisms by which the absence or abnormality of dystrophin leads to muscle weakness and wasting are not fully understood, but several hypotheses have been proposed.

One hypothesis suggests that the absence of dystrophin disrupts the dystrophin-associated glycoprotein complex (DGC), a group of proteins that interact with dystrophin and help maintain the structural integrity of muscle fibers. Disruption of the DGC can lead to increased susceptibility of muscle fibers to mechanical stress and damage.

Another hypothesis suggests that the absence of dystrophin results in impaired calcium homeostasis within muscle cells. Dystrophin normally helps regulate the flow of calcium ions in and out of muscle cells during muscle contraction. Without dystrophin, abnormal calcium handling may occur, leading to increased calcium influx and subsequent muscle fiber damage.

Furthermore, the absence of dystrophin may also lead to chronic inflammation within muscle tissue. Inflammatory processes can contribute to muscle fiber degeneration and impair muscle regeneration, further exacerbating muscle weakness and wasting in BMD.

It is important to note that the severity and progression of BMD can be influenced by various factors, including the specific mutation in the dystrophin gene, the amount of residual dystrophin produced, and other genetic and environmental factors that may modify disease expression.

Diagnosis of BMD typically involves a combination of clinical evaluation, family history assessment, muscle biopsy, and genetic testing. Muscle weakness and wasting, especially in the pelvic and shoulder girdle muscles, are characteristic features of BMD. Elevated levels of creatine kinase (CK), an enzyme released from damaged muscle fibers, can also be observed in blood tests.

Treatment for BMD primarily focuses on managing symptoms, improving quality of life, and slowing disease progression. This may involve a multidisciplinary approach, including physical therapy, respiratory support, orthopedic interventions, and medications to address specific symptoms or complications.

Research efforts are ongoing to develop potential gene therapies and other novel treatment approaches for BMD. These aim to restore or compensate for the lack of functional dystrophin in affected individuals, potentially offering more targeted and disease-modifying treatments in the future.

In conclusion, Becker muscular dystrophy is caused by genetic mutations in the dystrophin gene, leading to the absence or abnormality of the dystrophin protein. The exact mechanisms by which the absence of dystrophin results in muscle weakness and wasting are not fully understood, but disruption of the dystrophin-associated glycoprotein complex, impaired calcium homeostasis, and chronic inflammation are among the proposed mechanisms. Diagnosis involves clinical evaluation, family history assessment, muscle biopsy, and genetic testing. Treatment primarily focuses on symptom management and improving quality of life. Ongoing research aims to develop more targeted therapies for BMD.