Muscular dystrophies are a group of genetic disorders characterized by progressive muscle weakness and degeneration. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) stem from mutations in the dystrophin gene. While they share similar genetic origins, their clinical manifestations and prognosis differ significantly.
Understanding DMD and BMD:
DMD: It is an X-linked recessive disorder, but about 30% of the cases are due to de novo mutations. Boys are more commonly affected by DMD than girls. It's estimated to occur in about 1 in every 3600 male live-born infants. Some studies suggest that around 2 out of every 10,000 people in the United States have DMD.
BMD: Becker muscular dystrophy (BMD) starts later in life and people with it usually live longer. They generally have more dystrophin protein in their bodies. The incidence of BMD is 1 in 18,000 individuals.
DMD is typically caused by large deletions or duplications in the DMD gene, leading to a complete absence or non-functional dystrophin protein. As a result, affected individuals experience severe muscle weakness and loss of movement by early adolescence. The mutations in BMD allow for some production of a partially functional dystrophin protein. Consequently, the disease progression in BMD is milder and slower compared to DMD, with some individuals retaining movement into adulthood.
Genetic Basis of DMD & BMD: The Dystrophin gene is one of the largest genes in the human genome, spanning over 2.2 million base pairs and comprising 79 exons. Mutations in any of these exons can disrupt the reading frame of the gene, leading to the absence or alteration of dystrophin protein.
DMD: The majority of mutations are large deletions encompassing one or more exons, occurring in approximately 60-70% of cases. These deletions disrupt the open reading frame of the gene, resulting in premature termination of protein synthesis. Other mutations in DMD include point mutations, small insertions, and duplications, collectively contributing to the remaining cases. affected individuals typically lose independent ambulation by the age of 12. Respiratory and cardiac complications ensue, significantly impacting life expectancy.
BMD: Often associated with in-frame mutations that maintain the reading frame of the Dystrophin gene, allowing for the production of a truncated but partially functional protein. These mutations may involve single or multiple exons, preserving the essential structural domains of dystrophin and mitigating the severity of muscle degeneration. Depending on the type of mutations, some individuals may maintain ambulation beyond adolescence, while others experience progressive muscle weakness akin to DMD.
The diverse spectrum of mutations in the DMD gene gives rise to the variable clinical presentations observed in DMD and BMD. The location and size of the mutation influence the severity and progression of muscle weakness, as well as the age of onset.
Therapeutic Strategies: Although no cure exists for the diseases and the prognosis is poor, care strategies that focus on maintaining quality of life are:
Glucocorticoid Therapy: Studies have shown that glucocorticoid treatment is linked to improved pulmonary function, delayed scoliosis development, reduced incidence and progression of cardiomyopathy, and overall improved mortality.
Cardiomyopathy: Treatment with angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers is recommended. Early studies suggest that early treatment with ACE inhibitors may slow disease progression and prevent heart failure onset. Routine checkups should be performed with ECG and Echocardiogram.
Orthopedic Interventions: Physiotherapy to prevent contractures is the mainstay of orthopedic interventions, based on patient requirements.
Nutrition and Gentle Exercise play important roles.
Gene therapy: Includes medications that bind RNA and skip over the defective codon. This produces a shorter but potentially functional protein. Eteplirsen (an FDA approved drug) is an exon 51 skipping antisense oligonucleotide medication used for this purpose.
Through continued research and innovation, researchers strive to enhance the lives of affected individuals and their families.
-Written by Sohni Tagore
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