Becker Muscular Dystrophy (BMD) is a progressive disorder characterized by muscle weakness and wasting that generally appears later in childhood or adolescence. It is closely related to Duchenne Muscular Dystrophy (DMD), but the symptoms of BMD are less severe and progress at a much slower rate. Both conditions are classified as dystrophinopathies because they share a common biological origin: a change in the single gene responsible for producing a specific muscle protein. Understanding the cause of BMD requires examining how this genetic change affects the muscle’s structural components.
The Critical Role of Dystrophin
The underlying cause of Becker Muscular Dystrophy is a defect in the machinery that builds and maintains muscle fibers. Healthy muscle cells rely on a protein called Dystrophin, which functions as a molecular anchor situated just beneath the muscle cell membrane, known as the sarcolemma.
Dystrophin acts as a linkage, connecting the muscle fiber’s internal structural framework (the cytoskeleton and actin filaments) to proteins that span the cell membrane. This assembly forms the dystrophin-glycoprotein complex (DGC), which connects the internal structure to the extracellular matrix outside the cell.
This structural connection handles the mechanical stress of muscle movement. During contraction and relaxation, Dystrophin absorbs and distributes the force, preventing the sarcolemma from tearing. When this protein is compromised, the cell membrane becomes unstable and vulnerable to damage. Without this stabilization, muscle fibers degenerate and are gradually replaced by scar tissue and fat, leading to the progressive weakness seen in BMD.
The Specific Genetic Error
The blueprint for the Dystrophin protein is contained within the DMD gene, which is located on the X chromosome. Because this gene is one of the largest known human genes, it is susceptible to spontaneous errors. Becker Muscular Dystrophy arises from specific mutations within the DMD gene.
The most common genetic errors causing BMD are large-scale changes, such as the deletion or duplication of one or more exons (the coding segments of the gene). These errors prevent the gene from being read correctly, but the outcome differs from the more severe Duchenne form. In BMD, the mutation results in the production of Dystrophin, but the protein is shortened, internally deleted, or reduced in quantity.
The key distinction is that muscle cells still produce a Dystrophin protein that retains some function. This partially operational protein offers protection to the muscle fibers. The presence of this shortened, structural protein explains why muscle damage in BMD is slower and the onset of symptoms is delayed compared to the Duchenne type.
Determining Severity: The Reading Frame Hypothesis
The mechanism determining whether a mutation leads to the milder BMD or the severe DMD is explained by the “reading frame hypothesis.” Genes are read by the cell’s protein-building machinery in groups of three DNA bases, known as codons. Each codon specifies a single amino acid.
In BMD, the genetic change is usually an “in-frame” mutation, meaning the deletion or duplication removes a number of bases that is a multiple of three. Because the number of deleted bases is a multiple of three, the reading frame remains intact after the error. The cellular machinery continues reading the remaining code correctly, resulting in a shorter, structurally complete protein that retains some function.
Conversely, the more severe DMD is caused by an “out-of-frame” mutation, where the number of deleted or duplicated bases is not a multiple of three. This shifts the entire reading frame, causing all subsequent codons to be misread. This shift quickly encounters a premature stop signal, instructing the cell to halt production. This results in a severely truncated or non-functional protein that is rapidly degraded.
How Becker Muscular Dystrophy is Inherited
Becker Muscular Dystrophy follows an X-linked recessive pattern of inheritance because the DMD gene is located on the X chromosome. Males possess only one X chromosome and one Y chromosome, meaning a single copy of the mutated gene is sufficient to cause the disorder.
Females have two X chromosomes. If one X chromosome carries the mutation, the second, healthy X chromosome can often compensate by producing enough normal Dystrophin. This compensation means females are typically carriers and usually do not experience symptoms, though a small number of carriers can show mild muscle weakness or heart issues later in life.
A female carrier has a 50% chance of passing the affected X chromosome to her child during each pregnancy. A son who inherits the mutated X chromosome will develop BMD, while a daughter who inherits it will become a carrier. Males with BMD will pass the mutation to all of their daughters, making them obligate carriers, but none of their sons will inherit the condition.