Becker Muscular Dystrophy

Excerpt

Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving a mutation in the dystrophin gene. Progressive muscle weakness, most notably of the proximal lower limbs, is the primary manifestation of this condition. The onset of BMD symptoms varies widely between 5 and 60 years. In a study involving 67 individuals with BMD, most were found ambulant until their 40s or older, while a small group experienced earlier loss of ambulation. BMD symptoms usually appear at a later age than a similar X-linked disorder, Duchenne muscular dystrophy (DMD).

DMD and BMD may be easier to distinguish based on the age at which patients become wheelchair-dependent. Patients with DMD are wheelchair-dependent before age 13, while individuals with BMD may remain ambulatory even after age 16. Patients presenting with proximal muscle weakness before turning 12 may be hard to diagnose without genetic analysis.

BMD is currently considered a mild form of DMD rather than a distinct clinical entity. Consequently, interventional trials are more rarely conducted for BMD than DMD.

Skeletal muscle fibers (myocytes) arise from the fusion of contiguous embryonic muscle cells and are thus multinucleated. Multiple nuclei may be found close to the intracytoplasmic surface of the cell membrane (sarcolemma). Myocytes have abundant microfilaments, which give rise to the contractile apparatus of the myofibrils.

The repeating units of myofibrils are the sarcomeres, composed of interlaced actin and myosin filaments and perpendicularly oriented Z-bands. The T-tubule system is a sarcolemmal invagination into the myocyte involved in calcium storage and release during contraction. The sarcoplasm (myocyte cytoplasm) contains myoglobin, glycogen, creatine, creatine kinase (CK), lysosomes, mitochondria, and lipid vacuoles.

Actin binds to the subsarcolemmal cytoskeletal protein dystrophin, which interfaces with the extracellular matrix through transmembrane dystrophin-associated proteins. Dystrophin normally provides mechanical reinforcement, stabilizing the cell membrane. Dystrophin abnormality is the leading cause of BMD.