Becker muscular dystrophy

Becker muscular dystrophy results from in-frame mutations in the DMD gene on Xp21, which encodes dystrophin, a cytoskeletal protein that links the muscle fiber cytoskeleton (actin) to the extracellular matrix via the dystrophin-glycoprotein complex, stabilizing the sarcolemma during contraction. Unlike Duchenne muscular dystrophy (DMD), where frameshift mutations produce little to no functional dystrophin, Becker mutations preserve the reading frame, allowing production of a partially functional, truncated protein. This results in a less severe phenotype with later onset (typically age 5-15 years, though can present later), slower progression, and longer survival (often into 40s-60s) compared to DMD.

Clinical features include proximal muscle weakness (hip and shoulder girdle), calf pseudohypertrophy (due to fatty/fibrous infiltration), positive Gowers sign (using arms to rise from floor), and myalgia with exercise intolerance. Cardiac involvement, particularly dilated cardiomyopathy, may be a prominent feature and can sometimes precede skeletal muscle symptoms; cardiac evaluation is essential. Cognitive impairment is less common than in DMD.

Diagnosis involves markedly elevated serum creatine kinase (CK), genetic testing for DMD gene mutations (confirms diagnosis, distinguishes from DMD), and muscle biopsy showing dystrophin present but reduced/abnormal on immunohistochemistry or Western blot (contrasts with absent dystrophin in DMD).

Management is supportive: physical therapy, orthotics, corticosteroids (may slow progression, though less evidence than in DMD), cardiac monitoring and treatment (ACE inhibitors, beta-blockers), and genetic counseling given X-linked recessive inheritance (mothers are carriers; risk to male offspring). Emerging therapies include exon-skipping antisense oligonucleotides and gene therapy trials.

Key board differentiators: BMD vs DMD - BMD has later onset, slower progression, some retained dystrophin function (partial vs absent), and better prognosis. Both share the same gene locus but differ in mutation type (in-frame vs frameshift) per the Reading Frame Rule.