Clinical meaning
DMD results from loss-of-function mutations (65% large deletions, 10% duplications, 25% point mutations/small indels) in the DMD gene at Xp21.2, the largest human gene spanning 2.4 megabases. The reading frame rule predicts severity: out-of-frame mutations cause DMD (no functional dystrophin), while in-frame mutations cause the milder Becker muscular dystrophy (truncated but partially functional dystrophin). Dystrophin anchors the subsarcolemmal cytoskeleton to the dystrophin-associated glycoprotein complex, protecting the membrane during eccentric contractions. Loss of dystrophin leads to sarcolemmal microinjury, calcium-mediated protease activation, mitochondrial dysfunction, and chronic inflammatory fibrosis. The clinician manages the complete spectrum of DMD care including prescribing corticosteroids, initiating cardioprotective therapy, managing respiratory decline, overseeing molecular therapies (exon-skipping, gene therapy), and coordinating multidisciplinary care through disease progression.
Diagnosis & workup
Diagnostics & workup: - Order and interpret genetic testing: multiplex ligation-dependent probe amplification (MLPA) for deletions/duplications, sequencing for point mutations - Prescribe and interpret serial pulmonary function tests: FVC <80% predicted triggers nocturnal monitoring, <50% requires NIV evaluation - Order annual echocardiogram and cardiac MRI (more sensitive for early fibrosis detection) - Order annual DEXA scan for bone density monitoring while on corticosteroids - Evaluate serum CK, liver function (ALT/AST may be muscle-origin), renal function - Order sleep study for nocturnal hypoventilation when FVC <50% predicted - Monitor HbA1c and fasting glucose for steroid-induced diabetes