Duchenne muscular dystrophy
Duchenne muscular dystrophy is an X-linked recessive dystrophinopathy from absent dystrophin, causing early-onset, fulminant proximal weakness with loss of independent ambulation by the early teens and progressive cardiomyopathy. Diagnosis is by genetic testing for a DMD gene deletion/duplication; management is glucocorticoid therapy plus multidisciplinary cardiac, respiratory, and orthopedic surveillance.
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What this article covers
- Overview
Definition: Duchenne muscular dystrophy (DMD) is an X-linked recessive muscular dystrophy caused by absence of the dystrophin protein from an out-of-frame mutation (most often a deletion) in the DMD…
- Epidemiology
Most common childhood muscular dystrophy: DMD is the most common and most severe of the dystrophinopathies presenting in childhood.
- Risk factors
Male sex with an inherited or de novo DMD gene mutation: the dominant and essentially universal risk factor, given the X-linked recessive inheritance pattern.
- Pathophysiology
Absent dystrophin: an out-of-frame DMD gene mutation disrupts the reading frame and prevents production of functional dystrophin protein, which normally anchors the muscle cytoskeleton to the extracellular matrix at the sarcolemma.
- Clinical features
Early-onset, fulminant proximal weakness: symmetric proximal limb-girdle weakness typically becomes apparent in early childhood, well before the milder, adult-onset presentation sometimes seen with Becker muscular dystrophy.
- Differential diagnosis
Becker muscular dystrophy: Becker muscular dystrophy is the milder allelic dystrophinopathy from partial (not absent) dystrophin; onset is later (often not until adolescence or adulthood)…
- Diagnosis
Diagnostic basis: the diagnosis of DMD is established by genetic testing showing an out-of-frame deletion, duplication, or point mutation in the DMD gene that predicts absent dystrophin production…
- Management
First step - initiate daily oral glucocorticoids: prednisone (dose 0.75 mg/kg orally once daily; deflazacort 0.9 mg/kg orally once daily) is the first-line disease-modifying treatment once a…
- Complications
Dilated cardiomyopathy and heart failure: dilated cardiomyopathy develops in nearly all patients as the disease advances and is a leading cause of morbidity and mortality.
- Prognosis
Progressive functional decline: independent ambulation is typically lost by the early teenage years, followed by progressive upper limb and respiratory decline.
- Prevention
No primary prevention of the genetic defect: DMD cannot be prevented once the causative DMD gene mutation is present; prevention efforts focus on early detection and complication avoidance.
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