Definition and genetics
Duchenne muscular dystrophy (DMD) is a severe, progressive, X-linked recessive myopathy caused by loss-of-function variants in the DMD gene (Xp21.2), which encodes dystrophin — a large cytoskeletal protein that anchors the muscle-fibre membrane to the extracellular matrix. Out-of-frame (frame-disrupting) variants abolish functional dystrophin and produce the Duchenne phenotype; in-frame variants that retain partial function produce the milder allelic Becker muscular dystrophy. Roughly two-thirds of cases are inherited from a carrier mother and one-third arise de novo. Deletions or duplications of one or more exons account for ~70-80% of pathogenic variants; the remainder are point mutations or small insertions/deletions.
Epidemiology
DMD affects approximately 1 in 3,500-5,000 live male births, making it the most common inherited muscular dystrophy of childhood. Female carriers are usually asymptomatic but a minority are “manifesting carriers” with myopathy or cardiomyopathy.
Clinical features
Boys typically present between ages 2 and 5 with delayed motor milestones, frequent falls, toe-walking, a waddling gait, difficulty climbing stairs, and the classic Gowers sign (using the arms to “climb up” the legs to stand). Calf pseudohypertrophy, proximal-greater-than-distal weakness, and lost deep-tendon reflexes are characteristic. Global developmental delay and learning/behavioural difficulties are common because dystrophin is also expressed in brain. Without disease-modifying treatment, loss of ambulation historically occurred around age 9-12, followed by progressive respiratory failure and dilated cardiomyopathy in the second decade.
Diagnosis
A markedly elevated serum creatine kinase (CK) — often 10-100x the upper limit of normal — is the cardinal early biochemical clue and is present from birth, well before symptoms. Any boy with unexplained motor delay, a Gowers sign, or an incidentally elevated CK or transaminases (muscle-derived AST/ALT) warrants prompt evaluation. Genetic testing is the diagnostic gold standard: start with deletion/duplication analysis (MLPA or array CGH), which detects the majority of variants; if negative, proceed to DMD gene sequencing for point mutations. Muscle biopsy with dystrophin immunostaining is now reserved for cases where genetic testing is non-diagnostic but suspicion remains high.
See the full criteria: Duchenne Muscular Dystrophy.
Red flags
- Any boy not walking by 18 months, or a Gowers sign at any age.
- Unexplained CK elevation or “transaminitis” with normal GGT (muscle, not liver, source).
- Calf pseudohypertrophy with proximal weakness.
- Family history of a maternal-line male with childhood-onset weakness or unexplained cardiomyopathy.
Management overview
Care is multidisciplinary and proactive. Glucocorticoids (corticosteroid class) remain the backbone of disease-modifying therapy, prolonging ambulation and preserving respiratory and cardiac function; the dissociative steroid vamorolone offers a comparable efficacy class with a different side-effect profile. Mutation-specific antisense oligonucleotide exon-skipping agents restore the reading frame for amenable deletions, and a histone deacetylase inhibitor (givinostat) is approved as a non-steroidal adjunct. Gene-transfer (microdystrophin) therapy is an emerging class. Wrap-around care includes cardioprotection (ACE inhibitors/beta-blockers and surveillance echocardiography/MRI), respiratory monitoring with non-invasive ventilation, bone-health and growth/endocrine surveillance (glucocorticoid-related), scoliosis and contracture management, and genetic counselling with carrier testing of the mother. Do not initiate dosing without confirmed genetics and a neuromuscular specialist.
References
- Birnkrant DJ, et al. Lancet Neurol. 2018 (DMD Care Considerations, parts 1-3).
- Darras BT, et al. Dystrophinopathies. GeneReviews, 2022.
- Duchenne Muscular Dystrophy. StatPearls, 2024.
Decision support for qualified clinicians only — verify against current primary guidelines and your clinical judgement.