Duchenne muscular dystrophy

Description

X-linked recessive dystrophinopathy - absent dystrophin
Progressive proximal > distal weakness, onset early childhood
Severe end of dystrophinopathy spectrum (vs Becker - reduced, not absent, dystrophin)

~1 in 3500-5000 live male births
X-linked - affects males; carriers (females) usually asymptomatic, ~8-10% manifesting carriers get mild weakness/cardiomyopathy

DMD gene (Xp21) - largest human gene
Deletions (~65%), duplications (~10%), point mutations (~25%)
Out-of-frame mutation -> no functional dystrophin -> loss of sarcolemmal stability -> myofibre necrosis, fibro-fatty replacement
~1/3 de novo mutation - absence of family history does not exclude

CK markedly elevated (often >10-20x ULN) - first clue, often incidental (raised transaminases mistaken for liver disease)
Genetic testing (MLPA/deletion-duplication analysis +/- sequencing) - confirms, defines mutation for exon-skipping eligibility
Muscle biopsy (dystrophin absent on staining) - only if genetics inconclusive
Presentation: delayed walking, waddling gait, calf pseudohypertrophy, Gower sign, language/cognitive delay in a subset

MDT, disease-modifying + supportive

Corticosteroids (prednisone/prednisolone or deflazacort) - started once motor plateau reached (typically ~4-6yrs)
- Slows decline, delays loss of ambulation
- Vamorolone - newer steroid analogue, comparable efficacy with fewer growth/bone/behavioural side effects - increasingly used as alternative
- Monitor growth, BP, bone health (DEXA, vitamin D/calcium), cataracts, behaviour
Exon-skipping antisense oligonucleotides (eteplirsen, viltolarsen etc.) - mutation-specific (exon 51/53/45 amenable subgroups only), modest functional benefit
Gene therapy (delandistrogene moxeparvovec) - approved in some jurisdictions for younger ambulant boys; access/funding varies, evidence still maturing

Systems surveillance

Cardiac - echo/CMR from diagnosis, ACEi at first sign of dysfunction (dilated cardiomyopathy near-universal by adulthood)
Respiratory - annual spirometry, escalating to nocturnal NIV as FVC falls; cough-assist devices
Orthopaedic - scoliosis surveillance, contracture management, physiotherapy; spinal fusion if progressive curve
Bone health - steroid-induced osteoporosis surveillance, fracture prevention

Dilated cardiomyopathy - near-universal by adulthood
Cognitive/learning difficulties, autism spectrum - dystrophin isoforms expressed in brain
Scoliosis (post loss of ambulation), osteoporosis, contractures
Respiratory failure - restrictive pattern

Loss of independent ambulation typically ~10-13yrs (later with steroids)
Progressive respiratory + cardiac failure dominate later course
Historical death in teens/20s from respiratory failure - now often into 30s-40s with modern cardiorespiratory + steroid care
Cardiomyopathy now a leading cause of death as respiratory care has improved

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