Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X linked recessive dystrophinopathy from out of frame DMD mutations.

• Incidence 1 in 5,000 male births; one third are de novo mutations.

• Absent dystrophin causes progressive muscle necrosis and fibrofatty replacement.

• Loss of ambulation at 10 to 13 years untreated; death from respiratory or cardiac failure in the 20s to 30s, extended with care.

• Cardiomyopathy in nearly all by adolescence.

• Delayed walking, toe walking, frequent falls, Gowers manoeuvre, pseudohypertrophy of calves, waddling gait, at age 2 to 5.

• Cognitive and behavioural comorbidity (attention deficit, autism), reduced IQ in a third.

• Scoliosis, contractures, respiratory insufficiency, dilated cardiomyopathy, arrhythmia.

• CK 10 to 100 times upper normal (above 10,000 U/L).

• Genetic testing: MLPA or multiplex PCR for exon deletions/duplications (70%), sequencing for point mutations; muscle biopsy (absent dystrophin on immunostaining) if genetics negative.

• Female carrier testing, prenatal diagnosis.

• Baseline echocardiogram or cardiac MRI, spirometry, DEXA, vitamin D.

• Glucocorticoids from age 4 to 5 (before decline): prednisolone 0.75 mg/kg daily (or 10 days on/10 days off) or deflazacort 0.9 mg/kg daily; prolongs ambulation by 2 to 3 years. Monitor weight, growth, cataracts, hypertension, bone density, adrenal suppression (stress dose cover).

• Vamorolone 6 mg/kg daily as a steroid alternative. Givinostat 21 to 53 mg twice daily.

• Mutation specific: eteplirsen 30 mg/kg IV weekly (exon 51), golodirsen (exon 53), viltolarsen (exon 53), casimersen (exon 45); delandistrogene moxeparvovec gene therapy (ambulatory children 4 to 5 years).

• Cardiac: ACE inhibitor (perindopril) from age 10, add eplerenone, beta blocker.

• Respiratory: cough assist, nocturnal ventilation when FVC under 50%, vaccination.

• Orthopaedic and rehabilitation care, spinal fusion for scoliosis; bone health with vitamin D and bisphosphonates for fractures.

• Psychological support, genetic counselling.