Duchenne Muscular Dystrophy and Disease-Modifying Treatments

The dystrophinopathies are X-linked recessive disorders caused by mutations in the DMD gene. Mutations that disrupt the reading frame lead to absence of dystrophin and the Duchenne phenotype; mutations that preserve the frame produce a shortened but partly functional protein and the Becker phenotype. Roughly two thirds of mutations are large deletions or duplications. In a substantial proportion of cases the mutation is de novo, so the absence of a family history does not exclude the diagnosis.

Clinical course

Symptoms are usually noticed between two and five years of age: frequent falls, inability to run, difficulty climbing stairs, toe walking, a Gowers manoeuvre, calf pseudohypertrophy and a waddling gait. In the untreated natural history ambulation is lost in the early part of the second decade, after which scoliosis, restrictive lung disease and cardiomyopathy dominate. Corticosteroids and multidisciplinary standards of care have substantially delayed this course.

Diagnosis

Where there is clinical suspicion, creatine kinase is measured; it is typically 10 to 100 times the upper limit of normal. DMD deletion-duplication analysis (MLPA) follows, with gene sequencing if negative. Full characterisation of the mutation is needed not only for diagnosis but also to establish eligibility for mutation-specific treatment. Muscle biopsy is not required once a genetic diagnosis is made.

Corticosteroid treatment and management of adverse effects

Corticosteroids are the core treatment shown to delay loss of function in Duchenne. Prednisolone or deflazacort are used, in daily and intermittent regimens. Management of adverse effects determines whether treatment can be sustained.

• Weight gain: weight and height at every visit, dietetic advice.
• Short stature: growth chart surveillance, endocrine assessment.
• Bone fragility and vertebral fracture: enquiry about back pain, vitamin D and calcium, bisphosphonates where indicated.
• Cataract: annual ophthalmic examination.
• Behavioural change: attention to dose timing, psychological support.
• Glucose intolerance and hypertension: fasting glucose and blood pressure monitoring.
• Adrenal suppression: assumed in every patient; written instructions for stress dosing during illness, stress and surgery, together with an emergency card.

Vamorolone is a dissociative steroid approved for Duchenne in patients aged two years and above; assessments have reported that the decline in height percentile seen in the prednisone group was not observed with vamorolone.

Mutation-specific and other treatments

The information below is current as of October 2026. Eligibility depends on mutation type and these treatments are not suitable for every patient; decisions are made in an experienced centre using current product information.

• Exon-skipping therapies: antisense oligonucleotides that restore the reading frame by skipping specific exons and aim to produce a shortened but functional dystrophin. Eteplirsen (exon 51), golodirsen and viltolarsen (exon 53) and casimersen (exon 45) have been approved. Each can only be used in patients carrying an appropriate mutation. The approvals were granted through accelerated pathways based on increases in circulating dystrophin and the magnitude of clinical benefit remains a matter of debate.
• Givinostat: a histone deacetylase inhibitor that can be used in patients aged six years and above irrespective of mutation type. The EPIDYS study reported slowing of functional decline. The main monitoring concern is thrombocytopenia.
• Delandistrogene moxeparvovec: a single-dose therapy delivering a shortened micro-dystrophin gene via an AAVrh74 vector. The product information carries a boxed warning for severe acute liver injury including fatal acute liver failure. Patient selection requires an anti-AAVrh74 total binding antibody titre below a defined threshold, and deletions of exon 8 and/or 9 are a contraindication. In the EMBARK study the primary endpoint at 52 weeks was not met, with supportive results on timed function tests.
• Ataluren: held a conditional marketing authorisation in Europe for patients with nonsense mutations. On 28 March 2025 the European Commission decided not to renew the authorisation on the grounds that efficacy had not been confirmed, and the medicine is no longer authorised in Europe.

Care by stage

• Early ambulatory: corticosteroid decision, stretching programme, baseline functional measures, initiation of cardiac and respiratory surveillance, school arrangements.
• Late ambulatory: fall prevention, orthoses, timely wheelchair planning, weight management, bone health, scoliosis surveillance.
• Early non-ambulatory: seating system and posture, more frequent scoliosis surveillance, upper limb function, more frequent respiratory assessment, cardiac treatment.
• Late non-ambulatory: cough assistance and non-invasive ventilation, nutritional assessment and consideration of gastrostomy, pain, communication technology, transition to adult care.

Becker muscular dystrophy

The course is milder and more variable and most patients remain ambulant into adulthood. However, cardiomyopathy can be severe out of proportion to skeletal muscle involvement and in some patients the heart is the first and dominant problem. A patient with mild muscle findings still requires regular cardiac surveillance.