A diagnosis of Duchenne muscular dystrophy typically comes after a period of concern – a boy who is slower than other children to walk, who trips frequently, who has difficulty climbing stairs or rising from the floor, and who uses the characteristic Gowers' manoeuvre (walking his hands up his legs to stand up). The path to diagnosis often involves a GP noticing an elevated CK (creatine kinase) level, followed by genetic testing. For many families, the diagnosis arrives before there is time to understand what it means.
What it means has changed substantially over the past two decades. DMD remains a serious, life-limiting condition. But the management has improved to the point where the trajectory for boys diagnosed today looks very different from that of boys diagnosed a generation ago, and the therapeutic pipeline is more active than it has ever been. Understanding the current standard of care – and what is coming – is an important part of navigating this diagnosis.
Healthbooq (healthbooq.com/apps/healthbooq-kids) covers complex and progressive conditions in children and their families.
The Biology of DMD
DMD is caused by mutations in the DMD gene, which is located on the X chromosome and is one of the largest genes in the human genome. The gene encodes dystrophin, a protein that acts as a shock absorber within muscle cells, connecting the internal muscle fibre structure to the surrounding connective tissue. Without functional dystrophin, muscle fibres are damaged by normal mechanical activity and progressively replaced by fat and connective tissue.
Because the gene is X-linked, DMD almost exclusively affects males (who have one X chromosome). Females who carry one mutated copy are typically unaffected (or mildly affected) carriers. Approximately one-third of cases arise from new mutations, with no family history.
The mutation type matters for treatment purposes: most DMD mutations involve deletions of one or more exons of the dystrophin gene that disrupt the reading frame. Becker muscular dystrophy, which is caused by in-frame deletions that preserve some residual dystrophin production, is typically less severe.
Signs and Progression
The first signs of DMD usually appear between ages 2 and 5: delayed walking, waddling gait, difficulty with stairs, frequent falls, and the Gowers' manoeuvre when rising from the floor. Calf pseudohypertrophy – enlarged but weak calves caused by replacement of muscle with fat and connective tissue – is characteristic.
Without treatment, most boys lose independent walking between ages 8 and 12. Scoliosis typically develops after loss of ambulation. Cardiac involvement (dilated cardiomyopathy) begins in most individuals by early adolescence and is progressive; respiratory muscle weakness leads to declining forced vital capacity (FVC) and eventually to the need for non-invasive ventilatory support, typically in late adolescence or early adulthood. Cognitive and learning difficulties are somewhat more common than in the general population, related to the role of dystrophin isoforms in the brain.
Treatment
Corticosteroids (prednisolone or deflazacort) are the standard pharmacological treatment in DMD and have been shown in multiple randomised trials to slow muscle strength decline, extend ambulation by two to three years, delay onset of scoliosis, and improve cardiac and respiratory outcomes. The efficacy of steroids in extending ambulation and delaying the disease course is well-established; the evidence was reviewed comprehensively by Craig McDonald at UC Davis and the CINRG (Cooperative International Neuromuscular Research Group). Most boys in the UK are started on steroids in the primary school years and continue throughout life.
Cardiac management with ACE inhibitors and beta-blockers, introduced early even before symptoms develop, is standard practice and has improved survival significantly. Regular cardiac monitoring with echocardiogram and MRI is part of the multidisciplinary care pathway.
Respiratory support with non-invasive ventilation (typically BiPAP) is introduced when respiratory function declines, initially at night and then extending into daytime use. This has had one of the most significant impacts on life expectancy over recent decades.
New Therapies
The therapeutic landscape in DMD has changed substantially since 2016. Exon-skipping therapies use synthetic antisense oligonucleotides to cause the ribosome to skip over the mutated exon during dystrophin production, restoring a truncated but partially functional reading frame. Eteplirsen (Exondys 51), developed by Sarepta Therapeutics and targeting exon 51 skipping, was the first approved in the USA; golodirsen and viltolarsen target other exons. Eligibility depends on mutation type: approximately 13% of DMD patients have deletions amenable to exon 51 skipping; the broader exon 45, 51, and 53-skipping drugs together cover around 30% of the DMD population. These therapies are approved by the FDA but access through the NHS and NICE has been limited due to questions about the magnitude of clinical benefit.
Gene therapy approaches – delivering a truncated but functional version of the dystrophin gene (micro-dystrophin) using adeno-associated viral (AAV) vectors – have entered clinical trials. Delandistrogene moxeparvovec (Elevidys, Sarepta), a micro-dystrophin gene therapy, received conditional FDA approval in 2023 for boys aged 4-5 with DMD; its clinical utility is still being defined, and UK availability is uncertain.
CRISPR-based gene editing approaches and utrophin upregulation strategies (utrophin is a dystrophin paralogue that could compensate if upregulated) are in earlier stages of development.
Francesco Muntoni at UCL Great Ormond Street Institute of Child Health leads one of the largest European DMD research programmes, contributing to natural history studies, biomarkers, and clinical trials.
Multidisciplinary Care
The care of a child with DMD involves a large team: a paediatric neurologist or neuromuscular specialist, physiotherapist (maintaining range of motion and managing contractures), occupational therapist (adaptive equipment and home modifications), respiratory physiotherapist, cardiologist, orthopaedic surgeon (scoliosis management), dietitian, and educational psychologist. Specialist neuromuscular clinics, including those at Great Ormond Street Hospital, Alder Hey, and Newcastle, coordinate this care.
Muscular Dystrophy UK is the main UK charity supporting children with DMD and other muscular dystrophies, providing information, advocacy, and connections to the neuromuscular network.
Key Takeaways
Duchenne muscular dystrophy (DMD) is the most common severe muscular dystrophy in children, affecting approximately 1 in 3,500 to 5,000 male births. It is caused by mutations in the dystrophin gene on the X chromosome, resulting in progressive muscle weakness. Without corticosteroid treatment, most boys lose the ability to walk between ages 8 and 12; with steroids and current management, many retain walking into their mid-teens and beyond. The standard of care has improved significantly over the past two decades with corticosteroids and cardiac and respiratory monitoring, and a wave of new gene-based and exon-skipping therapies has entered clinical use and trials. Most young men with DMD now survive into their thirties and beyond.
