Duchenne and Becker muscular dystrophy

At a glance

• X-linked recessive disorders of the DMD gene (Xp21), which encodes dystrophin. Duchenne affects about 1 in 3,500 to 5,000 male births. Becker is milder and rarer.
• No dystrophin gives Duchenne (DMD). Reduced or truncated dystrophin gives Becker (BMD).
• CK is massively raised from birth. Diagnosis is genetic.
• With corticosteroids, ventilation and cardiac therapy, most men with DMD now live into their 30s. Adult physicians manage the cardiomyopathy, respiratory failure, bone fragility and steroid complications.
• About a third of cases are de novo. Carrier mothers can develop cardiomyopathy.

Genetics

• DMD is the largest human gene (79 exons, about 2.2 Mb), which explains the high new-mutation rate.
• Deletions of one or more exons cause about 65 to 70%, clustered in the exon 45 to 55 hotspot. Duplications cause about 10%, and small variants (nonsense, frameshift, splice) the rest.
• Reading-frame rule: an out-of-frame deletion disrupts translation and gives Duchenne. An in-frame deletion keeps a shorter protein and gives Becker. It predicts phenotype in about 90%.
• Inheritance: an affected boy's mother is a carrier in about two-thirds of cases. A carrier's sons have a 50% risk of being affected and her daughters a 50% risk of being carriers.
• Germline mosaicism: a mother who tests negative on blood can still have a second affected son. Quote a recurrence risk of several percent and offer prenatal testing in later pregnancies.
• Pitfall: CK is unreliable for carrier detection. Test the familial variant.

Recognition

Duchenne

• Early signs: delayed walking (after 18 months), speech delay, frequent falls, toe walking, difficulty running and climbing stairs.
• Gowers sign by about age 3 to 5: the child climbs up his legs with his hands to stand from the floor (proximal hip weakness).
• Calf pseudohypertrophy from fat and fibrous replacement. Waddling gait, lumbar lordosis.
• Loss of walking before age 13 (about age 10 to 12 untreated; later on steroids).
• Cognition: mean IQ about one standard deviation below average, with intellectual disability in about a third. ADHD, autism and specific learning disorders are common. Loss of brain dystrophin isoforms explains this, and it is not progressive.

Becker

• Onset usually after age 5, often in adolescence or adult life. Walking continues beyond 16, often into the 40s or later.
• Exercise-induced cramps, myalgia and myoglobinuria may be the only symptoms. Some men present with isolated raised CK.
• Cardiomyopathy can be out of proportion to the skeletal weakness and is the main cause of death. Some men need heart transplantation while still walking.

Manifesting carriers

• About 5 to 10% of carrier women have mild proximal weakness or myalgia, usually from skewed X inactivation.
• Dilated cardiomyopathy develops in a minority, sometimes without any weakness.

Investigations

Test	Finding and role
CK	10 to 100 times normal in DMD (often over 10,000 U/L), raised from birth. Falls later as muscle is replaced by fat. Raised but lower in BMD
ALT and AST	Raised from muscle. GGT is normal
DMD deletion/duplication analysis (MLPA or chromosomal microarray)	First-line. Detects about 75 to 80% of variants
DMD sequencing	Next, if deletion/duplication testing is negative. Finds nonsense and small variants, which matter for some targeted therapies
Muscle biopsy	Only if genetics is negative or uncertain. Absent dystrophin on immunohistochemistry (DMD) or reduced and patchy staining (BMD)
ECG, echo and cardiac MRI	At diagnosis and regularly. MRI shows late gadolinium enhancement in the inferolateral LV wall before the ejection fraction falls
Lung function	FVC, peak cough flow, overnight oximetry or polysomnography, CO2 monitoring

• EMG isn't needed for diagnosis.
• The variant determines eligibility for exon-skipping (specific deletions) and nonsense readthrough trials.

Management

Care follows the 2018 DMD Care Considerations (Birnkrant, Lancet Neurology), delivered by a multidisciplinary neuromuscular clinic.

Corticosteroids

• Start around age 4 to 6, before motor plateau, after vaccination is up to date (live vaccines before starting).
• Prednisolone 0.75 mg/kg/day or deflazacort 0.9 mg/kg/day. Deflazacort causes less weight gain but more cataracts and growth suppression.
• Benefit: walking prolonged by 2 to 3 years, less scoliosis surgery, slower respiratory and cardiac decline, and longer survival. Most centres continue after loss of walking.
• Vamorolone, a dissociative steroid, kept efficacy with less growth suppression and bone toxicity in VISION-DMD. Check its current Australian availability.
• Steroid harms to monitor: weight, short stature, delayed puberty, vertebral fractures, cataract, hypertension, glucose intolerance, behaviour.
• Adrenal suppression: give stress-dose hydrocortisone for illness, surgery or trauma, and never stop abruptly. Patients should carry a steroid alert card.

Newer and disease-modifying therapies

Therapy	Mechanism	Status
Exon-skipping antisense (eteplirsen exon 51, golodirsen and viltolarsen exon 53, casimersen exon 45)	Restore the reading frame to make a Becker-like protein	US accelerated approval on small dystrophin increases. Not approved in Europe
Ataluren	Readthrough of nonsense variants	Lost its EU authorisation after confirmatory trials failed
Givinostat	Histone deacetylase inhibitor	Slowed decline in the EPIDYS trial. US approval 2024 for age 6 and over
Delandistrogene moxeparvovec	AAV micro-dystrophin gene therapy	US approval; EMBARK missed its primary endpoint. Two deaths from acute liver failure in 2025 led to tighter restrictions, and 2025 consensus advises close liver and cardiac monitoring

• None of these replaces corticosteroids and multidisciplinary care. Refer interested families to a neuromuscular centre for trial and access advice.

Cardiac

• Dilated cardiomyopathy is nearly universal in DMD by the late teens and is now a leading cause of death.
• ACE inhibitor or ARB by age 10, even with normal function. A French trial (Duboc 2005) showed early perindopril reduced later mortality.
• Add a mineralocorticoid receptor antagonist (eplerenone or spironolactone) for fibrosis or dysfunction, and a beta-blocker for dysfunction or tachycardia. The 2025 ACTION committee consensus endorses this layered approach.
• Cardiac MRI detects early fibrosis. Imaging every 1 to 2 years until 10, then yearly.
• Arrhythmia, including AF and ventricular arrhythmia, rises with fibrosis. ICD decisions are individual.
• In BMD, follow heart failure guidelines and consider transplantation, which works well in selected men.

Respiratory

• Restrictive respiratory failure follows loss of walking: weak muscles, scoliosis and a weak cough.
• Nocturnal hypoventilation comes first: morning headache, fatigue, poor sleep, daytime sleepiness. See respiratory failure.
• NIV at night for symptoms, overnight hypercapnia or FVC under 50% predicted. Extend to daytime NIV, mouthpiece ventilation or tracheostomy as weakness progresses.
• Cough assist (mechanical insufflation-exsufflation) when peak cough flow falls below about 270 L/min. Under 160 L/min, airway clearance is ineffective.
• Influenza and pneumococcal vaccination. Treat chest infections early with antibiotics and airway clearance.
• Pitfall: oxygen alone in hypercapnic respiratory failure worsens CO2 retention. Ventilate.

Bone and endocrine

• Low bone density from immobility and steroids. Vertebral fractures are often silent: screen with lateral spine imaging.
• Treat vertebral or low-trauma long bone fractures with IV bisphosphonate (zoledronic acid). Keep vitamin D and calcium replete.
• Long bone fracture with sudden breathlessness or confusion suggests fat embolism.
• Delayed puberty from steroids: testosterone replacement from about age 12 to 14.

Orthopaedic and other

• Spinal fusion for progressive scoliosis after loss of walking, before respiratory function falls too far.
• Night splints, stretching and tendon surgery for contractures.
• Dysphagia, constipation and gastric dilatation in later disease. Weight loss in adulthood may need gastrostomy.

Anaesthesia and acute care

• Avoid succinylcholine and volatile anaesthetics: risk of rhabdomyolysis, hyperkalaemia and cardiac arrest. Use total IV anaesthesia.
• Assess cardiac and respiratory function before any procedure. Plan extubation to NIV.
• Give stress-dose steroids if the patient is on chronic corticosteroids.
• In the emergency department, a patient with DMD may look well on room air while hypercapnic. Check a blood gas and use his own NIV settings.

Australian practice

• Care runs through paediatric and adult neuromuscular clinics, with transition at 16 to 18.
• The NDIS funds equipment, home ventilation support, therapy and personal care.
• Duchenne isn't on the national newborn bloodspot panel. The Medicare-funded reproductive carrier screening item covers cystic fibrosis, spinal muscular atrophy and fragile X, not DMD.
• Families with a known variant can use prenatal diagnosis or preimplantation genetic testing.
• Muscular Dystrophy Australia and Save Our Sons provide family support.

Pitfalls

• Unexplained raised transaminases in a boy: check CK before a liver biopsy.
• Late diagnosis: a boy with delayed walking or speech and falls needs a CK.
• Negative maternal blood test doesn't remove recurrence risk (germline mosaicism).
• Becker with heart failure may walk normally. Ask about cramps, check CK and examine the calves in a young man with dilated cardiomyopathy.
• Carrier women need cardiac screening.
• Succinylcholine and volatile agents are contraindicated.
• Missing adrenal suppression in an unwell patient on long-term deflazacort.