Duchenne & Becker Muscular Dystrophy

Monogenic (Mendelian): 100%, DMD-gene mutations affecting dystrophin (~1/3 de novo)^[3]

Inheritance: X-linked recessive (DMD gene, dystrophin)

Males: Affected (hemizygous); out-of-frame mutations → absent dystrophin (DMD); in-frame mutations → truncated, partially functional dystrophin (BMD, milder)

Female carriers: ~10–30% develop dilated cardiomyopathy (often later onset, age 30–50); baseline echocardiogram essential before pregnancy

Mutation-specific cardiac risk (Landfeldt et al 2024^[7]):

• Mutations in exons 51 and 52 are significantly associated with lower risk of cardiomyopathy
• Deletions treatable by exon 53 skipping and mutations in the Dp116 coding region are associated with improved LVEF and prolonged cardiac dysfunction-free survival
• Mutations in exons 45–50 and 52 associated with earlier left ventricular systolic dysfunction
• Genetic modifiers (LTBP4, ACTN3) also influence LVEF and cardiomyopathy risk

Duchenne: 1 in 3,500 male births (most common muscular dystrophy)^[3]

Becker: 1 in 18,000 male births^[3]

Duchenne (severe):

• Onset <5 years, wheelchair-bound by teens
• Cardiomyopathy universal by late teens
• Death typically 20s-30s (respiratory/cardiac failure)

Becker (milder):

• Later onset, slower progression
• Cardiac involvement variable - can be predominant feature
• Longer survival (40s-60s)

Cardiac features: Dilated cardiomyopathy (posterolateral wall first), arrhythmias, conduction disease

CK: Markedly elevated (10-100x normal)

Genetic testing: DMD gene deletion/duplication analysis, then sequencing

Cardiac MRI: Early detection of fibrosis (inferolateral wall) - before EF drops

ECG: Tall R in V1, deep Q laterally, short PR

1. General measures:

• Corticosteroids, deflazacort (preferred in UK; high-quality evidence for preserved LVEF and improved fractional shortening vs no corticosteroid^[7]); prednisone/prednisolone also associated with improved EF and lower risk of cardiomyopathy (low-quality evidence^[7])
• Physiotherapy; respiratory support as disease advances
• Genetic counselling and family cascade testing, see the Genetic Testing page

2. Medical therapy, cardiac, early and proactive GDMT:

• BSH/ESC consensus^[1][2]: ACE inhibitor, beta-blocker and MRA use below have direct dystrophinopathy-specific trial evidence (cited per drug); SGLT2 inhibitor use and some device thresholds are extrapolated from general heart-failure evidence, as dystrophinopathy-specific evidence for those is more limited (flagged below)
• Doses and thresholds should be individualized for age, body size, respiratory function and overall prognosis rather than applied as a rigid step-ladder for every patient
• ACE inhibitor, START EARLY (even if LVEF normal):
  • Perindopril (most evidence in DMD, PERDU trial^[4]):
    • Start from age 10 (DMD) or at diagnosis (BMD) regardless of LVEF^[4]
    • 2 mg once daily → target 4–8 mg once daily
    • RCT evidence: proportion with LVEF <45% at 60 months was 4% (treated) vs 28% (untreated), p=0.02^[7]
    • Also associated with slower myocardial fibrosis progression on CMR (moderate-quality evidence^[7])
  • Ramipril (alternative): 1.25–2.5 mg once daily → target 5–10 mg once daily^[6]
  • Switch to ARNI (sacubitril/valsartan 24/26 → 97/103 mg twice daily) if LVEF drops to ≤40%; this recommendation is extrapolated from general heart-failure evidence, dystrophinopathy-specific ARNI trial data are limited^[5]
• Beta-blocker, add once LVEF <55% or LV dilatation:
  • Carvedilol (preferred, additional antioxidant properties):
    • Start 3.125 mg twice daily → target 12.5–25 mg twice daily (uptitrate every 2 weeks)
  • Bisoprolol (alternative): 1.25 mg once daily → 5–10 mg once daily
  • Caution: respiratory muscle weakness, monitor SpO₂; avoid in significant respiratory compromise
• MRA, add if LVEF <45%:
  • Eplerenone: 25 mg once daily → 50 mg once daily (preferred over spironolactone in males, avoids gynaecomastia)
    • RCT evidence: eplerenone significantly reduced LVEF decline at 12 months (median change −1.8% treated vs −3.7% untreated, p=0.032) and attenuated LVESV progression^[7]
  • Monitor K⁺ and eGFR; hold if K⁺ >5.5 mmol/L
• SGLT2 inhibitor, consider if LVEF <40%:
  • Dapagliflozin 10 mg or empagliflozin 10 mg once daily
  • Limited DMD-specific data but consistent HF benefit in HFrEF (DAPA-HF, EMPEROR-Reduced)

3. Device therapy:

• These thresholds are extrapolated from standard HFrEF device criteria (dystrophinopathy-specific device-trial evidence is limited); device decisions should individualise for skeletal-muscle/respiratory prognosis, functional status and patient/family goals of care
• ICD if LVEF ≤35% after GDMT optimisation (standard HFrEF criteria, extrapolated; consider life expectancy and functional status)
• CRT-D if LVEF ≤35% + LBBB + QRS ≥130 ms (standard HFrEF criteria, extrapolated)
• Wearable cardioverter defibrillator (LifeVest) may bridge to ICD in acute LV dysfunction

4. Advanced heart failure and/or transplant referral:

• Standard advanced-heart-failure/transplant pathways may apply for refractory cardiomyopathy in carefully selected patients, though respiratory and skeletal-muscle involvement often limit candidacy and require joint decision-making with respiratory medicine and the neuromuscular team

5. Emerging therapies:

• Exon-skipping therapy (eteplirsen, golodirsen), limited to specific mutation types; modest dystrophin restoration
• Microdystrophin gene therapy, phase 1/2 trials showing promising results

• Progressive dilated cardiomyopathy: leading to heart failure, now a leading cause of death as respiratory care has improved, and can be severe and disproportionate in Becker (transplant candidacy)^[1]
• Arrhythmia and conduction disease: atrial and ventricular
• Anaesthetic hazard: volatile agents and suxamethonium can trigger rhabdomyolysis and hyperkalaemia (TIVA preferred), which is not classic malignant hyperthermia
• Female carriers: carry an under-recognised DCM risk warranting surveillance

Cardiac disease major cause of death (especially as respiratory support improves survival)

Based on the AHA scientific statement on neuromuscular cardiac care^[2].

Advanced / complicated = established cardiomyopathy (LVEF decline or LGE), arrhythmia, or symptomatic heart failure.

Genotype-positive / phenotype-negative (G+/P−) = a confirmed pathogenic-variant carrier with no overt disease expression yet.

Disclaimer: This table is general guidance based on published guidelines and does not replace clinical judgement. The responsible clinician is accountable for determining the appropriate, individualised follow-up plan for each patient.

• 50% risk to male offspring - discuss prenatal testing/PGD
• Screen female carriers, with lifelong periodic cardiac surveillance even if asymptomatic - 20-30% develop cardiomyopathy (often late-onset)^[1]
• Start ACEi/ARB early - delays cardiomyopathy even with normal EF^[1]
• Multidisciplinary care essential (neurology, respiratory, cardiology)
• PRECONCEPTION cardiac screening ESSENTIAL for all female carriers - pregnancy may unmask subclinical dysfunction
• Pregnancy is generally lower risk with normal LVEF, and higher risk if LVEF <40%; assess individually rather than assigning a fixed mWHO class
• Annual cardiac screening (echo, ECG, Holter) from diagnosis in affected males; female carriers use a different, less frequent schedule (see Follow-up)^[1]