Duchenne & Becker Muscular Dystrophy (DMD/BMD)

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

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

Familial vs de novo: about one-third of cases arise de novo^[3], so a negative family history does not exclude a dystrophinopathy; the mother's carrier status, established by testing, sets the risk to her other children^[10]

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

Female carriers: estimated 7.3–16.7% lifetime risk of cardiomyopathy^[9], often later onset; higher figures in some series include milder imaging abnormalities. Baseline ECG and echo once carrier status is confirmed, and before pregnancy

Variant location and cardiac risk^[7]:

• Reported links between deletion location and cardiac risk are inconsistent across studies (exon 52, for example, appears in both higher- and lower-risk groups), so exon number alone should not be used to predict an individual's cardiac prognosis^[7]
• 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]

Cardiomyopathy: develops in almost all males with Duchenne by the late teens, and in most with Becker by adulthood; a minority of female carriers develop cardiomyopathy, often later in life.^[2][3]

Duchenne (severe):

• Onset <5 years with proximal weakness, Gowers' sign and calf pseudohypertrophy; loss of ambulation typically in the early teens, later with corticosteroids
• Cardiomyopathy universal by late teens, detectable on CMR before echocardiographic change
• Death typically 20s-30s (respiratory/cardiac failure)

Becker (milder):

• Later onset, slower progression
• Cardiac involvement variable - can be the predominant feature, sometimes presenting as DCM with little skeletal weakness
• Longer survival (40s-60s)

Female carriers: usually asymptomatic, but some develop skeletal weakness, myalgia or cardiomyopathy.^[2]

Cardiac features: Dilated cardiomyopathy (inferolateral wall first), resting sinus tachycardia, arrhythmias, conduction disease^[2][3]

CK: Markedly elevated (10-100x normal)

Genetic testing: DMD gene deletion/duplication analysis (e.g. MLPA) first, then sequencing

ECG: resting sinus tachycardia, tall R waves in V1 (R/S >1), deep narrow Q waves in the lateral and inferior leads, short PR.^[3]

Echocardiography: LV function and dimensions; image quality often falls with scoliosis and advancing disease, which is one reason CMR is preferred.^[2]

Cardiac MRI: the preferred modality where it can be performed without sedation.^[2][8]

• LGE before LVEF falls: fibrosis is detectable while LVEF is still normal
• Distribution: subepicardial LGE beginning in the basal inferolateral wall, spreading to the lateral and anterior walls and becoming mid-wall and more extensive with progression
• Prognosis: fibrosis burden predicts LVEF, rises with age and is lower with longer corticosteroid treatment^[8]
• Strain imaging can show reduced circumferential strain before LVEF declines

Surveillance:^[2]

• Duchenne: cardiac assessment at diagnosis and at least annually thereafter (2018 DMD Care Considerations; the earlier 2-yearly-until-age-10 interval is superseded), and more often once abnormalities appear
• Becker: at diagnosis and every 1–2 years
• Female carriers: baseline ECG and echo once carrier status is confirmed genetically, then usually every 3 years if reassuring^[9]
• Holter: once LV dysfunction is present, and for palpitations or syncope

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 foundational medical therapy:

• 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, consider early, once CMR shows myocardial fibrosis (LGE), even with preserved LVEF (specialist-led; the eplerenone trial enrolled boys with LGE and preserved EF):
  • 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 optimisation of foundational medical therapy (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: delandistrogene moxeparvovec (ELEVIDYS) is FDA-approved for ambulatory patients aged ≥4 years; since November 2025 it carries a boxed warning for acute serious liver injury and liver failure (deaths reported in non-ambulatory patients). Not routinely available in the UK; benefit is on skeletal muscle, and cardiac benefit is unproven

• 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

Burden: cardiac disease is a major cause of death, and its share has grown as respiratory support has improved survival.^[1][3]

Predictors of earlier LV dysfunction:^[7][8]

• Older age and greater LGE burden on CMR
• Variant location: some studies link particular deletions (e.g. exons 45–50, or those affecting the Dp116 region) with earlier or later cardiac involvement, but findings conflict and the evidence is low-certainty, so location should not by itself predict an individual's prognosis
• Shorter or absent corticosteroid treatment
• Genetic modifiers (e.g. LTBP4)

Arrhythmic risk: sustained ventricular arrhythmia and sudden death occur mainly in advanced cardiomyopathy; ICD decisions follow heart-failure criteria individualised to overall prognosis and goals of care (see Treatments).^[1][2]

Becker: cardiomyopathy can be disproportionate to skeletal weakness and is the main determinant of outcome in many patients, who may be transplant candidates.^[2]

Female carriers: cardiomyopathy in a minority, which can be severe; risk is not predicted by skeletal involvement.^[2]

mWHO class II–III or above: refer to a Pregnancy Heart Team before conception (see Pregnancy).

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 - estimated lifetime cardiomyopathy risk 7–17% (often late-onset)^[1][9]
• 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]