Becker muscular dystrophy

Overview

•X-linked recessive neuromuscular disorder caused by mutations in the DMD gene (Xp21) - same gene as Duchenne muscular dystrophy (DMD)

•Prevalence: ~1 in 18,000 male births; 3-4x less common than DMD

•Reading frame rule distinguishes BMD from DMD: BMD = in-frame mutation → truncated but partially functional dystrophin produced; DMD = out-of-frame mutation → no functional dystrophin

•Most common mutations: large intragenic deletions (~65-70%), followed by duplications and point mutations

💡

The in-frame vs out-of-frame distinction is the key molecular explanation for why BMD patients remain ambulatory into adulthood while DMD patients typically do not.

Presentation

•Onset typically adolescence/early adulthood (range: childhood to 30s-40s); slower progression than DMD

•Proximal lower limb weakness - difficulty rising from floor/chair, climbing stairs, running; Gowers' sign present

•Calf pseudohypertrophy - fatty/fibrous infiltration, not true muscle hypertrophy

•Proximal upper limb weakness - appears later in course

•Myalgia and exercise intolerance - common in earlier stages

•Cardiac symptoms - palpitations, dyspnoea, reduced exercise tolerance; dilated cardiomyopathy may precede or dominate skeletal muscle weakness

•Respiratory symptoms - exertional breathlessness, sleep-disordered breathing; appear later

⚠️

BMD can present primarily as cardiomyopathy with only mild limb symptoms - failure to consider the neuromuscular cause delays diagnosis.

Investigations

🥇 First-line

•Serum creatine kinase (CK) - markedly elevated, typically 5-100x upper limit of normal; reflects sarcolemmal disruption

•ECG and echocardiogram - screens for dilated cardiomyopathy and arrhythmias; at diagnosis and repeated regularly

•Pulmonary function tests (spirometry, FVC) - baseline and annual monitoring; detects restrictive pattern

🏆 Gold standard

•Genetic testing via MLPA (deletion/duplication analysis) followed by sequencing - confirms diagnosis, determines in-frame vs out-of-frame status, enables cascade testing

🥈 Second-line

•Muscle biopsy - if genetic testing inconclusive; immunohistochemistry shows reduced/patchy dystrophin (cf. absent in DMD)

•EMG - myopathic pattern (short-duration, low-amplitude polyphasic potentials); not required when genetic testing confirms

Differential diagnosis

Key differentials for BMD

Condition	Key distinguishing features
DMD	Earlier onset (childhood), loss of ambulation by early teens, absent dystrophin on biopsy, out-of-frame mutation
Limb-girdle MD	Autosomal inheritance, normal dystrophin, sarcoglycan or other protein deficiency on biopsy
SMA	Lower motor neurone pattern, denervation on EMG (not myopathic), SMN1 mutation
Inflammatory myopathy	Subacute onset, raised inflammatory markers, skin features (dermatomyositis), responds to immunosuppression, inflammatory infiltrate on biopsy

Management

•No curative treatment; multidisciplinary care coordinated through specialist neuromuscular centre

•Cardiac: Annual ECG and echocardiogram; ramipril (ACE inhibitor) or carvedilol (beta-blocker) used prophylactically even before symptoms develop; ICD/CRT for severe/symptomatic cardiomyopathy

•Respiratory: Annual PFTs; non-invasive ventilation (BiPAP) for nocturnal hypoventilation or FVC below threshold; cough assist devices

•Physiotherapy: Moderate-intensity endurance exercise is safe and beneficial in BMD; orthotic devices (e.g. ankle-foot orthoses) to support gait

•Genetic counselling: Cascade carrier testing for female relatives; prenatal diagnosis and preimplantation genetic diagnosis available for carrier females

⚠️

Corticosteroids are NOT routinely recommended in BMD - the evidence base is much weaker than in DMD and the risk-benefit ratio does not support their routine use.

Complications and prognosis

•Dilated cardiomyopathy - most serious complication; affects majority, often presenting in 2nd-3rd decade; leads to heart failure and arrhythmias

•Arrhythmias - ventricular arrhythmias and conduction defects

•Respiratory insufficiency - restrictive defect; nocturnal hypoventilation precedes daytime failure

•Loss of ambulation - most remain ambulatory well into middle age; rate of progression highly variable

•Prognosis: Survival into 5th-6th decade not uncommon; cardiac complications (dilated cardiomyopathy and arrhythmias) are the leading cause of death - cardiac severity does not correlate with skeletal muscle severity

🎯

A patient with mild limb weakness can still die from heart failure - regular cardiac surveillance and early cardioprotective therapy are the single most impactful interventions in BMD.