Facioscapulohumeral muscular dystrophy
Overview
Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited muscular dystrophy, with autosomal dominant inheritance and a unique genetic mechanism: aberrant DUX4 expression due to D4Z4 repeat contraction on chromosome 4q35, requiring a permissive 4qA haplotype.
Presentation
Characteristic descending pattern: face and shoulder girdle first, then upper arms, then lower limbs (foot drop), then pelvic girdle in advanced disease.
•Facial weakness - lagophthalmos, inability to whistle, horizontal smile; often first symptom but unnoticed
•Scapular winging - most striking sign; inability to elevate arms above head
•'Popeye arm' - prominent deltoid with wasted biceps/triceps (deltoid relatively spared)
•Foot drop - tibialis anterior weakness; often asymmetric
•Positive Beevor sign - umbilicus moves upward on neck flexion/partial sit-up; lower abdominals weaker than upper; highly specific for FSHD
•Sensorineural hearing loss - high-frequency; extramuscular feature, commoner with early-onset disease
•Coats-like retinal vasculopathy - typically subclinical; risk of exudative detachment if untreated; associated with severe/infantile-onset FSHD
Investigations
🥇 First-line
•Serum CK - mildly elevated (2-5x ULN) or normal; markedly elevated CK should prompt reconsideration of diagnosis
•EMG - myopathic pattern; nerve conduction studies normal (confirms primary muscle disorder)
🏆 Gold standard
•Genetic testing - Southern blot to quantify D4Z4 repeats on chromosome 4q35 with 4qA haplotype confirmation; <10 D4Z4 units on permissive 4qA allele is diagnostic for FSHD1
🥈 Second-line
•Muscle MRI - fatty infiltration in periscapular, facial, and lower limb muscles; maps disease extent
•Muscle biopsy - non-specific myopathic/inflammatory changes; only if genetic result uncertain
Differential diagnosis
Key differentials
| Condition | Distinguishing features |
|---|---|
| Myotonic dystrophy type 1 | Myotonia, cataracts, frontal balding, cardiac conduction defects |
| LGMD | Proximal limb weakness without facial involvement; genetic panel distinguishes |
| Polymyositis/dermatomyositis | Markedly elevated CK, inflammatory infiltrate on biopsy, rash in dermatomyositis |
| SMA | EMG shows denervation (neurogenic), not myopathic pattern |
Management
No approved disease-modifying treatment. Management is MDT-based and function-focused.
🥇 First-line
•Physiotherapy and aerobic/strength exercise - slows functional decline; avoid eccentric overload exercise
•Ankle-foot orthoses (AFOs) - for foot drop to reduce falls
•Scapular fixation (scapulodesis) - surgical option in selected patients with significant winging; improves shoulder abduction
•Ophthalmology surveillance - laser photocoagulation if active Coats-like retinal disease
🥈 Second-line
•Pain management - NSAIDs, amitriptyline or pregabalin depending on pain character
•Respiratory support - spirometry in non-ambulant patients; non-invasive ventilation (NIV) if FVC falls significantly
Prognosis and complications
•Near-normal lifespan; majority remain ambulant; ~20% become wheelchair-dependent
•Prognosis inversely correlates with D4Z4 repeat length - shorter repeats (1-3 units) = earlier onset, more severe disease, more extramuscular features
•Infantile-onset FSHD - very short D4Z4 arrays; facial diplegia in infancy, severe winging, higher rate of hearing loss and Coats-like retinopathy
•Respiratory failure - uncommon; most patients do not develop clinically significant compromise