Fascioscapulohumeral Muscular Dystrophy

First described by Landouzy and Dejerine in 1884. Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly inherited disorder with an initially restricted pattern of weakness. Early involvement of the facial and scapular stabilizer muscles results in a distinctive clinical presentation. Progression is descending, with subsequent involvement of either the distal anterior leg or hip-girdle muscles.¹ FSHD is now known to be associated with deletions on chromosome 4q35.²

• One of the most common inherited neuromuscular disorders, with an estimated prevalence of 1:20,000.³
• The disease is autosomal dominant, although 10-30% of cases appear to arise from a de novo mutation.³
• In the vast majority of cases, FSHD results from a heterozygous partial deletion of a critical number of repetitive elements (D4Z4) on chromosome 4q35. No causal gene has yet been identified.¹
• Frequency is higher in males but asymptomatic cases are more common in females.

• Usually presents in the first and third decades and 90% of patients show clinical features before age 20 years. Onset as early as infancy has been described but is rare. As many as one third of patients are asymptomatic.
• The disease tends to progress from the face downwards, with initial weakness starting in the muscles of the eye (orbicularis oculi), mouth and cheek.
• Patients may have difficulty with whistling or drinking through a straw.
• Weakness may be asymmetrical.
• Extraocular and pharyngeal muscles are spared.
• Shoulder weakness is also a common presenting symptom.
• Winging of the scapula is the most characteristic sign. The scapula is more lateral than normal and moves upwards with shoulder abduction.
• The deltoid muscle is usually is spared and weakness of shoulder abduction is predominantly due to weak scapula fixation.
• The anterior axillary fold slopes upwards. This is due to weakness of pectoralis major.
• Weakness of foot dorsiflexion and foot-drop due to weakness of tibialis anterior muscle is very characteristic. The posterior leg muscles are spared.
• The pelvic girdle muscles are often spared.
• Associated non-skeletal muscle manifestations include high-frequency hearing loss as well as retinal telangiectasias, both of which are rarely symptomatic.¹

Asymmetry and selective muscle group involvement help to distinguish this condition from other muscular dystrophies. Extraocular muscles, bulbar muscles, deltoids and respiratory muscles are usually spared.

• Amyotrophic lateral sclerosis
• Chronic inflammatory demyelinating polyradiculoneuropathy
• Congenital muscular dystrophies
• Congenital myopathies
• Dermatomyositis/polymyositis
• Diabetic neuropathy
• Endocrine myopathies
• Inherited metabolic disorders
• Limb-girdle muscular dystrophy
• Scapuloperoneal dystrophy

• Elevated serum creatine kinase.
• Imaging studies show a selective destructive process involving the anterior compartment muscles of the leg.
• Gene testing: one of the genes has been localized to chromosome band 4q35, but the affected gene or genes are still unknown. Molecular diagnosis has 98% accuracy.⁴
• Electrodiagnostic studies may reveal myopathic potentials.
• Muscle biopsy: marked perivascular inflammation is often present in muscle biopsies.⁵ Muscle biopsy is important to rule out other possible differential diagnoses if genetic testing is negative.

• No definitive therapy is available.
• Operative scapular fixation appears to produce significant benefits though these have to be balanced against postoperative immobilisation, need for physiotherapy and potential complications.⁶
• There is no evidence from randomised controlled trials to support any drug treatment.⁷ However, both strength training and albuterol appear safe with limited benefit on muscle strength and volume. The consequences of long term use are currently unknown.⁸

• Coats syndrome: retinal vasculopathy with telangiectasia, exudation and retinal detachment. Seen in 49-75% of affected individuals. If detected early, retinal photocoagulation may prevent serious consequences.⁹
• Hearing loss: Sensorineural deafness, which may be unilateral or bilateral.⁹
• Mental impairment and epilepsy: either or both may be seen in those patients with early onset. Patients with a large gene deletion tend to have a higher chance of showing CNS abnormalities.¹⁰
• Hypertension.
• Cardiac complications: Cardiac involvement may manifest not only as ECG abnormalities, e.g. bundle branch block, but also as left ventricular myocardial thickening.¹¹

• Size of deletion affects disease severity and thus prognosis.¹²
• Although FSHD is considered a relatively benign dystrophy, as many as 20% of patients eventually become wheelchair-bound.¹
• Ventilatory impairment is seen in fewer than 10% of patients.
• Life expectancy is normal in most patients.

Molecular diagnostic techniques are available for prenatal diagnosis.¹⁰