Facioscapulohumeral Muscular Dystrophy

Synonyms: Landouzy-Dejerine muscular dystrophy, Facioscapuloperoneal 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 stabiliser 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. Onset as early as infancy has been described but is rare. As many as one third of patients are asymptomatic.
• The degree of weakness or disability can vary widely between different affected members in a family, but can show even greater variation between people in different families.⁴
• Muscle pain is a frequent complaint, often in the early stages.
• Weakness may affect not only the facial muscles and shoulders and/or upper arms, but also the neck, forearms, wrists, fingers, hips, legs, ankles and the back muscles.⁴ Weakness may be asymmetrical.
• The disease tends to progress from the face downwards, with initial weakness starting in the muscles around the eye (orbicularis oculi), mouth and cheek. The extraocular and pharyngeal muscles are spared.
• Weakness of facial muscles can be suspected if the eyes remain slightly open when asleep, particularly in young children, or if the eyelids cannot be screwed tightly enough to bury the eyelashes.⁴
• Difficulties with pursing the lips to whistle, drinking through a straw or blowing up balloons are also suggestive.
• Winging of the scapula is the most characteristic sign. The scapula is more lateral than normal and moves upwards with shoulder abduction. There is selective weakness of the thoracoscapular muscles which may spare other shoulder muscles such as the deltoid muscle. This imbalance results in significant winging and loss of shoulder function.⁵
• The anterior axillary fold slopes upwards due to weakness of pectoralis major.
• Excessive aching around the shoulders, rounded shoulders and thin upper arms may be the first presenting signs or symptoms in teenagers and adults.⁴
• 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 also 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 localised to chromosome band 4q35, but the affected gene or genes are still unknown. Molecular diagnosis has 98% accuracy.⁶
• Electrodiagnostic studies may reveal myopathic potentials.
• Muscle biopsy: marked perivascular inflammation is often present in muscle biopsies.⁷ Muscle biopsy is important to rule out other possible differential diagnoses if genetic testing is negative.

• No definitive therapy is available.⁸
• Operative scapular fixation appears to produce significant benefits though these have to be balanced against postoperative immobilisation, need for physiotherapy and potential complications.⁵
• There is no evidence from randomised controlled trials to support any drug treatment.⁹ However, both strength training and albuterol (equivalent to salbutamol) appear safe with limited benefit on muscle strength and volume. The consequences of long term use are currently unknown.¹⁰
• The effectiveness of muscle pain to simple analgesia combined with anti-inflammatory agents is variable.⁴
• Because of recent reports suggesting an association with heart rhythm disorders in a few cases, affected people should see their GP or hospital doctor every few years for a heart check.⁴ A periodic eye check may also be appropriate.⁴
• If troublesome inflammation of the eyes occurs as a result of them remaining open at night, surgery to bring the eyelids closer can be offered if artificial tears alone are insufficient.⁴
• Driving licences, especially HGV or PSV, may be issued for a limited duration, with renewal subject to a satisfactory medical examination.⁴

• 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.¹¹
• Hearing loss: sensorineural deafness, which may be unilateral or bilateral.¹¹
• 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.¹²
• Hypertension
• Cardiac complications: a single case report found ECG abnormalities, e.g. bundle branch block, as well as left ventricular myocardial thickening.¹³

• Size of deletion affects disease severity and thus prognosis.¹⁴
• As many as 20% of patients eventually become wheelchair-bound,¹ but up to one third of patients remain unaware of symptoms at least into old age, but may have subtle detectable clinical signs. The majority of affected people come between these two extremes.⁴
• Males tend to develop symptoms earlier and more severely at a given age than females. By age 30 virtually all males with FSHD exhibit symptoms but only two-thirds of females do.⁴
• Life expectancy is not affected, except perhaps in the most severe cases with greatly impaired mobility and consequent greater risk of chest infections.⁴

• Molecular diagnostic techniques are available for prenatal diagnosis.¹²