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

Epidemiology

• It is 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, facioscapulohumeral muscular dystrophy (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.

Presentation

• It 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 the 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 the tibialis anterior muscle are 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

Differential diagnosis

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.

Investigations

• 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.

Management

• No definitive therapy is available.⁸ However, defining the genetic and molecular defects offers the potential for therapeutic intervention in the future.^9,10
• Operative scapular fixation appears to produce significant benefits, although 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.¹¹ 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.¹²
• The effectiveness of muscle pain to simple analgesia combined with anti-inflammatory agents is variable.⁴
• A reported association with heart rhythm disorders in some cases suggests that a cardiovascular review every few years (looking particularly for ECG abnormalities, hypertension and heart muscle thickening) is important.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 Research on involvement of the retina may give clues to the pathogenesis of the muscle dysfunction.¹³
• Driving licences, especially LGV or PCV, may be issued for a limited duration, with renewal subject to a satisfactory medical examination.⁴

Complications

• 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.¹⁴
• Hearing loss: sensorineural deafness, which may be unilateral or bilateral.¹⁴
• 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 central nervous system (CNS) abnormalities.¹⁵
• Hypertension.
• Cardiac complications: a single case report found ECG abnormalities, e.g. bundle branch block, as well as left ventricular myocardial thickening.^16,17

Prognosis

• Size of deletion affects disease severity and thus prognosis.¹⁸
• As many as 20% of patients eventually become wheelchair-bound;¹ however, 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 facioscapulohumeral muscular dystrophy (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

Prevention

• Molecular diagnostic techniques are available for prenatal diagnosis.¹⁵

Document references

1. Tawil R, Van Der Maarel SM; Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2006 Jul;34(1):1-15. [abstract]
2. Tawil R, Figlewicz DA, Griggs RC, et al; Facioscapulohumeral dystrophy: a distinct regional myopathy with a novel molecular pathogenesis. FSH Consortium. Ann Neurol. 1998 Mar;43(3):279-82. [abstract]
3. Kissel JT; Facioscapulohumeral dystrophy. Semin Neurol. 1999;19(1):35-43. [abstract]
4. Facioscapulohumeral muscular dystrophy, Muscular Dystrophy Campaign
5. Mummery CJ, Copeland SA, Rose MR; Scapular fixation in muscular dystrophy. Cochrane Database Syst Rev. 2003;(3):CD003278. [abstract]
6. Upadhyaya M, Cooper DN; Molecular diagnosis of facioscapulohumeral muscular dystrophy. Expert Rev Mol Diagn. 2002 Mar;2(2):160-71. [abstract]
7. Fitzsimons RB; Facioscapulohumeral muscular dystrophy. Curr Opin Neurol. 1999 Oct;12(5):501-11. [abstract]
8. Tawil R; Facioscapulohumeral muscular dystrophy. Neurotherapeutics. 2008 Oct;5(4):601-6. [abstract]
9. Sahenk Z, Mendell JR; The muscular dystrophies: distinct pathogenic mechanisms invite novel therapeutic Curr Rheumatol Rep. 2011 Jun;13(3):199-207. [abstract]
10. Padberg GW, van Engelen BG; Facioscapulohumeral muscular dystrophy. Curr Opin Neurol. 2009 Oct;22(5):539-42. [abstract]
11. Rose MR, Tawil R; Drug treatment for facioscapulohumeral muscular dystrophy. Cochrane Database Syst Rev. 2004;(2):CD002276. [abstract]
12. van der Kooi EL, Vogels OJ, van Asseldonk RJ, et al; Strength training and albuterol in facioscapulohumeral muscular dystrophy. Neurology. 2004 Aug 24;63(4):702-8. [abstract]
13. Fitzsimons RB; Retinal vascular disease and the pathogenesis of facioscapulohumeral muscular Neuromuscul Disord. 2011 Apr;21(4):263-71. Epub 2011 Mar 4. [abstract]
14. Fascioscapulohumeral muscular dystrophy 1A, Online Mendelian Inheritance in Man (OMIM)
15. Funakoshi M, Goto K, Arahata K; Epilepsy and mental retardation in a subset of early onset 4q35-facioscapulohumeral muscular dystrophy. Neurology. 1998 Jun;50(6):1791-4. [abstract]
16. Finsterer J, Stollberger C, Meng G; Cardiac involvement in facioscapulohumeral muscular dystrophy. Cardiology. 2005;103(2):81-3. Epub 2004 Nov 12. [abstract]
17. Hermans MC, Pinto YM, Merkies IS, et al; Hereditary muscular dystrophies and the heart. Neuromuscul Disord. 2010 Aug;20(8):479-92. [abstract]
18. Ricci E, Galluzzi G, Deidda G, et al; Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype. Ann Neurol. 1999 Jun;45(6):751-7. [abstract]

Internet and further reading

• Muscular Dystrophy Campaign