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Facioscapulohumeral muscular dystrophy (FSHD) is a rare familial disease with an estimated prevalence from 1/8,000 to 1/20,000. It is the third most common form of hereditary myopathy.

Onset occurs at any age. Disease progression is usually slow but some patients display periods of stability followed by periods of rapid deterioration. Early onset of FSHD is associated with more widespread muscle weakness. The initial manifestation is frequently facial weakness (difficulties whistling, smiling and closing the eyes) but the main complaint could be shoulder involvement (difficulties rising the arms, scapular winging and sloping shoulders). The disease progresses to include forearm weakness and wrist extension weakness. Abdominal and distal lower limb muscle, principally tibialis anterior, may also be affected early in the disease, while proximal lower leg muscles are affected later. Asymmetry of muscle involvement is frequently described. Significant clinical variability exists and atypical presentations have been reported. Sensory, cardiac and neurological signs may be present in rare cases.

Two genetic subtypes of FSHD have been identified: the classical form (FSHD1) which is associated with a pathogenic contraction of the D4Z4 repeat on a 4qA chromosome 4 and FSHD2 which is associated with mutations in SMCHD1 (18p11.32). In FSHD1, repeat contractions are associated with local hypomethylation and change in chromatin relaxation on chromosome 4 that increases the likelihood of toxic DUX4 (4q35.2) gene expression in skeletal muscle. In FSHD2, patients harboring mutation in SMCHD1 have a profound hypomethylation of chromosomes 4 and 10, allowing chromosome 4 to express the toxic DUX4 transcript.

Diagnosis of FSHD1 is achieved by identification of a D4Z4 pathogenic contraction (D4Z4 repeat number less than 10) on the permissive 4qA allele of chromosome 4. In this situation, the residual number of D4Z4 units inversely correlates with severity. SMCHD1 mutations should be screened when FSHD phenotype is not associated with the D4Z4 pathogenic contraction and in FSHD1 families diagnosed with between 7 to 10 D4Z4 repeats and a severe phenotype.

Atypical cases should be accurately studied to exclude a concomitant pathology. Differential diagnosis mainly includes limb-girdle muscular dystrophy but also neuromuscular diseases presenting with scapular winging such as glycogen storage disease due to acid maltase deficiency, late-onset endocrine myopathy, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, proximal neuropathies or neuronopathies.

Transmission is autosomal dominant in both FSHD1 and FSHD2. Penetrance in FSHD1 is incomplete and around 30% of carriers do not manifest the disease. Mosaicism may explain the occurrence of severe forms in children born to parents showing no signs of the disease. In some families, digenic inheritance of both FSHD1 and FSHD2 genetic conditions can modify the severity. Genetic counseling and prenatal diagnosis are therefore challenging.

Treatment is symptomatic, aiming towards prevention of joint stiffness and pain by passive mobilization and administration of antalgics. In severe cases, ventilator support may be required. Surgical treatment involves fixation of the scapula and may lead to an improvement in the range of motion of the arms.

Prognosis depends upon the extent of functional capacity loss. Life expectancy is not reduced unless respiratory functions are affected; however, this is a rare occurrence.