Diseases title

Facioscapulohumeral dystrophy )

Orpha Number: 269
Facioscapulohumeral muscular dystrophy, Facioscapulohumeral myopathy, FSH dystrophy, FSHD, Landouzy-Dejerine myopathy

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by progressive muscle weakness with focal involvement of the facial, shoulder and arm muscles.FSHD is a rare familial disease; prevalence is approximately 1:20,000, although this is likely to be an underestimate as the disease often remains undiagnosed. It is the 3rd most frequent form of myopathy.Onset occurs between three and 50 years of age and although disease progression is usually slow, some patients display periods of stability followed by periods of rapid deterioration. Early onset of the disease is associated with more widespread muscle weakness. The initial manifestation is facial weakness (difficulties whistling, smiling and closing the eyes) but it is often the shoulder involvement (difficulties lifting the arms, scapular winging and sloping shoulders) that causes patients to consult a physician. The disease progresses to include wrist extension weakness, involvement of the abdominal muscles, and weakness of the lower limbs principally affecting knee and foot extensor muscles. The pattern of clinical manifestations is variable and atypical presentations have been reported. Sensory, cardiac and neurological signs may be present in rare cases.FSHD is a genetic disease but the underlying molecular mechanism remains uncertain despite significant advances in the identification of several of the genes involved (FRG1, SLC25A4 and DUX4), leading to the suggestion that FSHD results from alterations in cell differentiation. The genetic anomaly has been localized to the long arm of chromosome 4 (4q35).Molecular diagnosis relies on the detection of a deletion within the D4Z4 repeat region at 4q35, with molecular test results being considered as positive if the number of repeats is lower than 10/11. However, this anomaly has not been detected in 5% of patients clinically diagnosed with FSHD. A correlation has been reported between the number of repeats and the severity of the disease. There are two variants (A and B) of chromosome 4 and FSHD only manifests in carriers of the 4qA variant.Transmission is autosomal dominant. Penetrance 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. Genetic counseling and prenatal diagnosis are therefore problematic.Treatment is symptomatic, aiming towards prevention of joint stiffness and pain by passive mobilization and administration of antalgics. In severe cases, ventilatory 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.The prognosis depends on the extent of loss of functional capacity but life expectancy is not reduced.
source: Orphanet