Facioscapulohumeral dystrophy

Facioscapulohumeral dystrophy (FSHD) is one of the most common inherited neuromuscular disorders, with an estimated prevalence of 1 : 20,000. The disease is autosomal dominant, although 10-30% of cases appear to arise from a de novo mutation. The disease presents with a characteristic pattern of weakness which affects predominantly the face and scapular stabilizer muscles. Symptoms usually begin in childhood, and > 90% of patients have some evidence of disease on examination by age 20. The course of the disease is slowly progressive, although many patients have long periods of relatively stable function. The cause of the disease is unknown, but recent studies have demonstrated genetic linkage to a locus on the long arm of chromosome 4 (4q35). Probes from this region detect an EcoR1 "short fragment" that cosegregates with FSHD in familiar cases and appears de novo in most sporadic cases. Although the size of the small fragment correlates inversely with disease severity, the exact relationship of the fragment to the pathogenesis of the clinical disease is unclear, and a specific FSHD gene has not been identified. FSHD is currently untreatable. Few therapeutic trials of the disorder, have been conducted, largely because little is known about the underlying mechanisms of muscle injury in this disease.