Facioscapulohumeral Muscular Dystrophy

Abstract

Facioscapulohumeral muscular dystrophy is the most prevalent dominantly-inherited muscular dystrophy after myotonic dystrophy. The most distinctive clinical features are the characteristic facial weakness and scapular winging. Whereas the pattern of muscle involvement is similar in many patients, the age at onset, rate of progression and overall disease severity is very variable. Symptomatic extra-muscular manifestations such as retinal exudative retinopathy or hearing loss are rare and limited to severely affected, infantile onset disease. The genetic cause of this dystrophy in the majority of cases is the epigenetic activation of the DUX4 gene, a gene normally only expressed in early development but not in somatic cells. The ectopic expression of DUX4, a transcription factor, in myofibers results in the activation of a number of deleterious mechanisms resulting in muscle weakness. No approved targeted treatment exists for facioscapulohumeral muscular dystrophy. However, the underlying disease mechanism is amenable to treatment using targeted antisense oligonucleotides, an approach being actively pursued by several pharmaceutical companies.