FSHD

What is Facioscapulohumeral Dystrophy (FSHD)?
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FSHD is an autosomal dominant disease associated with inappropriate expression of the double homeobox protein 4 gene (DUX4) on chromosome 4, in the 4q35 region in skeletal muscle. The segment is not part of any particular gene, but with mutations, overexpression interferes with the correct processing of genetic material, leading to DUX4 protein which is toxic to muscle fibers.

Characteristics of FSHD:

• Third most common form of muscular dystrophy
• Progressive weakness and atrophy of facial, periscapular, and humeral muscles
• Onset typically in second decade of life
• Variable pathologic findings, ranging from nonspecific myopathic changes to fibrosis and fatty infiltration
• May involve muscles of respiration and eyes; no cardiac involvement

FSHD typically first presents in the facial muscles and scapular region, creating the classic scapular winging. Proximal weakness of the pectoral and abductor muscles limit upper extremity function at the shoulder girdle. Biceps and triceps muscles are commonly involved early, and tibialis anterior involvement often results in a foot drop. Eventually, muscles including the forearm flexors and extensors and knee flexors and extensors may become weak. Weakness and wasting progress with approximately 20% of patients becoming wheelchair bound by age 50.

The classic onset of FSHD is in the teenage and early adult years, but it can present in infancy, which tends to be a more aggressive course. The disease is slowly progressive and typically asymmetric. Up to one-third of non-ambulatory patients have respiratory involvement. Cardiac involvement is not associated with FSHD. Retinal vasculopathy is common, as is hearing loss.  

Evaluation is often initiated based upon physical signs associated with disease expression. Diagnosis can be confused with LGMD, Pompe disease, polymyositis and other muscular dystrophies. Definitive diagnosis can be confirmed by genetic testing.

Currently there are no drugs or biological products specifically indicated for use in FSHD, with no disease-modifying treatments available. Symptomatic management is recommended with screening and monitoring for known associated conditions, including vision and pulmonary function. Therapeutic development is focusing on specific therapies directed at DUX4 toxicity.