Facioscapulohumeral dystrophy

Facioscapulohumeral dystrophy (FSHD), also known as facioscapulohumeral muscular dystrophy or Landouzy-Dejerine dystrophy, is a genetic muscle disorder characterized by progressive weakness and wasting of specific muscle groups, particularly those of the face (facio-), shoulder blades (scapulo-), and upper arms (humeral). It is one of the most common forms of muscular dystrophy. FSHD is caused by inappropriate expression of the DUX4 gene. In the most common form (FSHD1, approximately 95% of cases), this results from contraction of the D4Z4 repeat array on chromosome 4q35, while FSHD2 involves mutations in chromatin modifier genes such as SMCHD1 that lead to D4Z4 hypomethylation and DUX4 derepression. The disease typically presents with facial weakness (difficulty whistling, smiling, or closing the eyes completely), followed by weakness of the shoulder girdle muscles causing scapular winging — where the shoulder blades protrude prominently from the back. Upper arm weakness often follows, and the disease may progress to involve the abdominal muscles, hip girdle, and lower leg muscles (foot drop). The pattern of muscle involvement is often asymmetric, which is a distinguishing feature. Approximately 10-20% of affected individuals eventually require wheelchair use. Additional features can include high-frequency hearing loss, retinal vasculopathy (Coats disease), and in rare severe infantile-onset cases, intellectual disability and epilepsy. Currently, there is no cure or disease-modifying treatment for FSHD. Management is supportive and multidisciplinary, including physical therapy to maintain mobility, orthotic devices such as ankle-foot orthoses for foot drop, scapular fixation surgery in selected cases, and monitoring for extramuscular complications. Pain management is important, as chronic pain is a frequently underrecognized symptom. Several clinical trials are underway investigating therapies targeting DUX4 expression, including antisense oligonucleotides and other gene-silencing approaches, representing a promising area of active research.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Facioscapulohumeral dystrophy