Facioscapulohumeral

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary neuromuscular disorder characterized by progressive weakness of facial muscles, scapular winging, and weakness of the proximal shoulder girdle and upper arms. Onset most often occurs in adolescence or early adulthood, and the course is variable, typically slow to moderate in progression.

There are two main genetic forms. FSHD1 results from contraction of the D4Z4 macrosatellite repeat on chromosome 4q35 to 1–10 repeats, and disease expression requires a permissive 4qA subtelomeric haplotype with a functional DUX4 polyadenylation signal. FSHD2 is caused by mutations in SMCHD1 that lead to hypomethylation of the D4Z4 region; disease can occur with a normal repeat length if the 4qA haplotype is present. In both forms, abnormal expression of the DUX4 gene in skeletal muscle is thought to drive muscle degeneration.

Clinical features typically include facial weakness (e.g., difficulty closing the eyes or pursing the lips), scapular winging, and progressive proximal weakness of the shoulders and arms, which can impair overhead activities. The phenotype is highly variable, and some individuals experience additional distal involvement or mild symptoms.

Diagnosis relies on genetic testing: reduced D4Z4 repeat length on 4q35 with a 4qA haplotype for FSHD1, and SMCHD1 testing for suspected FSHD2. Muscle biopsy and imaging may support evaluation but are not always necessary. Management is multidisciplinary and supportive, emphasizing maintainting range of motion and strength through physical therapy, assistive devices, orthopedic procedures when needed, and genetic counseling. Prognosis varies, but many individuals retain functional independence into adulthood. FSHD is inherited in an autosomal dominant pattern with high but variable penetrance.