Facioscapulohumeral Muscular Dystrophy (FSHD)

Causes/Inheritance

Causes

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited neuromuscular disorder that causes weakness most prominently in the muscles of the face, shoulder blades, and upper arms. Over time, other muscles may also be involved.

FSHD is caused by changes in a specific region of chromosome 4 (4q35) that affect how a gene called DUX4 is regulated. DUX4 is normally active only during early development and is turned off in healthy adult muscle. In FSHD, this gene becomes inappropriately turned on in muscle cells, where it is toxic and contributes to muscle damage.

There are two main types of FSHD:

FSHD1 (about 95% of cases) is caused by a shortening (contraction) of a repeated DNA region called D4Z4 on chromosome 4. This change relaxes the structure of the DNA, allowing DUX4 to be turned on in muscle cells. In general, smaller repeat sizes are associated with earlier onset and more severe disease, although symptoms can vary widely.

FSHD2 (about 5% of cases) occurs when the D4Z4 region is normal in size, but other genetic changes, most commonly in the SMCHD1 gene on chromosome 18, alter how this region is controlled. This also leads to inappropriate activation of DUX4.

Inheritance

FSHD1 is inherited in an autosomal dominant pattern, meaning a person needs only one altered copy of the gene region to develop the condition. In some cases, the genetic change occurs spontaneously (de novo) in individuals with no family history.

FSHD2 has a complex inheritance pattern and may involve multiple genetic factors. Many cases of FSHD2 occur without a known family history.

A genetic counselor can help in understanding a family’s specific situation and planning for the future.

Additional reading

• Hamel J, Tawil R. Facioscapulohumeral Muscular Dystrophy: Update on Pathogenesis and Future Treatments. Neurotherapeutics. 2018 Oct;15(4):863-871. doi: 10.1007/s13311-018-00675-3.

Last reviewed April 2026.