Facioscapulohumeral muscular dystrophy (FSHD) is a type of muscular dystrophy, a group of heritable diseases that cause degeneration of muscle and progressive weakness. Per the name, FSHD tends to sequentially weaken the muscles of the face, those that position the scapula, and those overlying the humerus bone of the upper arm. These areas can be spared, and muscles of other areas usually are affected, especially those of the chest, spine, abdomen, and shin. Almost any skeletal muscle can be affected in severe disease. Abnormally positioned, or winged, scapulas are common, as is the inability to lift the foot, known as foot drop. The two sides of the body are often affected unequally. Weakness typically manifests at ages 15 – 30 years. FSHD can also cause hearing loss and blood vessel abnormalities in the back of the eye. FSHD is caused by a genetic mutation leading to deregulation of the DUX4 gene. Normally, DUX4 is expressed (i.e., turned on) in cells of the ovary and in very early human development, becoming repressed (i.e., turned off) by the time an embryo is several days old. In FSHD, DUX4 is inadequately repressed, allowing sporadic expression throughout life. Deletion of DNA in the region surrounding DUX4 is the causative mutation in 95% of cases, termed "D4Z4 contraction" and defining FSHD type 1 (FSHD1). FSHD caused by other mutations is FSHD type 2 (FSHD2). For disease to develop, also required is a 4qA allele, which is a common variation in the DNA next to DUX4.
The chances of a D4Z4 contraction with a 4qA allele being passed on to a child is 50% (autosomal dominant); in 30% of cases, the mutation arose spontaneously. Mutations of FSHD cause inadequate DUX4 repression by unpacking the DNA around DUX4, making it accessible to be copied into messenger RNA (mRNA). The 4qA allele stabilizes this DUX4 mRNA, allowing it to be used for production of DUX4 protein. DUX4 protein is a modulator of hundreds of other genes, many of which are involved in muscle function. How this genetic modulation causes muscle damage remains unclear.Signs, symptoms, family history, and diagnostic tests can suggest FSHD; genetic testing can provide definitive diagnosis. No intervention has proven effective for slowing progression of weakness. Screening allows for early detection and intervention for various disease complications. Symptoms can be addressed with physical therapy, bracing, and reconstructive surgery such as surgical fixation of the scapula to the thorax. FSHD affects up to 1 in 8,333 people, putting it in the three most common muscular dystrophies with myotonic dystrophy and Duchenne muscular dystrophy. Prognosis is variable. Many are not significantly limited in daily activity, whereas a wheel chair or scooter is required in 20% of cases. Life expectancy is not affected, although death can rarely be attributed to respiratory insufficiency due to FSHD.FSHD was first distinguished as a disease in the 1870s and 1880s when French physicians Louis Théophile Joseph Landouzy and Joseph Jules Dejerine followed a family affected by it, thus the initial name Landouzy–Dejerine muscular dystrophy.