Facioscapulohumeral muscular dystrophy (FSHD) is a type of muscular dystrophy that preferentially weakens the skeletal muscles of the face (Latin: facio), those that position the scapula (scapulo), and those in the upper arm, overlying the humerus bone (humeral). Weakness of the scapular muscles causes an abnormally positioned scapula (winged scapula). Other areas of the body usually develop weakness as well, such as the abdomen and lower leg, causing foot drop. The two sides of the body are often affected unequally. Symptoms typically begin in early childhood and become noticeable in the teenage years, with 95% of affected individuals manifesting disease by age 20 years. Non-muscular manifestations of FSHD include hearing loss and blood vessel abnormalities in the back of the eye.
FSHD is caused by complex genetic changes involving the DUX4 gene. In those without FSHD, DUX4 is expressed (ie: turned on) in early human development and later repressed (ie: turned off) in mature tissues. In FSHD, DUX4 is inadequately turned off, which can be caused by several different mutations, the most common being deletion of DNA in the region surrounding DUX4. This mutation is termed "D4Z4 contraction" and defines FSHD type 1 (FSHD1), making up 95% of FSHD cases. FSHD due to other mutations is classified as FSHD type 2 (FSHD2). Regardless of which mutation is present, disease can only result if the individual has a 4qA allele, which is a common variation in the DNA next to DUX4. Up to 30% of FSHD cases are due to a new mutation, which then is able to be passed on to children. FSHD1 follows an autosomal dominant inheritance pattern, meaning each child of an affected individual has a 50% chance of also being affected. How DUX4 expression causes muscle damage is unclear. Expression of DUX4 gene produces DUX4 protein, whose function is to modulate hundreds of other genes, many of which are involved in muscle function. Diagnosis is by genetic testing.There is no known cure for FSHD. No pharmaceuticals have proven effective for altering the disease course. Symptoms can be addressed with physical therapy, bracing, and reconstructive surgery. Surgical fixation of the scapula to the thorax is effective in reducing shoulder symptoms in select cases. FSHD is the third most common genetic disease of skeletal muscle (Duchenne/Becker muscular dystrophy being first and myotonic dystrophy being second), affecting 1 in 8,333 to 1 in 15,000 people. Prognosis is extremely variable, with many never facing significant limitations, although up to 20% of affected individuals become severely disabled, requiring use of a wheel chair or mobility scooter. Life expectancy is generally not affected, except in rare cases of respiratory insufficiency.The first description of an individual with FSHD is an autopsy report from 1852, although FSHD wasn't distinguished as a disease until the 1870s and 1880s when French physicians Landouzy and Dejerine followed a family affected by it; thus FSHD is sometimes referred to as Landouzy–Dejerine muscular dystrophy. In 1991, the association of most cases with the tip of chromosome 4 was established, which was discovered to be due to D4Z4 contraction in 1993. DUX4 was discovered in 1999, but it wasn't until 2010 that the genetic mechanism causing its expression was elucidated. In 2012, the predominant mutation of FSHD2 was discovered. In 2014, researchers published the first proposed pathophysiology definition of the disease and four viable therapeutic targets for possible intervention points.