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. Their work is predated by descriptions of probable individual FSHD cases. The significance of D4Z4 contraction on chromosome 4 was established in the 1990s. The DUX4 gene was discovered in 1999, found to be expressed and toxic in 2007, and in 2010 the genetic mechanism causing its expression was elucidated. In 2012, the gene most frequently mutated in FSHD2 was identified. In 2019, the first drug designed to counteract DUX4 expression entered clinical trials. Signs and symptoms Classically, weakness develops in the face, then the shoulder girdle, then the upper arm. These muscles can be spared and other muscles usually are affected. The order of muscle involvement can cause the appearance of weakness "descending" from the face to the legs. Distribution and degree of muscle weakness is extremely variable, even between identical twins. Musculoskeletal pain is very common, most often described in the neck, shoulders, lower back, and the back of the knee. Fatigue is also common. Muscle weakness usually becomes noticeable on one side of the body before the other, a hallmark of the disease. The right shoulder and arm muscles are more often affected than the left upper extremity muscles, independent of handedness. Otherwise, neither side of the body has been found to be at more risk. Classically, symptoms appear in those 15 – 30 years of age, although infantile onset, adult onset, and absence of symptoms despite having the causal genetics also occur. FSHD1 with a very large D4Z4 deletion (EcoRI 10-11 kb) is more strongly associated with infantile onset and severe weakness. On average, FSHD2 presents 10 year later than FSHD1. Otherwise, FSHD1 and FSHD2 are indistinguishable on the basis of weakness. Disease progression is slow, and long static phases, in which no progression is apparent, is not uncommon. Less commonly, individual muscles