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 rapidly deteriorate over several months. Face
Weakness of the muscles of the face is the most distinguishing sign of FSHD. It is typically the earliest sign, although it is rarely the initial complaint. At least mild facial weakness can be found in 90% or more with FSHD. One of the most common deficits is inability to close the eyelids, which can result in sleeping with the eyelids open and dry eyes. The implicated muscle is the orbicularis oculi muscle. Another common deficit is inability to purse the lips, causing inability to pucker, whistle, or blow up a balloon. The implicated muscle is the orbicularis oris muscle. A third common deficit is inability raise the corners of the mouth, causing a "horizontal smile," which looks more like a grin. Responsible is the zygomaticus major muscle.Weakness of various facial muscles contributes to difficulty pronouncing the letters M, B, and P. Facial expressions can appear diminished, arrogant, grumpy, or fatigued. Muscles used for chewing and moving the eyes are not affected. Difficulty swallowing is not typical, although can occur in advanced cases. FSHD is generally progressive, but it is not established whether facial weakness is progressive or stable throughout life.
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.