What is FSHD

FSHD (Facioscapulohumeral muscular dystrophy) gets its name because of the type of progressive loss of skeletal muscle, where weakness is usually noticeable across facial (facio), back (scapula) and upper arm (humeral) muscles.

FSHD is the most prevalent of the nine primary types of muscular dystrophy affecting adults and children. It is a genetic disorder. Previously, studies estimated the prevalence at around 1 in 20,000 people, but a 2014 Dutch study reported a much higher prevalence of 1 in 8,333.

FSHD is worldwide in distribution, affects both sexes equally, and has no particular racial, geographic, or ethnic distribution.

The age of onset can range from infancy to adulthood. The eventual extent and degree of muscle loss is also highly variable. The prognosis for FSHD includes a loss of muscular strength that limits both personal and occupational activities, and approximately one-quarter of patients over 50 years of age require the use of a wheelchair.

Estimated to affect about 870,000 individuals worldwide, the actual number of individuals with FSHD could be significantly higher due to undiagnosed cases.

Although the progression of FSHD is quite variable, it is usually relatively slow, with most patients developing noticeable muscle weakness by the age of 20 in males, and by the age of 30 in females.

Thirty percent of new FSHD patients have no prior family history of the disease and are a result of congenital spontaneous genetic mutation. Once present, however, FSHD is genetically transmissible in an autosomal dominant fashion. This means that an affected parent has a 50 percent chance of passing the genetic defect on to each child.

Approximately 95 percent of FSHD cases are known as Type 1 (chromosome 4-linked FSHD; also called FSHD1 or Type 1A). FSHD1 is linked to deletions of D4Z4 units on chromosome 4.

The remaining 5 percent of FSHD cases have normal-length D4Z4 regions on chromosome 4 and are called Type 2 (FSHD2, also called Type 1B). A majority of FSHD2 has now been linked to mutations on a gene called SMCHD1, on chromosome 18. There are still ~2% of FSHD cases of unknown genetic cause.

Both FSHD1 and FSHD2 have similar symptoms. Even though the genetic causes are distinct, both types appear to have the same end result at the molecular level: they cause the D4Z4 region to have less-than-normal levels of methylation, which allows the DUX4 gene to get expressed. So in spite of different genetics, FSHD1 and FSHD2 appear to be the same disease.

Infantile FSHD (IFSHD) is characterized by onset in early childhood, before age 5. There is no generally accepted estimate of its incidence, but it is rare.

This New York Times article describes the landmark discovery of the genetic mechanism of FSHD: Reanimated ‘Junk’ DNA Is Found to Cause Disease.