Women are less likely to be symptomatic, and if symptomatic have less severe manifestations.Remaining variations in disease course are attributed to unknown environmental factors. A single study found that disease course is not worsened by tobacco smoking or alcohol consumption, common risk factors for other diseases. Pregnancy
Pregnancy outcomes are overall good in mothers with FSHD; there is no difference in rate of preterm labor, rate of miscarriage, and infant outcomes. However, weakness can increase the need for assisted delivery.A single review found that weakness worsens, without recovery, in 12% of mothers with FSHD during pregnancy, although this might be due to weight gain or deconditioning. Epidemiology
The prevalence of FSHD ranges from 1 in 8,333 to 1 in 15,000. The Netherlands reports a prevalence of 1 in 8,333, after accounting for the undiagnosed. The prevalence in the United States is commonly quoted as 1 in 15,000.After genetic testing became possible in 1992, average prevalence was found to be around 1 in 20,000, a large increase compared to before 1992. However, 1 in 20,000 is likely an underestimation, since many with FSHD have mild symptoms and are never diagnosed, or they are siblings of affected individuals and never seek definitive diagnosis.Race and ethnicity have not been shown to affect FSHD incidence or severity.Although the inheritance of FSHD shows no predilection for biological sex, the disease manifests less often in women, and even when it manifests in women, they on average are less severely affected than affected males.
Restriction fragment length polymorphism (RFLP) analysis was the first genetic test developed and is still used as of 2020, although it is being phased out by newer methods. It involves dicing the DNA with restriction enzymes and sorting the resulting restriction fragments by size using southern blot. The restriction enzymes EcoRI and BlnI are commonly used. EcoRI isolates the 4q and 10q repeat arrays, and BlnI dices the 10q sequence into small pieces, allowing 4q to be distinguished. The EcoRI restriction fragment is composed of three parts: 1) 5.7 kb proximal part, 2) the central, variable size D4Z4 repeat array, and 3) the distal part, usually 1.25 kb. The proximal portion has a sequence of DNA stainable by the probe p13E-11, which is commonly used to visualize the EcoRI fragment during southern blot. The name "p13E-11" reflects that it is a subclone of a DNA sequence designated as cosmid 13E during the human genome project. Considering that each D4Z4 repeat is 3.3 kb, and the EcoRI fragment contains 6.9 kb of DNA that is not part of the D4Z4 repeat array, the number of D4Z4 units can be calculated. D4Z4 repeats = (EcoRI length - 6.9) / 3.3Sometimes 4q or 10q will have a combination of D4Z4 and D4Z4-like repeats due to DNA exchange between 4q and 10q, which can yield erroneous results, requiring more detailed workup. Sometimes D4Z4 repeat array deletions can include the p13E-11 binding site, warranting use of alternate probes.