Facioscapulohumeral muscular dystrophy (FSHD) is a progressive genetic disorder affecting the muscles of the face, shoulders, and upper arms, which later spreads to other muscle groups. As one of the more common inherited muscle disorders, its prevalence provides an important measure of the disease’s impact on public health. Determining the exact frequency of FSHD within the general population is complex, resulting in a range of reported figures across different studies and geographic regions. This variability stems from the unique genetic mechanisms and the wide spectrum of clinical presentation.
Global and Regional Frequency of FSHD
The estimated global prevalence for facioscapulohumeral muscular dystrophy generally falls within a range of one in 8,000 to one in 20,000 individuals worldwide. This means the condition affects between four and 12 people per 100,000 of the population. FSHD is recognized as the third most frequent hereditary muscular dystrophy, following Duchenne and myotonic muscular dystrophy.
The reported frequency of FSHD varies notably depending on the location and the methods used for case counting. Earlier reports in Europe suggested a prevalence of one in 17,000, while a study in central Italy found a rate closer to 4.6 per 100,000 people.
A significant study conducted in the Netherlands estimated the prevalence at 12 per 100,000, equivalent to approximately one in 8,333 individuals. This higher figure suggests that previous estimates may have substantially underestimated the true number of affected individuals. This Dutch study used a sophisticated “capture-recapture” methodology, which accounts for cases that might otherwise be missed by traditional registry-based surveillance. Estimates for the United States suggest a population of 16,000 to 38,000 patients.
Challenges in Accurate Case Counting
The wide range in prevalence figures is primarily due to the inherent complexity of identifying all affected individuals in a population. A significant factor is the highly variable severity of the disease, which ranges from severe childhood-onset cases to very mild or even asymptomatic adult carriers. Individuals with extremely mild symptoms may never seek a formal diagnosis, leading to an underestimation of total prevalence.
The difference between incidence—the rate of new cases—and prevalence—the total number of cases at a given time—also complicates accurate counting. FSHD does not typically shorten life expectancy, meaning that prevalent cases accumulate over many decades, making diagnosis lag a persistent issue. The average age of diagnosis for registered patients in one study was 42 years, indicating a substantial delay between symptom onset and formal identification.
Prevalence is often underestimated because a proportion of people who carry the genetic mutation are considered non-penetrant, meaning they never develop noticeable symptoms. The penetrance of the disease is also sex-dependent, with males generally showing a higher likelihood of developing symptoms at an earlier age than females. Relying solely on clinically diagnosed cases will always result in a lower-than-actual prevalence rate.
Distribution by Genetic Type and Demographics
Facioscapulohumeral muscular dystrophy is classified into two main genetic subtypes, FSHD1 and FSHD2. FSHD1 is the most common form, accounting for approximately 90 to 95 percent of all cases. This subtype is caused by a contraction of the D4Z4 repeat array on chromosome 4.
The remaining cases, approximately five to ten percent, are attributed to FSHD2, which results from a digenic mechanism involving a mutation in a chromatin modifier gene, most often SMCHD1. While the clinical presentation of the two subtypes is often indistinguishable, the genetic ratio significantly influences overall prevalence calculations.
The disease affects males and females across all racial and ethnic groups, with no specific population showing a predisposition. There is a distinction in the age of onset between the sexes, with men often presenting with outward symptoms earlier than women. The penetrance, or the probability of developing symptoms if the mutation is inherited, is also higher in males.