Facioscapulohumeral muscular dystrophy (FSHD) is a genetic condition characterized by the progressive weakening and loss of muscle tissue. The name describes the areas of the body most commonly affected first: “facio” for the face, “scapulo” for the shoulder blades (scapulae), and “humeral” for the upper arm bone (humerus). The weakness often begins in these regions, leading to signs such as difficulty smiling, whistling, or raising the arms above the head. While it starts in these areas, the weakness can eventually spread to other parts of the body, including the abdominal muscles and lower legs.
Global Prevalence and Incidence
Determining the exact number of people affected by FSHD globally is complex. Prevalence, which measures the total number of individuals with the condition in a population, is frequently cited to be between 1 in 8,000 and 1 in 20,000 people. A notable study from the Netherlands suggests the prevalence may be as high as 12 per 100,000, or 1 in 8,333 individuals, which is higher than many previous estimates.
These numbers are estimates for several reasons. Many individuals with FSHD have very mild symptoms that may go unrecognized by the person and their doctors, leading to undiagnosed cases. FSHD can also be misdiagnosed as other neuromuscular conditions, which affects the accuracy of prevalence data. There are also individuals who carry the genetic marker for FSHD but are asymptomatic.
Distinct from prevalence, incidence measures the rate of new diagnoses in a population over a specific period. One Dutch study calculated an incidence rate of approximately 52 new cases each year in the Netherlands. The combination of underdiagnosis, misdiagnosis, and asymptomatic carriers means the true number of people with the genetic basis for FSHD is likely higher than current clinical data suggests.
Variations in Prevalence by FSHD Type
FSHD is categorized into two types, FSHD1 and FSHD2, which are clinically similar but have different underlying genetic causes. FSHD1 is by far the more common form, accounting for approximately 95% of all diagnosed cases. This type is genetically associated with a contraction of a specific DNA segment on chromosome 4.
FSHD2 is considerably rarer, making up the remaining 5% of cases. The genetic basis for FSHD2 is not linked to the same DNA contraction on chromosome 4. While the muscle weakness and progression can appear identical in both types, the distinction is made through genetic testing. The overwhelming majority of individuals seeking a diagnosis will be found to have the genetic markers for FSHD1.
Demographic Factors in FSHD
FSHD appears in populations worldwide, without a significant concentration in any particular geographic area or ethnic group. It affects both males and females in approximately equal numbers. However, some studies have noted that the condition may be more readily recognized in males, who might show symptoms earlier or more severely, which could influence diagnosis rates.
The age of onset for FSHD symptoms is highly variable. Most commonly, the initial signs of muscle weakness appear during the teenage years, before the age of 20 in about 90% of individuals. However, the onset can range from early childhood, known as infantile-onset FSHD, to as late as the 40s or 50s. The infantile-onset form is less common and often associated with more severe symptoms.
The variability in age of onset means a person can carry the genetic mutation for FSHD for many years before any noticeable weakness develops. This wide window for the first appearance of symptoms contributes to challenges in tracking the condition. A person might not seek a diagnosis until the weakness interferes with daily activities.
Role of Genetics in Prevalence
The prevalence of FSHD is directly tied to its genetic underpinnings. FSHD is most often an autosomal dominant disorder, meaning that inheriting just one copy of the altered gene from one parent is sufficient to cause the condition. A parent with FSHD has a 50% chance of passing the condition on to each of their children. This inheritance pattern explains why FSHD often runs in families.
While frequently inherited, FSHD can also appear in individuals with no family history. These cases result from a de novo, or new, mutation. This is a genetic alteration that occurs for the first time in a family member due to a change in an egg, sperm, or the fertilized egg. These spontaneous mutations are estimated to account for 10% to 30% of all FSHD1 cases.
The existence of de novo mutations is a factor in the overall prevalence of FSHD. It ensures that the condition continues to appear in the general population, even without a known family history. This genetic mechanism, combined with the high probability of transmission from an affected parent, maintains the presence of FSHD across diverse populations.