Facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic condition which causes progressive muscle weakening, specifically muscles located in the upper torso area including muscles in the arms, face, and shoulders, or sometimes the legs.¹ 

Facioscapulohumeral is a latin term that stands for:

• Facio - face
• Scapula - shoulder blade
• Humeral - upper arms 

FSHD is a type of muscular dystrophy (MD), a group of genetic conditions characterised by progressive muscle weakness. FSHD is distinguished from other forms of MD by its primary focus impacting muscles located in the face, shoulder blades, and upper arms. While FSHD has a more targeted muscle pattern, it is important to note that different types of MS can affect various muscles throughout the body. There are over 30 types of MD with each type having its own characteristic in terms of muscles involved, assisting healthcare professionals to differentiate these conditions. FSHD is a common hereditary form of MD associated with asymmetry of the lower facial muscles, shoulder blade, and limb weakness.¹ Those diagnosed with FSHD often report that facial muscle weakness was the initial symptom they experienced.² 

Aetiology

FSHD can be inherited from either parent (70%) or it can arise from a genetic mutation in the DUX4 gene (30%). Normally, this gene is switched off and only plays a role during embryonic development. In people with FSHD, however, this gene becomes active again which leads to progressive muscle weakness.⁴ 

There are two types of FSHD which are classified according to the genetic mutation. While types 1 and 2 present the same clinical characteristics of muscle weakness and affect similar areas, they differ depending on their genetic origin.⁴

• Type 1: This type accounts for about 95% of reported cases. It is inherited in an ‘autosomal dominant’ manner and is linked to the loss of part of a repeated sequence in the D4Z4 region on chromosome 4⁴
• Type 2: Makes up roughly 5% of cases, which follows a ‘variable inheritance pattern’ and results from a pathway that does not involve a D4Z4 deletion⁴

Global prevalence

FSHD is the most prevalent type of MD with an estimated prevalence of around 5 per 100,000. Despite the fact that FSHD affects both male and females, it has been seen to affect women less severely compared to men meaning that women with FSHD tend to be diagnosed later in life. Additionally, females who are diagnosed often have less severe muscle weakness and symptoms compared to men with FSHD.² 

Geographical differences

Europe: FSHD is the most frequent type of MD, which has a higher prevalence in Europe with an average incidence of 5-12/100,000. It usually starts by causing muscle weakness in the face, shoulders, and arms, where it gradually spreads to the lower region, including the upper legs. This weakness is typically asymmetric, meaning that one side might be more affected than the other.³ 

Asia: FSHD prevalence in Asia varies across countries. Research states that those in the northeast Asian populations are less likely to develop FSHD1.⁶ For instance, a study conducted in China that collected all FSHD type 1 cases during 2001-2020 found that:⁵

Researchers had concluded that since this was the biggest FSHD1 study population, this allowed them to estimate that 0.75 people per million had FSHD1, and that 12% of people with FSHD1, whether they have symptoms or not, will lose their motor ability, including walking without assistance within 40 years from when they first noticed muscle weakness. FSHD is relatively rare in China with only a small number of people being diagnosed, and that the deterioration of the condition will slowly reduce their ability to walk over time.⁵ 

Africa: The prevalence of FSHD is less common in African countries. In Sub-Saharan Africa, there are few cases of FSHD and these cases have not been genetically confirmed. Some factors that might explain the low prevalence was the lack of resources and medical specialists to identify and diagnose FSHD in these regions, contributing to the under-reporting. It may also be due to genetic differences in these populations, which makes them less likely to develop FSHD.⁶ 

Demographic variations

Age of onset

FSHD typically occurs during adolescence or early adulthood. A cross-sectional study examining the age of onset of FSHD examined two groups of people with the condition; one group with 28 early-onset patients and the other group consisted of 28 patients who developed it at a typical age. They found that those who had early-onset FSHD experienced severe weakness and were more likely to be dependent on mobility aids such as a wheelchair. Systemic features like hearing loss were also identified, as well as a decrease in respiratory function. These findings suggest that those who have early-onset FSHD are more likely to experience more severe muscle weakness, higher increase of mobility aid dependence, and serious systemic issues.⁷

The age that someone is diagnosed with FSHD or experience related symptoms, might determine the severity of the disease. If someone experiences FSHD symptoms at a young age, they tend to experience severe complications of muscle weakness and other related problems compared to those who develop FSHD later in life. This association suggests that age could predict the severity of the disease and how it might progress over time. Researchers have found that the patients who developed FSHD earlier in life had severe muscle weakness and were much more dependent on wheelchairs compared to those with a more typical onset of the disease. This information can be crucial for healthcare professionals to help them manage and 

treat patients with early-onset FSHD.⁷ 

According to the Muscular Dystrophy Association, individuals usually experience symptoms during their teenage years or 20s. Some form of muscle weakness can occur “as early as infancy and as late as the 50s”. For some people, symptoms of the condition are so subtle that they do not realise they have it or that anything is wrong. In these situations, the condition might only be discovered when a relative with more obvious symptoms seeks medical attention. People often seek medical help once the weakness starts affecting areas such as the face, shoulders, or legs. At that point, many realise they had symptoms going back to childhood, or notice difficulties with simple everyday tasks like drinking through a straw.

Sex differences

• FSHD affects both males and females
• It has been reported that males experience more severe symptoms of FSHD such as muscle weakness, compared to females⁸
• Men usually start showing symptoms at a younger age compared to women

Familial vs. Sporadic cases

FSHD is often a familial condition, accounting for nearly 70-90% of diagnosed FSHD1 cases. For patients to inherit this, only one copy of the mutated gene from either parent is needed which increases their chances of developing FSHD1. In 10-30% of cases, the affected individual is usually the first in their family to have FSHD1. This genetic change can happen “as the result of a de novo constitutional or mosaic” mutation.¹ If an individual has been diagnosed with FSHD1, each of their children will have a 50% chance of inheriting the genetic change that causes the condition. If one person in a family is diagnosed with this condition, other family members should get tested to see if they have the same genetic change. Early diagnosis is also important during pregnancy, especially if a woman or her partner is known to carry the genetic change, as it can help determine whether their baby may inherit the condition.¹ 

Summary

Facioscapulohumeral Muscular Dystrophy (FSHD) is a progressive condition that leads to muscle weakness in the face, shoulder blades, and upper arms. It is usually inherited in an autosomal dominant manner, linked to genetic changes that activate the DUX4 gene, however, in some cases it can occur spontaneously without a family history. FSHD is known to have a higher prevalence in Europe compared to Asia and Africa, and research shows that men often experience more severe muscle weakness and a greater impact on daily life than women. Research suggests that people who develop FSHD symptoms at a younger age often experience more severe effects than those whose symptoms appear later in life. This highlights the importance of considering age when assessing the condition and that age might determine the severity of the condition. Additionally, early diagnosis is extremely important not only through genetic testing for individuals with a family history of FSHD, but also through prenatal screening if either parent carries the gene, to help determine whether their baby is at risk or inherits the same gene.