If you or a loved one is experiencing muscle weakness and difficulty with mobility, it's important to understand the early symptoms of genetic muscular dystrophies, like Facioscapulohumeral Muscular Dystrophy (FSHD). FSHD often begins subtly, so early recognition is often challenging. This article provides an overview of the early symptoms of FSHD, so you know what to look for. 

Early symptoms of FSHD don’t follow a specific pattern and progress at different rates between different people. Early symptoms are characterised by asymmetric, or uneven muscle weakness, usually in the face, back, and upper arm. The name “facioscapulohumeral” comes from the Latin words for face (facies), back (scapulae), and upper arm (humero).¹ Hallmark early symptoms of FSHD include, but are not limited to, facial weakness, shoulder blades that stick out, weakness in abdominal muscles causing a curved spine, or trouble raising arms above the head.² 

These symptoms can be early warning signs of FSHD. FSHD has a gradual progression, affecting various parts of the body. Keep reading to understand how FSHD is developed, more symptoms of FSHD, how FSHD is diagnosed, and how it can be managed to support daily life.

Introduction 

Facioscapulohumeral Muscular Dystrophy (FSHD) is an inherited muscular dystrophy disorder. Muscular dystrophy means the degeneration of muscles over time.³ FSHD causes muscle weakness, typically beginning in the face and upper body, but it can affect other muscle groups as well. Symptoms of FSHD may first present themselves in infancy and childhood. However, most people notice it in early adulthood (20-30 years old).⁴ FSHD is one of the most common forms of muscular dystrophy, with 4 cases per 100,000 people.³

There is no cure for FSHD, but its symptoms and effects can be managed through different therapies.⁴ This is why early recognition of symptoms is so important. The earlier symptoms are detected and FSHD is diagnosed, the earlier monitoring and support for weakening muscles can begin. 

This article will first explain what FSDH is and how it develops. Then it will review early signs and symptoms and discuss how the condition progresses over time. Finally, it will go over how FSHD is diagnosed, its impact on daily life, and the different management strategies available to help people affected by it. 

Understanding FSHD

FSHD is a genetic neuromuscular disorder, meaning it affects muscles and the nerves controlling them. It is caused by changes in DNA that lead to a gene called DUX4 being switched on in the muscle cells. Normally, this gene is turned off, but in FSHD it becomes active and produces a toxic protein that weakens muscle tissue over time.  

There are two types of FSHD. The most common one, accounting for 95% of cases, is FSHD1. This type occurs when a section of bases on chromosome 4, called D4Z4, is deleted. Chromosome 4 comes in two forms: 4qA and 4qB. If the D4Z4 deletion occurs on a 4qA chromosome, the DUX4 gene will be activated, leading to muscle degeneration and FSHD1. 

People with 4qB are protected from developing FSHD because the 4qB form does not have a feature called the polyadenylation site, which is responsible for reinforcing the message from DUX4. Without this site, the DUX4 gene cannot make its toxic protein.

FSHD2 is much rarer, accounting for 5% of cases. Similar to FSHD1, FSHD2 requires the individual to have the 4qA chromosome type that contains the polyadenylation site that allows for the toxic proteins to be made. However, for FSHD2 to occur, a different gene mutation occurs in the SMCHD1 gene. 

This gene controls the coiled shape of DNA, and when it is mutated, the D4Z4 section on chromosome 4 also changes shape. The new shape of the D4Z4 site switches on the DUX4 gene, causing individuals with 4qA to develop FSHD2.²

The muscles are affected by FSHD primarily through weakness and atrophy (shrinkage). The switching on of the DUX4 gene and creation of the toxic protein disrupt pathways such as growth and regeneration of muscle cells, most often leading to muscle cell death.⁵

Early signs and subtle onset

Hallmark early symptoms usually present themselves in the face, back, and upper arms. They may be mild at first because FSHD begins very subtly. 

Common early symptoms of FSHD include:

• Trouble whistling
• Trouble blowing up balloons
• Hard time sipping through a straw
• Eyes that don’t fully close during sleep 
• Shoulder blades that stick out (winging)
• Curved spine (lordosis, scoliosis)
• Difficulty raising arms above the head
• Difficulty doing pull-ups

Other symptoms may present themselves as FSHD progresses. These symptoms become worse and more noticeable as the muscles become weaker. More advanced symptoms of FSHD include:

• Difficulty doing sit-ups
• Ab weakness causing a protruding belly
• Loss of chest muscles
• Sunken chest 
• Foot drop (trouble lifting the foot)
• Difficulty going up stairs
• Difficulty standing up from a chair
• Pain
• Muscle Inflammation 
• Fatigue 

Retinal changes, cardiac changes, and hearing loss are also sometimes symptoms of FSHD, but these symptoms are uncommon, can only be discovered through special tests, and usually do not impact an individual’s well-being.¹^,²^,⁶

Occasionally, FSHD is misdiagnosed because of its wide range of symptoms. A common misdiagnosis of FSHD is polymyositis, a non-genetic disorder where the immune system attacks the muscles and causes inflammation.⁶ Other conditions frequently confused with FSHD include multiple sclerosis due to similar muscle weakness, fibromyalgia due to chronic pain and fatigue, or chronic fatigue syndrome.⁷ Having one or a few of these symptoms does not necessarily mean you have FSHD. If you or a loved one is exhibiting many of these symptoms, it's important to seek a medical professional’s opinion for a clear diagnosis. 

Diagnostic process

Since FSHD is a genetic disorder, it often runs in families. 70% of FSHD patients inherit it from a parent, while 30% of cases are due to spontaneous genetic mutation. A child of someone affected by FSHD has a 50% chance of inheriting FSHD, and family members always inherit the same type of FSHD.⁸ Even if you know FSHD runs in your family, it is still important to receive a proper diagnosis from a medical professional. 

When diagnosing FSHD, doctors will test for muscle weakness, ask for family medical history, and test for other conditions to rule them out.⁷ The most reliable way to test for FSHD is to test for the deleted D4Z4 section on chromosome four. A genetic test using a blood sample can be performed to determine if this deletion has occurred, which successfully identifies 95% of patients with FSHD. Not everyone needs a genetic test, though it is the most accurate way to diagnose FSHD. 

Other methods are less expensive, like a creatine kinase (CK) test, which measures the levels of CK in a blood sample. When muscles break down due to FSHD, CK levels are heightened. Electromyograms, or EMGs, can also be used to determine the electrical activity of muscles, which is often altered in individuals with FSHD.⁹ 

Once someone is diagnosed with FSHD, the next step is to determine which type they have, because this can guide therapy and management of the disorder. This is usually done through genetic testing.⁷

Impact on daily life and management strategies

Though FSHD begins subtly, its impacts advance as the disorder progresses. Tasks that require affected muscles can become more difficult, like lifting things above the head, stair climbing, or walking long distances. Weakness in abdominal and spinal muscles can lead to changes in posture and affect body structure and balance.¹⁰ As muscles degenerate over time, individuals may have to rely on braces or wheelchairs for mobility. 

There is no current cure for FSHD, but treatments and therapies can help manage the symptoms and maintain muscle strength and function. Physical therapy can be done to maintain mobility, while orthotics (structures like braces and supports) can support weakened limbs or muscles.¹¹ 

Pain and inflammation can be managed through medication. Surgical alterations can be made to the scapula, or shoulder blades, to stabilise them by attaching them to the ribs. This also provides some leverage to the arm.¹² Research is also rapidly progressing, with clinical trials testing gene-silencing approaches (turning off specific genes) and drugs that block harmful DUX4 activity.¹³

Summary 

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder that causes muscular degeneration and weakness, often becoming noticeable in a person’s 20s or 30s. Symptoms begin subtly and include facial weakness or shoulder blade winging, and may progress at different rates. In some cases, FSHD remains mild and barely noticeable, while in others it becomes more severe and debilitating. 

More common features include weakness in the face, shoulders, arms, torso, and legs. Because FSHD varies so widely, it’s important to see a doctor if you are experiencing any of these symptoms for a proper diagnosis, especially because early recognition can improve long-term living with FSHD. Although there is no cure for FSHD, its symptoms can be managed with therapy, medication, and lifestyle adjustments. Ongoing clinical trials offer hope for future treatment.