Understanding how facioscapulohumeral muscular dystrophy is diagnosed can help you know when to seek medical attention and what to expect during the testing process.

Who Should Undergo Diagnostics and When to Seek Them

Facioscapulohumeral muscular dystrophy, often called FSHD, is a condition that affects muscles in specific patterns, though these patterns can be hard to recognize at first. Many people with FSHD go years without a proper diagnosis because the early signs are subtle and easily mistaken for other problems. Knowing when to seek medical evaluation can make a significant difference in managing the condition and planning for the future.^[1]

If you notice that you or a family member is having difficulty with simple facial movements, this might be an early warning sign worth investigating. For example, if someone can’t purse their lips to whistle or drink through a straw, or if they sleep with their eyes slightly open because they can’t fully close them, these could be indicators of facial muscle weakness characteristic of FSHD. Similarly, if you find it increasingly difficult to raise your arms above shoulder level, or if your shoulder blades stick out and look like wings when you move your shoulders, these are patterns that warrant medical attention.^[2]

Young adults and teenagers should be particularly aware of these signs, as symptoms usually begin to appear before age 20 in about 90% of people with FSHD. However, the condition can show up at any point in life—some people don’t develop noticeable symptoms until much later, while in rare cases, children may show signs in early childhood or infancy. This wide variation in when symptoms appear makes it important not to dismiss muscle weakness as simply a result of poor fitness or aging.^[1]

Family history plays an important role in deciding whether to seek diagnostic testing. FSHD is an inherited condition passed down in families in an autosomal dominant pattern, which means that if one parent has the condition, each child has a 50% chance of inheriting it. If you have a parent or sibling diagnosed with FSHD and you begin experiencing any muscle weakness—even if it seems minor—it’s advisable to talk to a doctor about getting tested. However, it’s worth noting that between 10% and 30% of people with FSHD have no family history of the disease, meaning it can occur as a new genetic change in someone with no affected relatives.^[12]

Anyone experiencing unexplained weakness in the face, shoulders, upper arms, or lower legs should consider seeing a neurologist or a specialist in neuromuscular diseases. Pain that is chronic and hard to explain, alongside muscle weakness, is also common in FSHD and affects between 50% and 80% of people with the condition. If these symptoms are interfering with daily activities—such as reaching for objects, climbing stairs, or walking without tripping—a diagnostic evaluation becomes even more important.^[2]

Classic Diagnostic Methods

Diagnosing FSHD involves a combination of clinical evaluation and specialized testing. The process typically begins with a thorough physical examination by a doctor, often a neurologist, who will assess muscle strength, look for characteristic patterns of weakness, and observe physical signs that are common in FSHD. During this exam, the doctor will pay close attention to the muscles of the face, shoulders, and arms to identify the specific weaknesses that define this condition.^[2]

One of the most recognizable physical signs during an examination is something called scapular winging. This occurs when the shoulder blades protrude from the back and move upward toward the neck, making them look like wings. This happens because the muscles that normally hold the shoulder blades in place become weak. The doctor may also notice that facial muscles are weak on one or both sides, often more severely on one side than the other. Weakness in the muscles around the eyes can make it difficult for a person to fully close their eyelids, and weakness in the muscles around the mouth can make it hard to smile symmetrically or form certain expressions.^[2]

After the physical examination, the doctor will usually take a detailed medical history. This includes asking about when symptoms first appeared, how they have progressed over time, and whether anyone else in the family has experienced similar issues. Because FSHD runs in families, a positive family history can be an important clue, though the absence of family history doesn’t rule out the condition.^[12]

Blood tests are often part of the initial diagnostic workup. A common blood test measures the level of an enzyme called creatine kinase, or CK, which is released into the bloodstream when muscle tissue breaks down. In people with FSHD, creatine kinase levels are sometimes elevated, though they are not always high and a normal result does not exclude the diagnosis. This test helps the doctor understand whether there is ongoing muscle damage, but it is not specific to FSHD and can be elevated in many other muscle conditions as well.^[12]

Another test that may be performed is an electromyography, or EMG. This test measures the electrical activity of muscles and can help determine whether muscle weakness is due to a problem with the muscles themselves or with the nerves that control them. During an EMG, a thin needle is inserted into the muscle, and the electrical signals produced by the muscle are recorded. In FSHD, the EMG typically shows patterns consistent with a muscle disorder rather than a nerve disorder.^[12]

In some cases, a muscle biopsy may be recommended. This involves taking a small sample of muscle tissue, usually from the thigh or upper arm, and examining it under a microscope. While a muscle biopsy can show signs of muscle damage and help rule out other types of muscular dystrophy, it is not always necessary for diagnosing FSHD, especially if genetic testing is available and conclusive. The biopsy is more useful when the diagnosis is uncertain or when the genetic test results are not clear.^[12]

Additional tests may be needed to check for complications associated with FSHD. An eye examination can reveal changes in the blood vessels at the back of the eye, a condition known as retinal telangiectasias or, in more severe cases, Coats disease. These eye problems are often not noticeable to the person affected but can be detected during a routine eye exam. Hearing tests may also be ordered, as high-frequency hearing loss can occur in people with FSHD, though it is usually mild and may not cause noticeable symptoms.^[5]

An electrocardiogram, or ECG, might be performed to check the heart’s electrical activity. Although heart problems are rare in FSHD, some people may develop abnormal heart rhythms or other cardiac issues. Similarly, pulmonary function tests can assess lung capacity and breathing strength, as weakness in the muscles used for breathing can occur in advanced cases, though this is uncommon.^[12]

X-rays of the spine may be taken to check for scoliosis, which is an abnormal sideways curvature of the spine that can develop due to weakness in the back muscles. An exaggerated inward curve of the lower back, called lordosis, may also be seen on imaging, often resulting from weak abdominal muscles.^[12]

Because FSHD symptoms can overlap with those of other muscle disorders—such as limb-girdle muscular dystrophy, Pompe disease, or polymyositis—doctors often need to rule out these other conditions. This is done through a combination of clinical evaluation, family history, and additional tests. For example, Pompe disease can be identified through a specific enzyme test, and polymyositis, which is an inflammatory muscle disease, can be detected through blood tests that look for signs of inflammation.^[6]

Genetic Testing for Diagnosis

The most definitive way to diagnose FSHD is through genetic testing. This test looks for the specific genetic changes that cause the condition and can confirm the diagnosis even in people who have mild or no symptoms. Genetic testing is particularly important because it not only confirms whether someone has FSHD but can also provide information about the likely severity of the disease.^[4]

FSHD is caused by changes involving a region of DNA on chromosome 4 called D4Z4. In most people, this region contains between 11 and 100 repeated segments of DNA. In people with FSHD type 1, which accounts for about 95% of all cases, the number of these repeated segments is reduced to between 1 and 10. This contraction of the D4Z4 region leads to the activation of a gene called DUX4, which produces a protein that is toxic to muscle cells. The fewer repeats a person has, the more severe their symptoms are likely to be.^[5]

Genetic testing for FSHD type 1 measures the length of the D4Z4 region on chromosome 4. This is usually done through a blood test. The test identifies how many repeated segments are present and whether the contraction is on the chromosome 4 variant that is associated with FSHD, known as the 4qA allele. It’s important to note that not all contractions of the D4Z4 region cause disease—only those on chromosome 4 with the 4qA background lead to FSHD. Contractions on chromosome 10, which also has a D4Z4 region, do not cause the condition.^[6]

FSHD type 2, which accounts for about 5% of cases, is caused by a different genetic change. In this form, the D4Z4 region is not shortened, but a mutation in a different gene, most commonly the SMCHD1 gene on chromosome 18, leads to reduced methylation of the D4Z4 region. Methylation is a chemical modification that normally keeps genes turned off. When methylation is reduced, the DUX4 gene becomes active and produces the harmful protein. Genetic testing for FSHD type 2 involves checking for mutations in the SMCHD1 gene and assessing the methylation status of the D4Z4 region.^[5]

Both types of FSHD cause the same symptoms and are treated in the same way, so distinguishing between them is primarily important for genetic counseling and understanding inheritance patterns within families. Genetic testing can also be helpful for family planning, as it can determine whether someone who has no symptoms carries the genetic change and might pass it on to their children.^[4]

For individuals who have a family member with FSHD, genetic testing can provide clarity about their own risk. Because the condition is inherited in an autosomal dominant pattern, a person with an affected parent has a 50% chance of inheriting the mutation. Testing can be done before symptoms appear, which can be valuable for making informed decisions about health monitoring and life planning. However, some people choose not to be tested if they have no symptoms, preferring not to know their genetic status until or unless symptoms develop.^[4]

Prenatal genetic testing and pre-implantation genetic diagnosis are also available for couples who are planning to have children and want to know whether their baby will inherit FSHD. Prenatal testing can be done through procedures such as amniocentesis or chorionic villus sampling, which involve taking a sample of fluid or tissue from the pregnancy to analyze the baby’s DNA. Pre-implantation genetic diagnosis is performed as part of in vitro fertilization and allows embryos to be tested for the FSHD mutation before being implanted in the uterus.^[7]

Diagnostics Used for Clinical Trial Qualification

As research into treatments for FSHD progresses, clinical trials have become an important avenue for developing new therapies. To participate in these trials, patients must meet specific criteria, and diagnostic tests play a crucial role in determining eligibility. Understanding what tests are used to qualify for clinical trials can help people with FSHD prepare for potential participation and contribute to advancing research.^[15]

The first and most fundamental requirement for enrolling in an FSHD clinical trial is confirmation of the diagnosis through genetic testing. Researchers need to be certain that participants have FSHD rather than another muscle disorder, so genetic confirmation is almost always mandatory. For most trials, this means demonstrating a shortened D4Z4 repeat array on chromosome 4 (for FSHD type 1) or a mutation in the SMCHD1 gene with reduced methylation (for FSHD type 2). The genetic test results must clearly show that the participant meets the genetic criteria for FSHD.^[15]

Beyond genetic confirmation, clinical trials often require baseline assessments of muscle strength and function. These assessments help researchers understand the severity of a participant’s condition before any treatment begins and provide a starting point for measuring whether the treatment is effective. Common functional tests used in FSHD trials include measurements of how far a person can walk in six minutes, how much weight they can lift with specific muscle groups, and whether they can perform certain tasks like raising their arms or climbing stairs.^[11]

Muscle imaging is increasingly used in FSHD clinical trials to assess the extent of muscle damage and monitor changes over time. Magnetic resonance imaging, or MRI, is particularly useful because it can show which muscles are affected and how much fat has replaced normal muscle tissue. Some trials use MRI scans at the beginning of the study and then at regular intervals to see whether the treatment slows down or reverses muscle damage.^[6]

Blood tests are also a standard part of qualifying for clinical trials. In addition to measuring creatine kinase levels, researchers may test for the expression of specific genes or proteins related to FSHD. For example, some trials look for the presence of DUX4 protein or proteins that are turned on by DUX4, as these are markers of disease activity. These tests help identify participants whose disease is active and who might benefit most from the experimental treatment.^[15]

In some advanced trials, researchers may perform a muscle biopsy to measure the levels of DUX4 or other molecules directly in muscle tissue. This provides detailed information about what is happening at the cellular level and can help researchers determine whether a drug is reaching the muscle and having the intended effect. Not all trials require a biopsy, as it is an invasive procedure, but it can be valuable for understanding how well a treatment is working.^[15]

Screening for other health conditions is also part of the qualification process for clinical trials. Because some experimental treatments might affect the heart, lungs, or other organs, participants typically undergo a thorough medical evaluation to ensure they are healthy enough to participate safely. This may include an electrocardiogram to check heart function, pulmonary function tests to assess lung capacity, and routine blood tests to check liver and kidney function.^[11]

Finally, some trials have specific requirements related to the age, sex, or disease severity of participants. For example, a trial testing a treatment for early-stage FSHD might only enroll people who still have relatively good muscle strength and can walk independently. Other trials might focus on people with more advanced disease who need wheelchairs. Understanding the specific eligibility criteria for each trial is important for determining whether participation is an option.^[15]

Participating in a clinical trial can be an opportunity to access cutting-edge treatments that are not yet available to the general public, and the diagnostic tests required for enrollment ensure that the research is conducted safely and effectively. For individuals with FSHD, staying informed about ongoing trials and maintaining regular contact with a neuromuscular specialist can help identify opportunities to participate in research that may lead to new treatments in the future.^[15]