Facioscapulohumeral muscular dystrophy, or FSHD, is a genetic disorder characterized by the progressive weakening and loss of skeletal muscle. The condition’s name reflects the parts of the body it most characteristically affects: “facio” for the face, “scapulo” for the shoulder blades, and “humeral” for the upper arm. FSHD is one of the more prevalent types of muscular dystrophy. The condition’s onset and the extent of its progression can vary significantly among individuals as muscle fibers gradually degenerate and are replaced by fat and fibrous tissue.
Genetic Origins and Inheritance
Over 95% of cases, classified as FSHD type 1, are linked to a specific change on chromosome 4. This change involves a segment of DNA known as the D4Z4 macrosatellite repeat array. In unaffected individuals, this region contains from 11 to over 100 repeating DNA units, but in people with FSHD1, this array is contracted to only 1 to 10 repeats.
This contraction of the D4Z4 region leads to a change in the DNA’s structure, causing it to become less tightly packed, a state known as hypomethylation. The looser structure allows a gene within the D4Z4 region, called Double Homeobox 4 (DUX4), to be expressed. Normally, the DUX4 gene is silenced in most adult tissues, but in FSHD, its expression in muscle cells produces a toxic protein that leads to muscle cell damage and death.
FSHD is inherited in an autosomal dominant pattern, meaning only one copy of the altered chromosome from a single parent is sufficient to cause the disorder. An affected parent has a 50% chance of passing the genetic change on to each of their children. Approximately one-third of cases are considered “de novo,” occurring as a new mutation in an individual without any prior family history.
Recognizing the Symptoms
The presentation of FSHD is defined by a pattern of muscle weakness that often progresses slowly over many years. One of the earliest signs is weakness of the facial muscles. This can manifest as an inability to whistle, difficulty puffing out the cheeks, or trouble closing the eyes completely, which may lead to dry eyes. A person’s smile might appear flat or the face may seem less expressive.
As the condition progresses, weakness extends to the muscles around the shoulders and back. A sign is “scapular winging,” where the shoulder blades protrude from the back, especially when raising the arms. This occurs because the muscles that normally hold the scapula flat against the rib cage have weakened, making it difficult to lift objects or raise the arms above shoulder height.
A notable feature of FSHD is that the weakness is often asymmetrical, affecting one side of the body more than the other. Later-stage symptoms can include a weakening of the abdominal muscles, which may cause the lower back to curve inward, a posture known as lordosis.
Weakness can also develop in the lower extremities, particularly in the muscles at the front of the shin. This leads to “foot drop,” the inability to lift the front part of the foot when walking. To compensate, individuals may raise their knee higher than normal, a gait pattern known as steppage gait. The age of onset is highly variable, with symptoms appearing anywhere from early childhood to late adulthood.
The Diagnostic Process
Confirming a diagnosis of FSHD involves a combination of clinical observation and genetic analysis. A neurologist will perform a physical examination, looking for the classic pattern of muscle weakness and asymmetry associated with FSHD. While the clinical signs can be strong indicators, they are not sufficient for a conclusive diagnosis on their own.
The gold standard for diagnosing FSHD is genetic testing. This is done through a blood test, where DNA is analyzed for the contraction of the D4Z4 repeat array on chromosome 4. Finding between one and ten repeats confirms a diagnosis of FSHD type 1.
In cases where the clinical picture is unclear, other tests might be employed to rule out different neuromuscular conditions. An electromyography (EMG) test can show patterns of myopathic change, and a muscle biopsy may reveal variations in muscle fiber size. These tests are now used less frequently, as genetic testing provides a more direct and definitive answer.
Managing Daily Life and Progression
As there is currently no cure for FSHD, management focuses on mitigating symptoms, maintaining function, and preserving quality of life. A multidisciplinary approach involving various healthcare professionals is beneficial. Physical therapy aims to preserve muscle strength and flexibility through tailored, low-impact exercise programs like swimming, stationary cycling, and gentle stretching.
Occupational therapy provides practical solutions for adapting to the challenges of daily living. An occupational therapist can help individuals find new ways to perform tasks, such as using long-handled tools or modifying kitchen utensils. They also assist in selecting assistive devices like ankle-foot orthoses (AFOs) to counteract foot drop or scooters to conserve energy.
Pain management is another aspect of care, as chronic muscle and joint pain can be a common complaint. Regular monitoring by a healthcare team is also recommended to watch for potential non-muscular symptoms associated with FSHD. Some individuals may develop hearing loss or abnormalities in the blood vessels of the retina, which require specialized attention.
The progression of FSHD is typically slow, and proactive management can make a significant difference. Regular follow-ups with a neurologist and therapy team allow for adjustments to the management plan as needed. The goal is to implement strategies that support continued participation in personal, social, and professional activities.
Current Research and Therapeutic Development
The scientific community is actively engaged in research aimed at developing targeted treatments for FSHD. Advances in understanding the genetic cause of the condition have opened new doors for therapeutic intervention. The primary focus of this research is the DUX4 gene, whose expression is the root cause of muscle damage.
One strategy being explored is the development of therapies designed to suppress or silence the DUX4 gene. These approaches aim to prevent the toxic DUX4 protein from being produced in muscle cells. Researchers are investigating methods like antisense oligonucleotides, which are small molecules that can bind to the DUX4 messenger RNA and signal it for degradation.
Another avenue of research focuses on protecting muscle cells from the harmful effects of the DUX4 protein. These potential therapies would work to counteract its toxicity, reduce inflammation, and prevent muscle cell death. This could involve developing drugs that inhibit the pathways activated by DUX4 or that promote muscle regeneration.
Several of these potential treatments have advanced into clinical trials with human participants to evaluate their safety and effectiveness. While no disease-modifying therapy has yet been approved, the ongoing research and active clinical trials represent significant progress toward treatments that could one day slow or halt the progression of the disease.