Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder characterized by the progressive weakening and degeneration of skeletal muscles. It is one of the more common types of muscular dystrophy. The condition’s name provides a map to the typical onset of symptoms: “facio” refers to the face, “scapulo” to the shoulder blades, and “humeral” to the upper arms.
Clinical Presentation and Symptoms
Symptoms of FSHD often become noticeable before the age of 20. The initial signs frequently involve the facial muscles, leading to difficulties with closing the eyes tightly, whistling, or forming a smile. Children with the condition may sleep with their eyes slightly open.
Weakness then extends to the muscles stabilizing the shoulder blades. This results in scapular winging, where the shoulder blades protrude from the back when raising the arms. Weakness in the upper arm muscles can make lifting objects a challenge. A hallmark of FSHD is its asymmetry, with muscle weakness often more pronounced on one side of the body.
As the condition progresses, it can affect muscles in the lower body. Weakness in the abdominal muscles can cause the abdomen to protrude. The muscles in the lower legs may also weaken, leading to “foot drop,” a difficulty in lifting the front part of the foot while walking. This can result in a high-stepping gait to avoid tripping.
Beyond muscle weakness, individuals with FSHD experience other symptoms. Chronic pain, particularly in the shoulders, lower back, and neck, is a common complaint. Fatigue is another symptom that can impact daily life. The severity and rate of progression differ widely; some people experience mild symptoms, while others may face more disability, with about 20 percent requiring a wheelchair by age 50.
Genetic Basis of FSHD
The cause of FSHD is genetic. Approximately 95 percent of cases are classified as FSHD type 1, which is caused by the shortening of a specific DNA segment on chromosome 4. This area, known as the D4Z4 macrosatellite repeat array, normally contains a large number of repeating DNA units.
In individuals with FSHD1, the number of these repeats is reduced. This shortening changes the DNA’s chemical structure, making it more accessible. This accessibility allows for the production of a protein called Double Homeobox 4 (DUX4). The DUX4 gene is silent in most adult cells, but its activation in muscle cells is toxic, leading to cell death and inflammation.
The remaining cases are FSHD type 2. In FSHD2, the D4Z4 region is not contracted, but a mutation in a different gene, most commonly SMCHD1, prevents the DUX4 gene from being switched off. The result is the same as in FSHD1: the unwanted production of the toxic DUX4 protein. FSHD is inherited in an autosomal dominant pattern, meaning a person with the condition has a 50% chance of passing the genetic cause to each child.
The Diagnostic Journey
The diagnostic process for FSHD begins with a clinical evaluation by a physician, often a neurologist with experience in neuromuscular disorders. The doctor looks for the characteristic pattern of weakness, such as in the facial and shoulder muscles, and takes a detailed family history.
A doctor may order a blood test to measure creatine kinase (CK), an enzyme that leaks from damaged muscle. In FSHD, CK levels are normal or only mildly elevated, which helps differentiate it from other muscular dystrophies. This finding, combined with clinical symptoms, points toward a possible FSHD diagnosis.
The definitive diagnosis relies on genetic testing. A blood sample is analyzed to identify the specific genetic flaw. For suspected FSHD1, the test looks for the contraction of the D4Z4 repeat array on chromosome 4. If that test is negative, further analysis can identify mutations in genes like SMCHD1 to confirm FSHD2.
Managing FSHD and Therapeutic Approaches
There is no cure for FSHD, so management focuses on addressing symptoms and preserving quality of life. This is best achieved through a multidisciplinary care team. Physical therapy is a central component, aiming to maintain muscle strength and flexibility through gentle exercise and stretching.
Occupational therapists help individuals adapt to daily life by providing strategies and tools for activities at home and work, including assistive devices. Orthotic supports, such as ankle-foot orthoses for foot drop or back supports for weakened core muscles, can improve mobility and reduce pain. For some, surgical procedures like scapular fixation can improve shoulder range of motion.
Regular monitoring for non-muscular symptoms is also part of care. A small percentage of individuals with FSHD may experience issues such as hearing loss or retinal abnormalities that require attention from specialists. While no treatment stops or reverses muscle weakness, research is exploring therapies that target the root cause. These approaches aim to inhibit the DUX4 gene or its protein product, offering hope for future treatments.