Facioscapulohumeral Muscular Dystrophy (FSHD) is a progressive genetic disorder that causes skeletal muscles to weaken over time. It primarily impacts muscles in the face, shoulders, and upper arms, but can extend to affect most skeletal muscles throughout the body. FSHD is a complex condition with varied presentation and underlying genetic mechanisms.
Understanding Facioscapulohumeral Muscular Dystrophy
FSHD is a genetic disorder characterized by the gradual weakening of muscle tissue. The name “facioscapulohumeral” indicates the muscles most commonly affected first: “facio” for the face, “scapulo” for the shoulder blades, and “humeral” for the upper arms. While these areas are often where symptoms first appear, muscle weakness can spread to other skeletal muscles, including those in the torso, abdomen, lower legs, and hips.
There are two main types of FSHD: FSHD1 and FSHD2. FSHD1 accounts for about 95% of cases, while FSHD2 makes up the remaining 5%. Both types lead to similar clinical symptoms. Symptoms often become apparent in the teenage years, though onset can range from infancy to late adulthood.
Genetic Basis of FSHD
Both FSHD1 and FSHD2 share a common underlying mechanism: the abnormal activation of the DUX4 gene. This gene, normally silenced in most adult tissues, becomes active in muscle cells in individuals with FSHD. When activated, DUX4 produces proteins toxic to muscle cells, leading to their damage and weakening.
In FSHD1, this abnormal activation results from a shortening of a specific region on chromosome 4 called the D4Z4 repeat array. Individuals typically have between 11 and 100 D4Z4 units, but in FSHD1, this region is reduced to 1 to 10 units. This reduction weakens the “lock” that normally keeps the DUX4 gene silenced, allowing it to become active.
FSHD2, while clinically similar to FSHD1, involves mutations in other genes, such as SMCHD1 or DNMT3B. These mutations indirectly lead to the derepression of the DUX4 gene by affecting the epigenetic control of the D4Z4 region, causing a more open chromatin structure that allows DUX4 to be expressed. Approximately 30% of FSHD1 cases arise from new, spontaneous mutations rather than being inherited.
Recognizing the Signs of FSHD
The symptoms of FSHD can vary greatly in presentation, severity, and age of onset, even among individuals within the same family. Weakness in facial muscles is a common early sign, often making it difficult to whistle, purse the lips, or fully close the eyes during sleep, which can lead to dry eyes. Some individuals may also experience a reduced ability to display emotional expressions.
Weakness in the shoulder muscles is another hallmark of FSHD, frequently leading to “scapular winging,” where the shoulder blades protrude from the back. This can make it challenging to lift the arms above shoulder height. As the condition progresses, muscle weakness can extend to the lower legs, often causing “foot drop,” which makes it difficult to lift the front of the foot when walking and can increase the risk of tripping.
Abdominal muscle weakness is also common and can develop early, sometimes leading to an exaggerated inward curve of the lower spine, known as lumbar lordosis. Muscle weakness in FSHD is often asymmetric, meaning one side of the body may be more affected than the other.
Beyond muscle weakness, some individuals with FSHD may experience non-muscular symptoms. These include high-frequency hearing loss and abnormalities of blood vessels in the back of the eye, though these rarely lead to vision problems. Chronic pain is also a common symptom.
Diagnosis and Management of FSHD
Diagnosis of FSHD is primarily confirmed through genetic testing, which identifies the specific genetic changes associated with FSHD1 or FSHD2. Genetic testing for FSHD1 detects the shortening of D4Z4 repeat elements on chromosome 4. If FSHD1 is ruled out, testing for FSHD2, which involves mutations in genes like SMCHD1, may be pursued.
While genetic testing is the most definitive diagnostic method, other tests can provide supportive evidence or help rule out other neuromuscular disorders. Blood tests, such as measuring creatine kinase (CK) levels, can indicate muscle damage, as CK levels are often elevated in symptomatic FSHD patients. Neurological tests, including electromyography (EMG), which measures muscle electrical activity, can show characteristic alterations in FSHD. A muscle biopsy, where a small muscle sample is examined, can also reveal cellular abnormalities, though this procedure is less frequently performed now given the availability of genetic testing.
Currently, there is no cure for FSHD. Treatments focus on managing symptoms and improving quality of life.
Physical therapy helps maintain muscle strength and function, enhance mobility, and prevent falls. Occupational therapy and speech therapy can also assist with daily living activities. Orthotic devices, such as ankle-foot orthoses, can help manage foot drop.
In some cases of severe scapular winging, surgical interventions like scapulopexy or scapulodesis may be considered to stabilize the shoulder blade and improve arm function. The disease progresses slowly, and for most individuals, FSHD does not shorten life expectancy.