Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder characterized by the progressive weakening and loss of skeletal muscle. The condition derives its name from the muscles most frequently affected first: the face (facies), shoulder blades (scapula), and upper arms (humerus). While symptoms emerge between the ages of 15 and 30, the onset can range from infancy to later in adulthood.
The Genetic Cause of FSHD
Facioscapulohumeral muscular dystrophy is an inherited disorder with a complex genetic foundation. About 95% of cases are classified as FSHD type 1 (FSHD1). This form is linked to a specific region on chromosome 4, which contains a stretch of repeating DNA segments known as the D4Z4 macrosatellite repeat array. In unaffected individuals, this array is extensive, containing between 11 and 150 repeat units. FSHD1 occurs when this array is contracted, leaving only 1 to 10 units.
This contraction of the D4Z4 region leads to a change in the local DNA structure, causing it to become less tightly packed. This altered state allows a gene called DUX4, located within each D4Z4 repeat, to be expressed. The DUX4 gene is active only during early embryonic development and is silenced in most adult tissues. When activated in muscle cells, the DUX4 protein it produces is toxic, triggering processes that lead to muscle cell damage and death.
The remaining 5% of cases are classified as FSHD type 2 (FSHD2). Individuals with FSHD2 do not have a contracted D4Z4 array. Instead, they have mutations in other genes, most commonly SMCHD1, which are responsible for keeping the D4Z4 region silenced. These mutations cause the same outcome as in FSHD1, as the DNA structure around the DUX4 gene relaxes, leading to its toxic expression and subsequent muscle damage.
Characteristic Symptoms and Progression
The clinical presentation of FSHD follows a descending pattern of muscle involvement, though the severity and rate of progression differ significantly among individuals. Initial symptoms involve the facial muscles, leading to a reduced ability to form expressions. Affected individuals may find it difficult to smile, whistle, or close their eyes completely, and the face may develop a thin or expressionless appearance.
Weakness extends to the muscles that stabilize the shoulder blades. This results in a condition known as scapular winging, where the shoulder blades protrude noticeably from the back, especially when raising the arms. This can make lifting objects or reaching overhead challenging. Following this, the muscles of the upper arms, such as the biceps and triceps, weaken, while the deltoid muscles of the shoulder may remain comparatively strong.
As the condition progresses, muscle weakness can spread to the core and lower body. Weakness in the abdominal muscles can cause the pelvis to tilt forward, resulting in a swayback posture and a protruding abdomen. In the lower legs, the muscles responsible for lifting the front of the foot are affected, a condition called foot drop. This can cause the foot to drag during walking, increasing the risk of tripping and falls. The weakness is also often asymmetrical, affecting one side of the body more than the other.
How FSHD is Diagnosed
The diagnostic process for FSHD begins with a clinical evaluation. A neurologist will assess the patient’s muscle strength and look for the characteristic patterns of weakness associated with the condition. The presence of facial muscle weakness combined with scapular winging and weakness in the upper arms is highly suggestive of FSHD. The physician will also take a detailed family medical history to determine if other relatives have similar symptoms.
While a clinical examination can point towards a diagnosis, definitive confirmation comes from genetic testing. A blood sample is taken and sent for molecular analysis to examine the D4Z4 repeat array on chromosome 4. For FSHD1, the test measures the number of D4Z4 repeats; a finding of 1 to 10 repeats confirms the diagnosis. The number of repeats can correlate with the age of onset and severity, with fewer repeats often associated with an earlier presentation.
If the genetic test for FSHD1 is negative but the clinical symptoms are strongly indicative of the disorder, further testing may be done to look for mutations consistent with FSHD2. This involves sequencing genes like SMCHD1 to identify mutations known to cause the condition. While tests like electromyography (EMG) or muscle biopsy were used in the past, the accuracy of genetic testing has made it the primary diagnostic method.
Managing FSHD and Medical Interventions
Currently, there is no cure for FSHD; management focuses on addressing symptoms and preserving function. A multidisciplinary approach is employed, involving physical and occupational therapists. Physical therapy aims to maintain muscle flexibility and cardiovascular health through low-impact exercises like swimming and cycling, which can help without causing further muscle damage.
Occupational therapy provides strategies and adaptive tools to assist with daily living activities. Therapists may recommend modifications in the home or workplace to accommodate changing physical abilities. Assistive devices are a common part of managing FSHD. Ankle-foot orthoses (AFOs) can be prescribed to counteract foot drop, while walkers or scooters can help maintain independence for those with more significant mobility challenges.
Regular medical monitoring is part of comprehensive care, including tracking muscle weakness and watching for non-muscular symptoms. Some individuals with FSHD may develop hearing loss or retinal blood vessel abnormalities, which requires periodic screening. Ongoing research is focused on developing therapies that target the toxic DUX4 protein, offering potential future treatments.