Facioscapulohumeral muscular dystrophy (FSHD) is a genetic illness, inherited in an autosomal dominant fashion, that affects skeletal muscle tissue in affected individuals. Muscle groups involved include those of the face, shoulder girdle, and lower extremity that are affected asymmetrically. FSHD characteristically starts proximally in the face and spreads distally to affected muscle groups. Beyond musculature, 50% of FSHD patients also present with subclinical high-frequency hearing loss and retinovasculopathy.
The pathology of FSHD is a result of an intricate interaction of genetics, involving the protein product of the DUX4 gene and the chromosomal location and number of repeats of the D4Z4 macrosatellite. The result of this interaction is the inappropriate expression of the DUX4 protein product. The DUX4 gene is part of a larger D4Z4 macrosatellite located on chromosomes 4 and 10. In healthy individuals, the expression of the genes encoded on D4Z4 is epigenetically repressed due to increased methylation in these regions. Such repression requires that the total number of D4Z4 repeats falls between 11 and 100. In FSHD, the total number of D4Z4 repeats is between 1 and 10. Furthermore, the location of the decreased macrosatellite repeats must occur on chromosome 4 to cause pathology. Reductions in repeats on chromosome 10 have not shown to cause pathology.
FSHD further classifies into two subtypes, based on the route in which decreased methylation and a failure of epigenetic repression takes place. About 95% of cases of FSHD are type 1 in which D4Z4 repeats become lost. The remaining 5% of FSHD cases classify as type 2, in which methylation and epigenetics are affected in a deletion-independent manner. Regardless of the subtype, the end result of FSHD is the same. The DUX4 protein product that is normally only expressed in germline tissue becomes expressed in somatic cells, specially myocytes. DUX4 protein is especially toxic to myocytes, and this toxicity leads to cell death and the muscle atrophy seen in FSHD patients.
Due to the decreased severity and increased lifespan of affected patients, FSHD is one of the most prevalent types of muscular dystrophy currently known. FSHD carries a prevalence of approximately 3.2 to 4.6 per 100,000 and does not seem to affect any racial group more or less than others. However, FSHD does seem to have a decreased penetrance in women compared to men; this is seen in female patients not only being diagnosed at a more advanced age compared to men but also presenting with less severe pathology.
The onset of physical exam findings in FSHD can occur across the entire lifespan of an individual, but most frequently occur in the second decade of life. While disease severity varies widely between individuals, the development of symptoms typically occurs over a long period. Since FSHD is a genetic disease, the history of affected patients will most likely include a familial inheritance pattern. Parents of affected infants and toddlers may report noticing scapular winging or problems with closing eyes during sleep.
The most common initial physical exam finding seen in FSHD is difficulty in the abduction of the arms over the glenohumeral joint with asymmetric muscle involvement. Muscle involvement then moves towards the legs, affecting the distal-most muscles first, primarily the gastrocnemius and tibialis anterior. As the muscles of the trunk and spine are affected, FSHD patients can present with accentuated lumbar lordosis. FSHD differs from other muscular dystrophies with respect to the formation of muscle contractures. While other dystrophies involve contractures surrounding weak muscle groups, this is rarely the case in FSHD. Facial muscle involvement in FSHD includes lagophthalmos, a decrease in brow folds, a flattened or asymmetric smile, and an inability to tense superficial muscles of the head and neck.
In the upper extremities, muscle wasting of the shoulder girdle muscles with an anterior rounding pattern presents. The deltoid muscle is frequently spared in FSHD. As a result, the trapezius muscles appear tightly bound up. The combination of the deltoid and trapezius involvement often manifests as a poly hill sign, in which musculature gives the appearance of consecutive peaks and valleys.
The diagnostic criteria of FSHD have evolved from a cluster of clinical symptoms and laboratory findings to genetic analysis of suspected cases. While genetic testing is the current gold standard in evaluating patients, equivocal presentations are aided by electromyography (EMG) studies, Magnetic resonance imaging (MRI), laboratory tests, and muscle biopsies. FSHD is genetically confirmed in by the presence of eight or less D4Z4 repeats at the 4q35 gene locus of one or more alleles.
EMG studies are generally characterized by low amplitude, polyphasic potentials present for brief time intervals. MRI studies classically reveal normal muscle tissue interspersed with abnormal tissue. These MRI abnormalities are reflective of healthy muscle tissue being replaced by areas of fat and fibrous tissue.
Before the presence of fatty, fibrous replacement, T2 MRI images demonstrate increased water content of affected muscles. When muscle tissue is biopsied in FSHD patients, muscle fibers show alternating patterns of degeneration and regeneration, rounding, fibrosis, a higher number of internal nuclei, and inflammation from lymphocytes. Laboratory analysis from blood samples of FSHD patients can demonstrate an increase in creatine kinase; however, these levels do not reach beyond five times the upper limit.
There are currently no disease-modifying treatments for FSHD. To this end, the mainstay of management of FSHD is supportive care. This care primarily occurs in the context of physical therapy and rehabilitation exercises. A 2016 clinical trial of home exercise therapy investigated the utility of combined aerobic and strength training program in FSHD patients. The results demonstrated that individuals engaged in a 6-month program lead to statistically significant improvements in muscle function without further damaging diseased tissue. In cases of severe pathology, physical therapy alone may not be enough to correct functional limitations. Assistive devices are, therefore, useful and can be tailored to the specific needs of each patient. Foot drop can be partially corrected with the use of an ankle-foot-orthoses or in combination with knee-ankle-foot orthoses.
Severe scapular winging can be corrected thought scapular fixation via orthopedic surgery. While no randomized clinical trials have taken place examining the efficacy of this intervention, case reports have demonstrated both an improvement in shoulder abduction, pain, and activities of daily living. More thorough the investigation is therefore required to elucidate the utility of scapular fixation in the routine management of FSHD. Managing pain and fatigue in FSHD patients is essential as both of these symptoms can affect patient psychology. Chronic pain is manageable with analgesic and antidepressant therapy to improve the quality of life in FSHD patients.
FSHD can mimic many other genetic myopathies: particularly limb-girdle muscular dystrophy, subacute necrotizing encephalomyelopathy, acid maltase deficiency, myotonic dystrophy, and polymyositis. In cases of significant symptom overlap between myopathies, genetic testing remains the standard in distinguishing between disease pathology.
The prognosis in FSHD revolves around the quality of life in an affected individual. While the overall lifespan in these patients is not affected, roughly 20 percent of affected individuals will experience disability significant enough to require wheelchair use during the course of the disease.
The major complications seen in FSHD are chronic pain, impaired daily functioning, and these combine to impact psychological functioning negatively. Approximately 77 percent of FSHD patients will experience the presence of chronic pain. More rarely, FSHD complications evolve to include swallowing abnormalities, hearing loss, retinal disease, and difficulty breathing.
Research has shown that chronic pain present in FSHD patients can be modulated by a network of coping strategies, the interpretation of pain, and catastrophizing. These factors interact to influence an individual's psychological functioning and perception of pain intensity. Therefore, it is vitally important that patients receive education on this biopsychosocial model. By increasing social support and adjusting pain-related beliefs, patients will be able to increase their quality of life and improve the ability to perform activities of daily living.
The optimal approach to caring for patients with FSHD involves coordination across multiple specialties tailored to the unique needs of each individual. FSHD often presents with significant mobility limitations. Recent systematic reviews have highlighted the utility of telemedicine in reaching both patients in remote, underserved communities. Also, the value of including social workers in the primary care setting has proven integral to providing additional care benefits to patients. The approach is also applicable to patients with severe functional limitations. Since FSHD is a long term illness, access to care throughout the disease spectrum is of critical importance. Telemedicine can aid in bridging the gap between limitations in mobility and health care access. Expanding the role of social workers can aid in increasing coordination across multiple specialties. To this end, future patient care should emphasize both the increased role of social workers in care coordination and the use of telemedicine in adults with complex social and health needs. [Level 1]
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