Fascioscapulohumeral dystrophy (FSHD) is an inheritable neuromuscular disorder causing progressive weakness and atrophy of skeletal muscle of the face, upper arms, and shoulder girdles.6 FSHD is the third most common form of muscular dystrophy.6
FSHD results from a deletion of a fragment of DNA located on chromosome 4 in the region 4q35.4 Typically, the greater the deletion of this fragment the more severe the manifestation of disease.2 This deletion is found in 85-95% of patients with the clinical symptoms of FSHD.3 FSHD is an autosomal dominant disorder while, 10-30% of FSHD cases are sporadic.3 The mutation is highly penetrant, but presents with varying degrees of disability.3
Greater than 90% of patients have demonstrable symptoms by age 20.3 Patients usually present with slowly progressive, asymmetric weakness, although they may experience prolonged periods of relatively stable function.3 Progressive weakness and loss of skeletal muscle is observed in the face, upper arms, and shoulders with protruding shoulder blades.3 The ability of the eyes to close and of the mouth to smile or whistle typically are affected.3 Eventually weakness of the feet, abdomen, and hip girdle can also appear.6 It is reported that more than half of patients with FSHD have high-frequency hearing loss.7 Abnormalities of blood vessels of the retina have also been reported.7
- EMG typically will show abnormal results in skeletal muscle.2 The affected muscles will exhibit polyphasic motor unit potentials of low amplitude and short duration.3 As a result of traction-type injuries to the brachial plexus, abnormal sensory symptoms may develop with abnormal findings on electrophysiologic examination as distal denervation involving the hands and arms.3
- Serum creatine kinase (CK) levels are elevated in about 75% of affected individuals.3
- Using the DNA test for FSHD, the deletion of the EcoRI “short fragment” is found in 85-95% of patients with the clinical features of FSHD.3
- A muscle biopsy is valuable in cases where there is a negative family history and the diagnosis is still in doubt. It provides confirmation that the underlying disorder is myopathic in nature and helps to exclude other primary muscle diseases that may present similar to FSHD.3
The prognosis for FSHD can be variable.3 An affected parent’s disability from FSHD cannot accurately predict the severity of their affected child’s disease. Progressiveness and the extent of muscle loss may also vary among FSHD patients --- some may need a wheelchair3, whereas others have limited difficulties in activities of daily living (ADLs). Lifespan is usually not affected3.
Physiatrists can help monitor progress of FSHD and orthopedists can assist with mobility and functional problems of the musculoskeletal system. Physical therapy can also help patients maintain flexibility, while occupational therapy can aid in teaching the patient how to best use physical aids as they are needed to perform ADLs.
Though there is no known cure for FSHD, a definitive molecular diagnosis is helpful to:
- Alleviate the affected individual’s anxiety of having a previously undiagnosed disorder
- Provide useful information for the prognosis for the individual’s particular disease
- Provide individuals information regarding genetic counseling and family planning
It is hoped that ongoing molecular genetic research will lead to therapies and cures for the many patients with neurogenetic disorders.
Athena Diagnostics, Inc. is proud to announce the introduction of its FSHD DNA testing service. This assay provides a diagnosis for the physican and the patient so that appropriate medical decisions can be made.
Methodology
Direct testing for the FSHD deletion mutation (a deletion on chromosome 4q35) is performed by EcoRI and EcoRI/BlnI restriction endonuclease digestion4 followed by Southern blot analysis of pulsed-field gel electrophoresed DNA hybridized with probe UR800.
