BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for Facioscapulohumeral Muscular Dystrophy

DESCRIPTION

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy and involves progressive weakness and wasting of the facial muscles (facio), and shoulder and upper arm (scapulohumeral) muscles. The weakness is often most evident in the muscles of the face, resulting in difficulty smiling and whistling, and reduced facial expression. The weakness in the shoulder muscles causes the scapula to protrude from the back (“winging of the scapula”). The muscles are typically affected asymmetrically, and with progression, the lower extremities, both proximal and distal, become involved. The severity of the disease is highly variable, ranging from mildly to severely affected, with approximately 20% of individuals eventually requiring a wheelchair. Non-muscular manifestations include retinal vascular abnormalities which can result in significant loss of vision; however, only about 1% of individuals with FSHD experience visual acuity loss.  Most people with FSHD will eventually develop high-frequency hearing loss, which is usually not noticeable, and only detected by audiogram. FSHD usually presents between the ages of 6 and 20 years, and life expectancy is not shortened. It is estimated that 4-5 people per 100,000 populations have FSHD. FSHD tends to progress slowly and affects males and females equally. 

FSHD is likely to be caused by inappropriate expression of the gene DUX4 in muscle cells. The most common form of FSHD (95%) is designated FSHD1, and these individuals have a D4Z4 allele of between 1 and 10 repeat units. The remaining 5% of individuals who don’t have FSHD1 are designated as FSHD2, which is clinically indistinguishable from FSHD1. If FSHD1 testing is negative, testing for FSHD2 and testing of the SMCHD1 gene should be considered.

There is currently no treatment or prevention of symptoms of FSHD. Clinical management is directed at surveillance to identify possible FSHD-related complications and to improve quality of life (e.g., assist devices, physical therapy, orthoses to improve mobility and prevent falls).

POLICY

IMPORTANT REMINDERS

ADDITIONAL INFORMATION 

Genetic testing is considered laboratory-developed services and subject only to the general laboratory operational regulation under the Clinical Laboratory Improvement Amendments (CLIA) of 1988. Laboratories performing clinical tests must be certified for high complexity testing under CLIA.

There is a lack of well-designed evidence-based studies in peer review journals to determine whether the genetic testing for facioscapulohumeral muscular dystrophy in individuals with no clinical signs of the disease would change the individual’s medical management. Further studies are needed to establish the clinical utility of these tests and the long-term follow-up of the individuals.

SOURCES 

American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine. (2015, July) Evidence-based guideline summary: evaluation, diagnosis, and management of facioscapulohumeral muscular dystrophy: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Retrieved June 3, 2016 from http://www.guideline.gov (NGC: 010776).

BlueCross BlueShield Association. Medical Policy Reference Manual. (2:2017). Genetic testing for facioscapulohumeral muscular dystrophy (2.04.105). Retrieved March 22, 2017 from BlueWeb. (14 articles and/or guidelines reviewed)

Gaillard, M., Roche, S., Dion, C., Tasmadjian, A., Bouget, G., Salort-Campana, E., et al. (2014). Differential DNA methylation of the D4Z4 repeat in patients with FSHD and asymptomatic carriers. Neurology, 83 (8), 733-742. Abstract retrieved March 21, 2017 from PubMed database.

Lee, G. D., Chen, V. M., Barnes, A. C., Goldman, D. R., & Duker, J. S. (2014). Retinal telangiectasis detected during a vision screening examination in a child with hearing loss led to the diagnosis of facioscapulohumeral muscular dystrophy. Journal of American Association for Pediatric Ophthalmology and Strabismus, 18 (3), 303-305. Abstract retrieved March 21, 2017 from PubMed database.

Lemmers, R. J., O'Shea, S., Padberg, G. W., Lunt, P. W., & van der Maarel, S. M. (2012). Best practice guidelines on genetic diagnostics of facioscapulohumeral muscular dystrophy: Workshop 9th June 2010, LUMC, Leiden, the Netherlands. Neuromuscular Disorders, 22 (5), 463-470.

Narayanaswami, P., Weiss, M., Selcen, D., David, W., Raynor, E., Carter, G., et al. (2014). Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular and Electrodiagnostic Medicine. Neurology, 83 (16), 1453-1463.

Pastorello, E., Cao, M., & Trevisan, C. P. (2012). Atypical onset in a series of 122 cases with facioscapulohumeral muscular dystrophy. Clinical Neurology and Neurosurgery, 114 (3), 230-234. (Level 4 evidence - Independent review)

Ricci, G., Zatz, M., & Tupler, R. (2014). Facioscapulohumeral muscular dystrophy: more complex than it appears. Current Molecular Medicine, 2014. Abstract retrieved May 21, 2015 from PubMed database.

Statland, J., Donlin-Smith, C. M., Tapscott, S. J., van der Maarel, S., & Tawil, R. (2014). Multiplex screen of serum biomarkers in facioscapulohumeral muscular dystrophy. Journal of Neuromuscular Disease, 1, (2), 181-190. Abstract retrieved May 21, 2015 from PubMed database.

Tawil, R., van der Maarel, S., Padberg, G. W., & van Engelen, B. G. M. (2010). 171st ENMC international workshop:  Standards of care and management of facioscapulohumeral muscular dystrophy. Neuromuscular Disorders, 20 (7), 471-475.

van der Maarel, S. M., Tawil, R., & Tapscott, S. J. (2011). Facioscapulohumeral muscular dystrophy and DUX4: breaking the silence. Trends in Molecular Medicine, 17 (5), 252-258. (Level 5 evidence)

Winston, J., Duerden, L., Mort, M., Frayling, I., Rogers, M., & Upadhyaya, M. (2015). Identification of two novel SMCHD1 sequence variants in families with FSHD-like muscular dystrophy. European Journal of Human Genetics (2015) 23, 67-71. (Level 5 evidence - Independent review)

ORIGINAL EFFECTIVE DATE:  1/11/2014

MOST RECENT REVIEW DATE:  5/11/2017

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