Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018
Marfan Syndrome (MFS) is a systemic connective tissue disorder that has a high degree of clinical variability and overlapping phenotypes with other syndromes and disorders. In Marfan syndrome, many body systems can be affected, including the heart, blood vessels, bones, tendons, cartilage, eyes, nervous system, skin and lungs. In most cases, Marfan syndrome is inherited. The pattern is autosomal dominant, occurring equally in men and women and can be inherited from just one parent with Marfan syndrome. The gene is fibrillin-1 or FBN-1. Individuals who have Marfan syndrome have a 50 percent chance of passing along the disorder to each of their children.
The diagnosis of most suspected connective tissue disorders can be made based on clinical findings and family history. As with other connective tissue disorders, Marfan syndrome is associated with a predisposition to the development of progressive thoracic aortic aneurysm (TAAs) and dissection (TAAD). Accurate diagnosis can lead to changes in clinical management, including surveillance of the aorta and surgical repair of the aorta when necessary, as well as surveillance for multisystem involvement in syndromic forms of TAAD.
Genetic testing for Marfan syndrome, thoracic aortic aneurysm and dissection and related disorders is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Genetic testing panels for Marfan syndrome, thoracic aortic aneurysms and dissections and related disorders that are not limited to focused mutation testing are considered investigational.
Genetic testing for Marfan syndrome, thoracic aortic aneurysms and dissections and related disorders is considered medically appropriate if ANY ONE of the following are met:
Individual presents with signs and symptoms of connective tissue disorder and ALL of the following are met:
Definitive diagnosis cannot be made using established criteria
Testing limited to 1 or more of the following genes:
Individual is asymptomatic with ALL of the following:
Known familial pathogenic mutation
Targeted mutation testing limited to 1 or more of the following:
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
Laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). Laboratories that offer LDTs must be licensed by CLIA for high-complexity testing.
American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery. (2010). Guidelines for the diagnosis and management of patients with thoracic aortic disease. Journal of the American College of Cardiology, 55 (14), 27-129.
American College of Medical Genetics. (2012, January). ACMG Practice Guidelines. Evaluation of the adolescent or adult with some features of Marfan syndrome. Retrieved May 6, 2015 from http://www.acmg.net.
BlueCross BlueShield Association. Evidence Positioning System. (3:2020). Genetic testing for Marfan syndrome, thoracic aortic aneurysms and dissections, and related disorders (2.04.129). Retrieved November 10, 2020 from http://www.evidencepositioningsystem.com. (14 articles and/or guidelines reviewed)
Campens, L., Callewaert, B., Mosquera, L., Renard, M., Symoens, S., De Paepe, A., et al. (2015). Gene panel sequencing in heritable thoracic aortic disorders and related entities - results of comprehensive testing in a cohort of 264 patients. Orphanet Journal of Rare Diseases, 10 (9). DOI 10.0086/s13023-014-0221-6. (Level 3 evidence)
Guisti, B., Nistri, S., Sticchi, E., De Cario, R., Abbate, R., Gensini, G., et al. (2016). A case based approach to clinical genetics of thoracic aortic aneurysm/dissection. BioMed Research International, 9579654. Abstract retrieved March 22, 2017 from PubMed database.
Proost, D., Vandeweyer, G., Meester, J., Salemink, S., Kempers, M., Ingram, C., et al. (2015). Human mutation. Performant mutation identification using targeted next-generation sequencing of 14 thoracic aortic aneurysm genes. Official Journal Human Genome Variation Society. Retrieved June 22, 2013 from PubMed database.
Schubert, J. A., Landis, B. J., Shikany, A. R., Hinton, R. B., & Ware, S. M. (2016). Clinically relevant variants identified in thoracic aortic aneurysm patients by research exome sequencing. American Journal of Medical Genetics Part A, 170A (5), 1288-1294. Abstract retrieved March 22, 2017 from PubMed database.
Wooderchak-Donahue, W., VanSant-Webb, C., Tyrdik, T., Plant, P., Lewis, T., Stocks, J., et al. (2015). Clinical utility of a next generation sequencing panel assay for Marfan and Marfan-like syndromes featuring aortopathy. American Journal of Medical Genetics. Abstract retrieved June 22, 2015 from PubMed database.
ORIGINAL EFFECTIVE DATE: 10/10/2015
MOST RECENT REVIEW DATE: 1/14/2021
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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