BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for Marfan Syndrome, Thoracic Aortic Aneurysms and Dissections and Related Disorders

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.





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

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 (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.




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