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Coverage criteria policies

Genetic Testing for Connective Tissue, Skeletal, and Integumentary Disorders

These services may or may not be covered by your HealthPartners plan. Please see your plan documents for your specific coverage information. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage.

Administrative Process

Prior authorization is required for genetic testing for connective tissue, skeletal, and integumentary disorders.

For prenatal diagnostic genetic testing, see the Genetic Testing: Carrier Screening, Prenatal Screening, Prenatal Diagnosis, and Infertility Evaluation coverage policy.

For genetic testing for multiple congenital anomalies, see the Genetic Testing for Neurodevelopmental Disorders, Epilepsy and Seizure Disorders, and Multiple Congenital Anomalies coverage policy.


Indications that are covered

Single-gene and multiple-gene analysis for these conditions is covered when criteria 1-3 listed below are met:

  • Ehlers-Danlos syndrome (EDS), vascular type
  • Epidermolysis bullosa/Kindler syndrome
  • Hereditary hemorrhagic telangiectasia
  • Inherited ichthyoses
  • Legius syndrome
  • Loeys-Dietz syndrome
  • Marfan syndrome
  • Neurofibromatosis, types 1 and 2
  • Ocular albinism
  • Osteogenesis imperfecta and/or dentinogenesis imperfecta
  • Schwannomatosis
  • Thoracic Aortic Aneurysm and Dissection (TAAD)
  1. The test is ordered by a board-certified cardiologist; dermatologist; neurologist; ophthalmologist; rheumatologist; or geneticist; a licensed, certified genetic counselor; or an advanced-practice nurse in cardiology; dermatology, neurology; ophthalmology, rheumatology, or genetics, and is expected to directly impact management of one of the above specific, clinically-suspected, connective tissue, skeletal, or integumentary disorders.
  2. The member has received genetic counseling with a board-certified genetic counselor or medical geneticist who is not affiliated with the commercial testing laboratory, if applicable.
  3. The member has a personal history consistent with the condition being evaluated or a first-degree blood relative has been diagnosed with the condition being evaluated.

Genetic testing for connective tissue, skeletal, and integumentary disorders other than those listed above is subject to a review for medical necessity, based on current clinical literature and expert recommendations, unless listed below as an indication that is not covered.

Indications that are not covered

  1. Genetic testing for connective tissue, skeletal, and integumentary disorders is not covered and is considered not medically necessary when test results will not directly impact the treatment or management of a condition because the testing is not expected to restore or maintain the member’s health, prevent deterioration of the member’s condition, nor prevent the reasonably likely onset of a health problem or detect an incipient problem.
  2. Repeat testing of a unique analyte using the identical method of analysis is not covered and is considered not medically necessary because it is not considered an appropriate frequency of care.
  3. Multiple-gene panels that include genes not associated with the specific condition under evaluation are not covered and are considered not medically necessary because they are not considered an appropriate type of service for the member’s condition.
  4. Single-gene and multiple-gene assays for the following conditions are considered experimental/investigational, because reliable evidence does not permit conclusions concerning safety, effectiveness, or effect on health outcomes, including, but not limited to:
  • Anhidrotic ectodermal dysplasia
  • Ehlers-Danlos syndrome, except as described above
  • Familial partial lipodystrophy
  • Isolated abdominal aortic aneurysm
  • Hereditary multiple osteochondromas
  • Homocystinuria
  • Mitral valve prolapse syndrome
  • Osteoporosis
  • Peripheral pulmonary stenosis
  • Pseudoxanthoma elasticum


First-degree relative is an individual’s parent, sibling, or child

Genetic refers to inherited traits or disorders, or those that result from acquired changes in genetic makeup.

Genetic Testing involves analysis of human genetic material (such as DNA or chromosomes) to identify whether a person has a particular inherited trait or disorder, or an acquired genetic change, or whether he or she carries a gene that could lead to a specific disease or condition.

If available, codes are listed below for informational purposes only, and do not guarantee member coverage or provider reimbursement. The list may not be all-inclusive.




Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); genomic sequence analysis panel, must include sequencing of at least 9 genes, including FBN1, TGFBR1, TGFBR2, COL3A1, MYH11, ACTA2, SLC2A10, SMAD3, and MYLK


Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity syndrome); duplication/deletion analysis panel, must include analyses for TGFBR1, TGFBR2, MYH11, and COL3A1

CPT Copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association


This information is for most, but not all, HealthPartners plans. Please read your plan documents to see if your plan has limits or will not cover some items. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage. These coverage criteria may not apply to Medicare Products if Medicare requires different coverage. For more information regarding Medicare coverage criteria or for a copy of a Medicare coverage policy, contact Member Services at 952-883-7979 or 1-800-233-9645.


  1. Beary, J. F. (2015). Osteogenesis imperfecta: Clinical features and diagnosis. In: H. F. Firth & E. TePas (Eds.). UpToDate. Location: Waltham, MA.
  2. Bruckner, A. L. (2015). Diagnosis of epidermolysis bullosa. In: J. L. Hand & R. Corona (Eds.). UpToDate. Location: Waltham, MA.
  3. Choate, K. (2016). Overview of the inherited ichthyoses. In: J. L. Hand & R. Corona (Eds.). UpToDate. Location: Waltham, MA.
  4. Evans, D. G. (2017). Neurofibromatosis type 2. In: J. S. Loeffler, P. Y. Wen, & A. F. Eichler (Eds.). UpToDate. Location: Waltham, MA.
  5. Has, C. (2015). Kindler syndrome. In: J. L. Hand & R. Corona (Eds.). UpToDate. Location: Waltham, MA.
  6. Hayes, Inc. (2014). Nonsyndromic peripheral pulmonary stenosis; PPS.  Philadelphia, PA: Hayes, Inc.
  7. Hayes, Inc. (2015). Ehlers-Danlos syndrome (EDS), classic type. Philadelphia, PA: Hayes, Inc.
  8. Hiratzka, L. F., Bakris, G. L., Beckman, J. A., Bersin, R. M., Carr, V. F., Casey, D. E., . . . Williams, D. M. (2010). 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation, 121, e266-e369.
  9. B. R. Korf. (2015). Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis. In: M. C. Patterson, H. V. Firth, & E. TePas (Eds.). UpToDate. Location: Waltham, MA.
  10. Miner, G. H., Faries, P. L., Costa, K. D., Hanss, B. G., & Marin, M. L. (2015). An update on the etiology of abdominal aortic aneurysms: implications for future diagnostic testing. Expert Review of Cardiovascular Therapy, 13, 1079-1090.
  11. Pauker, S. P., & Stoler, J. (2016). Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. In: P. H. Schur & P. L. Roman (Eds.). UpToDate. Location: Waltham, MA.
  12. Pepin, M. G., Schwarze, U., Rice, K. M., Liu, M., Leistritz, D., & Byers, P. H. (2014). Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). Genetics in Medicine, 16, 881-888.
  13. Picker, J. D., & Levy, H. L. (2014). Homocystinuria caused by cystathionine beta-synthase deficiency. In: R. A. Pagon, M. P. Adam, H. H. Ardinger, S. E. Wallace, A. Amemiya, L. J. H. Bean, . . . K. Stephens (Eds.). GeneReviews. Location: Seattle, WA.
  14. Pislaru, S., & Enriquez-Sarano, M. (2017). Definition and diagnosis of mitral valve prolapse. In: C. M. Otto & S. B. Yeon (Eds.). UpToDate. Location: Waltham, MA.
  15. Regalado, E. S., Guo, D. C., Estrera, A. L., Buja, L. M., & Milewicz, D. M. (2014). Acute aortic dissections with pregnancy in women with ACTA2 mutations. American Journal of Medical Genetics Part A, 164A, 106-112.
  16. Regalado, E. S., Guo, D. C., Prakash, S., Bensend, T. A., Flynn, K., Estrera, A., . . . Milewicz, D. M. (2015). Aortic disease presentation and outcome associated with ACTA2 mutations. Circulation: Cardiovascular Genetics, 8, 457-464.
  17. Shalhub, S., Black, J. H., Cecchi, A. C., Xu, Z., Griswold, B. F., Safi, H. J., . . . McDonnell, N. B. (2014). Molecular diagnosis in vascular Ehlers-Danlos syndrome predicts pattern of arterial involvement and outcomes. Journal of Vascular Surgery, 60, 160-169.
  18. Shovlin, C. (2017). Clinical manifestations and diagnosis of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome). In: L. L. K. Leung & J. S. Timauer (Eds.). UpToDate. Location: Waltham, MA.
  19. Tis, J. E. (2017). Benign bone tumors in children and adolescents. In: W. Phillips & M. M. Torchia (Eds.). UpToDate. Location: Waltham, MA.
  20. Wellbrock, J., Sheikhzadeh, S., Oliveira-Ferrer, L., Stamm, H., Hillebrand, M., Keyser, B., . . . Fiedler, W. (2014). Overexpression of Gremlin-1 in patients with Loeys-Dietz syndrome: implications on pathophysiology and early disease detection. PLoS One, 9, e104742.
  21. Wooderchak-Donahue, W., VanSant-Webb, C., Tvrdik, T., Plant, P., Lewis, T., Stocks, J., . . . Bayrak-Toydemir, P. (2015). Clinical utility of a next generation sequencing panel assay for Marfan and Marfan-like syndromes featuring aortopathy. American Journal of Medical Genetics Part A, 167A, 1747-1757.
  22. Wright, M. J., & Connolly, H. M. (2016). Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders. In: H. C. Dietz & S. B. Yeon (Eds.). UpToDate. Location: Waltham, MA.
  23. Wright, T. S. (2016). The genodermatoses. In: H. V. Firth, J. L. Hand, & R. Corona (Eds.). UpToDate. Location: Waltham, MA.
  24. Zarate, Y. A., Sellars, E., Lepard, T., Tang, X., & Collins, R. T. (2016). Aortic dilation, genetic testing, and associated diagnoses. Genetics in Medicine, 18, 356-363.

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Policy activity

  • 06/21/2016 - Date of origin
  • 09/01/2017 - Effective date
Review date
  • 06/2017
Revision date
  • 09/01/2017

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