Description

Marfan syndrome is a genetic disorder in which the body’s connective tissue is abnormal. The disorder affects many parts of the body; primarily, blood vessels, bones, connective tissue of the heart, covering of the spinal cord, eyes and lungs. Marfan syndrome diagnosis relies on a set of strict major and minor criteria known as the Ghent nosology, a scoring system developed to aid in the clinical diagnosis of Marfan syndrome. Two fundamental features of the Ghent nosology are aortic root dilatation and ectopia lentis. In the absence of a family history of Marfan syndrome, the presence of aortic root dilatation and ectopia lentis are sufficient to diagnose Marfan syndrome. Without these two conditions or a combination of systemic features described in the Ghent nosology, genetic testing may be required

to confirm a diagnosis. Even with the availability of genetic testing, establishing a diagnosis of Marfan syndrome depends heavily upon significant clinical findings.

Genetic Testing for Marfan Syndrome and Related Conditions

Effective Date: 03/01/2023
Revision Date: 03/01/2023
Review Date: 03/01/2023
Policy Number: HUM-0505-016

Coverage Determination

Any state mandates for genetic testing for familial TAAD, LDS or Marfan syndrome take precedence over this medical coverage policy.

Genetic testing may be excluded by certificate.

Please consult the member’s individual certificate regarding Plan coverage. Apply General Criteria for Genetic Tests when disease- or gene-specific criteria are not available on a medical coverage policy. For information regarding general criteria for genetic tests, please refer to Genetic Testing Medical Coverage Policy.

Familial Thoracic Aortic Aneurysm and Dissection (TAAD) – ACTA2, FBN1, LOX, MYH11, MYLK, PRKG1, SMAD3, TGFB2, TGFBR1 and TGFBR2 Genes

Humana members may be eligible under the Plan for genetic testing for familial TAAD when the following criteria are met:

• Pre- and post-test genetic counseling; AND
• Individual to be tested is affected and is being considered for prophylactic surgery for aortic dissection; OR
• Individual to be tested is unaffected and has an affected first-degree relative with a known pathogenic or likely pathogenic variant

Testing strategy: Test for known familial variant (KFV).

Loeys-Dietz Syndrome (LDS) – TGFBR1 and TGFBR2 Genes

Humana members may be eligible under the Plan for TGFBR1 and TGFBR2 gene testing for LDS when the following criteria are met:

• Pre- and post-test genetic counseling; AND
• Individual to be tested has an affected first-degree relative with a pathogenic or likely pathogenic variant. Testing strategy: Test for KFV; OR

To confirm or establish a diagnosis of LDS when at least 2 of the following are present:

• Aortic/arterial aneurysms/tortuosity
• Arachnodactyly
• Bicuspid aortic valve and patent ductus arteriosus
• Blue sclerae
• Camptodactyly
• Cerebral, thoracic or abdominal arterial aneurysms and/or dissections
• Cleft palate/bifid uvula
• Club feet
• Craniosynostosis
• Eosinophilic esophagitis/gastritis
• Ocular hypertelorism
• Pectus carinatum or pectus excavatum
• Scoliosis
• Talipes equinovarus
• Widely spaced eyes

Testing strategy: Begin with TGFBR2 gene sequencing. If negative, proceed with TGFBR1 gene sequencing.

Marfan Syndrome – FBN1 Gene

Humana members may be eligible under the Plan for FBN1 gene testing for Marfan syndrome when the following criteria are met:

• Pre- and post-test genetic counseling; AND
• Individual to be tested has an affected first-degree relative with a known pathogenic or likely pathogenic variant. Testing strategy: Test for KFV; OR
• Individual to be tested does not meet clinical diagnostic criteria for Marfan syndrome but diagnosis is highly suspected

Testing strategy: Begin with FBN1 gene sequencing. If negative, proceed to FBN1 gene deletion/duplication analysis.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Coverage Limitations

Humana members may NOT be eligible for genetic testing for TAAD, LDS or Marfan syndrome for any genes, indications or tests other than those listed above including, but may not be limited to:

• LDS for any gene other than TGFBR1 and TGFBR2 (81410, 81411)
• Marfan syndrome for any gene other than FBN1 (81410, 81411)
• TAAD for any gene (alone or in a panel) other than ACTA2, FBN1, LOX, MYH11, PRKG1, SMAD3, TGFB2, TGFBR1 and TGFBR2 including, but may not be limited to:
  • BGN
  • COL3A1*
  • EFEMP2
  • FBN2
  • FLNA
  • FOXE3
  • HCN4
  • MAT2A
  • MFAP5
  • MYLK
  • NOTCH1
  • SLC2A10
  • SMAD2
  • TGFB3
• To diagnose Marfan syndrome when a diagnosis can be established using clinical diagnostic criteria

* For information regarding COL3A1 gene testing for Ehler's Danlos syndrome, please refer to Genetic Testing for Ehlers-Danlos Syndrome Medical Coverage Policy.

These are considered experimental/investigational as they are not identified as widely used and generally accepted for the proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Humana members may NOT be eligible under the Plan for genetic testing for familial TAAD, LDS or Marfan syndrome when the individual to be tested is unaffected and an affected first-, second- or third-degree relative IS available for genetic testing (if the relative is unavailable [eg, deceased, declines genetic testing or inability to contact] for testing, apply disease or gene-specific criteria for the unaffected individual). This is considered not medically necessary as defined in the member’s individual certificate. Please refer to the member’s individual certificate for the specific definition.

Additional information about LDS, Marfan syndrome and TAAD may be found from the following websites:

Background

• National Library of Medicine
• The Marfan Foundation

Medical Alternatives

Alternatives to genetic testing for LDS and TAAD include, but may not be limited to, the following:

• Imaging (eg, angiography, echocardiography, computed tomography [CT], magnetic resonance imaging [MRI])

Physician consultation is advised to make an informed decision based on an individual’s health needs.

Humana may offer a disease management program for this condition.

The member may call the number on his/her identification card to ask about our programs to help manage his/her care.

Any CPT, HCPCS or ICD codes listed on this medical coverage policy are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes. Inclusion of a code does not guarantee coverage and or reimbursement for a service or procedure.