Description

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome is the most common form of hereditary stroke disorder and is caused by mutations of the NOTCH3 gene. This disorder is characterized by adult-onset (typically occurring before 60 years of age) recurrent ischemic stroke, cognitive decline progressing to dementia, history of migraine with aura, mood disturbance, apathy and diffuse white matter lesions and subcortical infarcts on neuroimaging.

Genetic testing may be used to aid in the diagnosis of CADASIL in a symptomatic individual when there are atypical findings on brain magnetic resonance imaging (MRI) and a family history of stroke or dementia. Genetic testing has also been proposed for an asymptomatic individual who has a first- or second-degree relative with a known pathogenic variant or who has been diagnosed with CADASIL.

For information regarding genetic testing for the following, please refer to Genetic Testing Medical Coverage Policy:

• DNA banking or preservation
• General population screening
• Individual 17 years of age or younger for adult-onset conditions
• Interpretation and reporting for molecular pathology procedure
• Polygenic risk score (PRS) and single nucleotide polymorphisms (SNPs)
• Repeat germline or somatic genetic testing
• Retrieved archival tissue

Humana recognizes that the field of genetic testing is rapidly changing and that other tests may become available.

Coverage Determination

Any state mandates for genetic testing 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 and Pharmacogenomics Tests when disease- or gene-specific criteria are not available on a medical coverage policy. For information regarding General Criteria for Genetic and Pharmacogenomics Tests, please refer to Genetic Testing Medical Coverage Policy.

CADASIL (NOTCH3 Gene)

Humana members may be eligible under the Plan for NOTCH3 gene testing to confirm a diagnosis of CADASIL when the following criteria are met:

1. Pre- and post-test genetic counseling; AND

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

• Individual has an affected first-, second- or third-degree relative with a pathogenic or likely pathogenic variant in the NOTCH3 gene (genetic testing should be limited to the known familial variant [KFV]); OR
• Individual exhibits 1 or more of the following characteristics of CADASIL:
  • Cognitive deficits; OR
  • Ischemic episodes; OR
  • Migraine headache with aura; OR
  • Mood disturbances (eg, adjustment disorder, apathy, bipolar disorder, delusional episodes, hallucinatory syndrome, moderate to severe depression or panic disorder); AND
• Individual to be tested has a first- or second-degree relative with a history of stroke or dementia; AND
• Presence of white matter hyperintensity lesions and/or lacunar infarcts detected by brain MRI

Coverage Limitations

Humana members may NOT be eligible under the Plan for genetic testing for CADASIL for any genes, indications or tests other than those listed above. This is considered experimental/investigational as it is not identified as widely used and generally accepted for any other proposed use 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 CADASIL for the following:

• KFV analysis using a multigene panel that includes the KFV

Background

Additional information about CADASIL may be found from the following websites:

• National Library of Medicine

Medical Alternatives

Alternatives to genetic testing for CADASIL include, but may not be limited to, the following:

• MRI of the brain
• Skin biopsy

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.

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

No code(s) identified

CPT® Category III Code(s)

Description

Comments

HCPcs Code(s)

Description

Comments

50265

Genetic counseling, under physician supervision, each 15 minutes

References

1. ECRI Institute. ECRIgene Genetic Test Hotline Response. NOTCH3 testing to diagnose or assess risk for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). https://www.ecri.org. Published April 2018. Accessed March 3, 2023.
2. Hayes, Inc. Genetic Test Evaluation (GTE) Report (ARCHIVED). Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). https://evidence.hayesinc.com. Published April 16, 2008. Updated April 18, 2012. Accessed March 3, 2023.
3. MCG Health. CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) - NOTCH3 gene. 26th edition. https://www.mcg.com. Accessed March 3, 2023.
4. Merck Manual: Professional Version. Vascular cognitive impairment and dementia. https://www.merckmanuals.com. Updated February 2023. Accessed March 3, 2023.
5. National Center for Biotechnology Information (NCBI). Genetic Testing Registry. CADASIL. https://www.ncbi.nlm.nih.gov/gtr. Published March 15, 2000. Updated March 14, 2019. Accessed March 3, 2023.
6. UpToDate, Inc. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). https://www.uptodate.com. Updated February 2023. Accessed March 3, 2023.

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Genetic Testing for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Syndrome Effective Date: 04/27/2023 Revision Date: 04/27/2023 Review Date: 04/27/2023 Policy Number: HUM-0586-005

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

UpToDate, Inc. Early-onset dementia in adults. https://www.uptodate.com. Updated February 2023. Accessed March 3, 2023.

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Genetic Testing for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Syndrome Effective Date: 04/27/2023 Revision Date: 04/27/2023 Review Date: 04/27/2023 Policy Number: HUM-0586-005

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

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

Appendix A

Pre- and Post-Test Genetic Counseling Criteria

Pre- and post-test genetic counseling performed by any of the following qualified medical professionals:

• Genetic counselor who is board-certified or board-eligible by the American Board of Medical Genetics and Genomics (ABMGG) or American Board of Genetic Counseling, Inc (ABGC) and is not employed by a commercial genetic testing laboratory; OR
• Genetic clinical nurse (GCN) or advanced practice nurse in genetics (APNG) who is credentialed by the Genetic Nursing Credentialing Commission (GNCC) or the American Nurses Credentialing Center (ANCC) and is not employed by a commercial genetic testing laboratory; OR
• Medical geneticist who is board-certified or board-eligible by ABMGG; OR
• Treating physician who has evaluated the individual to be tested and has completed a family history of three generations

Appendix B

Family Relationships

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