Highmark Commercial Medical Policy - Pennsylvania

Medical Policy: L-231-001
Topic: Genetic Testing for Nonsyndromic Hearing Loss and Deafness
Section: Laboratory
Effective Date: July 1, 2018
Issue Date: July 2, 2018
Last Reviewed: March 2018

Prelingual hearing loss affects about 1 out of every 500 individuals. Approximately 20% of cases are attributed to environmental causes, including viral (cytomegalovirus) or bacterial (meningitis) infection, trauma, prenatal exposure to certain drugs, and other environmental factors. The remaining 80% of cases are thought to be genetic, either as part of a recognized genetic syndrome, or as isolated, nonsyndromic hearing loss (NSHL).

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

Known Familial Mutation Analysis may be considered medically necessary when the following are met:

Procedure Codes

GJB2 Sequencing may be considered medically necessary when the following are met: 

Procedure Codes

GJB6 Common Variant Analysis for 309kb and 232kb Deletions may be considered medically necessary when the following are met:

Procedure Codes

MT-RNR1 Targeted Mutation Analysis for m.1555A>G Mutation may be considered medically necessary when the following are met:

Procedure Codes

MT-RNR1 Sequencing may be considered medically necessary when the following are met:

Procedure Codes

MT-TS1 Sequencing may be considered medically necessary when the following are met:

Procedure Codes

Hearing Loss and Deafness Multigene Panel Testing

A multi-gene panel may be considered medically necessary when the following criteria are met: 

Procedure Codes
81400, 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408, 81430, 81431, 81479

Professional Statements and Societal Positions

  • In 2016, the International Pediatric Otolaryngology Group (IPOG) stated:

    • “In the setting of unilateral hearing loss, genetic testing has a limited role unless syndromic hearing loss is suspected.”

    • “After an audiogram and physical exam, comprehensive genetic testing (CGT) that relies on next generation sequencing (NGS) methodologies should guide subsequent workup in children with bilateral sensorineural hearing loss.”

    • “Diagnostic rates for single gene testing for GJB2/GJB6 vary significantly based on the patient's ethnicity, and do not outperform the diagnostic rates for comprehensive genetic testing. In cases where CGT is unavailable, single gene testing can be directed by the audiometric phenotype and ethnicity.”

    • The general consensus of the authors was that temporal bone imaging “should not be a routine part of the diagnostic algorithm for bilateral symmetric sensorineural hearing loss.”

  • In 2014, the American College of Medical Genetics and Genomics (ACMG) made the following recommendations:

  • A genetic evaluation is recommended for all cases of congenital deafness or hearing loss with onset in childhood or early adulthood. While the usefulness of ancillary testing (e.g. electrocardiogram, renal ultrasound, temporal bone imaging and ophthalmology examination) was mentioned, it was acknowledged that genetic testing via NGS panels would soon become more cost-effective. Cytomegalovirus (CMV) testing is important for cases of congenital hearing loss, but only accurate in the first 6 weeks of life.

  • Genetic testing to confirm a diagnosis of suspected syndromic hearing loss is recommended based on clinical findings. For apparently nonsyndromic hearing loss, a tiered approach was recommended: If the personal and family history is suggestive of a particular gene, single gene testing should be performed first. For simplex cases and cases with apparent autosomal recessive inheritance, the next step should be testing of GJB2 and GJB6. If single-gene testing is not diagnostic, testing via NGS panels, whole exome sequencing, or whole genome sequencing should be considered.

  • The statement stopped short of endorsing the use of NGS panels as a first-tier test, but noted they are “rapidly replacing” sequencing of the GJB2 and GJB6 loci and would soon be a more cost-effective alternative.

  • An expert-authored review of nonsyndromic hearing loss states:

  • “A comprehensive deafness-specific genetic panel that includes all genes implicated in nonsyndromic hearing loss and nonsyndromic hearing loss mimics is recommended as the initial genetic test.”

  • “Performing sequence analysis of GJB2 alone is not cost-effective unless it is limited to persons with severe-to-profound congenital nonsyndromic hearing loss. Offering single- gene testing of GJB2 reflexively to everyone with congenital hearing loss without regard to the degree of hearing loss is not evidence based and not cost effective.”

  • An expert-authored review on hereditary hearing loss and deafness likewise states that a multi-gene test is recommended for apparent nonsyndromic hearing loss, while individuals with features of syndromic hearing loss should be diagnosed with targeted genetic testing. Ancillary cardiac, ophthalmologic and renal evaluations are only recommended on the basis of genetic test results or clinical findings.

  • An expert-authored review on mitochondrial NSHL6 states that the diagnosis should be suspected in individuals with moderate-to-profound hearing loss and a family history suggestive of maternal inheritance (e.g. no transmission through a male), or onset of hearing loss after exposure to an aminoglycoside antibiotic.

    • To confirm the diagnosis: MT-RNR1 testing, beginning with targeted analysis for the m.1555A>G mutation, is recommended following aminoglycoside exposure. In the absence of aminoglycoside exposure, testing of both MT-RNR1 and MTTS1 is recommended. If these tests fail to confirm a diagnosis, mitochondrial genome sequencing can be considered.

    • An alternative strategy is to perform a multi-gene panel that includes both MT-RNR1 and MT-TS1, plus other genes of interest.

Place of Service: Outpatient

Genetic testing for NSHL is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of business

Denial Statements

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.


Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

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The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer: If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

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