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CE / CME
Integrating Genetics Into Pediatric SNHL Care Planning: The Role of Audiology
Physician Assistants/Physician Associates: 0.50 AAPA Category 1 CME credit
Physicians: maximum of 0.50 AMA PRA Category 1 Credit™
Nurse Practitioners/Nurses: 0.50 Nursing contact hour
Released: July 30, 2026
Expiration: July 29, 2027
Activity
Integrating Genetic Testing Results in SNHL Management Planning
Comprehensive gene panel testing for hearing loss is increasingly used to evaluate congenital, childhood-onset, progressive, and familial SNHL. It can clarify etiology, inform recurrence risk, guide surveillance for syndromic features, and support discussions on management planning, including cochlear implant and gene therapy counseling for certain genotypes.5,6
However, audiology HCPs often encounter genetic testing results that include both clear pathogenic and VUS findings. The clinical challenge here is not to simply read the results, but to translate them appropriately and explain the phenotype and which findings change the management planning.
Patient Case 2: Sarah, 2-Month-Old Girl With Bilateral Severe to Profound SNHL
As an audiologist practicing in an academic setting, you are with Sarah and her family. Sarah is a 2-month-old girl who was referred for audiologic follow-up after her newborn hearing screening. Diagnostic testing is consistent with bilateral severe to profound SNHL, with diagnostic ABR showing absent or markedly elevated responses bilaterally. Tympanometry returns normal, and otoacoustic emissions are absent.
Sarah’s mother had an uncomplicated pregnancy and delivery, and there is no known history of childhood hearing loss in the family. Congenital CMV testing was not performed in the newborn period.
Physical findings identify no obvious dysmorphic features, renal symptoms, pigmentary differences, vestibular complaints, or cardiac history documented to date.
Comprehensive gene panel testing for hearing loss was ordered by the genetics team. Her genetic testing results identify 1 pathogenic variant in GJB2, which is associated with autosomal recessive nonsyndromic SNHL, and a VUS in MYO7A, a gene associated with both nonsyndromic and syndromic (ie, Usher syndrome) hearing loss depending on the genotype and inheritance context.7,8
Sarah’s family asks, “Does this mean Sarah has Usher syndrome? Does this change whether we pursue cochlear implants? Are there any gene therapies available?”
Principles of Variant Classification
Genetic testing typically classifies any identified variants into 1 of 5 categories: pathogenic, likely pathogenic, benign, likely benign, and VUS. Per the ACMG and Association of Molecular Pathology’s widely used framework, these classifications are based on multiple evidence types, including population frequency, predictions, functional data, co-occurrence and segregation studies, case-based observations, and consistency with the known disease.9,10
For audiology HCPs, the key point here is that variant classification does not equal a diagnosis. That is, variants cannot be interpreted in isolation.11 Although 1 variant might be identified as “pathogenic,” whether it explains the patient’s hearing loss depends on several factors, such as the gene-disease relationship, inheritance pattern, zygosity, and phase. Further consideration should determine whether the phenotype matches the expected disease, whether any other variants are required and identified, and whether additional clinical features are present that suggest a syndromic diagnosis.
For example, a single pathogenic variant in an autosomal recessive gene may only indicate carrier status unless a second pathogenic or likely pathogenic variant is identified. In turn, a VUS generally should not be used as evidence for a genetic diagnosis.7
What Is a VUS?
A VUS is a genetic finding for which the available evidence is insufficient to classify it as pathogenic or benign. It is neither a positive nor a negative result, hence the “uncertain” in its naming convention.
Furthermore, a VUS should not be used as a basis for clinical decision-making. Instead, genetics should work to determine if the VUS is pathogenic or benign before using it to inform management planning in genetic hearing loss.7,9
In Sarah’s case, the MYO7A VUS finding does not establish a diagnosis of MYO7A-related hearing loss or Usher syndrome. It should not, by itself, trigger a need for syndromic surveillance, change her cochlear implant candidacy, or confirm a definitive recurrence risk. The appropriate response is to interpret the VUS in context with other key factors and coordinate with genetics for follow-up, which might include parental testing, segregation analysis, periodic reanalysis, and phenotype-driven evaluation.
This principle does not ask audiology HCPs to reclassify a VUS independently. Rather, HCPs must understand how its uncertainty should be communicated to families and how it affects management planning for the specific patient.
Feedback on Counseling About a VUS
Although a VUS does not confirm a molecular diagnosis, it should not be dismissed as irrelevant either. The appropriate response is to explain the uncertainty of the variant, avoid overinterpretation, and coordinate with genetics for follow-up to inform contextual interpretation and need for reclassification.9 Furthermore, cochlear implant evaluation should proceed based on audiologic and developmental criteria.
Linking Genotype to Prognosis
As mentioned, a genetic diagnosis also informs patients’ prognosis. This can support counseling with families about the expected natural history of their child’s hearing loss and management planning, including cochlear implant and gene therapy evaluation. But the level of confidence in determining prognosis highly depends on the genetic testing results.5,6
When Genotype Is Informative
For audiology HCPs, a confirmed genotype can inform counseling on whether patients’ hearing loss is expected to be stable or progressive; vestibular, visual, renal, cardiac, or other features may emerge; anatomy or neural integrity may affect cochlear implant outcomes; family members may benefit from testing; and patients may be eligible for gene therapy or clinical trial participation.5,6
For example, many children with severe to profound genetic SNHL are candidates for timely cochlear implant evaluation, and earlier access to sound through appropriately selected amplification or implantation supports enhanced spoken language development and communication skills when that is the family’s goal.12
When Genotype Is Not Diagnostic…Yet
In Sarah’s case, genetic testing results do not yet provide a clear molecular explanation for her hearing loss. A single pathogenic GJB2 variant is insufficient to confirm autosomal recessive nonsyndromic GJB2-related hearing loss unless a second pathogenic or likely pathogenic variant is found. The MYO7A VUS does not establish a MYO7A-related hearing loss diagnosis.
Therefore, Sarah’s phenotype, developmental needs, imaging, medical evaluation, and family goals should inform counseling on cochlear implant evaluation. Although her genetic findings remain relevant, they should not override standard assessment of cochlear implant eligibility.13,14
A balanced statement to share with Sarah’s family may include: “Sarah’s genetic testing results provide us with useful information, but they do not yet confirm an explanation for her hearing loss. The uncertain MYO7A finding does not mean Sarah has Usher syndrome. From an audiology standpoint, we should continue timely evaluation for her hearing intervention options, including cochlear implant evaluation if the team agrees she meets eligibility criteria.”
Identifying Surveillance Needs for Syndromic vs Nonsyndromic Hearing Loss
If pediatric patients have a confirmed genetic SNHL diagnosis associated with retinal degeneration, renal or thyroid disease, cardiac arrhythmia, or other syndromic manifestations, targeted surveillance is clinically appropriate. For example, a confirmed Usher syndrome diagnosis supports annual ophthalmologic evaluation and longitudinal surveillance of patients’ visual health.15
We now know that a VUS alone is not sufficient to diagnose syndromic SNHL. However, it can justify careful phenotype review and discussion with genetics, especially when the specified gene is associated with clinically important syndromic outcomes. For example, in Sarah’s case, it would be appropriate to not tell her family she has Usher syndrome based on the VUS finding. Audiology HCPs may then ask themselves if there are other clinical features that increase suspicion of relevant syndromic manifestations, such as vestibular delay, balance concerns, or visual symptoms. This approach recognizes that some syndromic features may not yet be apparent in infancy.3
The HCP should coordinate with genetics to determine if parental testing, phase determination, or periodic reanalysis is appropriate, and consider whether baseline ophthalmology evaluation is reasonable for Sarah based on her overall clinical picture and genetic findings, not because a VUS is diagnostic. This is critical to understand because overinterpreting a VUS can cause unnecessary anxiety, inappropriate referrals, and misdirected care. However, ignoring it entirely is not the answer either. If ignored, patients may see missed opportunities for careful follow-up and future reclassification.
Balanced Discussions With Families About Gene Therapy
The good news is that the treatment landscape for genetic hearing loss is rapidly evolving with the expansion of gene therapy. When counseling families about gene therapy for pediatric SNHL, your communication must be accurate, specific, and restrained.
As of April 2026, the FDA granted accelerated approval to lunsotogene parvec-cwha, a dual adeno-associated virus vector-based gene therapy. It is indicated to treat pediatric and adult patients with severe to profound or profound SNHL associated with OTOF variants (molecularly confirmed), preserved outer hair cell function, and no prior cochlear implant.16,17
This does not mean that gene therapy is available or appropriate for all cases of genetic SNHL. That is, most genetic etiologies of pediatric SNHL remain outside the approved indication for gene therapy, and those that may be relevant are currently in clinical trials or preclinical development.
A useful counseling framework for discussing gene therapy with families generally comprises:
- Naming the gene and inheritance pattern: “Eligibility for gene therapy highly depends on the exact gene and variant pattern identified via genetic testing.”
- Avoiding broad promises: “A genetic testing result does not automatically mean a gene therapy is available or appropriate.”
- Distinguishing between an approved vs investigational treatment option: “The FDA recently approved a gene therapy for OTOF-related hearing loss; others remain in clinical development.”
- Connecting families to appropriate specialists: “Questions about eligibility for gene therapy should be reviewed with genetics, otology/neurotology, and centers experienced with genotype-specific treatment pathways.”
- Continuing standard management planning: “Emerging gene therapies should not delay timely hearing access with cochlear implant, spoken language development, or family-centered communication support.”
In Sarah’s case, genetic testing results do not confirm a diagnosis of biallelic OTOF-related hearing loss. Therefore, it would be inappropriate to suggest to her family that this gene therapy is a treatment option at this time.
A family-focused, balanced statement to share with Sarah’s family might look like: “Gene therapy is advancing quickly, and 1 option was recently approved by the FDA for a specific OTOF-related hearing loss. Sarah’s current genetic findings do not confirm that diagnosis, so she would not qualify for this treatment option. The next steps are to continue standard management planning and complete genetic counseling with an expert’s interpretation of the results. We can revisit the discussion on her eligibility for gene therapy if new findings emerge.”
Feedback on Gene Therapy Discussion
Gene therapy for genetic hearing loss is genotype specific and should be discussed accurately without overpromising its availability or potential benefit. In addition, a single VUS finding or pathogenic variant in a recessive gene does not establish eligibility for a gene therapy, especially since neither confirms a molecular diagnosis. The appropriate response is to acknowledge the family’s question and explain that eligibility for gene therapy requires a confirmed and relevant genotype. HCPs should then coordinate with genetics and otology/neurotology as needed and continue evidence-based management planning, including cochlear implant evaluation when appropriate.
Key Takeaways
A pathogenic variant is clinically meaningful only in the correct context. For recessive inheritance patterns, 1 pathogenic variant may indicate carrier status, but it does not confirm etiology unless a second causative variant is identified.
A VUS should not be used to confirm a molecular diagnosis, nor should it independently inform patients’ eligibility for cochlear implant, presence of syndromic vs nonsyndromic disease, or major clinical decisions. That said, HCPs must not ignore a VUS finding entirely. It should be interpreted in the context of key patient-specific factors and documented, discussed in genetic counseling, and potentially reanalyzed in follow-up.
Although genetic findings can inform prognosis, standard audiologic, developmental, imaging, and medical criteria remain central for management planning. That is why evaluation for cochlear implant must remain phenotype driven and should not be delayed due to genetic testing access or interpretation.
In cases of syndromic SNHL, surveillance strategies should be targeted, and a confirmed syndromic diagnosis should prompt HCPs to develop an appropriate plan. VUS findings may support further evaluation or surveillance if the clinical phenotype raises concern, but they should not be overinterpreted.
Finally, counseling on gene therapy must be genotype specific. This is critical because the landscape is expanding with the recent FDA approval of gene therapy for OTOF-related hearing loss. Most gene therapies for genetic SNHL remain investigational. Therefore, families should receive accurate and informative counseling that does not overpromise on its availability or benefit.
Patient Case 2: Resolution With Sarah and her Family
In resolving the patient case with Sarah and her family, you explain to her parents that her genetic testing results do not establish a definitive molecular diagnosis. The MYO7A VUS finding does not mean Sarah has Usher syndrome, and it should not delay cochlear implant evaluation. You refer the family for follow-up with genetics to discuss whether parental testing, variant phasing, or future reanalysis may clarify the findings.
Next, you emphasize the need for timely management of Sarah’s severe to profound SNHL, including management planning with established hearing technologies, early intervention, and communication support. This includes a referral for cochlear implant evaluation.
You then discuss the syndromic surveillance strategy in collaboration with genetics and the broader care team, with special care taken not to present the VUS finding as diagnostic.
Finally, you acknowledge the family’s question about gene therapy, stating that advances are significant and evolving. Although there is an FDA-approved therapy for molecularly confirmed biallelic OTOF-related hearing loss, you tell the family that Sarah’s current genetic findings do not indicate eligibility for that treatment option. You encourage them to revisit this question if additional genetic information becomes available.