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Optimizing Genetic Evaluation in Pediatric Sensorineural Hearing Loss: A Practical Guide for Hearing Specialists
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
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Gene Therapy for Pediatric SNHL
Gene therapy is changing the therapeutic landscape for select forms of genetic SNHL. For otolaryngology HCPs, these developments create a new counseling challenge. Like Noah’s case, families may ask you about gene therapy early in patient care, sometimes before a genetic diagnosis is confirmed or standard hearing interventions are trialed.
The HCP’s role is to provide accurate, genotype-specific counseling that helps patients’ families distinguish approved therapies from investigational approaches, avoid therapeutic misconceptions, and preserve timely access to established interventions like amplification and cochlear implants.
We will now move on to patient case 2, which will help contextualize how HCPs should communicate with patients’ families about gene therapy while continuing to employ comprehensive, standard-of-care management planning.
Patient Case 2: Eli, 9-Month-Old Boy
Eli is a 9-month-old boy who failed his newborn hearing screening bilaterally. Diagnostic auditory brainstem response confirmed bilateral severe to profound SNHL, with evidence of intact outer hair cell function by intact otoacoustic emissions. He was fitted for hearing aids at 3 months of age, but aided behavioral responses remain limited. Early intervention services were started.
After evaluation, MRI shows normal bilateral cochlear nerves and no cochlear malformation. There are no renal, retinal, cardiac, thyroid, pigmentary, craniofacial, or vestibular findings documented to date.
Genetic testing with a comprehensive hearing loss panel identifies biallelic pathogenic variants in the OTOF gene. Like Noah, Eli’s genetic testing results are consistent with autosomal recessive OTOF-related hearing loss.
Eli’s parents show you several articles that they found online about gene therapy for genetic hearing loss. They ask, “Since there is now a gene therapy for this, should we hold off on cochlear implant evaluation? We do not want to do anything now that could prevent Eli from getting better treatment later.”
Eligibility for Gene Therapy Is Genotype Specific
As previously mentioned, patient eligibility for gene therapy is not simply determined by a genetic hearing loss diagnosis. So the first step in counseling is to establish whether the child’s molecular diagnosis is relevant to an approved or investigational gene therapy. Patient eligibility is further dependent on multiple factors, including the specific gene mutation, variant and inheritance pattern, severity and configuration of hearing loss, cochlear anatomy (ie, hair cell function), neural integrity, age, developmental status, and prior cochlear implant status.14,15
Of course, eligibility also might be influenced by the gene therapy’s regulatory status, label if approved, and other trial-related factors.
The FDA’s approval of lunsotogene parvec-cwha is directly relevant to Eli’s case because his genetic testing results confirm a diagnosis of severe to profound OTOF-related hearing loss. In addition, Eli has preserved outer hair cell function and no prior cochlear implant. This means he qualifies for lunsotogene parvec-cwha gene therapy based on its indication; however, otolaryngology HCPs should not assume patient eligibility based on genetic testing alone. Additional clinical and treatment-center evaluations are required.
An example statement to share with Eli’s parents during gene therapy counseling: “Eli’s genetic testing results show the same gene mutation for which a gene therapy has been approved. That makes a referral to a center experienced in OTOF-related treatment evaluation appropriate. They may or may not find that he is eligible. At the same time, we need to review the full eligibility criteria, his ear anatomy findings, and his current management plan before deciding what approach is best.”
OTOF-Related Hearing Loss: Why It Is Different
Remember, OTOF encodes otoferlin, which is an essential protein for synaptic transmission to the auditory nerve. The auditory nerve is structurally intact and cochlear outer hair cell function may be preserved, but signal transmission from the cochlear inner hair cells to the auditory nerve is impaired.3
This biology helps explain why OTOF-related hearing loss is distinct from other genetic causes. OTOF mutations are currently the leading target for gene therapy in genetic hearing loss.
Of note, to receive lunsotogene parvec-cwha gene therapy for OTOF-related hearing loss, patients must not have a cochlear implant in the affected ear.14,15 This creates a real clinical sequencing issue for otolaryngology HCPs. Families may worry that a cochlear implant will affect their child’s future eligibility for gene therapy. Therefore, this concern must be addressed directly, without allowing uncertainty to delay interventions for auditory access. Most important is to avoid a long delay in receiving one of these 2 treatments, as there is only a limited window of age for achieving maximum benefit from auditory interventions.
Feedback on Poll Question 6
Eli’s OTOF-related hearing loss diagnosis makes a discussion with his family about gene therapy clinically relevant. However, the appropriate response is not to stop standard care. Otolaryngology HCPs should refer patients for gene therapy evaluation and simultaneously preserve timely access to amplification, early intervention, and cochlear implant evaluation. Of course, these interventions may require careful sequencing considerations, particularly if prior cochlear implant affects patient eligibility for other interventions. Finally, HCP uncertainty should not drive therapeutic inertia.
Approved vs Investigational SNHL Interventions
Because families often use the term “gene therapy” broadly, otolaryngology HCPs must counsel them by distinguishing the categories that identify SNHL interventions as approved, investigational, or available via compassionate use or expanded access.
An approved therapy has a regulatory indication from the FDA for a defined population. For OTOF-related hearing loss, the FDA’s accelerated approval of lunsotogene parvec-cwha means that this gene therapy is no longer purely theoretical or investigational. It is indicated for use in the United States to treat pediatric and adult patients with severe to profound or profound SNHL associated with biallelic OTOF variants (molecularly confirmed), preserved outer hair cell function, and no prior cochlear implant.13,14
In turn, investigational therapies comprise those that are in clinical development. That means clinical trials are underway to evaluate the specific therapy’s safety, efficacy, dosing, delivery, and durability within a defined patient population. A trial may involve a therapy that shows promise but is not yet approved for a given indication or patient population.
Now, before therapies become investigational or approved, they are first studied within preclinical research. This is where animal models, vector development, delivery studies, and early translational work occur. Of note, preclinical research should not be presented to families as an available treatment pathway.16,17
A family-friendly explanation to Eli’s parents might look like: “While a gene therapy is approved for a specific genetic hearing loss diagnosis, others are being studied in clinical trials and many more are still at the laboratory stage. The next step is not to simply ask whether gene therapy exists. Instead, we need to determine if there is an approved or trial-based option for Eli’s exact genotype and clinical profile.”
Avoiding Therapeutic Misconceptions
Therapeutic misconceptions in pediatric SNHL occur when families overestimate the likelihood that an investigational or newly approved intervention will directly benefit their child. They also might underestimate the uncertainty, risks, and burdens associated with the specific intervention, especially when participating in clinical trials.18
One of the largest sources of therapeutic misconception is stories in the media that emphasize dramatic responses in individual clinical trial participants.19 Other examples include confusion between clinical trial vs real-world outcomes, misunderstanding eligibility criteria, assuming gene therapy applies to all SNHL diagnoses, and believing that newer equals better. The latter often presents when families think standard of care should be paused until emerging therapies are pursued.
For otolaryngology HCPs, the goal is not to dampen hope, but to make hope operationally safe.
A balanced response to Eli’s parents might include: “Gene therapy is an important advancement in genetic hearing loss, and Eli’s genotype confirms its relevancy. But gene therapy is not always the right choice for children with OTOF-related hearing loss, nor is it always available. Also, not all patients improve after gene therapy. We need to complete an expert review of eligibility, risks, timing, and patient-specific factors for gene therapy. At the same time, we should continue the standard steps in care that will protect Eli’s language development.”
Feedback on Poll Question 7
Counseling on gene therapy in pediatric SNHL must be personalized per patients’ genotype and clinical needs. That means an approved therapy for OTOF-related hearing loss should not be assumed to be indicated and available to patients with GJB2-related hearing loss. For Sofia, standard care should proceed, including cochlear implant evaluation when audiologic and developmental criteria support it. Emerging therapies can be discussed with Sofia’s family in a balanced way, but they should not be urged to delay established interventions. The only exception to this rule is if a qualified care team identifies a specific, time-sensitive therapy pathway that applies to the child’s genotype and clinical profile.
Maintaining Standard Hearing Management in the Era of Gene Therapy
For pediatric patients with severe to profound SNHL, delays in access to sound and language can have lasting developmental consequences.20 Therefore, emerging therapies should be integrated into standard care planning but not interrupt it.
Standard management should continue to include21:
- Prompt confirmation and monitoring of auditory thresholds
- Family-centered communication support
- Imaging to assess cochlear anatomy and function
- Early intervention and language access planning
- Appropriately fit amplification or cochlear implant evaluation when indicated
- Genetic testing to inform interpretation, inheritance, recurrence risk, and family testing
- Referral to genotype-specific therapy centers when relevant
For Eli, practical management does not simply center on gene therapy vs cochlear implant. Rather, how can his care team evaluate his eligibility for OTOF-directed gene therapy while preserving timely access to standard hearing interventions to avoid developmental delay? It may require otolaryngology HCPs to employ parallel rather than sequential planning.
Coordinating Referral and Care Pathways
Finally, otolaryngology HCPs generally are responsible for coordinating transitions in care from diagnosis to intervention, following 5 key steps in the process. The outline below highlights these steps within the context of our patient cases: Noah and Eli.
Step 1: Confirm patients’ molecular diagnosis. That includes reviewing genetic testing results with an expert and confirming that any positive results for biallelic pathogenic or likely pathogenic OTOF variants are consistent with the phenotype.
Step 2: Assess patient-specific features to determine whether available audiology, imaging, and clinical findings are sufficient to evaluate treatment eligibility. This often includes ear-specific hearing profiles (ie, cochlear anatomy and hair cell functionality).
Step 3: Refer patients with OTOF-related hearing loss to a center with expertise in gene therapy as indicated. Experienced HCPs in pediatric otology/neurotology, OTOF-related hearing loss, and gene therapy can advise on patient eligibility, timing, delivery, risks, monitoring, and how treatment might impact cochlear implantation.
Step 4: Continue cochlear implant evaluation. Do not allow the referral for gene therapy evaluation to establish an open-ended pause in standard management. Maintain cochlear implant evaluation timelines, especially when aided benefit is limited.
Step 5: Align family expectations. Explain that gene therapy may be relevant, but eligibility, timing, benefit, durability, and risks require individualized evaluation.
Key Takeaways
Gene therapy counseling in pediatric SNHL must be precise, genotype-specific, and integrated within standard care planning. This conversation is now clinically relevant for children with molecularly confirmed OTOF-related hearing loss. That is because of the recently approved gene therapy that exists for this specific population. However, patient eligibility further depends on clinical and treatment-specific criteria, and evaluation should occur in parallel with standard hearing management.
For children with other genetic hearing loss etiologies, such as GJB2, an OTOF-directed gene therapy should not be recommended. Families should be counseled on this, stating that the research is evolving. Furthermore, current management planning should remain focused on timely hearing access, early intervention, cochlear implant evaluation when appropriate, and genetically informed longitudinal care.
The otolaryngology HCP’s role is to preserve both hope and treatment momentum when managing pediatric SNHL. That is done best when HCPs acknowledge there are emerging therapies and refer patients appropriately, while preventing delays in accessing standard interventions that support auditory and language development.