Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes.

Importance: In the US, most childhood-onset bilateral sensorineural hearing loss is genetic, with more than 120 genes and thousands of different alleles known. Primary treatments are hearing aids and cochlear implants. Genetic diagnosis can inform progression of hearing loss, indicate potential syndromic features, and suggest best timing for individualized treatment. Objective: To identify the genetic causes of childhood-onset hearing loss and characterize severity, progression, and cochlear implant success associated with genotype in a single large clinical cohort. Design, Setting, and Participants: This cross-sectional analysis (genomics) and retrospective cohort analysis (audiological measures) were conducted from 2019 to 2022 at the otolaryngology and audiology clinics of Seattle Children's Hospital and the University of Washington and included 449 children from 406 families with bilateral sensorineural hearing loss with an onset younger than 18 years. Data were analyzed between January and June 2022. Main Outcomes and Measures: Genetic diagnoses based on genomic sequencing and structural variant analysis of the DNA of participants; severity and progression of hearing loss as measured by audiologic testing; and cochlear implant success as measured by pediatric and adult speech perception tests. Hearing thresholds and speech perception scores were evaluated with respect to age at implant, months since implant, and genotype using a multivariate analysis of variance and covariance. Results: Of 406 participants, 208 (51%) were female, 17 (4%) were African/African American, 32 (8%) were East Asian, 219 (54%) were European, 53 (13%) were Latino/Admixed American, and 16 (4%) were South Asian. Genomic analysis yielded genetic diagnoses for 210 of 406 families (52%), including 55 of 82 multiplex families (67%) and 155 of 324 singleton families (48%). Rates of genetic diagnosis were similar for children of all ancestries. Causal variants occurred in 43 different genes, with each child (with 1 exception) having causative variant(s) in only 1 gene. Hearing loss severity, affected frequencies, and progression varied by gene and, for some genes, by genotype within gene. For children with causative mutations in MYO6, OTOA, SLC26A4, TMPRSS3, or severe loss-of-function variants in GJB2, hearing loss was progressive, with losses of more than 10 dB per decade. For all children with cochlear implants, outcomes of adult speech perception tests were greater than preimplanted levels. Yet the degree of success varied substantially by genotype. Adjusting for age at implant and interval since implant, speech perception was highest for children with hearing loss due to MITF or TMPRSS3. Conclusions and Relevance: The results of this cross-sectional study suggest that genetic diagnosis is now sufficiently advanced to enable its integration into precision medical care for childhood-onset hearing loss.

An off-the-shelf otoacoustic-emission probe for hearing screening via a smartphone.

Otoacoustic emissions (OAEs) provide information about the function of the outer hair cells of the cochlea. In high-income countries, infants undergo OAE tests as part of the screening protocols for hearing. However, the cost of the necessary equipment hinders early screening for hearing in low- and middle-income countries, which disproportionately bear the brunt of disabling hearing loss. Here we report the design and clinical testing of a low-cost probe for OAEs. The device, which has a material cost of approximately US$10, uses an off-the-shelf microphone and off-the-shelf earphones connected to a smartphone through a headphone jack. It sends two pure tones through each of the headphone's earbuds and algorithmically detects the distortion-product OAEs generated by the cochlea and recorded via the microphone. In a clinical study involving 201 paediatric ears across three healthcare sites, the device detected hearing loss with 100% sensitivity and 88.9% specificity, comparable to the performance of a commercial device. Low-cost devices for OAE testing may aid the early detection of hearing loss in resource-constrained settings.

Performing tympanometry using smartphones.

Background: Tympanometry is used as part of a battery of tests for screening of middle ear function and may help diagnose middle ear disorders, but remains available only on expensive test equipment. Methods: We report a low-cost smartphone-based tympanometer system that consists of a lightweight and portable attachment to vary air pressure in the ear and measure middle ear function. The smartphone displays a tympanogram and reports peak acoustic admittance in realtime. Our programmable and open-source system operates at 226 Hz and was tested on 50 pediatric patient ears in an audiology clinic in parallel with a commercial tympanometer. Results: Our study shows an average agreement of 86 ± 2% between the 100 tympanograms produced by the smartphone and commercial device when five pediatric audiologists classified them into five classes based on the Liden and Jerger classification. Conclusion: Given the accessibility and prevalence of budget smartphones in developing countries, our open-source tool may help provide timely and affordable screening of middle ear disorders.