Genetic Causes of Hearing Loss in a Large Cohort of Cochlear Implant Recipients.
Ontology highlight
ABSTRACT:
SUBMITTER: Seligman KL
PROVIDER: S-EPMC9128025 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
Publications
Genetic Causes of Hearing Loss in a Large Cohort of Cochlear Implant Recipients.
Seligman Kristen L KL Shearer A Eliot AE Frees Kathy K Nishimura Carla C Kolbe Diana D Dunn Camille C Hansen Marlan R MR Gantz Bruce J BJ Smith Richard J H RJH
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 20210622 4
Understanding genetic causes of hearing loss can determine the pattern and course of a patient's hearing loss and may also predict outcomes after cochlear implantation. Our goal in this study was to evaluate genetic causes of hearing loss in a large cohort of adults and children with cochlear implants. We performed comprehensive genetic testing on all patients undergoing cochlear implantation. Of the 459 patients included in the study, 128 (28%) had positive genetic testing. In total, 44 genes w ...[more]
Similar Datasets
Project description:Introduction Candidacy criteria for cochlear implantation in the United States has expanded to include children with single-sided deafness (SSD) who are at least 5 years of age. Pediatric cochlear implant (CI) users with SSD experience improved speech recognition with increased daily device use. There are few studies that report the hearing hour percentage (HHP) or the incidence of non-use for pediatric CI recipients with SSD. The aim of this study was to investigate factors that impact outcomes in children with SSD who use CIs. A secondary aim was to identify factors that impact daily device use in this population. Methods A clinical database query revealed 97 pediatric CI recipients with SSD who underwent implantation between 2014 and 2022 and had records of datalogs. The clinical test battery included speech recognition assessment for CNC words with the CI-alone and BKB-SIN with the CI plus the normal-hearing ear (combined condition). The target and masker for the BKB-SIN were presented in collocated and spatially separated conditions to evaluate spatial release from masking (SRM). Linear mixed-effects models evaluated the influence of time since activation, duration of deafness, HHP, and age at activation on performance (CNC and SRM). A separate linear mixed-effects model evaluated the main effects of age at testing, time since activation, duration of deafness, and onset of deafness (stable, progressive, or sudden) on HHP. Results Longer time since activation, shorter duration of deafness, and higher HHP were significantly correlated with better CNC word scores. Younger age at device activation was not found to be a significant predictor of CNC outcomes. There was a significant relationship between HHP and SRM, with children who had higher HHP experiencing greater SRM. There was a significant negative correlation between time since activation and age at test with HHP. Children with sudden hearing loss had a higher HHP than children with progressive and congenital hearing losses. Conclusion The present data presented here do not support a cut-off age or duration of deafness for pediatric cochlear implantation in cases of SSD. Instead, they expand on our understanding of the benefits of CI use in this population by reviewing the factors that influence outcomes in this growing patient population. Higher HHP, or greater percentage of time spent each day using bilateral input, was associated with better outcomes in the CI-alone and in the combined condition. Younger children and those within the first months of use had higher HHP. Clinicians should discuss these factors and how they may influence CI outcomes with potential candidates with SSD and their families. Ongoing work is investigating the long-term outcomes in this patient population, including whether increasing HHP after a period of limited CI use results in improved outcomes.
| S-EPMC10213360 | biostudies-literature
Project description:ImportanceIn 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.ObjectiveTo 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 participantsThis 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 measuresGenetic 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.ResultsOf 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 relevanceThe 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.
| S-EPMC9857764 | biostudies-literature
Project description:ObjectivesThe variability in outcomes of cochlear implantation is largely unexplained, and clinical factors are not sufficient for predicting performance. Genetic factors have been suggested to impact outcomes, but the clinical and genetic heterogeneity of hereditary hearing loss makes it difficult to determine and interpret postoperative performance. It is hypothesized that genetic mutations that affect the neuronal components of the cochlea and auditory pathway, targeted by the cochlear implant (CI), may lead to poor performance. A large cohort of CI recipients was studied to verify this hypothesis.DesignThis study included a large German cohort of CI recipients (n = 123 implanted ears; n = 76 probands) with a definitive genetic etiology of hearing loss according to the American College of Medical Genetics (ACMG)/Association for Molecular Pathology (AMP) guidelines and documented postoperative audiological outcomes. All patients underwent preoperative clinical and audiological examinations. Postoperative CI outcome measures were based on at least 1 year of postoperative audiological follow-up for patients with postlingual hearing loss onset (>6 years) and 5 years for children with congenital or pre/perilingual hearing loss onset (≤6 years). Genetic analysis was performed based on three different methods that included single-gene screening, custom-designed hearing loss gene panel sequencing, targeting known syndromic and nonsyndromic hearing loss genes, and whole-genome sequencing.ResultsThe genetic diagnosis of the 76 probands in the genetic cohort involved 35 genes and 61 different clinically relevant (pathogenic, likely pathogenic) variants. With regard to implanted ears (n = 123), the six most frequently affected genes affecting nearly one-half of implanted ears were GJB2 (21%; n = 26), TMPRSS3 (7%; n = 9), MYO15A (7%; n = 8), SLC26A4 (5%; n = 6), and LOXHD1 and USH2A (each 4%; n = 5). CI recipients with pathogenic variants that influence the sensory nonneural structures performed at or above the median level of speech performance of all ears at 70% [monosyllable word recognition score in quiet at 65 decibels sound pressure level (SPL)]. When gene expression categories were compared to demographic and clinical categories (total number of compared categories: n = 30), mutations in genes expressed in the spiral ganglion emerged as a significant factor more negatively affecting cochlear implantation outcomes than all clinical parameters. An ANOVA of a reduced set of genetic and clinical categories (n = 10) identified five detrimental factors leading to poorer performance with highly significant effects ( p < 0.001), accounting for a total of 11.8% of the observed variance. The single strongest category was neural gene expression accounting for 3.1% of the variance.ConclusionsThe analysis of the relationship between the molecular genetic diagnoses of a hereditary etiology of hearing loss and cochlear implantation outcomes in a large German cohort of CI recipients revealed significant variabilities. Poor performance was observed with genetic mutations that affected the neural components of the cochlea, supporting the "spiral ganglion hypothesis."
| S-EPMC10583923 | biostudies-literature
Project description:Tinnitus is a common symptom in cochlear implant (CI) recipients. There is no clear evidence of the influence of tinnitus on hearing-related quality of life (QoL) in this population. The aim of this study was to assess the relationship between hearing-related QoL measured by the Speech, Spatial and Qualities of Hearing scale (SSQ12) and tinnitus annoyance or perceived change in tinnitus annoyance after cochlear implantation. The study sample consisted of 2322 implanted adults across France, Germany, Ireland, Italy, the Netherlands, Sweden and the United Kingdom. Information relating to QoL measured using the SSQ12 and tinnitus annoyance and change in tinnitus annoyance, assessed using single-item questions, were collected one or more years post-implantation. The relationship between SSQ12 score and tinnitus annoyance or change in tinnitus annoyance was analysed using linear models adjusted for age and unilateral versus bilateral implants. Tukey pairwise tests were used to compare mean SSQ12 scores across levels of tinnitus annoyance and changes. Tinnitus prevalence was 33.9% post-implantation. Recipients with tinnitus had a significantly lower SSQ12 score than recipients without tinnitus. SSQ scores varied significantly with tinnitus annoyance, age and unilateral versus bilateral implants. Overall, CI recipients who experienced less bothersome tinnitus reported better hearing-related QoL. Healthcare professionals should be aware of the influence of tinnitus on CI recipients' hearing to manage patient expectations.
| S-EPMC9402917 | biostudies-literature
Project description:The aim of this study was to assess comparative behavior domain in patients with cochlear implants, using caretaker assessment. A prospective cross-sectional study was conducted. Of 106 patients with hearing loss and receiving cochlear implants were included along with their caretakers. The caretaker' perspective questionnaire-22 was implemented covering emotions, education, and social relationships domain. A repeated measure ANOVA was used to statistical analysis. The implantation elicited a slight reduction in emotions scores domain as well as slight increase in social relationships scores from pre-cochlear implants to 12 months in all aged (6-10 years: - 10.7, 95%CI - 8.4 to 12.9; 4.2, 95%CI 3.0-5.5, 11-20 years: - 8.6, 95%CI - 6.7 to 10.5; 2.5, 95%CI 1.6-3.3, 21-59 years: - 6.8, 95%CI - 4.9 to 8.6; 2.0, 95%CI 1.3-2.7, and older 60 years: - 12.1, 95%CI - 9.5 to 14.6; 3.6, 95%CI 2.7-4.5, respectively). However, the education scores domain has slight increase only in aged 21-59 years group (1.8, 95%CI 0.7-2.8). A long-term after cochlear implants (12 months), but not after only 6 months elicits a statistically significant increase the social relationships scores and the reduction in negative emotions scores in all aged at implantation. However, the education scores have slight increase only in aged 21-59.
| S-EPMC6841886 | biostudies-literature
Project description:BACKGROUND: Studies using vocoders as acoustic simulators of cochlear implants have generally focused on simulation of speech understanding, gender recognition, or music appreciation. The aim of the present experiment was to study the auditory sensation perceived by cochlear implant (CI) recipients with steady electrical stimulation on the most-apical electrode. METHODOLOGY/PRINCIPAL FINDINGS: Five unilateral CI users with contralateral residual hearing were asked to vary the parameters of an acoustic signal played to the non-implanted ear, in order to match its sensation to that of the electric stimulus. They also provided a rating of similarity between each acoustic sound they selected and the electric stimulus. On average across subjects, the sound rated as most similar was a complex signal with a concentration of energy around 523 Hz. This sound was inharmonic in 3 out of 5 subjects with a moderate, progressive increase in the spacing between the frequency components. CONCLUSIONS/SIGNIFICANCE: For these subjects, the sound sensation created by steady electric stimulation on the most-apical electrode was neither a white noise nor a pure tone, but a complex signal with a progressive increase in the spacing between the frequency components in 3 out of 5 subjects. Knowing whether the inharmonic nature of the sound was related to the fact that the non-implanted ear was impaired has to be explored in single-sided deafened patients with a contralateral CI. These results may be used in the future to better understand peripheral and central auditory processing in relation to cochlear implants.
| S-EPMC3378545 | biostudies-other
Project description:The peroxisome is a ubiquitous organelle in rodent cells and plays important roles in a variety of cell types and tissues. It is previously indicated that peroxisomes are associated with auditory function, and patients with peroxisome biogenesis disorders (PBDs) are found to have hearing dysfunction, but the specific role of peroxisomes in hearing remains unclear. In this study, two peroxisome-deficient mouse models (Atoh1-Pex5-/- and Pax2-Pex5-/- ) are established and it is found that peroxisomes mainly function in the hair cells of cochleae. Furthermore, peroxisome deficiency-mediated negative effects on hearing do not involve mitochondrial dysfunction and oxidative damage. Although the mammalian target of rapamycin complex 1 (mTORC1) signaling is shown to function through peroxisomes, no changes are observed in the mTORC1 signaling in Atoh1-Pex5-/- mice when compared to wild-type (WT) mice. However, the expression of large-conductance, voltage-, and Ca2+ -activated K+ (BK) channels is less in Atoh1-Pex5-/- mice as compared to the WT mice, and the administration of activators of BK channels (NS-1619 and NS-11021) restores the auditory function in knockout mice. These results suggest that peroxisomes play an essential role in cochlear hair cells by regulating BK channels. Hence, BK channels appear as the probable target for treating peroxisome-related hearing diseases such as PBDs.
| S-EPMC10369297 | biostudies-literature
Project description:Tricellulin (also known as MARVELD2) is considered as a central component of tricellular tight junctions and is distributed among various epithelial tissues. Although mutations in the gene encoding tricellulin are known to cause deafness in humans (DFNB49) and mice, the influence of its systemic deletion in vivo remains unknown. When we generated tricellulin-knockout mice (Tric(-/-)), we found an early-onset rapidly progressive hearing loss associated with the degeneration of hair cells (HCs); however, their body size and overall appearance were normal. Tric(-/-) mice did not show any morphological change pertaining to other organs such as the gastrointestinal tract, liver, kidney, thyroid gland and heart. The endocochlear potential (EP) was normal in Tric(-/-) mice, suggesting that the tight junction barrier is maintained in the stria vascularis, where EP is generated. The degeneration of HCs, which occurred after the maturation of EP, was prevented in the culture medium with an ion concentration similar to that of the perilymph. These data demonstrate the specific requirement of tricellulin for maintaining ion homeostasis around cochlear HCs to ensure their survival. The Tric(-/-) mouse provides a new model for understanding the distinct roles of tricellulin in different epithelial systems as well as in the pathogenesis of DFNB49.
| S-EPMC4683410 | biostudies-literature
Project description:Wolfram syndrome type 1 gene (WFS1), which encodes a transmembrane structural protein (wolframin), is essential for several biological processes, including proper inner ear function. Unlike the recessively inherited Wolfram syndrome, WFS1 heterozygous variants cause DFNA6/14/38 and wolfram-like syndrome, characterized by autosomal dominant nonsyndromic hearing loss, optic atrophy, and diabetes mellitus. Here, we identified two WFS1 heterozygous variants in three DFNA6/14/38 families using exome sequencing. We reveal the pathogenicity of the WFS1 variants based on three-dimensional (3D) modeling and structural analysis. Furthermore, we present cochlear implantation (CI) outcomes in WFS1-associated DFNA6/14/38 and suggest a genotype-phenotype correlation based on our results and a systematic review. We performed molecular genetic test and evaluated clinical phenotypes of three WFS1-associated DFNA6/14/38 families. A putative WFS1-NCS1 interaction model was generated, and the impacts of WFS1 variants on stability were predicted by comparing intramolecular interactions. A total of 62 WFS1 variants associated with DFNA6/14/38 were included in a systematic review. One variant is a known mutational hotspot variant in the endoplasmic reticulum (ER)-luminal domain WFS1(NM_006005.3) (c.2051 C > T:p.Ala684Val), and the other is a novel frameshift variant in transmembrane domain 6 (c.1544_1545insA:p.Phe515LeufsTer28). The two variants were pathogenic, based on the ACMG/AMP guidelines. Three-dimensional modeling and structural analysis show that non-polar, hydrophobic substitution of Ala684 (p.Ala684Val) destabilizes the alpha helix and contributes to the loss of WFS1-NCS1 interaction. Also, the p.Phe515LeufsTer28 variant truncates transmembrane domain 7-9 and the ER-luminal domain, possibly impairing membrane localization and C-terminal signal transduction. The systematic review demonstrates favorable outcomes of CI. Remarkably, p.Ala684Val in WFS1 is associated with early-onset severe-to-profound deafness, revealing a strong candidate variant for CI. We expanded the genotypic spectrum of WFS1 heterozygous variants underlying DFNA6/14/38 and revealed the pathogenicity of mutant WFS1, providing a theoretical basis for WFS1-NCS1 interactions. We presented a range of phenotypic traits for WFS1 heterozygous variants and demonstrated favorable functional CI outcomes, proposing p.Ala684Val a strong potential marker for CI candidates.
| S-EPMC10088283 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to assess barriers to rehabilitation care for pediatric cochlear implant (CI) recipients.Study designCross-sectional questionnaire study.SettingTertiary medical center.PatientsParents of children who received a CI from October 1996 to June 2013.Main outcome measure(s)Factors related to access to and barriers in audiology and speech therapy services, factors related to CI use, and performance with CI using the Parents' Evaluation of Aural/Oral Performance of Children (PEACH).ResultsThirty-five parents participated in the study (21 rural residents and 14 urban residents). Distance was a significant barrier to audiology services for rural participants compared with urban participants (p = 0.01). Consistent CI use was complicated by mechanical complications or malfunction in 70% of rural children compared with 33% of urban children (p = 0.05). Only 10% of rural children were able to access speech therapy services at diagnosis compared with 42% of urban children (p = 0.04). Low socioeconomic (SES) status and Medicaid insurance were associated with a lack of local speech therapists and medical/mechanical CI complications. Higher parental educational attainment was associated with higher PEACH scores in quiet conditions compared with families with lower parental education (p = 0.04).ConclusionsRural children are often delayed in receipt of CI rehabilitation services. Multiple barriers including low SES, insurance type, and parental education can affect utilization of these services and may impact the recipient language development. Close follow-up and efforts to expand access to care are needed to maximize CI benefit.
| S-EPMC5940514 | biostudies-literature