Dataset Information

Full etiologic spectrum of pediatric severe to profound hearing loss of consecutive 119 cases.

ABSTRACT: Determining the etiology of severe-to-profound sensorineural hearing loss (SP-SNHL) in pediatric subjects is particularly important in aiding the decision for auditory rehabilitation. We aimed to update the etiologic spectrum of pediatric SP-SNHL by combining internal auditory canal (IAC)-MRI with comprehensive and state-of-the-art genetic testings. From May 2013 to September 2020, 119 cochlear implantees under the age of 15 years with SP-SNHL were all prospectively recruited. They were subjected to genetic tests, including exome sequencing, and IAC-MRI for etiologic diagnosis. Strict interpretation of results were made based on ACMG/AMP guidelines and by an experienced neuroradiologist. The etiology was determined in of 65.5% (78/119) of our cohort. If only one of the two tests was done, the etiologic diagnostic rate would be reduced by at least 21.8%. Notably, cochlear nerve deficiency (n = 20) detected by IAC-MRI topped the etiology list of our cohort, followed by DFNB4 (n = 18), DFNB1 (n = 10), DFNB9 (n = 10) and periventricular leukomalacia associated with congenital CMV infection (n = 8). Simultaneous application of state-of-the-art genetic tests and IAC-MRI is essential for etiologic diagnosis, and if lesions of the auditory nerve or central nerve system are carefully examined on an MRI, we can identify the cause of deafness in more than 65% of pediatric SP-SNHL cases.

SUBMITTER: Kim YS

PROVIDER: S-EPMC9296524 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Full etiologic spectrum of pediatric severe to profound hearing loss of consecutive 119 cases.

Kim Young Seok YS Kim Yoonjoong Y Jeon Hyoung Won HW Yi Nayoung N Lee Sang-Yeon SY Kim Yehree Y Han Jin Hee JH Kim Min Young MY Kim Bo Hye BH Choi Hyeong Yun HY Carandang Marge M Koo Ja-Won JW Kim Bong Jik BJ Bae Yun Jung YJ Choi Byung Yoon BY

Scientific reports 20220719 1

Determining the etiology of severe-to-profound sensorineural hearing loss (SP-SNHL) in pediatric subjects is particularly important in aiding the decision for auditory rehabilitation. We aimed to update the etiologic spectrum of pediatric SP-SNHL by combining internal auditory canal (IAC)-MRI with comprehensive and state-of-the-art genetic testings. From May 2013 to September 2020, 119 cochlear implantees under the age of 15 years with SP-SNHL were all prospectively recruited. They were subjecte ...[more]

PMID: 35853923

Similar Datasets

Project description:Importance:Pediatric-onset unilateral and asymmetric sensorineural hearing loss (SNHL) is a common condition, but in most patients, the cause remains unclear; thus, determination of the hearing outlook is difficult. Objective:To analyze the etiologic and audiologic characteristics of pediatric-onset unilateral and asymmetric SNHL. Design, Setting, and Participants:In this retrospective cohort study performed from January 1, 2008, through December 31, 2016, patients at a tertiary referral center who were diagnosed with pediatric-onset unilateral or asymmetric SNHL were divided into 3 groups according to their hearing levels: unilateral hearing loss with scaled-out levels (UHL-SO), unilateral hearing loss with residual hearing (UHL-RH), and asymmetric hearing loss (AHL). Main Outcomes and Measures:Basic demographic data, family and medical histories, audiologic results, imaging findings, and genetic results were ascertained and compared among patients of the 3 groups. Results:A total of 133 patients (mean [SD] age, 9.1 [10.9] years; 63 [47.4%] male and 70 [52.6%] female), including 50 with UHL-SO, 42 with UHL-RH, and 41 with AHL, were enrolled for analyses. Of 50 patients with UHL-SO, 49 (98.0%) had stable hearing levels with time, whereas 10 of 42 patients with UHL-RH (23.8%) and 18 of 41 patients with AHL (43.9%) revealed progressive or fluctuating hearing loss. Inner ear malformations detected with temporal bone high-resolution computed tomography, particularly cochlear aperture stenosis, were detected at higher rates in patients with UHL-SO (9 of 31 [29.0%]) and UHL-RH (6 of 24 [25.0%]) than in those with AHL (1 of 30 [3.3%]). In contrast, screening for mutations in 3 common deafness genes-GJB2, SLC26A4, and MTRNR1-achieved definite diagnosis in a higher percentage of patients with AHL (10 of 37 [27.0%]) than patients with UHL-SO (0 of 33) and UHL-RH (1 of 25 [4.0%]). Conclusions and Relevance:The UHL-SO and UHL-RH conditions share a common or similar etiopathogenesis different from that of AHL. Imaging studies and genetic testing might be prioritized during the respective general etiologic workups for patients with UHL and AHL. Regular hearing checkups are warranted for patients with UHL and AHL because a certain proportion of patients might sustain progression in SNHL.

Project description:BackgroundTinnitus is defined as the subjective perception of sound in the absence of an external stimulus, and tinnitus disorder becomes relevant when it is associated with emotional distress, cognitive dysfunction, and/or autonomic arousal. Hearing loss is recognized as the main risk factor for the pathogenesis of tinnitus. However, clinical guidelines for tinnitus disorder provide little direction for those who have severe-to-profound hearing loss including those who are pre-lingually Deaf. The aim of this scoping review was to catalogue what is known from the existing literature regarding the experience and management of tinnitus in adults who have a severe-to-profound hearing loss.SummaryA scoping review was conducted following the Preferred Reporting Item for Systematic Reviews and Meta-analysis extension for Scoping Reviews. Records were included if they reported an evaluation of tinnitus in adults who had severe-to-profound hearing loss. The online databases Ovid (MEDLINE, EMBASE and PsycINFO), CINAHL, ProQuest, Scopus, and Google Scholar were searched using the search terms 'tinnitus' (as a MESH term) and 'deaf' OR 'profound hearing loss. Thirty-five records met the inclusion criteria for this review and were cataloged according to three major themes: Impact of tinnitus in deaf adults; Primary treatment of tinnitus in deaf adults; and Cochlear implant studies where tinnitus was a secondary outcome. Tinnitus symptom severity was assessed before and after intervention using tinnitus validated questionnaires in 29 records, with six further records using other assessment tools to measure tinnitus severity. Participants using cochlear implants were included in 30 studies. Medication, repetitive transcranial magnetic stimulation (rTMS), electrical promontory stimulation, and behavioral self-control therapy were each reported in single records.Key messagesThis scoping review cataloged the experience, assessment, and treatment of tinnitus in adults who have severe-to-profound hearing loss. It is shown that there is very limited research reported in this field. Although this review included many records, most focused on the provision of cochlear implants for severe-to-profound hearing loss, with assessment and measurement of tinnitus as a baseline or secondary outcome. Largely missing in the literature are empirical studies that seek firstly to understand the nature of the experience of tinnitus by people with no or little residual access to external sound.

Project description:OBJECTIVES:We, herein, report two novel USH2A variants from two unrelated Korean families and their clinical phenotypes, with attention to severe or more than severe sensorineural hearing loss (SNHL). METHODS:Two postlingually deafened subjects (SB237-461, M/46 and SB354-692, F/34) with more than severe SNHL and also with suspicion of Usher syndrome type II (USH2) were enrolled. A comprehensive audiological and ophthalmological assessments were evaluated. We conducted the whole exome sequencing and subsequent pathogenicity prediction analysis. RESULTS:We identified the following variants of USH2A from the two probands manifesting more than severe SNHL and retinitis pigmentosa (RP): compound heterozygosity for a nonsense (c.8176C>T: p.R2723X) and a missense variant (c.1823G>A: p.C608Y) in SB237, and compound heterozygosity for two frameshift variants (c.14835delT: p.S4945fs & c.13112_13115delAAAT: p.G4371fs) in SB354. Based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, two novel variants, c.1823G>A: p.C608Y and c.14835delT: p.Ser4945fs, can be classified as "uncertain significance" and "pathogenic," respectively. The audiogram exhibited more than severe SNHL and a down-sloping configuration, necessitating cochlear implantation. The ophthalmic examinations revealed typical features of RP. Interestingly, one proband (SB 354-692) carrying two truncating compound heterozygous variants exhibited more severe hearing loss than the other proband (SB 237-461), carrying one truncation with one missense variant. CONCLUSION:Our results provide insight on the expansion of audiological spectrum encompassing more than severe SNHL in Korean subjects harboring USH2A variants, suggesting that USH2A should also be included in the candidate gene of cochlear implantation. A specific combination of USH2A variants causing truncating proteins in both alleles could demonstrate more severe audiological phenotype than that of USH2A variants carrying one truncating mutation and one missense mutation, suggesting a possible genotype-phenotype correlation. The understanding of audiological complexity associated with USH2A will be helpful for genetic counseling and treatment starategy.

Project description:BackgroundHearing loss increases the risk of poor outcomes across a range of life domains. Where hearing loss is severe or profound, audiological interventions and rehabilitation have limited impact. Hearing dogs offer an alternative, or additional, intervention. They live permanently with recipients, providing sound support and companionship.MethodsA single-centre, randomised controlled trial (RCT) evaluated the impacts of a hearing dog on mental well-being, anxiety, depression, problems associated with hearing loss (responding to sounds, fearfulness/social isolation), and perceived dependency on others. Participants were applicants to the UK charity 'Hearing Dogs for Deaf People'. Eligibility criteria were as follows: first-time applicant; applying for a hearing dog (as opposed to other support provided by the charity). Participants were randomised 1:1 to the following: receive a hearing dog sooner than usual [HD], or within the usual application timeframe (wait-list [WL] comparator). The primary outcome was mental well-being (Short Warwick-Edinburgh Mental Well-Being Scale) 6 months (T1) after HD received a hearing dog. The cost-effectiveness analysis took a health and social care perspective.ResultsIn total, 165 participants were randomised (HD n = 83, WL n = 82). A total of 112 (67.9%) were included in the primary analysis (HD n = 55, WL n = 57). At T1, mental well-being was significantly higher in the HD arm (adjusted mean difference 2.53, 95% CI 1.27 to 3.79, p < 0.001). Significant improvements in anxiety, depression, functioning, fearfulness/social isolation, and perceived dependency, favouring the HD arm, were also observed. On average, HD participants had used fewer statutory health and social care resources. In a scenario whereby costs of provision were borne by the public sector, hearing dogs do not appear to be value for money. If the public sector made a partial contribution, it is possible that hearing dogs would be cost-effective from a public sector perspective.ConclusionsHearing dogs appear to benefit recipients across a number of life domains, at least in the short term. Within the current funding model (costs entirely borne by the charity), hearing dogs are cost-effective from the public sector perspective. Whilst it would not be cost-effective to fully fund the provision of hearing dogs by the public sector, a partial contribution could be explored.Trial registrationThe trial was retrospectively registered with the International Standard Randomised Controlled Trial Number (ISRCTN) registry on 28.1.2019: ISRCTN36452009 .

Project description:Severe to profound sensorineural hearing loss (SNHL) requires cochlear implantation (CI) for auditory rehabilitation. Etiologic diagnoses can contribute to candidacy selection and decision-making regarding the timing of successful CI. However, few studies have been performed to address the etiologic spectrum of severe SNHL in the population where there is no consanguineous marriage and the majority of SNHL cases are sporadic in small sized families. The authors sought to comprehensively understand the etiologies of Korean cochlear implantees by incorporating the targeted resequencing of 204 candidate deafness genes (TRS-204) and a phenotype-driven candidate gene approach.Ninety-three that consented to molecular genetic testing and underwent at least one molecular genetic test were included. Patients with a characteristic Phenotypic marker were subject to Sanger sequencing to detect variants in corresponding candidate genes. The rest of patients without any prominent phenotype were tested on GJB2. Next, TRS-204 was applied in GJB2-negative cases without any phenotypic marker. In addition, the sibling recurrence-risk of SNHL among families with non-diagnostic genotypes after TRS-204 was performed to gain insight of etiologies in non-diagnostic cases.Overall, we could find causative variants in 51 (54.8%) of the 93 cochlear implantees. Thirty (32.3%) probands could be diagnosed by direct Sanger sequencing of candidate genes selected by their phenotypes. GJB2 sequencing added 10 subjects to the group with a diagnostic genotype. TRS-204 could detect a causative variant from additional 11 cases (11.8%). We could not detect any pathogenic deletion or duplication on 204 target genes. The sibling recurrence-risk of SNHL among 42 genetically undiagnosed families with 0.03 (1/38) was significantly lower than among genetically diagnosed recessive families with 0.19 (7/37).Despite that the majority of severe or more degree of SNHL occurs sporadically in Koreans, at least 54.8% of such cases that were willing to join the genetic study in the Korean population are monogenic Mendelian disorders with convincing causative variants. This study also indicates that a substantial portion of unsolved cases after applying our current protocol are predicted to have non-genetic or complex etiology rather than a Mendelian genetic disorder involving new genes beyond the 204 target genes.

Dataset Information

Full etiologic spectrum of pediatric severe to profound hearing loss of consecutive 119 cases.

Publications

Full etiologic spectrum of pediatric severe to profound hearing loss of consecutive 119 cases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets