Moderate Sensorineural Hearing Loss Research Articles

Epidemiological Profile of Hearing Deficiency in a Tertiary Care Hospital (2019-2022)

Abstract Introduction This study is an attempt to view the demographic profile of individuals presenting with hearing loss in an urban referral hospital with the help of available database of pure tone audiometry results over a three years period. Materials and methods It is adescriptive epidemiologicalstudy over a period of 3 years conducted in the Department of Otorhinolaryngology (ORL) of an urban referral hospital.The subjects presented with a complain of hearing loss were investigated with pure tone audiometry. Subjects below 10 years of age or with gross mental or physical disabilities were excluded. The results of pure tone audiometry done were analyzed followed by systematic analysis. Results A total number of 3536individuals inclusive of1980 males and1556 females were studied. Nearly, 570 individuals suffered B/L hearing loss (16%) which was again mostly Sensori-neural. Sensori-neural hearing loss was the most common hearing loss near about 52%.Mixed Hearing loss accounted for 13%.Conductive hearing loss accounted for 35 %. Mild hearing loss (25-40dB) accounted for maximum bulk of the patients.The bulk of the population comprised of people in their middle age (30-60) and elderly (>60 years). Conclusion The demographic profile of hearing loss in an urban population is the ground work for any comprehensive planning to resolve the issue. In our study the increased burden of mild to moderate sensorineural hearing loss as seen in the elderly population and increased prevalence of conductive hearing loss as seen in the young population shows us how respective management protocols can be instituted for the target populations.

Comprehensive analysis of two hotspot codons in the TUBB4B gene and associated phenotypes

Our purpose was to elucidate the genotype and ophthalmological and audiological phenotype in TUBB4B-associated inherited retinal dystrophy (IRD) and sensorineural hearing loss (SNHL), and to model the effects of all possible amino acid substitutions at the hotspot codons Arg390 and Arg391. Six patients from five families with heterozygous missense variants in TUBB4B were included in this observational study. Ophthalmological testing included best-corrected visual acuity, fundus examination, optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Audiological examination included pure-tone and speech audiometry in adult patients and auditory brainstem response testing in a child. Genetic testing was performed by disease gene panel analysis based on genome sequencing. The molecular consequences of the substitutions of residues 390 and 391 on TUBB4B and its interaction with α-tubulin were predicted in silico on its three-dimensional structure obtained by homology modelling. Two independent patients had amino acid exchanges at position 391 (p.(Arg391His) or p.(Arg391Cys)) of the TUBB4B protein. Both had a distinct IRD phenotype with peripheral round yellowish lesions with pigmented spots and mild or moderate SNHL, respectively. Yet the phenotype was milder with a sectorial pattern of bone spicules in one patient, likely due to a genetically confirmed mosaicism for p.(Arg391His). Three patients were heterozygous for an amino acid exchange at position 390 (p.(Arg390Gln) or p.(Arg390Trp)) and presented with another distinct retinal phenotype with well demarcated pericentral retinitis pigmentosa. All showed SNHL ranging from mild to severe. One additional patient showed a variant distinct from codon 390 or 391 (p.(Tyr310His)), and presented with congenital profound hearing loss and reduced responses in ERG. Variants at codon positions 390 and 391 were predicted to decrease the structural stability of TUBB4B and its complex with α-tubulin, as well as the complex affinity. In conclusion, the twofold larger reduction in heterodimer affinity exhibited by Arg391 substitutions suggested an association with the more severe retinal phenotype, compared to the substitution at Arg390.

Remote or in-clinic? The effect of service delivery mode on hearing aid output: study protocol for a double-blinded, randomised trial in adults with mild to moderate sensorineural hearing loss

BackgroundTeleaudiology can potentially improve access to hearing healthcare services. Remote hearing aid fittings offer a new mode of service delivery that removes barriers of geography and access to an audiologist. Real-ear measurements (REMs) are the gold standard for hearing aid output verification but require in-clinic appointments. This study will investigate whether remote hearing aid fittings can provide clinically equivalent outcomes when compared to current, in-clinic, best practice guidelines.Research designA repeated measure, double-blinded crossover design will be used. Participants will be randomly allocated to one of two groups to determine order of intervention, balanced for degree of hearing loss.Study sampleSixty adults with mild to moderate hearing loss and at least 1 year of experience with hearing aids will be recruited.Data collection and analysisParticipants will complete two hearing aid fitting protocols, one using an in-clinic fitting process and the other using a remote (at-home) fitting process. In-clinic fittings will include REMs with adjustments to standard (NAL-NL2) prescription targets. The two fitting protocols will then be randomly assigned to participants in a crossover design, so participants and researchers will be blinded to the order of the two fitting protocols. Participants will then have a 4-week period with follow-up appointments for participant-directed gain adjustment. For each fitting protocol, participants will complete objective measurements of final hearing aid output with REMs, speech-in-noise testing, subjective measurements of hearing aid performance, and quality of life measurements. They will then begin an identical period of living with, adjusting, and objective assessment with the other fitting protocol. Data will be analysed as repeated measures with statistical control for potential confounding variables.ResultsData will compare the four-frequency average real-ear aided response (4FREAR) for hearing aids programmed in-clinic and hearing aids programmed remotely, after participant-directed gain adjustments. Secondary measures will assess clinically significant differences in estimated speech intelligibility, hearing-related quality of life, hearing aid benefit, sound quality and preference, and speech-in-noise ability.ConclusionsThis study will inform the development of best practice guidelines for remote hearing aid fittings. If no clinically significant differences are found between in-clinic and remote fit hearing aids, it has the potential to expand teleaudiology initiatives.Trial registrationAustralian New Zealand Clinical Trial Registry, ACTRN12623000028606p. Date of registration: 12 January 2023.

The congenital hearing phenotype in GJB2 in Queensland, Australia: V37I and mild hearing loss predominates.

GJB2 was originally identified in severe, non-syndromic sensorineural hearing loss (SNHL), but was subsequently associated with mild and moderate SNHL. Given the increasing utilisation of genetic testing pre-conceptually, prenatally, and neonatally, it is crucial to understand genotype-phenotype correlations. This study evaluated the nature and frequency of GJB2 variants in an Australian paediatric population with varying degrees of SNHL ascertained through newborn hearing screening. Audiograms from individuals with GJB2 variants and/or a GJB6 deletion (GJB6-D13S11830) were retrospectively reviewed (n = 127). Two-thirds were biallelic (homozygous/compound heterozygous) for pathogenic/likely pathogenic variants of GJB2 and/or GJB6 (n = 80). The most frequent variant was c.109 G > A, followed by c.35delG and c.101 T > C. Compared to biallelic carriage of other GJB2 variants, c.109 G > A positive individuals (homozygous/compound heterozygous) were more likely to have mild HL at their initial and latest audiograms (p = 0.0004). Biallelic carriage of c.35delG was associated with moderately-severe or greater SNHL at both initial and latest audiograms (p = 0.007). The c.101 T > C variant presented with milder SNHL and U-shaped audiograms (p = 0.02). In this agnostically identified cohort, mild SNHL predominated in GJB2/GJB6 carriers in contrast to previous studies targeting individuals with significant loss. Consequently, c.109 G > A, associated with milder phenotypes, was the most frequent. This study provides valuable data to support prognostic confidence in genetic counselling.

The Impact of Age-Related Hearing Loss on Working Memory among Older Individuals: An Event-Related Potential Study.

Age-related hearing loss (ARHL) may affect working memory (WM), which impacts problem-solving, decision-making, language comprehension, and learning. Limited research exists on how ARHL affects WM using N-back tasks, but studying this is crucial for understanding neural markers and associated cognitive processes. Our study explores the impact of ARHL on WM using behavioral and electrophysiological measures and how it correlates with speech-in-noise scores in older individuals with ARHL. The study involved two groups, each with 20 participants aged 60-80. Group 1 had individuals with mild to moderate sensorineural hearing loss, while Group 2 had age- and education-matched controls with normal or near-normal hearing. Participants underwent audiological assessments and completed cognitive tests, including simple reaction time and N-back tests. During the performance of cognitive tasks, a simultaneous electroencephalography was recorded. Data analysis included behavioral and event-related potentials, source estimation, and functional connectivity analysis. The study revealed significantly poor accuracy, longer reaction time, and smaller P300 amplitude among individuals with ARHL, even after controlling for general slowing. Individuals with ARHL experience compromised neural activity, particularly in the temporal and parietal regions, which are vital for cognition and WM. Furthermore, individuals with ARHL exhibited poor communication between the superior temporal gyrus and insulae regions among the brain regions mediating WM during the 1-back task. Also, the study found a strong correlation between hearing measures and WM outcomes. The study findings suggest that individuals with ARHL have impaired WM compared to those with normal hearing. This indicates a potential link between ARHL and cognitive decline, which could significantly affect daily life and quality of life. The widely used WM test with simultaneous EEG recording and source estimation analysis would further validate the usefulness of the study in assessing WM in this population.

Acoustic change complex findings in mild and moderate sensorineural hearing loss

BackgroundAuditory electrophysiological tests of the cortex, which are processed in or close to the auditory cortex, are brain reactions to sound. A variation in a continuous stimulus causes the acoustic change complex potential (ACC), which is a wave following the P1-N1-P2 response.ObjectiveTo measure the amplitude and latency of different components of ACC in normal subjects and across individuals with mild and moderate degrees of sensorineural hearing loss (SNHL).Patients and methodsThe study includes 100 individuals with the age ranged from 10 to 50 years with different degrees of SNHL. The ACC was evoked by a change of second formant in the middle of ongoing steady-state synthetic, 3 formant vowels (ooee). The total duration was 500 ms. Changing occurred at 250 ms.ResultsThe SNHL subgroups showed statistically significantly longer P1 and N1 latencies. N1 and P2 amplitudes of ACC onset response were larger with a statistical significance as compared to controls. Post hoc analysis revealed no statistically significant difference between mild and moderate SNHL on ACC parameters. Age showed a significant negative correlation with ACC N1 and P2 latency, ACC P1 and N1 amplitude, and onset P2 latency. Onset response P1 latency was significantly higher in children than adults. Median ACC P1 amplitude significantly increased in children than adults.ConclusionACC is a reliable tool for testing the auditory cortex function of detecting difference in sounds presented that can be recorded readily in patients with mild and moderate SNHL.

Relationship of Serum Prestin Levels to the Severity of Sensorineural Hearing Loss.

Prestin is an outer hair cell (OHC) protein responsible for increasing cochlear sensitivity and has been proposed as a biomarker.We aimed to evaluate whether the serum prestin level is related to the severity of chronic sensorineural hearing loss (SNHL). Ninetysubjects were recruited from the patient base at Samarra public hospitals and clinics in Iraq from January to October of 2022. They were divided into three groups equally: agroup of healthy people without hearing loss (G0), a group with moderate SNHL (G1), and a group with severe SNHL (G2). The subjects ranged from 20 to 80 years of age and included 51 males and 39 females. Blood samples were collected, then serum was separated, and enzyme-linked immunosorbent assays were performed to quantify the levels of prestin. Hearing thresholds were sequentially statistically higher across the three groups. While prestin levels were significantly higher in G1 and G2 than that in G0, there were no differences between the G1 and G2 levels. Serum prestin levels were positively correlated with hearing thresholds in G1, but not G2. Our results suggest that in the clinical setting, prestin is sensitive to chronic mild to moderate SNHL (i.e., up to 40-60 dB), not more severe loss.This range is consistent with the added sensitivity provided by OHCs in the cochlea and provides support for prestin as a biomarker of OHC-mediated SNHL.

MPZL2—a common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population

BackgroundMutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss.MethodsIn this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing.ResultsApart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency.ConclusionsWe concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2.

Evaluation of Hearing Status in Various Type of Cerebral Palsy Children in a Tertiary Hospital

Background: Cerebral palsy (CP) in children are frequently associated with sensorineural pathology.
 Objectives: To assess the severity of hearing impairment in children with CP and correlate the auditory impairment with different types of CP.
 Materials & Methods: This cross-sectional study was conducted in the Department of Pediatric neurology and Autolaryngiology- Head and Neck Surgery BSMMU, during March to September 2011. Diagnosed CP patients were included consecutively. After taking informed written consent, proper history and clinical examinations was done and severity of hearing loss was assessed.
 Results: Among the 50 children with CP, Tympanometry result revealed that negative middle ear pressure was present in 32% in spastic quadriplegia(SQ), 24% in spastic hemiplegia (SH), 16% in spastic diplegia (SD) and 24% in mixed type. Eustachian tube dysfunction was present in 62.5% in spastic hemiplegia. In TOAE result 52% were pass and 48% were referred and ABR were suggested. On the basis of result of TOAE, those were referred, initially they were encountered as hearing impairment in this study. Among them, in SQ were 18%, SH were 12% and mixed. Follow up auditory brain stem response revealed mild, moderate and severe sensorineural hearing loss were 8% in spastic quadriplegic type and the spastic diplegia and athetoid group were 2% only mild, Moderate sensorineural hearing were 2% in spastic hemiplegia group.
 Conclusion: Spastic Quadriplegic cerebral palsy patients had the maximum incidence of hearing impairment. Perinatal asphyxia and prematurity were the main risk factor of hearing impairment.
 BANGLADESH J CHILD HEALTH 2022; VOL 46 (1) : 19-22

The Importance of Mitochondrial Disease Testing in Young Adults With New Onset Sensorineural Hearing Loss.

Sensorineural hearing loss (SNHL) occurs commonly as part of mitochondriopathies and varies in severity and onset. In this study, we characterized hearing with specific consideration for hearing loss as a potential early indicator of mitochondrial disease (MD). We hypothesize that genetic testing at the earliest detection of SNHL may lead to an earlier MD diagnosis. We reviewed the clinical and audiometric data of 49 patients undergoing genetic testing for MD. One-third of individuals with molecularly confirmed MD presented with SNHL. On average, patients had hearing loss at least 10 years before genetic testing. The collective audiometric profile includes mild to moderate SNHL at lower frequencies and moderate SNHL at 2 kHz and higher frequencies. This study suggests that screening for SNHL could be an early indicator of MD. We propose that the audiometric profile for those with a MD diagnosis may have clinical triage utility.

Postmeningitic pediatric hearing loss from non-type b Haemophilus influenzae

BackgroundPostmeningitic hearing loss from Haemophilus influenzae (H. influenzae) is increasingly due to encapsulated serotypes other than type b (Hib) and nontypeable strains (collectively, nHiB H. influenzae). Pediatric hearing loss after nHib H. influenzae meningitis remains poorly described. MethodsRetrospecive case series of nHiB H. influenzae meningitis cases identified from a microbiologic database at Children's Hospital Colorado from 2000 to 2020. Literature regarding nHiB H. influenzae and H. influenzae postmeningitic hearing loss was also reviewed. ResultsEleven cases of nHib H. influenzae meningitis (median age 15.9 months) were identified due to serotype f (36 %), serotype a (27 %), and nontypable strains (36 %). Seven (64 %) patients were male, 55 % were white and 18 % were Hispanic or Latino. Hearing loss was initially identified in 4 children (40 %), with two patients with moderate conductive hearing loss (CHL) and one child with unilateral moderate sensorineural (SNHL) hearing loss patients recovering normal hearing. One patient with bilateral profound sensorineural hearing loss and associated labyrinthitis ossificans required cochlear implantation. All children (4) with identified hearing loss were noted to have additional intracranial sequelae, which included empyema (2), sinus thrombosis (2), and seizures (2). Of patients receiving steroids, 25 % had hearing loss on initial testing, compared to 66 % of those who did not receive steroids. ConclusionsnHib H. influenzae can cause both transient and permanent postmeningitic hearing loss. Steroids may offer otoprotection in nHib H. influenzae meningitis similar to Hib meningitis. Given the limited literature, further study is needed to better characterize hearing outcomes after nHib H. influenzae meningitis.

Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome.

Kabuki syndrome 1 (KS1; OMIM:147920), which is characterized by distinctive dysmorphic facial features (such as arched eyebrows, long palpebral fissures with eversion of the lower lid, and large protuberant ears), intellectual disability, short stature, and dermatoglyphic and skeletal abnormalities, is brought on by pathogenic variants in KMT2D (OMIM:602113). In this work, three individuals with novel pathogenic KMT2D gene variants had their longitudinal audiological manifestations and ear structural characteristics outlined. The longitudinal audiological data from neonatal hearing screening and a battery of several hearing tests were evaluated. The battery of hearing tests included tympanometry, distortion product otoacoustic emission (DPOAE), click-evoked air-conduction auditory brain-stem response (AC-ABR), click-evoked bone-conduction auditory brain-stem response (BC-ABR), narrow band CE-chirp auditory steady-state response (NB CE-chirp ASSR), and pure-tone audiometry (PTA). Phenotype identification and whole exome sequencing (WES) were performed on recruited individuals. All three patients (two females and on male; last evaluations at 14 months, 11 months, and 5.7 years, respectively) failed the newborn hearing screening, and the audiological follow-up data revealed mild to profound fluctuating hearing loss, which was directly influenced by the incidence and severity of otitis media with effusion (OME). When OME occurred, the AC-ABR thresholds increased from 30-75 dBnHL to 45-90 dBnHL. The threshold for the BC-ABR and BC-PTA was between 25 and 50 dBnHL, indicating mild to moderate sensorineural hearing loss (SNHL). The high-resolution computed tomography (HRCT) pictures indicated that all three patients had middle and inner ear abnormalities. Middle ear anomalies showed as diminished mastoid gasification and ossicle dysplasia. Cochlear dysplasia, a dilated vestibule, fusion of the vestibule with the horizontal semicircular canals, and a short and thick horizontal semicircular canal were visible on images of the inner ear. This study recruited three individuals with three novel pathogenic variants (c.5104C>T, c.10205delA, and c.12840delC) of KMT2D who were identified at ages 27 days, 2 months, and 5.5 years. Hearing characteristics of three individuals with three novel pathogenic variants of KMT2D range from mild to profound fluctuating hearing loss with mild to moderate SNHL. HRCT scans showed that all three individuals had anatomical middle and inner ear abnormalities. KS 1 patients must get clinical therapy for OME, frequent auditory monitoring, and prompt intervention.

How can the routine use of face masks by medical professionals affect hearing-impaired patients’ perception of speech? A case–control study

BackgroundFacemasks are routinely used among healthcare providers, especially after the COVID-19 pandemic. However, they negatively impact speech perception. Our study investigated how speech perception using the word discrimination score (WDS) was affected by wearing surgical and KN95 masks while dealing with hearing-impaired healthcare recipients.MethodThis case–control study included 60 participants [15 with normal hearing and 45 with varied degrees of sensorineural hearing loss (SNHL)], for whom word discrimination scores (WDS) were evaluated under various mask conditions.ResultsOn applying repeated measures of two-way analysis of variance (RM two-way ANOVA), there was statistically significant interaction (p = 0.0018), meaning that the level by which the mask affects the WDS depends on the underlying hearing level. Both main factors showed a statistically significant effect (p < 0.0001). Surgical masks had a lesser impact on speech discrimination compared to KN 95.ConclusionsIt was concluded that KN95 severely impacted the WDS among all groups relative to surgical mask and the no-mask condition. Although the high-frequency SNHL (HF-SNHL) group had mild hearing loss in the pure tone audiometry (PTA) average, they showed lower WDS relative to the mild to moderate flat SNHL (MM-SNHL). Moderately severe to severe SNHL expressed the worst values. As a result, the surgical mask is recommended over the KN95 mask since it provides better speech discrimination while giving adequate protection. These findings should be taken into consideration as they will have an impact on communication, especially in situations like hospitals where the patients must understand the instructors and healthcare providers very well.

Novel GPR156 variants confirm its role in moderate sensorineural hearing loss

Hereditary hearing loss (HL) is a genetically heterogeneous disorder affecting people worldwide. The implementation of advanced sequencing technologies has significantly contributed to the identification of novel genes involved in HL. In this study, probands of two Turkish families with non-syndromic moderate HL were subjected to exome sequencing. The data analysis identified the c.600G > A (p.Thr200Thr) and c.1863dupG (p.His622fs) variants in GPR156, which co-segregated with the phenotype as an autosomal recessive trait in the respective families. The in silico predictions and a minigene assay showed that the c.600G > A variant disrupts mRNA splicing. This gene belongs to the family of G protein-coupled receptors whose function is not well established in the inner ear. GPR156 variants have very recently been reported to cause HL in three families. Our study from a different ethnic background confirms GPR156 as a bona fide gene involved in HL in humans. Further investigation towards the understanding of the role of GPCRs in the inner ear is warranted.

Temporal Ordering and Auditory Resolution in Individuals with Sensorineural Hearing Loss.

Introduction Peripheral hearing loss, besides causing inadequate auditory input, can lead to distortions in the tonotopic auditory map and reorganization of neural networks. Therefore, the processing of temporal aspects of a sound stimulus and, consequently, the effectiveness of human communication can be negatively impacted. Objective To test the temporal ordering and auditory resolution of people with mild and moderate sensorineural hearing loss and to compare them with the those of people with normal hearing. Methods A total of 19 right-handed individuals aged 16 to 59 years with mild to moderate postlingually acquired symmetric bilateral sensorineural hearing loss participated in the study. They were submitted to frequency and duration pattern tests and a random gap detection test. Results The mean correct response rate in the frequency pattern test was of 66.3%, and, in the duration pattern test, 71.7%. The mean threshold in the random gap detection test was of 14.1 ms. A comparison with the criteria established for normal subjects without peripheral hearing loss revealed that more than half the subjects had abnormal results in the temporal ordering test, while a smaller fraction had reduced temporal resolution. Conclusions The performance of the subjects with acquired sensorineural hearing loss was poorer than that of the participants without peripheral hearing loss. Their results on the temporal ordering test were also poorer than in the temporal resolution test, demonstrating the importance of analyzing both these auditory skills in people with peripheral hearing loss.

Novel Variant in CEP250 Causes Protein Mislocalization and Leads to Nonsyndromic Autosomal Recessive Type of Progressive Hearing Loss.

Genetic hearing loss is the most common hereditary sensorial disorder. Though more than 120 genes associated with deafness have been identified, unveiled causative genes and variants of diverse types of hearing loss remain. Herein, we identified a novel nonsense homozygous variant in CEP250 (c.3511C>T; p.Gln1171Ter) among the family members with progressive moderate sensorineural hearing loss in nonsyndromic autosomal recessive type but without retinal degeneration. CEP250 encodes C-Nap1 protein belonging to the CEP protein family, comprising 30 proteins that play roles in centrosome aggregation and cell cycle progression. The nonsense variant in CEP250 led to the early truncating protein of C-Nap1, which hindered centrosome localization; heterologous expression of CEP250 (c.3511C>T) in NIH3T3 cells within cilia expression condition revealed that the truncating C-Nap1 (p.Gln1171Ter) was not localized at the centrosome but was dispersed in the cytosol. In the murine adult cochlea, Cep250 was expressed in the inner and outer hair cells. Knockout mice of Cep250 showed significant hair cell degeneration and progressive hearing loss in auditory brainstem response. In conclusion, a nonsense variant in CEP250 results in a deficit of centrosome localization and hair cell degeneration in the cochlea, which is associated with the progression of hearing loss in humans and mice.

Evaluation of Factors Affecting Hearing Aid Use in Children.

The purpose of this study was to determine the factors affecting hearing aid use in children and investigate how these factors affected their subjective auditory performance. The study was carried out with 34 children aged three to six years who had mild or moderate sensorineural hearing loss and had used a bilateral hearing aid for at least six months. The daily hearing aid usage times of children were collected with the help of data logging software. Parent-child interactions were assessed with the Maternal Behavior Rating Scale (MBRS) and Child Behavior Rating Scale (CBRS) scores. To assess the parents' levels of knowledge about hearing devices, the Hearing Aid Awareness Question Form for Parents, which was prepared by the researchers, was used. Finally, to evaluate the subjective hearing performance of the children, the Parents' Evaluation of Aural/Oral Performance of Children (PEACH) survey was implemented. Strong and significant correlations were found between the MBRS and CBRS scores, the results obtained from some questions in the Hearing Aid Awareness Question Form for Parents, the overall PEACH score, the QUIET subscale score, and the NOISE subscale score (p<0.001). According to the multivariate linear regression analyses, it was observed that the use of the pediatric clip hearing aids holder (question 17) had a significant effect in decreasing both the overall PEACH score (β=-3.07, p=0.008) and the PEACH-NOISE subscale score (β=-1.88, p=0.012). A unit increase in the score given to question 24 of the Hearing Aid Awareness Question Form for Parents (i.e., using the hearing aids longer) caused a 2.35-fold increase in the PEACH-NOISE subscale score, a 1.74-fold increase in the PEACH-QUIET subscale score, and a 4.06-fold increase in the overall PEACH score. Parent-child interaction and parents' knowledge about hearing aid use are important factors affecting hearing aid use in children. These factors also affect the children's subjective auditory performance. Parents should be given detailed information about hearing aid use and be more sensitive and responsive in their interactions with their children.

Maximizing the Detection of Copy Number Variants in the Highly Homologous Deafness-Infertility Syndrome Locus in Standard-of-care Testing

Genome-wide chromosomal microarrays (CMA) can identify pathogenic copy number variants (CNVs) associated with patients’ clinical indications but also have the potential to detect incidental findings and carrier status for recessive disorders. Patients can benefit from maximizing the detection and reporting of potentially clinically significant CNVs from this standard-of-care genome-wide test in accordance with professional guidelines (1); however, accurate detection of specific CNVs can be limited by the technology used and the complexity of the genomic regions under consideration. One example of this complexity is in the detection of disease-causing variants in the STRC gene associated with DFNB16, the second most frequent cause of autosomal recessive nonsyndromic hearing loss (NSHL), which is a common sensory disorder with high genetic heterogeneity. DFNB16 is estimated to account for up to 16% of individuals with NSHL (2). Most pathogenic STRC alterations are deletions encompassing all or part of the gene. These deletions often extend into the neighboring gene CATSPER2, which is associated with male fertility. Homozygous, contiguous deletions involving both STRC and CATSPER2 cause deafness-infertility syndrome (DIS), a contiguous gene deletion syndrome characterized by nonsyndromic, congenital to post-lingual onset of mild to moderate bilateral sensorineural hearing loss in both males and females and exclusive male infertility. Several studies have reported that 1%–2% of individuals are asymptomatic heterozygous carriers for a deletion of STRC with or without CATSPER2 (2, 3). The high frequency of STRC deletions has also led to reports of “pseudodominant inheritance,” in which a parent and child both have hearing loss as a result of homozygous STRC deletions (3, 4).

Siblings with 4H leukodystrophy – A rare cause of hypomyelination

A 35-year-old man presented with slowly progressive ataxia since childhood, failure of development of secondary sexual characteristics, primary infertility, delayed dentition, and moderate sensorineural hearing loss on both sides. On physical examination, there were unerupted first molar teeth on both sides, lack of axillary and facial hair and a small-sized penis. He underwent a magnetic resonance imaging (MRI) examination of the brain which showed diffuse hypomyelination with relative sparing of bilateral posterior limbs of the internal capsule, the ventrolateral nucleus of the thalamus, and optic radiations, along with a hypoplastic anterior pituitary gland. Hence, 4H leukodystrophy was suggested radiologically which made us curious to ask for family history which revealed similar symptoms (absence of secondary sexual characters) in his younger male sibling. MRI brain screening was also performed for the sibling, which showed diffuse cerebral hypomyelination.

Effects of sensorineural hearing loss on formant-frequency discrimination: Measurements and models

This study concerns the effect of hearing loss on discrimination of formant frequencies in vowels. In the response of the healthy ear to a harmonic sound, auditory-nerve (AN) rate functions fluctuate at the fundamental frequency, F0. Responses of inner-hair-cells (IHCs) tuned near spectral peaks are captured (or dominated) by a single harmonic, resulting in lower fluctuation depths than responses of IHCs tuned between spectral peaks. Therefore, the depth of neural fluctuations (NFs) varies along the tonotopic axis and encodes spectral peaks, including formant frequencies of vowels. This NF code is robust across a wide range of sound levels and in background noise. The NF profile is converted into a rate-place representation in the auditory midbrain, wherein neurons are sensitive to low-frequency fluctuations. The NF code is vulnerable to sensorineural hearing loss (SNHL) because capture depends upon saturation of IHCs, and thus the interaction of cochlear gain with IHC transduction. In this study, formant-frequency discrimination limens (DLFFs) were estimated for listeners with normal hearing or mild to moderate SNHL. The F0 was fixed at 100 Hz, and formant peaks were either aligned with harmonic frequencies or placed between harmonics. Formant peak frequencies were 600 and 2000 Hz, in the range of first and second formants of several vowels. The difficulty of the task was varied by changing formant bandwidth to modulate the contrast in the NF profile. Results were compared to predictions from model auditory-nerve and inferior colliculus (IC) neurons, with listeners’ audiograms used to individualize the AN model. Correlations between DLFFs, audiometric thresholds near the formant frequencies, age, and scores on the Quick speech-in-noise test are reported. SNHL had a strong effect on DLFF for the second formant frequency (F2), but relatively small effect on DLFF for the first formant (F1). The IC model appropriately predicted substantial threshold elevations for changes in F2 as a function of SNHL and little effect of SNHL on thresholds for changes in F1.