Sudden Hearing Loss Research Articles

Genomic and phenotypic landscapes of X-linked hereditary hearing loss in the Chinese population

BackgroundHearing loss (HL) is the most common sensory birth deficit worldwide, with causative variants in more than 150 genes. However, the etiological contribution and clinical manifestations of X-linked inheritance in HL remain unclear within the Chinese HL population. In this study, we focused on X-linked hereditary HL and aimed to assess its contribution to hereditary HL and identify the genotype–phenotype relationship.MethodsWe performed a molecular epidemiological investigation of X-linked hereditary HL based on next-generation sequencing and third-generation sequencing in 3646 unrelated patients with HL. We also discussed the clinical features associated with X-linked non-syndromic HL-related genes based on a review of the literature.ResultsWe obtained a diagnostic rate of 52.72% (1922/3646) among our patients; the aggregate contribution of HL caused by genes on the X chromosome in this cohort was ~ 1.14% (22/1922), and POU3F4 variants caused ~ 59% (13/22) of these cases. We found that X-linked HL was congenital or began during childhood in all cases, with representative audiological profiles or typical cochlear malformations in certain genes. Genotypic and phenotypic analyses showed that causative variants in PRPS1 and AIFM1 were mainly of the missense type, suggesting that phenotypic variability was correlated with the different effects that the replaced residues exert on structure and function. Variations in SMPX causing truncation of the protein product were associated with DFNX4, which resulted in typical audiological profiles before and after the age of 10 years, whereas nontruncated proteins typically led to distal myopathy. No phenotypic differences were identified in patients carrying POU3F4 or COL4A6 variants.ConclusionsOur work constitutes a preliminary evaluation of the molecular contribution of X-linked genes in heritable HL (~ 1.14%). The 15 novel variants reported here expand the mutational spectrum of these genes. Analysis of the genotype–phenotype relationship is valuable for X-linked HL precise diagnostics and genetic counseling. Elucidation of the pathogenic mechanisms and audiological profiles of HL can also guide choices regarding treatment modalities.

Hearing restoration by gene replacement therapy for a multisite-expressed gene in a mouse model of human DFNB111 deafness

Gene therapy has made significant progress in the treatment of hereditary hearing loss. However, most research has focused on deafness-related genes that are primarily expressed in hair cells with less attention given to multisite-expressed deafness genes. MPZL2, the second leading cause of mild-to-moderate hereditary deafness, is widely expressed in different inner ear cells. We generated a mouse model with a deletion in the Mpzl2 gene, which displayed moderate and slowly progressive hearing loss, mimicking the phenotype of individuals with DFNB111. We developed a gene replacement therapy system mediated by AAV-ie for efficient transduction in various types of cochlear cells. AAV-ie-Mpzl2 administration significantly lowered the auditory brainstem response and distortion product otoacoustic emission thresholds of Mpzl2-/- mice for at least seven months. AAV-ie-Mpzl2 delivery restored the structural integrity in both outer hair cells and Deiters cells. This study suggests the potential of gene therapy for MPZL2-related deafness and provides a proof of concept for gene therapy targeting other deafness-related genes that are expressed in different cell populations in the cochlea.

Splice-altering variant of PJVK gene in a Mauritanian family with non-syndromic hearing impairment.

PJVK gene was recently shown to create hypervulnerability to sound in humans and was the first human gene implicated in non-syndromic hearing impairment due to neural defect. Targeted next-generation sequencing of over 150 known deafness genes was performed in the proband. Sanger sequencing was used to validate the PJVK variant and confirm familial segregation of the disease. A minigene-based assay has been performed to assess the impact of the variant on splicing. We identified a novel c.550-6A > G acceptor splice-site variant in the PJVK gene in the homozygous state in a Mauritanian child with severe to profound congenital deafness. The substitution was located in intron 4. The effect of the variation was demonstrated by a minigene assay which showed that the variation, an insertion of an additional 5 bp, created a new splice site resulting in the appearance of a premature stop codon (p.Phe184Tyrfs*26) and likely a truncated protein. This result constitutes a new splice-site variant report in the PJVK gene leading to DFNB59 type associated with autosomal recessive non-syndromic hearing impairment (ARNSHI).

Case Report: - Sudden sensorineural hearing loss and vertigo due to inner ear hemorrhage

Sudden deafness is a common cause of emergency consultation in otology. Usually, despite investigations, no etiology is known. Intracochlear hemorrhage is a rare cause of sudden sensorineural hearing loss (SSNHL) and may be associated with various labyrinthine disorders. In such cases, magnetic resonance imaging (MRI) is the clef of the diagnosis. We report the case of a 70-year-old patient who was referred to our department for sudden hearing loss, tinnitus, and vertigo. Otoscopic and neurological examinations were normal, and pure-tone audiometry revealed left profound sensorineural hearing loss. Videonystagmography (VNG) revealed left vestibular deficit. MRI demonstrated a high signal intensity inside the cochlea on unenhanced T1-weighted images, and no other abnormalities were found; in particular, no enhancement after intravenous administration of gadolinium. No etiology was identified. Vertigo disappeared rapidly with corticosteroid treatment and hyperbaric oxygen therapy, but hearing did not improve. Intra-labyrinthine hemorrhage causing SSNHL is rare, and the hearing prognosis is poor.

Preliminary Validation of Measures of Experienced, Perceived, and Internalized Stigma Among Adults Who Are d/Deaf or Hard of Hearing in the United States and Ghana.

In this article, we examine the psychometric performance of 3 scales measuring experienced, perceived, and internalized d/Deaf or hard of hearing (d/DHH) stigma among adult (18 and older) populations of individuals who are d/DHH, including those who have been d/DHH since before they developed language (lifelong) and those who became d/DHH after they developed language (acquired) in the United States and Ghana. The preliminary validation study took place in the Greater Accra and Eastern regions of Ghana and across the United States. In the United States, all data were collected online via self-administered surveys in English. In Ghana, trained interviewers who are d/DHH and fluent in Ghanaian Sign Language conducted interviews with participants who are lifelong d/DHH using a video survey. Ghanaian participants with acquired d/DHH status were surveyed by trained hearing interviewers. We calculated polychoric correlation matrices between the measures to remove redundant and unrelated items and used exploratory factor analysis to create the final scales. We also tested the association between the factor scores and a simple summing method for calculating the scale. The study sample included people who have been d/DHH since before they developed language (Ghana: n = 171, United States n = 100) and people who became d/DHH after they developed language (Ghana: n = 174, United States: n = 219). The final experienced, perceived, and internalized scales included six, seven, and five items, respectively. All three scales performed well as unidimensional measures across all four samples. Across the four samples, the experienced, perceived, and internalized stigma scales yielded ordinal αs ranging from 0.725 to 0.947, 0.856 to 0.935, and 0.856 to 0.935, respectively. It would be acceptable to operationalize all stigma scales as sum-of-item scores. The scales performed well and appear to provide a valid means of measuring different types of stigma among diverse groups of people who are d/DHH. Future work should refine and validate these scales in additional contexts.

A Village in the Southeastern Region of Iran Harboring the c.716T>A (p.Val239Asp) Mutation in SLC26A4.

After GJB2, SLC26A4 is the second most common contributor to autosomal recessive nonsyndromic hearing loss (ARNSHL) worldwide. In this study, we used Exome Sequencing (ES) to present a village with 31 individuals affected by hereditary hearing loss (HHL) in southeastern Iran near the border of Pakistan. The village harbored the known pathogenic missense SLC26A4 (NM_000441.2):c.716T>A (p.Val239Asp) mutation, which has a founder effect attributed to Pakistan, Iran's southeastern neighbor. Our findings, in addition to unraveling the molecular cause of non-syndromic hearing loss in these patients and further confirming the common ancestry and migration story between the people of this region and Pakistan, provide further insight into the genetic background of this region and highlight the importance of understanding the mutation spectrum of GJB2 and SLC26A4 in different regions to choose cost-effective strategies for molecular genetic testing.

Preliminary Validation of Stigma Measures Among Parents of Children Who Are d/Deaf or Hard of Hearing in the United States and Ghana

Objectives: Parents are integral to the development and overall well-being of their child. Previous research has studied the emotional effects parenting experiences have on parents. However, parents caring for children with disabilities have unique parenting experiences, filled with both victories and challenges. Parenting a child with disabilities can bring additional responsibilities as parents respond to their child’s special needs. Specifically, parents of children who are d/Deaf or hard of hearing (d/DHH) are required to make ongoing life-changing decisions about their child’s life, including mode of communication, medical care, and education. Across the world, many adults who are d/DHH experience stigma. However, less is known about the stigma faced by children who are d/DHH and their parents. Measuring the nature and magnitude of stigma-affecting parents of children who are d/DHH could offer insights into how to additionally support these parents. Nonetheless, there is a gap in validated scales to measure stigma among parents of children who are d/DHH. In response, we developed and preliminarily validated five measures of stigma among parents of children who are d/DHH. Design: Measures were developed through a mixed-method process: (1) a scoping literature review, (2) a modified Delphi process consisting of two group discussions (n = 3, n = 4) and two individual discussions with parents of children who are d/DHH from high-income countries (HICs) and low- and middle-income countries (LMICs), (3) cognitive interviews with parents of children who are d/DHH in the United States (U.S.) (n = 5) and Ghana (n = 5), and (4) a pretest of the survey in the U.S. (n = 28) and Ghana (n = 30). Modifications to the measures were made after each stage. This article focuses on evaluating the psychometric performance of the developed measures. Parents were recruited in the U.S. (n = 100) and Ghana (n = 173). Convenience sampling was used in both countries. In Ghana, survey administration was in-person with trained interviewers collecting data on tablets. In the U.S. data were collected online through self-administered surveys. Results: The final five scales measured: (1) parental observation of stigma their child experiences (seven items), (2) parental perceptions of stigma toward their child (eight items), (3) parental secondary experienced stigma (eight items), (4) perceived parental secondary stigma (five items), and (5) parental internalized stigma (seven items). All scales performed strongly and similarly across both country samples. The scales had ordinal αs ranging from 0.864 to 0.960, indicating strong reliability. Conclusions: This study provides a set of preliminarily validated stigma measures to capture the experience of parents of children who are d/DHH. Measuring stigma among parents is critical to understanding parental mental health, as parental well-being affects the health and development of their child. Furthermore, measuring observed stigma by parents can allow the researcher to gain an understanding of the stigma experienced by children who are d/DHH that they may not be able to communicate. Further studies testing these measures across other countries and with more diverse samples are needed.

Development and Preliminary Validation of Stigma Measures for Care Partners of Persons Who Are d/Deaf or Hard of Hearing.

A great deal of literature documents the significant demands, both physical and psychosocial, that care partners experience when providing care to persons with a range of health conditions. There is, however, far less research available on care partners of adult persons who are d/Deaf or hard of hearing (d/DHH). In response to this gap, the authors developed measures of d/DHH stigma among care partners as part of the work of the Lancet Commission on Hearing Loss' Measures, Models, and Stigma Reduction Subgroup. The measures examined in this article are part of a larger set of parallel measures to enable comparison of stigma measurement across groups. The present study describes the preliminary validation of five stigma scales specifically tailored for use to assess the prevalence and effect of stigma on the care partners of adult people who are d/DHH in the United States. Care partners in this context are defined broadly and can include spouses, partners, adult children, siblings, and friends of persons who are d/DHH. The scales describe the care partner's own assessment of how the person who is d/DHH experiences and perceives stigma as well as the care partner's own internalized, experienced, and perceived stigma as a result of their association with a person who is d/DHH. This latter set of three scales describes secondary stigma, or the stigma a person experiences related to their association with a member of a stigmatized group. Measures were developed through a process that included a literature review, Delphi groups with people who became d/DHH after they developed spoken language, cognitive interviews, and a pretest. An online, self-administered preliminary validation survey was conducted with 151 care partners. Results support the internal reliability of each of the five stigma scales (ordinal α's all greater than 0.9) and that each scale is assessing a single factor. Additional testing is needed to confirm the validity of these measures. After further validation, they can be used to assess the prevalence and effect of stigma on care partners of persons who are d/DHH and to evaluate the success of interventions developed to address stigma and its effects both on the care partner and the person who is d/DHH and receiving the care.

Retrieval practice and word learning in children who are hard of hearing

Purpose Many children who are deaf and hard of hearing (DHH) show poorer auditory word-learning skills than children with typical hearing (TH). The goal of this study was to test the effect of retrieval practice on word learning in children who are hard of hearing (HH). Method Twenty-six TH children and 16 children who are HH completed a speech perception and a vocabulary test, and a rapid word-learning game to learn new words under no retrieval, immediate retrieval, and spaced retrieval conditions. Result Linear mixed-effect models revealed that learning condition and time predicted 48% of the variance in word recognition, and age predicted 15% of word recall variance. We observed no differences in word recognition and recall between TH children and children who are HH. Children learned and remembered more words in the immediate and spaced retrieval practice conditions than in the no retrieval condition. Conclusion Retrieval practice is more effective for word learning and retention than passive exposure (no retrieval). Clinical and educational practices for children who are DHH could combine explicit instruction using targeted exposures and retrieval of new words with naturalistic approaches. Future studies should assess retrieval practice in real-life interventions to inform clinical and educational practices.

Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review

Objective This systematic literature review aimed to study the relationship between CML and hearing loss. Database review Chronic myeloid leukemia (CML) is a hematological malignancy associated with high levels of white blood cells (WBCs). Changes in otolaryngology are observed in CML. Methodology This systematic literature review of the literature was conducted by searching the MEDLINE/PubMed, Scopus, WPRIM, LILAC Sand SciELO databases. Studies published between 2013 and 2023 that met inclusion criteria were included. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to evaluate the quality of studies. Results Of the 142 identified articles, 13 were included for final evaluation with a total sample size of 75 cases diagnosed with CML with hearing defect. CML patients with WBCs above 250 x 109/L were at higher risk of ototoxicity. Males accounted for 85% of cases; with a mean age of 38.9 years. Hearing loss as the first manifestation of CML was among 61.5% of cases, it was bilateral in 83.3% of cases, and in 90% of cases were irreversible defect. Conclusion Acute sudden hearing loss has been associated with high levels of WBC in patients with CML. Neither aggressive leukoreduction nor leukapheresis has positive effect on the reversibility of the hearing loss.

Metabolic Syndrome and Its Effect the Prognosis of Sudden Hearing Loss: A Clinical Study

Metabolic Syndrome and Its Effect the Prognosis of Sudden Hearing Loss: A Clinical Study

Unilateral Hearing Loss and Auditory Asymmetry in Mitochondrial Disease: A Scoping Review.

Background/Objectives: Mitochondrial transfer RNA mutations are one of the most important causes of hereditary hearing loss in humans. In most cases, its presentation is bilateral and symmetrical; however, there are numerous cases of single-sided presentation or asymmetrical onset described in the literature that may represent a diagnostic challenge. The aim of this review is to present the evidence of auditory asymmetry in mitochondrial diseases, highlighting the possible presence of cases with atypical presentation. Methods: A review of the English literature to date on hearing loss and mitochondrial diseases was performed using PubMed, Scopus, and Google Scholar databases. The literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for scoping review. Results: A total of 10 full-text articles were included in this review, comprising 25 patients with single-sided or asymmetrical hearing loss associated with mitochondrial disease. Conclusions: Sensorineural hearing loss due to mitochondrial disease can represent a complex diagnostic challenge in cases of asymmetric or unilateral presentation. It is critical to recognize this clinical variant and to diagnose it in daily clinical practice.

Genetic analysis of TRIOBP and MYO15A variants in Iranian families with autosomal recessive non-syndromic hearing loss

BackgroundDeafness is a prevalent sensory and neurological disorder that impacts over 466 million individuals globally. Congenital deafness is the most prevalent birth defect, occurring in approximately 2–3 out of every 1000 births. It is recognized as a highly diverse condition. >50% of congenital deafness has genetic causes and the rest is due to environmental causes or both. With the development of next-generation sequencing and bioinformatics tools, whole-exome sequencing has been proposed as one of the effective methods for diagnosing genetics of hearing loss. MethodFive Iranian Autosomal recessive non-syndromic hearing loss (ARNSHL) families negative for GJB2 (NM_004004.6) gene mutations from Sistan and Baluchestan province were selected for further study by whole-exome sequencing analysis. The analysis procedure was performed using multiple bioinformatics tools and websites after filling the consent form and extracting DNA from whole blood using the salting out method. After detecting the variants in priority and confirming them in the probands by Sanger sequencing, other family members were studied to confirm the variant within the family. ResultsAfter analyzing the families recruited for this study, four known genes along with known and novel variants were discovered. Mutations found in the MYO15A, SLC26A4, TRIOBP and TECTA genes among which, the variants found in TRIOBP (NM_001039141.3, p.R283X) and MYO15A (NM_016239.4, p.P2880Rfs*19) were novel. Other known variants were TECTA (NM_005422.4, p.W1534X) and SLC26A4 (NM_000441.2, p.V239D). No genes or variants that might contribute to hearing loss have been identified within one of the families. ConclusionOur study's findings support previous research that has identified SLC26A4, MYO15A, and TECTA genes as common genetic factors following GJB2 in our population.

Sudden Hearing Loss in the Active Duty Population: An Epidemiological Study.

Hearing loss among military personnel is a well-known challenge, reported as the second most common VA service-connected disability. Although most hearing loss occurs gradually, a subset occurs suddenly and significantly impacts quality of life and military readiness and is considered as a medical emergency. This study aims to evaluate the incidence of sudden hearing loss among different subpopulations within the military system to better identify at-risk groups. This study was a retrospective population-based study reviewing all cases of diagnosed sudden hearing loss between January 1, 2016 and December 31, 2021 within active duty service members in the U.S. DoD. Statistical analysis of multiple subpopulations was performed. There were 2,650 cases of sudden hearing loss diagnosed in active duty service members during the study period, with an average incidence of 32.9 cases per 100,000 people per year, compared with 5 to 27 cases per 100,000 people per year reported in civilian populations. Senior officers demonstrated significantly increased rates of sudden hearing loss with 103.9 cases per 100,000 people per year, likely as a result of increased age, as did Air Force personnel with 45.1 cases per 100,000 people per year. There was no difference in incidence based on military occupational specialty, though service members located overseas were noted to have decreased incidence compared with those stationed within the USA. There was no significant difference during the years before coronavirus-19 pandemic (2016-2019) compared to the years following the start of the pandemic (2020-2021). Sudden hearing loss appears to occur more frequently in military personnel than in the civilian population. The increased incidence in senior officers is likely driven by increased age, though further evaluation into the discrepancies between reported incidence of hearing loss among enlisted service members and officers is warranted. Although military occupational specialty did not demonstrate any significant difference in incidence, for thus far unknown reasons those in the Air Force demonstrated increased rates of sudden hearing loss. Although other potentially at-risk groups were identified, focused efforts to better understand contributing factors to elevated incidence in senior officers and Air Force personnel will help to better mitigate the incidence and effects of sudden hearing loss.

Novel GJB2 mutation c.188delT compound with c.235delC causing non-syndromic hearing loss in a Chinese family: A case report.

Congenital sensorineural hearing loss is a significant global health issue, primarily driven by genetic factors, such as mutations in the GJB2 gene. This report presents a Chinese girl with congenital deafness and a novel mutation of the GJB2 gene. A newborn Chinese girl exhibited signs of congenital deafness. Congenital deafness was confirmed through comprehensive newborn hearing screenings that included otologic, audiologic, and physical examinations. Genetic analysis revealed a compound heterozygous mutation involving c.188delT and c.235delC in the GJB2 gene, indicating a genetic basis for her hearing loss. The patient underwent cochlear implantation, which resulted in stable auditory outcomes. Despite follow-up difficulties, stable auditory outcomes were achieved post-cochlear implantation, highlighting the potential efficacy of this intervention in GJB2-related hearing loss. This case study enriches our understanding of GJB2 mutations and underscores the critical role of genetic testing in diagnosing congenital sensorineural hearing loss. It emphasizes the necessity for early intervention and sustained interdisciplinary care to enhance the quality of life for patients with genetic hearing impairment.

Novel PTPRQ variants associated with hearing loss in a Chinese family PTPRQ variants in Chinese hearing loss.

Hearing loss is one of the most prevalent congenital sensory disorders. Over 50% of congenital hearing loss cases are attributed to genetic factors. The PTPRQ gene encodes the protein tyrosine phosphatase receptor Q, which plays an important role in maintaining the structure and function of the stereocilia of hair cells. Variants in the PTPRQ gene have been implicated in hereditary sensorineural hearing loss. Utilizing next-generation sequencing technology, we identified novel compound heterozygous variants (c.977G>A:p.W326X and c.6742C>T:p.Q2248X) in the PTPRQ gene within a Chinese national lineage, marking the first association of these variants with hereditary sensorineural hearing loss. Our findings further emphasize the critical role of PTPRQ in auditory function and contribute to a more comprehensive understanding of PTPRQ-associated hearing loss mechanisms, aiding in clinical management and genetic counseling.

Assessing vocabulary knowledge in written and signed languages of immigrant DHH learners – examining convergent validity

ABSTRACT Language assessment is a central aspect not only of language education in the general population, but also amongst heterogeneous, low-incidence populations. One such population are immigrant deaf and hard-of-hearing learners (IDML) who are bimodal-multilingual and whose languages development often includes the spoken, written, and/or signed languages of the host country in addition to learners’ home language(s) (Cannon and Marx 2024) [“Scoping review of research methodologies across language studies with deaf and hard-of-hearing multilingual learners.” International Review of Applied Linguistics in Language Teaching 62 (2): 1009–1037]. Language assessment with these learners is complicated due to a lack of expected norms for the population and a lack of appropriate instruments for signed languages in general (Pizzo and Chilvers 2019) [“Assessment of Language and Literacy in Children Who Are d/Deaf and Hard of Hearing.” Education Sciences 9 (3): 223]. This is a major issue for both research and pedagogy. In order to address this in the German context, a comparison of available assessment instruments focusing on vocabulary knowledge in written German and German Sign Language was carried out. The aim of this exploratory study was (1) to examine available language assessments, (2) to test them with a small sample representing the target population in order to determine their convergent validity, and (3) to provide recommendations for researchers and practitioners for their use. The results shed light on the potential for existing instruments to provide necessary and useful information for assessment in research and schools.

A base editor for the long-term restoration of auditory function in mice with recessive profound deafness.

A prevalent recessive mutation (c.2485C>T, p.Q829X) within the OTOF gene leads to profound prelingual hearing loss. Here we show that in Otof mice harbouring a mutation (c.2482C>T, p.Q828X) homozygous to human OTOF that faithfully mimics the hearing-loss phenotype, a base editor (consisting of the deaminase ABE7.10max and the Cas9 variant SpCas9-NG) packaged in adeno-associated viruses and injected into the inner ear of the mice via the round-window membrane effectively corrected the pathogenic mutation, with no apparent off-target effects. The treatment restored the levels of the otoferlin protein in 88% of the inner hair cells and stably rescued the auditory function of the mice to near-wild-type levels for over 1.5 years while improving synaptic exocytosis in the inner hair cells. We also show that an adenine base editor that targets the prevalent human OTOF mutation restored hearing in humanized mice to levels comparable to those of the wild-type counterparts. Base editors may be effective for the treatment of hereditary deafness.

Cochlear implantation and partial deafness - A retrospective review on processor programming

Background To decide what programming parameters to use for cochlear implants (CIs) in partial deaf patients can be challenging. Objective The processor programming form, categorised as electrical complement (EC), electro-acoustic-stimulation (EAS) or electric stimulation (ES), and difficulties switching programming form were investigated. Methods A retrospective investigation of medical records and audiograms was conducted in adult patients intended for EC and EAS. Results Eighty-four ears (80 patients) were included. Twenty ears were initially fitted with EC, 32 with EAS, 30 with ES and 2 with both EC and EAS. Sixty-four ears met the criteria to use EC or EAS at initial fitting, however only 54 ears were fitted with EC or EAS initially. Twenty-eight patients altered between at least two programming forms and six of those experienced difficulties to adapt to a new form when their low-frequency hearing deteriorated. Twenty-five percent of patients initially fitted with EC or EAS switched programming form within two years. Discussion Further studies on how to choose the most beneficial sound processor programming parameters for EC and EAS, and when to change between programming forms, are warranted as well as clear guidance on choosing the right candidates for EC and EAS.

Oral English is Oral and I am Deaf: Deaf and Hard of Hearing on Trial Phonetics and Phonology In Nigeria

Oral English is Oral and I am Deaf: Deaf and Hard of Hearing on Trial Phonetics and Phonology In Nigeria