The Association of Race With Decreased Access to Pediatric Hearing Healthcare in the United States.

Successful intervention to support a child with congenital hearing loss requires early identification and consistent access to frequent professional services. In the early 2000s, the United States implemented an initiative, Early Hearing Detection and Intervention (EHDI), to provide timely identification and treatment of congenital hearing loss. This national program aims to screen hearing by 1 month of age, diagnose hearing loss by 3 months of age, and provide intervention to infants with hearing loss by 6 months of age. To date, the United States is successfully implementing hearing screening by 1 month of age but continually struggling to diagnose and treat congenital hearing loss promptly for many infants. This article begins by exploring the current state of American children and families, focusing on social determinants of health, specifically race and poverty. The objective is to understand how race affects social determinants of health, and ultimately hearing healthcare access for children. A narrative literature review spanning public health, sociology, and hearing research was completed to inform this work. The current body of literature supports the conclusion that race and racism, separate from poverty, lead to decreased access to pediatric hearing healthcare. Interventions targeting these issues are necessary to improve timely access to hearing loss diagnosis and treatment for American children.

Importancia del citomegalovirus congénito en el programa de cribado auditivo neonatal / Importance of congenital cytomegalovirus in the neonatal hearing screening program

Introducción En recién nacidos, la hipoacusia secundaria a una infección congénita por citomegalovirus (CMVc), pese a su baja prevalencia, puede generar un grave problema en el desarrollo personal y la integración social de los pacientes. Por ello, es importante incluir la determinación del ADN de CMV como herramienta del cribado neonatal. Materiales y métodos Hemos realizado un estudio retrospectivo de 5 años, mediante la descripción de las CMVc en la Comunidad Autónoma del País Vasco en los recién nacidos que no superaron el cribado auditivo en el programa de detección precoz de hipoacusia. Se describen los tiempos de detección, confirmación (incidencia) e intervención (tratamiento). Resultados De 18.782 sujetos estudiados, 58 (3 por cada 1.000 nacidos vivos) presentaron hipoacusia. De ellos, se confirmó CMVc en 4pacientes (una mujer y 3hombres).El tiempo promedio para el cribado auditivo fue de 6,5 días (DE:±3,69) y para detectar el CMV mediante reacción en cadena de la polimerasa en orina y saliva fue de 4,2 días (DE:±3,94).El tiempo para confirmar la hipoacusia mediante PEATC e intervención audiológica fue de 2,2 meses (DE:±0,957) y 5 meses (DE:±3,741), respectivamente. Se realizaron 4adaptaciones audioprotésicas y un implante coclear. Discusión y conclusión El cribado auditivo neonatal se ha consolidado como un buen programa de salud pública. La determinación del ADN viral permite un diagnóstico y tratamiento precoz, específico e interdisciplinar, en el que la otorrinolaringología tiene un papel fundamental. Nuestro estudio resalta la importancia de incluir la reacción en cadena de la polimerasa del CMV como herramienta de cribado universal. (AU)

Introduction In newborns, hearing loss secondary to congenital cytomegalovirus (CMVc) infection, despite its low prevalence, can cause a serious problem in the personal development and social integration of patients. Therefore, it is important to include the determination of CMV DNA as a neonatal screening tool. Materials and methods We have carried out a 5-year retrospective study, by describing the CMVc in the Autonomous Community of the Basque Country (Spain) in newborns who did not pass the hearing screening in the early hearing loss detection program. The times of detection, confirmation (incidence) and intervention (treatment) are described. Results Of 18,782 subjects studied, 58 (3 per 1,000 live births) presented hearing loss. Of these, CMVc is guaranteed in 4patients (one woman and 3men). The mean time to hearing screening was 6.5 days (SD: ±3.69) and to detect CMV by polymerase chain reaction in urine and saliva was 4.2 days (SD: ±3.94). Time to confirm hearing loss by BAEP and audiological intervention 2.2 (SD: ±0.957) and 5 months (SD: ±3.741), respectively. Four hearing aid adaptations and one cochlear implant were performed. Discussion and conclusion Neonatal hearing screening has established itself as a good public health program. The determination of viral DNA allows an early, specific and interdisciplinary diagnosis and treatment, in which otorhinolaryngology plays a fundamental role. Our study highlights the importance of including CMV polymerase chain reaction as a universal screening tool. (AU)

Cribado auditivo neonatal universal e hipoacusia diferida o de desarrollo tardío / Universal neonatal hearing screening and delayed hearing loss or late-developmental hearing loss

Objetivo Determinar el porcentaje de niños que presentan una hipoacusia bilateral permanente posnatal para estudiar su incidencia, los factores de riesgo relacionados, su diagnóstico y su tratamiento.MétodosEstudio retrospectivo de recogida de datos de niños diagnosticados de hipoacusia fuera del periodo neonatal en la Unidad de Hipoacusia del Hospital Universitario Central de Asturias, desde abril de 2014 hasta abril de 2021.ResultadosUn total de 52 casos cumplieron los criterios de inclusión. La tasa de detección de hipoacusias congénitas del programa de cribado neonatal en el mismo periodo de estudio fue de 1,5 niños por cada 1000 recién nacidos al año; sumando las hipoacusias posnatales da como resultado una tasa de hipoacusia bilateral infantil de 2,7 niños por 1000 (55,5% y 44,4%, respectivamente). Presentan factores de riesgo de hipoacusia 35, siendo 23 de riesgo retrococlear. La edad media de la derivación fue de 91,9 meses (18-185). La adaptación audioprotésica se indicó en 44 casos (84,6%). En 8 casos (15,4%) se indicó la implantación coclear.DiscusiónAunque la hipoacusia congénita representa la mayoría de las sorderas en la infancia, la hipoacusia posnatal tiene una incidencia importante. Esta puede responder principalmente a: 1) que el deterioro auditivo puede surgir en los primeros años de vida, 2) que la hipoacusia leve, así como las pérdidas auditivas en frecuencias graves son indetectables por el cribado neonatal en algunos casos, 3) que algunos niños pueden presentar falsos negativos en los resultados.ConclusiónLa hipoacusia posnatal requiere la identificación de factores de riesgo y el seguimiento a largo plazo de los niños que la sufren, ya que es preciso que sea detectada y tratada precozmente. (AU)

Objective To determine the percentage of children with permanent bilateral postnatal hearing loss in order to study its incidence, related risk factors, diagnosis and treatment.MethodsRetrospective study to collect data on children diagnosed with hearing loss outside the neonatal period in the Hearing Loss Unit of the Hospital Universitario Central de Asturias, from April 2014 to April 2021.Results52 cases met the inclusion criteria. The detection rate of congenital hearing loss in the neonatal screening programme in the same study period was 1.5 children per thousand newborns per year, adding postnatal hearing loss results in a rate of infant bilateral hearing loss of 2.7 children per thousand (55.5% and 44.4% respectively). Thirty-five children presented risk factors for hearing loss, of which 23 were at retrocochlear risk. The mean age at referral was 91.9 (18-185) months. Hearing aid fitting was indicated in 44 cases (84.6%). Cochlear implantation was indicated in eight cases (15.4%).DiscussionAlthough congenital hearing loss accounts for the majority of childhood deafness, postnatal hearing loss has a significant incidence. This may be mainly due to: 1) that hearing impairment may arise in the first years of life, 2) that mild hearing loss as well as hearing loss in severe frequencies are undetectable by neonatal screening in some cases, 3) that some children may have false negative results.ConclusionPostnatal hearing loss requires identification of risk factors and long-term follow-up of children with hearing loss, as it needs to be detected and treated early. (AU)

Alterações auditivas em recém-nascidos de gestantes com diagnóstico de covid-19: uma revisão sistemática / Hearing changes in newborns whose mothers had been diagnosed with COVID-19 during pregnancy: A systematic review / Alteraciones auditivas en recién nacidos de mujeres embarazadas con diagnóstico de covid-19: una revisión sistemática

Introdução: A integridade do sistema auditivo é essencial para o desenvolvimento das habilidades auditivas e aquisição da linguagem da criança. Considerando a alta prevalência de perda auditiva em recém-nascidos, devido a infecções congênitas que ocorrem durante a gestação, há a necessidade de investigar os efeitos da Covid-19 na audição do RN. Objetivo: Verificar a associação entre perda auditiva em neonatos de gestantes diagnosticadas com COVID-19. Estratégia de Pesquisa: A busca de artigos científicos foi realizada nas bases de dados Medline (Pubmed), LILACS, SciELO, Scopus, Web of Science e Bireme sem restrição de idioma, período e localização. Para complementar e evitar viés de risco foi realizada uma busca por literatura cinzenta no Google Acadêmico. Critérios de Seleção: A revisão sistemática foi conduzida de acordo com as recomendações do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) e incluiu estudos que pontuaram ≥ 6 pontos de acordo com o protocolo de pontuação qualitativa proposto por Pithon et al. (2015). Análise dos dados: Os artigos elegíveis foram analisados e quantificados seguindo os critérios propostos no presente estudo com juízes cegos nas etapas de recuperação. Resultados: foram recuperados 29 artigos com potencial de inclusão, dos quais 6 responderam à questão norteadora com potencial de elegibilidade. Quatro estudos encontrados não detectaram associação entre infecção materna por COVID-19 e perda auditiva congênita. Conclusão: A infecção por COVID-19 durante a gravidez não parece ser fator de risco para perda auditiva congênita e não foram verificadas alterações auditivas impactantes que comprometessem estes neonatos por infecção vertical. (AU)

Introduction: The integrity of the auditory system is essential for children to develop auditory skills and acquire language. Considering the high prevalence of hearing loss in newborns due to congenital infections that occur during pregnancy, there is a need to investigate the effects of COVID-19 on newborns' hearing. Objective: To verify the association between hearing loss in newborns whose mothers had been diagnosed with COVID-19 during pregnancy. Research Strategy: Scientific articles were searched in the MEDLINE (PubMed), LILACS, SciELO, Scopus, Web of Science, and BIREME databases, without restrictions on the language, time, and place of study. The grey literature was also searched in Google Scholar to complement the sample and avoid risk bias. Selection Criteria: The systematic review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and included studies that scored ≥ 6 points according to the protocol for qualitative scoring proposed by Pithon et al. (2015). Data analysis: It was performed using a specific form for systematic reviews prepared by two researchers in Excel®. Results: 29 potentially eligible articles were retrieved, six of which answered the research question. Four studies did not detect an association between maternal COVID-19 infection and congenital hearing loss. Conclusion: COVID-19 infection during pregnancy does not seem to be a risk factor for congenital hearing loss and there were no impacting hearing changes due to vertical infection that might affect these newborns. (AU)

Introducción: La integridad del sistema auditivo es fundamental para el desarrollo de las habilidades auditivas y la adquisición del lenguaje de los niños. Considerando la alta prevalencia de hipoacusia (HL) en recién nacidos (RN), debido a infecciones congénitas que ocurren durante el embarazo, surge la necesidad de investigar los efectos del Covid-19 en la audición del recién nacido. Objetivo: Verificar la asociación entre hipoacusia en neonatos de gestantes diagnosticadas con COVID-19. Estrategia de investigación: La búsqueda de artículos científicos se realizó en las bases de datos Medline (Pubmed), LILACS, SciELO, Scopus, Web of Science y Bireme, sin restricción de idioma, período y ubicación. Para complementar y evitar sesgos de riesgo, se realizó una búsqueda de literatura gris en Google Scholar. Criterios de selección: La revisión sistemática se realizó de acuerdo con las recomendaciones de los Elementos de información preferidos para revisiones sistemáticas y metanálisis (PRISMA). Los estudios que obtuvieron una puntuación ≥ 6 puntos según el protocolo de puntuación cualitativa propuesto por Pithon et al. (2015). Análisis de datos: Se realizó mediante un formulario específico para revisión sistemática elaborado por dos investigadores del Programa Excel®. Resultados: se recuperaron 29 artículos con potencial de inclusión, de los cuales 6 respondieron a la pregunta orientadora Cuatro estudios encontrados no detectaron una asociación entre la infección materna por COVID-19 y la pérdida auditiva congénita. Conclusión: La infección por COVID-19 durante el embarazo no parece ser un factor de riesgo para la pérdida auditiva congénita y no hubo cambios auditivos impactantes que pudieran comprometer a estos recién nacidos debido a la infección vertical. (AU)

Barriers to and Facilitators of Early Hearing Detection and Intervention in the United States: A Systematic Review.

OBJECTIVES: Early hearing detection and intervention (EHDI) is guided by the 1-3-6 approach: screening by one month, diagnosis by 3 mo, and early intervention (EI) enrollment by 6 mo. Although screening rates remain high, successful diagnosis and EI-enrollment lag in comparison. The aim of this systematic review is to critically examine and synthesize the barriers to and facilitators of EHDI that exist for families, as they navigate the journey of congenital hearing loss diagnosis and management in the United States. Understanding barriers across each and all stages is necessary for EHDI stakeholders to develop and test novel approaches which will effectively reduce barriers to early hearing healthcare. DESIGN: A systematic literature search was completed in May and August 2021 for empirical articles focusing on screening, diagnosis, and EI of children with hearing loss. Two independent reviewers completed title and abstract screening, full-text review, data extraction, and quality assessments with a third independent reviewer establishing consensus at each stage. Data synthesis was completed using the Framework Analysis approach to categorize articles into EHDI journey timepoints and individual/family-level factors versus system-level factors. RESULTS: Sixty-two studies were included in the narrative synthesis. Results revealed that both individual/family-level (e.g., economic stability, medical status of the infant including middle ear involvement) and system-level barriers (e.g., system-service capacity, provider knowledge, and program quality) hinder timely diagnosis and EI for congenital hearing loss. Specific social determinants of health were noted as barriers to effective EHDI; however, system-level facilitators such as care coordination, colocation of services, and family support programs have been shown to mitigate the negative impact of those sociodemographic factors. CONCLUSIONS: Many barriers exist for families to obtain appropriate and timely EHDI for their children, but system-level changes could facilitate the process and contribute to long-term outcomes improvement. Limitations of this study include limited generalizability due to the heterogeneity of EHDI programs and an inability to ascertain factor interactions.

Hearing screening test in neonates born to COVID-19-positive mothers.

SARS-CoV-2, the responsible virus for the COVID-19 pandemic, has demonstrated neurotropic properties indicated by cases presenting with auditory and vestibular system insults. The expression of ACE-2 receptors in the placenta and the detection of IgM antibodies against the virus in the fetuses of pregnant women suffering from COVID-19 render vertical transmission of the infection to the fetus possible. Thus, our study aims to examine whether, similar to other viruses like CMV, SARS-CoV-2 is responsible for congenital hearing loss. This is a retrospective study in a regional pediatric hospital. The medical records of newborns (n = 111) born by mothers positive for COVID-19 during pregnancy who underwent screening hearing tests with Transient Evoked Otoacoustic Emissions (TEOAE) and Automatic Auditory Brainstem Response (AABR) from February 2020 to June 2022 were reviewed. Neonates with additional aggravating factors for congenital hearing loss were excluded from the study. For the study period, nine mothers were found positive during the first trimester, twenty mothers in the second trimester, and eighty-three mothers in the third trimester. TEOAEs test and AABR test scored PASS bilaterally in all neonates tested. CONCLUSION: Infection with COVID-19 during pregnancy was not a risk factor for hearing loss, similar to other studies. WHAT IS KNOWN: • The pathogenetic mechanism of the viral-induced impairment of the organ of Corti includes direct damage to the hair cells and indirect damage due to the induction of the innate inflammatory response. • Early data suggested that the SARS-CoV-2 virus also has neurotropic properties with manifestations from the sensory epithelia. WHAT IS NEW: • Although the intrauterine infection remains controversial, the expression of the ACE-2 receptor on the placenta and the detection of IgM antibodies, as well as the covid-19 genome in fetuses, make the vertical transmission tenable. • In our study, the newborn hearing screening results indicate that COVID-19 infection during pregnancy is not a risk factor for hearing loss.

Evaluación de la competencia pragmática de cuatro adultos españoles con discapacidad auditiva congénita a través del Protocolo Rápido de Evaluación Pragmática - Revisado / Assessing the pragmatic competence of four spanish adults with congenital hearing loss through Protocolo Rápido de Evaluación Pragmática - Revisado

Numerosos estudios apuntan a las dificultades del lenguaje oral que pueden presentar las personas con discapacidad auditiva a lo largo de su desarrollo. No obstante, se conoce poco acerca del nivel de competencia pragmática que alcanzan y cómo esta área se desarrolla. En esta investigación se pretenden abordar las características pragmáticas de cuatro adultos españoles con discapacidad auditiva congénita a través del Protocolo Rápido de Evaluación Pragmática Revisado (PREP-R), que evalúa diferentes niveles de pragmática: textual, enunciativa e interactiva y, además,aporta un índice de habilidad pragmática general, específica y de base gramatical. Los participantes fueron evaluados mediante videograbaciones de muestras de lenguaje espontáneo en conversación con un familiar. Los resultados indican que, en general, los cuatro sujetos presentan un buen nivel de competencia pragmática, que se manifiesta a la hora de ajustar los actos de habla. Sin embargo, para regular su lenguaje, tienden a utilizar conductas compensatorias como: estrategias verbales que les permiten ganar tiempo extra para la construcción de sus emisiones, empleo de actos verbales y/o paraverbales compensatorios y el uso de gestos que completan su producción verbal. Estos datos indican que, aunque los participantes de este estudio presentan buenas habilidades pragmáticas, es necesario seguir desarrollando estrategias a nivel de intervención que les permitan comunicarse sin dificultades en diferentes contextos y con distintos interlocutores.

Numerous studies reveal the oral language difficulties that people with hearing loss may present throughout their development. However, little is known about the level of pragmatic competence they achieve and how this area evolves. This research aims to address the pragmatic characteristics of four Spanish adults with congenital hearing loss through Protocolo Rápido de Evaluación Pragmática -Revisado (PREP-R, which can be translated as Quick Protocol for Pragmatic Evaluation -Revised). This test assesses different levels of pragmatics: textual, enunciative, and interactional, and also provides an indicator for general, specific, and grammatically-based pragmatic ability. The participants were assessed by videotaping spontaneous speech samples in conversation with a family member. The results indicate that, in general, the four subjects present an adequate level of pragmatic competence, which is manifested in their adjustment of speech acts. Nevertheless, they show a tendency to use compensatory behaviors toregulate their speech, such as verbal strategies that allow them to gain extra time to construct their utterances, compensatory verbal and/or paraverbal acts, and gestures that complement their verbal productions. These data indicate that, although the participants of this study show good pragmatic skills, it is necessary to continue developing intervention strategies that allow them to communicate without difficulties in different contexts and with different communication partners.

A mutation of EYA1 gene in a Chinese Han family with Branchio-Oto syndrome.

ABSTRACT: Branchio-Oto (BO) syndrome is one of the common syndromic forms of hearing loss. In this study, we aimed to characterize the clinical and genetic features of BO syndrome in a Chinese deaf family.The proposita in this study was a 29-years-old Chinese female with hearing loss, microtia, anterior concave auricle, and right branchial fistula. The family members agreed to undergo clinical examination. We collected blood samples from 7 family members, including 4 affected by the syndrome. Genomic DNA was extracted and subjected to Sanger sequencing. In addition, bioinformatics software SWISS MODEL was used to predict the protein encoded by EYA transcriptional coactivator and phosphatase 1 (EYA1) gene.Intra-familial consistency can be observed in the clinical phenotypes of BO syndrome in this family. EYA1 c.1627C>T (p.Gln543Ter) mutation was identified as the pathogenic cause in this family.This study reports a mutation associated with BO syndrome in a Chinese Han family. We highlight the utility of genetic testing in the diagnosis of BO syndrome. Thus, we believe that this report would provide a basis for the diagnosis of similar diseases in the future.

Embryonic Origins of Virus-Induced Hearing Loss: Overview of Molecular Etiology.

Hearing loss, one of the most prevalent chronic health conditions, affects around half a billion people worldwide, including 34 million children. The World Health Organization estimates that the prevalence of disabling hearing loss will increase to over 900 million people by 2050. Many cases of congenital hearing loss are triggered by viral infections during different stages of pregnancy. However, the molecular mechanisms by which viruses induce hearing loss are not sufficiently explored, especially cases that are of embryonic origins. The present review first describes the cellular and molecular characteristics of the auditory system development at early stages of embryogenesis. These developmental hallmarks, which initiate upon axial specification of the otic placode as the primary root of the inner ear morphogenesis, involve the stage-specific regulation of several molecules and pathways, such as retinoic acid signaling, Sonic hedgehog, and Wnt. Different RNA and DNA viruses contributing to congenital and acquired hearing loss are then discussed in terms of their potential effects on the expression of molecules that control the formation of the auditory and vestibular compartments following otic vesicle differentiation. Among these viruses, cytomegalovirus and herpes simplex virus appear to have the most effect upon initial molecular determinants of inner ear development. Moreover, of the molecules governing the inner ear development at initial stages, SOX2, FGFR3, and CDKN1B are more affected by viruses causing either congenital or acquired hearing loss. Abnormalities in the function or expression of these molecules influence processes like cochlear development and production of inner ear hair and supporting cells. Nevertheless, because most of such virus-host interactions were studied in unrelated tissues, further validations are needed to confirm whether these viruses can mediate the same effects in physiologically relevant models simulating otic vesicle specification and growth.

Cell Type-Specific Expression Analysis of the Inner Ear: A Technical Report.

OBJECTIVE: The cellular diversity of the inner ear has presented a technical challenge in obtaining molecular insight into its development and function. The application of technological advancements in cell type-specific expression enable clinicians and researchers to leap forward from classic genetics to obtaining mechanistic understanding of congenital and acquired hearing loss. This understanding is essential for development of therapeutics to prevent and reverse diseases of the inner ear, including hearing loss. The objective of this study is to describe and compare the available tools for cell type-specific analysis of the ear, as a means to support decision making in study design. STUDY DESIGN: Three major approaches for cell type-specific analysis of the ear including fluorescence-activated cell sorting (FACS), ribosomal and RNA pulldown techniques, and single cell RNA-seq (scRNA-seq) are compared and contrasted using both published and original data. RESULTS: We demonstrate the strength and weaknesses of these approaches leading to the inevitable conclusion that to maximize the utility of these approaches, it is important to match the experimental approach with the tissue of origin, cell type of interest, and the biological question. Often, a combined approach (eg, cell sorting and scRNA-seq or expression analysis using 2 separate approaches) is required. Finally, new tools for visualization and analysis of complex expression data, such as the gEAR platform (umgear.org), collate cell type-specific gene expression from the ear field and provide unprecedented access to both clinicians and researchers. LEVEL OF EVIDENCE: N/A Laryngoscope, 131:S1-S16, 2021.

An Integrative Review of Current Practice Models and/or Process of Family-Centered Early Intervention for Children Who Are Deaf or Hard of Hearing.

Over the past few decades, there has been an increasing shift toward emphasizing the importance of the child's family taking an active role in the habilitation process through family-centered early intervention (FCEI) programs. Accordingly, the Health Professions Council of South Africa recommends that early intervention services following confirmation of hearing loss must be family-centered within a community-based model of service delivery that is culturally congruent. The aim of this study was to explore and document current evidence reflecting trends in FCEI for children who are deaf or hard of hearing (DHH) by identifying and describing current practice models and/or processes of FCEI for these children. This study describes our first steps in formulating a framework for FCEI for children who are DHH in South Africa. An integrative literature review was conducted. Sage, Science Direct, PubMed, and Google Scholar databases were searched for studies published in English between January 2009 and January 2019 reporting on FCEI programs for children who are DHH. Studies that focused on the following were excluded from the study: speech and language outcomes of children, youth, and adults who are DHH; education for children who are DHH; universal newborn hearing screening; professionals' roles in early hearing detection and intervention; diagnosis of hearing loss; and sign language. Kappa statistics were performed to determine agreement between reviewers. Twenty-two studies were included in the review. Cohen's kappa revealed a substantial agreement (κ = 0.8) between reviewers for data extraction and synthesis in terms of the articles that met the criteria for inclusion in the review. Findings were discussed under 5 themes: caregiver involvement; caregiver coaching/information sharing; caregiver satisfaction; challenges with FCEI; and telehealth. Generally, there is sufficient evidence for FCEI, with caregivers indicating the need for full involvement in their children's care. Methods of caregiver involvement involving caregiver coaching/information sharing need to be culturally and linguistically appropriate, with sensitivities around time and manner. This increases caregiver satisfaction with intervention programs and improves outcomes for children who are DHH. Challenges identified by the studies raise implications for early hearing detection and intervention programs, as well as Departments of Health and Social Welfare. These included logistical challenges, professional-related challenges, and caregiver-related challenges. Various aspects of FCEI have been reported in the review. Findings of these studies have significant implications for the formulation of quality FCEI programs to ensure contextually relevant and contextually responsive care of children who are DHH.

Deficiency of large tumor suppressor kinase 1 causes congenital hearing loss associated with cochlear abnormalities in mice.

Mammalian auditory hair cells are not spontaneously replaced. Their number and coordinated polarization are fairly well-maintained and both these factors might be essential for the cochlear amplifier. Cell cycle regulation has critical roles in regulating appropriate cell size and cell number. However, little is known about the physiological roles of the Hippo pathway, which is one of the most important signaling cascades that regulates cell growth, differentiation, and regenerative capacity in the cochlear sensory epithelium. Herein, we investigated the in vivo role of the large tumor suppressor 1 (LATS1), an essential kinase in the Hippo/yes-associated protein pathway, in the cochlea using the LATS1 knockout mice. LATS1 was expressed in hair cells and supporting cells. It was strongly expressed on the surface of the cuticular plate of the organ of Corti. We found that LATS1 knockout caused congenital hearing loss due to the irregular orientation and slightly reduced number of hair cells, whereas the number of supporting cells remained unchanged. On the surface of the hair cells, the kinocilium and stereocilia were dispersed during and after morphogenesis. However, the expression of the receptor-independent polarity regulators, such as Par3 or Gαi, was not affected. We concluded that LATS1 has an indispensable role in the maturation of mammalian auditory hair cells, but not in the development of the supporting cells, and thus, has a role in the hearing acquisition.

Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients.

USH2A is a common causal gene of retinitis pigmentosa (RP), a progressive blinding disease due to retinal degeneration. Genetic alterations in USH2A can lead to two types of RP, non-syndromic and syndromic RP, which is called Usher syndrome, with impairments of vision and hearing. The complexity of the genotype-phenotype correlation in USH2A-associated RP (USH2A-RP) has been reported. Genetic and clinical characterization of USH2A-RP has not been performed in Japanese patients. In this study, genetic analyses were performed using targeted panel sequencing in 525 Japanese RP patients. Pathogenic variants of USH2A were identified in 36 of 525 (6.9%) patients and genetic features of USH2A-RP were characterized. Among 36 patients with USH2A-RP, 11 patients had syndromic RP with congenital hearing problems. Amino acid changes due to USH2A alterations were similarly located throughout entire regions of the USH2A protein structure in non-syndromic and syndromic RP cases. Notably, truncating variants were detected in all syndromic patients with a more severe retinal phenotype as compared to non-syndromic RP cases. Taken together, truncating variants could contribute to more serious functional and tissue damages in Japanese patients, suggesting important roles for truncating mutations in the pathogenesis of syndromic USH2A-RP.

Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation.

Aims: This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods: A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results: A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion: A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.

Are dogs with congenital hearing and/or vision impairments so different from sensory normal dogs? A survey of demographics, morphology, health, behaviour, communication, and activities.

The births of domestic dogs with pigment deletion and associated congenital hearing and/or vision impairments are increasing, as a result of mutations of certain genes expressing popular coat colour patterns (Merle, piebald, Irish spotting). The future of these dogs is often pessimistic (early euthanasia or placement in rescues/fosters, lack of interactions and activities for adults). These pessimistic scenarios result from popular assumptions predicting that dogs with congenital hearing/vision impairments exhibit severe Merle-related health troubles (cardiac, skeletal, neurological), impairment-related behavioural troubles (aggressiveness, anxiety), and poor capacities to communicate, to be trained, and to be engaged in leisure or work activities. However, there is no direct scientific testing, and hence no evidence or refutation, of these assumptions. We therefore addressed an online questionnaire to owners of 223 congenitally sensory impaired (23 vision impaired, 63 hearing impaired, 137 hearing and vision impaired) and 217 sensory normal dogs from various countries. The sensory normal cohort was matched in age, lifetime with owner, breed and sex with the sensory impaired cohort, and was used as a baseline. The questionnaire assessed demographics, morphology, sensory impairments, health and behavioural troubles, activities, and dog-owner communication. Most hearing and/or vision impaired dogs exhibited abnormal pigment deletion in their coat and irises. Vision impaired dogs additionally exhibited ophthalmic abnormalities typically related to Merle. The results are opposed to all above-listed assumptions, except for neurological troubles, which were more frequently reported in sensory impaired dogs. However, we suggest that this finding could be partially accounted for by a lack of diagnosis of breed-related drug sensitivity and impairment-related compulsive behaviours. Results about communication and activities are particularly optimistic. The need for future studies of numerous dogs from various breeds tested for Merle, piebald and medical-drug-resistance genes, and the beneficial effects that present and future research may have on the future of sensory impaired dogs, are discussed.

Genomic analysis of inherited hearing loss in the Palestinian population.

The genetic characterization of a common phenotype for an entire population reveals both the causes of that phenotype for that place and the power of family-based, population-wide genomic analysis for gene and mutation discovery. We characterized the genetics of hearing loss throughout the Palestinian population, enrolling 2,198 participants from 491 families from all parts of the West Bank and Gaza. In Palestinian families with no prior history of hearing loss, we estimate that 56% of hearing loss is genetic and 44% is not genetic. For the great majority (87%) of families with inherited hearing loss, panel-based genomic DNA sequencing, followed by segregation analysis of large kindreds and transcriptional analysis of participant RNA, enabled identification of the causal genes and mutations, including at distant noncoding sites. Genetic heterogeneity of hearing loss was striking with respect to both genes and alleles: The 337 solved families harbored 143 different mutations in 48 different genes. For one in four solved families, a transcription-altering mutation was the responsible allele. Many of these mutations were cryptic, either exonic alterations of splice enhancers or silencers or deeply intronic events. Experimentally calibrated in silico analysis of transcriptional effects yielded inferences of high confidence for effects on splicing even of mutations in genes not expressed in accessible tissue. Most (58%) of all hearing loss in the population was attributable to consanguinity. Given the ongoing decline in consanguineous marriage, inherited hearing loss will likely be much rarer in the next generation.

Follow-up after failed newborn hearing screening: Parental and primary care provider awareness.

PURPOSE: The current loss to follow-up rate after failed newborn hearing screening (NBHS) is 34.4%. Previous studies have found that lack of parental and primary care provider (PCP) awareness of NBHS results are significant contributors to loss to follow-up. The objective of this study was to identify factors associated with parental and PCP awareness of NBHS results. MATERIALS AND METHODS: Retrospective cohort study. A survey asking about demographics and knowledge of NBHS testing and results was offered to parents in the waiting room of an urban pediatric primary care office. Included were biological parents ≥18 years of age of children ≤10 years of age born in Pennsylvania. Each child's chart was reviewed for PCP documentation of NBHS results. The odds of knowing NBHS results were evaluated using logistic regression. RESULTS: The survey was completed by 304 parents. 74.0% were aware of their child's NBHS results. Child age ≥1 year old (OR: 0.49, 95%CI[0.29, 0.82], P = 0.007) and Hispanic ethnicity (OR: 0.38, 95%CI[0.16, 0.89], P = 0.03) were associated with decreased odds of a parent knowing NBHS results. In addition, fewer fathers knew the results of their child's NBHS compared with mothers (OR: 0.33, 95%CI[0.18, 0.62], P < 0.001). However, parental awareness was not associated with birthing facility or insurance type. 222 charts were reviewed for NBHS documentation, revealing PCP awareness in 95.5% of cases and no associations with any of the factors examined. CONCLUSIONS: Factors associated with parents not knowing NBHS results included being the parent of an older child, Hispanic, or the father.