Childhood Deafness Research Articles

Generation and Genetic Correction of USH2A c.2299delG Mutation in Patient-Derived Induced Pluripotent Stem Cells.

Usher syndrome (USH) is the leading cause of inherited combined hearing and vision loss. As an autosomal recessive trait, it affects 15,000 people in the United States alone and is responsible for ~21% of inherited blindness and 3 to 6% of early childhood deafness. Approximately 2/3 of the patients with Usher syndrome suffer from USH2, of whom 85% have mutations in the USH2A gene. Patients affected by USH2 suffer from congenital bilateral progressive sensorineural hearing loss and retinitis pigmentosa which leads to progressive loss of vision. To study the molecular mechanisms of this disease and develop a gene therapy strategy, we generated human induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMCs) obtained from a patient carrying compound heterozygous variants of USH2A c.2299delG and c.1256G>T and the patient’s healthy sibling. The pluripotency and stability were confirmed by pluripotency cell specific marker expression and molecular karyotyping. Subsequent CRISPR/Cas9 genome editing using a homology repair template was used to successfully correct the USH2A c.2299delG mutation back to normal c.2299G in the generated patient iPSCs to create an isogenic pair of lines. Importantly, this manuscript describes the first use of the recombinant Cas9 and synthetic gRNA ribonucleoprotein complex approach to correct the USH2A c.2299delG without additional genetic effects in patient-derived iPSCs, an approach that is amenable for therapeutic genome editing. This work lays a solid foundation for future ex vivo and in vivo gene therapy investigations and these patient’s iPSCs also provide an unlimited resource for disease modeling and mechanistic studies.

Hearing Threshold of Auditory Brainstem Response in Term Neonates with Hyperbilirubinemia

Background:Neonatal jaundice is a common cause of premature neonatal hearing loss and is a major cause of childhood deafness, especially in developing countries. The aim of this study was evaluating Hearing threshold of Auditory Brainstem Response (ABR) in term neonates admitted with hyperbilirubinemia at a range of exchange transfusion and near exchange transfusion. Methods: This cross-sectional study was performed on 134 healthy term infants admitted due to hyperbilirubinemia in the neonatal care unit of Besat Hospital in Hamadan from March 2017 to September 2017. All neonates were evaluated by Otoacoustic Emission (OAE) and ABR after admission in neonatal ward and after treatment by intensive phototherapy or blood exchange. Data were collected and analyzed through SPSS software and using Chi-square and Mann-Whitney tests. The significance level was considered at 0.05 for all statistical tests. Results: The mean weight of newborns was 3000 ±350 gr and the mean of gestational age was 39± 2 weeks. Bilirubin concentration of the infants was 36.9±9.2 mg/dL. There was a significant difference between hearing loss on auditory brainstem response in term neonates according to hyperbilirubinemia in blood exchange range (P = 0.001). However, there was no significant difference between hearing loss on auditory brainstem response in term neonates according to the gestational age, sex and phototherapy (P > 0.05). Conclusion: Our findings indicated that high bilirubin levels in the range of exchange transfusion can be an important risk to the auditory system, which without creating kernicterus, can interfere with auditory tests.

“It's an emotional rollercoaster” the spatial and temporal structuring of affect in diagnosing childhood hearing loss

Despite well-established screening for hearing problems, and objective, diagnostic techniques aimed at dispelling uncertainty, some parents spend months waiting for clear diagnosis of their child's hearing loss. In the clinical setting, providers use international best-practice policies in diagnosing and managing childhood deafness, yet limited attention is given to the role of emotion in this context. Drawing on socio-spatial and temporal theories we conceptualise the clinical waiting room and soundproof booth of a paediatric hearing clinic as affective spacio-temporal places that both constrain and evoke emotion. Tensions between parents and professionals grew, and emotion and affect were problematised in the clinical setting where temporal notions held significance. We consider contentious or difficult areas in the management of childhood deafness through a number of cases of parents experiencing uncertainty as they grapple with decisions for their children. Alternative spaces and experiences in non-medical settings that hold value for parents are discussed in considering new approaches to managing childhood deafness.

Emotion as Motivator: Parents, Professionals and Diagnosing Childhood Deafness

ABSTRACT Diagnosing deafness is a culturally situated practice generating considerable research in health sciences but limited work in anthropology. Diagnosis fast-tracks parents into a medical and education pathway but can also create tension for parents and professionals. Drawing on ethnographic fieldwork, we argue that in this biomedical context, emotions are often understood by professionals as impairing for parents, and hence problematic for the treatment process. In contrast emotions are characterized by parents as motivational and tools for decision making on a pathway that is experienced as a source of stress.

Congenital Cytomegalovirus Prevention, Awareness and Policy Recommendations - A Scoping Study.

Congenital cytomegalovirus (cCMV) is known to cause childhood deafness, neurodevelopmental disability and death. Simple hygiene precautions are effective in reducing maternal risk of CMV infection. To review i) awareness of CMV infection and available primary prevention strategies both in the community and amongst health professionals ii) available cCMV information sources in the literature, grey literature and published professional guidelines. Scoping study to i) identify literature pertaining to cCMV awareness amongst parents and health professionals using MedLine and CINAHL databases via EBSCO ii) review one high income country's guidelines and recommendations regarding cCMV infection and pregnancy (example country Australia) iii) grey literature for parental information. Worldwide awareness of cCMV and of available prevention strategies amongst women and health professionals are poor. Findings internationally suggest at least half of maternity care health professionals do not routinely provide advice to women regarding simple hygiene precautions that can reduce their risk of infection during pregnancy. Though information resources regarding cCMV are available, they are frequently not included within general healthy pregnancy advice and require individuals to search for 'congenital cytomegalovirus'. cCMV is a preventable cause of serious congenital disability and death. Prevention opportunities are being missed because most women are not aware of cCMV or how to reduce their risk of infection in pregnancy, in part due to poor health professional awareness. New strategies to disseminate cCMV information to the community and to support health professionals to embed cCMV advice within routine pregnancy counselling is required.

Can Bears Ski? by Raymond Antrobus

Reviewed by: Can Bears Ski? by Raymond Antrobus Deborah Stevenson, Editor Antrobus, Raymond Can Bears Ski?; illus. by Polly Dunbar. Candlewick, 2020 [40p] Trade ed. ISBN 9781536212662 $16.99 Reviewed from digital galleys R 5-8 yrs Our protagonist bear cub goes through his day missing things—greeting from friends, the leadups to jokes—and he is puzzled by adults repeatedly asking him, “Can bears ski?” (“I shrug. I’m not sure I heard him right”). A conversation between Bear Dad and teacher leads to a visit to an audiologist, where therapy and hearing aids eventually open up the sounds of the world and reveal that the repeated question is actually “Can you hear me?” (“Whoa . . . is life this loud?”). Noted British poet Antrobus draws on his own personal experience of childhood deafness in a narrative that succinctly conveys the isolation of deafness but also the complexity of sensory experience—Little Bear is awakened by his dad’s thumping vibrations as well as his calls, and his focus on the crunch of the snow means the more distant greeting of a friend goes unheard. The book realistically avoids a magic wand approach and acknowledges the cognitive strain of working to hear people (and the normal kid strain of having to keep track of small, easy-to-misplace devices). Dunbar’s digital art recalls the work of Laura Vaccaro Seeger in its sturdy coziness, and the love between Dad and child is evident in every shared scene. This would be a useful partner to those books about kids learning they need glasses, and it would also help ease the way of youngsters going the hearing aid route. Copyright © 2020 The Board of Trustees of the University of Illinois

Role of Genetic Factors in the Causation of Non-Syndromic Hearing Loss (NSHL) in Indian Population

Hearing loss affects about 70 million people worldwide, which can be inherited as either syndromic or non-syndromic forms. Approximately 50% of all childhood deafness is caused due to gene defects. The Non-syndromic hearing loss (NSHL) is extremely heterogenous trait inherited as autosomal recessive, autosomal dominant and X-linked and also due to mitochondrial mutations. In the present review genes causing non-syndromic hearing loss (NSHL) are classified based on their molecular function. GJB2 is most prominent deafness causing gene among the different populations including India, followed by other genes. The recent technological advances in target-enrichment methods and next generation sequencing has overcome the barriers possessed by the earlier methods and laid the path for comprehensive analysis of all the known genes causing non-syndromic hearing loss. The review mainly emphases on the genes causing non-syndromic hearing loss in Indian population and their molecular function. Identifying the genes responsible for hearing loss enables otolaryngologists, geneticist to apply molecular diagnosis by offering genetic testing which helps in prevention of the condition of non-syndromic hearing loss, proper diagnosis, management, pre-natal diagnosis and to offer genetic counselling.

We must now put in place an updated, comprehensive newborn screening program for deaf and hard-of-hearing infants

We must now put in place an updated, comprehensive newborn screening program for deaf and hard-of-hearing infants

A proposal for comprehensive newborn hearing screening to improve identification of deaf and hard-of-hearing children

Early intervention for newborns who are deaf or hard-of-hearing leads to improved language, communication, and social–emotional outcomes. Universal physiologic newborn hearing screening has been widely implemented across the United States with the goal of identifying newborns who are deaf or hard-of-hearing, thereby reducing time to diagnosis and intervention. The current physiologic newborn hearing screen is generally successful in accomplishing its goals but improvements could be made. In the past ten years, genetic testing has emerged as the most important etiological diagnostic test for evaluation of children with deafness and congenital cytomegalovirus has been recognized as a major cause of childhood deafness that may be treatable. A comprehensive newborn hearing screen that includes physiologic, genetic, and cytomegalovirus testing would have multiple benefits, including (1) identifying newborns with deafness missed by the current physiologic screen, (2) providing etiologic information, and (3) possibly decreasing the number of children lost to follow up. We present a framework for integrating limited genetic testing and cytomegalovirus screening into the current physiologic newborn hearing screening. We identify needed areas of research and include an overview of genome sequencing, which we believe will become available over the next decade as a complement to universal physiologic newborn hearing screening.

A new MRI severity score to predict long-term adverse neurologic outcomes in children with congenital Cytomegalovirus infection

Background Congenital cytomegalovirus (CMV) infection is one of the main causes of deafness in childhood. It frequently causes serious long-term neurological sequelae. In children who are asymptomatic at birth, tests to accurately predict these sequelae are still unavailable. Aims We describe different brain MRI patterns of congenital CMV infection correlated with clinical data and propose a new MRI severity score to early predict long-term neurological sequelae. Materials and methods We explored clinical records and neuroimaging data of 224 neonates and children with congenital Cytomegalovirus infection, 180 of them did not meet inclusion criteria. Forty-four babies met inclusion criteria and were enrolled in the study. We retrospectively collected clinical data concerning hospitalization, 2 years outpatient follow-up and brain MRI findings of those 44 children, symptomatic and asymptomatic at birth. Clinical data were then correlated with children’s brain MRI examinations. We defined neurological and sensorial impairment (hearing or visual) as “adverse neurological outcomes”. Brain MRI score was constructed assigning different values to white matter and ventricular dilation. Results In 44 children enrolled in the study we found that 28/35 (80%) with abnormal and 2/9 (22,2%) with normal MRI examination developed adverse neurological outcomes (OR = 3.6) (95% IC 1.0–12.0). Infants who were symptomatic at birth showed a probability of MRI brain lesions 3.2 times higher than those who were asymptomatic. Ten out of 17 (59%) children who were asymptomatic at birth showed MRI-WM alterations or ventriculomegaly. Conclusions Brain MRI abnormalities, such as WM alterations and ventriculomegaly, expressed as MRI score higher than 2 are associated with an increased probability of long-term adverse neurological outcome in congenitally CMV infected infants, symptomatic and asymptomatic at birth.

Mutation spectrum and hotspots of the common deafness genes in 314 patients with nonsyndromic hearing loss in Heze area, China

Background: Although, half of the childhood deafness is genetically related, the molecular etiology of hearing impairment has not been demonstrated explicitly. In addition, the mutation spectrums of deafness genes vary among different areas and ethnics.Objectives: To know more about the mutation spectrums of deafness genes in China, we tested the mutations of three common deafness genes (GJB2, SLC26A4, and mtDNA12SrRNA) in a particular deafness population from Heze area.Materials and methods: SNPscan technology was utilized to perform mutation screening for these three common deafness genes in 314 nonsyndromic deaf patients from Heze area.Results: 38.21% (120/314) of these 314 patients with nonsyndromic hearing loss from Heze area were related to the genetic defects in these three deafness genes, including 20.06% (63/314) for GJB2, 15.29% (48/314) for SLC26A4, and 2.87% (9/314) for mtDNA12SrRNA. Furthermore, the mutation hotspots in three deaf genes were GJB2 235delC, SLC26A4 c.919-2A > G, and mtDNA12SrRNA 1555A > G, respectively, distinct from hotspots reported in other regions worldwide.Conclusion: Our results disclosed a special and unique mutation spectrum of these three common deaf genes in Heze deaf population.

Mouse screen reveals multiple new genes underlying mouse and human hearing loss.

Adult-onset hearing loss is very common, but we know little about the underlying molecular pathogenesis impeding the development of therapies. We took a genetic approach to identify new molecules involved in hearing loss by screening a large cohort of newly generated mouse mutants using a sensitive electrophysiological test, the auditory brainstem response (ABR). We review here the findings from this screen. Thirty-eight unexpected genes associated with raised thresholds were detected from our unbiased sample of 1,211 genes tested, suggesting extreme genetic heterogeneity. A wide range of auditory pathophysiologies was found, and some mutant lines showed normal development followed by deterioration of responses, revealing new molecular pathways involved in progressive hearing loss. Several of the genes were associated with the range of hearing thresholds in the human population and one, SPNS2, was involved in childhood deafness. The new pathways required for maintenance of hearing discovered by this screen present new therapeutic opportunities.

Parent-to-parent support for the families of deaf children identified by the newborn hearing screen

ABSTRACTParent-to-parent support for the families of deaf children has been provided in an East London district as an adjunct to the existing Early Support programme. Two parents of deaf children were employed as Parent Support Workers. They were members of a multi-disciplinary team of audiologists, teachers of the deaf and a specialist speech therapist. A questionnaire was used to obtain the views of the parents of a 10-year cohort of 35 deaf children who had received the peer support. There were high levels of satisfaction. Twenty-two respondents (63%) judged that a parent who had a shared experience was the person best placed to offer help and advice immediately following the diagnosis of childhood deafness with 27 (77%) considering the counselling and guidance of the teacher or therapist as most useful in the pre-school period after this initial period. An overwhelming 34 (97%) would recommend peer support as being useful. Twelve professionals, including five teachers, submitted free text on their views of the support. This was evaluated using thematic analysis. There were concerns about training and governance of the Parent Support Workers, with one teacher considering that the role may conflict with that of the teacher. However, ten professionals considered it to be a beneficial addition to existing programmes and none wanted it withdrawn. Most recognised that the “shared experience” of caring for a deaf child enabled the support workers to get close to families and provide a link with the home, which helped the parents engage with the intervention of the multi-disciplinary team.

Parental Conceptualizations of Autism and Deafness in British Deaf Children.

The co-occurrence of childhood deafness and autism raises complex challenges for diagnosis and family support. In this article, we explore with hearing and Deaf parents their observations of the interaction between deafness and autism and identify how the intersections of deafness and autism are conceptualized in everyday life. Eight parents participated (two of whom were Deaf BSL users) in semi-structured interviews in either BSL or spoken English. Data analysis was underpinned by a phenomenological approach in the hermeneutic tradition. Findings are discussed in terms of parents' perceptions of the relevance of deafness to their understanding of autism for their particular child, the effects of autism on sign and spoken language development and the relationship between deafness and autism in terms of their own and others' attributions of their children's characteristics. The significance of the findings for parental contributions' to diagnostic assessment and the tailoring of family support are considered.

Traumatization and Trauma Cases: Childhood Adversity and Deafness

The association between adverse childhood experience and later adult psychological health has been well-documented. Thus, the presence of adult, parental, low income, social support and adult adversity are the avenues through which adverse childhood presents its influence upon psychological and somatic health deficits during adulthood.

Predicament and Pilgrimage: Hearing Families of Deaf Children in Mexico City

ABSTRACTIn this article, I trace the most salient features of Mexican families’ complex journeys as they coped with the “predicament” of childhood deafness. Framing support seeking through the theoretical lens of pilgrimage brings into focus family introspection and captures their tenacity while facing culture-specific obstacles. Ultimately, families realized their quests were not about “fixing” their children’s hearing, but finding more reliable communication in sign language. Pilgrimage, as a metaphor for the journeys described by participants, helps us understand families’ realizations that the biomedical options most commonly available in Mexico City were of limited efficacy, and reveals collective desire for alternatives to these options.

Factors causing severe deafness in childhood

No abstract available.

Screening of Newborn Hearing at a Tertiary Care Hospital in South India.

Hearing loss can have a devastating impact on the cognitive development and psychological well-being of children and their families. Newborn hearing screening should be given special attention especially in a country like ours where the burden of this disability is heavy. Screening all newborns irrespective of risk factors helps in better detection, and hence further management can be initiated at appropriate time. To implement newborn hearing screening at Vanivilas hospital and to estimate the incidence of hearing loss among the high risk groups. To create awareness about the need for detecting childhood deafness among parents and general population. To develop a centre of excellence for evaluation, intervention and rehabilitation for hearing impaired in a tertiary care hospital. Prospective study. All neonates born in Vanivilas Hospital attached to Bangalore Medical College and Research Institute underwent hearing screening using four stage protocols with otoacoustic emission (OAE) tests and final confirmation with Brainstem evoked response audiometry (BERA) tests. May 2015-May 2017. Number of newborns screened were 26,487, and 19 (0.717/1000) newborns were detected to have hearing impairment. The incidence of hearing loss among high risk group was 0.188/1000, and among the non risk group was 0.528/1000. Newborn hearing screening must be made mandatory and multi-staged protocol based screening for hearing loss should be implemented. This will make newborn screening programme more efficient and also will help in initiating treatment at an early stage so that further damage can be prevented.

Functional reorganization of the conceptual brain system after deafness in early childhood.

The neurodevelopmental consequences of deafness on the functional neuroarchitecture of the conceptual system have not been intensively investigated so far. Using functional magnetic resonance imaging (fMRI), we therefore identified brain areas involved in conceptual processing in deaf and hearing participants. Conceptual processing was probed by a pictorial animacy decision task. Furthermore, brain areas sensitive to observing verbal signs and to observing non-verbal visual hand actions were identified in deaf participants. In hearing participants, brain areas responsive to environmental sounds and the observation of visual hand actions were determined. We found a stronger recruitment of superior and middle temporal cortex in deaf compared to hearing participants during animacy decisions. This region, which forms auditory cortex in hearing people according to the sound listening task, was also activated in deaf participants, when they observed sign language, but not when they observed non-verbal hand actions. These results indicate that conceptual processing in deaf people more strongly depends on language representations compared to hearing people. Furthermore, additionally enhanced activation in visual and motor areas of deaf versus hearing participants during animacy decisions and a more frequent report of visual and motor features in the property listing task suggest that the loss of the auditory channel is partially compensated by an increased importance of visual and motor information for constituting object knowledge. Hence, our results indicate that conceptual processing in deaf compared to hearing people is more strongly based on the language system, complemented by an enhanced contribution of the visuo-motor system.

Present Scenario of Childhood Deafness: A Tertiary Level Health Care Study

Introduction
 Hearing loss is the most common sensory deficit in humans today. Approximately 63 million people in India suffer from significant auditory impairment.
 Materials and Methods
 Fifty children of 0-7 years age group, presented to a tertiary level center in Kolkata were assessed by objective and behavioural audiological tests.
 Result
 Mean age of presentation was found to be 40.5 months. No risk factor could be identified in 72% of the cases. 47% fell into the profoundly deaf category.
 Discussion
 Numerous studies agree that half of the infants with sensorineural hearing loss have no risk factors at birth and thus would be missed by a targeted hearing screening. 
 Conclusion
 India certainly faces a worse situation regarding childhood deafness. Implementation of universal neonatal hearing screening along with pre-school hearing assessment can certainly change the scenario.