Delayed detection of congenital hearing loss in high risk infants.

OBJECTIVE--To examine the methods used to investigate children at high risk of congenital hearing impairment, and to see whether the introduction of evoked response audiometry has reduced the mean age at which hearing loss is identified. DESIGN--Clinicians who notified children to the national congenital rubella surveillance programme were asked retrospectively to complete a questionnaire examining the methods used to identify hearing impairment and the age at testing in two consecutive five year cohorts. The presence or absence of hearing loss was confirmed by obtaining the results of audiometric evaluations and, whenever possible, a recent pure tone audiogram. SETTING--The United Kingdom. PATIENTS--Children notified to the national congenital rubella surveillance programme and born in 1978-87 in whom IgM specific for rubella was detected shortly after birth. MAIN OUTCOME MEASURES--The age at which hearing loss was identified and the degree of loss in decibels at 250, 500, 1000, 2000, and 4000 Hz measured by pure tone audiometry. RESULTS--61 (52%) Of 117 children born in 1978-82 had a hearing impairment of 40 dB or greater in both ears. The mean loss was 93 dB. In the following five years 75 (47%) of 159 children had impaired hearing, their mean loss being 96 dB. The age at which the hearing loss was confirmed decreased from 11.6 to 9.8 months as a result of earlier auditory evoked response testing. Nevertheless, only eight (13%) of the children with hearing impairment born in 1978-82 and 16 (21%) of those born in 1983-7 had these tests performed in the first six months of life. CONCLUSIONS--Unacceptable delays in identifying hearing loss occurred in this high risk group because of failure to arrange auditory evoked response testing in early infancy. Evoked response audiometry is sensitive and specific and should be undertaken within the first few months of life for all infants known to be at risk of sensorineural hearing loss.     

Waardenburg syndrome in the Turkish deaf population

Waardenburg Syndrome (WS) is an autosomal, dominantly inherited disorder that accounts for more than 2% cases of congenital deafness. The aim of this study is to determine the WS incidence among deaf pupils. Dysmorphological examination was performed on 720 children who were attending 7 special schools in Turkey and who had hearing disabilities. All subjects in the study were examined for WS diagnostic criteria. We detected 49 patients (6.8%) with WS among the 720 children examined. Six patients had WS type 1 (12.2%) and 43 had type 2 (87.8%). We observed 2 to 5 major diagnostic criteria for WS. Out of all the subjects in the study, only two patients have deaf first degree relatives. All subjects had been previously examined by physicians for deafness but none of them had been then diagnosed to have Waardenburg Syndrome. Instead, they were all misdiagnosed as to have nonsyndromic deafness. Awareness of WS diagnostic criteria by the physicans will provide accurate diagnosis for many deaf pupils and their first degree relatives who are able-to-hear WS patients and whose children are at risk for deafness.     

Provision of hearing aids: does specialist assessment cause delay?

OBJECTIVE--To identify the main delay in the provision of hearing aids for people with impaired hearing and identify possible problems and short-comings caused by a community based hearing aid dispensing service. DESIGN--Prospective cohort analysis based on data collected from patients on the duration of hearing impairment, from the referral letters in respect of the general practitioners'' findings on otoscopy, and from the ear, nose, and throat assessment in the clinic with respect to the outcome of specialist otoscopy and management of the hearing impairment. SETTING--General ear, nose, and throat outpatient clinic. PATIENTS--100 Consecutive patients aged 19-94 referred by general practitioners for the provision of hearing aids or for assessment and treatment of impaired hearing. RESULTS--Most patients with impaired hearing did not seek medical advice for at least a year. The time from referral by the general practitioner to the provision of a hearing aid was under two months. General practitioners consistently recognised normality on otoscopy but failed to recognise abnormality in eight of 45 cases. Seven patients required further investigation to exclude serious disease and nine had conditions amenable to surgery. CONCLUSIONS--The main cause of delay in treating impaired hearing is failure by patients to seek help promptly. Specialist assessment of patients with impaired hearing is preferable and does not necessarily cause delay in providing hearing aids. The provision of hearing aids should remain a hospital based service.     

Limb reduction defects in the first generation and deafness in the second generation of intrauterine exposed fetuses to diethylstilbestrol

Maternal treatment with diethylstilbestrol (DES) during pregnancy can produce vaginal adenocarcinoma and other abnormalities of the vagina in her daughters when they reach adolescence or adulthood, miscarriages and absence of full term infants. Concerning malformations in newborns whose mothers were treated with DES, clitoromegaly and malformations of the uterus were reported in females and genital lesions in males. However, the frequencies of major congenital anomalies were not greater than expected. We report three cases of limb reduction defects (LRD) in the first generation of children whose mothers were treated with DES during pregnancy, and two children (one male, one female) with deafness in the second generation after intrauterine exposure to DES. The LRD were not associated with other congenital anomalies. The malformed children with LRD were born between 1965 and 1973. The deafness was also isolated. The two mothers who have no hearing problems and who are healthy were exposed in utero to DES in 1963 and 1965, respectively. Their children were born in 1989 and 1994, respectively. In conclusion, the association of LRD and hearing loss with intrauterine exposure to DES could be coincidental. However, some hypothesis may explain these associations. Congenital hearing loss in the second generation may suggest a transgenerational effect.     

Application of deafness diagnostic screening panel based on deafness mutation/gene database using invader assay

Despite progress in identification of deafness genes, clinical application has lagged due to the genetic heterogeneity of deafness. We designed and tested a comprehensive and simple diagnostic strategy to simultaneously detect deafness gene mutations based on a mutation/gene database followed by Invader assay screening of 41 known mutations of nine known deafness genes. Three hundred thirty-eight Japanese patients with congenital or childhood-onset (up to age 10) bilateral sensorineural hearing loss participated in this study. A total of 100 (29.6%) subjects had at least one mutation in GJB2, SLC26A4, and/or the mitochondrial 12S rRNA, indicating that these are the three major causative genes in Japanese deafness patients. The present study demonstrated that the Invader assay has excellent sensitivity and accuracy, and its application to deafness mutation screening will greatly improve medical management and facilitate extensive genetic counseling for hearing impairment.     

Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study

Although etiological studies have shown genetic disorders to be a common cause of congenital/early-onset sensorineural hearing loss, there have been no detailed multicenter studies based on genetic testing. In the present report, 264 Japanese patients with bilateral sensorineural hearing loss from 33 ENT departments nationwide participated. For these patients, we first applied the Invader assay for screening 47 known mutations of 13 known deafness genes, followed by direct sequencing as necessary. A total of 78 (29.5%) subjects had at least one deafness gene mutation. Mutations were more frequently found in the patients with congenital or early-onset hearing loss, i.e., in those with an awareness age of 0-6 years, mutations were significantly higher (41.8%) than in patients with an older age of awareness (16.0%). Among the 13 genes, mutations in GJB2 and SLC26A4 were mainly found in congenital or early-onset patients, in contrast with mitochondrial mutations (12S rRNA m.1555A>G, tRNA(Leu(UUR)) m.3243A>G), which were predominantly found in older-onset patients. The present method of simultaneous screening of multiple deafness mutations by Invader assay followed by direct sequencing will enable us to detect deafness mutations in an efficient and practical manner for clinical use.     

Identification and Clinical Implications of Novel MYO15A Mutations in a Non-consanguineous Korean Family by Targeted Exome Sequencing

Mutations of MYO15A are generally known to cause severe to profound hearing loss throughout all frequencies. Here, we found two novel MYO15A mutations, c.3871C>T (p.L1291F) and c.5835T>G (p.Y1945X) in an affected individual carrying congenital profound sensorineural hearing loss (SNHL) through targeted resequencing of 134 known deafness genes. The variant, p.L1291F and p.Y1945X, resided in the myosin motor and IQ2 domains, respectively. The p.L1291F variant was predicted to affect the structure of the actin-binding site from three-dimensional protein modeling, thereby interfering with the correct interaction between actin and myosin. From the literature analysis, mutations in the N-terminal domain were more frequently associated with residual hearing at low frequencies than mutations in the other regions of this gene. Therefore we suggest a hypothetical genotype-phenotype correlation whereby MYO15A mutations that affect domains other than the N-terminal domain, lead to profound SNHL throughout all frequencies and mutations that affect the N-terminal domain, result in residual hearing at low frequencies. This genotype-phenotype correlation suggests that preservation of residual hearing during auditory rehabilitation like cochlear implantation should be intended for those who carry mutations in the N-terminal domain and that individuals with mutations elsewhere in MYO15A require early cochlear implantation to timely initiate speech development.     

High incidence of profound deafness in an isolated community

In a Muslim Israeli Arab village, different types of hearing loss affect some 2% of the inhabitants. Most cases of profound deafness are due to recessive mutations in the Connexin-26 gene. Since in this community, marriages are by preference within the family (consanguineous), for many of the couples from the village the risk for an affected child is high. There are 30 families living in the village in which both parents have normal hearing and at least one child has a profound hearing defect. In these families, the birth of a child with profound deafness did not change family planning. The rate of marriage was similar for the siblings of deaf children as for other individuals in the village. The major problems were encountered by the deaf individuals themselves; in particular, most of the women were not married. Because of the distinctive nature of this particular problem, different types of screening programs were envisaged. However, all of them are problematic. Therefore, as a first step it was decided to begin a program including individual genetic counseling together with education of the entire population on practical aspects of human genetics.     

Retrospective diagnosis of congenital rubella.

One hundred and five children and adolescents with impaired hearing and 19 with impaired vision underwent in vitro tests (lymphocyte responsiveness and serum antibody to rubella) for retrospective diagnosis of intrauterine rubella. Tests yielded results consistent with intrauterine rubella in 30 (29%) of the patients with impaired hearing but only one (5%) of those with impaired vision. In addition, the reported incidence (10.8%) of rubella as a cause of deafness was obtained by questioning parents before the tests. Of 27 patients with impaired hearing of unknown aetiology but reported rubella contact during the pregnancy, seven (26%) had test results consistent with intrauterine rubella. The incidence of intrauterine rubella as a cause of deafness is probably underestimated when the diagnosis is based on the presence of several classic features.     

Functional characterization of a novel Cx26 (T55N) mutation associated to non-syndromic hearing loss

Mutations of the GJB2 gene, encoding connexin 26, are the most common cause of hereditary congenital hearing loss in many countries and account for up to 50% of cases of autosomal-recessive non-syndromic deafness. By contrast, only a few GJB2 mutations have been reported to cause an autosomal-dominant form of non-syndromic deafness. Here, we report a family from Southern Italy affected by non-syndromic autosomal dominant post-lingual hearing loss, due to a novel missense mutation in the GJB2 gene, a threonine to asparagine amino acid substitution at codon 55 (T55N). Functional studies indicated that the mutation T55N produces a protein that, although expressed to levels similar to those of the wt counterpart, is deeply impaired in its intracellular trafficking and fails to reach the plasma membrane. The mutation T55N is located at the apex of the first extracellular loop of the protein, a region suggested to play a role in protein targeting and a site for other two mutations, G59A and D66H, causing dominant forms of deafness.     

不同听力曲线分型突发性耳聋患者听阈水平及临床特征分析

摘要 目的：探讨不同听力曲线分型突发性耳聋患者听阈水平及临床特征分析。方法：前瞻性选取我院2019年10月至2022年10月我院收治的80例突发性耳聋患者作为研究对象。采集患者临床特征信息。检测所有患者听阈水平。采用秩和检验进行多组间差异分析;采用Spearman检验进行相关性分析;采用多元线性回归模型进行回归分析。结果：平坦下降组、低频下降组、高频下降组和全聋组在侧别、性别、糖尿病、耳鸣、眩晕、耳闷胀感亚组间差异显著（P<0.05）,而在年龄、高血压和脑梗塞亚组间无显著差异（P＞0.05）;平坦下降组、低频下降组、高频下降组和全聋组在极重度、重度、中度、轻度、正常亚组间差异显著（P<0.05）;突发性耳聋患者听力曲线分型与侧别、性别、糖尿病、耳鸣眩晕、耳闷胀感、听阈水平密切相关（P<0.05）,而与年龄、高血压、脑梗塞无关（P＞0.05）;多元线性回归结果显示,耳鸣、眩晕、耳闷胀感、听阈水平、侧别是影响突发性耳聋患者听力曲线分型的独立危险因素（P<0.05）。结论：突发性耳聋不同听力曲线分型患者间存在临床特征及听阈水平的差异,临床可依据患者独特疾病特征构建精准的治疗策略进行干预。     

Neonatal detection of the 35delG mutation of the GJB2 gene in families at risk for deafness

About half of congenitally deaf children that have a recessively inherited sensorineural deafness are born from normal-hearing parents and have no risk factor for hearing loss. Mutation 35delG in the connexin-26 gene is in European populations the basis for around half of all recessively inherited prelingual sensorineural deafness. The aim of our study was to assess the efficacy and utility of the 35delG mutation of the connexin-26 gene analysis for neonates at familial risk, from DNA isolated from Guthrie newborn screening cards. Newborns who had consanguineous parent and/or a familial history of deafness underwent connexin-26 gene analysis from DNA isolated from Guthrie cards and two hearing screening tests (transient evoked otoacoustic emissions, and auditory brainstem recordings). 24 newborns were includes in this pilot study; one of them is homozygous for the 35delG mutation and had abnormal hearing screening tests; all the others newborns had normal connexin gene and at least one normal hearing screening test. Detection on connexin-26 gene mutation is feasible in selected at-risk newborns on one additional blood spot on Guthrie card.     

Deafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disorders

Connexin 26 (Cx26, GJB2) mutations are the major cause of hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. Mouse models show that Cx26 deficiency can cause congenital deafness with cochlear developmental disorders, hair cell degeneration, and the reduction of endocochlear potential (EP) and active cochlear amplification. However, the underlying deafness mechanism still remains undetermined. Our previous studies revealed that hair cell degeneration is not a primary cause of hearing loss. In this study we investigated the role of EP reduction in Cx26 deficiency-induced deafness. We found that the EP reduction is not associated with congenital deafness in Cx26 knockout (KO) mice. The threshold of auditory brainstem response (ABR) in Cx26 KO mice was even greater than 110 dB SPL, demonstrating complete hearing loss. However, the EP in Cx26 KO mice varied and not completely abolished. In some cases, the EP could still remain at higher levels (>70 mV). We further found that the deafness in Cx26 KO mice is associated with cochlear developmental disorders. Deletion of Cx26 in the cochlea before postnatal day 5 (P5) could cause congenital deafness. The cochlea had developmental disorders and the cochlear tunnel was not open. However, no congenital deafness was found when Cx26 was deleted after P5. The cochlea also displayed normal development and the cochlear tunnel was open normally. These data suggest that congenital deafness induced by Cx26 deficiency is not determined by EP reduction and may result from cochlear developmental disorders.     

Genetic characteristics of recessive sensorineural hearing loss

Genetic characteristics of recessive sensorineural hearing impairment mediated by 5 recessive genes were studied. One of these is responsible for early progressive hearing loss, others causing congenital deafness. The incidence of early progressive recessive hearing loss in a population is 1:20,000, gene frequency being 0.007; the incidence of heterozygotes for this gene is 1.4%. The incidence of each of 4 forms of recessive congenital hearing loss in a population is 1.125:10,000, the frequency of these genes being 0.0106; the incidence of heterozygotes for each of these genes is 2.1%. The total frequency of all recessive genes for sensorineural hearing impairment is 0.0494 and the incidence of heterozygotes for all genes is 9.9%. The frequency of different genotypes for recessive genes specifying sensorineural hearing loss was established, based on the data obtained.     

Long-Term Asymmetric Hearing Affects Cochlear Implantation Outcomes Differently in Adults with Pre- and Postlingual Hearing Loss

In many countries, a single cochlear implant is offered as a treatment for a bilateral hearing loss. In cases where there is asymmetry in the amount of sound deprivation between the ears, there is a dilemma in choosing which ear should be implanted. In many clinics, the choice of ear has been guided by an assumption that the reorganisation of the auditory pathways caused by longer duration of deafness in one ear is associated with poorer implantation outcomes for that ear. This assumption, however, is mainly derived from studies of early childhood deafness. This study compared outcomes following implantation of the better or poorer ear in cases of long-term hearing asymmetries. Audiological records of 146 adults with bilateral hearing loss using a single hearing aid were reviewed. The unaided ear had 15 to 72 years of unaided severe to profound hearing loss before unilateral cochlear implantation. 98 received the implant in their long-term sound-deprived ear. A multiple regression analysis was conducted to assess the relative contribution of potential predictors to speech recognition performance after implantation. Duration of bilateral significant hearing loss and the presence of a prelingual hearing loss explained the majority of variance in speech recognition performance following cochlear implantation. For participants with postlingual hearing loss, similar outcomes were obtained by implanting either ear. With prelingual hearing loss, poorer outcomes were obtained when implanting the long-term sound-deprived ear, but the duration of the sound deprivation in the implanted ear did not reliably predict outcomes. Contrary to an apparent clinical consensus, duration of sound deprivation in one ear has limited value in predicting speech recognition outcomes of cochlear implantation in that ear. Outcomes of cochlear implantation are more closely related to the period of time for which the brain is deprived of auditory stimulation from both ears.     

单侧人工耳蜗植入对学龄前耳聋儿童听觉言语康复的效果影响因素分析

目的:探讨单侧人工耳蜗植入(cochlear implantation,CI)对学龄前耳聋儿童听觉语言康复的治疗效果以及相关影响因素。方法:将我院自2017年1月至2017年12月行CI治疗的学龄前儿童72例行作为研究对象,通过问卷调查手术患儿的相关资料,对可能影响患儿听觉言语康复效果的因素和听觉行为分级(Categories of auditory performance,CAP)以及言语可懂程度分级(Speech intelligibility rating,SIR)结果进行二分类变量的单因素分析,再进行多分类变量的Logistic回归分析评估患儿的治疗效果和影响康复效果的因素。结果:耳聋患儿CI植入年龄、术前平均残余听力、术前佩戴助听器时间、使用人工耳蜗时间和术后语训时间等因素和CAP增长倍数之间有明显的相关性(P0.05),除了上述因素之外还有术前语训时间等因素与治疗后患儿SIR增长倍数存在相关性(P0.05);CI植入年龄、术前平均残余听力和术前佩戴助听器时间对患儿术后CAP的恢复具有影响(P0.05);CI植入年龄、术前佩戴助听器时间、术前语训时间等因素对患儿SIR恢复产生影响(P0.05)。结论:患儿植入人工耳蜗的年龄、术前平均残余听力、术前佩戴助听器时间和术前言语训练时间是影响学龄前耳聋患儿术后听力言语功能恢复的主要因素。     

HEARING IMPAIRMENT IN CHILDREN

Abnormal behavior in children may frequently be caused by impairment of hearing. Early detection of the impairment and of the cause are of utmost importance, not only to prevent irreversible changes where that is possible, but to permit early beginning of special training for children who are permanently deaf.Recent studies have shown that deafness of infants may follow rubella in the mother in early pregnancy, or kernicterus caused by Rh incompatibilities. Measures to control these disorders are being investigated. Adequate and careful treatment of diseases of the nose, as well as surgical drainage of infected ears when necessary, are important factors in the prevention of hearing loss in children.     

Predicting the Perceived Sound Quality of Frequency-Compressed Speech

The performance of objective speech and audio quality measures for the prediction of the perceived quality of frequency-compressed speech in hearing aids is investigated in this paper. A number of existing quality measures have been applied to speech signals processed by a hearing aid, which compresses speech spectra along frequency in order to make information contained in higher frequencies audible for listeners with severe high-frequency hearing loss. Quality measures were compared with subjective ratings obtained from normal hearing and hearing impaired children and adults in an earlier study. High correlations were achieved with quality measures computed by quality models that are based on the auditory model of Dau et al., namely, the measure PSM, computed by the quality model PEMO-Q; the measure qc, computed by the quality model proposed by Hansen and Kollmeier; and the linear subcomponent of the HASQI. For the prediction of quality ratings by hearing impaired listeners, extensions of some models incorporating hearing loss were implemented and shown to achieve improved prediction accuracy. Results indicate that these objective quality measures can potentially serve as tools for assisting in initial setting of frequency compression parameters.     

Congenital Perceptive Deafness: Role of Intrauterine Rubella

Rubella antibody was detected in 85 (61%) of 139 children aged from 6 months to 7 years with congenital perceptive deafness. Of the 112 children who were aged under 4 years 61 (54%) had rubella antibody (seropositive) compared with 7·1% in randomly selected children of the same age. A close correlation was found between the presence of antibody in children with perceptive deafness and (1) a maternal history of rash or contact in early pregnancy, and (2) with the presence of other rubella-type defects. Intrauterine rubella was thought to be the cause of the deafness in 82 (59%) of the 139 children, in 60 of whom deafness was the only rubella defect detected. Thus intrauterine rubella should be considered a likely cause of congenital perceptive deafness in a child under 4 years in whom rubella antibody is present.     

Long-term functional outcomes after 10 years of bilateral cochlear implantat use

The aims were to determine the benefit of bilateral cochlear implantation in a 20 years old patient implanted in Croatia on hearing and speech development. The male patient, after 10 years of deafness, got cochlear implants Med-EL Combi 40+ on both sides in one-stage surgery. The etiology of his deafness was posttraumatic meningitis. Auditory capacity and speech recognition tests were performed for both ears separately and together Average hearing level on the right ear with right cochlear implant switched on started at 62 dB 1 month after the cochlear implantation and was on 55 dB after 10 years. Average hearing level on the left ear with left cochlear implant switched on started at 55 dB 1 month after the cochlear implantation and was on 32 dB after 10 years. Average hearing level on the both ears with 2 cochlear implants switched on started at 35 dB 1 month after the cochlear implantation and was on 27 dB after 10 years. Long-term functional outcomes with bilateral cochlear implantation provides advantages over unilateral implantation including improved hearing level, speech perception in noise and improved sound localization.