Sudden hearing loss in a family with GJB2 related progressive deafness

Mutations of GJB2, the gene encoding connexin 26, have been associated with prelingual, sensorineural hearing loss of mild to profound severity. One specific mutation, the 35delG, has accounted for the majority of mutations detected in the GJB2 gene in Caucasian populations. Recent studies have described progression of hearing loss in a proportion of cases with GJB2 deafness. We report an unusual family with four 35delG homozygous members, in which the parents were deaf-mute whilst both children had a postlingual progressive hearing loss. Furthermore, the son suffered from sudden hearing loss.     

Bone-anchored hearing aids in unilateral inner ear deafness

In nine patients with unilateral deafness and normal hearing in the contralateral ear, measurements of sound localization and speech perception were obtained before intervention, with a conventional contralateral routing of sound (CROS) hearing aid and later with a bone-anchored hearing aid (BAHA) implanted in the deaf ear. Sound localization did not show any differences between the three conditions. Speech perception using short, everyday sentences showed a reduction in the head-shadow effect of 2 dB for both the conventional CROS hearing aid and the BAHA in comparison to the unaided condition. Patients' real-life experiences of the three conditions were evaluated using the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire. The results showed a significant benefit with the BAHA in situations involving background noise and reverberation and a reduced aversion to loud sounds in comparison to the unaided and conventional CROS conditions.     

助听器配戴与感音性聋患者的言语识别

目的：感音性耳聋者的纯音听力水平与选配助听器的声增益特性对言语识别率提高的讨论。方法：８５例６岁～９０岁双耳感音性聋者单耳选配耳背式助听器,经１年以上随访,对助听耳的纯音听力、最佳言语识别率、助听器的声增益特性进行分析。结果：８５例助听耳平均言语识别率为６０±２４％,裸耳言语识别率为 ５０±２６％,平均残留听力水平（１２５Ｈｚ～８ ０００Ｈｚ）为 ５５±１１ｄＢＨＬ。结论：８５例感音性耳聋者助听耳的言语识别率（Ｙ）与残留听力水平（Ｘ）之间的相关关系为：Ｙ＝－０．８０８Ｘ＋１０４。     

GJB2 gene mutations in childhood deafness

The frequency of childhood deafness is estimated at 1:1,000 and at least half of these cases are genetic. Recently, mutations in the GJB2 gene have been found in a great number of familial and sporadic cases of congenital deafness in Caucasians. The most common mutation (70%) is the frameshift mutation of a single guanine in position 35 (35delG). More than 20 mutations in the GJB2 gene are associated with DFNB1, a prevalent type of autosomal recessive non-syndromic neurosensory deafness. Last year we initiated a systematic screening programme to evaluate the causes of deafness in the population of prelingually deaf children who are referred to our cochlear implant programme. All of the deaf children and their parents undergo a comprehensive medical review, directed to identify causes of acquired deafness and manifestations of syndromic hearing impairment. DNA is extracted from the blood of all of the children. The technique AS-PCR (allele-specific polymerase chain reaction) is used for the identification of the mutation 35delG. Screening for other GJB2 gene mutations is carried out by single-strand conformation polymorphisms (SSCP). Our results on the identification of DFNB1 will be presented, as well as a discussion on the implications of an aetiological diagnosis in cochlear implantation.     

Temporal bone imaging in GJB2 deafness

OBJECTIVE: To describe temporal bone findings on computed tomography (CT) imaging in GJB2-related hearing loss (HL). We asked whether evaluation of the temporal bone is required in individuals with biallelic GJB2 mutations. STUDY DESIGN: Randomized, blinded, controlled, prospective measurement. METHODS: Blood from 264 pediatric cochlear implant users was analyzed for mutations in the GJB2 gene. Thirty-six aspects of the temporal bone on CT imaging were evaluated in 53 individuals (106 ears) with biallelic disease causing GJB2 mutations. A subset of patients was age matched and compared with normally hearing individuals. Subjects with biallelic GJB2 mutations were tested for mutations in the SLC26A4 gene to rule out Pendred syndrome as a confounding cause of large vestibular aqueduct syndrome. RESULTS: Approximately 53% of ears of subjects (72% of subjects) with biallelic GJB2 mutations had at least one temporal bone anomaly. The most common findings were 1) dilated endolymphatic fossa (28%); 2) hypoplastic modiolus (25%); 3) large vestibular aqueduct (8%); 4) hypoplastic horizontal semicircular canal (8%); 5) hypoplastic cochlea (4%). Compared with normally hearing individuals, the GJB2 group had hypoplasia of the cochlear nerve canal, lateral semicircular canal vestibule, internal auditory canal (t tests, P < .001), and were 11 times more likely to have a hypoplastic modiolus. Dilated endolymphatic fossae were 1.4 times more common in the GJB2 group, and large vestibular aqueducts were 3 times more common in the GJB2 group, as compared with normally hearing controls. CONCLUSIONS: Temporal bone anomalies are common in GJB2-related HL, and imaging of the temporal bone should be included in routine evaluation of these individuals.     

Using assessment of higher brain functions of children with GJB2-associated deafness and cochlear implants as a procedure to evaluate language development

OBJECTIVE: While investigators have reported that patients with GJB2-associated deafness and cochlear implants have preferable language development, the mechanisms of this phenomenon remains unknown. The goal of the present study was to assess higher brain functions of patients with GJB2-related and GJB2-unrelated deafness as a method of evaluating language development. METHODS: Eight children with cochlear implants were subjected to genetic testing for GJB2 and underwent the Raven colored progressive matrices test, Rey's auditory verbal learning test, Rey's complex figure test, the standardized language test for aphasia, the picture vocabulary test, and the standardized comprehension test for abstract words. RESULTS: Three children were diagnosed with GJB2-related deafness, and five children were diagnosed with GJB2-unrelated deafness. All three GJB2-related cases demonstrated normal range higher brain functions and fair language development. By contrast, one GJB2-unrelated case showed a semantic disorder, another demonstrated a visual cognitive disorder with dyslexia, and another had attention deficit-hyperactivity disorder. CONCLUSIONS: Children with GJB2-unrelated deafness showed a high frequency of heterogeneous disorders that can affect proper language development. This difference between children with GJB2-related and GJB2-unrelated deafness may account for the improved language development in children with GJB2-related deafness and cochlear implants. Further, genetic diagnosis of the non-syndromic hearing loss represents a useful tool for the preoperative prediction of outcomes following a cochlear implant procedure.     

Auditory and language skills of children using hearing aids

IntroductionHearing loss may impair the development of a child. The rehabilitation process for individuals with hearing loss depends on effective interventions.ObjectiveTo describe the linguistic profile and the hearing skills of children using hearing aids, to characterize the rehabilitation process and to analyze its association with the children's degree of hearing loss.MethodsCross-sectional study with a non-probabilistic sample of 110 children using hearing aids (6–10 years of age) for mild to profound hearing loss. Tests of language, speech perception, phonemic discrimination, and school performance were performed. The associations were verified by the following tests: chi-squared for linear trend and Kruskal–Wallis.ResultsAbout 65% of the children had altered vocabulary, whereas 89% and 94% had altered phonology and inferior school performance, respectively. The degree of hearing loss was associated with differences in the median age of diagnosis; the age at which the hearing aids were adapted and at which speech therapy was started; and the performance on auditory tests and the type of communication used.ConclusionThe diagnosis of hearing loss and the clinical interventions occurred late, contributing to impairments in auditory and language development.     

Cochlear implantation for children with GJB2-related deafness

OBJECTIVES/HYPOTHESIS: Mutations in GJB2 are a common cause of congenital sensorineural hearing loss. Many children with these mutations receive cochlear implants for auditory habilitation. The purpose of the study was to compare the speech perception performance of cochlear implant patients with GJB2-related deafness to patients without GJB2-related deafness. STUDY DESIGN: Retrospective case review. METHODS: Pediatric cochlear implant recipients who have been tested for GJB2 mutation underwent chart review. All patients received cochlear implantation at a tertiary referral center, followed by outpatient auditory habilitation. Charts were reviewed for cause and duration of deafness, age at time of cochlear implantation, intraoperative and postoperative complications, duration of use, and current age. Results of standard tests of speech perception administered as a part of the patients' auditory habilitation were reviewed. RESULTS: Twenty patients with GJB2 mutations were compared with 27 patients without GJB2 mutations. There was no statistical difference between patients with and without GJB2-related congenital sensorineural hearing loss with regard to open-set and closed-set speech recognition performance at 12, 24, and 36 months after cochlear implantation. Surgical complications were uncommon. CONCLUSION: Pediatric patients with congenital sensorineural hearing loss without other comorbid conditions (eg, developmental delay, inner ear malformations) perform well when they receive cochlear implantation and auditory habilitation. The presence or absence of GJB2 mutation does not appear to impact speech recognition performance at 12, 24, and 36 months after implantation.     

Cochlear implants, vibrators and hearing aids in the rehabilitation of postlingual deafness

Three groups of postlingually deaf adults were formed by non-random selection. The subjects with some residual hearing were fitted with a powerful hearing aid (HA group, n = 10). The others received either a single-channel vibrotactile aid (V group, n = 8) or a single-channel intracochlear implant (CI group, n = 10). Training containing individual counselling and rehearsal in small groups was arranged. During the follow-up (CI group 2.0 yrs, V group 1.8 yrs, HA group 2.6 yrs), the subject's achievement was assessed by a repetition of audiological testing and written questionnaires. Whereas the HA group obtained the highest scores in the audiological tests, the CI group found the implant most beneficial in everyday life. No significant improvement in the test scores was observed during the follow-up. The extent of personal training, after an initial training period and motivation of the user, did not affect the test scores or the subjective evaluation.     

Auditory responses in cochlear implant users with and without GJB2 deafness

OBJECTIVE/HYPOTHESIS: It is reasonable to suppose that the pattern of sensorineural damage along the length of the cochlea depends on the etiology of a hearing loss (HL). In GJB2-related deafness, we hypothesize that gap junction deficits are uniformly distributed and will result in similar damage along the length of the cochlea as compared with non-GJB2 subjects. We assessed this by measuring patterns of neural activity and hearing from apical versus basal cochlear implant electrode regions. STUDY DESIGN: This was a prospective, blind, controlled study. METHODS: Blood from 301 pediatric cochlear implant users was analyzed for mutations in GJB2 by direct sequencing. After exclusion of patients with monoallelic GJB2 mutations, associated syndromes, or risk factors for HL that were not congenital, 39 children with biallelic GJB2 mutations and 58 without GJB2 mutations were evaluated. Hearing was measured before implantation at frequencies ranging from 250 Hz to 8 kHz. After implantation, neural activity at the apical and basal ends of the implanted array was measured using electrically evoked compound action potentials of the auditory nerve (ECAPs) and evoked stapedius reflexes (ESRs). RESULTS: GJB2 and non-GJB2 groups were not significantly different with respect to sex, age at implantation, duration of auditory deprivation, hearing aid use, duration of aided hearing, ear implanted, implant model, or depth of insertion (P>.05). Children with GJB2-related HL had greater similarities between low- and high-frequency residual hearing and between neural activity electrically evoked at apical and basal regions of the cochlea as compared with children with non-GJB2-related HL who demonstrated larger deficits in basal regions. CONCLUSION: Results suggest more consistent spiral ganglion survival along the length of the cochlea in GJB2-related HL as compared with non-GJB2-related HL, which appears to involve a decreasing gradient of spiral ganglion survival from the apex to the base of the cochlea. Our findings support our premise that in GJB2-related HL, dysfunction of gap junctions likely occurs to a similar degree in the apical and basal regions of the cochlea. This knowledge might be used to customize implantable devices for patients with HL in the future.     

Clinical experiments with hearing aids with amplitude compression.

The model for audiological rehabilitation in Denmark is brief-described. Clinical experiments have not demonstrated a general superiority of the compression hearing aids compared to the conventional hearing aids. In situations with negligible background noise the compression hearing aid tends to provide the best comprehension of speech. However, in situations with background noise the conventional hearing aid is generally preferred by hearing impaired persons. The attitude with regard to compression hearing aids differs among Danish hearing clinics. One clinic with a very positive attitude delivers compression hearing aids to 27% of the total clientele. In several clinics it has been observed that patients with a perceptive impairment who are using the hearing aid for the first time may benefit from compression during the early stages of hearing aid adjustment. In many cases, however, these patients prefer less compression as they continue to use their hearing aids in daily life. It is pointed out, that in connection with compression hearing aids it is especially important to provide careful instruction about the possibilities and limitations of the hearing aid.     

Post-lingual deafness: benefits of cochlear implants vs. conventional hearing aids

The technological advances in cochlear implants and processing strategies have enabled subjects affected by severe to profound hearing loss to hear sounds and recognize speech in various different degrees. The variability of hearing outcomes in subjects with post-lingual deafness has been significant and cochlear implant indications have been extended to include an ever larger population.ObjectiveThis paper aims to look into the groups of post-lingual deafness patients to find where cochlear implants have yielded better outcomes than conventional hearing aids.Materials and MethodsReview the literature available on databases SciELO, Cochrane, MEDLINE, and LILACS-BIREME. The publications selected for review were rated as A or B on evidence strength on the day of the review. Their authors analyzed and compared hearing aids and cochlear implants in populations of post-lingually deaf patients. Study Design: Systematic review.ResultsEleven out of the 2,169 papers searched were found to be pertinent to the topic and were rated B for evidence strength. Six studies were prospective cohort trials, four were cross-sectional studies and one was a clinical trial.ConclusionThe assessment done on the benefits yielded by post-lingually deaf subjects from cochlear implants showed that they are effective and provide for better results than conventional hearing aids.     

散发性耳聋GJB2基因突变分析

目的 通过分析内蒙古鄂尔多斯和呼和浩特地区散发性耳聋患者GJB2 235delC点突变,以探讨散发性耳聋患者的分子病因学。方法 对131例(汉族92例,蒙古族39例) 散发性耳聋患者进行耳聋病因学问卷调查、纯音听阈及声导抗测试。聚合酶链反应(polymerase chain reaction PCR)扩增目的片段并用限制性内切酶对其进行GJB2 235delC基因突变检测,对酶切检测结果呈阳性的样本用直接测序法进行验证。对50例健康中国人和100例健康加拿大白种人行限制性内切酶GJB2 235delC点突变检测,作为阴性对照。结果 131例散发性耳聋患者全部为感音神经性聋。在该群体中4例(汉族3例,蒙古族1例)存在GJB2 235delC纯合性突变;3例(汉族2例,蒙古族1例)存在GJB2 235delC杂合性突变。50例健康中国人对照组中检测出1例GJB2 235delC点突变携带者,100例健康加拿大白种人中未检测到GJB2 235delC点突变。结论 GJB2 235delC点突变是中国人散发性感音神经性耳聋的分子病因学之一。内蒙古地区汉族、蒙古族GJB2 235delC突变频率无明显差异,对GJB2 235delC点突变的基因筛查可以明确一些散发性耳聋患者的病因,从而对基因突变引起的散发性耳聋的早期诊断、遗传咨询及防聋治聋起到重要作用。     

Differences in hearing levels between siblings with hearing loss caused by GJB2 mutations

ObjectiveHearing loss caused by GJB2 mutations is inherited in an autosomal recessive manner (DFNB1); thus siblings of an affected child have a 25% chance of also being affected. Hearing loss among subsequent siblings carrying the same GJB2 mutation is a concern for parents and a frequent topic of enquiry during genetic counseling. Evidence exists for genotype-phenotype correlations of GJB2 mutations; however, no analysis of differences in hearing among siblings, in whom the common genetic background may decrease variation, has been reported. The purpose of the present study was to investigate hearing differences between siblings with identical GJB2 mutations.MethodsWe examined the hearing levels of 12 pairs of siblings; each pair had the same pathogenic GJB2 mutations. Differences in hearing acuity between sibling pairs detected by auditory evaluation.ResultsNo significant correlation was detected between the average hearing levels of first and second affected siblings. Average differences in acoustic threshold >30 dB were observed between four pairs of siblings, whereas the remaining eight pairs had average threshold values within 20 dB of one another.ConclusionOur results indicate that auditory acuity would be expected to approximate that found in the first child in approximately 70% of subsequent children with GJB2-mediated hearing loss, whereas 30% of subsequent siblings would have average differences of >30 dB.     

GJB2 mutations in the Swiss hearing impaired

OBJECTIVE: Mutations in the GJB2 gene encoding connexin 26 (Cx26) protein are a major cause for nonsyndromic autosomal recessive and sporadic deafness. However, its contribution to hearing impairment in Switzerland remains undefined. To determine the frequency and type of GJB2 mutations in the Swiss hearing-impaired population diagnosed under the age of 2 yr and at 2 yr and older and to assess the effectiveness of denaturing high-performance liquid chromatography (DHPLC) in screening for mutation in GJB2. METHODS: Thirty-four patients with hearing impairment underwent mutation screening of the single coding exon of GJB2 with DHPLC followed by bidirectional sequencing to identify sequence alterations. RESULTS: GJB2 mutations were more common in children diagnosed with hearing impairment under the age of 2 yr compared to the group 2 yr and older. In patients under age 2 yr, 9 of 20 (45%) harbored 13 GJB2 mutations including a common 313del14nt mutation; four of these patients were homozygous or compound heterozygous for GJB2 mutations. In contrast, 2 of 14 patients in the 2 yr and older group (14%) had a single mutation in GJB2. The 35delG mutation was exclusively found in 5 patients under the age of 2 yr. DHPLC for mutation screening was 100% sensitive and 83% specific for detecting sequence alterations in GJB2. CONCLUSIONS: In Switzerland, GJB2 mutations are a major cause of nonsyndromic hearing impairment in children under the age of 2. Similar to other populations, GJB2 mutations are uncommon in the affected Swiss patients identified after 2 yr. Although 35delG mutation is common in the hearing-impaired children under the age of 2, it was absent in patients diagnosed with hearing impairment after the age of 2. DHPLC is a highly sensitive tool for detection of GJB2 mutations.