Connexin 26 and connexin 30 mutations in children with nonsyndromic hearing loss

OBJECTIVES/HYPOTHESIS: Mutations in the connexin 26 (Cx26) or gap junction beta 2 gene are the leading cause of hereditary nonsyndromic sensorineural hearing loss in Caucasians. The Cx26 coding region of 68 children with nonsyndromic sensorineural hearing loss was sequenced to determine the frequency and type of Cx26 mutations in this population. Screening was also performed for a common connexin 30 (Cx30) or gap junction beta 6 mutation (del [GJB6-D13S1830]). Children also underwent audiological testing to determine whether any correlation exists between Cx26 mutations and severity of hearing loss. STUDY DESIGN: In all, 68 children with nonsyndromic sensorineural hearing loss were screened for Cx26 and Cx30 mutations by polymerase chain reaction and direct sequencing. METHODS: Genomic DNA was amplified by polymerase chain reaction using primers that flank the entire Cx26 coding region. Screening for the 342-kb Cx30 deletion was performed using primers that amplified the breakpoint junction of the deletion. The amplicons were then sequenced in both directions and analyzed for mutations. Audiometric testing, including pure-tone audiometry and auditory evoked brainstem response, was also performed to determine the degree of hearing loss. RESULTS: Twenty-seven of 68 children tested had mutations in Cx26 with 35delG being the most prevalent. Ten additional Cx26 mutations were detected including a novel compound heterozygote. Two children were heterozygous for the Cx30 del (GJB6-D13S1830) mutation. CONCLUSION: Cx26 and Cx30 mutations were present in 41.2% of children tested in the study population. Audiometric data supported previous studies demonstrating a greater degree of hearing loss in subjects who are homozygous for the 35delG mutation.     

Connexin26 mutations associated with nonsyndromic hearing loss

OBJECTIVE: Mutations in the GJB2 gene are a major cause of autosomal recessive and sporadic types of congenital deafness. The 35delG mutation is the most frequent type of mutation in white populations. However, several other forms were reported, such as 167delT among Ashkenazi Jews and R143W in Africans. The present study investigated the mutations of connexin26 (Cx26) found in patients with nonsyndromic hearing loss (NSHL) and newborns in the Korean population. STUDY DESIGN: The sequencing data for 147 unrelated patients with congenital NSHL and 100 audiologically screened newborns were included in this prospective study. METHODS: Genomic DNA samples from all patients and newborns were sequenced in both directions for detection of Cx26 mutations. RESULTS: Thirteen different types of mutations were found in the patients and newborns. V27I and E114G are the popular types of polymorphic mutations in both groups. 235delC-deletion and frameshift--was detected in patients (15 in 294 alleles) and newborns (1 in 200 alleles). 35delG was rarely found in both group. In addition to above mutations, several types of mutations--S85P, K41R, S72C, V84A, 176-191del, and 299-300del-were identified. The family study of the 235delC showed a typical autosomal recessive trait of NSHL in their audiological evaluation of hearing threshold. CONCLUSION: The frequency of 235delC allele showed much higher in the patients (5%) than in newborns (0.5%). We rarely found 35delC mutant in both groups. These results suggest that the different types of Cx26 mutations affect autosomal recessive NSHL according to ethnic background.     

感音神经性听力损失的MRI特征

感音神经性听力损失(SNHL)是耳科常见疾病,主要表现为听力损失伴或不伴耳鸣、眩晕、耳闷等症状,SNHL病因复杂多样,目前尚未有一个确切的病因。近年来磁共振影像技术(MRI)得到了较好的发展和运用,内听道MRI在显示软组织方面更具优势,可用来研究SNHL患者的内耳疾病,如研究小脑前下动脉来进一步阐述内耳微循环,轧造影显示梅尼埃病患者膜迷路积水,以及功能MRI对脑区活动的研究等等。本文主要以内听道MRI影像学特征来探讨SNHL的潜在病因,为耳科医生诊疗SNHL提供新思路。     

Spectrum and frequency of GJB2 mutations in a cohort of 264 Portuguese nonsyndromic sensorineural hearing loss patients

Abstract

Objective: To assess the spectrum and prevalence of mutations in the GJB2 gene in Portuguese nonsyndromic sensorineural hearing loss (NSSHL) patients. Design: Sequencing of the coding region, basal promoter, exon 1, and donor splice site of the GJB2 gene; screening for the presence of the two common GJB6 deletions. Study sample: A cohort of 264 Portuguese NSSHL patients. Results: At least one out of 21 different GJB2 variants was identified in 80 (30.2%) of the 264 patients analysed. Two mutant alleles were found in 53 (20%) of these probands, of which 83% (44/53) harboured at least one c.35delG allele. Twenty-seven (10.2%) of the probands harboured only one mutant allele. Subsequent analysis revealed that the GJB6 deletion del(GJB6-D13S1854) was present in at least 7.4% (2/27) of the patients carrying only one mutant GJB2 allele. Overall, one in five (55/264) of the patients were diagnosed as having DFNB1-related NSSHL, of which the vast majority (53/55) harboured only GJB2 mutations. Conclusions: This study provides clear demonstration that mutations in the GJB2 gene are an important cause of NSSHL in Portugal, thus representing a valuable indicator as regards therapeutical and rehabilitation options, as well as genetic counseling of these patients and their families.     

Sudden sensorineural hearing loss after heroin injection

Sudden sensorineural hearing loss is a symptom of cochlear injury. Potential aetiologies are vascular diseases, viral infections, allergic reactions, autoimmune disorders, and traumatic rupture of the intralabyrinthe membrane. Unlike in unilateral cases bilateral sensorineural hearing loss is often associated with specific disease entities. We report a case of sudden bilateral deafness after intravenous heroin abuse. The putative pathophysiological mechanisms are discussed.     

急性低频感音神经性聋的短期临床疗效分析

目的探讨小剂量、短疗程皮质类固醇激素对急性低频感音神经性聋的疗效。方法选取28例(30耳)急性低频感音神经性聋患者作为研究对象,随机分为强的松治疗组16例(耳)与对照组12例(14耳),两组患者在口服等剂量强的松基础上,对照组加用血管扩张剂和神经营养剂治疗,1周后观察疗效。结果两组患者总有效率(完全恢复和部分恢复)为83.3%(25/30),总治愈率(完全恢复)46.7%(14/30);激素治疗组的有效率87.5%(14/16),治愈率50.0%(8/16),对照组有效率78.6%(11/14),治愈率42.9%(6/14),两组间的疗效比较,差异无统计学意义(P>0.05)。结论急性低频感音神经性聋的治疗有别于突发性耳聋,治疗上无需使用血管扩张剂及神经营养剂等,初始小剂量皮质类固醇激素治疗本病有效。     

Familial nonsyndromic hearing loss with incomplete partition type II caused by novel DSPP gene mutations

Background: Familial nonsyndromic hearing loss (NSHL) with incomplete partition type II (IP-II) is a very rare condition.

Aims/Objectives: To determine the audiological feature, inheritance patterns and genetic etiology of familial NSHL with IP-II in a Chinese family with eight family members.

Material and methods: Clinical data were collected from all eight family members, selected deafness genes were sequenced in proband and whole genome sequencing of seven family members was performed.

Results: The proband were a pair of male nonidentical twins (III:1, III:2). Three patients in this family, including the twins and their father (II:1), were diagnosed with bilateral NSHL with IP-II, and no mutation was found in the genes of SLC26A4, GJB2, GJB3, mitochondrial 12S rRNA, and MITF. Whole genome sequencing data indicated de novo mutations of the gene DSPP, c.3085A?>?G and c.3087C?>?T, which resulted in p.N1029D and co-segregated with deafness phenotype, were the underlying genetic etiology.

Conclusion and significance: Familial NSHL with IP-II is extremely rare. In this family, de novo DSPP gene mutations, were considered to be the most probable genetic etiology. And this is the first report to reveal DSPP gene mutations leading to familial NSHL with IP-II.     

影响突发性聋疗效的相关因素研究

目的探讨突发性聋预后的相关因素,指导其预后判断。方法回顾性分析2007年10月-2012年7月710例（748耳）突发性聋患者,应用有序Logistic回归分析,筛选与突发性聋预后相关的因素,对于有统计学意义的因素用非参数检验再次验证,以指导预后分析。结果年龄、病程、伴眩晕症状、治疗前耳聋程度、伴糖尿病与疗效有相关性;性别、耳聋侧别、伴高血压与疗效无相关性,病程长短与疗效有统计学意义（P〉0．05）;不伴眩晕的患者治疗有效率要明显高于伴眩晕的患者（P〈0．05）;糖尿病患者与非糖尿病患者的有效率比较有统计学意义（P〈0．05）;初诊听阈程度与疗效差异有统计学意义（P〈0．05）。结论影响突发性聋预后的因素有年龄、病程、伴发症状、伴糖尿病、治疗前耳聋稃彦．     

Connexin 26 mutations and nonsyndromic hearing impairment in northern Finland

OBJECTIVE: The aims of the present study were to evaluate the role of the gap junction protein beta-2 gene (GJB2), encoding connexin 26 (Cx26), in children with moderate to profound prelingual nonsyndromic sensorineural hearing impairment (HI) and to investigate the carrier frequencies of the GJB2 gene mutations in a control population in Northern Finland. METHODS: Mutation analysis was performed by direct sequencing and carrier detection by conformation sensitive gel electrophoresis further confirmed by direct sequencing. RESULTS: Cx26 mutations were found in 15 of 71 (21.1%) (67 families) children with HI. Homozygosity for the mutation 35delG was shown to be the cause of HI in 13 of 15 (86.7%) children. Homozygosity for the M34T genotype was found in one child, and compound heterozygosity for the M34T/V37I genotype was found in another. Five families of those with suspected familial HI (29.4%) and six families out of those with sporadic HI (12.0%) had a homozygous or compound heterozygous mutation. The carrier frequency for the mutation 35delG was 1 of 78 (4 of 313) and that for the M34T was 1 of 26 (12 of 313). CONCLUSION: 35delG/35delG genotype was found to be a significant cause of moderate to profound prelingual nonsyndromic sensorineural HI in Northern Finland. M34T/M34T genotype was seen in only one child, but the carrier frequency of the M34T allele was about three times higher than that of the 35delG mutation.     

Acute sensorineural hearing loss immediately following a local anaesthetic dental procedure

Acute sensorineural hearing loss is an uncommon phenomenon. We describe the first case of a 42-year-old lady who presented with acute sensorineural hearing loss occurring immediately after a dental procedure. Possible mechanisms are discussed. She was treated with high dose oral steroids, low molecular weight dextran and vasodilators with benefit.     

Pediatric sudden sensorineural hearing loss after diving

OBJECTIVE: Sensorineural hearing loss after diving from a low height has been rarely reported especially in children. METHODS: We present and discuss a new case of pediatric sudden sensorineural hearing loss after diving. RESULTS AND CONCLUSION: Medical and surgical approaches (indications and timing of explorative tympanotomy) to this occurrence are still controversial.     

多频稳态诱发电位(ASSR)的临床应用研究(36例极重度感音神经性耳聋幼儿及32例成人感音神经性耳聋患者ASSR测试结果分析)

目的旨在探讨ASSR与ABR在极重度感音神经性耳聋幼儿及成人感音神经性耳聋患者测试中的临床应用价值.方法对36例(72耳)小于3岁极重度感音神经性耳聋幼儿分别行ASSR和ABR测试;对32例(64耳)成人感音神经性耳聋患者分别行ASSR和电测听测试.结果①极重度感音神经性耳聋幼儿ABR均未引出V波,而ASSR在0.5 kHz、1 kHz、2 kHz、4 kHz的引出率分别为66.67%、86.11%、88.89%、94.44%,ASSR在0.5 kHz、1 kHz、2 kHz、4 kHz的阈值均数、标准差分别为82.56±9.26 dB HL、90.31±6.94 dB HL、88.12±7.93 dB HL、88.62±8.12 dB HL.②对成人感音神经性耳聋患者0.5 kHz、1 kHz、2 kHz、4 kHz ASSR测试阈值与电测听语频听阈(dB HL)进行配对两两比较的t检验,各组P值均大于0.05,无显著性差异.结论ASSR有助于极重度感音神经性耳聋幼儿残余听力的客观评估,尤以高频听阈为佳;ASSR与电测听在感音神经性耳聋诊断上有良好的一致性.     

ACEMg supplementation ameliorates progressive Connexin 26 hearing loss in a child

Mutations in the gene encoding Connexin 26 are the most common cause of genetic hearing loss. The hearing loss is typically stable but may be progressive. The reason for progression is unknown. Antioxidants have been associated with attenuation of hearing loss from other insults. One antioxidant regimen consists of beta-carotene (metabolized to vitamin A), vitamin C, vitamin E, and magnesium (ACEMg). We present a child with Connexin 26 related hearing loss who experienced progressive hearing loss over 7 years of observation. He was given ACEMg daily for 3 years, during which time his progressive hearing loss was ameliorated.     

急性低频感音神经性耳聋的临床观察

目的探讨急性低频感音神经性耳聋(acute low-tone sensorineural hearing loss,ALHL)的临床特点和疗效,提高对该疾病的诊断和认识。方法回顾性分析62例ALHL患者的临床表现、听力学检查和治疗情况,总结其临床发展规律。结果发病年龄以青中年为主,女性明显多于男性,多为单耳发病,表现为耳闷或伴耳鸣,听力下降,不伴眩晕,所有患者纯音听阈均表现为轻中度低频感音神经性耳聋,治疗前后分别为(38.71±6.82)dB和(20.56±9.44)dB,两者比较差异具有统计学意义(P<0.05)。鼓室图"A"型,49例(80.9%)镫骨肌反射引出,40例(64.5%)Metz试验阳性,62例ABR均正常。62例患者治疗前DPOAE在0.5～1 kHz的引出率仅为18.7%,反应幅值明显降低,治疗后DPOAE在0.5～1 kHz的引出率提高至43.8%,幅值亦有所提高。结论 ALHL以突发的耳闷和(或)伴耳鸣为主要表现,常单耳发病,青中年女性为主,听力学定位诊断为蜗性聋,仅累及低频区,皮质类固醇激素治疗有较好的疗效。     

Post operative sensorineural hearing loss after middle ear surgery

Mild Sensorineural hearing loss subsequent to middle ear surgery has till today been an important complication to middle ear surgery inspite of advances in surgical techniques, operative instruments, monitoring devices and better treatment options. Lack of proper knowledge about this problem is because of under reporting of exact magnitude of hearing loss on account of difficulty in measuring hearing threshold of patients in immediate postoperative period as it may lead to post operative infection and discomfort to the patient. In our study of 80 cases carried out at ENT department, Baroda Medical College and S.S.G Hospital, Baroda, we have utilized weber’s lateralisation principle and measured bone conduction thresholds of patients undergoing middle ear surgery for evaluation of postoperative Sensorineural loss as a result of middle ear surgery. Probable causes of post operative hearing loss in a patient undergoing middle ear surgery are, noise due to drills, continuous suction irrigation, vibrations, inner ear injury, manipulation of ossicles and a few unknown reasons.     

老年与中青年突发性聋的疗效比较

目的 了解老年与中青年突发性聋患者的不同临床特征和疗效。方法 回顾 分析123例（129耳）突发性聋资料,分成两组：老年组（60≥岁）72例（76耳）,中青年组（＜60岁）51例（53耳）。所有患者行皮质类固醇激素、能量合剂等治疗,一部分患者加用高压氧和东菱克栓酶辅助治疗,5例上述治疗无效患者行甲强龙鼓室灌注治疗。结果分析用χ2检验和ｔ检验。结果 两组治疗后的总有效率（痊愈、显效、有效之和）分别为59.2％和69.8％,差异无统计学意义（χ2＝3.26,P＞0.05）,总显效率（痊愈、显效之和）为34.2％和56.6％,差异有统计学意义（χ2＝6.37,P＜0.05）。患者发病至就诊时间差异有统计学意义（t=2.14,P＜0.05）。治疗前健患侧听力差分别为(28.5±13.9)dB和(42.1±28.2)dB ,差异有统计学意义（t=3.64,P＜0.01）。老年组患者合并糖尿病、高血脂症（25/76,48/76）的比例较中青年组（9/53,12/53）高。结论 老年突发性聋患者往往有基础的听力损失,发病呈渐进性和隐匿性,虽然总有效率与中青年患者相似,但显效率较低。类固醇激素鼓室灌注经圆窗渗透对一般治疗无效的部分患者仍有效。     

A cohort study of patients with tinnitus and sensorineural hearing loss in a Swedish population

Objective

We aimed to describe a large cohort of patients with tinnitus and sensorineural hearing loss (SNHL) in Sweden, and also to explore the possibility of finding potential possible differences between various diagnoses within SNHL. It is also of great interest to see how a multidisciplinary team was used in the different subgroups and the frequency of hearing aids use in patients with tinnitus.

Methods

Medical records of all patients who had received the diagnosis SNHL in Östergötland County, Sweden between 2004 and 2007 were reviewed. Patients between 20 and 80 years with tinnitus and a pure tone average (PTA) lower than 70 dB HL were included in the study. Patients were excluded from the analyses if they had a cochlear implantation, middle ear disorders or had a hearing loss since birth or childhood. The investigators completed a form for each included patient, covering background facts, and audiograms taken at the yearly check up.

Results

Of a total 1672 patients’ medical record review, 714 patients were included. The majority of patients (79%) were in the age group over 50 years. In male patients with bilateral tinnitus, the PTA for the left ear was significantly higher than for the right ear. The results regarding the configuration of hearing loss revealed that 555 patients (78%) had symmetric and 159 (22%) asymmetric hearing loss. Retrocochlear examinations were done in 372 patients and MRI was the most common examination.In all patients, 400 had no hearing aids and out of those 220 had unilateral tinnitus and 180 patients had bilateral tinnitus. 219 patients had a PTA > 20 dB HL and did not have any hearing aid. Results demonstrated that the Stepped Care model was not used widely in the daily practice. In our study, patients with bilateral-, unilateral hearing loss or Mb Ménière were the most common patients included in the Stepped Care model.

Conclusion

In a large cohort of patients with SNHL and tinnitus, despite their hearing loss only 39% had hearing aids. It was observed that the medical record review often showed a lack of information about many background factors, such as; patients’ general health condition, which could be a quality factor that needs improvement. Our results show that the Stepped Care model could be an effective option for providing a better access for tinnitus-focused treatment, although the number of patients in this study who were included in the Stepped Care model was low.     

Middle cranial fossa arachnoid cysts causing sensorineural hearing loss

Arachnoid cyst of the middle cranial fossa has never been reported to present with sensorineural hearing impairment. We report the case of a 15-year-old girl who complained of progressive hearing loss on the right side for 4 years. The pure tone audiometry revealed sensorineural hearing loss with an average of 63 dB, and the auditory brain stem response demonstrated absence of all waves on the right side. Magnetic resonance imaging showed giant arachnoid cysts occupying the bilateral middle cranial fossa and extending to the parietal and prepontine areas with the atrophic change of the right facial-acoustic nerve cord and a decrease in signal intensity of the right cochlea and vestibule. The cystoperitoneal shunting procedure was suggested, but the parents hesitated about the surgical treatment. The patient has not received any surgical intervention, and her hearing has been stable for 1 year during the follow-up period. This case represents the first report that sensorineural hearing loss is a possible presenting symptom when arachnoid cysts of the middle cranial fossa are massive.     

Epileptiform electroencephalogram abnormality in children with congenital sensorineural hearing loss

Objectives

This work was designed to study electroencephalogram findings in children with congenital sensorineural hearing loss and correlate these findings with the SNHL parameters as duration, etiology, severity, and type.

Methods

Ninety children with bilateral congenital sensorineural hearing loss served as the study group. They were free from any neurological disorders or symptoms that are commonly associated with abnormal electroencephalogram as convulsions or loss of consciousness. Twenty children having normal hearing with no history of otological or neurological disorders served as the control group. All children participating in the study were subjected to full medical and audiological history, otological examination, neurological examination, audiological evaluation and electroencephalogram recording.

Results

Mean age of the children in the control group was 3.56 ± 2.1 years and mean age of the children in the study group was 3.8 ± 2.2 years. While none of the control children had abnormal electroencephalogram, 38 (42.2%) of children with congenital SNHL had epileptiform electroencephalogram abnormality. The epileptiform abnormality was generalized in 14 children (36.8%), focal temporal in 17 children (44.7%) and focal other than temporal in 7 children (18.4%). According to the hemispheric side affected, the abnormality was right in 14 children (36.8%), left in 10 children (26.3%) and bilateral in 14 children (36.8%). No statistically significant predominance of specific site or side of the epileptiform abnormality was found. Similarly, no statistical significant prevalent of the epileptiform abnormality was found in relation to the age or sex of children, duration of hearing loss or etiology of hearing loss (i.e., genetic vs. neonatal insults). On the other hand, the epileptiform abnormality was statistically prevalent in children with moderate degree of hearing loss, and in children with auditory neuropathy spectrum disorder.

Conclusions

The epileptiform electroencephalogram abnormality is a common finding in children with congenital sensorineural hearing loss especially those with auditory neuropathy spectrum disorder, suggesting the affection of the central nervous system despite the absence of neurological symptoms or signs. These findings raise the question of the requirement of medical treatment for those children and the effect of such treatment in their rehabilitation.     

聪耳熄鸣丸治疗感音神经性耳聋、耳鸣的疗效观察

目的 研究聪耳熄鸣丸治疗感音神经耳聋、耳鸣的临床疗效。方法 随机选取来我院就治的感音神经性聋、伴耳鸣病人120例,分治疗组和对照组进行对比。结果 治疗组和对照组对耳鸣的疗效,分别为68％和40％;治疗组和对照组对耳聋的疗效分别为68％和50％,有显著性差异。结论 聪耳熄鸣丸是治疗感音神经性耳聋,耳鸣的有效药物。