Analysis of genotypes on 850 newborns with SLC26A4 single-allele mutation and the phenotypes of those with second variant / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.

Potencial miogênico evocado vestibular cervical em crianças e adolescentes com aqueduto vestibular alargado: revisão sistemática / Cervical vestibular evoked myogenic potential in children and adolescents with enlarged vestibular aqueduct: systematic review

RESUMO Objetivo Reunir os parâmetros encontrados no potencial miogênico evocado vestibular cervical (cVEMP) em crianças e adolescentes com síndrome do aqueduto vestibular alargado (SAVA) e identificar as possíveis alterações, quando comparados aos valores encontrados em normo-ouvintes da mesma faixa etária. Estratégia de pesquisa Revisão sistemática cadastrada na base PROSPERO, elaborada por meio de busca nos bancos de dados virtuais, a partir dos unitermos selecionados. Critérios de seleção Incluídos artigos científicos disponíveis na íntegra que relataram a avaliação com o uso do cVEMP na faixa etária entre 0 e 18 anos, com diagnóstico de SAVA, sem restrição de idioma e ano de publicação; excluídos estudos em paciente com algum distúrbio, outras patologias otoneurológicas e população fora da faixa etária estimada. Resultados Foram identificados 984 registros, a partir da pesquisa nas bases de dados consultadas e selecionados 5 artigos. Em um total de 133 pacientes que realizaram o cVEMP, foi observada presença de resposta na maioria dos casos, sem diferença significativa nas latências, mas com aumento na amplitude e diminuição nos limiares do cVEMP. Conclusão O teste cVEMP é recomendado na avaliação de crianças e adolescentes com SAVA e as características de aumento na amplitude e diminuição nos limiares podem ser utilizadas como parâmetros clínicos na identificação da referida síndrome, juntamente com a história clínica do paciente e os exames de imagem. No entanto, é imprescindível a realização de mais estudos com o exame cVEMP, ainda, em crianças e adolescentes com SAVA, para a melhor padronização dos valores encontrados, a fim de efetivar o diagnóstico correto.

ABSTRACT Purpose To gather the parameters found in the cervical vestibular evoked myogenic potential (cVEMP) in children and adolescents with enlarged vestibular aqueduct syndrome (SAVA) and identify the possible changes, when compared to the values found in normal hearing people of the same age group. Research strategy Systematic review registered in the PROSPERO database, prepared through a search in virtual databases, based on the selected keywords. Selection criteria Included scientific articles available in full that reported the evaluation using cVEMP in the 0 and 18 years old group , with a diagnosis of SAVA, without restrictions of language and year of publication; Studies on patients with any disorder other than otoneurological ones and populations outside the proposed age range were excluded. Results 984 records were identified from the search in the databases consulted and 5 articles were selected. In a total of 133 patients who underwent cVEMP, the presence of a response was observed in most cases, with no significant difference in latencies, but with an increase in amplitude and a decrease in cVEMP thresholds. Conclusion The cVEMP test is recommended in the evaluation of children and adolescents with SAVA and the characteristics of increase in amplitude and decrease in thresholds can be used as clinical parameters in the identification of this syndrome, together with the patient's clinical history and imaging exams. However, it is essential to carry out more studies with the cVEMP test, also in children and adolescents with SAVA, to better standardize the values found, in order to make the correct diagnosis.

Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct

OBJECTIVES: To investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families. METHODS: Sanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents respectively. To predict and visualize the potential functional outcome of the novel variant, model building, structure analysis, and in silico analysis were further conducted. RESULTS: The results showed that the proband from family I harbored a compound heterozygote of SLC26A4 c.1174A>T (p.N392Y) mutation and c.1181delTCT (p.F394del) variant in exon 10, potentially altering Pendrin protein structure. In family II, the proband was identified in compound heterozygosity with a known mutation of c.919-2A>G in the splice site of intron 7 and a novel mutation of c.1023insC in exon 9, which results in a frameshift and translational termination, consequently leading to truncated Pendrin protein. Sequence homology analysis indicated that all the mutations localized at high conservation sites, which emphasized the significance of these mutations on Pendrin spatial organization and function. CONCLUSION: In summary, this study revealed two compound heterozygous mutations (c.1174A>T/c.1181delTCT; c.919- 2A>G/c.1023insC) in Pendrin protein, which might account for the deafness of the two probands clinically diagnosed with EVA. Thus this study contributes to improve understanding of the causes of hearing loss associated with EVA and develop a more scientific screening strategy for deafness.

Anatomical Variations in Patients with Ménière Disease: A Tomography Study

Abstract Introduction The etiology of Ménière disease (MD), a difficult-to-treat condition with great morbidity, remains controversial in the literature. The possible clinical and diagnostic impact of anatomical variations of the temporal bone among patients with MD has been recently studied. Objective To identify anatomical variations of the temporal bone associated with the diagnosis of MD. Methods Thirty-seven patients were included, although each ear was considered separately (n = 74). A case group (nA = 33) was composed of the affected ears of patients with definiteMDand a control group (nB = 41) was used consisting of the ears of individuals who did not meet the criteria for MD and of the contralateral ears from patients with unilateral disease. Tomographic images from the individuals included in the study were submitted to a blinded and systematic evaluation regarding a broad variety of anatomical variations of the temporal bone. Obtained data were compared statistically between the groups and after stratifying the study sample. Significance level was set at 0.05. Results Among the affected ears, it was observed an increased number of tomographic scans in which the vestibular aqueduct could not be identified (p = 0.01, Fisher exact test). No statistically significant differences were observed when comparing the affected and contralateral ears frompatients with unilateral MD, between affected ears from patients with unilateral and bilateral disease or between contralateral ears of patients with unilateral affection and patients without the disease. Conclusion Some anatomical variations might be more frequent in the affected ears of patients with MD, such as the lower rates of individualization of the vestibular aqueduct.

Síndrome de acueducto vestibular dilatado: a propósito de un caso / Enlarged vestibular aqueduct syndrome: a case report

El acueducto vestibular dilatado es el hallazgo más encontrado en imágenes radiológicas de pacientes con hipoacusia neurosensorial (1,2). La frecuencia del síndrome de acueducto vestibular dilatado continúa siendo subestimada, situación que ha llevado a subdiagnosticar pacientes con esta condición. El propósito del reporte de caso y su discusión es aclarar los aspectos más importantes del diagnóstico clínico, audiológico e imagenológico de esta patología, así como considerarla parte del diagnóstico diferencial de pacientes en estudio de hipoacusia.

Large vestibular aqueduct is the most frequent condition found in radiological imaging of patients with sensorineural hearing loss. The frequency of this syndrome continues to be underestimated, which has lead to underdiagnosis. The purpose of this case report and its discussion is to clarify the most important aspects of the clinical diagnosis, audiology and radiology, as well as rise attention to the importance of this entity as part of the differential diagnosis in hearing loss workup.

Mutation analysis and prenatal diagnosis for 12 families affected with hereditary hearing loss and enlarged vestibular aqueduct / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To carry out mutation analysis and prenatal diagnosis for 12 families affected with hearing loss and enlarged vestibular aqueduct from southern Zhejiang province.</p><p><b>METHODS</b>Clinical data and peripheral venous blood samples of 38 members from the 12 families were obtained. Mutations of 4 genes, namely SLC26A4, GJB2, c.538C to T and c.547G to A of GJB3, m.1555A to G and m.1494C to T of 12S rRNA, were detected by PCR and Sanger sequencing. Maternal contamination was excluded by application of STR detection during prenatal diagnosis.</p><p><b>RESULTS</b>Among the probands from the 12 families, 11 were found to be compound heterozygotes or homozygotes and 25 were heterozygotes. All of the families were detected with IVS7-2A to G mutations, and 4 had a second heterozygous mutation (c.2168A to G of the SLC26A4 gene). Four rare pathogenic mutations, namely IVS5-1G to A, c.946G to T, c.1607A to G and c.2167C to G, were detected in another four families. In addition, the partner of proband from pedigree 3 was identified with compound heterozygous mutations of c.235delC and c.299-300delAT, and proband of pedigree 5 has carried a mutation of c.109G to A in GJB2. For SLC26A4 gene, prenatal diagnostic testing has revealed heterozygous mutations in 6 fetuses and compound heterozygous mutations in 2 fetuses.</p><p><b>CONCLUSION</b>IVS7-2A to G and c.2168A to G of the SLC26A4 gene were the most common mutations in southern Zhejiang. Such mutations can be found in most families affected with hearing loss and enlarged vestibular aqueduct, which may facilitate genetic counseling and prenatal diagnosis for such families.</p>

Identification of a novel SLC26A4 mutation in a child with enlarge vestibular aqueduct syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze mutations of SLC26A4 gene and explore their origins for a patient with enlarge vestibuar aqueduct syndrome.</p><p><b>METHODS</b>Clinical data and peripheral venous blood samples were collected from the patient and her parents. Genome DNA was extracted from the peripheral blood. All of the 21 exons of the SLC26A4 gene were amplified with PCR and subjected to directly sequencing.</p><p><b>RESULTS</b>The patient was found to have carried two mutant alleles of the SLC26A4 gene, namely c.1522A to G and c.1229C to T, which were inherited from her father and mother, respectively.</p><p><b>CONCLUSION</b>SLC26A4 c.1522A to G is likely to be a pathogenic mutation. Above results may facilitate genetic counseling and prenatal diagnosis for this family.</p>

Auditory Outcome of Cochlear Implantation in Adolescent and Adult Patients with Enlarged Vestibular Aqueduct and Biallelic SLC26A4 Mutations / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mutations of the SLC26A4 gene cause congenital hearing loss and enlarged vestibular aqueduct (EVA). A considerable proportion of patients with SLC26A4 mutations have significant residual hearing at birth that eventually worsen and become the cause for cochlear implantation (CI) later in their adolescence or adulthood. We analyzed the auditory outcome and prognostic factors of CI in patients with EVA and biallelic SLC26A4 mutations showing progressive early-onset hearing loss, who eventually had implantation in their adolescent or adult periods. SUBJECTS AND METHOD: Sixteen patients with EVA carrying biallelic SLC26A4 mutations who received CI after 12 years of age were included for analysis. The outcome and prognostic factors of CI were analyzed. The postoperative follow-up period ranged from 3 to 48 months. RESULTS: The age at CI ranged from 12 to 44 years. The categories of auditory performance score was significantly improved after CI from 3.1 to 4.9 (p < 0.05). The mean sentence scores improved significantly in the auditory-visual and auditory-only conditions (p < 0.05). The significant prognostic factors were measurable bone conduction thresholds, preoperative residual hearing, recent history of sudden aggravation of hearing loss, and preoperative speech intelligibility rating scores. There was a tendency of lower postoperative sentence scores in the group with homozygous H723R mutation, but statistical significance was not reached. CONCLUSION: Despite the early-onset of hearing loss, significant improvement in auditory performance can be expected after CI in adolescent and adult patients with EVA and biallelic SLC26A4 mutations. Significant prognostic factors should be considered in selecting candidates and preoperative counseling for CI.

A Novel Frameshift Mutation of SLC26A4 in a Korean Family With Nonsyndromic Hearing Loss and Enlarged Vestibular Aqueduct

OBJECTIVES: We aimed to identify the causative mutation for siblings in a Korean family with nonsyndromic hearing loss (HL) and enlarged vestibular aqueduct (EVA). The siblings were a 19-year-old female with bilateral profound HL and an 11-year-old male with bilateral moderately severe HL. METHODS: We extracted genomic DNA from blood samples of the siblings with HL, their parents, and 100 controls. We performed mutation analysis for SLC26A4 using direct sequencing. RESULTS: The two siblings were compound heterozygotes with the novel mutation p.I713LfsX8 and the previously described mutation p.H723R. Their parents had heterozygous mono-allelic mutations. Father had p.I713LfsX8 mutation as heterozygous, and mother had p.H723R mutation as heterozygous. However, novel mutation p.I713LfsX8 was not detected in 100 unrelated controls. CONCLUSION: Both mutations identified in this study were located in the sulfate transporter and anti-sigma factor antagonist domain, the core region for membrane targeting of SulP/SLC26 anion transporters, which strongly suggests that failure in membrane trafficking by SLC26A4 is a direct cause of HL in this family. Our study could therefore provide a foundation for further investigations elucidating the SLC26A4-related mechanisms of HL.

Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism

ABSTRACT Objective Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnosed by neonatal screening. The aim of this study was to examine the SLC26A4 mutation spectrum and prevalence among congenital hypothyroidism (CH) patients in the Guangxi Zhuang Autonomous Region of China and to establish how frequently PS causes hearing impairment in our patients with CH. Subjects and methods Blood samples were collected from 192 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the SLC26A4 gene together with their exon-intron boundaries were screened by next-generation sequencing. Patients with SLC26A4 mutations underwent a complete audiological evaluation including otoscopic examination, audiometry and morphological evaluation of the inner ear. Results Next generation sequencing analysis of SLC26A4 in 192 CH patients revealed five different heterozygous variations in eight individuals (8/192, 4%). The prevalence of SLC26A4 mutations was 4% among studied Chinese CH. Three of the eight were diagnosed as enlargement of the vestibular aqueduct (EVA), no PS were found in our 192 CH patients. The mutations included one novel missense variant p.P469S, as well as four known missense variants, namely p.V233L, p.M147I, p.V609G and p.D661E. Of the eight patients identified with SLC26A4 variations in our study, seven patients showed normal size/location of thyroid gland, and one patients showed a decreased size one. Conclusions The prevalence of SLC26A4 pathogenic variants was 4% among studied Chinese patients with CH. Our study expanded the SLC26A4 mutation spectrum, provided the best estimation of SLC26A4 mutation rate for Chinese CH patients and indicated the rarity of PS as a cause of CH.

Locus DFNB4 -acueducto vestibular dilatado- comportamiento audio-vestibular / Locus DFNB4 -enlarged vestibular aqueduct- behavior audio vestibular / Locus DFNB4 - aqueduto vestibular dilatada - comportamentoaudio-vestibular

Introducción: el acueducto vestibular dilatado, denominado en la literatura internacional EVA, porEnlarged Vestibular Aqueduct, ha sido reportadopor afectar hasta el 15% de la población pediátrica con hipoacusia neurosensorial. En su génesis compartecon Pendred en el Locus DFNB4, el Gen SLC26A4en el cromosma 7q22-31.1. No se conoce bienel comportamiento y la evolución de esta entidad,debido a la gran variabilidad genotípica y fenotípicaque presenta...

Introduction: Dilated Vestibular Aqueduct, known in the international literature Enlarged Vestibular Aqueduct (EVA) has been reported to affect up to 15% of the pediatric population with hearing loss Sensory Neuro. In its genesis shares with pendred in the locus DFNB4 the SLC26A4 gene in the cromosma 7q22-31.1. It is not well understood and evolution behavior of this entity, due to the great variability genotypic and phenotypic presented...

Introdução: Aqueduto vestibular dilatada conhecido na literatura internacional Enlarged Vestibular Aqueduct (EVA) tem sido relatada a afetar até 15% da população pediátrica com perda auditiva sensorial neuro. Em suas ações genesis com Pendred no Locus DFNB4 o gene SLC26A4 na 7q22-31.1 cromosma. Elenão é bem compreendida e o comportamento de evolução dessa entidade, devido à grande variabilidade genotípica e fenotípica apresentada...

HRCT and MRI image of bilateral large vestibular aqueduct syndrome / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore. HRCT and MRI three-dimensional fast imaging employing steady state ac-quisition(3D-FIESTA) imaging features and clinical characteristics of bilateral large vestibular aqueduct syndrome(LVAS).@*METHOD@#The imaging and clinical features of 14 cases of bilateral LVAS identified over a 5-year periodwere retrospectively analyzed. All patients underwent HRCT and MRI 3D-FIESTA scanning of head and neck;MRI three dimensional reconstructions of internal acoustical meatus were also completed at the same time.@*RESULT@#Audiogram showed mild to moderate hearing loss and was progressive. The cut-off values for the coronal midpointand operculum planes on the HRCT scan to diagnose an EVA were 1. 5 mm and 4. 3 mm respectively; the averagevalue was 2. 4 mm. VA expansion degree were not linked to the degree of hearing loss. MRI showed VA andlymph sac abnormalities. Concomitant image finding was cochlear hypoplasia.@*CONCLUSION@#HRCT and MRI 3D-FI-ESTA are important examinations for accurate diagnosis of LVAS. HRCT can acquire the specific size of reamedVA. MRI and 3D reconstructions of internal acoustical meatus can noninasive show more intuitive display ofLVAS and other inner ear malformations than HRCT.

Cochlear Implantation in Isolated Large Vestibular Aqueduct Syndrome: Report of Three Cases and Literature Review

Introduction Large vestibular aqueduct syndrome (LVAS) is characterized by the enlargement of the vestibular aqueduct associated with sensorineural hearing loss. It is the most common radiographically detectable inner ear anomaly in congenital hearing loss. LVAS may occur as an isolated anomaly or in association with other inner ear malformations. Objective To report three cases of isolated LVAS with a focus on preoperative assessment, surgical issues, and short-term postoperative follow-up with preliminary auditory habilitation outcomes. Resumed Report One girl and two boys with LVAS were assessed and cochlear implantation was performed for each. Various ways of intraoperative management of cerebrospinal fluid gusher and postoperative care and outcomes are reported. Conclusion Cochlear implantation in the deaf children with LVAS is feasible and effective.(AU)

Etiologies and clinical features of 19 cases with bilateral acute sensorineural hearing loss / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the etiologies and clinical features for bilateral acute sensorineural hearing loss (bi-ASNHL).</p><p><b>METHODS</b>The clinical data of 19 cases presenting with bi-ASNHL were retrospectively analyzed, including the clinical features, systemic examinations, laboratory examinations, audiology and radiology results, as well as the prognosis.</p><p><b>RESULTS</b>There were 15 non-otologic diseases in 19 patients, accounting for 78.9% of the total cases, most of which were disorders with multisystem and multi-organ disorder. The central nervous system diseases including fungal meningitis, tuberculous meningitis, and viral encephalitis in 3 patients. The clinical features of deafness were bilateral, progressive, accompanied with fever, headache, dizziness, nausea, vomiting and change of mental status. There was a decrease in speech recognition score (SRS), and speech recognition threshold (SRT) was obviously inferior to pure tone average (PTA) disproportionally. Diseases of immune system including antineural cytoplasmic antibody (ANCA)-associated systemic vasculitis (AASV), relapsing polychondritis (RP), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) in 5 patients. They showed the characteristics of bilateral, progressive and simultaneous autoimmune disease. Hematological and endocrine system diseases including diabetes mellitus, leukemia, and thyroid hypofunction in 5 patients. The deafness had the characteristics of symmetry and progressivity. Otologic diseases including large vestibular aqueduct syndrome (LVAS) and sudden sensorineural hearing loss (SSNHL) in 4 patients; Drug-induced sensorineural deafness happened in 2 patients. After the treatment aimed at the causes, 1 case was cured, 3 patients were markedly effective, 7 patients were effective, and 8 patients were ineffective(including dead and refusal cases), with a total effective rate of 57.9%.</p><p><b>CONCLUSIONS</b>The most of bi-ASNHL cases are often associated with systemic diseases. Clinicians should analyze the history and clinical characteristics in detail, and complete specific laboratory examinations, audiology and imaging examinations in order to reveal the causative diseases. It should be treated aimed at the etiology.</p>

Study on 2,747 cases of inner ear malformation for its classification in patient with sensorineural hearing loss / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#Analyze the data of the patients with sensorineural hearing loss in China and study the classification and incidence of inner ear malformationsby the high-resolution computed tomography.@*METHOD@#The investigation took a retrospective review of CT findings relating to the 2,747 cases of outpatients. The inner ear malformations diagnosed by CT were classified according to the methods proposed by Sennaroglu.@*RESULT@#(1)843 cases of inner ear malformations were found in 2747 cases of patients with sensorineural hearing loss by CT examination. The incidence of inner ear malformation was 30.69%(843/2747). (2) The epidemiological information of 843 cases of inner ear malformation according to Sennaroglu's classification was as follows: cochlea was 52. 31%(441/843), simple vestibular aqueduct was 40.33%(340/843), simple vestibular/ semicircular canal/internal auditory canal were 7. 35%(62/843) of the group. (3) 441 cases of cochlea malformation were consisted of these types of malformation: Michel deformity was 1.13% (5/441), cochlear aplasia was 1. 81% (8/441), common cavity deformity was 3. 17% (14/441), incomplete partition type I was 8. 62% (38/441), cochlea hypoplasia was 9. 07% (40/441) and incomplete partition type II was 76. 19% (336/441) of the group.@*CONCLUSION@#The results suggested that 30. 69% cases of inner ear malformation can be found in patients with sensorineural hearing loss, which is more higher than reported by the high-resolution computed tomography. Sennaroglu's classification is instructively significant in investigating the status of inner ear malformations.

The research progress of unilateral enlargement of the vestibular aqueduct / 临床耳鼻咽喉头颈外科杂志

Unilateral enlargement of the vestibular aqueduct (EVA)is a relatively rare disease. Bilateral EVA was found to be more common than unilateral EVA. There are significant differences in clinical features and molecular etiology between unilateral EVA and bilateral one. This article reviewed related researches of the unilateral EVA in clinical characteristics, molecular etiology and pathogenic mechanism.

The application value of MRI in the children with sensorineural hearing loss before cochlear implantation / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate diagnostic value and clinical application of MRI in the children with sensorineural hearing loss (SNHL) before cochlear implantation.@*METHOD@#MRI images of 80 children with the diagnosis of SHNL were retrospectively analyzed in combination with the latest classification of inner ear malformation.@*RESULT@#There were 152 ears of inner ear malformation of 80 cases (160 ears), including 38 ears of cochlear malformation, 33 ears of vestibular malformation, 41 ears of semicircular canal malformation, 37 ears of vestibular aqueduct enlargement, 40 ears of internal auditory canal malformation, and 46 ears of cochlear nerve malformation.@*CONCLUSION@#MRI can provide detailed and reliable anatomical information for children with SNHL before cochlear implantation, and help to make the classification diagnosis. Therefore MRI is of great clinical significance for operation plan guidance and prognosis assessment.

Imaging and audiology analysis of the congenital inner ear malformations / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate imaging and audiology features of temporal bone and analyze the classification and prevalence of inner ear abnormalities in children with sensorineural hearing loss.@*METHOD@#Children who were diagnosed with sensorineural hearing loss were examined by high resolution CT and the inner ear fluid of MRI. And each chart was retrospectively reviewed to determine the imaging and audiology features.@*RESULT@#There were 125 patients(232 ears) found with inner ear malformation in 590 children with SNHL. About 21.71% of the inner ear malformation occurred in severe and profound hearing loss ears, and 12.85% occurred in r moderate hearing loss ears. The inner ear malformation rate in normal hearing ears were 13.59%.@*CONCLUSION@#CT and MRI examinations of temporal bone are important diagnostic tools to indentify inner ear malformations. Inner ear malformations are almost bilateral and hearing loss are profoud. Cochleo-vestibular malformations and large vestibular aqueduct are the 2 most frequent deformities. Among the children with SNHL, deformity rate in the severe and profound hearing loss ears is higher than that in moderate hearing loss ear. Inner ear malformations can exist in people with normal hearing.

Analysis the relationship between SLC26A4 mutation and current diagnosis of inner ear malformation in children with sensorineural hearing loss / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#Explore the relationship between the pathogenic mutations of SLC26A4 gene and inner ear malformation, and analyze the feasibility of genetic testing to help current diagnosis in part of children with sensorineural hearing loss.@*METHOD@#2094 cases of children were detected by SLC26A4 with the method of DNA sequence. CT phenotypes of those children were classified according to the method proposed by Sennaroglu. We analyzed the relationship between the pathogenic mutations of gene and the CT phenotypes.@*RESULT@#(1) 685 cases of inner ear malformations were found in 2094 cases of children with sensorineural hearing loss by CT examination (371 cases of cochlea malformation were consisted of the follow types of malformation. Michel deformity was 6 cases, cochlea aplasia was 8 cases, common cavity deformity was 12 cases, incomplete partition type I was 27 cases, cochlea hypoplasia was 30 cases and Mondini malformation was 288 cases); Vestibular aqueduct was 265 cases; Vestibular/semicircular canal/internal auditory canal were 49 cases, normal was 1409 cases. (2) The DNA sequence results revealed that 465 cases carried pathogenic mutations (Bi-allelic mutations) of SLC26A4 gene, among which 135 cases were homozygous, 330 cases were compound heterozygous. (3) Pathogenic mutations of SLC26A4 gene detected 100% (465/465) in the group related to vestibular aqueduct malformation.@*CONCLUSION@#The results suggest that pathogenic mutation of SLC26A4 gene is closely related to the CT phenotype of vestibular aqueduct malformation. Detecting of pathogenic mutations for hearing loss is binging the possibility to identify children with inner malformations at an early stage. As a consequence, it will improve the current diagnosis and therapeutical option.

Analysis the relationship between the found ways and first diagnosis age for large vestibular aqueduct children / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the found ways and first diagnosis age of children with large vestibular aqueduct, and their relations with hearing loss.@*METHOD@#Medical histories of 122 cases of children diagnosed with large vestibular aqueduct by HRCT or MRI had been collected from January 2009 to April 2014 in our hospital children's hearing diagnosis center clinic. Found ways comprise of accepting universal newborn hearing screening (UNHS) group and unaccepting UNHS group. Accepting UNHS children were divided into two ears unpassing group, single ear unpassing group and passing group. The patients in unaccepting UNHS group were divided into not sensitive to sounds, speech stunting, sudden hearing loss, and other group. Analysis the relationship between the found ways and first diagnosis age and their relations with hearing loss.@*RESULT@#There are 84 cases (68.85%) accepting UNHS, the average age of first diagnosis was (17.24 ± 17.08) months; 37 cases (31.15%) are not accepting UNHS. The average age of first diagnosis was (30.92 ± 18.21) months. The average first diagnosis age of accepting UNHS group was more earlier than the unaccepting UNHS group. The difference was statistically signif- icant (P 0.05). In unaccepting UNHS group ,the average first diagnosis age of the mild-to-moderate hearing loss group was later than the very severe hearing loss group (P < 0.01).@*CONCLUSION@#Most of large vestibular aqueduct children can be found and receive diagnosis early by UNHS. But part of these patients with late-onset or progressive hearing loss, especially these with mild-to-moderate hearing loss cannot be found early, which should arouse our attention.