Enlarged Vestibular Aqueduct Patients Research Articles

Correlation of temporal bone HRCT, SLC26A4 gene and hearing loss in enlarged vestibular aqueduct

Objective:To explore the correlation between high-resolution computed tomography（HRCT） of temporal bones, SLC26A4 gene mutation and hearing loss in patients with enlarged vestibular aqueduct（EVA）. Methods:The medical records of 257 subjects hospitalized for moderate to severe sensorineural hearing loss in the Department of Otolaryngology Head and Neck Surgery, Hainan General Hospital between May 2018 to 2021 were retrospectively reviewed. All included cases received audiological examination, HRCT scanning of temporal bones and SLC26A4 gene sequencing. According to the Valvassori standard, cases with the diameter from the common peduncle of the semicircular canal to the midpoint of the outer orifice of the vestibular aqueduct（MP） over 1.5 mm, or the diameter of the outer orifice of the vestibular aqueduct（OP） more than 2.0 mm were diagnosed as EVA. There were 22 cases（44 ears） of EVA in the study, aged between 6 months to 17 years old. Based on the hearing changes at birth and during growth, 18 ears of which were classified into the stable hearing group, while the other 26 ears in the unstable group. Moreover, all involved cases were grouped by MP（1.5 to <3.0 mm and ≥3.0 mm） and OP（2.0 to <4.0 mm and ≥4.0 mm）. SPSS 25.0 software was applied in the study. The correlation between hearing loss and MP and OP was analyzed. The results of HRCT of temporal bones and SLC26A4 gene sequencing were compared as well. Results:Though the size of MP and OP was not statistically different between the stable and hearing groups in EVA ears（P>0.05）, it was significantly correlated with the severity of hearing loss（P<0.05）. Of the 22 EVA patients diagnosed by HRCT, 21 were positive for SLC26A4 gene mutation. The positive rate of EVA by SLC26A4 gene sequencing was highly consistent with HRCT（Kappa=0.975）. Conclusion:The size of MP and OP in EVA patients was related to the degree of hearing loss, but not to the stable nature of hearing loss. Temporal bone HRCT scanning and SLC26A4 gene sequencing are highly consistent in the diagnosis of EVA. The latter has no radiation and can be combined with hearing screening for early diagnosis of EVA.

Hearing loss patterns in enlarged vestibular aqueduct syndrome: Do fluctuations have clinical significance?

ObjectivesTo reveal hearing loss patterns in patients with enlarged vestibular aqueduct (EVA) syndrome according to demographic and clinical characteristics. MethodsA retrospective, longitudinal study design was utilized to identify patients with EVA. Ears of patients were categorized into one of four cohorts: progressive fluctuating, progressive non-fluctuating, stable fluctuating, and stable non-fluctuating patterns. Pairwise and group comparisons were performed with non-parametric tests to assess vestibular aqueduct (VA) morphology, clinical, and demographic variables between hearing loss pattern cohorts. Rates of hearing loss in the subgroups were determined utilizing a mixed linear effects model. Results44 patients (25 female, 19 male, median diagnosis age: 8.06 years) met inclusion criteria. 16 individuals demonstrated unilateral EVA and 29 had bilateral EVA, resulting in 74 total ears with EVA. Amongst the four cohorts, differences in operculum widths amongst groups were statistically significant (p = 0.049) while VA midpoint widths were not (p = 0.522). Progressive hearing loss ears without fluctuations demonstrated a 3.20 dB per year (p < 0.001) progression while progressive hearing loss ears with fluctuations reported a rate of 3.52 dB loss per year (p < 0.001). ConclusionHearing fluctuations occur similarly in EVA patients with stable and progressive hearing loss. With the exception of increased rates of hearing loss progression for fluctuating progressive hearing loss patients, vestibular aqueduct morphology, demographic, and clinical characteristics commonly reported are likely not strong predictors for whether patients will or will not experience fluctuating patterns of hearing loss.

Contralateral hearing loss in children with a unilateral enlarged vestibular aqueduct

ObjectiveTo evaluate the long-term ipsi- and contralateral hearing of patients with a unilateral enlarged vestibular aqueduct (EVA). Study designMulticenter retrospective cohort study. SettingThree tertiary otology and audiology referral centers. Patients and diagnostic interventionsA total of 34 children with a unilateral enlarged vestibular aqueduct as identified on CT and/or MR imaging were evaluated with pure tone and speech perception audiometry. Mean outcome measuresRadiologic measurements of the vestibular aqueduct, ipsi- and contralateral hearing loss, ipsi- and contralateral hearing loss progression over time and DNA test results. ResultsAll patients in this cohort with unilateral EVA presented with hearing loss. Hearing loss was progressive in 38% of the ipsilateral ears. In 29% of the children, hearing loss was also found in the contralateral ear without EVA. In 90%, the contralateral hearing was stable, with a mean follow up of 4.2 years. We found a significant correlation between the severity of the hearing loss and the size of the EVA. A genetic diagnosis associated with EVA and/or SNHL was found in only 7%. ConclusionAbout a third of the children with unilateral EVA are at risk of developing hearing loss in the contralateral ear. This indicates that at least in some patients with a unilateral EVA, a bilateral pathogenic process underlies the hearing loss, in contrary to what the imaging results suggest. These findings are important for counseling of EVA patients and their parents and have implications for follow up.

Systematic Review on Vestibular Symptoms in Patients With Enlarged Vestibular Aqueducts.

Enlarged vestibular aqueduct (EVA) is a congenital condition that can lead to various outcomes in pediatric patients including hearing loss and vestibular dysfunction. Our goal was to critically appraise the literature on the proportion of patients with EVA who report vestibular dysfunction, determine relevant risk factors for the development of these symptoms, and describe vestibular tests and interventions used to improve outcomes. A systematic review was performed in accordance with the PRISMA guidelines. We queried the EMBASE, Ovid Medline, and Cochrane Library databases for relevant literature. Studies were included if they had n > 10, reported vestibular symptoms or vestibular function testing in patients with EVA, and were published in English. Nonhuman studies, systematic reviews, and review articles were excluded. Of 808 identified studies, 20 met inclusion criteria. Subjective vestibular symptoms included dizziness, episodic vertigo, and imbalance. Seventeen studies reported subjective vestibular symptoms, ranging from 2% to 71% of patients between studies. Seventeen studies performed some form of vestibular function test, including physical exam maneuvers (Dix-Hallpike), caloric testing, electronystagmography, and vestibular evoked myogenic potentials. Of those who had vestibular function testing, 7% to 92% had an abnormal result. Two studies identified head trauma as a risk factor. One study successfully treated patients with BPPV using the Epley maneuver, but other vestibular symptoms were not targeted with treatment. The degree to which vestibular symptoms impact patients with EVA varies significantly. Performing vestibular function testing may help identify asymptomatic patients with vestibular dysfunction. Future studies should target improving treatment of vestibular symptoms in EVA patients. Laryngoscope, 132:873-880, 2022.

Genetic architecture and phenotypic landscape of SLC26A4-related hearing loss.

Mutations of coding regions and splice sites of SLC26A4 cause Pendred syndrome and nonsyndromic recessive hearing loss DFNB4. SLC26A4 encodes pendrin, a transmembrane exchanger of anions and bases. The mutant SLC26A4 phenotype is characterized by inner ear malformations, including an enlarged vestibular aqueduct (EVA), incomplete cochlear partition type II and modiolar hypoplasia, progressive and fluctuating hearing loss, and vestibular dysfunction. A thyroid iodine organification defect can lead to multinodular goiter and distinguishes Pendred syndrome from DFNB4. Pendred syndrome and DFNB4 are each inherited as an autosomal recessive trait caused by biallelic mutations of SLC26A4 (M2). However, there are some EVA patients with only one detectable mutant allele (M1) of SLC26A4. In most European-Caucasian M1 patients, there is a haplotype that consists of 12 variants upstream of SLC26A4, called CEVA (Caucasian EVA), which acts as a pathogenic recessive allele in trans to mutations affecting the coding regions or splice sites of SLC26A4. This combination of an M1 genotype with the CEVA haplotype is associated with a less severe phenotype than the M2 genotype. The phenotype in EVA patients with no mutant alleles of SLC26A4 (M0) has a very low recurrence probability and is likely to be caused by other factors.

Application value of high-throughput gene copy number variation detection in the diagnosis of enlarged vestibular aqueduct

Objective: To explore the application value of high-throughput gene detection method of copy number variations (CNV) in the diagnosis of enlarged vestibular aqueduct (EVA). Methods: A total of 46 nonsyndromic hearing loss patients with EVA were recruited between May 2014 and December 2016 from Department of Otolaryngology of Xiangya Hospital, Central South University. A high-throughput multiplex analysis method based on double ligation and multiple fluorescent PCR was designed and performed to detect CNV in the three EVA-related genes (SLC26A4, FOXI1 and KCNJ10). The data were analyzed by GeneMapper v4.1. Healthy volunteers (n=100) were selected as normal controls. Results: A total of 46 EVA patients were detected (32 males, 14 females, aged 1 to 26 years). In 4 EVA patients, deletions of exons 1-3 of SLC26A4 gene (4/46, 8.7%) were detected, which were not reported in the database of genomic variants (DGV), and were absent in 100 normal controls. There was no CNV detected in FOXI1 and KCNJ10 in the study. Conclusions: In the current study, three known EVA-related genes were designed as the target area for CNV detection by high-throughput ligation-dependent probe amplification (HLPA) analysis. This method can be used as a supplementary analysis of point mutation detection of hearing loss, which helps achieve the accurate genetic diagnosis of EVA.

Vestibular impairment in cochlear implanted children presenting enlarged vestibular aqueduct and enlarged endolymphatic sac

Enlarged vestibular aqueduct (EVA) is a common finding in tomodensitometry. When cranial MRI is performed, enlarged endolymphatic sac (EES) can also be found. Profound hearing loss is a common finding in these patients but a few studies have investigated vestibular function after cochlear implantation (CI) in EVA and EES patients. Our main objective was to find out whether in EVA children candidates to CI, a higher endolymphatic sac (ES) volume was predictive for higher rates of postsurgical vestibular complications. MethodsWe retrospectively included EVA children who benefited from CI, during the last 2 years. Two groups were constituted according to the presence or not of a vestibular impairment (decrease in the VOR gain on the VHIT test on one of the semicircular canals and/or a loss of cVEMPs) 6 months after CI. Endolymphatic volume of both VA and ES was measured for each patient. ResultsFifteen patients were included. The mean endolymph volume was significantly higher in the impaired group (0.40 cm3 ± 0.23, range 0.08–0.70) than in the non-impaired group (0.11 cm3 ± 0.07, range 0.04–0.29; p = 0.029). Four children of the impaired group were followed during one year. At the end of vestibular rehabilitation, all children recovered a lateral canal function and a saccular function. ConclusionIn EVA children, a combined EES appears to increase the risk of severe post CI vestibular impairment. To minimize this risk prior CI surgery, besides tomodensitometry, MRI measurement of the ES volume should be systematically performed.

Torticollis in children with enlarged vestibular aqueducts

ObjectivesTo evaluate the association between torticollis and enlarged vestibular aqueduct (EVA). MethodsAn online/phone survey was administered to parents of 133 children diagnosed with the following disorders: EVA, GJB2 (Connexin 26) mutations associated congenital hearing loss and epistaxis (control). The survey included questions regarding symptoms of torticollis, vertigo, and hearing loss. ResultsPatients with EVA had a 10-fold greater odds of having torticollis than controls (31% vs. 4%; OR = 10.6; 95% CI: 2.9, 39.2). No patients with GJB2 had a reported history of torticollis. Torticollis preceded the diagnosis of hearing loss in most (87%) patients with EVA who had a reported history of torticollis. EVA patients were more likely to have reported motor delay than controls (40% vs. 15%; p = 0.002). EVA patients with prior torticollis (80%; 12/15) were more likely to have balance impairment than EVA patients without prior torticollis (12%; 4/33; p < 0.001). Twelve patients had a reported history of paroxysmal torticollis, all of whom had EVA. ConclusionTorticollis in infants may be a marker of EVA. Infants with torticollis should be monitored closely for hearing loss and motor delay, especially when the torticollis is paroxysmal.

Analysis of the correlation between radiological and audiological features of patients with enlarged vestibular aqueduct

Objective: The radiological and audiological results of patients with hearing loss associated with enlarged vestibular aqueduct (EVA) were analyzed statistically to explore the association between them. Methods: In this retrospective study, we screened 64 patients (128 ears) with EVA diagnosed in the Department of Otorhinolaryngology, Shengjing Hospital of China Medical University from January 2012 to June 2016, who met the inclusion criteria and the exclusion criteria at the same time, including 37 males (74 ears) and 27 females (54 ears), aged from 6 months to 17 years, all of whom showed varying degrees of sensorineural hearing loss (SNHL). The imaging observations included the midpoint measurement (MP) and the operculum measurement(OP) of the temporal bone HRCT, the long signal area cross-sectional area (ES(L)), the short signal area cross-sectional area (ES(S)), as well as the largest total signal area cross-sectional area (ES(T)) of the endolymphatic sac(ES) of the cochlear MRI. The audiological observations included collecting detailed medical history and subjective and/or objective audiological examinations to determine the character and degree of hearing loss. According to the progress and changes of hearing loss, they were divided into hearing stability group (86 ears) and fluctuation/progression group (42 ears). SPSS22.0 statistical software was used to carry out statistical analysis of the imaging measurement results. Results: The sizes of MP and OP were smaller in the stable group than those in the fluctuating/progressive group, and the difference was statistically significant (P<0.05). For ES(L), ES(S) or ES(T), there was no significant difference between the stable group and the fluctuating/progressive group (P>0.05). For the 13 patients with asymmetric hearing loss, the sizes of MP, OP, ES(L), ES(S) or ES(T) were not significantly different between the mild side and the serious side (P>0.05). For the ears whose ES(L)/ES(S) was>2 or the ES(S)/ES(L) was>2, the proportion was not significantly different between the stable group and the fluctuating/progressive group (P>0.05). Conclusions: For patients with EVA,the smaller the enlarged vestibular aqueduct is,the more likely it is congenital severe sensorineural hearing loss. Patients with significantly enlarged vestibular aqueduct often exhibit volatility/progressive hearing loss. The degree of enlargement of the endolymphatic vessels and endolymphatic sac is not related to the degree of hearing loss. For EVA patients with asymmetric hearing loss, the mild or serious side of hearing loss is random, which is not affected by the degree of enlargement of the vestibular aqueduct and endolymphatic sac. The degree of hearing loss in patients with EVA is not related to the ratio of ES(L)/ES(S).

Audiometric findings in children with unilateral enlarged vestibular aqueduct

ObjectiveTo evaluate the prevalence of bilateral hearing loss in children with unilateral enlarged vestibular aqueduct (EVA) at a single institution. MethodsA retrospective case review was performed at a tertiary care pediatric referral center involving children with radiologic findings of unilateral EVA and normal labyrinthine anatomy of the contralateral ear diagnosed via CT and/or MRI. The main outcome measure of interest is the number of patients with unilateral EVA who were diagnosed with bilateral hearing loss. ResultsSixty-one pediatric patients were identified. The mean audiometric follow-up was 48.2 months (0–150). Three (4.9%) patients with unilateral EVA were noted to have bilateral hearing loss, and this rate was not significantly different (p = 1.0) from the rate reported in a comparison group of patients with contralateral hearing loss (6.0%) without an EVA. The pure-tone average (defined as the average dB HL at 500, 1000, 2000, and 4000 Hz) in the group with bilateral hearing loss was 31.3 dB HL in the better hearing ear and 79.6 dB HL in the worse hearing ear, with the difference being statistically significant (p = 0.02). In the unilateral EVA patients without contralateral hearing loss (n = 56, 91.8%), the PTA was 9.4 dB HL in the better hearing ear and 51.9 dB HL in the worse hearing ear, with the difference being statistically significant (p < 0.001). Two patients (3.3%) with unilateral EVA were found to have hearing within normal limits bilaterally. The EVA was ipsilateral to the worse hearing ear in all cases. ConclusionThe prevalence of bilateral hearing loss in children with unilateral EVA appears to be low. Specifically, it may be no different than the rate of contralateral hearing loss in children with unilateral hearing loss without an EVA. The present report is somewhat different than the previously described prevalence in the literature. This difference could be related to the imaging type and diagnostic criteria used, the patients included, the source of the identified patents, and the overall population of patients studied.

Hearing loss in unilateral and bilateral enlarged vestibular aqueduct syndrome

ObjectiveTo investigate any meaningful differences in hearing between patients with unilateral and bilateral enlarged vestibular aqueduct (EVA). EVA is a common radiological finding in children presenting with hearing loss. We hope to provide insight into the pathogenesis of EVA and provide further guidelines for unilateral EVA management. We hypothesized that hearing loss in unilateral EVA would be similar to that seen in bilateral EVA. MethodsA longitudinal retrospective study design was used. Three measures of hearing, pure tone average (PTA) word recognition score (WRS) and speech awareness threshold (SAT) and radiologic morphologies were tested for difference across unilateral versus bilateral ear EVA status. Linear mixed effects models were used to identify differences while accounting for time and multiple measurements per ear. ResultsUsing Cincinnati criteria, 89 ears fit inclusion criteria, 75 of which were from patients with bilateral EVA compared to 14 ears from patients with unilateral EVA. No significant differences across bilateral status were observed in audiological measurements. Models showed that speech recognition threshold (SRT) (p = 0.925), word recognition score (WRS)(p = 0.521) and pure tone average (PTA) of air and bone conduction from 250 to 4000 Hz (p = 0.281–0.933) were not statistically different with respect to bilateral status. Wilcoxon rank-sum tests showed no statistical difference in vestibular aqueduct width or operculum size (VA)(p = 0.234, p = 0.623). Each year after the first audiogram was associated with significantly greater SRT (p = 0.003) decreased WRS (0.014) and increased PTA (0.003.). Greater midpoint width was associated with significantly lower SRT (p = 0.004) WRS (<0.001) and PTA (<0.001.) ConclusionOur results indicate no statistically significant difference in hearing ability with respect to bilateral EVA status, suggesting that unilateral EVA patients require close follow-up. Our results also demonstrate the progressive nature of EVA and a relationship between VA midpoint width and hearing loss severity.

Targeted Next-Generation Sequencing Facilitates Genetic Diagnosis and Provides Novel Pathogenetic Insights into Deafness with Enlarged Vestibular Aqueduct

Enlarged vestibular aqueduct (EVA) is an inner-ear malformation associated with sensorineural hearing impairment. Most EVAs are associated with Pendred syndrome and nonsyndromic autosomal recessive deafness-4 (DFNB4), two autosomal-recessive disorders caused by mutations in SLC26A4. However, many EVA patients cannot have a confirmed diagnosis by screening common SLC26A4 mutations, constituting an enigma in genetic diagnosis. To enable comprehensive genetic examination and explore the etiologies of EVA, we designed a next-generation sequencing panel targeting the entire length of 3 Pendred syndrome/DFNB4 genes (SLC26A4, FOXI1, and KCNJ10) and exons of 10 other genes related to EVA and performed genetic testing in 50 EVA families without confirmative results on screening for SLC26A4 hotspots (c.919-2A>G and p.H723R). Bi-allelic SLC26A4 mutations were identified in 34 families and EYA1 mutations in two families, yielding a diagnostic rate of 72% (36 of 50). In addition, two variants were identified in KCNJ10 and FOXI1, but findings did not support the previous hypothesis that mutations in these two genes are probable contributors to EVA through recessive inheritance or digenic inheritance with SLC26A4. Of note, a large SLC26A4 deletion was confirmed in one step using our panel. These results show the utility of a next-generation sequencing-based panel to address EVA families by identifying various types of gene mutations with satisfactory diagnostic yields and provide novel insights into the pathogenesis of EVA.

Vestibular Manifestations in Subjects With Enlarged Vestibular Aqueduct.

To describe the results of a thorough evaluation in a large series of patients with an enlarged vestibular aqueduct (EVA), focusing on vestibular manifestations with etiological considerations. Retrospective chart review of patients with EVA. Tertiary referral center. A total of 22 EVA patients with a median age of 8 years (6 mo-35 yr) who underwent both audiovestibular and radiologic examinations. Patient demographics, radiologic findings, audiologic results, vestibular symptoms, findings of neurotologic examinations, and laboratory evaluations were collected and analyzed. Standard descriptive statistics were used to summarize patient characteristics. Subjects who had a history of vertigo attack were categorized as "vestibulopathy group," while subjects without any history of vertigo as "non-vestibulopathy group." Of the 41 ears included, 37 (90.2%) had hearing loss on initial audiometric evaluations. Among the 22 patients, 14 (63.6%) complained of dizziness. Of the 14 vertiginous patients, seven had recurrent episodes, five had a history of single attack, and two presented with postural imbalances. There were no significant differences between vestibulopathy and non-vestibulopathy groups with regard to the relationship between the development of vestibular symptoms and aqueductal size, hearing threshold, or age at first visit. Four of the 22 (18.2%) patients developed secondary benign paroxysmal positional vertigo (BPPV) and all patients complained of simultaneous decreases in hearing. Our results demonstrate that patients may develop vestibular symptoms during their clinical course, and all patients with an enlarged vestibular aqueduct should be cautioned regarding the potential development of vestibular pathology. Moreover, the non-negligible incidence of secondary BPPV mandates positional tests when evaluating EVA patients with vertigo.

Should children with an enlarged vestibular aqueduct be restricted from playing contact sports?

Should children with an enlarged vestibular aqueduct be restricted from playing contact sports?

Position of the Internal Aperture of Vestibular Aqueduct in Patients With Enlarged Vestibular Aqueduct.

To investigate the position of the internal aperture of vestibular aqueduct and its relationship to hearing level in patients with enlarged vestibular aqueduct (EVA). The size of the common crus and the position of the internal aperture of vestibular aqueduct were compared among control subjects, EVA patients with and without other inner ear malformations. Auditory steady-state response thresholds were compared between EVA patients with different positions of internal apertures. The common crus in EVA patients was shorter than in control subjects (p < 0.05). The internal aperture of the vestibular aqueduct opened solely into the common crus in control subjects, simultaneously into the common crus and vestibule in almost 45% of EVA patients, solely into the common crus, and the vestibule in almost 30 and 25% of EVA patients, respectively. Auditory steady-state response thresholds at 2000 and 4000 Hz were higher in EVA patients whose internal apertures of vestibular aqueducts opened simultaneously into the common crus and vestibule than in those whose internal apertures opened solely into the common crus. The common crus is shorter in EVA patients than in control subjects. The internal aperture of the vestibular aqueduct opens solely into the common crus in control subjects. It opens simultaneously into the common crus and vestibule in almost half of the EVA patients. The EVA patients whose internal apertures of vestibular aqueducts open solely into the common crus may have better hearing than those whose internal apertures open simultaneously into the common crus and vestibule.

Morphometric Study of the Vestibular Aqueduct in Patients With Enlarged Vestibular Aqueduct.

To test whether there are significant differences in the morphologic features of the enlarged vestibular aqueduct (EVA) and its anatomic relationships with adjacent structures between EVA patients with and without other inner ear malformations. The morphology of vestibular aqueduct, volume of vestibule, and anatomic location of facial nerve (FN) were compared among 3 groups. Group A, 18 control subjects; group B, 32 EVA patients without other inner ear malformations; group C, 14 EVA patients with other inner ear malformations. The isthmus of the aqueduct and vestibular volume in group C were larger than those in group B (P < 0.05). Positive correlations were identified between the length of the aqueduct and the vestibular volume in groups B and C. The vertical FN segment in group C located more anteriorly than that in groups A and B (P < 0.05). Compared with EVA patients without other inner ear malformations, the aqueduct, and vestibule in EVA patients with other inner ear malformations are larger, the vertical FN segment locates more anteriorly.

Cochlear implantation in patients with enlarged vestibular aqueduct. A case series with literature review

Objectives: To report our institutional experience of the management of patients with enlarged vestibular aqueduct (EVA) and compare it to the literature.Methods: We carried out a retrospective review of patients’ records from 1993 to 2015. The age, sex, associated malformations, relevant past medical history, genetic screening results, possible surgical incident, implant model and duration of follow- up, outcome in terms of Categories of Auditory Performance (CAP scores), and integration or resuming mainstream school or work were recorded.Results: We had 11 patients (six boys and five girls) with EVA who underwent cochlear implant surgery in our center during the 22-year study period, out of a total of 827 implanted (1.3%). The mean age at surgery was 8.9 years ranging from 0.6 to 35 years. EVA was bilateral in 10 cases, isolated anatomical finding in seven cases, and associated with other malformations in four. Cochlear implantation was bilateral in five cases and unilateral in six. The mean follow- up duration was 48.3 months (range: 3–120). No postoperative complication was observed and all the patients could regain a serviceable hearing, attending normal school and working normally.Conclusion: EVA is frequently observed in the deaf population without an identifiable cause. The hearing loss is usually progressive and may result in cochlear implantation which has proved its efficiency in rehabilitating EVA patients.

Novel compound heterozygous mutations in SLC26A4 gene in a Chinese Han family with enlarged vestibular aqueduct

ObjectiveTo identify the disease-related SLC26A4 mutants in a Chinese Han pedigree associated with Enlarged vestibular aqueduct (EVA). MethodsEVA diagnosis was based on the family history, clinical examinations, systematically audiometric evaluations, high-resolution computed tomography (HRCT) of the temporal bone, and magnetic resonance imaging (MRI) of inner ear. Sanger sequencing and mutation analysis of the SLC26A4 gene were performed in all members of this family to identify the disease-related SLC26A4 mutants. Mutations in the SLC26A4 gene were compared with 200 ethnically matched control persons to exclude common polymorphism. ResultsAll members in this family were negative for systemic and thyroid diseases. There were three subjects (I-2, II-2 and II-3) with bilateral sensorineural deafness since childhood. Temporal bone HRCT scans and inner ear MRI showed bilateral enlarged vestibular aqueduct with Mondini malformation in II-2 and II-3. A novel SLC26A4 splice-site mutation c.1001 + 5G > C was identified in compound heterozygosity with the mutation c.919-2A > G in the proband and in II-2. This novel compound heterozygote of two splice site mutations was not found in 200 normal hearing Chinese Han controls. ConclusionsA novel splice site mutation of c.1001 + 5G > C was identified, and the novel compound heterozygote of two splice site mutations, c.1001 + 5G > C and c.919-2A > G, in the SLC26A4 gene has been linked to hearing impairment in EVA patients.

Bilateral Sequential Cochlear Implantation in Patients With Enlarged Vestibular Aqueduct (EVA) Syndrome.

To analyze audiometric outcomes after bilateral cochlear implantation in patients with isolated enlarged vestibular aqueduct (EVA) syndrome and associated incomplete partition (IP) malformations. Secondary objective was to analyze rate of cerebrospinal fluid (CSF) gusher in patients with IP-EVA spectrum deformities and compare this with the existing literature. Retrospective chart review. Thirty-two patients with EVA syndrome who received unilateral or bilateral cochlear implants between June 1999 and January 2014 were identified in the University Hospitals Case Medical Center cochlear implant database. Isolated EVA (IEVA) and Incomplete Partition Type II (IP-II) malformations were identified by reviewing high-resolution computed tomography (HRCT) imaging. Demographic information, age at implantation, surgical details, postimplantation audiometric data including speech reception thresholds (SRT), word, and sentence scores were reviewed and analyzed. Intra- and postoperative complications were analyzed as well and compared with the literature. Seventeen patients (32 implanted ears) had pediatric cochlear implantation for EVA-associated hearing loss. Data from 16 controls (32 implanted ears) were used to compare audiometric and speech outcomes of EVA cohort. Mean age at implantation was 6.8 years for EVA cohort and 6.0 years for controls. There was no statistically significant difference in long-term postoperative SRT, monaurally aided word scores, and binaurally tested word scores between pediatric EVA group and controls. The EVA patients had a long-term mean sentence score of 85.92%. A subset of EVA patients implanted at mean age of 3.18 years (n = 15 ears) had similar audiometric outcomes to another control group with Connexin 26 mutations (n = 20 ears) implanted at a similar age. Further subset analysis revealed no significant differences in age at implantation, SRT, and word scores in patients with IEVA and IP-II malformation. There was no significant association between size of vestibular aqueduct and age at implantation. There was no CSF gusher or other intra- or postoperative complications reported in our series. Bilateral sequential cochlear implantation can be performed safely in patients with EVA. Audiometric outcomes are excellent and comparable to pediatric cochlear implant patients with no malformations. CSF gusher rates can be minimized by trans-round window approach. Further long-term studies are needed to identify differences within IP-EVA spectrum deformities, audiometric outcomes, and proportions of EVA patients who will need cochlear implantation for hearing rehabilitation.

Diagnostic Value of SLC26A4 Mutation Status in Hereditary Hearing Loss With EVA: A PRISMA-Compliant Meta-Analysis.

Many SLC26A4 mutations have been identified in patients with nonsyndromic enlarged vestibular aqueduct (EVA). However, the roles of SLC26A4 genotypes and phenotypes in hereditary deafness remain unexplained. This study aims to perform a meta-analysis based on the PRISMA statement to evaluate the diagnostic value of SLC26A4 mutant alleles and their correlations with multiethnic hearing phenotypes in EVA patients. The systematic literature search of the PubMed, Wiley Online Library, EMBASE, Web of Science, and Science Direct databases was conducted in English for articles published before July 15, 2015. Two investigators independently reviewed retrieved literature and evaluated eligibility. Discrepancy was resolved by discussion and a third investigator. Quality of included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale. Data were synthesized using random-effect or fixed-effect models. The effect sizes were estimated by measuring odds ratios (ORs) with 95% confidence interval (CI). Twenty-five eligible studies involved 2294 cases with EVA data. A total of 272 SLC26A4 variations were found in deafness with EVA and 26 mutations of SCL26A4 had higher frequency. The overall OR was 646.71 (95% CI: 383.30-1091.15, P = 0.000). A total of 22 mutants were considered statistically significant in all ethnicities (ORs >1, P < 0.05). In particular, 8 mutants were specificity of EVA phenotypes in mutations of SLC26A4 for Asia deafness populations (ORs >1, P < 0.05), 4 mutants for Europe and North America (ORs >1, P < 0.05), and the IVS7-2A>G mutations in SLC26A4 were found to have the highest frequency in deafness individuals with EVA phenotype (62.42%). Moreover, subgroups for studies limited to cases with EVA phenotype, 11 mutants relevant risks (RRs) were P < 0.05, especially for IVS7-2A>G bi-allelic mutants assayed in a deafness population (RR = 0.880, P = 0.000). Diagnostic accuracy of SLC26A4 mutation results also identified the significant association of IVS7-2A>G (AUC = 0.99, 95% CI: 0.97-0.99) and p.H723R (AUC = 0.99, 95% CI: 0.98-1.00) detecting deafness with EVA. To conclude, the IVS7-2A>G and H723R in SLC26A4 present a significant predicting value and discriminatory ability for clinical use on diagnosis of EVA within a deafness population.