Enlarged Vestibular Aqueduct Research Articles

Molecular etiology of hearing impairment associated with nonsyndromic enlarged vestibular aqueduct in East China

Recessive mutations in SLC26A4 and in rarer cases double heterozygous mutations of FOXI1/SLC26A4 and KCNJ10/SLC26A4 lead to hearing impairment associated with enlarged vestibular aqueduct (EVA), the most common inner ear malformation. In our large cohort study, we addressed several important questions to the molecular etiology of this disorder. The overall prevalence of SLC26A4 mutations in nonsyndromic childhood sensorineural hearing loss (11.2%, 37/330) were determined by sequencing of SLC26A4 in 330 hearing impaired children who did not undergo inner ear radiologic imaging prior to their genetic test. The penetrance of EVA in bi-allelic SLC26A4 mutation carriers (100%, 37/37) was determined by follow-up computed tomography scanning. Combined with the study of 140 additional probands diagnosed with nonsyndromic EVA, we characterized the mutation spectrum of SLC26A4 in East China, which consisted of 19 novel SLC26A4 mutations and differed from those reported in other regions of China.

Hyperbaric oxygen therapy for sudden sensorineural hearing loss in large vestibular aqueduct syndrome

We report the first use in Australia of hyperbaric oxygen therapy for sudden hearing loss following head trauma in a child with large vestibular aqueduct syndrome. A 12-year-old boy with large vestibular aqueduct syndrome presented with significant hearing loss following head trauma. He was treated with steroids and hyperbaric oxygen therapy, with good improvement of hearing thresholds on audiography. This case represents the first reported use of hyperbaric oxygen therapy for this indication in Australia, following a few previous reports of patients in Japan. We review the literature on management of acute sensorineural hearing loss in large vestibular aqueduct syndrome. The reported case demonstrates a potentially beneficial therapy for a rare condition that usually results in an inevitable decline in hearing. Hyperbaric oxygen therapy can be tolerated well by children, and may represent a potential treatment for sudden sensorineural hearing loss in patients with large vestibular aqueduct syndrome.

Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome

BackgroundPendred syndrome (PS) and nonsyndromic hearing loss associated with enlarged vestibular aqueduct (EVA) are caused by SLC26A4 mutations. The Okinawa Islands are the southwestern-most islands of the Japanese archipelago. And ancestral differences have been reported between people from Okinawa Island and those from the main islands of Japan. To confirm the ethnic variation of the spectrum of SLC26A4 mutations, we investigated the frequencies of SLC26A4 mutations and clinical manifestations of patients with EVA or PS living in the Okinawa Islands.MethodsWe examined 22 patients with EVA or PS from 21 unrelated families in Okinawa Islands. The patient’s clinical history, findings of physical and otoscopic examinations, hearing test, and computed tomography (CT) scan of the temporal bones were recorded. To detect mutations, all 21 exons and the exon–intron junctions of SLC26A4 were sequenced for all subjects. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for SLC26A4 and calculations using the comparative CT (2−ΔΔCT) method were used to determine the pathogenicity associated with gene substitutions.ResultsSLC26A4 mutations were identified in 21 of the 22 patients. We found a compound heterozygous mutation for IVS15 + 5G > A/H723R in nine patients (41%), a homozygous substitution of IVS15 + 5G > A in six patients (27%), and homozygous mutation for H723R in five patients (23%). The most prevalent types of SLC26A4 alleles were IVS15 + 5G > A and H723R, which both accounted for 15/22 (68%) of the patients. There were no significant correlations between the types of SLC26A4 mutation and clinical manifestations. Based on qRT-PCR results, expression of SLC26A4 was not identified in patients with the homozygous substitution of IVS15 + 5G > A.ConclusionsThe substitution of IVS15 + 5G > A in SLC26A4 was the most common mutation in uniquely found in patients with PS and EVA in Okinawa Islands. This suggested that the spectrum of SLC26A4 mutation differed from main islands of Japan and other East Asian countries. The substitution of IVS15 + 5G > A leads to a loss of SLC26A expression and results in a phenotype of PS and EVA.

Evaluation of unilateral sensorineural hearing loss in the pediatric patient

ObjectivesThis study is a review of our series of pediatric patients with unilateral sensorineural hearing loss (USNHL) to report abnormalities on imaging studies, review genetic and ophthalmologic results, and survey audiometric findings. MethodsThis study is a retrospective chart review of all pediatric patients with USNHL seen between 1/1/03 and 12/31/08 at our institution. The study was approved by the institutional review board. ResultsEighty-nine cases were identified with audiometric findings confirming unilateral hearing thresholds greater than 20dBHL with no conductive component. There were 48 males and 41 females. Average age of diagnosis was 7 years. One audiogram showed low-frequency loss, 17 mid-frequency, 29 high-frequency, and 32 flat. Ten patients were diagnosed by auditory brainstem response testing at another institution, with thresholds not available for review. Eleven percent of patients progressed to bilateral loss. Sixty-one patients underwent computed tomography of temporal bones (CTTB). Twenty of 61 scans identified 34 anomalies including 15 enlarged vestibular aqueducts (EVAs), 8 Mondini, and 3 superior semicircular canal dehiscences (SSCDs). Thirty-one of 89 patients underwent magnetic resonance imaging (MRI). Three of these 31 patients had positive findings including 1 EVA, 1 Mondini, and 1 asymmetric internal auditory canal. When CTTB was positive, no additional lesions were detected on MRI. When CTTB was negative and MRI was done in 20 patients, 2 additional lesions were detected by MRI. Fourteen patients had genetics evaluation of which 6 had positive findings, including CHARGE, VACTERL, Goldenhar, and 3 were heterozygous for a Connexin mutation. ConclusionsCTTB is an effective diagnostic tool for USNHL. MRI should be considered in patients with negative CTTB. Genetics and ophthalmologic evaluations are recommended for patients with risk factors or an abnormal clinical examination. Close follow-up is essential due to high rate of hearing loss progression.

Significance of unilateral enlarged vestibular aqueduct

To describe the clinical phenotype of pediatric patients with unilateral enlarged vestibular aqueduct (EVA) and then to compare the findings to two clinically related phenotypes: bilateral EVA and unilateral hearing loss without EVA. In view of clinical observations and previously published data, we hypothesized that patients with unilateral EVA would have a much higher rate of contralateral hearing loss than patients with unilateral hearing loss without EVA. Retrospective cohort study. Patients with unilateral or bilateral EVA were identified from a database of children with sensorineural hearing loss who were seen at a tertiary care institution between 1998 and 2010. Those with imaging findings consistent with well-established EVA criteria were identified. A comparative group of patients with unilateral hearing loss without EVA was also identified. The following specific outcome measurements were analyzed: 1) hearing loss phenotype, 2) laterality of EVA and hearing loss, 3) midpoint and operculum vestibular aqueduct measurements, and 4) genetic test results. Of the 144 patients who met our inclusion criteria, 74 (51.4%) had unilateral EVA. There was a strong correlation between the presence of hearing loss and ears with EVA. Fifty-five percent of patients with unilateral EVA had hearing loss in the contralateral ear; in most of these patients, the hearing loss was bilateral. Contralateral hearing loss occurred in only 6% of patients with unilateral hearing loss without EVA. No significant differences were found in temporal bone measurements between the ears of patients with unilateral EVA and ipsilateral hearing loss and all ears with EVA and normal hearing (P = .4). There was no difference in the rate of hearing loss progression in patients with unilateral EVA between ears with or without EVA (16 of 48 [33.3%] vs. 9 of 27 [33.3%], respectively; P = 1.0). There was no difference in the rate of hearing loss progression in patients with bilateral and unilateral EVA (41 of 89 ears [46.1%] vs. 25 of 75 ears [33.3%], respectively; P = .1); however, both EVA groups had higher rates of progression compared to patients with unilateral hearing loss without EVA. There was a strong correlation between the presence of hearing loss at 250 Hz and the risk of more severe hearing loss and progressive hearing loss. Patients with bilateral EVA and SLC26A4 mutations had a higher rate of progression than patients who had no mutations (P = .02). No patients with unilateral EVA had Pendred syndrome. Children with unilateral EVA have a significant risk of hearing loss progression. Hearing loss in the ear contralateral to the EVA is common, suggesting that unilateral EVA is a bilateral process despite an initial unilateral imaging finding. In contrast to bilateral EVA, unilateral EVA is not associated with Pendred syndrome and may have a different etiology. Temporal bone measurements, hearing loss severity, and hearing loss at 250 Hz were all correlated with the risk of progressive hearing loss. Clinicians should become knowledgeable regarding the implications of this disease process so that families can be counseled appropriately.

Compound heterozygous mutations of SLC26A4 in 4 Chinese families with enlarged vestibular aqueduct

ObjectiveEnlarged vestibular aqueduct is the most common inner ear malformation in individuals with sensorineural hearing loss. Mutations in SLC26A4 can cause non-syndromic EVA. To date, more than 170 SLC26A4 mutations have been described. The aim of the present study was to detect and report genetic causes of four unrelated Chinese families with hearing loss. MethodsWe evaluated 4 families presenting bilateral enlarged vestibular aqueducts and describe the clinical and molecular characteristics of 5 patients. ResultsThe SLC26A4 gene was sequenced in 23 members of these 4 Chinese families with EVA, and the patients were found to carry 4 compound heterozygous mutations, p.G197R and p.S391R, IVS7-2A>G, p.I188T and c.1746 del G, p.V659L and p.T410M, and p.T94I and p.G197R, none of which have been reported previously. ConclusionsThese results emphasize the necessity of considering the complete DNA sequencing of the SLC26A4 gene in molecular diagnosis of deafness, especially when phenotypes such as congenital, invariable, and progressive hearing loss with EVA are present.

Pediatric sudden sensorineural hearing loss: Diagnosed causes and response to intervention

ObjectiveSudden sensorineural hearing loss (SSNHL) is an underappreciated issue in pediatric patient care. The goal of this study was to identify children who met the criteria for SSNHL and examine the etiologies, useful diagnostic studies, and treatment outcomes for these patients. MethodsA retrospective medical records review was performed in patients meeting the criteria for SSNHL seen at a tertiary care pediatric hospital from 2007 to 2012. Information collected included age, gender, audiometric evaluations, onset and duration of hearing loss, additional symptoms, diagnostic studies and response to any medical management. The Institutional Review Board approved this project. Results12/20 patients were male. Mean age was 11.41 years (3 months–24 years). Hearing loss was bilateral in 9/20 patients. Degree of hearing loss ranged from mild to profound across frequencies. Probable etiologies were viral of unknown type (n=12), late presentation of congenital CMV (n=1), noise-related (n=1), non organic (n=1), enlarged vestibular aqueduct (EVA) (n=1), one with both acute Epstein–Barr virus (EBV) and significant ototoxic exposure (n=1), one had significant ototoxic exposure and an inflammatory cerebrovascular incident (n=1), and unknown (n=2). Diagnostic studies included temporal bone computed tomography (CT) (n=15) and/or magnetic resonance imaging (MRI) (n=15), Lyme titers (n=9), streptococcal throat culture (n=1) and EBV (n=1) and mumps titers (n=1). Positive diagnostic studies included 1 MRI consistent with congenital CMV, and one CT that showed an EVA. 15/20 patients received systemic steroids, 3 received antivirals, and 4 got antibiotics. Response to steroids varied from complete resolution of SSNHL to worsening. Symptoms reported, in addition to the hearing loss included tinnitus (n=9), vertigo (n=9), sensation of a blocked ear (n=6), and otalgia (n=4). ConclusionsThe incidence of SSNHL in pediatric patients is unknown. Etiologies of SSNHL include viral, EVA, ototoxicity, noise, and non-organic. Most studies were non-diagnostic although 2/22 CT/MRI provided an etiology. Identification of other causes required careful history review. The incidence of SSNHL in the pediatric population needs to be studied, and the timing, dosage, route and efficacy of steroids further evaluated.

Molecular analysis of SLC26A4 gene in patients with nonsyndromic hearing loss and EVA: Identification of two novel mutations in Brazilian patients

The SLC26A4 gene has been described as the second gene involved in most cases of sensorineural non-syndromic hearing loss, since the first is the GJB2 gene. Recessive mutations in the SLC26A4 gene encoding pendrin, an anion transporter, are responsible for non-syndromic hearing loss associated with an enlarged vestibular aqueduct (EVA) and Pendred syndrome, which causes early hearing loss and affects the thyroid gland. Typically, the hearing loss is profound and prelingual. However, in some individuals, hearing impairment may develop later in childhood and then progress. Over 200 different SLC26A4 mutations have been reported, with each ethnic population having its own distinctive mutant allele series including a few prevalent founder mutations. ObjectivePerform the screening of the 20 coding exons of SLC26A4 gene in Brazilian deaf individuals with EVA. Patients and methodsAmong the 23 unrelated non-syndromic hearing loss Brazilian patients with EVA, in whom no deafness-causing mutations of the GJB2 gene, the direct sequencing was performed to screen the 20 exons and their flanking regions of the SLC26A4 gene. ResultsThe sequencing results revealed 9 cases (39%) carrying 13 different SLC26A4 mutations, including 11 known mutations (279delT, V138F, T193I, IVS8+1G>A, T410M, Q413R, R409H, L445W, IVS15+5G>A, V609G, and R776C) and 2 novel mutation (G149R and P142L). ConclusionThe SLC26A4 mutations have a high carrying rate in non-syndromic hearing loss Brazilian patients. The identification of a disease-causing mutation can be used to establish a genotypic diagnosis and provide important information to the patients and their families.

Sensorineural hearing loss caused by mutations in two alleles of both GJB2 and SLC26A4 genes

BackgroundMost studies of the molecular etiology of sensorineural hearing loss have described deafness as a monogenic disease encompassing double-allele mutations for patients with autosomal recessive deafness. Here, we report the first case of autosomal recessive genetic deafness in an enlarged vestibular aqueduct syndrome (EVAS) patient with biallelic mutations in two deafness genes. MethodsTemporal computed tomography (CT), complete physical and otoscopic examinations, and an audiological study, including tympanometry, pure-tone audiometry or auditory steady-state response (ASSR), were carried out. Exon 2 of GJB2 and the coding exons of SLC26A4 were sequenced. ResultsA patient with an enlarged vestibular aqueduct was found to carry c.1229C>T/c.1079C>T compound heterozygous mutations in SLC26A4.This individual also carried c.257C>G/c.299-300delAT compound heterozygous mutations in GJB2. As a result, the recurrent risk of the patient's siblings increased significantly from 25% for typical autosomal recessive deafness to 43.75%. ConclusionsThe findings of the present study challenge the traditional diagnostic strategy in which testing is generally considered complete upon identification of a double-allele mutation within one gene, with significant implications for genetic counseling and risk prediction. Our results suggest that, with advances in sequencing technology, it will be possible and necessary to test all known deafness genes in the near future, as this will likely allow more accurate genetic counseling of patients.

High prevalence of inner-ear and/or internal auditory canal malformations in children with unilateral sensorineural hearing loss

ObjectiveRadiological and genetic examination has recently advanced for diagnosis of congenital hearing loss. The aim of this study was to elucidate the prevalence of inner-ear and/or internal auditory canal malformations in children with unilateral sensorineural hearing loss (USNHL) for better management of hearing loss and genetic and lifestyle counseling. MethodsWe conducted a retrospective study of charts and temporal bone computed tomography (CT) findings of 69 consecutive patients 0–15 years old with USNHL. In two cases, genetic examination was conducted. ResultsOf these patients, 66.7% had inner-ear and/or internal auditory canal malformations. The prevalence of malformations in infants (age <1 year) was 84.6%, which was significantly higher than that in children 1–15 years old (55.8%; p<0.01). Almost half of the patients (32; 46.4%) had cochlear nerve canal stenosis; 13 of them had cochlear nerve canal stenosis alone, and in 19 it accompanied other malformations. Internal auditory canal malformations were observed in 22 subjects (31.8%), 14 (20.3%) had cochlear malformations, and 5 (7.2%) had vestibular/semicircular canal malformations. These anomalies were seen only in the affected ear, except in two of five patients with vestibular and/or semicircular canal malformations. Two patients (2.9%) had bilateral enlarged vestibular aqueducts. Mutations were found in SLC26A4 in one of the two patients with bilateral large vestibular aqueducts. The prevalence of a narrow internal auditory canal was significantly higher in subjects with cochlear nerve canal stenosis (50.0%) than in subjects with normal cochlear nerve canals (11.1%; p<0.01). There were no correlations between the type and number of malformations and hearing level. ConclusionsThe prevalence of inner-ear and/or internal auditory canal malformations detected by high-resolution temporal bone CT in children with USNHL was very high. Radiological and genetic examination provided important information to consider the pathogenesis and management of hearing loss. Temporal bone CT should be recommended to children with USNHL early in life. SLC26A4 mutation also should be examined in cases with bilateral enlarged vestibular aqueduct.

Molecular Epidemiology and Functional Assessment of Novel Allelic Variants of SLC26A4 in Non-Syndromic Hearing Loss Patients with Enlarged Vestibular Aqueduct in China

BackgroundMutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations are responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA). The mutation spectrum of SLC26A4 varies widely among ethnic groups. To investigate the incidence of EVA in Chinese population and to provide appropriate genetic testing and counseling to patients with SLC26A4 variants, we conducted a large-scale molecular epidemiological survey of SLC26A4.MethodsA total of 2352 unrelated non-syndromic hearing loss patients from 27 different regions of China were included. Hot spot regions of SLC26A4, exons 8, 10 and 19 were sequenced. For patients with one allelic variant in the hot spot regions, the other exons were sequenced one by one until two mutant alleles had been identified. Patients with SLC26A4 variants were then examined by temporal bone computed tomography scan for radiological diagnosis of EVA. Ten SLC26A4 variants were cloned for functional study. Confocal microscopy and radioisotope techniques were used to examine the membrane expression of pendrin and transporter function.ResultsOf the 86 types of variants found, 47 have never been reported. The ratio of EVA in the Chinese deaf population was at least 11%, and that in patients of Han ethnicity reached at least 13%. The mutational spectrum and mutation detection rate of SLC26A4 are distinct among both ethnicities and regions of Mainland China. Most of the variants caused retention of pendrin in the intracellular region. All the mutant pendrins showed significantly reduced transport capability.ConclusionAn overall description of the molecular epidemiological findings of SLC26A4 in China is provided. The functional assessment procedure can be applied to identification of pathogenicity of variants. These findings are valuable for genetic diagnosis, genetic counseling, prenatal testing and pre-implantation diagnosis in EVA families.

Augmented Ocular Vestibular Evoked Myogenic Potentials to Air-Conducted Sound in Large Vestibular Aqueduct Syndrome

To demonstrate the value of recording air-conducted ocular Vestibular Evoked Myogenic Potentials (oVEMP) in a patient with bilaterally enlarged vestibular aqueducts. Cervical VEMP and oVEMP were recorded from a patient presenting with bilateral hearing loss and imbalance, attributable to large vestibular aqueduct syndrome. The stimuli were air-conducted tone bursts at octave frequencies from 250 to 2000 Hz. Amplitudes and thresholds were measured and compared with the normal response range of 32 healthy control subjects. oVEMP reflexes demonstrated pathologically increased amplitudes and reduced thresholds for low-frequency tone bursts. Cervical VEMP amplitudes and thresholds were within normal limits for both ears across all frequencies of stimulation. This study is the first to describe the augmentation of AC oVEMPs in an adult with large vestibular aqueduct syndrome.

Acoustically evoked short latency negative responses in hearing loss patients with enlarged vestibular aqueduct

This study aims to assess the diagnostic value of the acoustically evoked short latency negative response (ASNR) during the auditory brainstem response (ABR) test for enlarged vestibular aqueduct (EVA). The ABR test was performed on 175 subjects with severe and profound hearing loss from July 2008 to August 2011. Patients were submitted to high-resolution computed tomography scans for the temporal bone of the inner ear, and were diagnosed with EVA (EVA group; n=24 cases, 46 ears), no inner ear deformity (no deformity group; n=136 cases, 272 ears), or other inner ear deformity (other deformities group; n=15 cases, 29 ears). The prevalence of ASNR was 26/46 ears (56.52%) in the EVA group, 10/272 ears (3.67%) in the no deformity group, and 3/29 ears (10.34%) in the other deformities group. The rate of ASNR in the EVA group was higher than that in other groups (p<0.05). The rate of ASNR is positively correlated with EVA. Therefore, the recording of ASNRs could be a valuable method for discovering EVA.

251 Molecular Etiology of Childhood Hearing Impairment Associated with Non-Syndromic Enlarged Vestibular Aqueduct in Southeastern China

BackgroundMutations in SLC26A4, and in rarer cases double heterozygous mutations of FOXI1/SLC26A4 or KCNJ10/SLC26A4, lead to childhood hearing impairment associated with non-syndromic enlarged vestibular aqueduct (EVA), the most common inner...

The relationship between vestibular aqueduct diameter and sensorineural hearing loss is linear: a review and meta-analysis of large case series

Inner ear homeostasis is dependent on the vestibular aqueduct and its content, the endolymphatic duct. Narrow and enlarged vestibular aqueducts have both been associated with hearing loss in Ménière's and large vestibular aqueduct syndromes. This review investigated the correlation between vestibular aqueduct diameter and pure tone average, and the effect of measurement site (i.e. the midpoint or the external aperture). A systematic review of the literature and meta-analysis of large case series published on the Allied and Complementary Medicine, British Nursing Index, Cumulative Index to Nursing and Allied Health, Embase, Health Business Elite, Health Management Information Consortium, Medline, PsycInfo and PubMed databases. References and personal books were also scrutinised. A linear relationship between vestibular aqueduct diameter and hearing loss was observed, with a projected increase of 6 dBHL per unit of vestibular aqueduct diameter (95 per cent confidence interval, 2-10; p = 0.003). This relationship was independent of measurement site. This dose-dependent or linear relationship supports the role of flow and/or pressure change as aetiological factors in the pathogenesis of hearing loss, as per Poiseuille's law. This aetiological association is strengthened by the fact that the observed relationship is independent of measurement site.

A novel insertion-induced frameshift mutation of the SLC26A4 gene in a Korean family with Pendred syndrome

Pendred syndrome (PS) is an autosomal recessive disorder characterized by congenital bilateral sensorineural hearing loss, goiter, and incomplete iodide organification. Patients with PS also have structural anomalies of the inner ear such as enlarged vestibular aqueducts (EVA) and Mondini's malformation. The goiter, which is a major clinical manifestation of PS, usually develops around adolescence. PS is caused by biallelic mutations of the SLC26A4 gene, while nonsyndromic bilateral EVA is associated with zero or one SLC26A4 mutant allele.We report here a Korean family including a young female with PS who had goiter and progressive, fluctuating sensorineural hearing loss that could be partially recovered by oral steroid treatment. Genetic investigation revealed compound heterozygous mutations for p.R677AfsX11, a novel frameshift mutation, and p.H723R in the SLC26A4 gene. Our findings provide detailed information regarding the distribution of mutant alleles for PS and may serve as a foundation for studies to comprehend the genetic portion of syndromic hearing loss.

Unilateral Enlarged Vestibular Aqueduct in Children

Objective: 1) Describe the likelihood of contralateral hearing loss (HL) in patients with unilateral enlarged vestibular aqueduct (UEVA). 2) Detemine the positve predictive value of genetic testing in patients with UEVA. 3) Determine the correlation of temporal bone measurements in patients with UEVA. Method: Patients were identified from a database of children with sensorineural hearing loss (HL) and enlarged vestibular aqueduct (EVA) between 1998 and 2010. A group of patients with unilateral HL without EVA was also identified. Outcomes measured were HL phenotype, laterality of EVA, midpoint and operculum measurements, and genetic tests. Results: Fifty-five percent of patients with UEVA had HL in the contralateral ear. There was no difference in the rate of HL progression in patients with bilateral and unilateral EVA ( P = .1). However, both EVA groups had higher rates of progression compared to patients with unilateral HL alone. A correlation was shown for the presence of HL at 250 Hz and the risk of more severe HL and progressive HL. Patients with bilateral EVA and SLC26A4 mutations had a higher rate of progression than patients who had no mutations ( P = .02). No patients with UEVA had Pendred syndrome. Conclusion: Children with unilateral EVA have a significant risk of HL progression. Hearing loss in the contralateral ear is common, suggesting that unilateral EVA is a bilateral process. Temporal bone measurements, HL severity, and HL at 250 Hz were correlated with the risk of progressive HL.

Neural Response Telemetry in Pediatric Cochlear Implantation

Objective: 1) Evaluate the neural response telemetry (NRT) of patients with inner ear anomalies, and determine correlations between NRT and postoperative speech recognition thresholds (SRT). 2) Determine if higher incidence of negative intraoperative NRT exists in pediatric patients with inner ear anomalies, namely enlarged vestibular aqueduct syndrome (EVAS). Method: Retrospective chart review of pediatric patients who underwent cochlear implantation at a tertiary care pediatric referral center from 2001 to present. Patients with inner ear anomalies were age matched to controls without anomalies. Associations between abnormal NRT and perilymphatic gusher and correlations between NRT and audiometry were assessed. Results: Twenty-seven subjects with radiographic evidence of EVAS were evaluated; 35 ears implanted. Median age of implantation was 77.5 months. NRT was normal in 69%, abnormal 11%, marginal 6%, missing 4%. Intraoperative data revealed a perilymphatic gusher in 8 patients (23%); of which 50% had abnormal NRT compared to 8% among patients without gusher ( P = .03). Postoperative audiometric data were available for 8 out of 35 ears. No significant correlations between intraoperative and postoperative NRT with postoperative SRT at 1 kHz, 2 kHz, 4 kHz ( P &gt; .2). There appeared to be a correlation between intraoperative NRT and postoperative SRT at 500 kHz (ρ = 0.68, P = .14); this was not statistically significant. Conclusion: The presence of perilymphatic gusher at the time of cochlear implantation in patients with enlarged vestibular aqueduct syndrome (EVAS) seems to be related to abnormal NRT. There is no significant correlation between intraoperative and postoperative NRT and speech recognition thresholds (SRT) at 1 kHZ, 2 kHz, and 4 kHz in patients with EVAS.

Misdiagnosis of otosclerosis in a patient with enlarged vestibular aqueduct syndrome: a case report

IntroductionIn the present case we report on the mismanagement of a patient misdiagnosed with otosclerosis, who was subsequently found to have enlarged vestibular aqueduct syndrome bilaterally. This highlights the need to not only be vigilant in pre-operative assessment of otosclerosis but also in post-operative investigations of stapedectomy failures.Case presentationOur patient, a 56-year-old Caucasian Australian woman, lost the hearing in her right ear following a stapedectomy approximately 25 years ago. It is thought that preoperative imaging was not conducted, while an inadequate (unmasked) audiogram was used to formulate the initial diagnosis of otosclerosis. The hearing in her left ear deteriorated to the point that a cochlear implant was now being considered for her right ear. Imaging performed as part of our pre-cochlear implant battery revealed bilateral enlarged vestibular aqueducts and thus the decision to proceed with a right cochlear implant was made following discussion with our patient and her family in regard to not only general surgical risks but specifically the remote risk that the surgical drilling required during the procedure could risk a deterioration of the hearing in her left ear because of the enlarged vestibular aqueduct on that side.ConclusionsThis report illustrates a case of misdiagnosis and mismanagement of bilateral enlarged vestibular aqueduct resulting in profound hearing loss. Fortunately our patient has been successfully implanted with a right cochlear implant with remarkable outcomes.

Novel mutations in the SLC26A4 gene

ObjectivesMutations in the SLC26A4 gene (7q22.3–7q31.1) are considered one of the most common causes of genetic hearing loss. There are two clinical forms related to these mutations: syndromic and non-syndromic deafness. The first one is named Pendred Syndrome (PS) when deafness is associated with thyroid goiter; the second is called DFNB4, when no other symptoms are present. Both are transmitted as an autosomal recessive trait, but simple heterozygotes can develop both forms of deafness. Actually it is thought that Pendred Syndrome occurs when both alleles of SLC26A4 gene are mutated; DFNB4 seems due to monoallelic mutations. PS and DFNB4 can be associated with inner ear malformations. In most of the cases (around 80%), these consist in Enlarged Vestibular Aqueduct (EVA). EVA can also be present without SLC26A4 mutations.Understanding the role of new SLC26A4 variants should facilitate clinical assessment, as well as diagnostic and therapeutic approaches. This investigation aims to detect and report genetic causes of two unrelated Italian boys with hearing loss. MethodsPatients and family members underwent clinical, audiological and genetic evaluations. To identify genetic mutations, DNA sequencing of SLC26A4 gene (including all 21 exons, exon-intron boundaries and promoter region) was carried out. ResultsBoth probands were affected by congenital, progressive and fluctuating mixed hearing loss. Temporal bone imaging revealed a bilateral EVA with no other abnormalities in both cases. Probands were heterozygotes for previously undescribed mutations in the SLC26A4 gene: R409H/IVS2+1delG (proband 1) and L236P/K590X (proband 2). No other mutations were detected in GJB2, GJB6 genes or mitochondrial DNA (mit-DNA). ConclusionsThe IVS2+1delG and K590X mutations have not yet been described in literature but there is some evidence to suggest that they have a pathological role. The results underlined the importance of considering the complete DNA sequencing of the SLC26A4 gene for differential molecular diagnosis of deafness, especially in those patients affected by congenital, progressive and fluctuating mixed hearing loss with bilateral EVA.