Enlarged vestibular aqueduct and Mondini Malformation: audiological, clinical, radiologic and genetic features

Abstract Purpose When referring to enlarged vestibular aqueduct (EVA) we should differentiate between nonsyndromic enlarged vestibular aqueduct (NSEVA) and Pendred Syndrome (PDS), a disease continuum associated with pathogenic sequence variants of Pendrin’s Gene (SLC26A4) in about half of the cases. The study was aimed to analyse the clinical and audiological features of a monocentric cohort of Caucasian patients with NSEVA/PDS, their genetic assessment and morphological inner ear features. Methods We retrospectively reviewed the audiologic, genetic and anamnestic data of 66 patients with NSEVA/PDS followed by our audiology service. Results SLC26A4 mutations was significantly correlated with the presence of PDS rather than NSEVA (p < 0.019), with the expression of inner ear malformations (p < 0.001) and with different severity of hearing loss (p = 0.001). Furthermore, patients with PDS showed significantly worse pure tone audiometry (PTA) than patients with NSEVA (p = 0.001). Anatomically normal ears presented significantly better PTA than ears associated with Mondini Malformation or isolated EVA (p < 0.001), but no statistically significative differences have been observed in PTA between patients with Mondini Malformation and isolated EVA. Conclusion NSEVA/PDS must be investigated in all the congenital hearing loss, but also in progressive, late onset, stepwise forms. Even mixed or fluctuating hearing loss may constitute a sign of a NSEVA/PDS pathology. Our findings can confirm the important role of SLC26A4 mutations in determining the phenotype of isolated EVA/PDS, both for the type/degree of the malformation, the hearing impairment and the association with thyroid dysfunction.

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Genetic Determinants of Non-Syndromic Enlarged Vestibular Aqueduct: A Review

Audiology Research ◽

10.3390/audiolres11030040 ◽

2021 ◽

Vol 11 (3) ◽

pp. 423-442 ◽

Cited By ~ 1

Author(s):

Sebastian Roesch ◽

Gerd Rasp ◽

Antonio Sarikas ◽

Silvia Dossena

Keyword(s):

Hearing Loss ◽

Large Fraction ◽

Developed Countries ◽

Genetic Determinants ◽

Genetic Origin ◽

Enlarged Vestibular Aqueduct ◽

Vestibular Aqueduct ◽

Hearing Function ◽

Ear Malformations ◽

Renal Tubular

Hearing loss is the most common sensorial deficit in humans and one of the most common birth defects. In developed countries, at least 60% of cases of hearing loss are of genetic origin and may arise from pathogenic sequence alterations in one of more than 300 genes known to be involved in the hearing function. Hearing loss of genetic origin is frequently associated with inner ear malformations; of these, the most commonly detected is the enlarged vestibular aqueduct (EVA). EVA may be associated to other cochleovestibular malformations, such as cochlear incomplete partitions, and can be found in syndromic as well as non-syndromic forms of hearing loss. Genes that have been linked to non-syndromic EVA are SLC26A4, GJB2, FOXI1, KCNJ10, and POU3F4. SLC26A4 and FOXI1 are also involved in determining syndromic forms of hearing loss with EVA, which are Pendred syndrome and distal renal tubular acidosis with deafness, respectively. In Caucasian cohorts, approximately 50% of cases of non-syndromic EVA are linked to SLC26A4 and a large fraction of patients remain undiagnosed, thus providing a strong imperative to further explore the etiology of this condition.

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Role of Computed Tomography and Magnetic Resonance Imaging in detecting the Prevalence of inner ear anomalies among cochlear implant candidates

QJM ◽

10.1093/qjmed/hcab106.007 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Alaa Nasser Hussain Zaher ◽

Tougan Taha Abd El Aziz ◽

Ahmed Samy Abdelrahman

Keyword(s):

Magnetic Resonance Imaging ◽

Computed Tomography ◽

Hearing Loss ◽

Cochlear Implant ◽

Inner Ear ◽

Resonance Imaging ◽

High Resolution Computed Tomography ◽

Vestibular Aqueduct ◽

Incomplete Partition ◽

Ear Anomalies

Abstract Background Hearing loss management using cochlear implants in patients with inner ear anomalies has long been discussed in the otology community. Magnetic resonances imaging (B,/IRI) and Computed tomography (CT) play important roles in the preoperative assessment of inner ear abnormalities such as cochlear nerve deficiency and variant anatomy as these abnormalities may not only affect the decision of the implantation procedure or the patient's prognosis regarding auditory improvement, but also the risk of complications. Objective To examine the prevalence of inner ear anomalies among cochlear implant recipients in patients with congenital sensorineural hearing loss among the pediatric age group in the Demerdash hospital, Ain Shams university using High resolution computed tomography (HRCT) and MRI imaging. Methods A retrospective descriptive study over the course of 9 months that included all patients that are candidates for cochlear implant referred to the Radiology department, Ain Shams University Hospitals for a preoperative imaging in the form of CT and VIRI scans. Results CT and MRI scans of 33 patients who had congenital hearing loss and were candidates for cochlear implantation with total 66 ears were reviewed. Inner ear anomalies were identified in 8 patients representing a prevalence (24.2%) with 14 ear diseased. Anomalies were seen bilaterally in 6 patients and unilaterally in 2 patients. Among the 14 diseased ear, 9 ears (64.3%) were seen with incomplete partition Il, 7 ears (50%) were seen with enlarged vestibular aqueduct, 4 ears (28.6%) were seen with cochlear hypoplasia, 3 ears (21.4%) were seen with semicircular canal aplasia, 2 ears (14.3%) were seen with incomplete partition type I, 2 ears (14.3%) were seen with cochlear nerve aplasia, 2 ears with cochlear aplasia (14.3%), I ear (7.1%) was seen with common cavity ear (7.1%) with complete labyrinthine aplasia. Conclusion Prevalence of inner ear anomalies among cochlear implant candidates was 24.2%. This result is consistent with results worldwide and the most common anomalies were Incomplete partition Il and large vestibular aqueduct. Abbreviations Computed tomography (CT), Magnetic resonance imaging (MRI), High resolution computed tomography (HRCT), Internal auditory canal (IAC), Cerebellopontine angle (CPA).

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Hearing Loss in Inner Ear Malformations

Encyclopedia of Otolaryngology, Head and Neck Surgery ◽

10.1007/978-3-642-23499-6_440 ◽

2013 ◽

pp. 1143-1150

Author(s):

Gonca Sennaroglu ◽

Levent Sennaroglu

Keyword(s):

Hearing Loss ◽

Inner Ear ◽

Inner Ear Malformations ◽

Ear Malformations

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Study on the relationship between the pathogenic mutations of SLC26A4 and CT phenotypes of inner ear in patient with sensorineural hearing loss

Bioscience Reports ◽

10.1042/bsr20182241 ◽

2019 ◽

Vol 39 (3) ◽

Author(s):

Lihua Wu ◽

Yunliang Liu ◽

Jianman Wu ◽

Sheng Chen ◽

Shupin Tang ◽

...

Keyword(s):

Hearing Loss ◽

Ct Scan ◽

Inner Ear ◽

Gene Mutations ◽

Pathogenic Mutation ◽

Vestibular Aqueduct ◽

Slc26a4 Gene ◽

Pathogenic Mutations ◽

Inner Ear Malformation ◽

Single Allele

Abstract To investigate the possible association of pathogenic mutations of SLC26A4 and computerized tomography (CT) phenotypes of inner ear, and explore the feasibility of using the method of gene sequence analysis. A total of 155 patients with bilateral hearing loss carrying SLC26A4 gene mutations were further subjected to high-resolution temporal bone CT and thyroid B ultrasound tests. The potential relationship between the pathogenic mutations of gene and the CT phenotypes were analyzed. As a result, 65 patients (41.9%, 65/155) carried SLC26A4 gene mutations, and 27 cases were detected with pathogenic mutations of SLC26A4 where IVS7-2A>G (55.6%, 15/27) was the most common pathogenic mutation. Amongst them, 19 patients carrying bi-allelic SLC26A4 mutations were all confirmed to have inner ear malformation by CT scan including four cases of enlarged vestibular aqueduct (EVA) and 15 cases of Mondini dysplasia (MD). However, there was only one in eight cases of single allele pathogenic mutation who was confirmed to have EVA by CT scan. Further, only one patient with EVA was confirmed to be slightly higher of total T3 than normal by thyroid ultrasound scan and thyroid hormone assays. These findings suggested that CT detection and SLC26A4 gene detection are efficient methods to diagnose EVA, which can complement each other. Also, the bi-allelic pathogenic mutations of SLC26A4 are more likely to induce inner ear malformation than single allele pathogenic mutation.

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Gene therapy for hearing loss

Human Molecular Genetics ◽

10.1093/hmg/ddz129 ◽

2019 ◽

Vol 28 (R1) ◽

pp. R65-R79 ◽

Cited By ~ 16

Author(s):

Ryotaro Omichi ◽

Seiji B Shibata ◽

Cynthia C Morton ◽

Richard J H Smith

Keyword(s):

Gene Therapy ◽

Hearing Loss ◽

Inner Ear ◽

Viral Vectors ◽

Therapeutic Potential ◽

Late Onset ◽

Science Research ◽

Gene Replacement ◽

Age Related ◽

Genetic And Environmental Factors

Abstract Sensorineural hearing loss (SNHL) is the most common sensory disorder. Its underlying etiologies include a broad spectrum of genetic and environmental factors that can lead to hearing loss that is congenital or late onset, stable or progressive, drug related, noise induced, age related, traumatic or post-infectious. Habilitation options typically focus on amplification using wearable or implantable devices; however exciting new gene-therapy-based strategies to restore and prevent SNHL are actively under investigation. Recent proof-of-principle studies demonstrate the potential therapeutic potential of molecular agents delivered to the inner ear to ameliorate different types of SNHL. Correcting or preventing underlying genetic forms of hearing loss is poised to become a reality. Herein, we review molecular therapies for hearing loss such as gene replacement, antisense oligonucleotides, RNA interference and CRISPR-based gene editing. We discuss delivery methods, techniques and viral vectors employed for inner ear gene therapy and the advancements in this field that are paving the way for basic science research discoveries to transition to clinical trials.

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Enlarged Vestibular Aqueduct in Pediatric SNHL

Otolaryngology ◽

10.1016/j.otohns.2008.05.533 ◽

2008 ◽

Vol 139 (2_suppl) ◽

pp. P104-P104

Author(s):

Karuna Dewan ◽

Judith C. Lieu

Keyword(s):

Hearing Loss ◽

Cochlear Implant ◽

Sensorineural Hearing Loss ◽

Temporal Bone ◽

Pediatric Population ◽

Sensorineural Hearing ◽

Enlarged Vestibular Aqueduct ◽

Vestibular Aqueduct ◽

Current Estimation ◽

Temporal Bone Ct

Problem Current diagnostic criteria for enlarged vestibular aqueduct (EVA), >1.5mm at the midpoint, was determined in the pre-CT era by Valvassori. Recent research, based on 73 CTs from children with no sensorineural hearing loss (SNHL), suggests new criteria for the diagnosis of EVA—midpoint of >0.9mm or operculum >1.9mm. We evaluated the proposed new radiographic, Cincinnati criteria for the diagnosis of EVA. Methods In a retrospective cohort study, we reviewed temporal bone CT scans of 130 pediatric cochlear implant recipients to measure the vestibular aqueduct midpoint and opercular width and 5 other temporal bone dimensions. Results The Cincinnati criteria identified 44% of patients with EVA versus 16% with the Valvassori criterion (P < 0.01). Of those with EVA, 45% were unilateral and 55% were bilateral using Cincinnati criteria; 64% were unilateral and 36% bilateral using Valvassori criterion (P<0.01). Right and left side measurements of vestibular aqueduct operculum (r=0.67, P<0.01) and midpoint (r=0.58, P<0.01) correlated substantially. The Cincinnati criteria diagnosed 70 ears with EVA classified as normal using the Valvassori criterion (P<0.01). Of these 70 ears, 59 had no other medical explanation for their hearing loss. Conclusion The Cincinnati criteria identified a large percentage of pediatric cochlear implant patients with EVA who otherwise had no known etiology for their deafness. Significant correlations between right and left side measurements suggest that EVA may not be morphologically asymmetric as previously thought. Significance The Cincinnati criteria potentially alters the current estimation of the most common etiologies of bilateral severe-to-profound sensorineural hearing loss in the pediatric population. Support KD is a Doris Duke Clinical Research Fellow, supported by the Doris Duke Foundation.

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