Hearing loss in unilateral and bilateral enlarged vestibular aqueduct syndrome

Archibald, Hunter; Ascha, Mustafa; Gupta, Amit; Megerian, Cliff A.; Otteson, Todd D.

doi:10.1016/j.ijporl.2018.12.023

Cited by 22 publications

(11 citation statements)

References 16 publications

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“…The presence of IP‐II was associated with a 2.44 hazard ratio (95% CI, 1.04 to 5.72). Similar to previous findings, laterality was not associated with increased hazard for our predetermined confidence level 24 …”

Section: Resultssupporting

confidence: 91%

Predictive Modeling and Risk Stratification of Patients With Enlarged Vestibular Aqueduct

et al. 2021

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Objectives/Hypothesis: To investigate patient-specific characteristics that independently predict for progressive hearing loss in patients with enlarged vestibular aqueduct (EVA). Utilize multivariable predictive models to identify subgroups of patients with significantly different progression risks.Study Design: Retrospective analysis of patients evaluated at an academic tertiary care center. Cohort included 74 ears of patients with a diagnosis of EVA as defined by the Cincinnati criteria.Methods: Hearing trajectories were characterized, and a Kaplan-Meier estimator was utilized to determine progressive phenotype probabilities across the first 10 years after diagnosis. Cox proportional hazard regression was used to identify patient characteristics that independently altered this probability. Stratified risk groups were delineated from generated nomogram scores.Results: Male gender was associated with a 4.53 hazard ratio for progressive hearing loss (95% confidence interval [CI], 2.53 to 12.59). Each millimeter increase in operculum size was independently associated with an 80.40% increase in expected hazard (95% CI, 40.18 to 120.62). Each dB increase in air pure tone average at time of diagnosis decreased expected hazard by 1.59% (95% CI, À3.02 to À0.17). The presence of incomplete partition type II was associated with a 2.44 hazard ratio (95% CI, 1.04 to 5.72). Risk groups stratified by median nomogram score evidenced the discriminative ability of our model with the progression probability in the high-risk group being six times higher at 1 year, nearly five times greater at 3 years, and three times greater at 9 years.Conclusions: EVA patient characteristics can be used to predict hearing loss probability with a high degree of accuracy (C-index of 0.79). This can help clinicians make more proactive management decisions by identifying patients at high risk for hearing loss.

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Section: Resultssupporting

confidence: 91%

Predictive Modeling and Risk Stratification of Patients With Enlarged Vestibular Aqueduct

et al. 2021

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“…As a result, over the last two decades there have been several studies aimed at exploring associations between patient factors and HL severity/progression. Examples of common factors explored are initial severity of HL, gender, EVA laterality, number of mutated alleles in the Pendrin gene, dimensions of the endolymphatic duct and sac, and presence of other abnormalities of the bony labyrinth (9–13). Our recent prognostic factor systematic review of EVA HL has confirmed that these specific factors should be further investigated to affirm their individual prognostic roles in EVA HL (14).…”

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confidence: 90%

Enlarged Vestibular Aqueduct: Disease Characterization and Exploration of Potential Prognostic Factors for Cochlear Implantation

Saeed

Rajai

Nash

et al. 2022

Otology &Amp; Neurotology

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Objectives:There is an unmet need to match the anticipated natural history of hearing loss (HL) in enlarged vestibular aqueduct (EVA) with clinical management strategies. The objectives of this study are therefore to provide a detailed case characterization of an EVA cohort and explore the relationship between candidate prognostic factors and timing of cochlear implant (CI) surgery.Study Design:A multicenter retrospective review of patients diagnosed with EVA.Setting:Patient data recruitment across three CI centers in the UK.Patients:One hundred fifty patients with a radiological diagnosis of EVA from January 1995 to January 2021.Main Outcome Measures:Age at audiological candidacy for CI and age at first implant surgery.Results:EVA was predominately a bilateral condition (144/ 150) with increased prevalence in women (M:F, 64:86). 51.7% of patients failed new-born hearing screening, with 65.7% having HL diagnosed by 1 year. Initial moderate to severe and severe to profound HL were reported most frequently. In 123 patients, median age that audiological candidacy for CI was met for at least one ear was 2.75 years. Median age at first CI was 5 years (140/150).Pendred syndrome (confirmed in 73 patients) and ethnicity, were not significantly associated with earlier CI surgery. Multivariate linear regression demonstrated that male patients have first CI surgery significantly earlier than females (coefficient −0.43, 95% CI [−0.82, −0.05), p-value = 0.028).Conclusions:This large UK EVA cohort provides evidence that patients should be closely monitored for CI candidacy within the first 3 years of life. Significantly, male gender is emerging as an independent prognostic factor for earlier assessment and first CI surgery.

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“…The reported variability of the auditory phenotype associated with EVAs (Arjmand and Webber 2004;Gopen et al 2011;Griffith and Wangemann 2011) may be another explanation for the observed differences in severity of HL in both studies. In literature, many prognostic factors such as genotype, EVA size and morphology, age, head trauma, and gender are reported as underlying explanations for this variability, although some of these studies draw contradicting conclusions (Alemi and Chan 2015;Archibald et al 2019;Ascha et al 2017;Gopen et al 2011;Miyagawa et al 2014;Rah et al 2015;Saeed et al 2021). In the same line, Song et al reported intrafamilial differences in the severity of hearing loss in siblings with the same biallelic variants in SLC26A4 (Song et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Exploring the missing heritability in subjects with hearing loss, enlarged vestibular aqueducts, and a single or no pathogenic SLC26A4 variant

et al. 2021

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Pathogenic variants in SLC26A4 have been associated with autosomal recessive hearing loss (arHL) and a unilateral or bilateral enlarged vestibular aqueduct (EVA). SLC26A4 is the second most frequently mutated gene in arHL. Despite the strong genotype–phenotype correlation, a significant part of cases remains genetically unresolved. In this study, we investigated a cohort of 28 Dutch index cases diagnosed with HL in combination with an EVA but without (M0) or with a single (M1) pathogenic variant in SLC26A4. To explore the missing heritability, we first determined the presence of the previously described EVA-associated haplotype (Caucasian EVA (CEVA)), characterized by 12 single nucleotide variants located upstream of SLC26A4. We found this haplotype and a delimited V1-CEVA haplotype to be significantly enriched in our M1 patient cohort (10/16 cases). The CEVA haplotype was also present in two M0 cases (2/12). Short- and long-read whole genome sequencing and optical genome mapping could not prioritize any of the variants present within the CEVA haplotype as the likely pathogenic defect. Short-read whole-genome sequencing of the six M1 cases without this haplotype and the two M0/CEVA cases only revealed previously overlooked or misinterpreted splice-altering SLC26A4 variants in two cases, who are now genetically explained. No deep-intronic or structural variants were identified in any of the M1 subjects. With this study, we have provided important insights that will pave the way for elucidating the missing heritability in M0 and M1 SLC26A4 cases. For pinpointing the pathogenic effect of the CEVA haplotype, additional analyses are required addressing defect(s) at the RNA, protein, or epigenetic level.

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Hearing loss in unilateral and bilateral enlarged vestibular aqueduct syndrome

Cited by 22 publications

References 16 publications

Predictive Modeling and Risk Stratification of Patients With Enlarged Vestibular Aqueduct

Predictive Modeling and Risk Stratification of Patients With Enlarged Vestibular Aqueduct

Enlarged Vestibular Aqueduct: Disease Characterization and Exploration of Potential Prognostic Factors for Cochlear Implantation

Exploring the missing heritability in subjects with hearing loss, enlarged vestibular aqueducts, and a single or no pathogenic SLC26A4 variant

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