2017 Sec 1 Green Book

Fig. 1. Flow diagram of enlarged vestibular aqueduct (EVA) study population. *HL ¼ hearing loss; **HF ¼ high frequency. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary. com.]

were defined within the following framework: mild loss (20–39 dB), moderate loss (40–54 dB), moderately severe loss (55–69 dB), severe loss (70–89 dB), and profound loss ( > 90 dB).

loss without EVA from 1998 to 2010. Patients included in the study were required to meet the following criteria: 1) diagnosis of EVA was consistent with the previously published and well- established criteria; 9,11 2) a complete audiometric assessment was performed and at least 3 months of audiometric follow-up data were available; and 3) genetic testing ( GJB2, SLC26A4 ) was performed if offered at our institution at the time of the hearing loss evaluation (Fig. 1). Exclusion criteria included temporal bone dysmorphology that would prevent measure- ments, aural atresia, known syndromic hearing loss, documented ototoxicity, or a history of temporal bone fractures, meningitis, hydrocephalus with a shunt, autoimmune inner ear disease, or auditory neuropathy. Demographic data, audiometric data, temporal bone measurements, and genetic test results were obtained for study patients. This study was approved by the institutional review board and was in compliance with Health Insurance Portability and Accountability Act of 1996 regulations. Audiometric Data A pure tone average (PTA) for each ear was derived by averaging the audiometric findings at 500, 1,000, 2,000, and 4,000 Hz at the initial and most recent audiometric evaluation. A PTA for each ear was also derived for the high frequencies (high- frequency PTA [HFPTA]) by averaging the audiometric findings at 4,000, 6,000, and 8,000 Hz. An additional subanalysis was performed on the individual 250-Hz pure tone frequency. Progressive hearing loss was defined as a 10 dB or greater increase in PTA over a follow-up period of at least 3 months. Patients with an initial PTA 90 dB were eliminated from fur- ther analysis with regard to progressive SNHL. Progressive hearing loss was evaluated as absolute change in PTA values as well as a rate of change in PTA (in decibel loss per year), which takes into account the time between audiologic visits. When reporting PTA values for patients with asymmetric bilateral hearing loss, the better-hearing ear was used for describing the hearing phenotype for that patient. The levels of hearing loss

Temporal Bone CT Analysis Measurement of the various structures of the temporal bone seen on CT scans was carried out according to a previously published algorithm. 9,11 All patients in the study had CT scans available for review. Briefly, the width of the aqueduct was meas- ured at both the operculum (a line perpendicular to the posterior surface of the petrous pyramid going to the most lateral or pos- terolateral pixel in the medial wall of the operculum) and at the midpoint between the coronal plane of the operculum and the coronal plane of the posterior wall of the crus commune or upper vestibule. The vestibular aqueduct was considered enlarged when its width exceeded the 95th percentile of normal temporal bones at either the operculum or the midpoint (1.9 mm and 0.9 mm, respectively; Fig. 2). All measurements were performed by two neuroradiologists ( C . B . and M . H .). When there was a discrep- ancy between the measurements performed by these two physicians, the mean of the two measurements was used. Genomic DNA was isolated from blood and buccal swab tissues using the Puregene DNA purification Kit (Gentra Sys- tems, Minneapolis, MN) or the Roche MagNA Pure Compact system (Roche Diagnostics Corporation, Indianapolis, IN) according to the manufacturers’ instructions. Coding exons and at least 50 base pairs of the adjacent intronic regions of the GJB2 (NC_000013 and NM_86849), MTRNR1 (NC_001807) and SLC26A (NC_000007.13 and NM_000441) genes were amplified by polymerase chain reaction (PCR), followed by bidirectional sequencing using the BigDye Terminator Cycle Sequencing Kit (Applied Biosystems by Life Technologies, Foster City, CA). Methodology for GJB2 , GJB6, MTRNR1 , and SLC26A4 Genetic Testing

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