Volumetry improves the assessment of the vestibular aqueduct size in inner ear malformation.

OBJECTIVES: Enlarged vestibular aqueduct (EVA) is a common finding associated with inner ear malformations (IEM). However, uniform radiologic definitions for EVA are missing and various 2D-measurement methods to define EVA have been reported. This study evaluates VA volume in different types of IEM and compares 3D-reconstructed VA volume to 2D-measurements. METHODS: A total of 98 high-resolution CT (HRCT) data sets from temporal bones were analyzed (56 with IEM; [cochlear hypoplasia (CH; n = 18), incomplete partition type I (IPI; n = 12) and type II (IPII; n = 11) and EVA (n = 15)]; 42 controls). VA diameter was measured in axial images. VA volume was analyzed by software-based, semi-automatic segmentation and 3D-reconstruction. Differences in VA volume between the groups and associations between VA volume and VA diameter were assessed. Inter-rater-reliability (IRR) was assessed using the intra-class-correlation-coefficient (ICC). RESULTS: Larger VA volumes were found in IEM compared to controls. Significant differences in VA volume between patients with EVA and controls (p < 0.001) as well as between IPII and controls (p < 0.001) were found. VA diameter at the midpoint (VA midpoint) and at the operculum (VA operculum) correlated to VA volume in IPI (VA midpoint: r = 0.78, VA operculum: r = 0.91), in CH (VA midpoint: r = 0.59, VA operculum: r = 0.61), in EVA (VA midpoint: r = 0.55, VA operculum: r = 0.66) and in controls (VA midpoint: r = 0.36, VA operculum: r = 0.42). The highest IRR was found for VA volume (ICC = 0.90). CONCLUSIONS: The VA diameter may be an insufficient estimate of VA volume, since (1) measurement of VA diameter does not reliably correlate with VA volume and (2) VA diameter shows a lower IRR than VA volume. 3D-reconstruction and VA volumetry may add information in diagnosing EVA in cases with or without additional IEM.

Molecular epidemiology and functional assessment of novel allelic variants of SLC26A4 in non-syndromic hearing loss patients with enlarged vestibular aqueduct in China.

BACKGROUND: Mutations 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. METHODS: A 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. RESULTS: Of 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. CONCLUSION: An 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.