Mutations of SLC26A4 are associated with the clinical features in patients with bilateral enlargement of the vestibular aqueduct

Abstract

Enlargement of the vestibular aqueduct (EVA) is an inner ear malformation associated with both non-syndromic and syndromic forms of sensorinural hearing loss and dizziness, including Pendred's syndrome. Mutation of SLC26A4 has been found in many patients with EVA, although the mechanism by which this mutation gives rise to the malformation is still unclear. In this study, we subclassified fifteen patients with bilateral EVA into an ‘enlarged’ or ‘borderline’ group based on axial CT imaging, and examined the correlation of the SLC26A4 genotype with the clinical features. Two mutant SLC26A4 alleles were found in 89% of the ‘enlarged’ cases and 33% of the ‘borderline’ cases. Mondini's dysplasia was detected in 67% of the ‘enlarged’ cases and 33% of the ‘borderline’ cases. Episodes of dizziness occurred in 33% of the ‘enlarged’ cases and 17% of the ‘borderline’ cases, and goiter was present in 22% of the ‘enlarged’ cases and 17% of the ‘borderline’ cases. Serum thyroglobulin levels were elevated in 50% of patients with either mutant allele. Mutational analysis of SLC26A4 may facilitate the diagnosis of Pendred's syndrome and non-syndromic recessive deafness in patients with EVA.