Large vestibular aqueduct syndrome: audiological, radiological, clinical, and genetic features.

PURPOSE The aim of this study was to analyze the clinical, audiological, radiological, and genetic features of a group of patients affected with large vestibular aqueduct syndrome. MATERIALS AND METHODS Seventeen patients affected with large vestibular aqueduct syndrome (LVAS), diagnosed by means of high-resolution magnetic resonance imaging of the inner ear, with 3-dimensional reconstructions of the labyrinth and by high-resolution spiral computed tomography of the temporal bone, performed only on the oldest patients, have been submitted to a complete audiological evaluation, a thyroid functional and ultrasonographic study, and a molecular study of the PDS gene. RESULTS The clinical presentation of LVAS was very variable in our group of patients. The enlarged vestibular aqueduct was bilateral in 15 cases and unilateral in 2; it was the only malformation of the labyrinth in 12 patients, whereas it was associated with other inner ear anomalies in the other 5. The hearing loss was very variable in degree (from mild to profound), age at onset, and progression. Moreover, among the 17 patients, 10 were clinically affected by Pendred's syndrome (PS), 3 by distal renal tubular acidosis associated with large vestibular aqueduct, whereas in 3 patients the large vestibular aqueduct was not syndromal. Finally, we identified mutations in the PDS gene in 5 of 10 patients with PS. CONCLUSIONS Our data underscore the frequent role of the large vestibular aqueduct syndrome in the pathogenesis of sensorineural hearing loss and the overall wide variability in its audiological features. It is also highlighted that LVAS is often part of some syndromal diseases, most of which are PS, which is often misdiagnosed because of the varying degree of thyroid symptoms. This study also underscores the possible role of hydro-electrolyte and acid-base endolymphatic fluid disorders in the pathogenesis of enlarged vestibular aqueduct syndrome.