Audiovestibular findings in patients with enlargement of the vestibular aqueduct caused by mutations of SLC 26 A 4, ATP 6 V 1 B 1 or SIX 1

Abstract

Enlargement of the vestibular aqueduct (EVA) is the most common malformation of the inner ear. EVA can be observed in various disorders including DFNB 4/Pendred syndrome, branchio-oto-renal/branchio-oto (BOR/BO) syndrome, and distal renal tubular acidosis (dRTA). Characteristic phenotypes of EVA include progressive, fluctuating hearing loss (HL), and repetitive vertigo. In this study, we compared the audiovestibular findings in patients with mutations of SLC 26 A 4, ATP 6 V 1 B 1 or SIX 1 to clarify whether the anatomical enlargement itself was related to the characteristic phenotypes. We enrolled five Pendred syndrome patients with SLC 26 A 4 mutations, one dRTA patient with ATP 6 V 1 B 1 mutations and two BO syndrome patients with a SIX 1 mutation. One patient with a SIX 1 mutation showed unilateral EVA, and the others had bilateral EVA. All five patients with SLC 26 A 4 mutations had progressive HL, fluctuating HL and/or repetitive vertigo. A patient with ATP 6 V 1 B 1 mutations also showed repetitive progression HL, fluctuating HL and repetitive vertigo. Fluctuating HL and repetitive vertigo were not recognized in two patients with SIX 1 mutation, although one patient showed slight progression of HL. There were no significant positive associations in patients with SLC 26 A 4 mutations between EVA widths and pure tone averages, and the widths and maximum slow phase velocities. These findings suggested that EVA itself had no relationship with either progressive, fluctuating HL, nor repetitive vertigo. The product of SLC 26 A 4, the Cl-/HCO 3- exchanger pendrin, and the product of the ATP 6 V 1 B 1, B 1-subunit of H+-ATPase, can play a role in the maintainance of endolymph pH homeostasis. Therefore, a disruption of endolymph pH homeostasis can be associated with the characteristic phenotypes.