DFNA9 is a progressive audiovestibular dysfunction with a microfibrillar deposit in the inner ear

Objectives: Several mutations in the COCH gene were recently identified in American and European families with DFNA9, an autosomal dominant progressive sensorineural hearing loss with onset in high frequencies, Our]preliminary vestibular studies in one American family indicated progressive vestibular dysfunction, More complete vestibular studies in European families have shown vestibular abnormalities in the affected individuals. Our temporal bone studies on two families with DFNA9 revealed, in addition to neurosensory degeneration, a unique acidophilic deposit in the membranous labyrinths of the affected individuals. The purposes of this study were 1) to further investigate the vestibular abnormalities in members of one American family for the purposes of genotype-phenotype correlation and 2) to investigate the electron microscopic structure of the acidophilic deposit to obtain further insights into the pathogenesis of DFNA9, Study Design: Prospective analysis. Methods: Extensive vestibular testing was performed in some unaffected and affected members of a family with DFNA9, One temporal bone was analyzed by electron microsccopy of celloidin-embedded tissue. Results and Conclusions: The findings indicate progressive vestibular dysfunction in many of the patients affected with hearing loss. Thus, despite different mutations in the COCH gene, the American and European families manifest auditory and vestibular dysfunction. Electron microscopic analysis shows the spiral ligament to be enriched for a highly branched non-banded microfibrillar substance that is decorated with glycosaminoglycan granules. Additionally, the spiral ligament lacks the 67-nm-thick straight periodically banded bundles of type II collagen that are normally abundant in this structure. A speculative pathogenetic model is proposed for this unique disease and its relationship with other late-onset or adult onset audiovestibular diseases and Meniere's disease is investigated.