Genetic disorders of the vestibular system

Abstract

Purpose of review: This review highlights the current body of literature related to the genetics of inherited vestibular disorders and provides a framework for the characterization of these disorders. We emphasize peripheral causes of vestibular dysfunction and highlight recent advances in the field, point out gaps in understanding, and focus on key areas for future investigation.

Recent findings: The discovery of a modifier gene that leads to a more severe Usher syndrome phenotype calls into question the assumption that Usher syndrome is universally a monogenic disorder. Despite the use of several investigational approaches, the genetic basis of Menière's disease remains poorly understood. Evidence for a vestibular phenotype associated with DFNB1 suggests that mutations in other genes causally related to nonsyndromic hearing loss also may have an unrecognized vestibular phenotype.

Summary: Our understanding of the genetic basis for vestibular disorders is superficial. Significant challenges include defining the genetics of inherited isolated vestibular dysfunction and understanding the pathological basis of Menière's disease. However, improved characterization of inherited vestibular dysfunction, coupled with advanced genetic techniques such as targeted genome capture and massively parallel sequencing, provides an opportunity to investigate these diseases at the genetic level.

Figure 1. Classification of vestibular disorders

This simplistic classification may not fit all vestibular disorders, as the causative lesions for some disorders have yet to be identified. BPPV, benign paroxysmal positional vertigo.