Vestibular function in families with inherited autosomal dominant hearing loss

Abstract

The inner ear contains the developmentally related cochlea and peripheral vestibular labyrinth. Given the similar physiology between these two organs, hearing loss and vestibular dysfunction may be expected to occur simultaneously in individuals segregating mutations in inner ear genes. Twenty-two different genes have been discovered that when mutated lead to non-syndromic autosomal dominant hearing loss. A review of the literature indicates that families segregating mutations in 13 of these 22 genes have undergone formal clinical vestibular testing. Formal assessment revealed vestibular dysfunction in families with mutations in ten of these 13 genes. Remarkably, only families with mutations in the COCH and MYO7A genes self-report considerable vestibular challenges. Families segregating mutations in the other eight genes do not self-report significant balance problems and appear to compensate well in everyday life for vestibular deficits discovered during formal clinical vestibular assessment. An example of a family (referred to as the HL1 family) with progressive hearing loss and clinically-detected vestibular hypofunction that does not report vestibular symptoms is described in this review. Notably, one member of the HL1 family with clinically-detected vestibular hypofunction reached the summit of Mount Kilimanjaro.

Characterization of Vestibular Phenotypes in Patients with Genetic Hearing Loss

“…In our study, 19 mutated deafness genes associated with vestibular phenotypes were identified, and AD was the most common inheritance pattern. Variations in COCH, MYO7A, TECTA, WFS1, and POU4F3 with AD inheritance patterns and CDH23, GJB2, and SLC26A4 with AR inheritance patterns are associated with vestibular phenotypes [6,9,[13][14][15][28][29][30][31]42,43]. However, other genes such as DIAPH1, PMXL2, EYA4, GRHL2, KCNQ4, MYH9, and NLRP3 with AD inheritance patterns and MPZL2, MYO15A, and WFS1 with AR inheritance patterns have not been reported regarding their association with vestibular phenotypes.…”

“…Furthermore, we investigated the clinical characteristics of the vestibular phenotypes of the identified genes. Although vestibular phenotypes with hereditary hearing loss have been reported previously [9,, most of these studies enrolled few patients or described vestibular symptoms/results of vestibular function tests that focused on specific genes causing hearing loss.…”

“…Compared with hereditary hearing loss, relatively little is known about the genetic causes of vestibular disorders. The vestibular organ has cellular structures that share histological and functional homologies with those in the ear cochlea, thereby making possible the speculation that variations causing hearing loss may also induce vestibular phenotypes, such as dizziness, vertigo, and disequilibrium [9]. Although symptoms can vary, the vestibular phenotypes in patients with genetic hearing loss are manageable because central compensation mechanisms typically alleviate them, and symptoms are unlikely to be severe unless a patient has a complete bilateral vestibular loss [10].…”

“…Fewer than 20 genes responsible for vestibular disorders and hearing loss have been identified. However, the vestibular phenotypes and functions in patients with variations in these genes are poorly characterized [9,. Additionally, more genes and variations should be expected in cases of genetic hearing loss with vestibular phenotypes because of the involvement of multiple cochlear and vestibular epithelial and neuronal cells.…”