Peripheral Vestibular Dysfunction Is a Common Occurrence in Children With Non-syndromic and Syndromic Genetic Hearing Loss

Abstract

Hearing loss (HL) is the most common sensory deficit in humans and is frequently accompanied by peripheral vestibular loss (PVL). While often overlooked, PVL is an important sensory dysfunction that may impair development of motor milestones in children and can have a significant negative impact on quality of life. In addition, many animal and in vitro models of deafness use vestibular hair cells as a proxy to study cochlear hair cells. The extent of vestibular end organ dysfunction associated with genetic pediatric hearing loss is not well-understood. We studied children with a known genetic cause of hearing loss who underwent routine preoperative vestibular testing prior to cochlear implantation between June 2014 and July 2020. Vestibular testing included videonystagmography, rotary chair, video head impulse testing, and/or vestibular evoked myogenic potentials. Etiology of HL was determined through history, physical examination, imaging, laboratory testing, and/or genetic testing. Forty-four children (21 female/23 male) met inclusion criteria; 24 had genetic non-syndromic and 20 had genetic syndromic forms of HL. Mean age at the time of testing was 2.8 ± 3.8 years (range 7 months−17 years). The most common cause of non-syndromic HL was due to mutations in GJB2 (n = 13) followed by MYO15A (3), MYO6 (2), POU3F4 (2), TMPRSS3 (1), CDH23 (1), TMC1 (1), and ESRRB (1). The most common forms of syndromic HL were Usher syndrome (4) and Waardenburg (4), followed by SCID/reticular dysgenesis (3), CHARGE (2), CAPOS (1), Coffin-Siris (1), Jervell and Lange-Nielsen (1), Noonan (1), peroxisome biogenesis disorder (1), Perrault (1), and Trisomy 21 (1). Overall, 23 patients (52%) had PVL. A larger proportion of children with syndromic forms of HL had PVL (12/20, 60%) compared with children with genetic non-syndromic HL (11/24, 46%), though without statistical significant (p = 0.3). The occurrence of PVL varied by affected gene. In conclusion, PVL is a common finding in children with syndromic and non-syndromic genetic HL undergoing vestibular evaluation prior to cochlear implantation. Improved understanding of the molecular physiology of vestibular hair cell dysfunction is important for clinical care as well as research involving vestibular hair cells in model organisms and in vitro models.

Novel POU3F4 variants identified in patients with inner ear malformations exhibit aberrant cellular distribution and lack of SLC6A20 transcriptional upregulation

“…Clinical findings concerning the two patients presented here are summarized in Table 1 . The clinical features displayed by the two patients corresponded to the typical hallmarks associated with genetic defects in POU3F4 , that are an IP3, EVA, intraoperative CSF gusher, HL often associated with mental deficits and/or vestibular dysfunction ( Wang et al, 2021 ).…”

A Single-Cell Level Comparison of Human Inner Ear Organoids and the Human Cochlea and Vestibular Organs

“…Current knowledge of these pathophysiological mechanisms is often missing, biased towards cochlear neurosensory epithelium, and disregards the spatiotemporal expression of genes and proteins during (human) inner ear development. Additionally, there is increasing awareness for vestibular dysfunction associated with SNHL (Wang et al, 2021). This manuscript motivates the importance of developing human inner ear atlases containing the whole inner ear throughout different stages of development.…”

Balance and Vestibular Deficits in Pediatric Patients with Autism Spectrum Disorder: An Underappreciated Clinical Aspect

“…VEMP testing was performed by a licensed audiologist and a trained assistant according to the procedure described in detail in our previous work [ 10 ]. All other vestibular testing was performed according to protocols also detailed previously [ 11 , 12 ]. All systems used were from Natus Medical Inc., except for VNG and rotary chair systems.…”