Characterization of Vestibular Phenotypes in Patients with Genetic Hearing Loss

Abstract

Background: The vestibular phenotypes of patients with genetic hearing loss are poorly understood. Methods: we performed genetic testing including exome sequencing and vestibular function tests to investigate vestibular phenotypes and functions in patients with genetic hearing loss. Results: Among 627 patients, 143 (22.8%) had vestibular symptoms. Genetic variations were confirmed in 45 (31.5%) of the 143 patients. Nineteen deafness genes were linked with vestibular symptoms; the most frequent genes in autosomal dominant and recessive individuals were COCH and SLC26A4, respectively. Vestibular symptoms were mostly of the vertigo type, recurrent, and persisted for hours in the genetically confirmed and unconfirmed groups. Decreased vestibular function in the caloric test, video head impulse test, cervical vestibular-evoked myogenic potential, and ocular vestibular-evoked myogenic potential was observed in 42.0%, 16.3%, 57.8%, and 85.0% of the patients, respectively. The caloric test revealed a significantly higher incidence of abnormal results in autosomal recessive individuals than in autosomal dominant individuals (p = 0.011). The genes, including SLC26A4, COCH, KCNQ4, MYH9, NLRP3, EYA4, MYO7A, MYO15A, and MYH9, were heterogeneously associated with abnormalities in the vestibular function test. Conclusions: In conclusion, diverse vestibular symptoms are commonly concomitant with genetic hearing loss and are easily overlooked.

Comparison of vestibular function in hereditary hearing loss patients with GJB2, CDH23, and SLC26A4 variants

“…Therefore, patients with variants in genes responsible for HL may exhibit a phenotype of vestibular dysfunction in addition to the HL phenotype. In a recent comprehensive study on the vestibular phenotype in patients with hereditary HL, decreased vestibular function in caloric tests, cVEMP, and oVEMP was observed in 42%, 57.8%, and 85% of patients, respectively 25 , indicating that vestibular dysfunction is common in patients with hereditary HL. However, few studies have specifically investigated vestibular function in patients with hereditary HL.…”

“…Regarding vestibular symptoms, 73% (11/15) of patients with SLC26A4 variants complained of vestibular symptoms, whereas less than 10% of patients with GJB2 (1/13) and CDH23 variants (1/11) complained of vestibular symptoms. In a study on the vestibular symptoms of 627 patients with hereditary hearing loss, 22.8% had these symptoms; moreover, the symptoms were common among patients with COCH and SLC26A4 variants 25 . Our previous large cohort study showed that only three of 75 (4%) patients with GJB2 variants and one out of 25 (4%) patients with DFNB12 complained of episodes of vestibular symptoms 7 , 15 .…”