Vestibular Phenotype-Genotype Correlation in a Cohort of 35 European Usher Syndrome Patients.

Purpose: The aim of the study was to investigate genotype-phenotype correlations in Usher syndrome (USH).

Method: Thirty-five USH patients were included, categorized into three genetic-based groups: USH1 (n = 11), USH2 (n = 22), and USH4 (n = 2). The functional and emotional impact of dizziness and equilibrium was assessed using the Dizziness Handicap Inventory (DHI), the Hospital Anxiety and Depression Scale (HADS), and the Activities-Specific Balance Confidence (ABC) Scale. Participants underwent pure-tone threshold testing, bithermal caloric testing, rotary chair testing (RCT), video head impulse test (vHIT), ocular (oVEMP) and cervical (cVEMP) vestibular evoked myogenic potentials, and posturography. Genotype-phenotype associations were analyzed.

Results: Total DHI could only distinguish USH1 (25.71 ± 21.04) from USH2 (50.13 ± 22.54, p = .024) but not between the three groups (p = .084). ABC and HADS could not also distinguish between the three USH subgroups (p = .286 and .180). Hearing loss in USH1 was significantly greater than in USH2 and USH4 (p < .001). USH1 showed greater caloric weakness than USH2 and USH4 (p < .004). RCT was not completed in USH4 but could distinguish between USH1 and USH2 (sinus 0.16 Hz, p = .033; sinus 0.32 Hz, p = .011; and sinus 0.64 Hz, p = .003). vHIT in USH1 demonstrated lower overall gain than in USH2 and USH4 (p < .001). USH1 showed higher number of absent cVEMP responses in the right and/or left ear when compared to USH2/USH4 (p < .001). USH1 showed a higher number of absent oVEMP responses in the right and/or left ear when compared to USH2 and USH4 (right ear, p < .007; left ear, p < .023). In posturography, no relevant differences were found between the three USH groups.

Conclusions: Contemporary hearing and vestibular assessment successfully differentiated between distinct USH groups. However, varying degrees of vestibular dysfunction were observed across all groups.