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

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

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.

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.

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