Predictors of a positive genetic panel in early adult-onset sensorineural hearing loss

Introduction: Early adult-onset sensorineural hearing loss (EAOSNHL) occupies a distinct clinical and genetic space compared to congenital and pediatric-onset hearing loss. While multi-gene panels have revolutionized diagnostics, their yield in EAOSNHL remains low compared to childhood cases. Hence, this study aimed to bridge the diagnostic gap by identifying key predictors of a positive genetic panel in EAOSNHL.

Methods: A retrospective cohort study of patients with symmetric, bilateral EAOSNHL and age of onset before 50-years old seen by a multidisciplinary, tertiary care hearing loss genetics clinic at the University of Pennsylvania from August 2019 to December 2024 was conducted. Patients with Meniere’s disease were excluded. Data regarding demographics, medical and family history, disease characteristics, and genetic screening results was collected and analyzed with logistic regression and Fisher exact tests.

Results: Of the 135 patients [mean age of onset 35.3 + 16.3 years, 101 (74.8%) female] analyzed, 44 (32.6%) had a pathogenic or likely pathogenic variant (PLPV) detected on their hearing loss panel, with 13 (9.6%) definitive diagnoses and 11 (8.1%) completely negative panels. Severe-to-profound hearing loss (HL) was significant for PLPV (OR 2.70, p=0.018), and presence of first-degree relatives with EAOSNHL (FDR) (OR 4.30, p=0.035) was significant for definitive diagnosis. On multivariable analysis, among other combinations, having at least two of HL before 30, FDR, and severe-to-profound HL was significant for PLPV (OR 2.74, p=0.016) and definitive diagnosis (OR 3.04, p=0.042). Having at least three of mild-to-moderate HL, tinnitus, fullness, otalgia, and vertigo was significant for a negative panel (OR 5.02, p=0.016).

Conclusions: The characteristics identified in this study may help clinicians better select candidates for genetic testing, thereby improving diagnostic yield and resource utilization. Patients with negative results who were anticipated to have PLPV or definitive diagnoses may benefit from additional testing for novel genetic mutations.