Clinical and Genetic Features in EYA1-Associated Branchio-Oto Syndrome: Cochlear Nerve Deficiency in Five of Thirteen Patients

Abstract

Background/Objectives: Branchio-oto syndrome (BOS) is an autosomal dominant disorder primarily associated with pathogenic variants in EYA1, mainly characterized by branchial anomalies, auricular abnormalities, and hearing loss. However, the co-occurrence of inner ear malformations in BOS remains understudied, especially severe malformations. This study aimed to investigate the clinical and genetic characteristics of patients with EYA1-associated BOS, with emphasis on cochlear nerve deficiency (CND). Methods: From January 2020 to April 2026, patients diagnosed with EYA1-associated BOS at an otology outpatient clinic in a tertiary hospital were included. Clinical manifestations, audiological assessments, imaging and genetic findings were analyzed. Results: Thirteen patients (six females and seven males) from eight unrelated families aged 0.3–58.3 years were enrolled. Branchial cleft fistulas and preauricular pits were each observed in 76.9% (10/13) of patients. The mean pure-tone average was 74.3 ± 20.7 dB HL. Eight EYA1 variants (four truncating, two large deletions, and two splicing) were identified. Among these, five were novel (c.320_329del, c.518del, c.1307dupT, c.1475+1G>A, and exon 12–18 deletion). CND was detected in 38.5% (5/13) of patients and 26.9% (7/26) of ears. Patients with CND carried either truncating variants (n = 3) or large deletions (n = 2) of EYA1. No CND was observed in patients with splicing variants. Conclusions: This study identifies five novel EYA1 pathogenic variants and suggests that CND may be a relatively common radiologic feature in EYA1-associated BOS, particularly among patients with truncating variants or large deletions, although larger studies are needed to confirm this association.