Genetic variants and audiometric patterns in nonsyndromic enlarged vestibular aqueduct Chinese children with complete...

Enlarged vestibular aqueduct (EVA) is one of the most common inner ear malformations (IEMs) leading to hearing loss in children. Although its genetic and clinical characteristics have been studied, its manifestations in completely deaf children in China, especially those with or without incomplete partition type II (IP-II), are not yet fully understood. We conducted a comprehensive analysis of 123 pediatric EVA children with complete hearing loss. Participants were classified into isolated EVA (IEVA, n = 93) and IP-II with EVA (IP-II & EVA, n = 30) groups, with 30 age-, sex-, and hearing status-matched subjects with no IEMs. Evaluations included audiologic tests and genetic screening for common deafness-associated variants. Pure-tone audiometry revealed significantly lower hearing thresholds in IEVA ears compared to those with no IEMs (1 kHz: p < 0.001; 2 kHz: p = 0.005; pure-tone average: p = 0.013). Ai-bone gap (ABG) was more prevalent in IEVA than IP-II & EVA cases (p = 0.019). Acoustically evoked short latency negative response (ASNR) was detected in 66.67% of IEVA and 63.33% of IP-II & EVA ears, significantly higher than controls. Genetic screening of 52 patients revealed pathogenic variants in 66.03%, with SLC26A4 c.919-2A > G being the predominant mutation. Biallelic mutations were significantly more common in IP-II & EVA compared to IEVA patients (p = 0.022).

EVA patients exhibit distinct audiometric patterns and genetic variants based on their inner ear morphology. The higher prevalence of biallelic SLC26A4 mutations in IP-II & EVA children suggests a stronger genetic component in this phenotype, potentially influencing clinical management strategies.

• The genetic and clinical characteristics of patients with enlarged vestibular aqueduct (EVA) have been studied. However, its manifestations in completely deaf children in China, especially those with or without incomplete partition type II (IP-II), are not yet fully understood.

• Isolated enlarged vestibular aqueduct (IEVA) patients demonstrated lower hearing thresholds but higher air-bone gap (ABG) rates compared to IP-II with EVA (IP-II & EVA) cases. The SLC26A4 c.919-2A > G mutation emerged as predominant, with biallelic mutations occurring more frequently in IP-II & EVA cases. These findings may guide clinical management strategies for affected children.