Heterogeneous group of genetically determined auditory neuropathy spectrum disorders

Abstract

BackgroundAuditory Neuropathy Spectrum Disorder (ANSD) is often missed by common hearing screening tests, still accounting for up to 10% of hearing impairments. ANSD has an underlying genetic factor being mostly caused by pathogenic variants in 13 genes.MethodsWe examined 122 children with impaired hearing, including 102 pediatric patients (mean age was 3.7±4.1 years) with sensorineural hearing loss (SNHL) of varying severity and 20 children with a clinically confirmed ANSD (mean age was 5.65±4.63 years). For children with SNHL, we genotyped the most frequent variants (c.35delG, c.167delT, c.235delC, c.313-326del14 and c.358-360delGAG) in theGJB2gene using quantitative PCR. For children with a clinically confirmed ANSD, we performed the whole exome sequencing and studied the obtained variants in a custom panel of 248 genes.ResultsOur findings show that fifty-six (54.9%) SNHL patients carried homozygous variants inGJB2gene. In 12 (60%) ANSD patients, we detected variants in nucleotide sequences of theOTOF(25%),CDH23, TMC1, COL11A1, PRPS1andHOMER2genes (8 of which had not been previously described). Transient Evoked Otoacoustic Emissions testing revealed differences at 500 Hz (AS, p = 0.04181) and 4000 Hz (AD, p = 0.00126) between the ANSD and SNHL patient groups. The Auditory Steady-State Response (ASSR) test demonstrated significant differences at all frequencies (p < 0.01). When comparing the results obtained from the pure-tone audiometry and ASSR tests in ANSD patients revealed statistically significant differences at 500 (AD, AS) and 1000 (AD) Hz.ConclusionsThese findings indicate that audiologists and otorhinolaryngologists should use the ASSR test in clinical practice for differential diagnosis of auditory neuropathies. According to the survey data from the parents of hearing-impaired children, rehabilitation was more successful in SNHL patients compared to ANSD patients.