Early audiological phenotype in patients with mutations in the USH2A gene

Abstract

Introduction: Nowadays, due to universal newborn hearing screening (UNHS) the number of children with mild-to-moderate hearing loss diagnosed in the first year of life has increased significantly. Aside from that, identification of the genetic cause improves the genetic counselling of the families and allows to reveal possible comorbidities which may need a special approach.

Objective: To present the characteristics of the early audiologic phenotype in hearing impaired patients with biallelic mutations in the USH2A gene based on systematic analysis of the audiological data.

Patients and methods: 13 patients with mutations in the USH2A gene underwent audiological examination. Most of them were found among a large group of infants with bilateral nonsyndromic sensorineural hearing loss (SNHL) examined under 12 months.

Results: Eight out of eleven children failed UNHS and were initially diagnosed as having bilateral nonsyndromic SNHL. Seven children underwent an audiological assessment before the age of 9 months. The earliest audiological examination was carried out at 1 and 3 months. The children with pathogenic variants in the USH2A gene in our examined group were identified in the first year of life via UNHS. The hearing threshold levels (HTL) for the USH2A group are compactly distributed between 51.25 dB and 66.25 dB, quartiles are 54 dB and 63.4 dB, with a median of 60 dB. The audiological profile of patients with biallelic USH2A mutations differs from audiograms of patients who had STRC-related hearing loss. We have not found any significant elevation in hearing thresholds in the first decade of life. We also estimated the prevalence of the USH2A and STRC mutations among GJB2-negative infants with bilateral nonsyndromic SNHL examined under 12 months, and it was 7.5% and 16.1%, respectively.

Conclusion: According to our results, the early hearing phenotype in pediatric patients with biallelic mutations in the USH2A- gene is characterized by nonsyndromic mild-to-moderate SNHL in the first decade of life. Our results indicate that the presence of mutations in the USH2A or STRC genes can be expected in a child with congenital mild-to-moderate nonsyndromic SNHL. This information is of practical importance for parents, as they have to know the prognosis of hearing loss for their child from the very beginning. Post-screening follow-up should include adequate clinical, genetic, and social support for children and their parents.

Keywords: Congenital mild-to-moderate nonsyndromic sensorineural hearing loss; GJB2; Retinitis pigmentosa; STRC genes; USH2A; Universal newborn hearing screening; Usher syndrome type II.