The Importance of Early Genetic Diagnostics of Hearing Loss in Children

Abstract

Hearing loss is one of the most common sensory deficits. It carries severe medical and social consequences, and therefore, universal newborn hearing screening was introduced at the beginning of this century. Affected patients can have hearing loss as a solitary deficit (non-syndromic hearing loss) or have other organs affected as well (syndromic hearing loss). In around 60% of cases, congenital hearing loss has a genetic etiology, where disease-causing variants can change any component of the hearing pathway. Genetic testing is usually performed by sequencing. Sanger sequencing enables analysis of the limited number of genes strictly preselected according to the clinical presentation and the prevalence among the hearing loss patients. In contrast, next-generation sequencing allows broad analysis of the numerous genes related to hearing loss, exome, or the whole genome. Identification of the genetic etiology is possible, and it makes the foundation for the genetic counselling in the family. Furthermore, it enables the identification of the comorbidities that may need a referral for specialty care, allows early treatment, helps with identification of candidates for cochlear implant, appropriate aversive/protective management, and is the foundation for the development of novel therapeutic options.

Novel GRHL2 Gene Variant Associated with Hearing Loss: A Case Report and Review of the Literature

“…The importance of genetic testing in hearing loss is not deniable. In addition to enabling identification of the genetic etiology and informed genetic counselling, it facilitates clinical interventions and targeted clinical monitoring to identify comorbidities, as reviewed in [18]. The known genetic etiology of hearing loss can also be an important factor when choosing a profession since it can, in some cases, predict the deterioration of hearing related to a noisy working environment [24].…”

“…The variant annotation and filtration were performed using Variant Annotation and Filter Tool (VarAFT; Version 2.17) [17]. Rare variants with a minor allele frequency less than 5% in genes reported to be related to syndromic and non-syndromic hearing loss were further evaluated; the gene list was previously reported in [18]. Further variant filtering and selection of candidate variants were done on the basis of data available in The Human Gene Mutation Database Professional (HGMD) [19], the Deafness Variation Database Version 8.2.1 (DVD) (deafnessvariationdatabase.org) [20], and Clinvar [21].…”

Diagnostic Assessment of Progressive Fluctuating Sensorineural Hearing Loss in Children

“…The chain-termination method of sequencing enables analysis of a small amount of genes, predetermined, according to the initial clinical findings and the professional judgement of the health care professional involved [15]. In contrast, next-generation sequencing permits analysis of a far greater amount of genes related to HL [15].…”

“…The chain-termination method of sequencing enables analysis of a small amount of genes, predetermined, according to the initial clinical findings and the professional judgement of the health care professional involved [15]. In contrast, next-generation sequencing permits analysis of a far greater amount of genes related to HL [15]. Proper genetic testing enables family counselling, documents related comorbidities that may need to be further addressed, allows early and proper intervention and finally assists in the development of novel therapeutic approaches [15].…”

“…In contrast, next-generation sequencing permits analysis of a far greater amount of genes related to HL [15]. Proper genetic testing enables family counselling, documents related comorbidities that may need to be further addressed, allows early and proper intervention and finally assists in the development of novel therapeutic approaches [15]. The evolution of Next Generation (Massively Parallel) sequencing, where vast numbers of genes can be sequenced quickly and relatively thrifty, represents the immediate present and future in genetic evaluation of PFSNHL [6].…”