Cochlear Implantation Outcome in Children with DFNB1 locus Pathogenic Variants

Abstract

Almost 60% of children with profound prelingual hearing loss (HL) have a genetic determinant of deafness, most frequently two DFNB1 locus (GJB2/GJB6 genes) recessive pathogenic variants. Only few studies combine HL etiology with cochlear implantation (CI) outcome. Patients with profound prelingual HL who received a cochlear implant before 24 months of age and had completed DFNB1 genetic testing were enrolled in the study (n = 196). LittlEARS questionnaire scores were used to assess auditory development. Our data show that children with DFNB1-related HL (n = 149) had good outcome from the CI (6.85, 22.24, and 28 scores at 0, 5, and 9 months post-CI, respectively). A better auditory development was achieved in patients who receive cochlear implants before 12 months of age. Children without residual hearing presented a higher rate of auditory development than children with responses in hearing aids over a wide frequency range prior to CI, but both groups reached a similar level of auditory development after 9 months post-CI. Our data shed light upon the benefits of CI in the homogenous group of patients with HL due to DFNB1 locus pathogenic variants and clearly demonstrate that very early CI is the most effective treatment method in this group of patients.

Functional Polymorphism of MMP9 and BDNF as Potential Biomarker of Auditory Neuroplasticity in Prelingual Deafness Treatment With Cochlear Implantation—A Retrospective Cohort Analysis

“…The findings suggest that the age at implantation is the largest factor contributing to auditory development in very young patients. Still, other factors have also been proposed to explain some implanted children’s language deficits, including etiology of deafness, developmental delay, age at onset of deafness, age at diagnosis of hearing impairment, involvement and participation in rehabilitation programs, and various environmental factors, such as the parents’ educational status ( Abdurehim et al., 2017 ; Angeli et al., 2011 ; de Raeve, 2010 ; Eppsteiner et al., 2012 ; Kral et al., 2016 ; Leigh et al., 2013 ; Levine et al., 2016 ; Oziębło et al., 2020 ; Park et al., 2017 ; Reinert et al., 2010 ; Shearer et al., 2017 ). Data of etiologic diagnosis of congenital deafness show that up to 60% of cases have a genetic background.…”

“…They are expressed in membranous labyrinth (encode connexin 26 and connexin 30, respectively), and these mutations affect the function of the organ of Corti and as a consequence lead to deafness ( Oziębło et al., 2020 ). There are some hypotheses proposed to explain the exact mechanism leading to DFNB1-related deafness, such as loss of function of ion channels or malfunction of supporting cells; however, these do not give a full understanding of the phenomenon ( Chen et al., 2014 ; Kikuchi et al., 2000 ; Oziębło et al., 2020 ). In this context, there appears to be a need to identify a possible marker that may help to identify children, whose prognosis for auditory skills development is not promising.…”

Prospective cohort study reveals MMP-9, a neuroplasticity regulator, as a prediction marker of cochlear implantation outcome in prelingual deafness treatment.

“…Patients were implanted with the same type of device, by the same experienced surgeon, and had their speech processor activated before 2 nd birthday; they also received the same rehabilitation program and their auditory development was observed for 18 months after CI activation. The literature already indicates that etiological homogeneity, such as mutations in the DFNB1 locus, have a predictive value for cochlear implantation outcome [6,7,[10][11][12]. Following this lead, our analyses focused on the subgroup of children with DFNB1-related deafness, which was further divided into patients with CI activated before and after 1 year of life.…”

“…For clinicians, it is di cult to preoperatively predict how well an individual patient will perform with a CI. Only a part of the variance in performance can be accounted for by known factors, such as age of implantation, etiology of hearing loss, existence of comorbidities, and others [1][2][3][4][5][6][7][8][9][10][11][12].…”

“…In over 50% of cases, a genetic etiology of deafness has been con rmed by mutations in the GJB2 and GJB6 genes in the DFNB1 locus [6]. The presence of pathogenic variants in the DFNB1 locus causes malfunctioning of the organ of Corti, although the molecular mechanism behind it is still under investigation [6,13,14]. Delivery of electrical stimulation to the auditory pathway involves an interplay between implant software and brain tissue (wetware) [1,4].…”