Comprehensive Etiologic Analyses in Pediatric Cochlear Implantees and the Clinical Implications

Abstract

Cochlear implantation is the treatment of choice for children with profound sensorineural hearing impairment (SNHI), yet the outcomes of cochlear implants (CI) vary significantly across individuals. To investigate the CI outcomes in pediatric patients with SNHI due to various etiologies, we prospectively recruited children who underwent CI surgery at two tertiary referral CI centers from 2010 to 2021. All patients underwent comprehensive history taking, next generation sequencing (NGS)-based genetic examinations, and imaging studies. The CI outcomes were evaluated using Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scores. Of the 160 pediatric cochlear implantees (76 females and 84 males) included in this study, comprehensive etiological work-up helped achieve clinical diagnoses in 83.1% (133/160) of the patients, with genetic factors being the leading cause (61.3%). Imaging studies identified certain findings in 31 additional patients (19.3%). Four patients (2.5%) were identified with congenital cytomegalovirus infection (cCMV), and 27 patients (16.9%) remained with unknown etiologies. Pathogenic variants in the four predominant non-syndromic SNHI genes (i.e., SLC26A4, GJB2, MYO15A, and OTOF) were associated with favorable CI outcomes (Chi-square test, p = 0.023), whereas cochlear nerve deficiency (CND) on imaging studies was associated with unfavorable CI outcomes (Chi-square test, p < 0.001). Our results demonstrated a clear correlation between the etiologies and CI outcomes, underscoring the importance of thorough etiological work-up preoperatively in pediatric CI candidates.

Precision Medicine Approach to Cochlear Implantation

“…Better speech outcome than in cases without identified genetic etiology (6,7,17) Imaging study (MRI)…”

“…All in all, implantees with an identified genetic etiology tend to achieve better speech outcomes than those with an unidentified etiology [ 6 , 7 , 12 ], although some variants are related to poor CI outcomes [ 13 ]. The information acquired from MGT can also be used to counsel patients and their families on expected outcomes after CI and the time required to reach those results.…”

“…In the era of personalized medicine, attempts have been made to associate CI performance with the etiology of hearing loss [ 6 - 8 ] and to establish surgical techniques that can maximize performance according to individual cochlear dimensions [ 9 , 10 ]. In this review, we discuss the implications of a personalized diagnosis (both genetic and nongenetic) and how it relates to the performance of CI and decision-making in patients with prelingual and postlingual hearing loss ( Table 1 ) [ 6 - 8 , 11 - 49 ].…”

Genetic Underpinnings and Audiological Characteristics in Children with Unilateral Sensorineural Hearing Loss

“…interpreted the images according to the morphological features of the cochlea, vestibule, semicircular canal, vestibular aqueduct, cochlear aperture, and cochlear nerve. Cochlear nerve deficiency (CND) is defined as the absence or reduction in the caliber of the cochlear nerve compared with the facial nerve 9 .…”

“…Identifying the molecular basis is crucial for predicting outcomes and enabling personalized medicine in children with SNHL 9 . Although USNHL has been occasionally reported in patients with Waardenburg syndrome (WS) 10 and some types of non-syndromic SNHI (such as variants in the GJB2, GJB3, TECTA, and COCH genes) 11 , the genetic underpinnings have not been comprehensively investigated in children with USNHL.…”