Hearing Features and Cochlear Implantation Outcomes in Patients With PathogenicMYO15AVariants: a Multicenter Observational Study

Abstract

Objectives: Recessive variants in the MYO15A gene constitute an important cause of sensorineural hearing impairment (SNHI). However, the clinical features of MYO15A-related SNHI have not been systemically investigated. This study aimed to delineate the hearing features and outcomes in patients with pathogenic MYO15A variants.Design: This study recruited 40 patients with biallelic MYO15A variants from 31 unrelated families. The patients were grouped based on the presence of N-terminal domain variants (N variants). The longitudinal audiological data and for those undergoing cochlear implantation, the auditory and speech performance with cochlear implants, were ascertained and compared between patients with different genotypes.Results: At the first audiometric examination, 32 patients (80.0%) presented with severe to profound SNHI. Patients with at least one allele of the N variant exhibited significantly better hearing levels than those with biallelic non-N variants (78.2 ± 23.9 dBHL and 94.7 ± 22.8 dBHL, respectively) (p = 0.033). Progressive SNHI was observed in 82.4% of patients with non-profound SNHI, in whom the average progression rate of hearing loss was 6.3 ± 4.8 dBHL/year irrespective of the genotypes. Most of the 25 patients who underwent cochlear implantation exhibited favorable auditory and speech performances post-implantation. Conclusions:The hearing features of patients with biallelic pathogenic MYO15A variants are characterized by severe to profound SNHI, rapid hearing progression, and favorable outcomes with cochlear implants. Periodic auditory monitoring is warranted for these patients to enable early intervention.

Revisiting Genetic Epidemiology with a Refined Targeted Gene Panel for Hereditary Hearing Impairment in the Taiwanese Population

“…Chen et al used multivariate generalized estimating equations analyses on 707 audiological records of 227 patients and concluded that hearing levels in patients with GJB2 mutations could be estimated using the following formula: predicted hearing level in dBHL = 3.78 + 0.96 x baseline hearing level in dBHL + 0.55 x duration of follow-up in year [ 9 ]. For patients with MYO15A mutations, an average progression rate for non-profound SNHI was 6.3 ± 4.8 dBHL per year [ 10 ]. In contrast, there is a paucity of studies that delineate the prognosis of hearing-impaired patients with negative genetic results.…”

“…To date, more than 200 genes have been implicated in HHI ( , last accessed on 19 February 2023). Because of its impact on speech/language development and cognitive functions [ 6 , 7 ], it is crucial to intervene in HHI early in life, and genetic testing assists in its prognostication and selection of management [ 8 , 9 , 10 , 11 , 12 ].…”

Application of Genetic Information to Cochlear Implantation in Clinical Practice

“…Genetic diagnosis plays a critical role in enabling clinicians to make informed decisions about electrode selection for cochlear implantation. Preservation of low and mid-frequency hearing has been observed in the early stages of certain genetic hearing impairments, such as pathogenic variants in the genes MYO15A [35,36], CDH23 [37], or TMPRSS3 [38]. How- ever, a significant proportion of this residual hearing tends to gradually deteriorate over time [35][36][37][38].…”

“…Preservation of low and mid-frequency hearing has been observed in the early stages of certain genetic hearing impairments, such as pathogenic variants in the genes MYO15A [35,36], CDH23 [37], or TMPRSS3 [38]. How- ever, a significant proportion of this residual hearing tends to gradually deteriorate over time [35][36][37][38]. Therefore, for individuals with MYO15A, CDH23, or TMPRSS3 variants seeking cochlear implantation, electrode selection must consider both the preservation of residual hearing and the progression of SNHI, with a thin electrode of sufficient length being the preferred choice.…”