Auditory Outcome after Cochlear Implantation in Children with DFNB7/11 Caused by Pathogenic Variants in <b><i>TMC1</i></b> Gene

Abstract

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Non-syndromic hereditary hearing loss is characterized by extreme genetic heterogeneity. So far, more than 100 pathogenic or likely pathogenic variants in &lt;i&gt;TMC1&lt;/i&gt; gene have been reported in patients with autosomal recessive hearing loss (HL) DFNB7/11. The prevailing auditory phenotype of individuals with DFNB7/11 is congenital, profound, bilateral HL, but the functional outcome after cochlear implantation (CI) described in the literature is variable. The objective of this work is to evaluate the auditory outcome after CI in pediatric patients with DFNB7/11, born to non-consanguineous parents. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A retrospective analysis of genetic and audiological data of DFNB7/11 patients followed up in a single Italian otolaryngology clinic was performed. Cases with biallelic pathogenic variants in &lt;i&gt;TMC1&lt;/i&gt; were selected from the cohort of children with non-syndromic hearing loss who had undergone CI and had been molecularly characterized by multigene panel testing. All patients underwent extensive audiological assessment, and the auditory outcome after CI was evaluated. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; DFNB7/11 was diagnosed in a total of 3 patients from 2 non-consanguineous families; a novel disease-causing variant in &lt;i&gt;TMC1&lt;/i&gt; was detected [c.962G&amp;#x3e;A p.(Trp321*)]. All the affected children showed the typical DFNB7/11 phenotype characterized by prelingual, severe-to-profound HL. The patients showed an excellent functional outcome after CI; speech perception, nonverbal cognition, and speech performance were comparable to those of patients with DFNB1 deafness. &lt;b&gt;&lt;i&gt;Discussion/Conclusion:&lt;/i&gt;&lt;/b&gt; Our results do not support the variable auditory outcome reported in the literature, which may be affected by several social and environmental factors and by the genetic background.

Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic TMC1 Variants

“…Previous work has shown variable auditory outcome in patients with pathogenic biallelic TMC1 variants [ 19 , 21 , 22 , 23 ]. Most reports are small case series with heterogeneous samples, which makes it difficult to assess the full effect of a particular genotype.…”

“…Most reports are small case series with heterogeneous samples, which makes it difficult to assess the full effect of a particular genotype. Recent study reported three patients with pathogenic compound heterozygous TMC1 variants demonstrating excellent functional outcome after Cis [ 22 ]. Interestingly, one of the patients in this study was compound heterozygous for the Finnish enriched TMC1 c.1534C>T, p.(Arg512*) variant [ 22 ].…”

“…Recent study reported three patients with pathogenic compound heterozygous TMC1 variants demonstrating excellent functional outcome after Cis [ 22 ]. Interestingly, one of the patients in this study was compound heterozygous for the Finnish enriched TMC1 c.1534C>T, p.(Arg512*) variant [ 22 ]. Another study reported 19 patients from 12 consanguineous Saudi families with pathogenic homozygous TMC1 variants with variable auditory outcome after Cis [ 19 ].…”

Skeletal muscle weakness in older adults home-restricted due to COVID-19 pandemic: a role for full-body in-bed gym and functional electrical stimulation

“…Awaiting development of implantable devices for muscle stimulation, as effective as pacemakers for cardiac arrhythmias [10], implantable stimulators for ventilation supports [11,12] or cochlear implants for hearing loss [13,14], education of sedentary patients to perform home physical exercises could be an effective low-cost alternative during and after hospitalization [15][16][17]. Cardiovascular and ventilation physical rehabilitation protocols of surgical patients are well-established approaches, whose main goal is to reverse muscle weakness [18,19].…”

To contrast and reverse skeletal muscle weakness by Full-Body In-Bed Gym in chronic COVID-19 pandemic syndrome

“…Besides eventual pharmacological treatment, a home-based physical exercise approach is helpful in counteracting muscle atrophy. Awaiting development of implantable devices for muscle stimulation, as effective as pacemakers for cardiac arrhythmias, 5 implantable stimulators for ventilatory supports, 6,7 or cochlear implants for hearing loss, 8,9 education of sedentary patients to perform home physical exercises could be an effective low-cost alternative during and after hospitalization. [10][11][12] Cardiovascular and respiratory physical rehabilitation protocols of surgical patients are well established approaches, whose main goal is to reverse muscle weakness/atrophy.…”