Hearing loss: Conductive versus sensorineural

Hearing loss has a significant impact on quality of life, and may even compromise an individual’s ability to work and their safety – we use our hearing to constantly detect and react to environmental hazards around us. Hearing loss can have a profound impact on a person’s life. This is especially true for certain patient groups. For instance, the elderly, and those with co-existing problems that affect their ability to communicate (such as dementia, cerebrovascular disease or psychiatric disorders). Even those without co-morbidities suffer the burden of disease where communication is impaired: the young who are developing their speech and language skills and adults with language barriers or other impediments to their speech. The hearing apparatus is made up of conductive and sensorineural pathways, which may be affected by pathology, leading to deafness. This article describes the aetiology of conductive and sensorineural deafness, details the relevant clinical assessment and outlines management strategies in community practice.

De Novo ACTG1 Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser–Winter Syndrome

Actin molecules are fundamental for embryonic structural and functional differentiation; γ-actin is specifically required for the maintenance and function of cytoskeletal structures in the ear, resulting in hearing. Baraitser–Winter Syndrome (B-WS, OMIM #243310, #614583) is a rare, multiple-anomaly genetic disorder caused by mutations in either cytoplasmically expressed actin gene, ACTB (β-actin) or ACTG1 (γ-actin). The resulting actinopathies cause characteristic cerebrofrontofacial and developmental traits, including progressive sensorineural deafness. Both ACTG1-related non-syndromic A20/A26 deafness and B-WS diagnoses are characterized by hypervariable penetrance in phenotype. Here, we identify a 28th patient worldwide carrying a mutated γ-actin ACTG1 allele, with mildly manifested cerebrofrontofacial B-WS traits, hypervariable penetrance of developmental traits and sensorineural hearing loss. This patient also displays brachycephaly and a complete absence of speech faculty, previously unreported for ACTG1-related B-WS or DFNA20/26 deafness, representing phenotypic expansion. The patient’s exome sequence analyses (ES) confirms a de novo ACTG1 variant previously unlinked to the pathology. Additional microarray analysis uncover no further mutational basis for dual molecular diagnosis in our patient. We conclude that γ-actin c.542C > T, p.Ala181Val is a dominant pathogenic variant, associated with mildly manifested facial and cerebral traits typical of B-WS, hypervariable penetrance of developmental traits and sensorineural deafness. We further posit and present argument and evidence suggesting ACTG1-related non-syndromic DFNA20/A26 deafness is a manifestation of undiagnosed ACTG1-related B-WS.

AUDIOMETRIC ASSESSMENT IN POST COVID-19 PATIENTS: A CROSS-SECTIONAL STUDY IN A TERTIARY CARE HOSPITAL OF KARACHI - PAKISTAN

Objective: To assess audiometry investigations in patients having complaint of tinnitus, vertigo or hearing impairment after recovery from COVID-19 disease, having no external or middle ear diseases. Study Design: Cross-sectional study. Place and Duration of Study: United Medical and Dental College, Creek General hospital, Korangi, Karachi Pakistan, from March to May 2021. Methodology: A total of 60 patients were included in this study who had recovered from the primary COVID-19 infection and reported with the complaints of tinnitus, vertigo and hearing loss. Pure tone audiogram was assessed for sensorineural deafness, its severity and frequencies affected. Pearson Chi square test was used to see the relation of symptoms with severity of hearing loss. Results: There were 42 (70%) males and 18 (30%) female patients with age range from 18-50 years with mean age of 28.4 ± 8.1 years. Tinnitus was the most common complaint (83.3%) followed by hearing loss (28.3%) and vertigo (23.3%) patients. None of the patients with complaint of hearing loss had normal pure tone audiogram in either right or left ear (p=0.000). Patients with all the three complaints had more hearing impairment where majority had moderate or severe hearing loss (p=0.000). All patients with isolated complaint of vertigo (9 patients) had normal audiogram in both ears (p=0.000). Conclusion: Auditory and vestibular system involvement in reasonably common in COVID-19 patients. Tinnitus is the most frequent symptom and it should be investigated with full audiological investigations.

Partial Duplication of the Lateral Semicircular Canal—A Novel Anatomical Malformation in a Child with Barakat Syndrome

Several known genetic causes of sensorineural deafness are associated with dysplasia of inner ear structures, including the cochlea and labyrinth. Here, we present a child with Barakat syndrome and sensorineural hearing loss, found to have multiple inner ear anomalies including partial duplication of the posterior limb of the left lateral semicircular canal. To our knowledge, duplication of the semicircular canal has not previously been reported. This finding expands our understanding of the range of anatomical variations observed in congenital inner ear malformations, and further characterizes the phenotypic manifestations of Barakat syndrome.

Genomic analysis of childhood hearing loss in the Yoruba population of Nigeria

Although variant alleles of hundreds of genes are associated with sensorineural deafness in children, the genes and alleles involved remain largely unknown in the Sub-Saharan regions of Africa. We ascertained 56 small families mainly of Yoruba ethno-lingual ancestry in or near Ibadan, Nigeria, that had at least one individual with nonsyndromic, severe-to-profound, prelingual-onset, bilateral hearing loss not attributed to nongenetic factors. We performed a combination of exome and Sanger sequencing analyses to evaluate both nuclear and mitochondrial genomes. No biallelic pathogenic variants were identified in GJB2, a common cause of deafness in many populations. Potential causative variants were identified in genes associated with nonsyndromic hearing loss (CIB2, COL11A1, ILDR1, MYO15A, TMPRSS3, and WFS1), nonsyndromic hearing loss or Usher syndrome (CDH23, MYO7A, PCDH15, and USH2A), and other syndromic forms of hearing loss (CHD7, OPA1, and SPTLC1). Several rare mitochondrial variants, including m.1555A>G, were detected in the gene MT-RNR1 but not in control Yoruba samples. Overall, 20 (33%) of 60 independent cases of hearing loss in this cohort of families were associated with likely causal variants in genes reported to underlie deafness in other populations. None of these likely causal variants were present in more than one family, most were detected as compound heterozygotes, and 77% had not been previously associated with hearing loss. These results indicate an unusually high level of genetic heterogeneity of hearing loss in Ibadan, Nigeria and point to challenges for molecular genetic screening, counseling, and early intervention in this population.

The Tietz syndrome associated with cardiac malformation: a case report with literature review

Background Tietz syndrome is a very rare clinical entity characterized by the association of profound bilateral congenital sensorineural deafness and generalized hypopigmentation of skin, eyes, and integuments (snow white appearance). It is an autosomal dominant syndrome due to a mutation in the melanocyte inducing transcription factor (MITF) gene. The association of a heart malformation has never been reported in this syndrome. Case presentation We report two cases of two cousins aged 5 years and 20 months respectively with a history of first degree consanguineous parents. Both girls presented with diffuse hypopigmentation of the skin, blond hair, blue eyes, and bilateral diffuse retinal hypopigmentation at ocular fundus exam. Bilateral profound sensorineural hearing loss was confirmed by auditory brainstem response in both cases. Echocardiography revealed a cardiac malformation such as interventricular communication in the older cousin and interatrial communication in the younger cousin. The family investigation did not reveal a similar case among ancestors. The diagnosis of Tietz syndrome was based on clinical criteria and pedigree. The older cousin underwent a total optical correction and a right unilateral cochlear implantation followed by speech therapy with a satisfactory result after a follow-up of two years. Unfortunately, the little cousin died following a head trauma. Conclusions Tietz syndrome is a rare autosomal dominant genetic disorder, characterized by generalized albinism with bilateral profound hearing loss. It results from a nontruncating mutation in the basic domain of in the MITF gene. Its management must include, in addition to hearing and ophthalmic rehabilitation, the research and treatment of cardiac malformations which may be life-threatening.

Transcanal endoscopic treatment for congenital middle ear cholesteatoma in children

Background To investigate the feasibility and efficacy of transcanal endoscopic treatment for congenital middle ear cholesteatoma in children. Methods Eleven children diagnosed with congenital middle ear cholesteatoma were collected at Huazhong University of Science and Technology Union Shenzhen Hospital from January 2016 to December 2020. The retrospective study of their operation process, comparison of pre- and post-operative hearing result, surgical complications through the surgical video. Results Eleven children received total ear endoscopic surgery under general anesthesia. One of them received planned second operation to reconstruct the ossicular chain. At six months after operation, 11 children underwent re-examination. The mean bone conduction hearing threshold had no significant change (P>0.05), the mean air conduction hearing threshold was significantly decreased (P<0.05), and the air-bone conduction difference was significantly reduced (P<0.05). In 11 children, the air-bone conduction difference were all reduced to less than 20 dB, and 7 cases were reduced to less than 10 dB. All the children were followed up so far without sensorineural deafness, facial paralysis and other serious complications, as well as no recurrence. Conclusion Otoendoscope can provide a wide-angle field of vision and advantages in small surgical trauma, quick healing, avoiding repeated dressing changes and high acceptance of secondary surgery. Intraoperative application of 30° and 45° otoendoscope can effectively reduce residuals. Otoendoscope is widely used as a surgical method in the treatment of congenital middle ear cholesteatoma in children.

Abstract 1122‐000051: Isolated Diplacusis Due to Ipsilateral Temporal Lobe Infarction: A Case Report

Introduction : Double hearing or Diplacusis is a synchronous double perception of a sound and can have Binauralis or Monauralis pattern, with inner ear disorders being the main culprit [1] . Other forms of Auditory illusions have been reported as a co‐manifestation of stroke syndromes, but none as an isolated presentation [1][2] . This is a case of a 77‐year‐old male with acute onset isolated Diplacusis in a patient due to a right temporal lobe ischemic infarct. To our knowledge, this is the first case report of an isolated diplacusis due to cortical infarct. Methods : A case presentation with Pubmed search of review articles and case reports. Results : The patient had a past medical history of sensorineural deafness in his left ear. He described any sound heard as the same quality but occurring with an echo heard a fraction of a second later in his right ear. There was no decreased hearing quality or tinnitus reported in his right ear. His drug screen test was negative. His examination was only remarkable for a sensorineural hearing loss pattern on his left ear. His (NIHSS) was zero, and no other cranial nerve abnormalities were detected. His MRI was significant for a punctate restricted diffusion on the right temporal lobe, resembling an ischemic infarct (Figure). Conclusions : Isolated diplacusis can present as acute ischemic stroke in the temporal lobe. Further studies are needed to understand its pathophysiology.

Syndromic Deafness Gene ATP6V1B2 Controls Degeneration of Spiral Ganglion Neurons Through Modulating Proton Flux

ATP6V1B2 encodes the V1B2 subunit in V-ATPase, a proton pump responsible for the acidification of lysosomes. Mutations in this gene cause DDOD syndrome, DOORS syndrome, and Zimmermann–Laband syndrome, which share overlapping feature of congenital sensorineural deafness, onychodystrophy, and different extents of intellectual disability without or with epilepsy. However, the underlying mechanisms remain unclear. To investigate the pathological role of mutant ATP6V1B2 in the auditory system, we evaluated auditory brainstem response, distortion product otoacoustic emissions, in a transgenic line of mice carrying c.1516 C &gt; T (p.Arg506∗) in Atp6v1b2, Atp6v1b2Arg506*/Arg506*. To explore the pathogenic mechanism of neurodegeneration in the auditory pathway, immunostaining, western blotting, and RNAscope analyses were performed in Atp6v1b2Arg506*/Arg506* mice. The Atp6v1b2Arg506*/Arg506* mice showed hidden hearing loss (HHL) at early stages and developed late-onset hearing loss. We observed increased transcription of Atp6v1b1 in hair cells of Atp6v1b2Arg506*/Arg506* mice and inferred that Atp6v1b1 compensated for the Atp6v1b2 dysfunction by increasing its own transcription level. Genetic compensation in hair cells explains the milder hearing impairment in Atp6v1b2Arg506*/Arg506* mice. Apoptosis activated by lysosomal dysfunction and the subsequent blockade of autophagic flux induced the degeneration of spiral ganglion neurons and further impaired the hearing. Intraperitoneal administration of the apoptosis inhibitor, BIP-V5, improved both phenotypical and pathological outcomes in two live mutant mice. Based on the pathogenesis underlying hearing loss in Atp6v1b2-related syndromes, systemic drug administration to inhibit apoptosis might be an option for restoring the function of spiral ganglion neurons and promoting hearing, which provides a direction for future treatment.