Developmental anomalies of the hearing organ, the cochlea, are diagnosed in approximately one-fourth of individuals with congenital deafness. Most patients with cochlear malformations remain etiologically undiagnosed due to insufficient knowledge about underlying genes or the inability to make conclusive interpretations of identified genetic variants. We used exome sequencing for genetic evaluation of hearing loss associated with cochlear malformations in three probands from unrelated families. We subsequently generated monoclonal induced pluripotent stem cell (iPSC) lines, bearing patient-specific knockins and knockouts using CRISPR/Cas9 to assess pathogenicity of candidate variants. We detected FGF3 (p.Arg165Gly) and GREB1L (p.Cys186Arg), variants of uncertain significance in two recognized genes for deafness, and PBXIP1(p.Trp574*) in a candidate gene. Upon differentiation of iPSCs towards inner ear organoids, we observed significant developmental aberrations in knockout lines compared to their isogenic controls. Patient-specific single nucleotide variants (SNVs) showed similar abnormalities as the knockout lines, functionally supporting their causality in the observed phenotype. Therefore, we present human inner ear organoids as a tool to rapidly validate the pathogenicity of DNA variants associated with cochlear malformations.

BACKGROUND: To report the presentation, diagnostic process, management and results of cochlear implantation of patients diagnosed with Bjornstad syndrome with profound sensorineural hearing loss (SNHL).
UNASSIGNED: A retrospective report of two siblings with Bjornstad syndrome suffering profound SNHL unresponsive to conventional hearing aids treated with bilateral simultaneous cochlear implantation.
METHODS: Tertiary-referral center.
RESULTS: Cochlear implant surgeries of two siblings (four ears) with profound SNHL and bilateral inner ear anomaly (incomplete partition type 1) were performed without complications. Postoperative audiometric measurements showed a significiant improvement in pure-tone threshold and a word recognition score. In the literature review, no previous case of Bjornstad syndrome treated with cochlear implantation has been reported.
CONCLUSIONS: Cochlear implantation is an effective, safe, and ultimate treatment option for Bjornstad syndrome with profound SNHL not responding to hearing aids.

Auditory nerve dysplasia (AND) can encompass various conditions of the auditory nerve (AN), ranging from true aplasia to hypoplasia. The purpose of this review is to discuss the prospect of cochlear implantation (CI) and subsequent auditory speech rehabilitation for AN abnormality. Studies of different authors when working with this category of children, possible results and methods of diagnostics of the AN condition are presented.
Дисплазия слухового нерва может охватывать различные состояния слухового нерва, начиная от истинной аплазии до гипоплазии. Целью обзора является обсуждение перспективы проведения кохлеарной имплантации и последующей слухоречевой реабилитации при аномалии слухового нерва. Представлены исследования различных авторов о работе с данной категорией детей, возможные результаты и методы диагностики состояния слухового нерва.

OBJECTIVE: To report on our experience with the slim modiolar electrode (SME) especially focusing on the wide range of etiologies including inner ear anomalies, tumors, ossifications, and even revision surgeries.
METHODS: All the cochlear implantation cases performed from June 2018 to September 2019 by a single surgeon was prospectively recruited. The molecular/radiological etiology of hearing loss, intraoperative outcomes, and radiographic studies of cases where the SME was implanted was reviewed to evaluate compatibility of SME for the wide range of etiologies. For cases where SME replaced the other electrode as a revision, audiologic assessment was also made.
RESULTS: Among the 99 ears implanted during the study period, the SME was successfully implanted in 86 ears. These SME cases comprised inner ear anomaly/cochear nerve deficiency (n = 21) including cochlear hypoplasia type IV with the modiolus, intracochlear schwannoma (n = 1), far advanced otosclerosis (n = 1) and 7 revision cases. The SME was successfully used in 7 revision surgeries to replace the existing electrode. Shorter spiral diameter and decreased intracochlear position index for SME was found compared with their previous electrodes. Four out of the 6 patients who received revision implantation showed better speech perception after their surgeries.
CONCLUSIONS: The SME can be implanted in any cases unless the integrity of the modiolus is totally compromised. Due to its slim design and tight modiolar-hugging feature, good functional outcome can also be anticipated. Additionally, it is suitable for revision surgeries possibly allowing better hearing outcomes which may be attributed to its closer proximity to the modiolus.

BACKGROUND: Dizziness is not a common symptom in the lateral semicircular canal (LSCC) dysplasia, and nystagmus findings has been rarely described in LSCC dysplasia.
OBJECTIVE: To investigate the characteristics of spontaneous and positional nystagmus in patients with LSCC dysplasia.
METHODS: Patterns of spontaneous and positional nystagmus of twelve patients with LSCC dysplasia, who visited our clinic with a chief complaint of dizziness, were investigated.
RESULTS: LSCC dysplasia was observed unilaterally in 4, and bilaterally in 8 patients. Non-rotatory dizziness with various onset times was the most common description of dizziness, and unilateral caloric weakness was observed in 82% of patients. Direction-fixed nystagmus, in which the direction of spontaneous nystagmus was same with that of positional nystagmus, was observed in 9 patients, and direction-changing positional nystagmus, in which the direction of nystagmus was changed from that of spontaneous nystagmus by positioning maneuvers, was observed in 3 patients, of whom down-beating or direction-changing spontaneous nystagmus was observed in one patient each.
CONCLUSIONS: While direction-fixed horizontal nystagmus is the most commonly observed type of nystagmus in LSCC dysplasia, atypical spontaneous nystagmus, such as down-beating nystagmus or direction-changing spontaneous nystagmus, may be observed in patients with bilateral LSCC dysplasia.

BACKGROUND: Patients with sensorineural hearing loss suffer concomitant vestibular dysfunction that is more prevalent in patients with inner ear anomaly and could be aggravated with cochlear implantation. To assess the vestibular dysfunction in patients with cochlear implantation, we compared their results with those of patients with and without inner ear anomaly.
METHODS: This is a historical cohort study lasting for 20 years on 50 patients with cochlear implantation. All patients underwent dynamic posturography and Bruininks-Oseretsky Test.
RESULTS: Twenty-two (44%) of the participants showed some types of inner ear anomaly. The frequency of abnormal Bruininks-Oseretsky Test was 45.5% and 10.7% (P = .005, odds ratio [OR] = 6.9). Abnormal composite was seen in 77.3% and 21.4%, respectively (P < .001; OR = 12.5). The mean strategy score in the fifth condition of the sensory organization test was 25.0 ± 20.4 in patients with inner ear anomaly, whereas it was 44.1 ± 18.9 in those without it (P = .001).
CONCLUSIONS: Balance capability in cochlear implantation patients with inner ear anomaly compared to those without inner ear anomaly was worse. More vestibular rehabilitation treatment plans are suggested for these patients.

OBJECTIVE: This study was performed to evaluate the frequency of bony cochlear nerve canal (BCNC) stenosis and its clinical significance in pediatric patients with unilateral sensorineural hearing loss (SNHL) of unknown etiology.
METHODS: We analyzed the medical records and temporal bone computed tomography (CT) results of patients less than 13 years of age with a diagnosis of unilateral SNHL of unknown etiology between July 2007 and July 2017. We compared the BCNC diameter between both sides and analyzed the age at diagnosis, degree of hearing loss, and accompanying inner ear anomalies.
RESULTS: In 42 patients, the mean age at diagnosis was 7.4 ± 3.6 years, and the average hearing level in the affected ear was 87.9 ± 20.0 dB HL (decibels hearing level). The average diameter of the BCNC was 1.22 ± 0.75 mm on the affected side and 1.96 ± 0.52 mm on the normal side. The most suitable criterion for BCNC stenosis appeared to be a diameter of 1.2 mm by the recursive partitioning procedure. With application of this criterion, the rate of BCNC stenosis was significantly greater on the affected side than on the normal side (52.4% vs. 4.8%, respectively; P < 0.05). A narrow internal acoustic canal was found in two patients, and vestibular and cochlear anomalies were found in three patients each.
CONCLUSIONS: Our results suggest that it is reasonable to set a diameter of 1.2 mm as a cutoff for BCNC stenosis, and also that BCNC stenosis is a common cause of unilateral SNHL of unknown etiology in childhood.

CONCLUSIONS: The present study revealed that various etiologies are involved in single-sided deafness (SSD), and that the cause of SSD and asymmetrical hearing loss (AHL) differed greatly between congenital/early-onset cases and adult cases. Clarification of the etiology is the first step toward providing appropriate intervention.
OBJECTIVE: The study aimed to clarify the etiology of SSD and AHL patients.
METHODS: The etiology of a total of 527 SSD or AHL patients who visited Shinshu University Hospital between 2006 and 2016 were analyzed by imaging as well as serological tests for mumps virus, and CMV DNA testing.
RESULTS: In our cohort of congenital/early-onset SSD (n = 210), the most prevalent cause in children was cochlear nerve deficiency (43.7%; 87 of 199 patients undergoing CT and/or MRI), followed by CMV infection, mumps infection, anomalies of the inner ear, ANSD, and other rare etiologies. In contrast, half of the adult SSD patients presented with idiopathic sensorineural hearing loss, followed by various types of otitis media, cerebellopontine angle tumor and other rare etiologies.

OBJECTIVE: Gusher in inner ear malformations is common in patients with incomplete partition type I and type III. It is also common in less severe form as oozing in incomplete partition type II and large vestibular aqueduct. It is important to prevent cerebrospinal fluid (CSF) escape around the electrode to prevent meningitis.
METHODS: The custom-made device was produced by Med-El Company. It has a \"cork\"-like stopper instead of the usual silicon ring to prevent gusher. There are two types of electrodes of different lengths. The standard one is 25mm (contact space 1.7mm) and the short one is 20mm (contact space 1.3mm). It was used in 50 patients with different inner ear malformations.
RESULTS: Thirteen patients had gusher, and 11 patients oozing during cochleostomy. One patient with initial prototype of the cork electrode had to be revised because of persistent oozing around the electrode. Another patient had slow extrusion of the electrode most probably due to CSF pulsation and had to be revised. Both patients had no more CSF fistula.
CONCLUSIONS: CSF fistula in inner ear malformations is a serious situation which may lead to recurrent meningitis. The new electrode with \"cork\" stopper looks promising in preventing the postoperative CSF leak around the electrode.

Combination of middle and inner ear anomaly is extremely rare. We describe a case where there was inner and middle ear anomaly on the right side and inner ear anomaly on the left side. This patient also had anomalous interposition of air cells between the middle and inner ear on the right side which precluded the use of cochlear implant. No such findings have been reported till date to the best of our knowledge.