scholarly journals Detailed clinical features and genotype–phenotype correlation in an OTOF-related hearing loss cohort in Japan

2021 ◽  
Author(s):  
Yoh-ichiro Iwasa ◽  
Shin-ya Nishio ◽  
Hidekane Yoishimura ◽  
Akiko Sugaya ◽  
Yuko Kataoka ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Clinical Characteristics ◽  
Clinical Information ◽  
Auditory Neuropathy ◽  
Hearing Level ◽  
Phenotype Correlation ◽  
Profound Hearing Loss ◽  
Genotype Phenotype Correlation ◽  
Auditory Performance

AbstractMutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype–phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype–phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a “typical” phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85–90% of the patients showed a hearing level of 20–39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed “true” auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype–phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype–phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Detailed Clinical Features and Genotype-Phenotype Correlation in an OTOF-Related Hearing Loss Cohort in Japan

2021 ◽  
Author(s):  
Yoh-ichiro Iwasa ◽  
Shin-ya Nishio ◽  
Hidekane Yoishimura ◽  
Akiko Sugaya ◽  
Yuko Kataoka ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Clinical Characteristics ◽  
Clinical Information ◽  
Auditory Neuropathy ◽  
Hearing Level ◽  
Phenotype Correlation ◽  
Profound Hearing Loss ◽  
Genotype Phenotype Correlation ◽  
Auditory Performance

Abstract OTOF is one of the most frequent causes of hereditary hearing loss and a main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in the patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 65 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.8%) showed a “typical” phenotype, prelingual and severe-to-profound hearing loss. Forty-seven patients (72.3%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39dB with cochlear implant and a CAP scale (Categories of Auditory Performance) level 6 or better. Although truncating mutations and p.R1939Q were clearly related to severe phenotype, almost half of patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.H513R, p.I1573T and p.E1910K showed “true” auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Cochlear Implant Outcomes in Patients with Neurosarcoidosis

2021 ◽  
pp. 1-7
Author(s):  
Dario Ebode ◽  
Fleur Cohen-Aubart ◽  
Stéphanie Trunet ◽  
Evelyne Ferrary ◽  
Ghizlène Lahlou ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Case Series ◽  
Corticosteroid Treatment ◽  
Auditory Neuropathy ◽  
Disease Exacerbation ◽  
Profound Hearing Loss ◽  
Hearing Recovery ◽  
Speech Performance

<b><i>Introduction:</i></b> Audiovestibular symptoms are rare in sarcoidosis, but they may also be the first manifestation of the disease. Sudden or progressive bilateral hearing loss is usually associated with vestibular impairment. The mechanism of hearing loss remains unclear, but clinical presentation and magnetic resonance imaging suggest a retrocochlear site for the lesion in most patients. Several cases of hearing recovery after corticosteroid treatment have been reported. In patients with severe or profound hearing loss, the benefit of cochlear implantation is challenging to predict in the case of auditory neuropathy and is rarely described. We present a case series of cochlear implantation in patients with documented neurosarcoidosis. <b><i>Results:</i></b> Seven cases of cochlear implantation in 4 patients with neurosarcoidosis are reported. All of the patients showed a great improvement very quickly in both quiet and noise. Speech performance remained stable over time with a follow-up ranging from 4 to 11 years, even in patients who had disease exacerbation. <b><i>Conclusion:</i></b> Cochlear implantation is possible in deaf patients with neurosarcoidosis. The excellent benefit obtained in our patients suggests a particular type of neuropathy, but endocochlear involvement cannot be entirely ruled out.

Outcome of Cochlear Implantation in Postmeningitis Profound Sensorineural Hearing Loss at Rajavithi Hospital

2021 ◽  
Vol 104 (2) ◽  
pp. 260-263
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Cochlear Implantation ◽  
Sensorineural Hearing ◽  
Preoperative Imaging ◽  
Profound Hearing Loss ◽  
Language Status ◽  
Auditory Performance ◽  
Electrode Insertion ◽  
One Year

Background: Bacterial meningitis is one of the major factors in the etiology of acquired sensorineural hearing loss in children and adults. Cochlear implantation in these patients is challenging because of inner ear ossification and fibrosis, and this procedure sometimes achieves poorer outcomes in this scenario than with other causes of sensorineural hearing loss. There has been little research into the factors affecting the outcomes of this procedure. Objective: To evaluate the outcomes of cochlear implantation in patients with postmeningitis profound sensorineural hearing loss and to evaluate the factors that affect the results. Materials and Methods: A retrospective review was conducted of thirty patients who were diagnosed with post meningitis profound hearing loss and underwent cochlear implantation at Rajavithi Hospital between 2001 and 2016. Preoperative language status, duration of deafness, preoperative imaging, and degree of electrode insertion were recorded. Categories of auditory performance-II test (CAP-II) was evaluated in all cases, one year postoperative. Results: Thirty postmeningitis deafness patients underwent cochlear implantation. The median age at diagnosis of meningitis and age at implantation were 41 years (range 1 to 75) and 49.50 years (range 3 to 75), respectively. The median duration of deafness was 12 months (range 4 to 300), and the overall mean CAP-II at one year after surgery was 5.47±2.21. The postlinguistic group had a significantly higher CAP-II score than the prelinguistic one (p=0.006). Electrodes were successfully totally inserted in 19 patients (63.3%) and partially inserted in 11 (36.7%). The average CAP-II score in the group with fully-inserted electrodes was significantly higher than in the group with partially-inserted electrodes (p=0.045). There was no correlation between CAP-II score and age at meningitis diagnosis (p=0.069), age at time of surgery (p=0.105), duration of deafness (p=0.506), or preoperative CT (p=0.228) or MRI abnormality (p=0.078). Conclusion: Cochlear implantation in patients with postmeningitis profound hearing loss had high success rates and favorable outcomes. Preoperative language status and degree of electrode insertion were factors that affected auditory performance results. Keywords: Cochlear implantation, Postmeningitis hearing loss, Sensorineural hearing loss, Meningitis, Rajavithi Hospital

Cochlear Implantation Outcomes in Children With CDH23 Mutations–Associated Hearing Loss

2021 ◽  
pp. 019459982110574
Author(s):  
Kaitian Chen ◽  
Bixue Huang ◽  
Jincangjian Sun ◽  
Yue Liang ◽  
Guanxia Xiong
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Hearing Level ◽  
Case Review ◽  
Retrospective Case ◽  
Profound Hearing Loss ◽  
Tertiary Referral Center ◽  
Cadherin 23

Objective Mutations in the cadherin 23 gene ( CDH23) have been reported to cause cochlear damage, but few studies have investigated the auditory and speech outcome of patients after cochlear implantation. Here, we describe the genetic, auditory, and postoperative outcomes of patients with CDH23 mutations who received cochlear implants. Study Design Retrospective case review. Setting Tertiary referral center. Methods Targeted deafness-related gene panels were sequenced in Chinese families with profound sensorineural hearing loss. The clinical features of subjects carrying potentially pathogenic CDH23 mutations were analyzed. Results Between 2017 and 2019, we identified 5 children with prelinguistically profound hearing loss at our center who harbored 6 variants of CDH23 that segregated with the disease. Of these, 4 variants were novel (c.2591G>T, c.4785G>C, c.5765A>G, and c.9280_9281insTT). All affected individuals had a loss of outer hair cell function, with an average residual hearing level of 3 to 10 dB SPL. Cochlear implantations were arranged for the patients at 11 to 36 months of age. All children made gains in their hearing, language, and speech performances 14 to 120 months after surgery. Their auditory outcomes improved during follow-up intervals. Conclusion This study revealed that children with congenital cochlear defects caused by CDH23 variants can acquire an acceptable auditory and speech outcome after cochlear implantation. Early genetic detection and prenatal counseling for rare deafness genes such as CDH23 remain a priority for the future.

scholarly journals Cochlear Implantation after Bacterial Meningitis in Infants Younger Than 9 Months

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
B. Y. Roukema ◽  
M. C. Van Loon ◽  
C. Smits ◽  
C. F. Smit ◽  
S. T. Goverts ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Bacterial Meningitis ◽  
Cochlear Implants ◽  
Cochlear Implantation ◽  
Speech Intelligibility ◽  
Pneumococcal Meningitis ◽  
Profound Hearing Loss ◽  
Young Infants ◽  
Key Points ◽  
Auditory Performance

Objective. To describe the audiological, anesthesiological, and surgical key points of cochlear implantation after bacterial meningitis in very young infants.Material and Methods. Between 2005 and 2010, 4 patients received 7 cochlear implants before the age of 9 months (range 4–8 months) because of profound hearing loss after pneumococcal meningitis.Results. Full electrode insertions were achieved in all operated ears. The audiological and linguistic outcome varied considerably, with categories of auditory performance (CAP) scores between 3 and 6, and speech intelligibility rating (SIR) scores between 0 and 5. The audiological, anesthesiological, and surgical issues that apply in this patient group are discussed.Conclusion. Cochlear implantation in very young postmeningitic infants is challenging due to their young age, sequelae of meningitis, and the risk of cochlear obliteration. A swift diagnostic workup is essential, specific audiological, anesthesiological, and surgical considerations apply, and the outcome is variable even in successful implantations.

Clinical characteristics and genotype–phenotype correlation of hearing loss patients withSLC26A4mutations

2007 ◽  
Vol 127 (12) ◽  
pp. 1292-1297 ◽  
Author(s):  
Hiroaki Suzuki ◽  
Aki Oshima ◽  
Koji Tsukamoto ◽  
Satoko Abe ◽  
Kozo Kumakawa ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Characteristics ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation

scholarly journals Severe or Profound Sensorineural Hearing Loss Caused by Novel USH2A Variants in Korea: Potential Genotype-Phenotype Correlation

2020 ◽  
Vol 13 (2) ◽  
pp. 113-122 ◽  
Author(s):  
Sang-Yeon Lee ◽  
Kwangsic Joo ◽  
Jayoung Oh ◽  
Jin Hee Han ◽  
Hye-Rim Park ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Cochlear Implantation ◽  
Usher Syndrome ◽  
Sensorineural Hearing ◽  
Compound Heterozygous ◽  
Compound Heterozygosity ◽  
Phenotype Correlation ◽  
Truncating Mutation ◽  
Genotype Phenotype Correlation

Objectives. We, herein, report two novel <i>USH2A</i> variants from two unrelated Korean families and their clinical phenotypes, with attention to severe or more than severe sensorineural hearing loss (SNHL).Methods. Two postlingually deafened subjects (SB237-461, M/46 and SB354-692, F/34) with more than severe SNHL and also with suspicion of Usher syndrome type II (USH2) were enrolled. A comprehensive audiological and ophthalmological assessments were evaluated. We conducted the whole exome sequencing and subsequent pathogenicity prediction analysis.Results. We identified the following variants of <i>USH2A</i> from the two probands manifesting more than severe SNHL and retinitis pigmentosa (RP): compound heterozygosity for a nonsense (c.8176C>T: p.R2723X) and a missense variant (c.1823G>A: p.C608Y) in SB237, and compound heterozygosity for two frameshift variants (c.14835delT: p.S4945fs & c.13112_13115delAAAT: p.G4371fs) in SB354. Based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, two novel variants, c.1823G>A: p.C608Y and c.14835delT: p.Ser4945fs, can be classified as “uncertain significance” and “pathogenic,” respectively. The audiogram exhibited more than severe SNHL and a down-sloping configuration, necessitating cochlear implantation. The ophthalmic examinations revealed typical features of RP. Interestingly, one proband (SB 354-692) carrying two truncating compound heterozygous variants exhibited more severe hearing loss than the other proband (SB 237-461), carrying one truncation with one missense variant.Conclusion. Our results provide insight on the expansion of audiological spectrum encompassing more than severe SNHL in Korean subjects harboring <i>USH2A</i> variants, suggesting that <i>USH2A</i> should also be included in the candidate gene of cochlear implantation. A specific combination of <i>USH2A</i> variants causing truncating proteins in both alleles could demonstrate more severe audiological phenotype than that of <i>USH2A</i> variants carrying one truncating mutation and one missense mutation, suggesting a possible genotype-phenotype correlation. The understanding of audiological complexity associated with <i>USH2A</i> will be helpful for genetic counseling and treatment starategy.

scholarly journals Validating clinical characteristic of primary failure of eruption (PFE) associated with PTH1R variants

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cristina Grippaudo ◽  
Isabella D’Apolito ◽  
Concetta Cafiero ◽  
Agnese Re ◽  
Pietro Chiurazzi ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Mutational Analysis ◽  
Clinical Signs ◽  
Open Bite ◽  
Clinical Severity ◽  
Mixed Dentition ◽  
Phenotype Correlation ◽  
Posterior Teeth ◽  
Primary Failure Of Eruption ◽  
Genotype Phenotype Correlation

Abstract Background Primary failure of eruption (PFE) is a hereditary condition, and linkage with variants in the PTH1R gene has been demonstrated in many cases. The clinical severity and expression of PFE is variable, and the genotype–phenotype correlation remains elusive. Further, the similarity between some eruption disorders that are not associated with PTH1R alterations is striking. To better understand the genotype–phenotype correlation, we examined the relationship between the eruption phenotype and PTH1R genotype in 44 patients with suspected PFE and 27 unaffected relatives. Sanger sequencing was employed to analyze carefully selected PFE patients. Potential pathogenicity of variants was evaluated against multiple genetic databases for function prediction and frequency information. Results Mutational analysis of the PTH1R coding sequence revealed 14 different variants in 38 individuals (30 patients and 8 first-degree relatives), 9 exonic and 5 intronic. Their pathogenicity has been reported and compared with the number and severity of clinical signs. In 72.7% of patients with pathogenic variants, five clinical and radiographic criteria have been found: involvement of posterior teeth, involvement of the distal teeth to the most mesial affected, supracrestal presentation, altered vertical growth of the alveolar process and posterior open-bite. In cases with mixed dentition (3), the deciduous molars of the affected quadrant were infraoccluded. Discussion The probability of an affected patient having a PTH1R variant is greater when five specific clinical characteristics are present. The likelihood of an eruption defect in the absence of specific clinical characteristics is rarely associated with a PTH1R mutation. Conclusions We report here that systematic clinical and radiographic observation using a diagnostic rubric is highly valuable in confirming PFE and offers a reliable alternative for accurate diagnosis.

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