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Objective: Acute sensorineural hearing loss represents a spectrum of conditions characterized by sudden onset hearing loss. The "Clinical Practice Guidelines for the Diagnosis and Management of Acute Sensorineural Hearing Loss" were issued as the first clinical practice guidelines in Japan outlining the standard diagnosis and treatment. The purpose of this article is to strengthen the guidelines by adding the scientific evidence including a systematic review of the latest publications, and to widely introduce the current treatment options based on the scientific evidence., Methods: The clinical practice guidelines were completed by 1) retrospective data analysis (using nationwide survey data), 2) systematic literature review, and 3) selected clinical questions (CQs). Additional systematic review of each disease was performed to strengthen the scientific evidence of the diagnosis and treatment in the guidelines., Results: Based on the nationwide survey results and the systematic literature review summary, the standard diagnosis flowchart and treatment options, including the CQs and recommendations, were determined., Conclusion: The guidelines present a summary of the standard approaches for the diagnosis and treatment of acute sensorineural hearing loss. We hope that these guidelines will be used in medical practice and that they will initiate further research., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest in this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

MYH9-related disorder (MYH9-RD) is characterized by congenital macrothrombocytopenia and granulocyte inclusion bodies. MYH9-RD is often misdiagnosed as chronic immune thrombocytopenia. In this study, we investigated age at definitive diagnosis and indicative thrombocytopenia in 41 patients with MYH9-RD from the congenital thrombocytopenia registry in Japan. Our cohort comprises 54.8% adults over 18 years at confirmed diagnosis. We found a significant difference (p < 0.0001) between the median age at definitive diagnosis of 25.0 years and for indicative thrombocytopenia it was 9.0 years. Our findings strongly suggest diagnostic delay of MYH9-RD in Japan. Our registry system will continue to contribute to this issue., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Several methods are used for hearing loss screening; however, their benefits are uncertain. In this study, we aimed to determine the predictive factors of acute sensorineural hearing loss for clinical application by primary care doctors., Methods: This retrospective, cross-sectional study included 365 patients with acute sensorineural hearing loss without prior therapy. The patients' clinical data, demographic information, and medical histories were obtained, and they were asked about comorbidities. In addition, we assessed lifestyle factors such as stress level, alcohol consumption, marital status, and socioeconomic level. Logistic regression analysis was performed to investigate the diagnostic predictive ability of the selected factors associated with acute sensorineural hearing loss. The hearing levels of all patients were evaluated using pure tone audiometry., Results: We identified significant predictive factors for acute sensorineural hearing loss. The absence of hyperacusis was a predictive factor for sudden sensorineural hearing loss. Younger age, female sex, and marital status were predictive factors for acute low-tone hearing loss. High body mass index, high socioeconomic level, low alcohol consumption, high stress level, hyperacusis, and vertigo/dizziness were predictive factors for Ménière's disease. High body mass index and ear fullness were predictive factors for perilymph fistula. Low stress level was a predictive factor for acoustic tumours., Conclusions: Our findings can be used to distinguish between the types of acute sensorineural hearing loss. Symptoms, physical status, and lifestyle factors identified during this study are useful markers for predicting acute sensorineural hearing loss occurrence., (© 2022. The Author(s).)

Etiological studies have shown genetic disorders to be a major cause of sensorineural hearing loss, but there are a limited number of comprehensive etiological reports based on genetic analysis. In the present study, the same platform using a diagnostic DNA panel carrying 63 deafness genes and the same filtering algorithm were applied to 10,047 samples obtained from social health insurance-based genetic testing of hearing loss. The most remarkable result obtained in this comprehensive study was that the data first clarified the genetic epidemiology from congenital/early-onset deafness to late-onset hearing loss. The overall diagnostic rate was 38.8%, with the rate differing for each age group; 48.6% for the congenital/early-onset group (~5y.o.), 33.5% for the juvenile/young adult-onset group, and 18.0% for the 40+ y.o. group. Interestingly, each group showed a different kind of causative gene. With regard to the mutational spectra, there are certain recurrent variants that may be due to founder effects or hot spots. A series of haplotype studies have shown many recurrent variants are due to founder effects, which is compatible with human migration. It should be noted that, regardless of differences in the mutational spectrum, the clinical characteristics caused by particular genes can be considered universal. This comprehensive review clarified the detailed clinical characteristics (onset age, severity, progressiveness, etc.) of hearing loss caused by each gene, and will provide useful information for future clinical application, including genetic counseling and selection of appropriate interventions., (© 2021. The Author(s).)

We present detailed comparative analyses to assess population-level differences in patterns of genetic deafness between European/American and Japanese cohorts with non-syndromic hearing loss. One thousand eighty-three audiometric test results (921 European/American and 162 Japanese) from members of 168 families (48 European/American and 120 Japanese) with non-syndromic hearing loss secondary to pathogenic variants in one of three genes (KCNQ4, TECTA, WFS1) were studied. Audioprofile characteristics, specific mutation types, and protein domains were considered in the comparative analyses. Our findings support differences in audioprofiles driven by both mutation type (non-truncating vs. truncating) and ethnic background. The former finding confirms data that ascribe a phenotypic consequence to different mutation types in KCNQ4; the latter finding suggests that there are ethnic-specific effects (genetic and/or environmental) that impact gene-specific audioprofiles for TECTA and WFS1. Identifying the drivers of ethnic differences will refine our understanding of phenotype-genotype relationships and the biology of hearing and deafness.

Background: The TWNK gene encodes the twinkle protein, which is a mitochondrial helicase for DNA replication. The dominant TWNK variants cause progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, while the recessive variants cause mitochondrial DNA depletion syndrome 7 and Perrault syndrome 5. Perrault syndrome is characterized by sensorineural hearing loss in both males and females and gonadal dysfunction in females. Patients with Perrault syndrome may present early-onset cerebellar ataxia, whereas middle-age-onset cerebellar ataxia caused by TWNK variants is rare., Case Presentation: A Japanese female born to consanguineous parents presented hearing loss at age 48, a staggering gait at age 53, and numbness in her distal extremities at age 57. Neurological examination revealed sensorineural hearing loss, cerebellar ataxia, decreased deep tendon reflexes, and sensory disturbance in the distal extremities. Laboratory tests showed no abnormal findings other than a moderate elevation of pyruvate concentration levels. Brain magnetic resonance imaging revealed mild cerebellar atrophy. Using exome sequencing, we identified a homozygous TWNK variant (NM&#95;021830: c.1358G>A, p.R453Q)., Conclusions: TWNK variants could cause middle-age-onset cerebellar ataxia. Screening for TWNK variants should be considered in cases of cerebellar ataxia associated with deafness and/or peripheral neuropathy, even if the onset is not early.

Background: To date, there have been few conventional algorithms for the treatment of idiopathic sudden sensorineural hearing loss (SSNHL), as there have been only limited reports with high evidence levels. Objectives: To propose an evidence- and trend-based treatment algorithm for SSNHL. Methods: We referred not only to the evidence for each treatment, but also to trends related to treatment selection in Japan based on epidemiologic surveys, and considered the balance of the advantages and disadvantages with regard to each patient's condition. Results: We propose an algorithm that begins with the grade of SSNHL severity as the prognosis of SSNHL is strongly related to the severity of hearing loss. We selected systemic corticosteroid therapy as the first-line therapy, and Intra-tympanic corticosteroid therapy as salvage therapy. We also proposed the use of prostaglandin E1 with corticosteroids for the treatment of SSNHL patients with severe hearing loss. According to the data obtained from an epidemiologic survey, we decided time limits for the application of each treatment. Conclusion: An algorithm for the treatment for SSNHL is presented according to the results of epidemiologic surveys in Japan. It is expected that this algorithm can provide a guide to choosing the suitable treatment for SSNHL patients.

Background: CEP250 encodes the C-Nap1 protein which belongs to the CEP family of proteins. C-Nap1 has been reported to be expressed in the photoreceptor cilia and is known to interact with other ciliary proteins. Mutations of CEP250 cause atypical Usher syndrome which is characterized by early-onset sensorineural hearing loss (SNHL) and a relatively mild retinitis pigmentosa. This study tested the hypothesis that the mild cone-rod dystrophy (CRD) and SNHL in a non-consanguineous Japanese family was caused by CEP250 mutations., Methods: Detailed ophthalmic and auditory examinations were performed on the proband and her family members. Whole exome sequencing (WES) was used on the DNA obtained from the proband., Results: Electrophysiological analysis revealed a mild CRD in two family members. Adaptive optics (AO) imaging showed reduced cone density around the fovea. Auditory examinations showed a slight SNHL in both patients. WES of the proband identified compound heterozygous variants c.361C>T, p.R121*, and c.562C>T, p.R188* in CEP250. The variants were found to co-segregate with the disease in five members of the family., Conclusions: The variants of CEP250 are both null variants and according to American College of Medical Genetics and Genomics (ACMG) standards and guideline, these variants are classified into the very strong category (PVS1). The criteria for both alleles will be pathogenic. Our data indicate that mutations of CEP250 can cause mild CRD and SNHL in Japanese patients. Because the ophthalmological phenotypes were very mild, high-resolution retinal imaging analysis, such as AO, will be helpful in diagnosing CEP250-associated disease.

Some Japanese monosyllables contain consonants that are not easily discernible for individuals with sensorineural hearing loss. However, the acoustic features that make these monosyllables difficult to discern have not been clearly identified. Here, this study used the autocorrelation function (ACF), which can capture temporal features of signals, to clarify the factors influencing speech intelligibility. For each monosyllable, five factors extracted from the ACF [Φ(0): total energy; τ 1 and ϕ 1 : delay time and amplitude of the maximum peak; τ e : effective duration; W ϕ (0) : spectral centroid], voice onset time, speech intelligibility index, and loudness level were compared with the percentage of correctly perceived articulations (144 ears) obtained by 50 Japanese vowel and consonant-vowel monosyllables produced by one female speaker. Results showed that median effective duration [(τ e ) med ] was strongly correlated with the percentage of correctly perceived articulations of the consonants (r = 0.87, p < 0.01). (τ e ) med values were computed by running ACFs with the time lag at which the magnitude of the logarithmic-ACF envelope had decayed to -10 dB. Effective duration is a measure of temporal pattern persistence, i.e., the duration over which the waveform maintains a stable pattern. The authors postulate that low recognition ability is related to degraded perception of temporal fluctuation patterns.

GATA3 is a member of the GATA family of transcription factors. Heterozygous GATA3 abnormalities are associated with hypoparathyroidism, sensorineural deafness, and renal abnormality (HDR syndrome). However, this triad of symptoms does not occur in all HDR patients and other clinical features may be present in some cases. We report the clinical phenotypes and the molecular analysis of GATA3 in five Japanese HDR patients, including two familial cases. All five patients had hypoparathyroidism and sensorineural deafness, however renal abnormalities were absent in four patients. In addition, two patients with different mutations of GATA3 had female genital tract abnormalities. Sequence analysis of GATA3 demonstrated three novel (R262G, c1063delC and C318) and two reported mutations (c.432insG and c.1051-1G>T). Transient transfection assay using the GATA3 activating reporter system revealed that the transactivating activity of the R262G, c.1063delC, C318S and c.432insG mutants were markedly decreased, indicating that all four mutations are loss-of-function. In conclusion, this study reiterates the clinical variability in HDR syndrome and identifies three novel mutations of GATA3.

A retrospective diagnosis of congenital cytomegalovirus infection was made for 3 of 26 students (12%) with either bilateral profound or severe sensorineural hearing loss at a School for the Deaf in Japan by detecting viral DNA with real-time polymerase chain reaction from dried umbilical cords that had been preserved at home.

Purpose: To determine the visual characteristics of Japanese subjects with the Waardenburg syndrome type 2., Methods: The visual functions of 11 albino patients who were identified from the screening of 240 children attending a school for children with a hearing deficit were studied. The ophthalmological examinations included eye position, visual acuity, biomicroscopy, ophthalmoscopy, visual field by confrontation or Goldmann's perimetry, stereoacuity by the Titmus test, and color vision by the Ishihara pseudoisochromatic plates., Results: A combination of congenital sensory deafness and partial ocular albinism without lateral displacement of the lacrimal puncta was observed in 11 (4.6%) of the students with hearing deficit. All these children had sectorial heterochromia irides with local retinal hypopigmentation. Lid deformities were not present. The retinal vasculature was normal, and macular hypoplasty was not found. Other than 1 eye with hyperopic amblyopia, no serious visual disturbance was found in these patients., Conclusions: The 11 students were classified as having Waardenburg syndrome type 2. None had a critical visual deficit, and all had partial heterochromia irides and retinal hypopigmentation.

There have been many reports of a high rate of hearing impairment in divers. A prospective study was performed to determine whether sensorineural hearing acuity in the same divers deteriorated faster than in a normal population as they continued diving. After an observation period of approximately 5 years, audiometric examination was performed on a group of professional fishery divers who had normal hearing or sensorineural hearing loss at the time of initial study. Thirty-three ears of 18 divers were included in statistical analyses. The average hearing deterioration in the divers in 5 years, after elimination of the aging effect, was 6.6 dB (SD 4.5) and was statistically significant. We concluded that the hearing acuity of our subjects deteriorated faster than that of normal Japanese.

Objectives/hypothesis: Mutations in the mitochondrial genome may predispose people to sensorineural hearing loss. An adenine to guanine point mutation in the tRNA(Leu(UUR)) gene at nucleotide 3,243 is one of the deaf-related mutations. This mutation is reported to be associated with 0.9% of diabetes mellitus patients. However, the prevalence of this mutation in hearing-impaired patients still remains unknown. The aim of this study was to determine the prevalence of this mutation among bilaterally sensorineural hearing-impaired patients in Japan., Study Design: Retrospective survey of 100 patients with bilateral sensorineural hearing loss without any evident causes., Methods: Mitochondrial DNA fragments from the patients were amplified by polymerase chain reaction, followed by a restriction enzyme fragment length polymorphism method., Results: Three patients with this mutation were identified. Their clinical profiles were different from the category which had been considered as hearing loss caused by this mitochondrial gene mutation., Conclusions: The mutation is associated with approximately 3% of bilateral sensorineural hearing loss cases of unknown origin and is possibly distributed widely in sensorineural hearing-impaired patients in Japan.

Five Japanese families showing aminoglycoside-induced hearing loss were genetically as well as clinically investigated. A mitochondrial mutation at nucleotide 1555 was found in 28 out of 32 subjects. One hundred American control subjects did not show any evidence of the mutation at nucleotide 1555, suggesting that the 1555 A-->G (A1555G) mitochondrial mutation may be found more frequently among populations in the Asian continent. Many subjects who harbor this mitochondrial mutation exhibit a mild, high-frequency, progressive hearing loss even without aminoglycoside injection. The results presented here appear to support the hypothesis that the A1555G mutation may play a more general role in causing hearing loss.

Special emphasis was placed on the epidemiology, diagnosis and prognosis of Ménière's disease. The correct spelling was based on the epitaph of Dr. Prosper Ménière. The diagnostic criteria of the Ménière's Disease Research Committee of Japan were tabulated. Results of the epidemiological survey in Japan were compared with the data from various other countries. For the purpose of early diagnosis, a tentative plan for the differential diagnosis according to the initial symptom was presented. A review of the course and prognosis of the disease was discussed.