Norio Kasai

Better speech performance in cochlear implant patients with GJB2-related deafness

OBJECTIVE We applied mutation screening in seven cochlear implant users to identify those persons with GJB2-related deafness to determine whether etiology of deafness was predictive of speech performance after implantation. METHODS Direct sequence of GJB2 was conducted over seven cochlear implant users with prelingual hearing impairment and their speech, language and cognitive performance was examined. RESULTS The three persons with GJB2-related deafness had a mean vocabulary of 1243 words compared to a mean vocabulary of 195 words in the four children with GJB2-unrelated deafness, although the number of patients examined here was limited. The developmental quotient (DQ) of cognitive ability also was higher in those children with GJB2-related deafness. CONCLUSIONS These preliminary results suggest that better speech performance after cochlear implantation may be observed in persons with GJB2-related deafness. In the future, detailed phenotypic studies and mutation screening for non-syndromic hearing loss may play an important role in the preoperative assessment of prelingually-deafened children.

Language development of a multiply handicapped child after cochlear implantation

The presence of additional handicaps in hearing-impaired children makes the prediction of language ability after cochlear implantation unreliable. Only limited follow-up data on developmental improvement after implantation among multiply handicapped children is available. The present study reports the course of development (audiological and linguistic) after cochlear implantation in one subject with moderate mental retardation. Preoperatively, his language development showed 34 months delay when compared to chronological age. The difference had shortened to 23 months by 2 years post-surgery. The subjects cognitive delay had not changed upon 2-year follow-up. The cochlear implant can be credited to his improvement in language development.

A Gene for Fluctuating, Progressive Autosomal Dominant Nonsyndromic Hearing Loss, DFNA16, Maps to Chromosome 2q23-24.3

The sixteenth gene to cause autosomal dominant nonsyndromic hearing loss (ADNSHL), DFNA16, maps to chromosome 2q23-24.3 and is tightly linked to markers in the D2S2380-D2S335 interval. DFNA16 is unique in that it results in the only form of ADNSHL in which the phenotype includes rapidly progressing and fluctuating hearing loss that appears to respond to steroid therapy. This observation suggests that it may be possible to stabilize hearing through medical intervention, once the biophysiology of deafness due to DFNA16 is clarified. Especially intriguing is the localization of several voltage-gated sodium-channel genes to the DFNA16 interval. These cationic channels are excellent positional and functional DFNA16 candidate genes.

High-throughput screening for GJB2 mutations—its clinical application to genetic testing in prelingual deafness screening for GJB2 mutations

OBJECTIVES Mutations in connexin26 (GJB2) are one of the most frequent causes of prelingual hearing impairment. Several different types of one-base deletions in exon2 were the most common type of GJB2 mutation regardless of ethnicity, including 35delG in American-European populations, 235delC in Japanese population and 167delT in Ashkenazi Jewish population. Various types of one-base substitutions were also considered to be causative mutations of GJB2 associated hearing impairment. This article describes a rapid and high-throughput screening procedure for the detection of one-base deletion/substitution in GJB2 with less invasive sampling procedure in the implication for the clinical application. METHODS 53 hearing-impaired children and 50 healthy controls were admitted to take part in this study program. DNA samples obtained from buccal swab were used to amplify the exon2 of GJB2, and single run with an automated sequencer was used to identify the one-base deletion. Single-base substitutions were also screened by primer-extension procedure with dye terminators. The presence of both types of mutations was confirmed by direct sequence of the GJB2 exon2. RESULTS Two of 50 controls (4%) included one-base deletion in GJB2 as heterozygote. 14 of 53 hearing impaired cases (26.4%) contained deletion in GJB2 either as homozygote (five cases) or heterozygote (nine cases) form. Sequencing analysis of whole exon2 of GJB2 identified all these deletions as 235delC. Primer-extension analysis revealed additional mutations with single base substitutions in three cases with compound heterozygote with 235delC. CONCLUSIONS Rapid screening procedure of GJB2 can be potentially useful for the identification of prelingual deafness.

Quantification of TECTA and DFNA5 expression in the developing mouse cochlea.

TECTA and DFNA5 are the mouse orthologues of the human deafness-associated genes TECTA and DFNA5. To determine how expression of these genes is regulated during development, relative mRNA abundance was examined in mice by non-radioactive RT-PCR. TECTA mRNA was detected on embryonic day 15 (E15), increased to its highest level on postnatal day 3 (P3) and then dramatically decreased by P15. Low levels persisted (adulthood, P45 to 67) with mean mRNA abundance after P15 less than 25% of P3 levels. DFNA5 mRNA expression was constant throughout these time points. These results imply that TECTA is transcribed at a particularly high level during tectorial membrane morphogenesis. In contrast, DFNA5 is present in both the developing and mature cochlea.

Language development in Japanese children who receive cochlear implant and/or hearing aid

OBJECTIVES This study aimed to investigate a wide variety of factors that influence auditory, speech, and language development following pediatric cochlear implantation (CI). STUDY DESIGN Prospective collection of language tested data in profound hearing-impaired children. HYPOTHESIS Pediatric CI can potentially be effective to development of practical communication skills and early implantation is more effective. METHODS We proposed a set of language tests (assessment package of the language development for Japanese hearing-impaired children; ALADJIN) consisting of communication skills testing (test for question-answer interaction development; TQAID), comprehensive (Peabody Picture Vocabulary Test-Revised; PVT-R and Standardized Comprehension Test for Abstract Words; SCTAW) and productive vocabulary (Word Fluency Test; WFT), and comprehensive and productive syntax (Syntactic processing Test for Aphasia; STA). Of 638 hearing-impaired children recruited for this study, 282 (44.2%) with >70 dB hearing impairment had undergone CI. After excluding children with low birth weight (<1800 g), those with >11 points on the Pervasive Developmental Disorder ASJ Rating Scale for the test of autistic tendency, and those <2 SD on Ravens Colored Progressive Matrices for the test of non-verbal intelligence, 190 children were subjected to this set of language tests. RESULTS Sixty children (31.6%) were unilateral CI-only users, 128 (67.4%) were CI-hearing aid (HA) users, and 2 (1.1%) were bilateral CI users. Hearing loss level of CI users was significantly (p<0.01) worse than that of HA-only users. However, the threshold level, maximum speech discrimination score, and speech intelligibility rating in CI users were significantly (p<0.01) better than those in HA-only users. The scores for PVT-R (p<0.01), SCTAW, and WFT in CI users were better than those in HA-only users. STA and TQAID scores in CI-HA users were significantly (p<0.05) better than those in unilateral CI-only users. The high correlation (r=0.52) has been found between the age of CI and maximum speech discrimination score. The scores of speech and language tests in the implanted children before 24 months of age have been better than those in the implanted children after 24 months of age. CONCLUSIONS We could indicate that CI was effective for language development in Japanese hearing-impaired children and early CI was more effective for productive vocabulary and syntax.

Deletion mapping of split hand/split foot malformation with hearing impairment: a case report

Split hand/split foot malformation (SHFM), which typically appears as lobster-like limb malformation, is a rare clinical condition caused by a partial deletion of chromosome 7q. Hearing impairment sometimes accompanies syndromic SHFM cases; a case of inner and middle ear malformation with SHFM is described in this report. We conducted a genetic evaluation of this patient and found a deleted region that overlaps a previously reported locus of SHFM as well as a DFNB14 locus that can cause nonsyndromic hearing impairment by autosomal recessive inheritance.

Cervical lymph node extirpation for the diagnosis of malignant lymphoma.

PurposeLymph node enlargement in the neck is a common presentation of malignant lymphoma (ML) and requires tissue sampling for accurate diagnosis. Although delayed diagnosis may be critical for some patients, unnecessary biopsy should be avoided wherever possible. This study examined the process for determining the necessity to perform a biopsy and evaluated the value of an open biopsy as a diagnostic tool to enable definite subclassification of the disease.MethodsThe subjects included 20 patients with suspected ML who underwent cervical lymph node extirpation at Okayama Saiseikai general hospital between 2007 and 2010. The decision to perform a biopsy was made based on the results of sonographic evaluation, fine needle aspiration cytology (FNAC), and serum levels of lactate dehydrase (LDH) and soluble interleukin-2 receptor (sIL-2r).ResultsThe diagnosis was ML in 15 patients (75%), Castleman’s disease in 1 (5%), and benign lymphadenopathy in 4 (20%).ConclusionsA lymph node biopsy remains the gold standard for the diagnostic evaluation of ML. Sonographic evaluation combined with serum levels of LDH and sIL-2r is useful in determining the need for biopsy. Many of the cases of ML where it was difficult to determine whether a biopsy should be performed were relatively low grade and critical conditions could be avoided by close observation of the patient.

Monosyllable speech perception of Japanese hearing aid users with prelingual hearing loss: implications for surgical indication of cochlear implant.

OBJECTIVE The monosyllable speech perception ability after years of educational intervention was compared between prelingually deafened pediatric hearing aid users and their cochlear implant counterparts. DESIGN An open-set monosyllabic speech perception test was conducted on all subjects. The test required subjects to indicate a corresponding Japanese character to that spoken by the examiner. Fifty-two subjects with prelingual hearing impairment (47 hearing aid users and 5 cochlear implant users) were examined. RESULTS Hearing aid users with average pure-tone thresholds less than 90 dB HL demonstrated generally better monosyllable perception than 70%, which was equivalent or better performance than that of the cochlear implant group. Widely dispersed speech perception was observed within the 90-99 dB HL hearing-aid user group with most subjects demonstrating less than 50% speech perception. In the cluster of >100 dB HL, few cases demonstrated more than 50% in speech perception. The perception ability of the vowel part of each mora within the cochlear implant group was 100% and corresponding to that of hearing aid users with moderate and severe hearing loss. CONCLUSION Hearing ability among cochlear implant users can be comparable with that of hearing aid users with average unaided pure-tone thresholds of 90 dB HL, after monosyllabic speech perception testing was performed.

Assessment package for language development in Japanese hearing-impaired children (ALADJIN) as a test battery for the development of practical communication.

Objectives: The measurement of language development in hearing-impaired children is an important step in assessing the appropriateness of an intervention. We proposed a set of language tests (the Assessment Package for Language Development in Japanese Hearing-Impaired Children [ALADJIN]) to evaluate the development of practical communication skills. This package consisted of communication skills (TQAID), comprehensive (PVT-R and SCTAW) and productive vocabulary (WFT), comprehensive and productive syntax (STA), and the STRAW. Methods: A total of 638 children with greater than 70-dB hearing impairment were subjected to this set of language tests. Additional tests, including the PARS, the RCPM, and parental questionnaires, were administered to assess the backgrounds of the children. Results: A trimodal distribution was observed among hearing-impaired children by the histogram-based analysis of each test. Conclusions: The ALADJIN is a useful Japanese-language evaluation kit for hearing-impaired children.