Predictors of cochlear implant outcomes in pediatric auditory neuropathy: A matched case-control study.

OBJECTIVES: Current evidence supports the benefits of cochlear implants (CIs) in children with hearing loss, including those with auditory neuropathy spectrum disorder (ANSD). However, there is limited evidence regarding factors that hold predictive value for intervention outcomes. DESIGN: This retrospective case-control study consisted of 66 children with CIs, including 22 with ANSD and 44 with sensorineural hearing loss (SNHL) matched on sex, age, age at CI activation, and the length of follow-up with CIs (1:2 ratio). The case and control groups were compared in the results of five open-set speech perception tests, and a Forward Linear Regression Model was used to identify factors that can predict the post-CI outcomes. RESULTS: There was no significant difference in average scores between the two groups across five outcome measures, ranging from 88.40% to 95.65%. The correlation matrix revealed that younger ages at hearing aid fitting and CI activation positively influenced improvements in speech perception test scores. Furthermore, among the variables incorporated in the regression model, the duration of follow-up with CIs, age at CI activation, and the utilization of two CIs demonstrated prognostic significance for improved post-CI speech perception outcomes. CONCLUSIONS: Children with ANSD can achieve similar open-set speech perception outcomes as children with SNHL. A longer CI follow-up, a lower age at CI activation, and the use of two CIs are predictive for optimal CI outcome.

An Umbrella Review of Cochlear Implant Outcomes in Children With Auditory Neuropathy.

PURPOSE: The objective of this overview of systematic reviews (SRs; umbrella review) was to systematically summarize and critically appraise current evidence of cochlear implant (CI) outcomes in children with auditory neuropathy spectrum disorder (ANSD). METHOD: This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. The methodological quality and the risk of bias in the included SRs were assessed using A MeaSurement Tool to Assess systematic Reviews 2 checklist and the Risk of Bias in Systematic Reviews tool, respectively. RESULTS: According to eight included SRs, children with ANSD achieve CI outcomes (speech perception performance) similar to their peers with sensorineural hearing loss. In children with postsynaptic ANSD (cochlear nerve deficiency), cochlear nerve hypoplasia is associated with better speech recognition outcomes compared with cochlear nerve aplasia, especially in the absence of additional disabilities. Except for one study, the overall quality of the included SRs was critically low, and except for three studies, evidence of a high risk of bias was identified in other included SRs. CONCLUSIONS: Current evidence supports CI benefits for children with ANSD. To improve the quality of evidence, well-designed, prospective studies with appropriate sample sizes, using valid outcome measures, clarifying matching criteria, and taking into account the role of confounding factors are essential.

Analysis of specific risk factors of neurodevelopmental disorder in hearing-impaired infants under ten months of age: "EnTNDre" an opening research stemming from a transdisciplinary partnership.

INTRODUCTION: Approximately 20% of children born with severe to profound hearing loss (HL) have an associated disorder that poses a neurodevelopmental risk [1]. The objective of this study is to identify the criteria and profiles of deaf infants at risk of neurodevelopmental disorders (NDD) to provide early intervention. METHODS: Twenty-two infants aged three to ten months with bilateral congenital deafness were included. Each child attended a consultation with a psychiatrist specializing in the development of hearing-impaired infants as part of their ENT follow-up. The quality of their early development was analyzed using the Olliac grid and well-known postural and sensorimotor criteria. The children were then classified into three groups: normal examination (Group 1), evident NDD (Group 2), and intermediate examination (Group 3). Early medical history, the etiology of deafness, cerebral imaging, and vestibular test results were collected and compared in the different groups. RESULTS: The average age of the children at the time of observation was seven months (3-10 months). All had sensorineural HL, with identified causes in 13 out of 22 cases: five cases of connexin 26 gene mutation, three cases of CHARGE syndrome, two CMV infections, one Usher syndrome, one GATA3 mutation, and one LHPL5 mutation. The average score on the Olliac grid was nine (0-15), and abnormal postural and sensorimotor behaviors were found in 15 cases out of 22 (68%). 27% of the children were classified in Group 1, 45% in Group 2, and 27% in Group 3. Children with non-isolated HL, abnormal brain MRI (8/22), malformations outside the auditory system (10/22), vestibular impairments (9/22), and/or CMV infections (2/22) were distributed as follows: 2/6 in Group 1, 9/10 in Group 2, and 3/6 in Group 3. 8/22 children had suffered perinatal complications (0/6 in Group 1, 6/10 in Group 2, and 2/5 in Group 3). Only one child had a first-degree relative with NDD. He belonged to Group 2. DISCUSSION: To our knowledge, this paper is the first to describe the development of infants with congenital deafness. It is based on an observation time that had been included in the procedure of multidisciplinary evaluations prior to cochlear implantation (CI), thanks to the partnership between a psychiatric center for deaf children and an ENT-pediatric implantology service. This consultation was aimed at assessing the quality of neurodevelopment and identifying NDD without a specific referral, with good acceptability for families. Using the Olliac grid and postural and sensorimotor criteria developed to be assessed in the routine care consultation, we identified evident early signs of NDD in 45% of infants. This group (Group 2) requires early, targeted, developmental support. Some children in an intermediate zone (Group 3) require further observation and support. CONCLUSION: The very early identification of NDD seems to be relevant in the care of hearing-impaired infants. The use of the Olliac grid and developmental scales seems relevant to identifying infants at risk for NDD.

Recurrent Benign Paroxysmal Positional Vertigo in DFNB16 Patients with Biallelic STRC Gene Deletions.

OBJECTIVE: Deletions of STRC gene (DFNB16) account for 12% of isolated congenital mild to moderate hearing loss (HL). In mice, the stereocilin protein, encoded by STRC , is present in the vestibular kinocilium embedded in the otoconial membrane of the utricular macula. Despite this, effects on vestibular function have not been widely investigated. The aim of this study was to investigate the prevalence of benign paroxysmal positional vertigo (BPPV) in a cohort of DFNB16 patients. STUDY DESIGN: Observational descriptive epidemiological study. SETTING: Single-center study, in a tertiary referral center. PATIENTS: Older than 5 years, with a genetic diagnosis of HL related to biallelic STRC gene deletions, diagnosed between 2015 and 2021. INTERVENTION: Patients or their parents were interviewed to determine whether they had experienced vertigo or episodes of BPPV. MAIN OUTCOME MEASURE: Criteria were at least five acute episodes of rotatory vertigo, each lasting less than 1 minute, episodes triggered by changes in specific head position, and an absence of neurological symptoms. RESULTS: Sixty-four patients having mild (33%) to moderate (66%) HL were included. Median age was 15 years (range, 6-48 yr). Prevalence of BPPV was 39% (25 of 64). Median age of first onset was 13 years (range, 3-18 yr). CONCLUSIONS: This study showed recurrent BPPV and early age of onset in patients with biallelic STRC gene deletions. BPPV may be associated with the HL phenotype in patients with STRC gene deletions. It is important to inform patients and families of this potential risk such that appropriate management can be proposed.

[Neonatal hearing screening]. / Le dépistage néonatal de la surdité.

Neonatal hearing screening has been developped in a large number of countries. The rational to build such nationwide programs is robust. The prevalence of hearing impairment of various etiologies is high (1/1,000), diagnosis of hearing impairment in infants is uneasy and is made most of the time after the age of 18 months when treatment is less efficient and, last, appropriate test to screen for hearing impairment are available: Otoacoustic Emission and Auditory Evoked Potential. In France the screening is organised at the regional level. The organization of such a program is complexe. Midwifes and nurses should be trained to informed the parents and to perform the test. If the test is abnormal the infant will be oriented to a specialzed department of pediatrics for appropriate diagnosis and treatment.

TITLE: Le dépistage néonatal de la surdité. ABSTRACT: Le dépistage néonatal de la surdité doit être systématiquement proposé aux familles en maternité depuis l'arrêté du 23 avril 2012. La justification de ce dépistage repose sur une prévalence élevée de la surdité (autour de 1/1 000), l'existence de tests de dépistage fiables que sont les oto-émissions acoustiques et les potentiels évoqués auditifs automatisés, l'existence d'un retard important au diagnostic en l'absence de dépistage, et le bénéfice prouvé d'une prise en charge précoce. Le dépistage néonatal de la surdité permet également un bilan étiologique précoce. L'organisation actuelle de ce dépistage repose sur les Agences régionales de santé, qui s'appuient, selon les régions, sur les réseaux de périnatalité ou les centres régionaux de dépistage néonatal. La formation du personnel de maternité concerne le circuit du dépistage néonatal, l'utilisation des appareils et l'information aux familles. Le discours doit être standardisé : il s'agit de réaliser des tests d'audition, qui peuvent ne pas être concluants et sont alors répétés le lendemain ; si besoin, on revérifiera l'audition après la sortie de la maternité. En aucun cas, un diagnostic de surdité ne doit être évoqué en maternité. En cas de test anormal, une étape de re-test est prévue dans le premier mois après la naissance, avant d'adresser l'enfant dans un centre de diagnostic et de prise en charge de la surdité, où l'annonce diagnostique et la prise en charge sont multidisciplinaires. L'organisation régionale du dépistage néonatal de la surdité a conduit à une hétérogénéité des organisations et à l'absence de données nationales annuelles. Une enquête de 2015 (Santé publique France) a montré que plus de 94 % des nouveaux nés sont dépistés, avec un taux de surdité de 0,9 pour 1 000.

Auditory processing disorder in children: the value of a multidisciplinary assessment.

PURPOSE: Auditory processing disorder (APD) may affect 0.2-5% of the paediatric population. The diagnosis of APD remains difficult because of polymorphic symptoms possibly entangled with other difficulties. The purpose of this study was to evaluate a new multi-disciplinary assessment in the French language. METHODS: The battery of tests was composed of: (a) APD targeted speech assessment: speech perception in noise, a dichotic test, temporal processing tests (patterns); (b) Psychometric assessment: sustained auditory attention, sustained visual attention, evaluation of cognitive functions; (c) phonemic identification and discrimination; (d) ENT examination, tonal and vocal audiometry and ABR recordings. The diagnosis was made if two of the targeted speech tests were 2 standard deviations (SDs) below the mean or if only one of the tests was 3 SDs below. The auditory attention tests, as well as the phonemic identification and discrimination tests were complementary to the diagnostic battery. However, they did not allow for the diagnosis of APD. RESULTS: 50 children suspected of APD benefited from this protocol, and 12 were excluded from the study. A diagnosis of APD was confirmed in 17 children (45%). 59% of the patients had associated disorders. The most effective tests for diagnosing APD were dichotic testing (p = 0.001) and pattern recognition (frequency, p = 0.001). The sustained auditory attention test (p = 0.01) and the phonemic identification and discrimination test reinforced the diagnosis of APD. CONCLUSION: It seems important to evaluate children suspected of APD with a multi-disciplinary protocol. It makes it possible to diagnose APD children, but also to identify attentional difficulties and cognitive disorders that may be associated.

Arterial spin labeling brain MRI study to evaluate the impact of deafness on cerebral perfusion in 79 children before cochlear implantation.

Age at implantation is considered to be a major factor, influencing outcomes after pediatric cochlear implantation. In the absence of acoustic input, it has been proposed that cross-modal reorganization can be detrimental for adaptation to the new electrical input provided by a cochlear implant. Here, through a retrospective study, we aimed to investigate differences in cerebral blood flow (CBF) at rest prior to implantation in children with congenital deafness compared to normally hearing children. In addition, we looked at the putative link between pre-operative rest-CBF and the oral intelligibility scores at 12 months post-implantation. Finally, we observed the evolution of perfusion with age, within brain areas showing abnormal rest-CBF associated to deafness, in deaf children and in normally hearing children. In children older than 5 years old, results showed a significant bilateral hypoperfusion in temporal regions in deaf children, particularly in Heschl's gyrus, and a significant hyperperfusion of occipital regions. Furthermore, in children older than 5 years old, whole brain voxel-by-voxel correlation analysis between pre-operative rest-CBF and oral intelligibility scores at 12 months post-implantation, showed significant negative correlation localized in the occipital regions: children who performed worse in the speech perception test one year after implantation were those presenting higher preoperative CBF values in these occipital regions. Finally, when comparing mean relative perfusion (extracted from the temporal regions found abnormal on whole-brain voxel-based analysis) across ages in patients and controls, we observed that the temporal perfusion evolution was significantly different in deaf children than in normally hearing children. Indeed, while temporal perfusion increased with age in normally hearing children, it remained stable in deaf children. We showed a critical period around 4 years old, where in the context of auditory deprivation, there is a lack of synaptic activity in auditory regions. These results support the benefits of early cochlear implantation to maximize the effectiveness of auditory rehabilitation and to avoid cross-modal reorganization.

Mutation m.3395A > G in MT-ND1 leads to variable pathologic manifestations.

A non-synonymous mtDNA mutation, m.3395A > G, which changes tyrosine in position 30 to cysteine in p.MT-ND1, was found in several patients with a wide range of clinical phenotypes such as deafness, diabetes and cerebellar syndrome but no Leber's hereditary optic neuropathy. Although this mutation has already been described, its pathogenicity has not been demonstrated. Here, it was found isolated for the first time, allowing a study to investigate its pathogenicity. To do so, we constructed cybrid cell lines and carried out a functional study to assess the possible consequences of the mutation on mitochondrial bioenergetics. Results obtained demonstrated that this mutation causes an important dysfunction of the mitochondrial respiratory chain with a decrease in both activity and quantity of complex I due to a diminution of p.MT-ND1 quantity. However, no subcomplexes were found in cybrids carrying the mutation, indicating that the quality of the complex I assembly is not affected. Moreover, based on the crystal structure of p.MT-ND1 and the data found in the literature, we propose a hypothesis for the mechanism of the degradation of p.MT-ND1. Our study provides new insights into the pathophysiology of mitochondrial diseases and in particular of MT-ND1 mutations.

High prevalence of congenital deafness on Reunion Island is due to a founder variant of LHFPL5.

Reunion Island is a French oversea department in the Indian Ocean with 1.6/1000, an estimated prevalence of deafness that is almost double as compared to the mainland France. Twelve children having isolated bilateral prelingual profound deafness along with motor delay attributed to vestibular areflexia were enrolled. Their mean walking age was 19 months. Electroretinography and temporal bone CT-scans were normal in all cases. A novel homozygous frameshift lipoma HMGIC fusion partner-like 5 (LHFPL5) variant c.185delT p.(Phe62Serfs*23) was identified using whole-exome sequencing. It was found in seven families. Four patients from two different families from both Reunion Island and mainland France, were compound heterozygous: c.185delT p.(Phe62Serfs*23) and c.472C > T p.(Arg158Trp). The phenotype observed in our patients completely mimics the hurry-scurry (hscy) murine Tmhs knock-out model. The recurrent occurrence of same LHFPL5 variant in Reunion Island is attributed to common ancestor couple born in 1693.

Intra-cochlear electrode tip fold-over.

Cochlear implantation has been performed safely for over two decades but still has various minor and major complications. We report two cases of an unusual complication of electrode implantation: tip fold-over of the electrode array within the cochlea. Both cases required undergoing explantation and re-implantation. The frequent use of fine and pre-curved electrodes particularly with the use of an insertion tool necessitates routine postoperative radiological evaluation of the electrode array. Our cases demonstrate the benefit of systematic imaging including the possible use of the Cone Beam CT intraoperatively.

Unilateral Sensorineural Hearing Loss: Medical Context and Etiology.

OBJECTIVE: Unilateral sensorineural hearing loss (USNHL) is known to impact on school performance and social skills during childhood, but the etiologies remain unclear. The aim of this study was to assess various etiologies and to study the clinical contexts in this population. METHODS: The study is a retrospective review. Characteristics of hearing loss (HL), audiometric parameters, imaging, and genetic and medical contexts were analyzed. RESULTS: Eighty children were included. USNHL was profound in 68%, could be progressive in 19%, and become bilateral in 7.5% of cases. Inner ear malformations were identified in 41% of cases; cochlear nerve deficiency (CND) was frequent (33%). Cytomegalovirus (CMV) infection and genetic syndromes were confirmed in 10 and 6% of cases, respectively. CONCLUSION: Long-term hearing follow-up remains useful in USNHL as it can become bilateral. Looking to etiology, MRI should be the gold standard, as CND is frequently observed and screening for CMV infection should be systematic. Genetic etiologies appear to be different compared to bilateral HL. Further genetic research in this domain is needed.

Pain After Cochlear Implantation: An Unusual Complication?

OBJECTIVE: To analyze clinical signs and better define the underestimated long-term pain after implantation, to discuss etiological hypothesis, and to propose our department treatment algorithm and results. STUDY DESIGN AND SETTING: Retrospective review of children implanted with complaints of atypical pain in the area of device implantation, not in the immediate postoperative period, more than or equal to 4 on the Visual Analog Pain Scale (VAPS: 0-10) in the ENT pediatric department of Trousseau and Necker Enfants Malades Hospitals between 1998 and 2015. PATIENTS: All patients had full clinical and electrophysiological checking, and had normal functioning device. Exclusion criteria were: related history of local trauma, ongoing skin infection, magnet displacement, and device failure. INTERVENTION(S): Treatments and outcomes were reviewed, with a minimum of 6 months follow up. Two groups were analyzed: Group PS: pain associated with local swelling (n = 9) and Group P: isolated pain (n = 11). The first-line treatment was medical. In Group PS, anti-inflammatory, pain medication, and antibiotics were used at the same time; in Group P, only anti-inflammatory and pain medication was used. MAIN OUTCOME MEASURE(S): Success was defined when complete resolution of pain and swelling (pain scale = 0). RESULTS: Twenty cases out of the 1,448 implanted patients in our department (1.4%) were included. Average age at first occurrence of pain was 15 years (3-22 yr). Mean delay between surgery and pain complaint was 5.8 years (0.25-14). Mean follow up was 2 years (0.5-5 yr).First line medical treatment was successful in eight cases (40%). Of the 12 patients who failed medical treatment and required surgery, two had resolution of pain with magnet change and 10 had resolution with reimplantation. (5/9 patients in Group PS and 7/11 in Group P).Microbiology was performed in 10/20 cases and analysis of explanted devices was performed in 7/10 cases. Positive microbiological culture of soft tissues was positive for 3/10 cases, biofilm was positive for 5/7 cases.Pain in the area of the implanted device can occur shortly after surgery or on long-term follow up. It has been seen in all device types. Pain may be clinically underestimated, as low VAPS grade (<5) or intermittent pain may be not reported. Low-grade infections might be a hypothesis to explain these pain. Management may include medical or surgical intervention. CONCLUSION: Pain in the implanted area can be a major complication leading to implant non-use. Rate may be underestimated because of the lack of medical report. At explantation, we recommend systematic evaluation of biofilm and device failure regardless of the suspected etiology of the pain.

Efficiency of Melatonin as Compared to Pentobarbital for Audiometry Brainstem Response in Children With Associated Disorders.

PURPOSE: Outpatient pediatric audiometry brainstem response (ABR) uses various techniques (no drug, hydroxyzine, pentobarbital, melatonin). The aim of this study was to evaluate the efficiency of melatonin as compared to pentobarbital in children with associated disorders. METHOD: This was a retrospective study that took place in a tertiary care center. Eighty-three children (34 girls and 49 boys) had performed ABR under pentobarbital (GPent) or melatonin (GMel) between 2013 and 2014 and were included. All children had associated neurological or behavioral disorders or had failed a previous ABR using another technique. Success rate, defined as completed binaural investigation, delay, and duration of sleep (minutes), as well as side effects, were compared between GPent and GMel. RESULTS: There were 56 patients in GMel and 27 in GPent, with a mean age at test of 3 years and 10 months (1-13 years) and 4 years and 1 month (1-14.5 years), respectively. Success rate was 76.8% and 88.8%, respectively (p > .05), sleep duration was 23 and 153 min (p < .0001), and mean delay was 35 and 54 min. No side effects have been reported. CONCLUSIONS: Melatonin is a drug widely used, particularly for electroencephalogram in children. Sleep duration allowed a success rate that was comparable to pentobarbital. Melatonin seems to be an efficient alternative to pentobarbital for pediatric ABR.

Pediatric cochlear implantation in residual hearing candidates.

OBJECTIVES: To propose categories for the various types of residual hearing in children and to review the outcomes of cochlear implantation (CI) in children with these different hearing conditions. METHODS: We identified 53 children with residual hearing who had received a cochlear implant. Five groups were arbitrarily defined based on auditory features: G1, characterized by low-frequency residual hearing (n=5); G2, characterized by severe sensorineural hearing loss (SNHL) and low speech discrimination (n=12); G3, characterized by asymmetric SNHL (n=9); G4, characterized by progressive SNHL (n=15); and G5, characterized by fluctuating SNHL (n=12). The main audiometric features and outcomes of the groups were analyzed. RESULTS: The mean age at implantation was 10.15 years (range, 2.5-21 years). The mean preoperative score for the discrimination of open-set words was 48%; this score increased to 74% at 12 months and 81% at 24 months after the CI procedure (G1 to G5, respectively: 79/62/77%, 50/81/88%, 59/75/86%, 35/74/67%, and 39/69/80%). Children who were implanted after 10 years of age did not improve as much as those who were implanted at a younger age (open-set word list speech perception [OSW] score at 12 months: 62% vs 83%; P=.0009). Shorter delays before surgery were predictive of better performance (P=.003). Inner ear malformation and SLC26A4 mutations were not predictive of the outcome. CONCLUSIONS: CIs provide better results compared with hearing aids in children with residual hearing. Factors that may impact the benefits of CIs in patients with residual hearing are age, delay in performing the CI procedure, which ear is implanted, and initial underestimation of the patient's hearing difficulties.

Hearing outcomes in functional surgery for middle ear malformations.

OBJECTIVES: To standardize the information for families of children having functional surgery for middle ear malformations, we describe the audiometric results of the subgroup of patients with the most favorable anatomic conditions: viable auditory canal, intact tympanic membrane, mobile stapes, and corresponding to a Jahrsdoerfer score of 8 or higher. STUDY DESIGN: Case series, tertiary referral center. METHODS: Charts of patients undergoing functional surgery for congenital middle ear malformations were reviewed for demographic data, preoperative Jahrsdoerfer score, ossicular chain status, type of ossiculoplasty, and audiometric data before and 6 months postsurgery. RESULTS: Eighteen consecutive interventions were performed on 13 patients (average age of 9 years, 8 girls and 5 boys) between 2004 and 2011. The ossiculoplasties performed were as follows: incus repositioning (4), double-layer tragal cartilage (5), intact native chain reconstruction (3), and partial ossicular prosthesis (6). Mean air bone gap (ABG) was 40.8 ± 12.4 dB preoperatively and 20.9 ± 12.9 dB postoperatively (p < 0.0001). Preoperative and postoperatively mean air conduction PTA thresholds were 49.9 ± 9.5 and 30.0 ± 14.1 dB, respectively (p < 0.0001). All ears operated on except one had air conduction improvement. There were no complications. CONCLUSION: Functional surgery for congenital middle ear malformations gives variable hearing outcomes. In this study, with the most favorable anatomic conditions, 12 ears (67%) of 18 had air conduction improvement below 30 dB.

Congenital cytomegalovirus is the second most frequent cause of bilateral hearing loss in young French children.

OBJECTIVE: To estimate the prevalence of congenital cytomegalovirus (cCMV) among causes of bilateral hearing loss in young French children. STUDY DESIGN: Children <3 years old with hearing loss were prospectively included at their first visit to a referral center. Cytomegalovirus polymerase chain reaction was performed on dried blood spots from Guthrie cards. Medical records were reviewed. RESULTS: One hundred children with bilateral hearing loss were included at a median age of 15 months; the prevalence of cCMV was 8% (8/100) (95% CI, 2.7%-13.3%) in this population and 15.4% (8/52) in the subpopulation of children with profound bilateral hearing loss. Delayed neurodevelopment and brain abnormalities on computed tomography scan were found more often in children with cCMV than in children with hearing loss without cCMV (P = .027, P = .005). In 6 of 8 cCMV cases, cCMV infection had not been diagnosed before the study. CONCLUSIONS: In a comprehensive study of the causes of bilateral hearing loss in young French children, cCMV is the second most frequent cause of hearing loss after connexin mutations. It underlines that a majority of French children with hearing loss and cCMV are not diagnosed early and therefore may not benefit from early intervention including the possibility of neonatal antiviral treatment. These results make the case for promoting systematic cytomegalovirus screening in neonates with confirmed hearing loss identified through neonatal hearing screening.

Cochlear implantation and congenital deafness: perceptive and lexical results in 2 genetically pediatric identified population.

OBJECTIVE: To evaluate the perceptive and linguistic results in 2 predefined genetic population of children with implants. STUDY DESIGN: Retrospective cohort study. SETTING: Otolaryngology department of a tertiary referral hospital. PATIENTS: Among 336 children with prelingual deafness who underwent implantation in our department between 1997 and 2007, 85 with GJB2 gene-related (Cx) deafness and 30 patients with Waardenburg syndrome (WaardS) were included. Mean age at implantation was 4.7 years (range, 15 mo to 16.5 yr) in the Cx group and 4.8 years (range, 16 mo to 16 yr) in the WaardS group. The mean follow-up period was 6.5 years (range, 19 mo to 12 yr) in the Cx group and 7.1 years (range, 27 mo to 13.5 yr) in the WaardS group. More than 75% of the families in both groups scored 4 and 5 when using the Mary Pat Moeller rating (p > 0.05). A psychoneurological evaluation was performed in one third of the patients in both groups. MAIN OUTCOME MEASURES: Patients underwent linguistic and perceptive evaluations at 12, 24, 36, and 48 months: speech perception with closed-set and open-set words, speech production (Level 1 = vocalizations to Level 5 = complex sentences), and lexical comprehension with EVIP/GaelP (Peabody Picture Vocabulary Test) tests that ranged in 5 levels (-2 SD to +2 SD). RESULTS: Score results for open-set words were 38.5%, 57.5%, 69%, and 75% in the Cx group and 30.5%, 59%, 67.5%, and 78% in the WaardS group (p > 0.05) at 12, 24, 36, and 48 months. The proportion of children in Levels 4 and 5 of speech production was 27%, 42%, 57.5%, and 58% in the Cx group and 23%, 33%, 55%, and 66% in the WaardS group (p > 0.05). Lexical result at Level -2 SD at 1 year was 90% in the Cx group and 85% in the WaardS group and that at 4 years was 70% in the Cx group and 65% in the WaardS group (p > 0.05). CONCLUSION: Perceptive and linguistic evolutions for both populations were of good quality, but lexical evaluation showed residual language difficulties in both groups.

Stapedectomy in children: causes and surgical results in 35 cases.

OBJECTIVES: To study children who had undergone stapedectomy at an age younger than 16 years to determine the causes (particularly frequency of congenital anomalies vs otosclerosis) and to analyze the functional results over the short-term, 1-year, and long-term postsurgery time course. DESIGN: Ten-year retrospective study covering 1998 to 2008. SETTING: Pediatric tertiary care centers. PATIENTS: A total of 33 patients (35 ears) underwent stapes surgery from October 1998 to October 2008. MAIN OUTCOME MEASURE: Sex, age, preoperative and postoperative audiometric test results, associated anomalies, type of surgery (stapedotomy or partial stapedectomy), method of stapes surgery, and complications. RESULTS: The median age of patients at surgery was 13.4 years, ranging from 3.3 to 15.9 years. The major cause, which was found in 25 of 35 ears (71%), was nonprogressive conductive hearing loss due to congenital stapes fixation. The second most common cause, which was found in 6 of 35 ears (17%), was otosclerosis with progressive conductive or mixed hearing loss. Three ears presented posttraumatic stapes luxation (1 child aged 3.3 years at surgery). In 1 ear, the cause was osteogenesis imperfecta. Twenty-two ears were treated via the drill or laser-assisted small fenestra technique, and 13 ears were treated by a partial removal of the footplate covered by fascia. Early functional results were good, with a median postoperative air-bone gap of 9.8 dB, and 94% of the results were considered good or very good. There was no significant difference between early, 1-year, and longer-term audiometric results. CONCLUSIONS: Congenital fixation is the major indication for stapedectomy in children younger than 16 years. Functional results are good and remain stable over time.

Screening of SLC26A4, FOXI1 and KCNJ10 genes in unilateral hearing impairment with ipsilateral enlarged vestibular aqueduct.

OBJECTIVE: To investigate the implication of SLC26A4, FOXI and KCNJ10 genes in unilateral hearing impairment associated with ipsilateral inner ear malformation (Enlargement of the vestibular aqueduct and/or Mondini dysplasia). METHODS: We have gathered 25 patients presenting unilateral hearing impairment and ipsilateral enlarged vestibular aqueduct. For each of the patients, we have analyzed SLC26A4, FOXI1 and KCNJ10 genes sequences. RESULTS: The analysis of SLC26A4 revealed only eight heterozygous SLC26A4 sequence variants, three of them being novel (p.Met147Ile, p.Asn538Asn and p.Leu627Arg). None of the patients carried a second mutation on the other allele. Moreover, the SLC26A4 locus was excluded by segregation analysis in two families. No mutations were present in FOXI1 and KCNJ10 genes. CONCLUSIONS: Together, these data suggest that SLC26A4, FOXI1 and KCNJ10 are not major determinants in unilateral deafness and enlarged vestibular aqueduct compared with their implication in Pendred syndrome and non-syndromic bilateral enlarged vestibular aqueduct.

Temperature-sensitive auditory neuropathy associated with an otoferlin mutation: Deafening fever!

Transient deafness associated with an increase in core body temperature is a rare and puzzling disorder. Temperature-dependent deafness has been previously observed in patients suffering from auditory neuropathy. Auditory neuropathy is a clinical entity of sensorineural deafness characterized by absent auditory brainstem response and normal otoacoustic emissions. Mutations in OTOF, which encodes otoferlin, have been previously reported to cause DFNB9, a non-syndromic form of deafness characterized by severe to profound prelingual hearing impairment and auditory neuropathy. Here we report a novel mutation in OTOF gene in a large family affected by temperature-dependent auditory neuropathy. Three siblings aged 10, 9 and 7 years from a consanguineous family were found to be affected by severe or profound hearing impairment that was only present when they were febrile. The non-febrile patients had only mild if any hearing impairment. Electrophysiological tests revealed auditory neuropathy. Mapping with microsatellite markers revealed a compatible linkage in the DFNB9/OTOF region in the family, prompting us to run a molecular analysis of the 48 exons and of the OTOF intron-exon boundaries. This study revealed a novel mutation p.Glu1804del in exon 44 of OTOF. The mutation was found to be homozygous in the three patients and segregated with the hearing impairment within the family. The deletion affects an amino acid that is conserved in mammalian otoferlin sequences and located in the calcium-binding domain C2F of the protein.