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Cochleovestibular dysfunctions are rare conditions misrecognized. A homozygous pathogenic variation c.1561C > T (p.Arg521*) in RIPOR2 (RHO family interacting cell polarization regulator 2) has been identified by WES in Tunisian siblings suffering from congenital bilateral profound hearing and vestibular dysfunctions. In contrast to the vestibular areflexia observed in our patients, deaf Ripor2 KO mouse model and our zebrafish model have normal vestibular function. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the implementation of France's neonatal hearing loss screening programme years after its launch, and to estimate permanent bilateral neonatal hearing loss (PBNHL) prevalence and distribution by severity. Methods: This descriptive study used aggregated regional data on all births in France in 2015–2016. Screening coverage, refusal rate, positive predictive value (PPV), proportion of children with suspected PBNHL, PBNHL prevalence and distribution by severity were calculated. Results: Eight hundred thousand neonates were eligible for the screening programme per year. Between 2015 and 2016, screening coverage increased (83.3% vs. 93.8%; p < 0.001), and the refusal rate remained stable (0.1%). In 2016, when considering the additional tests performed several weeks after birth, the proportion of suspected PBNHL neonates decreased (1.4% vs. 0.9%) while the PPV increased (4.7% vs. 7.6%). In 2015, the estimated prevalence of PBNHL (moderate to profound) was 0.09% (95% CI 0.08–0.10). Among neonates with >= 41 decibels deficit, 56.8%, 16.6%, and 26.6% had moderate, severe and profound hearing loss, respectively. Conclusion: The national target of 90% screening coverage was exceeded. The additional test could be useful to avoid overcrowding in diagnostic structures. Diagnostic data quality must be improved to confirm PBNHL prevalence and distribution by severity. [ABSTRACT FROM AUTHOR]

Purpose: Deafness in infancy has longlasting consequences on brain organization. To achieve the best developmental outcomes in case of profound deafness, cochlear implantation (CI) needs to take place in a critical period during the first year of life, before the cross-modal reorganization of the brain due to auditory deprivation stabilises, preventing the typical development of the auditory cortices. Despite its importance for implantation outcomes, the nature of this critical period and the underlying neural reorganization have not been fully explored. Materials and methods: To fill this knowledge gap, we investigated the cortical responses of 12-month-old profoundly deaf infants and their age-matched controls to sounds produced by a human voice as compared to non-human sounds using functional near-infrared spectroscopy (fNIRS). The deaf infants were tested before undergoing CI surgery and wore hearing aids, allowing them to perceive low frequencies. Human voice stimuli have been shown to trigger brain responses early in development, possibly due to its evolutionary relevance for survival. Results: We found increased brain responses to the human voice in the deaf infants in the bilateral fronto-temporal areas, and their responses correlated with their residual hearing thresholds. These results suggest that even the limited sound stimulation that these deaf infants receive due to their residual hearing allowed the temporal cortices to develop sensitivity to the human voice prior to implantation. The hearing control group showed an inverted hemodynamic response to both voice and non-voice stimuli in the left parietal and right temporal areas, suggesting that by 12 months of age, they habituate rapidly to these very familiar stimuli. While both groups showed an inverted response to the non-voice stimuli, they differed in their responses to voice stimuli. Conclusions: We hypothesize that the responses found in deaf infants to human voice can be consider a good cochlear implant prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. Methods We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). Results Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. Conclusions Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

Background The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools. Methods We collected data on women with a primary infection and an infected child aged at least 1 year at the time of analysis. An accurate determination of the timing of the primary infection was based upon serial measurements of immunoglobulin (Ig) M and IgG and on IgG avidity in sera collected at each trimester. The case outcome was assessed according to a structured follow-up between birth and 48 months. Results We included 255 women and their 260 fetuses/neonates. The dating of the maternal infection was prospective in 86% of cases and retrospective in 14%. At a median follow-up of 24 months, the proportion of sensorineural hearing loss and/or neurologic sequelae were 32.4% (95% confidence interval [CI] 23.72–42.09) after a maternal primary infection in the first trimester, 0 (95% CI 0–6.49) after an infection in the second trimester, and 0 (95% CI 0–11.95) after an infection in the third trimester (P <.0001). Conclusions These results suggest that a cytomegalovirus infection can be severe only when the virus hits the fetus in the embryonic or early fetal period. Recent guidelines recommend auditory follow-ups for at least 5 years for all infected children. This raises parental anxiety and generates significant costs. We suggest that auditory and specialized neurologic follow-ups may be recommended only in cases of a maternal infection in the first trimester. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. Methods: We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). Results: Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. Conclusions: Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy. [ABSTRACT FROM AUTHOR]

Lymphatic malformations are benign malformations frequently occurring in the head and neck. Retropharyngeal location is rare, can be life threating and its management is particularly challenging. Over a three-year period, three patients presented with symptomatic (dyspnea and/or dysphagia) retropharyngeal lymphatic malformation. All were treated using a radiofrequency ablation of lymphatic malformation through a trans-oral approach. No major complications occurred following the surgery. During the follow-up, no recurrence was noted and all patients were asymptomatic. Radiofrequency ablation in the management of retropharyngeal lymphatic malformations is a simple technique with very good results and allows a fast recovery with minimum morbidity and a short hospital stay. [ABSTRACT FROM AUTHOR]

Sudden sensorineural hearing loss (SSNHL) is relatively rare and its physiopathology remains unclear, particularly in children. Our goal was to evaluate clinical characteristics, etiologies, management, treatment outcomes and prognostic factors in the pediatric population. We performed a retrospective chart review of all children registered for SSNHL between August 2004 and September 2017 in a tertiary care pediatric hospital. We analysed data regarding clinical symptoms, audiological characteristics, diagnostic investigations and treatment outcomes. Thirty-five patients were included. Mean age was 12 years (range 4–18 years). Male:female ratio was 15:20. Hearing loss was left-sided for 18 patients, right-sided for 12 patients and bilateral for 5 patients. Degree of hearing loss varied from mild to profound across frequencies in the 40 ears studied. Thirty-four patients had associated otologic symptoms: the most frequent was tinnitus (28 ears), followed by vertigo (23 ears), otalgia (5 ears) and sensation of blocked ear (5 ears). Twenty-nine patients received systemic steroids and 3 intra-tympanic steroids. In the treated group, 69% had improvement on the audiograms (14% total, 55% partial). Vestibular tests were performed in 16 patients and were abnormal in 10 patients. Radiological examination included computed tomography scan (n = 16) and/or magnetic resonance imaging (n = 33). They revealed 2 bilateral enlarged vestibular aqueducts, 1 labyrinthitis, 1 intra-cochlear haemorrhage. SSNHL can affect speech and language development in children. There are differences among the pediatric population, including inner ear malformation and immune disease. Specific work up is proposed. Appropriate diagnosis and therapeutic management are discussed. • Pediatric acute deafness is important to recognize as it affects speech development. • Specific workup should be proposed as etiologies are different from adults. • Associated otologic symptoms do not seem to be prognostic factors. • Intra-tympanic injections should be considered as salvage therapy in children. • We encourage practitioners to publish their experience to beef up limited data. [ABSTRACT FROM AUTHOR]

Mutations in MED12 gene have been described in association with syndromic and non-syndromic X-linked intellectual disability (XLID). Up to date at least three distinct XLID syndromes have been described: FG syndrome, Lujan-Fryns syndrome (LS) and Ohdo syndrome (OSMKB). In the last years, thanks to the massive use of next generation sequencing techniques (NGS) it has been possible to discover at least 16 others MED12 mutations and to expand the phenotype of MED12 -related disorders. Here we report three subjects from a large non-consanguineous family presenting with a mild to severe ID, important speech delay, behavior problems, dysmorphic facial features and hearing loss. NGS allows us to detect the MED12 missense variant c.3883C > T (p.(Arg1295Cys)) carried by the three patients. This variant has been reported in 2016 by Hu et al. in one family from a big cohort of XLID families. This clinical report contributes to expanding the phenotype associated with MED12 -mutations. [ABSTRACT FROM AUTHOR]