HDR syndrome: Large cohort and systematic review.

HDR syndrome is a rare disease characterized by hypoparathyroidism, deafness, and renal dysplasia. An autosomal dominant disease caused by heterozygous pathogenic GATA3 variants, the penetrance of each associated condition is variable. Literature reviews have provided some answers, but many questions remain, in particular what the relationship is between genotype and phenotype. The current study examines 28 patients with HDR syndrome combined with an exhaustive review of the literature. Some conditions such as hearing loss are almost always present, while others described as rare initially, do not seem to be so rare after all (genital malformations and basal ganglia calcifications). By modeling pathogenic GATA3 variants found in HDR syndrome, we found that missense variations appear to always be located in the same area (close to the two Zinc Finger domain). We describe new pathogenic GATA3 variants, of which some seem to always be associated with certain conditions. Many audiograms were studied to establish a typical audiometric profile associated with a phenotype in HDR. As mentioned in the literature, hearing function should always be assessed as early as possible and follow up of patients with HDR syndrome should include monitoring of parathyroid function and vesicoureteral reflux in order to prevent complications.

Pediatric Cholesteatoma Follow-Up: Residual and Recurrence in 239 Cases with Over 5-Year Hindsight.

INTRODUCTION: Pediatric cholesteatoma is an aggressive disease which requires long-term evaluation to assess management strategies. The objective was to determine optimal follow-up duration in pediatric cholesteatoma to detect residual and recurrent diseases. METHODS: This cohort study was set in a tertiary referral center. All consecutive patients with a minimum 5-year follow-up were included. Medical history, initial extension, surgical procedures, and follow-up were collected. The main outcome measure were Kaplan-Meier survival curves of residual and recurrence cumulative incidence. RESULTS: Totally 239 ears with the first tympanoplasty between 2008 and 2014 were studied including 25% congenital. At first surgery (S1), mean age was 8.4 years and mean follow-up time 7.9 years. Mastoidectomy was performed in 69% and stapes was absent in 38% of cases. Notably, 83% (199 ears) had a second procedure (S2) of which 186 were planned. After S1, maximum cumulated incidence of residual was 45% [95%CI, 38%; 52%] at 74 months, with probability of residual of 39% at 3 years. After S2 (n = 199), maximum cumulated residual incidence was 21% [95%CI, 12%; 32%] at 62 months and 16% at 3 years. Concerning recurrence, maximum cumulated incidence after S1 (n = 239) was reached at 98 months with 21% [95%CI, 12%; 32%], 13% at 3 years and 16% at 5 years. Congenital disease had significantly less residuals after S1 (p = 0.02), but similar recurrence rate (p = 0.66) compared with acquired. CONCLUSIONS AND RELEVANCE: We recommend MRI follow-up of at least 5 years after the last surgery for residual disease and clinical follow-up of at least 10 years to detect recurrence. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

RIPOR2: A new gene of non-syndromic cochleovestibular dysfunction, discrepancy between human pathology and animal models.

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.

A 22q13.1 duplication in mosaicism including SOX10.

Waardenburg syndrome (WS) is characterized by the association of sensorineural hearing loss and pigmentation abnormalities. Among the four types, WS Type 2 (WS2) is the only one without a remarkable distinguishing feature. Here, we report a patient initially diagnosed with WS2 who exhibits a 446 kb mosaic duplication in chromosome 22q13.1, encompassing SOX10, and detected using whole genome sequencing in a trio. The patient, a 46,XY boy, presents with profound bilateral sensorineural hearing loss, right heterochromia iridium, left bright blue iris, and skin-depigmented areas in the abdomen and limbs. Vestibular and imaging tests are normal, without inner ear or olfactory bulb malformations. Bilateral cochlear implantation did not prevent language and speech delays. Moderate congenital chronic constipation and neurodevelopmental difficulties were also present. Given the few genes included in this duplicated region (only one OMIM gene with dominant inheritance), this report provides further delineation of the phenotype related to duplications encompassing the entire SOX10 gene.

Genetic Evaluation of Prelingual Hearing Impairment: Recommendations of an European Network for Genetic Hearing Impairment.

The cause of childhood hearing impairment (excluding infectious pathology of the middle ear) can be extrinsic (embryofoetopathy, meningitis, trauma, drug ototoxicity, noise trauma, etc [...].

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.

French adaptation and validation of parents' evaluation of aural/oral performance of children (PEACH) scale in children.

OBJECTIVE: Hearing loss can seriously impact children's quality of life. Disease-specific questionnaires are required to optimise medical care. This study aims to translate, adapt and validate the French version of the PEACH score for the auditory performance of children. DESIGN: This is a controlled, prospective study, conducted between April and October 2020. The translation was conducted using a forward-backward technique, and statistical validation was conducted with a test and re-test, on a patient population and a control population. STUDY SAMPLE: Patients were included if they were 1-11 years old, and had at least 30 dB hearing loss in one ear. The mean age was 6 years for the 39 patients and 3.9 years for the 34 controls. RESULTS: Reproducibility, measured by Spearman's coefficient between global scores of the test and re-test was 0.78 (p < 0.001). The test was internally consistent (Cronbach's alpha was 0.89) and item per item construct validity was satisfactory. The ROC curve showed a moderate area under the curve (0.74 p < 0.001) with 67% sensitivity and 73% specificity. CONCLUSIONS: The French PEACH had good statistical properties, although a brief 13-item questionnaire, and can be used for evaluation of the disease-specific quality of life for young children with hearing loss.

French adaptation and validation of the Speech, Spatial and Qualities of Hearing scale for Parents (SSQ-P) and for Children (SSQ-Ch).

OBJECTIVES: Hearing loss can seriously impact children's daily life. This study aims to translate and validate the French versions of the hearing performance questionnaires, SSQ-Parent (for 5-18 years old children), and SSQ-Children (for 11-18 years old children). DESIGN: This controlled prospective trial was conducted between April and October 2020. The forward-backward translation method was used, and a test-retest procedure was carried out on a case and a control population. Cases had at least 30 dBHL hearing loss. STUDY SAMPLE: 54 cases (mean age 10.4 years old) and 32 controls (mean age 12.5 years old) answered the SSQ-Parent. 35 cases (mean age 13.1 years old) and 35 controls (mean age 14.3 years old) answered the SSQ-Children. RESULTS: Spearman's correlation coefficients between global scores of the test and re-test were 0.91 (p < 0.001) for SSQ-Parent, and 0.89 (p < 0.001) for SSQ-Children. Both tests were discriminant (respectively, global score 57.8 vs 92 p < 0.001, 61.2 vs 92.6 p < 0.001), and internally consistent (Cronbach's alpha 0.94 and 0.97). Items-global score correlation was satisfactory. ROC curves showed high area under curve for the SSQ-Children (0.990), and SSQ-Parent (0.988). CONCLUSION: The SSQ-Parent and SSQ-Children revealed excellent statistical properties, and can be used for the evaluation of hearing performance of children.

Long-term outcomes of retrospective case series of middle ear implantation with Vibrant Soundbridge in children with congenital aural atresia.

PURPOSE: to assess audiological performance in quiet and noise, quality of life and side effects of Vibrant Soundbridge (VSB) in children with congenital aural atresia (CAA). METHODS: A retrospective study including consecutive patients with unilateral or bilateral CAA implanted with VSB from 2009 to 2020 in a tertiary referral centre. RESULTS: 18 patients with CAA and a present stapes were included (3 simultaneous bilateral VSB implants) and 21 ears: 17 VSB were attached to the short incus process, and four to the stapes. Age at implantation ranged from 4.7 to 15.8 years. Average follow-up was 6.5 years (± 3.7 years). In unilateral VSB, air conduction pure tone average (ACPTA) thresholds increased from 75.3 ± 15.2 to 32.6 ± 8.3 dB post-operatively (VSB activated) (n = 15; p < 0.01). The speech reception threshold (SRT) and the word recognition score (WRS) were significantly improved from 81.5 ± 10.4 to 43.9 ± 7.6 dB and 0% to 84.8 ± 8.5% postoperatively (n = 15; p < 0.01). The signal to noise ratio (SNR) was significantly improved from 2.1 ± 2.9 dB VSB inactivated to 0.3 ± 2.7 dB VSB activated (n = 15; p < 0.01). There was no significant difference in performance according to floating mass transducer (FMT) placement. 5/15 children were non-users at last follow-up in unilateral VSB and 0/3 in bilateral. CONCLUSIONS: CAA ears with VSB activated had a significant improvement of ACPTA, WRS, SRT and SNR. A third of patients with unilateral CAA became non-users at last follow-up. The main challenge is to target the indications for the implantation of the VSB to avoid its discontinuation.

Robot-Assisted Transcanal Endoscopic Ear Surgery for Congenital Cholesteatoma.

Congenital cholesteatoma accounts for 25% of cholesteatoma cases in children. Transcanal Endoscopic Ear Surgery (TEES) is ideal for these patients because it offers a wide endoscopic view of the middle ear and a minimally invasive approach. The two main limitations are the loss of one operative hand and a narrow external auditory canal in younger children. Here, we present the case of a 3-year-old patient with a Potsic stage III congenital cholesteatoma adherent to the incus and branches of the stapes. A robotic-assisted TEES procedure was performed, during which a robotic arm with 6 degrees of freedom held a 0°, 2.9 mm wide endoscope, enabling the surgeon to work in a narrow environment with both hands. The procedure's duration was 2 h and 9 min, including 16 min for the installation and draping of the robotic arm. After a trans-canal approach, the cholesteatoma was dissected from the ossicles using both a needle (or sickle knife) and suction to stabilize the ossicles and limit the risk of hearing trauma. The cholesteatoma was debulked to reduce its size, allowing it to be pushed under the malleus anteriorly and then separated from other adherences before removal. A tragal cartilage graft was used to reinforce the tympanic membrane.

Retinal Phenotype of Patients with CLRN1-Associated Usher 3A Syndrome in French Light4Deaf Cohort.

Purpose: Biallelic variants in CLRN1 are responsible for Usher syndrome 3A and non-syndromic rod-cone dystrophy (RCD). Retinal findings in Usher syndrome 3A have not been well defined. We report the detailed phenotypic description of RCD associated with CLRN1 variants in a prospective cohort. Methods: Patients were clinically investigated at the National Reference Center for rare ocular diseases at the Quinze-Vingts Hospital, Paris, France. Best-corrected visual acuity (BCVA) tests, Goldmann perimetry, full-field electroretinography (ffERG), retinal photography, near-infrared reflectance, short-wavelength and near-infrared autofluorescence, and optical coherence tomography (OCT) were performed for all patients. Results: Four patients from four unrelated families were recruited. Mean follow-up was 11 years for three patients, and only baseline data were available for one subject. Median BCVA at baseline was 0.2 logMAR (range, 0.3-0). ffERG responses were undetectable in all subjects. The III4e isopter of the Goldmann visual field was constricted to 10°. The retinal phenotype was consistent in all patients: small whitish granular atrophic areas were organized in a network pattern around the macula and in the midperiphery. OCT showed intraretinal microcysts in all patients. Upon follow-up, all patients experienced a progressive BCVA loss and further visual field constriction. Four distinct pathogenic variants were identified in our patients: two missense (c.144T>G, p.(Asn48Lys) and c.368C>A, p.(Ala123Asp)) and two frameshift variants (c.176del, p.(Gly59Valfs*13) and c.230dup, p.(Ala78Serfs*52)). Conclusions: RCD in Usher 3A syndrome has some distinctive features. It is a severe photoreceptor dystrophy with whitish granular posterior pole appearance and cystic maculopathy.

[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.

The role of computed tomography and magnetic resonance imaging for preoperative pediatric cochlear implantation work-up in academic institutions.

OBJECTIVE: The goal of the study is to investigate the association of pertinent preoperative temporal bone computed tomography (CT) and brain magnetic resonance imaging (MRI) results and intraoperative surgical findings and complications of pediatric cochlear implantation reported in academic settings. METHODS: This is a retrospective review of cochlear implant patients who received a pre-operative temporal bone CT and MRI of the brain between 2005 and 2012 at academic pediatric otolaryngology practices within children's hospitals in the United States and France. Scans were reviewed in a double-blind fashion and compared to intraoperative findings. RESULTS: 91 children were analyzed (mean age 5.54 +/- 0.58 years). A small facial recess identified on CT was associated with difficult insertion of electrodes (P = 0.0003). A prominent sigmoid sinus noted on CT was associated of difficult insertion of electrodes (P = 0.01), iatrogenic tegmen dehiscence (P = 0.005), as well as difficult round window access (P = 0.025). No specific CT finding was found to be associated with external auditory canal injury, perilymphatic gusher, or iatrogenic facial nerve injury. MRI brain and internal auditory canal findings were not predictive of surgical outcomes. CONCLUSIONS: Preoperative CT and MRI remain an important planning tool for pediatric cochlear implantation, particularly in academic institutions. The findings of our study demonstrate that a detailed assessment of both preoperative CT and MRI are valuable for teaching and surgical planning.

Malformations Associated With Pediatric Congenital Cholesteatomas.

OBJECTIVE: To describe malformations associated with pediatric congenital cholesteatomas of the middle ear. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: One hundred and seventy-three cases of middle ear congenital cholesteatoma (CC) in 171 children operated between 2007 and 2017. INTERVENTIONS: Demographic, clinical, and surgical data were collected from operative reports. MAIN OUTCOME MEASURES: We first described the type and rate of malformations associated with CC. Secondly, we compared cholesteatoma features in two subgroups: anterior superior (AS) versus posterior superior (PS) starting point. Third, we compared demographic, clinical, and surgical data between patients with and without malformation. RESULTS: CC was associated with malformations in 17 cases (17/173; 9.8%). The main malformation was preauricular fistula (8/173; 4.6%). Other malformations were: one first branchial cleft, two labio palatine cleft, one nasal cyst, two preauricular fibrochondroma, and five other malformations. PS congenital cholesteatomas were diagnosed in older children (4.6 versus 8.6 years, p < 0.05) and had greater extension in middle ear than the AS cholesteatoma (39.7% versus 95.8%, p < 0.05). We did not find any significant difference between these two groups regarding the associated malformations. We did not find a difference in clinical presentation of CC between patients with and without associated malformation. CONCLUSIONS: We found various associated malformations in 9.8% of CC cases with no statistical difference in the malformation rate between AS and PS groups. All the malformations were located in the craniofacial region suggesting that genes implicated in craniofacial development may play a role in the pathophysiology of CC.

PRPS1 loss-of-function variants, from isolated hearing loss to severe congenital encephalopathy: New cases and literature review.

We describe two sporadic and two familial cases with loss-of-function variants in PRPS1, which is located on the X chromosome and encodes phosphoribosyl pyrophosphate synthetase 1 (PRS-1). We illustrate the clinical variability associated with decreased PRS-1 activity, ranging from mild isolated hearing loss to severe encephalopathy. One of the variants we identified has already been reported with a phenotype similar to our patient's, whereas the other three were unknown. The clinical and biochemical information we provide will hopefully contribute to gain insight into the correlation between genotype and phenotype of this rare condition, both in females and in males. Moreover, our observation of a new family in which hemizygous males display hearing loss without any neurological or ophthalmological symptoms prompts us to suggest analysing PRPS1 in cases of isolated hearing loss. Eventually, PRPS1 variants should be considered as a differential diagnosis of mitochondrial disorders.

Pediatric sudden sensorineural hearing loss: Experience in a pediatric ENT emergency care center.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.