Development of a new clinical tool to evaluate the balance abilities of children with bilateral vestibular loss: The Geneva Balance Test.

Introduction: Vestibular deficits are considered rare in children, but the lack of systematic screening leads to underdiagnosis. It has been demonstrated that chronic vestibular dysfunction impacts the normal psychomotor development of children. Early identification is needed to allow for clinical management, ensuring better global development. For this purpose, our research group has developed the Geneva Balance Test (GBT), aiming to objectively quantify the balance capacity of children over a broad age range, to screen for bilateral vestibulopathy (BV), and to quantify the improvement of balance abilities in children. Methods: To determine the capacity of the GBT to quantify the balance capacity of children with BV, we conducted an observational prospective study with three populations: 11 children with BV, and two age-matched control groups composed of (1) 15 healthy subjects without the vestibular or auditory disorder (HS) and (2) 11 pediatric cochlear implant recipients (CIs) without vestibular disorders. Results of the three populations have been compared in three different age sub- groups (3-5, 6-9, and ≥10 years), and with results of a short, modified version of the Bruininks-Oseretsky test of Motor proficiency Ed. 2 (mBOT-2). Results: Statistical analyses demonstrated significant differences in the scores of the GBT between children aged 3-5, 6-9, and ≥10 years with BV and in both control populations (HS and CI). BV scores reflected poorer balance capacities at all ages. Children in the youngest CI sub-group (3-5 years) showed intermediate GBT scores but reached HS scores at 6-9 years, reflecting an improvement in their balance capacities. All the results of the GBT were significantly correlated with mBOT-2 results, although only a few BV completed the entire mBOT-2. Discussion: In this study, the GBT allowed quantifying balance deficits in children with BV. The BOT-2 test is not validated for children <4.5 years of age, and the GBT seems to be better tolerated in all populations than the mBOT-2. Furthermore, mBOT-2 results saturated, reaching maximum values by 6-9 years whereas the GBT did not, suggesting that the GBT could be a useful tool for monitoring the development of balance capacities with age and could be used in the follow-up of children with severe vestibular disorders.

[Molecular genetic diagnosis in children with cochlear implants in the Western french speaking part of Switzerland]. / Diagnostic génétique moléculaire des enfants implantés cochléaires en Suisse romande.

Hearing loss is the most frequent sensory deficit at birth. Newborn hearing screening helps with early identification and clinical management of hearing deficits. A cochlear implantation is advised for profound hearing loss. Previously, an etiologic diagnosis was difficult to obtain, and many laboratory tests were required. Today, genetics has up to 60% success rate in etiologic diagnosis and is now part of the international pediatric ENT recommendations. The Centre Universitaire Romand des Implants Cochléaires (CURIC) follows children with cochlear implants. From 2015 to 2021, 26 implanted children received testing, with a 73% success rate. The genetic diagnosis helped guide their clinical management and helped to avoid unnecessary and costly clinical testing.

Le déficit auditif (DA) est le déficit neurosensoriel le plus fréquent à la naissance. Le dépistage auditif permet l'identification et la prise en charge précoces des problèmes d'audition. Dans le cas de surdités profondes, une implantation cochléaire est conseillée. Auparavant, le diagnostic étiologique était difficile à poser malgré de nombreux examens complémentaires. Depuis 10 ans, la médecine génétique aboutit à un diagnostic étiologique dans 60% des cas et fait partie des recommandations internationales d'ORL pédiatrique. Le Centre universitaire romand des implants cochléaires prend en charge les enfants implantés. Entre 2015 et 2021, 26 enfants implantés ont eu une analyse génétique, dont 73% avec succès. Ceci permet d'orienter la prise en charge spécifiquement au profil génétique et diminue les examens complémentaires.

Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss.

PURPOSE: Hearing loss is characterized by an extensive genetic heterogeneity and remains a common disorder in children. Molecular diagnosis is of particular benefit in children, and permits the early identification of clinically-unrecognized hearing loss syndromes, which permits effective clinical management and follow-up, including genetic counselling. METHODS: We performed whole-exome sequencing with the analysis of a panel of 189 genes associated with hearing loss in a prospective cohort of 61 children and 9 adults presenting mainly with isolated hearing loss. RESULTS: The overall diagnostic rate using exome sequencing was 47.2% (52.5% in children; 22% in adults). In children with confirmed molecular results, 17/32 (53.2%) showed autosomal recessive inheritance patterns, 14/32 (43.75%) showed an autosomal dominant condition, and one case had X-linked hearing loss. In adults, the two patients showed an autosomal dominant inheritance pattern. Among the 32 children, 17 (53.1%) had nonsyndromic hearing loss and 15 (46.7%) had syndromic hearing loss. One adult was diagnosed with syndromic hearing loss and one with nonsyndromic hearing loss. The most common causative genes were STRC (5 cases), GJB2 (3 cases), COL11A1 (3 cases), and ACTG1 (3 cases). CONCLUSIONS: Exome sequencing has a high diagnostic yield in children with hearing loss and can reveal a syndromic hearing loss form before other organs/systems become involved, allowing the surveillance of unrecognized present and/or future complications associated with these syndromes.

Home respiratory polygraphy in obstructive sleep apnea syndrome in children: Comparison with a screening questionnaire.

OBJECTIVES: The prevalence of obstructive sleep apnea syndrome (OSAS) in children referred for sleep-disordered breathing reaches up to 59%. We aimed to test the adequacy of a questionnaire compared to home respiratory polygraphy (HRP), in 45 subjects (5-16 years-old), without maxillofacial malformations nor other comorbidities, presenting with symptoms compatible with OSAS. METHODS: All children passed a 12-items questionnaire (Obstructive Airway Child test: OACT) and the HRP. OSAS was classified in severity according to the apnea-hypopnea index (AHI). RESULTS: With HRP, 60% and 15% children were detected to have at least mild (AHI ≥1) and moderate (AHI >5) OSAS, respectively. The sensitivity of the questionnaire to detect mild and moderate OSAS was good (93% and 71%, respectively) but the specificity was very low (11% and 34%). However, an OACT score under 61 showed a very good negative predictive value for moderate and severe OSAS (87%). With the questionnaire, we could have avoided a complementary PSG or HRP in 25/45 (56%) of our subjects as in children with mild OSAS and without comorbidities only clinical observation is usually advised. CONCLUSIONS: The OACT questionnaire has shown to be a good and quick instrument to exclude moderate and severe OSAS in our population of children without maxillofacial malformations. Indeed children scoring under 61 could avoid a constraining and expensive sleep exam. However, if the score is above this cut-off, the performance to recognize OSAS is low and the child's evaluation must be completed by a HRP or PSG.

Molecular characterization of pathogenic OTOA gene conversions in hearing loss patients.

Bi-allelic loss-of-function variants of OTOA are a well-known cause of moderate-to-severe hearing loss. Whereas non-allelic homologous recombination-mediated deletions of the gene are well known, gene conversions to pseudogene OTOAP1 have been reported in the literature but never fully described nor their pathogenicity assessed. Here, we report two unrelated patients with moderate hearing-loss, who were compound heterozygotes for a converted allele and a deletion of OTOA. The conversions were initially detected through sequencing depths anomalies at the OTOA locus after exome sequencing, then confirmed with long range polymerase chain reactions. Both conversions lead to loss-of-function by introducing a premature stop codon in exon 22 (p.Glu787*). Using genomic alignments and long read nanopore sequencing, we found that the two probands carry stretches of converted DNA of widely different lengths (at least 9 kbp and around 900 bp, respectively).

LARS2-Perrault syndrome: a new case report and literature review.

BACKGROUND: Perrault syndrome is a rare recessive and genetically heterogeneous disorder characterized by sensorineural hearing loss in males and females and gonadal dysgenesis in females. Mutations in seven different genes have been identified: HARS2, HSD17B4, CLLP, C10orf, ERAL1, TWNK and LARS2. To date, 19 variants have been reported in 18 individuals with LARS2-Perrault syndrome. CASE PRESENTATION: Here we describe the case of an 8-year-old girl with compound heterozygous missense mutations in the LARS2 gene. We identified two missense mutations [c.457A > C, p.(Asn153His) and c.1565C > A, p.(Thr522Asn)] and subsequent familial segregation showed that each parent had transmitted a mutation. CONCLUSIONS: These results have implications for genetic counseling and provide insight into the functional role of LARS2. This case highlights the importance of an early diagnosis. Systematic genetic screening of children with hearing loss allows the early identification of a Perrault syndrome in order to ensure specific endocrinological surveillance and management to prevent secondary complications. Clinical data are compared with the other cases reported in the literature.

Successful home respiratory polygraphy to investigate sleep-disordered breathing in children.

OBJECTIVE: Sleep-disordered breathing (SDB) in children is common. Interest in sleep tests, such as polygraphy (PG), which can be performed in a non-attended setting, are gaining is increasing. PG has, however, been little studied in children with co-morbidities other than obstructive sleep apnea (OSA), and in particular, if performed in a non-attended setting. We report on the feasibility and interpretability of implementing PGs at home versus in hospital. METHODS: PGs were analyzed according to the setting (hospital or home) and sequence (initial or subsequent) in which they were performed. Non-interpretability was defined as absent or unreliable oxygen saturation by pulse oximetry (SpO2), or airflow and respiratory inductance plethysmography flow trace signals during the time analyzed. RESULTS: We retrospectively analyzed 400 PGs; 332/400 were initial PGs. Indications were: suspected OSA (65%), obesity (13%), craniofacial malformations (5%), neuromuscular disease (4%), and other (13%) which included prematurity. 16% were recorded in hospitals and 84% at home. The mean age was 5.7 ± 5.8 years and 7.3 ± 4.5 years for the hospital and home groups, respectively. Interpretability was similar in both settings (87%). In the 68 subsequent PGs, interpretability was 84% when performed for follow-up and 96% when repeated for non-interpretability. Non-interpretability was predominantly due to a failure of the SpO2 channel. CONCLUSIONS: PG performed at home is both feasible and interpretable for a variety of indications. Non-interpretability was not predictable in association with the setting, anthropometric data, or indication, independently of the sequence (initial or subsequent PG) in which the parameters were analyzed.

[Genetics of hearing disorders in children]. / Génétique des troubles auditifs chez l'enfant.

The majority of early hearing disorders are of genetic origin. In view of the genetic heterogeneity, high-throughput sequencing analysis of a panel of genes involved in hearing loss is the most effective and economical approach, providing a diagnostic yield of around 40 % today. The determination of a molecular diagnosis makes it possible to: i) adapt the audiological care; ii) to search for possible somatic problems associated with so-called syndromic hearing loss; (iii) to avoid unnecessary additional examinations in isolated hearing loss; (iv) to establish accurate genetic counseling for relatives, or even to provide early diagnosis; and (v) to lay the foundation for potential future molecular hearing loss therapies in selected cases.

La majorité des troubles auditifs précoces est d'origine génétique. La détection rapide et la prise en charge adaptée limitent l'impact développemental; de même, un diagnostic étiologique précis améliore le suivi des patients. Au vu de l'hétérogénéité génétique des troubles auditifs, l'analyse par séquençage à haut débit d'un panel de gènes constitue l'approche la plus efficace et économique avec un rendement actuel d'environ 40 %. Le diagnostic moléculaire permet: 1) d'adapter la prise en charge audiologique; 2) de rechercher d'éventuels problèmes somatiques associés; 3) d'éviter des examens complémentaires inutiles dans les déficits auditifs isolés; 4) d'établir un conseil génétique pour les apparentés, voire de proposer un diagnostic précoce; 5) d'établir les bases d'une éventuelle thérapie génique future.

Sniffin' Away the Feeding Tube: The Influence of Olfactory Stimulation on Oral Food Intake in Newborns and Premature Infants.

Because of their immaturity, many premature infants are fed via nasogastric tube. One objective of the neonatal care is to feed infants orally early. The olfactory function of premature infants is developed before birth and odorants have a significant impact on nutrition in infants. The aim of the study was to test whether odor stimulation has a positive effect on the transition from gavage to oral feeding in infants. Participants were premature infants with gestational age of more than 27 weeks, with full or partial gavage feeding, stable vital parameters and without invasive ventilation. Before each feeding procedure an odorant was presented in front of the infant's nose. Infants were randomized into 1 of 3 groups and received either rose odor (not food-associated), vanilla odor (food-associated), or placebo (no odor). The primary outcome of the study was defined as the time until complete oral nutrition. About 150 children born at a postnatal age of 9.5 ± 7.8 days were included in this study. The duration until complete oral nutrition was reached after 11.8 ± 7.7 (vanilla), 12.2 ± 7.7 (rose), and 12.9 ± 8.8 (control) days. A nearly linear relation between odor presentation frequency and effect size was detectable. For infants that received the intervention for more than 66.7% of the time the length of gavage feeding (8 ± 5.4) and hospitalization (11 ± 6.5) was significantly lower in the vanilla group when compared with control (15 ± 7.3 and 21 ± 13.7, respectively). Odor stimulation with vanilla has an impact on oral feeding in premature infants, however the odor has to be presented on regular basis.

Development of an International Odor Identification Test for Children: The Universal Sniff Test.

OBJECTIVE: To assess olfactory function in children and to create and validate an odor identification test to diagnose olfactory dysfunction in children, which we called the Universal Sniff (U-Sniff) test. STUDY DESIGN: This is a multicenter study involving 19 countries. The U-Sniff test was developed in 3 phases including 1760 children age 5-7 years. Phase 1: identification of potentially recognizable odors; phase 2: selection of odorants for the odor identification test; and phase 3: evaluation of the test and acquisition of normative data. Test-retest reliability was evaluated in a subgroup of children (n = 27), and the test was validated using children with congenital anosmia (n = 14). RESULTS: Twelve odors were familiar to children and, therefore, included in the U-Sniff test. Children scored a mean ± SD of 9.88 ± 1.80 points out of 12. Normative data was obtained and reported for each country. The U-Sniff test demonstrated a high test-retest reliability (r27 = 0.83, P < .001) and enabled discrimination between normosmia and children with congenital anosmia with a sensitivity of 100% and specificity of 86%. CONCLUSIONS: The U-Sniff is a valid and reliable method of testing olfaction in children and can be used internationally.

Taste disorders after tonsillectomy: a long-term follow-up.

In a former study, taste disturbances after tonsillectomy seemed to be more frequent than expected. Eight percent of patients reported subjective taste disorders 6 months after tonsillectomy. Fifteen patients from the initial trial, who reported taste disorders after tonsillectomy, were contacted again for this long-term follow-up. A telephone interview using the same questionnaire addressing the current self-estimate of taste function was performed. At 32 ± 10 months following surgery, two (0.9%) patients still reported suffering from taste disturbance. This long-term follow-up study shows that dysgeusia following tonsillectomy occurs in approximately 1% of patients. These data should be considered when patients are informed about complications after tonsillectomy.

Taste disturbance following tonsillectomy--a prospective study.

OBJECTIVES/HYPOTHESIS: Persistent taste disturbance is a rare complication after tonsillectomy and mainly documented by case reports or a few retrospective and prospective trials with a limited number of patients. None could clarify frequency, time course, or prognosis of long-lasting dysgeusia after tonsillectomy. The aim of the study was to provide a symptom-based follow-up after tonsillectomy to assess postoperative taste disorders. STUDY DESIGN: Prospective clinical trial. METHODS: From December 2007 to June 2009 adult patients undergoing tonsillectomy were asked to take part in the trial. Two hundred twenty-three patients (119 female, 104 male; mean age, 33 ± 13 years) were included. The day prior to surgery, and 2 weeks and 6 months after tonsillectomy a standardized questionnaire was completed by patients. The questionnaire focused on taste function, taste disorders, pain, foreign body sensation, and bleeding episodes after tonsillectomy. RESULTS: One hundred eighty-eight (2 weeks) and 181 (6 months) patients returned the questionnaires. Thirty-two percent (n = 60) of patients reported taste disorders after tonsillectomy 2 weeks postoperatively and 15 patients (8%) at 6-month follow-up. Metallic and bitter parageusia were most frequently reported. The mean ratings of gustatory function were significantly lower 2 weeks after surgery (P < .001) and reached preoperative values 6 months after surgery. Almost 30% of patients reported postoperative bleeding, 10% long-lasting postoperative pain, and 20% foreign body sensation. CONCLUSIONS: Long-lasting taste disturbance (metallic and bitter parageusia) after tonsillectomy is more frequent than previously reported. Long-lasting pain and foreign body sensation seem to be common symptoms. With regard to these results, a thorough preoperative explanation is mandatory.

Recovery from long-lasting post-tonsillectomy dysgeusia.

Transient post-tonsillectomy taste dysgeusia (PTD) is a common complaint. Long-lasting PTD is less frequent but has significant consequences on patients' quality of life, with some cases leading to medicolegal issues. Treatment options and knowledge about mechanisms and factors favoring PTD are limited. PTD may result from direct surgical injury, tongue compression, inflammatory processes or side effects of local anesthetics. Some authors also claim that dietary zinc deficiency plays a role in the development of PTD. Although this latter cause had not yet received a lot of attention, we report a case of a female patient who reported a 4-year PTD and recovered within 2 months after oral intake of zinc sulfate. This clinical observation, together with recent findings on significant improvement of taste disorders after zinc treatments for other causes, opens again the question of what extent zinc deficiency plays a role in PTD.

Chemosensory function in Wegener's granulomatosis: a preliminary report.

Despite the fact that Wegener's granulomatosis affects the nasal and paranasal cavities and the cranial nerves regularly, chemosensory impairments have not been reported. The objective of this study is to test the three chemosensory systems, olfaction, taste, and intranasal trigeminal function in Wegener disease patients. We tested olfactory, gustatory, and intranasal trigeminal function in nine patients (5 women, 4 men, mean age 57 years) with confirmed Wegener's granulomatosis. Olfaction was tested with the Sniffin'Sticks, gustatory function with the "Taste strips" and intranasal trigeminal function with a lateralization task. One patient had anosmia (11%), four patients had hyposmia (44%) and four patients were normosmic (45%). Gustatory testing function showed pathological taste strip results in five patients (55%) and normal results in three patients (33%). One patient did not undergo taste testing. Intranasal trigeminal function was lowered in five patients (56%) and normal in four patients (44%). Neither previous nasal surgery status nor endoscopic status was associated to a higher frequency in pathological scores for any of the three chemical senses. In conclusion, these preliminary results suggest a consistent affection in chemosensory functions in Wegener's granulomatosis patients.

Retronasal olfactory function in Parkinson's disease.

OBJECTIVES/HYPOTHESIS: Orthonasal olfaction is severely altered in PD patients. Retronasal olfactory function has been shown to be preserved under certain conditions even in the absence of orthonasal function. This study was undertaken to investigate retronasal versus orthonasal olfactory function in Parkinson's disease (PD). STUDY DESIGN: Prospective study. METHODS: A total of 45 PD patients (mean age, 61 years; range 26-82 years) underwent orthonasal olfactory testing with a standardized olfactory test (Sniffin' Sticks) and retronasal olfactory testing with a 10-item identification kit based on aromatized powders. RESULTS: Regarding orthonasal tests, all PD patients scored within the range of hyposmia and functional anosmia. The mean correct orthonasal identification score for PD patients was 56% +/- 2.6%, and the mean retronasal identification rate was 60% +/- 3%. There was no significant difference between ortho- and retronasal odor identification (P = .15). CONCLUSIONS: The present study shows that retronasal and orthonasal olfactory function are severely impaired in PD patients, and this impairment is of similar magnitude for both functions. The contribution of this finding to the food-intake behavior of PD patients is discussed.