Mild Bilateral Hearing Loss Research Articles

Polygenic Risk Scores and Hearing Loss Phenotypes in Children

Monogenic causes of childhood hearing loss are well established, as are polygenic risk contributions to age-related hearing loss. However, an untested possibility is that polygenic risk scores (PRS) also contribute to childhood hearing loss of all severities, alongside environmental and/or monogenic causes. To examine the association between a PRS for adult hearing loss and childhood hearing loss phenotypes. This cross-sectional study used a unique population-based dataset spanning normal hearing to profound loss, combining 2 contemporaneous population cohorts in Australia. This included the Child Health CheckPoint, a national population-based cross-sectional study nested within the Longitudinal Study of Australian Children, and the Victorian Childhood Hearing Longitudinal Databank (VicCHILD), a statewide population-based longitudinal data bank open to every child with congenital hearing loss in Victoria, Australia. The analysis took place from March to August 2023. Genotype data were generated from saliva- or blood-derived DNA using global single-nucleotide variations arrays. Based on genotype data, PRS was computed using published UK Biobank genome-wide association study results for self-reported hearing difficulty in individuals aged 40 to 69 years. Hearing outcomes were classified by laterality (bilateral, unilateral), severity (mild, moderate, severe or worse) and types (sensorineural, conductive, mixed, auditory neuropathy, atresia). Analyses included multinominal logistic regressions of PRS with hearing outcomes. Overall, 1488 CheckPoint study children (49.8% boys, aged 11-12 years) and 527 VicCHILD study children (55.2% boys, aged 0-13 years) with hearing and genotype data were included. A 1-SD increment in PRS was associated with higher odds of mild (odds ratio [OR], 1.3; 95% CI, 1.0-1.6), moderate (OR, 5.1; 95% CI, 3.2-8.1), and severe or worse (OR, 5.3; 95% CI, 3.9-7.3) unilateral hearing loss compared with normal hearing. Similarly, the PRS was associated with increased odds of mild, moderate, and severe or worse bilateral hearing loss (per-SD ORs, 3.9-6.6) and all hearing loss types (per-SD ORs, 8.5-10.6). In this cross-sectional study, a PRS initially developed for adult hearing difficulty was associated with wide-ranging childhood hearing loss phenotypes, partly explaining hearing phenotype variations despite shared genetic and environmental factors (eg, preterm birth). Large-scale studies with objectively defined hearing phenotypes are crucial for refining PRS and predicting high-risk children.

Pre-school hearing screening is necessary to detect childhood hearing loss after the newborn period: a study exploring risk factors, additional disabilities, and referral pathways

Objective To explore strategies for detecting childhood hearing loss, aside from newborn hearing screening. Design A retrospective review of medical records on the modes of detection of hearing loss, risk factors for late-onset hearing loss, hearing loss degree, aetiology, additional disabilities, and timelines from referral to intervention. Study sample Children, born 2006 to 2015, enrolled for intervention whose hearing loss was detected up to age 7 years but not from newborn hearing screening (n = 326). Results Universal pre-school hearing screening detected 38% of the cohort at 4–5 years of age. Risk factors for late-onset hearing loss were present in 36% of children, 80% of whom had a reported family history. Sixty-nine percent had mild bilateral or unilateral hearing loss. Children with additional disabilities faced significantly longer delays from referral to intervention. Children self-referred due to parent concern had more severe degree of hearing loss than those referred from screening. Conclusion Most children with hearing loss detected after the newborn period do not have any known risk factors for late-onset hearing loss. Pre-school hearing screening is needed for comprehensive detection of hearing loss in early childhood. More work is needed towards improving timely diagnosis and intervention for children with additional disabilities.

Emanuel syndrome due to unusual pattern

BackgroundThe hallmarks of Emanuel syndrome are pre- and postnatal growth retardation, microcephaly, global developmental delay, ear anomalies, and in males, heart, kidney, and genital abnormalities.ResultsThis study describes the atypical features of Emanuel syndrome, a rare chromosomal disorder. The patient had several physical features that are common in Emanuel syndrome, such as microcephaly, hypotonia, and ear anomalies. However, he exhibited certain unusual characteristics, including the lack of a prominent forehead, epicanthic folds, and a downward slanting palpebral fissure. There was infratentorial brain involution with a minor infarction in the left cerebral hemisphere and cerebellar hypoplasia on the magnetic resonance imaging (MRI) scan of the brain. Additionally, the patient had bilateral mild hearing loss and an aberrant epileptogenic pattern on the electroencephalogram (EEG). Orodental examination showed a long philtrum, everted fissured thick lower lip, highly attached labial frenum, and prominent median palatine raphe. The karyotype revealed 45XY t(11;22)(p15.5;q11.22), which is different from the typical karyotype of Emanuel syndrome.ConclusionsThis case sheds light on the possibility of alternative genetic mechanisms, beyond chromosomal abnormalities, in patients presenting with multiple congenital anomalies and facial dysmorphism.

Impact of Hearing Aids on Language Outcomes in Preschool Children With Mild Bilateral Hearing Loss.

This study aimed to investigate the role of hearing aid (HA) usage in language outcomes among preschool children aged 3-5 years with mild bilateral hearing loss (MBHL). The data were retrieved from a total of 52 children with MBHL and 30 children with normal hearing (NH). The association between demographical, audiological factors and language outcomes was examined. Analyses of variance were conducted to compare the language abilities of HA users, non-HA users, and their NH peers. Furthermore, regression analyses were performed to identify significant predictors of language outcomes. Aided better ear pure-tone average (BEPTA) was significantly correlated with language comprehension scores. Among children with MBHL, those who used HA outperformed the ones who did not use HA across all linguistic domains. The language skills of children with MBHL were comparable to those of their peers with NH. The degree of improvement in audibility in terms of aided BEPTA was a significant predictor of language comprehension. It is noteworthy that 50% of the parents expressed reluctance regarding HA use for their children with MBHL. The findings highlight the positive impact of HA usage on language development in this population. Professionals may therefore consider HAs as a viable treatment option for children with MBHL, especially when there is a potential risk of language delay due to hearing loss. It was observed that 25% of the children with MBHL had late-onset hearing loss. Consequently, the implementation of preschool screening or a listening performance checklist is recommended to facilitate early detection.

Impact of room acoustics and visual cues on speech perception and talker localization by children with mild bilateral or unilateral hearing loss

Impact of room acoustics and visual cues on speech perception and talker localization by children with mild bilateral or unilateral hearing loss

Language and health-related quality of life outcomes of children early-detected with unilateral and mild bilateral hearing loss.

We aimed to describe the language and health-related quality of life (HRQoL) outcomes of children early-identified with unilateral or mild bilateral permanent hearing loss. This was a cross-sectional community-based study of children with mild bilateral or unilateral permanent hearing loss (including unilateral auditory neuropathy spectrum disorder (ANSD)), drawn from a population-based databank in Victoria, Australia. Enrolment in this databank is independent of early intervention and amplification approaches. Language and caregiver-reported HRQoL outcomes are described by type and degree of loss at three timepoints across child development: at age 2 years (n = 255), 5-7 years (n = 173) and 9-12 years (n = 45). Across all age groups, average language outcomes were poorer than population normative scores by between a half to two thirds of a standard deviation. Children with mild bilateral hearing loss demonstrated poorer average language outcomes than children with unilateral hearing loss, particularly at younger ages. Children with unilateral ANSD showed language outcomes comparable to their peers with unilateral profound hearing loss. Children had poorer HRQoL psychosocial scores compared to physical scores, without obvious patterns of outcomes linked to degree or type of hearing loss. This study demonstrates children with early-identified unilateral or mild bilateral hearing loss have average language and HRQoL outcomes poorer than population normative expectations from an early age. These outcomes are observed at later ages across childhood. These findings provide a contemporary description of language and quality of life outcomes for children identified but not targeted by universal newborn hearing screening and raise questions of how to provide better support for these populations of children and their families.

Mild matters: trial learnings and importance of community engagement in research for early identified bilateral mild hearing loss.

Early identification of mild hearing loss has resulted in early hearing amplification without adequate evidence of effectiveness. This paper describes learnings from a pilot trial, combined with a qualitative study, to highlight the importance of community engagement in designing research studies to determine whether early amplification benefits young children with bilateral mild hearing loss. PART 1 of the study is a proof-of-concept non-blinded multi-centre randomised controlled trial (RCT) of hearing device fitting vs. no fitting aimed to gather preliminary data and determine its acceptability/feasibility in children <2 years old with bilateral mild hearing loss. PART 2 is a qualitative study to understand the barriers/enablers to RCT participation. Of 40 potentially eligible families, nine (23%) declined, three were uncontactable (7%), 26 (65%) ineligible: of these, nine (35%) did not meet hearing threshold inclusion criteria, 11 (42%) were already fitted or had made decisions on fitting hearing device, two (7%) had conductive loss and four (16%) were ineligible for other reasons. Two of 11 (18%) eligible families were randomised. With the limited sample size, outcome measures were not compared between groups. Both participants completed the trial, reported the RCT to be acceptable, and neither changed group post-enrolment. Whilst recruitment uptake could potentially be increased by altering the eligibility criteria, better communication with and reimbursement of clinicians as recruiters, and improving awareness of the study amongst external stakeholders, the RCT methodology does not conform to family-centred practice, and potentially raises ethical concerns regarding potential adverse consequences of not offering early amplification. Parental perception of losing control over choice of management due to randomisation is not an easily modifiable factor. Alternative methodological approaches without randomisation are required to determine whether hearing amplification benefits infants with mild hearing loss.Clinical Trial Registration: identifier [ACTRN12618001608257].

Isolated tinnitus – premonitory symptom of an evolving auditory dysfunction: a retrospective analysis

Background: Tinnitus manifests frequently with hearing loss. Isolated tinnitus in patients with self-professed normal hearing may have underlying auditory dysfunction. Methods: We retrospectively reviewed the audiometry record of our department from January 2019 to October 2021. Pure tone audiometry thresholds of patients with isolated tinnitus were analyzed along with the demographics, degree and type of hearing loss. Results: Of 255 (132 males/123 females) patients, mean age 39.7±15.2 years (range: 10-80 years), tinnitus was maximum (49%) prevalent among 20-40 years group, 5.8% among the pediatric population and 8.6% amidst ≥60 years populace. Males predominated (52%) throughout except at 21-30 years age. 83% exhibited some degree of hearing loss (42% bilateral minimal loss, 11% bilateral mild hearing loss). 7% right ears (mostly &gt;50 years age group) and 11% left ears showed greater than mild hearing loss. Bilateral tinnitus presented more (52%) followed by left tinnitus (29%) than right (19%). Mild hearing loss predominated right tinnitus presentation while minimal loss was recorded in left and bilateral tinnitus. However, greater than mild degree of hearing loss was clustered among bilateral tinnitus (14%) followed by left tinnitus (11%) than right tinnitus (6%). 18% had sensorineural deafness and all these patients had bilateral tinnitus. 30% had high frequency hearing loss and 39% among these had 4 kHz dip. Conclusions: Isolated tinnitus may be a premonitory symptom of an underlying or an evolving auditory dysfunction. Bilateral tinnitus followed by left tinnitus presentation warrant higher index of suspicion.

Speech Understanding in Complex Environments by School-Age Children with Mild Bilateral or Unilateral Hearing Loss.

Numerous studies have shown that children with mild bilateral (MBHL) or unilateral hearing loss (UHL) experience speech perception difficulties in poor acoustics. Much of the research in this area has been conducted via laboratory studies using speech-recognition tasks with a single talker and presentation via earphones and/or from a loudspeaker located directly in front of the listener. Real-world speech understanding is more complex, however, and these children may need to exert greater effort than their peers with normal hearing to understand speech, potentially impacting progress in a number of developmental areas. This article discusses issues and research relative to speech understanding in complex environments for children with MBHL or UHL and implications for real-world listening and understanding.

The association of auditory function measures with low-level methylmercury from oceanic fish consumption and mercury vapor from amalgam: The Seychelles Child Development Study Nutrition 1 Cohort

BackgroundSome authors have reported that low-level exposure to methylmercury (MeHg) adversely impacts measures of auditory function. These reports, however, are not consistent in their findings. Consequently, we examined auditory function in a population exposed to low-level methylmercury (MeHg) exposure from fish consumption and to mercury vapor (Hg0) from dental amalgams. We analyzed their associations with the participants hearing acuity, absolute and interwave ABR latencies, and otoacoustic emissions (distortion product/DPOAE and click evoked/CEOAE). DesignWe administered an audiometry test battery to 246 participants from the Seychelles Child Development Study (SCDS) Nutrition Cohort 1 (NC1) at 9 years of age. The test battery included standard pure-tone audiometry, tympanometry, Auditory Brainstem Responses (ABR) and Distortion Product and Click Evoked Otoacoustic Emissions (DPOAE and CEOAE) testing. We measured prenatal MeHg exposure in maternal hair and postnatal MeHg in children’s hair. We approximated prenatal Hg0 exposure using maternal amalgam surface area and postnatal Hg0 using children amalgam surface area. Complete exposure records and audiometric data were available on 210 participants and in them we analyzed the association of MeHg and Hg0 exposures with auditory outcomes using covariate-adjusted linear regression models adjusted for sex and tympanometric pressure. ResultsHg exposures were similar for both sexes. Seven of the 210 evaluable participants examined had either a mild (5) or moderate (2) hearing loss. Four had a mild monaural hearing loss and 3 had either a mild (1) or moderate (2) bilateral hearing loss. No participant had greater than a moderate hearing loss in either ear. Hg exposures were higher in participants with either a mild or moderate hearing loss, but these differences were not statistically significant. Among the 210 with complete data, neither prenatal nor postnatal MeHg nor Hg0 exposure was statistically significantly associated with any of the ABR endpoints (p > 0.05 for all 72 associations). Neither prenatal nor postnatal Hg0 exposure was associated with any of the OAE endpoints (p > 0.05). MeHg exposure was statistically associated with 6 of the 56 DPOAE endpoints (p-values between 0.0001 and 0.023), but none of the 40 CEOAE endpoints. Two of the associations occurred with prenatal MeHg exposures and 1 of those would suggest a beneficial effect. Four of the other associations occurred with postnatal MeHg exposures with only 2 found in left ears of both males and females and the other 2 in the left and right ear of females at only one frequency. ConclusionOverall, these data do not present a clear and consistent pattern to suggest that the auditory system is negatively affected by low-level methylmercury exposure due to dietary consumption of oceanic fish or mercury vapor exposure from dental amalgams.

Language and quality of life in Swedish children with mild hearing loss

ABSTRACT This study explored the impact of mild bilateral sensorineural hearing loss (MBHL) on language development and health-related quality of life (HRQoL) and investigated the relationship between these outcomes in school-aged children. Participants comprised 16 children (9 girls, 7 boys) between 9–12 years (mean 11.2 years) with MBHL born in Sweden. Language was assessed by a Speech Pathologist and children self-reported their HRQoL. Results showed mean scores for language and HRQoL were not significantly different to normative means. Two children (12.5%) met the criterion for language disorder (LD) and another two children were considered at risk for poor HRQoL. The participants scored poorest on the language skills of formulating of sentences and following concepts and directions, and on the HRQoL domain of psychosocial wellbeing, although none significantly below normative means. A trend in the data showed a moderate positive correlation between overall language ability and HRQoL scores. Participant demographic factors of sex and hours of hearing aid use explained 15% of the variation in HRQoL outcomes; however, this was not statistically significant (p = .65). The hours of hearing aid use accounted for 27.5% of the variance in outcomes for language which was significant (p = .05). Overall, these results indicate that some children with MBHL are at risk of LD and poor HRQoL as they progress through school.

LARS2 variants can present as premature ovarian insufficiency in the absence of overt hearing loss.

Premature ovarian insufficiency (POI) affects 1 in 100 women and is a leading cause of female infertility. There are over 80 genes in which variants can cause POI, with these explaining only a minority of cases. Whole exome sequencing (WES) can be a useful tool for POI patient management, allowing clinical care to be personalized to underlying cause. We performed WES to investigate two French sisters, whose only clinical complaint was POI. Surprisingly, they shared one known and one novel likely pathogenic variant in the Perrault syndrome gene, LARS2. Using amino-acylation studies, we established that the novel missense variant significantly impairs LARS2 function. Perrault syndrome is characterized by sensorineural hearing loss in addition to POI. This molecular diagnosis alerted the sisters to the significance of their difficulty in following conversation. Subsequent audiology assessment revealed a mild bilateral hearing loss. We describe the first cases presenting with perceived isolated POI and causative variants in a Perrault syndrome gene. Our study expands the phenotypic spectrum associated with LARS2 variants and highlights the clinical benefit of having a genetic diagnosis, with prediction of potential co-morbidity and prompt and appropriate medical care, in this case by an audiologist for early detection of hearing loss.

A new FOXE1 homozygous frameshift variant expands the genotypic and phenotypic spectrum of Bamforth–Lazarus syndrome

Bamforth-Lazarus syndrome is a rare autosomal recessive disease caused by biallelic loss-of-function variants in the FOXE1 gene. The condition is characterized by congenital hypothyroidism due to thyroid agenesis or thyroid hypoplasia, cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis. To date, seven pathogenic variants have been reported in the FOXE1 gene causing Bamforth-Lazarus syndrome. Here we report a novel homozygous loss-of-function variant in the FOXE1 gene NM_004473.4:c.141dupC:p.(Leu49Profs*75) leading to congenital hypothyroidism due to thyroid agenesis, scalp hair abnormalities, cleft palate, small areola, cafe-au-lait spots, mild bilateral hearing loss, skin abnormalities, and facial dysmorphism. We describe the evolving phenotype in the patient with age and review previous variants reported in FOXE1. This report further expands the clinical and molecular spectrum of Bamforth-Lazarus syndrome.

Hearing aid benefits in children with mild bilateral hearing loss: AUDIO-INFANS study

ObjectivesThere is a lack of consensus regarding the definition, consequences, and management of mild bilateral hearing loss in children. The objective of this study is to analyze the benefit of hearing aids in children with mild bilateral hearing loss by evaluating their functional hearing. MethodsThis retrospective study included 57 children with mild bilateral hearing loss between 20 dB HL and 40 dB HL. Pure tone and speech audiometry thresholds were assessed with and without hearing aids. Two groups were subsequently formed: group E with an effective use of hearing aids (>10 h/day), and group IE whose use of hearing aids was deemed ineffective (<10 h/day). ResultsWithout hearing aids, the initial median of hearing level was 35 dB HL and 36 dB HL in the right and left ears, respectively, compared to 23 dB HL and 25 dB HL with hearing aids. The Lafon test performed on 25 children at 55 dB HL and 65 dB HL showed results ranging from 0% to 100% without hearing aids and from 90% to 100% with hearing aids. Scores obtained with hearing aids were significantly higher than those without them at an average speech level. Median age at diagnosis and at prescription were found to significantly influence the daily use of hearing aids. ConclusionsOur results show that in the case of mild bilateral hearing loss, hearing aids have positive effects on the functional hearing of children and help them to no longer be disadvantaged. This study highlights the need to provide regular support to these children to ensure their optimal care in the event of hearing-related problems. Coordination between the different professionals working with these children is also necessary for their follow-up and appropriate management.

Long QT and Hearing Loss in High-Risk Infants Prospective Study Registry.

The objective of this study is to determine the prevalence of an abnormal electrocardiogram showing a prolonged QTc greater than 450ms in infants with unilateral or bilateral sensorineural hearing loss. We conducted a prospective study of healthy term infants (≥37weeks gestational age) who failed their newborn auditory brainstem response hearing screen, were seen by an audiologist and diagnosed as having sensorineural hearing loss during follow-up to 1 year of age. In infants with a diagnosis of hearing loss, we collected a detailed family history and performed an ECG between 2 and 6months of age. We obtained follow-up for 1year by calling the parent requesting the hearing and cardiac status of their child. Two of the 40 infants with sensorineural hearing loss (5%) had a QTc greater than 450ms. Both had mild bilateral hearing loss and genetic testing did not identify a known mutation for long QT syndrome. The remaining 38 infants had QTc intervals of ≤ 450ms. One patient diagnosed with bilateral severe sensorineural hearing loss had a normal ECG (QTc = 417ms). Several months after the ECG was performed, the infant's mother contacted the study cardiologist after she learned that the infant's maternal grandmother was diagnosed with a cardiomyopathy and arrhythmias. Genetic testing was recommended even though the child was asymptomatic and was positive for a pathogenic mutation in the KCNQ1 gene. We speculate that molecular genetic testing in infants with hearing loss may become the standard of care rather than targeted electrocardiograms.Clinical Trial Registration NCT02082431 https://www.clinicaltrials.gov/ct2/show/NCT02692521?cond=NCT02692521&rank=1 .

MO021: Alport syndrome manifestation in twins

Abstract BACKGROUND AND AIMS Alport syndrome (AS) is a hereditary renal disease characterized by progressive loss of kidney function and often accompanied by sensorineural hearing loss and ocular abnormalities [1]. The variety of symptoms and their severity is closely associated with mode of inheritance, type of mutation, as well as the sex of the patient [2]. In cases of twins with Alport syndrome, genotype–phenotype manifestation shows a large intrafamilial heterogeneity, although only few reports have been published. In this case series, we describe three different manifestations of three unrelated families with AS with twin pattern. METHOD Molecular analysis by next-generation sequencing was performed on individuals with suspected AS in Vilnius University Hospital Santaros Klinikos. Only patients with confirmed pathogenic AS variants and presence of the twin sibling were included in this study. Clinical, genetic, and laboratory data were reviewed and compared among the siblings and their family members. RESULTS Case 1: Two heterozygous twin sisters with two compound heterozygous pathogenic variants c.4702C &amp;gt; T and c.3247G &amp;gt; C in COL4A3 gene led to autosomal recessive AS. The first sister with a history of nephritis from a childhood reached kidney failure at the age of 33. Further investigations revealed mild bilateral sensorineural hearing loss and no ocular lesions. Her 33-year-old heterozygous twin sister had a similar past history consisting of hematuria since the age of 5 and preeclampsia during her first pregnancy at the age of 30. However, at the age of 33, this patient still had preserved kidney function with eGFR &amp;gt;45 mL/min/1.73 m3. She also suffered by mild bilateral hearing loss while no ocular abnormalities were found. Case 2: Heterozygous pathogenic variant c.2623G &amp;gt; A in COL4A5 gene in female heterozygous twin and her relatives (her mother, son and granddaughter) led to X-linked AS while her twin brother was born healthy. The 51-year-old female’s medical history revealed hematuria since 7 years of age. Her kidney function gradually declined and the patient reached kidney failure at the age of 43 years. Family screening showed a history of kidney disease. Her mother developed hematuria and proteinuria at the age of 20 years and kidney failure at 60 years. The patient's son reached kidney failure at his 20s and he also had bilateral sensorineural hearing loss and typical ocular lesions. Her granddaughter has experienced persistent hematuria and proteinuria since 2 months old, but no extrarenal manifestations were discovered. Case 3: Two heterozygous twin brothers with heterozygous pathogenic variant c.593G &amp;gt; T in COL4A3 gene led to autosomal dominant AS. A 53-year-old male has experienced persistent hematuria and proteinuria since the age of 26. At the age of 53, kidney biopsy was performed where FSGS, thin and split glomerular basement membrane were observed. Further examination showed mild bilateral sensorineural hearing loss and no ocular abnormalities. Family screening revealed that multiple family members had a history of kidney disease. Patient's 55-year-old twin brother experienced persistent hematuria since early adulthood; however, he did not show any signs of hearing loss or ocular abnormalities. Elder brother demonstrated hematuria as well. The patient's deceased father reached kidney failure at the age of 69; however, no hearing abnormalities were found. CONCLUSION Observing genotype–phenotype manifestations suggest that some pathogenic variants demonstrate intrafamilial phenotypic variability. Therefore, despite having identical mutations, twins can manifest AS differently.

Hearing aid use in 11-year-old children with mild bilateral hearing loss: Associations between parent and child ratings and datalogging

ObjectiveThis study examined the hearing aid use in older school-aged children with mild bilateral hearing loss. More specifically, it investigated children's and parents' estimation of use in comparison to datalogging as well as explored the situations children used their hearing aids. Methods and materialsSixteen children with mild bilateral hearing loss and their parents participated. Of those, 14 children used hearing aids. Children and parents completed a questionnaire on hours of hearing aid use and situations hearing aids were used. Datalogging of the hearing aids was recorded and compared to the outcome of the questionnaires. ResultsDatalogging indicated average hearing aid use time was 6.6 h. Children significantly overestimated their use of their hearing aids while approximately half the parents overestimated their child's use. Children used their hearing aids most often at school and in the car. ConclusionChildren with mild bilateral hearing loss overestimate the amount of time they are wearing their hearing aids. This may impact counselling and intervention on the use of hearing aids. Therefore, school-aged children should be included in the discussions around potentially increasing use of hearing aids.

EP200: Noonan syndrome associated with focal occipital alopecia in a patient with RAF1 variant: A case report and literature review

Noonan syndrome (NS) is a heterogenous condition characterized by distinctive craniofacial features, cardiac defects, and neurodevelopmental changes and is caused by variants in one of seven genes coding for proteins within the Ras-MAPK pathway. Pathogenic variants in RAF1 account for approximately 3-17% of cases and are associated with a high prevalence of severe hypertrophic cardiomyopathy (HCM) and pulmonary hypertension (PHTN). Cerebrovascular and Chiari I malformations, although rare, have also been described in individuals with RAF-1 NS. To our knowledge, the presence of congenital occipital alopecia in an individual with NS has not been previously reported. We report a patient with a de novo pathogenic heterozygous RAF1 gene sequence variant, c.770C>T (p.Ser257Leu), with atypical scalp findings. Our proband was a 4-week-old female dichorionic, diamniotic twin born at 35 weeks 2 days gestation to nonconsanguineous parents. At birth, her length was 45.7 cm (14th centile), weight was 2656 g (69th centile), and head circumference was 34.5 cm (97th centile). The mother was 38 at the time of birth. There was no history of maternal or gestational diabetes. Prenatal ultrasound was concerning for cystic hygroma. The immediate neonatal course was complicated by acute respiratory failure, left ventricular outflow tract obstruction with concern for coarctation on echocardiogram, poor feeding, and failed newborn hearing screen which prompted transfer to a tertiary NICU for further management. At the time of consultation, the following problems had been identified: bilateral cataracts, significant redundant posterior neck folds that showed fatty soft tissue neck mass without a cystic component, and hypertrophic cardiomyopathy with elevated pulmonary arterial pressures. Physical exam was notable for relative macrocephaly with turricephaly, lowset, posteriorly rotated ears, redundant posterior neck folds, and a focal, 1cm circular area of alopecia at the midline occipital region. These findings were concerning for a RASopathy. Imaging of her superficial midline scalp defect with brain MRI showed a suspected atretic encephalocele, but CT did not reveal any occipital bony defects. After re-evaluation, it was confirmed that there was no intracranial connection or bony defect at the area of the congenital alopecia nor at the level of the suboccipital skin thickening/redundancy. Chromosomal microarray was nondiagnostic and thus exome sequence analysis was preformed which detected the pathogenic RAF1 variant. The diagnosis of RAF1 NS accounts for nearly all of the physical changes seen in our patient, particularly the severe degree of PHTN and HCM, with the exception of her occipital alopecia. Since our initial consultation, the patient continues to grow along NS-specific curve, has persistent mild bilateral hearing loss, and has had interval placement of gastric tube secondary to oral feeding difficulties. There has been mild improvement in cardiac function, septal hypertrophy, and PHTN. She remains seizure-free. This report expands the phenotype of RAF1 Noonan syndrome to include congenital focal alopecia. We recommend that NS should be added to the differential when this same scalp finding is present. Although the presence of this physical finding in our patient was not definitively associated with any underlying structural CNS or bony changes, this case highlights the importance of investigating with detailed cranial and spinal imaging to better characterize cerebral morphology and guide genetic testing in suspected RASopathy cases. Additional cases with this finding are needed to better understand potential associations.

Parent-Reported Stress and Child Behavior for 4-Year-Old Children with Unilateral or Mild Bilateral Hearing Loss.

Children with unilateral or mild bilateral hearing loss are increasingly identified in early childhood. Relatively little is known about how hearing loss affects their developmental trajectory or whether it contributes to parenting stress for these parents. This study aimed to examine child behavior and parenting stress in parents of children with unilateral/mild bilateral hearing loss compared to children with typical hearing. This prospective study involved 54 children with unilateral/mild bilateral hearing loss identified at a median age of 4.5months (IQR 2.6, 6.5) and 42 children with typical hearing. At age 48months, child behavior and parenting stress were measured. Auditory and language results were also analyzed in relation to child behavior and parenting stress. Parents of these children did not report significantly more parenting stress or behavior problems than parents of children with typical hearing. However, both parenting stress and child behavior were related to functional hearing in noise.

Audiologists’ perspectives on management of mild bilateral hearing loss in infants and young children

Objective Universal newborn hearing screening programs have led to early identification of infants with congenital mild bilateral hearing loss (MBHL). The current lack of evidence-based protocols to guide audiological management of infants with MBHL has led to clinical equipoise about fitting of hearing aids. The purpose of this study was to increase understanding about the perspectives of paediatric audiologists on factors influencing their management of MBHLin infants and young children. Design A qualitative descriptive research methodology involving semi-structured interviews with audiologists. Study sample Twenty-three paediatric audiologists in diagnostic and rehabilitation settings in Victoria, Australia. Results Three main themes that influenced management were identified. These include: (1) evidence, or the lack of it, influences audiologists’ practice; (2) audiologists recognise the need to be fluid; and (3) family characteristics and parents’ perspectives. “Audiologists delivering family-centred practice” was identified as an overarching theme across these factors. Conclusions Audiologists recognised the importance of adopting a family-centred approach in their management of MBHL in infants and young children. Embodied in their practice was the acknowledgement of limited evidence, the consideration of multiple child and family factors, and the incorporation of perspectives of parents and families in adopting a fluid approach to provide individualised services.