The Role of Motion Sensitivity and Headaches on Vestibular Rehabilitation Outcomes in Pediatric Vestibular Migraines.

OBJECTIVE: To determine the utility of the motion sensitivity quotient (MSQ) in diagnosing pediatric vestibular migraine (VM) and to characterize the role of motion sensitivity and headache control on vestibular rehabilitation (VR) outcomes in pediatric VM. STUDY DESIGN: Retrospective cohort analysis. SETTING: Pediatric tertiary referral center. PATIENTS: Children (≤18 years old) with dizziness who completed vestibular testing from January 2016 to August 2022, diagnosed with either VM or another vestibular disorder. INTERVENTIONS: VR, which included MSQ testing. MAIN OUTCOME MEASURES: Initial MSQ, number and duration of vestibular physical therapy (PT) sessions, PT goals met, and posttreatment MSQ. RESULTS: Two hundred fifty-seven patients met study criteria. MSQ was not a reliable diagnostic marker in pediatric VM as there was no difference in initial MSQ between VM and non-VM patients (9.4 vs. 7.8 in non-VM, p = 0.014). Both VM (n = 116) and non-VM (n = 141) patients demonstrated significant improvement in MSQ after VR (p = 0.004). However, VM patients tended to be less likely to meet at least one PT goal (60 vs. 77% in non-VM, p = 0.016, d = 0.37), although not significant. VM patients with more frequent headaches had significantly higher initial MSQ (p = 0.008). VM patients with more frequent headaches or higher initial MSQ tended to require increased number and longer duration of VR (small/medium effect size although not statistically significant after Bonferroni correction). CONCLUSION: VR is an effective treatment for both VM and non-VM pediatric patients. VM patients, especially those with severe motion sensitivity or poorly controlled headaches, may be less responsive to VR and may require increased frequency and duration of VR. Our findings propose the importance of counseling pediatric patients with severe motion sensitivity or uncontrolled migraines regarding realistic expectations of their VR course.

The Girl With the Bleeding Earlobe Mass.

ABSTRACT: Pilomatrixomas, also known as epithelioma calcificans, are benign tumors of hair follicle matrix cells that are often mistaken for other lesions, especially cutaneous abscesses. We report an illustrative case in which a teenage girl developed a red, swollen earlobe that required multiple care visits and interventions until definitive diagnosis and treatment were provided. Although the lesion was initially treated as an abscess, it continued to progress in size and discomfort. The correct diagnosis was established after imaging and complete excision with pathologic examination. Ultimately, our patient was subjected to avoidable procedures that carried the risk of potentially negative cosmetic sequelae before the proper intervention. Although abscesses are common, it is important for clinicians to avoid incision and drainage of lesions, unless the diagnosis is certain.

Cortical processing of location and frequency changes of sounds in normal hearing listeners.

Sounds we hear in our daily life contain changes in the acoustic features (e.g., frequency, intensity, and duration or "what" information) and/or changes in location ("where" information). The purpose of this study was to examine the cortical auditory evoked potentials (CAEPs) to the change within a stimulus, the acoustic change complex (ACC), in frequency (F) and location (L) of the sound in normal hearing listeners. Fifteen right-handed young normal hearing listeners participated in the electroencephalographic (EEG) recordings. The acoustic stimuli were pure tones (base frequency at 250 Hz) of 1 s, with a perceivable change either in location (L, 180°), frequency (F, 5% and 50%), or both location and frequency (L+F) in the middle of the tone. Additionally, the 250 Hz tone of 1 sec without any change was used as a reference. The participants were asked to listen passively to the stimuli and not to move their heads during the testing. Compared to the reference tone, by which only the onset-CAEP was elicited, the tones containing changes (L, F, or L+F) elicited both onset-CAEP and the ACC. The waveform analysis of ACCs from the vertex electrode (electrode Cz) showed that, larger sound changes evoked larger peak amplitudes [e.g., (L+50%F)- > L-change; (L+50%F)- > 5%F-change] and shorter the peak latencies ([(L+5%F)- < 5%F-change; 50%F- < 5%F-change; (L+50%F)- < 5%F-change] . The current density patterns for the ACC N1' peak displayed some differences between L-change vs. F-change, supporting different cortical processing for "where" and "what" information of the sound; regardless of the nature of the sound change, larger changes evoked a stronger activation than smaller changes [e.g., L- > 5%F-change; (L+5%F)- > 5%F-change; 50%F- > 5%F-change] in frontal lobe regions including the cingulate gyrus, medial frontal gyrus (MFG), superior frontal gyrus (SFG), the limbic lobe cingulate gyrus, and the parietal lobe postcentral gyrus. The results suggested that sound change-detection involves memory-based acoustic comparison (the neural encoding for the sound change vs. neural encoding for the pre-change stimulus stored in memory) and involuntary attention switch.

Socioeconomic Disparities in Pediatric Single-Sided Deafness.

OBJECTIVE: To explore socioeconomic disparities in pediatric single-sided deafness (SSD) treatment. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral academic center. METHODS: The charts of 190 pediatric patients with SSD were reviewed for demographic and clinical characteristics. Socioeconomic variables included race and insurance status. ZIP codes were used to obtain additional socioeconomic data from the American Community Survey, including mean and median income, percentage of families below the poverty level, and employment status. Socioeconomic status (SES) was classified by insurance status and income. Treatment outcomes were analyzed by socioeconomic variables. RESULTS: There were 105 males and 85 females with a mean follow-up of 55.2 months and a mean age at diagnosis of 4.4 years. Sixty-three percent of children received treatment at last follow-up. Thirty-five percent of children had public insurance and 65% had private insurance. Treatment rates were similar in the private and public insurance groups (60.6% vs 66.7%, P = .42), but device type was different between groups (P = .02). Consistent device use was associated with private insurance (47.5% vs 38.9%, P = .003) and high SES (94.4% vs 80%, P = .04) on univariate but not on multivariate analysis. Aided audiometry results were similar between SES groups. No association was found between sex, race, income level, poverty level, or employment status and treatment outcomes. CONCLUSION: Insurance type and SES were not associated with SSD treatment outcomes in children, although device use may be higher in children with private insurance and higher SES. Further research should focus on strategies to reduce barriers to treatment and improve adherence.

International Pediatric Otolaryngology Group (IPOG) Consensus Recommendations: Congenital Cholesteatoma.

OBJECTIVE: To provide recommendations to otolaryngologists and allied physicians for the comprehensive management of children who present with signs and symptoms of congenital cholesteatoma. METHODS: A two-iterative Delphi method questionnaire was used to establish expert recommendations by the members of the International Pediatric Otolaryngology Group, on the preoperative work-up, the perioperative considerations, and follow-up. RESULTS: Twenty-two members completed the survey, in 14 tertiary-care center departments representing 5 countries. The main consensual recommendations were: a precise otoscopic description of the quadrants involved, extensive audiological workup (bilateral tonal, vocal audiometry, and BERA), and a CT scan are required. Facial nerve monitoring and a combination of microscope and telescope are recommended for surgical removal. Clinical and audiological follow-up should be pursued yearly for at least 5 years. First MRI follow-up should be done at 18 months postoperatively if the removal violated the matrix. MRI follow-up duration depends on the initial extent of the cholesteatoma. CONCLUSION: The goal of preoperative and follow-up consensus from International Pediatric Otolaryngology Group participants is to help manage infants and children with congenital cholesteatoma. The operative techniques may vary, and experienced surgeons must perform these procedures.

Imaging findings in pediatric single-sided deafness and asymmetric hearing loss.

OBJECTIVE: To examine the imaging findings on computer tomography (CT) and magnetic resonance imaging (MRI) in pediatric single-sided deafness (SSD) and asymmetric hearing loss (ASH). METHODS: The medical records of 189 pediatric patients with SSD and ASH were retrospectively reviewed, and imaging findings were compared. SSD was defined as unilateral profound hearing loss and contralateral normal hearing ear. In the ASH group, ASHw was defined as the worse hearing ear with profound hearing loss, while ASHb was defined as the better hearing ear with mild-moderate hearing loss. RESULTS: There were 170 patients with SSD and 19 patients with ASH. In the SSD group, 83 patients (48.8%) had imaging findings associated with hearing loss. In the ASH group, such imaging findings were found in six (31.6%) of the ASHw and in five (26.3%) of the ASHb ears. The most common finding in the SSD group was cochlear nerve deficiency (50.6%), followed by cochlear dysplasia (39.8%) and enlarged vestibular aqueduct (26.5%). In the ASH groups, cochlear dysplasia was seen in three (50%) of ASHw ears and in two (40%) of the ASHb ears, and enlarged vestibular aqueduct was seen in three (50%) of ASHw ears and in two (40%) of the ASHb ears. CONCLUSION: Imaging studies identified the etiology in half of the cases of SSD and in one-third of ASH patients. Our findings strongly support the use of imaging studies in the evaluation of pediatric SSD and ASH. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1007-1010, 2020.

The Clinical Journey of Patients with Riboflavin Transporter Deficiency Type 2.

PURPOSE: To identify symptoms and health care interactions with patients with riboflavin transporter deficiency (RTD) type 2 prior to diagnosis. METHODS: Parents of children with riboflavin transporter deficiency type 2 (n = 10) were interviewed to collect data on the patient's clinical journey. RESULTS: The average diagnostic delay was 27.6 months. Neurologists were the most commonly visited clinician (90%). Common symptoms during the first year of the patient's clinical journey included abnormal gait and/or ataxia (70%), nystagmus (50%), and upper body muscle weakness (40%). Prior to diagnosis, optic atrophy, sleep apnea, breath-holding spells, and dysphagia were commonly observed. Hearing loss was only reported in 40% of subjects prior to diagnosis. Riboflavin responsive megaloblastic anemia is reported for the first time. Mitochondrial disease was the most common suspected diagnosis (30%). CONCLUSION: Despite clinical variability, common early symptoms of riboflavin transporter deficiency type 2 exist that can better allow clinicians to more rapidly identify riboflavin transporter deficiency type 2.

Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel.

PURPOSE: Pathogenic variants in GJB2 are the most common cause of autosomal recessive sensorineural hearing loss. The classification of c.101T>C/p.Met34Thr and c.109G>A/p.Val37Ile in GJB2 are controversial. Therefore, an expert consensus is required for the interpretation of these two variants. METHODS: The ClinGen Hearing Loss Expert Panel collected published data and shared unpublished information from contributing laboratories and clinics regarding the two variants. Functional, computational, allelic, and segregation data were also obtained. Case-control statistical analyses were performed. RESULTS: The panel reviewed the synthesized information, and classified the p.Met34Thr and p.Val37Ile variants utilizing professional variant interpretation guidelines and professional judgment. We found that p.Met34Thr and p.Val37Ile are significantly overrepresented in hearing loss patients, compared with population controls. Individuals homozygous or compound heterozygous for p.Met34Thr or p.Val37Ile typically manifest mild to moderate hearing loss. Several other types of evidence also support pathogenic roles for these two variants. CONCLUSION: Resolving controversies in variant classification requires coordinated effort among a panel of international multi-institutional experts to share data, standardize classification guidelines, review evidence, and reach a consensus. We concluded that p.Met34Thr and p.Val37Ile variants in GJB2 are pathogenic for autosomal recessive nonsyndromic hearing loss with variable expressivity and incomplete penetrance.

Radiologic recognition of cochlear implant magnet displacement.

Despite various studies that have demonstrated risk of cochlear implant magnet displacement following MRI, minimal literature is available on radiologic recognition of magnet displacement. Current literature emphasizes the status and placement of the electrode component of the implant. This case report examines the consequences of a delay in radiologic diagnosis of a displaced magnet including hospital admission, unnecessary radiation, and prolonged patient discomfort. Additionally, it provides a framework for successful radiologic recognition of a displaced magnet, detailing specific imaging modalities and magnet characteristics that should be evaluated to expedite and facilitate radiologic recognition of displacement.

Ocular Vestibular Evoked Myogenic Potentials: Normative Findings in Children.

BACKGROUND: To add to the limited body of literature on ocular vestibular evoked myogenic potential (oVEMP) responses in children and to assess a different montage for oVEMP recording. PURPOSE: To evaluate the characteristics of the oVEMP response in children and compare the results with that of a group of healthy adults. RESEARCH DESIGN: Prospective descriptive study from a tertiary referral center. STUDY SAMPLE: Twenty-two children (mean age = 6.3 yr, standard deviation = ±1.5, range = 3.5-8.9 yr) were recruited from families whose parent(s) were employed by the Cincinnati Children's Hospital Medical Center (CCHMC). Pediatric participants were categorized by age into three groups for data analysis. The comparison adult group of ten participants were members of the employee staff at CCHMC. DATA COLLECTION AND ANALYSIS: Audiometric assessment was completed in all participants. The latency, amplitude, and threshold of the oVEMP responses were recorded using a modified electrode montage with reference at the chin and compared between the pediatric and adult participants. RESULTS: All participants completed testing and had bilateral measurable oVEMP responses using a 105-dB nHL, 500-Hz tone burst stimulus. Comparison between right and left ears across all participants for each oVEMP characteristic found no statistically significant difference. oVEMP testing showed no significant differences with respect to latency, amplitude, interaural amplitude asymmetry, and threshold of response as a function of age. CONCLUSIONS: oVEMP responses for ages ≥3 did not differ from responses in adults.

Vestibular pathology in children with enlarged vestibular aqueduct.

OBJECTIVES/HYPOTHESIS: To establish the prevalence of abnormal vestibular test findings in children with enlarged vestibular aqueduct (EVA) and determine if these findings correlate with clinical symptoms, radiographic findings (EVA size and laterality), audiometric findings, and genetic testing in these patients. STUDY DESIGN: Prospective cohort. METHODS: Patients 3 to 12 years of age with hearing loss and imaging findings consistent with EVA treated at our tertiary care institution were sequentially enrolled from 2009 to 2011. The following six outcome measurements were analyzed: audiometric findings, EVA laterality, temporal bone measurements, genetic testing, vestibular testing (cervical-evoked myogenic potentials, posturography, rotational chair, and calorics), and vestibular symptoms. RESULTS: Twenty-seven patients with EVA (mean age 9.2 years, 48% female) were enrolled in and completed the study. Vertigo was reported in six patients. Twenty-four of 27 (89%) had at least one abnormal vestibular test result. Midpoint and operculum size correlated with directional preponderance (P = .042 and P = .032, respectively). Also, high-frequency pure tone average (HFPTA) correlated with unilateral weakness (P = .002). Walking at a later age correlated with abnormal posturography results. There was no correlation between EVA laterality and vestibular test findings. CONCLUSION: We found a high rate of vestibular pathology in children with EVA; however, the prevalence of abnormal vestibular test findings in this patient population was not correlated with vestibular symptoms. Enlarged vestibular aqueduct size, HFPTA, and walking at a later age were correlated with abnormal vestibular test findings. In view of these results, it may be prudent to consider vestibular testing in children with these clinical characteristics. LEVEL OF EVIDENCE: 2b. Laryngoscope, 126:2344-2350, 2016.

High-frequency sensorineural hearing loss in children.

OBJECTIVES/HYPOTHESIS: Determine the prevalence of high-frequency sensorineural hearing loss (HFSNHL) in our hearing loss population and a diagnostic algorithm for these patients. STUDY DESIGN: Retrospective case series. METHODS: We identified patients diagnosed with sensorineural hearing loss (SNHL) at our pediatric tertiary care institution from 1981 to 2010. Based on audiometric profiles, these patients were subdivided into those with a flat SNHL configuration and those with HFSNHL. Imaging and genetic testing data and data regarding age at diagnosis, laterality, and risk factors were obtained for both groups. Comparisons were then made between the two groups. RESULTS: Of 2,867 patients included in the study, 7.6% had HFSNHL. Age at diagnosis was significantly higher in HFSNHL patients (8.3 years vs. 6.1 years; P < .0001). These patients also had a significantly higher proportion of unilateral versus bilateral loss (49.1% vs. 26.1%; P < .0001); unilateral losses were also less severe. Genetic testing showed no significant difference between groups in the proportion of patients tested or in those who tested positive. Similarly, imaging data revealed no difference in the proportion of patients tested in the two groups; however, overall diagnostic yield was significantly higher in flat SNHL patients (29.5% vs.17.3; P = .02). CONCLUSIONS: The positive predictive value of simple genetic testing is similar to that of imaging studies. However, given cost differences between genetic testing and imaging, it is prudent to perform genetic testing as the initial diagnostic test. Determination of whether high-throughput, multigene diagnostic platforms offer an added benefit in the evaluation of children requires further study. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1236-1240, 2016.

Diagnostic Evaluation of Children with Sensorineural Hearing Loss.

The cause of pediatric sensorineural hearing loss is diverse, comprising genetic, acquired, and idiopathic conditions. Identifying the specific cause requires that children undergo thorough otolaryngologic and audiometric evaluations, which generally include laboratory tests and temporal bone imaging studies. Clinical genetics and ophthalmologic consultations are also frequently warranted. A sequential diagnostic approach has been shown to be both prudent and cost-effective. Although a definitive cause is being established, amplification and a comprehensive treatment strategy should be initiated to ensure that developmental, auditory, and speech and language delays are minimized.

Molecular genetics of MARVELD2 and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss.

Pathogenic mutations of MARVELD2, encoding tricellulin, a tricelluar tight junction protein, cause autosomal recessive non-syndromic hearing loss (DFNB49) in families of Pakistan and Czech Roma origin. In fact, they are a significant cause of prelingual hearing loss in the Czech Roma, second only to GJB2 variants. Previously, we reported that mice homozygous for p.Arg497* variant of Marveld2 had a broad phenotypic spectrum, where defects were observed in the inner ear, heart, mandibular salivary gland, thyroid gland and olfactory epithelium. The current study describes the types and frequencies of MARVELD2 alleles and clinically reexamines members of DFNB49 families. We found that MARVELD2 variants are responsible for about 1.5 % (95 % CI 0.8-2.6) of non-syndromic hearing loss in our cohort of 800 Pakistani families. The c.1331+2T>C allele is recurrent. In addition, we identified a novel large deletion in a single family, which appears to have resulted from non-allelic homologous recombination between two similar Alu short interspersed elements. Finally, we observed no other clinical manifestations co-segregating with hearing loss in DFNB49 human families, and hypothesize that the additional abnormalities in the Marveld2 mutant mouse indicates a critical non-redundant function for tricellulin in other organ systems.

Mutation analysis of the SLC26A4, FOXI1 and KCNJ10 genes in individuals with congenital hearing loss.

Pendred syndrome (PDS) and DFNB4 comprise a phenotypic spectrum of sensorineural hearing loss disorders that typically result from biallelic mutations of the SLC26A4 gene. Although PDS and DFNB4 are recessively inherited, sequencing of the coding regions and splice sites of SLC26A4 in individuals suspected to be affected with these conditions often fails to identify two mutations. We investigated the potential contribution of large SLC26A4 deletions and duplications to sensorineural hearing loss (SNHL) by screening 107 probands with one known SLC26A4 mutation by Multiplex Ligation-dependent Probe Amplification (MLPA). A heterozygous deletion, spanning exons 4-6, was detected in only one individual, accounting for approximately 1% of the missing mutations in our cohort. This low frequency is consistent with previously published MLPA results. We also examined the potential involvement of digenic inheritance in PDS/DFNB4 by sequencing the coding regions of FOXI1 and KCNJ10. Of the 29 probands who were sequenced, three carried nonsynonymous variants including one novel sequence change in FOXI1 and two polymorphisms in KCNJ10. We performed a review of prior studies and, in conjunction with our current data, conclude that the frequency of FOXI1 (1.4%) and KCNJ10 (3.6%) variants in PDS/DFNB4 individuals is low. Our results, in combination with previously published reports, indicate that large SLC26A4 deletions and duplications as well as mutations of FOXI1 and KCNJ10 play limited roles in the pathogenesis of SNHL and suggest that other genetic factors likely contribute to the phenotype.

Codeine-related adverse drug reactions in children following tonsillectomy: a prospective study.

OBJECTIVES/HYPOTHESIS: To prospectively determine factors associated with codeine's adverse drug reactions (ADRs) at home in a large homogenous population of children undergoing outpatient tonsillectomy. STUDY DESIGN: Prospective, genotype blinded, observational study with a single group and repeated ADR measures documented by parents at home. METHODS: A total of 249 children 6 to 15 years of age scheduled for tonsillectomy were enrolled. The primary outcome was number of daily codeine-related ADRs. We examined the number and type of ADR by race and by days and further modeled factors potentially associated with ADR risk in a subcohort of white children. Sedation following a dose of codeine was a secondary outcome measure. Parents recorded their children's daily ADRs and sedation scores during postoperative days (POD) 0 to 3 at home. RESULTS: Diaries were returned for 134 children, who were given codeine. A total of 106 (79%) reported at least one ADR. The most common ADRs were nausea, lightheadedness/dizziness for white children and nausea, and vomiting for African American children. In a subcohort of white children ≤ 45 kg, increased ADR risk was associated with the presence of one or more full function CYP2D6 alleles (P < 0.001), POD (P < 0.001), and sex (P = 0.027). Increased pain intensity (P = 0.009) and PODs 0 and 1 (P = 0.001) contributed to a higher sedation risk. Neither obstructive apnea nor predicted CYP2D6 phenotype were associated with sedation risk. CONCLUSIONS: Our results provide evidence that multiple factors are associated with codeine-related ADRs and support the FDA recommendation to avoid codeine's routine use following tonsillectomy in children.

Genetic analysis through OtoSeq of Pakistani families segregating prelingual hearing loss.

OBJECTIVE: To identify the genetic cause of prelingual sensorineural hearing loss in Pakistani families using a next-generation sequencing (NGS)-based mutation screening test named OtoSeq. STUDY DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS AND METHODS: We used 3 fluorescently labeled short tandem repeat (STR) markers for each of the known autosomal recessive nonsyndromic (DFNB) and Usher syndrome (USH) locus to perform a linkage analysis of 243 multigenerational Pakistani families segregating prelingual hearing loss. After genotyping, we focused on 34 families with potential linkage to MYO7A, CDH23, and SLC26A4. We screened affected individuals from a subset of these families using the OtoSeq platform to identify underlying genetic variants. Sanger sequencing was performed to confirm and study the segregation of mutations in other family members. For novel mutations, normal hearing individuals from ethnically matched backgrounds were also tested. RESULTS: Hearing loss was found to co-segregate with locus-specific STR markers for MYO7A in 32 families, CDH23 in 1 family, and SLC26A4 in 1 family. Using the OtoSeq platform, a microdroplet PCR-based enrichment followed by NGS, we identified mutations in 28 of the 34 families including 11 novel mutations. Sanger sequencing of these mutations showed 100% concordance with NGS data and co-segregation of the mutant alleles with the hearing loss phenotype in the respective families. CONCLUSION: Using NGS-based platforms like OtoSeq in families segregating hearing loss will contribute to the identification of common and population-specific mutations, early diagnosis, genetic counseling, and molecular epidemiology.

Performance evaluation of the next-generation sequencing approach for molecular diagnosis of hereditary hearing loss.

OBJECTIVE: To evaluate the performance of a next-generation sequencing (NGS)-based targeted resequencing genetic test, OtoSeq, to identify the sequence variants in the genes causing sensorineural hearing loss (SNHL). STUDY DESIGN: Retrospective study. SETTING: Tertiary children's hospital. SUBJECTS AND METHODS: A total of 8 individuals presenting with prelingual hearing loss were used in this study. The coding and flanking intronic regions of 24 well-studied SNHL genes were enriched using microdroplet polymerase chain reaction and sequenced on an Illumina HiSeq 2000 sequencer. The filtered high-quality sequence reads were mapped to reference sequence, and variants were detected using NextGENe software. RESULTS: A total of 1148 sequence variants were detected in 8 samples in 24 genes. Using in-house developed NGS data analysis criteria, we classified 810 (~71%) of these variants as potential true variants that include previously detected pathogenic mutations in 5 patients. To validate our strategy, we Sanger sequenced the target regions of 5 of the 24 genes, accounting for about 29.2% of all target sequence. Our results showed >99.99% concordance between NGS and Sanger sequencing in these 5 genes, resulting in an analytical sensitivity and specificity of 100% and 99.997%, respectively. We were able to successfully detect single base substitutions, small deletions, and insertions of up to 22 nucleotides. CONCLUSION: This study demonstrated that our NGS-based mutation screening strategy is highly sensitive and specific in detecting sequence variants in the SNHL genes. Therefore, we propose that this NGS-based targeted sequencing method would be an alternative to current technologies for identifying the multiple genetic causes of SNHL.

Significance of unilateral enlarged vestibular aqueduct.

OBJECTIVES/HYPOTHESIS: To describe the clinical phenotype of pediatric patients with unilateral enlarged vestibular aqueduct (EVA) and then to compare the findings to two clinically related phenotypes: bilateral EVA and unilateral hearing loss without EVA. In view of clinical observations and previously published data, we hypothesized that patients with unilateral EVA would have a much higher rate of contralateral hearing loss than patients with unilateral hearing loss without EVA. STUDY DESIGN: Retrospective cohort study. METHODS: Patients with unilateral or bilateral EVA were identified from a database of children with sensorineural hearing loss who were seen at a tertiary care institution between 1998 and 2010. Those with imaging findings consistent with well-established EVA criteria were identified. A comparative group of patients with unilateral hearing loss without EVA was also identified. The following specific outcome measurements were analyzed: 1) hearing loss phenotype, 2) laterality of EVA and hearing loss, 3) midpoint and operculum vestibular aqueduct measurements, and 4) genetic test results. RESULTS: Of the 144 patients who met our inclusion criteria, 74 (51.4%) had unilateral EVA. There was a strong correlation between the presence of hearing loss and ears with EVA. Fifty-five percent of patients with unilateral EVA had hearing loss in the contralateral ear; in most of these patients, the hearing loss was bilateral. Contralateral hearing loss occurred in only 6% of patients with unilateral hearing loss without EVA. No significant differences were found in temporal bone measurements between the ears of patients with unilateral EVA and ipsilateral hearing loss and all ears with EVA and normal hearing (P = .4). There was no difference in the rate of hearing loss progression in patients with unilateral EVA between ears with or without EVA (16 of 48 [33.3%] vs. 9 of 27 [33.3%], respectively; P = 1.0). There was no difference in the rate of hearing loss progression in patients with bilateral and unilateral EVA (41 of 89 ears [46.1%] vs. 25 of 75 ears [33.3%], respectively; P = .1); however, both EVA groups had higher rates of progression compared to patients with unilateral hearing loss without EVA. There was a strong correlation between the presence of hearing loss at 250 Hz and the risk of more severe hearing loss and progressive hearing loss. Patients with bilateral EVA and SLC26A4 mutations had a higher rate of progression than patients who had no mutations (P = .02). No patients with unilateral EVA had Pendred syndrome. CONCLUSIONS: Children with unilateral EVA have a significant risk of hearing loss progression. Hearing loss in the ear contralateral to the EVA is common, suggesting that unilateral EVA is a bilateral process despite an initial unilateral imaging finding. In contrast to bilateral EVA, unilateral EVA is not associated with Pendred syndrome and may have a different etiology. Temporal bone measurements, hearing loss severity, and hearing loss at 250 Hz were all correlated with the risk of progressive hearing loss. Clinicians should become knowledgeable regarding the implications of this disease process so that families can be counseled appropriately.