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.

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 METHODS: The ClinGen Hearing Loss Expert Panel collected published data and shared unpublished information from contributing laboratories and clinics regarding the two variants.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.

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.

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.

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.

High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays.

BACKGROUND: Despite current knowledge of mutations in 45 genes that can cause nonsyndromic sensorineural hearing loss (SNHL), no unified clinical test has been developed that can comprehensively detect mutations in multiple genes. We therefore designed Affymetrix resequencing microarrays capable of resequencing 13 genes mutated in SNHL (GJB2, GJB6, CDH23, KCNE1, KCNQ1, MYO7A, OTOF, PDS, MYO6, SLC26A5, TMIE, TMPRSS3, USH1C). We present results from hearing loss arrays developed in two different research facilities and highlight some of the approaches we adopted to enhance the applicability of resequencing arrays in a clinical setting. RESULTS: We leveraged sequence and intensity pattern features responsible for diminished coverage and accuracy and developed a novel algorithm, sPROFILER, which resolved >80% of no-calls from GSEQ and allowed 99.6% (range: 99.2-99.8%) of sequence to be called, while maintaining overall accuracy at >99.8% based upon dideoxy sequencing comparison. CONCLUSIONS: Together, these findings provide insight into critical issues for disease-centered resequencing protocols suitable for clinical application and support the use of array-based resequencing technology as a valuable molecular diagnostic tool for pediatric SNHL and other genetic diseases with substantial genetic heterogeneity.

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.

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.

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.

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.

A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness.

BACKGROUND: South Africa has one of the highest incidences of multidrug-resistant tuberculosis (MDR-TB) in the world. Concomitantly, aminoglycosides are commonly used in this country as a treatment against MDR-TB. To date, at least five mutations are known to confer susceptibility to aminoglycoside-induced hearing loss. The aim of the present study was to develop a rapid screening method to determine whether these mutations are present in the South African population. METHODS: A multiplex method using the SNaPshot technique was used to screen for five mutations in the MT-RNR1 gene: A1555G, C1494T, T1095C, 961delT+C(n) and A827G. A total of 204 South African control samples, comprising 98 Mixed ancestry and 106 Black individuals were screened for the presence of the five mutations. RESULTS: A robust, cost-effective method was developed that detected the presence of all five sequence variants simultaneously. In this pilot study, the A1555G mutation was identified at a frequency of 0.9% in the Black control samples. The 961delT+C(n) variant was present in 6.6% of the Black controls and 2% of the Mixed ancestry controls. The T1095C, C1494T and A827G variants were not identified in any of the study participants. CONCLUSION: The frequency of 0.9% for the A1555G mutation in the Black population in South Africa is of concern given the high incidence of MDR-TB in this particular ethnic group. Future larger studies are warranted to determine the true frequencies of the aminoglycoside deafness mutations in the general South African population. The high frequencies of the 961delT+C(n) variant observed in the controls suggest that this change is a common non-pathogenic polymorphism. This genetic method facilitates the identification of individuals at high risk of developing hearing loss prior to the start of aminoglycoside therapy. This is important in a low-resource country like South Africa where, despite their adverse side-effects, aminoglycosides will continue to be used routinely and are accompanied with very limited or no audiological monitoring.

Aminoglycoside ototoxicity in Nicaraguan children: patient risk factors and mitochondrial DNA results.

OBJECTIVE: Aminoglycoside ototoxicity remains a major problem in developing countries and accounts for 3 percent to 30 percent of hearing loss. This high prevalence rate may be related to genetic susceptibility from mitochondrial mutations in the 12S rRNA gene, comorbidity factors, or unregulated use of the medication. This study investigates the risk factors and prevalence of mtDNA mutations in serum from rural Nicaragua children with aminoglycoside-related hearing loss. STUDY DESIGN: Cross sectional study. SUBJECTS: Deaf children from rural Nicaragua. METHODS: Mitochondrial DNA isolated from serum collected from 31 deaf children with childhood or in utero exposure to gentamicin was amplified, sequenced, and analyzed for mutations in the 12S rRNA gene. RESULTS: No known pathologic mutations of the 12S rRNA gene were identified in this subpopulation of deaf children. In addition, patients with gentamicin exposure were often likely to have other comorbidity factors. CONCLUSION: These results suggest that genetic susceptibility is not a major factor in the high rate of gentamicin ototoxicity in this population sample. The high prevalence of gentamicin ototoxicty in this population is presumed to be due to unrestricted access to the drug.

Hearing loss progression and contralateral involvement in children with unilateral sensorineural hearing loss.

OBJECTIVES: We undertook this study to determine the rate of hearing loss progression in the affected ear of children with unilateral sensorineural hearing loss and without an enlarged vestibular aqueduct, and the rate of new-onset hearing loss in the contralateral ear. METHODS: We searched the database at our pediatric tertiary care center to identify patients who met the inclusion criteria, examining demographic variables, audiometric data, and presumptive causes. RESULTS: We identified 198 patients. At presentation, they showed slight left-sided and male predominances. Of 142 patients who had sufficient audiometric follow-up for us to evaluate progression, 21% showed ipsilateral progression and 10.6% developed new-onset hearing loss in the contralateral ear. Isolated high-frequency loss was identified in 11 patients (5.6%), 8 of whom had sufficient follow-up for us to identify progression. Two showed progression; 4 others with progression in the ipsilateral ear developed new-onset high-frequency loss in the contralateral ear. Temporal bone anomalies were identified in 26 children (13%), and these children were more likely to have profound hearing loss than were those without temporal bone anomalies (46% versus 23%). CONCLUSIONS: The findings suggest that unilateral sensorineural hearing loss may not always be a unilateral process, but that it may be the initial manifestation of bilateral auditory dysfunction.

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.

Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss is associated with the 12S rRNA C1494T mutation in three Han Chinese pedigrees.

We report here the clinical, genetic and molecular characterization of three Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic bilateral hearing loss. Clinical evaluation revealed the wide range of severity, age-at-onset and audiometric configuration of hearing impairment in matrilineal relatives in these families. The penetrances of hearing loss in these pedigrees were 28%, 20%, and 15%, with an average of 21%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees were 21%, 13% and 8%, with an average of 14%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA C1494T mutation, in addition to distinct sets of mtDNA polymorphism belonging to Eastern Asian haplogroups F1a1, F1a1 and D5a2, respectively. This suggested that the C1494T mutation occurred sporadically and multiplied through evolution of the mtDNA. The absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in their mtDNA suggests that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the C1494T mutation in those Chinese families. In addition, the lack of significant mutation in the GJB2 gene ruled out the possible involvement of GJB2 in the phenotypic expression of the C1494T mutation in those affected subjects. However, aminoglycosides and other nuclear modifier genes play a modifying role in the phenotypic manifestation of the C1494T mutation in these Chinese families.

Prevalence and etiology of hearing loss in rural Nicaraguan children.

OBJECTIVE/HYPOTHESIS: The prevalence and causes of pediatric hearing loss (HL) in the developing world are largely unknown. Infectious sequelae, ototoxic medications, and genetic causes may play a larger role in developing countries. In addition, the significance of GJB2 mutation gene in poorly developed areas remains unclear. The intent of this study is to investigate the prevalence and etiology of HL in children living in a remote, impoverished region of northern Nicaragua. STUDY DESIGN: Cross-sectional study. METHODS: Clinical data from two sources were analyzed: data from screening examinations performed in rural schools in the Department of Jinotega, Nicaragua (group A) and pediatric HL patients seen at the Otolaryngology and Audiology Clinic in Jinotega, Nicaragua (group B). Patients with congenital HL were offered a genetic test for GJB2 mutations. Comparisons were made using parametric (analysis of variance) and nonparametric (Kruskal-Wallis) tests. RESULTS: School-based screening examinations (group A) revealed a high prevalence of significant HL (>30 dB) of 18%. The majority of these children had normal otoscopic examinations (58%). A family history of HL was seen in 24% of children who failed screening exams. Positive family history was more common in patients with HL (P < .01) and in specific schools (P < .05). Clinic-based evaluations (group B) reveal a population with predominantly severe-profound HL. Physical dysmorphism was common, yet identifiable syndromic HL was rare. Although familial HL was common (33%), there were no pathologic GJB2 mutations. Other common risk factors in this population were maternal infection during pregnancy, neonatal distress, low birth weight or prematurity, and gentamicin exposure. CONCLUSIONS: HL in this rural, third world environment is more prevalent, and the etiologies responsible in this study group are different from those encountered in industrialized nations. Poor perinatal health care, infectious causes, gentamicin exposure, and hereditary HL are potentially preventable causes that play a major role in this population.

The influence of mutations in the SLC26A4 gene on the temporal bone in a population with enlarged vestibular aqueduct.

OBJECTIVE: To correlate genetic and audiometric findings with a detailed radiologic analysis of the temporal bone in patients with enlarged vestibular aqueduct (EVA) to ascertain the contribution of SLC26A4 gene mutations to this phenotype. DESIGN: A retrospective review of patients with EVA identified in a database of pediatric hearing-impaired patients. SETTING: A tertiary care pediatric referral center. PATIENTS: Seventy-one children with EVA and screening results for SLC26A4 mutations. MAIN OUTCOME MEASURES: Genetic screening results, audiometric thresholds, and radiographic temporal bone measurements. RESULTS: Seventy-one children with EVA were screened for SLC26A4 mutations. Mutations were found in 27% of children overall, while only 8% had biallelic mutations. The mean initial pure-tone average (PTA) was 59 dB; the mean final PTA was 67 dB. A bilateral EVA was found in 48 (67%) of the children; a unilateral EVA was found in 23 (33%). Progressive hearing loss (in at least 1 ear) was seen in 29 (41%) of the patients. The strongest genotype-phenotype interaction was seen in children with a bilateral EVA. Among children with SLC26A4 mutations, there was a significantly wider vestibular aqueduct at the midpoint and a wider vestibule width (P < .05) than in children without the mutation. Among patients with a bilateral EVA, children with any SLC26A4 mutation were more likely to have a more severe final PTA (64 dB vs 32 dB), larger midpoint measurement (2.1 vs 1.1 mm), and larger operculum measurement (3.0 vs 2.0 mm) than those without the mutation in their better-hearing ear (P < .05). CONCLUSIONS: In a population of pediatric patients with an EVA and hearing loss, SLC26A4 mutations are a contributor to the phenotype. Our data suggest that other genetic factors also have important contributions to this phenotype. The presence of an abnormal SLC26A4 allele, even in the heterozygous state, was associated with greater enlargement of the vestibular aqueduct, abnormal development of the vestibule, and possibly a stable hearing outcome.

The role of CMV inflammatory genes in hearing loss.

HYPOTHESIS: The purpose of this study is to test the hypothesis that virally encoded immunomodulatory genes play a role in cytomegalovirus (CMV)-related hearing loss. OBJECTIVE: Cytomegalovirus is the leading cause of infectious-related congenital sensorineural hearing loss worldwide. Unfortunately, little is known about the pathophysiology of CMV-related injury to the developing ear. METHODS: Viral mutagenesis techniques were developed that allow the deletion of a specific viral immunomodulatory gene, macrophage inflammatory protein (MIP) 1alpha homolog. We assessed the extent to which this gene product contributed to auditory pathologic findings in the guinea pig (GP) model. Eighteen weanling GPs (250-350 g) were used under an Institutional Animal Control and Use Committee-approved protocol. We analyzed preinoculation hearing using auditory brainstem response recordings. Intracochlear inoculations were performed on one group of six GPs with sterile viral media, 6 GPs with wild-type (WT) CMV virus, and 6 GPs with mutant "knockout" (KO) virus (with deleted MIP-1alpha homolog). Auditory brainstem responses were then obtained on postinoculation Days 7, 14, 21, and 28. RESULTS: There was a significant difference in hearing between the KO group and the WT group, with significantly better hearing in the KO group. A comparison of the KO group to the sham group revealed no significant hearing differences between the groups. The WT group had significant threshold shifts by dose at all frequencies meeting our criteria of hearing loss (>30 dB). There were no statistical differences in the sham or KO group. CONCLUSION: Virally encoded immunomodulatory genes such as MIP-1alpha seem to play a significant role in CMV-related hearing loss. This study is the first demonstration of the role of specific viral immune modulation genes in the in vivo pathogenesis of CMV-induced hearing loss in a relevant animal model.

The large vestibular aqueduct: a new definition based on audiologic and computed tomography correlation.

OBJECTIVE: The study goal was to determine the prevalence and clinical significance of a large vestibular aqueduct (LVA) in children with sensorineural hearing loss (SNHL). STUDY DESIGN AND SETTING: We conducted a retrospective review of a pediatric SNHL database. One hundred seven children with SNHL were selected and their radiographic and audiometric studies were evaluated. Radiographic comparisons were made to a group of children without SNHL. RESULTS: A vestibular aqueduct (VA) larger than the 95th percentile of controls was present in 32% of children with SNHL. Progressive SNHL was more likely to occur in ears with an LVA and the rate of progressive hearing loss was greater than in ears without an LVA. The risk of progressive SNHL increased with increasing VA size as determined by logistic regression analysis. CONCLUSIONS: An LVA is defined as one that is >or=2 mm at the operculum and/or >or=1 mm at the midpoint in children with nonsyndromic SNHL. An LVA appears to be more common than previously reported in children with SNHL. A linear relationship is observed between VA width and progressive SNHL. SIGNIFICANCE: The finding of an LVA in children with SNHL provides diagnostic as well as prognostic information.