Mid-frequency Sensorineural Hearing Loss Research Articles

Symptom: Vertigo After Labyrinthectomy

Symptom: Vertigo After Labyrinthectomy

Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss

The genetic heterogeneity of sensorineural hearing loss (SNHL) is a major hurdle to the detection of disease-causing variants. We aimed to identify underlying causal genes associated with mid-frequency hearing loss (HL), which contributes to less than about 1% of SNHL cases, by whole exome sequencing (WES). Thirty families segregating mid-frequency SNHL, in whom biallelic GJB2 mutations had been previously excluded, were selected from among 851 families in our DNA repository of SNHL. DNA samples from the probands were subjected to WES analysis and searched for candidate variants associated with SNHL. We were able to identify the genetic aetiology in six probands (20%). In total, we found three pathogenic and three likely pathogenic variants in four genes (COL4A5, OTOGL, TECTA, TMPRSS3). One more proband was a compound heterozygote for a pathogenic variant and a variant of uncertain significance (VUS) in MYO15A gene. To date, MYO15A and TMPRSS3 have not yet been described in association with mid-frequency SNHL. In eight additional probands, eight candidate VUS variants were detected in five genes (DIAPH1, MYO7A, TECTA, TMC1, TSPEAR). Seven of these 16 variants have not yet been published or mentioned in the available databases. The most prevalent gene was TECTA, identified in 23% of all tested families. Furthermore, we confirmed the hypothesis that a substantive portion of cases with this conspicuous audiogram shape is a consequence of a genetic disorder.

A Missense POU4F3 Variant Associated with Autosomal Dominant Midfrequency Hearing Loss Alters Subnuclear Localization and Transcriptional Capabilities.

Background The pathogenic variant, POU class 4 transcription factor 3 (POU4F3), is reported to cause autosomal dominant nonsyndromic hearing loss (ADNSHL). Previously, we have examined a four-generation midfrequency sensorineural hearing loss (MFSNHL) family (no. 6126) and established POU4F3 c.602T>C (p.Leu201Pro) as a potential disease-causing variant. Objectives We explored the structural and functional alterations that the c.602T>C (p.Leu201Pro) variant enforces on the POU4F3 protein. Methods We utilized wild-type (WT) and mutant (MUT) POU4F3 c.602T>C plasmid incorporation into HeLa cells to assess functional changes, by immunofluorescence and luciferase assays. To predict protein structural alterations in the MUT versus WT POU4F3, we also generated 3D structures to compare both types of POU4F3 proteins. Results The WT POU4F3 is ubiquitously present in the nucleus, whereas the MUT form of POU4F3 exhibits a more restricted nuclear presence. This finding is different from other publications, which report a cytoplasmic localization of the MUT POU4F3. We also demonstrated that, as opposed to WT POU4F3, the MUT POU4F3 had 40% reduced luciferase activity. Conclusions The reduced nuclear presence, combined with reduced transcriptional activity, suggests that the POU4F3 c.602T>C variant alters cellular activity and may contribute to the pathogenicity of POU4F3-related hearing loss. It, also, provides more evidence of the pathophysiological characteristics of MFSNHL.

How Does the "Cookie-Bite" Audiogram Shape Perform in Discriminating Genetic Hearing Loss in Adults?

"Cookie-bite" or U-shaped audiograms-specifically, those showing midfrequency sensorineural hearing loss (HL)-are traditionally taught to be associated with genetic HL; however, their utility as a screening tool has not been reported. We aim to determine the performance of a cookie-bite audiogram shape in stratifying patients carrying putative loss-of-function variants in known HL genes from wild-type controls. We merged audiometric and exome sequencing data from adults enrolled in a large biobank at a tertiary care center. Of 321 patients, 50 carried a putative loss-of-function variant in an HL gene. The cookie-bite shape was present in 9 of those patients, resulting in low sensitivity (18%) and positive predictive value (15%) in stratifying genetic carrier status; 84% of patients with a cookie-bite audiogram did not carry a genetic variant. A cookie-bite audiogram should not be used to screen adults for possible genetic testing.

Clinical Practice Guideline: Ménière's Disease.

Ménière's disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid (endolymph) volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Conventional imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many and typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies. The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.

Clinical Practice Guideline: Ménière's Disease Executive Summary.

Ménière's disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many, and approaches typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies. The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.

A CASE OF MID-FREQUENCY SENSORINEURAL HEARING LOSS

Introduction: Mid-frequency sensorineural hearing loss (MFSNHL) is an unusual audiometric finding with a debatable etiology with unclear long-term results. In general, the middle frequencies are affected first, and the process progresses slowly to include all frequencies. There are also some cases where provocative factors have been reported. Purpose: The aim of the work is to present a clinical case in our practice of the rare occurrence of mid-frequency acoustic hearing loss and its diagnostic approach. Material and methods: The patient has undergone a number of manual and instrumental tests to confirm or reject a specific cause of the hearing loss condition. Results: A 52-year-old man was hospitalised with complaints of hearing loss for about a year, judging by the growing difficulty in making a phone call. Conclusions: Generally, a U-shaped audiogram is thought to indicate hearing loss of genetic origin. However, this type of deafness is not unique to one particular type of genetic mutation. There are also numerous descriptions of non-genetic mid-frequency hearing loss in the literature. In the particular clinical case presented by us, it was concluded that this was a hearing loss, possibly of hereditary nature, after excluding another provocative cause, as well as due to anamnestic data on premature hearing loss in one of the parents.

Characteristics of Mid-Frequency Sensorineural Hearing Loss Progression.

To characterize the progression of mid-frequency sensorineural hearing loss (MFSNHL) over time. A retrospective chart review spanning 2012 to 2017 was performed at a tertiary care audiology and neurotology center. Our cohort included 37 patients met the criteria for MFSNHL also known as "cookie bite hearing loss." It was defined as having a 1, 2, and 4 kHz average pure tone audiometry greater than 10 dB in intensity compared with the average threshold at 500 Hz and 8 kHz. Average age at initial presentation was 11.8 years (range, 8 mo to 70 yr). Across all individuals, the average mid-frequency threshold was 47 dB, compared with 27 dB at 500 Hz and 8 kHz. Twenty-three patients (62%) had multiple audiograms with 4-year median follow up time. Average values across all frequencies (0.5, 1, 2, 4, 8 kHz) in the initial audiogram was 37 dB, compared with an average of 39 dB demonstrated on final audiogram. Of those with serial audiograms, only five patients demonstrated threshold changes of 10 dB or more. Of these five patients, only one was found to have clinical worsening of MFSNHL. MFSNHL is an uncommon audiometric finding with unspecified long-term outcomes. We demonstrated that most patients (96%) with MFSNHL do not experience clinical worsening of their hearing threshold over almost 4 years of follow up. Future prospective studies aimed at collecting longer-term data are warranted to further elucidate the long-term trajectory of MFSNHL patients.

Expression pattern of EYA4 in the common marmoset (Callithrix jacchus) cochlea.

The eyes absent (EYA)-like genes are essential for the formation of sensory organs among fly (Drosophila melanogaster) and mammals. EYA4, one of the vertebrate genes of Eya family, is reported to be causative for late-onset mid-frequency sensorineural hearing loss in humans, while Eya4-deficient mice exhibited congenital profound deafness and otitis media with effusion due to the eustachian tube dysmorphology. Because of the species difference in the phenotype, the pathophysiology of EYA4 in the human cochlea has yet to be elucidated. Here, we examine the expression pattern of EYA4 in the cochlea of common marmoset (Callithrix jacchus), a non-human primate. The results indicated a distinct expression pattern of EYA4 in the adult marmoset cochleae, especially strong in all supporting cells, while in mouse their expressions were diminished. Interestingly, EYA4 expression in the hair cells, supporting cells and neurons was co-localized with sine oculis homeobox-SIX1, a transcription factor essential for the transcriptional activity of EYA4. The results revealed inter-species differences in the expression pattern of EYA4 gene in supporting cells between primates and rodents. The results also indicated a fundamental role of EYA4 in the primate auditory cells. Experiments with primate models such as marmosets or with human cochlear cells may provide cues about the unknown pathogenesis of EYA4-related hearing loss.

Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss

BackgroundTo date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL.MethodsSubjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling.ResultsPathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive.ConclusionsTECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.

SLC44A4 mutation causes autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss.

Clinical, genetic, and functional investigations were performed to identify the causative mutation in a distinctive Chinese family with postlingual non-syndromic mid-frequency sensorineural hearing loss. Whole-exome sequencing revealed SLC44A4, which encodes the choline transport protein, as the pathogenic gene in this family. In the zebrafish model, downregulation of slc44a4 using morpholinos led to significant abnormalities in the zebrafish inner ear and lateral line neuromasts and contributed, to some extent, to disabilities in hearing and balance. SH-SY5Y cells transfected with SLC44A4 showed higher choline uptake and acetylcholine release than that of cells transfected with mutant SLC44A4. We concluded that mutation of SLC44A4 may cause defects in the Choline- acetylcholine system, which is crucial to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury, leading to hearing loss.

SLC44A4 mutation causes autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss.

Clinical, genetic, and functional investigations were performed to identify the causative mutation in a distinctive Chinese family with postlingual non-syndromic mid-frequency sensorineural hearing loss. Whole-exome sequencing revealed SLC44A4, which encodes the choline transport protein, as the pathogenic gene in this family. In the zebrafish model, downregulation of slc44a4 using morpholinos led to significant abnormalities in the zebrafish inner ear and lateral line neuromasts and contributed, to some extent, to disabilities in hearing and balance. SH-SY5Y cells transfected with SLC44A4 showed higher choline uptake and acetylcholine release than that of cells transfected with mutant SLC44A4. We concluded that mutation of SLC44A4 may cause defects in the Choline- acetylcholine system, which is crucial to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury, leading to hearing loss.

Research progress in pathogenic genes of hereditary non-syndromic mid-frequency deafness.

Hearing impairment is considered as the most prevalent impairment worldwide. Almost 600 million people in the world suffer from mild or moderate hearing impairment, an estimated 10% of the human population. Genetic factors play an important role in the pathogenesis of this disorder. Hereditary hearing loss is divided into syndromic hearing loss (associated with other anomalies) and non-syndromic hearing loss (not associated with other anomalies). Approximately 80% of genetic deafness is non-syndromic. On the basis of the frequency of hearing loss, hereditary non-syndromic hearing loss can be divided into high-, mid-, low-, and total-frequency hearing loss. An audiometric finding of mid-frequency sensorineural hearing loss, or a "bowl-shaped" audiogram, is uncommon. Up to now, merely 7 loci have been linked to mid-frequency hearing loss. Only four genetic midfrequency deafness genes, namely, DFNA10 (EYA4), DFNA8/12 (TECTA), DFNA13 (COL11A2), DFNA44 (CCDC50), have been reported to date. This review summarizes the research progress of the four genes to draw attention to mid-frequency deafness genes.

Auditory phenotype in Stickler syndrome: results of audiometric analysis in 20 patients.

Hearing loss in Stickler syndrome has received little attention due to the often more disabling ocular, orofacial and skeletal manifestations. Estimates suggest a global prevalence of sensorineural hearing loss (SNHL) ranging from 50% to about 100% though, depending on the underlying Stickler genotype. By performing extensive audiometric analysis in Stickler patients, we aimed to further elucidate the auditory phenotype. Twenty molecularly confirmed Stickler patients (age 10-62year), of whom sixteen with type 1 Stickler syndrome (COL2A1 mutation) and four with type 2 Stickler syndrome (COL11A1 mutation) underwent an otological questionnaire, clinical examination, pure tone and speech audiometry, tympanometry and otoacoustic emission testing. Cross-sectional and longitudinal regression analysis of the audiograms was performed to assess progression. In type 1 Stickler syndrome, 75% demonstrated hearing loss, predominantly in the high frequencies. No significant progression beyond presbyacusis was observed. All type 2 Stickler patients exhibited mild-to-moderate low- and mid-frequency SNHL and moderate-to-severe high-frequency SNHL. In both types, hearing loss was observed in childhood. Otoacoustic emissions were only detectable in 7/40 ears and had very low amplitudes, even in frequency bands with normal hearing on pure tone audiometry. Type 1 Stickler syndrome is characterized by a mild high-frequency SNHL, emerging in childhood and non-progressive. Absent otoacoustic emissions are a frequent finding. Patients with type 2 Stickler syndrome exhibit early-onset moderate SNHL affecting all frequencies with a sloping audiogram. Taking into account the visual impairment in many patients, we recommend regular auditory follow-up in patients with Stickler syndrome, especially in childhood.

Hearing disorders in Turner's syndrome: a survey from Iran.

Turner syndrome (TS) is one of the most frequently encountered sex-linked chromosomal abnormalities, occurring in one per 2,000 female births. These patients present with short stature and failure to begin puberty. In this syndrome, there are multiple organ abnormalities, including auditory disorders. TS patients were referred to the ENT clinic by a pediatric endocrinologist. A questionnaire was filled out and the patients went through a complete otologic examination. They were then referred to the audiology clinic to undergo audiologic test battery plus high-frequency pure tone audiometry. From a total of 48 ears examined, 11 (22.9 %) had a normal audiometry. Mid-frequency sensorineural hearing loss (SNHL), high-frequency SNHL, combined and mixed hearing loss were diagnosed in 6 (12/5 %), 20 (41/7 %), 6 (12/5 %) and 1 (2/1 %) ear, respectively. Tympanogram results showed normal compliance (A, As, Ad) in the majority of cases. B and C patterns were found in a few cases. Speech discrimination score was normal in all patients whereas speech reception threshold was normal in 92 % of the ears. Audiometry abnormality especially SNHL is common in TS patients, with the high-frequency pattern being the most frequent.

Histopathology of Nonsyndromic Autosomal Dominant Midfrequency Sensorineural Hearing Loss

Autosomal dominant, nonsyndromic, midfrequency sensorineural hearing loss (SNHL) is a well-known clinical entity. There are no reported histopathologic studies of temporal bones from individuals with such a hearing loss. To describe the otopathology in 2 affected individuals from 2 different kindreds with nonsyndromic, dominant, midfrequency SNHL. Both subjects belonged to multigenerational families with nonsyndromic, autosomal dominant SNHL showing a cookie-bite pattern. Temporal bones were removed at autopsy and studied by light microscopy. Cytocochleograms were constructed for hair cells, stria vascularis, and cochlear neuronal cells. Subject 1 (a 77-yr-old man) from Kindred A was diagnosed in early childhood with an SNHL that was progressive, reaching profound levels by adulthood. Both cochleae showed complete loss of inner and outer hair cells, moderate to severe diffuse atrophy of the stria vascularis, and severe loss of cochlear neurons, including the peripheral dendrites. The hearing loss in Subject 2 (an 82-yr-old man from Kindred B) began in late childhood, was slowly progressive, and involved the higher frequencies later in life. Histopathology showed loss of outer and inner hair cells in the basal turn of the cochlea, moderate to severe loss of stria vascularis, but relative preservation of peripheral dendrites and cochlear neurons. The main histopathologic abnormalities were loss of hair cells, stria vascularis, and cochlear neurons in 1 case and loss of hair cells and stria vascularis in the second case. Our results are consistent with the hypothesis that dysfunction and loss of hair cells may have been the primary histopathologic correlate for the midfrequency hearing losses in these 2 subjects.

The Natural History of Patients Treated for FGFR3-Associated (Muenke-Type) Craniosynostosis

Muenke-type craniosynostosis is defined as fibroblast growth factor receptor 3 (FGFR3)-associated coronal craniosynostosis with or without mental retardation. With complementary genetic information, more precise diagnosis and long-term functional outcome of cranial vault remodeling in affected patients can be studied, and additional distinct features of Muenke syndrome can now be investigated. This study was undertaken to assess craniofacial growth and long-term functional outcome in patients with Muenke-type craniosynostosis. A chart review of all FGFR3 patients at The Children's Hospital of Philadelphia who had undergone cranial vault remodeling for unicoronal or bicoronal synostosis (n = 16) was performed. Need for reoperation, midface surgery, and functional corrections were assessed. Audiology and orthodontic records were reviewed. All patients underwent cranial remodeling during infancy. Repeated intracranial surgery was performed or is currently scheduled for aesthetic reasons only (n = 7). Sexual dimorphism with male preponderance in FGFR3 unicoronal synostosis was detected. Despite dental crowding amenable to palatal expansion in patients with bicoronal synostosis, significant midface hypoplasia was not observed. Sensorineural hearing loss with a distinctive pattern was present in all patients who had undergone audiology testing. Patients with FGFR3-associated craniosynostosis demonstrate a sexual dimorphism, with a male preponderance for unicoronal synostosis. A secondary major intracranial procedure is required for recurrent supraorbital retrusion in at least 43 percent of patients. A secondary or tertiary extracranial forehead contouring procedure should be anticipated in nearly all patients. No patient required any midface correctional procedure. These patients demonstrate characteristic bilateral, symmetric, low- to mid-frequency sensorineural hearing loss.

Mid-frequency sensorineural hearing loss: aetiology and prognosis

An audiometric finding of mid-frequency sensorineural hearing loss (MFSNHL), or a U-shaped pattern, is uncommon. The objective of this study is to investigate the aetiology and prognostic significance of MFSNHL. Tertiary academic referral centre-based retrospective case review and review of audiograms to determine the prevalence of this audiometric finding. Patients with a pure tone threshold average at 1, 2, and 4 kHz at least 10 dB greater than the average at 0.5 and 8 kHz were included in this study; 35 patients met these criteria. The mean age of the patients was 34.6 years old (range 4-71 years). Twelve patients (33 per cent) were under 18 years of age. Serial audiograms were obtained for 14 patients. The notes were reviewed for any pertinent otologic history, subsequent diagnoses, management and disease course. The prevalence of MFSNHL in this practice setting is less than 1 per cent. The average hearing threshold in the mid-frequencies was 44 dB, which was 17 dB and 20 dB lower than at 0.5 Hz and 8 kHz, respectively. The pure tone average (0.5, 1, 2 kHz) was 40 dB. Sixteen patients (44 per cent) required amplification. Of all patients, 22 had hereditary hearing loss, eight had idiopathic hearing loss, and five adults had vestibular schwannomas. MFSNHL is an infrequent audiometric finding. The great majority of these cases are of presumed hereditary or idiopathic aetiology, although 22 per cent of adults had vestibular schwannomas. This series presents the causes and prognosis of this audiometric pattern.

Turner's syndrome and hearing disorders in women aged 16–34

Forty women with Turner's syndrome aged 16–34 years were tested clinically and audiometrically according to their ear problems and hearing. A high incidence of middle-ear infections was demonstrated. A mid-frequency sensorineural hearing loss was frequently diagnosed and could be correlated to the karyotype. The dip showed a progression with age. Middle-ear problems were more common among women with a dip. An early high-frequency hearing loss could be noted in the present group among the older women. In some cases this had already led to social hearing problems and use of hearing aids. When comparing these women with a group of elderly Turner women the dip was not as deep, the maximum peak was seen in the 2 kHz region and social hearing problems and hearing aids were not as frequent. If no dip was found no major hearing problems could be detected or expected in future life. The data emphasize the importance of early audiological evaluation and information about predisposition to hearing impairment in Turner's syndrome.

Temporomandibular joint symptoms in patients with midfrequency sensorineural hearing loss.

It was hypothesized that a correlation exists between a specific form of sensorineural hearing loss and temporomandibular joint dysfunction and/or parafunction, with the audiometric configuration of the loss showing a notch (poorest threshold) at 1000 or 2000 Hz in the range from 250 through 4000 Hz. Fifty patients at audiology clinics who showed this audiometric configuration were compared with 50 control patients, matched for age, sex, and severity of loss. The midfrequency notch group reported more symptoms of temporomandibular joint dysfunction (p less than 0.005), including more temporomandibular joint pain (p less than 0.0001), tenderness (p less than 0.025), and jaw noises (p less than 0.05). The notch group also reported significantly more bruxism (p less than 0.001) and clenching (p less than 0.001). Patients found having this midfrequency notch have been predominantly female (64% in this study), the percentage who are female increasing with age. The findings demonstrate a relationship between the form of sensorineural hearing loss studied and symptoms of temporomandibular joint dysfunction.