Central mimics of benign paroxysmal positional vertigo: an illustrative case series.

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder that is diagnosed based solely on clinical findings. Rarely, central lesions can present with positional vertigo and nystagmus, mimicking BPPV. Recognised red flags that may help distinguish central mimics from BPPV include the presence of additional neurological symptoms and signs, atypical nystagmus patterns, and the absence of a sustained response to repositioning manoeuvres. We present seven cases that illustrate how heuristic bias may affect the detection of these features in practice. Furthermore, our cases suggest that isolated downbeat positional nystagmus (simulating anterior canal BPPV) and apogeotropic horizontal nystagmus on the supine roll test (simulating horizontal canal BPPV) should be considered additional red flags.

The Pediatric Vestibular Symptom Questionnaire: A Validation Study.

OBJECTIVE: To develop and validate the Pediatric Vestibular Symptom Questionnaire (PVSQ) and quantify subjective vestibular symptom (ie, dizziness, unsteadiness) severity in children. STUDY DESIGN: One hundred sixty-eight healthy children (female, n = 91) and 56 children with postconcussion dizziness or a vestibular disorder (female, n = 32), between ages 6 and 17 years, were included. The PVSQ contains questions regarding vestibular symptom frequency during the previous month. The Strengths and Difficulties Questionnaire (SDQ), a brief behavioral screening instrument, was also completed. RESULTS: The PVSQ showed high internal consistency (10 items; Cronbach α = 0.88). A significant between-group difference was noted with higher (ie, worse) PVSQ scores for children with vestibular symptoms (P < .001); no significant differences were noted between patient groups. The optimal cut-off score for discriminating between individuals with and without abnormal levels of vestibular symptoms was 0.68 out of 3 (sensitivity 95%, specificity 85%). Emotional and hyperactivity SDQ subscale scores were significantly worse for patients compared with healthy participants (P ≤ .01). A significant relationship was noted between mean PVSQ and SDQ (parent-rated version) hyperactivity and total scores for patients (P ≤ .01) and the SDQ (self-rated) emotional, hyperactivity, and total score (P ≤ .01) in healthy controls. However, mean SDQ subscale and total scores were within normal ranges for both groups. CONCLUSIONS: Self-reported vestibular symptoms, measured by the PVSQ, discriminated between children presenting with vestibular symptoms and healthy controls and should be used to identify and quantify vestibular symptoms that require additional assessment and management.

Mobile telephone use effects on perception of verticality.

Low-level radiofrequency (RF) signals may produce disorientation and nausea. In experiment I, we assessed mobile phone effects on graviception in nine symptomatic subjects after mobile telephone use and 21 controls. The mobile handset was strapped to each ear for 30 min in pulsed emission, continuous RF emission, or no emission test mode, respectively. The subjective visual vertical and horizontal (SVV/SVH) were tested from min 25 of exposure. There was no exposure effect; however, there was an ear effect, with the SVV/SVH being shifted to the opposite direction of the ear exposed. This could be due to thermal or RF effects or handset weight. In experiment II, we assessed the handset weight effect on 18 normal controls. After baseline SVV/SVH, the switched off handset was strapped to either ear; the SVV/SVH was repeated 25 min later. A significant ear effect was found. We compared the observed ear effect SVV/SVH change in the experiment II group to the continuous exposure ear effect change in the experiment I group, and the difference was not significant. The ear effect was attributed to a minor head tilt due to the handset weight, or proprioceptive stimulation of neck muscle affecting the perception of verticality.

Natural history and retinal structure in patients with Usher syndrome type 1 owing to MYO7A mutation.

PURPOSE: To evaluate the phenotypic variability and natural history of ocular disease in a cohort of 28 individuals with MYO7A-related disease. Mutations in the MYO7A gene are the most common cause of Usher syndrome type 1, characterized by profound congenital deafness, vestibular arreflexia, and progressive retinal degeneration. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-eight patients from 26 families (age range, 3-65 years; median, 32) with 2 likely disease-causing variants in MYO7A. METHODS: Clinical investigations included fundus photography, optical coherence tomography, fundus autofluorescence (FAF) imaging, and audiologic and vestibular assessments. Longitudinal visual acuity and FAF data (over a 3-year period) were available for 20 and 10 study subjects, respectively. MAIN OUTCOME MEASURES: Clinical, structural, and functional characteristics. RESULTS: All patients with MYO7A mutations presented with features consistent with Usher type 1. The median visual acuity for the cohort was 0.39 logarithm of the minimum angle of resolution (logMAR; range, 0.0-2.7) and visual acuity in logMAR correlated with age (Spearman's rank correlation coefficient, r = 0.71; P<0.0001). Survival analysis revealed that acuity ≤ 0.22 logMAR was maintained in 50% of studied subjects until age 33.9; legal blindness based on loss of acuity (≥ 1.00 logMAR) or loss of field (≤ 20°) was reached at a median age of 40.6 years. Three distinct patterns were observed on FAF imaging: 13 of 22 patients tested had relatively preserved foveal autofluorescence surrounded by a ring of high density, 4 of 22 had increased signal in the fovea with no obvious hyperautofluorescent ring, and 5 of 22 had widespread hypoautofluorescence corresponding to retinal pigment epithelial atrophy. Despite a number of cases presenting with a milder phenotype, there seemed to be no obvious genotype-phenotype correlation. CONCLUSIONS: MYO7A-related ocular disease is variable. Central vision typically remains preserved at least until the third decade of life, with 50% of affected individuals reaching legal blindness by 40 years of age. Distinct phenotypic subsets were identified on FAF imaging. A specific allele, previously reported in nonsyndromic deafness, may be associated with a mild retinopathy.

Vestibular involvement in peripheral neuropathy: a review.

OBJECTIVE: This paper reviews the current literature on involvement of the vestibular division of the eighth cranial nerve in peripheral neuropathies. The literature abounds with references to auditory neuropathy, which is frequently related to more generalized neuropathies, but there is a marked paucity of work regarding vestibular neuropathy. A brief overview of neuropathies and the anatomy of the vestibulocochlear nerve provide the background for a review of the literature of vestibular nerve involvement in a range of neuropathies. DESIGN: A literature search including textbooks, and peer-reviewed published journal articles in online bibliographic databases was conducted. STUDY SAMPLE: Two databases for medical research were included in this review. RESULTS: The review of the literature indicates that vestibular involvement is a common and consistent finding in many peripheral neuropathies of different aetiologies. Specifically, if patients present unsteadiness/ataxia out of proportion to objective signs of somatosensory loss or muscle weakness. CONCLUSION: This review concludes that vestibular neuropathy, is common in peripheral neuropathy and should be identified to optimize patient management and rehabilitation.

Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder comprising retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous with three distinctive clinical types (I-III) and nine Usher genes identified. This study is a comprehensive clinical and genetic analysis of 172 Usher patients and evaluates the contribution of digenic inheritance. METHODS: The genes MYO7A, USH1C, CDH23, PCDH15, USH1G, USH2A, GPR98, WHRN, CLRN1 and the candidate gene SLC4A7 were sequenced in 172 UK Usher patients, regardless of clinical type. RESULTS: No subject had definite mutations (nonsense, frameshift or consensus splice site mutations) in two different USH genes. Novel missense variants were classified UV1-4 (unclassified variant): UV4 is 'probably pathogenic', based on control frequency <0.23%, identification in trans to a pathogenic/probably pathogenic mutation and segregation with USH in only one family; and UV3 ('likely pathogenic') as above, but no information on phase. Overall 79% of identified pathogenic/UV4/UV3 variants were truncating and 21% were missense changes. MYO7A accounted for 53.2%, and USH1C for 14.9% of USH1 families (USH1C:c.496+1G>A being the most common USH1 mutation in the cohort). USH2A was responsible for 79.3% of USH2 families and GPR98 for only 6.6%. No mutations were found in USH1G, WHRN or SLC4A7. CONCLUSIONS: One or two pathogenic/likely pathogenic variants were identified in 86% of cases. No convincing cases of digenic inheritance were found. It is concluded that digenic inheritance does not make a significant contribution to Usher syndrome; the observation of multiple variants in different genes is likely to reflect polymorphic variation, rather than digenic effects.

Patient-reported auditory functions after stroke of the central auditory pathway.

BACKGROUND AND PURPOSE: Auditory functional limitations experienced by patients after stroke of the central auditory pathways remain underinvestigated. Purpose- To measure patient-reported hearing difficulties in everyday life in nonaphasic patients with stroke of the auditory brain versus normal control subjects. To examine how hearing difficulties correlate with auditory tests and site of lesion in individual cases. METHODS: We recruited 21 individuals with auditory brain stroke (excluding those with aphasia) diagnosed on the basis of a brain MRI conducted 1 to 2 weeks after the stroke and assessed in the chronic stage of stroke. Twenty-three controls matched for age and hearing were also recruited. All subjects completed the Amsterdam Inventory for Auditory Disability (consisting of subscales of sound detection, recognition, localization, speech in quiet, speech in noise) and underwent baseline audiometry and central auditory processing tests (dichotic digits, frequency and duration patterns, gaps in noise). RESULTS: Sound recognition and localization subscores of the inventory were significantly worse in case subjects versus control subjects, with severe and significant functional limitation (z score >3) reported by 9 out of 21 case subjects. None of the inventory subscales correlated with audiometric thresholds, but localization and recognition subscales showed a moderate to strong correlation with dichotic digits (left ear) and pattern tests. CONCLUSIONS: A substantial proportion of patients may experience and report severe auditory functional limitations not limited to speech sounds after stroke of the auditory brain. A hearing questionnaire may help identify patients who require more extensive assessment to inform rehabilitation plans.

Diagnostic accuracy and usability of the EMBalance decision support system for vestibular disorders in primary care: proof of concept randomised controlled study results.

BACKGROUND: Dizziness and imbalance are common symptoms that are often inadequately diagnosed or managed, due to a lack of dedicated specialists. Decision Support Systems (DSS) may support first-line physicians to diagnose and manage these patients based on personalised data. AIM: To examine the diagnostic accuracy and application of the EMBalance DSS for diagnosis and management of common vestibular disorders in primary care. METHODS: Patients with persistent dizziness were recruited from primary care in Germany, Greece, Belgium and the UK and randomised to primary care clinicians assessing the patients with (+ DSS) versus assessment without (- DSS) the EMBalance DSS. Subsequently, specialists in neuro-otology/audiovestibular medicine performed clinical evaluation of each patient in a blinded way to provide the "gold standard" against which the + DSS, - DSS and the DSS as a standalone tool (i.e. without the final decision made by the clinician) were validated. RESULTS: One hundred ninety-four participants (age range 25-85, mean = 57.7, SD = 16.7 years) were assigned to the + DSS (N = 100) and to the - DSS group (N = 94). The diagnosis suggested by the + DSS primary care physician agreed with the expert diagnosis in 54%, compared to 41.5% of cases in the - DSS group (odds ratio 1.35). Similar positive trends were observed for management and further referral in the + DSS vs. the - DSS group. The standalone DSS had better diagnostic and management accuracy than the + DSS group. CONCLUSION: There were trends for improved vestibular diagnosis and management when using the EMBalance DSS. The tool requires further development to improve its diagnostic accuracy, but holds promise for timely and effective diagnosis and management of dizzy patients in primary care. TRIAL REGISTRATION NUMBER: NCT02704819 (clinicaltrials.gov).

Sudden sensorineural hearing loss.

Sudden sensorineural hearing loss is usually unilateral and can be associated with tinnitus and vertigo. In most cases the cause is not identified, although various infective, vascular, and immune causes have been proposed. A careful examination is needed to exclude life threatening or treatable causes such as vascular events and malignant diseases, and patients should be referred urgently for further assessment. About half of patients completely recover, usually in about 2 weeks. Many treatments are used, including corticosteroids, antiviral drugs, and vasoactive and oxygen-based treatments. Although no treatment is proven, we recommend a short course of oral high-dose corticosteroids. There is much to learn about pathogenesis of sudden sensorineural hearing loss, and more clinical trials are needed to establish evidence-based management.

Mutations in the USH1C gene associated with sector retinitis pigmentosa and hearing loss.

PURPOSE: To determine the molecular cause of sector retinitis pigmentosa and hearing loss in two affected siblings. METHODS: Direct DNA sequencing of the USH1C gene was performed in two affected siblings. Putative pathogenic sequence changes were assayed in their parent's chromosomes and in control chromosomes. Clinical examination included visual acuity measurement, visual field measurement, electrophysiologic assessment, and fine matrix mapping. Retinal imaging with fundus photography, scanning laser ophthalmoscope (fundus autofluorescence), and optical coherence tomography was performed. Hearing and vestibular function was also assessed. RESULTS: The siblings were aged 42 years and 40 years, and both were compound heterozygotes for the p.R103H missense change and the novel splice site change c.2227-1G>A in the USH1C gene. Both alleles were found to be in trans. Neither allele was identified in a panel of 866 control chromosomes, and both were considered pathogenic. Both siblings had sector retinitis pigmentosa restricted to the inferior and nasal retina. Fundus autofluorescence imaging showed a clear demarcation between normal and abnormal areas of retina, which corresponded to areas of reduced sensitivity on fine matrix mapping and loss of visual field. Both siblings had severe hearing loss but were able to develop language. CONCLUSION: We report a novel molecular cause of sector retinitis pigmentosa associated with hearing loss representing a new phenotype associated with mutations in the USH1C gene.

Nonsense mutation in TMEM126A causing autosomal recessive optic atrophy and auditory neuropathy.

PURPOSE: To define the phenotype and elucidate the molecular basis for an autosomal recessively inherited optic atrophy and auditory neuropathy in a consanguineous family with two affected children. METHODS: Family members underwent detailed ophthalmologic, electrophysiological, and audiological assessments. An autozygosity mapping strategy using high-density single nucleotide polymorphism microarrays and microsatellite markers was used to detect regions of genome homozygosity that might contain the disease gene. Candidate genes were then screened for mutations by direct sequencing. RESULTS: Both affected subjects had poor vision from birth and complained of progressive visual loss over time. Current visual acuity ranged from 6/60 to 6/120. Fundus examination revealed bilateral temporal optic nerve pallor in both patients with otherwise normal retinal findings. International-standard full-field electroretinograms were normal in both individuals, with no evidence of generalized retinal dysfunction. Pattern cortical visual evoked potentials were grossly abnormal bilaterally in both cases. The pattern electroretinogram N95:P50 ratio was subnormal, and the P50 was of shortened peak time bilaterally in both patients. The electrophysiological findings were consistent with bilateral retinal ganglion cell/optic nerve dysfunction. Audiological investigation in both siblings revealed abnormalities falling within the auditory neuropathy/dysynchrony spectrum. There were no auditory symptoms and good outer hair cell function (as demonstrated by transient evoked otoacoustic emissions) but impaired inner hair cell/neural function with abnormal stapedial reflex thresholds and abnormal or absent auditory brainstem-evoked responses. The single nucleotide polymorphism microarray data demonstrated a 24.17 Mb region of homozygosity at 11q14.1-11q22.3, which was confirmed by microsatellite marker analysis. The candidate target region contained the transmembrane protein 126A (TMEM126A) gene, and direct sequencing identified a previously described nonsense mutation (c.163C>T; p.Arg55X). CONCLUSIONS: We describe the first detailed phenotyping of patients with autosomal recessive TMEM126A-associated optic atrophy and auditory neuropathy. These findings will facilitate the identification of individuals with this recently described disorder.

Computer-based auditory training (CBAT): benefits for children with language- and reading-related learning difficulties.

This article reviews the evidence for computer-based auditory training (CBAT) in children with language, reading, and related learning difficulties, and evaluates the extent it can benefit children with auditory processing disorder (APD). Searches were confined to studies published between 2000 and 2008, and they are rated according to the level of evidence hierarchy proposed by the American Speech-Language Hearing Association (ASHA) in 2004. We identified 16 studies of two commercially available CBAT programs (13 studies of Fast ForWord (FFW) and three studies of Earobics) and five further outcome studies of other non-speech and simple speech sounds training, available for children with language, learning, and reading difficulties. The results suggest that, apart from the phonological awareness skills, the FFW and Earobics programs seem to have little effect on the language, spelling, and reading skills of children. Non-speech and simple speech sounds training may be effective in improving children's reading skills, but only if it is delivered by an audio-visual method. There is some initial evidence to suggest that CBAT may be of benefit for children with APD. Further research is necessary, however, to substantiate these preliminary findings.

Saccadic eye movements and anti-epileptic drugs.

Saccadic eye movements can be used to evaluate different aspects of brain function, and in this article we are concerned with possible applications in relation to anti-epileptic drug treatment. Recent improvements in the technology of measurement have improved the sensitivity and objectivity of the measures. Here we review the neurophysiology of saccades, their classification, their anatomical basis and cortical control, and then published research articles concerned with the influence of anti-epileptic drugs on saccades and their parameters. It seems likely that certain anti-epileptic drugs (especially those acting on ion channels) exert their effect on saccades through ion channels, and this may have relevance to clinical and pharmacogenetic studies.

Mobile telephone use effects on peripheral audiovestibular function: a case-control study.

Low level radio-frequency (RF) signals may produce disorientation, headache and nausea. This double blind study tested nine case-subjects, who complained of various symptoms after prolonged mobile telephone use and 21 control subjects. Each subject underwent a series of trials, in which a dummy mobile telephone exposure system was held to each ear for 30 min in (a) pulsed, (b) continuous RF emission or, (c) no emission test modes. In the active pulsed and continuous modes the same mean power as the output of a typical handset was delivered at a carrier frequency of 882 MHz and at a maximum specific absorption rate (SAR) value of 1.3 W kg(-1) (+/- 30%). In Experiment I (auditory), transient evoked otoacoustic emissions (TEOAE), which assess the outer hair cells in the inner ear, were conducted. In Experiment II (vestibular) the vestibulo-ocular reflex was recorded by video-oculography (VOG), at baseline and immediately post exposure. There were no significant TEOAE changes from baseline to post-exposure recording for any of the exposures and no significant differences in the TEOAEs' change from baseline to post exposure between cases and controls. The VOG did not identify any effect of the exposure on the vestibular end organ in either cases or controls. In conclusion, 30 min exposure to mobile phone RF did not show any immediate effects on vestibulocochlear function as measured by TEOAE and the VOR.

Development and assessment of the vestibular system.

Paediatric vestibular assessment is necessary in various situations, yielding invaluable information relating to diagnoses and allowing for the formulation of appropriate rehabilitative strategies when considering the management of children with vestibular and balance problems, alone or in association with hearing impairment or other developmental disorders. The development and assessment of the vestibular system is considered in this article.

The role of the interhemispheric pathway in hearing.

The corpus callosum consists of heavily myelinated fibres connecting the two hemispheres. Its caudal portion and splenium contain fibres that originate from the primary and second auditory cortices, and from other auditory responsive areas. The anterior commissure in humans is much smaller than the corpus callosum, and it also contains interhemispheric fibres from auditory responsive cortical areas. The corpus callosum is exclusively present in placental mammals, while in acallosal mammals, most of the corpus callosum-related functions are carried out by the anterior commissure. The exact contribution of these two structures and of interhemispheric transfer in hearing in humans is still a matter of debate. In more recent years, human behavioural studies which employ psychoacoustic tasks designed to tap into interhemispheric transfer, combined with sophisticated neuroimaging paradigms, have helped to interpret information from animal experiments and post-mortem studies. This review will summarize and discuss the available information of the contributions of the human interhemispheric pathway in hearing in humans from behavioural, neuroimaging and histopathological studies in humans.

Auditory interhemispheric transfer deficits, hearing difficulties, and brain magnetic resonance imaging abnormalities in children with congenital aniridia due to PAX6 mutations.

OBJECTIVE: To assess auditory processing, hearing difficulties, and brain magnetic resonance (MR) imaging abnormalities in children with panocular developmental aniridia due to PAX6 mutations. DESIGN: Case-control study. SETTING: Great Ormond Street Hospital and Institute of Child Health. PARTICIPANTS: Eleven case subjects with PAX6 mutations and 11 age-matched and sex-matched healthy control subjects. INTERVENTIONS: All subjects completed a structured hearing questionnaire, baseline audiometry, and central auditory tests (dichotic speech tests, frequency and duration pattern tests, and gaps-in-noise test). Case subjects underwent brain MR imaging with volumetry, and the results were compared with those of age-matched and sex-matched healthy control subjects randomly selected from the Radiology and Physics Unit database. MAIN OUTCOME MEASURES: Brain MR imaging, central auditory test results, and questionnaire scores. RESULTS: The corpus callosum area was significantly smaller on brain volumetry in the cases compared with the controls. The anterior commissure was small in 7 cases and was normal in 3 cases on visual inspection of brain MR images (conducted in 10 of 11 cases). Audiograms showed no abnormalities in any of the children. Central auditory test results were normal in all the controls and were abnormal in all the cases except for 1 case with a pattern of abnormalities consistent with reduced auditory interhemispheric transfer. The cases had greater difficulty localizing sound and understanding speech in noise than the controls. CONCLUSIONS: Despite normal audiograms, children with PAX6 mutations may experience auditory interhemispheric transfer deficits and have difficulty localizing sound and understanding speech in noise. In view of their additional visual difficulties, thorough audiological evaluation of these children is indicated to initiate appropriate management.

Visually Induced Dizziness in Children and Validation of the Pediatric Visually Induced Dizziness Questionnaire.

AIMS: To develop and validate the Pediatric Visually Induced Dizziness Questionnaire (PVID) and quantify the presence and severity of visually induced dizziness (ViD), i.e., symptoms induced by visual motion stimuli including crowds and scrolling computer screens in children. METHODS: 169 healthy (female n = 89; recruited from mainstream schools, London, UK) and 114 children with a primary migraine, concussion, or vestibular disorder diagnosis (female n = 62), aged 6-17 years, were included. Children with primary migraine were recruited from mainstream schools while children with concussion or vestibular disorder were recruited from tertiary balance centers in London, UK, and Pittsburgh, PA, USA. Children completed the PVID, which assesses the frequency of dizziness and unsteadiness experienced in specific environmental situations, and Strength and Difficulties Questionnaire (SDQ), a brief behavioral screening instrument. RESULTS: The PVID showed high internal consistency (11 items; α = 0.90). A significant between-group difference was noted with higher (i.e., worse) PVID scores for patients vs. healthy participants (U = 2,436.5, z = -10.719, p < 0.001); a significant difference was noted between individual patient groups [χ2(2) = 11.014, p = 0.004] but post hoc analysis showed no significant pairwise comparisons. The optimal cut-off score for discriminating between individuals with and without abnormal ViD levels was 0.45 out of 3 (sensitivity 83%, specificity 75%). Self-rated emotional (U = 2,730.0, z = -6.169) and hyperactivity (U = 3,445.0, z = -4.506) SDQ subscale as well as informant (U = 188.5, z = -3.916) and self-rated (U = 3,178.5, z = -5.083) total scores were significantly worse for patients compared to healthy participants (p < 0.001). CONCLUSION: ViD is common in children with a primary concussion, migraine, or vestibular diagnosis. The PVID is a valid measure for identifying the presence of ViD in children and should be used to identify and quantify these symptoms, which require specific management incorporating exposure to optokinetic stimuli.

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.

An unusual case of X-linked adrenoleukodystrophy with auditory processing difficulties as the first and sole clinical manifestation.

X-linked adrenoleukodystrophy (X-ALD) is characterized by demyelination that is associated with a deficient beta-oxidation of very long chain fatty acids. We report the unusual case of a male adult with X-ALD who was diagnosed at the age of 26 by a brain MRI performed because his brother had been diagnosed with a rapidly deteriorating form of X-ALD. His sole symptom was hearing difficulties in the presence of a normal audiogram since childhood. He has remained stable for seven years. Central auditory testing in our patient revealed severe deficits in several auditory processes. These findings correlated with involvement of the auditory pathway at the level of the trapezoid body, and posterior corpus callosum in particular, on his brain MRI. This case highlights not only the need for thorough audiological investigation of the patient who complains of hearing difficulties in the presence of a normal audiogram, but also that audiological investigations could be of value in the phenotypic evaluation of cases with adrenoleukodystrophy.