Extreme corneal fragility and thinning, which have a high risk of catastrophic spontaneous rupture, are the cardinal features of brittle cornea syndrome (BCS), an autosomal-recessive generalized ...connective tissue disorder. Enucleation is frequently the only management option for this condition, resulting in blindness and psychosocial distress. Even when the cornea remains grossly intact, visual function could also be impaired by a high degree of myopia and keratoconus. Deafness is another common feature and results in combined sensory deprivation. Using autozygosity mapping, we identified mutations in PRDM5 in families with BCS. We demonstrate that regulation of expression of extracellular matrix components, particularly fibrillar collagens, by PRDM5 is a key molecular mechanism that underlies corneal fragility in BCS and controls normal corneal development and maintenance. ZNF469, encoding a zinc finger protein of hitherto undefined function, has been identified as a quantitative trait locus for central corneal thickness, and mutations in this gene have been demonstrated in Tunisian Jewish and Palestinian kindreds with BCS. We show that ZNF469 and PRDM5, two genes that when mutated cause BCS, participate in the same regulatory pathway.
Auditory neuropathy (AN) is characterized by varying degrees of sensorineural hearing loss, an absent or severely abnormal auditory brainstem response, and normal otoacoustic emissions. The ...nomenclature for this condition reflects the concept that the site of lesion is proximal to the cochlea (e.g., cochlear nerve). Given this hypothesis, it is reasonable to expect limited benefit from cochlear implantation in patients with AN. However, a growing body of evidence shows the striking benefits of cochlear implantation in AN. To explore this topic, we reviewed our population of children with AN and, specifically, the performance results in those children having undergone cochlear implantation.
A retrospective case review of those patients diagnosed with AN from 1993 to 2001.
A tertiary pediatric referral center.
A diagnosis of AN reported from the Center for Hearing and Deafness Research, Cincinnati, OH, database.
Eighteen patients were diagnosed with AN (11 girls, 7 boys), with 3 sets of siblings, including 1 set of identical twins. Four patients with AN underwent implantation in the previous 5 years. Twelve out of the 18 patients had classic risk factors for AN (e.g., prematurity and hyperbilirubinemia). The degree of hearing loss varied in our patients, with a majority showing severe to profound deficits. All children with implants showed improvement in auditory and verbal development, but this improvement was variable.
The success of cochlear implantation in these patients suggests that some children with AN have an auditory system lesion that can be compensated for by cochlear implantation. This implies either an inner hair cell or inner hair cell-cochlear nerve junctional pathology that can be overcome by direct electrical stimulation.
Abstract
We present a case of unilateral acquired auditory neuropathy spectrum disorder (ANSD) due to an underlying cerebellar neoplasm. This is the third case in the literature of juvenile pilocytic ...astrocytoma presenting with auditory symptoms and mimicking the presentation of ANSD; it highlights the importance of imaging in acquired auditory neuropathy. We were able to make a diagnosis of acquired ANSD in our patient because he had a normal AABR in addition to his OAEs as part of his newborn hearing screen. Detailed neuro-otological assessment and radiological imaging is recommended in all cases of acquired ANSD in order to exclude an acquired compressive pathology.
Objective
To explore the views of children with cleft palate and their parents about daily life with otitis media with effusion and associated hearing loss.
Design
A qualitative study. Semistructured ...interviews were used to collect data from parents. Participatory techniques, including activities on a tablet computer, were used to collect data from children. Framework analysis was applied to interview transcripts.
Setting
Two English cleft units.
Participants
A purposive sample of parents of 37 children aged 0 to 11 years with experience of otitis media with effusion. Their children also took part if aged 6 to 11 years (n = 22).
Results
Themes related to the following: (1) emotions (frustration, anger, sadness, happiness, anxiety), (2) educational experiences (struggling at school, having to sit at the front of the class, requiring extra support, missing lessons for appointments or due to ear infections), (3) social interactions (isolation, communication, reliance on siblings, participation in activities).
Conclusions
A number of areas of interviewees' everyday life were affected by the presence of otitis media with effusion. Parents may need to be forewarned about the possible ongoing nature of this condition and its impact on a child's social and emotional experiences. Children may also benefit from age-appropriate information about otitis media with effusion and its treatment, including information on hearing tests, to help reduce any anxiety.
To medically and audiologically characterize a population of children diagnosed as having auditory neuropathy (AN).
Retrospective medical chart review.
We identified 22 patients from a pediatric ...otology clinic in a tertiary care pediatric hospital setting.
A genetic factor in AN is suggested by our identification of 3 families with 2 affected children and 2 other children with family histories that were positive for hearing loss. Clinical features common among our population included a history of hyperbilirubinemia (n = 11 50%), prematurity (n = 10 45%), ototoxic drug exposure (n = 9 41%), family history of hearing loss (n = 8 36%), neonatal ventilator dependence (n = 8 36%), and cerebral palsy (n = 2 9%). Full clinical and audiological data were available for 18 of the 22 children, including otoacoustic emissions, auditory brainstem responses with cochlear microphonics, and age-appropriate audiometric findings. Significantly, 9 of these 18 patients showed improvement in behavioral thresholds over time, indicating that a subset of children with AN may recover useful hearing levels. Also significant was the success of cochlear implantation in 4 children.
Management of AN in children requires serial clinical and audiometric evaluations, with a prominent role for behavioral testing. Prematurity, genetics, and hyperbilirubinemia appear to be significant factors in the development of AN; hyperbilirubinemia can be associated with spontaneous improvement of hearing thresholds. For those children not benefiting from amplification or FM systems, cochlear implantation remains a potentially successful method of habilitation.
To correlate clinical and audiometric findings with the radiologic appearance in patients with enlarged vestibular aqueduct.DESIGN A retrospective review of data from enlarged vestibular aqueduct ...patients identified in a pediatric hearing-impaired database of 1,200 patients. SETTING A tertiary care pediatric referral center.
Subjects were included for study with a radiographic diagnosis of enlarged vestibular aqueducts in at least one ear by a pediatric neuroradiologist.
Audiometric evaluations and radiographic temporal bone measurements.
Seventy-seven patients were identified with an enlarged vestibular aqueduct with a male-to-female ratio of 1:1.5. Patients were followed for a mean of 34 months (range, 0-179 months). Hearing loss was bilateral in 87% of cases. Vestibular symptoms were present in only three (4%) of the patients. Three patients (4%) suffered a sudden decrease in hearing after mild head trauma. Borderline enlargement of the vestibular aqueduct was associated with varying degrees of sensorineural hearing loss. Ninety-seven percent (64 of 66) of ears in control subjects with no sensorineural hearing loss had normal vestibular aqueduct measurements at the midpoint and operculum. Overall, the audiogram remained stable in 51% of ears, fluctuated in 28%, and progressively worsened in 21%. Measurements of the vestibular aqueduct at the midpoint and the operculum did not correlate with the audiometric threshold or the audiogram configuration. However, mean vestibular aqueduct size at the operculum was significantly larger in those with a progressive loss when compared with those with a fluctuating or stable hearing outcome.
Overall, audiometric thresholds remained generally stable, with sudden deterioration of hearing after head trauma seen in only three male patients. Progression of hearing loss after head trauma was not a significant finding in our patient population. Vestibular aqueduct opercular size alone showed a direct correlation with the audiometric outcome. Borderline enlarged vestibular aqueduct measurements appear to be associated with sensorineural hearing loss.
Our objective was to determine the diagnostic yield of laboratory testing, radiological imaging, and GJB2 mutation screening in a large cohort of patients with differing severities of idiopathic ...sensorineural hearing loss (SNHL).
We undertook a retrospective study of patients presenting with SNHL at our institution from 1993 to 2002.
Laboratory testing had an extremely low yield. Patients with unilateral SNHL had a significantly higher imaging yield than those with bilateral. The diagnostic yield of GJB2 screening was significantly higher in patients with severe to profound SNHL than in those with less severe SNHL. However, a relatively large number of patients with mild to moderate SNHL had positive GJB2 screens.
Based on diagnostic yields, we propose a cost-effective stepwise diagnostic paradigm to replace the more commonly used and costly simultaneous testing approach.
C.
Objectives/Hypothesis: The objectives were to correlate audiometric thresholds with radiological findings and to determine the prevalence of inner ear radiological abnormalities in patients with ...hearing loss and Waardenburg syndrome. Study Design: The study was a retrospective review of patients with Waardenburg syndrome identified in a pediatric hearing‐impaired population and human genetics clinic. Methods: Nine children with Waardenburg syndrome were identified. Eighty‐nine children without sensorineural hearing loss served as control subjects. Clinical data, audiometric thresholds, and radiographic temporal bone measurements in these children were analyzed. Results: Seven children were identified with hearing loss and Waardenburg syndrome. Four children had Waardenburg syndrome type 1, and three children had Waardenburg syndrome type 2. The overall prevalence of hearing loss in the total study population with Waardenburg syndrome was 78%. The mean pure‐tone average was 99 dB. All of the children had sensorineural hearing loss. The hearing outcome was stable in 86% of the children. Twelve temporal bones were available for radiological analysis by computed tomography. Enlargement of the vestibular aqueduct was found in 50% of the CT scans. There was a significant difference in measurements of vestibular aqueduct width at the midpoint between the patients with Waardenburg syndrome and the control group (P < .05). There were also significant differences in the measurements of the vestibule (P = .0484), internal auditory canal (P = .0092), and modiolus (P = .0045) between the children with Waardenburg syndrome and the control group. Conclusion: A profound sensorineural hearing loss was characteristic of the study population with Waardenburg syndrome. Overall, 100% of patients with hearing loss and Waardenburg syndrome had temporal bone anomalies on at least one measurement of their inner ear, and 50% had an enlargement of the vestibular aqueduct at the midpoint. As shown by computed tomography, enlargement of the vestibular aqueduct and the upper vestibule, narrowing of the internal auditory canal porus, and hypoplasia of the modiolus are features of Waardenburg syndrome.
To determine whether a stepwise diagnostic paradigm is more diagnostically efficient and cost-effective than a simultaneous testing approach in the evaluation of idiopathic pediatric sensorineural ...hearing loss (SNHL).
Prospective prevalence study.
Tertiary referral children's hospital.
Consecutive children (n = 150) presenting with idiopathic SNHL in the last 2 years.
All children were evaluated with full diagnostic evaluations including GJB2 screens, temporal bone computed tomography scans, and laboratory investigations.
1) Diagnostic yields of GJB2 screens, imaging, and laboratory results per SNHL category; 2) Cost analysis comparing a sequential versus a simultaneous testing approach.
Overall, 12.0% of patients had biallelic mutations in the GJB2 gene, whereas 30% of patients had an abnormality on temporal bone scan. Laboratory testing did not reveal the SNHL etiology in any patient. While maintaining diagnostic accuracy, significant cost savings were inferred by using a sequential diagnostic algorithm. Our data show children with severe to profound SNHL should first be tested with a GJB2 screen, as opposed to those with milder SNHL, who should undergo imaging as the initial testing step. In patients with initially positive GJB2 or imaging screens, logistic regression analysis significantly predicted negative results on further testing.
A stepwise diagnostic paradigm tailored to the level of the hearing loss in children with bilateral SNHL is more diagnostically efficient and cost effective than the more commonly used full, simultaneous testing approach. Laboratory investigation should not be routine but based on clinical history.
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