Contralateral deafness following unilateral suboccipital brain tumor surgery in a patient with large vestibular aqueduct--case report.
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A 68-year-old female developed contralateral deafness following extirpation of a left cerebellopontine angle epidermoid cyst. Computed tomography showed that large vestibular aqueduct was present. This unusual complication may have been caused by an abrupt pressure change after cerebrospinal fluid release, which was transmitted through the large vestibular aqueduct and resulted in cochlear damage. (+info)
Temporal bone computed tomography findings in bilateral sensorineural hearing loss.
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AIM: To examine the yield of computed tomography (CT) of the temporal bones when investigating sensorineural hearing loss (SNHL) and to identify factors associated with CT findings. METHODS: Retrospective analysis of 116 consecutively investigated children with bilateral SNHL at the audiology department of Great Ormond Street Hospital, London. Main outcome measures were CT results, hearing loss parameters, history, and clinical examination. RESULTS: A total of 33 (28.4%) CT scans were identified as abnormal. Children with profound and/or progressive hearing loss and/or craniofacial abnormalities were more likely to have an abnormal CT scan and together accounted for 25 abnormal CT scans. Sex, consanguineous parents, or family history of SNHL were not associated with CT findings. Dilated vestibular aqueduct was significantly correlated with the presence of progressive SNHL. CONCLUSIONS: All children with SNHL should undergo radiological investigation of the petrous bones/inner ear; abnormalities are more likely to be found in cases with craniofacial abnormalities, or profound or progressive hearing loss. The decision whether to perform a CT or magnetic resonance imaging will depend on scanner availability, expertise, and management considerations, but cochlear implant candidates will require both. (+info)
Enlarged vestibular aqueduct: a radiological marker of pendred syndrome, and mutation of the PDS gene.
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Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome. Since this is the most common radiological malformation of the cochlea in deaf patients, we investigated what proportion of such cases were due to mutation of the PDS gene. We assessed 57 patients referred with radiological evidence of vestibular aqueduct enlargement, by history, clinical examination, perchlorate discharge test and molecular analysis of the PDS locus. Forty-one patients (72%) had unequivocal evidence of Pendred syndrome. The finding of a single heterozygous mutation at the PDS gene in a further eight was strongly suggestive of a critical role for pendrin, the protein product of the PDS gene, in the generation of enlarged vestibular aqueducts in at least 86% (49/57 cases) of patients with this radiological malformation. Securing the diagnosis of Pendred syndrome may be difficult, especially in the single case. Goitre is an inconstant finding, and the perchlorate discharge test, although helpful, is of diagnostic value only if abnormal. Enlargement of the vestibular aqueduct should be considered as the most likely presentation of Pendred syndrome and should prompt specific investigation of that diagnostic possibility. Pendred syndrome might henceforth be recharacterized as deafness with enlargement of the vestibular aqueduct, which is sometimes associated with goitre. (+info)
Phenotypes associated with replacement of His by Arg in the Pendred syndrome gene.
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BACKGROUND: Pendred syndrome is often associated with inner ear malformations, especially enlarged vestibular aqueduct (EVA). Recently, mutations in the Pendred syndrome gene (PDS) have been reported in patients with EVA, in addition to those with classical Pendred syndrome. OBJECTIVE: The aim of this study was to investigate the genotype-phenotype correlations of PDS. METHODS: Each of the 21 exons and flanking splice regions of PDS was analysed by direct DNA sequencing in nine patients with EVA; allele-specific amplification was performed to confirm the mutation. Genetic analyses were compared with thyroid function tests, perchlorate discharge tests, thyroid volume and pure-tone audiogram. Magnetic resonance imaging was used to determine the volume of the endolymphatic duct and sac of each patient. RESULTS: A missense mutation, H723R, was identified in the homozygous state in three patients and in the heterozygous state in another three. Although none of the patients had goitre, increased serum thyroglobulin and an abnormal degree of iodide release were correlated with the number of mutant alleles identified. However, there was no relationship between the degree of hearing loss and the number of mutant alleles. CONCLUSION: The present study reveals that the number of mutant alleles correlates with the degree of subclinical thyroid abnormality, but not with the degree of hearing loss in Japanese patients with the PDS missense mutation H723R. (+info)
Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice.
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Mice that lack the winged helix/forkhead gene Foxi1 (also known as Fkh10) are deaf and display shaker/waltzer behavior, an indication of disturbed balance. While Foxi1 is expressed in the entire otic vesicle at E9.5, it becomes gradually restricted to the endolymphatic duct/sac epithelium and at E16.5 Foxi1 expression in the inner ear is confined to this epithelium. Histological sections, paintfill experiments and whole-mount hybridizations reveal no abnormality in inner ear development of Foxi1(-/-) mice before E13.5. Between E13.5 and E16.5 the membranous labyrinth of inner ears from null mutants starts to expand as can be seen in histological sections, paint-fill experiments and three-dimensional reconstruction. Postnatally, inner ears of Foxi1(-/-) mice are extremely expanded, and large irregular cavities, compressing the cerebellum and the otherwise normal middle ear, have replaced the delicate compartments of the wild-type inner ear. This phenotype resembles that of the human sensorineural deafness syndrome Pendred syndrome, caused by mutations in the PDS gene. In situ hybridization of Foxi1(-/-) endolymphatic duct/sac epithelium shows a complete lack of the transcript encoding the chloride/iodide transporter pendrin. Based on this, we would like to suggest that Foxi1 is an upstream regulator of pendrin and that the phenotype seen in Foxi1 null mice is, at least in part, due to defective pendrin-mediated chloride ion resorption in the endolymphatic duct/sac epithelium. We show that this regulation could be mediated by absence of a specific endolymphatic cell type--FORE (forkhead related) cells--expressing Foxi1, Pds, Coch and Jag1. Thus, mutations in FOXI1 could prove to cause a Pendred syndrome-like human deafness. (+info)
Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese.
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Molecular diagnosis makes a substantial contribution to precise diagnosis, subclassification, prognosis, and selection of therapy. Mutations in the PDS (SLC26A4) gene are known to be responsible for both Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct, and the molecular confirmation of the PDS gene has become important in the diagnosis of these conditions. In the present study, PDS mutation analysis confirmed that PDS mutations were present and significantly responsible in 90% of Pendred families, and in 78.1% of families with nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Furthermore, variable phenotypic expression by the same combination of mutations indicated that these two conditions are part of a continuous category of disease. Interestingly, the PDS mutation spectrum in Japanese, including the seven novel mutations revealed by this study, is very different from that found in Caucasians. Of the novel mutations detected, 53% were the H723R mutation, suggesting a possible founder effect. Ethnic background is therefore presumably important and should be noted when genetic testing is being performed. The PDS gene mutation spectrum in Japanese may be representative of those in Eastern Asian populations and its elucidation is expected to facilitate the molecular diagnosis of a variety of diseases. (+info)
Relationship between the external aperture and hearing loss in large vestibular aqueduct syndrome.
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BACKGROUND: Large vestibular aqueduct syndrome (LVAS) is a major cause of hearing loss in childhood. This study aimed at measuring external aperture of enlargement of the vestibular aqueduct (EVA) and analyzing relationship between the size of external aperture and hearing loss. METHODS: Diagnostic criteria of LVAS were based on hearing loss and CT images. CT images of temporal bone of 100 LVAS patients were collected and 60 control subjects were reviewed retrospectively in the past 10 years. A battery of audiometric and vestibular function tests were performed. The width of the vestibular aqueduct (VA) was measured on axial CT images of the temporal bone. RESULTS: One hundred patients (65 men, 35 women) were diagnosed as having the isolated EVA. Hearing loss mostly occurred in early childhood. The diagnosis age of LVAS was 7.7 years on average. The causes of hearing loss could not be confirmed by initial consult. Typically, audiometric curve is the high-frequency down-sloping configuration. 92% of the cases had severe or profound sonsorineural hearing loss (SNHL). The mean size of the external aperture was (7.5 +/- 1.2) mm in present LVAS. Statistical analysis showed that the degree of hearing loss is unrelated to the width of VA. CONCLUSIONS: LVAS is a distinct clinical entity characterized by fluctuating, progressive SNHL. The degree of hearing loss is unrelated to the size of external aperture of VA. The protective management and hearing aid have become the main therapies. The cochlear implantation might be performed if the hearing loss affected learning at school. (+info)
SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations.
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Sensorineural hearing loss is the most frequent sensory deficit of childhood and is of genetic origin in up to 75% of cases. It has been shown that mutations of the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4). While the prevalence of SLC26A4 mutations in Pendred's syndrome is clearly established, it remains to be studied in large cohorts of patients with nonsyndromic deafness and detailed clinical informations. In this report, 109 patients from 100 unrelated families, aged from 1 to 32 years (median age: 10 years), with nonsyndromic deafness and enlarged vestibular aqueduct, were genotyped for SLC26A4 using DHPLC molecular screening and sequencing. In all, 91 allelic variants were observed in 100 unrelated families, of which 19 have never been reported. The prevalence of SLC26A4 mutations was 40% (40/100), with biallelic mutation in 24% (24/100), while six families were homozygous. All patients included in this series had documented deafness, associated with EVA and without any evidence of syndromic disease. Among patients with SLC26A4 biallelic mutations, deafness was more severe, fluctuated more than in patients with no mutation. In conclusion, the incidence of SLC26A4 mutations is high in patients with isolated deafness and enlarged vestibular aqueduct and could represent up to 4% of nonsyndromic hearing impairment. SLC26A4 could be the second most frequent gene implicated in nonsyndromic deafness after GJB2, in this Caucasian population. (+info)