Familial Large Vestibular Aqueduct Syndrome

Griffith, Andrew J.; Arts, H. Alexander; Downs, J. Crawford; Innis, Jeffrey W.; Shepard, Neil T.; Sheldon, Susan; Gebarśki, Stephen S.

doi:10.1097/00005537-199608000-00009

Cited by 91 publications

(64 citation statements)

References 7 publications

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“…There does not appear to be an association of the presence of a cochlear anomaly with severity of hearing loss when other underlying genotypic and phenotypic correlations are accounted for in ears with EVA (4). Moreover, there is no correlation of the degree of enlargement of the vestibular aqueduct with degree of hearing loss in ears meeting typical diagnostic criteria for EVA (3,4). Therefore, these gross morphogenetic anomalies are not the direct cause of hearing loss in EVA.…”

Section: Introductionmentioning

confidence: 89%

“…The corresponding soft tissue abnormality is enlargement of the endolymphatic duct and sac (2), nonsensory epithelial organs whose primary function is thought to be ionic and osmotic regulation of endolymph. Hearing loss associated with EVA is predominantly sensorineural, variable in severity, and asymmetric or unilateral, with an onset in the first few years of life (3). EVA may be the sole radiologic abnormality or it may be associated with cochlear anomalies such as a reduced number of turns with an incomplete osseous partition.…”

Section: Introductionmentioning

confidence: 99%

“…In the mouse inner ear, pendrin functions as an exchanger of Cl -and HCO 3 - (13). It is expressed in nonsensory epithelial cells of the outer sulcus and spiral prominence of the cochlear duct, transitional cells surrounding the vestibular neuroepithelia, and mitochondria-rich cells of the endolymphatic sac (refs.…”

Section: Introductionmentioning

confidence: 99%

“…This question is relevant to strategies to prevent or retard progressive hearing loss in EVA. Moreover, the profound hearing loss and inner ear malformations in the Slc26a4 Δ/Δ mouse do not model the less severe phenotypes frequently observed in human EVA patients (3,4,9,10). We thus generated a mouse line in which we could reversibly activate and deactivate Slc26a4 expression to define the temporal requirements for pendrin in the auditory system and to model human EVA phenotypes.…”

Section: Introductionmentioning

confidence: 99%

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Mouse model of enlarged vestibular aqueducts defines temporal requirement of Slc26a4 expression for hearing acquisition

Choi¹,

Kim²,

Ito³

et al. 2011

J. Clin. Invest.

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108

131

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Mutations in human SLC26A4 are a common cause of hearing loss associated with enlarged vestibular aqueducts (EVA). SLC26A4 encodes pendrin, an anion-base exchanger expressed in inner ear epithelial cells that secretes HCO 3 -into endolymph. Studies of Slc26a4-null mice indicate that pendrin is essential for inner ear development, but have not revealed whether pendrin is specifically necessary for homeostasis. Slc26a4-null mice are profoundly deaf, with severe inner ear malformations and degenerative changes that do not model the less severe human phenotype. Here, we describe studies in which we generated a binary transgenic mouse line in which Slc26a4 expression could be induced with doxycycline. The transgenes were crossed onto the Slc26a4-null background so that all functional pendrin was derived from the transgenes. Varying the temporal expression of Slc26a4 revealed that E16.5 to P2 was the critical interval in which pendrin was required for acquisition of normal hearing. Lack of pendrin during this period led to endolymphatic acidification, loss of the endocochlear potential, and failure to acquire normal hearing. Doxycycline initiation at E18.5 or discontinuation at E17.5 resulted in partial hearing loss approximating the human EVA auditory phenotype. These data collectively provide mechanistic insight into hearing loss caused by SLC26A4 mutations and establish a model for further studies of EVA-associated hearing loss.

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mouse model of enlarged vestibular aqueducts defines temporal requirement of Slc26a4 expression for hearing acquisition

Choi¹,

Kim²,

Ito³

et al. 2011

J. Clin. Invest.

Self Cite

108

131

View full text Add to dashboard Cite

show abstract

“…Griffth et al 11 described a family case of hearing loss associated with EVA. Abe and Ussami 12 have also described 6 cases in 3 families with hearing loss associated with EVA.…”

Section: Discussionmentioning

confidence: 99%

Síndrome do aqueduto vestibular alargado: relato de 3 casos e revisão bibliográfica

Pinto

Mello

Marqui³

et al. 2005

Rev. Bras. Otorrinolaringol.

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A Síndrome do Aqueduto Vestibular Alargado (SAVA) é caracterizada por um alargamento do aqueduto vestibular associado a uma perda auditiva neurossensorial, algumas vezes mista, que pode ser congênita ou adquirida na infância. A disacusia pode ser dividida em leve, moderada ou profunda, associada com períodos de melhora ou de piora súbita. O alargamento do aqueduto vestibular é a anomalia da orelha interna mais comum. A SAVA é admitida como resultado de uma anormalidade genética no desenvolvimento do aqueduto vestibular anterior à quinta semana de gestação. A incidência de SAVA está entre 1% e 1,3%, podendo chegar a 7% dependendo da população examinada. O objetivo deste estudo é relatar 3 casos de SAVA atendidos no Núcleo de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço de São Paulo e no serviço de Radiologia do Hospital São Camilo - São Paulo, sendo que dois pacientes são irmãos somente por parte materna. Dois pacientes eram do sexo feminino, um do sexo masculino e a idade variou de 9 a 30 anos. O método diagnóstico de eleição é a TC de osso temporais. A conduta para os casos foi o tratamento conservador com ressalva a cuidados como traumatismos cranianos, barotraumas e, quando necessário, uso de próteses auditivas.

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Progressive Sensorineural Hearing Loss and a Widened Vestibular Aqueduct in Pendred Syndrome

Cremers¹,

Bolder²,

Admiraal³

et al. 1998

Arch Otolaryngol Head Neck Surg

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Pendred syndrome is an autosomal recessive inherited disorder. Obligatory features are profound deafness in childhood and defective organic binding of iodine in the thyroid gland. Therefore, goiter is a common symptom. Hypoplasia of the cochlea is another feature. Recently, the gene for Pendred syndrome was identified. We describe a boy whose sensorineural hearing loss in both ears progressed rapidly from about 50 to 60 dB at the age of 3 years and 3 months to more than 100 dB at the age of 4 years and 4 months. This loss was preceded by a medical history of a progressive hearing loss. The progressive nature of the hearing loss motivated a search for the cause. Dysplasia of the cochlea and a widened vestibular aqueduct were found. The results of thyroid function tests were normal, but he had an elevated level of thyroglobulin. The diagnosis of Pendred syndrome was confirmed by the positive results of a potassium perchlorate test, indicating defective organic binding of iodine in the thyroid gland. It is possible that the widened vestibular aqueduct was responsible for the increase in the hearing impairment. Aside from the branchio-otorenal syndrome, Pendred syndrome is the only other known genetic disorder with a widened vestibular aqueduct. If a child has progressive sensorineural deafness and a widened vestibular aqueduct, it is important to consider a diagnosis of Pendred syndrome. A widened vestibular aqueduct may help to elucidate the pathophysiologic characteristics of hearing loss in these genetic types of deafness in childhood.

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Familial Large Vestibular Aqueduct Syndrome

Cited by 91 publications

References 7 publications

Mouse model of enlarged vestibular aqueducts defines temporal requirement of Slc26a4 expression for hearing acquisition

Mouse model of enlarged vestibular aqueducts defines temporal requirement of Slc26a4 expression for hearing acquisition

Síndrome do aqueduto vestibular alargado: relato de 3 casos e revisão bibliográfica

Progressive Sensorineural Hearing Loss and a Widened Vestibular Aqueduct in Pendred Syndrome

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