<i>SLC26A4</i> Genotypes and Phenotypes Associated with Enlargement of the Vestibular Aqueduct

Abstract

Enlargement of the vestibular aqueduct (EVA) is the most common inner ear anomaly detected in ears of children with sensorineural hearing loss. Pendred syndrome (PS) is an autosomal recessive disorder characterized by bilateral sensorineural hearing loss with EVA and an iodine organification defect that can lead to thyroid goiter. Pendred syndrome is caused by mutations of the SLC26A4 gene. SLC26A4 mutations may also be identified in some patients with nonsyndromic EVA (NSEVA). The presence of two mutant alleles of SLC26A4 is correlated with bilateral EVA and Pendred syndrome, whereas unilateral EVA and NSEVA are correlated with one (M1) or zero (M0) mutant alleles of SLC26A4. Thyroid gland enlargement (goiter) appears to be primarily dependent on the presence of two mutant alleles of SLC26A4 in pediatric patients, but not in older patients. In M1 families, EVA may be associated with a second, undetected SLC26A4 mutation or epigenetic modifications. In M0 families, there is probably etiologic heterogeneity that includes causes other than, or in addition to, monogenic inheritance.

Sgk1 Sensitive Pendrin Expression in Murine Platelets

“…SLC26A4 is required for adequate development of the inner ear [7,8] and it has been suggested that the carrier is involved in thyroid iodide transport [5,9,10]. Pendrin mediates anion transport in airways [11,12] and contributes to renal tubular anion transport [6,13,14].…”

CT-Scans of Cochlear Implant Patients with Characteristics of Pendred Syndrome

“…It is defined through congenital SNHL or deafness and a malfunction of thyroid hormone synthesis. The genetic background is a mutation of the SLC26A4 gene, coding for a transmembrane protein with anion transport function, called Pendrin [3,4,5]. Pendrin is present in multiple organs, such as the kidney, the airways, the thyroid gland and the inner ear.…”

“…The over 160 known mutations of the SLC26A4 gene [4] can appear in a monoallelic or a biallelic fashion and lead to non-syndromic enlarged vestibular aqueduct (EVA) or Pendred syndrome [5]. Pendred syndrome is typically associated with biallelic mutations, whereas monoallelic mutations may lead to SNHL without further phenotypes [5].…”

“…There are two radiological findings, which are known to be associated with mutations of the SLC26A4 gene, either in a monoallelic or a biallelic manner. First one is an EVA, which is the most common finding in temporal bone imaging [4,9] in case of SNHL. EVA can be found either on one or both sides, however in case of Pendred syndrome, usually both sides are affected [9].…”

“…EVA could be found in numerous CT scan investigations of children with SNHL, not necessarily being diagnosed as Pendred syndrome according to genetic testing. In these cases EVA is defined as non-syndromic EVA [4]. …”