Evaluation of genotype-phenotype relationships in patients referred for endocrine assessment in suspected Pendred syndrome.

Design: Patients with Pendred syndrome have genotypic and phenotypic variability, leading to challenges in definitive diagnosis. Deaf children with enlarged vestibular aqueducts are often subjected to repeated investigations when tests for mutations in SLC26A4 are abnormal. This study provides genotype and phenotype information from patients with suspected Pendred syndrome referred to a single clinical endocrinology unit.

KCNJ10 mutations display differential sensitivity to heteromerisation with KCNJ16.

Background/aims: Mutations in the inwardly-rectifying K(+)-channel KCNJ10/Kir4.1 cause autosomal recessive EAST syndrome (epilepsy, ataxia, sensorineural deafness and tubulopathy). KCNJ10 is expressed in the distal convoluted tubule of the kidney, stria vascularis of the inner ear and brain glial cells.

Lack of significant association between mutations of KCNJ10 or FOXI1 and SLC26A4 mutations in Pendred syndrome/enlarged vestibular aqueducts.

Background: Pendred syndrome is a common autosomal recessive disorder causing deafness. Features include sensorineural hearing impairment, goitre, enlarged vestibular aqueducts (EVA) and occasionally Mondini dysplasia. Hearing impairment and EVA may occur in the absence of goitre or thyroid dyshormonogensis in a condition known as non-syndromic EVA.

Neurological features of epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome.

Aim: Recently, we reported a previously unrecognized symptom constellation comprising epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) associated with recessive mutations in the KCNJ10 gene. Here, we provide a detailed characterization of the clinical features of the syndrome to aid patient management with respect to diagnosis, prognostic counselling, and identification of best treatment modalities.

Method: We conducted a retrospective review of the detailed neurological and neuroradiological features of nine children (four females, five males; age range at last examination 6-20y) with genetically proven EAST syndrome.