Neurological Features of Epilepsy, Ataxia, Sensorineural Deafness, Tubulopathy Syndrome

Overview

Journal Dev Med Child Neurol

Date 2013 Aug 9

PMID 23924083

Citations 30

Authors

J Helen Cross

Ruchi Arora

Rolf A Heckemann

Roxana Gunny

Kling Chong

Lucinda Carr

Torsten Baldeweg

Ann-Marie Differ

Nicholas Lench

Sophie Varadkar

Tony Sirimanna

Evangeline Wassmer

Sally A Hulton

Milos Ognjanovic

Venkateswaran Ramesh

Sally Feather

Robert Kleta

Alexander Hammers

Detlef Bockenhauer

Affiliations

Soon will be listed here.

Abstract

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.

Results: All children presented with tonic-clonic seizures in infancy. Later, non-progressive, cerebellar ataxia and hearing loss were noted. Whilst seizures mostly responded well to treatment, ataxia proved to be the most debilitating feature, with three patients non-ambulant. All available magnetic resonance imaging (MRI) revealed subtle symmetrical signal changes in the cerebellar dentate nuclei. Moreover, four patients had a small corpus callosum and brainstem hypoplasia, and three had a small spinal cord. Regional quantitative volumetric analysis of the images confirmed the corpus callosum and brainstem hypoplasia and showed further patterns of variation from the norm.

Interpretation: The neurological features of EAST syndrome appear to be non-progressive, which is important for prognostic counselling. The spectrum of EAST syndrome includes consistent abnormalities on brain MRI, which may aid diagnosis. Further longitudinal documentation is required to determine the true natural history of the disorder.

Citing Articles

Expanding the genotypic and phenotypic spectrum of EAST/SeSAME syndrome: identification of a novel homozygous mutation (c.194 G > A) in KCNJ10 gene.

Yari A, Dalvand L, Moghaddam B, Khorasani N, Esmaeili F, Attari R Neurol Sci. 2024; 46(2):911-927.

PMID: 39607615 DOI: 10.1007/s10072-024-07834-9.

EAST (Epilepsy, Ataxia, Sensorineural Hearing Loss, and Renal Tubulopathy) Syndrome: A Rare Association Between Brain, Ear, and Kidney.

Vats A, Satpathy A, Sahoo B, Sahoo A, Nayak M Cureus. 2024; 16(9):e68909.

PMID: 39381482 PMC: 11459077. DOI: 10.7759/cureus.68909.

Spinocerebellar ataxia in the Bouvier des Ardennes breed is caused by a KCNJ10 missense variant.

Stee K, Van Poucke M, Pumarola M, Geerinckx L, Van Soens I, Bhatti S J Vet Intern Med. 2022; 37(1):216-222.

PMID: 36426918 PMC: 9889618. DOI: 10.1111/jvim.16594.

Kir5.1 channels: potential role in epilepsy and seizure disorders.

Staruschenko A, Hodges M, Palygin O Am J Physiol Cell Physiol. 2022; 323(3):C706-C717.

PMID: 35848616 PMC: 9448276. DOI: 10.1152/ajpcell.00235.2022.

EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies.

Lo J, Forst A, Warth R, Zdebik A Front Physiol. 2022; 13:852674.

PMID: 35370765 PMC: 8965613. DOI: 10.3389/fphys.2022.852674.

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