Neurological features of epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome
Open Access
- 8 August 2013
- journal article
- case report
- Published by Wiley in Developmental Medicine and Child Neurology
- Vol. 55 (9), 846-856
- https://doi.org/10.1111/dmcn.12171
Abstract
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. 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. 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. 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.Funding Information
- Research Councils UK
This publication has 32 references indexed in Scilit:
- Automatic morphometry in Alzheimer's disease and mild cognitive impairmentNeuroImage, 2011
- Altered electroretinograms in patients with KCNJ10 mutations and EAST syndromeJournal Of Physiology-London, 2011
- KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel functionProceedings of the National Academy of Sciences of the United States of America, 2010
- Neurological ChannelopathiesAnnual Review of Neuroscience, 2010
- Epilepsy, Ataxia, Sensorineural Deafness, Tubulopathy, andKCNJ10MutationsThe New England Journal of Medicine, 2009
- Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10Proceedings of the National Academy of Sciences of the United States of America, 2009
- Functional implications for Kir4.1 channels in glial biology: from K+ buffering to cell differentiationJournal of Neurochemistry, 2008
- Automatic segmentation of brain MRIs of 2-year-olds into 83 regions of interestNeuroImage, 2008
- What’s new in: “Genetics in childhood epilepsy”European Journal of Pediatrics, 2008
- Genetic Polymorphisms and Idiopathic Generalized EpilepsiesPediatric Neurology, 2007