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Title: Epidemiology and etiology of infantile developmental and epileptic encephalopathies in Tasmania.
Austin Authors: Ware, Tyson L;Huskins, Shannon R;Grinton, Bronwyn E;Liu, Yu-Chi;Bennett, Mark F;Harvey, Michael;McMahon, Jacinta;Andreopoulos-Malikotsinas, Danae;Bahlo, Melanie;Howell, Katherine B;Hildebrand, Michael S ;Damiano, John A;Rosenfeld, Alexander;Mackay, Mark T;Mandelstam, Simone;Leventer, Richard J;Harvey, A Simon;Freeman, Jeremy L;Scheffer, Ingrid E ;Jones, Dean L;Berkovic, Samuel F 
Affiliation: Department of Paediatrics Royal Hobart Hospital Hobart Tasmania Australia
Department of Pediatrics University of Melbourne Melbourne Victoria Australia
Florey Institute of Neuroscience and Mental Health Parkville Victoria Australia
Department of Radiology University of Melbourne Melbourne Victoria Australia
The Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
Department of Medical Biology University of Melbourne Melbourne Victoria Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
School of Medicine University of Tasmania Hobart Tasmania Australia
Department of Neurology Royal Hobart Hospital Hobart Tasmania Australia
Royal Children's Hospital Melbourne Victoria Australia
Murdoch Children's Research Institute Parkville Victoria Australia
Issue Date: Sep-2019 2019-07-22
Publication information: Epilepsia open 2019; 4(3): 504-510
Abstract: We sought to determine incidence, etiologies, and yield of genetic testing in infantile onset developmental and epileptic encephalopathies (DEEs) in a population isolate, with an intensive multistage approach. Infants born in Tasmania between 2011 and 2016, with seizure onset <2¬†years of age, epileptiform EEG, frequent seizures, and developmental impairment, were included. Following review of EEG databases, medical records, brain MRIs, and other investigations, clinical genetic testing was undertaken with subsequent research interrogation of whole exome sequencing (WES) in unsolved cases. The incidence of infantile DEEs was 0.44/1000 per year (95% confidence interval 0.25 to 0.71), with 16 cases ascertained. The etiology was structural in 5/16 cases. A genetic basis was identified in 6 of the remaining 11 cases (3 gene panel, 3 WES). In two further cases, WES identified novel variants with strong in silico data; however, paternal DNA was not available to support pathogenicity. The etiology was not determined in 3/16 (19%) cases, with a candidate gene identified in one of these. Pursuing clinical imaging and genetic testing followed by WES at an intensive research level can give a high diagnostic yield in the infantile DEEs, providing a solid base for prognostic and genetic counseling.
DOI: 10.1002/epi4.12350
ORCID: 0000-0002-1911-9808
Journal: Epilepsia open
PubMed URL: 31440733
ISSN: 2470-9239
Type: Journal Article
Subjects: developmental and epileptic encephalopathy
whole exome sequencing
Appears in Collections:Journal articles

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