Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/21920
Title: Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures.
Authors: Burgess, Rosemary;Wang, Shuyu;McTague, Amy;Boysen, Katja E;Yang, Xiaoling;Zeng, Qi;Myers, Kenneth A;Rochtus, Anne;Trivisano, Marina;Gill, Deepak;Sadleir, Lynette G;Specchio, Nicola;Guerrini, Renzo;Marini, Carla;Zhang, Yue-Hua;Mefford, Heather C;Kurian, Manju A;Poduri, Annapurna H;Scheffer, Ingrid E
Affiliation: T. Y. Nelson Department of Neurology and Neurosurgery, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Epilepsy Genetics Program, Boston Children's Hospital, Boston, MA
Department of Neurology, Harvard Medical School, Boston, MA..
Molecular Neurosciences, Developmental Neurosciences, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
Department of Neurology, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, United Kingdom..
Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Research Institute of the McGill University Health Centre; Montreal, Quebec, Canada
Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada..
School of Clinical Sciences, Monash University, Monash Health, Melbourne, Victoria, Australia
Florey Institute for Neuroscience and Mental Health, Melbourne, Victoria, Australia
Department of Neurology, Royal Children's Hospital, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Molecular Neurosciences, Developmental Neurosciences, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
Department of Pediatrics, Peking University First Hospital, Beijing, China..
Epilepsy Genetics Program, Boston Children's Hospital, Boston, MA..
Rare and Complex Epilepsies Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, Scientific Institute for Research and Health Care, Rome, Italy
Department of Paediatrics and Child Health, University of Otago Wellington, Wellington, New Zealand
Rare and Complex Epilepsies Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, Scientific Institute for Research and Health Care, Rome, Italy
Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Children's Hospital A. Meyer-University of Florence, Florence, Italy
Department of Pediatrics, Peking University First Hospital, Beijing, China
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA
Issue Date: 16-Oct-2019
EDate: 2019-10-16
Citation: Annals of neurology 2019; online first: 16 October
Abstract: Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the most severe developmental and epileptic encephalopathies. We delineate the genetic causes and genotype-phenotype correlations of a large EIMFS cohort. Phenotypic and molecular data were analyzed on patients recruited through an international collaborative study. We ascertained 135 patients from 128 unrelated families. Ninety-three of 135 (69%) had causative variants (42/55 previously reported) across 23 genes, including 9 novel EIMFS genes: de novo dominant GABRA1, GABRB1, ATP1A3; X-linked CDKL5, PIGA; and recessive ITPA, AIMP1, KARS, WWOX. The most frequently implicated genes were KCNT1 (36/135, 27%) and SCN2A (10/135, 7%). Mosaicism occurred in 2 probands (SCN2A, GABRB3) and 3 unaffected mothers (KCNT1). Median age at seizure onset was 4 weeks, with earlier onset in the SCN2A, KCNQ2, and BRAT1 groups. Epileptic spasms occurred in 22% patients. A total of 127 patients had severe to profound developmental impairment. All but 7 patients had ongoing seizures. Additional features included microcephaly, movement disorders, spasticity, and scoliosis. Mortality occurred in 33% at median age 2 years 7 months. We identified a genetic cause in 69% of patients with EIMFS. We highlight the genetic heterogeneity of EIMFS with 9 newly implicated genes, bringing the total number to 33. Mosaicism was observed in probands and parents, carrying critical implications for recurrence risk. EIMFS pathophysiology involves diverse molecular processes from gene and protein regulation to ion channel function and solute trafficking. This article is protected by copyright. All rights reserved.
URI: http://ahro.austin.org.au/austinjspui/handle/1/21920
DOI: 10.1002/ana.25619
ORCID: 0000-0002-2664-4395
0000-0002-2311-2174
0000-0001-7831-4593
PubMed URL: 31618474
Type: Journal Article
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.