John A Damiano1, Lucy Deng2,3, Wenhui Li1,4, Rosemary Burgess1, Amy L Schneider1, Nigel W Crawford5,6, Jim Buttery6,7, Michael Gold8, Peter Richmond9,10, Kristine K Macartney2,3, Michael S Hildebrand1,6, Ingrid E Scheffer1,5,6,11, Nicholas Wood2,3, Samuel F Berkovic1. 1. Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia. 2. National Centre for Immunisation Research and Surveillance, Children's Hospital at Westmead, Sydney, New South Wales, Australia. 3. Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia. 4. Department of Neurology, Children's Hospital of Fudan University, Shanghai, China. 5. Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia. 6. Murdoch Children's Research Institute, Parkville, Victoria, Australia. 7. Infection and Immunity, Monash Children's Hospital, Department of Paediatrics, Monash Centre for Health Care Research and Implementation, Monash University, Clayton, Victoria, Australia. 8. Discipline of Paediatrics, School of Medicine, Women's and Children's Hospital, University of Adelaide, Adelaide, South Australia, Australia. 9. Vaccine Trials Group, Wesfarmer's Centre of Vaccines and Infectious Disease, Telethon Kids Institute, and Department of General Paediatrics, Perth Children's Hospital, Nedlands, Western Australia, Australia. 10. Division of Paediatrics, School of Medicine, University of Western Australia, Perth, Western Australia, Australia. 11. Florey Institute of Neurosciences and Mental Health, Melbourne, Victoria, Australia.
Abstract
OBJECTIVE: Febrile seizures may follow vaccination. Common variants in the sodium channel gene, SCN1A, are associated with febrile seizures, and rare pathogenic variants in SCN1A cause the severe developmental and epileptic encephalopathy Dravet syndrome. Following vaccination, febrile seizures may raise the specter of poor outcome and inappropriately implicate vaccination as the cause. We aimed to determine the prevalence of SCN1A variants in children having their first febrile seizure either proximal to vaccination or unrelated to vaccination compared to controls. METHODS: We performed SCN1A sequencing, blind to clinical category, in a prospective cohort of children presenting with their first febrile seizure as vaccine proximate (n = 69) or as non-vaccine proximate (n = 75), and children with no history of seizures (n = 90) recruited in Australian pediatric hospitals. RESULTS: We detected 2 pathogenic variants in vaccine-proximate cases (p.R568X and p.W932R), both of whom developed Dravet syndrome, and 1 in a non-vaccine-proximate case (p.V947L) who had febrile seizures plus from 9 months. All had generalized tonic-clonic seizures lasting >15 minutes. We also found enrichment of a reported risk allele, rs6432860-T, in children with febrile seizures compared to controls (odds ratio = 1.91, 95% confidence interval = 1.31-2.81). INTERPRETATION: Pathogenic SCN1A variants may be identified in infants with vaccine-proximate febrile seizures. As early diagnosis of Dravet syndrome is essential for optimal management and outcome, SCN1A sequencing in infants with prolonged febrile seizures, proximate to vaccination, should become routine. ANN NEUROL 2020;87:281-288.
OBJECTIVE:Febrile seizures may follow vaccination. Common variants in the sodium channel gene, SCN1A, are associated with febrile seizures, and rare pathogenic variants in SCN1A cause the severe developmental and epileptic encephalopathy Dravet syndrome. Following vaccination, febrile seizures may raise the specter of poor outcome and inappropriately implicate vaccination as the cause. We aimed to determine the prevalence of SCN1A variants in children having their first febrile seizure either proximal to vaccination or unrelated to vaccination compared to controls. METHODS: We performed SCN1A sequencing, blind to clinical category, in a prospective cohort of children presenting with their first febrile seizure as vaccine proximate (n = 69) or as non-vaccine proximate (n = 75), and children with no history of seizures (n = 90) recruited in Australian pediatric hospitals. RESULTS: We detected 2 pathogenic variants in vaccine-proximate cases (p.R568X and p.W932R), both of whom developed Dravet syndrome, and 1 in a non-vaccine-proximate case (p.V947L) who had febrile seizures plus from 9 months. All had generalized tonic-clonic seizures lasting >15 minutes. We also found enrichment of a reported risk allele, rs6432860-T, in children with febrile seizures compared to controls (odds ratio = 1.91, 95% confidence interval = 1.31-2.81). INTERPRETATION: Pathogenic SCN1A variants may be identified in infants with vaccine-proximate febrile seizures. As early diagnosis of Dravet syndrome is essential for optimal management and outcome, SCN1A sequencing in infants with prolonged febrile seizures, proximate to vaccination, should become routine. ANN NEUROL 2020;87:281-288.
Authors: Ana Carla Mondek Rampazzo; Rafael Rodrigues Pinheiro Dos Santos; Fernando Arfux Maluf; Renata Faria Simm; Fernando Augusto Lima Marson; Manoela Marques Ortega; Paulo Henrique Pires de Aguiar Journal: Neurogenetics Date: 2021-05-03 Impact factor: 2.660
Authors: Veronica Hood; Anne T Berg; Kelly G Knupp; Sookyong Koh; Linda Laux; Mary Anne Meskis; Quratulain Zulfiqar-Ali; M Scott Perry; Ingrid E Scheffer; Joseph Sullivan; Elaine Wirrell; Danielle M Andrade Journal: Epilepsia Date: 2022-04-20 Impact factor: 6.740