SCN1A Variants in vaccine-related febrile seizures: A prospective study
John A. Damiano BSc (Hons)
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
J.A.D. and L.D. contributed equally to this study.Search for more papers by this authorLucy Deng MBBS
National Centre for Immunisation Research and Surveillance, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
J.A.D. and L.D. contributed equally to this study.Search for more papers by this authorWenhui Li MD
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Department of Neurology, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorRosemary Burgess PhD
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Search for more papers by this authorAmy L. Schneider BSc (Hons)
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Search for more papers by this authorNigel W. Crawford MBBS, PhD
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia
Murdoch Children's Research Institute, Parkville, Victoria, Australia
Search for more papers by this authorJim Buttery MD
Murdoch Children's Research Institute, Parkville, Victoria, Australia
Infection and Immunity, Monash Children's Hospital, Department of Paediatrics, Monash Centre for Health Care Research and Implementation, Monash University, Clayton, Victoria, Australia
Search for more papers by this authorMichael Gold MB,CHB
Discipline of Paediatrics, School of Medicine, Women's and Children's Hospital, University of Adelaide, Adelaide, South Australia, Australia
Search for more papers by this authorPeter Richmond MBBS
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
Division of Paediatrics, School of Medicine, University of Western Australia, Perth, Western Australia, Australia
Search for more papers by this authorKristine K. Macartney MD
National Centre for Immunisation Research and Surveillance, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
Search for more papers by this authorMichael S. Hildebrand PhD
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Murdoch Children's Research Institute, Parkville, Victoria, Australia
Search for more papers by this authorIngrid E. Scheffer MBBS, PhD
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia
Murdoch Children's Research Institute, Parkville, Victoria, Australia
Florey Institute of Neurosciences and Mental Health, Melbourne, Victoria, Australia
Search for more papers by this authorNicholas Wood MBBS, PhD
National Centre for Immunisation Research and Surveillance, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
Search for more papers by this authorCorresponding Author
Samuel F. Berkovic MD, FRS
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Address correspondence to Dr Berkovic, Epilepsy Research Centre, L2 Melbourne Brain Centre, 245 Burgundy Street, Heidelberg, VIC 3084, Australia. E-mail: [email protected]Search for more papers by this authorJohn A. Damiano BSc (Hons)
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
J.A.D. and L.D. contributed equally to this study.Search for more papers by this authorLucy Deng MBBS
National Centre for Immunisation Research and Surveillance, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
J.A.D. and L.D. contributed equally to this study.Search for more papers by this authorWenhui Li MD
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Department of Neurology, Children's Hospital of Fudan University, Shanghai, China
Search for more papers by this authorRosemary Burgess PhD
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Search for more papers by this authorAmy L. Schneider BSc (Hons)
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Search for more papers by this authorNigel W. Crawford MBBS, PhD
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia
Murdoch Children's Research Institute, Parkville, Victoria, Australia
Search for more papers by this authorJim Buttery MD
Murdoch Children's Research Institute, Parkville, Victoria, Australia
Infection and Immunity, Monash Children's Hospital, Department of Paediatrics, Monash Centre for Health Care Research and Implementation, Monash University, Clayton, Victoria, Australia
Search for more papers by this authorMichael Gold MB,CHB
Discipline of Paediatrics, School of Medicine, Women's and Children's Hospital, University of Adelaide, Adelaide, South Australia, Australia
Search for more papers by this authorPeter Richmond MBBS
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
Division of Paediatrics, School of Medicine, University of Western Australia, Perth, Western Australia, Australia
Search for more papers by this authorKristine K. Macartney MD
National Centre for Immunisation Research and Surveillance, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
Search for more papers by this authorMichael S. Hildebrand PhD
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Murdoch Children's Research Institute, Parkville, Victoria, Australia
Search for more papers by this authorIngrid E. Scheffer MBBS, PhD
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia
Murdoch Children's Research Institute, Parkville, Victoria, Australia
Florey Institute of Neurosciences and Mental Health, Melbourne, Victoria, Australia
Search for more papers by this authorNicholas Wood MBBS, PhD
National Centre for Immunisation Research and Surveillance, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
Search for more papers by this authorCorresponding Author
Samuel F. Berkovic MD, FRS
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Address correspondence to Dr Berkovic, Epilepsy Research Centre, L2 Melbourne Brain Centre, 245 Burgundy Street, Heidelberg, VIC 3084, Australia. E-mail: [email protected]Search for more papers by this authorAbstract
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
Potential Conflicts of Interest
The institution of S.F.B. and I.E.S. (University of Melbourne) receives payments for a patent for SCN1A testing held by Bionomics and licensed to various diagnostic companies. The remaining authors have nothing to report.
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