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Title: SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy.
Austin Authors: Vlaskamp, Danique R M;Shaw, Benjamin J;Burgess, Rosemary;Mei, Davide;Montomoli, Martino;Xie, Han;Myers, Candace T;Bennett, Mark F;XiangWei, Wenshu;Williams, Danielle;Maas, Saskia M;Brooks, Alice S;Mancini, Grazia M S;van de Laar, Ingrid M B H;van Hagen, Johanna M;Ware, Tyson L;Webster, Richard I;Malone, Stephen;Berkovic, Samuel F ;Kalnins, Renate M;Sicca, Federico;Korenke, G Christoph;van Ravenswaaij-Arts, Conny M A;Hildebrand, Michael S ;Mefford, Heather C;Jiang, Yuwu;Guerrini, Renzo;Scheffer, Ingrid E 
Affiliation: Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
IRCCS Stella Maris Foundation, Pisa, Italy
Klinikum Oldenburg, Zentrum für Kinder-und Jugendmedizin, Klinik für Neuropädiatrie u.angeborene Stoffwechselerkrankungen, Germany
Departments of Genetics and Neurology, University Medical Center Groningen, University of Groningen, the Netherlands
Pediatric Neurology Unit and Laboratories and Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, A. Meyer Children's Hospital, University of Florence, Italy
Department of Pediatrics and Pediatric Epilepsy Centre, Peking University First Hospital, Beijing, China
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle
Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
Department of Medical Biology, University of Melbourne, Australia
Caulfield, Melbourne, Australia
Department of Clinical Genetics, Academic Medical Centre, Amsterdam, the Netherlands
Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, the Netherlands
Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands
Tasmanian Health Service, Women's and Children's Services, Launceston General Hospital, Tasmania, Australia
TY Nelson Department of Neurology and Neurosurgery and Institute of Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Department of Neurosciences, Lady Cilento Children's Hospital, Brisbane, Australia
Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia
Centre of Epilepsy, Beijing Institute for Brain Disorders, China
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Australia
Florey Institute of Neurosciences and Mental Health, Australia
Issue Date: 2019
Date: 2018-12-12
Publication information: Neurology 2019; 92(2): e96-e107
Abstract: To delineate the epileptology, a key part of the SYNGAP1 phenotypic spectrum, in a large patient cohort. Patients were recruited via investigators' practices or social media. We included patients with (likely) pathogenic SYNGAP1 variants or chromosome 6p21.32 microdeletions incorporating SYNGAP1. We analyzed patients' phenotypes using a standardized epilepsy questionnaire, medical records, EEG, MRI, and seizure videos. We included 57 patients (53% male, median age 8 years) with SYNGAP1 mutations (n = 53) or microdeletions (n = 4). Of the 57 patients, 56 had epilepsy: generalized in 55, with focal seizures in 7 and infantile spasms in 1. Median seizure onset age was 2 years. A novel type of drop attack was identified comprising eyelid myoclonia evolving to a myoclonic-atonic (n = 5) or atonic (n = 8) seizure. Seizure types included eyelid myoclonia with absences (65%), myoclonic seizures (34%), atypical (20%) and typical (18%) absences, and atonic seizures (14%), triggered by eating in 25%. Developmental delay preceded seizure onset in 54 of 56 (96%) patients for whom early developmental history was available. Developmental plateauing or regression occurred with seizures in 56 in the context of a developmental and epileptic encephalopathy (DEE). Fifty-five of 57 patients had intellectual disability, which was moderate to severe in 50. Other common features included behavioral problems (73%); high pain threshold (72%); eating problems, including oral aversion (68%); hypotonia (67%); sleeping problems (62%); autism spectrum disorder (54%); and ataxia or gait abnormalities (51%). SYNGAP1 mutations cause a generalized DEE with a distinctive syndrome combining epilepsy with eyelid myoclonia with absences and myoclonic-atonic seizures, as well as a predilection to seizures triggered by eating.
DOI: 10.1212/WNL.0000000000006729
ORCID: 0000-0002-2664-4395
Journal: Neurology
PubMed URL: 30541864
Type: Journal Article
Appears in Collections:Journal articles

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