SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy. (8th January 2019)

• Record Type: Journal Article
• 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.
• Is Part Of: Neurology. Volume 92:Number 2(2019)
• Publication Date: 2019-01-08
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000006729
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To delineate the epileptology, a key part of the SYNGAP1 phenotypic spectrum, in a large patient cohort. Methods: 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. Results: 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%). Conclusions: 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.