1. SYNGAP1 encephalopathy A distinctive generalized developmental and epileptic encephalopathy
- Author
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Vlaskamp, DRM, Shaw, BJ, Burgess, R, Mei, D, Montomoli, M, Xie, H, Myers, CT, Bennett, MF, XiangWei, W, Williams, D, Maas, SM, Brooks, AS, Mancini, GMS, van de Laar, IMBH, van Hagen, JM, Ware, TL, Webster, RI, Malone, S, Berkovic, SF, Kalnins, RM, Sicca, F, Korenke, GC, van Ravenswaaij-Arts, CMA, Hildebrand, MS, Mefford, HC, Jiang, Y, Guerrini, R, Scheffer, IE, Vlaskamp, DRM, Shaw, BJ, Burgess, R, Mei, D, Montomoli, M, Xie, H, Myers, CT, Bennett, MF, XiangWei, W, Williams, D, Maas, SM, Brooks, AS, Mancini, GMS, van de Laar, IMBH, van Hagen, JM, Ware, TL, Webster, RI, Malone, S, Berkovic, SF, Kalnins, RM, Sicca, F, Korenke, GC, van Ravenswaaij-Arts, CMA, Hildebrand, MS, Mefford, HC, Jiang, Y, Guerrini, R, and Scheffer, IE
- 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.
- Published
- 2019