Research Publications


SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy

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; includes Bahlo, MF
Journal Article
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.
Wolters Kluwer
Population Health and Immunity
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Creation Date 2019-10-28 12:05:05 Last Modified 2019-10-30 09:51:09