SYNGAP1 encephalopathy
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Open Access
- 8 January 2019
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 92 (2), e96-e107
- https://doi.org/10.1212/wnl.0000000000006729
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.Keywords
This publication has 51 references indexed in Scilit:
- Evidence for APOBEC3B mutagenesis in multiple human cancersNature Genetics, 2013
- A balanced translocation disruptsSYNGAP1in a patient with intellectual disability, speech impairment, and epilepsy with myoclonic absences (EMA)Epilepsia, 2011
- Excess of De Novo Deleterious Mutations in Genes Associated with Glutamatergic Systems in Nonsyndromic Intellectual DisabilityAmerican Journal of Human Genetics, 2011
- Integrated analysis of clinical signs and literature data for the diagnosis and therapy of a previously undescribed 6p21.3 deletion syndromeEuropean Journal of Human Genetics, 2010
- A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of chromosome 6 associated with mental retardationAmerican Journal of Medical Genetics Part A, 2010
- Functional impact of global rare copy number variation in autism spectrum disordersNature, 2010
- Mutations inSYNGAP1in Autosomal Nonsyndromic Mental RetardationNew England Journal of Medicine, 2009
- Reduced Expression of the NMDA Receptor-Interacting Protein SynGAP Causes Behavioral Abnormalities that Model Symptoms of SchizophreniaNeuropsychopharmacology, 2009
- The Natural History of Myoclonic Astatic Epilepsy (Doose Syndrome) and Lennox‐Gastaut SyndromeEpilepsia, 2006
- Severe myoclonic epilepsy in infants – a review based on the Tokyo Women's Medical University series of 84 casesBrain & Development, 2001