STAG2 microduplication in a patient with eyelid myoclonia and absences and a review of EMA-related reported genes

International audienceXq25 microduplication involving exclusively STAG2 is a new distinctive cohesinopathy including mild to moderate intellectual disability, speech delay and facial dysmorphism. Seizures seem to be scarce, but detailed seizure type descriptions are missing. We report the case of an 8-year-old boy with mild intellectual disability and eyelid myoclonia with onset at age of 3 years, initially misinterpreted as tics. An ictal VIDEO-EEG documented eye closure elicited generalized 3 Hz spike-waves or polyspike-waves concomitant to eyelid myoclonia, sometimes associated to brief clinically observable absences. Intermittent photic stimulation revealed a photoparoxysmal response. Array CGH identified a 199 kb copy number gain in Xq25 including the whole STAG2 gene, inherited from his asymptomatic mother. To the best of our knowledge, this is the first case of STAG2 encephalopathy fulfilling all electroclinical criteria for epilepsy with eyelid myoclonia and absences (EMA), formally named Jeavons syndrome (JS). As for other Genetic Generalized Epilepsy syndromes, EMA/JS usually occurs in normally developing children. Intellectual disability of variable degree is occasionally reported. On the background of other genes responsible for Developmental and Epileptic Encephalopathies, linked to specific generalized seizure types or seizure combinations, we discuss the contribution of pathogenic variants in CHD2, SYNGAP1 and some other genes as, RORB, NEXMIF and KCNB1 to this peculiar EMA phenotype

Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study

Background: Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling. Methods: In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding. Findings: 9147 patients were included, of whom seizure outcomes were available for 8191 (89·5%) participants at 2 years, and for 5577 (61·0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77·5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74·0% (328 of 443) for vascular malformation, and 71·5% (2108 of 2948) for hippocampal sclerosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50·0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52·3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53·5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0–14% at 1 year and increased to 14–51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis. Interpretation: Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. Funding: None