Tommaso Lo Barco1, Anna Kaminska2, Roberta Solazzi3, Claude Cancés4, Giulia Barcia5, Nicole Chemaly6, Elena Fontana7, Isabelle Desguerre8, Laura Canafoglia9, Caroline Hachon Le Camus4, Emma Losito10, Laurent Villard11, Monika Eisermann2, Bernardo Dalla Bernardina12, Nathalie Villeneuve11, Rima Nabbout13. 1. Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, Imagine Institute, Paris Descartes University, Paris, France; Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Italy; PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Italy. Electronic address: tommaso.lobarco@univr.it. 2. Department of Clinical Neurophysiology, Necker-Enfants-Malades Hospital, AP-HP, Paris, France. 3. Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. 4. Department of Pediatric Neurology, Toulouse Children Hospital, Toulouse University Hospital, Toulouse, France. 5. Fédération de Génétique Médicale, Hôpital Necker-Enfants Malades, Paris, France. 6. Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, Imagine Institute, Paris Descartes University, Paris, France; Department of Paediatric Neurology, Necker-Enfants Malades Hospital, University of Paris, AP-HP, Paris, France. 7. Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Italy; Research Center for Pediatric Epilepsies Verona, Verona, Italy. 8. Department of Paediatric Neurology, Necker-Enfants Malades Hospital, University of Paris, AP-HP, Paris, France. 9. Neurophysiopathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. 10. Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, Imagine Institute, Paris Descartes University, Paris, France. 11. Pediatric Neurology Department, Timone Children Hospital, Reference Center for Rare Epilepsies, APHM, Marseille, France. 12. Research Center for Pediatric Epilepsies Verona, Verona, Italy. 13. Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, Imagine Institute, Paris Descartes University, Paris, France; Department of Paediatric Neurology, Necker-Enfants Malades Hospital, University of Paris, AP-HP, Paris, France. Electronic address: rima.nabbout@aphp.fr.
Abstract
OBJECTIVE: To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants. METHODS: Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings and archived video-EEGs of seizures and detailed characteristics of interictal and ictal EEG patterns for every patient. RESULTS: We recruited 15 previously unreported patients and analyzed 72 EEGs. Two distinct EEG patterns emerged, both triggered by eye closure. Pattern 1 (14/15 individuals) consisted of rhythmic posterior/diffuse delta waves appearing with eye-closure and persisting until eye opening (strongly suggestive of fixation-off sensitivity). Pattern 2 (9/15 individuals) consisted of diffuse polyspike-and-wave discharges triggered by eye closure (eye-closure sensitivity). Both patterns presented in 8/15. Including archived video-EEG clips of seizures from 9/15 patients, we analyzed 254 seizures. Of 224 seizures experienced while awake, 161 (72%) occurred at or following eye closure. In 119/161, pattern 1 preceded an atypical absence, myoclonic seizure or myoclonic absence; in 42/161, pattern 2 was associated with eyelid myoclonia, absences and myoclonic or atonic seizures. CONCLUSIONS: Fixation-off and eye closure were the main triggers for seizures in this SYNGAP1 cohort. SIGNIFICANCE: Combining these clinical and electroencephalographic features could help guide genetic diagnosis.
OBJECTIVE: To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants. METHODS:Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings and archived video-EEGs of seizures and detailed characteristics of interictal and ictal EEG patterns for every patient. RESULTS: We recruited 15 previously unreported patients and analyzed 72 EEGs. Two distinct EEG patterns emerged, both triggered by eye closure. Pattern 1 (14/15 individuals) consisted of rhythmic posterior/diffuse delta waves appearing with eye-closure and persisting until eye opening (strongly suggestive of fixation-off sensitivity). Pattern 2 (9/15 individuals) consisted of diffuse polyspike-and-wave discharges triggered by eye closure (eye-closure sensitivity). Both patterns presented in 8/15. Including archived video-EEG clips of seizures from 9/15 patients, we analyzed 254 seizures. Of 224 seizures experienced while awake, 161 (72%) occurred at or following eye closure. In 119/161, pattern 1 preceded an atypical absence, myoclonic seizure or myoclonic absence; in 42/161, pattern 2 was associated with eyelid myoclonia, absences and myoclonic or atonic seizures. CONCLUSIONS: Fixation-off and eye closure were the main triggers for seizures in this SYNGAP1 cohort. SIGNIFICANCE: Combining these clinical and electroencephalographic features could help guide genetic diagnosis.