Authors :
Elisa Hoffmann, MD – Schön Klinik Vogtareuth Germany
Gerhard Kluger, Prof – Schön Klinik Vogtareuth, Germany, PMU Salzburg, Austria
Pringsheim Milka, MD – Schön Klinik Vogtareuth, Germany, PMU Salzburg, Austria, TUM Klinikum Munich, German Heart centre, Germany
Maria Arelin, MD – Institute of Human Genetics Leipzig, Germany
Artem Borovikov, MD – Research Centre for Medical Genetics Moscow, Russia
Andrew Levy, MD – Technion Faculty of Medicine, Technion Israel Institute of Techology Haifa, Israel
Franziska Kusser, MD – LMU Munich, Department of Paediatric Neurology, Dr von Hauner Children’s Hospital, Munich, Germany
Tatjana Kovacevic-Preradovic, MD – GermanyEpilepsy Centre, Kleinwachau, Germany
Magdalena Krygier, MD – Department of Developmental Neurology, Medical University of Gdansk Debinki, Poland
Carla Marini, MD – Child Neurology and Psychiatry Unit, Paediatric Hospital G. Salesi, AOU delle Marche, Italy
Cyril Mignot, MD – AP-HP Sorbonne Université, Paris, France
Sonja Neuser, MD – Institute of Human Genetics, University of Leipzig, Leipzig, Germany
Henry Oppermann, MD – Institute of Human Genetics, University of Leipzig, Leipzig, Germany
Artem Sharkov, MD – Veltischev Research and Clinical Institute for Paediatrics and Paediatric Surgery, Pirogov Russian National Research Medical University, Moscow, Russia
Markus Wolff, MD – Swiss Epilepsy Centre, Zurich, Switzerland
Presenting Author: Kristina Fleckinger, MD – Schön Klinik Vogtareuth Germany
Rationale:
IQSEC2 is an X-chromosomal located gene playing an important role for an appropriate development of cognition and learning by supporting the formation and growth of dendritic spines, axonal elongation and branching in postsynaptic neurons. IQSEC2 mutations show a wide variability in phenotype, and are clinically associated with a mild to moderate intellectual disability, therapy resistant epilepsy/epileptic encephalopathy with multiple types of seizures, psychiatric features such as autism spectrum disorders and a regression in motor and linguistic skills. More severe courses were described in male patients.To date, epilepsy in this context has been poorly characterised in the literature, and the impact on the development of cognition and behaviour remains unclear. Methods:
Retrospective international multicentre analysis (Germany, Italy, Russia, Serbia, Poland, Switzerland) on IQSEC2 related phenotypes and their epilepsy characteristics in a case series of 26 pateints with IQSEC2. Data werde collected with a questionnaire filled by specialized physicians in the period from March 2023 to August 2025. Results:
Data were available from 26 patients (13 female, 13 male), with maternally inherited mutations in males, and in the majority de novo mutations in females. six of the patients had no seizures until data lock.The patients exhibited mild to moderate intellectual impairment with marked behavioural abnormalities, some with diagnosed autism spectrum disorders. According to parental reports, their development prior to the onset of epilepsy (mean 1.98 years, earlier in males) was generally unremarkable. Frequent seizure types included absences, tonic seizures, atonic drop attacks, and status epilepticus (once misinterpreted as FIRES). EEG recordings revealed regional slowing, status-like epileptiform potentials, modified sleep spindle complexes, and photosensitivity (n=2). Interestingly, we recognized a predominance in frontal areas. A positive effect on seizures under perampanel was observed in 80% of the treated patients. An other ASM with an effective potential in seizure reduction is valproic acid (50% oft he patients described less seizures). In some cases, behavioural modulation as well as improvements in motor skills and language were also noted. Conclusions:
Our case series complements previous publications and confirms some of their findings. There are some differences in terms of development and epilepsy. We also investigated therapeutic options and and whether perampanel represents a promising antiseizure medication. The number of cases remains low, so further data collection is necessary, ideally in form of an international registry.
Funding: None.