Influence of Seizures on Developmental Outcome in Individuals with stxbp1-related Disorders
Abstract number :
2.339
Submission category :
12. Genetics / 12A. Human Studies
Year :
2022
Submission ID :
2205013
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:27 AM
Authors :
Kim Marie Thalwitzer, – University Heidelberg; Jan Henje Döring, MD – University Hospital Heidelberg; Julie Xian, BA – Children's Hospital of Philadelphia; Afshin Saffari, MD – University Hospital Heidelberg; Sarah Ruggiero, MS, CGC – Children's Hospital of Philadelphia; Katie Rose Sullivan, MS – Children's Hospital of Philadelphia; Pia Zacher, MD – Epilepsy Center Kleinwachau; Bigna Bölsterli, MD – University Hospital Zürich; Alexandre Datta, MD, PD – University Hospital Basel; Christoph Kellinghaus, MD – Hospital Osnabrück; Jürgen Althaus, MD – Hospital Christopherus Kliniken Coesfeld; Adelheid Wiemer-Kruel, MD – Epilepsy Center Kork; Andreas van Baalen, MD, PD – University Hospital Kiel; Armin Pampel, MD – Johannes Wesling Hospital Minden; Michael Alber, MD – University Hospital Tübingen; Hilde Braakman, MD, PHD – Radboud University Medical Center; Otfried Debus, MD, PD – Clemenshospital Münster; Jonas Denecke, MD, PD – University Hospital Hamburg; Elke Hobbiebrunken, MD – University Hospital Göttingen; Ina Breitweg, MD – Kinderärzte Ammersee; Danielle Diehl, MD – University Hospital Giessen; Hans Christian Eitel, MD – Hospital Esslingen; Janina Gburek-Augustat, MD – University Hospital Leipzig; Martin Preisel, MD – University Hospital Salzburg; Jan-Ulrich Schlump, MD – University Hospital Witten/Herdecke; Mirjam Laufs, MD – University Hospital Kiel; Dilbar Mammadova, MD – University Hospital Erlangen; Carsten Wurst, MD – Hospital Suhl; Christine Prager, MD – University Hospital Berlin; Christa Löhr-Nilles, MD – Hospital Mutterhaus der Borromäerinnen Trier; Peter Martin, MD, Prof – Epilepsy Center Kork; Sven Garbade, Dr.phil., Dipl.-Psych. – University Hospital Heidelberg; Konrad Platzer, MD – University Hospital Leipzig; Ira Benkel-Herrenbrueck, MD – Sana Hospital Gerresheim; Kerstin Egler, MD – Hospital Sankt Elisabeth Neuburg; Walid Fazeli, MD – University Hospital Köln; Eva Runkel, MD – Hospital Aschaffenburg-Alzenau; Barbara Klein, MD – Hospital Frankfurt Höchst; Tobias Linden, MD – University Hospital Oldenburg; Julian Schröter, MD – University Hospital Heidelberg; Heike Steffeck, MD – Hospital Wolfsburg; Bastian Thies, MD – Kinderneurologie Thies; Florian von Deimling, MD – Hospital Coburg; Stefan Kölker, Prof, MD – University Hospital Heidelberg; Georg Friedrich Hoffmann, MD, Prof. Dr. med., Prof. h.c. mult. (RCH) – University Hospital Heidelberg; Ingo Helbig, MD – Children's Hospital of Philadlephia; Steffen Syrbe, MD, Prof – University Hospital Heidelberg
Rationale: Individuals with disease-causing variants in STXBP1 present with developmental delay, epilepsy, and abnormalities of behavior. To date, limited data on the impact of epilepsy on patient outcomes are available and additional endpoints beside seizure remission are missing. We present the phenotypic spectrum and outcomes of 54 individuals with STXBP1-related disorders, including 15 individuals without seizures.
Methods: Standardized questionnaires and examinations assessing clinical and diagnostic outcomes, genetic findings and developmental features were completed by caregivers and clinicians of individuals with pathogenic variants in STXBP1. The clinical and developmental spectrum was examined within clinically defined subgroups.
Results: Clinical data were included for 54 individuals with STXBP1-related disorders, including 41 with completed caregiver questionnaires and 43 with examinations performed by a clinician. The median age at inclusion was 5.0 years (IQR 3.3-7.9) with a maximum of 24 years. All individuals but one had mild to severe neurodevelopmental delays . Four individuals had age-appropriate motor skills (GMFCS 0 or 1). Most individuals (77.5%, n = 31/40) used gestures and sounds for expressive communication. 74.1% of individuals had seizures (n = 40/54). Focal-onset seizures were seen most frequently (57.7%, n = 30/52). A total of 17 children had generalized seizures (32.7%, n = 52) or infantile spasms (32.7%, n = 52). 72.2% (n = 26/36) had a maximum frequency of more than five seizures per day. 72.7% (n = 24/34) of individuals received a rescue medication at least once during the course of their epilepsy. Children with seizures had higher GMFCS scores (median 4 vs. 2, p = 0.01). Compared with focal-onset seizures, motor skills were decreased following the presence of epileptic spasms (GMFCS median 5 vs. 4, p = 0.02). All children with infantile spasms had a GMFCS score of 4 or 5 and had not achieved independent ambulation by time of study inclusion. Individuals with neonatal seizures had higher GMFCS scores than early-onset seizures and late-onset seizures (median 5 vs. 4 vs. 0.5, p = 0.03).
Conclusions: The overall spectrum of developmental outcomes in individuals with STXBP1-related disorders is diverse. Seizures, particularly infantile spasms and neonatal seizures, have a negative impact on motor development. Important developmental measures vary across subgroups and may represent valuable endpoints in potential therapeutic trials.
Funding: Dietmar Hopp Stiftung, The Hartwell Foundation, NINDS, Children’s Hospital of Philadelphia
Genetics