| Title: |
Natural History and Developmental Trajectories of Individuals With Disease-Causing Variants in STXBP1 |
| Authors: |
Thalwitzer, Kim M; Driedger, Jan H; Xian, Julie; Saffari, Afshin; Zacher, Pia; Bölsterli, Bigna K; McKeown Ruggiero, Sarah; Sullivan, Katie Rose; Datta, Alexandre N; Kellinghaus, Christoph; Althaus, Jurgen; Wiemer-Kruel, Adelheid; van Baalen, Andreas; Pampel, Armin; Alber, Michael; Braakman, Hilde M H; Debus, Otfried M; Denecke, Jonas; Hobbiebrunken, Elke; Breitweg, Ina; Diehl, Danielle; Eitel, Hans; Gburek-Augustat, Janina; Preisel, Martin; Schlump, Jan-Ulrich; Laufs, Mirjam; Mammadova, Dilbar; Wurst, Carsten; Prager, Christine; Löhr-Nilles, Christa; Martin, Peter; Garbade, Sven F; Platzer, Konrad; Benkel-Herrenbrueck, Ira; Egler, Kerstin; Fazeli, Walid; Lemke, Johannes R; Runkel, Eva; Klein, Barbara; Linden, Tobias; Schröter, Julian; Steffeck, Heike; Thies, Bastian; von Deimling, Florian; Illsinger, Sabine; Borggraefe, Ingo; Classen, Georg; Wieczorek, Dagmar; Ramantani, Georgia; Koelker, Stefan; Hoffmann, Georg F; Ries, Markus; Helbig, Ingo; Syrbe, Steffen |
| Publisher Information: |
American Academy of Neurology |
| Publication Year: |
2023 |
| Collection: |
PUB - Publications at Bielefeld University |
| Description: |
Thalwitzer KM, Driedger JH, Xian J, et al. Natural History and Developmental Trajectories of Individuals With Disease-Causing Variants in STXBP1. Neurology . 2023. ; BACKGROUND AND OBJECTIVES: Pathogenic variants in STXBP1 are among the major genetic causes of neurodevelopmental disorders. Despite the increasing number of individuals diagnosed without a history of epilepsy, little is known about the natural history and developmental trajectories in this subgroup and endpoints for future therapeutic studies are limited to seizure control.; METHODS: We performed a cross-sectional retrospective study using standardized questionnaires for clinicians and caregivers of individuals with STXBP1-related disorders capturing medical histories, genetic findings, and developmental outcomes. Motor and language function were assessed using Gross Motor Function Classification System scores (GMFCS) and a speech impairment score and were compared within and across clinically defined subgroups.; RESULTS: We collected data of 71 individuals with STXBP1-related disorders, including 44 previously unreported individuals. Median age at inclusion was 5.3 years (IQR = 3.5-9.3) with the oldest individual aged 43.8 years. Epilepsy was absent in 18/71 (25%) of individuals. The range of developmental outcomes was broad, including two individuals presenting with close to age-appropriate motor development. 29/61 (48%) individuals were able to walk unassisted and 24/69 (35%) were able to speak single words. Individuals without epilepsy presented with a similar onset and spectrum of phenotypic features but had lower GMFCS scores (median 3 vs. 4, p < 0.01) than individuals with epilepsy. Individuals with epileptic spasms were less likely to walk unassisted than individuals with other seizure types (6% vs. 58%, p < 0.01). Individuals with early epilepsy onset had higher speech impairment scores (p = 0.02) than individuals with later epilepsy onset.; DISCUSSION: We expand the spectrum of STXBP1-related disorders and provide clinical features ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1526-632X |
| Relation: |
info:eu-repo/semantics/altIdentifier/issn/1526-632X; info:eu-repo/semantics/altIdentifier/wos/001062101800008; info:eu-repo/semantics/altIdentifier/pmid/37407264 |
| Availability: |
https://pub.uni-bielefeld.de/record/2980741 |
| Rights: |
info:eu-repo/semantics/closedAccess |
| Accession Number: |
edsbas.6616D008 |
| Database: |
BASE |