1. Natural History and Developmental Trajectories of Individuals With Disease-Causing Variants in STXBP1.
- Author
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Thalwitzer, K.M., Driedger, J.H., Xian, J., Saffari, A., Zacher, P., Bölsterli, B.K., Ruggiero, S.M., Sullivan, K.R., Datta, A.N., Kellinghaus, C., Althaus, J., Wiemer-Kruel, A., Baalen, A. van, Pampel, A., Alber, M., Braakman, H.M.H., Debus, O.M., Denecke, J., Hobbiebrunken, E., Breitweg, I., Diehl, D., Eitel, H., Gburek-Augustat, J., Preisel, M., Schlump, J.U., Laufs, M., Mammadova, D., Wurst, C., Prager, C., Löhr-Nilles, C., Martin, P., Garbade, S.F., Platzer, K., Benkel-Herrenbrueck, I., Egler, K., Fazeli, W., Lemke, J.R., Runkel, E., Klein, B., Linden, T., Schröter, J., Steffeck, H., Thies, B., Deimling, F. von, Illsinger, S., Borggraefe, I., Classen, G., Wieczorek, D., Ramantani, G., Koelker, S., Hoffmann, G.F., Ries, M., Helbig, I., Syrbe, S., Thalwitzer, K.M., Driedger, J.H., Xian, J., Saffari, A., Zacher, P., Bölsterli, B.K., Ruggiero, S.M., Sullivan, K.R., Datta, A.N., Kellinghaus, C., Althaus, J., Wiemer-Kruel, A., Baalen, A. van, Pampel, A., Alber, M., Braakman, H.M.H., Debus, O.M., Denecke, J., Hobbiebrunken, E., Breitweg, I., Diehl, D., Eitel, H., Gburek-Augustat, J., Preisel, M., Schlump, J.U., Laufs, M., Mammadova, D., Wurst, C., Prager, C., Löhr-Nilles, C., Martin, P., Garbade, S.F., Platzer, K., Benkel-Herrenbrueck, I., Egler, K., Fazeli, W., Lemke, J.R., Runkel, E., Klein, B., Linden, T., Schröter, J., Steffeck, H., Thies, B., Deimling, F. von, Illsinger, S., Borggraefe, I., Classen, G., Wieczorek, D., Ramantani, G., Koelker, S., Hoffmann, G.F., Ries, M., Helbig, I., and Syrbe, S.
- Abstract
Contains fulltext : 296182.pdf (Publisher’s version ) (Open Access), 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 (GMFCS) scores 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 (interquartile range 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 2 individuals presenting with close to age-appropriate motor development. Twenty-nine of 61 individuals (48%) 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 and developmental trajectories in individuals with and without a history of epilepsy. Individuals with ep
- Published
- 2023