biostudies-literatureUnknownXian JNICHD NIH HHSNCATS NIH HHSNINDS NIH HHS<i>STXBP1</i>-related disorders are among the most common genetic epilepsies and neurodevelopmental disorders. However, the longitudinal epilepsy course and developmental endpoints have not yet been described in detail, which is a critical prerequisite for clinical trial readiness. Here, we assessed 1,281 cumulative patient-years of seizure and developmental histories in 162 individuals with <i>STXBP1</i>-related disorders and established a natural history framework. <i>STXBP1</i>-related disorders are characterized by a dynamic pattern of seizures in the first year of life and high variability in neurodevelopmental trajectories in early childhood. Epilepsy onset differed across seizure types, with 90% cumulative onset for infantile spasms by 6 months and focal-onset seizures by 27 months medRxiv : the preprint server for health sciences2023.05.10.23289776https://www.ebi.ac.uk/biostudies/studies/S-EPMC10197795biostudies-literatureDelineating clinical and developmental outcomes in <i>STXBP1</i>-related disorders.PMC10197795R01 NS131512K02 NS112600R01 NS127830U54 HD086984UL1 TR001878McKee JProsser BCunningham KThalwitzer KMKaufman MCRigby CSGoss JFitch EPierce SRRuggiero SMSullivan KRHelbig IBoland MSyrbe SXian JToib JFitter NBrimble EdeCampo DfalseDelineating clinical and developmental outcomes in <i>STXBP1</i>-related disorders.<i>STXBP1</i>-related disorders are among the most common genetic epilepsies and neurodevelopmental disorders. However, the longitudinal epilepsy course and developmental endpoints have not yet been described in detail, which is a critical prerequisite for clinical trial readiness. Here, we assessed 1,281 cumulative patient-years of seizure and developmental histories in 162 individuals with <i>STXBP1</i>-related disorders and established a natural history framework. <i>STXBP1</i>-related disorders are characterized by a dynamic pattern of seizures in the first year of life and high variability in neurodevelopmental trajectories in early childhood. Epilepsy onset differed across seizure types, with 90% cumulative onset for infantile spasms by 6 months and focal-onset seizures by 27 months 2023-01-01T00:00:00Z2023 May2025-04-22T13:56:30.937Z2025-04-06T00:51:57.143ZS-EPMC101977953721500610.1101/2023.05.10.23289776