This study evaluates the long-term developmental and clinical outcomes of SCN1A-positive Dravet syndrome (DS) over a 10-year period, identifying predictors of developmental outcomes and disease burden. The study followed 68 of 113 caregivers of SCN1A-positive DS patients, who completed questionnaires on clinical features, disease burden, and quality of life. Developmental outcomes worsened over time, with a significant increase in comorbidities such as autistic features, behavioral problems, and motor/mobility issues. Predictors of worse long-term developmental outcomes included poorer baseline language ability, more severe baseline epilepsy, and a worse SCN1A genetic score. The study also found that epilepsy severity at baseline had a negative impact on long-term developmental outcomes, highlighting the importance of early and focused therapies. Additionally, the study identified that sudden unexpected death in epilepsy (SUDEP) was not discussed with medical professionals by 35% of participants, and over 90% of caregivers reported a negative impact on their health and career opportunities. The study emphasizes the significant caregiver burden of illness and the need for further research on the impact of newer anti-seizure medications. The SCN1A genetic score was identified as a potential biomarker for disease outcome. The study also found that sleep disturbances were common in DS patients, with DIMS being the most frequent sleep disorder. The findings highlight the importance of addressing comorbidities and the underlying SCN1A channelopathy to improve quality of life for affected individuals and their caregivers.This study evaluates the long-term developmental and clinical outcomes of SCN1A-positive Dravet syndrome (DS) over a 10-year period, identifying predictors of developmental outcomes and disease burden. The study followed 68 of 113 caregivers of SCN1A-positive DS patients, who completed questionnaires on clinical features, disease burden, and quality of life. Developmental outcomes worsened over time, with a significant increase in comorbidities such as autistic features, behavioral problems, and motor/mobility issues. Predictors of worse long-term developmental outcomes included poorer baseline language ability, more severe baseline epilepsy, and a worse SCN1A genetic score. The study also found that epilepsy severity at baseline had a negative impact on long-term developmental outcomes, highlighting the importance of early and focused therapies. Additionally, the study identified that sudden unexpected death in epilepsy (SUDEP) was not discussed with medical professionals by 35% of participants, and over 90% of caregivers reported a negative impact on their health and career opportunities. The study emphasizes the significant caregiver burden of illness and the need for further research on the impact of newer anti-seizure medications. The SCN1A genetic score was identified as a potential biomarker for disease outcome. The study also found that sleep disturbances were common in DS patients, with DIMS being the most frequent sleep disorder. The findings highlight the importance of addressing comorbidities and the underlying SCN1A channelopathy to improve quality of life for affected individuals and their caregivers.