SCN1A Horizons A Natural History Study of SCN1A-related Epilepsies in the United Kingdom

Our aim is to define the seizure, neurodevelopmental, and behavioural characteristics of SCN1A-related epilepsies/Dravet syndrome in children and adults longitudinally over a period of three years. In addition, this study will compare missense and truncating genotypes in terms of i) rates of change of countable convulsive seizures per month and ii) rate of change in neurodevelopmental outcomes over time. The investigators will therefore prospectively study the natural history of SCN1A-related epilepsies and Dravet syndrome in the UK. In order to explore established and novel treatments, including new medications, it is important to not only document seizure frequency but also behaviour, learning and motor function. Treatment interventions are key to prevent the neurodevelopmental comorbidities of Dravet syndrome; as such sensitive measures of disease progression and a clear prospective description of the natural history of the disease across the lifespan is required to know whether therapies are transformative.

Although the decline in neurodevelopmental profile and motor function in patients with SCN1A-related epilepsies/Dravet syndrome have been described, no large scale long-term, prospective studies of cognition and motor function have been conducted in SCN1A-related epilepsies/Dravet syndrome with established measures.

The SCN1A/Dravet syndrome natural history study will provide a platform to systematically collect longitudinal validated outcome measures for SCN1A variant-carrying patients across the UK. The study will prospectively assess changes in cognition, behaviour, and quality of life, as well as other co-morbidities.

A number of important questions relating to the natural history of SCN1A-related epilepsies/Dravet syndrome over the lifespan remain unanswered:

• It is not understood the precise neurodevelopmental profile and decline of individuals with SCN1A-related epilepsies over time and which factors might modify this?
• There are no reliable biomarkers that can inform disease severity or treatment planning
• What impact does the underlying genotype have on the neurodevelopmental outcome?
• Do clinical features such as the occurrence of repeated episodes of status epilepticus and/or contraindicated medication use worsen the neurodevelopmental outcome?
• What is the seizure burden across different ages and does treatment response change over the lifespan?
• There is a lack of understanding of the comorbidity profile that individuals with SCN1A-related epilepsies experience over the lifespan
• More information is required on the socio-economic impact SCN1A-related epilepsies have on affected individuals, families and society

Patients meeting the following inclusion criteria will be considered eligible for this study:

• Patient and/or legally authorised representative must be willing and able to give informed consent/assent for participation in the study.
• Patient and parent/caregiver are willing and able (in the Investigator's opinion) to comply with all study requirements (including ability and willingness to comply with virtual visits).
• Participant has a confirmed pathogenic (class 5) or likely pathogenic (class 4. SCN1A variant, as demonstrated by genetic testing.

Exclusion criteria

Patient has any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or may affect the patient's ability to participate in the study.