ABSTRACT
Purpose: SCN8A developmental epileptic encephalopathy (SCN8A-DEE) is a rare and severe
genetic epilepsy syndrome characterized by early-onset developmental delay, cognitive
impairment, and intractable seizures. Variants in the SCN8A gene are associated with a broad
phenotypic spectrum and variable disease severity. A caregiver survey, solicited by the advocacy
group The Cute Syndrome Foundation (TCSF), was conducted to gather information on the
demographics/disease presentation, seizure history, and treatment of patients with SCN8Arelated epilepsies.
Methods: A 36-question online survey was developed to obtain de-identified data from
caregivers of children with SCN8A-related epilepsy. The survey included questions on genetic
diagnosis, disease manifestations/comorbidities, seizure severity/type, current/prior use of
antiseizure medicines (ASMs), and best/worst treatments per caregiver perception.
Results: In total, 116 survey responses (87 USA, 12 Canada, 12 UK, 5 Australia) were included
in the quantitative analysis. Generalized tonic/clonic was the most common seizure type at onset
and time of survey; absence and partial/focal seizures were also common. Most patients (77%)
were currently taking ≥2 ASMs; 50% had previously tried and stopped ≥4 ASMs. Sodium
channel blockers (oxcarbazepine, phenytoin, lamotrigine) provided the best subjective seizure
control and quality of life.
Conclusion: The SCN8A-DEE patient population is heterogeneous and difficult to treat, with
high seizure burden and multiple comorbidities. The high proportion of patients who previously
tried and stopped ASMs indicates a large unmet treatment need. Further collaboration between
families, caregivers, patient advocates, clinicians, researchers, and industry can increase
awareness and understanding of SCN8A-related epilepsies, improve clinical trial design, and
potentially improve patient outcomes.