Abstracts

Rationale: The SCN8A clinical spectrum embraces a variety of phenotypes with different prognoses, ranging from benign familial infantile epilepsy (BFIE) to severe epileptic encephalopathies (DEE), including patients without epilepsy. We conducted a retrospective natural history study of children and adults with SCN8A related diseases using investigator-observed and parent-reported outcome measures to obtain data that will be useful for targeted counseling and future clinical trial.

Methods: From our database of 512 patients with pathogenic SCN8A mutations enrolled through a collaborative network worldwide, we selected those with available clinical information at different time-points. Primary outcome measures were (1) medical history, including seizure types/frequency, cognitive/motor development, various medical interventions and comorbidities; (2) developmental history, evaluating all milestones domains; (3) EEG features, (4) genetic information (mutation / functional effect).

Results: We selected 291 patients with (1) DEE (n=198) presenting with early onset epilepsy, cognitive and motor regression starting before the second years of life. Seizures are drug-resistant, better responding to high doses of sodium channel blockers (SCBs) and to ketogenic diet. Premature death is reported in about 5% of cases. (2) Sporadic and familial patients with non progressive mild-to-moderate intellectual disability and neurological signs and with treatable focal epilepsy (n=43), or generalized epilepsy (n=28) better responding to valproate/ lamotrigine; (3) BFIE (n=17) with self-limiting epilepsy, responding to low doses of SCBs, normal cognition, and no other neurological deficits; (4) Patients with isolated cognitive and/or behavioral disturbances, or movement disorders (=5). This seems to be non-progressive disorders.

Conclusions: We identified different patterns of evolutions and different prognostic factors in individuals with different SCN8A phenotypes. This is the first study describing the long-term natural history of SCN8A related diseases, obtaining specific outcome measures for future prospective observational studies and for clinical trials, ultimately improving the care of individuals with SCN8A diseases.

Funding: Please list any funding that was received in support of this abstract.: This work has been partially funded by SCN8A Italy and by The CUTE syndrome foundation.