Abstracts

Rationale: SCN8A-related epilepsies range from a severe developmental and epileptic encephalopathy (DEE) to benign familial infantile epilepsy (BFIS), including cases of intermediate severity. Early mortality due to Sudden Unexpected Death in Epilepsy (SUDEP) has been estimated to occur in about 10% of reported SCN8A-epilepsy patients. We aimed to investigate the risk factors for early death in SCN8A. Methods: We reviewed the histories of 185 published and unpublished patients with SCN8A-epilepsy (128 DEE, 57 milder/benign cases), obtaining further details about the cause of death. Results: In this cohort, ten precocious deaths occurred, including all the eight previously published patients. Age at death ranged from 16 months to 17 years; the majority (7/10) died in early childhood.The overall mortality rate was 5.4% (10/185). One patient died for cancer, excluding this patient, the mortality rate was 4.8% (9/185). SUDEP occurred only in 3/185 patients (1,6%). The SUDEP rate was 5.1/1000-person-years, which is lower than the SUDEP rate for SCN1A- Dravet Syndrome (9.32/1000-person-years). Moreover, as we calculated the SUDEP rate on 101 SCN8A-patients, with available age at follow-up, this figure is likely to be an overestimate.We calculated the mortality rate for the different SCN8A-phenotypes:Among patients with severe DEE (128 patients), six patients (4.6%) died in early childhood (16 months-5 years), coincident with a relentless worsening of their epilepsy and neurological condition, followed in five by respiratory infection and respiratory failure leading to death.In the group of patients with milder DEE (52 patients), three died (5.4%) from definite /probable SUDEP. The two cases with definite SUDEP died at older age (15 and 17 years respectively).Among families with a benign phenotype (BFIS) (5 patients), only one patient died of cancer, at the age of 13 years. This dead was therefore likely unrelated to her SCN8A-BFIS.  Conclusions: Our data indicate that the early mortality rate in SCN8A patients (5.4%) is lower than previously estimated. Only SCN8A-DEE is associated with an increased risk of early death, which in a minority of cases is SUDEP (1,6%). Death most often occurs for other causes than SUDEP, in patients with severe SC8A-DEE during early childhood, in the setting of relentless worsening of their epilepsy and neurological condition, leading to respiratory failure that ultimately is fatal. Funding: No funding received.