Abstracts

Rationale: DEPDC5 gene, mapped to 22q12.2-q12.3, has been associated with a variety of familial epilepsies. Notably, DEPDC5 has never been linked to increased risk of sudden unexpected death in epilepsy (SUDEP). Methods: Case report. Results: We studied a three-generation, non-consanguineous, French-Canadian family with nine clinically affected individuals. Interestingly, all but one are males. The index case is a 39-year-old man who started having seizures at the age of 13 years. His seizures were characterized by a "dream-like" aura followed by loss of consciousness and tonic-clonic movements. Initially, seizures were mainly diurnal. In his mid-20s, the episodes became exclusively nocturnal. EEGs showed interictal epileptiform discharges over the right anterior-temporal region. Brain MRI was unremarkable. Two of the index case's paternal uncles suffered definite autopsy-confirmed SUDEP, at the ages of 58 and 50 years, respectively. Seizure-history in this family can be summarized by an onset before reaching adulthood, followed by subsequent progressive decrease in seizure frequency. Seizures were predominantly nocturnal secondarily generalized tonic-clonic. All the subjects were cognitively intact. There was no history of any cardiac symptomatology, cardiovascular risk factor, or definite cardiac condition. Genetic analysis of the index case revealed a pathogenic heterozygous variant in the DEDPC5 gene (p.Gln216, c.646C>T; ENST00000536766). The index case was also tested for genes associated with SUDEP, none of which showed mutations. All living affected relatives, as well as four healthy family members, were clinically evaluated and had DEPDC5 Sanger sequenced. All affected subjects and one healthy individual were found to carry the same DEPDC5 pathogenic variant as the index case. Conclusions: Several genes have been linked with SUDEP. These are associated with cardiac arrhythmias and/or severe epilepsies, both of which do not apply to this family's phenotype. The finding in this family suggests that DEPDC5 mutations may be a risk factor for SUDEP. Funding: This study was funded by Genome Canada and the Ontario Brain Institute (OBI).