Abstracts

Rationale: In recent years, many novel genetic mutations with a role in the etiology of epilepsy have been described. At the same time, genetic variants with a potential role in epileptic syndromes but with unknown clinical significance are being identified. In this study, we describe clinical epilepsy phenotypes of patients with positive genetic findings, in order to highlight the non-concordance of some of these electro clinical phenotypes with what has been described in the literature, as well as report phenotypes associated with genetic variants with previously unknown significance.Methods: A retrospective review of medical records was performed for 17 consecutive patients with epilepsy in the setting of known genetic or chromosomal abnormalities who were seen by a single provider between the years of 2006 and 2015 at a specialized center for children with developmental disabilities.Results: Among the 17 patients (4 boys, 13 girls), 6 girls had chromosomal abnormalities, and 3 of them presented with phenotypes not currently described in the literature. The 11 remaining patients had point mutations in genes with a known link to epilepsy. In this group, 3 of the variants have been described, but our patients’ clinical features were not concordant with what has been reported. Eight patients had genetic variants with previously unknown significance, and of these, four presented with phenotypes resembling those of other (previously reported) point mutations within the same gene, and four are, to our knowledge, novel phenotypes in the setting of these genetic variants. A summary description of the patients’ clinical phenotypes is provided in Table1.Conclusions: Phenotypes that are novel or non-concordant with the literature were found in 10 of our 17 patients with epilepsy and positive genetic diagnosis. A causal phenotype-genotype relationship cannot be conclusively stated, especially in this population with known developmental co-morbidities. However, these results provide a more complete picture of the range of possible clinical phenotypes found in the setting of these specific genetic variants.