Abstracts

Rationale: Patients with neurofibromatosis type 1 (NF1) have a fourfold increased risk of epilepsy compared to the normal population. The underlying mechanism linking NF1 to epilepsy is unknown. The aim of this study was to describe the course of epilepsy in NF1 patients and to identify potential genetic modifiers in patients with NF1 and epilepsy. Methods: We reviewed phenotypes of 51 patients diagnosed with NF1 and described epilepsy including neuroimaging and serial routine EEG recordings. Trio exome sequencing and analysis for pathogenic variants associated with the epilepsy phenotype was performed in patients diagnosed with Infantile Spasms (n = 3). Results: The prevalence of epilepsy in this NF1 cohort was 13.7 % (7 out of 51 patients). We identified three patients with Infantile Spasms (5.8%). Two patients had genetic generalized epilepsy and two patients had focal seizures with secondary generalization. 17 patients had macrocephaly, but structural MRI abnormalities explaining the course of epilepsy were absent. The prognosis of epilepsy and NF1 was good and 5 of the 7 patients became seizure free. Specifically, all three patients with Infantile Spasms promptly responded to steroid or vigabatrin therapy. Relapse of seizures were only seen in a single patient with NF1-related Infantile Spasms who had dyscognitive and secondary generalized seizures at the age of 3 ½ years. We identified possibly disease-related variants in various candidate genes for epilepsy in 2 of the 3 patients with Infantile Spasms. Conclusions: The overall epilepsy course in patients with NF1 is mild. The phenotypic spectrum included easily treatable Infantile Spasms with a good outcome, GGE, and non-lesional focal epilepsies. Genetic modifiers including de novo mutations in epilepsy-related candidate genes may explain the propensity of some patients with NF1 to present with seizures. Funding: Christian-Albrechts-University of Kiel, Schleswig-Holstein, Germany