Epilepsy in NF1: Epidemiologic, Genetic, and Clinical Features. A Monocentric Retrospective Study in a Cohort of 784 Patients

SIMPLE SUMMARY: Neurofibromatosis type 1 is a relatively frequent neurocutaneous and tumor predisposition syndrome, which has been associated with a variety of neurological manifestations, including an increased incidence of seizures. Epilepsy in NF1 has been investigated over time by a number of studies, but most of these works were performed on small samples and often suffered from selection biases. Our study aimed to provide additional epidemiologic, clinical, and molecular data to the literature by retrospectively analyzing a large cohort of consecutive unselected patients affected with NF1. Such data may provide a better insight into the matter to other authors and clinicians alike. ABSTRACT: An increased lifetime risk of epilepsy has been reported in neurofibromatosis type 1 (NF1) patients, ranging between 4% and 14%. To further analyze the correlation between NF1 and epilepsy, we retrospectively reviewed the epidemiologic, clinical, radiological, and molecular data of 784 unselected patients diagnosed with NF1 and referred to the neurofibromatosis outpatient clinics at the University Hospital of Padua. A crude prevalence of epilepsy of 4.7% was observed. In about 70% of cases, seizures arose in the context of neuroradiological findings, with the main predisposing factors being cerebral vasculopathies and hydrocephalus. In the absence of structural abnormalities, the prevalence of epilepsy was found to be 1.27%, which is approximately equal to the total prevalence in the general population. NF1 patients with seizures exhibit a higher incidence of intellectual disability and/or developmental delay, as well as of isolated learning disabilities. The comparison of causative NF1 mutations between the two groups did not reveal a specific genotype–phenotype correlation. Our data refine the current knowledge on epileptological manifestations in NF1 patients, arguing against the hypothesis that specific mechanisms, inherent to neurofibromin cellular function, might determine an increased risk of epilepsy in this condition.