Neurofibromatosis and Epilepsy

Abstract

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disease. The NF1 gene is located on chromosome 17q11.2 and codes for a large tumor suppressor protein, called neurofibromin. The prevalence is around 1 in 3,000 individuals, and it is inherited dominantly with a 98% penetrance, but with high phenotypic variability. Neurologic manifestations are mainly tumors, such as optic gliomas, focal areas of high T2-weighted magnetic resonance imaging signals known as unidentified bright objects, mental retardation or learning disabilities, and epilepsy. Other neurologic problems, including attention deficits and headaches, have been described. The prevalence of seizures in patients with NF1 is around 3.8 to 6%. This is considerably higher than the 1 to 2% reported for the general population, or the 4% of children who have experienced a seizure. The majority of classifiable seizures are focal in origin with or without secondary generalization. Most abnormal electroencephalography recordings reveal focal abnormalities. Overall, more than half of the electroencephalography studies are abnormal. The most frequent structural lesions found in patients with NF1 and epilepsy are tumors and malformations of cortical development. Other types of epilepsies and epileptic syndromes have also been described to be associated with NF1, such as West syndrome, Lennox-Gastaut syndrome, myoclonic epilepsy, epilepsy with generalized tonic-clonic seizures, childhood absence epilepsy, and juvenile myoclonic epilepsy. In patients with focal epilepsy, neuroimaging should be performed to exclude neoplastic and other types of focal lesions. In patients with NF1 and seizures, optimal management of antiepileptic drugs and eventually surgery should be considered.