Neurofibromatosis Type 1

Neurofibromatosis type 1 is one of the most common neurocutaneous disorders, affecting about 1 in 3000 individuals. It is inherited in an autosomal dominant fashion with near complete penetrance; however, it has variable expression. In half of NF1 cases, patients inherit the mutated NF1 gene from an affected parent. The other cases occur as a result of a mutation in the gene.

The NF1 gene is a tumor suppressor gene localized to chromosome 17 and mostly affects growth of Schwann cell and glial cell derived tissues both in the central and peripheral nervous system. Loss of function or expression due to a mutation leads to increase in cell proliferation resulting in development of glial tumors. Neurofibromas are the most common tumor in NF1 that often present in puberty and increase in number and size with age. Most are benign and rarely undergo malignant transformation.

The underlying cause of seizures in patients with NF1 is not always clear. NF1 cortical lesions have not been clearly found to be associated as an epileptic focus. In addition, the bright objects have not been found to be associated with focal EEG findings in patients with NF1. However, it has been suggested that a higher number of NBOs is associated with a higher risk for seizures. However, this does not eliminate that the cause of epilepsy might be genetic and probably related to NF1. More commonly, intracranial tumors seen in NF1 patients have been found to directly correlate with epilepsy.

Common clinical findings on exam include café au lait spots, neurofibromas, Lisch nodules, and optic gliomas. MRI brain imaging may show T2 signal change in the subcortical region in addition to tumors, often call neurofibroma bright objects (NBOs).

Other presenting symptoms may include cognitive dysfunction, pain in specific nerve distribution (usually due to presence of neurofibroma), seizures, changes in vision that may be related to optic gliomas, seizures from intracranial tumors, stenosis of major intracranial arteries leading to Moyamoya phenomenon, headaches, and progressive neurologic deficits.

Epilepsy is seen in about 4 to 7% of patients with NF1—double the risk factor compared to the general population. The onset of epilepsy can occur at any age and effects both genders equally.