Type I neurofibromatosis: a geno-oculo-dermatologic update

This review will focus on the recent clinical insights into type I neurofibromatosis (NF1), the most common geno-oculo-dermatosis. Advances in the treatment will also be reviewed.

NF1 shares phenotypic features with disorders such as Legius syndrome, type 2 neurofibromatosis (NF2), and multiple lentigenes syndrome. Molecular diagnostic testing aids in diagnosing young children with still-evolving clinical signs and distinguishes NF1 from these other conditions. The management of optic pathway gliomas (OPGs) remains controversial. OPGs may enlarge in later childhood and beyond such that longer ocular surveillance may be appropriate. Retinal nerve fiber layer thickness inversely correlates with OPGs and decreased vision. There is suspected correlation of cerebral arteriopathy risk with the presence of OPGs. Ciliary body cysts and retinal pigmentary abnormalities may also be markers of NF1. Studies continue to confirm the utility of Lisch nodules as a diagnostic marker in older children and adults and seem to correlate with underlying iris pigmentation and sunlight exposure. Promising therapies are being developed based on NF1's central role in the RAS/RHEB/mTOR signal transduction pathway.

Continuing advances are enhancing the diagnosis and management of NF1. Current clinical trials use agents that target the RAS/mTOR signal transduction pathway and alter microenvironmental factors that contribute to tumor progression.