Clinical and molecular features of neurofibromatosis types 1 and 2: a review of the literature

Neurofibromatosis is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. There are three types of neurofibromatosis: type 1 (96 of cases), type 2 (3 % of cases), and schwannomatosis (less than 1 % of cases). The NF1 gene is located on chromosome 17q11.2, which encodes for a tumor suppressor protein, neurofibromin, that functions as a negative regulator of Ras / MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinases ) / mTOR (mammalian target of rapamycin) signaling pathways. The NF2 gene is identified on chromosome 22q12, which encodes for merlin, a tumor suppressor protein related to the proteins ezrin, radixin and moesin that modulates the activity of PI3K/AKT, Raf/MEK/ERK, and mTOR signaling pathways. In contrast, molecular insights on the different forms of schwannomatosis remain unclear. Inactivating mutations in the tumor suppressor genes MARCB1 and LZTR1 are considered responsible for a majority of cases. Recently, treatment strategies to target specific genetic or molecular events involved in their tumorigenesis are developed. This study discusses molecular pathways and related targeted therapies for neurofibromatosis type 1, type 2, and schwannomatosis and reviews recent clinical trials which involve neurofibromatosis patients. The aim of the study is to present the features and pathophysiology of neurofibromatosis, as well as modern diagnostic and therapeutic strategies related to this pathology.