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

Abstract

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 .