NF2-Related Schwannomatosis (Formerly Neurofibromatosis Type 2)

NF2-related schwannomatosis (formerly neurofibromatosis type 2) (NF2) is a rare genetic disorder characterized by the development of tumors of the nervous system, particularly bilateral vestibular schwannomas.

The NF2 gene encodes merlin (also known as schwannomin), a tumor suppressor protein associated with the plasma membrane.  Patients with NF2 have one mutated NF2 allele and one healthy allele; when they develop a second mutation in the healthy allele, loss of function of the NF2 gene occurs (eg, a second-hit phenomenon).  Loss of function of the NF2 gene leads to dysregulation of cell-signaling pathways involved in cell growth, differentiation, and adhesion, resulting in the development of tumors.  Because merlin is expressed primarily in neural cells, loss of function results in multiple nervous system tumors.