Neurofibromatosis 2 (NF2) is an autosomal dominant disease that is characterized by tumors on the vestibular branch of the VIII cranial nerve, but other types of nervous system tumors usually occur as well (intracranial meningiomas, spinal tumors, and peripheral nerve tumors).

Pathogenesis

 Neurofibromatosis type 2 is an autosomal dominant disorder in which patients develop a range of tumors, most commonly bilateral acoustic schwannomas and multiple meningiomas. Gliomas, typically ependymomas of the spinal cord, also occur in these patients.

 Many individuals with neurofibromatosis type 2 also have non-neoplastic lesions, which include nodular ingrowth of Schwann cells into the spinal cord (schwannosis), meningioangiomatosis (a proliferation of meningeal cells and blood vessels that grows into the brain), and glial hamartia (microscopic nodular collections of glial cells at abnormal locations, often in the superficial and deep layers of the cerebral cortex).

 Café au lait spots are present, but Lisch nodules in the iris are not found. This disorder is much less common than neurofibromatosis type 1, having a frequency of 1 in 40,000 to 50,000.

 The NF2 gene, located on chromosome 22q12, is also a tumor-suppressor gene. The product of the NF2 gene, called merlin, shows structural similarity to the ezrin, radixin, moesin (ERM) family of proteins.

 These cytoskeletal proteins interact with actin on the one hand and membrane proteins on the cell surface on the other hand. It is thought that merlin regulates contact inhibition and proliferation of Schwann cells.

Etiology

 germline mutations in the NF2 gene