Neurofibromatosis 2 (NF2) is an autosomal dominant disorder that affects approximately 1 in 40,000 individuals. It is characterized by the development of bilateral vestibular schwannomas and other histologically benign intracranial, spinal, and peripheral nerve tumors. The only nontumorous manifestations of NF2 are cataract and retinal hamartoma. NF2 is fully penetrant by age 60 years, and half of all cases represent new mutations.
Syndromes related to NF2 include sporadic unilateral vestibular schwannoma, mosaic inactivation of the NF2 gene, schwannomatosis, and multiple meningiomas. NF2 is genetically and clinically distinct from von Recklinghausen disease or neurofibromatosis 1.
Positional cloning identified the gene for NF2 on chromosome 22q. It spans 110 kb with 16 constitutive exons and 1 alternatively spliced exon. The NF2 protein product is a member of the protein 4.1 family of cytoskeleton-associated proteins. These proteins play a critical role in maintaining membrane stability and cell shape by connecting integral membrane proteins to the spectrin–actin lattice of the cytoskeleton.
A large number of germ-line mutations have been detected in NF2 patients, with the majority predicted to result in gross protein truncation. Detection of somatic alterations in NF2-related tumors has supported the hypothesis that the NF2 gene acts as a true tumor suppressor in both schwannomas and meningiomas. NF2 also appears to play a role in the development of mesothelioma, although this tumor is not seen in patients with NF2.
Diagnosis of NF2 is currently dependent on clinical criteria, although genetic diagnosis may soon be feasible. Treatment of NF2-related tumors remains largely surgical. Advances in hearing augmentation, such as auditory brainstem implants, may improve the quality of life for many patients.