Neurofibromatosis Type 2

Abstract

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder (incidence 1:33 000-40 000) characterized by formation of central nervous system tumors, due to mutation in the NF2 gene on chromosome 22q12. Vestibular schwannomas are the hallmark lesion, affecting 95% of individuals and typically occur bilaterally. Schwannomas commonly occur on other nerves intracranially and in the spinal compartment, along with meningiomas, ependymomas, and gliomas. Although histologically benign, tumors are associated with significant morbidity due to multiple problems including hearing and vision loss, gait abnormalities, paralysis, pain, and seizures. Risk of early mortality from brainstem compression and other complications is significant. Severity of disease is higher when NF2 presents during childhood. Children have a more variable presentation, which can be associated with significant delays in recognition of the condition. Careful examination of the skin and eyes can identify important clinical signs of NF2 during childhood, allowing timely initiation of disease-specific surveillance and treatment. Monitoring for complications comprises clinical evaluation, along with functional testing including audiology and serial neuroimaging, which together inform decisions regarding treatment. Evidence for disease-specific medical treatment options is increasing, nevertheless most patients will benefit from multimodal treatment including surgery during their lifetime. Patient enrolment in international natural history and treatment trials offers the best opportunity to accelerate our understanding of the complications and optimal treatment of NF2, with a view to improving outcomes for all affected individuals.