NF2: Mutations and management of disease

NF2 is a dominantly inherited tumour predisposition syndrome caused by mutations in the NF2 gene on chromosome 22. Affected individuals inevitably develop schwannomas and to a decreasing frequency meningiomas and ependymomas with the classical disease feature being bilateral vestibular nerve schwannomas. Most patients currently become completely deaf, although rehabilitation with brain stem implants is improving this outcome. In excess of 50% of patients represent de novo mutations and as many as one third are mosaic for the causative mutation. Although truncating mutations (nonsense and frameshifts) are the most frequent germline event and cause the most severe disease, single and multiple exon deletions are common and a strategy for detection of these is vital for a sensitive analysis. NF2 represents a difficult management problem with most patients facing reduced life expectancy historically. Surgery remains the focus of current management although watchful waiting and occasionally radiation treatment have a role. In the future the development of tailored drug therapies aimed at the genetic level may herald a targeted systemic treatment for this devastating, life limiting condition.