The neurofibromatoses. An overview

The last two decades have seen clinical and molecular delineation of the di fferent forms of neurofibromatosis. Differentiation of these forms is not j ust an academic exercise: their natural history, management and genetic cou nselling are quite different. Of the numerical classifications of neurofibr omatosis proposed in the past, only neurofibromatosis type 1 (Nf1) and neur ofibromatosis type 2 (Nf2) are now well delineated clinically and have been shown to be distinct at the molecular level. For both forms of neurofibrom atosis, patients with clinical generalised disease have been demonstrated t o be mosaic at the molecular level, and features of segmental or mosaic Nf1 and Nf2 have been delineated. Other reported forms of neurofibromatosis ar e rarer; they include Watson syndrome, hereditary spinal neurofibromatosis, familial intestinal neurofibromatosis, autosomal dominant cafe-au-lait spo ts alone, autosomal dominant neurofibromas alone, and schwannomatosis, the latter believed to be a variant of Nf2. Further delineation is needed for i ndividuals having overlapping features of Noonan's syndrome and neurofibrom atosis (the so-called Noonan/neurofibromatosis syndrome) and the syndrome o f "multiple naevi, multiple schwannomas and multiple vaginal leiomyomas". I n this article we review the forms of neurofibromatosis which we believe ar e true clinical entities. Particular attention is given to the neurological manifestations of neurofibromatosis.