Clinical and genetic patterns of neurofibromatosis 1 and 2.

General introduction to the neurofibromatoses The diseases traditionally known as neurofibromatosis have now been formally separated into two types: neurofibromatosis type 1 or NFl (the type described by von Recklinghausen) and neurofibromatosis type 2 or NF2 (a much rarer form).' It is now recognised that although they have overlapping features, including an inherited propensity to neurofibromas and tumours of the central nervous system, they are indeed separate diseases and map to different chromosomes 17 for NFl and 22 for NF2. Furthermore, developmental abnormalities such as hamartomas occur in both types of neurofibromatosis, illustrating a need to define the role of the normal NF genes in development. There may also be further forms of neurofibromatosis, including NF3, NF4, multiple meningiomatosis, and spinal schwannomatosis, that do not fit precisely into current diagnostic classifications. These further forms may eventually map to different genes. For their clinical features, the reader is referred to a more detailed text.2 Segmental neurofibromatosis (NF5) is a localised form of neurofibromatosis affecting a region of the body. Here the cafe au lait patches, neurofibromas, and even Lisch nodules are all found ipsilateral to the tumours and not crossing the midline. Interestingly, individuals with segmental NF can have children with classic NFL.3 This implies either a common gene locus or possible gonadal mosaicism. There may be other partial forms of neurofibromatosis. For instance, in the case of NFl, some parents manifesting Lisch nodules alone