The Multiple Forms of Neurofibromatosis

Von Recklinghausen neurofibromatosis (NF)1 has multiple forms in several senses. First, there is the matter of heterogeneity: There is more than one disease designated by the term NF, for example "classical" NF as originally described by Von Recklinghausen2 and "acoustic" NF characterized by bilateral acoustic neunomas.3,4 Second, there is the matter of marked variability in the overall severity and progression of classical NF, the disorder to be considered in this review. NF can cause serious problems, and even death in the newborn period,5 or be associated with only a relatively mild or modest burden into the seventh decade and beyond. In almost all patients NF becomes obvious in the first year of life and some form of specific problems or compromise develops before age 20 years. NF is a heritable disorder, with a frequency of 1 in 3,000.6 This means it affects at least 80,000 Americans, making it much more common than is ordinarily supposed. Indeed, it is more common than Huntington chorea, Duchenne muscular dystrophy, and Tay-Sachs disease combined.4 However, in spite of its commonness,6-10 a realistic appreciation of NF's importance for pediatrics, and for medical care and research in general, is only a recent development. This long overdue change in emphasis reflects a recognition that NF's pathogenesis has bearing on a number of issues in basic biology, including neural crest embryology and genetic influences on the origin of cancer,1 the establishment of several NF clinical research programs, and the activities of several NF patient self-help groups.