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The “modern age” of neurofibromatosis began in 1981, with Riccardi's detailed clinical descriptions of the features and natural history of von Recklinghausen disease and the subsequent description of “central neurofibromatosis with bilateral acoustic neuroma.” With the availability of gene-based diagnosis, several distinct clinical syndromes have been identified: (1) neurofibromatosis type 1 (NF-1), also known as von Recklinghausen disease; (2) neurofibromatosis type 2 (NF-2), whose cardinal feature is the development of bilateral vestibular schwannomas; (3) segmental or mosaic NF-1; (4) Legius syndrome (SPRED1 mutation) leading to autosomal dominant transmission of café-au-lait spots, intertriginous freckling and macrocephaly; and (5) schwannomatosis. Both NF-1 and NF-2 occur equally in all ethnic groups. NF-1 occurs at an incidence of 1 in 3,000 live births, whereas NF-2 is much less common with an estimated incidence of 1 in 40,000 live births.
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NF-1 is inherited in an autosomal dominant fashion. Although the expressivity of NF-1 varies considerably, even among individuals in the same family who are genotypically identical, the disorder is considered to be 100% penetrant. Thus, apparent skipping of NF-1 between generations may be the result of misdiagnosis, nonpaternity, or the occurrence of a new mutation in the grandchild. Although a large number of NF1 mutations have been described, only two genotype-phenotype correlations have been noted. Individuals who have deletions of the entire NF1 gene have an increased risk of ...