Clinical diagnosis and atypical forms of NF1

Neurofibromatosis type 1 (NF1) (MIM 162200) is inherited as an autosomal dominant trait and affects all ethnic groups. In this chapter, we review the NIH clinical diagnostic criteria with particular emphasis on NF1 in different age groups. We also discuss atypical forms of NF1. Diagnosing young children without an NF1 family history is challenging since sporadic cases often present with only one of the NF1 signs during the first years and hence do not fulfill the NIH diagnostic criteria. Mutation analysis of the NF1 gene may thus be particularly useful in the youngest age group in confirming the diagnosis. In children over 5-6 years and in adults, NF1 can be diagnosed in over 90 % of cases using the NIH criteria. Café-au-lait macules are one of the key diagnostic signs of NF1 since they manifest at an early age and are the most invariable signs of NF1. However, the differential diagnosis of café-au-lait macules is not always simple since other lesions may mimic these pigment spots, and café-au-lait macules are found in numerous other syndromes apart from NF1. Solitary café-au-lait macules, common birth marks, occur also in 10-15 % of the general population.Two or more neurofibromas are a diagnostic sign of NF1, but it is worth noting that single neurofibromas are not uncommon in healthy individuals. If the diagnosis of NF1 is not certain, removing one or two cutaneous neurofibromas for histology is indicated. The differential diagnosis of neurofibromas includes common melanocytic nevi, lipomas, and schwannomas. This chapter addresses the differential diagnosis of selected syndromes with multiple tumors and those with pigment lesions.