Genetic analyses of mosaic neurofibromatosis type 1 with giant cafe-au-lait macule, plexiform neurofibroma and multiple melanocytic nevi

Neurofibromatosis type 1 (NF1) is a genodermatosis caused by heterozygous germ line variations in the NF1 gene. A second-hit NF1 aberration results in the formation of cafe-au-lait macules, cutaneous neurofibroma and plexiform neurofibroma (PNF). Mosaic NF1 (mNF1), caused by a postzygotic NF1 mutation, is characterized by localized or generalized NF1-related manifestations. Although NF1 and mNF1 are associated with pigmentary skin lesions, clinically recognizable melanocytic nevi that developed over PNF have not been reported. Here, we report the first case of multiple melanocytic nevi that developed on a giant cafe-au-lait macule and PNF. The PNF had biallelic NF1 deletions, a whole deletion of NF1 and a novel intragenic deletion involving exons 25-30. The deletions were not detected in the blood, which resulted in the diagnosis of mNF1. Furthermore, the nevus cells had not only biallelic NF1 deletions but also NRAS Q61R, a common mutation found in congenital melanocytic nevi. These analyses revealed the coexistence of the two different mosaic diseases, mNF1 and congenital melanocytic nevi. For a diagnosis of cases with atypical NF1-like symptoms, genetic analyses using blood and lesional tissues are useful and aid in genetic counseling.