Segmental Neurofibromatosis: The One-Hit, Two-Hit Theme Is Heard Again

Sensitive tools can establish the presence of segmental disease mechanisms at the molecular level. Neurofibromatosis type 1 (NF1) has a segmental form, featuring localized neurofibromas or café-au-lait macules (CALMs). To characterize the mutations associated with various NF presentations, investigators performed FISH and real-time quantitative PCR studies in three patients with distinct NF1-associated clinical manifestations (neurofibromas only, pigmentary changes only, and both).

In the first patient, who had 35 to 40 segmental neurofibromas, the researchers found evidence of one mutation in the leukocytes and lesional fibroblasts and another mutation in Schwann cells from a neurofibroma. The second patient had only hyperpigmentation and C…