While the effectiveness of MEK inhibitors such as selumetinib is established in <i>NF1</i>-associated inoperable plexiform neurofibromas, their use in managing hyperactive <i>KRAS</i>-driven epidermal nevi and hypertrophic neuropathy remains unproven, and this case, to our knowledge, is the first such case to be reported. This evidence concerns the gene MAP2K7 and plexiform neurofibroma.