Introduction: Epidermal nevus syndrome is a rare group of disorders characterized by the combination of congenital epidermal nevi and extracutaneous features, including skeletal, neurological, ocular, and other systemic findings. We report a case of keratinocytic epidermal nevus syndrome that includes a thymoma, bone dysplasia, and hypophosphatemia with elevated fibroblast growth factor 23 (FGF23) levels associated with postzygotic HRAS mutation.
Case report: A 14-year-old boy was admitted due to recent limping. The physical examination revealed multiple right-sided linear epidermal nevi along Blaschko's lines. Magnetic resonance imaging showed cystic lesions in cervical bones and thymoma, and x-ray examination showed cystic lesions in the hands. Biochemical studies demonstrated severe hypophosphatemia, normocalcemia, high normal PTH, low 25-hydroxyvitamin D and low 1,25-dihydroxyvitamin D levels. The serum FGF23 C-terminal level was normal, but the intact FGF23 level was found to be elevated. Genetic evaluation revealed a heterozygote mutation in the HRAS gene in both the keratinocytic epidermal nevus and thymoma but not in DNA extracted from blood lymphocytes, thus establishing the mutation as postzygotic.
Discussion: Postzygotic mutations in HRAS lead to elevation of FGF23 levels, as found in mutated PHEX, FGF23, DMP1, and ENPP1 genes, which lead to hypophosphatemia.
Conclusion: An identical postzygotic HRAS mutation was shown to be present in both keratinocytic epidermal nevus and thymoma and to be associated with bone lesions and hypophosphatemia due to elevated FGF23 levels. These may all be related to the HRAS mutation.