Cutaneous Skeletal Hypophosphatemia Syndrome in Association with a Mosaic Mutation.

Recent molecular genetic studies have revealed that Schimmelpenning-Feuerstein-Mims syndrome (SFMS), which presents as sebaceous nevi, is a mosaic RASopathy caused by postzygotic somatic activating mutations in , , or Some patients with SFMS also have hypophosphatemic rickets, called cutaneous skeletal hypophosphatemia syndrome (CSHS). We here report a pediatric case of biopsy-proven CSHS with mosaic mutation in the gene. A girl who showed extensive nevus sebaceous since birth had suffered progressive lower extremity deformity since the age of 5 years. We found hypophosphatemic rickets in laboratory and radiological studies. From the molecular study with skin tissue with nevus sebaceous, we identified a heterozygous mutation, c.182A>G (p.Gln61Arg), in exon 3 of by Sanger sequencing. However, we did not find this mutation in the peripheral blood and unaffected tissue, which demonstrated mosaic distribution of the mutation throughout the body. Given the rarity of the previous genetically proven CSHS cases, accumulation of more cases is needed to establish the role of Ras activation in skeletal manifestations in CSHS, which is likely due to excessive production of fibroblast growth factor 23.