Background
We recently demonstrated multilineage somatic mosaicism in cutaneous-skeletal hypophosphatemia syndrome (CSHS), which features epidermal or melanocytic nevi, elevated fibroblast growth factor-23 (FGF23) and hypophosphatemia, finding identical RAS mutations in affected skin and bone.
Objective
1) To provide an updated overview of CSHS; 2) To review its pathobiology; 3) To present a new CSHS patient; and 4) To discuss treatment modalities.
Methods
We searched PubMed for “nevus AND rickets,” and “nevus AND hypophosphatemia,” identifying cases of nevi with hypophosphatemic rickets or elevated serum FGF23. For our additional CSHS patient, we performed histopathologic and radiographic surveys of skin and skeletal lesions, respectively. Sequencing was performed for HRAS, KRAS, and NRAS to determine causative mutations.
Results
Our new case harbored somatic activating HRAS p.G13R mutation in affected tissue, consistent with previous findings. While the mechanism of FGF23 dysregulation is unknown in CSHS, interaction between FGF and MAPK pathways may provide insight into pathobiology. Anti-FGF23 antibody KRN23 may be useful in managing CSHS.
Limitations
Multilineage RAS mutation in CSHS was recently identified; further studies on mechanism are unavailable.
Conclusion
Patients with nevi in association with skeletal disease should be evaluated for serum phosphate and FGF23. Further studies investigating the role of RAS in FGF23 regulation are needed.