Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a multilineage somatic mosaic RASopathy - 20/07/16
Yale Center for Mendelian Genomics
Michael T. Collins, MD b, Keith A. Choate, MD, PhD a, ⁎Abstract |
Background |
We recently demonstrated multilineage somatic mosaicism in cutaneous skeletal hypophosphatemia syndrome (CSHS), which features epidermal or melanocytic nevi, elevated fibroblast growth factor (FGF)-23, and hypophosphatemia, finding identical RAS mutations in affected skin and bone.
Objective |
We sought to: (1) provide an updated overview of CSHS; (2) review its pathobiology; (3) present a new patient with CSHS; and (4) 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 FGF-23. For our additional patient with CSHS, 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.G13 R mutation in affected tissue, consistent with previous findings. Although the mechanism of FGF-23 dysregulation is unknown in CSHS, interaction between FGF and MAPK pathways may provide insight into pathobiology. Anti-FGF-23 antibody KRN-23 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 FGF-23. Further studies investigating the role of RAS in FGF-23 regulation are needed.
Le texte complet de cet article est disponible en PDF.Key words : congenital melanocytic nevus, cutaneous skeletal hypophosphatemia syndrome, epidermal nevus, fibroblast growth factor-23, mosaicism, nevus syndrome, rickets
Abbreviations used : CSHS, FGF, FGFR
Plan
Supported in part by a Clinical Scientist Development Award (Dr Choate) and Medical Student Research Fellowship (Mr Lim) from the Doris Duke Charitable Foundation, the Medical Scientist Training Program at Yale University (National Institutes of Health T32 GM007205) (Mr Lim), and the Yale Center for Mendelian Genomics (National Institutes of Health U54 HG006504). |
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Conflicts of interest: None declared. |
Vol 75 - N° 2
P. 420-427 - août 2016 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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