Lim Young H, Ovejero Diana, Derrick Kristina M, Collins Michael T, Choate Keith A
Departments of Dermatology, Pathology, and Genetics, Yale University School of Medicine, New Haven, Connecticut.
Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland; Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
J Am Acad Dermatol. 2016 Aug;75(2):420-7. doi: 10.1016/j.jaad.2015.11.012.
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.
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.
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.
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.
Multilineage RAS mutation in CSHS was recently identified; further studies on mechanism are unavailable.
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.
我们最近在皮肤骨骼低磷血症综合征（CSHS）中证实了多谱系体细胞镶嵌现象，该综合征的特征为表皮或黑素细胞痣、成纤维细胞生长因子（FGF）-23升高以及低磷血症，在受影响的皮肤和骨骼中发现了相同的RAS突变。
我们试图：（1）提供CSHS的最新概述；（2）回顾其病理生物学；（3）介绍一名新的CSHS患者；（4）讨论治疗方式。
我们在PubMed上搜索了“痣与佝偻病”以及“痣与低磷血症”，以确定患有低磷血症性佝偻病或血清FGF-23升高的痣病例。对于我们新增的CSHS患者，我们分别对皮肤和骨骼病变进行了组织病理学和影像学检查。对HRAS、KRAS和NRAS进行测序以确定致病突变。
我们的新病例在受影响组织中存在体细胞激活型HRAS p.G13R突变，与先前的发现一致。尽管CSHS中FGF-23失调的机制尚不清楚，但FGF和MAPK途径之间的相互作用可能有助于深入了解病理生物学。抗FGF-23抗体KRN-23可能对CSHS的治疗有用。
最近在CSHS中发现了多谱系RAS突变；目前尚无关于机制的进一步研究。
对于患有与骨骼疾病相关痣的患者，应评估其血清磷酸盐和FGF-23水平。需要进一步研究RAS在FGF-23调节中的作用。
