Linear nevus sebaceous syndrome with hypophosphatemic rickets with elevated FGF-23

Narazaki, Ryo; Ihara, Kenji; Namba, Noriyuki; Matsuzaki, Hiroshi; Ozono, Keiichi; Hara, Toshiro

doi:10.1007/s00467-011-2086-4

Cited by 14 publications

(13 citation statements)

References 14 publications

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“…We studied the effects of epidermal nevus ablation, and found that neither surgical excision nor laser ablation correlated with improvement in mineral status or patient-reported quality of life. Immunolocalization and qPCR studies did not detect FGF23 expression within nevi from all 5 patients, consistent with prior reports [19]. …”

Section: Reviewsupporting

confidence: 91%

“…While some case reports suggest a therapeutic response, the results are confounded by concomitant oral medication or lack of follow-up. CSHS/nevus syndrome patients may undergo potentially painful removal procedures with no improvement [13, 19]. Not all patients in whom phosphate levels normalized were subject to nevi removal and there is evidence that phosphaturia improves over time [44].…”

Section: Reviewmentioning

confidence: 99%

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Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a multilineage somatic mosaic RASopathy

Lim

Ovejero

Derrick

et al. 2016

Journal of the American Academy of Dermatology

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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.

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Section: Reviewsupporting

confidence: 91%

Section: Reviewmentioning

confidence: 99%

Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a multilineage somatic mosaic RASopathy

Lim

Ovejero

Derrick

et al. 2016

Journal of the American Academy of Dermatology

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“…It has been proposed that FGF23 is the putative phosphatonin, based on demonstration of its elevated blood levels in a patient with LNSS (56). Subsequent studies also found the same result (119)(120). In typical tumor-induced osteomalacia, symptoms tend to be resolved after removal of the tumor (117).…”

Section: Linear Nevus Sebaceous Syndrome (Lnss)mentioning

confidence: 95%

“…Excision of epidermal lesions with ENS may improve the hypophosphataemic rickets in some patients (47, 56), while it has failed to heal rickets in most patients (115)(116)118). Although it is possible that large amounts of FGF23 are autonomously secreted by LNS lesions, this factor was not found to be directly excreted from the LNS lesions (119). Further study is needed to understand the exact mechanism of how FGF23 is related to hypophosphatemic rickets in LNSS.…”

Section: Linear Nevus Sebaceous Syndrome (Lnss)mentioning

confidence: 99%

FGF23 and Phosphate Wasting Disorders

2013

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A decade ago, only two hormones, parathyroid hormone and 1,25(OH)2D, were widely recognized to directly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 (FGF23) in 2000 (1), our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteoblasts in the skeleton (2-3), it modulates kidney handling of phosphate reabsorption and calcitriol production. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimentalto humans. In this review, we will discuss the pathophysiology of FGF23 and hyper-FGF23 related renal phosphate wasting disorders (4 IntroductionAccording to pathogenesis, ricketsis classified into calicopenic rickets, phosphopenicrickets, and a miscellaneous group associated with direct inhibitors of mineralization ( 5). In general, most instances of nutritional rickets are calicopenic, whereas heritable causes are usually phosphopenic. In this review we focus on hypophosphatemic rickets or osteomalacia. The causes of hypophosphatemia are various, of whichthe most prominent one is decreased reabsorption of phosphate in the proximal tubule.Although renal tubular disease can result in excessive renal phosphate wasting, in most hypophosphatemic disordersno abnormalities are found in the proximal tubule (6-7). It is speculated that an unknown factor is responsible for this phenomenon. The discovery of fibroblast growth factor 23 (FGF23), a member of the Phosphate homeostasisPhosphate comprises about 1% of total body weight. About 85% of total body phosphate resides in the bone, 14% in the cells, and only 1% in the serum and extracellular fluids. Maintenance of serum phosphate within its normal range allows for optimal mineralization of bone without deposition in vascular and other soft tissues. Serum phosphate concentration is determined Xianglan Huang et al. www.boneresearch.org | Bone Research 121by the balance among intestinal absorption of phosphate from the diet, its storage in bone, and its excretion in the urine. The proximal tubule is responsible for the reabsorption of phosphate filtered at the glomerulus and is the primary regulator of phosphate balance in the body. Transportation in the proximal tubule is driven primarily by sodium-potassium ATPase, which is located in the baso-lateral membrane of the cell (8-11). Under normal conditions, about 85% of the filtered phosphate is reabsorbed via the sodium-phosphate co-transporter (NaPi2a and NaPi2c) in the proximal tubule (9, 11). Parathyroid hormone (PTH) is one of the most potent horm...

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“…This neuroectodermal disorder is characterised by involvement of the skeleton and central nervous systems in addition to ophthalmological, cardiovascular, urological and very rarely endocrine abnormalities like precocious puberty and vitamin D-resistant hypophosphataemic rickets. Elevated FGF-23 has consistently been seen in rickets associated with LNSS, but the source of excess FGF-23 still remains debatable 2…”

Section: Descriptionmentioning

confidence: 99%

Skin changes with rickets: looks can be deceptive

et al. 2018

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Linear nevus sebaceous syndrome with hypophosphatemic rickets with elevated FGF-23

Abstract: It is possible that an as-yet unidentified substance increases FGF-23 expression LNS lesions.

Cited by 14 publications

References 14 publications

Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a multilineage somatic mosaic RASopathy

Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a multilineage somatic mosaic RASopathy

FGF23 and Phosphate Wasting Disorders

Skin changes with rickets: looks can be deceptive

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