{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:40:41Z","timestamp":1792431641316,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a mosaic RASopathy caused by postzygotic, activating pathogenic variants in <jats:italic>HRAS<\/jats:italic>, <jats:italic>NRAS<\/jats:italic>, or <jats:italic>KRAS<\/jats:italic>. It is characterized by congenital epidermal, melanocytic, or sebaceous nevi, elevated FGF23 levels that cause renal phosphate wasting and rickets, and focal bone lesions. We report a 13\u2010year\u2010old girl with CSHS from Argentina. At 15\u2009days old, she was presented with an extensive epidermal nevus (pigmento\u2010keratotic phacomatosis). She developed valgus deformity of the right lower limb at the age of 2\u2009years. X\u2010rays showed extended skeletal involvement, poorly defined corticomedullary junctions, and lytic lesions located in the affected skin area. All the metaphyses showed rickets. Lab tests showed persistently low phosphatemia 2.1\u2009mg\/dL (NV: 3.8\u20136.2), with hyperphosphaturia and elevated alkaline phosphatase (ALP) 661\u2009IU\/L (NV\u2009&lt;\u2009300). The patient received treatment with oral phosphate salts and calcitriol, resulting in a favorable metabolic control until she was 6\u2009years old. At that time, she developed central precocious puberty and presented severe clinical compromise, with asthenia, chronic pain, weakness, reduced functional capacity, and loss of independent walking. Sanger sequencing test of the main hotspots of <jats:italic>HRAS<\/jats:italic>, <jats:italic>NRAS<\/jats:italic>, and <jats:italic>KRAS<\/jats:italic> was performed. A previously reported somatic variant, c.37G&gt;C (p.Gly13Arg) in <jats:italic>HRAS<\/jats:italic>, was detected in the DNA isolated from the affected skin tissue. Due to clinical, radiological, and biochemical worsening, with a decrease in phosphatemia (1.4\u2009mg\/dL) and an increase in ALP (2117\u2009IU\/L), the patient was initiated on burosumab at the age of 11\u2009years. After 3\u2009months, she reported improvement in her physical abilities. The x\u2010ray findings showed progressive healing of rickets in the long bones: ulna, radius, femur, tibia, and fibula. Phosphatemia and tubular reabsorption of phosphate increased gradually with the up\u2010titration of burosumab dose to 2\u2009mg\/kg. However, the patient developed hypercalciuria 6\u201312\u2009mg\/kg\/day (NV\u2009\u2264\u20094), with calcemia 9.6\u201310.8\u2009mg\/dL (NV 8.9\u201310.5) and normal parathormone (PTH) 26\u201353\u2009pg\/mL (NV: 12\u201395), and the dose of burosumab had to be reduced to 1.6\u2009mg\/kg every 2\u2009weeks. We report a girl with CSHS confirmed by somatic <jats:italic>HRAS<\/jats:italic> pathogenic variant. Conventional treatment was replaced by burosumab, with healing of bone rickets, and a clear improvement in mineral homeostasis and physical functioning after 2\u2009years of treatment.<\/jats:p>","DOI":"10.1002\/ajmg.a.64020","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:22:00Z","timestamp":1739251320000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Burosumab Treatment in a Girl With Cutaneous Skeletal Hypophosphatemia Syndrome: 2\u2010Year Follow\u2010Up"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6095-7080","authenticated-orcid":false,"given":"Mariana","family":"del Pino","sequence":"first","affiliation":[{"name":"Growth and Development Hospital de Pediatria Prof Dr Juan P Garrahan  Buenos Aires 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