{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T22:01:47Z","timestamp":1771106507768,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The Ras\/mitogen\u2010activated protein kinase (RAS\/MAPK) pathway regulates cell proliferation, and dysregulation of this pathway has been linked to the increased risk of malignancy in a subset of disorders known as RASopathies (e.g., NF1, Costello syndrome, Noonan syndrome). However, reports of malignancy are rare in cardiofaciocutaneous (CFC) syndrome, which is caused by heterozygous pathogenic variants in\n                    <jats:italic>BRAF<\/jats:italic>\n                    ,\n                    <jats:italic>MAP2K1<\/jats:italic>\n                    ,\n                    <jats:italic>MAP2K2<\/jats:italic>\n                    , and\n                    <jats:italic>KRAS<\/jats:italic>\n                    . Somatic pathogenic variants in\n                    <jats:italic>BRAF<\/jats:italic>\n                    are one of the most common drivers of Langerhans cell histiocytosis (LCH), a neoplastic disorder that can present with lesions in a variety of locations. However, despite the association of somatic\n                    <jats:italic>BRAF<\/jats:italic>\n                    variants and LCH, individuals with CFC syndrome are not thought to have higher rates of LCH. Here, we report two individuals with CFC syndrome and LCH and review the literature examining this potential association.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64294","type":"journal-article","created":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T07:25:39Z","timestamp":1761981939000},"page":"723-727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Langerhans Cell Histiocytosis in Cardiofaciocutaneous Syndrome"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3084-679X","authenticated-orcid":false,"given":"Laura","family":"Keehan","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Sleightholm","sequence":"additional","affiliation":[{"name":"Division of Hematology 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