{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:44:04Z","timestamp":1788997444876,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To describe the dermatological manifestations of CS; compare them with the literature findings; assess those discriminating CS from other RASopathies, including cardiofaciocutaneous syndrome (CFCS) and the main types of Noonan syndrome (NS); and test for dermatological phenotype\u2013genotype correlations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a 10\u2010year, large, prospective, multicentric, collaborative dermatological and genetic study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010one patients were enrolled. Hair abnormalities were ubiquitous, including wavy or curly hair and excessive eyebrows, respectively in 68% and 56%. Acral excessive skin (AES), papillomas and keratotic papules (PKP), acanthosis nigricans (AN), palmoplantar hyperkeratosis (PPHK) and \u2018cobblestone\u2019 papillomatous papules of the upper lip (CPPUL), were noted respectively in 84%, 61%, 65%, 55% and 32%. Excessive eyebrows, PKP, AN, CCPUL and AES best differentiated CS from CFCS and NS. Multiple melanocytic naevi (&gt;50) may constitute a new marker of attenuated CS associated with intragenic duplication in <jats:italic>HRAS<\/jats:italic>. Oral acitretin may be highly beneficial for therapeutic management of PPHK. No significant dermatological phenotype\u2013genotype correlation was determined between patients with and without <jats:italic>HRAS<\/jats:italic> c.34G&gt;A (p.G12S).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>This validated phenotypic characterization of a large number of patients with CS will allow future researchers to make a positive diagnosis, and to differentiate CS from CFCS and NS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.19996","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T07:47:00Z","timestamp":1712735220000},"page":"1818-1827","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dermatological manifestations in Costello syndrome: A prospective multicentric study of 31 <scp><i>HRAS<\/i><\/scp>\u2010positive variant 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