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We describe\u00a0a three\u2010generation family with a previously unreported\u00a0heterozygous\n                    <jats:italic>HRAS<\/jats:italic>\n                    variant c.175G&gt;A (p.Ala59Thr) causing a predominantly ectodermal phenotype. Exome and Sanger sequencing were used for genetic analysis. Dermatological and cardiac evaluations were performed, including skin biopsy and hair sample microscopy. A 14\u2010year\u2010old proband, her twin sister, mother, mother's father, and mother's paternal half\u2010brother all shared a phenotype of woolly and sparse hair, curly eyelashes, sparse eyebrows, ulerythema ophryogenes, keratosis pilaris, palmoplantar keratoderma, and low\u2010set posteriorly rotated ears. One patient required a gastrostomy after birth but otherwise classic CS features, including craniofacial anomalies, hypertrophic cardiomyopathy, and intellectual disability, were absent. We conducted a comparison supporting the attenuated CS phenotype associated with\n                    <jats:italic>HRAS<\/jats:italic>\n                    codon 58\u201360 variants. In conclusion,\n                    <jats:italic>HRAS<\/jats:italic>\n                    c.175G&gt;A (p.Ala59Thr) causes predominantly an ectodermal phenotype, consistent with milder\n                    <jats:italic>HRAS<\/jats:italic>\n                    \u2010related RASopathies involving codons 58\u201360 distinguishable from classic CS.\n                    <jats:italic>HRAS<\/jats:italic>\n                    variants should be considered in patients with ectodermal and CS\u2010like features for accurate genetic diagnosis and targeted management.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64277","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:44:27Z","timestamp":1760175867000},"page":"407-418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>HRAS<\/scp>\n                    Variant c.\n                    <scp>175G<\/scp>\n                    &gt;A (p.\n                    <scp>Ala59Thr<\/scp>\n                    ) Causes a Predominantly Ectodermal Phenotype Lacking Classic Costello Syndrome Features"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8754-8776","authenticated-orcid":false,"given":"Nikole","family":"Rautiainen","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eveliina","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaisa","family":"Kettunen","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, HUS Diagnostic Center University of Helsinki and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Outi","family":"Elomaa","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland and Research Programs Unit, Stem Cells and Metabolism Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirpa","family":"Kivirikko","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Department of Medical and Clinical Genetics University of Helsinki and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Jeskanen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katriina","family":"Lappalainen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelli","family":"Sj\u00f6blom","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juha","family":"Kere","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland and Research Programs Unit, Stem Cells and Metabolism Research Program University of Helsinki  Helsinki Finland"},{"name":"Department of Medicine Huddinge Karolinska Institutet  Huddinge Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katariina","family":"Hannula\u2010Jouppi","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liisa","family":"Harjama","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital  Helsinki 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