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In this study, we retrospectively analyzed the clinical data of 121 patients with a molecularly confirmed diagnosis of RASopathy, describing frequencies for clinical features in all organ systems as well as molecular data. The most common clinical diagnosis was Noonan Syndrome and the most frequently affected gene was <jats:italic>PTPN11<\/jats:italic> followed by <jats:italic>SOS1<\/jats:italic>, <jats:italic>RAF1<\/jats:italic>, <jats:italic>LZTR1<\/jats:italic>, and <jats:italic>RIT1<\/jats:italic>. All patients had distinctive craniofacial features indicative of the RASopathy spectrum but we report some atypical features regarding craniofacial shape, such as craniosynostosis and microcephaly. We also describe uncommon clinical characteristics such as aortic dilation, multivalvular heart disease, abnormalities of the posterior fossa, and uterine congenital anomalies in female patients. Furthermore, the presence of multiple giant cell granulomas was observed specifically in patients with <jats:italic>SOS1<\/jats:italic> variants. This comprehensive evaluation allows broadening the phenotypic spectrum of our population and their correlation with the genotype, which are essential to improve the recognition and the follow up of RASopathies as a multisystemic disease.<\/jats:p>","DOI":"10.1002\/ajmg.a.63905","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T12:10:22Z","timestamp":1730463022000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["New Insights Into the Spectrum of <scp>RASopathies<\/scp>: Clinical and Genetic Data in a Cohort of 121 Spanish Patients"],"prefix":"10.1002","volume":"197","author":[{"given":"Ana Isabel S\u00e1nchez","family":"Barbero","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease Unit Vall Hebron Research Institute  Barcelona Spain"},{"name":"Medicine Genetics Group Vall Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2350-6058","authenticated-orcid":false,"given":"Irene","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease Unit Vall Hebron Research Institute  Barcelona Spain"},{"name":"Medicine Genetics Group Vall Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Fern\u00e1ndez\u2010Alvarez","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease Unit Vall Hebron Research Institute  Barcelona Spain"},{"name":"Medicine Genetics Group Vall Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9lida","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology Hospital Vall d'Hebron  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Cueto\u2010Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease Unit Vall Hebron Research Institute  Barcelona Spain"},{"name":"Medicine Genetics Group Vall Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Lasa\u2010Aranzasti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease Unit Vall Hebron Research Institute  Barcelona Spain"},{"name":"Medicine Genetics Group Vall Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Trujillano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease Unit Vall Hebron Research Institute  Barcelona Spain"},{"name":"Medicine Genetics Group Vall Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"Masotto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease Unit Vall Hebron Research Institute  Barcelona Spain"},{"name":"Medicine Genetics Group Vall Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Garc\u00eda","family":"Arum\u00ed","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease Unit Vall Hebron Research Institute  Barcelona Spain"},{"name":"Medicine Genetics Group Vall Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo F.","family":"Tizzano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease Unit Vall Hebron Research Institute  Barcelona Spain"},{"name":"Medicine Genetics Group Vall Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11]]},"reference":[{"key":"e_1_2_25_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37259"},{"key":"e_1_2_25_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36374"},{"key":"e_1_2_25_4_1","volume-title":"GeneReviews\u00ae [Internet]","author":"Allanson Roberts A. 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