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Because of the common underlying RAS\/MAPK pathway dysregulation, RASopathy syndromes usually present with a typical spectrum of overlapping cardiovascular anomalies, although less common cardiac defects can occur. The identification of the causative genetic variants has enabled the recognition of specific correlations between genotype and cardiac phenotype. Characterization and understanding of genotype\u2013phenotype associations is not only important for counseling a family of an infant with a new diagnosis of a RASopathy condition but is also critical for their clinical prognosis with respect to cardiac disease, neurodevelopment and other organ system involvement over the lifetime of the patient. This review will focus on the cardiac manifestations of the most common RASopathy syndromes, the relationship between cardiac defects and causal genetic variation, the contribution of cardiovascular abnormalities to morbidity and mortality and the most relevant follow\u2010up issues for patients affected by RAS\/MAPK pathway diseases, with respect to cardiac clinical outcomes and management, in children and in the adult population.<\/jats:p>","DOI":"10.1002\/ajmg.c.32014","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T05:49:07Z","timestamp":1669009747000},"page":"440-451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The heart in\n                    <scp>RASopathies<\/scp>"],"prefix":"10.1002","volume":"190","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2283-3180","authenticated-orcid":false,"given":"Angelica Bibiana","family":"Delogu","sequence":"first","affiliation":[{"name":"Unit of Pediatrics, Pediatric Cardiology, Department of Woman and Child Health and Public Health Fondazione Policlinico Universitario A. 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Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"},{"name":"Department of Cardiac Surgery, Cardiology, Heart and Lung Transplantation Bambino Ges\u00f9 Children's Hospital, IRCSS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Kaski","sequence":"additional","affiliation":[{"name":"Centre for Pediatric Inherited and Rare Cardiovascular Disease University College London Institute of Cardiovascular Science  London UK"},{"name":"Centre for Inherited Cardiovascular Diseases Great Ormond Street Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Blandino","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Maiolo","sequence":"additional","affiliation":[{"name":"European Reference Network for rare, low\u2010prevalence, or complex disease of the heart (ERN GUARD\u2010Heart) University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, Naples, Italy. Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"},{"name":"Pediatric Cardiology Unit, Department of Pediatrics, Obstetrics and Gynecology \u201cSapienza\u201d University of Rome, Policlinico Umberto I  Rome Italy"},{"name":"Department of Cardiac Surgery, Cardiology, Heart and Lung Transplantation Bambino Ges\u00f9 Children's Hospital, IRCSS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Monda","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences University of Campania \u201cLuigi Vanvitelli,\u201d Monaldi Hospital  Naples Italy"},{"name":"European Reference Network for rare, low\u2010prevalence, or complex disease of the heart (ERN GUARD\u2010Heart) University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, Naples, Italy. Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Putotto","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Unit, Department of Pediatrics, Obstetrics and Gynecology \u201cSapienza\u201d University of Rome, Policlinico Umberto I  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Unit of Pediatrics, Pediatric Cardiology, Department of Woman and Child Health and Public Health Fondazione Policlinico Universitario A. 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