eprintid: 10163025 rev_number: 8 eprint_status: archive userid: 699 dir: disk0/10/16/30/25 datestamp: 2023-01-11 10:52:08 lastmod: 2023-11-22 07:10:06 status_changed: 2023-01-11 10:52:08 type: article metadata_visibility: show sword_depositor: 699 creators_name: Delogu, Angelica Bibiana creators_name: Limongelli, Giuseppe creators_name: Versacci, Paolo creators_name: Adorisio, Rachele creators_name: Kaski, Juan Pablo creators_name: Blandino, Rita creators_name: Maiolo, Stella creators_name: Monda, Emanuele creators_name: Putotto, Carolina creators_name: De Rosa, Gabriella creators_name: Chatfield, Kathryn C creators_name: Gelb, Bruce D creators_name: Calcagni, Giulio title: The heart in RASsopathies ispublished: pub divisions: UCL divisions: B02 divisions: D14 keywords: ATRIOVENTRICULAR-CANAL DEFECT, cardio-facio-cutaneous syndrome, CARDIOVASCULAR-ABNORMALITIES, congenital heart disease, Costello syndrome, EUROPEAN-SOCIETY, FACIO-CUTANEOUS SYNDROME, Genetics & Heredity, GENOTYPE-PHENOTYPE ANALYSIS, LEFT-VENTRICULAR HYPERTROPHY, Life Sciences & Biomedicine, NATURAL-HISTORY, Noonan syndrome, Noonan syndrome with multiple lentigines, NOONAN-LIKE SYNDROME, OF-FUNCTION MUTATIONS, RASopathy, Science & Technology, SYNDROME CLINICAL-FEATURES note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: The cardiovascular phenotype associated with RASopathies has expanded far beyond the original descriptions of pulmonary valve stenosis by Dr Jaqueline Noonan in 1968 and hypertrophic cardiomyopathy by Hirsch et al. in 1975. 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–phenotype 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-up issues for patients affected by RAS/MAPK pathway diseases, with respect to cardiac clinical outcomes and management, in children and in the adult population. date: 2022-11-21 date_type: published publisher: WILEY official_url: https://doi.org/10.1002/ajmg.c.32014 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1993396 doi: 10.1002/ajmg.c.32014 medium: Print-Electronic lyricists_name: Kaski, Juan Pablo lyricists_id: JPKAS28 actors_name: Dewerpe, Marie actors_id: MDDEW97 actors_role: owner full_text_status: public publication: American Journal of Medical Genetics Part C: Seminars in Medical Genetics volume: 190 number: 4 pagerange: 440-451 pages: 12 event_location: United States citation: Delogu, Angelica Bibiana; Limongelli, Giuseppe; Versacci, Paolo; Adorisio, Rachele; Kaski, Juan Pablo; Blandino, Rita; Maiolo, Stella; ... Calcagni, Giulio; + view all <#> Delogu, Angelica Bibiana; Limongelli, Giuseppe; Versacci, Paolo; Adorisio, Rachele; Kaski, Juan Pablo; Blandino, Rita; Maiolo, Stella; Monda, Emanuele; Putotto, Carolina; De Rosa, Gabriella; Chatfield, Kathryn C; Gelb, Bruce D; Calcagni, Giulio; - view fewer <#> (2022) The heart in RASsopathies. American Journal of Medical Genetics Part C: Seminars in Medical Genetics , 190 (4) pp. 440-451. 10.1002/ajmg.c.32014 <https://doi.org/10.1002/ajmg.c.32014>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10163025/1/Kaski_AJMG-C-22-0064.R1_Proof_.pdf