{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:38:22Z","timestamp":1791041902073,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,7,28]],"date-time":"2018-07-28T00:00:00Z","timestamp":1532736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08 HL94748"],"award-info":[{"award-number":["K08 HL94748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>Multifocal atrial tachycardia (MAT) has a well\u2010known association with Costello syndrome, but is rarely described with related RAS\/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Nonreentrant atrial tachycardias may cause cardiac compromise if sinus rhythm is not restored expeditiously. Typical first\u2010line supraventricular tachycardia anti\u2010arrhythmics (propranolol and digoxin) were generally not effective in restoring or maintaining sinus rhythm in this cohort, while flecainide or amiodarone alone or in concert with propranolol were effective anti\u2010arrhythmic agents for acute and chronic use. Atrial tachycardia resolved in all patients. However, a 4\u2010month\u2010old boy from the cohort was found asystolic (with concurrent cellulitis) and a second patient underwent cardiac transplant for heart failure complicated by recalcitrant atrial arrhythmia. While propranolol alone frequently failed to convert or maintain sinus rhythm, fleccainide or amiodarone, occasionally in combination with propranolol, was effective for RASopathy patient treatment for nonreentrant atrial arrhythmia. Our analysis shows that RASopathy patients may have nonreentrant atrial tachycardia with and without associated cardiac hypertrophy. While nonreentrant arrhythmia has been traditionally associated with Costello syndrome, this work provides an expanded view of RASopathy cardiac arrhythmia phenotype as we demonstrate mutant proteins throughout this signaling pathway can also give rise to ectopic and\/or MAT.<\/jats:p>","DOI":"10.1002\/ajmg.a.38854","type":"journal-article","created":{"date-parts":[[2018,7,29]],"date-time":"2018-07-29T07:25:13Z","timestamp":1532849113000},"page":"1711-1722","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2241-9828","authenticated-orcid":false,"given":"Mark D.","family":"Levin","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulagna C.","family":"Saitta","sequence":"additional","affiliation":[{"name":"Division of Genomic Medicine, Department of Pathology Children's Hospital Los Angeles and Keck\u2010USC School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen W.","family":"Gripp","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics A. 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