{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:51:02Z","timestamp":1753876262358,"version":"3.41.2"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T00:00:00Z","timestamp":1719619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>PTPN11 is ubiquitously expressed and has a variety of phenotypes even in a single heart. We examined LEOPARD syndrome (LS) in a patient with PTPN11 variants through pathological, electrophysiological, and anatomical studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case summary<\/jats:title>\n                  <jats:p>A 49-year-old man with no previous medical history was brought to our emergency department because of syncope. An electrocardiogram (ECG) revealed alternating bundle branch block, and echocardiography revealed hypertrophic cardiomyopathy-like morphology with systolic anterior motion of the posterior mitral valve. Atrioventricular block, left ventricular outflow tract (LVOT) obstruction, and ventricular tachycardia were considered the differential diagnoses; however, the treatment plan was difficult to determine. An electrophysiological study revealed the cause of the ECG abnormality to be accelerated idioventricular rhythm, and the programmed ventricular stimulation was negative. Genetic testing revealed LS with PTPN11 variant, which was speculated to be the cause of these various unique cardiac features. The cause of syncope was considered to be exacerbation of LVOT obstruction due to dehydration, and the patient was treated with oral beta-blockers. Implantable loop recorder observation for 1 year revealed no arrhythmia causing syncope, and an implantable cardioverter-defibrillator and pacemaker were deemed unnecessary for primary prevention of syncope. During 2.5 years of follow-up, the LVOT peak velocity fluctuated between 2.5 and 3.5 m\/s, but the patient remained stable with no recurrent syncope.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We confirmed that LS is distinct from other cardiomyopathies using characterization, physiological, electrophysiological, and pathological examinations. Evidence supporting a specific treatment strategy for LS is limited, and understanding the pathogenesis may help establish effective treatment strategies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjcr\/ytae309","type":"journal-article","created":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T11:56:31Z","timestamp":1719662191000},"source":"Crossref","is-referenced-by-count":0,"title":["LEOPARD syndrome with accelerated idioventricular rhythm and systolic anterior motion of the posterior mitral leaflet: a case report"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-0686","authenticated-orcid":false,"given":"Naotoshi","family":"Wada","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyoto Chubu Medical Center , 25, Yagi-Ueno, Yagi-cho, Nantan City, Kyoto 629-0197 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoji","family":"Keisuke","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyoto Chubu Medical Center , 25, Yagi-Ueno, Yagi-cho, Nantan City, Kyoto 629-0197 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6556-9052","authenticated-orcid":false,"given":"Tetsuya","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyoto Chubu Medical Center , 25, Yagi-Ueno, Yagi-cho, Nantan City, Kyoto 629-0197 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsuya","family":"Keira","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyoto Chubu Medical Center , 25, Yagi-Ueno, Yagi-cho, Nantan City, Kyoto 629-0197 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Tatsumi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyoto Chubu Medical Center , 25, Yagi-Ueno, Yagi-cho, Nantan City, Kyoto 629-0197 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,6,29]]},"reference":[{"key":"2024073119501691200_ytae309-B1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1750-1172-3-13","article-title":"LEOPARD syndrome","volume":"3","author":"Sarkozy","year":"2008","journal-title":"Orphanet J Rare Dis"},{"key":"2024073119501691200_ytae309-B2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12881-020-0986-5","article-title":"Molecular and clinical studies in 107 Noonan syndrome affected individuals with PTPN11 mutations","volume":"21","author":"Athota","year":"2020","journal-title":"BMC Med Genet"},{"key":"2024073119501691200_ytae309-B3","doi-asserted-by":"crossref","first-page":"6785","DOI":"10.1074\/jbc.M513068200","article-title":"PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects","volume":"281","author":"Kontaridis","year":"2006","journal-title":"J Biol Chem"},{"key":"2024073119501691200_ytae309-B4","first-page":"486","article-title":"Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: a Ras\/MAPK pathway syndrome","volume":"155A","author":"Alexander","year":"2011","journal-title":"Am J Med Genet A"},{"key":"2024073119501691200_ytae309-B5","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1002\/ajmg.a.38854","article-title":"Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients","volume":"176","author":"Levin","year":"2018","journal-title":"Am J Med Genet A"},{"key":"2024073119501691200_ytae309-B6","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1136\/jmg.40.9.704","article-title":"Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes","volume":"40","author":"Sarkozy","year":"2003","journal-title":"J Med Genet"},{"key":"2024073119501691200_ytae309-B7","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s12574-020-00477-7","article-title":"Systolic anterior motion of the posterior mitral leaflet in obstructive hypertrophic cardiomyopathy with Noonan syndrome","volume":"19","author":"Koide","year":"2021","journal-title":"J Echocardiogr"},{"key":"2024073119501691200_ytae309-B8","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1093\/eurheartj\/ehac262","article-title":"2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death","volume":"43","author":"Zeppenfeld","year":"2022","journal-title":"Eur Heart J"},{"key":"2024073119501691200_ytae309-B9","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1093\/eurheartj\/ehy037","article-title":"2018 ESC guidelines for the diagnosis and management of syncope","volume":"39","author":"Brignole","year":"2018","journal-title":"Eur Heart J"}],"container-title":["European Heart Journal - 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