{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:35:15Z","timestamp":1791999315356,"version":"4.4.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>We aimed to examine clinical features and outcomes of consecutive molecularly characterized patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      A retrospective, longitudinal multicenter cohort of consecutive children and adults with a genetic diagnosis of Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy between 2002 and 2019 was assembled. We defined a priori 3 different patterns of left ventricular remodeling during follow-up: (1) an increase in \u226515% of the maximal left ventricular wall thickness (MLVWT), both in mm and\n                      <jats:italic>z<\/jats:italic>\n                      -score (progression); (2) a reduction \u226515% of the MLVWT, both in mm and\n                      <jats:italic>z<\/jats:italic>\n                      -score (absolute regression); (3) a reduction \u226515% of the MLVWT\n                      <jats:italic>z<\/jats:italic>\n                      -score with a stable MLVWT in mm (relative regression). The primary study end point was a composite of cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator-shock.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      The cohort comprised 42 patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy, with a median age at diagnosis of 3.5 (interquartile range, 0.2\u201312.3) years. Freedom from primary end point was 92.7% (95% CI, 84.7%\u2013100%) 1 year after presentation and 80.9% (95% CI, 70.1%\u201390.7%) at 5 years. Patients with MLVWT\n                      <jats:italic>z<\/jats:italic>\n                      -score &gt;13.7 showed reduced survival compared with those with &lt;13.7. During a median follow-up of 3.7 years (interquartile range, 2.6\u20137.9), absolute regression was the most common type of left ventricular remodeling (n=9, 31%), followed by progression (n=6, 21%), and relative regression (n=6, 21%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These findings provide insights into the natural history of left ventricular hypertrophy, and can help inform clinicians regarding risk stratification and clinical outcomes in patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.122.003861","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T05:00:21Z","timestamp":1684386021000},"page":"350-358","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Natural History of Hypertrophic Cardiomyopathy in Noonan Syndrome With Multiple Lentigines"],"prefix":"10.1161","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9304-988X","authenticated-orcid":true,"given":"Emanuele","family":"Monda","sequence":"first","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Naples, Italy (E.M., R.A., M.L., M.C., M.G.R., G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1855-0900","authenticated-orcid":true,"given":"Aaron","family":"Prosnitz","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Levine Children\u2019s Hospital, Atrium Health, Charlotte, NC (A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Aiello","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Naples, Italy (E.M., R.A., M.L., M.C., M.G.R., G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0205-5235","authenticated-orcid":true,"given":"Michele","family":"Lioncino","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Naples, Italy (E.M., R.A., M.L., M.C., M.G.R., G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2064-237X","authenticated-orcid":true,"given":"Gabrielle","family":"Norrish","sequence":"additional","affiliation":[{"name":"Centre for Pediatric Inherited and Rare Cardiovascular Disease, Institute of Cardiovascular Science, University College London, United Kingdom (G.N., J.P.K.)."},{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (G.N., J.P.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Caiazza","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Naples, Italy (E.M., R.A., M.L., M.C., M.G.R., G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1888-373X","authenticated-orcid":true,"given":"Fabrizio","family":"Drago","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Cardiac Surgery, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Rome, Italy (F.D., G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9197-1854","authenticated-orcid":true,"given":"Meaghan","family":"Beattie","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Division of Genetics, Department of Pediatrics, Boston Children\u2019s Hospital, MA (M.B., S.D.C., A.E.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-9672","authenticated-orcid":true,"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Ospedale Pediatrico 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