{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:15:05Z","timestamp":1783577705728,"version":"3.55.0"},"reference-count":33,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"unspecified","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2022,11,21]]},"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The primary aim was to gain insight into the growth of the aortic root in children and young adults with Marfan syndrome (MFS). Furthermore, we aimed to identify a clinical profile of patients with MFS who require an aortic root replacement at a young age with specific interest in age, sex, height and fibrillin-1 (<jats:italic>FBN1<\/jats:italic>) genotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Aortic root dimensions of 97 patients with MFS between 0 year and 20 years and 30 controls were serially assessed with echocardiography. Trends were analysed using a linear mixed-effect model. Additionally, including only patients with MFS, we allowed trends to differ by sex, aortic root replacement and type of <jats:italic>FBN1<\/jats:italic> mutation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Average aortic root dilatation in patients with MFS became more pronounced after the age of 8\u2009years. In the MFS cohort, male patients had a significantly greater aortic root diameter than female patients, which was in close relationship with patient height. There was no difference in aortic root growth between children with dominant negative (DN) or haploinsufficient <jats:italic>FBN1<\/jats:italic> mutations. However, DN-<jats:italic>FBN1<\/jats:italic> variants resulting in loss of cysteine content were associated with a more severe phenotype. Eleven children needed an aortic root replacement. Compared with patients with MFS without aortic root surgery, these children had a significantly larger aortic root diameter from an early age.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study provides clinically useful longitudinal growth charts on aortic root growth in children and young adults with MFS. Children requiring prophylactic aortic root replacement during childhood can be identified at a young age. Our growth charts can help clinicians in decision making with regard to follow-up and prophylactic therapy. Loss of cysteine content in the <jats:italic>FBN1<\/jats:italic> protein was associated with larger aortic root dimensions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/openhrt-2022-002097","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T10:48:18Z","timestamp":1671619698000},"page":"e002097","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Growth of the aortic root in children and young adults with Marfan syndrome"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8592-9876","authenticated-orcid":false,"given":"Elroy","family":"van Els\u00e4cker","sequence":"first","affiliation":[{"name":"Paediatric Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arja S","family":"Vink","sequence":"additional","affiliation":[{"name":"Paediatric Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands"},{"name":"Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie A","family":"Menke","sequence":"additional","affiliation":[{"name":"Pediatrics, Amsterdam University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Pals","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Amsterdam University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Bokenkamp","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad C P M","family":"Backx","sequence":"additional","affiliation":[{"name":"Paediatric Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Hilhorst-Hofstee","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas A","family":"Blom","sequence":"additional","affiliation":[{"name":"Paediatric Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands"},{"name":"Pediatric Cardiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies E","family":"van der Hulst","sequence":"additional","affiliation":[{"name":"Paediatric Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"2025081710152304000_9.2.e002097.1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.21037\/acs.2017.11.10","article-title":"Natural history of aortic root aneurysms in Marfan syndrome","volume":"6","author":"Saeyeldin","year":"2017","journal-title":"Ann Cardiothorac Surg"},{"key":"2025081710152304000_9.2.e002097.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2009.11.040"},{"key":"2025081710152304000_9.2.e002097.3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.072785"},{"key":"2025081710152304000_9.2.e002097.4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1053\/j.pcsu.2008.01.005","article-title":"Thoracic aortic aneurysm syndrome in children","author":"Zanotti","year":"2008","journal-title":"Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu"},{"key":"2025081710152304000_9.2.e002097.5","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl457"},{"key":"2025081710152304000_9.2.e002097.6","doi-asserted-by":"publisher","DOI":"10.1007\/BF01959393"},{"key":"2025081710152304000_9.2.e002097.7","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1007\/s00246-018-1916-6","article-title":"Predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome","volume":"39","author":"Hoskoppal","year":"2018","journal-title":"Pediatr Cardiol"},{"key":"2025081710152304000_9.2.e002097.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(78)80601-5"},{"key":"2025081710152304000_9.2.e002097.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2010.03.019"},{"key":"2025081710152304000_9.2.e002097.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2008.02.006"},{"key":"2025081710152304000_9.2.e002097.11","doi-asserted-by":"crossref","unstructured":"Pals G , Syndrome M , Review A . 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