{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T05:47:25Z","timestamp":1775454445988,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Cardiovascular manifestations in pediatric Marfan syndrome (MFS) exhibit substantial heterogeneity. Early identification of patients at elevated risk of requiring cardiac surgery is essential to optimizing outcomes. This study aimed to determine phenotypic features associated with cardiovascular surgery in genetically confirmed pediatric MFS. Methods: Among the 1006 children evaluated, 214 with genetically verified MFS were included in the analysis. We categorized patients by the presence or absence of cardiac surgery during childhood. Systemic and cardiovascular features were assessed. We applied binary logistic regression to identify independent associated manifestations with surgical intervention. Results: 20\/214 patients (9.3%, 11.5 \u00b1 5.5 years) underwent cardiac surgery (50% aortic root replacement, 20% mitral valve surgery, 30% combined interventions). Extracardiac features\u2014Marfan-type facial features, pectus carinatum, pes planus, hindfoot deformity, and myopia of \u22653 diopters\u2014were significantly associated with an increased probability of surgery (OR 3.0\u20134.6). Tricuspid valve prolapse and pulmonary artery dilatation were more prevalent in surgical patients. Surgical patients exhibited higher systemic manifestation scores (9.2 vs. 5.2; p \u2264 0.05) per revised Ghent criteria (RGC). Conclusions: A higher systemic score (RGC) correlates with increased risk for surgery. Marfan-type facial features, pectus carinatum, pes planus, hindfoot deformity, and myopia \u2265 3 diopters were strongly associated with the need for early cardiac surgery. Comprehensive phenotypic assessment, including systemic manifestation scoring, enables risk stratification and supports timely surgical planning in pediatric MFS.<\/jats:p>","DOI":"10.3390\/children13040504","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:10:27Z","timestamp":1775448627000},"page":"504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic Associations of Early Cardiovascular Surgery in Pediatric Marfan Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3978-1804","authenticated-orcid":false,"given":"Veronika C.","family":"Stark","sequence":"first","affiliation":[{"name":"Pediatric Cardiology, Clinic for Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8337-5187","authenticated-orcid":false,"given":"Thomas S.","family":"Mir","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Clinic for Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caja","family":"Langkat","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Clinic for Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1895-8570","authenticated-orcid":false,"given":"Daniel","family":"Biermann","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Surgery, Clinic for Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna J.","family":"Kanitz","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Clinic for Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2556-6804","authenticated-orcid":false,"given":"Gerhard","family":"Schoen","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5096-8421","authenticated-orcid":false,"given":"Yskert","family":"von Kodolitsch","sequence":"additional","affiliation":[{"name":"Clinic for Heart Surgery and Vascular Surgery, Herz- und Diabeteszentrum NRW, Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Lang","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Clinic for Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6222-2683","authenticated-orcid":false,"given":"Rainer","family":"Kozlik-Feldmann","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Clinic for Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Huebler","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Surgery, Clinic for Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4449-7739","authenticated-orcid":false,"given":"Jakob","family":"Olfe","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Clinic for Pediatric Heart Medicine and Adults with Congenital Heart Disease, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s13023-015-0369-8","article-title":"Prevalence, Incidence, and Age at Diagnosis in Marfan Syndrome","volume":"10","author":"Groth","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/352337a0","article-title":"Marfan Syndrome Caused by a Recurrent de Novo Missense Mutation in the Fibrillin Gene","volume":"352","author":"Dietz","year":"1991","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102051","DOI":"10.1016\/j.jacadv.2025.102051","article-title":"Phenotypic Diversity of Marfan Syndrome","volume":"4","author":"Xu","year":"2025","journal-title":"JACC Adv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s13148-021-01204-4","article-title":"Genome-Wide Methylation Patterns in Marfan Syndrome","volume":"13","author":"Groenink","year":"2021","journal-title":"Clin. Epigenetics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"169","DOI":"10.14740\/cr2033","article-title":"A Review on the Role of DNA Methylation in Aortic Disease Associated With Marfan Syndrome","volume":"16","author":"Zhang","year":"2025","journal-title":"Cardiol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1093\/cvr\/cvaf248","article-title":"Myeloperoxidase Aggravates Thoracic Aortic Aneurysm Formation in Marfan Disease","volume":"122","author":"Mehrkens","year":"2026","journal-title":"Cardiovasc. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1038\/s41431-018-0164-9","article-title":"Association of Modifiers and Other Genetic Factors Explain Marfan Syndrome Clinical Variability","volume":"26","author":"Aubart","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1542\/peds.2008-0703","article-title":"Clinical and Molecular Study of 320 Children With Marfan Syndrome and Related Type I Fibrillinopathies in a Series of 1009 Probands With Pathogenic FBN1 Mutations","volume":"123","author":"Faivre","year":"2009","journal-title":"Pediatrics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s00246-012-0593-0","article-title":"Impact of Age and Gender on Cardiac Pathology in Children and Adolescents With Marfan Syndrome","volume":"34","author":"Mueller","year":"2013","journal-title":"Pediatr. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s00246-015-1101-0","article-title":"Aortic Involvement in Pediatric Marfan Syndrome: A Review","volume":"36","author":"Ekhomu","year":"2015","journal-title":"Pediatr. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1136\/adc.84.2.129","article-title":"Natural History of Cardiovascular Manifestations in Marfan Syndrome","volume":"84","year":"2001","journal-title":"Arch. Dis. Child."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/jmg.2009.072785","article-title":"The Revised Ghent Nosology for the Marfan Syndrome","volume":"47","author":"Loeys","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.echo.2008.02.006","article-title":"Regression Equations for Calculation of Z Scores of Cardiac Structures in a Large Cohort of Healthy Infants, Children, and Adolescents: An Echocardiographic Study","volume":"21","author":"Pettersen","year":"2008","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.amjcard.2009.11.040","article-title":"Nomograms for Aortic Root Diameters in Children Using Two-Dimensional Echocardiography","volume":"105","author":"Gautier","year":"2010","journal-title":"Am. J. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00246-018-2025-2","article-title":"Differences in Cardiovascular Manifestation of Marfan Syndrome Between Children and Adults","volume":"40","author":"Sabiniewicz","year":"2019","journal-title":"Pediatr. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.acvd.2019.09.010","article-title":"Incidence of Cardiovascular Events and Risk Markers in a Prospective Study of Children Diagnosed with Marfan Syndrome","volume":"113","author":"Hascoet","year":"2020","journal-title":"Arch. Cardiovasc. Dis."},{"key":"ref_17","first-page":"e002058","article-title":"Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome","volume":"11","author":"Takeda","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1086\/302582","article-title":"Cysteine Substitutions in Epidermal Growth Factor\u2013Like Domains of Fibrillin-1: Distinct Effects on Biochemical and Clinical Phenotypes","volume":"65","author":"Schrijver","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1086\/520125","article-title":"Effect of Mutation Type and Location on Clinical Outcome in 1,013 Probands with Marfan Syndrome or Related Phenotypes and FBN1 Mutations: An International Study","volume":"81","author":"Faivre","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1038\/s41436-021-01132-x","article-title":"Clinical Relevance of Genotype\u2013Phenotype Correlations beyond Vascular Events in a Cohort Study of 1500 Marfan Syndrome Patients with FBN1 Pathogenic Variants","volume":"23","author":"Arnaud","year":"2021","journal-title":"Genet. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/BPB.0000000000000798","article-title":"Marfan Syndrome in Children: Correlation between Musculoskeletal Features and Cardiac Z-Score","volume":"30","author":"Pisano","year":"2021","journal-title":"J. Pediatr. Orthop. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1001\/archpedi.162.9.882","article-title":"Incidence of Aortic Root Dilatation in Pectus Excavatum and Its Association With Marfan Syndrome","volume":"162","author":"Rhee","year":"2008","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"\u00c1gg, B., Benke, K., Szilveszter, B., P\u00f3los, M., Dar\u00f3czi, L., Odler, B., Nagy, Z.B., Tarr, F., Merkely, B., and Szabolcs, Z. (2014). Possible Extracardiac Predictors of Aortic Dissection in Marfan Syndrome. BMC Cardiovasc. Disord., 14.","DOI":"10.1186\/1471-2261-14-47"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1007\/s00246-024-03502-z","article-title":"Extracardiac Manifestations Fail to Predict the Severity of Cardiac Phenotype in Children and Young Adults with Marfan Syndrome","volume":"46","author":"John","year":"2025","journal-title":"Pediatr. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1007\/s00246-018-1880-1","article-title":"The Pulmonary Artery in Pediatric Patients with Marfan Syndrome: An Underestimated Aspect of the Disease","volume":"39","author":"Stark","year":"2018","journal-title":"Pediatr. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1111\/apa.16307","article-title":"Tricuspid Valve Prolapse as an Early Predictor for Severe Phenotype in Children with Marfan Syndrome","volume":"111","author":"Stark","year":"2022","journal-title":"Acta Paediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e228","DOI":"10.1161\/CIR.0000000000001265","article-title":"Cardiovascular Management of Aortopathy in Children: A Scientific Statement From the American Heart Association","volume":"150","author":"Morris","year":"2024","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ijcard.2005.01.040","article-title":"Determinants of Rapid Progression of Aortic Root Dilatation and Complications in Marfan Syndrome","volume":"106","author":"Lazarevic","year":"2006","journal-title":"Int. J. Cardiol."},{"key":"ref_29","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":"ref_30","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s13023-021-01882-6","article-title":"Potential Predictors of Severe Cardiovascular Involvement in Marfan Syndrome: The Emphasized Role of Genotype\u2013Phenotype Correlations in Improving Risk Stratification\u2014A Literature Review","volume":"16","author":"Stengl","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1097\/01.hco.0000139723.49937.43","article-title":"Timing of Aortic Surgery in the Marfan Syndrome","volume":"19","author":"Braverman","year":"2004","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jtcvs.2023.10.041","article-title":"Valve-Sparing Root Replacement in Children with Connective Tissue Disease: Long-Term Risk of Aortic Events","volume":"168","author":"Park","year":"2024","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/S0140-6736(22)01534-3","article-title":"Angiotensin Receptor Blockers and \u03b2 Blockers in Marfan Syndrome: An Individual Patient Data Meta-Analysis of Randomised Trials","volume":"400","author":"Pitcher","year":"2022","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1080\/14779072.2019.1704625","article-title":"Features of Marfan Syndrome Not Listed in the Ghent Nosology\u2013the Dark Side of the Disease","volume":"17","author":"Demolder","year":"2019","journal-title":"Expert Rev. Cardiovasc. Ther."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/4\/504\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:45:26Z","timestamp":1775450726000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/4\/504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["children13040504"],"URL":"https:\/\/doi.org\/10.3390\/children13040504","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]}}}