{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:02:25Z","timestamp":1790708545123,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF23OC0082100"],"award-info":[{"award-number":["NNF23OC0082100"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003035","name":"Aase og Ejnar Danielsens Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003035","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":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lymphatic disease represents a well\u2010described manifestation of Noonan syndrome (NS), yet the full phenotypic spectrum remains incompletely characterized, especially in asymptomatic individuals. We conducted a cross\u2010sectional study including 10 individuals with NS (four with peripheral lymphedema and six without) and 10 age\u2010 and sex\u2010matched cardiovascularly healthy controls. Central lymphatic anatomy was visualized using non\u2010contrast T2\u2010weighted MR\u2010lymphangiography, and peripheral lymphatic morphology and function were assessed with near\u2010infrared fluorescence (NIRF) imaging and strain gauge plethysmography (SGP). Variations in thoracic duct morphology were observed in 89% (8\/9) of NS individuals compared to 20% (2\/10) of controls. Thoracic lymphatic classifications (Biko\/Dori scale) differed significantly in NS individuals, both with and without lymphedema, compared with healthy controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Central lymphatic abnormalities were observed in five of nine NS individuals, including three without clinical signs of lymphatic disease. Abnormal peripheral conduction in collective vessels, characterized by retrograde or absent flow, was detected in all four NS individuals with lymphedema (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), while normal conduction was observed in asymptomatic NS individuals and controls. Findings from this study indicate that central lymphatic abnormalities may be present in NS regardless of symptom status, with abnormal peripheral conduction developing later in association with clinically manifest lymphedema. Central lymphatic abnormalities extend beyond clinically apparent disease and broaden the recognized phenotype, highlighting the value of lymphatic imaging for diagnosis and monitoring.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70146","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:20:25Z","timestamp":1777864825000},"page":"2211-2223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lymphatic Abnormalities in Noonan Syndrome Extend Beyond Clinically Apparent Disease"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5408-8701","authenticated-orcid":false,"given":"Inger Norlyk","family":"Sheyanth","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine Copenhagen University  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7472-4237","authenticated-orcid":false,"given":"Benjamin","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheyanth","family":"Mohanakumar","sequence":"additional","affiliation":[{"name":"AURA, Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Radiology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Ringgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, MR Research Center Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Dori","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Children's Hospital of Philadelphia and University of Pennsylvania, Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene Kib\u00e6k","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aalborg University Hospital  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uffe Birk","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8047-0015","authenticated-orcid":false,"given":"Vibeke Elisabeth","family":"Hjortdal","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine Copenhagen University  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241914827"},{"key":"e_1_2_11_3_1","volume-title":"Sequential MRI Evaluation of Lymphatic Abnormalities Over the Course of Fontan Completion","author":"Benjamin 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