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EDS is associated with various respiratory manifestations. Pulmonary hemorrhage has been previously reported in vascular EDS (vEDS); however, this manifestation remains not particularly well-defined in other subtypes of EDS. This study extends the clinical understanding of EDS, particularly non-vascular EDS, and expands etiological spectrum of pulmonary hemorrhage in children.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We retrospectively analyzed the records of patients diagnosed with EDS between January 2020 and November 2024 at our institute. All clinical data was extracted from the electronic medical records, including clinical presentation, physical examination, family history, and chest computed tomography scans. EDS was confirmed based on clinical manifestations, pathological biopsies, immunohistochemistry, immunofluorescence staining, and genetic testing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Our study identified eight patients with EDS who presented with pulmonary hemorrhage. Among these eight patients, nine gene mutations were identified, including four in <jats:italic>COL3A1<\/jats:italic>, two in <jats:italic>COL1A1<\/jats:italic>, one in <jats:italic>COL1A2<\/jats:italic>, one in <jats:italic>TNXB<\/jats:italic>, and one in <jats:italic>COL4A2<\/jats:italic>. We identified the mutations: IVS44\u2009+\u20091G\u2192A and c.1550\u00a0C\u2009&gt;\u2009T (p. Pro517Leu) of <jats:italic>COL3A1<\/jats:italic> gene as two novel mutations associated with vEDS. And we added pathogenic evidences of the mutations c.1550\u00a0C\u2009&gt;\u2009T (p. Pro517Leu) and c.3133G\u2009&gt;\u2009A (p. Ala1045Thr) in <jats:italic>COL3A1<\/jats:italic> gene.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Two novel and two pathogenic mutations in <jats:italic>COL3A1<\/jats:italic> gene associated with vEDS, <jats:italic>COL1A1<\/jats:italic>, <jats:italic>COL1A2<\/jats:italic>, <jats:italic>TNXB<\/jats:italic> gene mutations of non-vascular types underlying EDS and <jats:italic>COL4A2<\/jats:italic> gene associated with collagen synthesis were found in patients presenting with pulmonary hemorrhage. These findings would enhance clinical recognition of EDS and provide a sound basis to recommend that children with pulmonary hemorrhage be routinely examined for joint and skin hyperextension.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-03858-2","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T10:59:54Z","timestamp":1751367594000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers\u2013Danlos syndrome"],"prefix":"10.1186","volume":"20","author":[{"given":"Rong","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingfeng","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3011-0433","authenticated-orcid":false,"given":"Shunying","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"issue":"1","key":"3858_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/ajmg.c.31552","volume":"175","author":"F Malfait","year":"2017","unstructured":"Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. 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