Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers–Danlos syndrome
Abstract Background Ehlers–Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders with varying features depending on the EDS subtype. EDS is associated with various respiratory manifestations. Pulmonary hemorrhage has been previously reported in vascular EDS (vEDS);...
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BMC
2025-07-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03858-2 |
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| author | Rong Yang Haiming Yang Chen Shen Xingfeng Yao Jinrong Liu Huimin Li Shunying Zhao |
| author_facet | Rong Yang Haiming Yang Chen Shen Xingfeng Yao Jinrong Liu Huimin Li Shunying Zhao |
| author_sort | Rong Yang |
| collection | DOAJ |
| description | Abstract Background Ehlers–Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders with varying features depending on the EDS subtype. 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. Methods 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. Results Our study identified eight patients with EDS who presented with pulmonary hemorrhage. Among these eight patients, nine gene mutations were identified, including four in COL3A1, two in COL1A1, one in COL1A2, one in TNXB, and one in COL4A2. We identified the mutations: IVS44 + 1G→A and c.1550 C > T (p. Pro517Leu) of COL3A1 gene as two novel mutations associated with vEDS. And we added pathogenic evidences of the mutations c.1550 C > T (p. Pro517Leu) and c.3133G > A (p. Ala1045Thr) in COL3A1 gene. Conclusions Two novel and two pathogenic mutations in COL3A1 gene associated with vEDS, COL1A1, COL1A2, TNXB gene mutations of non-vascular types underlying EDS and COL4A2 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. |
| format | Article |
| id | doaj-art-afc137498a38455fae08b86f6a31d7bf |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-afc137498a38455fae08b86f6a31d7bf2025-08-20T03:45:32ZengBMCOrphanet Journal of Rare Diseases1750-11722025-07-0120111110.1186/s13023-025-03858-2Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers–Danlos syndromeRong Yang0Haiming Yang1Chen Shen2Xingfeng Yao3Jinrong Liu4Huimin Li5Shunying Zhao6Department of Respiratory Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Respiratory Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthLaboratory of Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Center for Children’s Health, Beijing Pediatric Research Institute, Beijing Children’ s Hospital, Capital Medical UniversityDepartment of Pathology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Respiratory Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Respiratory Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Respiratory Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthAbstract Background Ehlers–Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders with varying features depending on the EDS subtype. 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. Methods 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. Results Our study identified eight patients with EDS who presented with pulmonary hemorrhage. Among these eight patients, nine gene mutations were identified, including four in COL3A1, two in COL1A1, one in COL1A2, one in TNXB, and one in COL4A2. We identified the mutations: IVS44 + 1G→A and c.1550 C > T (p. Pro517Leu) of COL3A1 gene as two novel mutations associated with vEDS. And we added pathogenic evidences of the mutations c.1550 C > T (p. Pro517Leu) and c.3133G > A (p. Ala1045Thr) in COL3A1 gene. Conclusions Two novel and two pathogenic mutations in COL3A1 gene associated with vEDS, COL1A1, COL1A2, TNXB gene mutations of non-vascular types underlying EDS and COL4A2 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.https://doi.org/10.1186/s13023-025-03858-2ChildrenEhlers–Danlos syndromePulmonary hemorrhage |
| spellingShingle | Rong Yang Haiming Yang Chen Shen Xingfeng Yao Jinrong Liu Huimin Li Shunying Zhao Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers–Danlos syndrome Orphanet Journal of Rare Diseases Children Ehlers–Danlos syndrome Pulmonary hemorrhage |
| title | Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers–Danlos syndrome |
| title_full | Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers–Danlos syndrome |
| title_fullStr | Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers–Danlos syndrome |
| title_full_unstemmed | Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers–Danlos syndrome |
| title_short | Pediatric pulmonary hemorrhage observed in non-vascular and vascular Ehlers–Danlos syndrome |
| title_sort | pediatric pulmonary hemorrhage observed in non vascular and vascular ehlers danlos syndrome |
| topic | Children Ehlers–Danlos syndrome Pulmonary hemorrhage |
| url | https://doi.org/10.1186/s13023-025-03858-2 |
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