Multisystem Caliber-Persistent Arteriopathy Syndrome: A Novel Congenital Vasculopathy Associated with a Risk of Multiorgan Hemorrhage

Multisystem Caliber-Persistent Arteriopathy Syndrome: A Novel Congenital Vasculopathy Associated with a Risk of Multiorgan Hemorrhage | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Multisystem Caliber-Persistent Arteriopathy Syndrome: A Novel Congenital Vasculopathy Associated with a Risk of Multiorgan Hemorrhage Guangtao Xu, Fengxia Li, Xin Jin, Bo Hu, Jun Yuan, Chaoqun Shi, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8074903/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract This study delineates a novel multisystem caliber-persistent arteriopathy syndrome, fundamentally redefining the classical Dieulafoy's lesion from a localized gastrointestinal anomaly to a systemic congenital vasculopathy. Through integrated histopathological and genomic analysis of a forensic autopsy case, we identified pervasive arterial remodeling across seven organ systems— characterized by absent physiological tapering— indicating developmental angiogenic dysregulation. Whole-genome sequencing uncovered pathogenic variants in PDE8B , LRCH1 , and ADA genes, with functional enrichment analyses implicating dysregulated purine–cAMP signaling and cytoskeletal organization as core pathogenic mechanisms. These findings establish a genetic basis for the observed pan-vascular phenotype and highlight the necessity of systematic vascular screening in cases of unexplained multiorgan hemorrhage. This work provides a foundational framework for diagnosing and investigating congenital vascular malformations with hemorrhagic risk, urging a paradigm shift in clinical evaluation and etiological assessment. Health sciences/Diseases/Cardiovascular diseases/Vascular diseases Health sciences/Risk factors Caliber-persistent arteriopathy Congenital vasculopathy Dieulafoy lesion Systemic vascular malformation Whole-genome sequencing cAMP signaling Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8074903","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":544187110,"identity":"a6904bac-a3d1-4497-a9e4-5b55725ad4ea","order_by":0,"name":"Guangtao Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYLCCDwxsYFqCOOVAxYwzSNbCzANlE6dFPr7HTNrmD1/ihgPMB2/zMNjlEdRieIwtTTqHh83Y4ABbsjUPQ3IxYS1tzMekcyTY5AwO8JhJ8zAcSGwgrIWxTdrCgI3H4AD/N+K0yLMBbWFIANvCRpwWA7a0ZMueA2zGkofZjC3nGCQTYUvzGcMbP/4cS+w73vzwxpsKOyJsOQCmjgFjB8wlpB5kC8TQGiKUjoJRMApGwYgFAL3+MVACQtABAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-5846-9280","institution":"Jiaxing University","correspondingAuthor":true,"prefix":"","firstName":"Guangtao","middleName":"","lastName":"Xu","suffix":""},{"id":544187111,"identity":"54423a1f-89f7-4d81-a5df-ff3577f65a3e","order_by":1,"name":"Fengxia Li","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Fengxia","middleName":"","lastName":"Li","suffix":""},{"id":544187112,"identity":"3d4dc843-42bf-42c3-afb3-d97f495c2ce3","order_by":2,"name":"Xin Jin","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Jin","suffix":""},{"id":544187113,"identity":"59a28ec4-b738-429b-b2ce-73ff29455752","order_by":3,"name":"Bo Hu","email":"","orcid":"","institution":"Jiaxing Hospital of TCM","correspondingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Hu","suffix":""},{"id":544187114,"identity":"b7a50811-2a53-487f-bdf8-8a3ed7b8276b","order_by":4,"name":"Jun Yuan","email":"","orcid":"","institution":"Jiaxing Maternity and Child Health Care Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Yuan","suffix":""},{"id":544187115,"identity":"acfe8215-71f2-4153-8a0a-c87671ebdb13","order_by":5,"name":"Chaoqun Shi","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Chaoqun","middleName":"","lastName":"Shi","suffix":""},{"id":544187116,"identity":"26746ae2-27db-4c60-8f1e-f56339ee7b51","order_by":6,"name":"Deqing Chen","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Deqing","middleName":"","lastName":"Chen","suffix":""},{"id":544187117,"identity":"c1b909d3-7b46-4532-b15f-ba3dc89b1f5b","order_by":7,"name":"Xiansi Zeng","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Xiansi","middleName":"","lastName":"Zeng","suffix":""},{"id":544187118,"identity":"28a8b5e4-b3fa-4405-8944-3417ddabaa51","order_by":8,"name":"Wanlu Li","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Wanlu","middleName":"","lastName":"Li","suffix":""},{"id":544187119,"identity":"351079d1-81b2-4d84-a64b-cbb3aea2fb6a","order_by":9,"name":"Shipiao Chen","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Shipiao","middleName":"","lastName":"Chen","suffix":""},{"id":544187120,"identity":"95748a48-4232-4877-9f00-8c7fe808225f","order_by":10,"name":"Long Xu","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Long","middleName":"","lastName":"Xu","suffix":""},{"id":544187121,"identity":"63d22075-c329-4fdd-9130-06161b46b09a","order_by":11,"name":"Jia Zhu","email":"","orcid":"","institution":"Mayo Clinic","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Zhu","suffix":""}],"badges":[],"createdAt":"2025-11-10 09:00:54","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8074903/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8074903/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97861692,"identity":"54c555c0-a0c1-47d7-9258-f3305d41b85b","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":39081439,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/d68c81c54f3be4afa0862c83.docx"},{"id":97861666,"identity":"3d56aad2-3123-4548-a639-5463ad0e8d55","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":342,"visible":true,"origin":"","legend":"","description":"","filename":"rs8074903.json","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/da16deee5cc874aeb4db8a4d.json"},{"id":97861680,"identity":"b1c83525-264d-44ee-aca7-1cdfad217e26","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":105750,"visible":true,"origin":"","legend":"","description":"","filename":"rs80749032enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/1866683b2ae1d762702b56be.xml"},{"id":97899594,"identity":"a09ca00d-465f-4a45-9701-1bd55a6803e0","added_by":"auto","created_at":"2025-12-10 15:44:45","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1900146,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage10.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/a81f55fec2c1c498c9969ca2.jpeg"},{"id":97897820,"identity":"5013ca5c-558e-4eea-9723-5e6a468c465c","added_by":"auto","created_at":"2025-12-10 15:38:18","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4188120,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage11.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/e07ae580c488cfb1715083ee.jpeg"},{"id":97900129,"identity":"a898b430-f5c8-40f0-a6dd-7dc94b651829","added_by":"auto","created_at":"2025-12-10 15:45:14","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3532894,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/1d43c4209e042c27690a2c9d.jpeg"},{"id":97899540,"identity":"93c33616-a763-41f7-8df9-2ad5fa63f578","added_by":"auto","created_at":"2025-12-10 15:44:43","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2894413,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/2e19d8b49ff31c864a3ee6a8.jpeg"},{"id":97897829,"identity":"8f0d99e1-a622-4a3a-b2fe-1755e7397ccb","added_by":"auto","created_at":"2025-12-10 15:38:19","extension":"jpeg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3309508,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/68ec096eb89e93273d839a30.jpeg"},{"id":97861671,"identity":"3c612c86-c428-459e-b8ff-13c6c9b91022","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"jpeg","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4170145,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/3177d910cb9121822075507b.jpeg"},{"id":97899399,"identity":"0f14b7b4-6827-4f81-b77c-fbe9824fdc23","added_by":"auto","created_at":"2025-12-10 15:43:34","extension":"jpeg","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3104031,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/1ec94bc759dd349164b2fd3b.jpeg"},{"id":97861667,"identity":"fa9ae8a6-0e4f-4bce-850e-93f4479208b1","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"jpeg","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1903284,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/d6a129edac9d32cc14f2467b.jpeg"},{"id":97861673,"identity":"7430946c-e27b-487c-8dfb-85eb8f2bace4","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"jpeg","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3315680,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/38590125566db27b71f585a5.jpeg"},{"id":97900730,"identity":"adf48808-a501-40c3-bf3c-1d1d5c667654","added_by":"auto","created_at":"2025-12-10 15:45:47","extension":"jpeg","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2049556,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage9.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/5f8df88fbfb6ce38d9fcba3f.jpeg"},{"id":97861670,"identity":"e08a30dc-1738-495c-a19c-b896a76e4610","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":17427,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/5bbf4d7b4fd1acfe9cebdc0d.png"},{"id":97900245,"identity":"faa7eac5-41ee-4beb-9a33-3d58b4980ec1","added_by":"auto","created_at":"2025-12-10 15:45:20","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":602667,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/bfc9f1fe8863844cb6a277f1.png"},{"id":97900155,"identity":"6490568c-f8ae-403c-880a-bf4662c0ba0c","added_by":"auto","created_at":"2025-12-10 15:45:16","extension":"png","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":227962,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/93a7e994f74cb842dc8f3443.png"},{"id":97861690,"identity":"87f14e00-11ff-4f83-8c7d-6702918717eb","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1197461,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/2893fd9ca000ab1ed8993164.png"},{"id":97861682,"identity":"9d714073-d77e-411e-b8c5-d918c89960da","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"png","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1017421,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/096256228a9d4b2e5f252dd5.png"},{"id":97899410,"identity":"0a42a9f7-d8b8-4f50-87f5-3685e765c97f","added_by":"auto","created_at":"2025-12-10 15:43:43","extension":"png","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1053595,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/38fbebce233ae692b75526ec.png"},{"id":97861684,"identity":"30b4bf8f-cb42-41da-8699-c7033f2caf85","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"png","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1565301,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/affc2895ebe021ee33cb2b05.png"},{"id":97899401,"identity":"d825da23-651c-460a-98e0-1247f8d89e8e","added_by":"auto","created_at":"2025-12-10 15:43:37","extension":"png","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1032713,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/cc37cb997f241a64b30f4148.png"},{"id":97900214,"identity":"daaa1eb0-ac8d-48b4-a201-ba80e6a90123","added_by":"auto","created_at":"2025-12-10 15:45:18","extension":"png","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":711601,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/38fbf2a2b1a3a9c33428d489.png"},{"id":97899796,"identity":"e0082c58-a210-4463-8893-57c4735536ee","added_by":"auto","created_at":"2025-12-10 15:44:55","extension":"png","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1069207,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/5ebbdd65a196ce216dadcf04.png"},{"id":97899769,"identity":"20e74a2e-2764-46a3-8ce3-4b4b54442062","added_by":"auto","created_at":"2025-12-10 15:44:52","extension":"png","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":732411,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/2faf2642ec7aacedfa484eb7.png"},{"id":97861685,"identity":"6e26e456-5113-4655-928b-c52b33ca6074","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"xml","order_by":25,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":104395,"visible":true,"origin":"","legend":"","description":"","filename":"rs80749032structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/cbc875500c58e71484eacfc0.xml"},{"id":97861688,"identity":"d0965291-cf82-4eb3-9f54-2d581dd99630","added_by":"auto","created_at":"2025-12-10 08:55:52","extension":"html","order_by":26,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":114207,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1/7195a971f5b9aa3174b6a06f.html"},{"id":97903401,"identity":"86da7b19-efbb-45cc-ad05-e98ab0e37402","added_by":"auto","created_at":"2025-12-10 15:55:20","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4409442,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8074903/v1_covered_8a5a0209-5d01-47e1-be96-ab5af3ea451b.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Multisystem Caliber-Persistent Arteriopathy Syndrome: A Novel Congenital Vasculopathy Associated with a Risk of Multiorgan Hemorrhage","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Caliber-persistent arteriopathy, Congenital vasculopathy, Dieulafoy lesion, Systemic vascular malformation, Whole-genome sequencing, cAMP signaling","lastPublishedDoi":"10.21203/rs.3.rs-8074903/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8074903/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study delineates a novel multisystem caliber-persistent arteriopathy syndrome, fundamentally redefining the classical Dieulafoy's lesion from a localized gastrointestinal anomaly to a systemic congenital vasculopathy. Through integrated histopathological and genomic analysis of a forensic autopsy case, we identified pervasive arterial remodeling across seven organ systems\u0026mdash; characterized by absent physiological tapering\u0026mdash; indicating developmental angiogenic dysregulation. Whole-genome sequencing uncovered pathogenic variants in \u003cem\u003ePDE8B\u003c/em\u003e, \u003cem\u003eLRCH1\u003c/em\u003e, and \u003cem\u003eADA\u003c/em\u003e genes, with functional enrichment analyses implicating dysregulated purine\u0026ndash;cAMP signaling and cytoskeletal organization as core pathogenic mechanisms. These findings establish a genetic basis for the observed pan-vascular phenotype and highlight the necessity of systematic vascular screening in cases of unexplained multiorgan hemorrhage. This work provides a foundational framework for diagnosing and investigating congenital vascular malformations with hemorrhagic risk, urging a paradigm shift in clinical evaluation and etiological assessment.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","manuscriptTitle":"Multisystem Caliber-Persistent Arteriopathy Syndrome: A Novel Congenital Vasculopathy Associated with a Risk of Multiorgan Hemorrhage","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-10 08:55:43","doi":"10.21203/rs.3.rs-8074903/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"439f5d35-79e7-49db-87ee-65194864dcff","owner":[],"postedDate":"December 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":57898742,"name":"Health sciences/Diseases/Cardiovascular diseases/Vascular diseases"},{"id":57898743,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2025-12-10T08:55:43+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-10 08:55:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8074903","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8074903","identity":"rs-8074903","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}