This review shows that rare vascular diseases are not just isolated curiosities: many are driven by shared pathways of vascular fragility, abnormal remodeling, and delayed diagnosis. It highlights where genetics, imaging, and targeted therapies are already turning rare vascular biology into practical clinical decisions.
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Abstract: The aim of this paper is to synthesize current evidence regarding the pathophysiology, diagnostic advancements, and therapeutic strategies for rare vascular diseases, utilizing a diverse range of clinical and experimental studies to identify common themes in vascular dysfunction and management. The review utilises 66 original studies with 6238 total participants (topic deduplicated ΣN). This evidence map suggests that rare vascular disease is unified less by a single phenotype than by recurrent disruptions in vascular signaling, extracellular matrix integrity, endothelial behavior, and vascular smooth muscle cell homeostasis, with notable quantitative signals including a roughly 30% contribution of chromatin modifier and EPHB4 variants in vein of Galen malformations, a 25.7-year mean diagnostic delay in hereditary haemorrhagic telangiectasia, a 4.7% annual major vascular event risk in celiprolol-treated vascular Ehlers-Danlos syndrome, and partial response or stabilization in most reported kaposiform lymphangiomatosis cases treated with sirolimus. Across the major topics, the strongest recurring pattern is that molecularly defined subgroups—such as COL5A1-, DIAPH1-, VEGFC-, and NOTCH-related vasculopathies—help explain why these disorders present with widely different manifestations yet may still converge on shared pathways of remodeling, fragility, fibrosis, and hemorrhage. The review also highlights a practical clinical message: earlier recognition supported by targeted imaging and genetic evaluation may reduce misdiagnosis and enable more tailored surveillance or therapy in conditions that are otherwise discovered only after major complications. At the same time, the mapped evidence remains dominated by rare-disease observational and case-based literature, so therapeutic signals should be interpreted as promising rather than definitive. Future research should prioritize multicenter longitudinal cohorts and mechanism-linked interventional studies that connect genotype, vascular phenotype, and treatment response across these heterogeneous but biologically informative disorders.
Final search date and database lock: 2026-04-12 00:01:37 CEST
Plan: Pro (expanded craft tokens; source: Semantic Scholar)
Source: Semantic Scholar
Total Abstracts/Papers: 936470
Downloaded Abstracts/Papers: 1000
Included original and non-original Abstracts/Papers (all): 129
Included original Abstracts/Papers (Vote counting by direction of effect): 66
Reference Index (links used in paper): 75
Total participants (topic deduplicated ΣN): 6238
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The Evidence Object JSON is a separate machine-readable evidence product: a concentrated synthesis of results, topic-level evidence, and discussion across original and non-original studies. It can be directly input into your LLM, agent, or RAG workflow.
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[25] ATP-based therapy prevents vascular calcification and extends longevity in a mouse model of Hutchinson–Gilford progeria syndrome — https://doi.org/10.1073/pnas.1910972116
[28] A Novel Recurrent COL5A1 Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia — https://doi.org/10.1161/atvbaha.119.313885
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[78] Traumatic Arteriovenous Fistula of the Scalp in the Left Temporoparietal Region with Intra- and Extracranial Blood Supply — https://doi.org/10.1155/2016/8671472
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[101] European Reference Network for Rare Vascular Diseases (VASCERN) position statement on cerebral screening in adults and children with hereditary haemorrhagic telangiectasia (HHT) — https://doi.org/10.1186/s13023-020-01386-9
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