Clinical bottom line
Rare inherited connective tissue disorders with vascular complications, including vascular Ehlers-Danlos syndrome (vEDS), Marfan syndrome, and osteogenesis imperfecta (OI), present significant clinical challenges due to their predisposition to arterial fragility, aneurysm formation, and dissection. Current evidence underscores the importance of early diagnosis, vigilant cardiovascular monitoring, and individualized management strategies to mitigate life-threatening vascular events. While surgical and endovascular interventions may be necessary, they carry heightened risks in this population. Multidisciplinary care and tailored emergency protocols are essential to optimize outcomes. However, evidence remains limited by small case series and expert opinion, highlighting the need for further systematic study.
What the evidence shows
Inherited connective tissue disorders such as vEDS, Marfan syndrome, and OI share a common pathophysiology involving defective collagen or fibrillin-1, leading to vascular wall weakness and increased risk of arterial rupture or dissection (Elliott Perry et al., 2020; Ferri et al., 2009). Vascular Ehlers-Danlos syndrome, caused by COL3A1 mutations, is characterized by spontaneous arterial rupture, often in medium-sized arteries, with a median survival age in the fourth to fifth decade (Alayasa et al., 2025). Clinical management is complicated by the fragility of tissues, which elevates procedural risks.
Alayasa et al. (2025) reported on three vEDS cases illustrating challenges in emergency and elective management, emphasizing the need for cautious surgical approaches and the potential utility of celiprolol to reduce vascular events, consistent with prior observational data. Similarly, Patel et al. (2025) described a Stanford Type B aortic dissection in a patient with OI, highlighting that although OI primarily affects bone, vascular complications can be severe and require tailored endovascular or surgical intervention with heightened vigilance for procedural complications.
Marfan syndrome, linked to FBN1 mutations, predisposes to aortic root dilation and dissection, with echocardiography playing a pivotal role in surveillance (Elliott Perry et al., 2020; Lewin et al., 2007). Beta-blockers and angiotensin receptor blockers remain mainstays to slow aortic dilation, though evidence is largely extrapolated from observational cohorts. Emergency management protocols must account for connective tissue fragility, as detailed by Biggers et al. (2011), who advocate for specialized care pathways to reduce morbidity and mortality.
Dermatology Fundamentals (2026) and Ferri et al. (2009) provide comprehensive overviews of genodermatoses and connective tissue disorders, underscoring the multisystem involvement and the necessity for coordinated care. Echocardiography and imaging surveillance are critical for early detection of vascular complications (Lewin et al., 2007).
Caveats and uncertainty
The evidence base for management strategies in rare inherited connective tissue disorders with vascular complications is limited by small patient numbers, reliance on case reports and series, and lack of randomized controlled trials. Many recommendations derive from expert consensus or extrapolation from related conditions. The heterogeneity of phenotypes and genotypes complicates risk stratification and individualized treatment planning.
Pharmacologic interventions such as celiprolol in vEDS or angiotensin receptor blockers in Marfan syndrome show promise but require further validation in larger, controlled studies. Surgical and endovascular interventions carry increased procedural risk due to tissue fragility, and optimal timing and techniques remain under investigation. Emergency management protocols are often institution-specific and lack standardization.
Furthermore, the overlap in clinical features among connective tissue disorders can delay diagnosis, underscoring the need for heightened clinical suspicion and genetic testing where appropriate. Long-term outcomes data remain sparse, limiting prognostic counseling.
How this may change practice
Clinicians managing patients with rare inherited connective tissue disorders should prioritize early diagnosis through genetic testing and multidisciplinary evaluation. Regular cardiovascular imaging, particularly echocardiography and cross-sectional vascular imaging, is essential for surveillance of aneurysms and dissections.
Pharmacologic therapy aimed at reducing hemodynamic stress on vessels, such as beta-blockers or celiprolol, should be considered, acknowledging the current limitations in high-level evidence. Surgical and endovascular interventions require specialized expertise and careful risk-benefit assessment, ideally in centers experienced with connective tissue disorders.
Emergency departments and surgical teams should develop protocols tailored to the fragility of these patients’ tissues to minimize iatrogenic injury. Patient education on symptom recognition and avoidance of high-risk activities is critical.
Overall, this evidence supports a cautious, individualized approach integrating genetic diagnosis, vigilant monitoring, pharmacotherapy, and multidisciplinary care to improve outcomes in this vulnerable population.