Incidental asymptomatic artery dissection revealing vascular Ehlers-Danlos syndrome in a 52-year-old patient

    Authors

    Keywords

    arterial dissection, vascular Ehlers-Danlos syndrome, heritable connective tissue disorder

    DOI

    https://doi.org/10.15836/ccar2025.248

    Full Text

    **Introduction**: Vascular Ehlers-Danlos syndrome (vEDS) is a rare genetic connective tissue disorder caused by pathogenic variants in COL3A1, a gene encoding type III collagen. Consequent tissue fragility manifests in a specific clinical phenotype, as well as possible life-threatening complications such as spontaneous arterial dissection or rupture, bowel perforation, and uterine rupture. Initial presentation typically occurs in early adulthood, whereas median life expectancy is estimated at 51 years (1). While diagnosis may be guided by clinical criteria, molecular confirmation is required (2). **Case report**: A 52-year-old man with arterial hypertension and bilateral renal cysts was incidentally diagnosed with a left external iliac artery dissection during a routine computed tomography (CT) scan (**Figure 1**). He reported no inguinal pain and showed no signs of limb ischemia. Further assessment revealed a family history of vascular events: his father died at 55 from a ruptured aortic aneurysm, and his paternal grandfather experienced sudden death at 50. Physical examination showed subtle features suggestive of vEDS, including micrognathia, keloids, varicose veins, and flat feet with piezogenic papules. A subsequent CT scan revealed bilateral saccular aneurysms at the renal artery bifurcations (**Figure 2**), in addition to the previously identified iliac artery dissection. Next-generation sequencing identified a heterozygous COL3A1 missense mutation, p.Gly237Arg. This variant was classified as pathogenic, confirming a diagnosis of vEDS. The patient was started on celiprolol and irbesartan, as these medications have been shown to reduce the incidence of major arterial events in patients with vEDS (3). Lifestyle modifications were advised, and cascade genetic testing was recommended for relatives. FIGURE 1. Contrast-enhanced CT angiography (maximum intensity projection reconstruction, oblique coronal plane) showing a dissected left external iliac artery with an intimal flap (white arrows). FIGURE 2. Contrast-enhanced CT angiography showing a right renal artery aneurysm. A) maximum intensity projection reconstruction (oblique coronal), black arrow. B) axial plane, white arrow. **Conclusion**: Although most vEDS patients develop major arterial complications by the age of 40, disease onset is variable and may present later, as observed in our patient. Despite appropriate management, these patients remain at high risk of morbidity and mortality. This case emphasizes the importance of considering vEDS in asymptomatic adults with incidental vascular findings, subtle connective tissue signs, and a relevant family history, in order to enhance clinical awareness and diagnostic accuracy.

    Literature

    1. Pepin MG, Schwarze U, Rice KM, Liu M, Leistritz D, Byers PH. Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). Genet Med. 2014 December;16(12):881–8. https://doi.org/10.1038/gim.2014.72
    2. Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017 March;175(1):8–26. https://doi.org/10.1002/ajmg.c.31552
    3. Jeunemaitre X, Mousseaux E, Frank M, Adham S, Pitocco F, Billon C, et al. Efficacy of Irbesartan in Celiprolol-Treated Patients With Vascular Ehlers-Danlos Syndrome. Circulation. 2025 March 11;151(10):686–95. https://doi.org/10.1161/CIRCULATIONAHA.124.072849
    Cardiologia Croatica
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    Incidental asymptomatic artery dissection revealing vascular Ehlers-Danlos syndrome in a 52-year-old patient

    Extended Abstract
    Issue9-10
    Published
    Pages248-249
    PDF via DOIhttps://doi.org/10.15836/ccar2025.248
    arterial dissection
    vascular Ehlers-Danlos syndrome
    heritable connective tissue disorder

    Authors

    Anica Milinković*ORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Mia Dubravčić DošenORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Petra Grubić RotkvićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Tomislav KrčmarORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Ivana JurcaORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Sanda Huljev FrkovićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Majda Vrkić KirhmajerORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia

    *Correspondence email: anica.milinkovic@outlook.com

    Full Text

    Introduction: Vascular Ehlers-Danlos syndrome (vEDS) is a rare genetic connective tissue disorder caused by pathogenic variants in COL3A1, a gene encoding type III collagen. Consequent tissue fragility manifests in a specific clinical phenotype, as well as possible life-threatening complications such as spontaneous arterial dissection or rupture, bowel perforation, and uterine rupture. Initial presentation typically occurs in early adulthood, whereas median life expectancy is estimated at 51 years (1). While diagnosis may be guided by clinical criteria, molecular confirmation is required (2).

    Case report: A 52-year-old man with arterial hypertension and bilateral renal cysts was incidentally diagnosed with a left external iliac artery dissection during a routine computed tomography (CT) scan (Figure 1). He reported no inguinal pain and showed no signs of limb ischemia. Further assessment revealed a family history of vascular events: his father died at 55 from a ruptured aortic aneurysm, and his paternal grandfather experienced sudden death at 50. Physical examination showed subtle features suggestive of vEDS, including micrognathia, keloids, varicose veins, and flat feet with piezogenic papules. A subsequent CT scan revealed bilateral saccular aneurysms at the renal artery bifurcations (Figure 2), in addition to the previously identified iliac artery dissection. Next-generation sequencing identified a heterozygous COL3A1 missense mutation, p.Gly237Arg. This variant was classified as pathogenic, confirming a diagnosis of vEDS. The patient was started on celiprolol and irbesartan, as these medications have been shown to reduce the incidence of major arterial events in patients with vEDS (3). Lifestyle modifications were advised, and cascade genetic testing was recommended for relatives.

    FIGURE 1. Contrast-enhanced CT angiography (maximum intensity projection reconstruction, oblique coronal plane) showing a dissected left external iliac artery with an intimal flap (white arrows).

    FIGURE 2. Contrast-enhanced CT angiography showing a right renal artery aneurysm. A) maximum intensity projection reconstruction (oblique coronal), black arrow. B) axial plane, white arrow.

    Conclusion: Although most vEDS patients develop major arterial complications by the age of 40, disease onset is variable and may present later, as observed in our patient. Despite appropriate management, these patients remain at high risk of morbidity and mortality. This case emphasizes the importance of considering vEDS in asymptomatic adults with incidental vascular findings, subtle connective tissue signs, and a relevant family history, in order to enhance clinical awareness and diagnostic accuracy.

    Literature

    1. 1.
      Pepin MG, Schwarze U, Rice KM, Liu M, Leistritz D, Byers PH. Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). Genet Med. 2014 December;16(12):881–8.DOI
    2. 2.
      Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017 March;175(1):8–26.DOI
    3. 3.
      Jeunemaitre X, Mousseaux E, Frank M, Adham S, Pitocco F, Billon C, et al. Efficacy of Irbesartan in Celiprolol-Treated Patients With Vascular Ehlers-Danlos Syndrome. Circulation. 2025 March 11;151(10):686–95.DOI