Application of the 2017 criteria for vascular Ehlers‐Danlos syndrome in 50 patients ascertained according to the Villefranche nosology

Abstract

Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder due to heterozygous pathogenic COL3A1 variants. Arterial, intestinal, and/or uterine fragility is the disease hallmark and results in reduced life expectancy. The clinical diagnosis is not always straightforward and patients' selection for molecular confirmation depends on the characteristics of applied criteria, that is, the Villefranche criteria (in use until 2017) and their revision according to the new EDS nosology. Herein, we reassessed the clinical features of 50 molecularly proven vEDS patients, diagnosed according to the Villefranche nosology between 2000 and 2016,using the 2017 classification in order to explore its clinical application. Our findings indicate that the Villefranche criteria were particularly valuable for symptomatic patients, even if with a limited specificity. Our study also suggests that the revised vEDS criteria, although expected to be more specific, might have a poorer accuracy, principally in terms of sensitivity. Both sets of criteria are less effective in presymptomatic young patients, especially in the absence of a clear-cut family history.For these patients, the careful evaluation of the cutaneous, articular, and dysmorphic features and, above all, genetic testing remain crucial to set-up proper follow-up and surveillance before catastrophic vascular and intestinal events.

Multisystemic manifestations in a cohort of 75 classical Ehlers-Danlos syndrome patients: natural history and nosological perspectives

“…Indeed, miscarriages, premature rupture of membranes, preterm birth, vaginal laceration during delivery, and post-partum uterine hemorrhage were rare or sporadic as well as rectal and urethral prolapse that occurred only in the most severely affected individual. Uterine rupture in the last trimester of pregnancy, which is particularly significant in vEDS as it associates with a high mortality rate (~ 5%) in affected females [ 46 , 117 , 118 ], did never happen in our patients. Overall, though the small sample size, pregnancy-associated complications seem to be unusual in cEDS.…”

“…This case highpoints that while molecular diagnosis in patients with a full-blown phenotype is mainly confirmatory, in those with an incomplete presentation it turns out to be fundamental, since these individuals might not be diagnosed or even be misdiagnosed. Indeed, considering the clinical overlap not only between the different EDS subtypes but also with other HCTDs [1,9,28,30,32,[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49], differential diagnosis is not always forthright. Differential diagnosis includes the molecularly unsolved hEDS that shares with cEDS gJHM and more than a few (muco) cutaneous signs; however, hEDS patients usually show a lower degree of scarring and skin hyperextensibility and much more striking gJHM complications [1,7,28,29,50].…”

Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes

“…Among the different EDS forms, vascular EDS (vEDS, OMIM#130050) is the most severe type and is primarily characterized by life-threatening features of tissue fragility leading to arterial dissection or aneurysm, gastrointestinal ruptures, and pregnancy complications at a young age [92,93].…”

Vascular Ehlers-Danlos Syndrome: Pathological Variants, Recent Discoveries, and Theoretical Approaches

“…21,22 Since the Villefranche criteria were dated back to 1997, the nosology was then reviewed and updated by the “The 2017 international classification of the Ehlers-Danlos syndromes,” which claimed to be more accurate. 5,21,23…”

“…5,6,23 Since both nosology are not sensitive enough in presymptomatic young patients, the molecular genetic test remains the most reliable diagnostic method. 23…”