TY - JOUR
T1 - Vascular Ehlers-Danlos Syndrome
T2 - A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients
AU - Demirdas, Serwet
AU - van den Bersselaar, Lisa M
AU - Lechner, Rosan
AU - Bos, Jessica
AU - Alsters, Suzanne I M
AU - Baars, Marieke J H
AU - Baas, Annette F
AU - Baysal, Özlem
AU - van der Crabben, Saskia N
AU - Dulfer, Eelco
AU - Giesbertz, Noor A A
AU - Helderman-van den Enden, Apollonia T J M
AU - Hilhorst-Hofstee, Yvonne
AU - Kempers, Marlies J E
AU - Komdeur, Fenne L
AU - Loeys, Bart
AU - Majoor-Krakauer, Daniëlle
AU - Ockeloen, Charlotte W
AU - Overwater, Eline
AU - van Tintelen, Peter J
AU - Voorendt, Marsha
AU - de Waard, Vivian
AU - Maugeri, Alessandra
AU - Brüggenwirth, Hennie T
AU - van de Laar, Ingrid M B H
AU - Houweling, Arjan C
PY - 2024/4/16
Y1 - 2024/4/16
N2 - BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with a high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in COL3A1. The aim of this cohort study is to provide further insights into the natural history of vEDS and describe genotype-phenotype correlations in a Dutch multicenter cohort to optimize patient care and increase awareness of the disease. METHODS: Individuals with vEDS throughout the Netherlands were included. The phenotype was charted by retrospective analysis of molecular and clinical data, combined with a one-time physical examination.RESULTS: A total of 142 individuals (50% female) participated the study, including 46 index patients (32%). The overall median age at genetic diagnosis was 41.0 years. More than half of the index patients (54.3%) and relatives (53.1%) had a physical appearance highly suggestive of vEDS. In these individuals, major events were not more frequent ( P=0.90), but occurred at a younger age ( P=0.01). A major event occurred more often and at a younger age in men compared with women ( P<0.001 and P=0.004, respectively). Aortic aneurysms ( P=0.003) and pneumothoraces ( P=0.029) were more frequent in men. Aortic dissection was more frequent in individuals with a COL3A1 variant in the first quarter of the collagen helical domain ( P=0.03). CONCLUSIONS: Male sex, type and location of the COL3A1 variant, and physical appearance highly suggestive of vEDS are risk factors for the occurrence and/or early age of onset of major events. This national multicenter cohort study of Dutch individuals with vEDS provides a valuable basis for improving guidelines for the diagnosing, follow-up, and treatment of individuals with vEDS.
AB - BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with a high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in COL3A1. The aim of this cohort study is to provide further insights into the natural history of vEDS and describe genotype-phenotype correlations in a Dutch multicenter cohort to optimize patient care and increase awareness of the disease. METHODS: Individuals with vEDS throughout the Netherlands were included. The phenotype was charted by retrospective analysis of molecular and clinical data, combined with a one-time physical examination.RESULTS: A total of 142 individuals (50% female) participated the study, including 46 index patients (32%). The overall median age at genetic diagnosis was 41.0 years. More than half of the index patients (54.3%) and relatives (53.1%) had a physical appearance highly suggestive of vEDS. In these individuals, major events were not more frequent ( P=0.90), but occurred at a younger age ( P=0.01). A major event occurred more often and at a younger age in men compared with women ( P<0.001 and P=0.004, respectively). Aortic aneurysms ( P=0.003) and pneumothoraces ( P=0.029) were more frequent in men. Aortic dissection was more frequent in individuals with a COL3A1 variant in the first quarter of the collagen helical domain ( P=0.03). CONCLUSIONS: Male sex, type and location of the COL3A1 variant, and physical appearance highly suggestive of vEDS are risk factors for the occurrence and/or early age of onset of major events. This national multicenter cohort study of Dutch individuals with vEDS provides a valuable basis for improving guidelines for the diagnosing, follow-up, and treatment of individuals with vEDS.
U2 - 10.1161/CIRCGEN.122.003978
DO - 10.1161/CIRCGEN.122.003978
M3 - Article
C2 - 38623759
SN - 2574-8300
SP - e003978
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
ER -