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Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients
Serwet Demirdas1,2, Lisa M van den Bersselaar1, Rosan Lechner1
1Department of Clinical Genetics, Cardiovascular Institute, Erasmus Medical Center, University Medical Center, Rotterdam, the Netherlands (S.D., L.M.v.d.B., R.L., D.M.-K., H.T.B., I.M.B.H.v.d.L.).
Insights
Vascular Ehlers-Danlos syndrome (vEDS) affects individuals with specific COL3A1 variants, with male sex and certain variant locations increasing risks. This study highlights key factors for early diagnosis and improved management of vEDS.
Area of Science:
- Genetics
- Vascular Medicine
- Rare Diseases
Background:
- Vascular Ehlers-Danlos syndrome (vEDS) is a rare, life-threatening connective tissue disorder.
- It is characterized by a high risk of arterial, bowel, and uterine rupture.
- Pathogenic variants in the COL3A1 gene are the primary cause of vEDS.
Purpose of the Study:
- To investigate the natural history of vEDS in a Dutch multicenter cohort.
- To identify genotype-phenotype correlations in vEDS patients.
- To optimize patient care and raise disease awareness.
Main Methods:
- A cohort study including individuals with vEDS across the Netherlands.
- Phenotype assessment through retrospective analysis of clinical and molecular data.
- Inclusion of a one-time physical examination for participants.
Main Results:
- 142 individuals participated; 50% were female, and 32% were index patients.
- Physical appearance suggestive of vEDS was noted in over half of patients and relatives.
- Major events occurred more frequently and at a younger age in men compared to women.
- Aortic dissection risk was associated with COL3A1 variants in the first quarter of the collagen helical domain.
Conclusions:
- Male sex, COL3A1 variant type/location, and suggestive physical appearance are risk factors for major events in vEDS.
- Findings provide a basis for improved diagnostic and treatment guidelines for vEDS.
- This national cohort study enhances understanding and management of vEDS.
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 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.
