Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type

Pepin, Melanie; Schwarze, Ulrike; Superti-Furga, Andrea; Byers, Peter H.

doi:10.1056/nejm200003093421001

Cited by 1,344Connective tissue disorders researchDermatological and Skeletal DisordersCerebrovascular and genetic disorders

Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type

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Pepin, Melanie, Schwarze, Ulrike, Superti-Furga, Andrea, Byers, Peter H.·2000·New England Journal of Medicine

DOI 10.1056/nejm200003093421001

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Abstract

BACKGROUND: Ehlers-Danlos syndrome type IV, the vascular type, results from mutations in the gene for type III procollagen (COL3A1). Affected patients are at risk for arterial, bowel, and uterine rupture, but the timing of these events, their frequency, and the course of the disease are not well documented. METHODS: We reviewed the clinical and family histories of and medical and surgical complications in 220 index patients with biochemically confirmed Ehlers-Danlos syndrome type IV and 199 of their affected relatives. We identified the underlying COL3A1 mutation in 135 index patients. RESULTS: Complications were rare in childhood; 25 percent of the index patients had a first complication by the age of 20 years, and more than 80 percent had had at least one complication by the age of 40. The calculated median survival of the entire cohort was 48 years. Most deaths resulted from arterial rupture. Bowel rupture, which often involved the sigmoid colon, accounted for about a quarter of complications but rarely led to death. Complications of pregnancy led to death in 12 of the 81 women who became pregnant. The types of complications were not associated with specific mutations in COL3A1. CONCLUSIONS: Although most affected patients survive the first and second major complications, Ehlers-Danlos syndrome type IV results in premature death. The diagnosis should be considered in young people who come to medical attention because of uterine rupture during pregnancy or arterial or visceral rupture.

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vEDS is caused by mutations in COL3A1 encoding collagen III, which shows predominant expression in blood vessels and hollow organs.
“vEDS is caused by mutations in COL3A1 encoding collagen III that shows a predominant expression in blood vessels and hollow organs [94].”
From Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes (2019) · cites this paper as [94]
vEDS is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene encoding type III collagen (COLLIII).
“Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII)”
From Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome (2018) · cites this paper as [1]

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Authors: Pepin, M., Schwarze, U., Superti-Furga, A., & Byers, P. H.
Affiliations: University of Washington (US)
ORCID: Byers, Peter H.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2000-03-09
Volume: 342
Issue: 10
Pages: 673-680
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejm200003093421001
OpenAlex: W2313594428
Cited by: 1,344
References: 26
Citations by year: 2026: 44 · 2025: 44 · 2024: 58 · 2023: 47 · 2022: 58 · 2021: 69 · 2020: 75 · 2019: 56 · 2018: 50 · 2017: 56 · 2016: 53 · 2015: 64 · 2014: 75 · 2013: 73 · 2012: 65
FWCI: 13.27
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-21557, P01AR021557)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
Keywords: Ehlers-Danlos syndrome type IV, vascular Ehlers-Danlos syndrome, COL3A1 mutation, type III procollagen, arterial rupture, uterine rupture, pregnancy complications, premature mortality, survival, family history (medicine), genetic diagnosis
MeSH terms: Adolescent, Adult, Aged, Cause of Death, Child, Child, Preschool, Ehlers-Danlos Syndrome, Female, Genotype, Humans, Infant, Intestinal Perforation, Male, Middle Aged, Mutation, Phenotype, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Vascular Diseases, Survival Analysis

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Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type

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