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Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type
M Pepin1, U Schwarze, A Superti-Furga
1Department of Pathology, University of Washington, Seattle 98195-7470, USA.
Insights
Ehlers-Danlos syndrome type IV (EDS IV) causes premature death, often from arterial rupture, with most complications occurring by age 40. Early diagnosis is crucial for managing this vascular connective tissue disorder.
Area of Science:
- Genetics
- Vascular Biology
- Connective Tissue Disorders
Background:
- Ehlers-Danlos syndrome type IV (EDS IV), or vascular EDS, stems from COL3A1 gene mutations affecting type III procollagen.
- Patients with EDS IV face risks of arterial, bowel, and uterine rupture, but disease progression is not well-documented.
Purpose of the Study:
- To document the clinical course, complications, and survival rates in patients with Ehlers-Danlos syndrome type IV.
- To identify the frequency and timing of life-threatening events in EDS IV.
Main Methods:
- Retrospective review of clinical and family histories of 220 index patients and 199 affected relatives with confirmed EDS IV.
- Identification of COL3A1 mutations in 135 index patients.
Main Results:
- Complications were infrequent in childhood, with 25% of patients experiencing a first complication by age 20 and over 80% by age 40.
- Median survival was 48 years, with arterial rupture being the most common cause of death. Bowel rupture occurred in about 25% of cases.
- Pregnancy complications were fatal in 12 of 81 affected women. No clear association was found between complication types and specific COL3A1 mutations.
Conclusions:
- Ehlers-Danlos syndrome type IV leads to premature mortality, despite patients often surviving initial major complications.
- Diagnosis should be suspected in young individuals presenting with uterine, arterial, or visceral rupture.
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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