What is Ehlers-Danlos Vascular Type?

Ehlers-Danlos syndrome, vascular type (also known as EDS IV) is characterized by thin, translucent skin; easy bruising; characteristic facial appearance; and arterial, intestinal, and/or uterine fragility. Vascular rupture or dissection and gastrointestinal perforation or organ rupture are the presenting signs in 70% of adults. Arterial rupture may be preceded by aneurysm, arteriovenous fistulae, or dissection, but also may occur spontaneously. Neonates may present with clubfoot and/or congenital dislocation of the hips. In childhood, inguinal hernia, pneumothorax, and recurrent joint dislocation or subluxation are common. Pregnancy for women with the vascular type of EDS has as much as a 12% risk for death from peripartum arterial rupture or uterine rupture. One-fourth of individuals with EDS, vascular type experience a significant medical problem by age 20 years and more than 80% by age 40 years. The median age of death is age 48 years.


Diagnosis/testing. COL3A1 is the only gene associated with EDS, vascular type. The diagnosis of EDS, vascular type is based on clinical findings and confirmed by biochemical (protein-based) and/or molecular genetic testing. Biochemical studies in affected individuals demonstrate abnormalities of type III procollagen production, intracellular retention, reduced secretion, and/or altered mobility. Molecular genetic testing is available to individuals with the biochemically confirmed diagnosis of EDS, vascular type for genetic counseling purposes.


Management. Treatment may include surgery for arterial or bowel complications/rupture. Pregnant women with the vascular type of EDS should be followed in a high-risk obstetrical program. Affected individuals should be instructed to seek immediate medical attention for sudden unexplained pain. A MedicAlert® bracelet should be worn. Surveillance may include periodic arterial screening through venous subtraction angiography and MRI or CT without contrast material. However, arteriograms are not recommended because of the risk of vascular injury. Affected individuals should minimize risk of trauma by avoiding contact sports, heavy lifting, and weight training. Elective surgery is discouraged.


Genetic counseling. The vascular type of EDS is inherited in an autosomal dominant manner. About 50% of affected individuals have inherited the COL3A1 mutation from an affected parent and about 50% of affected individuals have a de novo disease-causing mutation. The risk to the sibs depends upon the genetic status of the proband's parents. If a parent of the proband is affected, the risk to the sibs is 50%. Offspring of an affected individual have a 50% chance of inheriting the mutation and developing the disorder. Both parental somatic mosaicism and parental germline mosaicism have been reported. Prenatal testing is clinically available for fetuses at 50% risk in families in which the underlying biochemical abnormality of type III collagen or the disease-causing mutation in COL3A1 has been identified.