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Vascular Ehlers-Danlos Syndrome.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
1999 Sep 2 [updated 2015 Nov 19].

Author information

1
Collagen Diagnostic Laboratory, University of Washington, Seattle, Washington
2
Departments of Pathology and Medicine, University of Washington, Seattle, Washington

Excerpt

CLINICAL CHARACTERISTICS:

Vascular Ehlers-Danlos Syndrome (vEDS) is characterized by thin, translucent skin; easy bruising; characteristic facial appearance (in some individuals); and arterial, intestinal, and/or uterine fragility. Vascular dissection or rupture, gastrointestinal perforation, or organ rupture are the presenting signs in the majority of adults identified to have vEDS. 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, recurrent joint subluxation or dislocation, and bruising can occur. Pregnancy for women with vEDS has an estimated 5.3% risk for death from peripartum arterial rupture or uterine rupture. One fourth of individuals with vEDS, confirmed by laboratory testing, experienced a major complication by age 20 years and more than 80% by age 40 years. The median age of death in this reviewed population was 50 years.

DIAGNOSIS/TESTING:

The diagnosis of vEDS is based on clinical findings and confirmed by identification of a heterozygous pathogenic variant in COL3A1. DNA sequence analysis detects >95% of pathogenic variants, while rare exon deletions are detected by COL3A1 deletion/duplication analysis or collagen screening and cDNA amplification. Analysis of collagens produced by cultured fibroblasts ("biochemical studies") from affected individuals can demonstrate abnormalities of type III procollagen production, intracellular retention, reduced secretion, and/or altered mobility in cells from some individuals in whom no pathogenic variant was detected by genomic sequencing.

MANAGEMENT:

Treatment of manifestations: Affected individuals are instructed to seek immediate medical attention for sudden, unexplained pain. Treatment may include medical or surgical management for arterial complications, bowel rupture, or uterine rupture during pregnancy. Surveillance: May include periodic arterial screening by ultrasound examination, magnetic resonance angiogram or computed tomography angiogram with and without venous contrast. Blood pressure monitoring on a regular basis is recommended to allow for early treatment if hypertension develops. Agents/circumstances to avoid: Trauma (collision sports, heavy lifting, and weight training); arteriography should be used with great caution and only to identify life-threatening sources of bleeding prior to surgical intervention because of the risk of vascular injury; routine colonoscopy in the absence of concerning symptoms or a strong family history of colon cancer; elective surgery unless the benefit is expected to be substantial. Evaluation of relatives at risk: The genetic status of at-risk relatives should be clarified through clinical evaluation and genetic testing. Pregnancy management: Preconception counseling is important and pregnant women should be followed in a high-risk obstetric program. Other: A MedicAlert® bracelet should be worn.

GENETIC COUNSELING:

vEDS is almost always inherited in an autosomal dominant manner but rare examples of biallelic inheritance have been reported. About 50% of affected individuals have inherited the COL3A1 pathogenic variant from an affected parent, and about 50% of affected individuals have a de novo pathogenic variant. Each child of an affected individual has a 50% chance of inheriting the pathogenic variant and developing the disorder. Both parental somatic/germline mosaicism and parental isolated germline mosaicism have been reported. Prenatal testing for pregnancies at increased risk is possible in families in which the pathogenic variant in COL3A1 has been identified. In rare families in which only the biochemical abnormality is known, analysis of cultured CVS cells can substitute.

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