Easy bruising and bleeding are particularly prominent in this subtype. The most feared complication

is the sudden rupture of medium-sized and large blood vessels, bowel, or gravid uterus, which characteristically occurs in the third–fourth decade of life, usually with fatal outcome. In a retrospective review of the natural history of more than 400 individuals with vascular EDS, it was shown that vascular and gastrointestinal (GI) complications were presenting signs in 70% of adults with vascular EDS. The median age of death was 48 years [20]. Inheritance of vascular EDS is autosomal dominant and family history is often positive RAD001 mw for sudden death in a close relative. About 50% of affected individuals this website have inherited the mutant gene (COL3A1) from an affected parent and 50% have a new (‘de novo’) disease-causing mutation. Laboratory investigation of platelet aggregation, clotting factors and bleeding time in patients with EDS or most other HCTD is usually normal. In certain EDS subtypes, especially in the vascular subtype, biochemical and molecular analyses are very helpful to confirm the diagnosis. To this purpose, a skin biopsy is required to obtain cultured skin fibroblasts. Biochemical study of the collagen types I, III and V includes SDS-polyacrylamide gel electrophoresis of radiolabelled collagens extracted from the cultured

fibroblasts. In the vascular subtype of EDS, biochemical analysis of type III procollagen identifies more than 95% of all patients. Molecular screening of the COL3A1 gene identifies virtually all mutations. A wide spectrum of COL3A1 mutations has been identified, the majority of which are point mutations leading to 上海皓元医药股份有限公司 substitutions for glycine in the triple helical region of the collagen molecule [21]. Vascular fragility is also a hallmark of Loeys–Dietz syndrome (LDS), which is caused by mutations in the TGFBR1

and TGFBR2 genes and which shows phenotypic overlap with vascular EDS (LDS type II). The natural course of this condition is even more aggressive than vascular EDS, with aortic dissections in young childhood and a mean age of death at 26 years. In contrast to vascular EDS, where surgery is used as a last resort because of the extremely high rate of peri-operative complications and death, aneurysms in LDS patients are amenable to early and aggressive surgical intervention. Vascular fragility has been associated also with specific mutations in type I collagen, causing an EDS-like phenotype [22], with type V collagen mutations in the classic EDS subtype [23], or with genetic defects of collagen-modifying enzymes in some rare EDS variants, such as the kyphoscoliotic subtype [24]. Although no treatment for EDS is yet available, a series of ‘preventive’ guidelines are applicable to all subtypes of this disorder. Patients with EDS should be instructed to avoid undue trauma, contact sports or heavy exercise [25].