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Early return of reflected pressure waves increases the load on central arteries and may increase the risk of aortic rupture in patients with Marfan's syndrome (MFS). To assess whether wave reflection is elevated in MFS, we used ultrasound and MRI to measure central pressure and flow waveforms in 26 patients (13-54 yr of age) and 26 age- and gender-matched controls. Aortic systolic and diastolic cross-sectional areas were measured at the ascending and descending aorta (AA and DA), diaphragm (DIA), and lower abdominal aorta (AB). From these measurements, local characteristic impedance (Z(0-xx)) and local reflection coefficients (Gamma(xx-yy)) were calculated. Calculated global wave reflection indexes were the augmentation index (AIx) and the ratio of backward to forward pressure wave (P(b)/P(f)). The aorta was wider in MFS patients at AA (P < 0.01) and DA (P < 0.01). Aortic pulse wave velocity was 42 cm/s higher in MFS patients (P < 0.05). Z(0-xx) was not different between groups, except at DA, where it was lower in MFS patients. In controls, Gamma(AA-DA) was 0.31 +/- 0.08, Gamma(DA-DIA) was 0.00 +/- 0.11, and Gamma(DIA-AB) was 0.31 +/- 0.16. Mean values of Gamma(xx-yy) were not different between MFS patients and controls. In controls, aging diminished Gamma(AA-DA) but increased Gamma(DIA-AB). Clear age-related patterns were absent in MFS patients. AIx or P(b)/P(f) was not higher in MFS patients than in controls. There were indications for enhanced wave reflection in young MFS patients. Our data demonstrated that the major determinants of AIx were pulse wave velocity and the effective length of the arterial system and, to a lesser degree, HR and P(b)/P(f).

Objectives: This report wants to focus on the risk of severe prematurity in patients with the hypermobility type of the Ehlers-Danlos syndrome (EDS), a heritable disorder of connective tissue. Although various obstetrical complications have been reported in patients with EDS, most reports specifically comment on the severe complications in patients with the vascular type of EDS, including uterine and arterial rupture. Pregnancy outcome in patients presenting the hypermobility type of EDS is poorly documented. Case: A 33-year-old nullipara was referred for preconceptual genetic counseling with a history of easy bruising, generalized joint hypermobility and chronic arthralgia and myalgia. The diagnosis of the hypermobility type of EDS was confirmed on clinical examination. During her first pregnancy, she underwent a prophylactic McDonald cerclage at 14 weeks’ gestation. Premature rupture of membranes occurred at 23 weeks’ gestation. A female infant was delivered at 26 weeks and died 3 h after birth. Electron-microscopic examination showed collagen fibre abnormalities in the fetus’ skin, which were compatible with the diagnosis of EDS. Conclusions: Patients with the hypermobility type of EDS can have an increased risk for pregnancy complications, including prematurity due to cervical incompetence and to premature rupture of membranes. We therefore demand the clinician’s alertness for possible signs of this underdiagnosed type of EDS and recommend the collaboration between the obstetrician and the medical geneticist in the obstetrical management of these patients.

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We have examined a large family in which eleven members have a form of autosomal dominant Ehlers-Danlos syndrome type IV. Analysis of fibroblast cultures from affected individuals showed a partial deficiency of type III collagen production. The protein produced was, however, normal in all aspects examined. Using a restriction site polymorphism associated with the structural gene for human type III collagen (COL3A1), we have found tight linkage between the low frequency polymorphic allele and the clinical expression of the disease (lod = 3.86 at 0 = 0), identifying the type III collagen gene as the disease locus.