Search

We have recently analysed by histological, protein and molecular DNA techniques 23 mutations of the collagen III gene (COL3A1), most of which cause premature arterial fragility, thin skin and variants of vascular Ehlers-Danlos syndrome. There were 14 glycine substitutions between residues 637 and 1021, eight exon skips between exons 7 and 45 and one small inframe deletion. The glycine substitutions produce a gradient of increasingly abnormal clinical phenotypes from exons 36 to 49 while the clinical severity of exon skips is much more variable. Each mutation is private for the affected family or individual concerned having the potential for early prenatal diagnosis and prevention.

Fifty-one patients with Ehlers-Danlos syndrome were investigated for abnormalities of platelets and coagulation. Thirty-eight were examined prospectively and 13 retrospectively. A bleeding history was taken from all patients; only four (8%) gave no history of a bruising or bleeding tendency. Nine patients (18%) had significant haemostatic abnormalities of whom four (8%) had a platelet release defect, three (6%) had a factor XI deficiency and two (4%) had a factor XIII deficiency. Additionally 16 patients (31%) had mild abnormalities of uncertain significance of whom four (8%) had prolonged bleeding times (three in association with platelet aggregation abnormalities), 13 (26%) had platelet aggregation abnormalities and two had a positive Hess test. Twenty-four patients (47%) had normal tests for haemostasis of whom 20 (39%) had a bleeding diathesis and four (8%) had no such tendency. Results were analysed according to the type of Ehlers-Danlos syndrome, but there was no pattern to the abnormalities. The high frequency of a bleeding tendency in Ehlers-Danlos patients with normal tests for haemostasis (83%) supports the conventional explanation for this clinical feature, that defects in the structural integrity of skin and blood vessels lead to easy bruising.

Immunofluorescence showed that cultured skin fibroblasts from 15 out of 17 patients with Ehlers-Danlos syndrome type IV retained abnormal amounts of type III collagen within the cytoplasm. This was not shown by fibroblasts from normal subjects or from patients with other inherited connective tissue diseases. The diagnosis of Ehlers-Danlos syndrome type IV may be facilitated by this finding.