Two inherited disorders of connective tissue have major cardiovascular 
complications, Marfan syndrome and Ehlers-Danlos syndrome type IV. Major 
progress has been made toward understanding both the genetic defect and the 
molecular pathogenesis of these two disorders. Marfan syndrome results from 
mutations in the FBN1 gene, which encodes fibrillin-1, an extracellular matrix 
component found in structures called microfibrils. Histologic characterization 
of the effect of FBN1 mutations on fibrillin-1 cellular processing and 
microfibril formation has provided insights into fibrillin-1 function. 
Ehlers-Danlos syndrome type IV results from mutations in the COL3A1 gene, which 
encodes the polypeptides in type III collagen. Despite advances in the molecular 
genetics of these two disorders, there is not a molecular diagnostic test for 
these syndromes based on the identification of gene mutations. Marfan syndrome 
remains primarily a clinical diagnosis. Biochemical analysis of the amount of 
type III collagen produced by dermal fibroblasts has proven to be a powerful 
diagnostic test for Ehlers-Danlos syndrome type IV.