The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility. Considerable clinical and genetic heterogeneity exists, and more than nine separate forms have been recognized. Recent advances in the molecular analysis of EDS have identify defects responsible for EDS VI (homozygous and compound heterozygous mutations in the
lysyl-hydroxylase gene),
EDS VIIA and
EDS VIIB (mutations in the type I collagene genes),
EDS VIIC (deficiency of
procollagen N-proteinase),
EDS IX (mutations in the MNK gene), and
EDS IV (mutations in the
type III collagen gene). Of the various types of
Ehlers-Danlos syndrome the most severe is type IV (
EDS IV). Early studies showed that fibroblasts from
EDS IV patients secreted lower than normal amounts of
type III procollagen (Pope et al., 1975). Later, the disease was linked to COL3A1, the gene encoding this
protein. More recently, with the publication of full length
cDNA and partial characterisation of the gene structure, detailed analysis of mutations in
EDS IV patients has become possible. Nineteen different mutations in the
type III procollagen gene have been reported in different families with
EDS IV. Recent results support the hypothesis that in
EDS IV, dominant inheritance should be assumed, in sporadic cases also, unless proven otherwise. Very little is known about the genetics or biochemicals defects responsible for the others EDS subtypes, but with the applications of the tools of molecular biology, analysis of these defects if now within reach.