EHLERS-DANLOS SYNDROME, DERMATOSPARAXIS (dEDS)

Scientific Background

The very rare, autosomal recessively inherited dermatosparaxis EDS (dEDS) is characterized by extremely fragile, loose skin that appears excessive, especially on the face, and resembles cutis laxa. Other symptoms include easy bruising, premature rupture of fetal membranes, fragile internal organs, large umbilical and inguinal hernias, as well as short stature and short fingers.

The molecular cause is a procollagen I-N proteinase deficiency that leads to the incorporation of immature pNa1(I) and pNa2(I) pro-collagen chains into collagen fibrils during maturation of the pro-α1 (I) and pro-α2 (I) collagen chains. As a result, the assembly of the collagen fibrils is disturbed so that pathogenic hieroglyphic-like structures are visible in a cross-section of the dermis under electron microscopy.

The ADAMTS2 gene codes for the procollagen I-N proteinase, a zinc metalloproteinase of the ADAMTS family, which separates the aminopropeptides of type I, type II and type III procollagens. ADAMTS (A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs type 1) are extracellular matrix anchor proteins. To date, 11 different inactivating ADAMTS2 variants have been described that lead to premature translational arrest or involve genomic rearrangements. The variants are mostly homozygous and more rarely combined heterozygous.

References

Brady et al. 2017, Am J Med Genet C 175:70 / Van Damme et al. 2016, Genet Med 18: / Colige et al. 2004, J Invest Dermatol 123:656 / Malfait et al. 2004, Am J Med Genet 131A:18