Ehlers-Danlos Syndrome dermatosparaxis Type (EDS type VIIC) [Q79.6]
Dr. rer. nat. Karin Mayer
The very rare, autosomal recessive inherited dermatosparaxis type of EDS (EDS type VIIC) is characterized by an extremely vulnerable, sagging skin which especially appears excessive in the face resembling cutis laxa. Further symptoms include propensity for hematoma formation, premature rupture of fetal membranes, fragility of internal organs, large inguinal and umbilical hernias as well as short stature and short fingers.
The molecular cause is a deficiency of the procollagen I N-proteinase. During the maturation of the pro-α1 (I) und pro-α2 (I) collagen chains this deficiency leads to incorporation of immature pNα1(I) und pNα2(I) procollagen chains into the collagen fibrils. As a result the structure of the collagen fibrils is severely impaired, so that in electron microscopy pathognomonic hieroglyphic like structures are visible in the cross-section of the dermis.
The ADAMTS2 gene codes for the procollagen I N-proteinase, a zinc metalloprotease of the ADAMTS family, which cleave the aminopropeptides of procollagens types I-III. ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) are anchor proteins of the extracellular matrix (ECM). So far only six different, activating ADAMTS2 mutations are described, which usually are found to be homozygous and less frequently in the compound heterozygous state. They include 3 genomic deletions which comprise one to three exons.