Classification of heritable connective tissue diseases
There are several different classifications that have been proposed. One classification is by the main collagenous structural property which has been altered.
• Tensile HCTDs: these disorders affect primarily type I or other (III, V) collagens, ECM proteins associated with these collagens, or elastin which are important for strength of bone, ligaments, tendons, skin, heart valves, and blood vessels. The disorders include: OI (collagen type I defect), EDS (collagen type I, III, or V defect; fibronectin defect, or enzyme deficiency), MFS (fibrillin-1 defect), congenital contractural arachnodactyly (CCA) (fibrillin-2 defect), pseudoxanthoma elasticum, cutis laxis, and supravalvular aortic stenosis (William syndrome caused by elastin gene deletion).
• Compressive HCTDs: these disorders affect multiple collagens and/or ECM proteins important for compression of cartilage and growth. Gene discovery has defined over 100 genes with various defects leading to abnormal collagens (types II, IX, X, XI), ECM proteins, defects in metabolic pathways (enzymes), defects in signal transduction and receptors, as well as others. The disorders include achondroplasias, epiphyseal chondrodysplasias (Stickler syndrome, spondyloepiphyseal dysplasia, and multiple epiphyseal dysplasia), metaphyseal chondrodysplasias, and others.
• Barrier HCTDs: these disorders affect type IV collagen (Alport syndrome) and type VII collagen (epidermolysis bullosa), which form barriers known as basement membranes.
