Connective tissue forms the supportive framework of the vertebrate body. Although variable in amount and composition from one organ system to another, a common feature of all connective tissues is the prominent presence of extracellular matrix (ECM) that contains several types of connective tissue cells.

Extracellular matrix (ECM)

ECM is composed of a variety of glycoproteins that assemble into a complex, organized meshwork. Until recently, the ECM was thought to serve mainly as a relatively inert scaffold providing support and stabilisation to the different tissues. It is now clear that the matrix plays a far more active and complex role in regulating the behavior of the cells that have contact with it, influencing their development, migration, proliferation, shape and function.

In most connective tissues, ECM glycoproteins are secreted by fibroblasts but also other members of the fibroblast family, such as chondroblasts (in cartilage) and osteoblasts (in bone), express matrix components.

Two main classes of structural protein components are found within the ECM: 

(1) proteoglycans, which are glycoproteins, covalently linked to polysaccharide chains, and

(2) fibrous proteins (e.g. collagen, elastin, fibronectin, etc.) which have both structural and adhesive functions.

The proteoglycans in connective tissue form a gel-like structure which resists compressive forces on the matrix and allows rapid diffusion of nutrients, metabolites and hormones between the blood and the tissue cells. The fibrous proteins resist stretching forces by collagen fibers and provide resilience by the rubberlike elastin fibers.

Hereditary Connective Tissue Diseases (HCTD)

Heritable connective tissue diseases are caused by mutations in a wide range of genes responsible for the synthesis of the different glycoprotein components, in genes involved in enzymatic modifications of these glycoproteins, or in genes that play a role in the organisation or homeostasis of the ECM. Several of those diseases are associated with specific symptoms in the skin but also affect the connective tissue of various organ systems, including the heart, blood vessels, joints, bone, eyes and lungs.

Three common examples of HCTD are Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), and Loeys-Dietz syndrome (LDS). Those diseases display some degree of phenotypical overlap of cardiovascular, skeletal, and cutaneous features.

MFS primarily shows abnormalities in cardiovascular system, eyes (e.g. ectobia lentis), bones (e.g. pectus deformity, joint laxity, scoliosis, wrist and thumb sign) and lungs (e.g. pneumothorax). The most common cardiovascular manifestation is an aortic aneurysm at the sinuses of Valsalva with a higher risk of aortic dissection / rupture and is thus associated with an elevated mortality rate.  

EDS is a clinically and genetically heterogenous group of connective tissue disorders. All subtypes show pathologies on the skin, joints, blood vessels and internal organs. More specifically, joint hypermobility, skin hyperextensibility and tissue fragility are the most common feautres. Aortic aneurysmal disease is present in up to 1/4 of patients. 

LDS is similar to MFS, but uniquely shows i.e. hypertelorism, abnormal uvula or cleft palate and widespread aortic and arterial aneurysm and tortuosity.