++

Some of the most common heritable disorders involve the major connective tissues of the body such as bone, skin, cartilage, blood vessels, and basement membranes. Identification of the causes of these disorders has underscored the important structural role of connective tissue proteins, such as the collagens, fibrillin, and elastin. However, these studies have also uncovered unanticipated defects in other proteins and enzymes involved in cell signaling and protein processing. The literature on connective tissue disorders is vast. Consequently, this chapter will focus on the classification and pathophysiology of these disorders and summarize the clinical features and management of the more common disorders.

++

The original classification of connective tissue diseases was based on the pattern of inheritance, the cluster of signs and symptoms, as well as radiologic and histologic features. Identification of the mutations causing the diseases has provided a rational framework for understanding the multiple manifestations of the diseases and has led to revisions in the classifications. Also, it has provided tests for prenatal diagnosis and important information for genetic counseling. The usefulness of these tests is likely to increase with the capability to analyze the complete genomes of patients. At the same time, the identification of mutations has thus far provided few new therapies. Also, as with many genetic diseases, the mutations are not always reliable predictors of clinical outcomes. For example, identical collagen I mutations in patients with osteogenesis imperfecta (OI) can be associated with clinical mild or lethal phenotypes for reasons that are not apparent. Also, the current classifications tend to overemphasize the etiologic differences between genetic diseases that are apparent in infants versus similar diseases that appear later in life. For example, small subsets of patients with initial diagnoses of postmenopausal osteoporosis, familial aortic aneurysms, or osteoarthritis have mutations in collagen genes similar to the mutations that are found in patients with OI or chondrodysplasia (CD).

++

Composition of Connective Tissues

++

Connective tissues contain a large number of complex macromolecules (Table 363-1). The most abundant components are three similar fibrillar collagens (types I, II, and III). They have about the same tensile strength as steel wires. The three fibrillar collagens are distributed in a tissue-specific manner: Type I collagen accounts for most of the protein of dermis, ligaments, tendons, and demineralized bone; type I and type III are the most abundant proteins of large blood vessels; and type II is the most abundant protein of cartilage.

++
Table Graphic Jump Location
Table 363-1 Constituents of Connective Tissues in Various Tissues 

Want access to your institution's subscription?

Sign in to your MyAccess Account while you are actively authenticated on this website via your institution (you will be able to tell by looking in the top right corner of any page – if you see your institution’s name, you are authenticated). You will then be able to access your institute’s content/subscription for 90 days from any location, after which you must repeat this process for continued access.

Ok

About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess account, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

AccessMedicine Full Site: One-Year Subscription

Connect to the full suite of AccessMedicine content and resources including more than 250 examination and procedural videos, patient safety modules, an extensive drug database, Q&A, Case Files, and more.

$995 USD
Buy Now

Pay Per View: Timed Access to all of AccessMedicine

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.