Questions and answers about heritable disorders of connective tissue - Health Topics - Pamphlet

Pamphlet by: Nat'l Inst. of Arthritis and Musculoskeletal & Skin Diseases, July 1, 2001

* What Is Connective Tissue?

* How Do People Get Gene Alterations?

* Who Gets HDCTs?

* Does Anything Increase the Chances of Having a Genetic Disease?

* How Does Genetic Counseling Help?

* What Are the Symptoms of a HDCT?

* How Do Doctors Diagnose HDCTs?

* What Treatments Are Available?

* What Research Is Being Done on HDCTs?

* Where Can People Find More Information about HDCTs?

This fact sheet describes a family of more than 200 disorders that affect connective tissues. These disorders result from alterations (mutations) in genes responsible for building tissues. Alterations in these genes may change the structure and development of skin, bones, joints, heart, blood vessels, lungs, eyes, and ears. Some mutations also change how these tissues work.

All of these diseases are directly related to mutations in genes, and thus are called "heritable." Some other connective tissue problems are not directly linked to mutations in tissue-building genes, although some people may be genetically predisposed to becoming affected. The disorders discussed in this fact sheet are called heritable (genetic) disorders of connective tissue (HDCTs). Many, but not all, of them are rare. (See Some Common Heritable Connective Tissue Disorders for a description of some of the more common HDCTs.)

Some Common Heritable Connective Tissue
Disorders

Physicians and scientists have identified more than 200
heritable connective tissue disorders. Some of the more
common ones are listed below. Some of these are really groups
of disorders and may be known by other names.

Ehlers-Danlos syndrome--The problems present in
Ehlers-Danlos syndrome (EDS), a group of approximately 10
disorders, include changes in the physical properties of skin,
joints, blood vessels, and other tissues such as ligaments and
tendons. People with EDS have some degree of joint
looseness, fragile small blood vessels, and abnormal scar
formation and wound healing. Soft, velvety skin stretches
excessively but returns to normal after being pulled. Some
forms of EDS can present problems with the spine, including
curved spine; the eyes; and weak internal organs, including the
uterus, intestines, and large blood vessels. Mutations in several
different genes are responsible for different symptoms in the
several types of EDS. In most cases, the genetic defect
involves collagen, the major protein-building material of bone.

Epidermolysis bullosa--The characteristic feature of
epidermolysis bullosa (EB) is blistering in the skin. Some forms
of the disease may involve the gastrointestinal tract, the
pulmonary system, muscle, or the bladder. Most forms are
evident at birth. This disorder can be both disabling and
disfiguring, and some forms may lead to early death. The
disease results when skin layers separate after minor trauma.
Defects of several proteins within the skin are at fault.

Marfan syndrome--People with Marfan syndrome tend to have
excessively long bones and are commonly thin, with long,
"spider-like" fingers. Other problems include skeletal
malformations, abnormal position of the lens of the eye, and
enlargement at the beginning part of the aorta, the major vessel
carrying blood away from the heart. If left untreated, an
enlarged aorta can lead to hemorrhage and even death. This
disorder results from mutations in the gene that makes
fibrillin-1, a protein important to connective tissue.

Osteogenesis imperfecta--People with osteogenesis
imperfecta (OI) have bones that fracture easily, low muscle
mass, and joint and ligament laxity. There are four major types
of OI ranging in severity from mild to lethal. The appearance of
people with OI varies considerably. Individuals may also have a
blue or gray tint to the sclera (whites of the eyes), thin skin,
growth deficiencies, and fragile teeth. They may develop
scoliosis, respiratory problems, and hearing loss. Also known
as "brittle bone disease," this disorder arises from mutations in
the two genes that make type I collagen, a protein important to
bones and skin. These mutations cause the body to make
either too little or poor-quality type I collagen.

What Is Connective Tissue?

Connective tissue is the material between the cells of the body that gives tissues form and strength. This "cellular glue" is also involved in delivering nutrients to the tissue, and in the special functioning of certain tissues. Connective tissue is made up of dozens of proteins, including collagens, proteoglycans, and glycoproteins. The combination of these proteins can vary between tissues. The genes that encode these proteins can harbor defects or mutations, which can affect the functioning of certain properties of connective tissue in selected tissues. This can lead to a HDCT.

How Do People Get Gene Alterations?

Either people inherit an altered gene from either or both parents, or--more rarely--an alteration occurs in a copy of the gene during the formation of the egg or sperm that gives rise to the individual. We have two copies of most genes: ones that we inherited from each parent. Males have one copy of each gene on the X chromosome, because they have only one X chromosome, and one copy of each gene on the Y chromosome. In contrast, women have two X chromosomes and therefore have two copies of X chromosome genes.