EXT1 and EXT2: Definition

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EXT1 and EXT2 are two genes that help bones grow normally. Changes in either gene cause a condition called hereditary multiple osteochondromas. People with this condition develop many bony growths, called osteochondromas, during childhood. Pathologists see these genes mentioned in reports on osteochondromas and on chondrosarcomas that grow from them.

This article explains what the EXT1 and EXT2 genes do, how changes in them cause hereditary multiple osteochondromas, and how doctors test for these changes.

What do the EXT1 and EXT2 genes do?

The EXT1 and EXT2 genes hold the instructions for two proteins, exostosin-1 and exostosin-2. The two proteins work together. They help build a sugar-coated molecule called heparan sulfate.

Heparan sulfate helps control how cartilage cells grow and turn into bone. This process happens at the growth plates, the areas near the ends of long bones where children’s bones grow. Without enough heparan sulfate, some cartilage cells grow in the wrong direction. They form a bony bump that sticks out from the side of the bone.

EXT1 sits on chromosome 8, and EXT2 sits on chromosome 11.

What is an osteochondroma?

An osteochondroma is a noncancerous bony growth covered by a cap of cartilage. It grows outward from the surface of a bone, usually near a growth plate. Osteochondromas often form near the knee, shoulder, or hip. They stop growing when a person stops growing.

Most people with an osteochondroma have only one. Fewer people have many, usually because of a change in EXT1 or EXT2.

What is hereditary multiple osteochondromas?

Hereditary multiple osteochondromas is a condition in which a person develops many osteochondromas. It is also called hereditary multiple exostoses. The condition affects at least 1 in 50,000 to 100,000 people.

A change, or mutation, in one copy of EXT1 or EXT2 causes the condition:

EXT1. Changes in EXT1 cause about 65 to 70 percent of cases. These cases tend to be more severe.
EXT2. Changes in EXT2 cause most of the remaining cases.
No change found. About 10 to 15 percent of people with the condition have no detectable change in either gene.

The growths can cause pain, uneven limb length, bowed bones, shorter height, and limited joint movement. Surgeons may remove growths that cause problems.

How does the condition run in families?

Hereditary multiple osteochondromas follows an autosomal dominant pattern. One changed copy of EXT1 or EXT2 is enough to cause the condition. A parent with the condition has a 50 percent chance of passing it to each child.

About 90 percent of people inherit the change from a parent. In about 10 percent, the change is new and appears for the first time in that person.

A tumor forms when a growth-plate cell also loses its second, healthy copy of the gene. This second change happens only in that cell and the growth that comes from it.

Can an osteochondroma turn into cancer?

Rarely, an osteochondroma can turn into a cancer called chondrosarcoma. The risk is higher in people with hereditary multiple osteochondromas than in people with a single growth. Lifetime risk estimates range from about 2 to 10 percent.

Most of these cancers are low grade, such as grade 1 chondrosarcoma. They usually grow from the cartilage cap of an osteochondroma. Warning signs include a growth that gets larger or starts to hurt after a person has stopped growing.

The pathologist examines a removed growth under the microscope. The pathologist looks for features that separate a noncancerous osteochondroma from a chondrosarcoma.

How do doctors test for EXT1 and EXT2 changes?

Doctors test for EXT1 and EXT2 changes with a genetic test, usually on a blood or saliva sample. The test looks for changes present from birth. Genetic testing can confirm the diagnosis and help identify family members who carry the same change.

A pathology report on an osteochondroma does not usually include EXT1 or EXT2 results. The report describes the growth itself. Your doctor may suggest genetic testing if you have several osteochondromas or a family history.

Questions to ask your doctor

Do I have one osteochondroma or several?
Could I have hereditary multiple osteochondromas?
Should I have genetic testing for EXT1 and EXT2?
Do my children or other family members need testing?
Did the pathologist see any signs of chondrosarcoma?
Which changes in my growths should I watch for?
How often do I need follow-up imaging?