FACT SHEET: Fragile X Testing in Adult Women

ABOUT YOUR OVARIES

Ovaries are special glands that only women have. Each month one of the ovaries also releases an egg which might be fertilized and grow to become a baby. The ovaries produce hormones and develop eggs in response to messages sent from the body's master gland in the brain, the pituitary. Normally the ovaries continue to work until a woman is about 50-52 years old (meaning she still gets her period), although natural pregnancies (achieved without medical assistance) are rare by the time a woman is in her mid-forties.

Sometimes the ovaries stop working at earlier ages. If this happens,

• a woman may be unable to get pregnant while still in her 20’s or 30’s. This may be due to a condition called “diminished ovarian reserve”, and this would be diagnosed with particular blood tests.
• a woman may go through menopause (no more periods) earlier than other women her age. If she goes through menopause before she turns 45, she will be diagnosed with “premature ovarian failure” or “early menopause”.

In 90% of these women the reason is not known why the ovaries have stopped working so early. Known causes of a very early menopause are: surgical removal of the ovaries, chemotherapy, pelvic radiation therapy, a genetic condition called Turner’s syndrome, and certain autoimmune diseases. Known causes of diminished ovarian reserve are similar, but again, there is no explanation in the vast majority of cases. Essentially, there are no effective treatments to reverse either condition.

How often does this happen? Only 1% of women go through menopause before age 40 and another 10% go through menopause between the ages of 40 and 45. We estimate that no more than 2% of women have diminished ovarian reserve based on limited scientific research.

ABOUT GENETICS

Genetic information is passed from parent to child on structures called genes, which are found in every cell of the body. Genes contain instructions that tell our bodies how to form and function properly. Our genes were passed to us by our parents, who, in turn, got their genes from their parents. Most of our genes are normal but everyone has a certain number of what are thought to be “abnormal” genes. Typically these abnormal genes do not cause us health problems and the only time we find out that we have them is after the birth of a child with a hereditary condition.

Genes are portions of a larger structure called DNA (deoxyribonucleic acid). Genetic testing involves analyzing an individual’s DNA to look for genetic alterations, or abnormal genes, that may indicate an increased chance for developing a specific disease or medical disorder.

WHAT DO GENES HAVE TO DO WITH THE OVARIES?

Recent scientific research has found that women with a particular gene may be more likely to go through early menopause than other women, and this same gene may cause the woman to have difficulty getting pregnant.

Research indicates that all of us are “carriers” of between 5-7 abnormal genes. Usually these genes do not cause us any significant health problems and we are not aware that we have them. Being a carrier of an abnormal gene is different than having a genetic condition. Individuals with a diagnosis of a genetic condition have some physical differences or problems. The problems are caused by their genes, which are telling their bodies to form or function abnormally. Individuals who are carriers of a particular gene can pass that gene on to their children.

Women with ovaries that stop working early may be carriers of a gene called “fragile X”. A "premutation" refers to a gene that is still turned on and working but the gene has an altered pattern of DNA. It is the premutation stage (“carrier”) that has been found to cause very early menopause (before age 40). About 5-6% of all women with menopause before age 40 are carriers of the fragile X gene. It is unknown what percentage of women with diminished ovarian reserve are carriers of this gene. Women with the full mutation do not experience this early shutdown of their ovaries.

The alteration of the fragile X gene in affected individuals is not caused by behavior or environmental factors. (As opposed to lung cancer, where the lung cell genetic structure can be altered by the individual’s behavior of smoking cigarettes.) Approximately 1 out of every 300 women in the general population is a carrier of a fragile X premutation. For most of these women, there will be no effect on their ability to get pregnant or on when their periods stop. Therefore, because most women do not have associated health problems, they do not know that they have this premutation.

FAMILY IMPACT

Because fragile X is an inherited medical condition, some blood relatives of the woman who is a carrier may also have this gene, as passed down from the previous generation. Fathers can pass on the gene alteration to their daughters only, while mothers can pass on the gene alteration to either sons or daughters.

The degree of the alteration in the fragile X gene can increase over several generations. A mother with the premutation can pass on a greater abnormality to her children, but fathers always pass on the same degree of alteration.  If the degree of abnormality increases, there is an increased possibility that a child will receive the full mutation and be mentally retarded (80% of sons with the full mutation will be mentally retarded vs. only 30% of daughters with the full mutation).  Also, recent scientific research has found that some elderly men who are carriers of fragile X may experience tremors. So any children, siblings or parents of someone who is a carrier of fragile X may also be a carrier of fragile X and may have some related health effects.

Therefore, deciding to have fragile X testing may have implications for your family members in addition to giving you information about your own health. Please understand, however, that your blood test results will only reflect your genes, so your test results will only tell you limited information on the results of any relative.

YOUR CHOICE

While there is nothing any individual can do to change this particular gene, it can be a relief to learn the reason for health events, like going through menopause much earlier than expected or not being able to become pregnant. The choice to have any medical tests is your own decision. We at the University of Virginia OB/GYN Department want to make sure we have given you enough information to make an informed decision for yourself on this fragile X screening test. Your medical care at the University of Virginia will be the same whether or not you chose to have this screening test.

Testing can be done with a blood sample. Your test results will become part of your medical record, as is true for any diagnostic test ordered by your clinician. If the test is ordered through a research study, however, the results may be confidential; check the consent form to be sure. Please speak with your health care provider about any questions or concerns you may have prior to having the test. If you have additional questions and would like to speak with a genetic counselor prior to the test or after the test, this can be arranged through the clinic as well. Genetic counseling may or may not be offered through research studies. Carriers of fragile X should be referred for genetic counseling. Our clinic phone numbers are: Midlife Health Center (434-243-4720) and Reproductive Medicine and Surgery (434-243-4590).

Helpful internet resource: www.fragilex.org (their focus is the full mutation, but it still may be helpful)

Written by the University of Virginia OB/GYN and Pathology Departments: LM Pastore, CD Williams, JV Pinkerton, L Silverman, LB Karns