Genetic: Triple X Syndrome

Definition

Triple X syndrome is a condition in which a female is born with an extra X chromosome in each cell of the body. Those who have the extra chromosome in only some of their body cells are said to have triple X mosaicism.

Description

Triple X syndrome is caused by the presence of an extra X chromosome in the cells of a female's body. It was discovered in 1959 by Patricia Jacobs, a researcher working in a hospital in Scotland. The patient was a thirty-five-year-old woman who had undergone premature menopause.

Although some girls with triple X syndrome have learning disabilities or developmental delays, many do not. There are no unusual physical or medical disabilities associated with the syndrome; many girls with very mild symptoms may never be diagnosed. Researchers do not know why the extra copy of the X chromosome causes an increase in height and learning problems in some girls with the syndrome.

Demographics

Triple X syndrome occurs in about one of every 900–1,000 girls born in the United States. It is estimated that between five and ten girls are born with the condition each day. As far as is known, the syndrome is equally common in all racial and ethnic groups. The only known risk factor for the syndrome is the mother's age; women who are thirty-five or older when they become pregnant are at increased risk of having a daughter with triple X syndrome.

Causes and Symptoms

The most common cause of triple X syndrome occurs when an egg carrying two copies of the X chromosome is involved in conception. The reason for the extra copy in the abnormal germ cell is a genetic error called nondisjunction. Nondisjunction is a random event and is

not caused by anything either of the baby's parents did or by any medications they may have taken.

During the normal process of germ cell formation, the paired chromosomes in the cell divide so that each daughter cell has only one member of the pair. In nondisjunction, one daughter cell gets both members of the chromosome pair and the other cell has none. If a germ cell carrying two copies of the X chromosome is fertilized by a normal germ cell from the other parent, the child will have three copies of the X chromosome. This genetic error is called a full trisomy X.

Some girls affected by triple X syndrome children have some body cells with the extra copy of the X chromosome and some body cells without the extra copy. This condition is called mosaic trisomy X. About half of women with triple X syndrome have the full trisomy X and the other half have mosaic trisomy X.

A Mother's Concern

The mother of a girl who was diagnosed with triple X syndrome at age ten remarks that one of the major difficulties in coping with the disorder is that little has been written about the syndrome, possibly because the symptoms are so mild in many girls. Her own daughter was diagnosed as the result of learning difficulties, particularly language skills. “Although our numbers are smaller than some of the other X and Y chromosome variations, I can't help but wonder where are all the other girls? According to the scientific literature, trisomy X occurs in approximately one out of 900 to 1,000 live female births. And yet our numbers have hovered in the hundreds of individuals for a condition that affects millions worldwide…. While we all hope for the best, in part because the symptoms can be so mild and there is such a small amount of literature concerning treatments, we eventually become resigned to accept that the problems we experience are just an unavoidable given that we have to deal with.”

The first national conference on triple X syndrome in the United States was held in October 2006. It is hoped that regular meetings will lead to new research and better understanding of the syndrome.

Not all girls born with triple X syndrome have noticeable symptoms of the condition, which is why they may not be diagnosed for some years. In addition, girls with the normal number of X chromosomes may also have these features that are symptomatic of triple X syndrome:

• Slightly lower weight at birth
• Taller than other girls and women in the family
• Less coordinated; somewhat higher risk of developing back problems
• Development of language skills may be slowed
• Less assertive and quieter than most girls
• Increased risk of depression
• Intelligence that may be slightly lower than that of other girls and women in the patient's family (Mental retardation is unusual.)

Girls with trisomy X go through puberty at the same age as girls with two X chromosomes and develop all the normal sexual characteristics of adult women. They are able to marry and have children, and do not need hormone treatments in order to become sexually mature. It is not yet known whether adult women with triple X syndrome undergo meno-pause at an earlier age than most women because the condition has not been studied long enough for researchers to follow a significant number of subjects through adult life into menopause.

Diagnosis

Triple X syndrome may never be diagnosed if the girl has no obvious symptoms. It can, however, be detected by amniocentesis before birth. Amniocentesis is a procedure in which the doctor withdraws a small amount of fluid from the sac that surrounds the baby in the mother's uterus and examines cells from the baby's tissues for genetic abnormalities. Triple X syndrome is sometimes discovered after birth if the girl has developmental delays or learning difficulties and is given a genetic evaluation.

Treatment

There is no specific treatment for triple X syndrome; many doctors do not consider it a major disability. Girls with the syndrome who do have learning disabilities or emotional problems are given the same types of therapy as other children with the same conditions. An individualized treatment plan can be drawn up with the help of the girl's doctor and teachers.

The most important aspect of treatment for the syndrome is love and support from the patient's family. According to a Danish researcher who started one of the first triple X support groups in the world, “If conditions at home are good, stable and stimulating…learning problems rarely have any serious consequences. However, most triple X girls need remedial teaching at school at one time or another, and it is important that they get this help if and when they need it.”

Prognosis

The prognosis for girls with triple X syndrome is generally good, particularly if their parents are loving and supportive. They are not at increased risk of other diseases as far as is known and have a normal life

expectancy. They are less likely to complete college than other girls, but almost all can finish high school with speech therapy or other additional help. While a few girls with triple X syndrome have some social difficulties, most are able to join the workforce, marry, and start families in adult life.

Prevention

Because triple X syndrome is thought to be caused by a spontaneous genetic mutation rather than an inherited genetic defect, there is no way to prevent it.

The Future

It is possible that the increasing numbers of women having children in their thirties or forties will lead to an increase in the number of girls born with triple X syndrome. Little research has been done on triple X syndrome considering the numbers of girls affected by it; however, the conference hosted by the University of California, Davis, in 2006 offered some possible new directions. Papers were presented on the treatment of language difficulties, depression, anxiety, and developmental differences in girls with triple X syndrome. Another presenter discussed the use of medications as part of treatment plans for these girls.

WORDS TO KNOW

Mosaicism: A condition in which a person has some body cells containing an abnormal number of chromosomes and other cells containing the normal number. Mosaicism results from random errors during the process of cell division that follows conception.

Nondisjunction: A genetic error in which one or more pairs of chromosomes fail to separate during the formation of germ cells, with the result that both chromosomes are carried to one daughter cell and none to the other. If an egg or sperm with a paired set of chromosomes is involved in the conception of a child, the child will have three chromosomes in its genetic makeup, two from one parent and one from the other.

Trisomy: A type of genetic disorder in which a cell contains three copies of a particular chromo-some instead of the normal two.

SEE ALSO Down syndrome; Dyslexia; Edwards syndrome; Klinefelter syndrome; Patau syndrome

For more information

WEB SITES

Genetics Home Reference. Triple X Syndrome. Available online at http://www.ghr.nlm.nih.gov/condition=triplexsyndrome (updated January 2006; cited June 10, 2008.)

Klinefelter Syndrome and Associates. Brief Introduction to Trisomy X. Available online at http://www.genetic.org/knowledge/support/action/200#Brief%20Introduction%20to%20Trisomy%20X (updated February 28, 2007; accessed June 11, 2008).

Mayo Clinic. Triple X Syndrome: What Causes It? Available online at http://www.mayoclinic.com/health/triple-x-syndrome/AN00351 (updated July 27, 2006; accessed June 11, 2008).

Pacific Northwest Regional Genetics Group. Sex Chromosome Problems Discovered through Prenatal Diagnosis: 47,XXX Syndrome. Available online in PDF format at http://mchneighborhood.ichp.edu/pacnorgg/media/Sex_Chrom/xxx_eng.pdf (updated July 2007; accessed June 11, 2008).

Turner Center, Risskov, Denmark. Triple-X Females: An Orientation. Available online at http://www.aaa.dk/TURNER/ENGELSK/TRIPLEX.HTM (accessed November 6, 2008).