What Is Triple X Syndrome? Symptoms, Causes, Diagnosis, Treatment, and Prevention

Triple X syndrome — also called trisomy X or 47,XXX — is a genetic disorder in which a woman carries an extra X chromosome in each of her cells. Although it’s a genetic disorder, triple X syndrome (which only affects women) is almost never inherited.

People have 46 chromosomes in each cell, including one pair of sex chromosomes. Normally, women have two X chromosomes (XX) per cell, while men have one X and one Y chromosome (XY), according to the National Institutes of Health. (1) In women with triple X syndrome, a third X chromosome is present, which is why it’s referred to as 47,XXX.

Sometimes, only some of a woman’s cells have three X chromosomes, while the others will have the usual two X chromosomes. This is a form of triple X syndrome called mosaicism (or 46,XX/47,XXX), notes the National Organization for Rare Disorders. (2)

Many women with triple X syndrome don’t experience any signs or symptoms of the disorder — which is one reason why experts believe the condition is widely underdiagnosed. However, other women can exhibit a wide range and severity of symptoms, with tall stature being the most common trait.

The physical, developmental, and behavioral characteristics associated with triple X syndrome may include:

• Tall stature (at or above the 75^th height percentile compared to other adolescent girls their age)
• Vertical skin folds that cover the inner corners of the eye
• Wide spacing between the eyes
• Small head circumference
• Decreased muscle tone (hypotonia)
• Curved fifth (“pinky”) fingers (clinodactyly)
• Delayed motor skills in early childhood, such as sitting and walking
• Speech and language development delays
• Dyslexia and other learning disabilities
• Behavioral and emotional problems, including anxiety and attention deficit hyperactivity disorder (ADHD)
• Premature ovarian failure (POF) or ovarian abnormalities
• Constipation or abdominal pains
• Flat feet
• Mild concavity of the breastbone

Seizures or kidney abnormalities — such as having a single kidney, or a malformed one — are possible, but occur less often. There have also been cases of heart abnormalities in women with triple X syndrome.

Sexual development in most girls with trisomy X is normal, and women don’t often experience fertility problems.

Women who have the mosaic form of triple X syndrome — they have 46,XX chromosomes in some of their cells — are thought to have milder signs and symptoms of the disorder, per past research. (3)

Although triple X syndrome is a genetic disorder, it’s not usually an inherited one; rather, the condition is caused by a random error in the development of reproductive cells. (1)

In most cases, trisomy X occurs when the cells from the mother’s egg or the father’s sperm divide incorrectly, creating an egg or sperm that has an extra X chromosome. In women with mosaicism, the extra chromosome arises from an incorrect cell division that randomly occurs when the embryo (the fertilized egg) develops. The additional X chromosome usually comes from the mother.

The risk of these errors occurring may be associated with higher-than-average maternal age, according to the UK's Rare Chromosome Disorder Support Group. (4)

An estimated 90 percent of women with triple X syndrome are undiagnosed, in part because they don’t show any signs or symptoms of the condition. (2)

Women who are suspected of having triple X syndrome can be diagnosed with a chromosome analysis, a type of genetic test that requires a blood sample, which can reveal the extra X chromosome. A genetic counselor can also provide more information about the condition.

Triple X syndrome can also be diagnosed before birth with noninvasive prenatal testing (NIPT), which can determine whether the fetus is at risk for chromosomal disorders. If the test shows an increased risk, the diagnosis can be confirmed with an amniocentesis, a test that analyzes the amniotic fluid surrounding the fetus, or a chorionic villus sampling (CVS), which removes a tissue sample from the placenta.

Prognosis of Triple X Syndrome

Women with triple X syndrome can be a little more likely to experience health problems than women without the condition, but these issues vary greatly from person-to-person.

There’s some evidence that autoimmune disorders, such as lupus and rheumatoid arthritis, are associated with trisomy X, notes the Association for X and Y Chromosome Variations. (5) Seizures and heart problems can also occur, though these are rare. Women may have trouble getting pregnant, and can develop premature ovarian failure (also known as premature ovarian insufficiency), in which a woman’s ovaries don’t work normally. Symptoms of premature ovarian failure include irregular periods, no periods, and trouble getting pregnant.

Girls and women with triple X syndrome tend to be more prone to mood disorders like anxiety or depression, and can benefit from counseling and support groups.

Triple X syndrome is a lifelong condition, but some of its symptoms — such as motor skill delays — appear earlier in childhood. Early intervention strategies, like speech therapy, physical therapy, and occupational therapy, can help some girls with trisomy X catch up to their peers or reach their full potential. (5)

There are no treatments for triple X syndrome, although there are ways to treat some of its symptoms.

Genetic Counseling

Women or mothers of women who’ve been diagnosed with triple X syndrome may want to meet with a genetic counselor, who can give you more information about how this condition might affect you or your family.

Early Intervention

Because babies with trisomy X can have poor muscle tone and motor skills, as well as language and speech delays, experts recommend that they get a physical assessment by the age of 4 months and a language examination in order to evaluate their development. (2) Early intervention services, like physical and speech therapy, can be very effective in reducing these delays. (5)

Counseling and Mood Disorder Treatment

Some girls with trisomy X may have attention disorders and be more prone to anxiety, particularly when they’re in school. Support groups can help girls cope with some of the emotional difficulties they may be experiencing, as can switching to a smaller classroom or being home-schooled part-time. (5)

Prevention of Triple X Syndrome

Triple X syndrome results from a random error that occurs in cells before or during the development of an embryo, and can’t be prevented, according to Nemours KidsHealth. (6)

Some women don’t have any symptoms of trisomy X, or only experience minor symptoms. Others will develop physical, behavioral, or emotional complications during adulthood or adolescence.

Some women with triple X syndrome can have premature ovarian failure, which can cause infertility issues or lead to early menopause. (5)

Triple X syndrome occurs in about 1 in 1,000 female births, though it’s actual prevalence is likely much higher, notes the Mayo Clinic. (7) Researchers estimate that about 90 percent of women with trisomy X won’t ever be diagnosed with the condition, in part because they may not have any symptoms of the disorder. (2)

Humans typically have 46 chromosomes (23 pairs) in each cell, including a pair of sex chromosomes. Females usually have two X chromosomes (XX) and males usually have one X and one Y chromosome (XY). (2) If a person has one or more additional sex chromosomes, they have a genetic condition called a sex chromosome aneuploidy (SCA).

People with one additional X or Y chromosome have a “trisomy” (“tri” means three). Trisomies are the most common sex chromosome aneuploidy, but there can also be “tetrasomies” (four sex chromosomes) or, rarely, “pentasomies” (five sex chromosomes).

Some of these conditions include:

• 47,XXY (Klinefelter syndrome): a chromosome condition in which a male carries an extra X chromosome. Males with the disorder can have infertility issues.
• 47,XYY (Jacob’s syndrome): a chromosome condition in which a male carries an extra Y chromosome. Males who have 47,XYY tend to be tall, but don’t tend to have infertility issues.
• 48,XXYY: a chromosome condition in males that results from having an extra X and Y chromosome.
• 48,XXXY: a chromosome condition in males that results from having two extra X chromosomes.
• 48,XXXX (tetrasomy X): a chromosome disorder in females that results from having an extra two X chromosomes.
• 49,XXXXY: a rare chromosome condition in males that results from having an extra three X chromosomes.
• 49,XXXXX (pentasomy X): a rare chromosome condition in females that results from having an extra three X chromosomes.

In general, people who have more chromosomes (such as those with tetrasomies and pentasomies) tend to have more pronounced symptoms than those with trisomies.

Favorite Advocacy Organization

Association for X and Y Variations (AXYS)

The AXYS is an advocacy, education, and support organization for people and families of people who have Y and Y chromosome variations. It provides support to individuals with the conditions and experts who serve them, as well as champions research and treatment options.