Triple X Syndrome
What is triple X syndrome?
Triple X syndrome is a rare genetic condition that affects only females. It can also be referred to as trisomy X syndrome or 47,XXX. A trisomy is a genetic condition in which there are three copies of a chromosome. Males and females are usually born with 46 chromosomes total, arranged in 23 pairs. One copy of each chromosome in the pair comes from the mother, and the other copy in the pair comes from the father. The 23rd chromosome pair is known as the sex chromosomes. Normally, females have two X chromosomes, while males have one X chromosome and one Y chromosome. Triple X syndrome happens when a female is born with an extra X chromosome, and therefore has a total of 47 chromosomes.
For some girls and women with triple X syndrome, all of their cells contain three X chromosomes. In other females with triple X syndrome, some cells have three X chromosomes while other have the usual two X chromosomes — this is referred to as mosaicism. The degree of mosaicism (the number of cells with three X chromosomes) may vary from a small percentage to close to 100%.
How common is triple X syndrome?
The condition occurs in about one out of every 1,000 female births. In the United States, about 150,000 females have triple X syndrome. However, it’s thought that the total number of affected females is higher because many are likely undiagnosed. For example, some sources estimate only 10% of the females with this condition are diagnosed.
Symptoms and Causes
What causes triple X syndrome?
Triple X syndrome is a genetic disorder caused by the presence of an extra X chromosome in females. However, it is not usually inherited from an affected parent. Most cases are caused by errors in chromosome replication and division during the formation of egg or sperm cells, and occur completely by chance.
Mothers of advanced maternal age (women who are greater than 35 years old at the time of delivery) appear to be at an increased risk to have a daughter with triple X syndrome. Individuals with mosaic triple X syndrome have cells with an extra X chromosome as the result of a random change that occurs some time during embryonic cell division.
What are the symptoms of triple X syndrome?
There is a great degree of variation among girls and women with triple X syndrome. Some individuals do not experience any symptoms or their symptoms are so mild that they go unnoticed. Other girls and women may have certain characteristics — as well as psychological or medical problems — associated with triple X syndrome. Symptoms may be more pronounced in females with a higher percentage of cells with three X chromosomes.
One consistent physical characteristic is that females with triple X are taller than girls of the same age and/or taller than predicted by their parents’ heights. Otherwise, the physical features may be subtle, including:
- Wide-spaced eyes (known as hypertelorism).
- Vertical skin folds that cover the inner corners of the eyes (known as epicanthal folds).
- Curved or bent little fingers (known as clinodactyly).
- Poor muscle tone (known as hypotonia).
In some cases, there may be medical problems, such as:
- Premature ovarian aging or failure: Early dysfunction and/or failure of the ovaries, which can be associated with fertility problems.
- Genito-urinary deformities or malfunctions: The ovaries and/or kidneys may be malformed.
- Differences in heart structure.
- Autoimmune conditions, such as hypothyroidism.
Some girls with triple X syndrome experience developmental delays or psychological or cognitive problems. These may include:
- Attention deficit disorder: It’s more likely that girls with triple X syndrome will have difficulty concentrating in school than girls without triple X syndrome.
- Mood disorders: Mood disorders most commonly include anxiety and depression.
- Developmental delays: Muscle weakness or poor muscle tone may lead to delays in development of motor skills, such as walking.
- Learning disabilities.
- Social problems: Girls with triple X syndrome may have problems with communication or social interactions. They may be prone to low self-esteem.
- Mild cognitive or intellectual impairment: IQ is often in the normal range and typically only 10 to 15 points lower than siblings.
Diagnosis and Tests
How is triple X syndrome diagnosed?
Sometimes triple X syndrome is suspected by prenatal testing before the baby is born. Even in these cases it’s important to get genetic testing after the baby is born to diagnose and confirm the presence of triple X syndrome. Developmental delays in female infants or children may be a sign of the disorder. Characteristic facial features may also indicate that a female has triple X syndrome.
If a genetic test is ordered, the pediatrician or other healthcare professional will take a blood sample for testing. These tests can include:
- Karyotype or chromosome microarray: This is used to assess the person for the presence of an extra X chromosome and to determine the degree of mosaicism (if any).
- Prenatal genetic testing: Pregnant women who are at higher risk for having a child with triple X syndrome — mothers of advanced maternal age or women with triple X syndrome themselves — may be advised to undergo prenatal genetic testing, such as non-invasive prenatal testing (NIPT), amniocentesis or chorionic villi sampling (CVS).
It is quite common for girls and women to remain undiagnosed, especially if they do not exhibit medical or developmental issues. Sometimes women discover that they have triple X syndrome if they have difficulty becoming pregnant. Some women may also experience premature ovarian failure, leading to early menopause.
Management and Treatment
How is triple X syndrome treated?
There is no cure for triple X syndrome. Treatment will depend on the individual symptoms, if any. Given the known association with certain conditions, additional screening tests may be required:
- Renal ultrasound to look at kidney structure.
- Cardiology consultation or EKG/echocardiogram to evaluate the heart.
- Neurology consultation if there’s concern for staring spells or atypical movements.
- Neuropsychological testing.
- Physical therapy, occupational therapy, speech therapy and/or other healthcare specialists to address needs.
- Referral to fertility specialist for counseling, and later for family planning.
- Women with triple X syndrome who are trying to get pregnant should also meet with a genetic counselor.
- Women with premature ovarian failure will require treatment with estrogen.
Pediatricians should monitor girls with the disorder to assess their growth and developmental progress. If there is concern for height that is too tall, typically a referral to a pediatric endocrinologist should be made for further evaluation. Endocrinologists are also the doctors who will prescribe estrogen if needed. At the earliest, this will happen between 10 to 12 years of age. Not all patients with triple X will require estrogen therapy.
Early diagnosis and intervention can help girls who might face developmental delays, such as delays in acquiring language and motor skills. Psychological counseling for children and adults may help to alleviate problems with social adjustment and stress. Support groups can be helpful for individuals and parents of girls with triple X syndrome.
How can triple X syndrome prevented?
There’s currently no way to prevent triple X syndrome. Genetic counseling and prenatal genetic testing are suggested in cases where a pregnancy may pose a higher risk of the disorder, such as advanced maternal age.
Outlook / Prognosis
What is the prognosis for girls and women with triple X syndrome?
Girls and women with triple X syndrome can lead normal lives. In many cases, there are no problems with sexual development or fertility.
In general, early diagnosis and intervention can help to reduce developmental delays. Girls should have regular medical check-ups and their growth and progress should be monitored. Psychological counseling can be beneficial in alleviating depression and anxiety, or other problems. Since symptoms can be widely variable, each patient should undergo comprehensive evaluation to determine her particular needs.
A note from Cleveland Clinic
If you or your child have triple X syndrome, talk to your healthcare provider about support groups and resources that might be available. In many cases, your provider can help connect you to these resources.
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