What is Triple X (XXX) Syndrome?

What is XXX syndrome?

Triple X syndrome, also called trisomy X or XXX syndrome, is a rare genetic condition that only affects people assigned female at birth. Most people are born with two sex chromosomes, either XX or XY. If you have two X chromosomes, you’re assigned female at birth; one X and one Y means you’re assigned male at birth. In triple X syndrome, there’s an extra X chromosome for three (XXX), and no Y chromosome is present. 

Approximately 1 in 1,000 female newborns are born with triple X syndrome, but many females with this condition will not be diagnosed at birth. This condition can easily go undiagnosed, as many people never show apparent symptoms. Let’s take a closer look at some of the signs and causes of trisomy X.

Symptoms of triple X syndrome

There’s no one-size-fits-all list of symptoms for triple X syndrome. Further, not everyone with triple X shows symptoms related to their extra X chromosome. The most common symptom shared by those with triple X syndrome is above-average height (think: taller than other females in their age group or taller than you’d expect, given their parents’ heights).

Other physical symptoms may include:

• Widely spaced eyes
• Vertical skin folds (epicanthal folds) that cover the inner corners of the eyes
• Curved or bent pinky fingers (clinodactyly)
• Weak muscle tone (hypotonia)
• Seizures
• Kidney problems
• Premature ovarian aging or failure

Other symptoms may not show up until a child is older, such as:

• Delayed speech and language development
• Delayed development of motor skills
• Behavioral problems
• Mood disorders, including anxiety and depression
• Signs of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder
• Slightly lower intelligence compared to their siblings
• Problems with focus, memory, and social interactions

Remember, these symptoms may be subtle or may not appear at all in many with triple X syndrome. Whether they experience symptoms or not, most people with trisomy X have normal sexual development and are able to conceive children when they are older (if they want!).

Causes of triple X syndrome

Triple X syndrome is a genetic disorder that isn’t usually inherited from a parent. Instead, the extra X chromosome comes from a random error during cell division. This error can either happen before conception, when an egg or sperm divides incorrectly, or during the embryo’s development. 

Incorrect cell division happens, and chromosomes fail to separate equally, is called nondisjunction. If nondisjunction occurs in an egg or sperm cell before conception and then that atypical egg or sperm cell leads to conception, all the child’s cells will have the extra X chromosome. When the cell division error happens during an embryo’s development after a pregnancy has been conceived, only some of the child’s cells will have the extra X chromosome. This is called mosaicism.

Typically, people have 46 chromosomes—23 from each biological parent. Those with trisomy X have 47 (thanks to their extra X chromosome), which is why this condition is sometimes called 47, XXX syndrome. If triple X syndrome is suspected after birth (usually due to the presence of some of the symptoms we talked about), a genetic test, such as a karyotype, can confirm the diagnosis. However, because not everyone with trisomy X will show signs or symptoms of the condition, some people with trisomy X may not be diagnosed until later in life, and some may never be aware that they have an extra X chromosome.

Trisomy X may be suspected during pregnancy if non-invasive prenatal screening (NIPS) reveals an increased risk for three X chromosomes in a female fetus, and the diagnosis can be confirmed through prenatal diagnostic tests such as amniocentesis. Since triple X syndrome only affects babies assigned female at birth, if Y chromosome material is detected in a pregnancy, we would not expect that pregnancy to have triple X syndrome. However, other sex chromosome differences can affect males, such as Klinefelter syndrome, where males have an extra copy of the X chromosome (XXY).

If you’re unsure whether you’re having a boy or girl, click here to learn how our Juno Birch™ Fetal Gender Test can give you the answer you’re looking for!