What Is Triple X Syndrome?

Triple X syndrome (trisomy X or 47, XXX) is a genetic condition that occurs when a female is born with three X chromosomes in all or most of her cells rather than the usual two. Signs and symptoms of triple X syndrome vary widely. Some people may have no signs or symptoms, while others may experience developmental, psychological, and medical symptoms. 

Triple X syndrome was first described in 1959 by Scottish geneticist Patricia Jacobs, who discovered a patient with premature ovarian failure had three X chromosomes. Since then, research shows that approximately 1 in 1,000 females are born with triple X syndrome, though only 10% are diagnosed in their lifetime.

This article describes the symptoms associated with triple X syndrome, how it is diagnosed, and the support and treatment options for people with it.

Triple X Syndrome Symptoms 

Signs and symptoms of triple X syndrome vary widely—some people may have no symptoms or may only be mildly affected, while others may have more noticeable symptoms. 

Though not everyone with triple X syndrome has apparent physical features associated with the condition, many have some or all of the following:

• Tall stature and long limbs (arms and legs) 
• Flat feet
• Curved pinky finger (clinodactyly)
• The skin of the upper eyelid covering the inner corner of the eye (epicanthal eyelid)
• Wide-spaced eyes (hypertelorism)
• Low muscle tone (hypotonia)

Many people with triple X syndrome experience a range of developmental, physical, and psychological symptoms, including:

• Speech delays 
• Learning disabilities (e.g., dyslexia) 
• Chronic constipation and abdominal pain 
• Attention deficit hyperactivity disorder (ADHD)
• Delayed social developmental 
• Motor skill developmental delays
• Anxiety 
• Seizures
• Hand tremors
• Kidney or genitourinary malformations 

Most people with triple X syndrome experience normal sexual development and fertility. Still, some have abnormal ovarian development (dysgenesis), menstrual irregularities, delayed or early onset puberty, or primary ovarian failure.

What Causes Triple X Syndrome?

Triple X syndrome is a genetic disorder not usually inherited from a biological parent. It occurs as a random chromosomal error during the formation of reproductive cells (egg and sperm) in one of the parents or early in an embryo’s development.

Typically, people have 46 chromosomes in each of their body’s cells. Two of these chromosomes—X and Y—are sex chromosomes that determine whether a person is born male or female. Females are usually born with XX sex chromosomes, but females born with trisomy X will have an extra copy of the X chromosome in each of their cells. 

While most people born with triple X have an extra copy of the X chromosome in all of their body’s cells, some only have an extra X in some of their cells. This is known as 46, XX/47, XXX mosaicism, associated with milder symptoms and fewer developmental and learning delays.

Triple X syndrome cannot be prevented and does not occur due to something a parent did or didn’t do before conception or during pregnancy. Some research suggests women of advanced maternal age (35 or older) are more likely to give birth to a child with triple X syndrome than younger people. However, other studies show that advanced maternal age does not significantly increase the risk.

How Is Triple X Syndrome Diagnosed?

Most babies born with triple X syndrome do not have any obvious physical signs or symptoms at birth. The condition is often undetected until early childhood, when parents express concern to a healthcare provider about their daughter’s developmental or language delays.

If a healthcare provider suspects triple X syndrome, they will take a blood sample and send it to the lab for an analysis of the chromosomes, which can detect extra X chromosomes in the cells.

In recent years, routine prenatal testing has increasingly detected triple X syndrome during pregnancy. Prenatal screening tests, such as noninvasive prenatal testing (NIPT) or chorionic villus sampling (CVS), can check for genetic disorders like triple X syndrome in fetuses. If NIPT or CVS results indicate that the fetus may have triple X syndrome, an amniocentesis (a procedure to test amniotic fluid) can be performed to confirm the diagnosis. 

Sometimes, a triple X syndrome diagnosis may be incidental and given when genetic testing is performed for a different medical condition. Because it often causes mild symptoms (if any), experts believe that only 10% of people with triple X syndrome get diagnosed. 

Treatment for Triple X Syndrome

There is no cure for triple X syndrome, but many treatments and interventions can help manage symptoms and improve quality of life. Treatment for triple X syndrome depends on individual symptoms and the age of diagnosis. 

Triple X syndrome treatments can include:

• Early intervention services: Children with triple X syndrome may benefit from early intervention services, such as speech and language therapy, occupational therapy, behavioral therapy, and physical therapy. These therapies can help improve motor skills, communication, social skills, and overall development.
• Education support services: People with triple X syndrome are usually of average intelligence but may experience learning difficulties, such as delayed language and reading skills or problems with memory and attention. Educational support, such as individualized education plans (IEPs) and classroom accommodations, can help support their success in school.
• Genetic counseling: Families of infants and children diagnosed with trisomy X may benefit from genetic counseling to better understand the disorder and how to support their child best. 
• Counseling: Some individuals with triple X syndrome may experience behavioral and emotional issues, such as anxiety, depression, and social difficulties. Counseling or psychotherapy can help address these issues and improve emotional well-being. 
• Hormone therapy: Sometimes, people born with triple X syndrome may experience menstrual irregularities or premature ovarian failure. Hormone therapy, such as hormonal birth control, may be recommended to regulate menstrual cycles.

Regular checkups with a healthcare provider are essential for infants and children with triple X syndrome. Along with parents, a healthcare provider can monitor a child’s development for developmental and neuropsychological delays or health problems that may occur. 

What Is the Prognosis? 

Most people with triple X syndrome lead full, healthy lives. They attend school, have careers, parent children, and live as long as their peers who do not have the disorder. Ongoing medical care and support from healthcare professionals ensure those with the condition get the appropriate care and support for any developmental, physical, or cognitive symptoms. 

Coping With Triple X Syndrome

Getting regular checkups to identify and manage any health, behavioral, or developmental issues that may arise is an important part of living with triple X syndrome. If you have a child with triple X syndrome, early intervention services can help address any developmental delays or social and emotional challenges your child experiences. 

Along with support from family members, friends, and professional therapists, many people affected by triple X syndrome find value in joining support groups. In this way, they can connect with others with similar challenges and experience a sense of community. 

Summary

Triple X syndrome is a genetic condition that occurs when females are born with three X chromosomes rather than two. While many people with the disorder have no symptoms, it can cause developmental, language, and social delays. Physical characteristics such as flat feet, low muscle tone, wide-spaced eyes, and tall stature are common.

Diagnosis can be made during pregnancy through routine prenatal screening tests or a blood test at any point in a female's life. Treatment options vary depending on the symptoms but may include early intervention services (e.g., speech therapy, occupational therapy), education support, and counseling. With the proper support, most women and girls with triple X syndrome can live healthy, fulfilling lives.