What is Triple X Syndrome?

Triple X syndrome is a rare genetic disorder that only affects people assigned female at birth (PAFAB). It is caused by an extra X chromosome which is the result of a random error in the genetic code during the development of the foetus. It is not hereditary. 

Overview

The development and traits of our bodies are instructed by genes - pieces of DNA that carry genetic information. Every individual has their own unique genetic code which tells the cells how to build and operate the organism. Sometimes an error can occur in the genes causing some alterations in development.

Triple X syndrome, also known as XXX syndrome, 47,XXX, and trisomy X, is a rare genetic disorder that only affects people assigned female at birth (PAFAB). It affects approximately one in every 1,000 PFAB of all ethnicities and racial backgrounds.¹ Most people with triple X syndrome don’t show symptoms, grow up healthily and lead normal lives. Symptoms of triple X syndrome may include developmental problems such as poor coordination, weak muscles and learning disabilities. Treatment for triple X syndrome varies based on the symptoms experienced by a patient.

Causes of triple X syndrome

Triple X syndrome is caused by an extra X chromosome present in a PAFAB’s genes. While it is a genetic disorder, trisomy X is not inherited and results from a random error in genes. 

Chromosomes are structures of genes that carry information about the development of the organism. Most people have 46 chromosomes, consisting of 23 pairs. The 23rd pair determine the sex of a person. PAFAB can only pass an X chromosome, while PAMAB (people assigned male at birth) can pass either an X or a Y chromosome.

• A foetus is genetically male when the 23rd chromosome pair consists of an X chromosome from the  egg and a Y chromosome from the sperm, resulting in an XY pair
• A foetus is genetically female when the last pair consists of an X chromosome  from an egg and an X chromosome from a sperm, resulting in an XY pair 

Women with triple X syndrome have three chromosomes (XXX) in total caused by a random error occurring during cell division, either before fertilisation or after. A genetic condition with an extra X chromosome in boys is called Klinefelter syndrome and affects PAMAB  in a different way.

The presence of an extra X chromosome in an XX embryo can be caused by:

• Nondisjunction triple XXX – An error in cell division during the development of sperm and egg cells. During cell division, chromosomes exchange pieces of genetic material and, if this process goes wrong, it can result in an egg or sperm with an extra copy of the X chromosome. This abnormal egg or sperm can contribute to the creation of an embryo which will then have three copies of the X chromosome instead of two. As this error can occur in both sperm and egg cells, the error can be passed to the embryo from both the maternal and paternal sides
• Mosaic triple XXX – Incorrect cell development in the early development of an embryo. This occurs after the sperm and egg cells have formed an embryo and may affect only some cells in the embryo. Those with a mosaic form of trisomy X experience milder and less obvious symptoms

The errors in cell division are rare and random. If you have a child with triple X syndrome, the risks of having another baby with an extra chromosome are extremely low.

Signs and symptoms of triple X syndrome

There is a range of symptoms caused by trisomy X. It is important to note that not all people with this condition will experience these physical or developmental differences, so the diagnosis must not be based on physical appearance alone. 

The most common physical manifestation of triple X Syndrome is tall stature, due to increased growth hormone production. Most women with the condition have healthy sexual development and fertility, however, they can experience early menopause or premature ovarian failure.¹ 

Occasional symptoms associated with triple X Syndrome are learning disabilities including difficulties with reading comprehension, written expression, mathematics, problem-solving skills, and processing speed. Those affected may also experience delays in language development, such as difficulty understanding instructions or using appropriate grammar when speaking. However, most people diagnosed with trisomy X are within the normal learning ability range. 

Other potential symptoms include physical growth delays, poor muscular coordination, speech articulation difficulties, and underdeveloped or absent secondary sex characteristics such as breast tissue. 

In rare cases, individuals may also display behaviour problems including obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), or autism spectrum disorder (ASD).¹

Other signs of trisomy X could be:

• Flat feet
• Widely spaced eyes
• An inward bowed-shaped breastbone
• Curved pinky finger
• Problems with the kidneys
• Seizures

Despite a range of potential symptoms, many carriers of trisomy X don’t show any obvious signs of the condition. 

Complications of triple X syndrome

Complications associated with this genetic condition can include low self-esteem and difficulties with learning and daily activities that can lead to problems in social situations. Some carriers may suffer early menopause or premature ovarian failure. 

Management and treatment for triple X syndrome

Most people with triple X syndrome do not require any medical treatment, although some may need help managing certain health implications associated with the condition. Trisomy X cannot be cured, however, it can be effectively managed with symptom-based treatments. Early management of symptoms can be key for healthy development leading to a normal and productive lifestyle. 

Regular checkups with a doctor are necessary for monitoring physical growth and development, as well as psychological well-being of a patient. Doctors can also evaluate the effectiveness of treatment and adjust the treatment plan if necessary.

There are several treatment options available once an individual is diagnosed with triple X syndrome which include:

• Hormone therapy – To treat hormonal abnormalities such as height, premature ovarian failure or fertility planning. Endocrinologists (doctors who deal with hormone disorders) may prescribe oestrogen to normalise the menstrual cycle or treat early menopause symptoms¹
• Occupational therapy – Helps to improve quality of life and increase productivity by supporting the daily activities of an individual. It aims at working on difficulties with coordination associated with the syndrome
• Counselling – Can potentially benefit the whole family by providing information about triple X syndrome and how to support someone l with the condition to lead a normal lifestyle. Psychological counselling helps with mental health concerns related to social difficulties due to impaired communication skills or attention deficits
• Genetic counselling  –  Consultations with a medical professional who specialises in genetics and reproductive health. Through genetic counselling, parents can learn about the risk factors of having a child with triple X Syndrome and discuss effective strategies for managing their child’s condition. Genetic counsellors can provide resources for further support such as support groups or financial assistance for medical treatments
• Educational assistance  – Treatment for delayed development should focus on providing educational interventions such as speech therapy or tutoring so individuals can reach their full potential

FAQs

How is triple X syndrome diagnosed?

You should see your doctor if you have concerns about the development of your child. There are several methods used to diagnose Triple X Syndrome. The most common method is through chromosome analysis (karyotyping). This test looks for any extra or missing chromosomes in a sample of cells and can be done through a blood sample.¹ 

Another option is prenatal genetic testing. This type of test screens for abnormalities in the foetus and can be done as early as ten weeks into pregnancy. Common tests used for prenatal screening are chorionic villus sampling (CVS) and amniocentesis.² CVS involves collecting a small sample of placental tissue while amniocentesis involves collecting fluid from around the foetus. Both CVS and amniocentesis produce highly accurate results and can detect chromosomal abnormalities such as an extra X chromosome. However, it should be noted that these tests carry a small risk of miscarriage; therefore, they should only be done if the risks outweigh any potential benefits.

Another tool used to diagnose Triple X Syndrome is array-comparative genomic hybridization (aCGH).³ This test can identify changes in chromosome lengths or structure within a single cell and can also be used during pregnancy to detect any chromosomal abnormalities. However, this method is very expensive and almost impossible to find in hospitals and testing centres. 

How can I prevent triple X syndrome?

As most cases of triple X syndrome are not inherited, it is an unpreventable disorder and there is nothing you can do to prevent its occurrence.  

Who is at risk of triple X syndrome?

There are no known established risk factors identified by research that contribute to the development of trisomy X, so there is nothing you can do wrong to get the disorder. 

However, there is some evidence of a correlation of advanced maternal age with the likelihood of having a baby with the disorder: PAFAB after 45 are more likely to give birth to a daughter with this condition.¹ This likely occurs because older eggs are more prone to errors during sex cell division. 

It is also possible that there could be a genetic component to triple X syndrome: some chromosomal conditions are caused by mutations in specific genes that act as triggers for certain types of genetic errors.

How common is triple X syndrome?

It is a rare disease which affects 1 in 1,000 PAFAB. However, only 10% of those with the condition will be diagnosed.¹

When should I see a doctor?

If you have any concerns about your child’s development and health, consult with your GP. The GP will discuss the signs and symptoms and will help to determine the next steps for diagnosis and treatment. Early diagnosis can prevent health complications and ensure better management of the symptoms. 

Summary

Triple X syndrome is a genetic disorder caused by the presence of an extra X chromosome in the genetic code of those assigned female at birth. It occurs due to a random mutation in a sperm/egg cell or foetus and is not hereditary. Only some people show symptoms and signs of the syndrome. Early intervention and management of the symptoms can lead to healthy growth and development. Most people with trisomy X have no difficulties with getting pregnant and do not pass the condition to their children.