Every cell in the human body typically has 23 pairs of chromosomes. The first 22 pairs are the same in males and females. The 23^rd pair is our sex chromosomes, where males typically have one X and one Y chromosome and females typically have two X chromosomes.

Incidence

Variations can occur with our sex chromosomes, resulting in individuals with extra or missing sex chromosomes. Generally, these types of genetic differences are quite common, occurring in about 1 in 500 to 1 in 1000 individuals.  The incidence may actually be higher since it is possible for individuals to have a sex chromosome difference and not be aware of them.

With the use of prenatal diagnosis, these sex chromosome differences are being identified in pregnancy more frequently and often as a finding that was not associated with the reason for testing. These sex chromosome differences likely would not have otherwise presented themselves in the pregnancy. It is thought that babies whose sex chromosome differences are found during pregnancy are developmentally more mildly affected than babies not diagnosed until after pregnancy.

Features

Features of these conditions are variable and depend on which chromosome is extra or missing.  Some features may be mild (like tall or short stature), or may lead to differences in development such as delayed speech or learning differences.  They may also be associated health issues involving puberty or the heart. Some prenatal screening and diagnostic testing can identify extra or missing X and/or Y chromosomes that may have otherwise gone undetected because of mild features. 

Some of the common sex chromosome differences that may be identified on prenatal screening include:  

Turner syndrome

Turner syndrome (also known as monosomy X) is a condition that occurs in females and is caused by a female having one X chromosome instead of two X chromosomes. The condition occurs in about 1/2500 newborn girls and in 1-1.5% of pregnancies. The overall prevalence is higher in pregnancy because many babies with Turner syndrome will miscarry before delivery. Most cases of Turner syndrome are not inherited.

A missing chromosome X can affect the development of each baby differently. In general, girls with Turner syndrome do not have an intellectual disability. Some common features include:

• Increased fluid at the back of the baby's neck in pregnancy (increased nuchal translucency or cystic hygroma)
• Extra folds of the skin on the back of the neck (webbed neck)
• Congenital heart defects
• Short stature
• Swelling of the hands and feet (lymphadema)
• Delayed puberty without the use of hormone replacement therapy
• Loss of ovarian function
• Infertility
• Learning disability
• Scoliosis

Turner syndrome karyotype

Illustration adapted from Genetic Counseling Aids, 7th Edition, Copyright 2020, permission for use granted by Greenwood Genetic Center

Triple X syndrome

Triple X syndrome (also called Trisomy X or 47, XXX) is a condition that occurs in females and is caused by females having an extra copy of the X chromosome. Girls with triple x syndrome typically have no physical features with the exception that they may be taller than average. Many girls with triple x syndrome may have no symptoms while some girls may experience learning disabilities and delayed language and speech. Most cases of Triple X syndrome are not inherited.

Klinefelter syndrome

Klinefelter syndrome (also called 47, XXY) is a condition that occurs in males and is caused by males having an extra copy of the X chromosome. Unless identified during the pregnancy through diagnostic testing, boys with Klinefelter syndrome are typically not identified until puberty as their symptoms are so mild. Physical features associated with this condition may include tall stature, development of breast tissue, reduced body and facial hair, infertility and small testes that produce a reduced amount of testosterone. Some of these features are due to this reduced testosterone. Treatment is available for some of these symptoms. Some individuals with Klinefelter syndrome may experience learning disabilities and delayed language and speech. Autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and mental health concerns have been reported to be associated with the condition. Most cases of Klinefelter syndrome are not inherited.

Jacob's syndrome

Jacob's syndrome (also called 47, XYY) is a condition that occurs in males and is caused by males having an extra copy of the Y chromosome. Boys with Jacob's syndrome typically have no physical features with the exception that they may be taller than average. Jacob's syndrome is associated with an increased risk of behavioural, learning, communication and social interaction difficulties. Most cases of Jacob's syndrome are not inherited.

Next steps

You may be hearing about sex chromosome differences because your prenatal screening test was positive or high risk for having a baby with a sex chromosome difference. If this is the case, your health care provider should offer to refer you for genetic counselling to review your test results and your options for additional testing.

Additional resources

Regional Genetics Centres

Genetics Home Reference

Turner Syndrome Society of Canada

Sources for this page:

Hook EB, Warburton D Turner syndrome revisited: review of new data supports the hypothesis that all viable 45,X cases are cryptic mosaics with a rescue cell line, implying an origin by mitotic loss. Hum Genet. 2014;133(4):417-424.

Linden MG and Bender MG. Fifty-one prenatally diagnosed children and adolescents with sex chromosome abnormalities. Am J Med Genet 2002; 110(1):11-8.

U.S. National Library of Medicine. Genetics home reference [Internet]. Bethesda (MD): U.S. National Library of Medicine; 2017. Available from: https://ghr.nlm.nih.gov