Thanks to the InterConnect Support for language on the intersex variations below.
Last updated February 19th, 2021.
This page offers descriptions of some of the more common intersex traits. Intersex is still often referred to as “differences of sex development” (DSD) by the medical community. [read interACT’s Statement on Intersex Terminology]
What is the definition of intersex?
Intersex is an umbrella term for unique variations in reproductive or sex anatomy. Variations may appear in a person’s chromosomes, genitals, or internal organs like testes or ovaries. Some intersex traits are identified at birth, while others may not be discovered until puberty or later in life.
People with intersex traits have always existed, but there is more awareness now about the diversity of human bodies. People with intersex bodies sometimes face discrimination, including in healthcare settings, as early as infancy. There are over 30 medical terms for specific combinations of intersex traits. Every intersex person is different.
Sex characteristics is a term that often refers to the internal and external traits of an individual’s body. Gender and sexual orientation are different concepts. Intersex people can have any gender identity and sexual orientation.
Potential causes of intersex traits include random genetic variations, changes in a person’s number of sex chromosomes, gonadal differences, natal exposure to unusual levels of sex hormones, or different responses to sex hormones. Intersex traits in and of themselves are not life-threatening, although they are sometimes associated with other serious medical symptoms, such as with salt-wasting congenital adrenal hyperplasia (SW CAH) and turner syndrome.
What are some examples of intersex variations?
The list below describes different medical terms for intersex traits.
46, XX salt-wasting Congenital Adrenal Hyperplasia (SWCAH)
A baby with XX chromosomes and CAH usually has a uterus and ovaries, and genitalia that may appear visibly different. This may include having a large clitoris, short vagina, and/or larger or different labia. Babies with other types of CAH may not have genital difference.
While genital differences on their own are almost never life-threatening, infants with CAH also have serious medical needs due to how their bodies produce stress hormones. 46, XX salt-wasting CAH (SWCAH) happens when there is a genetic mutation in enzymes of the adrenal gland, which sit on top of the kidneys. These enzymes are chemicals needed by the adrenal gland to make cholesterol into three important hormones that help to regulate the body’s functions: cortisol, aldosterone and androgen. If one of the enzymes needed to make cortisol and/or aldosterone is not working properly, the adrenal glands fail to work in a balanced way. They make too little cortisol and/or aldosterone, and more androgen than usual. When there is not enough cortisol or aldosterone, babies with SW CAH may become very sick. They can become dehydrated and lose blood pressure if not treated urgently.
Androgen Insensitivity Syndrome (AIS)
AIS happens when babies are born with testes and XY chromosomes, but their bodies are immune or unable to respond to androgens, a category of hormones including testosterone. Since a penis and scrotum develop under the influence of androgens, a baby with AIS may develop with genital differences, depending on their level of immunity to androgens.
Babies with complete AIS (CAIS) have no response to androgens and usually develop a vulva and typically sized clitoris, while babies with partial AIS (PAIS) may have genital differences, with external genitalia that appear on a spectrum. During development, the testes also make a hormone (Mullerian inhibiting substance, or MIS) that prevents formation of the uterus, Fallopian tubes, and a small part of the upper vagina. Children with testes and less sensitivity, or ability to respond to androgen, may go through a feminizing puberty on their own. Because testes do make some estrogen, and the body can turn androgen into estrogen, these children may have traits like breast development from their own hormones at puberty, and often supplement that with synthetic hormones to develop fully. Surgical removal of the testes (gonadectomy) may be recommended in PAIS because there may be a risk of cancer developing in the testes. The risk of cancer development before puberty in CAIS is very low, and it is accepted medical practice to leave CAIS testes in place for a more natural puberty. Because androgen also influences sperm formation, some adult men do not discover that they have minimal PAIS until they see a doctor for infertility.
46, XY complete gonadal dysgenesis (Swyer syndrome)
Swyer syndrome occurs when a baby is born XY chromosomes, but the testes do not develop. During prenatal development, these babies develop a vulva and a small uterus. The underdeveloped, would-be testes become fibrous tissue called “streaks”, which are neither testis nor ovary. These children need to take hormones in order to start any puberty. Because there is an increased risk of cancer developing in streak gonads, removal is commonly recommended.
46, XY partial gonadal dysgenesis
Partial gonadal dysgenesis in a baby with XY chromosomes causes development of testes that do not function at the same level as typical testes. Sometimes the testes disappear or regress. Babies’ genitals can vary in appearance depending on how much the testes function. Tumors occur about 20-30 % of the time.
5 alpha reductase-3 deficiency (5 ARD deficiency) and 17beta-hydroxysteroid dehydrogenase-3 deficiency (17 BHSD deficiency)
In 5 alpha reductase-3 deficiency (5 ARD deficiency) and 17beta-hydroxysteroid dehydrogenase-3 deficiency (17 BHSD deficiency), genetic mutations in XY babies with testes result in atypical levels of sex hormones. All hormones are made from cholesterol by enzymes, and these mutations change the function of enzymes needed to make androgens. Children with 5 ARD deficiency and 17 BHSD deficiency have XY chromosomes and testes, but their testes make a version of androgen that is weaker than usual. Babies may have a vulva or vary along the spectrum of genital difference. At puberty, when levels of androgen increase dramatically, the large amount of weaker androgens can cause changes such as deepening of the voice, growth of facial hair, and muscle development. If a child does not want these changes, puberty can be blocked by medication. There are reports of fertility in adults with 5 ARD, but not 17 BHSD deficiency.
In typical sex development, the fetus develops two tiny organs called “proto-gonads.” Usually these proto-gonads will become either testes or ovaries. Sometimes an ovotestis develops instead, which contains some ovary-type cells and some testis-type cells. Although a person may be born with two ovotestes, it is much more common for a person to be born with a typical ovary or testis on one side and an ovotestis on the other. People with ovotestes may have a typical genital appearance at birth, with either a vulva and labia or penis and scrotum, and some look more in-between. Because there may be many different chromosomal and internal anatomical combinations, children may need other tests to evaluate their unique situations. The testicular part of ovotestes may have an increased cancer risk.
Children with 46, XX chromosomes and ovaries may have atypical development of internal structures such as the vagina, the uterus, and the Fallopian tubes. MRKH sometimes also involves differences in development of the skeleton, internal ears, and in rarer cases, the heart, fingers and toes.
Hypospadias and Epispadias
Hypospadias happens when the urinary opening (urethra) is located below the usual position on the tip of the penis. It is one of the most common and visible genital variations. Hypospadias is the most common birth difference in children with XY chromosomes, seen in 1 out of every 125 to 300 live births. The cause of hypospadias is not known. The location of the opening of the urethra can vary from just below the tip of the penis down to just in front of the rectum. Bending of the penis, or chordee, is often seen with hypospadias, although they can occur separately.
Epispadias is similar to hypospadias because the urinary opening is not in its usual position. In epispadias, the urinary opening is located on the upper surface of the penis or in the middle of the clitoris. It is much less common than hypospadias. Epispadias usually happens in conditions called exstrophy, where the bladder, abdominal wall, and pelvis are not closed in the front as usual, but epispadias can also occur by itself.
Find more information via the Hypospadias and Epispadias Association, Inc.
X0 Turner Syndrome (TS)
Turner Syndrome happens when a person has one complete X chromosome, and their second X chromosome is absent or smaller than usual. This happens in about 1 in 2000 live births. Turner syndrome is sometimes found prenatally with amniocentesis. In TS, the level of hormones needed to start puberty is unusually low because of a difference in development of the ovaries, which are called “streak gonads.” TS can also be discovered in adolescence when puberty does not happen as expected. Many people with TS are petite, often under 5 feet tall. Other organs in the body, such as the heart, may also develop atypically.
Some people only have one X chromosome in some of their cells. This is called “mosaic Turner Syndrome.” The other cells can have XX or XY chromosomes. Physical difference in mosaic TS will depend on what proportion of the cells and tissues have typical XX or XY chromosomes. See the Turner Syndrome Society website for more details.
XXY Klinefelter syndrome
Klinefelter syndrome (or XXY syndrome) is a genetic condition in which a person has an extra copy of the X chromosome. Klinefelter syndrome isn’t inherited, but rather occurs only as a result of a random genetic error after conception. People born with Klinefelter syndrome may have low testosterone and reduced muscle mass, facial hair, and body hair. Most people with this condition produce little or no sperm. Some may choose testosterone replacement and fertility treatment.