Differences of Sex Development

The THRIVE program specializes in the care of individuals with Differences/ Disorders of Sex Development (DSDs). These include:

Androgen Insensitivity Syndrome

Androgen Insensitivity Syndrome (AIS) occurs when a person has an XY karyotype (typical male genes), but the body does not respond to androgens (“male hormones”). Therefore the individual develops into a typical looking female, but lacks the typical female internal reproductive organs (ovaries, uterus, cervix). Androgen Insensitivity occurs in about 1 in 65,000 females.

The gene that codes for sensitivity to androgens is on the X chromosome. It is possible for a woman to carry a copy of an ineffective gene, but not be affected due to having another X chromosome that is not affected. Women who are carriers have a 50% chance of passing the mutated gene on in each pregnancy.

Partial AIS often results in an individual being born with Ambiguous Genitalia or genital difference. However, Complete AIS diagnosis does not usually occur prenatally or at birth, due to typical looking external female genitalia (labia, clitoris, vaginal opening).  Often, affected girls will present to a doctor with a hernia. During the repair it can be discovered that the hernia contains an undescended testes. Sometimes, a diagnosis is not determined until a teen girl does not start her period, due to the lack of an internal female reproductive system.

Ambiguous Genitalia

Ambiguous Genitalia occurs when a baby is born with external genitalia that look neither typically female nor typically male. This term describes the look of the genitals and is not in itself a medical diagnosis. This can happen for multiple reasons and a team of geneticists, endocrinologists, and urologists will run tests to determine a recommendation for sex of rearing. Parental input on sex of rearing is very important for making this early decision. Often, with few exceptions, babies with ambiguous genitalia are otherwise physically healthy. However, if a condition called Congenital Adrenal Hyperplasia (CAH) is the cause of the genital ambiguity, this can be a medical emergency. Testing for CAH will be one of the first things the medical team will complete. Ambiguous genitalia occurs in about 1 in 4,500 births.

Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia (CAH) occurs when the adrenal gland produces too much androgen (“male hormones”). CAH is the most common DSD and the most common cause of ambiguous genitalia. Girls typically present with an enlarged clitoris and a narrow/small vagina. However, girls will often have a typical internal female reproductive system. Girls with CAH will need hormone replacement therapy and in some cases reconstructive surgery of the genitals.

Both females and males can be born with CAH and this condition occurs in about 1 in 10,000 births. Males born with CAH will have typical looking genitals at birth, but may develop pubic hair and a deep voice at a younger than normal age. Males will typically only need medical follow-up.

Mixed Gonadal Dysgenesis

MGD occurs when one gonad forms into an undescended testies and the other forms into a “streak” or malformed gonad. Often the chromosomes take on a 46 XY, 45 XO formation which causing the development of two different gonads. MGD is one of the most common DSD and a leading cause of ambiguous genitalia. In male patients this can be referred to as a very severe case of Hypospadias.  In most cases, those with MGD are determined to be and raised as male. Surgery often follows diagnosis to bring the testicle down out of the abdomen and remove the “streak” or malformed gonad due to concern that a tumor may develop within that gonad.


Hypospadias occurs when the hole of the penis (urethra) is located on the underneath of the penis instead of at the tip. Hypospadias is very common and can occur in various forms of severity/complexity. This condition occurs in about 1 in 200 births. It is thought to be more serious the closer the hole is to the base of the penis and therefore the furthest away from the tip. Curvature of the penis can complicate the condition. Some mild forms of hypospadias may not require surgery, but should be evaluated by an urologist.

Vaginal Agenesis

VA occurs when a female’s reproductive system does not fully develop while in the womb. This may take the form of a girl being born without a vagina or missing other internal reproductive organs. This condition affects about 1 in 6,000 female infants. All of these girls will have either an absent or incomplete vaginal canal, or absent uterus, and/or cervix. The external genitalia of those affected will look typical. Some affected girls will be diagnosed at birth, but some will not receive a diagnosis until a teen presents to a doctor for not having started her period.

Turner Syndrome

Turner Syndrome is a chromosomal condition that affects females. The most common feature is short stature, which becomes evident around age 5. Most affected girls do not undergo puberty unless they are receiving hormone replacement therapy. Often, before birth, ovarian tissues degenerates and do not function correctly. However, a small percentage of girls with Turner Syndrome retain normal ovarian function through young adulthood. Other medical complications that can be associated with Turner Syndrome, include skeletal abnormalities, kidney problems, and a heart defect that can be life threatening. Developmental delays, learning disabilities, and behavioral problems can also be associated with this condition.

Klienfelter Syndrome

Klienfelter Syndrome is a chromosomal condition that affects males. The chromosomes in this condition take on a 47 XXY formation, although more severe variants (i.e. 48 XXXY, 49 XXXXY) are possible. Boys with this condition typically have small testes that do not produce the typical amount of testosterone. This reduced amount of testosterone can lead to delayed/incomplete puberty, breast enlargement, reduced facial/body hair, and infertility. Some will present with genital differences such as undescended testes, hypospadias, and/or a very small penis.