Disorders of Sexual Differentiation Program

Disorders of sex differentiation, also known as disorders of sexual development or DSD, are conditions in which the sexual development that occurs during fetal growth does not happen as it should. DSD can develop genetically, be inherited or have no identifiable cause. The most common disorders in newborns are congenital adrenal hyperplasia and mixed gonadal dysgenesis.

Humans have 46 chromosomes in each cell of their bodies, or 23 pairs. The 23rd pair determines our gender; females have two X chromosomes, while males have one X and one Y chromosome. The chromosomes are referenced as 46, XX, for a normal female or 46, XY, for a normal male.

During fetal development the tissue that eventually becomes the gonads (ovaries or testes) receives signals based on the child’s genetics. There is a gene located on the top portion of the Y chromosome, called “SRY,” which, if present, will cause the gonad to become testes (indicating a male) around the sixth week of fetal life. This will also cause the regression of what would have been in the female reproductive tract. As the testes grow and start to produce testosterone, the penis, scrotum and urethra form.

In the absence of the “SRY” gene, the gonad will turn into an ovary (indicating a female). The female reproductive tract will continue to develop, forming the uterus and fallopian tubes. At the same time, what would have become the male reproductive organs goes away.

Besides the SRY gene, certain hormones can influence the development of the sexual organs. These hormones are secreted during the early weeks of pregnancy and include the anti-Müllerian hormone, testosterone hormone, and dihydrotestosterone, an active derivative of testosterone.

Children with DSD will normally have atypical-appearing genitalia (genitalia that do not look normal) at birth. Atypical genitalia may make determining the child’s sex more difficult. Children are quickly referred to one of our specialists for in depth analysis to determine the underlying disorder. Although most children with DSD will have atypical appearing genitalia not all children will. The appearance and severity of DSD varies greatly in each child.

There are many types of disorders of sexual differentiation (DSD) and atypical genitalia, and the symptoms each child experiences will vary greatly based on the type and severity of the disorder. Usually, these symptoms are picked up during fetal ultrasounds or shortly after birth upon physical examination. Some symptoms may include an enlarged clitoris which may take on an appearance of a small penis, a vaginal opening may appear closed, cloacal anomaly, hypospadias, or a scrotum that appears empty or separated. There are other features that may also be found.

A DSD is a diagnosis that can be both difficult to understand and explain to family members who are close to the child. It is important for families to educate themselves on the child’s specific disorder. The disorders below are some of the most common disorders of sex differentiation that cause atypical genitalia. There are other syndromes that can cause atypical genitalia and children with those disorders will also be seen at the CHOC Urology Center.

Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) is a genetic disorder in which the adrenal gland over produces androgens, a male hormone. Due to this, a child born with CAH will likely have genitalia that does not appear typical. With appropriate medical, surgical and psychosocial support, children with CAH can lead full and healthy lives and enjoy a normal life expectancy. Learn more about CAH and its treatment at CHOC Children’s.

Mixed Gonadal Dysgenesis
Mixed gonadal dysgenesis occurs in children who have a chromosomal abnormality that causes them to be born with two different gonads—an undescended testis and a dygenetic (malformed) “streak” gonad. Because these two gonads do not produce normal sex hormones, the child’s sexual organs do not develop as they should. The external genitalia on these children will vary between normal appearing female and normal appearing male. There is a wide range of internal and external features for these children and each case is handled individually in order to assign the most appropriate sex for the child.

Although less common then the two DSD above, the following disorders are also treated at the CHOC Urology Center Disorders of Sexual Differentiation Program.

Androgen Insensitivity Syndrome
Children with androgen insensitivity syndrome have a 46, XY karyotype for a normal male. The cells within the body in these children do not respond to the male sex hormone, androgen (testosterone). This will often cause the child to display female characteristics despite being genetically male. There are varying degrees to this disorder. A child may be completely androgen insensitive, which causes the child to appear completely female in their external genitalia or they may be partially insensitive in which the genitalia may not look clearly male or female at birth.

Androgen insensitivity syndrome is an X-linked recessive inherited genetic disorder. This means that male children born to mothers who carry the gene for this disorder have a 50% chance of having the disorder. Females born to mothers who carry the gene have a 50% chance of carrying the gene and passing it down to their children in the future.

Pure Gonadal Dysgenesis
Children with pure gonadal dysgensis syndrome have a 46, XY karytope of a normal male but have underdeveloped gonads and both internal and external female genitalia.

5-alpha-reductase Deficiency
Children with 5-alpha-reductase deficiency have a 46, XY karyotype of a normal male but have a deficient enzyme (5-alpha reductase) that prevents the body from being able to change testosterone into dihydrotestosterone. Dihydrotestosterone is needed to make a male fetus masculine. This deficiency is inherited by an autosomal recessive gene. This means that both the biological mother and father must carry the gene for the deficiency and pass it onto the child. If both the mother and father carry the gene, then each of their pregnancies will have a 12.5% chance of be affected. Female children will not be affected.

CHOC works directly with families to provide medical, surgical and pyschological support. Families looking for additional education, information and support may learn more about CAH at the CARES Foundation website. (CHOC does not endorse the information found at this or other sites.)

Treatments for disorders of sexual differentiation (DSD) vary depending on the degree and type of disorder. Each treatment plan is individualized to each child and their family. This is done by maintaining a close relationship between the family and the specialists at the CHOC Urology Center Disorders of Sexual Differentiation Program. The child’s family is directly involved in every step and decision made regarding their their child’s care. As the child ages, they too will become vital in helping to make decisions about their care.

Treatments for DSD can include management with medications or hormones, surgical management and/or psychosocial support. Treatments are determined on a case-by-case basis depending on the type and degree of the child’s disorder.

• Some surgeries may be required, while others may be optional. Surgeries may be needed for children whose conditions interfere with the child’s sexual or reproductive function or general health. Other surgeries may be completed to create genitalia that appear closer to the norm for the child’s sex or gender. Families will discuss all surgical options with our surgeons.
• Hormone replacement therapy is common for children with DSD and helps normalize their hormone levels during their entire life. The endocrinology team works closely with patients and their families to determine which hormonal medications are best now and in the future.

With proper medical, surgical and psychosocial care, most children with disorders of sexual differentiation (DSD) lead healthy, normal lives. Making an educated determination of the child’s sex is important both for treatment purposes, as well as for the emotional well-being of the child.

As a child with DSD grows, it is important for the child’s family to understand the difference between sex and gender. “Sex” is a biological term that refers to the sex chromosomes of a person. An XY chromosome pair is typical for a male and an XX chromosome pair is typical for a female. Gender refers to the personality and attitude of a person; instead of being biological, gender is more about how the person feels—masculine or feminine.

In some cases, children may decide that they identify more closely with the sex they were not assigned to after birth. If this is the case, our center is prepared to further discuss these concerns with the child and the family and alter the child’s care as needed.

Some children born with atypical genitalia may have internal reproductive organs that allow them to live normal, fertile lives. Other patients may experience reduced or absent fertility as adults, making it difficult or impossible to have a child of their own. A good social support system is important for the family and the child.