SLCH Multidisciplinary Team Offers Expertise in Diagnosing, Treating Disorders of Sex Development

For new parents of babies born with a disorder of sex development (DSD), the question, “Did you have a boy or girl?” is a painful, confusing one with no simple answer. DSDs encompass a group of congenital conditions in which a discrepancy exists between a baby’s external and internal genitals or there is discordance between a baby’s physical and genetic sex. Diagnosis and treatment is a complex process, and the decisions made by physicians and families are not always easy since they dramatically influence a baby’s physical being and self-image throughout his or her lifetime.

Recognizing the emotional urgency most parents have in regard to infants who present with ambiguous genitalia, St. Louis Children’s Hospital (SLCH) has formed a DSD team that has set a goal of meeting within 24 hours of the condition being identified. The expertise of pediatric specialists from endocrinology, urology, gynecology, genetics, psychology and ethics is critical, according to Rebecca Green, MD, PhD, SLCH pediatric endocrinologist and DSD team leader.

“Our goal is to optimize diagnosis and treatment of these complex patients by quickly tapping into the in-depth knowledge that can only be found at a leading pediatric facility like Children’s Hospital,” she says. “Our focus is on shared decision making between our team and our patients’ families. We provide parents with as much medical insight as we can, make recommendations based on our findings, and then work within the parents’ cultural, religious and social beliefs to develop a course of treatment.”

A changing mindset toward gender assignment

In the past, physicians felt they needed to quickly assign a baby’s gender without disclosing a lot of information to families that might cause them to become confused and upset. Often the gender assignment was based on the baby’s genital appearance rather than the chromosomal gender.

“That mindset has very much changed. Families need to understand what happened with the development of their baby’s genitals and gender. They need to understand our treatment recommendations and how we determined them. And they need to understand that we don’t have every answer, and what we predict is going to happen next for their child may be different than what actually occurs,” she says.

The first step in diagnosis and treatment is understanding as much as possible about the cause of the baby’s condition and determining if immediate medical intervention is needed. In addition to a thorough physical exam and an in-depth family history, the baby undergoes chromosome analysis, hormone testing, electrolyte tests, and ultrasound or MRI to evaluate whether internal sex organs are present. In some cases, this will be followed by more specific genetic testing. The information obtained from this comprehensive evaluation gives a clearer picture of what may have happened to cause the DSD.

“For instance, congenital adrenal hyperplasia—the most common DSD—is a genetic disease which is autosomal recessive. That means the parents of a child with congenital adrenal hyperplasia have a one in four chance of having another child with the same diagnosis. Consultation with a geneticist is vital to these parents,” says Paul Austin, MD, SLCH pediatric urologist and DSD team member. “Other causes for DSDs include the fetus being exposed to male hormones during development—perhaps secreted from an ovarian tumor—or a mutation that randomly occurs and causes hormonal imbalances.”

Once the test and examination results are completed, the DSD team comes together to determine into which of four categories the baby fits:

• 46 XX DSD—Chromosomes typical for a female, but genitalia that are atypical for a female, either ambiguous, indicating genitals that are not clearly male or female, or male appearing. Either ovaries or testes may be present.
• 46 XY DSD—Chromosomes typical for a male but with genitals that are ambiguous or female. Internally, testes may be normal, malformed or absent.
• Ovotesticular DSD—Both ovarian and testicular tissue exists, either in the same ovotestes or in the form of one ovary and one testis. The baby may have XX chromosomes, XY chromosomes or a mixture of cells, some with XX and some with XY; external genitals may be ambiguous or appear to be female or male.
• Sex chromosome DSD, such as 45 X (Turner syndrome) and 47 XXY (Klinefelter’s syndrome)—In these two examples, although no discrepancy exists between internal and external genitalia, there may be problems with sex hormone levels.

“The DSD team’s commitment is to assist the families in making the very best choice for the babies in regard to sex assignment,” says Dr. Green. “We realize that our recommendations are going to help define for these children how they see themselves throughout their lives and how they interact with others.”

The team also provides consultation for older children whose DSD was not diagnosed at birth. “We see a fair number of girls with Turner’s syndrome, which is the absence of part or all of one of the X chromosomes. These girls are phenotypically female—there is generally no question about their gender—but their ovaries fail to work properly,” says Dr. Green.

There also have been cases of discordance between adolescents’ physical and genetic sex. “This team approach benefits the children and their families and enables the multidisciplinary specialists to provide comprehensive, appropriate and thoughtful advice,” says Diane F. Merritt, MD, director, pediatric and adolescent gynecology at SLCH and a DSD team member. “How do you tell parents some of these difficult truths, like their teenage daughter may never be able to become pregnant or has a male karyotype because of a rare genetic disorder? The DSD team is an opportunity for specialists from multiple disciplines to thoroughly discuss each case and then decide on a course of treatment and how to best relay that information to parents and patients.”

Treatment options for DSDs: unraveling the variables

Treatment options for DSDs are as varied as the causes that result in genitals developing along atypical pathways. Medical management frequently involves gender-appropriate hormone replacement of some type.

“For example, in females with congenital adrenal hyperplasia, their adrenal glands produce too much male hormone. To prevent this, they are prescribed hydrocortisone, which reduces the production of male-type hormones by the adrenal glands. This treatment is important for normal growth and development throughout childhood and allows the ovaries to make the appropriate female hormones during puberty,” says Dr. Green.

Beyond medical therapy, one of the more controversial issues that the team and family must deal with is when to do any surgery to modify atypical genitalia.

“Sometimes the parents prefer that the surgery is done early to provide closure of the gender ambiguity and so their child does not have any memory of it,” says Dr. Austin.

Yet there is growing awareness that early reconstruction of the bladder and the vagina in baby girls may not prove to be functional as the young women reach puberty. Until recently, there has been little assessment of functional outcomes of genital surgery. Increasingly, the needs of the individual patients are being considered in regard to whether surgery is performed in infancy or after puberty is reached.

“Our ultimate goal is providing patients with genitals that are as normal and functional as possible, either for reproduction or sexual activity,” says Dr. Merritt. “If an initial surgical procedure results in scar tissue, normal function may be impeded and is challenging to correct with an additional operation. Some procedures may be done in stages, correcting the outward appearance in infancy, and then correcting the internal structures after puberty. It is possible to offer certain reconstructive genital surgeries at a time when the patient can participate in the decision and recovery process.”

One of the factors that may influence the timing of surgery is the level of the team’s confidence that the baby will be comfortable with his or her gender assignment as he or she grows. With many diagnoses, the history from prior patients with the same diagnosis provides the team with insight into the child’s likely gender identity. In some cases, however, the team and the family must face decision making with more uncertainty.

“Ultimately, the DSD team feels that decisions cannot be made for these children without their parents having a good understanding of their diagnosis and its implications, including both the knowns and the unknowns,” says Dr. Green. “Our team’s commitment to shared decision making means the parents’ voice is always an important factor in treatment decisions.”

It also means discussions among team members with varying views are important to ensuring the best decisions are made for patients. “There is always an open, free dialogue through which we learn from each other,” says Dr. Merritt. “We understand that everyone on the team is coming from a different discipline and may have another outlook. Our ability to listen to each other and understand different viewpoints is a strength that translates into exceptional care for our patients.”

Adds Dr. Austin, “Our team’s ethicist, Dr. Elliot Gellman, also keeps us focused on our patients and the families’ perspectives, rather than on biases each of us may have.”

Ongoing psychological support

Essential to treatment of patients with DSD and their families is ongoing psychological support. Russell Hoffmann, PhD, child psychologist and director of cultural initiatives at SLCH, has been instrumental in helping the DSD team provide support to parents as they deal with the emotions of having a baby with a DSD. His input has helped the team develop a timeline for disclosing age-appropriate information to children so they understand that their disorder is a natural part of who they are. In addition, Mary Michaeleen Cradock, PhD, interim director of child psychology at SLCH, and her colleagues in child psychology will be scheduling follow-up consultations with the children as they mature to ensure they are comfortable with their gender identities.

“Everyone engaged in the DSD group has found it to be tremendously useful in terms of their professional comfort and decision making for these complex patients,” says Dr. Green. “We are committed to providing care for these children and their families as long as needed. Our goal is to establish a permanent clinic specializing in diagnosing and treating disorders of sex development.”

To refer a patient for evaluation by the St. Louis Children’s Hospital disorders of sex development team, contact Children’s Direct at 800.678.HELP (4357)..

Source: Consensus Statement on Management of Intersex Disorders: Peter A. Lee, MD, PhD; Christopher P. Houk, MD; S. Faisal Ahmed, FRCPCH; Ieuan A. Hughes, FMedSci, FRCPCH in collaboration with the participants in the International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology

The DSD Team at Children’s Hospital

Endocrinology
Ana Maria Arbelaez, MD
Abby Hollander, MD
Paul Hruz, MD, PhD
Bess Marshall, MD
Arpita Vyas, MD
Neil White, MD, CDE

Ethics
Elliot Gellman, MD
Rebecca Dresser, JD

Genetics
Kathy Grange, MD
Beth Kozel, MD
Marwan Shinawi, MD
Marcia Willing, MD

Gynecology
Diane F. Merritt, MD
Valerie Ratts, MD

Psychology
Mary Michaeleen Cradock, PhD
April Nesin, PhD

Urology
Paul Austin, MD
Douglas Coplen, MD
Erica Traxel, MD