Michelle Knoll, MD, Discusses Differences of Sex Development (DSD) and the GUIDE Clinic

Michelle Knoll, MD, is a pediatric endocrinology fellow who works with the Children’s Mercy GUIDE Clinic. The GUIDE Clinic was founded in 2008 as a partnership among Gynecology, Genetics, Urology, Psychology, Social Work, Chaplaincy and Endocrinology to provide multidisciplinary support for those with differences of sex development (DSD).

Here, Dr. Knoll shares more about the clinic and recent research she conducted.

What are differences or disorders of sex development (DSD)?

Dr. Knoll: You may see slightly different terminology in various sources. The older terminology was disorders of sex development. The newer term “differences of sex development,” encompasses any variation of internal or external sex characteristics. It is estimated that 1 in 5,000 births has genital ambiguity, although the exact prevalence of DSDs is unknown.

Historically, sex assignment in those with atypical external genitals was based largely on potential surgical outcomes for genitoplasty (male sexual function, standing to urinate, etc.), and gender identity was thought to be flexible. In recent years, this paradigm has come under scrutiny, largely from individuals with DSDs who had early genital surgeries.

Are there standards of care to guide medical professionals caring for children with DSDs?

Dr. Knoll: Yes. A set of Consensus Guidelines was published in 2006 and recommends that sex assignment should be avoided prior to expert evaluation. Parents and families should participate in decision-making, and open communication with a multidisciplinary team is recommended. The document further states that there are multiple factors that influence sex assignment, including diagnosis, genital appearance, surgical options, need for replacement hormonal therapy, fertility potential, views of the family, and cultural norms. The 2016 update emphasized that probable adult gender identity should be the most important factor in sex assignment.

What is the clinic’s overall goal?

Dr. Knoll: The GUIDE Clinic’s goal is to provide multidisciplinary care for children with DSDs. With respect to sex assignment, our goals are 1) to assign male gender in the presence of functioning testicular tissue and 2) to reduce gender dysphoria. Gender dysphoria is when the child’s gender identity does not match the sex assigned at birth.

What types of patients are referred to the GUIDE Clinic?

Dr. Knoll: Infants generally are referred initially for genital atypia, though many are seen in the NICU due to concern of life-threatening conditions that may or may not be related to their atypia. Older children are referred when there is a concern for genital ambiguity, chromosomal mosaicism, or a discrepancy between genotypic and phenotypic sex. Work-up includes a thorough exam, hormonal testing, genetic testing, with possible imaging and surgery, depending on results.

If these children are infants, or very young when these decisions are made regarding sex assignment, how do you know if this is the right decision for them?

Dr. Knoll: Overall, the clinic has chosen to err on male gender assignment in cases where there is functioning testicular tissue, as there is evidence that prenatal androgen exposure is more likely to lead to a male gender identity. But, given that even individuals without DSDs can have gender dysphoria, gender dysphoria is difficult to predict.

To see if our sex assignment is more effective than historical numbers, we recently analyzed all patients seen in the GUIDE Clinic from April 2008 to June 2019 to determine the rate of sex assignment change and gender dysphoria in patients.

Can you summarize the big takeaways from your study?

Dr. Knoll: Overall, disorders of sexual development are complex. There isn’t a single path for everyone. Parents, providers and patients need to keep an open mind about gender and sexuality as the patient grows older.

We do not recommend reassignment of sex after age 3 because around 2 to 3 years of age, children develop their gender identity. After age 3, we recommend this process be patient driven, rather than medical or family driven. Prior to age 3, it’s important to note that if a child has testicular function, they seem to have a male identity as they grow older. We recommend avoiding performing cosmetic procedures in children.

And finally, any child with genital ambiguity should be seen by a multidisciplinary team like the GUIDE Clinic that has the experience and resources to help weigh the complex concerns involved.