Since 2013, the Children’s Mercy Super Q Express Clinic — held at both Children’s Mercy Hospital Kansas and the Adele Hall Campus — has helped patients with 22q11.2 deletion syndrome and 22q11.2 duplication. The multidisciplinary clinic coordinates care for patients and families affected by these complex and unpredictable genetic conditions. Instead of going to multiple appointments per month, patients see all their subspecialists in one day. 

“We are really the premiere site for 22Q patients in the Midwest, serving five states (Missouri, Kansas, Nebraska, Arkansas and Oklahoma) and are generally getting one to two new referrals a month,” 22Q Clinic founder Max Feldt, DO, Endocrinology, 
said. “We’ve been very fortunate to build the necessary resources and team members.”

Gaige, now a teenager, was diagnosed with 22Q11.2 deletion as a newborn at Children’s Mercy. “With the clinic, they all get together, talk about him as a whole person and are able to coordinate his care,” said Heather, Gaige’s mom. “We 
appreciate the way Gaige is treated: as an individual. It’s an amazing group, and Gaige really enjoys seeing the doctors.” 

As an infant, Rachel was diagnosed through Children’s Mercy genetic testing and has traveled with her family from Wichita to attend the 22Q Clinic since it opened. “It has been incredible what the 22Q Clinic has done for our daughter’s care,” said Rachel’s mom, Katie. “We’re grateful for the staff and the support network and would encourage anybody who has a child with 22Q to get plugged into this clinic. It’s a different level of care. Honestly, it’s just like a family.” 

David is one of the clinic’s many patients who make the trip up from Arkansas. “With multiple body systems affected, I believed we needed an interdisciplinary clinic where doctors can talk to each other,” said David’s dad, Ningning. “Children’s 
Mercy has a clinic that coordinates everything. Without those doctors, we wouldn’t have guidance to move forward. The growth of the clinic will be very helpful for kids and allow doctors to provide a more holistic picture of the patient’s condition.”

Tomi Pastinen, MD, PhD, Elin Grundberg, PhD, and Todd Bradley, PhD, Genomic Medicine Center, received a two-year, $550,000 award from the Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) for their project, “Early life epigenomic signatures, primed immune states and the development of Type 1 diabetes.”

Type 1 diabetes (T1D) is an autoimmune disease that develops when the immune system becomes dysregulated and attacks healthy pancreatic islet cells. This leads to chronic inflammation, tissue damage, and the loss of the ability to produce insulin. Islet inflammation is characterized by innate and adaptive immune processes that are proinflammatory. Some of the factors that influence immune state activation include genetic make-up, responses to pathogens, and environmental exposures. However, much remains unknown about early molecular determinants of T1D that might predict diagnosis.

“Our goal is to identify key epigenomic switches that determine the activity state of the immune system which lead to the development of type 1 diabetes. Identifying those switches could lead to early intervention,” said Dr. Grundberg.

In preliminary studies, Dr. Pastinen identified a cellular immune state that stratified at-risk children for T1D before immunological biomarkers of islet autoantibodies (IAA) were present. Building on those findings, this study’s objective is to test the hypothesis that children who have detectable IAA and are subsequently diagnosed with T1D have a primed immune system imprinted early in life. This primed immune state will be reflected by monocyte-specific molecular signatures representing increased proinflammatory activity together with increased vaccine antibody responses.

The study has two aims:

• Aim 1: Determine circulating immune cell populations and molecular pathways that contribute to primed immune cell states and subsequent development of T1D using single-nuclei multiomics.
• Aim 2: Identify antibody and cytokine serological determinants of primed or tolerant immune states that could predict T1D development.

“This work is significant because it will define the molecular and cellular features of early-life immune states and determine if these immune states could predict type 1 diabetes in later life,” said Dr. Bradley.

Please join us in congratulating these investigators.

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine condition that affects an estimated 6%-12% of women of reproductive age in the United States.¹ PCOS develops in genetically predisposed females where the severity of clinical expression is compounded by environmental, nutritional and lifestyle factors. The genetic predisposition mainly affects ovarian function, manifesting in a tendency toward ovulation dysregulation and hormonal imbalance, which favors androgen production.

Short- and long-term consequences of menstrual dysfunction and hormonal imbalance may include:

• Hirsutism and severe acne
• Depression and anxiety
• Insulin resistance/metabolic syndrome
• Sleep apnea
• Weight gain and type 2 diabetes
• Nonalcoholic fatty liver disease
• Heart disease
• Endometrial hyperplasia/cancer
• Anovulation/hypofertility

Early diagnosis and treatment of PCOS may benefit the adolescent cosmetically by reducing clinical manifestations of hyperandrogenism, as well as offer symptomatic relief of menstrual dysfunction. Most importantly, however, early diagnosis and management of PCOS may reduce the development of associated conditions and complications.

Addressing PCOS with a Multispecialty Program

The Children’s Mercy Kansas City Multispecialty Adolescent PCOS Program (MAPP) is led by Tania Burgert, MD, Pediatric Endocrinologist; Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine. Dr. Burgert has long been involved with the diagnosis and treatment of PCOS and is a well-recognized leader in the field, serving on the board of directors of the Androgen Excess and PCOS Society and on the medical/scientific advisory board of the PCOS Challenge.

To address the constellation of symptoms adolescents aged 13-21 with PCOS face, Dr. Burgert established one of the few multispecialty programs in the nation at Children’s Mercy.

Unique to the program is the array of clinical specialists involved in several dimensions of each patient’s care. The clinic includes endocrinologists who focus on metabolic and endocrine concerns; adolescent medicine specialists who address gynecological health and mental health needs, such as anxiety and depression; and dietitians who provide nutritional counseling to help achieve lifestyle and weight goals.

Multispecialty care enables the team to take an individualized treatment approach focused on educating patients and their families regarding what PCOS is and empowering them to take an active role in managing the condition.

To streamline care, MAPP clinicians see the patient in a central location, bringing services to the exam room and ensuring a unified diagnostic approach. At the conclusion of the appointment, the clinicians explain the patient’s diagnosis and give them a cohesive treatment plan with follow-up recommendations, serving as a central point of contact for all their questions and care.

Advancing Clinical Research

The MAPP at Children’s Mercy is also committed to the advancement of clinical research.

Children’s Mercy is the primary recruitment site for a National Institutes of Health-funded study, Trajectory of Ovarian Morphology During the Adolescent Reproductive Transition. Marla Lujan, PhD, Cornell University, is the principal investigator for the grant. Dr. Burgert and Dr. Romina Barral are the MAPP collaborators for this research, and Heidi Vanden Brink, PhD, is the postdoctoral fellow involved in this study.

The study examines ovarian morphology using 2D and 3D transabdominal ultrasound longitudinally during the first two years post menarche in the general adolescent population alongside tracking menstrual cyclicity and changes in reproductive hormones during this developmental window. The main goal of this ongoing study is to establish ovarian morphology as an early, reliable biomarker for normal versus aberrant reproductive maturation and a potentially early indicator of PCOS in the years immediately following menarche.

PCOS Patient Database Yields Original Research

The Children’s Mercy MAPP also established a REDCap database of over 500 MAPP patients for retrospective research to further the understanding of PCOS during adolescence. Recently, MAPP team members presented some findings of their research at the November 2020 Androgen Excess and PCOS Society and the April 2021 Pediatric Endocrine Society meetings. These studies include:

• Androgen Excess and PCOS Society Poster Presentation: Intraindividual Testosterone Variability Challenges the Diagnostic Process in Adolescents with PCOS. This poster included 73 adolescents seen in the MAPP and diagnosed with PCOS. Data suggested that a normal total testosterone at initial evaluation may not reliably rule out biochemical hyperandrogenism in adolescents. Total and free testosterone exhibit significant intraindividual variation when repeated within three months. Because biochemical hyperandrogenism is a central diagnostic feature of PCOS, caution should be used when relying on a single measurement for the diagnosis of PCOS in adolescents. Further prospective research is needed to corroborate these findings and to elucidate the relevance of other factors that may account for intraindividual variation.
• Pediatric Endocrine Society Oral Research Presentation: Transgender Identity Among Adolescents with PCOS. This abstract looked at 169 adolescents from the MAPP and found a slight difference in the prevalence of transgender identity between PCOS and non-PCOS, though not statistically significant. Interestingly, patients with greater degrees of hirsutism were more likely to identify as transgender. This may have implications for treatment goals in those who desire a transmasculine appearance or fear increased identity conflict with return of menstrual cycles. The team’s findings suggest that screening for gender dysphoria should be considered in practice recommendations for comprehensive adolescent PCOS programs.
• Pediatric Endocrine Society Presidential Poster Presentation: HbA1c as a Surrogate for Dysglycemia in Polycystic Ovary Syndrome (PCOS). Dysglycemia and insulin resistance are comorbidities of PCOS and may contribute to its pathophysiology, and therefore are important to reliably screen. In this study, investigators evaluated the agreement between HbA1c, a common clinical biomarker of dysglycemia, and oral glucose tolerance testing (OGTT)-derived measures of dysglycemia. The team found that although HbA1c is more clinically attractive, not requiring fasting blood measurements nor a two-hour time commitment, the findings did not support the use of HbA1c as a surrogate for assessments of dysglycemia in an adolescent population with PCOS. Low sensitivity suggests continued use of OGTT-derived metrics for dysglycemia in adolescents with PCOS. Interestingly, the research team noted that BMI may influence the ability of HbA1c to predict dysglycemia. Research is ongoing to elucidate the relevance of HbA1c uniquely in lean versus overweight populations.

Collaborate with the Children's Mercy Multispecialty Adolescent PCOS Program

The MAPP continues to build its database of adolescents diagnosed with PCOS. If you are interested in collaborating with Children’s Mercy to build a stronger database to study this patient population, please reach out to:

Tania Burgert, MD, Pediatric Endocrinologist 

tsburgert@cmh.edu

(816) 960-8803

For consults, admissions or transport call: 1 (800) GO MERCY / 1 (800) 466-3729.

Reference:

1. Centers for Disease Control website. Accessed 6/1/2021: https://www.cdc.gov/diabetes/basics/pcos.html.