Happy Fall to all of you! We are very pleased to share another update from our team about positive changes for the eXtraOrdinarY Kids Clinic teams and research happenings - new team members, research publications and presentations, and amazing research awards to our Turner syndrome team! I'm especially proud to share 2 new resources for families resulting from our research. First, a new book for parents "eXtraordinarY Babies: What You Need to Know When You Are Expecting or Have a New Baby with XXY" led by our amazing genetic counselor Susan Howell. Second, a booklet "A Guide to Medications for Behaviors and Mental Health in 48,XXYY Syndrome" led by our equally amazing pharmacist, Dr. Joanna Dreyer. The availability of these types of publications allows the impact of research efforts -- our efforts and YOUR efforts - to spread around the world. More details about these publications and others are below.

We are also announcing that we have exceeded our goals for enrollment of the eXtraordinarY Babies Study, now with 366 participants! Our goal now shifts from enrollment of new babies to retention of all the toddlers and school-age kids - we need to keep all participants in the study! Our long term goal is to understand and support outcomes all the way into adulthood, and the research database becomes so much more powerful as the kids get older (especially if everyone stays involved!). Our first babies to enroll are now reaching 8-9 years of age, and we have lots of important work ahead. So, PLEASE stay involved in the study, let us know of any problems or barriers to participation, or share any new ideas to help us keep everyone engaged. Also, INSIGHTS and GALAXY registries continue to grow, with important results coming from those studies. THANK YOU TO ALL THE STUDY FAMILIES, for all the efforts of your ongoing participation in our research.

Finally, as the season of giving is here, I encourage you all to think about the impact of our clinic and research program for your children and other families, and consider making a donation to support our efforts. We really need it and every $ amount helps! While clinic billing and research grants cover some of our expense, there is a big gap for which we depend on philanthropy to provide clinic coordination, genetic counseling, research participant travel costs, and educational materials for families like our new books. Donations also fund our summer X&Y variations internship program where we are educating trainees in all disciplines (medicine, psychology, speech therapy, genetic counseling) about X&Y variations and working hard to inspire them to pursue careers that will benefit your children. Thank you for this consideration and our direct tax-deductible donation link is:

childrenscoloradofoundation.org/extraordinarykidsclinic.

Thanks again for your involvement in our clinic and research, and it is always a pleasure to care for your eXtraOrdinarY Kids!

Sincerely, Nicole Tartaglia "Dr. T" and the eXtraOrdinarY Kids Team

• eXtraOrdinarY Kids and Turner Syndrome Clinic Updates
• Research updates for eXtraordinarY Babies Study, GALAXY, & INSIGHTS
• Publication and Presentation Announcements
• Summer Research Internship

We are very please to announce the addition of 2 new team members to the eXtraordinarY Kids Clinic Team. Deepika Patel, PsyD, is a Child Psychologist and will be joining our other psychologists (Drs. Wilson, Middleton, Swain, Janusz, Thompson, Hutaff-Lee, Louderman) conducting developmental and psychological evaluations. Ciara Gurley, PA is a Physician Assistant who will be supporting Dr. T with medical evaluations and medication management. They are both very experienced and selected from our existing teams at Children's Hospital Colorado, and are already great additions to our program. Welcome!

Left to right: Deepika Patel, PsyD, Dr. T, Ciara Gurley, PA

The eXtraOrdinary Kids Turner Syndrome Multidisciplinary Clinic (TSMDC) was established in 2015. This clinic serves over 100 families every year. Providers that staff the clinic include endocrinology, cardiology, ENT and audiology, psychology, neuropsychology, developmental pediatrics, sleep medicine, and genetic counseling. Our clinic also engages in several research studies and has been active in updating the International Guidelines for TS. Our providers and staff have presented presentations and posters at conferences throughout the world. We are planning for a 10-year anniversary celebration in 2025, so stay tuned for more information!

Developing Evidence-Based Genetic Counseling Materials for Families

The eXtraordinarY Babies Study team is excited to announce a new effort at developing evidence-based genetic counseling resources for families of children with X&Y chromosome variations. Understanding the complexities of sex chromosome variations can be challenging, and our goal is to create supportive materials that address the specific needs and concerns of these families.

Your Input Matters!
If you are participating in the eXtraordinarY Babies Study, we invite you to participate in two brief surveys designed to gather insights and feedback from families. Your experiences, challenges, and suggestions will be invaluable in shaping resources that are not only informative but also practical and empathetic.

What to Expect:
The surveys will cover topics such as:

• Key information you wish you had received about SCVs
• Common questions and concerns you encounter
• Preferred formats for receiving information (e.g., pamphlets, videos, online resources)
• Suggestions for additional topics that would be helpful to include

How to Participate:
The survey links will be sent to families participating in the eXtraordinarY Babies study by Email and will take approximately 10-15 minutes to complete. Your responses will be confidential and will directly influence the development of our counseling materials. We will also be reaching out to some families for participation in interviews about their experiences.

Thank you for helping us create resources that empower families on their genetic counseling journey! If you have any questions or need assistance, please don’t hesitate to reach out.

We are proudly closing enrollment of the eXtraordinarY Babies Study for the XXY and Trisomy X groups. We have a few spots left for babies with XYY between 6-12 months, and will continue to enroll new XXYY babies. The study now has 366 participants, which has far exceeded the original goal of 200. Great work to our Colorado and Nemours research teams! Current enrollment includes:

• XXY = 200
• XXX = 86
• XYY = 61
• Tetrasomy (XXYY, XXXY, XXX) = 19

This is a little bittersweet, however, as we love playing with those new little babies. Any parents of new infants are invited to reach out to the team to discuss a clinical visit to the eXtraordinarY Kids Clinic, and are encouraged to participate in GALAXY research which also put them on the list to learn about new research opportunities by our team and others around the country.

As our goal now shifts from enrollment of babies to retention of all the toddlers and school-age kids - we need to keep all participants in the study! Our long term goal is to understand and support outcomes all the way into young adulthood, and the research database becomes so much more powerful as the kids get older (especially if everyone stays involved!). Our first babies to enroll are now reaching 8-9 years of age, and we have lots of important work ahead. So, PLEASE stay involved in the study, let us know of any problems or barriers to participation, or share any new ideas to help us keep everyone engaged. And of course, THANK YOU TO ALL THE STUDY FAMILIES, for all the efforts of your participation.

GALAXY is a clinical research registry led by Dr. Shanlee Davis. This study is open to individuals with all X&Y variations - including those seen in our clinic or other GALAXY clinics (Nemours, Cornell, or Lurie Children's), or those who choose to enroll and participate from home. We use information from online questionnaires and from medical records to learn more about X & Y variations. This type of registry study is powerful because it allows us to learn a lot about different variations and expand beyond patients seen in clinic. By including participants outside of our clinics, we can capture more variability for more accurate data about all X&Y variations. The registry is supported financially by AXYS and The XXYY Project, and other patient-advocacy groups such as Living with XXY have helped support recruitment for this project.

The Turner Syndrome Anxiety Project is a collaboration between Turner Syndrome Colorado and the eXtraOrdinarY Kids Clinic and Research Team at Children’s Hospital Colorado to respond to parent and patient questions about anxiety in Turner syndrome. Check out our project website to see results from phase 1 of our project (phase 2 results are coming soon!) and to find some helpful resources for families.

Anxiety in Turner syndrome Phase 1: Engaging community to address barriers and facilitators to diagnosis and care

This study helped us learn more about what anxiety looks like in Turner syndrome across the lifespan. We aimed to learn about the life experience of girls with Turner syndrome and anxiety to help develop a screening tool to better detect anxiety in Turner syndrome patients. Participants completed a one-time online survey about their experience with anxiety symptoms, triggers, and coping mechanisms. A few participants also completed one-on-one interviews with our study team.

We created the InsighTS registry with help from the Turner Syndrome Global Alliance. InsighTS allows researchers to look at clinical data of individuals with TS. The long-term goal is to improve clinical care. It also provides an avenue for the TS community to take part in research and propose research topics. It is a collaborative effort between clinicians, researchers, TS advocates. InsighTS is enrolling participants with TS from all backgrounds. Participants can enroll while in their local clinics or online. InsighTS research focuses on patient-centered outcomes. The consortium aims to be transparent and share all results. The registry also serves as a framework for conducting future studies.

The findings suggest that mosaicism with a Trisomy X cell line may be more prevalent than previously reported. We observed differences between non-mosaic individuals and those with mosaic Trisomy X, noting a higher incidence of structural heart disease, aortic issues, and short stature in the non-mosaic group. Additionally, we found distinctions between individuals with mosaic Trisomy X and those with mosaic 46,XX, specifically that the former were more likely to experience neurodevelopmental concerns, a difference not previously highlighted in the literature. The Trisomy X cell line may offer unique insights that could influence counseling and clinical care.

This new book was inspired by our families and the hundreds of calls our clinic receives from families just learning of the diagnosis during their pregnancy or after newborn testing. This 65 page book includes 5 chapters addressing all the "Frequently Asked Questions" from our clinic and research experiences:

1. All About XXY
2. Genetic Testing for XXY
3. Pregnancy when the Baby has XXY
4. After Your Baby is Born
5. Parent Perspectives and Support

The book, authored by Susan Howell, MS (Genetic Counselor), Nicole Tartaglia, MD (Developmental Pediatrician), Shanlee Davis, MD (Pediatric Endocrinologist) and Chloe Alviz (Genetic Counseling Student) is full of great information and is now available for sale at Amazon. All proceeds benefit the clinic, so buy 1 for yourself, or maybe buy a bunch to donate to local libraries and OB/GYN or Pediatrics practices? (Click on the book cover for the link; or https://a.co/d/6vkQfYC).

We are also working on similar books on all the other X&Y variations conditions, and donations to our program help speed up these efforts. If you would like to sponsor publication of a similar book on your child's condition or sponsor translation of the book to different languages, contact Dr. T.

In September, Nicole Tartaglia, MD and Talia Thompson, PhD presented recent research findings at the 26th Society for the Study of Behavioral Phenotypes (SSBP) International Research Symposium in Bali, Indonesia. Dr. Thompson received the esteemed Leclezio-DeVris Prize for her presentation: Recognizing Anxiety in Turner Syndrome Early: Community Engaged Development of a Patient-Centered Outcome Measure. This award recognizes work in the area of socially responsive research, with a particular emphasis on community participation. The eXtraOrdinarY Kids team is extremely proud of the international recognition of Dr. Thompson and the Turner Syndrome Anxiety Project, and all the other team members and families who have participated in this project. Dr. Tartaglia also shared results from the eXtraordinarY Babies study in her presentation titled: Exploring Predictors of 36-month Language and Motor Outcomes in Children Prenatally Diagnosed with Sex Chromosome Trisomy to Inform Early Intervention Trials. International researchers were enthusiastic about the size of the study cohort and implications for results.

Rosemary O'Dell RN, MSN and Karen Regan RN attended the Pediatric Endocrine Nurse Society conference in April 2024 to present a poster on the important roles of nursing in a Turner syndrome multidisciplinary clinic. They won the "Best Poster" award for the conference, and the abstract was published in the Journal of Pediatric Nursing July/August 2024. This is another example of how the TS Clinic at Children's Hospital Colorado is a model of care for other clinics nationally.

Our team was delighted to join 28 XXYY families at a three-day event in Hope Valley, nestled in the stunning Peak District of Derbyshire, United Kingdom. Dr. T, Dr. Davis, Susan Howell, and Joanna Dreyer, PharmD attended the conference to present research and provide consultations to families. The weekend was a lot of work mixed with great fun, seeing some families and XXYY guys Dr. T met back in 2005 at the beginning of her research career. Dr. Dreyer presented about a research project funded by The XXYY Project, with important results about medication use for behavioral and emotional symptoms in XXYY syndrome. A great thanks to Jocelyn and Nicola as conference organizers, and all the wonderful welcoming families from the UK (and Germany)!

We are thrilled to provide updates on Dr. Dreyer's innovative project focused on medications for behavioral and emotional symptoms of XXYY syndrome.

The primary objective of this project is to conduct a comprehensive review of current medication practices and gather data on the efficacy and safety of various treatments for children with XXYY syndrome. This project will improve the quality of care for individuals with XXYY syndrome by providing resources for both medical professionals and families about medication use.

We’re in the final stages of preparing a scientific manuscript on medications in XXYY that will be a great reference for families and both medical and mental health providers. In addition, an amazing family-friendly resource is on the way (see below), which will include key findings from our latest research. Stay tuned for more updates—great things are coming!

The interdisciplinary eXtraOrdinarY Kids Team offers a Research Internship for trainees interested in learning more about sex chromosome variations and pediatric clinical research. The program is directed by Dr. Shanlee Davis, and the interdisciplinary team of mentors includes Developmental Pediatrics (Dr. Tartaglia), Pediatric Endocrinology (Dr. Davis), neuropsychology, psychology, genetic counseling, speech and occupational therapy, and study coordinators. Interns are matched with a mentor and a project suited to their experience and goals. In addition to working on their research project, interns attend career lectures, have the opportunity to assist with patient visits for our ongoing studies including the eXtraordinarY Babies study, and present their work at the eXtraordinarY eXpo at the end of each summer (see below). We hope to inspire future clinical researchers, and have had interns from the program go on to medical school and graduate school for psychology, genetic counseling, public health, and other related fields where they will have background and experience with sex chromosome variations.

If you want to learn more or know anyone who may be interested in applying, see link below:

Shalika Devireddy - Metabolomic Profiling in Klinefelter Syndrome: Linking Early Life Biomarkers to Later Outcomes

Maria Desperadel- Early developmental milestones in the eXtraordinarY Babies Study

Jeff Greenfield- Medical Problems in XXYY: A Case Study

Greyson Seale- Expanding the Behavioral Phenotype of Turner Syndrome

Giovanna Ruffolo -Anerobic Threshold in 47,XXY and Controls

Emma Todd- Sleep and Physical Activity Outcomes in Adolescents and Young Adults with Klinefelter Syndrome

Anastasia Zhivotov-Dietary Supplement in Infants and Toddlers in the eXtraordinarY Babies Study

Alyssa Keller- Perinatal History in Sex Chromosome Aneuploidies

Morgan Wills- Diagnostic and Health Outcomes of Turner Syndrome Patients with Ring X Chromosome

We hope everyone has a great Fall and Holiday Season

Email: extraordinarykids@UCdenver.edu

Web: www.extraordinarykidsclinic.org

Social Media: www.facebook.com/eXtraordinarYKids.org/

Donate: childrenscoloradofoundation.org/extraordinarykidsclinic