Publications

Peer-Reviewed Journal Articles

Peer-reviewed journal articles are academic publications that have been reviewed and approved by experts in the field. This process helps ensure that the research being published is high-quality and valid. Below are some of the peer-reviewed articles from our team.

2025

Neurodevelopmental and Mental Health Outcomes in a National Clinical Sample of Youth With Sex Chromosome Trisomies Compared With Matched Controls

Authors: Adriana Hall,  Anna Furniss, Nicole Tartaglia, Jennifer Janusz, Rebecca Wilson, Caitlin Middleton, Sydney Martin, Jacqueline Frazier, Michele Martinez-Chadrom, Jennifer Hansen-Moore, Chijioke Ikomi, Judith Ross, Maria Vogiaski, Leela Morrow, Dimitri Christakis, Rachel Lean, Natalie Nokoff, Laura Pyle, Shanlee Davis

Summary:

This study found that youth with sex chromosome trisomies (47,XXY, 47,XYY, and 47,XXX) have significantly higher rates of neurodevelopmental and mental health diagnoses compared to matched controls. They were more likely to be diagnosed with conditions such as anxiety, mood disorders, and other developmental issues, and were also more frequently prescribed psychotropic medications. Nearly half had encounters with behavioral health providers, compared to just 16.6% of controls. These findings highlight the urgent need for early screening and intervention in this population.

Testosterone Effects on Short-Term Physical, Hormonal, and Neurodevelopmental Outcomes in Infants with 47,XXY/Klinefelter Syndrome: The TESTO Randomized Controlled Trial

Authors: Shanlee Davis, Susan Howell, Jennifer Janusz, Najiba Lahlou, Regina Reynolds, Talia Thompson, Karli Swenson, Rebecca Wilson, Judith Ross, Philip Zeitler, and Nicole Tartaglia

Summary:

This was a double-blind randomized controlled trial of testosterone treatment in infants with 47,XXY (Klinefelter syndrome) during the infant mini puberty phase, focusing on physical, hormonal, and neurodevelopmental outcomes. Three monthly injections of testosterone 25mg resulted in:

  • Increase in linear growth, penile size, and lean mass. This confirms that this dose of testosterone was an adequate dose - we will have to see if these changes have long term benefits. 
  • No difference in development (motor, language, or cognitive skills). We do not know if differences may emerge as kids get older.
  • Suppression of the hypothalamic-pituitary-gonadal (HPG) axis, including the hormone inhibin B that is produced by the testicular cells that later support the process of making sperm (spermatogenesis). We want to measure markers of testicular function in the future to know if this has any long term impact.

Based on these results, we do not recommend every baby with XXY get testosterone shots. However, some boys, such as those with a small penis or low infant testosterone levels (ideally measured ~6 weeks of age) may benefit from treatment. Infants should be evaluated by a pediatric endocrinologist.

 

Research Priorities of Individuals and Families With Sex Chromosome Aneuploidies

Authors: Alexandra Carl, Samantha Bothwell, Fathia Farah, Karli Swenson, David Hong, Siddharth Prakash, John Strang, Nicole Tartaglia, Armin Raznahan, Judith Ross, INSIGHTS Consortium, GALAXY Consortium, Shanlee Davis

Summary:

The goal of this study was to determine the research priorities of patients and families. We surveyed participants in two registries. The INSIGHTS Registry is for individuals with Turner syndrome. The GALAXY Registry is for individuals with other X and Y variations. Intervention studies were a top priority. This shows a need for researchers to focus on clinical treatments. Within health topics, the priorities changed by X and Y variation. The top priorities in each group were:

  • Turner syndrome: anxiety, fertility, and social
  • Trisomy X: learning, healthcare access, and anxiety
  • Klinefelter syndrome: hormone treatments, fertility, and learning
  • XYY syndrome: fertility, learning, and suicidality
  • XXYY syndrome: social, quality of life, and hormone treatments

These results can help researchers decide what to study in the future.

 

Neurodevelopmental and Mental Health Outcomes in a National Clinical Sample of Youth With Sex Chromosome Trisomies Compared With Matched Controls

Authors: Adriana Hall, Anna Furniss, Nicole Tartaglia, Jennifer Janusz, Rebecca Wilson, Caitlin Middleton, Sydney Martin, Jacqueline Frazier, Michele Martinez-Chadrom, Jennifer Hansen-Moore, Chijioke Ikomi, Judith Ross, Maria Vogiaski, Leela Morrow, Dimitri Christakis, Rachel E Lean, Natalie Nokoff, Laura Pyle, Shanlee Davis

Summary:

The goal of this paper was to compare how often neurodevelopmental and mental health diagnoses occur in sex chromosome trisomies (47,XXY, 47,XYY, and 47,XXX) compared to individuals without those conditions. We looked at a large dataset from multiple children’s hospitals across the United States. This data showed us that individuals with the trisomies had neurodevelopmental and mental health diagnoses more often than individuals without a trisomy. We also found that individuals with the trisomies were more likely to be on medications like stimulants, SSRIs, and antipsychotics. These results highlight the need for screening and early intervention. 

 

Psychotropic Medication Use in 48,XXYY Syndrome

Authors: Joanna Dreyer, Susan Howell, Samantha Bothwell, Kayla Molison, Alexandra Carl, Karli Swenson, Shanlee Davis, Gail Decker; GALAXY consortia; Nicole Tartaglia

Summary:

Individuals with 48,XXYY syndrome can have behavior and mental health challenges. This can include ADHD, anxiety, depression, sleep disorders, irritability, and aggressive behaviors. We used data from a survey and medical records for this study. We found that 70% of the patients had taken a medication for behavior or mental health at some point in their life. Most common were stimulants for ADHD and anti-anxiety or anti-depressants. We found that patients often tried many similar medications before finding one that worked for them. Generally, patients found these medications helpful.

2024

Discordant Prenatal Cell-Free DNA Screening vs. Diagnostic Results of Sex Chromosome Aneuploidies: Implications for Newborn Screening and Genetic Counseling

Authors: Susan Howell, Shanlee Davis, Billie Carstens, Mary Hagg, Judith Ross, Nicole Tartaglia

 

Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry

Authors: Natalia Klamut, Samantha Bothwell, Alexandra Carl, Vaneeta Bamba, Wendy Brickman, Karen Klein, Roopa Kanakatti Shankar, Catherina Pinnaro, Patricia Fechner, Siddharth Prakash, Iris Gutmark-Little, Susan Howell, Nicole Tartaglia, Marybel Good, Kelly Ranallo, Shanlee Davis

Summary:

Mosaic Turner syndrome with a trisomy X cell line (47,XXX) is a rare form, affecting about 3-10% ofthose with Turner syndrome. Because it’s so uncommon, there’s not much research on it. This study aimed to compare a 45,X/47,XXX group to other forms of Turner syndrome: non-mosaic and mosaic with a typical female cell line (46,XX). The mosaic with trisomy X group had less participants with the following than the non-mosaic group:

  • Hearing loss
  • Heart conditions
  • Hip dysplasia
  • Primary ovarian insufficiency
  • Short stature
  • Swallowing disorders
  • Tissue swelling (lymphedema)
  • Vision concerns

For those over 10 years old, individuals with 45,X/47,XXX were more likely to develop breasts and have periods on their own. They also had a higher chance of being born with kidney and structural heart issues compared to those with the 45,X/46,XX type. These differences highlight why it’s important to consider 45,X/47,XXX differently from other forms of Turner syndrome.

 

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

Authors: Alexandra Carl, Marybel Good, Erica Haag, Christa Hutaff-Lee, Deanna Swain, Nicole Tartaglia, Casey Sakamoto, Talia Thompson

Summary:

We heard from the TS community that anxiety impacts quality of life. However, past research showed that the proportion of pediatric TS patients diagnosed with an anxiety disorder was similar to the general population. With the help of a Community Advisory Board, the team developed a survey that asked about anxiety symptoms, triggers, and solutions. A subset of participants then took part in interviews describing their or their child’s experience with anxiety. The top symptoms of anxiety reported by all participants was insomnia. The top triggers reported were ‘anticipation’, ‘uncertainty’, ‘lots happening at once’ and ‘dealing with conflict’. Participants tried a lot of strategies to help reduce anxiety. Helpful strategies included taking daily anxiety medications, taking a ‘mental health day’, and ongoing therapy.

 

Prevalence, Morbidity, and Mortality of Men with Sex Chromosome Aneuploidy in the Million Veteran Program

Authors: Shanlee Davis, Craig Teerlink, Julie Lynch, Bryan Gorman, Meghana Pagadala, Aoxing Liu, Matthew Panizzon, Victoria Merritt, Giulio Genovese, Judith Ross, Richard Hauger

 

An Extra X Chromosome Among Adult Women in the Million Veteran Program: A More Benign Perspective of Trisomy X

Authors: Shanlee Davis, Craig Teerlink, Julie Lynch, Natalia Klamut, Bryan Gorman, Meghana Pagadala, Matthew Panizzon, Victoria Merritt, Giulio Genovese, Judith Ross, Richard Hauger

 

Development and validation of a computable phenotype for Turner syndrome utilizing electronic health records from a national pediatric network

Authors: Sarah Huang, Vaneeta Bamba, Samantha Bothwell, Patricia Fechner, Anna Furniss, Chijioke Ikomi, Leena Nahata, Natalie Nokoff, Laura Pyle, Helina Seyoum, Shanlee Davis

 

Inspiring New Science to Guide Healthcare in Turner Syndrome: Rationale, design, and methods for the InsighTS Registry

Authors: Roopa Kanakatti Shankar, Alexandra Carl, Jennifer R Law, Vaneeta Bamba, Wendy J Brickman, Siddharth K Prakash, Tazim Dowlut-McElroy, Susan Howell, Iris Gutmark-Little, Karen O Klein, Catherina T Pinnaro, Kelly Ranallo, Marybel Good, Shanlee Davis

Summary:

The InsighTS registry was created in 2020, with help from the Turner Syndrome Global Alliance. InsighTS allows researchers to look at clinical data of individuals with TS, to hopefully improve clinical treatment and care. It also provides an avenue for the TS community to participate in research and propose research topics. InsighTS is a collaborative effort, with involvement across clinicians, researchers, self-advocates with TS and their families. We are continuing to enroll participants, improving the registry by collecting new data and getting a large variety of participants from all backgrounds. Participants can enroll while in their local clinics or online. By establishing InsighTS, we prioritize patient-centered research and transparency of research results, while also serving as a role-model for future rare disease registries.

 

High prevalence of obstructive sleep-disordered breathing in pediatric patients with Turner syndrome

Authors: Tiffany Pham, Shanlee Davis, Suhong Tong, Khaled A Campa, Norman R Friedman, Sarah A Gitomer

2023

The emotional journey of adapting to prenatally identified trisomy X

Authors: Talia Thompson, Jessica Tisher, Shanlee Davis, Christina Miller, Jillian Kirk, Nicole Tartaglia, Susan Howell

Summary:

This was a qualitative study aimed to describe the lived experience of parents of young daughters with prenatally identified trisomy X. Participants completed interviews and then the research team reviewed each interview to see what was similar across them. Based on those similarities, four themes were found:  Negative Diagnostic Experience, Hopeful Early Childhood, Persistent Ambiguity, and Coping with and Adapting to Uncertainty. Results suggest providers should carefully consider word choice and timing in delivery of diagnosis. Genetic counseling should provide expectant parents with current research specific to trisomy X and introduce developmental monitoring approaches. Additionally, they should be prepared to support families with a range of emotional responses. Genetic counselors can also help connect families with a daughter with trisomy X.

 

Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism

Authors: Shanlee Davis, Rhianna Urban, Angelo D'Alessandro, Julie A Reisz, Christine L Chan, Megan Kelsey, Susan Howell, Nicole Tartaglia, Philip Zeitler, Peter Baker

 

Information needs and health status in adolescents and young adults with differences of sex development or sex chromosome aneuploidies

Authors: Virginia Miller, Christina Miller, Shanlee Davis, Natalie Nokoff, Cindy Buchanan, Elizabeth Friedrich, Alexandra Carl, Sophia Strine, Maria Vogiatzi

 

Noninvasive prenatal screening (NIPS) results for participants of the eXtraordinarY babies study: screening, counseling, diagnosis, and discordance

Authors: Susan Howell, Shanlee Davis, Talia Thompson, Mariah Brown, Tanea Tanda, Karen Kowal, Amanda Alston, Judith Ross, Nicole Tartaglia

 

Neuropsychological and Mental Health Concerns in a Multicenter Clinical Sample of Youth with Turner Syndrome

Authors: Jessica Kremen, Shanlee Davis, Leena Nahata, Hillary Kapa, Taylor Dattilo, Christa Hutaff-Lee, Amy Tishelman, Canice Crerand

 

Early Social Behavior in Young Children with Sex Chromosome Trisomies (XXX, XXY, XYY): Profiles of Observed Social Interactions and Social Impairments Associated with Autism Spectrum Disorder (ASD)

Authors: Nienke Bouw, Hanna Swaab, Nicole Tartaglia, Lisa Cordeiro, Sophie van Rijn

2022

Hepatic Abnormalities in Youth with Turner Syndrome

Authors: Ishani Singh, Gillian Noel, Jennifer Barker, Kathryn Chatfield, Anna Furniss, Amber Khanna, Natalie Nokoff, Sonali Patel, Laura Pyle, Leena Nahata, F Sessions Cole, Chijioke Ikomi, Vaneeta Bamba, Patricia Fechner, Shanlee Davis

 

Supporting Students with Sex Chromosome Aneuploidies in Educational Settings: Results of a Nationwide Survey

Authors: Talia Thompson, Shanlee Davis, Jennifer Janusz, Erin Frith, Laura Pyle, Susan Howell, Richard Boada, Rebecca Wilson, Nicole Tartaglia

 

I Wish the School Had a Better Understanding of the Diagnosis’: Parent Perspectives on Educational Needs for Students with Sex Chromosome Aneuploidies

Authors: Talia Thompson, Nicole Stinnettt, Nicole Tartaglia, Shanlee Davis, Jennifer Janusz

 

Exploring Academic and Character Strengths in Students with Sex Chromosome Aneuploidies

Authors: Talia Thompson, Shanlee Davis, Stephanie Takamatsu, Susan Howell, Nicole Tartaglia

 

In-vivo skeletal muscle mitochondrial function in Klinefelter syndrome

Authors: Stephanie Cung, Laura Pyle, Kristin Nadeau, Dana Dabelea, Melanie Cree-Green, Shanlee Davis

 

The impact of sex chromosome trisomies (XXX, XXY, XYY) on gaze towards faces and affect recognition: a cross-sectional eye tracking study

Authors: Nienke Bouw, Hanna Swaab, Nicole Tartaglia, Lisa Cordeiro, Sophie van Rijn

 

Emotional reactivity and expressivity in young children with sex chromosome trisomies: evidence from psychophysiological and observational data

Authors: Kimberly C. Kuiper, Hanna Swaab, Nicole Tartaglia, Lisa Cordeiro, Sophie van Rijn

 

Early impact of X- and Y-chromosome variations (XXX, XXY, XYY) on social communication and social emotional development in 1-2-year-old children

Authors: Nienke Bouw, Hanna Swaab, Nicole Tartaglia, Anna Jansen, Sophie van Rijn

2021

Eosinophilic esophagitis in individuals with sex chromosome aneuploidies: Clinical presentations and management implications

Authors: Susan Howell, Catherine Buchanan, Shanlee Davis, Heather Miyazawa, Glenn Furuta, Nicole Tartaglia, Nathalie Nguyen

 

The impact of sex chromosome trisomies (XXX, XXY, XYY) on early social cognition: Social orienting, joint attention, and theory of mind

Authors: Nienke Bouw, Hanna Swaab, Nicole Tartaglia, Sophie van Rijn

 

A cross sectional study of early language abilities in children with sex chromosome trisomy (XXY, XXX, XYY) aged 1-6 years

Authors: Evelien Urbanus, Hanna Swaab, Nicole Tartaglia, Richard Boada, Sophie van Rijn

 

Clinical Phenotype and Management of Individuals with Mosaic Monosomy X with Y Chromosome Material Stratified by Genital Phenotype

Authors: Lindsey Guzewicz, Susan Howell, Canice Crerand, H Umbaugh, Natalie Nokoff, Jennifer Barker, Shanlee Davis

 

Transition-related discussions among adolescent females with Turner syndrome: Current practices and associated factors

Authors: Nisha Patel, Shanlee Davis, Leena Nahata 

2020

Neurodevelopmental and Mental Health Screening for Patients with Turner Syndrome in Pediatric Endocrine Clinics: Results of a Pediatric Endocrine Society Survey

Authors: Shanlee Davis, Canice Crerand, Christa Hutaff-Lee, Talia Thompson, Amy Tishelman, Omar Samara, Hailey Umbaugh, Leena Nahata, Jessica Kremen

 

Diminished ovarian reserve in girls and adolescents with Trisomy X Syndrome

Authors: Shanlee Davis, Katelyn Soares, Susan Howell, Melanie Cree-Green, Eliza Buyers, Joshua Johnson, Nicole Tartaglia

 

Early neurodevelopmental and medical profiles in children with sex chromosome trisomies: Background for the prospective eXtraordinarY Babies Study to identify early risk factors and targets for intervention

Authors: Nicole Tartaglia, Susan Howell, Shanlee Davis, Karen Kowal, Tanea Tanda, Mariah Brown, Cristina Boada, Amanda Alston, Leah Crawford, Talia Thomspon, Sophie van Rijn, Rebecca Wilson, Jennifer Janusz, Judith Ross

 

High prevalence of cardiometabolic risk features in adolescents with 47,XXY / Klinefelter syndrome

Authors: Shanlee Davis, Sophia DeKlotz, Kristin Nadeau, Megan Kelsey, Philip Zeitler, Nicole Tartaglia

 

A Mixed Methods Study of Physical Activity and Quality of Life in Turner Syndrome

Authors: Talia Thompson, Briana Zieba, Susan Howell, William Karakash, Shanlee Davis

 

A current survey of early childhood intervention services in infants and young children with sex chromosome aneuploidies

Authors: Talia Thompson, Susan Howell, Shanlee Davis, Rebecca Wilson, Jennifer Janusz, Richard Boada, Laura Pyle, Nicole Tartaglia

 

Testicular Function in Boys with 47,XYY and Relationship to Phenotype

Authors: Shanlee Davis, Luke Bloy, Timothy Roberts, Karen Kowal, Amanda Alston, Aysha Tahsin, Alyssa Truxon, Judith L Ross

 

Adaptive functioning in children and adolescents with Trisomy X: An exploratory analysis

Authors: Kristen Wigby, Lisa Cordeiro, Rebecca Wilson, Kathleen Angkustsiri, Tony J Simon, Nicole Tartaglia

 

Executive function in XXY: Comparison of performance-based measures and rating scales

Authors: Jennifer Janusz, Caroline Harrison, Cristina Boada, Lisa Cordeiro, Susan Howell, Nicole Tartaglia, Richard Boada

 

The behavioral profile of children aged 1–5 years with sex chromosome trisomy (47,XXX, 47,XXY, 47,XYY)

Authors: Evelien Urbanus, Hanna Swaab, Nicole Tartaglia, Lisa Cordeiro, Sophie van Rijn

Earlier publications

Invited Book Chapters

  • N Tartaglia, R Hansen, R Hagerman, “Advances in Genetics,” Chapter, Handbook of Developmental Disabilities, Eds. J Blacher, S. Odom, 2007, 98-128
  • R Wilson, S Howell, E Bennett, N Tartaglia, “Sex Chromosome Aneuploidies,” Chapter, The Handbook of Pediatric Neuropsychology, Ed. Andrew S Davis, 2010, Chapter 65
  • N Tartaglia, J Visootsak, “Sex Chromosome Aneuploidy Disorders” Chapter, Autism and Other Neurodevelopmental Disorders, American Psychiatric Publishing, Eds Sally Rogers and Robin Hansen, 2013, 195-226
  • C Hutaff-Lee, L Cordeiro, N Tartaglia, “Cognitive and Medical Features of Chromosomal Aneuploidy,” Chapter, Handbook of Clinical Neurology, V. 111, Eds. O Dulac, M Lassonde, H Sarnat, 2013, 273-279 (PMID 23622175)
  • L Cordeiro, N Tartaglia, “Sex Chromosome Aneuploidy: XXYY” Chapter in Brenner’s Encyclopedia of Genetics 2nd Edition, editors Stanley Maloy and Kelly Hughes, 2013, 369-371
  • K Messer, C D’Epagnier, S. Howell, N Tartaglia, “Sex Chromosome Aneuploidy: Trisomy X” Chapter in Brenner’s Encyclopedia of Genetics 2nd Edition, editors Stanley Maloy and Kelly Hughes, 2013, 195-197
  • S. Davis, A. Villagomez, S. Howell, C. Buchanan, N. Tartaglia. “48,XXYY Syndrome” Orpha.net Portal for Rare Diseases, 2018
  • Davis S and Ross J. “Klinefelter Syndrome.” Encyclopedia of Endocrine Diseases, 2nd Edition. Elsevier. Editor Ilpo Huhtaniemi. October 2018. ISBN 9780128121993
  • Davis S and Travers S. “Disorders of Puberty.” Endocrine Secrets, 7th Edition, Elsevier. Editor Michael McDermott. 2020.

Department of Pediatrics

CU Anschutz

Administrative Pavilion

13123 E. 16th Ave.

B065

Aurora, CO 80045

720-777-2715

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