Children's Hospital Colorado

X&Y Chromosome Variations Research

Neuroscience | February 22, 2016

For families

  • Children with sex chromosome aneuploidies (SCAs) can benefit from an interdisciplinary clinical approach due to their complex needs.
  • Families surveyed at Children's Hospital Colorado's eXtraordinarY Kids Clinic responded they were very satisfied with their care.
  • Parents of children seen in the clinic said they better understood how SCAs can contribute to multiple areas of their child's life.

For health professionals

  • Patients in the eXtraordinarY Kids Clinic are seen by multiple specialists from different disciplines and receive individualized care plans.
  • Surveyed families noted benefits of the clinical approach including improved understanding of the diagnosis and the support required to care for their children.
  • The clinic was selected as a national model of care for children with SCAs.

Since 2007, our eXtraordinarY Kids Clinic team has been conducting clinical research in X&Y chromosome variations in order to learn more about how people with X&Y chromosome variations think, feel and solve problems. Our research studies span many areas, including learning, language, emotions and motor skills. Through research, we hope to better understand the strengths and weaknesses in these areas for individuals with X&Y chromosome variations, as well as how genes on the X&Y chromosomes may influence these different areas.  

Research goals

The three main goals of our research include:

  1. To study the development, learning, behaviors, emotions and motor skills in children and young adults with X&Y chromosome variations.
  2. To study different genetic factors of the X and Y chromosomes to determine if they are associated with the strengths and weaknesses in learning, behavior and motor skills and to develop new laboratory tests to identify X&Y chromosome variations.
  3. To study the physical appearance and other medical problems common in children and adults with different forms of X&Y chromosome variations.

Our current research also includes learning more about changes that occur with hormone replacement (testosterone) in a subgroup of adolescent or young adult males with an extra X chromosome (XXY, also known as Klinefelter Syndrome). We are looking at changes in learning, behavior, emotions and motor skills before and after testosterone therapy, and in comparison to males with an extra X chromosome who do not receive testosterone.

Our current research for sex chromosome variations

We are currently recruiting subjects for our clinical trials: “The Effects of Testosterone Therapy in Young Adolescents with Klinefelter Syndrome” and “Research study of muscle, fat, and hormones in infant boys with Klinefelter syndrome (47,XXY).”

The Effects of Testosterone Therapy in Young Adolescents with Klinefelter Syndrome

This study investigates the effects of testosterone therapy on behavior, mood, problem solving, attention span and motor skills in adolescent males with Klinefelter syndrome in early puberty. During this period in early puberty, there is much variability in how and when doctors start testosterone therapy. This study will evaluate if there are benefits to starting testosterone therapy in early puberty.  

Participants with Klinefelter syndrome in early puberty (around ages 10 to 15) will be treated with either testosterone gel or a placebo (inactive) gel and followed for one year. Participants will be followed for changes in behavior, emotions, cognitive abilities, executive functioning, motor skills (strength, balance, coordination) and physical features (pubertal development, body habitus, gynecomastia).  

This study is conducted in Denver and includes 5 visits over 1 year. Study assessments include IQ and executive function assessment, motor skills assessment and behavioral questionnaires completed by the participant and caretakers. The testing is conducted in two sessions of approximately 3 ½ hours each over 1 to 2 days during select visits. Participants are provided with the study medication and gift cards as a token of appreciation. Travel to Denver, Colorado may be provided.

Assessments are completed as part of the research study, and a summary of research testing results will be provided. This study is funded by the National Institutes of Health (NIH).

Research study of muscle, fat, and hormones in infant boys with Klinefelter syndrome (47,XXY)

This research study in infant males with Klinefelter syndrome (47,XXY) will learn more about body composition (muscle and fat) and male hormones and look at the effect of testosterone shots on body composition. We know that older boys and men with Klinefelter syndrome often have more fat compared to muscle than adults without Klinefelter syndrome, but we do not know if this difference is present at birth or develops over time. We will also learn if body composition has an effect on motor skills development and whether testosterone makes it better.   

Duration of study participation is 3 months. Infants with Klinefelter syndrome who are between 6 and 15 weeks of age will get their body composition measured by a PEA POD, a pain-free and rapid measure of body composition. Infants in the study will also have a blood draw and a urine collection. They will also have an assessment by an occupational therapist to evaluate motor skills. Half of the participants will be randomly selected to get a low-dose testosterone shot every month for 3 months. The PEA POD and motor development assessment will be repeated at the end of the study for all participants. Compensation is provided. 

Infants 6-15 weeks old with a confirmed genetic diagnosis of 47,XXY (Klinefelter syndrome) who were born at a normal weight and have never received testosterone previously are eligible for this study.

Summary of previous research findings: Satisfaction and outcomes improve through interdisciplinary care approach

One In 400 children born with SCAs
168 Patients responded to satisfaction survey
95% Satisfied or very satisfied with clinic

The eXtraordinarY Kids Clinic at Children's Colorado addresses the complex needs of children with sex chromosome aneuploidies (SCAs) through an interdisciplinary approach.

We launched a survey in 2011 to evaluate satisfaction with clinical services provided by eXtraordinarY Kids Clinic team members, perceived benefits of the evaluations and overall satisfaction with Children’s Colorado clinical processes. Families were asked to rate their overall satisfaction with clinic operations and quality of care.

Results demonstrated high satisfaction for all team members; the highest satisfaction scores were reported for the genetic counselor who also serves as the clinic coordinator. The three most commonly reported benefits for parents from a clinic visit indicated an overall improved understanding of the child, the diagnosis and the support needed.

Download the research summary (.pdf) to read the full conclusion.

Can my child participate in a research study?

If you are interested in learning more about our current research studies and seeing if your child is eligible for a research project, please contact Susan Howell at 720-777-8361 or