Research Priorities of Individuals and Families with Sex Chromosome Aneuploidies

ABSTRACT Sex chromosome aneuploidies (SCAs) are chromosomal variations that result from an atypical number of X and/or Y chromosomes. Combined, SCAs affect ~1/400 live births, including individuals with Klinefelter syndrome (47,XXY), Turner syndrome (45,X and variants), Double Y syndrome (47,XYY), Trisomy X (47,XXX), and rarer tetrasomies and pentasomies. Individuals with SCAs experience a wide variety of physical health, mental health, and healthcare experiences that differ from the standard population. To understand the priorities of the SCA community we surveyed participants in two large SCA registries, the Inspiring New Science in Guiding Healthcare in Turner Syndrome (INSIGHTS) Registry and the Generating Advancements in Longitudinal Analysis in X and Y Variations (GALAXY) Registry. 303/629 (48.1% response rate) individuals from 13 sites across the United States responded to the survey, including 251 caregivers and 52 self-advocates, with a range of ages from 3 weeks to 73 years old and represented SCAs including Turner syndrome, XXX, XXY, XYY, XXYY, and combined rare tetrasomies and pentasomies. Results demonstrate the priorities for physical health and emotional/behavioral health identified by the SCA community, as well as preferred types of research. All SCA subtypes indicated intervention studies as the top priority, emphasizing the need for researchers to focus on clinical treatments in response to priorities of the SCA community. STATEMENTS RELATING TO ETHICS AND INTEGRITY POLICIES The data that support the findings of this study are available on request from the corresponding author. This study was funded by the Turner Syndrome Global Alliance, Association for X and Y Chromosome Variations, Living with XXY, the XXYY Project, and the University of Colorado School of Medicine Department of Pediatrics. Data collection and storage was supported by NIH/NCATS Colorado CTSA Grant Number UM1 TR004399. The authors do not have any conflicts of interest to disclose. This study was reviewed and approved by the Colorado Multiple Institutional Review Board (COMIRB # 20-0482 and # 19-3027). All participants provided informed consent for participation - participants under 18 years old provided assent along with parental informed consent prior to any study procedures. Contents are the authors’ sole responsibility and do not necessarily represent official NIH views.