Swenson Karli S, Bothwell Samantha, Zhivotov Anastasia, Sieverts Amanda, Devireddy Shalika, Shuff Kira, Nocon Kayla, Carl Alexandra, Molison Kayla, Grzybacz Lidia, Avila Brisa, Ikomi Chijioke, Cohen Lilian, Svoboda Ellie, Davis Shanlee
Department of Pediatrics, University of Colorado School of Medicine.
eXtraordinarY Kids Clinic, Developmental Pediatrics, Children's Hospital Colorado.
medRxiv. 2025 Jun 18:2025.06.17.25329799. doi: 10.1101/2025.06.17.25329799.
Sex chromosome aneuploidies (SCAs), including Klinefelter syndrome (47,XXY), Turner syndrome (45,X), XYY syndrome, trisomy X (47,XXX), and rarer tetrasomies and pentasomies, affect approximately 1 in 400 births and are associated with a wide range of developmental, cognitive, and physical health outcomes. While clinical research on SCAs has expanded over the past two decades, it is unclear whether the populations included in these studies reflect the demographic diversity of those affected. Assessing representation is critical to ensuring research findings are generalizable and applicable to diverse patient populations.
We conducted a systematic review of global clinical research on SCAs published in English between January 2004 and May 2024. Searches were performed in Ovid MEDLINE ALL, Embase, and Web of Science. Studies were included if they enrolled ≥10 participants and excluded if they were case reports, reviews, or meta-analyses. We extracted data from 1,474 studies on geographic location, participant karyotypes, and demographic metrics, including race, ethnicity, and socioeconomic status (SES) reported. Trends in demographic reporting were examined over time and by geographic region. For U.S.-based studies reporting race/ethnicity, we compared pooled participant demographics to national census data.
SCA research is concentrated within a small number of geographic areas, primarily in Europe (51.4%) and the U.S. (23.6%). Reporting rates of race or ethnicity for U.S. papers increased over the 20-year observation period, with an average increase of 1.5% ± 0.4% per year (p = 0.003), peaking in 2024 with 61.4% of U.S.-based papers presenting demographics. When reported, studies consistently overrepresented non-Hispanic White (p<0.001) and college-educated (p<0.001) participants relative to U.S. census benchmarks.
This systematic review reveals persistent gaps in the demographic reporting and representation of participants in SCA research. Even in the U.S., where population diversity is high, published studies do not reflect the expected racial, ethnic, and socioeconomic makeup of affected individuals. To ensure that research findings are equitable and clinically relevant, future studies should adopt standardized demographic reporting and prioritize inclusive enrollment strategies to reflect the full spectrum of individuals with SCAs.
性染色体非整倍体（SCAs），包括克兰费尔特综合征（47,XXY）、特纳综合征（45,X）、XYY综合征、三体X（47,XXX）以及更罕见的四体和五体，在每400例出生中约有1例受影响，并与广泛的发育、认知和身体健康结果相关。虽然过去二十年来关于SCAs的临床研究有所扩展，但尚不清楚这些研究中纳入的人群是否反映了受影响人群的人口统计学多样性。评估代表性对于确保研究结果具有普遍性并适用于不同患者群体至关重要。
我们对2004年1月至2024年5月期间以英文发表的关于SCAs的全球临床研究进行了系统综述。检索在Ovid MEDLINE ALL、Embase和Web of Science中进行。纳入的研究需招募≥10名参与者，排除病例报告、综述或荟萃分析。我们从1474项研究中提取了地理位置、参与者核型以及人口统计学指标的数据，包括报告的种族、民族和社会经济地位（SES）。研究了人口统计学报告随时间和地理区域的趋势。对于报告种族/民族的美国研究，我们将汇总的参与者人口统计学数据与国家人口普查数据进行了比较。
SCA研究集中在少数地理区域，主要在欧洲（51.4%）和美国（23.6%）。美国论文中种族或民族的报告率在20年观察期内有所增加，平均每年增加1.5%±0.4%（p = 0.003），在2024年达到峰值，61.4%的美国论文呈现了人口统计学数据。当进行报告时，相对于美国人口普查基准，研究始终过度代表非西班牙裔白人（p<0.001）和受过大学教育的参与者（p<0.001）。
这项系统综述揭示了SCA研究中参与者人口统计学报告和代表性方面持续存在的差距。即使在美国，人口多样性很高，但已发表的研究并未反映受影响个体预期的种族、民族和社会经济构成。为确保研究结果公平且具有临床相关性，未来的研究应采用标准化的人口统计学报告，并优先采用包容性招募策略，以反映SCA患者的全貌。
