142 - System-Based Diagnoses in Youth with XXY, XYY, and XXX: A PEDSnet Study

Poster Number: 142
Publication Number: 142.304

Shanlee Davis, University of Colorado School of Medicine, Denver, CO, United States; Anna Furniss, University of Colorado School of Medicine, Aurora, CO, United States; Natalie J. Nokoff, University of Colorado School of Medicine, Aurora, CO, United States; Nicole R. Tartaglia, University of Colorado School of Medicine, Aurora, CO, United States; Laura Pyle, University of Colorado Anschutz Medical Campus, Aurora, CO, United States

Background: Sex chromosome trisomies (SCT), including 47,XXY/Klinefelter syndrome, 47,XXX/Trisomy X, and 47,XYY occur in ~1 in 500 individuals and are now being identified prenatally through non-invasive prenatal screening. Knowledge on health risks among youth with SCT are primarily from small convenience samples or extrapolated from adult studies. The largest pediatric Health Learning System, PEDSnet, offers a unique opportunity to examine clinical outcomes among a large, nationally representative cohort of youth with SCT.

Objective: To compare prevalence of diagnoses organized by systems in youth with SCT compared to a general clinical population using the PEDSnet database.

Design/Methods: Electronic medical record data for all individuals with a diagnosis of XXY (n=1,198), XYY (n=253), and XXX (n=262) were obtained from PEDSnet and each matched to four different controls using propensity scores that included site, sex, age at last visit, duration in PEDSnet, race, ethnicity, and payor type. Log-binomial regression models with generalized estimating equations were used to calculate the relative risk (RR) and 95% confidence intervals (CI) between SCT cases and controls for any diagnoses within one of 15 different system-based SNOMED categories. Significance was set at 0.003 (Bonferroni correction). Prevalence of the three most frequent comorbid diagnoses for each SCT are reported.

Results: All three SCT conditions had significantly higher RR of diagnoses within the Endocrine, Cardiovascular, Mental Health, and Nervous system categories (see Figure). Males with XXY also had a higher risk of Genitourinary diagnoses and a lower risk of diagnoses in several other systems. The most frequent diagnoses with XXY were testicular hypogonadism (15%), ADHD (15%), and developmental delay (14%); XYY were ADHD (23%), developmental delay (19%), and autism (17%); and XXX were constipation (19%), developmental delay (17%), gastroesophageal reflux disease (14%).      Conclusion(s): In conclusion, SCT in youth is associated with an increased risk of comorbid diagnoses in some but not all body systems. With increased ascertainment of SCT in childhood, pediatricians should be aware of the comorbidities that these children are at risk for, and these data should be incorporated into clinical practice guidelines for managing care for children and adolescents with SCT.
System-Based Diagnoses in SCT Compared to Matched ControlsRelative Risk (RR, point estimates) with 95% confidence intervals (error bars) of diagnosis within the respective SNOMED categories for XXY (circles), XYY (squares), and XXX (diamonds) with a RR of 1.0 indicating the same risk between SCT cases and controls. * indicates a significant difference between cases and their matched controls; shown to the left of the error bars if RR is significantly lower in cases and to the right if significantly higher.