This is a continuation application for an additional 5 years of support for a comparative and prospective study of Fragile X Syndrome (FXS), an inherited neurodevelopmental disorder caused by a trinucleotide expansion of CGG repeats in the FMR1 gene on the X chromosome. FXS results in significant health and functional impairments that begin in early childhood and last a lifetime. It is the most common inherited cause of intellectual disability and autism, with substantial family burden and public health impacts. Critically, the great majority of knowledge about the FXS clinical phenotype derives from research on children, leaving adulthood a vast uncharted territory. The purpose of the proposed research is to investigate how the health and behavioral functioning of individuals with FXS change across adulthood and to identify factors that alleviate or worsen health and behavioral functioning during the adult years. It will be the first study to robustly address these questions beyond early adulthood. We address 3 Specific Aims. For Aim 1, we will determine profiles of health conditions and health care utilization for adults with FXS. Using a case-control design, we propose to examine the health of a newly ascertained cohort of 368 adults (age 18 to 80+) who have a code for FXS in their electronic health records (EHRs) – 162 women, 206 men, 77 nonwhite, and 291 white. These adults will be drawn from 11 health care systems comprising the Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN). Using EHRs, we will examine differences between adults with FXS and age- and sex-matched controls who do not have FXS with respect to health and health care utilization. We will probe differences between sub-groups of adults with FXS defined by age (early adulthood, midlife, older adulthood) as well as by sex and race. For Aim 2, using a longitudinal design that will span 18 years, we will define life course trajectories in health and behavioral functioning among adults with FXS and investigate age-related risk. Building on the 5 already- collected repeated measures, we will prospectively gather 3 additional rounds of data, resulting in up to 8 repeated measures over the 18-year period (n=182 dyads of adults with FXS and their premutation carrier mothers). By the end of the proposed study, the adults in our existing longitudinal sample will average 37 years of age, with 59% being age 35 or older (the oldest will be age 72). We will employ an accelerated longitudinal design to elucidate changes in health, executive functioning, communication, behavior problems, and daily living skills across adulthood. We will test for ages of increased risk and the effects of sex and autism on these trajectories. For Aim 3, using the same sample as in Aim 2, we will examine how life course trajectories of adults with FXS are associated with familial and social contextual determinants – family relationships, residential status of the adult with FXS, educational leve...