This study compares the developmental trajectories of pragmatic skills, the use of language in social contexts, among girls and boys with fragile X syndrome (FXS), Down syndrome (DS), and typical development (TD) and boys with autism spectrum disorder only (ASD-O) to determine whether individual differences in conversational discourse and narrative skills relate to FXS specifically or to either mental retardation (MR) or autism in general. The study will also compare potential mechanisms underlying these individual differences in pragmatic skills in FXS in comparison to DS and ASD-O. The specific aims of the study are to identify differences in pragmatic skills in conversation and narration that are syndrome specific to FXS or DS and determine the extent to which co-morbidity between FXS and autism may account for some apparent FXS group differences. Further, we will examine the extent to which pragmatic skills among boys and girls with FXS differ, specifically whether gender differences vary depending on the presence of MR or whether they also exist in children with DS or TD. Finally, we seek to identify possible mediators that account for anticipated group differences in the acquisition of conversational and narrative skills among children with FXS (who do and do not have ASD) in comparison to children with DS, ASD-O, or TD. Study participants will be 80 boys with FXS (40 with and 40 without ASD) who are 6-12 years, 60 girls with FXS (30 6-12 years with MR and 30 3-6 years without MR), 40 girls and 40 boys with DS 6-12 years, 40 boys with ASD and MR 6-12 years, and 30 TD girts and 30 TD boys 3-6 years. All participants will have nonverbal mental ages between 3 and 6 years. Children's pragmatic skills, including their initiations, contingency, perseveration, and repair strategies during conversation and their informativeness and cohesiveness during narration will be assessed annually for four years. Children's language content and structure (receptive vocabulary and expressive syntax), cognition (nonverbal cognitive level and attention), social-emotional behavior (anxiety and autistic characteristics), and family environment (responsiveness and support of home environment and maternal contingency) will also be examined annually. In addition, Fragile X Mental Retardation Protein (FMRP) analysis from blood samples will be completed on the girls and boys with FXS, and activation ratios will be computed for the girts with FXS. Growth curve methods will be used to quantify patterns of change over time in the overall level and rate of growth in pragmatic development. Pragmatic skills are essential for effective communication and pragmatic difficulties can compromise all aspects of communicative competence in daily interactions. Determining whether a unique pragmatic phenotype exists for FXS that is syndrome specific or related to gender, MR, or autism as well as identifying the potential mechanisms underlying pragmatic skills, have critically important implications for defining treatment protocols. [unreadable] [unreadable] [unreadable]