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Williams syndrome (WS) is a rare genetic syndrome. As with all rare syndromes, obtaining adequately powered sample sizes is a challenge. Here we present legacy data from seven UK labs, enabling the characterisation of cross-sectional and longitudinal developmental trajectories of verbal and non-verbal development in the largest sample of individuals with WS to-date. In Study 1, we report cross-sectional data between N = 102 and N = 209 children and adults with WS on measures of verbal and non-verbal ability. In Study 2, we report longitudinal data from N = 17 to N = 54 children and adults with WS who had been tested on at least three timepoints on these measures. Data support the WS characteristic cognitive profile of stronger verbal than non-verbal ability, and shallow developmental progression for both domains. Both cross-sectional and longitudinal data demonstrate steeper rates of development in the child participants than the adolescent and adults in our sample. Cross-sectional data indicate steeper development in verbal than non-verbal ability, and that individual differences in the discrepancy between verbal and non-verbal ability are largely accounted for by level of intellectual functioning. A diverging developmental discrepancy between verbal and non-verbal ability, whilst marginal, is not mirrored statistically in the longitudinal data. Cross-sectional and longitudinal data are discussed with reference to validating cross-sectional developmental patterns using longitudinal data and the importance of individual differences in understanding developmental progression.

Background: Down syndrome (DS) is associated with variable intellectual disability and multiple health and psychiatric comorbidities. The impact of such comorbidities on cognitive outcomes is unknown. We aimed to describe patterns of physical health and psychiatric comorbidity prevalence, and receptive language ability, in DS across the lifespan, and determine relationships with cognitive outcomes., Methods: Detailed medical histories were collected and cognitive abilities measured using standardised tests for 602 individuals with DS from England and Wales (age range 3 months to 73 years). Differences in prevalence rates between age groups and between males and females were determined using chi-squared or Fisher's exact tests. In adults, rates for psychiatric comorbidities were compared to expected population rates using standardised morbidity ratios (SMRs). Adapted ANCOVA functions were constructed to explore age and sex associations with receptive language ability across the lifespan, and regression analyses were performed to determine whether the presence of health comorbidities or physical phenotypes predicted cognitive abilities., Results: Multiple comorbidities showed prevalence differences across the lifespan, though there were few sex differences. In adults, SMRs were increased in males and decreased in females with DS for schizophrenia, bipolar disorder, and anxiety. Further, SMRs were increased in both males and females with DS for dementia, autism, ADHD, and depression, with differences more pronounced in females for dementia and autism, and in males for depression. Across the lifespan, receptive language abilities increasingly deviated from age-typical levels, and males scored poorer than females. Only autism and epilepsy were associated with poorer cognitive ability in those aged 16-35 years, with no relationships for physical health comorbidities, including congenital heart defects., Conclusions: Our results indicate the prevalence of multiple comorbidities varies across the lifespan in DS, and in adults, rates for psychiatric comorbidities show different patterns for males and females relative to expected population rates. Further, most health comorbidities are not associated with poorer cognitive outcomes in DS, apart from autism and epilepsy. It is essential for clinicians to consider such differences to provide appropriate care and treatment for those with DS and to provide prognostic information relating to cognitive outcomes in those with comorbidities.