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Funder: Economic and Social Research Council; Id: http://dx.doi.org/10.13039/501100000269, Funder: Newnham College, University of Cambridge; Id: http://dx.doi.org/10.13039/501100000663, Funder: University College, University of Oxford, Low inhibitory control (IC) is sometimes associated with enhanced problem-solving amongst adults, yet for young children high IC is primarily framed as inherently better than low IC. Here, we explore associations between IC and performance on a novel problem-solving task, amongst 102 English 2- and 3-year-olds (Study 1) and 84 Swedish children, seen at 18-months and 4-years (Study 2). Generativity during problem-solving was negatively associated with IC, as measured by prohibition-compliance (Study 1, both ages, Study 2 longitudinally from 18-months). High parent-reported IC was associated with poorer overall problem-solving success, and greater perseveration (Study 1, 3-year-olds only). Benefits of high parent-reported IC on persistence could be accounted for by developmental level. No concurrent association was observed between problem-solving performance and IC as measured with a Delay-of-Gratification task (Study 2, concurrent associations at 4-years). We suggest that, for young children, high IC may confer burden on insight- and analytic-aspects of problem-solving.

Previous studies suggest that tasks dependent on the mental number line may be difficult for Williams Syndrome (WS) and Down Syndrome (DS) groups. However, few have directly assessed number line estimation in these groups. The current study assessed 28 WS, 25 DS and 25 typically developing (TD) participants in non-verbal intelligence, number familiarity, visuo-spatial skills and number line estimation. Group comparisons indicated no differences in number line estimation. However, the WS group displayed difficulties with visuo-spatial skills and the DS group displayed difficulties with number familiarity. Differential relationships between number line estimation and visuo-spatial/number familiarity skills were observed across groups. Data is discussed in the context of assessment of skills in neurodevelopmental disorders.

It has been reported that approximate number sense (ANS) task performance is impaired in individuals with Williams syndrome (WS) and Down syndrome (DS). Research with infants has suggested this impairment is caused by sticky fixation in WS and sustained attention deficits for those with DS. This study examined looking patterns of older children and adults with WS (n = 24) and DS (n = 23) during an ANS task compared to typically developing controls matched for chronological age and those matched for mental age. Results showed that, although there were no group differences, looking patterns changed with chronological age for both the WS and DS groups. Looking behaviour related to ANS performance only in the WS group. Implications for interventions are discussed.

Funder: Economic and Social Research Council; doi: http://dx.doi.org/10.13039/501100000269, Funder: Williams Syndrome Foundation; doi: http://dx.doi.org/10.13039/501100000347, Objectives: Motor difficulties are present across a range of neurodevelopmental disorders, impacting on the development of other domains and on overall quality of life. One population that shows difficulties with their motor abilities is composed of individuals with Williams syndrome (WS). The purposes of the current study were to investigate the motor profile of individuals with WS and to investigate the relationships between physical activity and motor performance in this group. Methods: The motor performance of 36 individuals with WS was measured using the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT2-SF) short form. Physical activity was also measured using our novel questionnaire. Performance on both measures was compared with that of typically developing (TD) children aged 4 to 7 years (N = 40). Results: Results indicate that the individuals with WS (aged 12 to 50 years) performed at the level of TD 4- to 5-year olds with respect to overall motor ability. On examination of the motor profile, a relative strength in upper limb control and a relative weakness in balance were identified for this group. While a correlation was found between motor ability and the amount of physical activity that participants engaged in on a weekly basis in the TD group, no such relationship was found in the WS group. Conclusions: The motor problems that individuals with WS show in childhood persist into older childhood and adulthood, and akin to the WS cognitive profile, there are relative strengths and weaknesses in the WS motor profile. The lack of correlation between physical activity and motor ability in the WS group may be due to the lack of opportunity to access age- and ability-appropriate activities.

Objectives Motor difficulties are often reported in individuals with attention deficit hyperactivity disorder (ADHD). The aims of this study are to detail the motor profile of children with ADHD and to determine whether the motor impairment present in a large proportion of children with ADHD represents a phenotypic characteristic of ADHD or a co-occurring deficit. Methods Participants with ADHD (N = 51; age 8 to 15 years) and typically developing (TD) motor matched control children (N = 75; age 4 to 11 years) completed the largest battery of assessments of motor function that have been used with this population to date, as well as a measure of inhibition as a behavioural measure of ADHD characteristics. Parents/caregivers also completed questionnaires relating to ADHD symptomology and a retrospective report of their child’s motor milestone achievement. Results A motor deficit was observed in 47% of our ADHD sample. Few relationships were observed between ADHD core characteristics and motor competence. Furthermore, there was an uneven profile of motor performance across different motor tasks, relative to the TD children. Interestingly, it appears that motor milestone achievement is not delayed in ADHD. Conclusions Our findings suggest that the motor deficit observed in ADHD is not inherent to ADHD. The motor deficit observed in some children with ADHD does not represent a simple delay in development and is not observed in infancy with respect to reaching motor milestones.

Highlights • Parental depression relates to slower rate of expressive language development in young children with Down syndrome. • No association with parental depression was found for any other domain. • Parental depression and Down syndrome may constitute a double hit on expressive language development., Background and aims Down syndrome (DS) is often characterised by intellectual disability with particular difficulties in expressive language. However, large individual differences exist in expressive language across development in DS. In the general population, one of the factors associated with variability in this domain is parental depression. We investigated whether this is also the case in young children with DS. Methods Thirty-eight children with DS between 8 and 48 months of age participated in this study. Their parents reported on the children’s receptive and expressive vocabularies (MacArthur-Bates Communicative Development Inventory) and on parental depression. Furthermore, an experimenter-led standardized developmental assessment (Mullen Scales of Early Learning) was administered to the children to test five domains: gross motor, fine motor, visual reception, receptive language, and expressive language. Results A cross-sectional developmental trajectories analysis demonstrated that expressive language developed at a slower rate in children with DS whose parent reported depression than in those whose parent did not. No differences between groups were found in any other domain. Conclusion Parental depression is associated with slower rate of expressive language development in young children with DS. These findings suggest that DS and parental depression may constitute a double hit leading to increased difficulties in the development of expressive language.

Typically developing (TD) infants adapt to the social world in part by shifting the focus of their processing resources to the relevant aspects of a visual scene. Any impairment in visual orienting may therefore constrain learning and development in domains such as language. However, although something is known about visual orienting in infants at risk of autism, very little is known about it in infants/toddlers with other neurodevelopmental disorders. This is partly because previous studies focused on older children and rarely compared the children to both chronological age (CA)- and mental age (MA)-matched TD controls. Yet, if visual orienting is important for learning and development, then it is imperative to investigate it early in development and ascertain whether it relates to higher level cognitive functions such as language. We used eye-tracking technology to directly compare visual orienting in infants/toddlers with one of three neurodevelopmental disorders-Down syndrome (DS), fragile X syndrome (FXS) and Williams syndrome (WS)-matched on CA or MA to TD controls (~15 months). We also measured language ability using the Mullen Scales of Early Learning (MSEL). We found that the ability to disengage attention from a visual stimulus in order to shift it to another visual stimulus is related to language ability in infants/toddlers irrespective of group affiliation. We also found that, contrary to the literature, infants and toddlers with DS (but not WS) are slow at disengaging attention. Our data suggest that orienting attention constrains language development and is impaired in DS.

This cross-syndrome study focuses on sleep and its relationship with language development. Children with neurodevelopmental disorders present with language delay. Typical language development is constrained by numerous factors including sleep. Sleep is often disrupted in adolescents/adults with neurodevelopmental disorders. We therefore hypothesised that sleep may be disrupted, and correlate with language development, in infants/toddlers with neurodevelopmental disorders. To test our hypothesis, we obtained sleep and vocabulary size data from 75 infants/toddlers with one of three neurodevelopmental disorders (Down syndrome [DS], fragile X syndrome [FXS], Williams syndrome [WS]). Sleep was indeed disrupted in these children. It was also positively associated with receptive vocabulary size in the infants/toddlers with DS and WS (we could not test the relationship between sleep and language in FXS due to lack of power). We argue that disrupted sleep may be a common occurrence in very young children with neurodevelopmental disorders, and it may relate to their ability to acquire their first language.

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.

Highlights • A consideration of the causes of individual differences in Down syndrome, at the level of genes, epigenetics, brain, and behaviour, linking potential differences in early development with elevated risk for Alzheimer’s disease. • Evaluation of environmental (socioeconomic status) and genetic (chromosome 19 apolipoprotein APOE genotype, modulating risk for AD in adulthood) predictors of individual differences in early vocabulary development in a sample of 84 infants and young children with DS. Neither predictor accounted for significant amounts of variance, leaving the wide variability unexplained and likely arising from complex individual effects of the DS genotype. There was weak evidence that early development was faster for the APOE genotype conferring greater AD risk (ε4 carriers) consistent with recent observations in infant attention (D’Souza, Mason et al., 2020) • Proof of principle that prenatal and neonatal magnetic resonance imaging methods may be used to test the predictive power of measures of early brain structure for variation in DS infant cognitive development. Early brain development represents the concerted effect of the DS genotype. • The article argues for the importance of a multi-level, lifespan developmental approach to explore the origins of individual differences in DS cognition. It hypothesises that in this framework, dementia itself may be considered as a developmental disorder (Karmiloff-Smith et al., 2016)., In this article, we focus on the causes of individual differences in Down syndrome (DS), exemplifying the multi-level, multi-method, lifespan developmental approach advocated by Karmiloff-Smith (1998, 2009, 2012, 2016). We evaluate the possibility of linking variations in infant and child development with variations in the (elevated) risk for Alzheimer’s disease (AD) in adults with DS. We review the theoretical basis for this argument, considering genetics, epigenetics, brain, behaviour and environment. In studies 1 and 2, we focus on variation in language development. We utilise data from the MacArthur-Bates Communicative Development Inventories (CDI; Fenson et al., 2007), and Mullen Scales of Early Learning (MSEL) receptive and productive language subscales (Mullen, 1995) from 84 infants and children with DS (mean age 2;3, range 0;7 to 5;3). As expected, there was developmental delay in both receptive and expressive vocabulary and wide individual differences. Study 1 examined the influence of an environmental measure (socio-economic status as measured by parental occupation) on the observed variability. SES did not predict a reliable amount of the variation. Study 2 examined the predictive power of a specific genetic measure (apolipoprotein APOE genotype) which modulates risk for AD in adulthood. There was no reliable effect of APOE genotype, though weak evidence that development was faster for the genotype conferring greater AD risk (ε4 carriers), consistent with recent observations in infant attention (D’Souza, Mason et al., 2020). Study 3 considered the concerted effect of the DS genotype on early brain development. We describe new magnetic resonance imaging methods for measuring prenatal and neonatal brain structure in DS (e.g., volumes of supratentorial brain, cortex, cerebellar volume; Patkee et al., 2019). We establish the methodological viability of linking differences in early brain structure to measures of infant cognitive development, measured by the MSEL, as a potential early marker of clinical relevance. Five case studies are presented as proof of concept, but these are as yet too few to discern a pattern.

Background: Sleep variables have been linked to improved functioning of learning and memory throughout life, with most studies focusing on older children and adults. Since infancy is a time of outstanding plasticity, sleep variables could be particularly important for cognitive development in that age group. Methods: This is a longitudinal study collecting data from 40 infants at four different time points of 4, 6, 8 and 10 months. Sleep variables were assessed using actigraphy for a week, as well as a sleep questionnaire. Eye‐tracking was employed to examine developmental cognitive trajectories. Infants had to remember the location of a toy that had previously been linked to a sound and an eye‐tracker recorded whether they were searching the correct location upon hearing the sound. Results: Based on their trajectories between 4 and 10 months, infants were divided into two groups who shifted their response strategies at different time points. Those two groups also differed in other aspects of their looking patterns and scored increasingly differently in the Ages & Stages Questionnaire over time. Time spent awake in the night early in life was reduced in the group who changed their strategy earlier. Conclusions; While previous research examined the relation of infant sleep and cognitive functioning measured once, this paper provides first evidence that night wake time can serve as a marker for different cognitive trajectories.

In order to understand how language abilities emerge in typically and atypically developing infants and toddlers, it is important to embrace complexity in development. In this paper, we describe evidence that early language development is an experience-dependent process, shaped by diverse, interconnected, interdependent developmental mechanisms, processes, and abilities (e.g. statistical learning, sampling, functional specialization, visual attention, social interaction, motor ability). We also present evidence from our studies on neurodevelopmental disorders (e.g. Down syndrome, fragile X syndrome, Williams syndrome) that variations in these factors significantly contribute to language delay. Finally, we discuss how embracing complexity, which involves integrating data from different domains and levels of description across developmental time, may lead to a better understanding of language development and, critically, lead to more effective interventions for cases when language develops atypically.

Individuals with neurodevelopmental disorders like Williams syndrome and Down syndrome exhibit executive function impairments on experimental tasks (Lanfranchi, Jerman, Dal Pont, Alberti, & Vianello, 2010; Menghini, Addona, Costanzo, & Vicari, 2010), but the way that they use executive functioning for problem solving in everyday life has not hitherto been explored. The study aim is to understand cross-syndrome characteristics of everyday executive functioning and problem solving.Parents/carers of individuals with Williams syndrome (n=47) or Down syndrome (n=31) of a similar chronological age (m=17 years 4 months and 18 years respectively) as well as those of a group of younger typically developing children (n=34; m=8years 3 months) completed two questionnaires: the Behavior Rating Inventory of Executive Function (BRIEF; Gioia, Isquith, Guy, & Kenworthy, 2000) and a novel Problem-Solving Questionnaire.The rated likelihood of reaching a solution in a problem solving situation was lower for both syndromic groups than the typical group, and lower still for the Williams syndrome group than the Down syndrome group. The proportion of group members meeting the criterion for clinical significance on the BRIEF was also highest for the Williams syndrome group. While changing response, avoiding losing focus and maintaining perseverance were important for problem-solving success in all groups, asking for help and avoiding becoming emotional were also important for the Down syndrome and Williams syndrome groups respectively. Keeping possessions in order was a relative strength amongst BRIEF scales for the Down syndrome group.Results suggest that individuals with Down syndrome tend to use compensatory strategies for problem solving (asking for help and potentially, keeping items well ordered), while for individuals with Williams syndrome, emotional reactions disrupt their problem-solving skills. This paper highlights the importance of identifying syndrome-specific problem-solving strengths and difficulties to improve effective functioning in everyday life.

Even genetic disorders associated with monogenic aetiologies are characterized by complex and variable risk for poor outcomes, highlighting the need to follow trajectories longitudinally. Here, we investigated the longitudinal relationships between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) symptoms in a population at high risk for both: boys with fragile X syndrome. 59 boys with fragile X syndrome aged 3–10 years old at entry participated in this study, and were followed up one and two years after their first visit. As expected, we found strong relationships over three timepoints for ADHD symptoms (as measured by the parent-rated Conners scale) and ASD symptoms (as measured by the Social Communication Questionnaire [SCQ]). In addition, using structural equation modeling (SEM) we found that ADHD symptoms at time 2 predicted ASD symptoms at time 3, suggestive of a causal relationship. Importantly, these relationships hold when including chronological age at entry to the study, as well as when including severity of impairment as measured by IQ, and their effects on both ASD and ADHD symptoms do not reach significance. This result highlights the need to study outcomes longitudinally and it informs the comorbidity of the two symptom domains in FXS as well as their potential directionality, both of which have been little researched. In addition, our findings may suggest a future need to study how ADHD symptoms and their treatment impact individuals with ASD.

In typical infants, the achievement of independent locomotion has a positive impact on the development of both small-scale and large-scale spatial cognition. Here we investigated whether this association between the motor and spatial domain: (1) persists into childhood and (2) is detrimental to the development of spatial cognition in individuals with motor deficits, namely, individuals with attention deficit hyperactivity disorder (ADHD) and individuals with Williams syndrome (WS). Despite evidence of a co-occurring motor impairment in many individuals with ADHD, little is known about the developmental consequences of this impairment. Individuals with WS demonstrate impaired motor and spatial competence, yet the relationship between these two impairments is unknown. Typically developing (TD) children (N = 71), individuals with ADHD (N = 51), and individuals with WS (N = 20) completed a battery of motor tasks, a measure of independent exploration, and a virtual reality spatial navigation task. Retrospective motor milestone data were collected for the ADHD and WS groups. Results demonstrated a relationship between fine motor ability and spatial navigation in the TD group, which could reflect the developmental impact of the ability to manually manipulate objects, on spatial knowledge. In contrast, no relationships between the motor and spatial domains were observed for the ADHD or WS groups. Indeed, while there was evidence of motor impairment in both groups, only the WS group demonstrated an impairment in large-scale spatial navigation. The motor-spatial relationship in the TD, but not the ADHD and WS groups, suggests that aspects of spatial cognition can develop via a developmental pathway which bypasses input from the motor domain.

Sleep plays a key role in the consolidation of newly acquired information and skills into long term memory. Children with Down syndrome (DS) and Williams syndrome (WS) frequently experience sleep problems, abnormal sleep architecture, and difficulties with learning; thus, we predicted that children from these clinical populations would demonstrate impairments in sleep-dependent memory consolidation relative to children with typical development (TD) on a cognitive procedural task: The Tower of Hanoi. Children with DS (n = 17), WS (n = 22) and TD (n = 34) completed the Tower of Hanoi task. They were trained on the task either in the morning or evening, then completed it again following counterbalanced retention intervals of daytime wake and night time sleep. Children with TD and with WS benefitted from sleep for enhanced memory consolidation and improved their performance on the task by reducing the number of moves taken to completion, and by making fewer rule violations. We did not find any large effects of sleep on learning in children with DS, suggesting that these children are not only delayed, but atypical in their learning strategies. Importantly, our findings have implications for educational strategies for all children, specifically considering circadian influences on new learning and the role of children's night time sleep as an aid to learning.

Low inhibitory control (IC) is sometimes associated with enhanced problem-solving amongst adults, yet for young children high IC is primarily framed as inherently better than low IC. Here, we explore associations between IC and performance on a novel problem-solving task, amongst 102 English 2- and 3-year-olds (Study 1) and 84 Swedish children, seen at 18-months and 4-years (Study 2).Generativity during problem-solving was negatively associated with IC, as measured by prohibition-compliance (Study 1, both ages, Study 2 longitudinally from 18-months). High parent-reported IC was associated with poorer overall problem-solving success, and greater perseveration (Study 1, 3-year-olds only). Benefits of high parent-reported IC on persistence could be accounted for by developmental level. No concurrent association was observed between problem-solving performance and IC as measured with a Delay-of-Gratification task (Study 2, concurrent associations at 4-years). We suggest that, for young children, high IC may confer burden on insight- and analytic-aspects of problem-solving.

BACKGROUND: Studies in Down syndrome (DS) and Williams syndrome (WS) have suggested that mathematical abilities are impaired. However, it is unclear which domain-general or domain-specific abilities impact on mathematical development in these developmental disorders. METHOD: The current study examined the foundations of mathematical development across participants with WS (n = 24) and DS (n = 26) compared to typically developing (TD) children (n = 26) in relation to domain-general (i.e., general intelligence and visuospatial abilities) and domain-specific abilities (non-symbolic and symbolic number abilities). RESULTS: Developmental trajectories showed that mathematical abilities were delayed in line with overall mental age in DS and WS. Whilst visuospatial abilities predicted performance for DS and TD participants, this was not the case for the WS group, instead Approximate Number Sense abilities predicted mathematical development. CONCLUSIONS: These findings suggest that those with DS and WS may benefit from different mathematical intervention programmes.

Typically-developing (TD) infants can construct unified cross-modal percepts, such as a speaking face, by integrating auditory-visual (AV) information. This skill is a key building block upon which higher-level skills, such as word learning, are built. Because word learning is seriously delayed in most children with neurodevelopmental disorders, we assessed the hypothesis that this delay partly results from a deficit in integrating AV speech cues. AV speech integration has rarely been investigated in neurodevelopmental disorders, and never previously in infants. We probed for the McGurk effect, which occurs when the auditory component of one sound (/ba/) is paired with the visual component of another sound (/ga/), leading to the perception of an illusory third sound (/da/ or /tha/). We measured AV integration in 95 infants/toddlers with Down, fragile X, or Williams syndrome, whom we matched on Chronological and Mental Age to 25 TD infants. We also assessed a more basic AV perceptual ability: sensitivity to matching vs. mismatching AV speech stimuli. Infants with Williams syndrome failed to demonstrate a McGurk effect, indicating poor AV speech integration. Moreover, while the TD children discriminated between matching and mismatching AV stimuli, none of the other groups did, hinting at a basic deficit or delay in AV speech processing, which is likely to constrain subsequent language development.

Even in infancy children from low-SES backgrounds differ in frontal cortex functioning and, by the start of pre-school, they frequently show poor performance on executive functions including attention control. These differences may causally mediate later difficulties in academic learning. Here, we present a study to assess the feasibility of using computerized paradigms to train attention control in infants, delivered weekly over five sessions in early intervention centres for low-SES families. Thirty-three 12-month-old infants were recruited, of whom 23 completed the training. Our results showed the feasibility of repeat-visit cognitive training within community settings. Training-related improvements were found, relative to active controls, on tasks assessing visual sustained attention, saccadic reaction time, and rule learning, whereas trend improvements were found on assessments of short-term memory. No significant improvements were found in task switching. These results warrant further investigation into the potential of this method for targeting ‘at-risk’ infants in community settings.

Highlights • Visuospatial orienting efficiency increases with symptom severity in idiopathic ASD. • Children with Down syndrome and comorbid ASD display superior search performance. • Visuo-spatial orienting ability and visual search performance appears unrelated., Background Children with Down syndrome (DS) are at increased likelihood of Autism Spectrum Disorder (ASD) relative to the general population. To better understand the nature of this comorbidity, we examined the visuo-attentional processes associated with autistic trait expression in children with DS, focusing specifically on attentional disengagement and visual search performance. Method We collected eye-tracking data from children with DS (n = 15) and children with idiopathic ASD (iASD, n = 16) matched according to chronological age. Seven children with DS had a formal clinical diagnosis of ASD (DS+ASD). Results In children with iASD, but not DS, higher autistic trait levels were associated with decreased temporal facilitation on a gap-overlap task, implying increased visuospatial orienting efficiency. In all cases, higher autistic trait levels were associated with improved visual search performance according to decreased target detection latency. On a visual search task, children with DS+ASD outperformed their peers with DS-ASD, mirroring the phenotypic advantage associated with iASD. We found no evidence of a relationship between attentional disengagement and visual search performance, providing preliminary evidence of a differentiation in terms of underlying visuo-attentional mechanism. Conclusion We illustrate the value of progressing beyond insensitive behavioural measures of phenotypic description to examine, in a more fine-grained way, the attentional features associated with ASD comorbidity in children with DS.

Down syndrome (DS) is associated with intellectual disability and an ultra-high risk of developing dementia. Informant ratings are invaluable to assess abilities and related changes in adults with DS, particularly for those with more severe intellectual disabilities and/or cognitive decline. We previously developed the informant rated Cognitive Scale for Down Syndrome (CS-DS) to measure everyday cognitive abilities across memory, executive function, and language domains in adults with DS, finding CS-DS scores are a valid measure of general abilities, and are significantly lower for those with noticeable cognitive decline compared to those without decline. To further test the validity of the CS-DS in detecting changes associated with cognitive decline we collected longitudinal data across two time points, approximately 1.5-2 years apart, for 48 adults with DS aged 36 years and over. CS-DS total scores (78.83 ± 23.85 vs. 73.83 ± 25.35

Williams-Beuren syndrome (WBS, MIM 194050) is a rare condition, with striking physical and behavioural features,1–3 which occurs in 1/20 000-1/50 000 live births. Cases are generally sporadic; however, familial cases with an autosomal dominant mode of inheritance have been reported. It results in a complex phenotype with physical, cognitive, and behavioural aspects that include an uneven cognitive profile (WBSCP), with verbal tasks outstripping spatial tasks, and overall IQs in the 50-60 range. Physically, WBS phenotypes include a dysmorphic face, congenital heart disease (typically supravalvular aortic stenosis (SVAS)), growth retardation, hyperacusis, premature ageing, and often infantile hypercalcaemia. These features are caused by deletion of the Williams-Beuren syndrome critical region (WBSCR) at chromosomal position 7q11.23 on either the maternal or paternal chromosome 7. The deletion is thought to arise from recombination between misaligned repeat sequences flanking the WBSCR during meiosis. The breakpoints cluster within these repeat regions, so that most WBS patients have similar deletions of approximately 1.5 Mb. A few WBS patients have, however, been reported with smaller deletions (