A reassessment of Jackson's checklist and identification of two Down syndrome sub-phenotypes.

Down syndrome (DS) is characterised by several clinical features including intellectual disability (ID) and craniofacial dysmorphisms. In 1976, Jackson and coll. identified a checklist of signs for clinical diagnosis of DS; the utility of these checklists in improving the accuracy of clinical diagnosis has been recently reaffirmed, but they have rarely been revised. The purpose of this work is to reassess the characteristic phenotypic signs and their frequencies in 233 DS subjects, following Jackson's checklist. 63.77% of the subjects showed more than 12 signs while none showed less than 5, confirming the effectiveness of Jackson's checklist for the clinical diagnosis of DS. An association between three phenotypic signs emerged, allowing us to distinguish two sub-phenotypes: Brachycephaly, short and broad Hands, short Neck (BHN), which is more frequent, and "non-BHN". The strong association of these signs might be interpreted in the context of the growth defects observed in DS children suggesting decreased cell proliferation. Lastly, cognitive assessments were investigated for 114 subjects. The lack of association between the presence of a physical sign or the number of signs present in a subject and cognitive skills disproves the stereotype that physical characteristics are predictive of degree of ID.

Is the Age of Developmental Milestones a Predictor for Future Development in Down Syndrome?

Down Syndrome (DS) is the most common genetic alteration responsible for intellectual disability, which refers to deficits in both intellectual and adaptive functioning. According to this, individuals with Down Syndrome (DS) reach developmental milestones (e.g., sitting, walking, and babbling) in the same order as their typically developing peers, but later in life. Since developmental milestones are the first blocks on which development builds, the aims of the current study are to: (i) expand the knowledge of developmental milestone acquisition; and (ii) explore the relationship between developmental milestone acquisition and later development. For this purpose 105 children/adolescents with DS were involved in this study, divided in two groups, Preschoolers (n = 39) and School-age participants (n = 66). Information on the age of acquisition of Sitting, Walking, Babbling, and Sphincter Control was collected, together with cognitive, motor, and adaptive functioning. Sitting predicted later motor development, but, with age, it became less important in predicting motor development in everyday life. Babbling predicted later language development in older children. Finally, Sphincter Control emerged as the strongest predictor of motor, cognitive, language, and adaptive skills, with its role being more evident with increasing age. Our data suggest that the age of reaching the milestones considered in the study has an influence on successive development, a role that can be due to common neural substrates, the environment, and the developmental cascade effect.

One-carbon pathway and cognitive skills in children with Down syndrome.

This work investigates the role of metabolite levels in the intellectual impairment of subjects with Down syndrome (DS). Homocysteine, folate, vitamin B12, uric acid (UA), creatinine levels and MTHFR C677T genotype were analyzed in 147 subjects with DS. For 77 subjects, metabolite levels were correlated with cognitive tests. Griffiths-III test was administered to 28 subjects (3.08-6.16 years) and WPPSI-III test was administered to 49 subjects (7.08-16.08 years). Significant correlations were found among some metabolite levels and between homocysteine levels and MTHFR C677T genotype. Moreover, homocysteine, UA and creatinine levels resulted increased with age. We did not find any correlation between metabolites and cognitive test score in the younger group. Homocysteine showed statistically significant correlation with WPPSI-III subtest scores when its level is ≥ 7.35 µmol/L, remaining correlated in higher thresholds only for non-verbal area scores. Vitamin B12 showed correlations with all WPPSI-III subtest scores when its level is < 442 pg/mL. The relevance of the present findings is the detection of a specific metabolite threshold related with a better or worse cognitive score, suggesting that vitamin B12 and homocysteine may have a role in cognitive development in children with DS.

Plasma metabolome and cognitive skills in Down syndrome.

Trisomy 21 (Down syndrome, DS) is the main human genetic cause of intellectual disability (ID). Lejeune hypothesized that DS could be considered a metabolic disease, and we found that subjects with DS have a specific plasma and urinary metabolomic profile. In this work we confirmed the alteration of mitochondrial metabolism in DS and also investigated if metabolite levels are related to cognitive aspects of DS. We analyzed the metabolomic profiles of plasma samples from 129 subjects with DS and 46 healthy control (CTRL) subjects by 1H Nuclear Magnetic Resonance (NMR). Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to 94% accuracy) between the two groups. The univariate analysis revealed a significant alteration in 7 metabolites out of 28 assigned unambiguously. Correlations among the metabolite levels in DS and CTRL groups were separately investigated and statistically significant relationships appeared. On the contrary, statistically significant correlations among the NMR-detectable part of DS plasma metabolome and the different intelligence quotient ranges obtained by Griffiths-III or WPPSI-III tests were not found. Even if metabolic imbalance provides a clear discrimination between DS and CTRL groups, it appears that the investigated metabolomic profiles cannot be associated with the degree of ID.

Intellectual profile in school-aged children with borderline intellectual functioning.

BACKGROUND: Little is currently known about borderline intellectual functioning (BIF), a condition characterized by an intelligence quotient between one and two standard deviations below the average, that affects about 14% of the population. AIMS: The present study aimed to analyze the intellectual profile of school-aged children with BIF. METHOD AND PROCEDURE: The WISC-IV was administered to 204 children with BIF attending Italian primary and lower secondary school, and their profile was compared with that of a control group of typically developing (TD) children. RESULTS: The WISC-IV profile of the children with BIF differed from that of the TD children, and the former's performance was worse than the latter's in all the measures considered. The children with BIF also showed significant differences between the four main factor indices, scoring lowest for working memory, while the TD control group's profile was flat (as expected on the grounds of standardization criteria). No differences were found between the profiles of children with versus without a comorbid neurodevelopmental disorder. DISCUSSION: Our results support the hypothesis that individuals with BIF have a characteristic profile with specific weaknesses.

Numerical skills in children with Down syndrome. Can they be improved?

The present study aims to explore the impact of a numerical skills training program on the basic mathematical skills and logical thinking in children with Down syndrome (DS). The training program was built specifically for children with DS, bearing the strengths and weaknesses of their particular cognitive profile in mind. Two groups of children with DS took part in the study. All children were tested before and after the training on measures of numerical skills and logical thinking. One group of 27 children was trained in numerical skills twice a week for 2 months, for about 30min per session. A control group of 9 children was not involved in any training session. After training, children in the intervention group performed better in numerical tests, while those in the control group did not. These results suggest that our training program is both feasible and effective for children with Down syndrome.

Spatial-sequential and spatial-simultaneous working memory in individuals with Williams syndrome.

The aim of the present study was to compare visuospatial working memory performance in 18 individuals with Williams syndrome (WS) and 18 typically developing (TD) children matched for nonverbal mental age. Two aspects were considered: task presentation format (i.e., spatial-sequential or spatial-simultaneous), and level of attentional control (i.e., passive or active tasks). Our results showed that individuals with WS performed less well than TD children in passive spatial-simultaneous tasks, but not in passive spatial-sequential tasks. The former's performance was also worse in both active tasks. These findings suggest an impairment in the spatial-simultaneous working memory of individuals with WS, together with a more generalized difficulty in tasks requiring information storage and concurrent processing, as seen in other etiologies of intellectual disability.

Exploring spatial working memory performance in individuals with Williams syndrome: the effect of presentation format and configuration.

Williams syndrome (WS) is a neurodevelopmental disorder associated with an impaired capacity for visuospatial representation. Individuals with WS have a specific weakness in spatial processing, while visual components are relatively well preserved. This dissociation is apparent in working memory function too. The present study aimed to further investigate spatial working memory performance in individuals with WS, analyzing whether their impaired WM performance regards both simultaneous and sequential spatial formats, and whether presenting configurations differently might reduce their difficulties. These issues were examined by administering simultaneous and sequential spatial tasks, in which the information to be recalled was presented in random or arranged configurations. Our results showed that individuals with WS performed less well than typically developing (TD) children in the spatial-simultaneous task, but not in the spatial-sequential one. The presence of a pattern enhanced the performance of both groups, but the difference between the two groups' performance in the spatial simultaneous task remained, albeit to a lesser degree.

Numerical estimation in individuals with Down syndrome.

We investigated numerical estimation in children with Down syndrome (DS) in order to assess whether their pattern of performance is tied to experience (age), overall cognitive level, or specifically impaired. Siegler and Opfer's (2003) number to position task, which requires translating a number into a spatial position on a number line, was administered to a group of 21 children with DS and to two control groups of typically developing children (TD), matched for mental and chronological age. Results suggest that numerical estimation and the developmental transition between logarithm and linear patterns of estimates in children with DS is more similar to that of children with the same mental age than to children with the same chronological age. Moreover linearity was related to the cognitive level in DS while in TD children it was related to the experience level.

Memory coding in individuals with Down syndrome.

Previous research has identified a deficit in phonological short-term memory in individuals with Down syndrome. The present work aimed to analyze how a group of 30 individuals with Down syndrome performed in a picture span task compared with 30 typically developing children of the same mental age. The task involved four conditions (i.e., dissimilar, phonologically similar, visually similar, and long-name items) chosen to analyze the strategy used by individuals with Down syndrome to code visually presented nameable items. Individuals with Down syndrome performed less well than typically developing children. Both groups showed the visual similarity effect. Taken together, our results confirm that individuals with Down syndrome have a verbal working memory deficit, even when nameable items are presented visually. Mental age appears to be an important determinant of memory coding stage in individuals with Down syndrome.

Stress, locus of control, and family cohesion and adaptability in parents of children with Down, Williams, Fragile X, and Prader-Willi syndromes.

The present study analyzes differences in parental stress in families of children with Down, Williams, Fragile X, and Prader-Willi syndromes, exploring factors that influence parental stress, such as child's characteristics, parental locus of control, and family cohesion and adaptability. Differences between mothers and fathers are also investigated. Parents were given self-report questionnaires to assess family stress, parental locus of control, and family cohesion and adaptability. Results showed that stress levels were lower in families of children with Down syndrome and higher in those of children with Prader-Willi syndrome. Children's characteristics and their parents' locus of control were found to be related to family stress levels in all four syndromes, but several aspects specific to a given syndrome also came to light, as well as some shared and some gender-specific features relating to mothers and fathers.

Working memory and cognitive skills in individuals with Down syndrome.

This work is aimed at analyzing working memory (WM) components and their relationships with other cognitive processes in individuals with Down syndrome (DS). Particular attention is given to examine whether a verbal WM deficit is due to difficulties in verbal abilities often showed by individuals with DS, or whether it is a deficit per se. A group of 20 individuals with DS was compared to a group of 20 typically developing (TD) children matched on vocabulary comprehension and to a group of 20 TD children matched on general verbal intelligence. The groups received a battery of 3 verbal and 3 visuospatial WM tasks requiring different degrees of control, and tests assessing verbal abilities (WPPSI verbal scale, PPVT), nonverbal skills (WPPSI performance scale), and logical thinking (LO). The results revealed that individuals with DS have deficits in both central executive (control) and verbal components of the WM system, and the latter one is independent of the general verbal abilities deficit. The data suggest that the development of central executive proceeds at a slower rate in individuals with DS and differently from TD children with comparable verbal abilities. The performance of individuals with DS on high-control WM tasks requires additional general resources that are strictly linked to intelligence.

Working memory in individuals with fragile X syndrome.

The present research tests the hypothesis that fragile X syndrome (FXS) is associated with a deficit in working memory (WM) and the deficit is more pronounced the higher the control requirements of the task. To this purpose, 15 boys with FXS and 15 typically developing children, matched for mental age, assessed with Logical Operation Test, were tested with batteries of 4 verbal and 4 visuospatial WM tasks requiring different levels of control. Children with FXS showed a performance equal to controls, in WM tasks requiring low and medium-low control but significant impairment in correspondence with greater control requirements. Results show that boys with FXS present a WM deficit only when high control is required by the task, supporting the hypothesis that control can be a critical variable distinguishing WM functions and explaining intellectual differences. On the contrary the hypothesis that the FXS is associated with a visuospatial deficit was not supported.

Verbal and visuospatial working memory deficits in children with Down syndrome.

The hypothesis that deficits of children with Down syndrome on working memory tasks are more evident the higher the control required and for verbal than visuospatial tasks was tested. Two groups of children, one with Down syndrome, who ranged in age from 7 to 18, and a control group were assessed with batteries of verbal and visuospatial working memory tests requiring different levels of control. On tasks requiring low control, children with Down syndrome showed impairment of verbal but not visuospatial working memory tasks. As the requirement for control increased, they showed greater impairment on both tasks. Children with Down syndrome were comparatively better in visuospatial than verbal tasks. Implications of these results for working memory models and the role of working memory in intelligence were discussed.