Behavioral phenotype in Costello syndrome with atypical mutation: a case report.

Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly(12) promoting enhanced signaling through the MAPK and PI3K-AKT signaling cascades. In general, the cognitive profile in CS is characterized by intellectual disability ranging from mild to severe impairment. The first published descriptions of behavior in CS children underlined the presence of irritability and shyness at younger ages with sociable personality and good empathic skills after 4-5 years of age, however some recent studies have reported autistic traits. We report on a 7-year-old boy heterozygous for a rare duplication of codon 37 (p.E37dup) in HRAS, manifesting impaired social interaction and non-verbal communication and with circumscribed interests. These additional features improve phenotype delineation in individuals with rare HRAS mutations, facilitating the development of specific behavioral treatments which could lead to improvement in cases of autism spectrum disorder.

What and why understanding in autism spectrum disorders and williams syndrome: similarities and differences.

Children with autism spectrum disorders (ASD) and children with Williams syndrome (WS) show divergent social phenotypes, but also several similarities in their socio-cognitive deficits. Cross-syndrome direct comparisons could lead to a better understanding of mechanisms that determine deficits in social cognition in the two syndromes. A fundamental factor for social cognition is the ability to understand and predict others' actions (e.g. what action is being done and why it is being done when observing a goal-related act). Here we compared the understanding of others' actions in children with ASD, WS and in children with typical development. Comprehension of what motor act was being done and of why it was being done was assessed with or without contextual cueing using a computer-based task. The results showed that what understanding was impaired in the WS group, but not in the ASD group, which showed mental-age appropriate performance. Why understanding was impaired in both experimental groups. Autism Res 2014, 7: 421-432. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

A longitudinal study of the teacch program in different settings: the potential benefits of low intensity intervention in preschool children with autism spectrum disorder.

We conducted a longitudinal study of 30 preschool children with autism spectrum disorders (ASDs) to evaluate the potential benefits of the Treatment and Education of Autistic and related Communication Handicapped Children (TEACCH). Fifteen children following a low intensity TEACCH program were assessed four times for autism severity, adaptive functioning, language skills, maladaptive behaviors and parental stress and compared with a control group of 15 children following a non-specific approach. Findings suggest that a low intensity home and school TEACCH program may provide benefits for children with ASD by reducing autistic symptoms and maladaptive behaviors. Furthermore, a decrease in parental stress indicates that parents' involvement in the rehabilitation program is a crucial factor and contributes greatly to treatment efficacy.

Effect of duration of breastfeeding on neuropsychological development at 10 to 12 years of age in a cohort of healthy children.

AIM: The aim of this article was to explore the effect of duration of breastfeeding on neurocognitive development. METHOD: The long-term effect of breastfeeding on neurodevelopment was examined through a battery of neuropsychological tests in 1403 children (693 females, 710 males; mean age 11 y 9mo [SD 6mo], range: 10y 3mo-12y 8mo) who were originally recruited at 6 to 12 weeks of age for a clinical trial on acellular pertussis vaccines. An estimated IQ was obtained from scores of the vocabulary, similarities, block design, and coding tests. Breastfeeding data had been prospectively collected throughout the first year of life. Duration of exclusive breastfeeding was defined as the time during which children received breast milk without receiving any supplemental formula or food. Children were assessed at 10 to 12 years of age. We adjusted the analysis on test scores for multiple potential confounders. RESULTS: Multivariate analysis showed a significant association between exclusive breastfeeding duration and test scores in the vocabulary (odds ratio [OR] 0.05; confidence interval [CI] 0.00-0.10; p=0.04) and similarities (OR 0.06; CI 0.01-0.11; p=0.03) tests. These associations have a negligible effect size, however. Scores on one writing praxis test subcategory decreased with increasing duration of both exclusive breastfeeding (OR -0.06; CI -0.11 to -0.01; p=0.03) and breastfeeding irrespective of consumption of other foods (OR -0.06; CI -0.11 to -0.01; p=0.03). A negative association was also found between one subcategory of the California verbal learning test and breastfeeding duration longer than 6 months (OR -0.21; CI -0.42 to -0.01; p=0.04). INTERPRETATION: Breastfed healthy children may perform better on neuropsychological tests in the language domain at 10 to 12 years of age. However, the effect of breast milk on neuropsychological performance in healthy children may have a limited clinical relevance and is confounded by parental education.

Parent inclusion in Early Intensive Behavioral Intervention: the influence of parental stress, parent treatment fidelity and parent-mediated generalization of behavior targets on child outcomes.

Although early intensive behavior interventions have been efficient in producing positive behavior outcome in young children with Autism Spectrum Disorder, there is a considerable variety in the children's progress. Research has suggested that parental and treatment factors are likely to affect children's response to treatment. The purpose of the current study was to examine the interrelating factors that impact children's progress, highlighting the influence of parent inclusion in treatment provision captured by parental stress, how faithfully the parents followed the treatment protocols and the intensity of treatment provided at home. Twenty-four children received cross-setting staff- and parent-mediated EIBI, including continuous parent training and supervision. A comparison group of 20 children received eclectic intervention. Standardized tests were carried out by independent examiners at intake and after six months. The intervention group outperformed the eclectic group in measures of autism severity, developmental and language skills. Parent training and constant parent-mediated treatment provision led to reduced challenging behaviors from the children, increased treatment fidelity and child direct behavior change as measured by performance in correct responding on behavior targets. Variables of treatment progress and potential predictors of child outcome were analyzed in detail and mapped with regard to their relationships drawn from multiple regression analysis. Particularly, the study highlights an association between parental stress and staff treatment fidelity that interferes with decision making in treatment planning and consequently with positive behavior outcome. Such results provide important scientific and clinical information on parental and treatment factors likely to affect a child's response to treatment.

Neuropsychological performance 10 years after immunization in infancy with thimerosal-containing vaccines.

OBJECTIVE: Thimerosal, a mercury compound used as a preservative in vaccines administered during infancy, has been suspected to affect neuropsychological development. We compared the neuropsychological performance, 10 years after vaccination, of 2 groups of children exposed randomly to different amounts of thimerosal through immunization. METHODS: Children who were enrolled in an efficacy trial of pertussis vaccines in 1992-1993 were contacted in 2003. Two groups of children were identified, according to thimerosal content in vaccines assigned randomly in the first year of life (cumulative ethylmercury intake of 62.5 or 137.5 microg), and were compared with respect to neuropsychological outcomes. Eleven standardized neuropsychological tests, for a total of 24 outcomes, were administered to children during school hours. Mean scores of neuropsychological tests in the domains of memory and learning, attention, executive functions, visuospatial functions, language, and motor skills were compared according to thimerosal exposure and gender. Standard regression coefficients obtained through multivariate linear regression analyses were used as a measure of effect. RESULTS: Nearly 70% of the invited subjects participated in the neuropsychological assessment (N = 1403). Among the 24 neuropsychological outcomes that were evaluated, only 2 were significantly associated with thimerosal exposure. Girls with higher thimerosal intake had lower mean scores in the finger-tapping test with the dominant hand and in the Boston Naming Test. CONCLUSIONS: Given the large number of statistical comparisons performed, the few associations found between thimerosal exposure and neuropsychological development might be attributable to chance. The associations found, although statistically significant, were based on small differences in mean test scores, and their clinical relevance remains to be determined.