Dataset Information

Genetic and environmental vulnerabilities in children with neurodevelopmental disorders.

ABSTRACT: One might expect that children with varying genetic mutations or children raised in low socioeconomic status environments would display different deficits. Although this expectation may hold for phenotypic outcomes in older children and adults, cross-syndrome comparisons in infancy reveal many common neural and sociocognitive deficits. The challenge is to track dynamic trajectories over developmental time rather than focus on end states like in adult neuropsychological studies. We contrast the developmental and adult approaches with examples from the cognitive and social domains, and we conclude that static models of adult brain lesions cannot be used to account for the dynamics of change in genetic and environmentally induced disorders in children.

SUBMITTER: Karmiloff-Smith A

PROVIDER: S-EPMC3477396 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic and environmental vulnerabilities in children with neurodevelopmental disorders.

Karmiloff-Smith Annette A D'Souza Dean D Dekker Tessa M TM Van Herwegen Jo J Xu Fei F Rodic Maja M Ansari Daniel D

Proceedings of the National Academy of Sciences of the United States of America 20121008

One might expect that children with varying genetic mutations or children raised in low socioeconomic status environments would display different deficits. Although this expectation may hold for phenotypic outcomes in older children and adults, cross-syndrome comparisons in infancy reveal many common neural and sociocognitive deficits. The challenge is to track dynamic trajectories over developmental time rather than focus on end states like in adult neuropsychological studies. We contrast the d ...[more]

PMID: 23045661

Similar Datasets

Project description:Introduction De novo mutations contribute to a large proportion of sporadic psychiatric and developmental disorders, yet the potential role of environmental carcinogens as drivers of causal de novo mutations in neurodevelopmental disorders is poorly studied. Methods To explore environmental mutation vulnerability of disease-associated gene sets, we analyzed publicly available whole genome sequencing datasets of mutations in human induced pluripotent stem cell clonal lines exposed to 12 classes of environmental carcinogens, and human lung cancers from individuals living in highly polluted regions. We compared observed rates of exposure-induced mutations in disease-related gene sets with the expected rates of mutations based on control genes randomly sampled from the genome using exact binomial tests. To explore the role of sequence characteristics in mutation vulnerability, we modeled the effects of sequence length, gene expression, and percent GC content on mutation rates of entire genes and gene coding sequences using multivariate Quasi-Poisson regressions. Results We demonstrate that several mutagens, including radiation and polycyclic aromatic hydrocarbons, disproportionately mutate genes related to neurodevelopmental disorders including autism spectrum disorders, schizophrenia, and attention deficit hyperactivity disorder. Other disease genes including amyotrophic lateral sclerosis, Alzheimer’s disease, congenital heart disease, orofacial clefts, and coronary artery disease were generally not mutated more than expected. Longer sequence length was more strongly associated with elevated mutations in entire genes compared with mutations in coding sequences. Increased expression was associated with decreased coding sequence mutation rate, but not with the mutability of entire genes. Increased GC content was associated with increased coding sequence mutation rates but decreased mutation rates in entire genes. Discussion Our findings support the possibility that neurodevelopmental disorder genetic etiology is partially driven by a contribution of environment-induced germ line and somatic mutations.

Project description:Children with genetic neurodevelopmental disorders (NDDs) such as Down syndrome, Prader-Willi syndrome, and Fragile X syndrome may show a range of cognitive impairments, including impairments in executive functions (EF). EF are related to general intelligence, academic achievement, and literacy and mathematical skills. EF deficits are linked to a variety of clinically and socially important behaviors. Therefore, methods for improving EF in children with NDDs could be beneficial. One method for improving EF is through cognitive training. Research on commercial brain training programmes and video games suggests that EF can be improved through training, both in healthy adults and in children with NDDs. Computerized cognitive training (CCT) therefore represents a potentially viable intervention for children with NDDs. For training to be effective, it is important that an appropriate regimen is followed. Since children are likely to engage with training at home, the intentions of their parents to support them are therefore important. However, no research has investigated the attitudes of parents of children with NDDs to CCT. To address this, we developed a questionnaire based on the theory of planned behavior, which states that a person's intention to engage in a behavior is predicted by (1) their attitude toward the behavior, (2) their perception of subjective norms regarding the behavior (i.e., perceived social pressure), and (3) their perceived control over the behavior. The questionnaire was completed by parents of children with NDDs; 58 unique responses were retained for analyses. Parents reported low levels of knowledge of CCTs, and low levels of experience with CCTs (both their own experience and their child's experience). However, our results also show that parents of children with NDDs have positive beliefs about the potential of CCT to benefit their children and intend to support the use of CCT by their children. Linear modeling showed that, of the three constructs of the theory of planned behavior, only attitudes significantly predicted intention. Finally, parents' beliefs about the benefits of CCT correlated positively with positive attitudes toward such training. We also found limited evidence that parents of boys have more positive attitudes regarding CCT than parents of girls.

Dataset Information

Genetic and environmental vulnerabilities in children with neurodevelopmental disorders.

Publications

Genetic and environmental vulnerabilities in children with neurodevelopmental disorders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets