Outcome measures in Angelman syndrome.

Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children's functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials.

Bone health in children with Angelman syndrome at the ENCORE Expertise Center.

Angelman syndrome (AS) is a rare genetic disorder due to lack of UBE3A function on chromosome 15q11.2q13 caused by a deletion, uniparental paternal disomy (UPD), imprinting center disorder (ICD), or pathological variant of the UBE3A gene. AS is characterized by developmental delay, epilepsy, and lack of speech.

Hyperphagia, Growth, and Puberty in Children with Angelman Syndrome.

Angelman Syndrome (AS) is a rare genetic disorder caused by lack of maternal UBE3A protein due to a deletion of the chromosome 15q11.2-q13 region, uniparental paternal disomy, imprinting center defect, or pathogenic variant in the gene. Characteristics are developmental delay, epilepsy, behavioral, and sleep problems.

Autism Symptoms in Children and Young Adults With Fragile X Syndrome, Angelman Syndrome, Tuberous Sclerosis Complex, and Neurofibromatosis Type 1: A Cross-Syndrome Comparison.

Objective: The etiology of autism spectrum disorder (ASD) remains unclear, due to genetic heterogeneity and heterogeneity in symptoms across individuals. This study compares ASD symptomatology between monogenetic syndromes with a high ASD prevalence, in order to reveal syndrome specific vulnerabilities and to clarify how genetic variations affect ASD symptom presentation.

Methods: We assessed ASD symptom severity in children and young adults (aged 0-28 years) with Fragile X Syndrome (FXS, = 60), Angelman Syndrome (AS, = 91), Neurofibromatosis Type 1 (NF1, = 279) and Tuberous Sclerosis Complex (TSC, = 110), using the Autism Diagnostic Observation Schedule and Social Responsiveness Scale.

Examination of the genetic factors underlying the cognitive variability associated with neurofibromatosis type 1.

Purpose: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder associated with cognitive deficits. The NF1 cognitive phenotype is generally considered to be highly variable, possibly due to the observed T2-weighted hyperintensities, loss of heterozygosity, NF1-specific genetic modifiers, or allelic imbalance.

Methods: We investigated cognitive variability and assessed the contribution of genetic factors by performing a retrospective cohort study and a monozygotic twin case series.

Tuberous sclerosis complex: Concerns and needs of patients and parents from the transitional period to adulthood.

Introduction: Transitioning into adulthood and from pediatric services to adult healthcare are both challenging processes for young adults with rare chronic disorders such as tuberous sclerosis complex (TSC) and their parents. Adult healthcare systems are often less family-oriented and lack multidisciplinary care and experience with TSC, which can result in increased health risks and morbidity. Patient-driven data on care needs are necessary to optimize support for this vulnerable patient group.

Paediatric population neuroimaging and the Generation R Study: the second wave.

Paediatric population neuroimaging is an emerging field that falls at the intersection between developmental neuroscience and epidemiology. A key feature of population neuroimaging studies involves large-scale recruitment that is representative of the general population. One successful approach for population neuroimaging is to embed neuroimaging studies within large epidemiological cohorts.

Cortical dysplasia and autistic trait severity in children with Tuberous Sclerosis Complex: a clinical epidemiological study.

Tuberous Sclerosis Complex (TSC) is characterized by a high prevalence of autism spectrum disorders (ASD). Little is known about the relation between cortical dysplasia and ASD severity in TSC. We assessed ASD severity (using the Autism Diagnostic Observation Scale), tuber and radial migration line (RML) count and location, and cognitive functioning in 52 children with TSC and performed regression and mediation analyses.

Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior.

Importance: Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified.

Attention and motor deficits index non-specific background liabilities that predict autism recurrence in siblings.

Background: Recent research has demonstrated that subclinical autistic traits of parents amplify the effects of deleterious mutations in the causation of autism spectrum disorder (ASD) in their offspring. Here, we examined the extent to which two neurodevelopmental traits that are non-specific to ASD-inattention/hyperactivity and motor coordination-might contribute to ASD recurrence in siblings of ASD probands.

Methods: Data from a quantitative trait study of 114 ASD probands and their brothers, 26% of whom also had ASD, were analyzed.

Maternal depressive symptoms during pregnancy are associated with amygdala hyperresponsivity in children.

Depression during pregnancy is highly prevalent and has a multitude of potential risks of the offspring. Among confirmed consequences is a higher risk of psychopathology. However, it is unknown how maternal depression may impact the child's brain to mediate this vulnerability.

Cortical morphology as a shared neurobiological substrate of attention-deficit/hyperactivity symptoms and executive functioning: a population-based pediatric neuroimaging study.

Background: Attention-deficit/hyperactivity symptoms have repeatedly been associated with poor cognitive functioning. Genetic studies have demonstrated a shared etiology of attention-deficit/hyperactivity disorder (ADHD) and cognitive ability, suggesting a common underlying neurobiology of ADHD and cognition. Further, neuroimaging studies suggest that altered cortical development is related to ADHD.

Cognitive functioning in children with internalising, externalising and dysregulation problems: a population-based study.

Psychiatric symptoms in childhood are closely related to neurocognitive deficits. However, it is unclear whether internalising and externalising symptoms are associated with general or distinct cognitive problems. We examined the relation between different types of psychiatric symptoms and neurocognitive functioning in a population-based sample of 1177 school-aged children.

The association of gender, age, and intelligence with neuropsychological functioning in young typically developing children: The Generation R study.

Although early childhood is a period of rapid neurocognitive development, few studies have assessed neuropsychological functioning in various cognitive domains in young typically developing children. Also, results regarding its association with gender and intelligence are mixed. In 853 typically developing children aged 6 to 10 years old, the association of gender, age, and intelligence with neuropsychological functioning in the domains of attention, executive functioning, language, memory, sensorimotor functioning, and visuospatial processing was explored.

Relation of infant motor development with nonverbal intelligence, language comprehension and neuropsychological functioning in childhood: a population-based study.

Within a population-based study of 3356 children, we investigated whether infant neuromotor development was associated with cognition in early childhood. Neuromotor development was examined with an adapted version of Touwen's Neurodevelopmental Examination between 9 and 20 weeks. Parents rated their children's executive functioning at 4 years.

A Population-Based Imaging Genetics Study of Inattention/Hyperactivity: Basal Ganglia and Genetic Pathways.

Objective: Although attention-deficit/hyperactivity disorder (ADHD) is 1 of the most common neurodevelopmental disorders, little is known about the neurobiology. Clinical studies suggest basal ganglia morphology plays a role. Furthermore, hyperactivity/impulsivity symptoms have recently been linked to genetic pathways involved in dopamine/norepinephrine and serotonin neurotransmission and neuritic outgrowth.

White matter integrity and cognitive performance in school-age children: A population-based neuroimaging study.

Child and adolescent brain development are typically accompanied by marked improvements in a wide range of cognitive abilities. However, limited information is available surrounding the role of white matter in shaping cognitive abilities in children. The current study examined associations between white matter microstructure and cognitive performance in a large sample (n=778) of 6- to 10-year-old children.

What twin studies tell us about the heritability of brain development, morphology, and function: a review.

The development of brain structure and function shows large inter-individual variation. The extent to which this variation is due to genetic or environmental influences has been investigated in twin studies using structural and functional Magnetic Resonance Imaging (MRI). The current review presents an overview of twin studies using MRI in children, adults and elderly, and focuses on cross-sectional and longitudinal designs.

Cortical morphology in 6- to 10-year old children with autistic traits: a population-based neuroimaging study.

Objective: Recent evidence suggests that symptoms of social impairment in autism spectrum disorder (ASD) form a spectrum that extends into the general population. However, it is unclear whether the neuroanatomy of ASD also shows a similar continuum in the general population. Therefore, the goal of the present study was to investigate the relationship between cortical morphology and autistic traits along a continuum in a large population-based sample of young children.

Beyond classical inheritance: the influence of maternal genotype upon child's brain morphology and behavior.

Genetic variance has been associated with variations in brain morphology, cognition, behavior, and disease risk. One well studied example of how common genetic variance is associated with brain morphology is the serotonin transporter gene polymorphism within the promoter region (5-HTTLPR). Because serotonin is a key neurotrophic factor during brain development, genetically determined variations in serotonin activity during maturation, in particular during early prenatal development, may underlie the observed association.