A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case
ConclusionsThis is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carryingSHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can m...
Source: Journal of Neurodevelopmental Disorders - July 18, 2019 Category: Neurology Source Type: research

Children with facial paralysis due to Moebius syndrome exhibit reduced autonomic modulation during emotion processing
ConclusionResults support “embodied” theory, whereby the congenital inability to produce facial expressions induces alterations in the processing of facial expression of emotions. Such alterations may constitute a risk for emotion dysregulation. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - July 10, 2019 Category: Neurology Source Type: research

Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders
ConclusionsLooking for pathogenic variants in newly identified NDD genes enabled us to provide a molecular diagnosis to 14 patients and their close relatives and caregivers. This underlines the relevance of re-evaluation of existing exome data on a regular basis to improve the diagnostic yield and serve the needs of our patients. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 25, 2019 Category: Neurology Source Type: research

Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk
ConclusionThe understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 15, 2019 Category: Neurology Source Type: research

Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study
ConclusionsOur results show that dysfunction of stimulus-driven neural suppression plays a crucial role in the neural mechanism of visual abnormality in children with ASD. To the best of our knowledge, this is the first magnetoencephalography study to demonstrate the association between the severity of visual abnormality and lower attenuation ratios in children with ASD. Our results contribute to the knowledge of the mechanisms underlying visual abnormality in children with ASD, and may therefore lead to more effective diagnosis and earlier intervention. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 14, 2019 Category: Neurology Source Type: research

Using kinematic analyses to explore sensorimotor control impairments in children with 22q11.2 deletion syndrome
ConclusionsImpairments in sensorimotor control are seen on a range of visuo-manual tasks in children with 22q11.2DS but the extent of these impairments are largely unrelated to the severity of other psychopathological and intellectual impairments commonly found in children with 22q11.2DS. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 10, 2019 Category: Neurology Source Type: research

In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects?
ConclusionsOur 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 7, 2019 Category: Neurology Source Type: research

Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis
In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast.MethodsA 7-year longitudinal study of affect (mood, interest and pleasure) was conducted in individuals with CdLS (n = 44) and FXS (n = 95). The trajectories of low affect were explored, as well as associations between Time 1 behavioural characteristics and affect at Time 1 and Time ...
Source: Journal of Neurodevelopmental Disorders - June 7, 2019 Category: Neurology Source Type: research

Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed
ConclusionsFurther experimental comparisons are needed before Cogmed working memory training can be considered empirically validated for children with FXS, forming the basis of treatment recommendation. However, given that prior studies show no significant changes on these measures in FXS without treatment, that improvements were maintained for 3  months, and that blinded teachers reported improvements in the classroom, the modest benefits seen in both adaptive and non-adaptive groups overall are unlikely to be attributable to placebo or practice effects alone. Future analyses examining inter-individual differences ...
Source: Journal of Neurodevelopmental Disorders - April 15, 2019 Category: Neurology Source Type: research

Adaptation to different communicative contexts: an eye tracking study of autistic adults
ConclusionsDiminished gaze to faces when observing two people communicating may lead to fewer opportunities for social learning and subsequent reductions in social knowledge. Naturalistic measures of contextual modulation could help identify areas of need for individuals learning about the social world and could become treatment targets to improve everyday social learning. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - April 13, 2019 Category: Neurology Source Type: research

Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders
ConclusionsDisruption ofDMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - February 7, 2019 Category: Neurology Source Type: research

Static and dynamic postural control deficits in aging fragile X mental retardation 1 ( FMR1 ) gene premutation carriers
ConclusionOur findings indicate that agingFMR1 premutation carriers show static and dynamic postural control deficits relative to healthy controls implicating degenerative processes of spinocerebellar and cerebellar-brainstem circuits that may be independent of or precede the onset of FXTAS. Our finding that FXTAS+ and FXTAS − premutation carriers differed on their level of intentional AP sway suggests that neural mechanisms of dynamic postural control may be differentially impacted in patients with FXTAS, and its measurement may be useful for rapidly and precisely identifying disease presence and onset. (Source: Jou...
Source: Journal of Neurodevelopmental Disorders - January 21, 2019 Category: Neurology Source Type: research

Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study
ConclusionsThese findings suggest fragile X syndrome social deficits center on social anxiety without the prominent reduction in social interest associated with autism spectrum disorder. Specifically designed eye tracking techniques clarify the nature of social deficits in fragile X syndrome and may have applications to improve phenotyping and evaluate interventions targeting social functioning impairments. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - January 21, 2019 Category: Neurology Source Type: research

The reach-to-grasp movement in infants later diagnosed with autism spectrum disorder: a high-risk sibling cohort study
ConclusionsOur results support the growing literature indicating that children who are later diagnosed with ASD show impaired early motor performance. These results highlight the importance of early surveillance of children who are at elevated risk for ASD, and early initiatives should focus on early signs of the phenotype, including both movement and sensory differences (prodromal signs) prior to the emergence of diagnostic characteristics. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - December 27, 2018 Category: Neurology Source Type: research

Substance use and nicotine dependence in persistent, remittent, and late-onset ADHD: a 10-year longitudinal study from childhood to young adulthood
ConclusionsSUD and nicotine dependence are associated with a negative ADHD outcome. Results further emphasize the need for clinicians to comprehensively assess substance use when diagnosing ADHD in adolescents and adults. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - December 27, 2018 Category: Neurology Source Type: research

Cerebrospinal fluid and the early brain development of autism
ConclusionThe identification of early CSF abnormalities in children with ASD, along with emerging knowledge of the underlying pathogenic mechanisms, has the potential to serve as early stratification biomarkers that separate children with ASD into biological subtypes that share a common pathophysiology. Such subtypes could help parse the phenotypic heterogeneity of ASD and map on to targeted, biologically based treatments. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - December 13, 2018 Category: Neurology Source Type: research

Arterial spin labeling provides a reliable neurobiological marker of autism spectrum disorder
ConclusionsArterial spin labeling revealed hypoperfusion in children with ASD in regions critical to social perception and cognition. The left fusiform gyrus plays an important role in facial recognition, and greater CBF in this region was correlated with more normative facial recognition performance in children with ASD. This study takes an important first step in establishing CBF of the temporal lobes as a reliable marker of ASD. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - December 13, 2018 Category: Neurology Source Type: research

Imaging episodic memory during development and childhood epilepsy
AbstractEpilepsy affects 2.2 million adults in the USA, with 1 in 26 people developing epilepsy at some point in their lives. Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy as medial structures, and the hippocampus in particular, are prone to generating seizures. Selective anterior temporal resection (which removes the hippocampus) is the most effective intractable TLE treatment, but given the critical role of the mesial temporal lobe in memory functioning, resection can have negative effects on this crucial cognitive skill. To minimize the adverse impact of temporal lobe surgery on memory functioni...
Source: Journal of Neurodevelopmental Disorders - December 13, 2018 Category: Neurology Source Type: research

Applying a network framework to the neurobiology of reading and dyslexia
ConclusionsThese results contribute to the growing literature on the relationship between reading and brain network architecture. They suggest that an efficient network organization, i.e., one in which brain areas form cohesive resting-state networks, is important for skilled reading, and that dyslexia can be characterized by abnormal functioning of hub regions that map information between multiple systems. Overall, use of a connectomics framework opens up new possibilities for investigating reading difficulty, especially its commonalities across other neurodevelopmental disorders. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - December 13, 2018 Category: Neurology Source Type: research

What ’s missing in autism spectrum disorder motor assessments?
ConclusionsStandardized assessments of motor function have provided valuable information on motor impairments in ASD. However, significant limitations remain in the use of these measures in children with ASD. Moving forward, it is imperative that standardized measures of motor function receive greater validation testing in children with ASD to assess their potential application given the clinical heterogeneity of this condition. In addition, utilizing quantitative measures of motor function should allow for evaluation and comparison of individuals with ASD across the lifespan with varying cognitive and behavioral abilities...
Source: Journal of Neurodevelopmental Disorders - December 13, 2018 Category: Neurology Source Type: research

Aberrant structural and functional connectivity and neurodevelopmental impairment in preterm children
ConclusionFuture work in this domain should continue to leverage longitudinal evaluations of preterm infants which include both neuroimaging and detailed serial neurodevelopmental assessments to further characterize relationships between imaging measures and impairment, information necessary for advancing our understanding of modifiable risk factors underlying these disorders and best practices for improving neurodevelopmental trajectories in this high-risk clinical population. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - December 13, 2018 Category: Neurology Source Type: research

ADHD-related sex differences in fronto-subcortical intrinsic functional connectivity and associations with delay discounting
ConclusionsOur findings suggest fronto-subcortical functional networks are affected in children with ADHD, particularly girls, and relate to delay discounting. These results also provide preliminary evidence of greater disruptions in fronto-subcortical FC among girls with ADHD that is not due to elevated inattention symptom severity, intellectual reasoning ability, age, or head motion. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - December 13, 2018 Category: Neurology Source Type: research

Statistical learning as a window into developmental disabilities
AbstractUntil recently, most behavioral studies of children with intellectual and developmental disabilities (IDD) have used standardized assessments as a means to probe etiology and to characterize phenotypes. Over the past decade, however, tasks originally developed to investigate learning processes in typical development have been brought to bear on developmental processes in children with IDD.This brief review will focus on one learning process in particular —statistical learning—and will provide an overview of what has been learned thus far from studies using statistical learning tasks with different group...
Source: Journal of Neurodevelopmental Disorders - December 13, 2018 Category: Neurology Source Type: research

Inaugural annual special section of the intellectual and developmental disabilities research centers: developmental cognitive neuroscience and neurodevelopmental disorders
(Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - December 13, 2018 Category: Neurology Source Type: research

An emotion recognition subtyping approach to studying the heterogeneity and comorbidity of autism spectrum disorders and attention-deficit/hyperactivity disorder
ConclusionsSubgroups of youths can be identified that differ both in quantitative and qualitative aspects of emotion recognition abilities. Weak emotion recognition abilities across sensory domains are linked to an increased risk for ASD as well as ADHD, although emotion recognition impairments alone are neither necessary nor sufficient parts of these disorders. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - November 15, 2018 Category: Neurology Source Type: research

Language delay aggregates in toddler siblings of children with autism spectrum disorder
ConclusionsGreater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - October 22, 2018 Category: Neurology Source Type: research

Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome
ConclusionsBy adding granularity to our understanding of neurodevelopmental difficulties in XYY, these findings assist targeted clinical assessment of newly identified cases, motivate greater provision of specialized multidisciplinary support, and inform future efforts to integrate behavioral phenotypes in XYY with neurobiology.Trial registrationsClinicalTrials.govNCT00001246, “89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls.” (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - October 22, 2018 Category: Neurology Source Type: research

Emotional prosodic change detection in autism Spectrum disorder: an electrophysiological investigation in children and adults
ConclusionsOverall, change detection remains altered in people with autism. However, differences between children and adults with ASD evidence a trend toward normalization of vocal processing and of the automatic detection of emotion deviancy with age. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - September 18, 2018 Category: Neurology Source Type: research

Neurophysiological correlates of holistic face processing in adolescents with and without autism spectrum disorder
ConclusionOverall, our results suggest that  adolescents with ASD were able to utilize holistic processing to perceive a face within the Mooney stimuli. Delays in early processing, marked by the P1, and elongated elevation in gamma activity indicate that the neural systems supporting holistic processing are slightly altered suggesting a les s automatic and less efficient facial processing system.Trial registrationNon-applicable. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - August 30, 2018 Category: Neurology Source Type: research

Face processing in 22q11.2 deletion syndrome: atypical development and visual scanning alterations
ConclusionsThe current study brings new evidence of altered face exploration in 22q11.2DS and identifies developmental mechanisms that may contribute to difficulties impacting social interactions in the syndrome. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - August 29, 2018 Category: Neurology Source Type: research

Improving  social gaze behavior in fragile X syndrome using a behavioral skills training approach: a proof of concept study
ConclusionsThese results suggest that appropriate social gaze behavior can be successfully taught to boys with FXS using a  standardized behavioral skills training approach. Future studies will need to evaluate whether younger children with FXS might benefit from this treatment, and/or whether more naturalistic forms of behavioral skills training might be beneficial, before social gaze avoidance becomes established i n the child’s repertoire.Trial registrationClinicalTrials.gov,NCT02616796. Registered 30 November 2015. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - August 28, 2018 Category: Neurology Source Type: research

Exploring autism symptoms in an Australian cohort of patients with Prader-Willi and Angelman syndromes
ConclusionsPWS cases presented with greater symptoms associated with ASD compared to individuals with AS. Mental health issues associated with PWS may contribute to elevated symptoms of ASD, particularly in adolescents and adults with PWS. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - August 6, 2018 Category: Neurology Source Type: research

Visual subcircuit-specific dysfunction and input-specific mispatterning in the superior colliculus of fragile X mice
ConclusionsFmr1 is required for the proper development of visual circuit organization and function in the SC. We find that visual dysfunction is heterogeneously manifested in a subcircuit-specific manner inFmr1−/y mice, consistent with previous studies in human FXS patients. Further, we show a specific alteration of inputs to the SC from V1, but not the retina. Together, these data suggest thatFmr1 may function in distinct ways during the development of different visual subcircuits. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 28, 2018 Category: Neurology Source Type: research

Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome
ConclusionsOur results show that FXS biomarkers and maternal variables contribute differentially to the cognitive and behavioral features of the adolescent female with FXS. These findings can help in the design of treatment studies aimed at enhancing cognitive and behavioral abilities in the FXS population. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 20, 2018 Category: Neurology Source Type: research

Social skills in children with RASopathies: a comparison of Noonan syndrome and neurofibromatosis type 1
AbstractBackgroundGene mutations within the RAS-MAPK signaling cascade result in Noonan syndrome (NS), neurofibromatosis type 1 (NF1), and related disorders. Recent research has documented an increased risk for social difficulties and features of autism spectrum disorder (ASD) among children with these conditions. Despite this emerging evidence, the neuropsychological characteristics associated with social skills deficits are not well understood, particularly for children with NS.MethodsParents of children with NS (n = 39), NF1 (n = 39), and unaffected siblings (n = 32) between the...
Source: Journal of Neurodevelopmental Disorders - June 18, 2018 Category: Neurology Source Type: research

A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees
ConclusionsInclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 11, 2018 Category: Neurology Source Type: research

Load matters: neural correlates of verbal working memory in children with autism spectrum disorder
ConclusionsIn a working memory task, where the load was manipulated without changing executive demands, TD youth showed increasing recruitment with increasing load of the classic fronto-parietal brain areas and decreasing involvement in default mode regions. In contrast, although they modulated the default mode network, youth with ASD did not show the modulation of increasing brain activation with increasing load, suggesting that they may be unable to manage increasing verbal information. Impaired verbal working memory in ASD would interfere with the youths ’ success academically and socially. Thus, determining the n...
Source: Journal of Neurodevelopmental Disorders - June 1, 2018 Category: Neurology Source Type: research

Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex
ConclusionsWe found that genes related to mitochondrial function were differentially expressed in autism cerebral cortex and correlated with genes related to synaptic transmission. Our principal findings replicate across all datasets investigated. Further, these findings may potentially replicate in other diseases, such as in schizophrenia. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 1, 2018 Category: Neurology Source Type: research

Load matters: neural correlates of verbal working memory in children with autism spectrum disorder
ConclusionsIn a working memory task, where the load was manipulated without changing executive demands, TD youth showed increasing recruitment with increasing load of the classic fronto-parietal brain areas and decreasing involvement in default mode regions. In contrast, although they modulated the default mode network, youth with ASD did not show the modulation of increasing brain activation with increasing load, suggesting that they may be unable to manage increasing verbal information. Impaired verbal working memory in ASD would interfere with the youths ’ success academically and socially. Thus, determining the n...
Source: Journal of Neurodevelopmental Disorders - June 1, 2018 Category: Neurology Source Type: research

Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex
ConclusionsWe found that genes related to mitochondrial function were differentially expressed in autism cerebral cortex and correlated with genes related to synaptic transmission. Our principal findings replicate across all datasets investigated. Further, these findings may potentially replicate in other diseases, such as in schizophrenia. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - June 1, 2018 Category: Neurology Source Type: research

Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation
ConclusionsIn this patient with dystonia-deafness syndrome caused byACTB p.Arg183Trp heterozygosity, unprecedented brain imaging findings strongly indicate striatal neuronal/dopaminergic dysfunction as the underlying cause of the dystonia. Pallidal stimulation provided a substantial improvement of the severe generalized dystonia, which is largely sustained at 4-year follow-up, and we advise this treatment to be considered in such patients. We hypothesize that the pleiotropic manifestations of the dystonia-deafness syndrome caused by this mutation derive from diverse developmental functions of beta-actin in neural crest mig...
Source: Journal of Neurodevelopmental Disorders - May 22, 2018 Category: Neurology Source Type: research