scholarly journals Angelman Syndrome: An Autism Spectrum Disorder

2018 ◽  
Vol 6 (2) ◽  
pp. 56-60
Author(s):  
Andrew J. Kennedy ◽  
Jeffrey O. Henderson
Keyword(s):  
Angelman Syndrome ◽  
Motor Development ◽  
Neurodevelopmental Disorders ◽  
Muscle Tension ◽  
Autism Spectrum ◽  
Speech Impairment ◽  
Social Lives ◽  
Genetic Abnormalities ◽  
Ube3a Gene ◽  
Genetic Mechanisms

Neurodevelopmental disorders limit the mental, physical, and social lives of affected individuals and their families. These disorders are often related to genetic abnormalities having a distinct chromosomal location. The abnormalities can cause incorrect proteins to be formed or biochemical pathways to be blocked, predominately affecting brain development, but also having pleiotropic effects. Research into defining and correcting these genetic abnormalities is important to help distinguish between unique neurodevelopmental disorders so that proper clinical interventions are available for affected individuals. In the following review, Angelman syndrome, which results from UBE3A gene function being lost at maternal chromosome  15q11.2-q13, will be discussed. Angelman patients suffer from the defining characteristics of speech impairment, uncontrolled laughing and smiling, motor development issues, muscle tension, and possible ataxia. The genetic mechanisms of the disorder as well as possible therapies will be discussed, with future areas of research into genetic therapies to treat Angelman syndrome also put forth. Research into Angelman syndrome can provide an avenue for a clearer understanding of other neurodevelopmental disorders.

Developmental milestones in early childhood and genetic liability to neurodevelopmental disorders

2020 ◽  
Author(s):  
Laurie John Hannigan ◽  
Ragna Bugge Askeland ◽  
Helga Ask ◽  
Martin Tesli ◽  
Elizabeth Corfield ◽  
...  
Keyword(s):  
Language Development ◽  
Motor Development ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Probit Regression ◽  
Developmental Milestones ◽  
Genetic Liability ◽  
Polygenic Scores ◽  
Walking Age ◽  
Children First

BackgroundEarly developmental milestones, such as the age at first walking or talking, are associated with later diagnoses of neurodevelopmental disorders, but the relationship to genetic risk for neurodevelopmental disorders are unknown. Here, we investigate associations between genetic liability to autism spectrum disorder (autism), attention deficit hyperactivity disorder (ADHD), and schizophrenia and attainment of early-life language and motor development milestones.MethodsWe use data from a genotyped sub-set (N = 15 205) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). In this sample, we calculate polygenic scores for autism; ADHD and schizophrenia and predict maternal reports of children’s age at first walking and talking, motor delays at 18 months, language delays at 3 years, and a generalized measure of concerns about development. We use linear and probit regression models in a multi-group framework to test for sex differences.ResultsADHD polygenic scores predicted earlier walking age in both males and females (β=-0.037, pFDR=0.001), and earlier first use of sentences (β=-0.087, pFDR=0.032) but delayed language development at 3 years in females only (β=0.194, pFDR=0.001). Additionally, we found evidence that autism polygenic scores were associated with later walking (β=0.027, pFDR=0.024) and motor delays at 18 months (β = 0.065, pFDR=0.028). Schizophrenia polygenic scores were associated with a measure of general concerns about development at 3 years in females only (β=0.132, pFDR=0.024).ConclusionsGenetic liabilities for neurodevelopmental disorders show some specific associations with measures of early motor and language development in the general population, including the age at which children first walk and talk. Associations are generally small and occasionally in unexpected directions. Sex differences are evident in some instances, but clear patterns across different polygenic scores and outcomes are hard to discern. These findings suggest that genetic susceptibility for neurodevelopmental disorders is manifested in the timing of developmental milestones in infancy.

Angelman Syndrome due to a Maternally Inherited Intragenic Deletion Encompassing Exons 7 and 8 of the UBE3A Gene

2017 ◽  
Vol 152 (3) ◽  
pp. 132-136
Author(s):  
Athina Ververi ◽  
Lily Islam ◽  
Beverley Bewes ◽  
Louise Busby ◽  
Caroline Sullivan ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Angelman Syndrome ◽  
Array Cgh ◽  
De Novo ◽  
Uniparental Disomy ◽  
Genetic Mechanism ◽  
Paternal Allele ◽  
Speech Impairment ◽  
Intragenic Deletion ◽  
Ube3a Gene

Angelman syndrome (AS) is characterised by developmental delay, lack of speech, seizures, a characteristic behavioural profile with a happy demeanour, microcephaly, and ataxia. More than two-thirds of cases are due to an approximately 5-Mb interstitial deletion of the imprinted region 15q11.2q13, which is usually de novo. The rest are associated with point mutations in the UBE3A gene, imprinting defects, and paternal uniparental disomy. Small intragenic UBE3A deletions have rarely been described. They are usually maternally inherited, increasing the recurrence risk to 50%, and may be missed by conventional testing (methylation studies and UBE3A gene sequencing). We describe a boy with AS due to an 11.7-kb intragenic deletion. The deletion was identified by array-CGH and was subsequently detected in his affected first cousin and unaffected maternal grandfather, mother, and aunt, confirming the silencing of the paternal allele. The patient had developmental delay, speech impairment, a happy demeanour, microcephaly, and an abnormal EEG, but no seizures by the age of 4 years. Delineation of the underlying genetic mechanism is of utmost importance for reasons of genetic counselling, as well as appropriate management and prognosis. Alternative techniques, such as array-CGH and MLPA, are necessary when conventional testing for AS has failed to identify the underlying genetic mechanism.

scholarly journals Anxiety in Angelman Syndrome

2022 ◽  
Vol 127 (1) ◽  
pp. 1-10
Author(s):  
Stacey C. Grebe ◽  
Danica L. Limon ◽  
Morgan M. McNeel ◽  
Andrew Guzick ◽  
Sarika U. Peters ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Chromosome 15 ◽  
Limited Information ◽  
Measurement Instruments ◽  
Natural History Study ◽  
Developmental Behavior ◽  
Ube3a Gene ◽  
Specific Symptoms

Abstract Angelman Syndrome (AS) is a neurodevelopmental disorder most commonly caused by the impaired expression of the maternal UBE3A gene on chromosome 15. Though anxiety has been identified as a frequently present characteristic in AS, there are limited studies examining anxiety in this population. Studies of anxiety in other neurodevelopmental disorders have found disorder specific symptoms of anxiety and age specific displays of anxiety symptoms. However, there is a consistent challenge in identifying anxiety in people with neurodevelopmental disorders given the lack of measurement instruments specifically designed for this population. Given the limited information about AS and anxiety, the aims of the current project were to (a) examine symptoms of anxiety in children with AS and (b) determine the correlates of anxiety in children with AS. Participants included 42 adult caregivers of youth with AS in the AS Natural History study who completed the Developmental Behavior Checklist (DBC). The results found that 26% of the sample demonstrated elevated symptoms of anxiety and established a relationship between elevated anxiety in youth with AS and higher levels of irritability, hyperactivity, self-absorbed behaviors, and disruptive/antisocial behaviors. Findings from this research provide a foundation for tailoring evidence-based assessments and treatments for youth with AS and anxiety.

scholarly journals A Neural Network Reveals Motoric Effects of Maternal Preconception Exposure to Nicotine on Rat Pup Behavior: A New Approach for Movement Disorders Diagnosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Reza Torabi ◽  
Serena Jenkins ◽  
Allonna Harker ◽  
Ian Q. Whishaw ◽  
Robbin Gibb ◽  
...  
Keyword(s):  
Neural Network ◽  
Motor Development ◽  
Neurodevelopmental Disorders ◽  
Motor Behavior ◽  
Autism Spectrum ◽  
Nicotine Exposure ◽  
Motor Impairments ◽  
Movement Initiation ◽  
Rat Pups ◽  
Rat Pup

Neurodevelopmental disorders can stem from pharmacological, genetic, or environmental causes and early diagnosis is often a key to successful treatment. To improve early detection of neurological motor impairments, we developed a deep neural network for data-driven analyses. The network was applied to study the effect of maternal nicotine exposure prior to conception on 10-day-old rat pup motor behavior in an open field task. Female Long-Evans rats were administered nicotine (15 mg/L) in sweetened drinking water (1% sucralose) for seven consecutive weeks immediately prior to mating. The neural network outperformed human expert designed animal locomotion measures in distinguishing rat pups born to nicotine exposed dams vs. control dams (87 vs. 64% classification accuracy). Notably, the network discovered novel movement alterations in posture, movement initiation and a stereotypy in “warm-up” behavior (repeated movements along specific body dimensions) that were predictive of nicotine exposure. The results suggest novel findings that maternal preconception nicotine exposure delays and alters offspring motor development. Similar behavioral symptoms are associated with drug-related causes of disorders such as autism spectrum disorder and attention-deficit/hyperactivity disorder in human children. Thus, the identification of motor impairments in at-risk offspring here shows how neuronal networks can guide the development of more accurate behavioral tests to earlier diagnose symptoms of neurodevelopmental disorders in infants and children.

FMS Effects of a Motor Program for Children With Autism Spectrum Disorders

2021 ◽  
pp. 003151252110100
Author(s):  
Liangshan Dong ◽  
Bo Shen ◽  
YanLi Pang ◽  
Mingting Zhang ◽  
Yuan Xiang ◽  
...  
Keyword(s):  
Motor Development ◽  
Group Versus ◽  
Motor Program ◽  
Autism Spectrum ◽  
Control Group ◽  
Gross Motor Development ◽  
Children With Asd ◽  
Individualized Approach ◽  
Experimental Group ◽  
Ball Skills

The current study evaluated the effectiveness of a motor program that specifically targeted fundamental motor skills (FMS) in children with ASD. The experimental group (n=21) participated in a 9-week program with motor instructions for 80 minutes/day, three days/week, while the control group (n=29) did not participate in the program. We measured FMS (using the Test of Gross Motor Development-3) one-week before, one-week after, and two-months after the program. Children in the experimental group had significantly larger FMS improvements than the controls on both locomotor and ball skills immediately following the program, and these participants showed continuous improvement on locomotor, but not ball skills, at 2-months follow-up. In individual analyses, 80% of children in the experimental group versus 29% of children in the control group showed continuous locomotor skills improvement beyond their pre-test levels. These findings highlight the importance of both a long-term motor development intervention and an individualized approach for evaluating improved FMS among children with ASD.

scholarly journals A Bibliometric Insight of Genetic Factors in ASD: Emerging Trends and New Developments

2020 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Kang Wang ◽  
Weicheng Duan ◽  
Yijie Duan ◽  
Yuxin Yu ◽  
Xiuyi Chen ◽  
...  
Keyword(s):  
Genetic Factors ◽  
De Novo ◽  
Rapid Development ◽  
The United States ◽  
Research Area ◽  
Scientific Output ◽  
Autism Spectrum ◽  
De Novo Mutations ◽  
Emerging Trends ◽  
Genetic Abnormalities

Autism spectrum disorder (ASD) cases have increased rapidly in recent decades, which is associated with various genetic abnormalities. To provide a better understanding of the genetic factors in ASD, we assessed the global scientific output of the related studies. A total of 2944 studies published between 1997 and 2018 were included by systematic retrieval from the Web of Science (WoS) database, whose scientific landscapes were drawn and the tendencies and research frontiers were explored through bibliometric methods. The United States has been acting as a leading explorer of the field worldwide in recent years. The rapid development of high-throughput technologies and bioinformatics transferred the research method from the traditional classic method to a big data-based pipeline. As a consequence, the focused research area and tendency were also changed, as the contribution of de novo mutations in ASD has been a research hotspot in the past several years and probably will remain one into the near future, which is consistent with the current opinions of the major etiology of ASD. Therefore, more attention and financial support should be paid to the deciphering of the de novo mutations in ASD. Meanwhile, the effective cooperation of multi-research centers and scientists in different fields should be advocated in the next step of scientific research undertaken.

scholarly journals LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

2021 ◽  
Vol 7 (11) ◽  
pp. eaba1187
Author(s):  
Rina Baba ◽  
Satoru Matsuda ◽  
Yuuichi Arakawa ◽  
Ryuji Yamada ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Specific Inhibitor ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Control Of Gene Expression ◽  
Epigenetic Machinery ◽  
The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

scholarly journals Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Natasha Bertelsen ◽  
◽  
Isotta Landi ◽  
Richard A. I. Bethlehem ◽  
Jakob Seidlitz ◽  
...  
Keyword(s):  
Repetitive Behavior ◽  
Resting State Fmri ◽  
Neural Circuitry ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Typically Developing ◽  
Out Of Sample ◽  
Genetic Mechanisms ◽  
Social Communicative ◽  
The Eu

AbstractSocial-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97–99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.

scholarly journals Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Mark Wade ◽  
Heather Prime ◽  
Sheri Madigan
Keyword(s):  
Neurodevelopmental Disorders ◽  
Broad Class ◽  
Psychosocial Health ◽  
Recurrence Risk ◽  
Autism Spectrum ◽  
Functional Neuroanatomy ◽  
Early Screening ◽  
Environmental Liabilities ◽  
Hyperactivity Disorder ◽  
Significant Bearing

Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders—autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD)—to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment.

Sign in / Sign up

Export Citation Format

Share Document