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Journal of the American Academy of... May 2023To summarize the current state of the literature regarding emotion dysregulation (ED) in syndromic intellectual disabilities (S-IDs) in 6 of the most common forms of... (Review)
Review
OBJECTIVE
To summarize the current state of the literature regarding emotion dysregulation (ED) in syndromic intellectual disabilities (S-IDs) in 6 of the most common forms of S-IDs-Down syndrome, fragile X syndrome (FXS), tuberous sclerosis complex, Williams syndrome, Prader-Willi syndrome, and Angelman syndrome-and to determine future research directions for identification and treatment of ED.
METHOD
PubMed bibliographic database was searched from date of inception to May 2021. PRISMA 2020 guidelines were followed with the flowchart, table of included studies, list of excluded studies, and checklist provided. Filters applied included human research and English. Only original research articles were included in the final set, but review articles were used to identify secondary citations of primary studies. All articles were reviewed for appropriateness by 2 authors and summarized. Inclusion criteria were met by 145 articles (Down syndrome = 29, FXS = 55, tuberous sclerosis complex = 11, Williams syndrome = 18, Prader-Willi syndrome = 24, Angelman syndrome = 8).
RESULTS
Each syndrome review was summarized separately and further subdivided into articles related to underlying neurobiology, behaviors associated with ED, assessment, and targeted intervention. FXS had the most thorough research base, followed by Down syndrome and Prader-Willi syndrome, with the other syndromes having more limited available research. Very limited research was available regarding intervention for all disorders except FXS.
CONCLUSION
Core underlying characteristics of S-IDs appear to place youth at higher risk for ED, but further research is needed to better assess and treat ED in S-IDs. Future studies should have a standard assessment measure of ED, such as the Emotion Dysregulation Inventory, and explore adapting established curricula for ED from the neurotypical and autism spectrum disorder fields.
Topics: Child; Adolescent; Humans; Prader-Willi Syndrome; Angelman Syndrome; Down Syndrome; Autism Spectrum Disorder; Developmental Disabilities; Tuberous Sclerosis; Intellectual Disability; Fragile X Syndrome; Williams Syndrome; Emotions
PubMed: 36007813
DOI: 10.1016/j.jaac.2022.06.020 -
Journal of Neurosurgery. Pediatrics Jun 2022Drug-resistant epilepsy (DRE) affects many children. Vagus nerve stimulation (VNS) may improve seizure control; however, its role in children with genetic etiologies of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Drug-resistant epilepsy (DRE) affects many children. Vagus nerve stimulation (VNS) may improve seizure control; however, its role in children with genetic etiologies of epilepsy is not well described. The authors systematically reviewed the literature to examine the effectiveness of VNS in this cohort.
METHODS
In January 2021, the authors performed a systematic review of the PubMed/MEDLINE, SCOPUS/Embase, Cochrane, and Web of Science databases to investigate the impact of VNS on seizure outcomes in children with genetic etiologies of epilepsy. Primary outcomes included seizure freedom rate, ≥ 90% seizure reduction rate, and ≥ 50% seizure reduction rate. Secondary outcomes were seizure severity and quality of life (QOL), including cognitive, functional, and behavioral outcomes. A random-effects meta-analysis was performed.
RESULTS
The authors identified 125 articles, of which 47 with 216 nonduplicate patients were analyzed. Common diagnoses were Dravet syndrome (DS) (92/216 patients [42.6%]) and tuberous sclerosis complex (TSC) (63/216 [29.2%]). Seizure freedom was not reported in any patient with DS; the pooled proportion (95% CI) of patients with ≥ 50% seizure reduction was 41% (21%-58%). Secondary cognitive outcomes of VNS were variable in DS patients, but these patients demonstrated benefits in seizure duration and status epilepticus. In TSC patients, the pooled (95% CI) seizure freedom rate was 40% (12%-71%), ≥ 90% seizure reduction rate was 31% (8%-56%), and ≥ 50% reduction rate was 68% (48%-91%). Regarding the secondary outcomes of VNS in TSC patients, several studies reported decreased seizure severity and improved QOL outcomes. There was limited evidence regarding the use of VNS to treat patients with other genetic etiologies of epilepsy, such as mitochondrial disease, Rett syndrome, Doose syndrome, Landau-Kleffner syndrome, Aicardi syndrome, Angelman syndrome, ring chromosome 20 syndrome, and lissencephaly; variable responses were reported in a limited number of cases.
CONCLUSIONS
The authors conducted a systematic review of VNS outcomes in children with genetic etiologies of DRE. Among the most studied conditions, patients with TSC had substantial seizure reduction and improvements in QOL, whereas those with DS had less robust seizure reduction. Increased testing, diagnosis, and long-term follow-up studies are necessary to better characterize VNS response in these children.
Topics: Child; Humans; Quality of Life; Vagus Nerve Stimulation; Drug Resistant Epilepsy; Epilepsy; Seizures; Treatment Outcome; Vagus Nerve; Retrospective Studies
PubMed: 35303699
DOI: 10.3171/2022.1.PEDS222 -
Neurology International Jul 2021Angelman syndrome is a rare genetic disease affecting the central nervous system and neurobehavioral development causing severe mental, linguistic, and physical... (Review)
Review
Angelman syndrome is a rare genetic disease affecting the central nervous system and neurobehavioral development causing severe mental, linguistic, and physical disabilities. The purpose of this review was to analyze the most recent evidence regarding the rehabilitation of subjects affected by this syndrome. The review was carried out in accordance with the preferred reporting items for systematic reviews and meta-analyses. A total of 3661 studies were identified in the databases. Once the inclusion/exclusion criteria were applied, 15 studies were considered for the paper's preparation. The level of evidence of the studies was established according to the criteria of the Oxford Center for Evidence-Based Medicine-Levels of Evidence. From the selected studies, five rehabilitative approaches emerged: physiotherapy, applied behavioral analysis, toilet training, microswitch-cluster technology, and augmentative and alternative communication. Although the studies did not have a high level of evidence, the reported results appear to be encouraging and pave the way for further studies. It seems that individualized and multidisciplinary rehabilitation interventions help to improve patients' autonomy and quality of life. In some studies, the caregivers' role was fundamental to identify preferences and long-term improvements. Further studies on larger populations and with better methodological quality are needed to confirm the results.
PubMed: 34449677
DOI: 10.3390/neurolint13030036 -
Genes Jan 2023Status Epilepticus (SE) is a neurological emergency resulting from the failure of mechanisms of seizure termination or from the initiation of mechanisms that lead to... (Review)
Review
Status Epilepticus (SE) is a neurological emergency resulting from the failure of mechanisms of seizure termination or from the initiation of mechanisms that lead to prolonged seizures. The International League Against Epilepsy (ILAE) identified 13 chromosomal disorders associated with epilepsy (CDAE); data regarding SE occurrence in these patients is lacking. A systematic scoping review was conducted to outline current literature evidence about clinical features, treatments, and outcomes of SE in pediatric and adult patients with CDAE. A total of 373 studies were identified with the initial search; 65 of these were selected and regarded as SE in Angelman Syndrome (AS, = 20), Ring 20 Syndrome (R20, = 24), and other syndromes ( = 21). Non-convulsive status epilepticus (NCSE) is frequently observed in AS and R20. No specific, targeted therapies for SE in CDAE are available to date; anecdotal reports about SE treatment are described in the text, as well as various brief- and long-term outcomes. Further evidence is needed to precisely portray the clinical features, treatment options, and outcomes of SE in these patients.
Topics: Adult; Humans; Child; Status Epilepticus; Epilepsy; Seizures; Chromosome Disorders; Ring Chromosomes
PubMed: 36833226
DOI: 10.3390/genes14020299 -
Journal of Autism and Developmental... Jan 2019Movement disorders are reported in idiopathic autism but the extent to which comparable movement disorders are found in syndromic/co-morbid autism is unknown. A...
Movement disorders are reported in idiopathic autism but the extent to which comparable movement disorders are found in syndromic/co-morbid autism is unknown. A systematic search of Medline, Embase, PsychINFO and CINAHL on the prevalence of specific movement disorder in syndromic autism associated with specific genetic syndromes identified 16 papers, all relating to Angelman syndrome or Rett syndrome. Prevalence rates of 72.7-100% and 25.0-27.3% were reported for ataxia and tremor, respectively, in Angelman syndrome. In Rett syndrome, prevalence rates of 43.6-50% were reported for ataxia and 27.3-48.3% for tremor with additional reports of dystonia, rigidity and pyramidal signs. However, reliable assessment measures were rarely used and recruitment was often not described in sufficient detail.
Topics: Angelman Syndrome; Autistic Disorder; Comorbidity; Humans; Movement Disorders; Prevalence; Rett Syndrome
PubMed: 30014250
DOI: 10.1007/s10803-018-3658-y -
Research in Developmental Disabilities Feb 2020The aim of the review was to synthesise the literature on the types and effectiveness of interventions to improve sleep for individuals with Angelman Syndrome (AS).
OBJECTIVE
The aim of the review was to synthesise the literature on the types and effectiveness of interventions to improve sleep for individuals with Angelman Syndrome (AS).
METHOD
Four databases were searched using predetermined search terms. Data extraction was performed on studies to examine (a) participant characteristics (b) study design (c) intervention procedures (d) intervention duration (e) dependent (outcome)variables. Intervention outcomes were categorised as positive, negative or and certainty of evidence as a measure of quality was reported for each study.
RESULTS
Ten studies, including 54 participants with AS, met the inclusion criteria. Included studies comprised of both single subject designs (n = 3) and group-based designs (n = 7). Pharmacological interventions (n = 8) were the most commonly used followed by combined pharmacological and behavioral treatment (n = 1) or behavioral interventions as a single intervention (n = 1). Pharmacological interventions demonstrated both positive (n = 2) and mixed outcomes (n = 6) and were categorised at a suggestive level of evidence. Behavioral interventions as a sole intervention (n = 1) and as a combined intervention (with pharmacological intervention; n = 1) were found to have positive outcomes and was also categorised at a suggestive level of evidence.
CONCLUSION
This review found provisional evidence but weak evidence for the effectiveness of behavioral interventions, and mixed outcomes for the effectiveness of Melatonin for the treatment of sleep problems in AS. All 10 studies only achieved a suggestive level of certainty, therefore, further high-quality research is needed to evaluate interventions for the treatment of sleep problems in this population.
Topics: Angelman Syndrome; Behavior Therapy; Central Nervous System Depressants; Humans; Melatonin; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 31869773
DOI: 10.1016/j.ridd.2019.103554 -
The Lancet. Psychiatry Oct 2015Autism spectrum disorder (ASD) phenomenology is reported to be more common in individuals with some genetic syndromes than in the general population; however, no... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autism spectrum disorder (ASD) phenomenology is reported to be more common in individuals with some genetic syndromes than in the general population; however, no meta-analysis has provided prevalence data within and between syndromes. In this systematic review and meta-analysis, we aimed to synthesise data from a wide range of papers to provide accurate estimates about ASD phenomenology in genetic and metabolic syndromes.
METHODS
We identified syndromes reported as most likely to be associated with ASD. We searched Ovid PsycINFO, Ovid MEDLINE, Ovid Embase, and PubMed Central for English-language papers published from database creation up to early 2014 with use of syndrome-specific keywords and a set of ASD keywords. We screened and extracted papers that had ASD prevalence data for ten or more people within a genetic syndrome. With use of a prespecified set of reliable criteria, we applied quality weighting to papers and estimated a quality-effects prevalence of ASD phenomenology for each syndrome. We then calculated relative risks to compare ASD between all syndromes and also calculated odds ratios to compare prevalence with the general population taking the current estimate of one in 68 people.
RESULTS
We identified 168 papers reporting the prevalence of ASD phenomenology and found widely varying methods and quality of data. Quality-weighted effect prevalence estimates of ASD phenomenology were established for Rett's syndrome (female individuals only 61%), Cohen's syndrome (54%), Cornelia de Lange syndrome (43%), tuberous sclerosis complex (36%), Angelman's syndrome (34%), CHARGE syndrome (30%), fragile X syndrome (male individuals only 30%; mixed sex 22%), neurofibromatosis type 1 (18%), Down's syndrome (16%), Noonan's syndrome (15%), Williams' syndrome (12%), and 22q11.2 deletion syndrome (11%). Relative risks and the odds ratio compared with the general population were highest for Rett's syndrome and Cohen's syndrome. In all syndromes, odds ratios showed ASD phenomenology to be significantly more likely than in the general population.
INTERPRETATION
ASD phenomenology varied between syndromes, but was consistently more likely than in the general population. Further research is needed in these populations, including how ASD in genetic and metabolic syndromes differs from idiopathic autism and what that can tell us about the mechanisms underlying ASD.
FUNDING
Cerebra.
Topics: Autism Spectrum Disorder; Female; Genetic Diseases, Inborn; Humans; Male; Prevalence; Risk
PubMed: 26341300
DOI: 10.1016/S2215-0366(15)00376-4 -
Journal of Assisted Reproduction and... Jun 2018To determine whether a history of conception by assisted reproductive technology (ART) is associated with occurrence of one or more imprinting disorders of either... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To determine whether a history of conception by assisted reproductive technology (ART) is associated with occurrence of one or more imprinting disorders of either maternal or paternal origin.
METHODS
We implemented a systematic review of scholarly literature followed by comprehensive meta-analysis to quantitatively synthesize data from reports relating to use of ART to occurrence of any imprinting disorder of humans, including Beckwith-Wiedemann (BWS), Angelman (AS), Prader-Willi (PWS), and Silver-Russell (SRS) syndromes, as well as transient neonatal diabetes mellitus (TNDB) and sporadic retinoblasoma (RB).
RESULTS
The systematic review identified 13 reports presenting unique data from 23 studies that related conception following ART to occurrence of imprinting disorders. Multiple studies of four disorder were identified, for which meta-analysis yielded the following summary estimates of associations with a history of ART: AS, summary odds ratio (sOR) = 4.7 (95% confidence interval (CI) 2.6-8.5, 4 studies); BWS, sOR = 5.8 (95% CI 3.1-11.1, 8 studies); PWS, sOR = 2.2 (95% CI 1.6-3.0, 6 studies); SRS, sOR = 11.3 (95% CI 4.5-28.5, 3 studies). Only one study reported on each of TNDB and RB.
CONCLUSION
Published data reveal positive associations between history of ART conception and each of four imprinting disorders. Reasons for these associations warrant further investigation.
Topics: Chromosome Disorders; Female; Fertilization; Genomic Imprinting; Humans; Reproductive Techniques, Assisted; Risk Factors
PubMed: 29696471
DOI: 10.1007/s10815-018-1173-x -
Sleep Medicine Reviews Jun 2021Individuals with Rare Genetic Neurodevelopmental Disorders (RGND) present with significant sleep problems and circadian rhythm abnormalities of uncertain aetiology.... (Review)
Review
Individuals with Rare Genetic Neurodevelopmental Disorders (RGND) present with significant sleep problems and circadian rhythm abnormalities of uncertain aetiology. Abnormal melatonin secretion may play a role in sleep disturbance in individuals with higher incidence developmental disabilities, however, RGND research is limited. This review compared the melatonin profiles in a range of RGND with that of the general population and considered the impact of any differences on sleep. A systematic search identified 19 studies that met inclusion criteria. Each study was examined to extract data relating to the study design, participant characteristics, objectives, sleep measures and results, and melatonin measures and findings. Studies were evaluated using the BIOCROSS quality appraisal tool. Nine studies focussed on Smith-Magenis syndrome (SMS), the rest included individuals with Angelman (AS), Fragile-X (FXS), Prader-Willi (PWS), septo-optic dysplasia, PAX6/WAGR and Williams (WS) syndromes (N = 349). Individuals with RGND present with a range of sleep problems, particularly dyssomnias. The melatonin profile varied within and between RGND, with low nocturnal melatonin levels commonly reported. Understanding the relationship between specific sleep and melatonin parameters within RGND may help inform sleep intervention.
Topics: Humans; Melatonin; Neurodevelopmental Disorders; Sleep; Sleep Wake Disorders; Smith-Magenis Syndrome
PubMed: 33561678
DOI: 10.1016/j.smrv.2021.101433 -
Frontiers in Neuroscience 2018optical imaging is a powerful tool for revealing brain structure and function at both the circuit and cellular levels. Here, we provide a systematic review of findings... (Review)
Review
optical imaging is a powerful tool for revealing brain structure and function at both the circuit and cellular levels. Here, we provide a systematic review of findings obtained from imaging studies of mouse models of neurodevelopmental disorders, including the monogenic disorders fragile X syndrome, Rett syndrome, and Angelman syndrome, which are caused by genetic abnormalities of , and , as well as disorders caused by copy number variations (15q11-13 duplication and 22q11.2 deletion) and BTBR mice as an inbred strain model of autism spectrum disorder (ASD). Most studies visualize the structural and functional responsiveness of cerebral cortical neurons to sensory stimuli and the developmental and experience-dependent changes in these responses as a model of brain functions affected by these disorders. The optical imaging techniques include two-photon microscopy of fluorescently labeled dendritic spines or neurons loaded with fluorescent calcium indicators and macroscopic imaging of cortical activity using calcium indicators, voltage-sensitive dyes or intrinsic optical signals. Studies have revealed alterations in the density, stability, and turnover of dendritic spines, aberrant cortical sensory responses, impaired inhibitory function, and concomitant failure of circuit maturation as common causes for neurological deficits. Mechanistic hypotheses derived from imaging also provide new directions for therapeutic interventions. For instance, it was recently demonstrated that early postnatal administration of a selective serotonin reuptake inhibitor (SSRI) restores impaired cortical inhibitory function and ameliorates the aberrant social behaviors in a mouse model of ASD. We discuss the potential use of SSRIs for treating ASDs in light of these findings.
PubMed: 29970983
DOI: 10.3389/fnins.2018.00412