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Gaceta Medica de Mexico 2020Fragile X syndrome is the monogenetic condition that produces more cases of autism and intellectual disability. The repetition of CGG triplets (> 200) and their... (Review)
Review
Fragile X syndrome is the monogenetic condition that produces more cases of autism and intellectual disability. The repetition of CGG triplets (> 200) and their methylation entail the silencing of the FMR1 gene. The FMRP protein (product of the FMR1 gene) interacts with ribosomes by controlling the translation of specific messengers, and its loss causes alterations in synaptic connectivity. Screening for fragile X syndrome is performed by polymerase chain reaction. Current recommendation of the American Academy of Pediatrics is to test individuals with intellectual disability, global developmental retardation or with a family history of presence of the mutation or premutation. Hispanic countries such as Colombia, Chile and Spain report high prevalence of fragile X syndrome and have created fragile X national associations or corporations that seek to bring patients closer to available diagnostic and treatment networks.
Topics: Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Checklist; Child, Preschool; Female; Fragile X Mental Retardation Protein; Fragile X Syndrome; Gene Silencing; Genetic Testing; Humans; Intellectual Disability; Male; Mutation; Pedigree; Phenotype; Ribosomes; Sex Factors; Synaptic Transmission
PubMed: 32026885
DOI: 10.24875/GMM.19005275 -
The International Journal of Behavioral... Jul 2022Children and adolescents with intellectual disabilities (IDs) tend to have lower levels of physical activity and poorer mental health than their typically developing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Children and adolescents with intellectual disabilities (IDs) tend to have lower levels of physical activity and poorer mental health than their typically developing peers. Studies on the effects of physical activity on the mental health of children with IDs using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework are scarce.
METHODS
A systematic literature review using six databases (CINAHL, Eric, PsycINFO, PubMed, SPORTDiscus, and Web of Science) was conducted from January 2000 to September 2021. Studies reporting at least one physical activity intervention and mental health outcome in children and adolescents with IDs aged between 5 and 17 years were included in the meta-analysis. Preferred Reporting Items for Systematic Review and Meta-Analysis guideline, Comprehensive Meta-Analysis, and the RE-AIM framework were utilized.
RESULTS
A total of 15 studies that met the inclusion criteria were included in the meta-analysis. The effects of physical activity on mental health in children and adolescents with IDs were significant and large (Hedges' g = 0.897, p < 0.01), with medium effects on psychological health (Hedges' g = 0.542, p < 0.01) and large effects on cognitive function (Hedges' g = 1.236, p < 0.01). Randomized controlled trial (RCT) design and intervention components (> 120 minutes per week, therapeutic, and aerobic exercise) demonstrated the strongest effects. Moreover, study background (publication year, study location, and sample size), participant characteristics (age and sex), and Maintenance (RE-AIM framework) moderated the effects of physical activity on mental health. Based on the RE-AIM framework, there were higher proportions in the dimensions of Reach and Effectiveness than Adoption, Implementation, and Maintenance.
CONCLUSIONS
Physical activity appears to have positive effects on mental health, including psychological health and cognitive function, in children and adolescents with IDs. Physical activity interventions using the RE-AIM framework are recommended to assess short- and long-term impacts and translate scientific evidence into practice.
TRIAL REGISTRATION
The protocol for this meta-analysis was registered with PROSPERO ( CRD42021256543 ).
Topics: Adolescent; Child; Child, Preschool; Exercise; Humans; Intellectual Disability; Mental Health
PubMed: 35799257
DOI: 10.1186/s12966-022-01312-1 -
Journal of Mother and Child Mar 2022Joubert syndrome (JS; MIM PS213300) is a rare genetic autosomal recessive disease characterized by cerebellar vermis hypoplasia, a distinctive malformation of the... (Review)
Review
Joubert syndrome (JS; MIM PS213300) is a rare genetic autosomal recessive disease characterized by cerebellar vermis hypoplasia, a distinctive malformation of the cerebellum and the so-called "molar tooth sign." Other characteristic features are hypotonia with lateral ataxia, intellectual disability/mental retardation, oculomotor apraxia, retinal dystrophy, abnormalities in the respiratory system, renal cysts, hepatic fibrosis, and skeletal changes. Such pleiotropic characteristics are typical of many disorders involving primary cilium aberrations, providing a significant overlap between JS and other ciliopathies such as nephronophthisis, Meckel syndrome, and Bardet-Biedl syndrome. This review will describe some characteristics of JS associated with changes in 35 genes, and will also address subtypes of JS, clinical diagnosis, and the future of therapeutic developments.
Topics: Humans; Cerebellum; Abnormalities, Multiple; Eye Abnormalities; Retina; Polycystic Kidney Diseases; Intellectual Disability
PubMed: 36803942
DOI: 10.34763/jmotherandchild.20222601.d-22-00034 -
Orphanet Journal of Rare Diseases May 2021Calcium ions are involved in several human cellular processes including corticogenesis, transcription, and synaptogenesis. Nevertheless, the relationship between calcium... (Review)
Review
BACKGROUND
Calcium ions are involved in several human cellular processes including corticogenesis, transcription, and synaptogenesis. Nevertheless, the relationship between calcium channelopathies (CCs) and intellectual disability (ID)/global developmental delay (GDD) has been poorly investigated. We hypothesised that CCs play a major role in the development of ID/GDD and that both gain- and loss-of-function variants of calcium channel genes can induce ID/GDD. As a result, we performed a systematic review to investigate the contribution of CCs, potential mechanisms underlying their involvement in ID/GDD, advancements in cell and animal models, treatments, brain anomalies in patients with CCs, and the existing gaps in the knowledge. We performed a systematic search in PubMed, Embase, ClinVar, OMIM, ClinGen, Gene Reviews, DECIPHER and LOVD databases to search for articles/records published before March 2021. The following search strategies were employed: ID and calcium channel, mental retardation and calcium channel, GDD and calcium channel, developmental delay and calcium channel.
MAIN BODY
A total of 59 reports describing 159 cases were found in PubMed, Embase, ClinVar, and LOVD databases. Variations in ten calcium channel genes including CACNA1A, CACNA1C, CACNA1I, CACNA1H, CACNA1D, CACNA2D1, CACNA2D2, CACNA1E, CACNA1F, and CACNA1G were found to be associated with ID/GDD. Most variants exhibited gain-of-function effect. Severe to profound ID/GDD was observed more for the cases with gain-of-function variants as compared to those with loss-of-function. CACNA1E, CACNA1G, CACNA1F, CACNA2D2 and CACNA1A associated with more severe phenotype. Furthermore, 157 copy number variations (CNVs) spanning calcium genes were identified in DECIPHER database. The leading genes included CACNA1C, CACNA1A, and CACNA1E. Overall, the underlying mechanisms included gain- and/ or loss-of-function, alteration in kinetics (activation, inactivation) and dominant-negative effects of truncated forms of alpha1 subunits. Forty of the identified cases featured cerebellar atrophy. We identified only a few cell and animal studies that focused on the mechanisms of ID/GDD in relation to CCs. There is a scarcity of studies on treatment options for ID/GDD both in vivo and in vitro.
CONCLUSION
Our results suggest that CCs play a major role in ID/GDD. While both gain- and loss-of-function variants are associated with ID/GDD, the mechanisms underlying their involvement need further scrutiny.
Topics: Calcium; Calcium Channels, L-Type; Channelopathies; Child; DNA Copy Number Variations; Developmental Disabilities; Humans; Intellectual Disability
PubMed: 33985586
DOI: 10.1186/s13023-021-01850-0 -
BMC Genomics Dec 2021Intellectual disability (ID) can be caused by non-genetic and genetic factors, the latter being responsible for more than 1700 ID-related disorders. The broad ID... (Review)
Review
Intellectual disability (ID) can be caused by non-genetic and genetic factors, the latter being responsible for more than 1700 ID-related disorders. The broad ID phenotypic and genetic heterogeneity, as well as the difficulty in the establishment of the inheritance pattern, often result in a delay in the diagnosis. It has become apparent that massive parallel sequencing can overcome these difficulties. In this review we address: (i) ID genetic aetiology, (ii) clinical/medical settings testing, (iii) massive parallel sequencing, (iv) variant filtering and prioritization, (v) variant classification guidelines and functional studies, and (vi) ID diagnostic yield. Furthermore, the need for a constant update of the methodologies and functional tests, is essential. Thus, international collaborations, to gather expertise, data and resources through multidisciplinary contributions, are fundamental to keep track of the fast progress in ID gene discovery.
Topics: Genomics; Humans; Intellectual Disability
PubMed: 34930158
DOI: 10.1186/s12864-021-08227-4 -
Developmental Medicine and Child... Mar 2020Children with cerebral palsy (CP) have an increased risk of cognitive impairments. This narrative review of the literature discusses assessment of cognition in children... (Review)
Review
Children with cerebral palsy (CP) have an increased risk of cognitive impairments. This narrative review of the literature discusses assessment of cognition in children with CP, presents the most salient characteristics of cognitive functioning pertaining to each subtype, and discusses the relationships between brain injury, functioning, and intervention from a developmental perspective. A search for original studies of cognitive functioning in children with different subtypes of CP was performed. The search resulted in 81 unique hits. There were few studies with a representative sample of children with CP where all participants were individually assessed. Cognitive functioning in children with the most severe motor impairments were often assumed and not assessed. Furthermore, there was a confounding of IQ below 70 and intellectual disability, possibly leading to an overestimation of the prevalence of intellectual disability. Longitudinal neuropsychological studies, including also very young children and those with the most severe speech and motor impairments, as well as intervention studies, are called for. WHAT THIS PAPER ADDS: Few studies have assessed cognition in a representative sample of children with cerebral palsy. Cognition in children with severe motor impairment is often assumed, not assessed. Lack of assessment may lead to overestimating the prevalence of intellectual disability. Lowered cognitive functioning in older children highlights the need for longitudinal studies.
Topics: Cerebral Palsy; Child; Cognition; Cognitive Dysfunction; Humans; Intellectual Disability; Neuropsychological Tests
PubMed: 32010976
DOI: 10.1111/dmcn.14463 -
Colombia Medica (Cali, Colombia) 2023Fragile X syndrome is caused by the expansion of CGG triplets in the gene, which generates epigenetic changes that silence its expression. The absence of the protein... (Review)
Review
Fragile X syndrome is caused by the expansion of CGG triplets in the gene, which generates epigenetic changes that silence its expression. The absence of the protein coded by this gene, FMRP, causes cellular dysfunction, leading to impaired brain development and functional abnormalities. The physical and neurologic manifestations of the disease appear early in life and may suggest the diagnosis. However, it must be confirmed by molecular tests. It affects multiple areas of daily living and greatly burdens the affected individuals and their families. Fragile X syndrome is the most common monogenic cause of intellectual disability and autism spectrum disorder; the diagnosis should be suspected in every patient with neurodevelopmental delay. Early interventions could improve the functional prognosis of patients with Fragile X syndrome, significantly impacting their quality of life and daily functioning. Therefore, healthcare for children with Fragile X syndrome should include a multidisciplinary approach.
Topics: Humans; Child; Fragile X Syndrome; Autism Spectrum Disorder; Quality of Life; Intellectual Disability; Fragile X Mental Retardation Protein
PubMed: 37664646
DOI: 10.25100/cm.v54i2.5089 -
Revista de Neurologia Jul 2021Intellectual disability is a neurodevelopmental condition characterised by cognitive deficits and functional impairments in adaptive behaviour that occur during... (Review)
Review
Intellectual disability is a neurodevelopmental condition characterised by cognitive deficits and functional impairments in adaptive behaviour that occur during development. It should be noted that this generates a variety of symptomatology, which is why it is considered by neuropsychology as an axis of analysis. In this regard, emphasis will be placed on why neuropsychological screening is necessary in this condition. Such relevance lies, on the one hand, in determining whether the child's disability is due to alterations in the nervous system or to unfavourable conditions of the environment in which he/she develops. On the other hand, neuropsychological examination provides information on which areas of the brain are responsible for one or the other disability. It also makes it possible to identify the individual particularities of the child's development, that is, his/her performance profile (strengths and weaknesses), but not necessarily to establish the diagnosis of intellectual disability and, from there, decide on intervention programmes adapted to the characteristics and needs of each case.
Topics: Child; Child, Preschool; Cultural Characteristics; Developmental Disabilities; Humans; Infant; Intellectual Disability; Neurologic Examination; Neuropsychological Tests
PubMed: 34254662
DOI: 10.33588/rn.7302.2021025 -
Nature Reviews. Neuroscience May 2021Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and the leading monogenic cause of autism. The condition stems from loss of fragile... (Review)
Review
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and the leading monogenic cause of autism. The condition stems from loss of fragile X mental retardation protein (FMRP), which regulates a wide range of ion channels via translational control, protein-protein interactions and second messenger pathways. Rapidly increasing evidence demonstrates that loss of FMRP leads to numerous ion channel dysfunctions (that is, channelopathies), which in turn contribute significantly to FXS pathophysiology. Consistent with this, pharmacological or genetic interventions that target dysregulated ion channels effectively restore neuronal excitability, synaptic function and behavioural phenotypes in FXS animal models. Recent studies further support a role for direct and rapid FMRP-channel interactions in regulating ion channel function. This Review lays out the current state of knowledge in the field regarding channelopathies and the pathogenesis of FXS, including promising therapeutic implications.
Topics: Animals; Channelopathies; Fragile X Mental Retardation Protein; Fragile X Syndrome; Humans
PubMed: 33828309
DOI: 10.1038/s41583-021-00445-9 -
Disease Models & Mechanisms Feb 2023The fragile X-related disorders are an important group of hereditary disorders that are caused by expanded CGG repeats in the 5' untranslated region of the FMR1 gene or... (Review)
Review
The fragile X-related disorders are an important group of hereditary disorders that are caused by expanded CGG repeats in the 5' untranslated region of the FMR1 gene or by mutations in the coding sequence of this gene. Two categories of pathological CGG repeats are associated with these disorders, full mutation alleles and shorter premutation alleles. Individuals with full mutation alleles develop fragile X syndrome, which causes autism and intellectual disability, whereas those with premutation alleles, which have shorter CGG expansions, can develop fragile X-associated tremor/ataxia syndrome, a progressive neurodegenerative disease. Thus, fragile X-related disorders can manifest as neurodegenerative or neurodevelopmental disorders, depending on the size of the repeat expansion. Here, we review mouse models of fragile X-related disorders and discuss how they have informed our understanding of neurodegenerative and neurodevelopmental disorders. We also assess the translational value of these models for developing rational targeted therapies for intellectual disability and autism disorders.
Topics: Animals; Mice; Trinucleotide Repeat Expansion; Intellectual Disability; Neurodegenerative Diseases; Fragile X Mental Retardation Protein; Fragile X Syndrome; Mutation; Disease Models, Animal
PubMed: 36692473
DOI: 10.1242/dmm.049485