Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cognitive disorders affect thinking and perceptual processes and the acquisition of knowledge and new information. They have an enormous societal impact because special educational resources are required, and independent living often cannot be achieved. Learning problems may lead to behavioral disorders in the home and community. The pathogenesis of most mild and moderate cognitive disorders is poorly understood. Severe cognitive impairment is usually accompanied by somatic abnormalities, and an etiology can be identified in many cases. Specific treatments are available for disorders such as cogenital hypothyroidism, some metabolic acidurias, and congenital toxoplasmosis. Other disorders affecting cognition such as fetal alcohol syndrome, maternal cocaine and heroin exposure, HIV encephalopathy, and prematurity require aggressive prevention and education to reduce their occurrence. The recent advances in molecular genetics offer a faster and better method of diagnosing fragile X syndrome, now recognized as the most common inheritable cause of mental retardation. In the future, DNA analysis may elucidate the basis of many other cognitive disorders.
 ...
PMID:Cognitive disorders in children. 812 19

Cognitive disorders in children have traditionally been described in terms of clinical phenotypes or syndromes, chromosomal lesions, metabolic disorders, or neuropathology. Relatively little is known about how these disorders affect the chemical reactions involved in learning and memory. Experiments in fruit flies, snails, and mice have revealed some highly conserved pathways that are involved in learning, memory, and synaptic plasticity, which is the primary substrate for memory storage. These can be divided into short-term memory storage through local changes in synapses, and long-term storage mediated by activation of transcription to translate new proteins that modify synaptic function. This review summarizes evidence that disruptions in these pathways are involved in human cognitive disorders, including neurofibromatosis type I, Coffin-Lowry syndrome, Rubinstein-Taybi syndrome, Rett syndrome, tuberous sclerosis-2, Down syndrome, X-linked alpha-thalassemia/mental retardation, cretinism, Huntington disease, and lead poisoning.
 ...
PMID:Learning, memory, and transcription factors. 1259 82

After an overview of definitions of mental retardation and recent case law regarding mental retardation and the death penalty, this paper presents a study of factors associated with a mental retardation (MR) diagnosis among murder defendants. Subjects with a full-scale IQ< or =70 (n=42) were compared with other pretrial murder defendants (n=228) referred for forensic evaluation over a 5-year period. Subjects with an IQ< or =70 who were diagnosed with MR were compared with subjects with an IQ< or =70 who did not receive this diagnosis. Female murder defendants were more likely to receive a diagnosis of MR (p=0.03). MR was also more commonly diagnosed in subjects with an Axis I cognitive disorder (p=0.018). Having an IQ< or =70 was more common in subjects with a psychotic and substance use disorder (p=0.03) and did not necessarily lead to a diagnosis of MR in this subgroup. Implications for diagnosing MR among murder defendants are discussed.
 ...
PMID:The presence of low IQ and mental retardation among murder defendants referred for pretrial evaluation. 1669 21

Down syndrome (DS), affecting 1/700 live births, is the major genetic cause of mental retardation (MR), a cognitive disorder with hard impact on public health. DS brain is characterized by a reduced cerebellar volume and number of granular cells, defective cortical lamination and reduced cortical neurons, malformed dendritic trees and spines, and abnormal synapses. These neurological alterations, also found in trisomic mouse models, result from gene-dosage effects of Human Chromosome 21 (HC21) on the expression of critical developmental genes. HC21 sequencing, mouse ortholog gene identification and DS mouse model generation lead to determine HC21 gene functions and the effects of protein-dosage alterations in neurodevelopmental and metabolic pathways in DS individuals. Trisomic brain transcriptome of DS patients and trisomic mouse models identified some molecular changes determined by gene-overdosage and associated dysregulation of some disomic gene expression in DS brains. These transcriptional variations cause developmental alterations in neural patterning and signal transduction pathways that may lead to defective neuronal circuits responsible for the pathogenesis of MR in DS. Recently, the first altered molecular pathway responsible of some DS phenotypes, including neurological and cognitive disorders has been identified. In this pathway, two critical HC21 genes (DYRK1A and DSCR1) act synergistically to control the phosphorylation levels of NFATc and NFATc-regulated gene expression. Interestingly, the NFATc mice show neurological dysfunctions similar to those seen in DS patients and trisomic mouse models. Treatment of DS mouse model Ts65Dn with GABA(A) antagonists allowed post-drug rescue of cognitive defects, indicating a hopeful direction in clinical therapies for MR in children with DS.
 ...
PMID:Mental retardation and associated neurological dysfunctions in Down syndrome: a consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways. 1793 68

Infantile spasms syndrome (ISS) is a catastrophic pediatric epilepsy with motor spasms, persistent seizures, mental retardation, and in some cases, autism. One of its monogenic causes is an insertion mutation [c.304ins (GCG)(7)] on the X chromosome, expanding the first polyalanine tract of the interneuron-specific transcription factor Aristaless-related homeobox (ARX) from 16 to 23 alanine codons. Null mutation of the Arx gene impairs GABA and cholinergic interneuronal migration but results in a neonatal lethal phenotype. We developed the first viable genetic mouse model of ISS that spontaneously recapitulates salient phenotypic features of the human triplet repeat expansion mutation. Arx((GCG)10+7) ("Arx plus 7") pups display abnormal spasm-like myoclonus and other key EEG features, including multifocal spikes, electrodecremental episodes, and spontaneous seizures persisting into maturity. The neurobehavioral profile of Arx mutants was remarkable for lowered anxiety, impaired associative learning, and abnormal social interaction. Laminar decreases of Arx+ cortical interneurons and a selective reduction of calbindin-, but not parvalbumin- or calretinin-expressing interneurons in neocortical layers and hippocampus indicate that specific classes of synaptic inhibition are missing from the adult forebrain, providing a basis for the seizures and cognitive disorder. A significant reduction of calbindin-, NPY (neuropeptide Y)-expressing, and cholinergic interneurons in the mutant striatum suggest that dysinhibition within this network may contribute to the dyskinetic motor spasms. This mouse model narrows the range of critical pathogenic elements within brain inhibitory networks essential to recreate this complex neurodevelopmental syndrome.
 ...
PMID:A triplet repeat expansion genetic mouse model of infantile spasms syndrome, Arx(GCG)10+7, with interneuronopathy, spasms in infancy, persistent seizures, and adult cognitive and behavioral impairment. 2012 36

At present, the number of elderly people is rapidly increasing, which represents a significant threat in terms of their care when they fall ill. One of the most common aging diseases nowadays is dementia, whose symptoms sooner or later include loss of cognitive functioning. Cognitive disorders can vary from serious mental retardation to inability to recall things, to the loss or disorder of specific cognitive functions such as communication. These disorders not only affect the quality of people's own life but also impose a substantial burden on their families, particularly on their caregivers. Therefore, the aim of this article is to highlight the role of assistive technologies (ATs) for managing language impairments in dementia in order to improve patients' quality of life. In addition, ATs focused on training patients' memory are also mentioned, since they can help patients to maintain their language skills. Furthermore, these ATs can delay the need for institutional care, as well as significantly reduce costs on patient care. The importance of future research in the area of the development of ATs for managing the language impairments in dementia is also discussed. There is a general trend toward the personalization of patient needs and requirements in the area of ATs. For the purpose of this article, a method of literature review of available sources defining language disorders and providing characteristic features of language disorders in dementia is used. In addition, a method of comparison of different research studies exploring ATs focused on delaying language disorders in dementia in order to postpone patients' need for institutional care is also exploited.
...
PMID:Assistive technologies for managing language disorders in dementia. 2701 80

Objectives. To describe cognitive assessment including social cognition in SPG4 patients. Methods. We reported a series of nine patients with SPG4 mutation with an extensive neuropsychological examination including social cognition assessment. Results. None of our patients presented with mental retardation or dementia. All presented with mild cognitive impairment with a high frequency of attention deficit (100%), executive disorders (89%), and social cognition impairment (78%). An asymptomatic patient for motor skills presented with the same cognitive profile. No correlation was found in this small sample between cognitive impairment and motor impairment, age at disease onset, or disease duration. Conclusions. SPG4 phenotypes share some cognitive features of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cognitive disorders including executive disorders and social cognition impairment are frequent in SPG4 patients and might sometimes occur before motor disorders. Therefore, cognitive functions including social cognition should be systematically assessed in order to improve the clinical management of this population.
 ...
PMID:Cognitive Impairment Involving Social Cognition in SPG4 Hereditary Spastic Paraplegia. 2768 99