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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rearrangements of chromosome 15q, including isodicentric 15 chromosomes and interstitial duplications and triplications, have been previously reported in association with autism spectrum disorders. We have identified two boys with exceptionally large der(15) chromosomes that are tricentric and contain four copies of the proximal long arm, including the Prader Willi/Angelman critical region, and leading to hexasomy of the involved segment. Biallelic inheritance of maternal alleles and methylation analysis indicate that the markers are maternally derived. Clinical assessment of the boys indicated severe cognitive impairment associated with marked delays in gross and fine motor skills. Social and language deficits were present in both, although the severity of the mental retardation precluded diagnosis of autism (both were considered to have pervasive developmental disorder-not otherwise specified). Neurologic manifestations included infantile spasms evolving into intractable early-onset myoclonic seizures, psychomotor regression, and profound diffuse hypotonia. These patients represent the most severe end of the spectrum of phenotypes associated with segmental aneuploidy for chromosome 15q11-q13.
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PMID:Supernumerary tricentric derivative chromosome 15 in two boys with intractable epilepsy: another mechanism for partial hexasomy. 1514 47

After literature review, this paper presents the largest study to date (n = 270) of psychiatric and neurological characteristics of accused murderers in the United States. This retrospective record review of pretrial detainees undergoing competency to stand trial and criminal responsibility evaluations examined demographic characteristics, psychiatric diagnosis, substance use patterns, Intelligence Quotient (IQ), and results of electroencephalogram (EEG), neuroimaging (MRI or CT) and neurological examination. Substance use and mood/adjustment disorders were common. Neuroimaging was abnormal in 18% of subjects and was associated with lower Performance IQ. EEG and neurological exam findings were not associated with measured cognitive impairment. While 16% of subjects had a FS IQ < 70, only 6% were diagnosed with mental retardation. Subjects with a psychotic disorder (p = 0.001) or an anxiety disorder (p = 0.005) were more likely to use a knife than other subjects in the study. Violence risk assessment in these patients must not only involve inquiry about firearm availability.
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PMID:Psychiatric and neurological characteristics of murder defendants referred for pretrial evaluation. 1517 Nov 85

Homocystinuria is an inherited metabolic disease biochemically characterized by tissue accumulation of homocysteine. Affected patients present mental retardation and other neurological symptoms whose mechanisms are still obscure. In the present study, we investigated the effect of chronic hyperhomocysteinemia on rat performance in the Morris water maze task. Chronic treatment was administered from the 6th to the 28th day of life by s.c. injection of homocysteine, twice a day at 8-h intervals; control rats received the same volume of saline solution. Animals were left to recover until the 60th day of life. Morris water maze tasks were then performed, in order to verify any effect of early homocysteine administration on reference and working memory of rats. Results showed that chronic treatment with homocysteine impaired memory of the platform location and that homocysteine treated animals presented fewer crossings to the place where the platform was located in training trials when compared to saline-treated animals (controls). In the working memory task, homocysteine treated animals also needed more time to find the platform. Our findings suggest that chronic experimental hyperhomocysteinemia causes cognitive dysfunction and that might be related to the neurological complications characteristic of homocystinuric patients.
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PMID:Chronic hyperhomocysteinemia provokes a memory deficit in rats in the Morris water maze task. 1526 32

Fragile X syndrome is an X-linked form of mental retardation including, among others, symptoms such as stereotypic behaviour, hyperactivity, hyperarousal, and cognitive deficits. We hypothesized that hyperactivity and/or compromised attentional, cognitive functions may lead to impaired performance in cognitive tasks in Fmr1 knockout mice, the most widely used animal model of fragile X syndrome, and suggested that psychostimulant treatment may improve performance by acting on one or both components. Since hyperactivity and cognitive functions have been suggested to depend on striatal and prefrontal cortex dopaminergic dysfunction, we assessed whether amphetamine produced beneficial, positive effects by acting on dopaminergic corticostriatal systems. Our results show that Fmr1 knockout mice are not able to discriminate between a familiar object and a novel one in the object recognition test, thus showing a clear-cut cognitive impairment that, to date, has been difficult to demonstrate in other cognitive tasks. Amphetamine improved performance of Fmr1 knockout mice, leading to enhanced ability to discriminate novel versus familiar objects, without significantly affecting locomotor activity. In agreement with behavioural data, amphetamine produced a greater increase in dopamine release in the prefrontal cortex of Fmr1 knockout compared with the wild-type mice, while a weak striatal dopaminergic response was observed in Fmr1 knockout mice. Our data support the view that the psychostimulant ameliorates performance in Fmr1 knockout mice by improving merely cognitive functions through its action on prefrontal cortical dopamine, irrespective of its action on motor hyperactivity. These results indicate that prefrontal cortical dopamine plays a major role in cognitive impairments characterizing Fmr1 knockout mice, thus pointing to an important aetiological factor in the fragile X syndrome.
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PMID:Object recognition impairment in Fmr1 knockout mice is reversed by amphetamine: involvement of dopamine in the medial prefrontal cortex. 1534 70

Delta-catenin (delta-catenin) is a neuron-specific catenin, which has been implicated in adhesion and dendritic branching. Moreover, deletions of delta-catenin correlate with the severity of mental retardation in Cri-du-Chat syndrome (CDCS), which may account for 1% of all mentally retarded individuals. Interestingly, delta-catenin was first identified through its interaction with Presenilin-1 (PS1), the molecule most frequently mutated in familial Alzheimer's Disease (FAD). We investigated whether deletion of delta-catenin would be sufficient to cause cognitive dysfunction by generating mice with a targeted mutation of the delta-catenin gene (delta-cat(-/-)). We observed that delta-cat(-/-) animals are viable and have severe impairments in cognitive function. Furthermore, mutant mice display a range of abnormalities in hippocampal short-term and long-term synaptic plasticity. Also, N-cadherin and PSD-95, two proteins that interact with delta-catenin, are significantly reduced in mutant mice. These deficits are severe but specific because delta-cat(-/-) mice display a variety of normal behaviors, exhibit normal baseline synaptic transmission, and have normal levels of the synaptic adherens proteins E-cadherin and beta-catenin. These data reveal a critical role for delta-catenin in brain function and may have important implications for understanding mental retardation syndromes such as Cri-du-Chat and neurodegenerative disorders, such as Alzheimer's disease, that are characterized by cognitive decline.
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PMID:Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction. 1538 68

Down syndrome occurs every 1/1000 births and is the most frequent genetic cause of mental retardation. The genetic substrate of Down syndrome, an extra chromosome 21, was discovered by Lejeune, half-a-century ago, and the chromosome has been fully sequenced, although the gene(s) implicated in the mental retardation observed with the syndrome are still unknown. Observations of patients with partial trisomy of the 21q22.2 fragment suggest that most of the signs of the syndrome, including mental retardation, could be influenced by the region referred to as the Down Minimal Chromosomal Region-1 (DCR-1) for that reason. Using the extensive syntenies between human chromosome 21 and murine chromosome 16, Smith et al. (1995, 1997) developed transpolygenic mice with human chromosome 21 fragments covering the DCR-1. Here, we explored cognitive performances in mice over-expressing the genes carried by these fragments with the Morris water-maze and fear-conditioning procedures. The 152F7 transpolygenic mice had lower performance levels, compared to non-transgenic and other transgenic mice on most measurements in the water-maze. In fear-conditioning, all transgenic mice recorded lower performance levels compared to controls in the altered context stage. The 230E8, 141G6 and 285E6 mice failed to learn or react when the sound used as the conditional stimulus was added. These results showed that the 152F7 region played a crucial role in cognitive impairment, supporting the hypothesis of DYRK-1A gene involvement. However, the data presented here also suggest that other chromosomal regions within the DCR-1 may be involved in specific cognitive functions.
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PMID:Functional analysis of genes implicated in Down syndrome: 1. Cognitive abilities in mice transpolygenic for Down Syndrome Chromosomal Region-1 (DCR-1). 1552 May 13

Rett syndrome (RS), a neurological developmental disorder, is one of the commonest causes of cognitive impairment in girls and women. These patients are often initially misdiagnosed as idiopathic mental retardation, cerebral palsy, or autism. Despite several reports from the West, there are very few reports from the Indian population. We present four female children with RS and emphasize the importance of early diagnosis.
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PMID:Recent experience with Rett syndrome at a tertiary care center. 1562 43

Tuberous sclerosis complex is a multisystem disorder in which neurologic problems cause the greatest disability. High rates of mental retardation and autism spectrum disorders are associated with the diagnosis. Early-onset seizures and increased tuber burden are risk factors for cognitive impairment. Early-onset seizures, particularly infantile spasms, are risk factors for autism. Tubers within the temporal lobe and cerebellum are often mentioned as risk factors for autism, although the findings are inconsistent. Seizure control is important for developmental outcome and quality of life. Early behavioral assessment and therapeutic intervention, as well as seizure control, are the most effective means of promoting neurodevelopmental outcome.
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PMID:Cognitive and behavioral correlates of tuberous sclerosis complex. 1565 88

When evaluating children with mental retardation, subtle cerebral and cerebellar morphologic anomalies are often noted at Magnetic Resonance Imaging (MRI). Some, such as cerebellar cortical dysplasia (CCD), have been considered as subtle markers of cerebral dysgenesis. Their functional significance and their effect on brain function, remain unknown. To study supratentorial functional disturbances related to CCD we performed Positron-Emission-Tomography (PET) studies in two children with isolated CCD, in order to investigate the degree of involvement of supratentorial structures. One had developmental delay, motor disturbances and ataxia, and the other one only had mental retardation. PET studies revealed hypoperfusion and hypometabolism within the vermis, thalamus and the right striatum in one case, and hypometabolism in the basal ganglia and cerebellar deep grey nuclei in the other case. Our results could lead to a hypothesis explaining motor disturbances as well as cognitive impairment, and could suggest a pathological functional significance of CCD. Nevertheless, the relationship between these findings and mental retardation needs further investigation.
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PMID:Supratentorial functional disturbances in two children with cerebellar cortical dysplasia. 1568 60

The association between atypical laterality and mental retardation has been reported several times, particularly in Down syndrome (DS). We investigated common genetic correlates of these components of the syndrome, examining direction (number of right paw entries in the Collins test) and degree (absolute difference between the number of right paw entries and the number of left paw entries) in mice that had incorporated extra-contiguous HSA21 fragments covering DCR-1 (Down Chromosomal Region-1). As corpus callosum size is substantially reduced in DS, and as the structure has been suspected of playing a role in atypical laterality, we also measured the corpus callosum in these mice. Extra copies of two regions (F7 and E6) have been associated with an atypical degree of laterality (strongly reduced degree). Extra copies of E8, G6 and E6 are also linked to the reduced size of the corpus callosum, indicating that the abnormal number of fibers linking the two hemispheres is not associated with atypical laterality in DS. Together, these results indicate that some of the genes involved in atypical laterality and in the reduced size of the corpus callosum in DS are present on DCR-1. An extra copy of F7 and, to a lesser extent, an extra copy of E6, are also associated with cognitive impairment. These results support the hypothesis of common genetic correlates in atypical laterality and mental retardation in DS.
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PMID:Functional analysis of genes implicated in Down syndrome: 2. Laterality and corpus callosum size in mice transpolygenic for Down syndrome chromosomal region -1 (DCR-1). 1586 48


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