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

Trisomy 21 or Down syndrome (DS) is the most frequent genetic cause of mental retardation, affecting one in 800 live born human beings. Mice with segmental trisomy 16 (Ts65Dn mice) are at dosage imbalance for genes corresponding to those on human chromosome 21q21-22.3--which includes the so-called DS 'critical region'. They do not show early-onset of Alzheimer disease pathology; however, Ts65Dn mice do demonstrate impaired performance in a complex learning task requiring the integration of visual and spatial information. The reproducibility of this phenotype among Ts65Dn mice indicates that dosage imbalance for a gene or genes in this region contributes to this impairment. The corresponding dosage imbalance for the human homologues of these genes may contribute to cognitive deficits in DS.
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PMID:A mouse model for Down syndrome exhibits learning and behaviour deficits. 755 Mar 29

A comprehensive baseline of emotional functioning was established for adults with Down syndrome. Five emotional factors were studied using groups of (a) adults with Down syndrome (n = 30), (b) clinical control subjects with dementia of the Alzheimer type (n = 18), and (c) elderly control subjects without mental retardation (n = 25). Results of planned statistical comparisons showed indifference, pragnosia, and inappropriateness as primary emotional factors separating Down syndrome and Alzheimer disease groups from elderly control subjects without mental retardation. Indifference was also shown to covary with cognitive mental state, whereby increased levels of indifference were associated with decreased levels of cognitive functioning. The possibility of noncognitive variables signalling dementia of the Alzheimer type in individuals with Down syndrome was discussed.
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PMID:Detection of Alzheimer disease in individuals with Down syndrome. 763 29

The prevalence of clinical signs and neuropathological findings of Alzheimer's disease (AD) is high in Down's syndrome (DS). In the general population, the apolipoprotein E (ApoE) epsilon 4 isoform is an important risk for AD. We studied the allelic frequencies of ApoE in 26 DS cases fulfilling clinical diagnostic criteria for AD and in 26 DS controls matched for age, sex, and premorbid level of mental retardation. A meta-analysis of data available in the literature was used for comparison with allele frequencies in other AD and control populations. ApoE type 2, 3, or 4 allele frequencies were not significantly different in AD-DS cases and DS controls. The ApoE epsilon 4 frequency in DS cases with AD (0.14; CI, 0.06-0.26) was significantly lower than in any other AD population studied so far and it is within the range of nondemented controls from the general population. These findings suggest that ApoE epsilon 4 does not significantly affect the pathogenesis of AD in DS patients.
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PMID:A case-control study of apolipoprotein E genotypes in Alzheimer's disease associated with Down's syndrome. Dutch Study Group on Down's Syndrome and Ageing. 765 70

S100 beta, a calcium-binding brain protein, has been implicated in brain development and hippocampal neurophysiology including long-term potentiation. Its gene maps to chromosome 21, which is duplicated in Down syndrome. S100 beta levels are elevated in both Down syndrome and Alzheimer's disease, human neurodegenerative diseases associated with mental retardation and dementia. To investigate whether or not elevated S100 beta levels can cause brain dysfunctioning in mammals, transgenic mice carrying multiple copies of the human S100 beta gene were generated. Several independent lines of transgenic mice were compared to age-matched normal control mice of identical genetic background (CD1) by measuring their exploratory behaviors in novel situations. Transgenic mice exhibited a range of defects including female specific hyperactivity, lack of habituation to novelty and reduced T-maze spontaneous alternation rate. Although the neuroanatomical or physiological substrate of these abnormalities is unknown, they are similar to the behavioral manifestations of hippocampal dysfunction. The S100 beta mouse offers one of the first opportunities to investigate the relationship between over-expression of a human chromosome 21 gene product and abnormal behavior and brain functioning.
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PMID:Abnormal exploratory behavior in transgenic mice carrying multiple copies of the human gene for S100 beta. 770 19

Using a method of analysis which consists in the evaluation of the mitotic index of lymphocyte cultures to which different metabolites and anti-metabolites have been added, we studied various forms of mental retardation due to a chromosomal aberration and observed specific biochemical imbalances. Methotrexate sensitivity is characteristic of trisomy 21. A significant difference in purine synthesis pathway was observed between patients with Down syndrome without complications and those presenting with additional psychotic features. Inspite of a gene dosage effect for genes intervening in purine synthesis, lymphocytes from psychotic trisomy 21 patients seem unable to complete inosine synthesis. Lymphocytes from patients with Alzheimer's disease with or without trisomy 21 are excessively sensitive to exogenous glutamine.
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PMID:[Metabolic anomalies in trisomy 21: a method for analyzing lymphocyte cultures]. 774 68

Most adults with Down's syndrome (DS) develop neuropathology characteristic of Alzheimer's disease (AD) by the age of 40. Most of the non-dysjunction events in DS are of maternal origin. We postulated therefore that a shared genetic susceptibility to DS and AD would be associated with an increased frequency of AD among mothers, but not fathers, of individuals with DS. We further hypothesised that the shared susceptibility could involve an accelerated ageing process, leading to the birth of a child with DS to a relatively young mother and to an increased risk of dementia in the mother and her relatives. Families of 96 adults with DS and of 80 adults with other forms of mental retardation were ascertained through the New York State Developmental Disabilities services network. A semi-structured interview was used to obtain information on the presence or absence of non-stroke-related dementia and other disorders in parents. There was an increase in risk of dementia among mothers of DS probands compared with control mothers (risk ratio 2.6 [95% CI 0.9-7.3]). The risk of dementia among mothers who were 35 or younger when their DS children were born was 5 times that of control mothers (4.9 [1.6-15.4]). There was no increase in risk of dementia among mothers who were older (> 35 years) at the proband's birth (0.8 [0.2-3.4]). There was no difference in risk of dementia between fathers of DS cases and fathers of controls (1.2 [0.4-3.9]) and no discernible influence of age on this risk. Familial aggregation of dementia among mothers of adults with DS supports the hypothesis of a shared genetic susceptibility to DS and AD.
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PMID:Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome. 793 77

Over the past few years, molecular neurogenetics has developed into one of the most promising and active research fields. The new discipline applies modern molecular genetic techniques to the investigation of classical neurological disorders. In the following article, a definition of neurogenetic disease is introduced, the molecular basis of four groups of neurogenetic disorders is described and recent diagnostic developments are presented. The first group of diseases is caused by trinucleotide expansions. "Expanding" trinucleotide repeats were not known to occur in any species until about three years ago. Today, disorders such as Huntington's disease, spinocerebellar ataxia type 1, fragile X mental retardation, spinobulbar muscular atrophy and myotonic dystrophy are all known to be caused by the expansion of trinucleotides. The second group is characterized by chromosomal deletions or uniparental disomies. Lissencephaly and the Miller-Dieker syndrome, Prader-Willi and Angelman syndromes and Duchenne and Becker muscular dystrophies belong to this category. The third group includes those neurogenetic disorders that are mainly caused by point mutations such as the X-linked leukodystrophies, including Pelizaeus-Merzbacher disease and adrenoleukodystrophy, Charcot-Marie-Tooth syndrome type 1, familial forms of amyotrophic lateral sclerosis, several types of craniosynostoses and some CNS tumor syndromes. Finally, Alzheimer's and Parkinson's disease are discussed as representatives of group four, i.e. genetically heterogeneous neurological disorders.
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PMID:Molecular basis and diagnosis of neurogenetic disorders. 796 63

In 1986 in the Kuthar Valley in the Anantnag District of south Kashmir (northwestern India), we studied the population to ascertain the prevalence and pattern of various neurological diseases. A house-to-house survey was done in a rural population of 63,645 (according to a World Health Organization protocol, 1981). 616 cases of major neurological disorders were detected, yielding a prevalence of ratio of 9.67/1,000 as of prevalence day November 1, 1986. The prevalence ratios for various common neurological disorders were: epilepsy 2.47/1,000; stroke 1.43/1,000; paralytic poliomyelitis 2.18/1,000; mental retardation 2.09/1,000; deaf mutism 1.63/1,000, and cerebral palsy 1.24/1,000. Persons with these conditions constituted 92% of all neurological cases. Patients with motor neuron disease, Alzheimer's dementia or multiple sclerosis were not found.
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PMID:Prevalence and pattern of major neurological disorders in rural Kashmir (India) in 1986. 801 64

Down syndrome (DS) is a major cause of mental retardation and congenital heart disease. Besides a characteristic set of facial and physical features, DS is associated with congenital anomalies of the gastrointestinal tract, an increased risk of leukemia, immune system defects, and an Alzheimer-like dementia. Moreover, DS is a model for the study of human aneuploidy. Although usually caused by the presence of an extra chromosome 21, subsets of the phenotypic features of DS may be caused by the duplication of small regions of the chromosome. The physical map of chromosome 21 allows the molecular definition of the regions duplicated in these rare cases of partial trisomy. As a first step in identifying the genes responsible for individual DS features and their pathophysiology, a panel of cell lines derived from 16 such individuals has been established and the molecular break points have been determined using fluorescence in situ hybridization and Southern blot dosage analysis of 32 markers unique to human chromosome 21. Combining this information with detailed clinical evaluations of these patients, we have now constructed a "phenotypic map" that includes 25 features and assigns regions of 2-20 megabases as likely to contain the genes responsible. This study provides evidence for a significant contribution of genes outside the D21S55 region to the DS phenotypes, including the facies, microcephaly, short stature, hypotonia, abnormal dermatoglyphics, and mental retardation. This strongly suggests DS is a contiguous gene syndrome and augurs against a single DS chromosomal region responsible for most of the DS phenotypic features.
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PMID:Down syndrome phenotypes: the consequences of chromosomal imbalance. 819 71

We report the findings of a total population survey of Thugbah community in the Eastern Province of Saudi Arabia (SA) to determine its point prevalence of neurological diseases. During this two-phase door-to-door study, all Saudi nationals living in Thugbah were first screened by trained interviewers using a pretested questionnaire (sensitivity 98%, specificity 89%) administered at a face-to-face interview. Individuals with abnormal responses were then evaluated by a neurologist using specific guidelines and defined diagnostic criteria to document neurological disease. The questionnaire was readministered blind by a neurologist to all those with abnormal responses and a 1-in-20 random sample of those without abnormal responses, respectively. The family members of an individual with an abnormal response were also screened to improve accuracy. A total of 23,227 Saudis (98% of the eligible subjects) were screened and those residing in Thugbah on the reference date (22,630) were used to calculate the point prevalence rates. Forty-two percent of those screened were in the first decade of life and only 1.5% were more than 60 years old. There were marginally more females (50.2%) than males (49.8%). Consanguineous marriages especially between first cousins were present in 54.6%. The demographic characteristics of Thugbah community were similar to those in other parts of SA. The overall crude prevalence ratio (PR) for all forms of neurological disease was 131/1,000 population. All subsequent PRs are per 1,000 population. Headache syndromes were the most prevalent disorder (PR 20.7). The PR for all seizure disorders was 7.60, and the epilepsies (6.54) were more frequent than febrile convulsions (0.84). Mental retardation, cerebral palsy syndrome, and microcephaly were common pediatric problems with PRs of 6.27, 5.30 and 1.99, respectively. Stroke, Parkinson's disease, and Alzheimer's disease were uncommon with respective PRs of 1.8, 0.27 and 0.22. Central nervous system (CNS) malformations (0.49) such as hydrocephalus and meningomyelocele were more prevalent than spinal muscular atrophy (0.13), congenital brachial palsy (0.13) and narcolepsy (0.04). Multiple sclerosis was rare (0.04). Osteoarthritis and low back pain syndromes were the main non-neurological conditions seen. The major medical diseases that may be neurologically relevant were diabetes mellitus, hypertension, and connective tissue disorders.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A community survey of neurological disorders in Saudi Arabia: the Thugbah study. 827 77


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