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

Williams syndrome (WMS) is a genetic condition resulting from a hemideletion on chromosome 7 that causes cognitive impairment, and a variety of growth and physical abnormalities. Little is currently known about brain morphology in WMS, although one recent MRI report suggested that the central sulcus was abnormally short on its dorsal end compared to normal IQ controls. We sought to replicate this finding in a group of 28 persons with WMS in comparison to both an age and sex matched normal IQ control group (n = 22). In addition, we sought to test the specificity of this finding by a further comparison to an IQ matched control group (n = 20). Using high resolution isotropic voxel MRI, the dorsal and ventral extension of the central sulcus was traced and the distance from the interhemispheric and sylvian fissures was measured. The dorsal extension of the central sulcus in both hemispheres was significantly more distant from the interhemispheric fissure in WMS compared to the lower IQ group and to the normal control group (p's < 0.001). There was no significant difference between groups in the ventral end of the central sulcus. These results suggest that the abnormal dorsal end of the central sulcus may be a specific characteristic of WMS not shared with general mental retardation or low IQ.
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PMID:Foreshortened dorsal extension of the central sulcus in Williams syndrome. 1587 94

Thin corpus callosum has been recently observed in two patients with an autosomal dominant trait of hereditary spastic paraplegia (HSP) linked to a novel mutation in the spastin gene (SPG4). In the same two patients cerebellar atrophy has been found. Reportedly, in other members of the same family, there has been a variable presence of mental retardation. We report on the clinical and genetic investigation of an Austrian family with a novel mutation in the spastin gene. Genetic analysis of the SPG4 locus revealed a mutation (C1120A) and a known intronic polymorphism (996-47G>A) of the spastin gene. In one affected family member, previously undescribed dysplasia of the corpus callosum (CC) was found in conjunction with otherwise uncomplicated HSP. Dysplastic CC was not paralleled with cortical atrophy, cognitive impairment or other phenotypic variations. Two further affected family members showed the same mutation and polymorphism, but no evidence of CC abnormalities. We conclude that apparently pure HSP may present with MRI features of dysplastic CC. This finding extended the spastin-related phenotype which is distinct from previous reports of thin CC in HSP.
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PMID:Spastin related hereditary spastic paraplegia with dysplastic corpus callosum. 1600 77

VATER "association" is a common condition, with the diagnosis typically based on a characteristic constellation of congenital anomalies. Reported long-term follow-up information on VATER association is limited, thus making it difficult to prognosticate the future of infants and children with this condition. Further, there are few data on how often the initial diagnosis of VATER association is correct. Some information has been published on growth deficiency and mental retardation, but these data are minimal [Bull et al., 1985; Mapstone et al., 1986; Weaver et al., 1986] and for the most part look at children under the age of 10 years. We have undertaken a long-term follow-up of individuals with VATER association originally reported by Weaver et al. [1986] or diagnosed with VATER association by his associates and him after 1986. Out of the 50 patients, we were able to contact 20 individuals or families. Two of the 20 individuals had died: 1 at 3 days with cardiac failure due to a truncus arteriosus, and 1 at 4 years of unspecified cause. Two were unwilling to participate. Of the rest, we interviewed and examined seven persons, and interviewed another nine by telephone. Of the 16, 5 had some degree of cognitive impairment. These individuals were more likely to have congenital anomalies outside of the typical scope of VATER association, such as prune belly sequence or findings of CHARGE association. Of the nine individuals with a history of imperforate anus, five had partial or complete incontinence as adults leading to difficulties in maintaining employment. Height was at the 5th centile or less in 6 of 16 patients. Three of four patients who were trying to have children, had infertility. In two women, the infertility was thought to be related to congenital anomalies of the genitourinary system and multiple pelvic operations. We also present the long-term medical and neurologic problems in these individuals.
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PMID:Adults with VATER association: long-term prognosis. 1615 41

One of the most common chromosomal deletions is a loss of genetic material from the long arm of chromosome 18. Most individuals with this condition exhibit mental retardation (68%), yet previous attempts to link cognitive status to deletion size have not shown an association, possibly because cases with additional genetic abnormalities were included. We studied 46 participants ranging from 3 to 35 years of age who had a pure genetic abnormality by excluding those with mosaicism or complex genetic rearrangements. Our patients had terminal deletions ranging from a proximal breakpoint at 18q21.1 (greater genetic abnormality, larger deletion size) to a more distal breakpoint at 18q23 characterized with molecular genetic techniques. Cognitive ability, assessed with the age-appropriate measure (Bayley, 1993 , Differential Ability Scale, Wechsler Scales), ranged from IQ = 49 to 113, with a predominance of mild and moderate mental retardation. Using multivariate regression, deletion size breakpoint rank order was predicted by cognitive ability, age, and adaptive behavior (Vineland Adaptive Behavior Scales), accounting for 36% of the variance in deletion size. However, lower cognitive ability (beta = .34, p = .032) and younger age (beta = .296, p = .024) predicted a larger deletion size, but adaptive behavior (beta = .225, p = .15) did not. An additional multivariate regression showed that cognitive ability and age together accounted for 33% of the variance in deletion size, whereas univariate regression showed that cognitive ability accounted for 26% of the variance and age accounted for 11% of the variance. These findings suggest that degree of cognitive impairment is associated with genetic abnormality when a large sample of individuals with "pure" deletions of genetic material from chromosome 18 is examined.
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PMID:Cognitive ability predicts degree of genetic abnormality in participants with 18q deletions. 1621 85

Studies on human patients and animal models of disease have shown that disruptions in prenatal and early postnatal brain development are a root cause of mental retardation. Since proper brain development is achieved by a strict spatiotemporal control of neurogenesis, cell migration, and patterning of synapses, abnormalities in one or more of these events during prenatal development can lead to cognitive dysfunction after birth. Many of underlying causes of mental retardation must therefore be studied in developing brains. To aid in this research, live imaging using laser scanning microscopy (LSM) has recently allowed neuroscientists to delve deeply into the complex three-dimensional environment of the living brain to record dynamic cellular events over time. This review will highlight recent examples of how LSM is being applied to elucidate both normal and abnormal cortical development.
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PMID:Advanced microscopic imaging methods to investigate cortical development and the etiology of mental retardation. 1624 Apr 12

We have studied a male patient with significant developmental delay, growth failure, hypotonia, girdle weakness, microcephaly, and multiple congenital anomalies including atrial (ASD) and ventricular (VSD) septal defects. Detailed cytogenetic and molecular analyses revealed three de novo X chromosome aberrations and a karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32 approximately q22.2)del(X)(q22.3q22.3) was determined. The three X chromosome aberrations in the patient include: a pericentric inversion (inv 1) that disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively affecting no genes; and an interstitial deletion at Xq22.3 that results in functional nullisomy of several known genes, including a gene previously associated with X-linked nonsyndromic mental retardation, acyl-CoA synthetase long chain family member 4 (ACSL4). These findings suggest that the disruption of DMD and the absence of ACSL4 in the patient are responsible for neuromuscular disease and cognitive impairment.
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PMID:Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia, and multiple congenital anomalies. 1627 8

Down's syndrome (DS) associates with genetic-dependent dysregulation of the interferon (IFN) system. We used intracellular cytokine staining to analyse the percentages of IFN-gamma- and interleukin (IL)-4-producing T cells in the peripheral blood of patients with DS, individuals with mental retardation (MR), and healthy controls (HCs). The percentages of IFN-gamma-producing CD4(+) and CD8(+) T cells (IFGCs), namely Th1 (mean, 21.4+/-S.D. 1.3) and Tc1 (12.6+/-1.1), and the Th1/Th2 ratio (6.1+/-0.2) in DS were significantly higher than in MR (15.9+/-1.3, 7.9+/-0.6, 4.8+/-0.3) and in HCs (15.6+/-1.9, 7.2+/-1.1, 4.6+/-0.6). Most of the DS patients with high IFGC percentages were seropositive for anti-transglutaminase IgA. We found no correlation between sex, age, APOE genotypes, coexisting autoimmune diseases, susceptibility to infections, or degree of cognitive impairment and high IFGC percentages. This abnormality might thus contribute to immune dysfunction in DS without manifest clinical correlates.
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PMID:Interferon-gamma- and interleukin-4-producing T cells in Down's syndrome. 1628 22

Changes in PUFA (polyunsaturated fatty acid) metabolism can cause mental retardation and cognitive impairment. However, it is still unclear why altered levels of PUFAs result in neuronal dysfunction. Recent studies on the nematode Caenorhabditis elegans suggest that PUFA depletion may cause cognitive impairment by compromising communication among neurons. Pharmacological and electrophysiological experiments showed that animals devoid of most PUFAs release abnormally low levels of neurotransmitters. In addition, ultrastructural analysis revealed that synapses in these mutants are severely depleted of synaptic vesicles. The conclusion of these studies is that PUFAs are required to maintain a normal pool of synaptic vesicles at pre-synaptic sites, thus ensuring efficient neurotransmission.
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PMID:Polyunsaturated fatty acids and neurotransmission in Caenorhabditis elegans. 1641 87

Mutations in PQBP1 were recently identified in families with syndromic and non-syndromic X-linked mental retardation (XLMR). Clinical features frequently associated with MR were microcephaly and/or short stature. The predominant mutations detected so far affect a stretch of six AG dinucleotides in the polar-amino-acid-rich domain (PRD), causing frameshifts in the fourth coding exon. We searched for PQBP1 exon 4 frameshifts in 57 mentally retarded males in whom initial referral description indicated at least one of the following criteria: microcephaly, short stature, spastic paraplegia or family history compatible with XLMR, and in 772 mentally retarded males not selected for specific clinical features or family history. We identified a novel frameshift mutation (23 bp deletion) in two half-brothers with specific clinical features, and performed prenatal diagnosis in this family. We also found two different 21 bp in-frame deletions (c.334-354del(21 bp) and c.393-413del(21 bp)) in four unrelated probands from various ethnic origins, each deleting one of five copies of an imperfect seven amino-acid repeat. Although such deletions have not been detected in 1180 X chromosomes from European controls, the c. 334-354del(21 bp) was subsequently found in two of 477 Xs from Indian controls. We conclude that pathogenic frameshift mutations in PQBP1 are rare in mentally retarded patients lacking specific associated signs and that the 21 bp in-frame deletions may be non-pathogenic, or alternatively could act subtly on PQBP1 function. This touches upon a common dilemma in XLMR, that is, how to distinguish between mutations and variants that may be non-pathogenic or represent risk factors for cognitive impairment.
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PMID:Exonic microdeletions in the X-linked PQBP1 gene in mentally retarded patients: a pathogenic mutation and in-frame deletions of uncertain effect. 1649 39

An open prospective clinical study included 25 patients with childhood autism aged from 3 to 8 years (mean age 5 years 11 months). Patients received 2 therapeutic courses (15 intramuscular Cerebrolysin injections of 1.0 ml every other day per course) with 2 months interval and basic antipsychotic therapy using typical neuroleptics in age-adjusted dosages. The duration of the study was 180 days. Significant or very significant improvement was achieved after the 1st Cerebrolysin course in 38% patients, after the 2nd course in more than 50% and to the end of the follow-up (180th day) in 71% of patients. There were no cases of deterioration during the trial. The autism severity as measured by the CARS scale consistently decreased from the day 0 to the day 180--from 37.7 to 32.6 scores, respectively (p < 0.001) in all assessments as compared with the baseline. To the end of the study, the patients demonstrated a significant decrease in mental retardation by 0.2 years. A statistically significant improvement was achieved in cognitive activity, attention during task performing as well as in self-service (by 0.3 years), receptive and expressive speech, cognitive performance and perception (by 0.2 years), fine motor function (by 0.1 years). The combined therapy comprising neuroleptics and Cerebrolysin double course can be recommended for correction of behavioral disorders and cognitive dysfunction in patients with mild moderate and moderate/severe autism.
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PMID:[An effect of long-term cerebrolysin therapy in combination with neuroleptics on behavioral and cognitive disturbances in endogenous childhood autism]. 1654 70


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