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

Mental retardation has been categorized into severe mental retardation where genetics plays a very important role and mild mental retardation, in which genetics in some instances plays a role but in which cultural factors also matter a great deal. The pathogenetic, clinical and behavioral characteristics of genetically determined disorders associated with mental retardation differ greatly-as exemplified by two genetic disorders that have been clarified recently, namely Rett syndrome and the Williams syndrome. In the work-up of the developmentally disabled child, previous studies have shown that genetic studies are of have great importance and high yield. Early biochemical diagnosis in newborn screening has tremendous potential and has been strongly supported by NICHD-the PKU story being so much part of what NICHD has done. We must gain a better understanding of structure/function relationships, which becomes more and more possible with neuroimaging. A better understanding of neural plasticity can lead to correction by early intervention.
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PMID:Genetic causes of mental retardation. 1583 96

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

Williams syndrome (WS), caused by microdeletion of some 21 genes on chromosome 7q11.23, is characterized by dysmorphic features, mental retardation or learning difficulties, elastin arteriopathy, and striking neurocognitive and social-behavioral abnormalities. Recent studies of murine knockouts of key genes in the microdeleted region, LIM kinase 1 (LIMK1) and cytoplasmatic linker protein 2 (CYLN2), demonstrated significant functional and metabolic abnormalities, but grossly normal structure, in the hippocampal formation (HF). Furthermore, deficits in spatial navigation and long-term memory, major cognitive domains dependent on hippocampal function, have been described in WS. We used multimodal neuroimaging to characterize hippocampal structure, function, and metabolic integrity in 12 participants with WS and 12 age-, sex-, and IQ-matched healthy controls. PET and functional MRI studies showed profound reduction in resting blood flow and absent differential response to visual stimuli in the anterior HF in WS. Spectroscopic measures of N-acetyl aspartate, considered a marker of synaptic activity, were reduced. Hippocampal size was preserved, but subtle alterations in shape were present. These data demonstrate abnormalities in HF in WS in agreement with murine models, implicate LIMK1 and CYLN2 in human hippocampal function, and suggest that hippocampal dysfunction may contribute to neurocognitive abnormalities in WS.
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PMID:Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome. 1595 40

A case with de novo interstitial deletion of chromosome 7q21.1-q22: A patient with multiple congenital anomalies was found to have a de novo proximal interstitial deletion of chromosome 7q21.1-q22. The patient was 10.5 years of age, and manifestations include growth retardation (below 3rd percentile), mental retardation, mild microcephaly, hypersensitivity to noise, mild spasticity, short palpebral fissures, alternant exotropia, compensated hypermetropic astigmatism, hypotelorism, hypoplastic labia majora and minora, clinodactyly of fingers 4 and 5. Molecular studies revealed that the deletion had a paternal origin, while chromosomes of both parents cytogenetically were shown to be normal. Molecular, and fluorescence in situ hybridization (FISH) analyses confirmed no deletion at the Williams-Beuren Syndrome region. Some of the heterogeneous clinical findings were consistent with previously reported cases of same chromosomal breakpoints.
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PMID:A case with de novo interstitial deletion of chromosome 7q21.1-q22. 1608 Feb 95

In this two-part study, we assessed musical involvements in two samples of persons with Williams syndrome compared to others with mental retardation and also related musicality to anxiety and fears in Study 2. Relative to others with mental retardation, those with Williams syndrome were more likely to take music lessons, play an instrument, and have higher ratings of musical skills. In the Williams syndrome groups only, fewer externalizing symptoms were associated with listening to music, whereas less anxiety and fewer fears were associated with the frequency, duration, and skill in producing music as well as emotional responses to negatively toned music. Implications are discussed for future research on musical processing, musical interventions, and well-being in Williams syndrome and other groups.
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PMID:Music and anxiety in Williams syndrome: a harmonious or discordant relationship? 1608 Jul 73

We examined implicit and explicit memory in adults with Williams syndrome. An age-related dissociation was found; repetition priming (reflecting implicit memory) did not show change with age, but free recall (reflecting explicit memory) was markedly reduced. We also compared the performance of adults with Williams syndrome to adults with Down syndrome and those with unspecified mental retardation. A similar dissociation was observed in adults with Down syndrome but not in adults with unspecified mental retardation. An IQ-related dissociation was also found. Implicit and explicit memory, therefore, show different degrees of association with age and IQ, supporting theories of these memory processes. Results also suggest that Williams syndrome, similar to Down syndrome, may be associated with precocious aging, resulting in the loss of some cognitive abilities.
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PMID:Repetition priming in adults with Williams syndrome: age-related dissociation between implicit and explicit memory. 1621 50

The underlying cause of mental retardation remains unknown in up to 80% of patients. As chromosomal aberrations are the most common known cause of mental retardation, several new methods based on FISH, PCR, and array techniques have been developed over recent years to increase detection rate of subtle aneusomies initially of the gene rich subtelomeric regions, but nowadays also genome wide. As the reported detection rates vary widely between different reports and in order to compare the diagnostic yield of various investigations, we analyzed the diagnostic yield of conventional karyotyping, subtelomeric screening, molecular karyotyping, X-inactivation studies, and dysmorphological evaluation with targeted laboratory testing in unselected patients referred for developmental delay or mental retardation to our cytogenetic laboratory (n = 600) and to our genetic clinic (n = 570). In the cytogenetic group, 15% of patients showed a disease-related aberration, while various targeted analyses after dysmorphological investigation led to a diagnosis in about 20% in the genetic clinic group. When adding the patients with a cytogenetic aberration to the patient group seen in genetic clinic, an etiological diagnosis was established in about 40% of the combined study group. A conventional cytogenetic diagnosis was present in 16% of combined patients and a microdeletion syndrome was diagnosed in 5.3%, while subtelomeric screening revealed only 1.3% of causes. Molecular karyotyping with a 10 K SNP array in addition revealed 5% of underlying causes, but 29% of all diagnoses would have been detectable by molecular karyotyping. In those patients without a clear diagnosis, 5.6% of mothers of affected boys showed significant (>95%) skewing of X-inactivation suggesting X-linked mental retardation. The most common diagnoses with a frequency of more than 0.5% were Down syndrome (9.2%), common microdeletion 22q11.2 (2.4%), Williams-Beuren syndrome (1.3%), Fragile-X syndrome (1.2%), Cohen syndrome (0.7%), and monosomy 1p36.3 (0.6%). From our data, we suggest the following diagnostic procedure in patients with unexplained developmental delay or mental retardation: (1) Clinical/dysmorphological investigation with respective targeted analyses; (2) In the remaining patients without an etiological diagnosis, we suggest conventional karyotyping, X-inactivation screening in mothers of boys, and molecular karyotyping, if available. If molecular karyotyping is not available, subtelomeric screening should be performed.
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PMID:Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. 1691 49

Neuropsychological investigation of the development of the mnesic function in mental retardation has primarily focused on evaluating short-term memory (STM). Studies have often documented a reduced verbal short-term memory span in individuals with mental retardation and with Down syndrome in particular, compared to groups of mental age-matched controls. However, recent evidence suggests that verbal short-term memory is not equally impaired in all individuals with mental retardation. Findings in children with Williams syndrome are particularly relevant in this regard. Also, data concerning STM for visual information suggest that visual-object and visual-spatial working memory may be differently compromised in people with mental retardation. In particular, individuals with Williams syndrome exhibit specific difficulties in visual-spatial but not in visual-object working memory tasks compared to typically-developing children matched for mental age. Instead, people with Down syndrome show reduced performance in both visual-spatial and visual-object tests. Taken together, these results reinforce the view that intellectual disability is not a unitary condition characterized by homogeneous slowness of cognitive development but a variety of conditions in which some cognitive functions may be more disrupted than others. The finding that the working memory deficit in individuals with Williams and Down syndrome may be qualitatively differentiated also supports the hypothesis that it is not simply a manifestation of general cognitive impairment but, rather, the expression of a specific deficit of a discrete cognitive ability.
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PMID:Short-term memory deficits are not uniform in Down and Williams syndromes. 1696 45

MLPA analysis for a panel of syndromes with mental retardation (MRS-MLPA) was used for investigation of 258 mentally retarded and dysmorphic patients with normal conventional karyotypes (P064 probe set, MRC-Holland, for detection of (micro)deletions associated with 1p36-deletion, Sotos, Williams-Beuren, Prader-Willi, Angelman, Miller-Dieker, Smith-Magenis, and 22q11-deletion syndromes). Patients were initially referred for HR-CGH analysis and MRS-MLPA was performed retrospectively. MRS-MLPA analysis revealed imbalances in 15/258 patients (5.8%). Ten deletions were identified, including deletions of 1p36, 5q35 (Sotos syndrome), 7q11 (Williams-Beuren syndrome), 17p11 (Smith-Magenis syndrome), 15q11 (Angelman syndrome) and 22q11. Duplications were detected in 5q35, 7q11, 17p13, 17p11 and 22q11. We reviewed another 170 patients referred specifically for MRS-MLPA analysis. Eighty of these patients were referred with a clinical suspicion of a specific syndrome, which was confirmed in 17 patients (21.3%). The remaining 90 patients were referred because of mental retardation and dysmorphism but without suspicion of a specific syndrome. Seven imbalances, including four duplications, were detected in these 90 patients (7.8%). Clinical data regarding three patients investigated by MRS-MLPA are presented. The imbalances carried by these patients include a small interstitial 1p36 deletion, a small duplication of 5q35 (encompassing the NSD1 gene, which is deleted/mutated in Sotos syndrome) and a duplication of 7q11 (reciprocal of the Williams-Beuren syndrome deletion), respectively. MRS-MLPA allows testing for a number of micro-deletions/-duplications in a single experiment, thereby filling a gap between array techniques and single locus techniques. MRS-MLPA combined with Subtelomeric MLPA represents an attractive first test in a clinical algorithm for mental retardation.
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PMID:MLPA analysis for a panel of syndromes with mental retardation reveals imbalances in 5.8% of patients with mental retardation and dysmorphic features, including duplications of the Sotos syndrome and Williams-Beuren syndrome regions. 1709 Mar 94

Williams Syndrome (WS, [MIM 194050]) is a disorder caused by a hemizygous deletion of 25-30 genes on chromosome 7q11.23. Several of these genes including those encoding cytoplasmic linker protein-115 (CYLN2) and general transcription factors (GTF2I and GTF2IRD1) are expressed in the brain and may contribute to the distinct neurological and cognitive deficits in WS patients. Recent studies of patients with partial deletions indicate that hemizygosity of GTF2I probably contributes to mental retardation in WS. Here we investigate whether CYLN2 and GTF2IRD1 contribute to the motoric and cognitive deficits in WS. Behavioral assessment of a new patient in which STX1A and LIMK1, but not CYLN2 and GTF2IRD1, are deleted showed that his cognitive and motor coordination functions were significantly better than in typical WS patients. Comparative analyses of gene specific CYLN2 and GTF2IRD1 knockout mice showed that a reduced size of the corpus callosum as well as deficits in motor coordination and hippocampal memory formation may be attributed to a deletion of CYLN2, while increased ventricle volume can be attributed to both CYLN2 and GTF2IRD1. We conclude that the motor and cognitive deficits in Williams Syndrome are caused by a variety of genes and that heterozygous deletion of CYLN2 is one of the major causes responsible for such dysfunctions.
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PMID:Contribution of CYLN2 and GTF2IRD1 to neurological and cognitive symptoms in Williams Syndrome. 1727 Apr 52


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