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

Neurologic and cognitive function in neurofibromatosis type 1 (NF1) were assessed in a controlled pilot study of 13 pairs of siblings aged 6 to 27 years. One subject in each pair was affected with NF1, and the other, the control subject, was unaffected. Subjects with evidence of focal central nervous system disease were excluded. The 13 subjects with NF1 had no excess of mental retardation, attention-deficit disorder, or specific learning disorders (using Wilcoxon's Signed Rank Test and McNemar's Test for Symmetry). These subjects, however, had significantly higher scores for subtle neurologic abnormalities (21 vs 6) and significantly lower full-scale IQ scores (94 vs 105) than their unaffected siblings. The IQ scores of the affected subjects were not clustered at the lower end of the scale but showed a slight downward shift in distribution compared with those of their siblings. In addition, a visual-spatial orientation deficit was present in eight of nine affected subjects so evaluated. The findings suggest that subjects with NF1 have a widespread alteration of the brain during development that manifests as one or more specific types of neuropsychologic deficits.
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PMID:Neurofibromatosis type 1 (Recklinghausen's disease). Neurologic and cognitive assessment with sibling controls. 250 Aug 44

Areas of increased signal seen on magnetic resonance imaging (MRI) of the brain are frequently present in neurofibromatosis and are considered possible areas of dysplasia or heterotopias. Since Rosman and Pearce [Brain 1967; 90:829-838] have shown that neuronal heterotopias in deep cerebral white matter are associated with mental retardation in neurofibromatosis type 1 (NF-1), we hypothesized that these areas of increased signal seen on MRI should be associated with learning difficulties or incoordination in children with NF-1. Using MRI, we studied 31 children with NF-1 and attempted to correlate the presence of areas of increased signal with learning difficulties or incoordination. We found no association. This suggests that either these areas of increased signal are heterotopias which are not associated with learning difficulties or incoordination, or these areas of increased signal are not heterotopias and are not relevant to the study of learning problems or incoordination in children with NF-1.
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PMID:Magnetic resonance imaging evaluation of learning difficulties and incoordination in neurofibromatosis. 251 20

Multiple lentigines (LEOPARD) syndrome has been delineated as an autosomal dominant disorder with lentigines, cardiac abnormalities, variable mental retardation, and typical craniofacial features as the most characteristic findings. LEOPARD syndrome shows a great clinical overlap with neurofibromatosis type 1 (NF1). In this report we describe a de novo missense mutation (M 1035R) in exon 18 of the NF1 gene in a young woman with a prior diagnosis of LEOPARD syndrome. We hypothesize that some patients now diagnosed with LEOPARD syndrome have in fact a mutation in the NF1 gene, whereas in other patients with LEOPARD syndrome, a different gene might be involved.
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PMID:Neurofibromatosis type I gene mutation in a patient with features of LEOPARD syndrome. 880 36

We report on a rare patient screened as a putative carrier of a contiguous gene syndrome on the basis of a complex phenotype characterized by sporadic neurofibromatosis type 1 (NF1), dysmorphism, mental retardation and severe skeletal anomalies. A cytogenetically visible 17q11.2 deletion was detected in the patient's karyotype by high-resolution banding and confirmed by fluorescence in situ hybridization with yeast artificial chromosomes targeting the NF1 region. Analysis of the segregation from parents to proband of 13 polymorphic DNA markers, either contiguous or contained within the NF1 gene, showed that the patient is hemizygous at sites within the NF1 gene-the AAAT-Alu repeat in the 5' region of intron 27b, the CA/GT microsatellite in the 3' region of intron 27b, and the CA/GT microsatellite in intron 38- and at the extragenic D17S798 locus, distal to the 3' end of NF1. The patient may be an important resource in the identification of genes downstream of NF1 that may contribute to some of his extra-NF1 clinical signs.
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PMID:Characterization of a cytogenetic 17q11.2 deletion in an NF1 patient with a contiguous gene syndrome. 893 93

A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene deletions by comparing patient and parent genotypes at 10 intragenic polymorphic loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases), five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion. These five patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features, in contrast to previous reports of large NF1 deletions. All five deletions were de novo and occurred on the maternal chromosome. However, two patients showed partial LOH, consistent with somatic mosaicism for the deletion, suggesting that mosaicism may be more frequent in NF1 than previously recognised (and may have bearing on clinical severity). We suggest that large NF1 deletions (1) are not always associated with unusual clinical features, (2) tend to occur more frequently on maternal alleles, and (3) are an important mechanism for constitutional and somatic mutations in NF1 patients.
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PMID:Constitutional and mosaic large NF1 gene deletions in neurofibromatosis type 1. 964 87

A number of neurodevelopmental disorders are caused by defects in activity dependent neuronal plasticity, the process by which neuronal activity shapes developing neuronal circuits. These disorders are caused by genetic mutations or other factors that disrupt intracellular signaling pathways that link the cell surface with the nuclear machinery for gene expression. The signaling pathways disrupted by these disorders are involved in learning, memory and behavior as well as in the synaptic proliferation and pruning that occurs during normal development. Examples of neurodevelopmental disorders that target plasticity include X-linked disorders such as Rett, Fragile-X and Coffin-Lowry Syndromes as well as acquired disorders such as cretinism. Several other X-linked mental retardation syndromes as well as autosomal disorders including neurofibromatosis type 1 and tuberous sclerosis also involve signaling pathways involved in neuronal plasticity. Disruption of neuronal plasticity is a mechanism that may underlie a diverse group of neurodevelopmental disorders.
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PMID:Developmental disorders of activity dependent neuronal plasticity. 1140 58

Homologous recombination between poorly characterized regions flanking the NF1 locus causes the constitutional loss of approximately 1.5 Mb from 17q11.2 covering > or =11 genes in 5%-20% of patients with neurofibromatosis type 1 (NF1). To elucidate the extent of microheterogeneity at the deletion boundaries, we used single-copy DNA fragments from the extreme ends of the deleted segment to perform FISH on metaphase chromosomes from eight patients with NF1 who had large deletions. In six patients, these probes were deleted, suggesting that breakage and fusions occurred within the adjacent highly homologous sequences. Reexamination of the deleted region revealed two novel functional genes FLJ12735 (AK022797) and KIAA0653-related (WI-12393 and AJ314647), the latter of which is located closest to the distal boundary and is partially duplicated. We defined the complete reading frames for these genes and two expressed-sequence tag (EST) clusters that were reported elsewhere and are associated with the markers SHGC-2390 and WI-9521. Hybrid cell lines carrying only the deleted chromosome 17 were generated from two patients and used to identify the fusion sequences by junction-specific PCRs. The proximal breakpoints were found between positions 125279 and 125479 in one patient and within 4 kb of position 143000 on BAC R-271K11 (AC005562) in three patients, and the distal breakpoints were found at the precise homologous position on R-640N20 (AC023278). The interstitial 17q11.2 microdeletion arises from unequal crossover between two highly homologous WI-12393-derived 60-kb duplicons separated by approximately 1.5 Mb. Since patients with the NF1 large-deletion syndrome have a significantly increased risk of neurofibroma development and mental retardation, hemizygosity for genes from the deleted region around the neurofibromin locus (CYTOR4, FLJ12735, FLJ22729, HSA272195 (centaurin-alpha2), NF1, OMGP, EVI2A, EVI2B, WI-9521, HSA272196, HCA66, KIAA0160, and WI-12393) may contribute to the severe phenotype of these patients.
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PMID:Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions. 1146 90

A 20 year old male patient with sporadic neurofibromatosis type 1 (NF1) is described with a large deletion (1.5 Mb) involving the NF1 gene, dysmorphism, mental retardation, and unusual ocular and skeletal features. Several NF1 patients with a large NF1 deletion and associated dysmorphism, and a large number of neurofibromas for their age have been described. This study indicates that such large deletions can also involve flanking loci which affect ocular and skeletal development.
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PMID:A large deletion (1.5 Mb) encompassing the neurofibromatosis type 1 (NF1) gene in a patient with sporadic NF1 associated with dysmorphism, mental retardation, and unusual ocular and skeletal features. 1456 62

Detailed analyses of 20 patients with sporadic neurofibromatosis type 1 (NF1) microdeletions revealed an unexpected high frequency of somatic mosaicism (8/20 [40%]). This proportion of mosaic deletions is much higher than previously anticipated. Of these deletions, 16 were identified by a screen of unselected patients with NF1. None of the eight patients with mosaic deletions exhibited the mental retardation and facial dysmorphism usually associated with NF1 microdeletions. Our study demonstrates the importance of a general screening for NF1 deletions, regardless of a special phenotype, because of a high estimated number of otherwise undetected mosaic NF1 microdeletions. In patients with mosaicism, the proportion of cells with the deletion was 91%-100% in peripheral leukocytes but was much lower (51%-80%) in buccal smears or peripheral skin fibroblasts. Therefore, the analysis of other tissues than blood is recommended, to exclude mosaicism with normal cells in patients with NF1 microdeletions. Furthermore, our study reveals breakpoint heterogeneity. The classic 1.4-Mb deletion was found in 13 patients. These type I deletions encompass 14 genes and have breakpoints in the NF1 low-copy repeats. However, we identified a second major type of NF1 microdeletion, which spans 1.2 Mb and affects 13 genes. This type II deletion was found in 8 (38%) of 21 patients and is mediated by recombination between the JJAZ1 gene and its pseudogene. The JJAZ1 gene, which is completely deleted in patients with type I NF1 microdeletions and is disrupted in deletions of type II, is highly expressed in brain structures associated with learning and memory. Thus, its haploinsufficiency might contribute to mental impairment in patients with constitutional NF1 microdeletions. Conspicuously, seven of the eight mosaic deletions are of type II, whereas only one was a classic type I deletion. Therefore, the JJAZ1 gene is a preferred target of strand exchange during mitotic nonallelic homologous recombination. Although type I NF1 microdeletions occur by interchromosomal recombination during meiosis, our findings imply that type II deletions are mediated by intrachromosomal recombination during mitosis. Thus, NF1 microdeletions acquired during mitotic cell divisions differ from those occurring in meiosis and are caused by different mechanisms.
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PMID:High frequency of mosaicism among patients with neurofibromatosis type 1 (NF1) with microdeletions caused by somatic recombination of the JJAZ1 gene. 1525 18

The neurocutaneous syndromes are characterized by congenital dysplastic abnormalities involving the skin and nervous system. We included in the study 23 children diagnosed with different types of neurocutaneous syndrome (10 patients with tuberous sclerosis, 5 with Sturge-Weber syndrome and 8 with neurofibromatosis type 1 and epilepsy'. The factors studied included: age at onset of seizures, seizure types and frequency, seizure response of treatment, EEG, CT/MRI, neurologic, neuro-ophthalmologic and psychological examination. In 39.13% of cases the epilepsy onset preceded the clinical diagnosis of neurocutaneous disorders. The age of seizure onset ranged from 4 month to 5 years. The most common type of seizure appear to be complex partial. 21.73% of patients associated mental retardation. Therapeutical efficacy was variable depending on type of seizure and type of neurocutaneous syndromes.
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PMID:[Neurocutaneous syndromes and epilepsy. Report of 23 cases and review of the literature]. 1583 77


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