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

Facioscapulohumeral muscular dystrophy is one of the most prevalent muscular dystrophies in the world, resulting from the deletion of tandem repeats on chromosome 4q35. Extramuscular associations include sensorineural hearing loss, mental retardation, and epilepsy. These manifestations are commonly found in those with large deletions and early onset of weakness. A 26-year-old patient with a long-standing history of hearing loss, learning disabilities, and epilepsy presented with new-onset weakness and an elevated serum creatinine kinase level. Genetic testing confirmed sporadic facioscapulohumeral muscular dystrophy with a fragment length of 12 kilobases (normal > 35 kilobases). This unique presentation suggests that facioscapulohumeral muscular dystrophy should be considered in the differential diagnosis of children with cognitive impairment, seizures, and hearing loss.
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PMID:Facioscapulohumeral muscular dystrophy can be a cause of isolated childhood cognitive dysfunction. 1690 30

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

The laboratory hallmark of BCECTS is the rolandic discharge (RD) in the EEG of patients, occurring in a characteristic topographical, vigilance-related, event-related, and age-related pattern, disappearing during puberty. RDs are present in 2% of healthy children. About 8% of children with RDs have epilepsy. An increased prevalence rate of RDs is found in children with cognitive and behavioral disorders, with headaches and some genetic syndromes. In some patients, the cognitive disorders are transient but in others they are progressive, resulting in stable mental retardation after puberty. A recent study of 36 BCECTS patients addressed the following questions. (1) the possible relationship between the severity of RDs and the neuropsychological deficits; (2) the profile of neuropsychological deficits; (3) changes of cognition related to EEG changes; and (4) effects of therapy. No correlation was found between global IQ and the severity of the RDs. All the children had at least one specific learning disorder (sometimes long-lasting). When the children were treated, a correlation between cognitive and EEG improvement could not be demonstrated. Recently, 21 patients without epilepsy but with attention deficit and hyperactivity and/or learning disorders were studied: an open treatment trial with sulthiame resulted in improved sustained and selective attention. The neurobiology of RDs and their relationship to cognitive dysfunction and epilepsy requires further study.
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PMID:The spectrum from BCECTS to LKS: The Rolandic EEG trait-impact on cognition. 1710 66

Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases.
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PMID:Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci. 1712 46

Fragile-X-syndrome (FXS) is the most common type of inherited cognitive impairment. The underlying molecular alteration consists of a CGG-repeat amplification within the FMR-1 gene. The phenotype is only apparent once a threshold in the number of repeats has been exceeded (full mutation). The aim of this study was to characterize the FMR-1 CGG-repeat status in Argentine patients exhibiting mental retardation. A total of 330 blood samples from patients were analyzed by PCR and Southern blot analysis. Initially, DNA from 78 affected individuals were studied by PCR. Since this method is unable to detect high molecular weight alleles, however, we undertook a second approach using the Southern blotting technique to analyze the CGG repeat number and methylation status. Southern blot analysis showed an altered pattern in 14 out of 240 (6%) unrelated patients, with half of them presenting a mosaic pattern. Eight out of 17 families (47%) showed a (suggest deleting highlight). The characteristic FXS pattern was identified in 8/17 families (47%), and in 4 of these families 25% of the individuals presented with a mosaic model. The expansion from pre-mutation to full mutation was shown to occur both at the pre and post zygotic levels. The detection of FXS mutations has allowed us to offer more informed genetic counseling, prenatal diagnosis and reliable patient follow-up.
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PMID:Fragile-X mental retardation: molecular diagnosis in Argentine patients. 1712 14

Autism spectrum disorders (ASDs) are more frequently associated with tic disorders than expected by chance. Variable rates of comorbidity have been reported and common genetic and neurobiological factors are probably involved. The aim of this study was to determine the rate of tic disorders in a clinical sample (n = 105) of children and adolescents with ASDs and to describe the clinical characteristics of a group with comorbid ASDs and tics (n = 24). The overlap between tics and other repetitive movements and behaviors in ASDs was carefully assessed. Among individuals with ASDs, 22 percent presented tic disorders: 11 percent with Tourette disorder (TD), and 11 percent with chronic motor tics. All had various degrees of cognitive impairment. An association between the level of mental retardation and tic severity was found. It is concluded that the occurrence of tics in ASDs should not be overlooked and should be carefully evaluated.
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PMID:Tics and Tourette syndrome in autism spectrum disorders. 1717 71

The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers.
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PMID:Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. 1722 67

Autosomal recessive inheritance of non-syndromic mental retardation (ARNSMR) may account for approximately 25% of all patients with non-specific mental retardation (NSMR). Although many X-linked genes have been identified as a cause of NSMR, only three autosomal genes are known to cause ARNSMR. We present here a large consanguineous Turkish family with four mentally retarded individuals from different branches of the family. Clinical tests showed cognitive impairment but no neurological, skeletal, and biochemical involvements. Genome-wide mapping using Human Mapping 10K Array showed a single positive locus with a parametric LOD score of 4.92 in a region on chromosome 1p21.1-p13.3. Further analyses using polymorphic microsatellite markers defined a 6.6-Mb critical region containing approximately 130 known genes. This locus is the fourth one linked to ARNSMR.
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PMID:A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1-p13.3. 1730 43

Coffin-Lowry syndrome (CLS) is a rare form of X-linked mental retardation caused by mutations of the RSK2 gene, associated with cognitive impairment and skeletal malformations. We conducted the first morphometric study of CLS brain morphology by comparing brain volumes from two CLS families with healthy controls. Individuals with CLS consistently showed markedly reduced total brain volume. Cerebellum and hippocampus volumes were particularly impacted by CLS and may be associated with specific interfamilial RSK2 mutations. We provide preliminary evidence that the magnitude of hippocampus volume deviation from that of controls may predict general cognitive outcome in CLS.
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PMID:Altered neurodevelopment associated with mutations of RSK2: a morphometric MRI study of Coffin-Lowry syndrome. 1731 37

The CC2D1A gene family consists of two homologous genes, Freud-1/CC2D1A and Freud-2/CC2D1B, that share conserved domains, including several DM14 domains that are specific to this protein family, a C-terminal helix-loop-helix domain, and a C2 calcium-dependent phospholipid binding domain. Although the function of Freud-2 is unknown, Freud-1 has been shown to function as a transcriptional repressor of the serotonin-1A receptor gene that binds to a novel DNA element (FRE, 5'-repressor element). The DNA binding and repressor activities of Freud-1 are inhibited by calcium-calmodulin-dependent protein kinase. Recently, a deletion in the CC2D1A gene has been linked to nonsyndromic mental retardation. This deletion results in the truncation of the helix-loop-helix DNA binding and the C2 domains, crucial for Freud-1 repressor activity, and hence is predicted to generate an inactive or weakly dominant negative protein. The possible mechanisms by which inactivation of Freud-1 could lead to abnormal cortical development and cognitive impairment and the potential roles of Freud-1 gene targets are discussed.
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PMID:The Freud-1/CC2D1A family: transcriptional regulators implicated in mental retardation. 1739 59


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