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Epilepsia 2000Although for most children epilepsy is a relatively benign disorder, for some, epilepsy can be designated as "catastrophic" because the seizures are so difficult to... (Review)
Review
Although for most children epilepsy is a relatively benign disorder, for some, epilepsy can be designated as "catastrophic" because the seizures are so difficult to control and because they are strongly associated with mental retardation. The catastrophic childhood epilepsies include uncommon disorders such as early infantile epileptic encephalopathy with suppression burst, severe myoclonic epilepsy of infancy, and epilepsy with myoclonic-astatic seizures. There are other syndromes that are relatively common such as infantile spasms, Lennox-Gastaut syndrome, and Sturge-Weber syndrome. Many children with catastrophic epilepsy have the seizures as a result of underlying brain abnormalities that will inevitably lead to mental retardation whether or not they have seizures. In some patients, however, the mental retardation appears to be caused by the seizures. Developmental plasticity provides children with an opportunity to recover from significant brain injuries. However, the plasticity may also be the cause of the mental retardation. In such patients, control of the seizures may lead to more normal intellectual development. Thus, every effort should be made to control seizures in children with catastrophic epilepsy.
Topics: Anticonvulsants; Brain; Child; Child, Preschool; Encephalitis; Epilepsies, Myoclonic; Epilepsy; Humans; Infant; Intellectual Disability; Neuronal Plasticity; Outcome Assessment, Health Care; Severity of Illness Index; Spasms, Infantile; Sturge-Weber Syndrome
PubMed: 10885734
DOI: 10.1111/j.1528-1157.2000.tb01518.x -
Journal of Medical Genetics Jul 1998The fragile X syndrome is characterised by mental retardation, behavioural features, and physical features, such as a long face with large protruding ears and... (Review)
Review
The fragile X syndrome is characterised by mental retardation, behavioural features, and physical features, such as a long face with large protruding ears and macro-orchidism. In 1991, after identification of the fragile X mental retardation (FMR1) gene, the cytogenetic marker (a fragile site at Xq27.3) became replaced by molecular diagnosis. The fragile X syndrome was one of the first examples of a "novel" class of disorders caused by a trinucleotide repeat expansion. In the normal population, the CGG repeat varies from six to 54 units. Affected subjects have expanded CGG repeats (>200) in the first exon of the FMR1 gene (the full mutation). Phenotypically normal carriers of the fragile X syndrome have a repeat in the 43 to 200 range (the premutation). The cloning of the FMR1 gene led to the characterisation of its protein product FMRP, encouraged further clinical studies, and opened up the possibility of more accurate family studies and fragile X screening programmes.
Topics: Chromosome Fragile Sites; Chromosome Fragility; DNA Mutational Analysis; Female; Fragile X Mental Retardation Protein; Fragile X Syndrome; Genetic Testing; Humans; Intellectual Disability; Male; Minisatellite Repeats; Nerve Tissue Proteins; Phenotype; RNA-Binding Proteins; X Chromosome
PubMed: 9678703
DOI: 10.1136/jmg.35.7.579 -
Journal of Medical Genetics Jun 1991Non-specific X linked mental retardation (MRX) is mental retardation in persons of normal physical appearance who have no recognisable features apart from a... (Review)
Review
Non-specific X linked mental retardation (MRX) is mental retardation in persons of normal physical appearance who have no recognisable features apart from a characteristic pedigree. Review of published reports shows that there is clinical variability in the degree of mental retardation within families and genetic heterogeneity, based on gene localisation, between families. We propose a classification based on genetic localisation and a set of minimal clinical features that should be recorded in the hope of identifying possible specific phenotypes.
Topics: Genetic Linkage; Humans; Intellectual Disability; X Chromosome
PubMed: 1870094
DOI: 10.1136/jmg.28.6.378 -
Revista de Neurologia Oct 2006Mental retardation is a frequently occurring disorder with a major impact on the life of the affected person, the family and society, with an estimated incidence of 1-3%... (Review)
Review
INTRODUCTION
Mental retardation is a frequently occurring disorder with a major impact on the life of the affected person, the family and society, with an estimated incidence of 1-3% in developed countries. Among the etiologies that cause mental retardation it would appear that 30% have a genetic origin, 15% have an environmental origin, and the rest have an unknown origin. AIM. To report the genetic causes of mental retardation and the new molecular techniques used in order to reach a diagnosis. The identification of the causes of mental retardation is of great interest due to the consequences it has in the intervention, prognosis, estimation of risk of recurrence and its prevention.
DEVELOPMENT
Causes of mental retardation are extremely heterogeneous. Genetic causes can be classified as chromosomal alterations (aneuploidies, subtelomeric rearrangements, microdeletion or microduplication syndrome), monogenic, metabolic, or multifactorial alterations. Thanks to the development of high-resolution new techniques -comparative genomic hybridization (CGH) arrays, and multiplex ligation probe amplification (MLPA)- now we are able to detect microdeletions and microduplication all over the genome, which might be related with mental retardation.
CONCLUSIONS
The genetic causes of mental retardation are highly heterogeneous and complex. Nowadays and thanks to the new molecular techniques we are able to perform several studies, even though almost half of cases remain undiagnosed. In those undiagnosed cases with positive familial history a genetic counseling can be provided. However, in order to perform a prenatal or a preimplantational study a genetic diagnosis is required.
Topics: Chromosome Mapping; Female; Humans; Intellectual Disability; Male
PubMed: 17061189
DOI: No ID Found -
Mental Retardation Apr 1964
Topics: Humans; Intellectual Disability; Mental Health Services; Societies; Societies, Medical
PubMed: 14143147
DOI: No ID Found -
Neuropharmacology Jun 2011Fragile X mental retardation protein (FMRP) is highly enriched in neurons and binds to approximately 4% of mRNAs in mammalian brain. Its loss is a hallmark of fragile X... (Review)
Review
Fragile X mental retardation protein (FMRP) is highly enriched in neurons and binds to approximately 4% of mRNAs in mammalian brain. Its loss is a hallmark of fragile X syndrome (FXS), the most common form of mental retardation. In this review we discuss the mutation in the fragile X mental retardation-1 gene (FMR1), that leads to FXS, the role FMRP plays in neuronal cells, experiments from our own laboratory that demonstrate reductions of FMRP in additional psychiatric disorders (autism, schizophrenia, bipolar disorder, and major depressive disorder), and potential therapies to ameliorate the loss of FMRP. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
Topics: Animals; Autistic Disorder; Cerebellum; Female; Fragile X Mental Retardation Protein; Fragile X Syndrome; Humans; Intellectual Disability; Male; Mental Disorders; Mice; Molecular Targeted Therapy
PubMed: 21108954
DOI: 10.1016/j.neuropharm.2010.11.011 -
Frontiers in Neural Circuits 2013Psychiatric disorders are a diverse set of diseases that affect all aspects of mental function including social interaction, thinking, feeling, and mood. Although... (Review)
Review
Psychiatric disorders are a diverse set of diseases that affect all aspects of mental function including social interaction, thinking, feeling, and mood. Although psychiatric disorders place a large economic burden on society, the drugs available to treat them are often palliative with variable efficacy and intolerable side-effects. The development of novel drugs has been hindered by a lack of knowledge about the etiology of these diseases. It is thus necessary to further investigate psychiatric disorders using a combination of human molecular genetics, gene-by-environment studies, in vitro pharmacological and biochemistry experiments, animal models, and investigation of the non-biological basis of these diseases, such as environmental effects. Many psychiatric disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder, mental retardation, and schizophrenia can be triggered by alterations to neural development. The zebrafish is a popular model for developmental biology that is increasingly used to study human disease. Recent work has extended this approach to examine psychiatric disorders as well. However, since psychiatric disorders affect complex mental functions that might be human specific, it is not possible to fully model them in fish. In this review, I will propose that the suitability of zebrafish for developmental studies, and the genetic tools available to manipulate them, provide a powerful model to study the roles of genes that are linked to psychiatric disorders during neural development. The relative speed and ease of conducting experiments in zebrafish can be used to address two areas of future research: the contribution of environmental factors to disease onset, and screening for novel therapeutic compounds.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Disease Models, Animal; Embryonic Development; Humans; Intellectual Disability; Mental Disorders; Schizophrenia; Zebrafish
PubMed: 23637652
DOI: 10.3389/fncir.2013.00079 -
The Clinical Neuropsychologist Aug 2016To provide an historical perspective and overview of the phenotypes, mechanism, pathology, and epidemiology of the fragile X-associated tremor/ataxia syndrome (FXTAS)... (Review)
Review
OBJECTIVES
To provide an historical perspective and overview of the phenotypes, mechanism, pathology, and epidemiology of the fragile X-associated tremor/ataxia syndrome (FXTAS) for neuropsychologists.
METHODS
Selective review of the literature on FXTAS.
RESULTS
FXTAS is an X-linked neurodegenerative disorder of late onset. One of several phenotypes associated with different mutations of the fragile X mental retardation 1 gene (FMR1), FXTAS involves progressive action tremor, gait ataxia, and impaired executive functioning, among other features. It affects carriers of the FMR1 premutation, which may expand when passed from a mother to her children, in which case it is likely to cause fragile X syndrome (FXS), the most common inherited developmental disability.
CONCLUSION
This review briefly summarizes current knowledge of the mechanisms, epidemiology, and mode of transmission of FXTAS and FXS, as well as the neuropsychological, neurologic, neuropsychiatric, neuropathologic, and neuroradiologic phenotypes of FXTAS. Because it was only recently identified, FXTAS is not well known to most practitioners, and it remains largely misdiagnosed, despite the fact that its prevalence may be relatively high.
Topics: Ataxia; Executive Function; Female; Fragile X Mental Retardation Protein; Fragile X Syndrome; Humans; Intellectual Disability; Male; Neuropsychological Tests; Phenotype; Tremor
PubMed: 27356167
DOI: 10.1080/13854046.2016.1184652 -
Journal of Medical Genetics Mar 2006Mental retardation is more common in males than females in the population, assumed to be due to mutations on the X chromosome. The prevalence of the 24 genes identified... (Review)
Review
Mental retardation is more common in males than females in the population, assumed to be due to mutations on the X chromosome. The prevalence of the 24 genes identified to date is low and less common than expansions in FMR1, which cause Fragile X syndrome. Systematic screening of all other X linked genes in X linked families with mental retardation is currently not feasible in a clinical setting. The phenotypes of genes causing syndromic and non-syndromic mental retardation (NLGN3, NLGN4, RPS6KA3(RSK2), OPHN1, ATRX, SLC6A8, ARX, SYN1, AGTR2, MECP2, PQBP1, SMCX, and SLC16A2) are first discussed, as these may be the focus of more targeted mutation analysis. Secondly, the relative prevalence of genes causing only non-syndromic mental retardation (IL1RAPL1, TM4SF2, ZNF41, FTSJ1, DLG3, FACL4, PAK3, ARHGEF6, FMR2, and GDI) is summarised. Thirdly, the problem of recurrence risk where a molecular genetics diagnosis has not been made and what proportion of the male excess of mental retardation is due to monogenic disorders of the X chromosome are discussed.
Topics: Cerebellar Ataxia; Chromosome Mapping; Chromosomes, Human, X; Diagnosis, Differential; Genetic Markers; Humans; Intellectual Disability; Intelligence
PubMed: 16118346
DOI: 10.1136/jmg.2005.033043 -
Journal of Medical Genetics Jun 1991
Review
Topics: Genetic Linkage; Humans; Intellectual Disability; X Chromosome
PubMed: 1870092
DOI: 10.1136/jmg.28.6.361