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Archives of Disease in Childhood Jun 1981
Review
Topics: Female; Genetic Markers; Heterozygote; Humans; Intellectual Disability; Male; Prenatal Diagnosis; Sex Chromosome Aberrations; X Chromosome
PubMed: 7020610
DOI: 10.1136/adc.56.6.410 -
Journal of the American Academy of... Sep 1991During the past decade, noteworthy advances have taken place within the field of mental retardation. The application of advanced biological techniques in such areas as... (Review)
Review
During the past decade, noteworthy advances have taken place within the field of mental retardation. The application of advanced biological techniques in such areas as molecular genetics and neuroimaging has substantially improved our ability to identify the biological factors that underlie the origin and pathogenesis of an increasing number of mental retardation syndromes. Refined genetic and psychosocial assessments have highlighted the impressive degree of heterogeneity that is present within and across many mental retardation syndromes, stimulating increasing interest and study. This, the first of a two-part review, will focus on recent developments in biological and phenomenological aspects of mental retardation.
Topics: Adolescent; Brain Damage, Chronic; Child; Diagnosis, Differential; Humans; Intellectual Disability; Neurocognitive Disorders; Risk Factors
PubMed: 1938783
DOI: 10.1016/s0890-8567(10)80001-2 -
The Israel Medical Association Journal... Nov 2008
Review
Topics: Chromosome Aberrations; Comparative Genomic Hybridization; Genetic Counseling; Humans; Intellectual Disability; Karyotyping; Metabolism, Inborn Errors; Recurrence
PubMed: 19070297
DOI: No ID Found -
The Journal of Neuroscience : the... Nov 2010Down syndrome (DS) is the most common example of a neurogenetic aneuploid disorder leading to mental retardation. In most cases, DS results from an extra copy of human... (Review)
Review
Down syndrome (DS) is the most common example of a neurogenetic aneuploid disorder leading to mental retardation. In most cases, DS results from an extra copy of human chromosome 21 producing deregulated gene expression in brain that gives raise to subnormal intellectual functioning. Understanding the consequences of dosage imbalance attributable to trisomy 21 (T21) has accelerated because of recent advances in genome sequencing, comparative genome analysis, functional genome exploration, and the use of model organisms. This has led to new evidence-based therapeutic approaches to prevention or amelioration of T21 effects on brain structure and function (cognition) and has important implications for other areas of research on the neurogenomics of cognition and behavior.
Topics: Animals; Disease Models, Animal; Down Syndrome; Humans; Intellectual Disability
PubMed: 21068296
DOI: 10.1523/JNEUROSCI.3728-10.2010 -
ELife Oct 2023Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake in the brain results in intellectual...
Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake in the brain results in intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human brain organoids from induced pluripotent stem cells of healthy subjects and CTD patients. Brain organoids from CTD donors had reduced creatine uptake compared with those from healthy donors. The expression of neural progenitor cell markers SOX2 and PAX6 was reduced in CTD-derived organoids, while GSK3β, a key regulator of neurogenesis, was up-regulated. Shotgun proteomics combined with integrative bioinformatic and statistical analysis identified changes in the abundance of proteins associated with intellectual disability, epilepsy, and autism. Re-establishment of the expression of a functional SLC6A8 in CTD-derived organoids restored creatine uptake and normalized the expression of SOX2, GSK3β, and other key proteins associated with clinical features of CTD patients. Our brain organoid model opens new avenues for further characterizing the CTD pathophysiology and supports the concept that reinstating creatine levels in patients with CTD could result in therapeutic efficacy.
Topics: Humans; Intellectual Disability; Creatine; Glycogen Synthase Kinase 3 beta; Mental Retardation, X-Linked; Brain; Organoids
PubMed: 37830910
DOI: 10.7554/eLife.88459 -
Revista de Neurologia Sep 2013Despite the advances made in the field of genetics, neuroimaging and metabolic diseases, half the children with mental retardation remain without an aetiological... (Review)
Review
Despite the advances made in the field of genetics, neuroimaging and metabolic diseases, half the children with mental retardation remain without an aetiological diagnosis. A genetic base is estimated to be present in 40% of cases, environmental teratogens and prematurity in 20%, metabolic diseases in 1-5% and multifactor causes in 3-12%. The family history, the detailed medical records required by dysmorphology and the neurological examination will make it possible to establish or suspect a diagnosis in two thirds of the cases and, in the others, scanning tests will be able to confirm an aetiology. The order of the studies will be guided by the clinical picture: karyotype if a chromosome pathology is suspected, neuroimaging if there is some abnormality in the neurological examination and specific genetic or neurometabolic studies to confirm the clinical presumption. The estimated diagnostic performance of the different techniques is: karyotype, 9%; fragile X, 5%; subtelomeric abnormalities, 4%; neurometabolic diseases, 1%, and new microarray techniques, 19%. As a result of the higher performance and cost-benefit ratio, today the recommended procedure, as the first line of treatment for unexplainable cases of mental retardation, is the study of microarrays. Although the outcomes of these tests are complex and require confirmation and careful interpretation by a specialist in medical genetics, the advances in their technological development and resolution, together with lower costs make this technique a fundamental tool in the identification of the aetiology in these children.
Topics: Child; Child, Preschool; Developmental Disabilities; Female; Humans; Infant, Premature; Infant, Premature, Diseases; Intellectual Disability; Male; Molecular Diagnostic Techniques; Neurologic Examination; Prevalence; Teratogens
PubMed: 23897159
DOI: No ID Found -
Revista de Neurologia Feb 2006Attention deficit hyperactivity disorder (ADHD) is a common condition in children with mental retardation (MR), with a prevalence rate of between 4 and 15%. It is... (Review)
Review
INTRODUCTION
Attention deficit hyperactivity disorder (ADHD) is a common condition in children with mental retardation (MR), with a prevalence rate of between 4 and 15%. It is therefore necessary to examine the epidemiological characteristics of neurodevelopmental disorders in patients with MR, evaluate diagnostic protocols and especially update the pharmacological treatment of ADHD in children with MR.
DEVELOPMENT
The study of ADHD in patients with mild mental retardation is no different to that carried out in children without MR. No neuropsychological instruments are available to measure the executive functions properly in patients with severe mental retardation. Neuroleptic and psychostimulant agents are the two groups of drugs that are most commonly used to treat behavioural problems in children with MR. Methylphenidate is effective in three quarters of the children with MR at preschool ages. It has proved to be effective in the clinical profiles and in psychometric studies. Other forms of treatment, such as clonidine or fenfluramine, have also proved to be effective to a certain extent in patients with MR, especially in the clinical setting.
CONCLUSIONS
ADHD is more frequent in patients with MR than in the general population. The diagnostic methodology is usually the same as that used in patients without MR. Stimulation treatment is the most specifically indicated for the treatment of attentional and behavioural problems in these children.
Topics: Attention Deficit Disorder with Hyperactivity; Child; Humans; Intellectual Disability
PubMed: 16555215
DOI: No ID Found -
The European Journal of General Practice Dec 2022General practitioners (GPs) are increasingly confronted with people with both mild intellectual disability (MID) and mental health (MH) problems. Little is known about...
BACKGROUND
General practitioners (GPs) are increasingly confronted with people with both mild intellectual disability (MID) and mental health (MH) problems. Little is known about the type of MH problems for which people with MID visit their GP and the care provided.
OBJECTIVES
To identify the type and prevalence of MH disorders and MH-related complaints in people with MID in primary care and care provided, compared to people without ID.
METHODS
By linking the Netherlands Institute for Health Services Research's primary care databases, comprising electronic health records, with Statistic Netherlands' social services and chronic care databases, we identified 11,887 people with MID. In this four-year retrospective study, MH-related International Classification of Primary Care (ICPC) codes and care characteristics were compared between people with MID and without ID.
RESULTS
Of the people with MID, 48.8% had MH problems recorded vs. 30.4% of the people without ID, with significant differences in substance abuse, suicide attempts, and psychosis. Of the MID group, 80.3% were not registered by their GP with the ICPC code mental retardation. GPs provided more care to people with MID and MH problems than people without ID but with MH-problems regarding consultations (median 6.4 vs. 4.0 per year) and variety of prescribed medications (median 2.7 vs. 2.0 per year).
CONCLUSION
In primary care, the prevalence of MH problems and care provided is high in people with MID. To improve primary mental healthcare for this group, it is essential to increase GPs' awareness and knowledge on the combination of MID and MH.
Topics: Adult; Humans; Intellectual Disability; Retrospective Studies; Substance-Related Disorders; General Practitioners; Mental Health Services
PubMed: 36412308
DOI: 10.1080/13814788.2022.2142936 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2023Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global...
Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.
Topics: Humans; Male; Female; Child; Infant; Intellectual Disability; Mental Retardation, X-Linked; Obesity; Hypogonadism
PubMed: 36999477
DOI: 10.11817/j.issn.1672-7347.2023.220414 -
Journal of Neurochemistry Mar 2003Trisomy of human chromosome 21 is a major cause of mental retardation and other phenotypic abnormalities collectively known as Down syndrome. Down syndrome is associated... (Review)
Review
Trisomy of human chromosome 21 is a major cause of mental retardation and other phenotypic abnormalities collectively known as Down syndrome. Down syndrome is associated with developmental failure followed by processes of neurodegeneration that are known to supervene later in life. Despite a widespread interest in Down syndrome, the cause of developmental failure is unclear. The brain of a child with Down syndrome develops differently from that of a normal one, although characteristic morphological differences have not been noted in prenatal life. On the other hand, a review of the existing literature indicates that there are a series of biochemical alterations occurring in fetal Down syndrome brain that could serve as substrate for morphological changes. We propose that these biochemical alterations represent and/or precede morphological changes. This review attempts to dissect these molecular changes and to explain how they may lead to mental retardation.
Topics: Apoptosis; Brain; Cytoskeletal Proteins; Down Syndrome; Fetal Diseases; Gene Dosage; Humans; Intellectual Disability; Morphogenesis; Signal Transduction; Transcription, Genetic
PubMed: 12603815
DOI: 10.1046/j.1471-4159.2003.01614.x