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

Fetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in some children exposed to alcohol in the prenatal period. It is characterized mainly by physical and mental retardation, craniofacial anomalies and minor joint abnormalities. However, with the increasing incidence of FAS, there is a great variation in the clinical features of FAS. This article describes in detail these clinical features. Due to ethical reasons it is not possible to perform experiments on pregnant women. Hence to study the effects of alcohol, various animal and avian experimental models have been chosen. The various experimental findings and human correlation are described. The exact mechanism by which alcohol induces its teratogenic effects is not known. The possible mechanisms are discussed. Measures to prevent the occurrence of FAS have been suggested.
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PMID:Alcohol and the developing fetus--a review. 1120 51

Foetal alcohol syndrome is a syndrome with a rather high incidence. It is characterized by mental retardation, growth deficiency, a striking facial appearance (a.o. short palpebral fissures, short, upturned nose, hypoplastic philtrum, hypoplastic maxilla). Malocclusion and a disturbed facial growth may occur. Mental retardation can interfere with dental treatment.
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PMID:[Syndromes 19. Fetal alcohol syndrome]. 1138 71

Glial cells and their interactions with neurons play vital roles during the ontogeny of the nervous system and in the adult brain. Alcohol intake during pregnancy can cause mental retardation and neurobehavioral disorders as well as fetal alcohol syndrome (FAS). Clinical and experimental evidence indicate that in utero alcohol exposure induces structural and functional abnormalities in gliogenesis and in glial-neuronal interactions, suggesting a potential role of glial cells on ethanol-induced developmental brain abnormalities. In vivo studies have shown ethanol-associated alterations in the migration of neurons and radial glial as well as in astrogliogenesis and myelin development. In astrocytes in primary culture, ethanol has been found to (1) impair cell growth and differentiation, (2) decrease the levels of glialfibrillary acidic protein or GFAP (an astrocyte marker) and its gene expression and (3) interfere with the stimulatory effect of trophic factors affecting their release and receptor expression. Evidence also suggests that ethanol affects intracellular protein trafficking, which may mediate some effects of ethanol on astroglial cells. These findings suggest that glial cells are target of ethanol toxicity during brain development and may underlie the neurodevelopmental abnormalities observed after in utero alcohol exposure and in FAS.
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PMID:Glia and fetal alcohol syndrome. 1177 Aug 80

A major mechanism guiding neural development is through cell-cell and cell-matrix adhesions and signaling mediated by cell adhesion molecules (CAMs). The majority of CAMs have been grouped into three families: the cadherins, the integrins and the members of the immunoglobulin superfamily including L1. While the elucidation of new receptors and matrix components has become a frequent occurrence, the elucidation of the mechanisms by which they operate, and the function of those mechanisms in complex developmental events remains rudimentary. Members of all three families participate in differential adhesion, signal transduction and physical/mechanical effects. Each of these modes of action is a potential target for developmental neurotoxicants. In this brief review, the role of L1 in normal and abnormal neurodevelopment will be summarized. L1 is a cell surface transmembrane glycoprotein with a single copy gene on the X chromosome. There are two alternatively spliced exons, with the RSLE containing form found only on axons and growth cones of post-mitotic neurons. L1 mediates the following functions: adhesion, neurite extension, neuronal migration, and axon fasciculation. L1 is critical for normal neural development; humans with genetic defects in L1, termed corpus callosum hypoplasia, mental retardation, adducted thumbs, spasticity and hydrocephalus (CRASH) syndrome, and mice lacking expression of L1 have extensive neuropathologic and aberrant behaviors. The observation that patients with fetal alcohol syndrome share similar features to patients with CRASH has lead to the investigation of the effects of ethanol on L1. Physiologic concentrations of ethanol have been shown to inhibit L1 mediated neurite outgrowth in cerebellar granule neurons. Such inhibition may result from decreased expression, altered cell surface distribution, impaired signal transduction, or impaired interaction with the cytoskeleton. These data indicate that L1 and its associated signaling pathways are potentially targets for developmental neurotoxicants.
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PMID:L1 cell adhesion molecule signal cascades: targets for ethanol developmental neurotoxicity. 1177 Aug 84

Fetal alcohol syndrome (FAS) is the leading cause of mental retardation in western society. We investigated possible changes in glutamate receptor levels in neonatal animals following ethanol exposure using radioligand binding and western blot analysis. We used a vapor chamber to administer ethanol to neonatal Wistar rats 3 h a day from postnatal day (PND) 4-9. A separation control group was separated from their mothers for the same time and duration as the vapor treatment, while a normal control group was left to develop normally. Daily ethanol administrations resulted in decreased brain weight and body weight, as well as microencephaly (decreased brain:body weight ratio). Neither the affinity nor maximum binding of [(3)H]MK-801 (dizoclipine maleate) in the cortex of PND10 rats differed between treatment groups. Western blot analysis also failed to reveal any changes in NMDAR1, NMDAR2A, or NMDAR2B receptor levels. In contrast, the AMPA receptor subunit GluR1 was greatly reduced in vapor-treated pups compared with control pups, as revealed by western blot analysis. A similar reduction was found in westerns with an antibody recognizing the GluR2 and 4 subunits. These results indicate that ethanol reduces AMPA rather than NMDA receptors in the developing neocortex, possibly by blocking NMDA receptors during development.
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PMID:Neonatal ethanol exposure reduces AMPA but not NMDA receptor levels in the rat neocortex. 1203 20

Developmental neurotoxicity can be ascribed to in utero exposure to exogenous substances or to exposure of the fetus to endogenous compounds that accumulate because of genetic mutations. One of the best recognized human neuroteratogens is ethanol. The Fetal Alcohol Syndrome (FAS) is characterized by growth deficiency, particular facial features, and central nervous system (CNS) dysfunctions (mental retardation, microencephaly and brain malformations). Abuse of toluene by pregnant women can lead to an embryopathy (fetal solvent syndrome, (FSS)) whose characteristics are similar to FAS. Phenylketonuria (PKU) is a genetic defect in phenylalanine (Phe) metabolism. Offspring of phenylketonuric mothers not under strict dietary control are born with maternal PKU (mPKU), a syndrome with similar characteristics as FAS and FSS. While ethanol has been shown to cause neuronal death, no such evidence is available for toluene or Phe and/or its metabolites. On the other hand, alterations in astrocyte proliferation and maturation have been found, mostly in in vitro studies, which may represent a potential common mode of action for at least some of the CNS effects found in FAS, mPKU, and FSS. Further in vivo and in vitro studies should validate this hypothesis and elucidate possible molecular targets.
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PMID:Developmental neurotoxicity: do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria. 1205 59

Behavioral phenotypes were studied in four mental retardation syndromes using the Developmental Behavior Checklist (DBC). The four samples comprised fetal alcohol syndrome (FAS), Prader-Willi syndrome (PWS), fragile X syndrome (FRAX), and tuberosis sclerosis (TSC). Both on the item and the subscale level, there were clear behavioral differentiations across the four syndromes. FAS and FRAX proved to be most clearly differentiated from the other two samples, with PWS and TSC showing lower scores and less abnormal behavior profiles. Neither intelligence nor gender nor age contributed to variations in the number of behavior abnormalities. It was concluded that the DBC as a quantitative approach contributes significantly to the differentiation of behavioral phenotypes in various mental retardation syndromes.
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PMID:Behavioral phenotypes in four mental retardation syndromes: fetal alcohol syndrome, Prader-Willi syndrome, fragile X syndrome, and tuberosis sclerosis. 1221 Feb 96

Women at childbearing age often use alcohol and various illicit drugs such as cocaine and heroin. These agents pass through the human placenta and may affect the developing embryo and fetus. Indeed, large amounts of alcohol ingested by the pregnant woman may produce a specific syndrome manifested by prenatal and postnatal growth retardation, a variety of facial dysmorphic features and mental retardation. Ingestion of smaller amounts of alcohol will produce the fetal alcohol effects with only few and minor dysmorphic features but with developmental delay and some degree of intellectual impairment. Cocaine use during pregnancy may apparently result in an increase in the rate of congenital anomalies, of stillbirth and of intrauterine growth retardation. The use of heroin and opiates does not seem to increase the rate of major congenital anomalies, but it reduces fetal growth and increases the rate of intrauterine fetal death. Studies on the developmental outcome of children born to cocaine or heroin dependent mothers seem all to show psychomotor developmental delay at a young age. At school age these children have intellectual impairment and a very high rate of inattention and/or hyperactivity. We should therefore address our efforts in improving the environment of these children and in treating the early symptoms of inattention and hyperactivity, even before the child reaches school.
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PMID:The effects of alcohol and illicit drugs on the human embryo and fetus. 1222 27

The complex relationship between alcohol use and pregnancy involves socioeconomic, biomedical, psychological, and ethical factors. In recent years alcohol abuse on the part of women of childbearing age has been increasing steadily. Currently, a significant segment of the American population is at risk for an alcoholic pregnancy. Discussion includes a review of the literature concerning alcohol and pregnancy and covers the following: the symptomatology of fetal alcohol syndrome; prospective and epidemiologic human studies; animal models; etiology of fetal alcohol syndrome (FAS); maternal aspects of alcoholism and pregnancy and associated risk factors; paternal drinking and the theory of germ cell damage; use of ethanol in obstetrics; prevention of FAS; and questions to be answered in the future. The Fetal Alcohol Study Group of the Research Society of Alcoholism has promulgated a list of minimal criteria that must be met before a diagnosis of fetal alcohol syndrome (FAS) can be made. These criteria include prenatal and postnatal growth retardation and at least 2 of the following characteristic facial features: microcephaly, microopthalmia, and/or short palpebral fissures; and midfacial hypoplasia (defined as absent or rudimentary philtrum, thin vermilion border of upper lip, hypoplastic maxilla). The label "possible FAS" also is recommended if the criteria are not met, but congenital damage due to alcohol still is suspected. Virtually all infants with FAS have very low birth weights for their gestational age, usually at or below the third percentile. Body length and head circumference also are reduced to a similar degree. Mental retardation is the most debilitating and tragic aspect of this syndrome. Hyperactivity, hyperresponsiveness, hyperacusis, hypotonia, and tremulousness also are commonly described in FAS infants. Numerous studies involving large numbers of pregnant women have provided important data concerning the epidemiology and symptomatology of maternal alcohol use. All of these studies have been based on self reported use of alcohol, and the relationship of these reports to actual intake probably varies. Available prospective studies permit the estimation of the incidence of FAS in general and clarify to some extent the magnitude of risks an alcoholic woman has for giving birth to a defective child. Animal studies are very important in the study of alcohol and pregnancy because they provide an opportunity to control for variables that are seldom accounted for in human beings. One can control dosage and timing of ethanol administration, nutritional factors via pair feeding, and environment, and one can consider individual variation through cross strain comparisons.
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PMID:Pregnancy and alcohol. 1233 10

In utero exposure to ethanol is deleterious to fetal brain development. Children born with the fetal alcohol syndrome (FAS) display a number of abnormalities, the most significant of which are central nervous system (CNS) dysfunctions, such as microencephaly and mental retardation. An interaction of ethanol with glial cells, particularly astrocytes, has been suggested to contribute to the developmental neurotoxicity of this alcohol. At low concentrations (10-100 mM) ethanol inhibits the proliferation of astroglial cells in vitro, particularly when stimulated by acetycholine through muscarinic M3 receptors. Of the several signal transduction pathways activated by these receptors in astrocytes or astrocytoma cells, which are involved in mitogenic signaling, only some (e.g. protein kinase C (PKC) zeta, p70S6 kinase) appear to be targeted by ethanol at the same low concentrations which effectively inhibit proliferation. Inhibition of astroglial proliferation by ethanol may contribute to the microencephaly seen in FAS.
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PMID:Inhibition of muscarinic receptor-induced proliferation of astroglial cells by ethanol: mechanisms and implications for the fetal alcohol syndrome. 1252 Jul 58


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