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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 2%-5% of autistic children show cytogenetic evidence of the fragile X syndrome. This report tests whether infantile autism in multiplex autism families arises from an unusual manifestion of the fragile X syndrome. This could arise either by expansion of the (CGG)n trinucleotide repeat in FMR-1 or from a mutation elsewhere in the gene. We studied 35 families that met stringent criteria for multiplex autism. Amplification of the trinucleotide repeat and analysis of methylation status were performed in 79 autistic children and in 31 of their unaffected siblings, by Southern blot analysis. No examples of amplified repeats were seen in the autistic or control children or in their parents or grandparents. We next examined the hypothesis that there was a mutation elsewhere in the FMR-1 gene, by linkage analysis in 32 of these families. We tested four different dominant models and a recessive model. Linkage to FMR-1 could be excluded (lod score between -24 and -62) in all models by using probes DXS548, FRAXAC1, and FRAXAC2 and the CGG repeat itself. Tests for heterogeneity in this sample were negative, and the occurrence of positive lod scores in this data set could be attributed to chance. Analysis of the data by the affected-sib method also did not show evidence for linkage of any marker to autism. These results enable us to reject the hypothesis that multiplex autism arises from expansion of the (CGG)n trinucleotide repeat in FMR-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular analysis and test of linkage between the FMR-1 gene and infantile autism in multiplex families. 797 58

1. Fragile X syndrome is defined by the combination of a characteristic phenotype, cognitive impairment, the presence of a fragile site (gap) detectable in folate-free culture medium on Xq27.3 called FRA X A, and transcriptional inhibition, through overmethylation, of an mRNA protein-binding gene called FMR-1. 2. It is inherited in an atypical X-linked dominant way and affects about 1 in 1000 males and 1 in 2000 females; about 1 in 700 females is a carrier. 3. A characteristic but subtle phenotype includes an elongated face and mandible, large ears, macrocephaly with bizygomatic pinching, soft skin, inconsistent mitral valve prolapse, macroorchidism, mildly shortened stature in adulthood, and characteristic behavior that may resemble autism and attention deficit disorders. Intellectual impairment in affected individuals varies from mild to severe, with a majority of affected males within the moderate range of cognitive disability. Twenty percent of males with the mutation are phenotypically and intellectually unaffected. They ae called transmitting males. 4. Female heterozygotes may be indistinguishable from the general population, or they may have subtle physical signs or both physical and intellectual impairment. 5. Sensory motor integration is the therapy of choice for the learning disabilities in children with fragile X syndrome. The benefits of folic acid supplementation are equivocal. 6. A sensitive and understanding support system for the patient and extended family is an inseparable component of appropriate management of fragile X syndrome. 7. Molecularly the mutation is characterized by varying lengths of DNA fragments consisting of the trinucleotide CGG. It is repeated about 6 to 50 times in the normal population and approximately 51 to 200 times in unaffected individuals with a so-called premuation who are at risk for expansion and transmission to offspring. Individuals with over 200 repeats are usually affected and said to have a full mutation. 8. The physician caring for a family with fragile X syndrome should work with an experienced genetics center, counselor, and a laboratory with expertise.
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PMID:Fragile X syndrome. 799 87

The present study surveys autistic behavioral characteristics of 58 mentally retarded male adults with fragile-X syndrome. Results were compared with a control group of 58 fragile-X negative mentally retarded men, matched on age, cognitive level, living conditions and length of institutionalisation. We demonstrate that this and other controlled studies have not given much evidence for a specific association between fra(X) syndrome and the global diagnosis of autism. A high proportion of fra(X) adults display a limited number of specific behavioral characteristics that belong to the spectrum of pervasive developmental disorders. Non-functional body movements, unacceptable vocal and speech habits, social avoidance reactions and eccentric peculiarities are significantly different between the two groups. We further propose that the core features of autism, namely social indifference and severely disturbed social relations, are in general not found in the fra(X) group. On the contrary, they had a more positive general mood, were more sensitive to social contact and attention from others and approached not only new physical environments but also other people with great openness and interest. Moreover, we found that fra(X) adults had average interpersonal and communicative skills. This peculiar combination of "autistic-like" behavior and social sensitivity or openness could probably be accounted for by feelings of social anxiety. Finally implications of this "social anxiety" hypothesis for research and treatment are discussed.
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PMID:Fragile-X syndrome and autism: a prevalent association or a misinterpreted connection? 811 Apr 11

Chromosomal fragility and other chromosomal abnormalities were frequently observed in subjects with neuropsychiatric disorders, such as fragile X syndrome, autism or schizophrenia, but only for the first one the fragility is accepted to be associated to a specific pathology, so that it is used as a diagnostic marker. In this study the authors analyzed 50 schizophrenic males, searching for the rare fragile sites or other aberrations with the method suitable for fra(X) detection. Chromosomes from schizophrenic patients resulted more fragile than those from normal controls, especially chromosome 9. The authors discuss the implications of a possible association of these data with the aetiopathogenesis of schizophrenic syndrome.
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PMID:Evidence of chromosomal fragile sites in schizophrenic patients. 821 21

The fragile X syndrome is a common X-linked mental retardation and autism, affecting females as well as males. The fragile site X chromosomes were studied in a series of 153 mentally retarded boys of unknown etiology to determine the frequency of fragile X syndrome, and to assess the feasibility of making a clinical diagnosis of the fragile X syndrome in young boys before cytogenetic results were known. The 10 boys (6.4%) were positive for fra (X) (q27). The phenotype of fra (X) (q27) positive patients were typical except one who also had sex chromosomal mosaicism. There were three pairs of siblings among the fra (X) (q27) positive patients. Frequency of expression of the fragile site was in 10 to 47 per cent of cells. In addition, 19 boys showed a previously unsuspected chromosomal abnormality. The frequency of the fragile X syndrome in the present study is not significantly different from those in Caucasians and Japanese population. The fragile X syndrome can be recognized by noting key aspects of family history as well as the clinical features in mentally retarded boys.
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PMID:Fragile site X chromosomes in mentally retarded boys. 824 Jul 48

Many epidemiological studies have demonstrated the exceptionally high incidence of autism in children with the fragile X syndrome, and autism is often considered a "behavioral phenotype" of this syndrome. However, the discrepancies between the results of these studies disclosed strong effects of methodological flaws and demonstrated the need for gathering clinical data. Atypical "autistic-like" behaviors were then found to be common, early symptoms of the syndrome occurring against the background of early manifestations of mental retardation. These behaviors reflect these children's exquisite reactivity to change and contact with others. Avoidance of eye contact is the most significant feature. The appropriate diagnosis is not autism but phobia of social relationships. This highly specific vulnerability, which may be inherited, probably leads some of these patients to experience the fate of autistic children. It highlights the influence of environment on the clinical course and indirectly supports the role of early specialized care.
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PMID:[Autism and children with Fragile X syndrome]. 827 4

The fragile X syndrome is one of the main etiologies of mental retardation in human beings. Some of its specific cognitive and language disturbances are nowadays well known. Disturbances of behavior are frequent. They are akin to psychotic manifestations and are mainly described in terms of autistic syndromes. The question of the possible links between autism and the fragile X syndrome is being discussed since 1980. The authors give a synthetic and critic overview of the studies reporting on the frequency of co-occurrence of these syndromes and offer some reflexion on the true questions at stakes in the debate. They emphasize the determining role of future clinical research in autism in order to objectively contribute to the progression of knowledge in this field.
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PMID:[Cognitive disorders and psychiatric manifestations in the fragile X syndrome. Autism and fragile X]. 836 20

Autism is a syndrome with multiple etiologies, as is made clear both by the evidence of neurobiological research and by the catalog of disorders that present with autistic behaviors. What remains unclear are the specific neuropathological mechanisms that produce autistic behaviors; for example, is there a common neuroanatomic pathology for all cases of autism, or can autistic behaviors emerge from different pathological sequences within the brain? Although it is premature to generalize, neuropathological studies appear to have identified common abnormalities in the cerebellum and limbic system of at least five autistic subjects. These subjects, with variable levels of mental retardation, demonstrated marked Purkinje cell loss in the cerebellar hemispheres, together with retained fetal neuronal circuitry in cerebellar nuclei and increased neuronal packing in specific regions of the limbic system, amygdala, and hippocampus. The architecture of the cerebral cortex was not affected. Although our knowledge of brain functioning is incomplete, alterations of the kind noted in the cerebellum and limbic system could reasonably produce autistic behaviors. For more detail, readers are directed to a review of cerebellar contributions to higher functions by Schmahmann (1991). Neuroimaging studies allow less resolution of brain structure than do neuroanatomic studies, and the reported findings from neuroimaging are somewhat contradictory. However, a number of investigators have reported structural abnormalities in ventricle size and cerebral hemispheric asymmetry using CT. MRI, which offers greater resolution, has uncovered some consistent findings, along with a variety of nonspecific abnormalities. Common abnormalities include reduced volume of cerebellar hemispheres and vermal lobules--findings not inconsistent with the above-mentioned neuropathological defects. It is also interesting to note that individuals with fragile X syndrome have similar cerebellar findings. PET and NMR studies of autism are at a preliminary stage, but these methodologies allow insight into the functioning of the brain, rather than simply brain anatomy. Recent PET studies indicating decreased association between paired regions of the brains of autistic subjects are of interest, particularly if they can be confirmed and refined by additional studies. Neurophysiological studies also offer insight into brain function, but are subject to numerous methodological criticisms. Nevertheless, recent reports of diminished P300 waves and absent NC components in autistic subjects seem to indicate fundamental defects in attention and secondary processing, which could help explain the self-stimulatory behaviors often seen in autism. The disturbances in brain development associated with autism can be produced in a number of ways, and at different times during development of the nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The neurobiology and genetics of infantile autism. 846 65

Adaptive behavior in males with fragile X syndrome was longitudinally examined in 17 subjects, ages 1 to 17. Subjects received adaptive behavior evaluations on two occasions within one of three age periods. All domains of the Vineland Adaptive Behavior Scales increased from youngest to oldest age groups, yet older subjects (ages 10 to 17) showed significant declines in their adaptive behavior scores from first to second testing. A relative strength in Daily Living Skills and weakness in Socialization emerged only among older subjects. There was a significant relationship between adaptive behavior and mental age scores in all subjects. Discussion emphasized the parallels between declines in IQ and adaptive behavior as well as the need for further research on adaptive skills in young adults with fragile X syndrome.
J Autism Dev Disord 1993 Mar
PMID:Trajectory of adaptive behavior in males with fragile X syndrome. 846 93

Fifteen postpubertal males with fragile X syndrome (FRA(X)) and 15 non-FRA(X) males matched on IQ and age were assessed for their ability to identify the facially expressed emotions of happiness, sadness, anger, fear, disgust, and surprise. Emotions of happiness and sadness were the easiest to identify for both groups of participants. Regardless of etiology, individuals with higher IQ scores performed better at this task than did individuals with lower IQ scores. Results were consistent with findings in females having the fragile X mutation. The current study supported the notion that FRA(X) individuals are sensitive to facial emotion cues presented by others. This finding is discussed in the context of autism and gaze aversion.
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PMID:Facial emotion identification in males with fragile X syndrome. 867 19


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