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

Recent studies have demonstrated that biogenic amines have a function of facilitating formation and maintenance of synapses in diverse regions of the central nervous system in developing and adult animals. The normal number of synapses maintained by biogenic amines are crucial to acquire learning and memory. The level of biogenic amines was reported to decrease in the brain by several neurodevelopmental disorders associated with mental retardation and developmental disabilities such as Rett syndrome, autism and Down syndrome. Taken into consideration this fact together with the function of biogenic amines for synapses, the density of synapses appears to decrease considerably in the brains of patients suffered from the neurodevelopmental disorders. The synaptic overproduction during the critical period of development especially 1 year after birth has been considered as a background mechanism to provide plasticity for the developing brain. Synaptic overproduction does not appear to occur in the brains of patients suffered from the neurodevelopmental disorders, which they are observed mental retardation occurring in the first 1 year after birth. Along with the neurodevelopmental disorders, environmental factors (stress, drugs and nutrition) during pre- and post-natal critical developmental periods are known to change levels of biogenic amines in the brain. In fact, maternal stress has been shown to decrease the levels of serotonin and the density of synapses in the hippocampus of the offspring, and they showed developmental disabilities in the spatial learning and memory. A cascade appears to exist from either the child neurological disorders or the environmental factors to mental retardation and developmental disabilities by decreases in the levels of biogenic amines and synaptic density.
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PMID:A biogenic amine-synapse mechanism for mental retardation and developmental disabilities. 1173 35

In patients with Rett syndrome (RS), a peculiar type of disturbance in phasic chin muscle activity during rapid-eye-movement sleep (REMS) (e.g. an elevation of phasic inhibition index (PII) without an affection of tonic inhibition index (TII)) has been reported. The similar disturbance in REMS was reported not only in child patients with infantile spasms, severe myoclonic epilepsy in infancy (SMEI), severe nocturnal enuresis, and autism but also in adult patients with Parkinson's disease (PD). Except for SMEI and PD, patients with the other four clinical entities including RS could express autistic tendency. Since the responsible lesion for the occurrence of an elevation of PII with a normal TII value is likely to be in the pontine tegmentum, this subcortical structure is hypothesized to be involved in the appearance of autistic tendency.
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PMID:Disturbance of phasic chin muscle activity during rapid-eye-movement sleep. 1173 53

A possible role for Hoxa1 genotype in susceptibility to autism spectrum disorders was recently proposed. Furthermore, it has been demonstrated that Rett syndrome, which is categorized into pervasive developmental disorders the same as the autism spectrum disorders are, is associated with mutations in MECP2 gene. These findings suggest that the genetic backgrounds of these behavioral conditions may involve genes which also have an important role in the development of skull, because Hoxa1 is a key gene for skull development as well as for brain development and one of the clinical characteristics of Rett syndrome is deceleration in head growth. Together with this evolving knowledge, a series of ethical arguments concerning the indication of surgical treatment in patients with minor forms of trigonocephaly with autistic behaviors and/or hyperactivity leads us to hypothesize the presence of an autism subtype which may frequently be accompanied by specific morphological skull characteristics (autistic skull shape).
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PMID:Minor form of trigonocephaly is an autistic skull shape? A suggestion based on homeobox gene variants and MECP2 mutations. 1202 29

Although MECP2 was initially identified as the causative gene in classic Rett syndrome (RTT), the gene has now been implicated in several phenotypes that extend well beyond the clinically defined disorder. MECP2 mutations have been found in people with various disorders, including neonatal onset encephalopathy, X-linked recessive mental retardation (MRX), classic and atypical RTT, autism, and Angelman syndrome, as well as mildly affected females and normal carrier females. To make matters more complex, in approximately 20% of classic sporadic RTT cases and more than 50% of affected sister pairs, no mutation in MECP2 has been found. X-chromosome inactivation patterns can clearly affect the phenotypic expression in females, while the effect of the type and position of the mutation is more apparent in the broader phenotype than in RTT. Both males and females are at risk, although an excess of paternally derived mutations are found in most cases of classic RTT. Thus, because of the range of disparate phenotypes, the gene may account for a relatively large portion of mental retardation in the population.
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PMID:The phenotypic consequences of MECP2 mutations extend beyond Rett syndrome. 1211 34

Rett syndrome (RTT) is classically defined by meeting certain clinical diagnostic criteria. It affects mostly females, and one possible pathogenic mechanism was considered to involve mitochondrial function. This was based on the finding of ultrastructural alterations in the mitochondria and decreased respiratory chain enzyme activity. However, the principal etiology of RTT has since been found to be mutations in the MECP2 gene, which is located on the X chromosome. Molecular analysis has allowed the phenotype of MECP2 mutations to be broadened beyond RTT to include girls who have mild mental retardation, autism, and an Angelman syndrome phenotype, as well as males with severe encephalopathy. We present a girl with a previously described mutation in the MECP2 gene whose phenotype is of atypical RTT. She presented with hypotonia and developmental delay in infancy without a clear period of normal development. As part of her evaluation for hypotonia, a muscle biopsy and respiratory chain enzyme analysis showed a slight decrease in respiratory chain enzyme activity consistent with previous reports. This report supports broadening the phenotype of patients who should be considered for MECP2 mutation analysis to include cases of developmental delay and hypotonia without evidence of an initial period of normal development. Furthermore, it supports the hypothesis of an underlying secondary defect in energy metabolism contributing to the pathogenesis of RTT.
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PMID:Infantile hypotonia as a presentation of Rett syndrome. 1221 Mar 19

Rett syndrome is a neuro-developmental disorder related to autistic behavior. Persons with autism have previously been found to have hyperpeptiduria. We here report a significantly higher level of peptides in the first fasting morning urine from 53 girls with Rett syndrome (both classical and congenital) compared with 53 healthy girls. This elevation in urinary peptides was similar to that in 35 girls with infantile autism. As in persons with autism, the individual levels of urinary peptides in the Rett syndrome group varied, and about a fifth were within the normal range. Levels of peptides were lower in girls with classic Rett syndrome than in girls with congenital Rett syndrome. This may be due to different etiological causes or to active and stagnant phases of the disease. Urine from girls with Rett syndrome was found to have higher frequency and higher levels of some urinary peptides that may cause inhibition of brain maturation and epilepsy
Autism 2002 Sep
PMID:Urinary peptides in Rett syndrome. 1221 21

Rett syndrome is a progressive neurologic disorder affecting girls in early childhood with loss of achieved psychomotor abilities and mental retardation. Six sedated female patients (4 to 15 years of age) with a diagnosis of Rett syndrome were studied with [(18)F]fluorodeoxyglucose (FDG) and underwent positron emission tomography scanning of the brain. Relative tracer concentrations between different areas of the brain were assessed, and results were compared with 18 age-matched control subjects. Patients were divided into two age groups: 3 to 8 years of age and 9 to 15 years of age. A relative decrease in [(18)F]FDG uptake in the lateral occipital areas in relation with the whole brain and a relative increase in the cerebellum was evident in both age groups (P < 0.001, unpaired Student t test). A relative increase in frontal tracer uptake was observed in the younger group. Sensorimotor areas and relations between cortical and subcortical structures were preserved in all patients. Changes in glucose cerebral metabolism resemble the regional distribution of normal children less than 1 year of age, likely reflecting a maturational arrest. Changes in frontal areas parallel those in postmortem N-methyl-D-aspartate receptor densities and could correlate with different clinical stages of the disease. This pattern differs from those described in Down syndrome, autism, and Alzheimer's disease.
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PMID:Brain glucose metabolism in Rett Syndrome. 1221 12

Mutations in the coding region of the methyl-CpG-binding protein 2 ( MECP2) gene cause Rett syndrome and have also been reported in a number of X-linked mental retardation syndromes. Furthermore, such mutations have recently been described in a few autistic patients. In this study, a large sample of individuals with autism was screened in order to elucidate systematically whether specific mutations in MECP2 play a role in autism. The mutation analysis of the coding sequence of the gene was performed by denaturing high-pressure liquid chromatography and direct sequencing. Taken together, 14 sequence variants were identified in 152 autistic patients from 134 German families and 50 unrelated patients from the International Molecular Genetic Study of Autism Consortium affected relative-pair sample. Eleven of these variants were excluded for having an aetiological role as they were either silent mutations, did not cosegregate with autism in the pedigrees of the patients or represented known polymorphisms. The relevance of the three remaining mutations towards the aetiology of autism could not be ruled out, although they were not localised within functional domains of MeCP2 and may be rare polymorphisms. Taking into account the large size of our sample, we conclude that mutations in the coding region of MECP2 do not play a major role in autism susceptibility. Therefore, infantile autism and Rett syndrome probably represent two distinct entities at the molecular genetic level.
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PMID:Mutation analysis of the coding sequence of the MECP2 gene in infantile autism. 1238 70

Despite considerable interest in Rett syndrome, there have been few studies of associated behavioral and emotional problems. In the present study, 143 girls with Rett syndrome were compared on the Developmental Behavior Checklist with 85 girls with severe to profound mental retardation of mixed etiologies. After controlling for the effects of physical disabilities, we found that the girls with Rett syndrome presented more "autistic-relating" and fewer antisocial behaviors. A subsample of children with autism was also compared to the girls with Rett syndrome on autistic-relating behaviors, revealing that the Rett syndrome group did not present with classic autistic behavioral features The implications of these results for the identification of a Rett syndrome behavioral phenotype are discussed.
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PMID:Towards a behavioral phenotype for Rett syndrome. 1247 62

The methyl-CpG binding protein 2 (MeCP2) gene has recently been identified as the gene responsible for Rett syndrome (RS), a pervasive developmental disorder considered by many to be one of the autism spectrum disorders. Most female patients with MeCP2 mutations exhibit the classic features of RS, including autistic behaviors. Most male patients with MeCP2 mutations exhibit moderate to severe developmental delay/mental retardation. Ninety nine patients from the South Carolina autism project (SCAP) were screened for MeCP2 mutations, including all 41 female patients from whom DNA samples were available plus the 58 male patients with the lowest scores on standard IQ tests and/or the Vineland Adaptive Behavior Scale. No pathogenic mutations were observed in these patients. One patient had the C582T variant, previously reported in the unaffected father of an RS patient. Two other patients had single nucleotide polymorphisms in the 3' UTR of the gene, G1470A and C1516G. These variants were seen in 12/82 and 1/178 phenotypically normal male controls, respectively. The findings from this and other studies suggest that mutations in the coding sequence of the MeCP2 gene are not a significant etiological factor in autism.
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PMID:Absence of MeCP2 mutations in patients from the South Carolina autism project. 1255 43


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