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

We conducted a case-controlled, catch-up study of a cohort of boys born with macrocephaly in order to determine whether infantile macrocephaly is a risk marker for the later development of autism spectrum disorders. Our results show that infantile macrocephaly was associated with an increased risk of developing autism spectrum disorders (odds ratio 5.44, 95% CI 1.11-52.15; p=0.03). These findings suggest that neurobiological differences during infancy may predict behavioural manifestations of autism spectrum disorders.
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PMID:Association between idiopathic infantile macrocephaly and autism spectrum disorders. 1155 82

Although neuropathologic studies have centered on small samples, it is accepted that brains of autistic individuals tend to be large, on average. Knowledge regarding the cause of this macrocephaly is limited. Postmortem studies reveal little in terms of cortical dysplasia. Some of these studies suggest increased cell-packing density in subcortical structures. These neuronomorphometric studies have been subjective or based their conclusions on measures of neuronal density. Our study sought the possible presence of increased cell-packing density by using the Gray Level Index. The Gray Level Index is defined as the ratio of the area covered by Nissl-stained elements to unstained area in postmortem samples. Analyzed images included Brodmann's cortical areas 9, 21, and 22 of 9 autistic patients (7 males, 2 females; mean age of 12 years, with a range of 5 to 28 years) and 11 normal controls (7 males, 4 females; mean age of 14 years, with a range of 3 to 25 years). The overall multivariate test revealed significant differences both between autistic patients and controls (P = .001) and between hemispheres (P = .025). Follow-up univariate tests showed significant diagnosis-dependent effects in feature distance (P = .005), the standard deviation in distance (P = .016), and feature amplitude (P = .001). The overall mean Gray Level Index was 19.4% in controls and 18.7% in autism (P = .724). In autism, an increased number of minicolumns, combined with fewer cells per column (or their greater dispersion), results in no global difference in neuronal density.
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PMID:Neuronal density and architecture (Gray Level Index) in the brains of autistic patients. 1226 31

Mental deficiency, alterations in performance, and central nervous system (CNS) abnormalities are discussed in the following overgrowth syndromes: Sotos syndrome, Weaver syndrome, Proteus syndrome, neurofibromatosis type 1, fragile X syndrome, syndromes with neonatal hypoglycemia, Simpson-Golabi-Behmel syndrome, hemihyperplasia, Sturge-Weber syndrome, Bannayan-Riley-Ruvalcaba/Cowden syndrome, macrocephaly-autism syndrome, PEHO syndrome, chromosomal syndromes, and other miscellaneous syndromes.
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PMID:Mental deficiency, alterations in performance, and CNS abnormalities in overgrowth syndromes. 1256 Oct 58

This study examined the frequency and cognitive correlates of enlarged head circumference in a sample of 63 children with autism between the ages of 4 and 14. Consistent with prior evidence, macrocephaly occurred at a significantly higher frequency than in a normal reference sample. Head circumference was not associated with language or executive functioning, nor was it related to verbal or nonverbal IQ. Head circumference was, however, correlated with discrepancies between verbal and nonverbal IQ scores, independent of absolute level of verbal ability. Children with discrepantly high nonverbal abilities had a mean standardized head circumference that was more than 1 SD greater than in the reference sample, and that was significantly greater than in autistic children with a relative verbal advantage or no discrepancy in cognitive abilities, for whom mean head circumference was within normal limits. This convergence of physical and cognitive features suggests a possible etiologically significant subtype of autism.
J Autism Dev Disord 2003 Apr
PMID:Brief report: cognitive correlates of enlarged head circumference in children with autism. 1275 62

Macrocephaly is one of the most consistent physical findings reported in autistic individuals. Previous studies attempted to determine if macrocephaly is associated with risk for autism. This study hypothesizes that an abnormal acceleration in head growth during early development, rather than macrocephaly, is associated with autism risk. To investigate this hypothesis, head circumference data were examined in 251 individuals from 82 multiplex (at least two individuals with autism) and 113 sporadic (no family history) families with autism. This examination included longitudinal measurements for 79 individuals. Nineteen percent of the original 251 individuals were found to have macrocephaly (head circumference >97%). Abnormal acceleration in head growth was defined as an increase of 25 or more percentile points in head circumference between two consecutive measurements. Thirty-five percent of individuals with multiple head circumference records had an abnormal increase in head circumference. Furthermore, autistic individuals with accelerated head growth in early childhood displayed higher levels of adaptive functioning and less social impairment. This study confirms the presence of abnormal acceleration in head growth during the first and second months of life in a subgroup of autistic individuals.
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PMID:Accelerated head growth in early development of individuals with autism. 1566 69

Although the cause of autism is undetermined, a general consensus has been that some type of early aberrant neural development underlies the disorder. Given the increased prevalence of macrocephaly in autism, one theory of abnormal neural development implicates early brain growth resulting in larger brain and head size in autism. Surface area measurements of the midsagittal section of the corpus callosum can be used as an index of neural development and white-matter integrity because the corpus callosum is the major white-matter structure that interconnects the two cerebral hemispheres. The purpose of this study was to obtain corpus callosum surface area, shape, and contour in a sample of non-mentally retarded autistic subjects with macrocephaly (n = 12) and compare them with those of matched (n = 8), typically developing control subjects with benign macrocephaly. No significant differences were found in surface area, shape, or contour between groups, nor did corpus callosum surface area relate to measures of IQ or picture vocabulary. These findings suggest no unique difference in overall regional corpus callosum surface area in autism with macrocephaly.
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PMID:Macrocephaly, corpus callosum morphology, and autism. 1579 21

The genetic aetiology of autism remains elusive. Occasionally, individuals with Cowden syndrome (a cancer syndrome) and other related hamartoma disorders such as Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like conditions, are characterised by germline PTEN mutations, and may have neurobehavioural features resembling autism as well as overgrowth and macrocephaly. Therefore, we undertook PTEN gene mutation analysis in 18 subjects mainly prospectively ascertained with autism spectrum disorder and macrocephaly. Of these 18 autistic subjects (13 males and five females; ages 3.1-18.4 years) with a head circumference range from 2.5 to 8.0 standard deviations above the mean, three males (17%) carried germline PTEN mutations. These three probands had previously undescribed PTEN mutations: H93R (exon 4), D252G (exon 7), and F241S (exon 7). They had the larger head circumference measurements amongst all our study subjects. The three residues altered in our patients were highly evolutionarily conserved. We suggest that PTEN gene testing be considered for patients with autistic behaviour and extreme macrocephaly. The gene findings may impact on recurrence risks as well as medical management for the patient.
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PMID:Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. 1580 58

Autism is a childhood-onset neuropsychiatric disorder characterized by marked impairments in social interactions and communication, with restricted stereotypic and repetitive patterns of behavior, interests, and activities. Genetic epidemiology studies indicate that a strong genetic component exists to this disease, but these same studies also implicate significant environmental influence. The disorder also displays symptomatologic heterogeneity, with broad individual differences and severity on a graded continuum. In the search for phenotypes to resolve heterogeneity and better grasp autism's underlying biology, investigators have noted a statistical overrepresentation of macrocephaly, an indicator of enlarged brain volume. This feature is one of the most widely replicated biological findings in autism. What then does brain enlargement signify? One hypothesis invoked for the origin of macrocephaly is a reduction in neuronal pruning and consolidation of synapses during development resulting in an overabundance of neurites. An increase in generation of cells is an additional mechanism for macrocephaly, though it is less frequently discussed in the literature. Here, we review neurodevelopmental mechanisms regulating brain growth and highlight one underconsidered potential causal mechanism for autism and macrocephaly--an increase in neurogenesis and/or gliogenesis. We review factors known to control these processes with an emphasis on nuclear receptor activation as one signaling control that may be abnormal and contribute to increased brain volume in autistic disorders.
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PMID:Macrocephaly and the control of brain growth in autistic disorders. 1628 Jan 93

In a comprehensive set of experiments in this issue of Neuron, Kwon et al. demonstrate that conditional inactivation of Pten leads to behavioral abnormalities and neuropathological changes. Pten mutants displayed reduced social interaction and heightened responses to sensory stimuli. Additionally, neuronal hypertrophy, as well as macrocephaly was observed. Based on rare human mutations in PTEN and the PI3K pathway, the authors suggest they have produced a potential animal model of autism with macrocephaly.
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PMID:Pten and the brain: sizing up social interaction. 1667 93

CNS deletion of Pten in the mouse has revealed its roles in controlling cell size and number, thus providing compelling etiology for macrocephaly and Lhermitte-Duclos disease. PTEN mutations in individuals with autism spectrum disorders (ASD) have also been reported, although a causal link between PTEN and ASD remains unclear. In the present study, we deleted Pten in limited differentiated neuronal populations in the cerebral cortex and hippocampus of mice. Resulting mutant mice showed abnormal social interaction and exaggerated responses to sensory stimuli. We observed macrocephaly and neuronal hypertrophy, including hypertrophic and ectopic dendrites and axonal tracts with increased synapses. This abnormal morphology was associated with activation of the Akt/mTor/S6k pathway and inactivation of Gsk3beta. Thus, our data suggest that abnormal activation of the PI3K/AKT pathway in specific neuronal populations can underlie macrocephaly and behavioral abnormalities reminiscent of certain features of human ASD.
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PMID:Pten regulates neuronal arborization and social interaction in mice. 1667 86


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