Macrocephaly in children with autism spectrum disorders.
ABSTRACT Research indicates the presence of macrocephaly or abnormally large head circumferences in children with autism and spectrum-related disorders, compared with their typically developing peers. Previous research, however, centered on non-nationally representative, clinic-based samples of children and adults with autism spectrum disorders. Moreover, these samples were typically small. The present study represents results of a nationally representative, community-based sample of children with and without autism spectrum disorders, derived from the Early Childhood Longitudinal Study Birth Cohort. Results reveal statistically nonsignificant differences in the head circumferences of children with autism spectrum disorders across three time points, compared with children without autism spectrum disorders. These results may be considered highly generalizable, because they are derived from a nationally representative, community-based sample of children with and without autism spectrum disorders from the Early Childhood Longitudinal Study Birth Cohort.
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ABSTRACT: With a complex and extremely high clinical and genetic heterogeneity, autism spectrum disorders (ASD) are better dissected if one takes into account specific endophenotypes. Comorbidity of ASD with epilepsy (or paroxysmal EEG) has long been described and seems to have strong genetic background. Macrocephaly also represents a well-known endophenotype in subgroups of ASD individuals, which suggests pathogenic mechanisms accelerating brain growth in early development and predisposing to the disorder. We attempted to estimate the association of gene variants with neurodevelopmental disorders in patients with autism-epilepsy phenotype (AEP) and cranial overgrowth, analyzing two genes previously reported to be associated with autism and macrocephaly. We analyzed the coding sequences and exon-intron boundaries of GLIALCAM, encoding an IgG-like cell adhesion protein, in 81 individuals with Autism Spectrum Disorders, either with or without comorbid epilepsy, paroxysmal EEG and/or macrocephaly, and the PTEN gene in the subsample with macrocephaly. Among 81 individuals with ASD, 31 had concurrent macrocephaly. Head circumference, moreover, was over the 99.7th percentile ("extreme" macrocephaly) in 6/31 (19%) patients. Whilst we detected in GLIALCAM several single nucleotide variants without clear pathogenic effects, we found a novel PTEN heterozygous frameshift mutation in one case with "extreme" macrocephaly, autism, intellectual disability and seizures. We did not find a clear association between GLIALCAM mutations and AEP-macrocephaly comorbidity. The identification of a novel frameshift variant of PTEN in a patient with "extreme" macrocephaly, autism, intellectual disability and seizures, confirms this gene as a major candidate in the ASD-macrocephaly endophenotype. The concurrence of epilepsy in the same patient also suggests that PTEN, and the downstream signaling pathway, might deserve to be investigated in autism-epilepsy comorbidity. Working on clinical endophenotypes might be of help to address genetic studies and establish actual causative correlations in autism-epilepsy.BMC Medical Genetics 02/2014; 15(1):26. · 2.54 Impact Factor
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ABSTRACT: Despite the widely-held understanding that the biological changes that lead to autism usually occur during prenatal life, there has been relatively little research into the functional development of the brain during early infancy in individuals later diagnosed with autism spectrum disorder (ASD). This review explores the studies over the last three years which have investigated differences in various brain regions in individuals with ASD or who later go on to receive a diagnosis of ASD. We used PRISMA guidelines and selected published articles reporting any neurological abnormalities in very early childhood in individuals with or later diagnosed with ASD. Various brain regions are discussed including; the amygdala; cerebellum; frontal cortex and lateralised abnormalities of the temporal cortex during language processing. This review discusses studies investigating head circumference, electrophysiological markers and inter-hemispheric synchronisation. All the recent findings from the beginning of 2009 across these different aspects of defining neurological abnormalities are discussed in light of earlier findings. The studies across these different areas reveal the existence of atypicalities in the first year of life, well before ASD is reliably diagnosed. Cross-disciplinary approaches are essential to elucidate the pathophysiological sequence of events that lead to ASD.Behavioural neurology 08/2013; · 1.25 Impact Factor
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ABSTRACT: Numerous clinical studies over the past decades have concluded that there is an association between autism spectrum disorders (ASD) and large head size. Lately, some studies have reported conflicting results. The present study was conducted with a view to assess the presence of macrocephaly in a community-representative group of pre-school children with ASD. The prevalence of ASD in this general population was 0.8%. Thirty-three children (5 girls, 28 boys) recruited after general population screening for ASD, and diagnosed with ASD (two-thirds not globally delayed) were assessed as regards growth parameters; height, weight, and head circumference (HC), at birth and at comprehensive medical-psychiatric diagnostic examinations at a mean age of 3 years. Macrocephaly in the present study was defined as HC above the 97th percentile, and ≥2 SD above recorded length/height. Only one of the 33 children (3%) had macrocephaly which is similar to the general population prevalence. Another 9% had a big but proportional head. None of the children were microcephalic. In this community-based study we found no evidence to support a strong link between a large head size and ASD. Conclusions must be guarded because of the relatively small number of ASD cases included.Research in developmental disabilities 01/2014; · 4.41 Impact Factor