Macrocephaly in Children and Adults With Autism

ArticleinJournal of the American Academy of Child & Adolescent Psychiatry 36(2):282-90 · March 1997with68 Reads
DOI: 10.1097/00004583-199702000-00019 · Source: PubMed
Abstract
To explore the frequency and onset of macrocephaly in autism and its relationship to clinical features. Head circumferences at birth, during early childhood, and at the time of examination were studied in a community-based sample of autistic children and adults. The authors investigated whether head circumference at the time of examination was associated with clinical features. Fourteen percent of the autistic subjects had macrocephaly: 11% of males and 24% of females. In most, the macrocephaly was not present at birth; in some it became apparent in early and middle childhood as a result of increased rate of head growth. A small relationship was noted between head circumference percentile and less severe core features of autism. Neither macrocephaly nor head circumference percentile was associated with nonverbal IQ, verbal status, seizure disorder, neurological soft signs or minor physical anomalies in the autistic subjects. Macrocephaly is common in autism and usually is not present at birth. Rates of head growth may be abnormal in early and middle childhood in some (37%) children with autism. Macrocephaly does not define a homogeneous subgroup of autistic individuals according to clinical features.
    • "In the context of ASD, there is some evidence that children with ASD are taller than TD children (Davidovitch et al. 1996; Lainhart et al. 1997; Miles et al. 2000; Dissanayake et al. 2006; Chawarska et al. 2011). There are reports of increased body length in boys with ASD beginning by 4.8 months of age (Chawarska et al. 2011), or greater height in children with ASD by 3 years (Lainhart et al. 1997; Dissanayake et al. 2006 ). These studies suggest that somatic overgrowth accounts for enlargement in head circumference (Dissanayake et al. 2006; Chawarska et al. 2011). "
    Full-text · Chapter · Dec 2016 · Neuromolecular medicine
    • "Megalencephaly generally refers to abnormal size of the brain. However, brain size can be confounded by body size, and there is evidence indicating that children with ASD are taller than typically developing children [Chawarska et al., 2011; Davidovitch, Patterson, & Gartside, 1996; Dissanayake, Bui, Huggins, & Loesch, 2006; Lainhart et al., 1997; Miles, Hadden, Takahashi, & Hillman, 2000]. Therefore, we have since revised our definition of this subgroup to include only children with brain size that is disproportionate to height or disproportionate megalencephaly (ASD-DM). "
    [Show abstract] [Hide abstract] ABSTRACT: A recurring finding in autism spectrum disorder research is that head and brain growth is disproportionate to body growth in early childhood. Nordahl et al. (2011) demonstrated that this occurs in approximately 15% of boys with autism. While the literature suggests that brain growth normalizes at older ages, this has never been evaluated in a longitudinal study. The current study evaluated head circumference and total cerebral volume in 129 male children with autism and 49 age-matched, typically developing controls. We determined whether 3-year-old boys with brain size disproportionate to height (which we call disproportionate megalencephaly) demonstrated an abnormal trajectory of head growth from birth and whether they maintained an enlarged brain at 5 years of age. Findings were based on longitudinal, structural MRI data collected around 3, 4, and 5 years of age and head circumference data from medical records. At 3 years of age, 19 boys with autism had enlarged brains while 110 had brain sizes in the normal range. Boys with disproportionate megalencephaly had greater total cerebral, gray matter, and white matter volumes from 3-5 years compared to boys with autism and normal sized brains and typically developing boys, but no differences in body size. While head circumference did not differ between groups at birth, it was significantly greater in the disproportionate megalencephaly group by around 2 years. These data suggest that there is a subgroup of boys with autism who have brains disproportionate to body size and that this continues until at least 5 years of age. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    Full-text · Article · Jun 2016
    • "Our findings, like those of previous (Seifert et al. 2010) and more recent studies (Edmonson et al. 2014; Zeidán-Chuliá et al. 2014), indicate a role for astrocyte–neuron interaction in the pathogenesis of ASD and epilepsies and suggest that astroglial dysfunction deserves additional investigation in AEP. Interestingly , phenotypic dissection in over 200 patients (Valvo et al. 2013) has also suggested that macrocephaly (defined as head circumference [HC] greater than the 97th percentile ), together with generalized somatic overgrowth, predisposes to early-onset seizures in idiopathic ASD (Lainhart et al. 1997). It is tempting to hypothesize that shared pathogenic mechanisms might explain the concurrence of brain/cranial overgrowth, seizures (or paroxysmal EEG activity), and the neurobehavioral dysfunction characterizing ASD and thus allow the definition of an even more selective endophenotype (namely, the macrocephaly autism–epilepsy phenotype, MAEP). "
    [Show abstract] [Hide abstract] ABSTRACT: The frequent co-occurrence of autism spectrum disorders (ASD) and epilepsy, or paroxysmal EEG abnormalities, defines a condition termed autism–epilepsy phenotype (AEP). This condition results, in some cases , from dysfunctions of glial inwardly rectifying potassium channels (Kir), which are mainly expressed in astrocytes where they mediate neuron–glia communication. Macrocephaly is also often comorbid with autism–epilepsy (autism–epilepsy phenotype with macrocephaly, MAEP), and it is tempting to hypothesize that shared pathogenic mechanisms might explain concurrence of these conditions. In the present study, we assessed whether protein pathways involved, along with Kir channels, in astrocyte–neuron interaction at the tripartite synapse play a role in the etiopathogenesis of MAEP. Using a targeted resequencing methodology, we investigated the coding regions of 35 genes in 61 patients and correlated genetic results with clinical features. Variants were subdivided into 12 classes and clustered into four groups. We detected rare or previously unknown predicted deleterious missense changes in GJA1, SLC12A2, SNTA1, EFNA3, CNTNAP2, EPHA4, and STXBP1 in seven patients and two high-frequency variants in DLG1 in six individuals. We also found that a group of variants (predicted deleterious and non-coding), segregating with the comorbid MAEP/AEP subgroups, belong to proteins specifically involved in glutamate transport and metabolism (namely, SLC17A6, GRM8, and GLUL), as well as in potassium conductance (KCNN3). This “endophenotype-oriented” study, performed using a targeted strategy, helped to further delineate part of the complex genetic background of ASD, particularly in the presence of coexisting macrocephaly and/or epilepsy/paroxysmal EEG, and suggests that use of stringent clinical clustering might be an approach worth adopting in order to unravel the complex genomic data in neurodevelopmental disorders.
    Article · Nov 2015
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