Head circumference and height in autism: A study by the collaborative program of excellence in autism

Abstract

Data from 10 sites of the NICHD/NIDCD Collaborative Programs of Excellence in Autism were combined to study the distribution of head circumference and relationship to demographic and clinical variables. Three hundred thirty-eight probands with autism-spectrum disorder (ASD) including 208 probands with autism were studied along with 147 parents, 149 siblings, and typically developing controls. ASDs were diagnosed, and head circumference and clinical variables measured in a standardized manner across all sites. All subjects with autism met ADI-R, ADOS-G, DSM-IV, and ICD-10 criteria. The results show the distribution of standardized head circumference in autism is normal in shape, and the mean, variance, and rate of macrocephaly but not microcephaly are increased. Head circumference tends to be large relative to height in autism. No site, gender, age, SES, verbal, or non-verbal IQ effects were present in the autism sample. In addition to autism itself, standardized height and average parental head circumference were the most important factors predicting head circumference in individuals with autism. Mean standardized head circumference and rates of macrocephaly were similar in probands with autism and their parents. Increased head circumference was associated with a higher (more severe) ADI-R social algorithm score. Macrocephaly is associated with delayed onset of language. Although mean head circumference and rates of macrocephaly are increased in autism, a high degree of variability is present, underscoring the complex clinical heterogeneity of the disorder. The wide distribution of head circumference in autism has major implications for genetic, neuroimaging, and other neurobiological research.

Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin

“…Recent data from 10 sites of the NICHD/NIDCD Collaborative Programs of Excellence in Autism showed a rate of absolute macrocephaly of 17.3% for autistics vs. 3% for normal controls (p<0.0004; Lainhart et al 2006). In light of these findings along with our finding of macrocephaly in the offspring of prenatally infected mice (Fatemi et al 2002a), the observed alterations in microcephalin expression have the potential to be important for future studies investigating microcephalin and autism.…”

“…Two of these proteins, AQP4 and CX43, are likewise altered in autistic brain (Fatemi et al unpublished observations) and a third may be implicated in the macrocephaly, which is commonly observed in autistic subjects (Fombonne et al 1999;Lainhart et al 2006) as well as in our animal model (Fatemi et al 2002a). Most importantly, the weight of accumulated evidence so far showing presence of gliosis (Fatemi et al 2002b), pyramidal cell atrophy (Fatemi et al 2002a), and upregulation of nucleolin, as well as previous supportive evidence (Aronsson et al 2001;Aronsson et al 2002), showing persistence of influenza viral RNA in brain implicate a potential viral effect on the developing fetal brain.…”

Medical Comorbidities in Autism: Challenges to Diagnosis and Treatment

“…Measurements of head circumference in childhood has suggested that approximately 20% of autistic children show a frank macrocephaly of greater than 98% for age and sex. 5 Numerous epidemiologic studies have provided evidence for a genetic basis for autism. Linkage studies have identified a number of candidate genes of promise; however, despite modern technology, approximately only 6% to 15% of individuals with autism will be found to have an identifiable genetic diagnosis.…”

Autism genetics: Methodological issues and experimental design

“…In fact, macrocephaly (i.e., head circumference >97th percentile) has been consistently described in approximately 20% of autistic children [55,58,59], serotonin blood levels are elevated in 20%50% of autistic subjects [47], and increased urinary excretion rates of oligopeptides and multiple solutes is found in 20-60% of autistic patients, with significant interethnic differences [50,60,61]. The implementation of these endophenotypes in our studies is detailed in the following section.…”