Head circumference is an independent clinical finding associated with autism

Abstract

Occipitofrontal circumference (OFC) is one of the few physical findings in autism that varies significantly from the norm and is distinct and measurable. As part of a study of genetic heterogeneity of autism, we scrutinized data from a large sample of patients with idiopathic autism (N = 137), using OFC as the categorizing variable. The OFC standard deviation (OFCSD) values of the autistic propositi (0.61+/-1.6) varied significantly from that of the normal population (0.0+/-1.0), (P<0.001). Comparison of the macrocephalic (OFCSD > 2.0, N = 32) with the normocephalic individuals (-2 SD < OFCSD < +2 SD, N = 95) showed no significant differences in sex ratio, morphological status, IQ, seizure prevalence, or recurrence risks. The macrocephalic individuals were slightly less apt than those with normocephaly to have a family history of Attention Deficit Hyperactivity Disorder (ADHD) (P<0.05). Each clinical subgroup of autism propositi, defined on the basis of phenotypic status, type of onset, seizure history, or IQ, had a higher than normal mean OFC indicating that macrocephaly is an independent clinical trait in autism. As in the non-autistic population, macrocephaly was highly familial with 45% of the macrocephalic and 37% of the normocephalic propositi having at least one macrocephalic parent. Microcephaly, however, was an independent significant variable that predicted the presence of other phenotypic or genetic traits and outcome. The microcephalic patients were more likely to have abnormal physical morphology, structural brain malformations, lower IQ, and seizures. Their sex ratio was closer to normal, and their relatives had a higher incidence of seizures.

Larger Brains in Medication Naive High-Functioning Subjects with Pervasive Developmental Disorder

“…Kanner, the first to report on autism, noticed the presence of enlarged heads in some children with autism (Kanner, 1943). Several subsequent studies have replicated this finding both in children and in adults (Aylward, Minshew, Field, Sparks, & Singh, 2002;Bailey, Luthert, & Bolton, 1993;Davidovitch, Patterson, & Gartside, 1996;Fidler, Bailey, & Smalley, 2000;Fombonne, 2000;Gillberg & de Souza, 2002;Lainhart et al, 1997;Miles, Hadden, Takahashi, & Hillman, 2000;Stevenson, Schroer, Skinner, Fender, & Simenseh, 1997;Woodhouse, Bailey, Rutter, Bolton, & Baird, 1996). Likewise, neuropathological studies have reported increased brain weight in a subset of subjects with autism.…”

Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis

“…At the end of this process, 27 studies were selected, each assessing patients with idiopathic autism (i.e., DSM-IV diagnoses of either Autistic Disorder, Asperger's Disorder or Pervasive Developmental Disorder Not Otherwise Specified, PDD-NOS), measuring head circumference in autistic patients and providing the percentage of macrocephalic individuals (Bolton et al, 1994;Bailey et al, 1995;Woodhouse et al, 1996;Davidovitch et al, 1996;Stevenson et al, 1997;Lainhart et al, 1997;Skjeldal et al, 1998;Fombonne et al, 1999;Ghaziuddin et al, 1999;Fidler et al, 2000;Miles et al, 2000;Gillberg and de Souza, 2002;Deutsch and Joseph, 2003;Torrey et al, 2004;Dementieva et al, 2005;Lainhart et al, 2006;Sacco et al, 2007;Van Daalen et al, 2007;Webb et al, 2007;Miles et al, 2008;Chawarska et al, 2011;Davidovitch et al, 2011;Ververi et al, 2012;Chaste et al, 2013;Froehlich et al, 2013;Grandgeorge et al, 2013;Cederlund et al, 2014). For each selected study, macrocephaly was defined as a head circumference above the 97 th percentile.…”

Adjustment for Whole Brain and Cranial Size in Volumetric Brain Studies: A Review of Common Adjustment Factors and Statistical Methods

“…In some disorders there appears to be an overall shift in mean brain volume that goes beyond what might be expected from body-size considerations. For example, in autistic children, whole brains are, on average, larger than in matched, typically developing individuals [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] (although microcephaly is also sometimes observed, if infrequently, in autistic children). 26 In contrast, it has been reported that children with attention-deficit/hyperactivity disorder have smaller whole brain volumes than normal, 29 though this finding is controversial.…”