Accelerated head growth in early development of individuals with autism

doi:10.1016/j.pediatrneurol.2004.08.005

Pediatric Neurology

Volume 32, Issue 2, February 2005, Pages 102-108

https://doi.org/10.1016/j.pediatrneurol.2004.08.005 Get rights and content

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.

Introduction

Macrocephaly (head circumference >97th percentile) is a consistent physical finding in individuals with autism. Kanner first reported an association between autism and increased head circumference in his initial description of 11 children with autism [1]. Despite numerous subsequent studies [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], there is limited understanding of the link between autism and macrocephaly.

Macrocephaly in autism has been investigated via retrospective [6], [7], [12], prospective [8], and familial studies [4]. In addition, several studies have compared head circumference in normal or clinical control subjects (e.g., individuals with language disorders or tuberous sclerosis complex) and individuals with autism [2], [4], [12]. The autism groups consistently had a greater occurrence of macrocephaly than either normal or clinical control subjects, with the percentage of macrocephaly in autism samples ranging from 14% to 34%.

Despite the consistent findings of macrocephaly in autism, sex and developmental change appear to differentially influence macrocephaly patterns. For instance, the rates of macrocephaly with respect to sex ranged from twice as low to five times greater for males than females [6], [13]. Two patterns of head circumference growth were observed in autism with respect to age: a linear increase in the rate of macrocephaly across age groups [7] and an increase in early childhood that normalizes with maturation [2]. Several studies examined head circumference in early development of children with autism and determined that macrocephaly is typically not present at or shortly after birth [8], [11]. Other investigators, using neuroimaging and postmortem examination results, suggested that macrocephaly in individuals with autism was associated with an enlarged brain [14], [15], [16] and that the brain volume is increased in 2- to 5-year-old children with autism [2], [17], [18]. Despite these varied research findings, all of the studies concluded that macrocephaly is an important clinical feature related to autism and should be investigated further.

Most recently, Courchesne et al. [19] suggested that autism is characterized by a reduced head size at birth and a sudden increase in head size between 1 to 2 months, as well as between 6 to 14 months. The authors emphasized that the sudden and excessive growth in their autism sample was a potential early indicator of autism risk, which well preceded any behavioral signs of the disorder.

The current study is based on the hypothesis that accelerated head growth is associated with autism risk and that macrocephaly is a secondary manifestation of accelerated head growth. This hypothesis was tested by examining both macrocephaly and the rate of head circumference growth during early childhood in participants from a larger genetic epidemiology study of autism. In addition, using standard measures of adaptive and behavioral functioning, clinical correlates in the subset of individuals with accelerated head growth were examined.

Section snippets

Participants

Two hundred fifty-one affected individuals from 195 autism families ascertained for a genetic linkage research were included in this study. Families were ascertained through clinical referrals and active recruitment through lay organizations providing services to autism families. The participants represent an independent sample of individuals from families in our ongoing genetic studies. Informed consent was obtained from all families. Ascertainment of families and evaluation of affected

Results

Of the 251 autistic patients who participated, 183 (73%) were males and 68 (27%) were females. This 2.7:1 male to female ratio is not significantly different from the 3:1 ratio observed in the general autism population [33]. The average age of patients when they entered the study was 8.15 years with a standard deviation of 4.43 years. Demographics and family status (multiplex vs sporadic) of these patients are presented in Table 1. Eighty-four percent of participants were Caucasian. The sample

Discussion

Autism is a behaviorally defined disorder with diagnosis dependent on history and observation of behavioral, social, and communication impairments, making early diagnosis problematic. Although the onset of autism occurs before 3 years of age, the average age of diagnosis is usually later and can stretch to 6 years of age [34]. Recent studies suggest that macrocephaly in some individuals may be a risk factor for autism. If this hypothesis is true, the physical finding of macrocephaly in autism

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View all citing articles on Scopus

: Dementieva YA, Vance DD, Donnelly SL, Elston LA, Wolpert CM, Ravan SA, DeLong GR, Abramson RK, Wright HH, Cuccaro ML. Accelerated head growth in early development of individuals with autism.

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Original articlesAccelerated head growth in early development of individuals with autism

Introduction

Section snippets

Participants

Results

Discussion

Lancet

J Am Acad Child Adolesc Psychiatry

Brain Dev

Brain Dev

Lancet

J Am Acad Child Adolesc Psychiatry

Autistic disturbances of affective contact

Nervous Child

Effects of age on brain volume and head circumference in autism

Neurology

Macrocephaly in autism and other pervasive developmental disorders

Dev Med Child Neurol

A case-control family history study of autism

J Child Psychol Psychiatry Allied Disciplines

Head circumference measurements in children with autism

J Virol

Microcephaly and macrocephaly in autism

J Autism Dev Disord

Head circumference in autism and other pervasive developmental disorders

J Child Psychol Psychiatry

Predictors of cognitive test patterns in autism families

J Child Psychol Psychiatry

An MRI study of brain size in autism

Am J Psychiatry

A clinicopathological study of autism

Brain

Brain weight in autismNormal in the majority of cases, megalencephalic in rare cases

Neurology

Unusual brain growth patterns in early life in patients with autistic disorderAn MRI study

Neurology

Original articles
Accelerated head growth in early development of individuals with autism