Macrocephaly in autism and other pervasive developmental disorders

Area of Science:

• Neurodevelopmental disorders
• Genetics and heritability

Background:

• Macrocephaly, defined as a head circumference significantly larger than average, is observed in various neurodevelopmental conditions.
• The prevalence and familial contribution of macrocephaly in autism spectrum disorder (ASD) require further investigation.

Purpose of the Study:

• To determine the prevalence of macrocephaly in children with autism and related pervasive developmental disorders.
• To assess the familial aggregation of head circumference in families of children with autism.
• To compare macrocephaly rates in autism with a comparison group with tuberous sclerosis complex (TSC) or seizure disorders.

Main Methods:

• A study involving 41 children diagnosed with autism and 21 children with TSC or unspecified seizure disorders.
• Head circumference measurements were taken for probands and 133 first-degree relatives to assess familiality.
• Statistical comparison with published normative data and within the study groups.

Main Results:

• Macrocephaly was significantly more prevalent in children with autism (12.2%) and their first-degree relatives (15.5%) compared to normative data.
• The comparison group with TSC/seizure disorders also showed higher than normative rates (9.5% in probands, 8.3% in relatives), but the association was stronger in autism.
• Head circumference and extreme macrocephaly scores demonstrated moderate heritability (H2 = 0.47).

Conclusions:

• The elevated prevalence of macrocephaly in relatives of children with autism suggests it may be a familial risk factor in autism's pathogenesis.
• Macrocephaly is a heritable trait that is disproportionately associated with autism spectrum disorder.
• These findings highlight the potential role of genetic factors influencing head growth in the development of autism.