Is macrocephaly expected in autism?

From the Guidelines

Macrocephaly is not expected in all cases of autism, but it is more common in individuals with autism spectrum disorder (ASD), occurring in approximately 15% of cases, as defined by a head circumference greater than 2 standard deviations above the mean for age and sex 1.

Key Points

• Macrocephaly is a well-known phenotype within idiopathic ASD cases, with estimates suggesting that around 15% of ASD cases have macrocephaly 1.
• The increased head size typically develops in the first few years of life, often following a normal head circumference at birth, and is believed to result from abnormal brain growth patterns, particularly excessive neuronal proliferation and altered connectivity in early development.
• Brain imaging studies have shown increased brain volume, especially in the frontal and temporal lobes, in individuals with ASD and macrocephaly 1.
• However, since macrocephaly occurs in only a subset of autism cases, it is considered a potential marker rather than a diagnostic criterion.
• When evaluating a child with suspected autism, head circumference should be measured as part of the comprehensive assessment, but normal head size does not rule out autism, and macrocephaly alone is not sufficient for diagnosis.

Recommendations

• Head circumference should be measured in all children with suspected autism as part of a comprehensive assessment 1.
• PTEN testing should be considered in patients with ASD and macrocephaly, as PTEN mutations have been associated with an increased risk of ASD and macrocephaly 1.
• A comprehensive genetic evaluation, including fragile X syndrome and MECP2 testing, should be considered in patients with ASD and other clinical features suggestive of a genetic syndrome 1.

From the Research

Macrocephaly in Autism

• Macrocephaly, or an abnormally large head size, has been associated with autism in several studies 2, 3, 4.
• However, the prevalence of macrocephaly in autism varies across studies, with some reporting a higher frequency 3, 4 and others finding no significant association 5.
• A study published in 2013 found that 22% of autism cases with macrocephaly had mutations in the PTEN gene, suggesting a possible genetic link between the two conditions 2.
• Another study from 1997 reported that 14% of autistic subjects had macrocephaly, which was not present at birth in most cases and became apparent in early and middle childhood due to increased rate of head growth 3.
• In contrast, a 2014 study found that only 3% of pre-school children with autism had macrocephaly, similar to the general population prevalence 5.

Prevalence of Macrocephaly in Autism

• The prevalence of macrocephaly in autism has been estimated to be around 20% in some studies 4.
• However, other studies have reported lower frequencies, ranging from 3% to 16.7% 5, 4.
• The variation in prevalence rates may be due to differences in study populations, definitions of macrocephaly, and methodologies used 2, 5, 3, 4.

Clinical Implications

• The presence of macrocephaly in autism may have implications for clinical diagnosis and treatment 2, 3.
• Studies have reported associations between macrocephaly and certain genetic mutations, such as PTEN, which may inform genetic testing and counseling 2.
• However, the relationship between macrocephaly and autism symptoms is not fully understood, and further research is needed to elucidate the clinical significance of macrocephaly in autism 3, 6.