PTEN gene mutations in patients with macrocephaly and classic autism: A systematic review

Autism Spectrum Disorder (ASD) is a neurological disorder characterized by massive damage in various fields of development. Impaired social interaction and communication skills, unusual behavior or interests, and repetitive activities are considerably disabling in these patients. There are several challenges in diagnosis of ASD patients such as co-existing epilepsy, difference in clinician attitudes and possibly multifactorial etiology of autistic behavior among children and adults. Research in recent years has emphasized a possible connection between mutations in PTEN and macrocephaly (head circumference > 97th centile).

Articles in English Language were searched from international databases including Medline (PubMed), Google Scholar, Scopus, and CINHAL from January 1998 to January 2016.

The results showed that among 2940 patients with behavioral disorders, 2755 individuals had ASD, and 35 cases with macrocephaly had mutations in PTEN. About 77% of the articles (7/9) analyzed mutations in PTEN in patients with head circumference more than 2SD away from the mean, but did not check mutations in this gene in other ASD patients without macrocephaly. To the best of our knowledge, this study is the first systematic review on human PTEN mutations and classical autistic behavior.

We conclude that the presence of macrocephaly may not be sufficient to examine the PTEN mutation in this group; however, surveying this gene in all cases of macrocephaly seems to be necessary.