Neurodevelopmental disorders in children with macrocephaly: A prevalence study and PTEN gene analysis
Hirofumi Kurata1, Kentaro Shirai2, Yoshiaki Saito1
1Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Purpose:
To clarify the relationship between macrocephaly and neurodevelopmental disorders, as well as identify the prevalence of PTEN mutations in autism spectrum disorders with macrocephaly in Japan.
Subjects And Methods:
Diagnostic and other medical information of children with macrocephaly younger than 4years (n=93) were collected for analysis. PTEN gene mutation analysis was conducted in another set of 16 macrocephalic individuals aged 3-22years.
Results:
Sixteen macrocephalic children were associated with neurodevelopmental disorders, including autism spectrum disorders (ASDs) (n=6), autistic traits (n=5), intellectual disability (n=5), attention deficit hyperactivity disorder (n=1), developmental coordination disorders (n=1), and language disorder (n=1). Male gender was significantly linked to these disorders, whereas a family history and degree of macrocephaly were not significantly linked to the diagnosis. A novel mutation in the PTEN gene was identified in a 16-year-old girl with autism, mental retardation, language delay, extreme macrocephaly (+4.7SD) with a prominent forehead, and digital minor anomalies.
Conclusion:
Children with macrocephaly, particularly males, are at a higher risk of neurodevelopmental disorders, rather than progressive etiologies, such as hydrocephalus and neurodegenerative disorders. The data provide a basis for routine health checks for young children in Japan, including the follow-up management and possible screening of PTEN mutations in children with ASDs and macrocephaly.
