Neurodevelopmental disorders in children with macrocephaly: A prevalence study and PTEN gene

Plupose: To clarify the relationship between macrocephaly and neurodevelopmental disorders, as well as identify the prevalence of PTEN niutations in autism spectrum disorders with macrocephaly in Japan. Subjects and methods: Diagnostic and other medical information of children with macrocephaly younger than 4 years (n = 93) were collected for analysis. PTEN gene mutation analysis was conducted in another set of 16 macrocephalic individuals aged 3-22 years. Result: 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 (+4.7 SD) 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. (C) 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.