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.
Insights
Children with macrocephaly, especially males, face a higher risk of neurodevelopmental disorders. This study also identified PTEN gene mutations in some autism spectrum disorder cases, suggesting potential screening benefits.
Area of Science:
- Neuroscience
- Genetics
- Pediatrics
Background:
- Macrocephaly, or an unusually large head circumference, is a clinical finding that can be associated with various neurodevelopmental conditions.
- Understanding the link between macrocephaly and specific disorders is crucial for early diagnosis and intervention.
Purpose of the Study:
- To investigate the relationship between macrocephaly and neurodevelopmental disorders in young children.
- To determine the prevalence of PTEN gene mutations in individuals with autism spectrum disorders (ASDs) and macrocephaly in Japan.
Main Methods:
- Collected diagnostic and medical data from 93 children under 4 years old with macrocephaly.
- Conducted PTEN gene mutation analysis in 16 individuals with macrocephaly aged 3-22 years.
Main Results:
- Sixteen macrocephalic children exhibited neurodevelopmental disorders, including ASDs, intellectual disability, and ADHD.
- Male gender was significantly associated with these disorders; PTEN gene mutation was found in one case of severe autism with macrocephaly.
Conclusions:
- Macrocephaly in children, particularly males, indicates an elevated risk for neurodevelopmental disorders.
- Routine health checks and potential PTEN mutation screening are recommended for Japanese children with macrocephaly and ASDs.
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.
