A Novel PTEN Frameshift Variant in a Child With Autism Spectrum Disorder and Macrocephaly: A Case Report

TL;DR

A four-year-old girl with autism and macrocephaly was found to have a new PTEN gene variant, highlighting the need for early genetic testing in similar cases.

Contribution

The paper reports a novel PTEN frameshift variant in a child with autism and macrocephaly, expanding the clinical spectrum of PHTS.

Findings

The child exhibited macrocephaly, developmental delay, and autism, with a novel PTEN frameshift variant identified.

MRI showed megalencephaly and corpus callosum thickening, supporting a PHTS diagnosis.

The case emphasizes the importance of genetic testing for PTEN-related disorders in children with autism and macrocephaly.

Abstract

PTEN hamartoma tumor syndrome (PHTS) is a rare genetic condition associated with neurodevelopmental disorders, macrocephaly, and increased cancer risk. We report the case of a four-year-old girl with congenital hypothyroidism, progressive macrocephaly, and global developmental delay, later diagnosed with autism spectrum disorder (ASD). Brain MRI revealed megalencephaly with prominent extra-axial spaces and a diffusely thickened corpus callosum. Genetic testing identified a novel frameshift variant in the PTEN gene. This case highlights clinical findings that should raise suspicion for PHTS and was documented to emphasize the importance of recognizing PTEN-related disorders in children presenting with autism and macrocephaly, particularly when oncologic manifestations are not yet evident, thereby supporting early genetic diagnosis and appropriate surveillance.

Figures