Brain Morphological Analysis in PTEN Hamartoma Tumor Syndrome

Abstract

Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a spectrum of hereditary cancer syndromes caused by germline mutations in PTEN. PHTS has been recently gathering interest, because of its high rate of neurological comorbidities including macrocephaly, autism spectrum disorder, and intellectual dysfunction. However, detailed brain morphology and connectivity of PHTS remain unclear. This is the first quantitative magnetic resonance imaging (MRI) study to report brain structure and fiber pathways in PHTS.

METHODS: The 16 structural T1-weighted and 9 diffusion-weighted MR images at 3 Tesla scanners from 12 PHTS patients and gender- and age-matched neurotypical controls were used for structural and high-angular resolution diffusion MRI (HARDI) tractography analyses.

RESULTS: Mega-corpus callosum was observed in 75%, polymicrogyria in 33%, periventricular white matter lesions in 83%, and heterotopia in 17% of the PHTS participants. While gyrification index and hemispheric cortical thickness showed no significant differences between the two groups, significantly increased global and regional brain volumes, and regionally thicker cortices in the patients with PHTS were observed. HARDI tractography showed increased volume and length of callosal pathways, and length of the bilateral inferior longitudinal fasciculi (ILF), bilateral inferior frontooccipital fasciculi, and right uncinated fasciculus. The fractional anisotropy and apparent diffusion coefficient (ADC) values of brain pathways were not significantly different between groups, except for an increase in ADC of the left ILF in PHTS.

CONCLUSION: Our results showed, for the first time, an association between specific brain regions/pathways and PTEN mutations.

Keywords: PTEN hamartoma tumor syndrome, structural brain MRI, DTI, megalencephaly, mega corpus callosum