Polymicrogyria is Associated With Pathogenic Variants in PTEN.

Area of Science:

• Neuroscience
• Genetics
• Radiology

Background:

• Pathogenic variants in the phosphatase and tensin homologue (PTEN) gene are associated with congenital brain malformations.
• The frequency and clinical impact of cortical malformations in PTEN variant patients remain unclear.

Purpose of the Study:

• To systematically characterize brain malformations in patients with PTEN variants.
• To assess the clinical relevance of these brain malformations.

Main Methods:

• Systematic search of a radiology database for brain MRIs in patients with PTEN variants.
• Review of MRI scans for cortical abnormalities.
• Evaluation of EEG data and medical records for epilepsy and developmental delay.

Main Results:

• 54% of 22 patients with PTEN variants exhibited polymicrogyria (PMG) or atypical gyration.
• PTEN variants associated with PMG affected the phosphatase or C2 domains.
• Epilepsy was infrequent (2/12) in patients with PMG.
• A trend toward increased global developmental delay, intellectual disability, and motor delay was observed in individuals with cortical abnormalities.

Conclusions:

• Malformations of cortical development, especially PMG, are an under-recognized phenotype in PTEN variant patients.
• These malformations may correlate with cognitive and motor delays.
• Epilepsy risk appears lower than previously reported for PMG.