Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is a rare genetic disorder that was identified in an Old Order Mennonite pediatric population. It is characterized by abnormal brain development, an abnormally large brain, cognitive disability, and severe, therapy-resistant epilepsy. PMSE is caused by mutations in the gene STRADA.
A team of researchers, led by Peter Crino, at the University of Pennsylvania, Philadelphia, has now provided insight into how mutations in STRADA cause PMSE by analyzing a human PMSE brain and mice.
Specifically, their data indicate that the lack of STRAD-alpha protein caused by the STRADA gene mutations results in the protein LKB1 being abnormally localized, and that this leads to activation of the mTOR signaling pathway, thereby promoting abnormal cell growth and brain development.
The authors suggest that early treatment with the mTOR inhibitor rapamycin, which is used in the clinic to prevent rejection of organ transplants, and other mTOR inhibitors may prevent the devastating neurological features of PMSE.
In an accompanying commentary, Lucy Osborne, at the University of Toronto, Canada, discusses how the data generated by Crino and colleagues adds PMSE to a group of disorders caused by uncontrolled mTOR pathway activation and characterized by benign tumors and malformations of the brain.
The research appears in the Journal of Clinical Investigation.
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
Cite This Page: