A new study published in Nature Neuroscience explores a genetic link between congenital hydrocephalus (CH) — a condition where fluid-filled spaces in the brain (ventricles) become enlarged — and autism.
Duke Neurosurgery’s Tyrone DeSpenza, Jr., MD, PhD, was lead author of the study that found that mutations in the PTEN gene — already associated with autism — are a common cause of CH and ventricle enlargement.
Using mouse models, the researchers discovered that these mutations lead to excessive growth of certain brain cells, causing a blockage in fluid flow and increased fluid production, which contributes to brain abnormalities. These changes also disrupt brain activity, particularly in inhibitory neurons, which help regulate brain signaling.
Importantly, the study found that targeting a specific biological pathway (mTORC1) with the drug everolimus after birth can reverse ventricle enlargement, improve brain function, and increase survival.
“By demonstrating how PTEN mutations disrupt cerebrospinal fluid dynamics and alter cortical networks, this study opens the door for non-surgical treatment options for CH patients with refractory neurodevelopmental phenotypes after cerebrospinal fluid diversion, offering promising avenues for personalized therapies aimed at optimizing brain development,” said DeSpenza.
The study also provides insight into why some cases do not respond well to traditional fluid-draining procedures and strengthens the connection between brain fluid dynamics and autism-related brain changes.