Early detection and treatment of congenital ventriculomegaly (CCV), a disease in which the fluid-filled ventricles of a fetus’s brain swell in a condition called hydrocephalus, can help clinicians prevent developmental and neurological problems in affected infants. A new study led by researchers at the Massachusetts General Brigham Neuroscience Institute has identified some of the genetic mutations involved in this condition, which is common along with autism and other developmental disorders. The survey results are scientific translational medicine.
A significant number of patients have developmental delays, and up to 10% exhibit autism spectrum disorders. Our findings link CCV to neurodevelopmental disorders and position CCV as a potential early neuroimaging correlate of autism risk. ”
Christopher T. Karl, MD, PhD, senior author, director of pediatric neurosurgery, Brigham Neuroscience Institute, Massachusetts
Kahle is also the Nicholas T. Zervas Endowed Chair in Neurosurgery at Harvard Medical School and a researcher at the Broad Institute of MIT and Harvard University.
For this study, Kahle and colleagues analyzed genetic data from approximately 2,700 children with congenital ventriculomegaly and their parents and combined the results with information from brain development datasets and mouse models to identify potential causative mutations.
The researchers found that about 25% of cases are associated with rare, deleterious genetic mutations, many of which are in genes important for how brain cells grow and organize during early brain development. In mice, suppressing these genes impaired both brain fluid movement and the structure of the cerebral cortex, which is responsible for higher-order functions such as reasoning, memory, and language, and caused the ventricles to swell.
The findings suggest that congenital ventriculomegaly is not simply a fluid circulation problem, but often reflects an underlying developmental problem in the brain itself. The authors suggest a combination of prenatal imaging and genetic testing to identify cases before birth.
“While neurosurgical interventions are often life-saving and effective, in some cases they fail to improve ventricular size or neurodevelopmental outcomes, exposing patients to future infections and long-term dependence on drainage shunts,” Kahle said. “Genomic testing may ultimately refine patient selection and identify whether surgical or nonsurgical treatment is best in individual circumstances.”
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Reference magazines:
Arrington, G. Others. (2026) Developmental genetic determinants of the human cerebrospinal fluid ventricular system. Science translational medicine. DOI: 10.1126/scitranslmed.aec4386. https://www.science.org/doi/10.1126/scitranslmed.aec4386
