Which are the causes of Congenital bilateral perisylvian syndrome?

Congenital bilateral perisylvian syndrome (CBPS) is a rare neurological disorder primarily caused by abnormal development of the cerebral cortex, specifically within the perisylvian regions of the brain. While the exact etiology remains under investigation, it is believed to result from a combination of genetic predispositions and early prenatal disruptions to neuronal migration during brain development.

What causes Congenital bilateral perisylvian syndrome?

The fundamental cause of Congenital bilateral perisylvian syndrome is a developmental malformation known as polymicrogyria, where the brain surface develops an excessive number of small, abnormal folds. This structural abnormality occurs during the second trimester of pregnancy, a critical window when neurons are migrating to their final positions in the brain. Think of it like a construction project where the "blueprints" for the brain's architecture were interrupted, leading to the disorganized folding patterns that characterize Congenital bilateral perisylvian syndrome.

Is Congenital bilateral perisylvian syndrome hereditary?

The genetic landscape of Congenital bilateral perisylvian syndrome is complex and heterogeneous. While some cases appear to be sporadic—meaning they occur without a clear family history—others demonstrate patterns of inheritance, including X-linked, autosomal dominant, and autosomal recessive transmission. Researchers have identified mutations in several genes linked to cortical development, such as SRPX2, COL18A1, and GPR56, which may contribute to the development of Congenital bilateral perisylvian syndrome in certain individuals. However, many patients do not have a mutation in these known genes, suggesting that other, yet-to-be-discovered genetic factors play a significant role.

Are there environmental triggers or other risk factors?

Beyond genetics, environmental factors occurring during pregnancy may contribute to the brain malformations seen in Congenital bilateral perisylvian syndrome. These triggers generally act by disrupting the blood supply or the chemical environment of the developing fetal brain. Potential factors include:

• In utero infections: Exposure to viruses such as Cytomegalovirus (CMV), which can cause inflammation and disrupt neuronal migration.


• Vascular insults: Any event that reduces oxygen or blood flow to the developing fetal brain during the mid-gestation period.


• Metabolic factors: Rare metabolic conditions that interfere with the biochemical processes required for healthy neuronal organization.

How does current research approach the etiology of the syndrome?

Currently, the medical community is shifting toward a more nuanced understanding of Congenital bilateral perisylvian syndrome by utilizing advanced genomic sequencing, such as Whole Exome Sequencing (WES). Researchers are working to distinguish between "causes"—the primary genetic or environmental events that initiate the condition—and "risk factors," which may increase the likelihood of the condition occurring but are not sufficient on their own to trigger it. With 45 members in the DiseaseMaps.org community sharing their experiences, we are learning more about the phenotypic diversity of the condition, which helps researchers correlate specific genetic findings with clinical symptoms.

Next steps

• Consult with a clinical geneticist to discuss the possibility of genetic testing and family counseling.


• Schedule an evaluation with a pediatric neurologist to review brain imaging (MRI) and discuss the specific nature of the perisylvian malformations.


• Connect with the DiseaseMaps.org community to share experiences and learn from others living with Congenital bilateral perisylvian syndrome.


• Participate in clinical research registries or natural history studies to help scientists better understand the long-term progression of this condition.

Medical disclaimer: This information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

References

• Orphanet: Congenital bilateral perisylvian syndrome (ORPHA:3153).


• NIH Genetic and Rare Diseases Information Center (GARD): Bilateral perisylvian polymicrogyria.


• OMIM (Online Mendelian Inheritance in Man): Perisylvian polymicrogyria, bilateral (Entry #300105).


• PubMed: Current literature reviews on cortical malformations and polymicrogyria.