Klinefelter Syndrome: a neurodevelopmental disease of the synapse

Children with KS display a spectrum of phenotypic manifestations, including abnormal neurocognitive phenotypes. However, due to the limited research focusing on the central nervous system (CNS), our understanding of the neurobiology of KS at the cellular and molecular levels remains largely unclear.

In this study, we utilized brain organoids derived from pluripotent stem cells to explore the mechanisms underlying early brain developmental defects in KS patients. We demonstrate that KS organoids display altered neurogenesis, gliogenesis, and glutamate signaling pathways. We believe these early alterations contribute to the abnormal brain development and later cognitive phenotypes in KS patients.