LAYER-SPECIFIC CORTICAL NEUROPATHOLOGY IN JOUBERT SYNDROME: A POSTMORTEM CASE–CONTROL STUDY

Joubert syndrome (JS) is a rare autosomal recessive ciliopathy characterized by the molar tooth sign and associated with malformations in the cerebellum and brainstem. Although JS is considered to have a relatively well-preserved cerebral cortex, this assumption is due to limited neuropathological research. In particular, lobe and layer-specific cortical analyses in infants with JS are extremely restricted. This study aimed to investigate cortical lamination in different lobes in JS. Brain tissue samples were examined from a 4-month-old male infant diagnosed with Joubert syndrome (Council of Forensic Medicine) and a matched control (4-month-old, male infant with non-neurological causes of death). Samples were taken from the frontal, temporal, parietal, and occipital lobes. Paraffin-embedded sections were stained with Cresyl violet (Nissl stain). The sections were examined under a light microscope to evaluate their cytoarchitecture (neuronal size, shape, and laminar organization). In JS, significant differences were observed in cellular and laminar organization. The frontal cortex exhibited marked disorganization consistent with impaired early cortical maturation. In the occipital cortex, layer IV was significantly reduced. Furthermore, the granular and supragranular layers were sharply demarcated. This pattern indicates selective vulnerability of the granular layer, which represents the principal thalamocortical target zone. Although the temporal cortex was largely preserved, layer IV was not fully differentiated. In contrast, the parietal cortex was similarly immature in both groups, exhibiting laminar profiles reflecting postnatal development. These findings suggest that JS is associated with specific cortical and laminar organization differences and extends beyond classic brainstem pathology.