Abstract

Background: Congenital nephrosis syndrome is caused by a dysfunctional glomerular filtration barrier. The condition is characterized by worsening proteinuria, hypoalbuminemia, and life-threatening generalized edema. Central nervous system involvement may also occur. Patients with this condition have been reported to exhibit global developmental delay, hypotonia, psychomotor debility, and rare epileptic seizures. They may also exhibit pachygyria, cortical dysplasia, cerebellar atrophy, meningeal heterotopies and hemispheric hypomyelination. Materials and results: This report presents the case of an infant with congenital nephrosis syndrome who was unresponsive to corticosteroids. A comprehensive neuropathological examination revealed subtle brain abnormalities, including subcortical and meningeal neuronal heterotopies, as well as abrupt interruptions of the cortical layering due to abnormally penetrating meningeal vessels. These findings, which have not been reported thus far, resulted in disruption of the normal cortical organization. Conclusions: During development, podocytes are present in the artery wall alongside other critical cells, such as pericytes. They play a crucial role in ensuring glomerular filtration in the kidneys. Defects in podocytes are a recognized cause of congenital nephrosis syndrome. Interestingly, podocytes exhibit remarkable metabolic and morphological similarities to developing neurons that target the cortex. Additionally, they are widely represented in the developing artery walls, including those in the brain during angiogenesis. Due to their pivotal role in arterial vessel development, podocyte defects may affect penetrating meningeal vessels and disrupt the corresponding cortical organization. This can result in focal abnormalities of cortical lamination. However, this defect likely occurs after neuronal cortical migration is complete because no neuronal migration defects were observed.

Keywords

congenital nephrosis syndrome, podocytes, meningeal vessel wall, BBB, cortical disruption, neuronal heterotopies