Choroid plexus and perivascular space abnormalities in CerTra syndrome: neuroimaging and histological findings

Ceramide transporter syndrome (CerTra syndrome) is a rare neurodevelopmental disorder caused by pathogenic variants in CERT1 gene encoding ceramide transporter (CERT). These variants disrupt ceramide transport and sphingolipid homeostasis, leading to a clinical phenotype that includes developmental delay, movement abnormalities, and structural brain anomalies. Despite growing recognition of this condition, detailed neuroimaging and neuropathological characterization remain limited. Here, we present a 12-year-old girl with a pathogenic CERT1 variant complicated by sudden unexplained death, who presented with unreported neuroimaging abnormalities in choroid plexus (ChP) and perivascular space (PVS). Clinical Magnetic Resonance Imaging (MRI) obtained approximately 10 years prior to death, as well as postmortem MRI, revealed bilateral cystic enlargement of the ChP and prominent PVS filled with abundant proteinaceous material in white matter. Neuropathological examination demonstrated marked ChP epithelial disorganization, reduced aquaporin-1 (AQP1) expression, cyst formation, and focal calcifications, which may be associated with disturbances in cerebrospinal fluid (CSF) dynamics. These findings raise the possibility that CERT1 variants may be associated with ChP architectural changes and altered perivascular clearance.