Leptomeningeal angiomatosis (LMA) in Sturge-Weber syndrome (SWS) typically presents with cortical calcifications on computed tomography (CT) scans and is often accompanied by enlarged, low-signal deep medullary veins seen on susceptibility-weighted magnetic resonance imaging (MRI) that lack flow-void signs on T2-weighted MRI. However, subcortical calcifications on CT and concurrent developmental venous anomaly (DVA), visible as deep medullary veins with prominent flow-void signs on T2-weighted MRI, are uncommon. We describe atypical clinicopathological features in a surgical case of a 6-year-old female patient with SWS, who had early-onset intractable epilepsy due to LMA, complicated by subcortical calcifications and DVA on neuroimaging. Presurgical MRI revealed a hypoplastic left frontal lobe covered with an LMA, and a DVA extending from the ipsilateral frontal periventricular white matter to the deep middle cerebral vein. She underwent resection of the left central and prefrontal regions and remained seizure-free postoperatively. Histopathology confirmed the presence of an LMA, dilated veins in the subcortical white matter, focal microscopic polymicrogyria, and cortical pseudolaminar sclerosis consistent with focal cortical dysplasia type IIIc. Four atypical findings were observed: (1) absent or minimal cortical calcifications; (2) clearly defined areas of fibrillary gliosis bordered by a linear band of prominent calcifications, encasing non-dilated veins in the subcortical white matter; (3) a localized cortical venous malformation; and (4) subarachnoid arterial abnormalities, including fibromuscular intimal thickening, internal elastic lamina degeneration, irregular medial thickness, and segmental medial losses replaced by dense calcifications. These findings, considered in the context of the intrinsic cerebral venous system, suggest that the non-dilated white matter veins encased by calcified gliosis represent superficial medullary veins, while the dilated veins correspond with deep medullary veins draining into the DVA. The latter possibly serve as collateral venous drainage pathways, compensating for abnormal cortical and subarachnoid venous development. The observed arterial abnormalities likely reflect secondary regressive changes.

Mutations in ZBTB20,  which encodes a transcription factor, are linked to epiphyseal dysplasia and articular degeneration in humans. This study investigates the role of ZBTB20 in regulating articular cartilage growth and integrity during postnatal development and its implications for early-onset osteoarthritis (OA) in mice. We assessed the spatiotemporal expression of ZBTB20 in articular cartilage using immunostaining and generated an inducible cartilage-specific Zbtb20 knockout mouse model. The impacts of Zbtb20 deletion on cartilage thickness, zonal organization, cellular proliferation, and apoptosis were analyzed. We employed histology, microcomputed tomography, in situ hybridization, RNA-sequencing (RNA-seq), and cleavage under targets and tagmentation (CUT&Tag) to evaluate structural and molecular changes in knees from six to eight male mice per group. ZBTB20 expression in human OA cartilage was analyzed using publicly available datasets. ZBTB20 was expressed in postnatal developing and adult articular chondrocytes. Postnatal Zbtb20 deletion resulted in progressive thickening of articular cartilage in knees, with a 1.9-fold increase at two months of age, particularly in the deep and calcified zones. This was accompanied by chondrocyte overproliferation and differentiation defects, leading to early-onset cartilage degeneration by six months. RNA-seq and CUT&Tag analyses revealed that ZBTB20 directly regulates a broad set of genes essential for cartilage growth, chondrocyte differentiation, and extracellular matrix organization. Moreover, ZBTB20 expression was significantly reduced in aging-related OA cartilage in both mice and humans, and inducible deletion of Zbtb20 in adult cartilage resulted in severe spontaneous OA-like changes in mice. ZBTB20 is essential for postnatal articular cartilage development and homeostasis, with a protective role in aging-related OA progression.