Concurrent Von Hippel-Lindau disease and enhanced S-cone syndrome leading to a distinct retinal phenotype

Von Hippel-Lindau (VHL) disease and Enhanced S-cone syndrome (ESCS) are rare inherited disorders that independently predispose to vision-threatening retinal pathology through distinct mechanisms: VHL through hypoxia-induced activation of several angiogenic factors, which lead to the development of retinal capillary hemangioblastoma (RCH), and ESCS by disrupting photoreceptor development through NR2E3 variants. We describe the coexistence of these two conditions in a pediatric patient, confirmed by multimodal imaging, electroretinography, and genetic testing.

A retrospective case report.

A 13-year-old girl presented with poor vision in both eyes, mainly in dim light. Fundus examination revealed multiple small hypopigmented areas distributed nasally and temporally along the inferior arcades in both eyes, and multiple small RCHs distributed in all quadrants with superonasal exudations and macular choroidal neovascular membrane (CNVM) in the left eye. Full-field electroretinography (ff-ERG) showed nonrecordable rod responses, broadened rod-cone and cone responses, and a markedly reduced 30-Hz flicker amplitude. While the right eye was successfully managed conservatively, targeted focal laser and intravitreal anti-vascular endothelial growth factor (VEGF) therapy led to regression of neovascular lesions and visual improvement in the left eye. Whole-exome sequencing identified a heterozygous VHL c.452T > C (p.Ile151Thr) variant and a homozygous NR2E3 c.932G > A (p.Arg311Gln) variant.

Both VHL disease and ESCS manifested their characteristic retinal findings of RCH, along with the typical electrophysiological features and the CNVM associated with ESCS.