Septo-optic dysplasia (SOD) is a heterogeneous neurodevelopmental disorder classically defined by optic nerve hypoplasia, hypothalamo-pituitary dysfunction, and midline brain abnormalities, although the full triad is not consistently present. This review synthesises current evidence on the developmental, endocrine, ophthalmic, and neuroradiological dimensions of the SOD/optic nerve hypoplasia spectrum. Shared embryological origins of the optic pathways, hypothalamus, and pituitary, together with disruption of inductive signalling pathways and pathogenic variants in developmental regulators including SOX2, HESX1, SOX3, and OTX2, provide a mechanistic basis for combined ocular and pituitary phenotypes. Clinically, affected children may present with nystagmus, strabismus, visual impairment, neonatal hypoglycaemia, or evolving pituitary hormone deficiencies, and remain at risk of neurodevelopmental morbidity. Neuroradiological studies have expanded the phenotype beyond classical midline defects to include malformations of cortical development and SOD-plus presentations. Current evidence supports longitudinal endocrine surveillance, detailed ophthalmic assessment, and multidisciplinary care, including timely hormone replacement and developmental support where indicated.
Von Hippel-Lindau disease (VHL) is a rare autosomal dominant hereditary tumour predisposition syndrome affecting multiple organ systems, including the retina, central nervous system, kidneys, pancreas, adrenal glands, and inner ear. It is caused by pathogenic variants in the VHL gene, resulting in loss of functional pVHL, abnormal stabilization of hypoxia-inducible factor (HIF)-alpha subunits, and activation of downstream transcriptional programmes involved in angiogenesis, metabolism, cell survival, and tumour growth. Clinically, VHL is characterized by a spectrum of benign and malignant neoplasms that require lifelong surveillance and multidisciplinary management. Retinal hemangioblastomas are among the earliest manifestations and may provide the first clue to diagnosis of this multisystem disorder. Historically, management has relied on screening, surveillance, and local treatment according to lesion size, location, symptoms, and malignant potential. The emergence of HIF-2 alpha-targeted therapy, particularly belzutifan, has begun to change this paradigm by offering a mechanism-based systemic treatment option for selected VHL-associated tumours. In this review, we summarize the ocular and systemic manifestations of VHL, its genetic and molecular basis, genotype-phenotype correlations, contemporary surveillance strategies, current local therapies, and the emerging role of HIF-2 alpha inhibition in reshaping management.
