Optic Nerve Hypoplasia Syndrome: A Review of the Epidemiology and Clinical Associations

Background: Optic nerve hypoplasia (ONH) has developed into a leading cause of congenital blindness. The frequently associated features of hypopituitarism and absent septum pellucidum were felt to have embryonic linkage as “septo-optic dysplasia” or “de Morsier’s syndrome.” More recent studies have suggested these associations are independent of one another. This review provides an assessment of the historical and recent evidence linking neuroradiologic, endocrinologic and developmental morbidity in patients with ONH. The prenatal risk factors, heritability, and genetic mutations associated with ONH are described. Results: Recognition of the critical association of ONH with hypopituitarism should be attributed to William Hoyt, not Georges de Morsier. De Morsier never described a case of ONH or recognized its association with hypopituitarism or missing septum pellucidum. Hypopituitarism is caused by hypothalamic dysfunction. This, and other more recently identified associations with ONH, such as developmental delay and autism, are independent of septum pellucidum development. Other common neuroradiographic associations such as corpus callosum hypoplasia, gyrus dysplasia, and cortical heterotopia may have prognostic significance. The predominant prenatal risk factors for ONH are primiparity and young maternal age. Presumed risk factors such as prenatal exposure to drugs and alcohol are not supported by scrutiny of the literature. Heritability and identified gene mutations in cases of ONH are rare. Conclusion: Children with ONH require monitoring for many systemic, developmental, and even life-threatening problems independent of the severity of ONH and presence of brain malformations including abnormalities of the septum pellucidum. “Septo-optic dysplasia” and “de Morsier’s syndrome” are historically inaccurate and clinically misleading terms.