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.