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

Abstract

Opinion statement 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.

Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study

“…The majority of cases of SOD are sporadic, and several etiologies including maternal drug and alcohol abuse have been suggested (11,20) . Possibly due to teen pregnancies and/or substance abuse (details not found in the EMR), 8% of the patients in our study were placed for adoption at birth.…”

Temporal expression of CD184(CXCR4) and CD171(L1CAM) identifies distinct early developmental stages of human retinal ganglion cells in embryonic stem cell derived retina

“…RGC death is the cause of blindness in two prominent diseases, glaucoma, and optic nerve hypoplasia. Optic nerve hypoplasia is the most common cause of congenital blindness, the etiology of which is unknown and therapy non-existent (Borchert, 2012; Garcia-Filion and Borchert, 2013). Glaucoma is the leading cause of irreversible blindness worldwide, a disease about which much is known but that still lacks a cure (Almasieh et al, 2012; Weinreb et al, 2014).…”

Genetic causes of optic nerve hypoplasia

“…Given that most ONH cases are isolated within their respective families, research into the causal factors of ONH has focused on environmental effects. Many environmental risk factors for ONH have been reported, including maternal alcohol abuse during pregnancy, young maternal age, primiparity, maternal use of recreational drugs, anticonvulsants or antidepressants 6. However, familial cases of ONH also exist,7 8 suggesting genetic aetiologies.…”