Biological pathways leading to septo-optic dysplasia: a review.

Background: The precise etiology of septo-optic dysplasia (SOD) remains elusive, to date a complex interaction between genetic predisposition and prenatal exposure to environmental factors is believed to come into play. Being SOD such a heterogeneous condition, disruption of many developmental steps in the early forebrain development might occur. The knowledge of genes possibly determining SOD phenotype should be improved, therefore in this review the authors attempt to highlight the genetic pathways and genes related to this clinical condition.

Main body: Literature search was conducted and updated in November 2023, using PubMed and Google Scholar to identify primary research articles or case reports with available full text using the following search string "case reports," "humans," "septo-optic dysplasia," "optic nerve hypoplasia," with a recognized genetic diagnosis. Moreover, a review of genetic pathways with an involvement in SOD etiology was conducted. This review thus represents the authors' perspective based on selected literature. The several pathways presented might be already associated to other disease phenotypes and interplay with genes and pathways known to have a role in SOD determination. Those pathways may converge and thus, the implicated genes may function as cascading regulators at multiple levels.

Conclusion: The present data suggest that genes other than HESX1, SOX2, SOX3, and OTX2 might be investigated in candidate individuals with a clinical diagnosis of SOD corresponding to the presence of at least two diagnostic criteria, particularly in the presence of additional syndromic anomalies.