The Role of Retinoic Acid in Explaining the Prevalence of Strabismus for Children with Fetal Alcohol Spectrum Disorder: A Literature Review

Abstract

Background: Fetal Alcohol Spectrum Disorder (FASD) encompasses a range of neurodevelopmental conditions caused by prenatal alcohol exposure (PAE), affecting up to 5% of the population. Among its comorbidities, strabismus– a misalignment of the eyes– shows a significantly higher prevalence in children with FASD. Retinoic acid (RA), a metabolite of vitamin A, is crucial for extraocular muscle development. PAE disrupts RA metabolism, potentially mediating the relationship between FASD and strabismus.

Aim: To elucidate the biochemical and physiological pathways linking PAE to strabismus and specifically, focusing on the role of disrupted RA metabolism and its impact on extraocular muscle development and ocular alignment.
Methods: 746 articles relating to strabismus, FASD, and RA were identified using 5 databases. Of these, 67 articles were extracted based on relevance and full-text accessibility.

Results: PAE disrupts RA metabolism through competitive inhibition, reducing RA production by up to 87% and altering RA receptor expression. These disruptions may contribute to the development of strabismus by impairing the formation of extraocular muscles and the cerebellum, as supported by findings from both animal models and human studies under FASD-like conditions.

Conclusion: The disrupted RA metabolism caused by PAE provides a plausible explanation for the increased prevalence of strabismus in children with
FASD. Further research into genetic and epigenetic markers could enhance clinical assessments and promote earlier diagnosis and intervention, especially for regions with higher FASD prevalence. Understanding these mechanisms is crucial for optimizing medical interventions and mitigating the severity of outcomes following PAE.