ARV1 Gene: Another example for one gene many faces

Abstract Background: ARV1 mutation is known to present as Developmental epileptic encephalopathy (DEE)-38. However, the phenotypic spectrum has been expanding ever since it was reported in 2016. Along with the seizures and developmental delay other unique clinical features include ophthalmological abnormalities and movement disorders in the form of ataxia and dystonia especially in those with missense mutation. These manifestations mimic the common ataxia telangiectasia. Elevation of alpha feto-protein levels is an important investigative marker in the diagnosis of ataxia telangiectasia and some ataxia with oculomotor apraxia syndromes. ARV1can also be associated with increased alpha feto-protein. There are no reports evaluating alpha feto-protein levels in ARV1 mutation, which is significant in the context of ocular abnormalities with ataxia. Results: We report a case of ARV1 mutation presenting with ataxia, ocular abnormalities and elevated alpha feto-protein levels, thus mimicking autosomal recessive cerebellar ataxias. This study provides a comprehensive literature review of the cases reported so far, thus expanding the understanding of the spectrum of presentation, and helps in correlating the clinical picture with the underlying causative genetic mutation. Conclusion: ARV1gene is another example of one gene with phenotypic pleiotropy. Though presentation with DEE is a common presentation, a few of them especially those with missense mutations can present with ataxia and ocular abnormalities. All cases with ataxia who have increased alpha feto-protein levels and seizures should be tested for ARV1 gene when testing for ataxia genes is negative. Underlying genetic mechanism can explain the varying clinical manifestations of ARV1 gene.