Abstract
ARV1 mutation is known to present as developmental and epileptic encephalopathy (DEE)-38. However, the phenotypic spectrum has been expanding ever since it was reported in 2016. Along with 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 closely mimic ataxia telangiectasia. Elevation of alpha-fetoprotein levels is an important investigative marker in the diagnosis of ataxia telangiectasia and ataxia with oculomotor apraxia syndromes. ARV1 can also be associated with increased alpha-fetoprotein. There are no reports evaluating alpha-fetoprotein levels in cases with ARV1 mutation, which is significant in the context of ocular abnormalities with ataxia. We report a case of ARV1 mutation presenting with ataxia, ocular abnormalities, and elevated alpha-fetoprotein 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. ARV1 gene is another example of one gene with phenotypic pleiotropy. Though presentation with DEE is common, a few, especially those with missense mutations, can present with ataxia and ocular abnormalities. All cases presenting with ataxia who have increased alpha-fetoprotein levels and seizures should be tested for the ARV1 gene, when testing for ataxia genes is negative. The underlying genetic mechanism can explain the varying clinical manifestations of the ARV1 gene.
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Mahesh Kamate diagnosed and was involved in the management of the patient. He will act as guarantor of the study. Thanuja Basavanagowda collected the data and drafted the paper. The final manuscript was approved by all the authors.
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Kamate, M., Basavanagowda, T. ARV1 Gene: A Novel Cause of Autosomal Recessive Cerebellar Ataxia with Elevated Alpha Fetoprotein. Cerebellum (2023). https://doi.org/10.1007/s12311-023-01606-5
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DOI: https://doi.org/10.1007/s12311-023-01606-5