Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review

Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, classic phenotype composed of optic atrophy, diabetes mellitus type 1, insipidus, and deafness. syndrome, however, phenotypically heterogenous with variable clinical manifestations age onset. We describe four cases genetically confirmed presentations, including acute-on-chronic vision loss, dyschromatopsia, tonic pupils. All patients had only three diabetes, none exhibited phenotype. MRI revealed varying degree classical features associated nerve, cerebellar, brainstem atrophy. The cohort’s genotype presentation supported reported phenotype–genotype correlations for Wolfram, where missense lead to milder, later-onset spectrum. When early onset atrophy and/or are present patient, diagnosis should be considered, as crucial appropriate referrals management conditions. Nevertheless, condition also considered otherwise unexplained, given phenotypic