Optic Atrophy Predominant WFS1 Disorder—A Case–Control Study

Our cohort of patients with WS1 showed uncharacteristically mild vision loss and minimal syndromic features, suggesting that a milder alternative phenotype with WFS1 mutations is possible in contrast to the traditional DIDMOAD syndrome. Compared with other OA syndromes, these patients with WS1 showed significant associations with arcuate visual field defects and trends toward superior/inferior peripapillary RNFL thinning. This suggests that relative preservation of papillomacular bundle fibers and thus milder central visual acuity loss may be a unifying feature in their phenotype. This series expands the clinical spectrum of WS1 and should encourage further work to study the pathogenic role of wolframin in vision loss. Clinicians should consider Wolfram syndrome in cases of adult-onset, symmetric, near-isolated OA, especially in cases with arcuate field defects, which are more commonly seen than in other genetic syndromes.