WDR81 Mutation in Two Siblings: A Case Report and Review of Literature

The WDR81 gene is critically involved in autophagy, endosomal trafficking, and neurodevelopment. Pathogenic variants in this gene are associated with autosomal recessive disorders, such as cerebellar ataxia, intellectual disability, and disequilibrium syndrome. Despite recent advances, the full phenotypic spectrum remains incompletely characterized.

We report two female siblings carrying a homozygous missense variant in the WDR81 gene. The elder sister (age 15) presented with developmental regression, optic atrophy, motor neuropathy, and pes equinovarus. The younger sister (age 6) exhibited astigmatism, gait disturbance, and mild intellectual disability. Both were born to apparently non-consanguineous parents. Genetic testing confirmed the variant in both patients, and their clinical findings were compared with previously reported cases in the literature.

These cases expand the clinical spectrum of WDR81-related disorders. Our observations highlight the gene's central role in neurodevelopment and emphasize the need for further investigation into its diverse systemic effects.