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

Abstract Introduction: The WDR81 gene plays a crucial role in autophagy, endosomal trafficking, and neurodevelopment. Pathogenic variants in this gene are associated with autosomal recessive disorders such as cerebellar ataxia, mental retardation, and disequilibrium syndrome. Despite recent advances, the phenotypic spectrum remains incompletely defined. Case Presentation: We report two female siblings carrying a homozygous missense variant in the WDR81 gene. The older 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 reportedly non-consanguineous parents. Genetic testing confirmed the variant in both patients, and clinical findings were compared with previously reported cases in the literature. Conclusion: These cases contribute to the expanding clinical spectrum of WDR81-related disorders. Our observations underscore the gene’s central role in neurodevelopment and suggest a need for continued investigation into its diverse systemic effects.