Case Report: Hermansky-Pudlak syndrome type 1 in the Russian Federation presenting with genotype-phenotype discordance

Background Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder caused by defects in the biogenesis of lysosome-related organelles (LROs) across multiple tissues. This condition typically presents with a triad of oculocutaneous albinism, platelet dysfunction, and visceral complications. Hermansky-Pudlak syndrome type 1 (HPS-1), caused by pathogenic variants in the HPS1 gene, carries a high risk for progressive pulmonary fibrosis. Case presentation This case report describes a genetically confirmed case of HPS-1 in a 10-year-old girl with an unusual clinical phenotype, particularly regarding ophthalmological and gynecological findings. She presented with oculocutaneous albinism, bleeding diathesis despite normal platelet counts, foveal hypoplasia, and an atypical absence of iris transillumination (score 0/5 on a standardized scale). Next-generation sequencing (NGS) identified compound heterozygous pathogenic variants in the HPS1 gene (NM_000195.5:c.397G > T and c.972dup). Pelvic ultrasound revealed marked uterine hypoplasia. Conclusion This case describes a rare phenotype associated with these HPS1 variants, illustrating the clinical variability of the syndrome. Our findings support the importance of NGS-based diagnostics and the need for multidisciplinary long-term monitoring, including ophthalmological, pulmonary, gastrointestinal, and hematological surveillance. Reporting atypical presentations is important for improving our understanding of the clinical spectrum of rare disorders such as HPS, with national registries serving as a valuable tool to collect such rare phenotypic data.