ALPK1-Associated ROSAH Syndrome in a Polish Pedigree

ROSAH syndrome is a rare autosomal dominant autoinflammatory disorder caused by gain-of-function mutations in the ALPK1 gene, characterized by retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis, and headache. We present three related female patients (two sisters and their aunt) with a long-standing history of decreased visual acuity, recurring macular oedema, and progressive retinal dystrophy, as well as systemic involvement including anhidrosis, splenomegaly, headache, and arthritis. All our patients come from one family, with a total of 11 people suffering from ophthalmologic diseases with profound vision loss. Described three patients had confirmed pathogenic variant c.710C>T; p.Thr237Met in the ALPK1 gene and extensive ophthalmic assessment. This case series highlights the importance of genetic testing and multimodal imaging in unexplained familial retinal dystrophies and underlines intrafamilial phenotypic variability. Moreover, it emphasizes ROSAH syndrome as an important differential diagnosis for inherited inflammatory vitreoretinopathies.