Utilizing different genomic technologies and analysis pipelines, we link the disease-causing variant in ALPK1 (ɑ-kinase 1 [MIM 607347], c.710C>T, [p.Thr237Met]) to ROSAH syndrome in all five families. This evidence concerns the gene ALPK1 and retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome.