Vertebrates have two isoforms: topoisomerase IIα and β. Type II topoisomerase β is encoded by TOP2B. For TOP2B, a number of germline pathogenic variants have been identified as causative for human diseases, including Hoffman syndrome, ablepharon-macrostomia syndrome with immunodeficiency, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations syndrome. Here, TOP2B is linked to ablepharon macrostomia syndrome.