Revisiting TOP2B-related phenotypes: Three new cases and literature review

DNA Topoisomerase IIβ (TOP2B) acts on DNA topology during transcription and has a critical role in neural development. Heterozygous pathogenic changes in its encoding gene, TOP2B (MIM *126431), has been linked with three overlapping phenotypes characterized by immunodeficiency, acral and urogenital anomalies: Hoffman, BILU and Ablepharon-macrostomia-like syndrome. We herein report on a mother and two sons with distinct TOP2B-phenotype. Two males reported further delineated genital phenotype of males and all reported patients were reviewed for genotype-phenotype correlation. We believe the patients reported herein along with the previously defined 11 represent a phenotypic spectrum from mild-to-severe immunological, acral and urogenital involvement, for which we propose the acronym "TOP2B-related Immunodeficiency and Congenital Anomalies Spectrum (TICAS)".