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

DNA Topoisomerase II beta (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 genotypephenotype 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).

Automated summary

DNA Topoisomerase II beta (TOP2B) is involved in DNA topology during transcription and plays a critical role in neural development. Pathogenic changes in the TOP2B gene have been associated with overlapping immunodeficiency, acral, and urogenital anomalies. In this study, we report on a family with distinct TOP2B-associated phenotypes and propose a new acronym, TICAS, to describe the phenotypic spectrum observed in these patients.