CASE REPORT article
Front. Pediatr.
Sec. Pediatric Immunology
Volume 13 - 2025 | doi: 10.3389/fped.2025.1542268
This article is part of the Research TopicChallenges And Advances In Primary Antibody Deficiencies Diagnosis, Treatment And Follow-upView all 3 articles
Infantile epileptic spasms syndrome as a new phenotype in TOP2B deficiency caused by a de novo variant:A case report and literature review
Provisionally accepted- Wuxi Children’s Hospital, Wuxi, Jiangsu Province, China
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Type II DNA topoisomerases (EC5.99.1.3) are enzymes that catalyze topological changes during DNA replication and gene transcription in an ATP-dependent manner.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, Ablepharonmacrostomia syndrome (AMS) with immunodeficiency, B-cell immunodeficiency, distal limb anomalies and urogenital malformations (BILU) syndrome. To date, only 14 patients with the above diseases from seven families have been reported in PubMed.Herein, we describe an additional case of a child who presented with Infantile epileptic spasms syndrome (IESS) as the first symptom, B-cell immunodeficiency, dysmorphic facial features and a pathogenic variant in TOP2B. The c.1901A>G variant in TOP2B is new to our study, which further enriches the genotype of TOP2B deficiency. Our patient manifested as a typical triad: infantile spasms, hypsarrhythmia on EEG and developmental arrest at the age of seven months. Although epilepsy and neurodevelopmental disorders have been reported in patients with TOP2B deficiency, typical IESS has not been described previously. IESS in our patient further expands the phenotype of TOP2B. The patient was started on monthly intravenous immunoglobulin (IVIG) replacement therapy after being diagnosed with TOP2B deficiency and since then has not suffered from severe infections. TOP2B deficiency is a group of heterogeneous diseases, which is ultra-rare. Results in our study extend the phenotype and genotype spectrum of TOP2B deficiency. TOP2B may be a causative gene for WS.
Keywords: case report, Type II topoisomerase β, West syndrome, B-cell immunodeficiency, Neurodevelopmental disorders
Received: 09 Dec 2024; Accepted: 04 Jun 2025.
Copyright: © 2025 Li, Zhu, Yao, Yang and Hua. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Guo-min Li, Wuxi Children’s Hospital, Wuxi, 214023, Jiangsu Province, China
Ying Hua, Wuxi Children’s Hospital, Wuxi, 214023, Jiangsu Province, China
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