Diagnostic and therapeutic approach to children with Nijmegen breakage syndrome in relation to development of lymphoid malignancies

Introduction and objective: Nijmegen breakage syndrome (NBS) is a rare chromosomal instability disorder. The majority of patients carry founder mutation in the NBN gene (c.657_661del5). Characteristic features of the NBS include progressive microcephaly, dysmorphic facial features, immunodeficiency, and high predisposition to malignancy with cumulative cancer incidence by the age of 20 years, and amounted to over 70%. The aim of study is to present the latest methods of diagnosis, potential cancer risk factors and treatment of lymphoid malignancies in children with NBS. Review methods: To review the evidence using PubMed and Google Scholar search which included articles published between 2009–2021, focusing on articles published between 2013–2021. Abbreviated description of the state of knowledge: The average delay in diagnosis of NBS ranges from 4–5 years. Neonatal screening of T-cell excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) seems favourable in NBS. There are no specific protocols for the treatment of lymphoid malignancies in children with NBS, and full- dose chemotherapy is the most frequently applied method. Reducing the doses of chemotherapy does not significantly reduce the toxicity. Main cause of death is cancer progression and treatment-related mortality mostly associated with infectious complications. Patients with diagnosed cancer who received haematopoietic stem cell transplantation (HSCT) had significantly higher 20-year OS than those who did not (42.7% vs. 30.3%). Summary: Further meta-analysis is essential to establish the best monitoring and treatment regimen in patients with NBS and lymphoid malignancies.