Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies-A Review.

The view of paediatric cancer as a genetic disease arises as genetic research develops. Germline mutations in cancer predisposition genes have been identified in about 10% of children. Paediatric cancers are characterized by heterogeneity in the types of genetic alterations that drive tumourigenesis. Interactions between germline and somatic mutations are a key determinant of cancer development. In 40% of patients, the family history does not predict the presence of inherited cancer predisposition syndromes and many cases go undetected. Paediatricians should be aware of specific symptoms, which highlight the need of evaluation for cancer syndromes. The quickest possible identification of such syndromes is of key importance, due to the possibility of early detection of neoplasms, followed by presymptomatic genetic testing of relatives, implementation of appropriate clinical procedures (e.g., avoiding radiotherapy), prophylactic surgical resection of organs at risk, or searching for donors of hematopoietic stem cells. Targetable driver mutations and corresponding signalling pathways provide a novel precision medicine strategy.Therefore, there is a need for multi-disciplinary cooperation between a paediatrician, an oncologist, a geneticist, and a psychologist during the surveillance of families with an increased cancer risk. This review aimed to emphasize the role of cancer-predisposition gene diagnostics in the genetic surveillance and medical care in paediatric oncology.

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.

Multiple sclerosis in a child with neurofibromatosis type I - clinical management of a challenging case.

A 13-year-old girl with neurofibromastosis (NF1) was admitted to the Department of Paediatric Haematology, Oncology and Transplantology due to progressive vision loss in September 2018. The patient was diagnosed with optic nerve gliomas and chemotherapy was initiated. During the treatment, the girl experienced muscle weakness in the lower limbs, and uncharacteristic lesions were detected in the spinal cord. Eventually, the girl was diagnosed with MS. The described case is one of the few reports of a child with coexisting NF1 and MS. The coincidence of these diseases is unusual and requires a multidisciplinary approach. Vision impairment in patients suffering from NF1 is typically associated with optic nerve gliomas, although it can be caused by other factors, such as MS, which is proven to have a higher prevalence in the NF1 population. Extensive ophthalmological diagnostics may not be conclusive, thus there is a need for the thorough neurological evaluation of patients with NF1 and visual deficits.