Challenges of screening germline predispositions in children

Abstract

Genetic predisposition is a major cause of childhood cancer. Multiple cancer-predisposing syndromes have been identified, including Li-Fraumeni syndrome (LFS), neurofibromatosis type 1, APC-related adenomatous polyposis, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia 1, ataxia telangiectasia, RUNX1 deficiency, Fanconi anemia, Bloom syndrome, and PTEN hamartoma tumor syndrome. LFS is a prototypical genetically predisposing condition. Accordingly, individualized therapy, surveillance, risk reduction, and family counseling are needed when a patient is diagnosed with LFS. More ethically important problems are encountered in a pediatric LFS patient, including the identification of patients requiring screening, the age at screening, the process of obtaining informed consent from children, and the responsibility of following a pediatric patient with a genetic predisposition. Therefore, it is crucial to determine whether planned genetic testing has direct benefits for pediatric patients. In this context, TP53 testing may be justified in a pediatric cancer patient with suspected LFS, given the importance of decisions such as the use of radiotherapy and the screening of family members as hematopoietic stem cell transplantation donors, the surveillance of subsequent cancers, and counseling for family members. In this review article, I have discussed these issues and indicated some consensus among various clinicians, including adult hematologists.