Genomic Newborn Screening for Pediatric Cancer Predisposition Syndromes: A Holistic Approach.

Simple Summary: Overall, this review offers a comprehensive and insightful exploration of the significance, implementation, and challenges of genomic newborn screening for pediatric cancer predisposition syndromes (CPSs). It emphasizes the importance of next-generation sequencing (NGS) in uncovering germline mutations that are responsible for CPSs in childhood malignancies. It delves into the selection criteria for screening, ethical considerations, gene panel selection, and the integration of established and emerging genes in CPS into large-scale newborn screening programs in healthcare systems. It also stresses the importance of early detection and its potential impact on pediatric care and outcomes, thus providing valuable information for healthcare professionals, researchers, and policymakers in the field of pediatric oncology and genetics. As next-generation sequencing (NGS) has become more widely used, germline and rare genetic variations responsible for inherited illnesses, including cancer predisposition syndromes (CPSs) that account for up to 10% of childhood malignancies, have been found. The CPSs are a group of germline genetic disorders that have been identified as risk factors for pediatric cancer development. Excluding a few "classic" CPSs, there is no agreement regarding when and how to conduct germline genetic diagnostic studies in children with cancer due to the constant evolution of knowledge in NGS technologies. Various clinical screening tools have been suggested to aid in the identification of individuals who are at greater risk, using diverse strategies and with varied outcomes. We present here an overview of the primary clinical and molecular characteristics of various CPSs and summarize the existing clinical genomics data on the prevalence of CPSs in pediatric cancer patients. Additionally, we discuss several ethical issues, challenges, limitations, cost-effectiveness, and integration of genomic newborn screening for CPSs into a healthcare system. Furthermore, we assess the effectiveness of commonly utilized decision-support tools in identifying patients who may benefit from genetic counseling and/or direct genetic testing. This investigation highlights a tailored and systematic approach utilizing medical newborn screening tools such as the genome sequencing of high-risk newborns for CPSs, which could be a practical and cost-effective strategy in pediatric cancer care. [ABSTRACT FROM AUTHOR]