Germline predisposition to glial neoplasms in children and young adults: A narrative review

Gliomas are the most common malignancies of the central nervous system (CNS). A significant proportion of both low- and high-grade gliomas in children, adolescents, and young adults have specific genetic events which can be traced to the germline. Despite integration of genomic findings in recent CNS tumor classifications, germline origins of these genetic events are seldom highlighted. These cancer predisposition syndromes can predispose the individual and family members to multiple cancers in different organs beyond the CNS and to other non-oncologic manifestations caused by the genetic dysfunction. Recent molecular discoveries and careful surveillance have resulted in improved survival and reduced morbidity for many of these conditions. Importantly, identifying a genetic predisposition can alter treatment of the existing malignancy, by mandating the use of a different protocol, targeted therapy, or other novel therapies. Hence, prompt diagnosis is sometimes crucial for these young patients. High index of suspicion and early referral to genetic testing and counseling are important and may be beneficial to these families. In this review, we discuss the clinical manifestations, genetics, tumor management, and surveillance in these patients. These provide insights into the complex mechanisms in glioma-genesis that can impact the treatment and survival for these patients and families in the future.