Inherited disorders as a risk factor and predictor of neurodevelopmental outcome in pediatric cancer

Abstract

Each year in the United States, an average of one to two children per 10,000 develop cancer. The etiology of most childhood cancer remains largely unknown but is likely attributable to random or induced genetic aberrations in somatic tissue. However, a subset of children develops cancer in the setting of an underlying inheritable condition involving a germline genetic mutation or chromosomal aberration. Despite overall improved survival rates for children with cancer over recent decades, many patients experience neurological and neurocognitive complications during the course of their illness and/or as late effects of treatment. Improvements in therapy, longer survival times, and improved imaging techniques have all increased both the time that patients are at risk and the ability to detect such complications. How an underlying inherited disorder influences the incidence, timing, etiology, and treatment of such sequelae has not been extensively documented, but evidence exists for an increased risk for secondary malignancies and in some cases life-threatening sensitivity/toxicity to conventionally dosed cancer treatments, thus emphasizing the need for the early recognition of such syndromes. This review outlines the major tumor- and treatment-related neurodevelopmental sequelae in pediatric cancer patients, with particular attention to children with an underlying inheritable disorder.

Brain Tumors and Syndromes in Children

“…Small molecule inhibitors, that act against a particular function of a protein causing tumors, have been developed and are being tested, also in tumor predisposition syndromes. 87 For example, a range of small molecule inhibitors are tested in clinical trials to inhibit growth of neurofibroma and vestibular schwannoma in individuals with NF1 88 and NF2, respectively. 89 In TSC, loss of function mutations in TSC1/TSC2, encoding for the proteins hamartin and tuberin, disrupt the complex of these two proteins and activate mTOR signaling.…”

Neuro-Oncology Training for the Child Neurology Resident

“…Trainees should be familiar with hereditary disorders that predispose to central nervous system tumors. 5 -8 These can be accomplished at all types of training programs by incorporating a didactic lecture series as well as expanding the residents’ clinical experiences by providing increased exposure to this patient population.…”

Timely identification of children with cancer

“…In case of known mutations close meshed preventive examinations should be scheduled, aiming to diagnose the disease as early as possible and to improve the prognosis. In some cases, known mutations allow for performing preemptive therapeutic interventions [7,34].…”