Several genetic tumor syndromes have associated central nervous system (CNS) neoplasms. The spectrum of syndromes that have intracranial tumor manifestations includes ataxia telangiectasia, Cowden syndrome, familial adenomatous polyposis, hereditary non-polyposis-related colorectal cancer, Li-Fraumeni syndrome, Gorlin syndrome, neurofibromatosis types 1 and 2, multiple endocrine neoplasia type 1, tuberous sclerosis complex, von Hippel-Lindau disease, and Turcot syndrome. Many of these disorders are inherited in an autosomal dominant fashion, and identification of the associated genetic defects has led to improved understanding of the molecular pathways involved in tumorigenesis, helping pave the way to the emergence of molecularly targeted therapeutics. Recognition of individuals and families at risk for such tumors is critical to improve clinical care and optimize proper genetic counseling. To contribute effectively, the radiologist should recognize the common varieties of tumors and characteristic neuroimaging manifestations seen in each familial syndrome. A fundamental understanding of the genetics and molecular pathogenesis of these tumors is critical in understanding the development of specific and unique tumors in each entity. In this article, we review the most common genetic tumor syndromes with associated intracranial neoplasms, with emphasis on recent genetic and molecular biology data, clinical manifestations, and management as well as the controversies and current recommendations for screening and surveillance. A detailed overview of all the major and pertinent CNS imaging features will be elucidated, including computed tomography, magnetic resonance imaging, and, in relevant cases, magnetic resonance spectroscopy. RSNA, 2016.

Juvenile xanthogranulomatosis (JXG) represents a subset of non-Langerhan cell histiocytosis that typically manifests in younger children with skin lesions. Unresectable central nervous system (CNS) disease is difficult to treat. We describe the case of a 13-year-old successfully treated with adjuvant radiation therapy for symptomatic intracranial and leptomeningeal JXG. An extensive literature review was performed to identify all previous CNS JXG cases utilizing radiation, of which six of eight total patients demonstrated temporary or long-term improvement of neurologic disease. This suggests that radiation should be considered in cases unresponsive to conventional treatment options.