Genetic Syndromes Associated with Central Nervous System Tumors

Abstract

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.

Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan

“…The high frequency of TERT promoter mutation occurred in SHH MBs of adult patients [40]. Genetic syndromes with germline mutations associated with MBs [41][42][43] included Gorlin syndrome (heterozygous germline pathogenic variant in PTCH1 or SUFU) [44,45], CMMR-D syndrome (biallelic deleterious germline mutations in MMR genes (MLH2, MSH2, MSH6, and PMS2)) [46], Li-Fraumeni syndrome (germline mutation of TP53) [47,48], familial adenomatous polyposis syndrome (germline APC muttaion) [4,49], and Cowden syndrome (germline mutation of PTEN) [41,50]. In our cohort series, we identified somatic mutations in BRCA2, PALB2, MSH6, PMS2, PTCH1, SUFU, TP53, APC, and PTEN from RNA-Seq data analysis.…”

Synchronous Primary Brain Tumors in the Pediatric Age Group. Report of Two Cases and Review of the Literature

“…Five out of the 12 reported pediatric cases (41.6%) developed the second tumor 6 to 21 years following radiation therapy to the first tumor. Radiation therapy was focal in 2 cases, craniospinal in 2 cases, and whole brain in 1 case) [2,4,10,12,15,21,25,29]. Our first case did not have any genetic predisposition syndromes, the second case was never tested.…”

“…Histopathologically, they usually constituted of meningiomas and astrocytomas and are more common in patients with known underlying genetic syndromes or after radiation therapy for previous brain tumors [1,[5][6][7][8][9]11,22]. We performed a comprehensive literature review and identified a total of twelve pediatric cases with synchronous/ metachronous brain tumors [2,4,10,12,15,21,25,26,27,29]. In this report, we describe two rare cases of children with multiple brain tumors exhibiting different histologic subtypes and occurring simultaneously in the same patient.…”

“…To the best of our knowledge, we believe that our case is the first to describe a child with both a supratentorial anaplastic ependymomas and a pilocytic astrocytoma. One study reported a case of an 8-month-old girl suffering from a frontal lobe ependymoma in association with a cerebellopontine angle meningioma without any genetic predisposition [29]. Upon review of the adult occurrences of this manifestation, two cases were found in the literature having a meningioma and an ependymoma simultaneously [19,24].…”

“…Synchronous and metachronous brain tumors are rare in children and present a diagnostic and therapeutic challenge [2,4,10,12,15,21,25,29]. In addition, malignant transformation in children is not a frequent occurrence and can be missed if high index of suspicion is not present [1][2][3][4][5]7,[10][11][12][13]15,17,19,20,[22][23][24][25][26][27]29].…”