title: A heritable form of SMARCE1-related meningiomas with important implications for follow-up and family screening.
abstract: Childhood meningiomas are rare. Recently, a new hereditary tumor predisposition syndrome has been discovered, resulting in an increased risk for spinal and intracranial clear cell meningiomas (CCMs) in young patients. Heterozygous loss-of-function germline mutations in the SMARCE1 gene are causative, giving rise to an autosomal dominant inheritance pattern. We report on an extended family with a pediatric CCM patient and an adult CCM patient and several asymptomatic relatives carrying a germline SMARCE1 mutation, and discuss difficulties in genetic counseling for this heritable condition. Because of the few reported cases so far, the lifetime risk of developing meningiomas for SMARCE1 mutation carriers is unclear and the complete tumor spectrum is unknown. There is no surveillance guideline for asymptomatic carriers nor a long-term follow-up recommendation for SMARCE1-related CCM patients as yet. Until more information is available about the penetrance and tumor spectrum of the condition, we propose the following screening advice for asymptomatic SMARCE1 mutation carriers: neurological examination and MRI of the brain and spine, yearly from diagnosis until the age of 18 and once every 3 years thereafter, or in between if there are clinical symptoms. This advice can also be used for long-term patient follow-up. More data is needed to optimize this proposed screening advice.
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands. e.h.gerkes@umcg.nl.
authors.forename: E H
authors.initials: EH
authors.lastname: Gerkes
authors.affiliation: Department of Neurology, Child neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Fock
authors.affiliation: Department of Pathology and Medical Biology, Pathology division, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: W F A
authors.initials: WF
authors.lastname: den Dunnen
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: van Belzen
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C A
authors.initials: CA
authors.lastname: van der Lans
authors.affiliation: Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: E W
authors.initials: EW
authors.lastname: Hoving
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: I E
authors.initials: IE
authors.lastname: Fakkert
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Smith
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development, Manchester Academic Health Sciences Centre (MAHSC), St. Mary's Hospital, University of Manchester, Manchester, UK.
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: M J W
authors.initials: MJ
authors.lastname: Olderode-Berends
mesh_terms: D000328:Adult; D002648:Child; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008579:Meningioma / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D010375:Pedigree
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C504738:SMARCE1 protein, human
keywords: Childhood; Clear cell meningioma; Germline; Hereditary; SMARCE1; Tumor predisposition syndrome