title: Cerebral cavernous malformations associated to meningioma: High penetrance in a novel family mutated in the PDCD10 gene.
abstract: Multiple familial meningiomas occur in rare genetic syndromes, particularly neurofibromatosis type 2. The association of meningiomas and cerebral cavernous malformations (CCMs) has been reported in few patients in the medical literature. The purpose of our study is to corroborate a preferential association of CCMs and multiple meningiomas in subjects harbouring mutations in the PDCD10 gene (also known as CCM3). Three members of an Italian family affected by seizures underwent conventional brain Magnetic Resonance Imaging (MRI) with gadolinium contrast agent including gradient echo (GRE) imaging. The three CCM-causative genes were sequenced by Sanger method. Literature data reporting patients with coexistence of CCMs and meningiomas were reviewed. MRI demonstrated dural-based meningioma-like lesions associated to multiple parenchymal CCMs in all affected individuals. A disease-causative mutation in the PDCD10 gene (p.Gln112PhefsX13) was identified. Based on neuroradiological and molecular data as well as on literature review, we outline a consistent association between PDCD10 mutations and a syndrome of CCMs with multiple meningiomas. This condition should be considered in the differential diagnosis of multiple/familial meningioma syndromes. In case of multiple/familial meningioma the use of appropriate MRI technique may include GRE and/or susceptibility-weighted imaging (SWI) to rule out CCM. By contrast, proper post-gadolinium scans may aid defining dural lesions in CCM patients and are indicated in PDCD10-mutated individuals.
authors.affiliation: Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, Policlinico Tor Vergata University Hospital, Italy Department of Biomedicine and Prevention, Tor Vergata University, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Garaci
authors.affiliation: Medical Genetics Unit, Policlinico Tor Vergata University Hospital, Italy Department of Biomedicine and Prevention, Tor Vergata University, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Marsili
authors.affiliation: Service de Génétique Moléculaire Neurovasculaire, Centre de Référence des Maladies Vasculaires Rares du Cerveau et de l'Oeil (CERVCO), France Génétique des Maladies Vasculaires UMR-S1161, Université Paris Diderot, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Riant
authors.affiliation: Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, Policlinico Tor Vergata University Hospital, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Marziali
authors.affiliation: Service de Génétique Moléculaire Neurovasculaire, Centre de Référence des Maladies Vasculaires Rares du Cerveau et de l'Oeil (CERVCO), France.
authors.forename: Michaelle
authors.initials: M
authors.lastname: Cécillon
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pasquarelli
authors.affiliation: Medical Genetics Unit, Policlinico Tor Vergata University Hospital, Italy Department of Biomedicine and Prevention, Tor Vergata University, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sangiuolo
authors.affiliation: Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, Policlinico Tor Vergata University Hospital, Italy Department of Biomedicine and Prevention, Tor Vergata University, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Floris
authors.affiliation: Medical Genetics Unit, Policlinico Tor Vergata University Hospital, Italy Department of Biomedicine and Prevention, Tor Vergata University, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.affiliation: Service de Génétique Moléculaire Neurovasculaire, Centre de Référence des Maladies Vasculaires Rares du Cerveau et de l'Oeil (CERVCO), France Génétique des Maladies Vasculaires UMR-S1161, Université Paris Diderot, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Tournier-Lasserve
authors.affiliation: Medical Genetics Unit, Policlinico Tor Vergata University Hospital, Italy Department of Medical, Oral and Biotechnological Sciences, Gabriele D'Annunzio University, Italy f.brancati@igenetica.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000235:genetics*; D008579:Meningioma / Q000235:genetics*; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins
keywords: Magnetic resonance imaging; PDCD10.; cerebral cavernous malformation; multiple meningioma