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. 2015 Jun;28(3):289-93.
doi: 10.1177/1971400915591688.

Cerebral cavernous malformations associated to meningioma: High penetrance in a novel family mutated in the PDCD10 gene

Francesco Garaci  1 , Luisa Marsili  2 , Florence Riant  3 , Simone Marziali  4 , Michaelle Cécillon  5 , Roberto Pasquarelli  6 , Federica Sangiuolo  2 , Roberto Floris  1 , Giuseppe Novelli  2 , Elisabeth Tournier-Lasserve  3 , Francesco Brancati  7
Affiliations

Cerebral cavernous malformations associated to meningioma: High penetrance in a novel family mutated in the PDCD10 gene

Francesco Garaci et al. Neuroradiol J. 2015 Jun.

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.

Keywords: Magnetic resonance imaging; PDCD10.; cerebral cavernous malformation; multiple meningioma.

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Figures

Figure 1.
Figure 1.
Pedigree of the reported family with cerebral cavernous malformations (CCMs) and multiple meningiomas recurring in multiple affected subjects. Males and females are represented as squares and circles, respectively. The arrow indicates the index case. The filled circles represent affected individuals. The circle labelled ‘N’ indicates the healthy relative who did not carry the familial mutation.
Figure 2.
Figure 2.
Index case II-6 axial gradient echo image (a) shows multifocal ‘black dots’ (arrows) characteristic of Zabramski type IV cerebral cavernous malformations (CCMs) (punctate microhaemorrage); axial (b) and coronal (c), (d) T1-weighted post-gadolinium images demonstrate multiple strongly enhanced extra-dural based masses (arrows) and diffuse dural thickness (arrowheads).
Figure 3.
Figure 3.
Patient II-3 axial gradient echo image (a) shows multiple foci of hypointesity, consistent with multiple cavernomas; axial (b) and coronal (c), (d) GD T1-WI demonstrate multiple dural lesions with intense enhancement and slight dural thickness (arrows).
Figure 4.
Figure 4.
Patient III-3 axial T2-weighted image (a) shows a subcortical hypointense lesion (arrow) with central hyperintense spot due to bloods in different stages and hypointense hemosiderin rim likely consistent with a cerebral cavernous malformation (CCM) (gradient echo (GRE) images not available); coronal (b) and sagittal (c) T1-weighted post-gadolinium image demonstrate fronto-basal extra-axial hyperintense lesion consistent with meningioma (arrow) and contralateral subtle dural thickness (arrowheads).
See this image and copyright information in PMC

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References

    1. Riemenschneider MJ, Perry A, Reifenberger G. Histological classification and molecular genetics of meningiomas. Lancet Neurol 2006; 5: 1045–1054. - PubMed
    1. DeAngelis LM. Brain tumors. N Engl J Med 2001; 11; 344: 114–123. - PubMed
    1. Shen Y, Nunes F, Stemmer-Rachamimov A, et al. Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas. BMC Med Genomics 2009; 2: 42. - PMC - PubMed
    1. Whittle IR, Smith C, Navoo P, et al. Meningiomas. Lancet 2004; 8; 363: 1535–1543. - PubMed
    1. Haasdijk RA, Cheng C, Maat-Kievit AJ, et al. Cerebral cavernous malformations: From molecular pathogenesis to genetic counselling and clinical management. European J Hum Genet 2012; 20: 134–140. - PMC - PubMed

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