Background: Idiopathic basal ganglia calcification (IBGC), also known as Fahr's disease, is a rare disorder characterized by widespread cerebral calcifications, an autosomal dominant pattern of inheritance and clinical and genetic heterogeneity. The recently identified IBGC gene, SLC20A2, encodes for type III sodium-dependent phosphate transporter 2 and its loss-of-function mutations may lead to the regional accumulation of inorganic phosphate in the brain, causing calcium phosphate deposition. Objective: To describe the clinical, neuroimaging and genetic findings in an Italian family with IBGC. Methods: The family members underwent clinical and radiological examination in order to diagnose IBGC according to standard criteria and screening for SLC20A2 gene mutations. The affected subjects also underwent neuropsychological longitudinal assessments and functional neuroimaging investigations. Results: The 2 affected family members harbored a novel missense mutation, G1618A, in the SLC20A2 gene, leading to gly540-to-arg (G540R) substitution in a highly conserved residue. This is the first SLC20A2 gene mutation associated with familial IBGC reported in the Italian population and is damaging according to all prediction programs. In the index case we observed a fair correlation between cortical areas with no calcifications but with significant hypometabolism at [18F]FDG-PET (inferior frontal premotor cortex) and the neuropsychological picture dominated by dynamic aphasia and buccofacial apraxia. Conclusion: These findings expand the catalog of SLC20A2 mutations identified to date and add dynamic aphasia to the spectrum of neuropsychological deficits reported in IBGC, supporting the use of functional neuroimaging studies for better investigation of genotype-phenotype correlations.

1.
Maeda K, Idehara R, Nakamura H, Hirai A: Anticipation of familial idiopathic basal ganglia calcification? Intern Med 2012;51:987.
2.
Hsu SC, Sears RL, Lemos RR, Quintáns B, Huang A, Spiteri E, Nevarez L, et al: Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification. Neurogenetics 2013;14:11-22.
3.
Wang C, Li Y, Shi L, Ren J, Patti M, Wang T, de Oliveira JR, Sobrido MJ, Quintáns B, Baquero M, Cui X, Zhang XY, Wang L, Xu H, Wang J, Yao J, Dai X, Liu J, Zhang L, Ma H, Gao Y, Ma X, Feng S, Liu M, Wang QK, Forster IC, Zhang X, Liu JY: Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet 2012;44:254-256.
4.
Manyam BV: What is and what is not ‘Fahr's disease'. Parkinsonism Relat Disord 2005;11:73-80.
5.
Nicolas G, Pottier C, Charbonnier C Guyant-Maréchal L, Le Ber I, Pariente J, Labauge P; French IBGC Study Group: Phenotypic spectrum of probable and genetically confirmed idiopathic basal ganglia calcification. Brain 2013;136:3395-3407.
6.
Luria AR, Tsvetkova LS: Towards the mechanisms of ‘dynamic aphasia'. Acta Neurol Psychiatr Belg 1967;67:1045-1057.
7.
Robinson G, Shallice T, Bozzali M, Cipolotti L: Conceptual proposition selection and the LIFG: neuropsychological evidence from a focal frontal group. Neuropsychologia 2010;48:1652-1663.
8.
Katzev M, Tüscher O, Hennig J, Weiller C, Kaller CP: Revisiting the functional specialization of left inferior frontal gyrus in phonological and semantic fluency: the crucial role of task demands and individual ability. J Neurosci 2013;33:7837-7845.
9.
Ogar J, Slama H, Dronkers N, Amici S, Gorno-Tempini ML: Apraxia of speech: an overview. Neurocase 2005;11:427-432.
10.
Josephs KA, Duffy JR, Fossett TR, Strand EA, Claassen DO, Whitwell JL, Peller PJ: Fluorodeoxyglucose F18 positron emission tomography in progressive apraxia of speech and primary progressive aphasia variants. Arch Neurol 2010;67:596-605.
11.
Kwon M, Lee JH, Oh JS, Koh JY: Isolated buccofacial apraxia subsequent to a left ventral premotor cortex infarction. Neurology 2013;80:2166-2167.
12.
Hempel A, Henze M, Berghoff C, Garcia N, Ody R, Schröder J: PET findings and neuropsychological deficits in a case of Fahr's disease. Psychiatry Res 2001;108:133-140.
13.
Benke T, Karner E, Seppi K, Delazer M, Marksteiner J, Donnemiller E: Subacute dementia and imaging correlates in a case of Fahr's disease. J Neurol Neurosurg Psychiatry 2004;75:1163-1165.
14.
Mariën P, Saerens J, Nanhoe R, Moens E, Nagels G, Pickut BA, Dierckx RA, De Deyn PP: Cerebellar induced aphasia: case report of cerebellar induced prefrontal aphasic language phenomena supported by SPECT findings. J Neurol Sci 1996;144:34-43.
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