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Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification

2013; Oxford University Press; Volume: 136; Issue: 11 Linguagem: Inglês

10.1093/brain/awt255

1460-2156

Gaël Nicolas, Cyril Pottier, Camille Charbonnier, Lucie Guyant‐Maréchal, Isabelle Le Ber, Jérémie Pariente, Pierre Labauge, Xavier Ayrignac, Luc Defebvre, David Maltête, Olivier Martinaud, Romain Lefaucheur, Olivier Guillin, David Wallon, Boris Chaumette, Philippe Rondepierre, Nathalie Derache, Guillaume Fromager, S. Schaeffer, Pierre Krystkowiak, Christophe Verny, Snejana Jurici, Mathilde Sauvée, Marc Vérin, Thibaud Lebouvier, Olivier Rouaud, Christel Thauvin‐Robinet, Stéphane Rousseau, Anne Rovelet‐Lecrux, Thierry Frébourg, Dominique Campion, Didier Hannequin, Patrick Ahtoy, Mathieu Anheim, Jérôme Augustin, Xavier Ayrignac, Françoise Billé-Turc, Dominique Campion, Boris Chaumette, Michel Clanet, Luc Defebvre, Gilles Defer, Nathalie Derache, Mira Didic, Franck Durif, Emmanuel Flamand‐Roze, Guillaume Fromager, Maurice Giroud, Alice Goldenberg, Olivier Guillin, Lucie Guyant‐Maréchal, Didier Hannequin, Cécile Hubsch, Snejana Jurici, Pierre Krystkowiak, Pierre Labauge, Antoine Layet, Isabelle Le Ber, Thibaud Lebouvier, Romain Lefaucheur, David Maltête, Olivier Martinaud Donald Morcamp, Gaël Nicolas, Özlem Özkul, Jérémie Pariente, Cyril Pottier, Philippe Rondepierre, Olivier Rouaud, B Salle, Mathilde Sauvée, S. Schaeffer, Christel Thauvin‐Robinet, Catherine Thomas-Antérion, Christine Tranchant, Aude Triquenot, Yvan Vaschalde, Marc Vérin, Christophe Verny, Marie Vidailhet, David Wallon,

Parathyroid Disorders and Treatments

Idiopathic basal ganglia calcification is characterized by mineral deposits in the brain, an autosomal dominant pattern of inheritance in most cases and genetic heterogeneity. The first causal genes, SLC20A2 and PDGFRB, have recently been reported. Diagnosing idiopathic basal ganglia calcification necessitates the exclusion of other causes, including calcification related to normal ageing, for which no normative data exist. Our objectives were to diagnose accurately and then describe the clinical and radiological characteristics of idiopathic basal ganglia calcification. First, calcifications were evaluated using a visual rating scale on the computerized tomography scans of 600 consecutively hospitalized unselected controls. We determined an age-specific threshold in these control computerized tomography scans as the value of the 99th percentile of the total calcification score within three age categories: 60 years. To study the phenotype of the disease, patients with basal ganglia calcification were recruited from several medical centres. Calcifications that rated below the age-specific threshold using the same scale were excluded, as were patients with differential diagnoses of idiopathic basal ganglia calcification, after an extensive aetiological assessment. Sanger sequencing of SLC20A2 and PDGFRB was performed. In total, 72 patients were diagnosed with idiopathic basal ganglia calcification, 25 of whom bore a mutation in either SLC20A2 (two families, four sporadic cases) or PDGFRB (one family, two sporadic cases). Five mutations were novel. Seventy-one per cent of the patients with idiopathic basal ganglia calcification were symptomatic (mean age of clinical onset: 39 ± 20 years; mean age at last evaluation: 55 ± 19 years). Among them, the most frequent signs were: cognitive impairment (58.8%), psychiatric symptoms (56.9%) and movement disorders (54.9%). Few clinical differences appeared between SLC20A2 and PDGFRB mutation carriers. Radiological analysis revealed that the total calcification scores correlated positively with age in controls and patients, but increased more rapidly with age in patients. The expected total calcification score was greater in SLC20A2 than PDGFRB mutation carriers, beyond the effect of the age alone. No patient with a PDGFRB mutation exhibited a cortical or a vermis calcification. The total calcification score was more severe in symptomatic versus asymptomatic individuals. We provide the first phenotypical description of a case series of patients with idiopathic basal ganglia calcification since the identification of the first causative genes. Clinical and radiological diversity is confirmed, whatever the genetic status. Quantification of calcification is correlated with the symptomatic status, but the location and the severity of the calcifications don't reflect the whole clinical diversity. Other biomarkers may be helpful in better predicting clinical expression.