El Chehadeh Salima, Faivre Laurence, Mosca-Boidron Anne-Laure, Malan Valérie, Amiel Jeanne, Nizon Mathilde, Touraine Renaud, Prieur Fabienne, Pasquier Laurent, Callier Patrick, Lefebvre Mathilde, Marle Nathalie, Dubourg Christèle, Julia Sophie, Sarret Catherine, Francannet Christine, Laffargue Fanny, Boespflug-Tanguy Odile, David Albert, Isidor Bertrand, Le Caignec Cédric, Vigneron Jacqueline, Leheup Bruno, Lambert Laetitia, Philippe Christophe, Cuisset Jean-Marie, Andrieux Joris, Plessis Ghislaine, Toutain Annick, Goldenberg Alice, Cormier-Daire Valérie, Rio Marlène, Bonnefont Jean-Paul, Thevenon Julien, Echenne Bernard, Journel Hubert, Afenjar Alexandra, Burglen Lydie, Bienvenu Thierry, Addor Marie-Claude, Lebon Sébastien, Martinet Danièle, Baumann Clarisse, Perrin Laurence, Drunat Séverine, Jouk Pierre-Simon, Devillard Françoise, Coutton Charles, Lacombe Didier, Delrue Marie-Ange, Philip Nicole, Moncla Anne, Badens Catherine, Perreton Nathalie, Masurel Alice, Thauvin-Robinet Christel, Des Portes Vincent, Guibaud Laurent
FHU TRANSLAD, Centre de Référence Maladies Rares "Anomalies du Développement et Syndromes Malformatifs" de l'Est, Centre de Génétique, CHU de Dijon, France.
GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.
Am J Med Genet A. 2016 Jan;170A(1):116-29. doi: 10.1002/ajmg.a.37384. Epub 2015 Sep 30.
Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.
Xq28重复包含MECP2，在患有严重神经发育障碍的男性患者中已有描述，这些患者伴有肌张力减退和痉挛、严重学习障碍、刻板动作以及反复肺部感染。我们报告了30例受影响患者的标准化脑磁共振成像（MRI）数据，这些患者携带涉及不同大小（228 kb至11.7 Mb）MECP2的Xq28重复。本研究的目的是寻找复发性畸形，并试图确定成像特征的差异是否可以用重复大小的差异来解释。我们发现93%的患者存在脑MRI异常，如胼胝体异常（n = 20）、白质（WM）体积减小（n = 12）、脑室扩张（n = 9）、T2加权图像上涉及脑室周围后WM的异常高信号增加（n = 6）以及小脑蚓部发育不全（n = 5）。枕额周长在5例患者中>+2SD，在4例患者中<-2SD，差异很大。在9例侧脑室扩张的患者中，6例有涉及L1CAM的重复。唯一患有双侧室管膜下结节性异位的患者也携带FLNA基因重复。我们未能证明脑室周围WM高信号/髓鞘形成延迟与IKBKG基因重复之间存在相关性。因此，我们得出结论，涉及MECP2的Xq28重复患者存在一些相似但非特异性的脑异常。因此，这些成像特征不能构成诊断线索。基因型-表型相关性未能证明重复节段中结节性异位、脑室扩张、WM异常与FLNA、L1CAM或IKBKG的存在之间分别存在关系。
