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Large national series of patients with Xq28 duplication involving MECP2 : Delineation of brain MRI abnormalities in 30 affected patients
Author(s) -
El Chehadeh Salima,
Faivre Laurence,
MoscaBoidron AnneLaure,
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,
BoespflugTanguy Odile,
David Albert,
Isidor Bertrand,
Le Caignec Cédric,
Vigneron Jacqueline,
Leheup Bruno,
Lambert Laetitia,
Philippe Christophe,
Cuisset JeanMarie,
Andrieux Joris,
Plessis Ghislaine,
Toutain Annick,
Goldenberg Alice,
CormierDaire Valérie,
Rio Marlène,
Bonnefont JeanPaul,
Theve Julien,
Echenne Bernard,
Journel Hubert,
Afenjar Alexandra,
Burglen Lydie,
Bienvenu Thierry,
Addor MarieClaude,
Lebon Sébastien,
Martinet Danièle,
Baumann Clarisse,
Perrin Laurence,
Drunat Séverine,
Jouk PierreSimon,
Devillard Françoise,
Coutton Charles,
Lacombe Didier,
Delrue MarieAnge,
Philip Nicole,
Moncla Anne,
Badens Catherine,
Perreton Nathalie,
Masurel Alice,
ThauvinRobinet Christel,
Portes Vincent Des,
Guibaud Laurent
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37384
Subject(s) - flna , gene duplication , hypotonia , hyperintensity , corpus callosum , lateral ventricles , medicine , periventricular leukomalacia , magnetic resonance imaging , cardiology , pathology , radiology , gestational age , biology , pregnancy , biochemistry , genetics , filamin , cytoskeleton , gene , cell
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. © 2015 Wiley Periodicals, Inc.