Further delineation of theMECP2duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features
Authors: Miguet Marguerite , Faivre Laurence , Amiel Jeanne , Nizon Mathilde , Touraine Renaud , Prieur Fabienne , Pasquier Laurent , Lefebvre Mathilde , Thevenon Julien , Dubourg Christèle , Julia Sophie , Sarret Catherine , Remerand Ganaëlle , Francannet Christine , Laffargue Fanny , Boespflug-Tanguy Odile , David Albert , Isidor Bertrand , Vigneron Jacqueline , Leheup Bruno , Lambert Laetitia , Philippe Christophe , Béri-Dexheimer Mylène , Cuisset Jean-Marie , Andrieux Joris , Plessis Ghislaine , Toutain Annick , Guibaud Laurent , Cormier-Daire Valérie , Rio Marlene , Bonnefont Jean-Paul , Echenne Bernard , Journel Hubert , Burglen Lydie , Chantot-Bastaraud Sandrine , Bienvenu Thierry , Baumann Clarisse , Perrin Laurence , Drunat Séverine , Jouk Pierre-Simon , Dieterich Klaus , Devillard Françoise , Lacombe Didier , Philip Nicole , Sigaudy Sabine , Moncla Anne , Missirian Chantal , Badens Catherine , Perreton Nathalie , Thauvin-Robinet Christel , AChro-Puce Réseau , Pedespan Jean-Michel , Rooryck Caroline , Goizet Cyril , Vincent-Delorme Catherine , Duban-Bedu Bénédicte , Bahi-Buisson Nadia , Afenjar Alexandra , Maincent Kim , Héron Delphine , Alessandri Jean-Luc , Martin-Coignard Dominique , Lesca Gaëtan , Rossi Massimiliano , Raynaud Martine , Callier Patrick , Mosca-Boidron Anne-Laure , Marle Nathalie , Coutton Charles , Satre Véronique , Caignec Cédric Le , Malan Valérie , Romana Serge , Keren Boris , Tabet Anne-Claude , Kremer Valérie , Scheidecker Sophie , Vigouroux Adeline , Lackmy-Port-Lis Marilyn , Sanlaville Damien , Till Marianne , Carneiro Maryline , Gilbert-Dussardier Brigitte , Willems Marjolaine , Van Esch Hilde , Portes Vincent Des , El Chehadeh Salima 
Published: April 2018

The Xq28 duplication involving theMECP2gene (MECP2duplication) has been mainly described in male patients with severe developmental delay (DD) associated with spasticity, stereotypic movements and recurrent infections. Nevertheless, only a few series have been published. We aimed to better describe the phenotype of this condition, with a focus on morphological and neurological features. Through a national collaborative study, we report a large French series of 59 affected males with interstitialMECP2duplication. Most of the patients (93%) shared similar facial features, which evolved with age (midface hypoplasia, narrow and prominent nasal bridge, thick lower lip, large prominent ears), thick hair, livedo of the limbs, tapered fingers, small feet and vasomotor troubles. Early hypotonia and global DD were constant, with 21% of patients unable to walk. In patients able to stand, lower limbs weakness and spasticity led to a singular standing habitus: flexion of the knees, broad-based stance with pseudo-ataxic gait. Scoliosis was frequent (53%), such as divergent strabismus (76%) and hypermetropia (54%), stereotypic movements (89%), without obvious social withdrawal and decreased pain sensitivity (78%). Most of the patients did not develop expressive language, 35% saying few words. Epilepsy was frequent (59%), with a mean onset around 7.4 years of age, and often (62%) drug-resistant. Other medical issues were frequent: constipation (78%), and recurrent infections (89%), mainly lung. We delineate the clinical phenotype ofMECP2duplication syndrome in a large series of 59 males. Pulmonary hypertension appeared as a cause of early death in these patients, advocating its screening early in life.