Further delineation of the MECP2 duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features

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

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.