Clinical research Molecular characterization of a cohort of 73 patients with infantile spasms syndrome Nadia Boutry-Kryza a, b , Audrey Labalme c , Dorothee Ville d , Julitta de Bellescize e , Renaud Touraine f , Fabienne Prieur f , Sarra Dimassi b, c, g , Anne-Lise Poulat d , Marianne Till c , Massimiliano Rossi b, c , Emilie Bourel-Ponchel h , Aline Delignières i , Anne-Gaelle Le Moing i , Clotilde Rivier j , Vincent des Portes d, g, k , Patrick Edery b, c, g , Alain Calender a, g, l , Damien Sanlaville b, c, g , Gaetan Lesca b, c, g, * a Department of Molecular Genetics, Lyon University Hospital, Lyon, France b CRNL, CNRS UMR 5292, INSERM U1028, Lyon, France c Department of Genetics, Lyon University Hospital, Lyon, France d Reference Center for Tuberous Sclerosis and Rare Epileptic Syndromes, Lyon University Hospital, Lyon, France e Epilepsy, Sleep and Pediatric Neurophysiology Department, Lyon University Hospital, Lyon, France f Department of Genetics, Hospital Nord, Saint-Etienne University Hospital, France g Claude Bernard Lyon I University, Lyon, France h Pediatric Functional Exploration of the Nervous System Service, Hospital Nord, Amiens University Hospital, Amiens, France i Department of Neurology, Hospital Nord, Amiens University Hospital, Amiens, France j Department of Pediatrics, Hospital Nord-Ouest, Villefranche sur Saone, France k CNRS UMR 5403, Institut des Sciences Cognitives, L2C2, Bron, France l INSERM U1052, Lyon, France article info Article history: Received 12 May 2014 Accepted 30 November 2014 Available online 11 December 2014 Keywords: West syndrome Infantile spasms syndrome CDKL5 STXBP1 MEF2C SCN2A abstract Infantile Spasms syndrome (ISs) is a characterized by epileptic spasms occurring in clusters with an onset in the first year of life. West syndrome represents a subset of ISs that associates spasms in clusters, a hypsarrhythmia EEG pattern and a developmental arrest or regression. Aetiology of ISs is widely het- erogeneous including many genetic causes. Many patients, however, remain without etiological diag- nosis, which is critical for prognostic purpose and genetic counselling. In the present study, we performed genetic screening of 73 patients with different types of ISs by array-CGH and molecular analysis of 5 genes: CDKL5, STXBP1, KCNQ2, and GRIN2A, whose mutations cause different types of epileptic encephalopathies, including ISs, as well as MAGI2, which was suggested to be related to a subset of ISs. In total, we found a disease-causing mutation or CNV (Copy Number Variation) in 15% of the patients. These included 6 point mutations found in CDKL5 (n ¼ 3) and STXBP1 (n ¼ 3), 3 microdeletions (10 Mb in 2q24.3, 3.2 Mb in 5q14.3 including the region upstream to MEF2C, and 256 kb in 9q34 dis- rupting EHMT1), and 2 microduplications (671 kb in 2q24.3 encompassing SCN2A, and 11.93 Mb in Xq28). In addition, we discuss 3 CNVs as potential risk factors, including one 16p12.1 deletion, one intronic deletion of the NEDD4 gene, and one intronic deletion of CALN1 gene. The present findings highlight the efficacy of combined cytogenetic and targeted mutation screening to improve the diagnostic yield in patient with ISs. Ó 2014 Elsevier Masson SAS. All rights reserved. 1. Introduction Infantile Spasms syndrome (ISs) is an age-related epilepsy syndrome, occurring usually in the first year of life. Incidence is estimated between 2 and 5/10,000 infants [Lux and Osborne, 2004]. Electroclinical spasms (ES) usually occur in clusters and are characterized, in most cases, by the characteristic interictal EEG pattern of hypsarrhythmia. West syndrome (WS) represents * Corresponding author. Service de Génétique HFME, 59 Boulevard Pinel, 69677 Bron, Cedex, France. Tel.: þ33 (0) 4 2785 5573; fax: þ33 (0) 4 7212 9710. E-mail address: gaetan.lesca@chu-lyon.fr (G. Lesca). Contents lists available at ScienceDirect European Journal of Medical Genetics journal homepage: http://www.elsevier.com/locate/ejmg http://dx.doi.org/10.1016/j.ejmg.2014.11.007 1769-7212/Ó 2014 Elsevier Masson SAS. All rights reserved. European Journal of Medical Genetics 58 (2015) 51e58