Molecular characterization of a cohort of 73 patients with infantile spasms syndrome

Eur J Med Genet. 2015 Feb;58(2):51-8. doi: 10.1016/j.ejmg.2014.11.007. Epub 2014 Dec 11.


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 heterogeneous including many genetic causes. Many patients, however, remain without etiological diagnosis, 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 = 3) and STXBP1 (n = 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 disrupting 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.

Keywords: CDKL5; Infantile spasms syndrome; MEF2C; SCN2A; STXBP1; West syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calmodulin / genetics
  • Carrier Proteins / genetics
  • Child
  • Child, Preschool
  • DNA Copy Number Variations
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Female
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Infant, Newborn
  • KCNQ2 Potassium Channel / genetics
  • MEF2 Transcription Factors / genetics
  • Male
  • Munc18 Proteins / genetics
  • Mutation
  • NAV1.2 Voltage-Gated Sodium Channel / genetics
  • Nedd4 Ubiquitin Protein Ligases
  • Protein-Serine-Threonine Kinases / genetics
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Spasms, Infantile / genetics*
  • Syndrome
  • Ubiquitin-Protein Ligases / genetics


  • CALN1 protein, human
  • Calmodulin
  • Carrier Proteins
  • Endosomal Sorting Complexes Required for Transport
  • KCNQ2 Potassium Channel
  • KCNQ2 protein, human
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • Munc18 Proteins
  • NAV1.2 Voltage-Gated Sodium Channel
  • Receptors, N-Methyl-D-Aspartate
  • SCN2A protein, human
  • STXBP1 protein, human
  • EHMT1 protein, human
  • Histone-Lysine N-Methyltransferase
  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, human
  • Ubiquitin-Protein Ligases
  • Protein-Serine-Threonine Kinases
  • CDKL5 protein, human
  • MAGI2 protein, human
  • N-methyl D-aspartate receptor subtype 2A