Mutation screening of the CDKL5 gene in cryptogenic infantile intractable epilepsy and review of clinical sensitivity

Eur J Paediatr Neurol. 2011 Sep;15(5):432-8. doi: 10.1016/j.ejpn.2011.01.005. Epub 2011 Jul 20.


Purposes: To perform CDKL5 mutation screening in Thai children with cryptogenic infantile intractable epilepsy and to determine the clinical sensitivity of CDKL5 screening when different inclusion criteria were applied.

Methods: Children with cryptogenic infantile intractable epilepsy were screened for CDKL5 mutation using multiplex ligation-dependent probe amplification and DNA sequencing. The clinical sensitivity was reviewed by combining the results of studies using similar inclusion screening criteria.

Results: Thirty children (19 girls and 11 boys) with a median seizure onset of 7 months were screened. Almost a half had infantile spasms and one fifth had stereotypic hand movements. A novel c.2854C>T (p.R952X) was identified in an ambulatory girl who had severe mental retardation, multiple types of seizures without Rett-like features. Her mother had a mild intellectual disability, yet her grandmother and half sister were normal despite having the same genetic alteration (random X-inactivation patterns). The pathogenicity of p.R952X identified here was uncertain since healthy relatives and 6 female controls also harbor this alteration. The clinical sensitivity of CDKL5 mutation screening among females with Rett-like features and negative MECP2 screening was 7.8% while the clinical sensitivity among females having cryptogenic intractable seizures with an onset before the ages of 12, 6 and 3 months were 4.7, 11.6 and 14.3%, respectively.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Intellectual Disability / genetics
  • Male
  • Mutation / genetics*
  • Pedigree
  • Prospective Studies
  • Protein Serine-Threonine Kinases / genetics*
  • Spasms, Infantile / diagnosis*
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / physiopathology
  • Thailand
  • X Chromosome Inactivation / genetics


  • Protein Serine-Threonine Kinases
  • CDKL5 protein, human