CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature

Neuropediatrics. 2016 Dec;47(6):361-367. doi: 10.1055/s-0036-1586730. Epub 2016 Sep 6.

Abstract

Cyclin-dependent kinase-like 5 (CDKL5) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases of CDKL5 gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype-genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159.2:c.2225_2228del (p.Glu742Afs*41)) in exon 15 of CDKL5. All boys have a more severe phenotype than the female patient. In boys with early onset of seizures and poor development with absent or poor eye contact, CDKL5 gene-related EIEE can be suspected and epilepsy-associated genes should be analyzed for early etiological diagnosis. Early genetic diagnosis would be the cornerstone in personalized treatment in the future.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Child, Preschool
  • Epilepsy / genetics*
  • Estonia
  • Female
  • Genetic Association Studies
  • Genetic Testing
  • Humans
  • Infant
  • Male
  • Mutation / genetics*
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics*
  • Spasms, Infantile / genetics*

Substances

  • Protein Serine-Threonine Kinases
  • CDKL5 protein, human