CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy

Neurology. 2008 Sep 23;71(13):997-9. doi: 10.1212/01.wnl.0000326592.37105.88.

Abstract

Objective: To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations.

Methods: Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis.

Results: We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep.

Conclusions: This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adolescent
  • Brain Diseases / genetics*
  • Child
  • Child, Preschool
  • Epilepsy / genetics*
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Mutation, Missense*
  • Polymorphism, Single Nucleotide / genetics*
  • Protein-Serine-Threonine Kinases / genetics*

Substances

  • Protein-Serine-Threonine Kinases
  • CDKL5 protein, human