Rett Syndrome and CDKL5 Deficiency Disorder: From Bench to Clinic

Int J Mol Sci. 2019 Oct 15;20(20):5098. doi: 10.3390/ijms20205098.

Abstract

Rett syndrome (RTT) and CDKL5 deficiency disorder (CDD) are two rare X-linked developmental brain disorders with overlapping but distinct phenotypic features. This review examines the impact of loss of methyl-CpG-binding protein 2 (MeCP2) and cyclin-dependent kinase-like 5 (CDKL5) on clinical phenotype, deficits in synaptic- and circuit-homeostatic mechanisms, seizures, and sleep. In particular, we compare the overlapping and contrasting features between RTT and CDD in clinic and in preclinical studies. Finally, we discuss lessons learned from recent clinical trials while reviewing the findings from pre-clinical studies.

Keywords: clinical trials; glutamate toxicity; interneurons; preclinical modeling; seizures; sleep.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Diagnosis, Differential
  • Disease Management
  • Disease Susceptibility
  • Epileptic Syndromes / diagnosis*
  • Epileptic Syndromes / etiology*
  • Epileptic Syndromes / therapy*
  • Humans
  • Methyl-CpG-Binding Protein 2 / genetics
  • Methyl-CpG-Binding Protein 2 / metabolism
  • Mutation
  • Outcome Assessment, Health Care
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Rett Syndrome / diagnosis*
  • Rett Syndrome / etiology*
  • Rett Syndrome / therapy*
  • Spasms, Infantile / diagnosis*
  • Spasms, Infantile / etiology*
  • Spasms, Infantile / therapy*
  • Translational Research, Biomedical

Substances

  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Protein Serine-Threonine Kinases
  • CDKL5 protein, human

Supplementary concepts

  • CDKL5 deficiency disorder