Variant of Rett syndrome and CDKL5 gene: clinical and autonomic description of 10 cases

Neuropediatrics. 2012 Feb;43(1):37-43. doi: 10.1055/s-0032-1308856. Epub 2012 Mar 19.

Abstract

Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene.

Aims: In recent years more than 60 patients with mutations in the CDKL5 gene have been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls.

Methods: 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all subjects an evaluation of the autonomic system was performed using the Neuroscope.

Results: Common features were gaze avoidance, repetitive head movements and hand stereotypies. The autonomic evaluation disclosed eight cases with the Forceful breather cardiorespiratory phenotype and two cases with the Apneustic breather phenotype.

Conclusions: The clinical picture remains within the RTT spectrum but some symptoms are more pronounced in addition to the very early onset of seizures. The cardiorespiratory phenotype was dominated by Forceful breathers, while Feeble breathers were not found, differently from the general Rett population, suggesting a specific behavioral and cardiorespiratory phenotype of the RTT the Hanefeld variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autonomic Nervous System Diseases / etiology*
  • Autonomic Nervous System Diseases / genetics
  • Brain / pathology
  • Child
  • Child, Preschool
  • Disability Evaluation
  • Electroencephalography
  • Epilepsy / etiology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Methyl-CpG-Binding Protein 2 / genetics
  • Mutation / genetics*
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics*
  • Rett Syndrome / complications*
  • Rett Syndrome / diagnosis
  • Rett Syndrome / genetics*
  • Severity of Illness Index

Substances

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