Rett Syndrome

Kate Sears

Neuroscience II

History and Prevalance

  • Discovered in 1966

  • Recognized in 1983

  • Approximately 1 in 8,500-15,000 girls

  • Extremely rare in boys

Symptoms

  • Slowing of Head Growth

  • Reduction of Brain 

  • Cognitive Impairment 

  • Autistic-Like Features

  • Prognosis is poor

Symptoms 

Stages of Rett

I:  Early Onset or Subtle Slowing of Development

II: Rapid Destruction of Development

III: Pseudo-Stationary or Plateau 

IV: Late Motor Deterioration 

Classification 

  • Neurodevelopmental and Neuropsychiatric 

  • Misdiagnosed
  • A Combination of Disorders and Syndromes
  • Controversy over DSM-V

Genetics

  • Gene Identified in 1999

  • Spontaneous Mutation (De Novo)

  • Germ Cells, usually paternal

  • X-Linked

  • X-Inactivation

Epigenetics

Changes that occur after initial action of genes that affect chromosomes or nucleotides but not the original DNA sequence. 

  • MeCP2 is a known epigenetic factor
  • X-Chromosome Inactivation 
  • "reader" of DNA methlyation markers

http://www.resverlogix.com/programs/epigenetics#.VTbBKiFViko

MeCP2

  • Methyl CpG binding protein 2

  • Found in Neurons and Glia

  • Basic Nuclear Protein

  • Loss of function

  • Transcriptional Repressor 

http://www.intechopen.com/books/chromatin-remodelling/rett-syndrome. 

MeCP2 Function

  • Exact Function Unclear
  • Gene Expression
  • Chromatin Modification
  • In the brain: Maintaining Synapses
  • Alternative Splicing

MeCP2 

  • Regulates the Regulators
  • Modified by environmental factors and neuronal activities.

http://ghr.nlm.nih.gov/gene/MECP2

Current Research 

Links to Autism 

  • Environmental Factors
  • Parental Health/Age
  • Neurotransmitters

MeCP2 Research

Four exons: Infinite expression

  • "Multi-Functional Global Regulator"
  • Mutation location and type correlated to diseases

Gene Therapy

Systemic Delivery:

 MeCP2

IGF-1 

BDNF

Questions?

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