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?