Neurodevelopment Disorders

Basics of brain development

  • Neuron overproduction and selection

Synaptogensis

  • Dendrites starting to have synapses

Down Syndrome

  • Genetic disorder caused by a triplication of chromosome 21

  • Distinct physical attributes

  • 30% born with heart defects

  • GI tract problems

  • 10% have comorbid seizures

Delayed developmental milestones

Reduced cogntiive abilites

Explicit long-term memory deficits

Fragile X

  • >200 CGG repeats on the X chromosome

    • Reduces production of FMRP protein —- too much sunthesis of some proteins

    • mGluR5

  • Distinct physical attributes

  • Anxious, hypersensitive, impulsive, ADD-like symptoms

  • Delayed language development and intellectual disabilities

RETT Syndrome

  • X-linked mutation of gene for MeCP2 protein (this protein normally binds to chromosomes and either enhances or represses gene expression, playing a crucial role in the development and function of neurons in the brain). This mutation leads to the characteristic symptoms of Rett Syndrome, including loss of purposeful hand skills, gait abnormalities, and cognitive impairment.)

  • All cells have MeCP2 (it turns on/ off genes)

  • Almost 100% seen in females

  • Normal development until for 6-18 months

    • Then regress - lose language, lose purposeful movement, hand flopping

    • Develop autistic behaviors

    • Progressive motor problems

    • Underdeveloped cognitive abilities

    • Respiratory and GI problems

    • Prefrontal and frontal cortex fails to develop

Only one X chromosome is mutated, not both

If both X chromosomes are mutated = death

Treatments

  1. How does gene therapy work?

  • Mutated gene (replace that gene with a normal gene)

  • Problems with Gene therapy (too much MeCP2 is just as bad as not enough)

  • All cells have MeCP2

  • Can cause liver failure and ultimately death

  1. Gene Editing

  • Morally questionable

  1. RNA editing

  2. Re-activate X-chromosome