Learning Objectives
- Define Genetic Anticipation and its mechanism.
- Identify the specific trinucleotide sequences and inheritance patterns for Huntington, Myotonic Dystrophy, Fragile X, and Friedreich Ataxia.
- Utilize high-yield mnemonics to recall clinical manifestations.
1. Concept of Genetic Anticipation
Trinucleotide repeat diseases often exhibit anticipation, where the disease becomes more severe or has an earlier onset in successive generations. This is due to the expansion of repeat sequences during gametogenesis (oogenesis or spermatogenesis).
2. Summary Table of Repeat Diseases
| Disease | Repeat | Inheritance | High-Yield Mnemonic |
|---|---|---|---|
| Huntington Disease | (CAG)n | Autosomal Dominant | Caudate has ACh and GABA ↓ |
| Myotonic Dystrophy | (CTG)n | Autosomal Dominant | Cataracts, Toupee (balding), Gonadal atrophy |
| Fragile X Syndrome | (CGG)n | X-linked Dominant | Chin (protruding), Giant Gonads |
| Friedreich Ataxia | (GAA)n | Autosomal Recessive | Ataxic GAAit |
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3. High-Yield Clinical Pearls
- Huntington: Expansion typically occurs during spermatogenesis. Clinical hallmark is chorea and aggression.
- Fragile X: Expansion occurs during oogenesis. Most common inherited intellectual disability.
- Friedreich Ataxia: The only Autosomal Recessive disorder in this group. Associated with hypertrophic cardiomyopathy.
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