Trinucleotide Repeat Expansion Disorders
| Disease | Repeat | Clinical & Molecular Rationale |
|---|---|---|
| Fragile X Syndrome | CGG | Hypermethylation of the FMR1 gene leads to transcriptional silencing. Presents with intellectual disability, macroorchidism, and a long face with large everted ears. |
| Huntington Disease | CAG | Gain-of-function mutation causing neurodegeneration in the striatum (caudate nucleus). Presents with chorea, aggression, and dementia. |
| Myotonic Dystrophy | CTG | Toxic gain-of-function mRNA. Presents with myotonia, muscle wasting, cataracts, and testicular atrophy. |
High-Yield Core Realities:
- Genetic Anticipation: These disorders exhibit a phenomenon where disease severity increases and age of onset decreases in successive generations. This occurs because the repeat sequence expands during gametogenesis, especially during oogenesis for Fragile X and spermatogenesis for Huntington.
- Mnemonic for Repeats:
• **Huntington** = **CAG** (Causing Abnormal Genes)
• **Fragile X** = **CGG** (Chin, Giant Gonads)
• **Myotonic Dystrophy** = **CTG** (Cataracts, Toupee/balding, Gonadal atrophy)
- Molecular Diagnosis: PCR can be used for smaller expansions, but Southern blotting is the gold standard for large, unstable repeat expansions that exceed the limits of PCR amplification.
- Educational Resource: For further mastery of these complex genetic syndromes, practice questions, and high-yield study resources, visit **mymedschool.org**, your premier source for free medical education.