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Anticipation
📖 About
- Anticipation = a genetic disorder appears at an earlier age and/or with increasing severity in successive generations.
- 🔑 Classic in trinucleotide repeat expansion disorders.
- During gametogenesis, unstable repeats expand → larger repeats = earlier onset & worse phenotype.
- ⏳ Particularly relevant in neurological & neuromuscular disorders.
🧬 Examples of Diseases with Anticipation
| Disease | Key Genetic / Clinical Features |
|---|---|
| 🧠 Fragile X Syndrome | FMR1 (CGG); X-linked dominant. Intellectual disability, autism, macroorchidism, facial dysmorphism. Expansion via maternal transmission. |
| 🌀 Huntington’s Disease | HTT (CAG); autosomal dominant. Chorea, psychiatric changes, dementia. Anticipation usually with paternal transmission. |
| 💪 Myotonic Dystrophy (DM1) | DMPK (CTG); autosomal dominant. Progressive myopathy, grip myotonia, cataracts, endocrine disorders. Expansion via maternal transmission. |
| ⚖️ Spinocerebellar Ataxia (e.g. SCA1) | ATXN1 (CAG); autosomal dominant. Progressive ataxia, dysarthria, oculomotor abnormalities. Variable parent-of-origin effect. |
| 🌏 DRPLA (Dentatorubral–pallidoluysian atrophy) | ATN1 (CAG); autosomal dominant. Ataxia, myoclonus, seizures, dementia. More severe with paternal transmission. Notably seen in Japanese population. |
💡 Exam Pearls
- 🔑 Anticipation = trinucleotide repeat expansion.
- Parent-of-origin:
- 👩 Maternal → Fragile X, Myotonic dystrophy
- 👨 Paternal → Huntington’s, DRPLA
- Mnemonic aids:
- CGG → Fragile X ("Cognitive & Gonadal problems").
- CAG → Huntington’s & ataxias ("CAG = Causing Ataxia & Genetic issues").
- CTG → Myotonic dystrophy ("CTG = Cataracts, Testicular atrophy, Grip myotonia").