Learning Objectives
- Define Genomic Imprinting and the role of DNA methylation.
- Distinguish between Prader-Willi and Angelman syndromes based on parent-of-origin.
- Recognize the clinical triads and mnemonics for both disorders.
- Understand the role of Uniparental Disomy in imprinting defects.
1. Concept of Imprinting
Imprinting is an epigenetic process where one gene copy is silenced (usually via methylation), depending on which parent it came from. Only one “active” copy remains. Disease occurs if that single active copy is deleted or mutated.
2. Comparison of Syndromes (Chromosome 15)
| Feature | Prader-Willi Syndrome | Angelman Syndrome |
|---|---|---|
| Silent Allele | Maternal genes are silenced. | Paternal UBE3A is silenced. |
| Defect | The paternal allele is deleted/mutated. | The maternal allele is deleted/mutated. |
| Symptoms | Hyperphagia, obesity, hypotonia, hypogonadism. | Ataxia, laughter, seizures, and intellectual disability. |
| Uniparental Disomy | 25% due to Maternal UPD. | 5% due to Paternal UPD. |
3. High-Yield Mnemonics
POP: Prader-Willi, Obesity/overeating, Paternal allele deleted.
MAMAS: Maternal allele deleted, Angelman syndrome, Mood (laughter), Ataxia, Seizures.
HAILS the Angels: Hand-flapping, Ataxia, Intellectual disability, Laughter, Seizures.
Activity