Bit · Genetics
Prader-Willi vs Angelman
Two syndromes from the same chromosomal region (15q11–q13), but you get whichever one is broken by which parent was supposed to contribute the working copy. Genomic imprinting at its most testable.
Mechanism
Both syndromes are caused by loss of function at the same locus — 15q11–q13. The pivot is imprinting: at this locus, only one parent's copy is expressed for any given gene. The other parent's copy is silenced (imprinted).
- Prader-Willi — you lose the paternal contribution. Either deletion of paternal 15q11–q13 (~70%) or maternal uniparental disomy (~25%, two maternal copies, zero paternal).
- Angelman — you lose the maternal contribution. Either deletion of maternal 15q11–q13 or paternal uniparental disomy. The specific gene of interest in Angelman is UBE3A.
So the chromosomal region looks the same. The parental origin of the working copy decides the disease.
Differentiator Table
| Prader-Willi | Angelman | |
| Missing parental contribution | Paternal | Maternal |
| Most common mechanism | Paternal deletion 15q11–q13 | Maternal deletion 15q11–q13 |
| Key affected gene | Multiple paternally-expressed genes in region | UBE3A |
| Infancy | Hypotonia, poor feeding, failure to thrive | Normal early; delays noted later |
| Childhood | Hyperphagia, obesity, short stature, hypogonadism | Severe intellectual disability, no speech |
| Behaviour / appearance | Almond-shaped eyes, narrow forehead, food-seeking | Inappropriate laughter, hand-flapping, ataxic gait ('happy puppet') |
| Seizures | Uncommon | Common |
| Intellectual disability | Mild to moderate | Severe |
The Pivot
Two questions decide it:
- Which parent's chromosome was deleted (or duplicated as UPD)? Paternal loss → Prader-Willi. Maternal loss → Angelman.
- Clinical: hyperphagia and obesity vs. seizures and inappropriate laughter? Same answer.
NBME often gives you the parental origin directly. Don't overthink — the imprinting rule does the work.
NBME-Style Stem
A 3-year-old boy is brought in for hyperphagia, obesity, hypogonadism, and developmental delay. As an infant he had profound hypotonia and required tube feeding. Karyotype shows a deletion at 15q11–q13. Methylation studies show the deletion is on the chromosome inherited from his father. Which of the following is the most likely diagnosis?
Concept Anchor
At the 15q11–q13 locus, only one parent's copy of each gene is expressed — lose that one and the disease appears. Paternal loss gives you Prader-Willi; maternal loss gives you Angelman.