Foundations · Year 1 · from Foundations
Case 2: Prader-Willi Syndrome (Genomic Imprinting)
Clinical Image
Source: Wikipedia - Prader-Willi syndrome - CC BY-SA 3.0
Case Presentation
A 5-year-old boy is referred for evaluation of obesity and developmental delay. His mother reports that as a newborn he was very floppy and had difficulty feeding, requiring a feeding tube for several months. Around age 2, he developed insatiable appetite and began gaining weight rapidly despite dietary restriction. He has mild intellectual disability and behavioral problems including tantrums. Physical examination reveals central obesity, small hands and feet, almond-shaped eyes, and small genitalia (hypogonadism). Genetic testing reveals a deletion of the paternal chromosome 15q11-13 region. The geneticist explains genomic imprinting: certain genes are expressed only from the maternal or paternal copy, with the other silenced by epigenetic modifications. The genes in this region that cause Prader-Willi syndrome are normally expressed only from the paternal chromosome; when the paternal copy is deleted, there is no functional expression because the maternal copy is imprinted (silenced). Interestingly, deletion of the same region on the maternal chromosome causes a completely different syndrome (Angelman syndrome) because different genes in the region are maternally expressed. Management includes strict dietary control, growth hormone therapy, and behavioral interventions.
Key Learning Points
- Genomic imprinting creates parent-of-origin effects: certain genes are expressed only from maternal or paternal alleles, with the other copy epigenetically silenced
- Prader-Willi syndrome results from loss of paternally-expressed genes at 15q11-13 (deletion, uniparental disomy, or imprinting defect); Angelman syndrome results from loss of maternally-expressed genes in the same region
- The same chromosomal deletion causes different diseases depending on the parent of origin, demonstrating that genetic diseases can depend on more than just the DNA sequence