Prader-Willi Syndrome Lecture Notes

Overview

Prader-Willi Syndrome (PWS) is a genetic disorder.
Affects infants with poor feeding and low muscle tone.
In childhood, leads to overeating, intellectual disability, and low sex hormones.

Caused by lack of expression of genes on chromosome 15.
Key genes involved: SNRPN (Small Nuclear Ribonucleoproteins Polypeptide N) and a cluster of SnoRNAs (Small Nucleolar RNAs).
Normally, genes from the mother are silenced (imprinting), and only the paternal genes are expressed.
Epigenetic silencing involves adding methyl groups to DNA.

Deletion of paternal genes in the Prader-Willi region.
- Deletion often includes OCA2, affecting pigmentation.
Maternal Uniparental Disomy.
- Two maternal chromosome 15 copies lead to all genes being silenced.
- Results from nondisjunction and trisomy rescue.
Mutation in the Imprinting Center.
- Affects sex-specific methylation, leading to gene silencing.
- Epimutation can occur if methylation isn’t erased.
Translocation.
- Chromosomes swap material, disrupting SNRNP and SnoRNAs.

Newborns: low muscle tone, poor sucking reflex, failure to thrive.
Late infancy: overeating due to hypothalamic dysfunction.
Risk of obesity, type 2 diabetes, obstructive sleep apnea.
Distinct physical features: almond-shaped eyes, narrow forehead, thin upper lip, small hands and feet.
Developmental delay and low IQ.
Hypothalamus issues affect GnRH and growth hormone secretion.

Diagnosis involves genetic mutation testing.
Management includes:
- Restricting food access (locking food storage).
- Growth hormone therapy to improve height and lean body mass.
No effective medicines or surgeries for controlling overeating.

PWS is an imprinting disorder affecting the paternal copy of chromosome 15.
Causes low muscle tone in infancy and obesity, developmental issues in childhood.