Prader-Willi syndrome and Angelman syndrome

Overview

Definition: genetic syndromes caused by microdeletion (at 15q11-q13) in combination with genomic imprinting or uniparental disomy.
- Genomic inprinting: an epigenetic phenomenon that results in silencing of one of the alleles of a gene depending on whether the allele was paternally or maternally inherited.
- Uniparental disomy: a chromosomal abnormality in which offspring receive two copies of one chromosome from one parent and no copies from the other parent
Etiology: The resulting condition depends on the affected gene copy.
- Angelman syndrome
  - Deletion or mutation of maternal UBE3A (chromosome 15) gene copy and paternal gene methylation (silencing)
  - In ∼ 5% of cases, it results from paternal uniparental disomy (i.e. both copies of chromosome 15 are inherited from the father).
- Prader-Willi syndrome
  - Deletion or mutation of paternal gene copy and maternal gene methylation (silencing)
  - Caused by maternal uniparental disomy in about 20–35% of cases
Diagnosis: genetic tests
- Fluorescence in situ hybridization (FISH)

Clinical features
- Muscular hypotonia and poor feeding in infants
- Increased appetite (hyperphagia) and obesity
- Cryptorchidism, hypogonadism, genital hypoplasia
- Facial dysmorphia (e.g., almond-shaped eyes, thin upper lip)
- Developmental delays (e.g., delayed achievement of milestones), intellectual disability
- Behavioral problems (e.g., temper tantrums, stubbornness, obsessive-compulsive behavior)
Treatment
- Calorie restriction
- Substitution of growth hormone and sex hormones
Complications
- Sleep apnea (most common)
- Type 2 diabetes mellitus
- Choking episodes
- Gastric distention and rupture