Home Page
References OMIM Gene GeneReviews HGMD HGNC
last update : 19-04-2011
Symbol PWS
Location 15q11.2-q13
Name Prader-Willi syndrome
Corresponding gene SNRPN , SNORD116@ , NDN , MAGEL2 , OCA2
Other symbol(s) DEL15Q12, UPD15M
Main clinical features
  • hypotonia and feeding difficulties in early infancy, followed in early childhood by excessive eating and obesity, distinctive facial features, acromicria, short stature, hypogonadism, developmental delay, mild to moderate mental retardation, distinctive behavioral phenotype with temper tantrum and obsessive compulsive mannerisms
  • plasma ghrelin is increased 3- to 4-fold , linked to obesity
  • loss of MAGEL2 contributes to endocrine dysfunction of hypothalamic origin in individuals with PWS (PMID: 21248145))
  • Genetic determination chromosomal
    genomic disorder
    Prevalence ~1/22,000 livebirths but with a population prevalence of ~1/54,000
    Function/system disorder multisystem/generalized
    mental retardation
    Type MCA/MR
    Gene product
    Name contiguous gene syndrome, including five paternally expressed genes that encode polypeptides : SNURF-SNRPN, MKRN3, MAGEL2, and NDN. SNRPN is a small ribonuclear protein involved in alternative mRNA splicing. No abnormal gene product associated with PWS has been identified
    Gene mutationChromosome rearrangementEffectComments
      deletion haploinsufficiency genomic disorder, typically deleted region between BP1-BP3 (class I), or between BP2-BP3 (class II) on the paternal chromosome
      uniparental disomy absent protein maternal UPD, associated with advanced maternal age (trisomy rescue)
    imprinting defect   absent protein microdeletions or LOI at the 3'end of the ICR
  • paternal deletions in ~ 65-70 p.cent of cases, maternal UPD in ~ 20-30p.cent, imprinting defect in ~ 5 p.cent
  • loss of the regulatory psnoRNAs (shorter RNAs psnoRNAs, processed snoRNAs) could be a significant contribution to the etiology of PWS and substitution of the short psnoRNAs could be a therapeutic principle for the disease (PMID: 20053671)); paternally inherited 236kb microdeletion confirms a significant role for the SNORD116 C/D box snoRNA cluster in PWS (PMID: 20588305))
  • associated with the loss of several species of small nucleolar RNAs (snoRNAs) (PMID: 20876107))
  • advanced maternal age at childbirth is a predisposing factor for the development of upd(15)mat because of increased M1 errors (PMID: 21633360))
  • in Prader-Willi Syndrome, loss of MAGEL2 may likewise abolish leptin responses in POMC hypothalamic neurons, which could contribute to the hyperphagia and obesity (PMID: 23341784))
  • Genotype/Phenotype correlations
  • UPD patients tend to have a less severe phenotype than deletion patients (facial appearance, hypopigmentation, seizures, mental retardation, behavioral problems)
  • class I patients tend to have more severe cognitive and behavioral problems than class II patients
  • atypical larger deletions extending distally have an extended PWS phenotype more severe than classical PWS