Genetic Subtype-Phenotype Analysis of Growth Hormone Treatment on Psychiatric Behavior in Prader-Willi Syndrome

Genes (Basel). 2020 Oct 23;11(11):1250. doi: 10.3390/genes11111250.

Abstract

Prader-Willi syndrome (PWS) is a complex multisystemic condition caused by a lack of paternal expression of imprinted genes from the 15q11.2-q13 region. Limited literature exists on the association between molecular classes, growth hormone use, and the prevalence of psychiatric phenotypes in PWS. In this study, we analyzed nine psychiatric phenotypes (depressed mood, anxiety, skin picking, nail picking, compulsive counting, compulsive ordering, plays with strings, visual hallucinations, and delusions) recognized in PWS and investigated associations with growth hormone treatment (GHT), deletions (DEL) and uniparental disomy (UPD) in a cohort of 172 individuals with PWS who met the criteria for analysis. Associations were explored using Pearson chi-square tests and univariable and multivariable logistic regression analyses to control for confounding exposures. This observational study of the largest dataset of patients with PWS to date suggested the following genetic subtype and phenotype correlations in psychiatric behaviors: (1) skin picking was more frequent in those with DEL vs. UPD; (2) anxiety was more common in those with UPD vs. DEL; and (3) an increased frequency of anxiety was noted in the UPD group treated with GHT compared to the DEL group. No other significant associations were found between the genetic subtype or GHT including for depressed mood, nail picking, compulsive counting, compulsive ordering, playing with strings, and visual hallucinations. Further studies will be required before any conclusions can be reached.

Keywords: PWS genetic subtype–phenotype correlations; PWS molecular classes; Prader-Willi syndrome (PWS); growth hormone treatment; natural history; psychiatric behavioral phenotype.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Growth Hormone / therapeutic use*
  • Humans
  • Longitudinal Studies
  • Male
  • Mental Disorders / drug therapy*
  • Mental Disorders / genetics
  • Middle Aged
  • Prader-Willi Syndrome / drug therapy*
  • Prader-Willi Syndrome / genetics*
  • Prader-Willi Syndrome / psychology
  • Problem Behavior / psychology
  • Uniparental Disomy / genetics*
  • Young Adult

Substances

  • Growth Hormone