title: Causes of death in Prader-Willi syndrome: Prader-Willi Syndrome Association (USA) 40-year mortality survey.
abstract: Prader-Willi syndrome (PWS) is a rare, complex, neurodevelopmental genetic disorder that is associated with hyperphagia and morbid obesity in humans and leads to a shortened life expectancy. This report summarizes the primary causes of death and evaluates mortality trends in a large cohort of individuals with PWS.
  
  
  
  The US Prader-Willi Syndrome Association (PWSA (USA)) syndrome-specific database of death reports was collected through a cursory bereavement program for PWSA (USA) families using a brief survey created in 1999. Causes of death were descriptively characterized and statistically examined using Cox proportional hazards.
  
  
  
  A total of 486 deaths were reported (263 males, 217 females, 6 unknown) between 1973 and 2015, with mean age of 29.5 ± 16 years (2 months-67 years); 70% occurred in adulthood. Respiratory failure was the most common cause, accounting for 31% of all deaths. Males were at increased risk for presumed hyperphagia-related accidents/injuries and cardiopulmonary factors compared to females. PWS maternal disomy 15 genetic subtype showed an increased risk of death from cardiopulmonary factors compared to the deletion subtype.
  
  
  
  These findings highlight the heightened vulnerability to obesity and hyperphagia-related mortality in PWS. Future research is needed to address critical vulnerabilities such as gender and genetic subtype in the cause of death in PWS.Genet Med advance online publication 17 November 2016.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas, USA.|Department of Pediatrics, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Merlin G
authors.identifier: 0000-0001-9283-7809
authors.initials: MG
authors.lastname: Butler
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Ann M
authors.identifier: 0000-0001-9283-7809
authors.initials: AM
authors.lastname: Manzardo
authors.affiliation: Prader-Willi Syndrome Association (USA), Sarasota, Florida, USA.
authors.forename: Janalee
authors.initials: J
authors.lastname: Heinemann
authors.affiliation: Prader-Willi Syndrome Association (USA), Sarasota, Florida, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Loker
authors.affiliation: Bronson Children's Hospital, Kalamazoo, Michigan, USA.
authors.forename: James
authors.identifier: 0000-0002-9934-6022
authors.initials: J
authors.lastname: Loker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011218:Prader-Willi Syndrome / Q000235:genetics / Q000401:mortality*; D016019:Survival Analysis; D055815:Young Adult