Survival trends from the Prader-Willi Syndrome Association (USA) 40-year mortality survey

Abstract

PurposePrader-Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia and morbid obesity with increased cardiopulmonary and hyperphagia-related mortality. Survival trends in PWS were evaluated to assess the impact of modern interventions on mortality risk.MethodsThe Prader-Willi Syndrome Association (USA) 40-year mortality syndrome-specific database of 486 death reports was utilized to examine survival trends in PWS and cohort effects for recent deaths (years 2000-2015, N=331) relative to deaths prior to 2000 (N=94). Cox proportional hazards regression modeling was applied to generate log rank statistics and Kaplan-Meier curves examining sex, cause of death, and cohort.ResultsRisk for all-cause mortality in PWS was 1.5 (95% confidence interval (CI)=1.2-1.9) times higher for the Early than the Recent era cohort reflected in female cardiac failure (hazard ratio (HR)=1.8; 95% CI=1.3-2.6), pulmonary embolism (HR=6.1; 95% CI=1.7-22), and gastrointestinal-related (HR=3.2; 95% CI=1.1-7.4) causes. Accidental deaths in males increased in the Recent era cohort (HR=5.7; 95% CI=1.2-27.1), possibly due to enhanced weight management and mobility. Risk of death from respiratory failure was unchanged.ConclusionWe report measurable increases in survival effecting cardiovascular and gastrointestinal-related causes in PWS most likely attributable to earlier diagnosis and proactive interventions to prevent morbid obesity. More research is needed to address underlying vulnerability to respiratory failure, an unchanged mortality risk in PWS.