Comorbidities, Endocrine Medications, and Mortality in Prader-Willi Syndrome-A Swedish Register Study

Background: Prader-Willi Syndrome (PWS) is a rare, genetic, multi-systemic disorder. Its main characteristics are muscular hypotonia, behavioral problems, intellectual disability, endocrine deficiencies, hyperphagia, and a high risk of morbid obesity and related comorbidities. This study aimed to investigate the rate of comorbidity, prescription of endocrine medications, and mortality in individuals with PWS compared to the general population. Methods: The association between PWS and outcomes were investigated in a matched cohort study of individuals born in the period of 1930-2018 with data from Swedish national health and welfare registers. Each individual was matched with 50 non-PWS comparisons. The associations between PWS, outcomes and prescribed endocrine medications were estimated through Cox proportional hazard models, presented as Hazard Ratios (HR) with 95% Confidence Intervals (CIs). Results: Among 360 individuals (53% men) with PWS, 16% had diabetes mellitus, 6% heart failure, 4% vein thrombosis, 2% atrial fibrillation, 2% coronary heart disease, and 1% pulmonary embolism. Individuals with PWS had an increased rate of heart failure (HR: 23.85; 95% CI: 14.09-40.38), diabetes mellitus (HR: 17.49; 95% CI: 12.87-23.74), vein thrombosis (HR: 10.44; 95% CI: 5.69-19.13), pulmonary embolism (HR: 5.77; 95% CI: 2.27-14.67), atrial fibrillation (HR: 5.19; 95% CI: 2.48-10.86), and coronary heart disease (HR: 3.46; 95% CI: 1.50-7.97) compared to non-PWS individuals. Somatotropin was prescribed in 63%, antidiabetics in 18%, and thyroid hormones in 16% of the PWS individuals (<1%, 2%, and 3%, respectively, in non-PWS individuals). The rate of mortality was fifteen times higher in PWS than in non-PWS, with a mean age at death of 42 years. Conclusions: The rates of diabetes mellitus and cardiovascular comorbidities were higher in individuals with PWS. As expected, the prescription of somatotropin was high, but the endocrine prescription pattern also reflected the high prevalence of diabetes mellitus and thyroid illness. Although the mean age at death was older than previously reported, a higher awareness and intensified efforts to avoid obesity, as well as the prevention and early treatment of cardiovascular and endocrine comorbidity, are crucial aims in the care of people with PWS.