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

Abstract

Background Prader-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. Methods The PWSA (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. Results Risk for all-cause mortality in PWS was 1.5 (95%CI=1.2–1.9) times higher for the Early than the Recent era cohort reflected in female cardiac failure (HR=1.8; 95%CI=1.3–2.6), pulmonary embolism (HR=6.1; 95%CI=1.7–22), and GI-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. Conclusions We report measurable increases in survival effecting cardiovascular and GI-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.

Prader–Willi syndrome and early‐onset morbid obesity NIH rare disease consortium: A review of natural history study

“…b The average BMI was low for an obesity syndrome as 56% of our PWS participants were less than 12 years of age. 1.0 (0.4, 2.2) 2.4 (0.0, 13.1) mortality database Manzardo et al, 2017). Our study of the mortality incidence rate in PWS per 100 years of exposure is novel and showed a low rate, not significantly different than that observed in the EMO group.…”

Respiratory Syncytial Virus in Infants and Children with Prader-Willi syndrome

“…Children with PWS are at high risk for mortality from respiratory infections. This risk is likely due to their hypotonia and inability to adequately cough to clear respiratory secretions [8]. Our survey showed that receiving the Synagis vaccine was associated with a lower incidence of contracting RSV, whereas those who were unable to get the vaccine had a significantly higher risk of contracting the virus.…”

“…Respiratory infections were the primary cause of death for children with PWS <1 year of age and account for 50% of deaths for children less than 2 years of age [6]. Multiple studies have confirmed that respiratory failure/infections are a common cause of mortality in young children with PWS [7,8].…”

Newborn screening for Prader–Willi syndrome is feasible: Early diagnosis for better outcomes

“…In summary, the ultimate goal is to change the face of PWS by early identification and awareness which will permit proactive monitoring of the diet, and exercise and treatment with growth hormone at an early age thus preventing co‐morbidities associated with PWS and reducing the current high mortality rate (Butler et al, ; Manzardo et al, ). The methylation testing used for diagnosis of PWS would also have the added benefit of detecting Angelman syndrome (AS).…”