Age Distribution, Comorbidities and Risk Factors for Thrombosis in Prader–Willi Syndrome

Abstract

Prader–Willi syndrome (PWS) is an imprinting disorder caused by lack of expression of the paternally inherited 15q11.2–q13 chromosome region. The risk of death from obesity-related complications can worsen with age, but survival trends are improving. Comorbidities and their complications such as thrombosis or blood clots and venous thromboembolism (VTE) are uncommon but reported in PWS. Two phases of analyses were conducted in our study: unadjusted and adjusted frequency with odds ratios and a regression analysis of risk factors. Individuals with PWS or non-PWS controls with exogenous obesity were identified by specific International Classification of Diseases (ICD)-9 diagnostic codes reported on more than one occasion to confirm the diagnosis of PWS or exogenous obesity in available national health claims insurance datasets. The overall average age or average age per age interval (0–17 year, 18–64 year, and 65 year+) and gender distribution in each population were similar in 3136 patients with PWS and 3945 non-PWS controls for comparison purposes, with exogenous obesity identified from two insurance health claims dataset sources (i.e., commercial and Medicare advantage or Medicaid). For example, 65.1% of the 3136 patients with PWS were less than 18 years old (subadults), 33.2% were 18–64 years old (adults), and 1.7% were 65 years or older. After adjusting for comorbidities that were identified with diagnostic codes, we found that commercially insured PWS individuals across all age cohorts were 2.55 times more likely to experience pulmonary embolism (PE) or deep vein thrombosis (DVT) than for obese controls (p-value: 0.013; confidence interval (CI): 1.22–5.32). Medicaid-insured individuals across all age cohorts with PWS were 0.85 times more likely to experience PE or DVT than obese controls (p-value: 0.60; CI: 0.46–1.56), with no indicated age difference. Age and gender were statistically significant predictors of VTEs, and they were independent of insurance coverage. There was an increase in occurrence of thrombotic events across all age cohorts within the PWS patient population when compared with their obese counterparts, regardless of insurance type.

Pharmacodynamic Gene Testing in Prader-Willi Syndrome

“…Among typical persons with venous thromboembolism (VTE), Liu et al (2017) determined that twice as many had MTHFR compound genotypes compared to single mutations of MTHFR, and this finding was not associated with elevated serum homocysteine levels. This is of relevance to PWS as there is an increased risk of VTE (Butler et al, 2020).…”

Prader–Willi Syndrome and Hypogonadism: A Review Article

“…The biological contraindications are comparable to those outlined for sex steroid supplementation in post-menopausal women and Turner syndrome or the use of oral contraceptive pills in normal women. In PWS, the levels of sex steroids are normalised by supplementation and consequently, the pre-existent elevated risk for thromboembolic events in PWS [ 48 ] and the pre-existent risk for breast cancer are not increased. Furthermore, hormone replacement therapy (HRT) with oestradiol is commonly used in PWS instead of alkyl oestradiol, the active ingredient in contraceptive pills that have a different safety profile.…”

Hypogonadism in Women with Prader-Willi Syndrome—Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion

“…HHT can increase the risk of thrombosis [97]. As patients with PWS already have a higher risk of thrombotic events [98], it is important to avoid any other risk factors for thrombosis, if possible. Due to lower levels of sex hormones, HRT is less thrombogenic than hormone contraception [51,99,100].…”