Prevalence of, and risk factors for, physical ill‐health in people with Prader‐Willi syndrome: a population‐based study

Abstract

The medical findings from a population‐based study of Prader‐Willi syndrome (PWS) are discussed (in which birth incidence of PWS was estimated at 1:22 000 and death rate at over 3% per annum). In this study the prevalence of specific medical disorders that might account for a shortened life expectancy were investigated. Of all people with a possible diagnosis of PWS, only those meeting clinical criteria and/or with a confirmed genetic diagnosis were included in the study. Sixty‐six individuals, 40 males and 26 females with a mean age of 19 years (range of 0 to 46 years) agreed to participate in the population‐based study group. A prevalence rate of 25% for non‐insulin dependent diabetes mellitus (NIDDM) was found in adults. Mean age at onset was 20 years. Those with NIDDM had a higher past maximum body weight and a greater likelihood of positive family history. Nearly 50% across the age groups reported a history of recurrent respiratory infections. High rates of fractures (29%), leg ulceration (22% in adults), sleep disorders (20%), and severe scoliosis (15% in childhood) were also reported. It is postulated that hypotonia is a possible contributory factor to the risk of strabismus, scoliosis, and respiratory infections. Other causes of morbidity, in particular the high rates of NIDDM, may be due to a failure to manage over‐eating resulting in severe obesity. Early diagnosis and clear guidance to families about these risks and how they might be prevented is recommended. It is hypothesized that the high pain threshold may result in the presence of some illness not being apparent.

Socio-economic burden of rare diseases: A systematic review of cost of illness evidence

“…The study raises awareness about the lack of research on the socio-economic impact of rare diseases, which can be substantial, as well as methodological issues related to the comparability of the available evidence across borders which need to be addressed in future research. Prevalence 1:2,500 -3,600 newborns (13)(14) 1:3,600 male infants (18) 1:3,600 males; 1:4,000 -6,000 females (20) A: 1:5,000 -10,000 males B: 1:20,000 -34,000 males (21) 8-150:100,00 children (22) Type I 1:100,000; Type II 1:250,000; Type III 1:50,000 to 1:280,000; Type IV 1:75,000; Type VI 1:250,000 (23)(24)(25)(26)(27) 74:100,000 women; 13:100,000 men (30) 1:22,000 newborns (32) 1:150,000 (NMD) (35) 5:100,000 (37) Prevalence (per 100,000 population) (16) A c c e p t e d M a n u s c r i p t 33 A c c e p t e d M a n u s c r i p t 34 9-57% (14)(15)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61) n/a 15-81% (15,(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61) DMD 541,593 (65) n/a n/a 1...…”

“…This results in obesity due to hyperphagia, poor muscle tone, sex glands produce little or no hormones, as well as often below average intelligence and learning difficulties (31). Estimations of the incidence of PWS vary depending on the study and country studied, but it is in the region of 1:22,000 births (32), with an EU prevalence of 1.6:100,000 population (16).…”

Prader-Willi syndrome

“…77 Based on a population study, the death rate has been estimated at 3% per year. 65 Another large study suggested a sixfold relative risk of death in PWS versus other developmentally disabled individuals. 77 Two multicenter series of individuals who died of PWS have been reported, 78,79 and an extensive case and literature review of 64 cases of death in PWS was done.…”

“…63,64 Impaired glucose tolerance and diabetes mellitus. Up to 25% of adults with PWS (particularly those with significant obesity) have noninsulin-dependent diabetes mellitus 65 with a mean age of onset of 20 years. A study of a large French cohort with PWS (ages: 2-18.8 years) revealed the presence of impaired glucose tolerance in 4% of individuals (mean age: 10.2 years) but no diabetes mellitus in those younger than 20 years of age.…”

Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome

“…3,7 Obesity can only be prevented by strict control over access to food, and, so far, various medications and surgical procedures to control eating behaviour have proved ineffective or with significant side effects. 3,8 The hyperphagia has a variable age of onset, and, so far, no identified precipitating factor or underlying mechanism has accounted for this phenotypic change.…”