The Italian registry for patients with Prader–Willi syndrome

Abstract

Background Prader–Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients’ care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. Materials and methods The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. Results A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019–2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment. Conclusions The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.

Prader–Willi syndrome in a large sample from Spain: general features, obesity and regular use of psychotropic medication

“…The current treatment with GH was significantly associated with the mUPD genetic variant in our sample (Table 1), coinciding with a British study (Soni et al 2007). The decrease in the use of GH treatment among adults in our sampleas it happens elsewhere (e.g., Salvatore et al 2023)is striking despite its beneficial effects in reducing fat body mass and increasing lean body mass, as demonstrated in randomised (Sode-Carlsen et al 2012;Reus et al 2013) or naturalistic (Pellikaan et al 2021) clinical trials, as well as the improvement of metabolic health and the reduction of cardiovascular risk and mortality supported by recent reviews (Yang 2020;Rosenberg et al 2021).…”

“…The decrease in the use of GH treatment among adults in our sample – as it happens elsewhere (e.g., Salvatore et al . 2023) – is striking despite its beneficial effects in reducing fat body mass and increasing lean body mass, as demonstrated in randomised (Sode‐Carlsen et al . 2012; Reus et al .…”

“…Prader-Willi syndrome (PWS), a genetically determined disorder (see Driscoll et al 2023 for an updated overview), is the most frequent cause of early onset obesity and is associated with physical dysfunctions (Goldstone et al 2008), mainly infantile central hypotonia, hypogonadism, short stature and distinctive facial features (Holm et al 1993). It also causes intellectual and developmental delays or disabilities and behavioural disturbances (hyperphagia, chronic skin-picking, obsessions, impulsivity and mood swings) (Rice & Einfeld 2015;Butler et al 2016a;Butler et al 2018;Rice et al 2018;Salvatore et al 2023).…”