OR27-5 Malignancies in Prader-Willi Syndrome: Practical Recommendations Based on a Large International Cohort

Abstract

Abstract Introduction Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, pituitary hormone deficiencies, neurodevelopmental delay, high pain threshold, hypotonia and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of a cluster of paternally expressed genes on chromosome 15q11.2-q13 called the PWS critical region, mostly due to paternal deletion (DEL) or maternal uniparental disomy. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health. Multiple genes in the PWS critical region have been associated with the development of malignancies and obesity is a risk factor for many types of malignancies. The aim of this study was to investigate the prevalence and pathogenesis of malignancies and to provide clinical recommendations for screening in patients with PWS. Methods We collected information on a (for rare disorders) exceptionally large cohort of 706 patients with PWS (160 children, 546 adults). All patients had visited the seven participating centers in Europe and Australia. Data was collected retrospectively from medical records on past or current malignancies, the type of malignancy and risk factors for malignancies. Genotype, age, gender, body mass index (BMI), tobacco use, presence of type 2 diabetes mellitus, growth hormone treatment and sex hormone replacement therapy were assessed in relation to the occurrence of malignancies. Additionally, we systematically searched the literature for information about the relationship between genes in the PWS critical region and malignancies. Results Seven adults (age range 18-55 years old) had been diagnosed with malignancies (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, adenocarcinoma of the stomach, cholangiocarcinoma, parotid adenocarcinoma and colorectal carcinoma). Genetic subtype was DEL for 100% of the patients with malignancies, compared to 58% in patients without a malignancy (p=0.045). Age, gender, BMI, tobacco use, type 2 diabetes mellitus, growth hormone treatment and sex hormone replacement were not significantly related to the presence of malignancies. Conclusion In conclusion, malignancies are rare in patients with PWS. Remarkably, patients with the DEL genetic subtype have a significantly higher risk of developing malignancies compared to patients with other genotypes. Although malignancies are rare in PWS, participation in regular national screening programs for cervical, breast and colon cancer is important as the high pain threshold and intellectual disability make presentation of physical complaints less reliable. We recommend to perform additional diagnostic testing in case of symptoms suggestive of paraneoplastic syndrome, localizing symptoms, loss of appetite or unexplained weight loss. Presentation: Tuesday, June 14, 2022 10:45 a.m. - 11:00 a.m.