Malignancies in Prader-Willi Syndrome: Results From a Large International Cohort and Literature Review

Abstract

Context Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of the PWS critical region, a cluster of paternally expressed genes on chromosome 15q11.2-q13. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health. Objective To investigate the prevalence and risk factors of malignancies in patients with PWS and to provide clinical recommendations for cancer screening. Methods We included 706 patients with PWS (160 children, 546 adults). We retrospectively collected data from medical records on past or current malignancies, the type of malignancy and risk factors for malignancy. Additionally, we searched the literature for information about the relationship between genes on chromosome 15q11.2-q13 and malignancies. Results Seven adults (age range 18-55 years old) had been diagnosed with a malignancy (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, stomach adenocarcinoma, biliary cancer, parotid adenocarcinoma and colon cancer). All patients with a malignancy had a paternal 15q11-13 deletion. The literature review showed that several genes on chromosome 15q11.2-q13 are related to malignancies. Conclusion Malignancies are rare in patients with PWS. Therefore, screening for malignancies is only indicated when clinically relevant symptoms are present such as unexplained weight loss, loss of appetite, symptoms suggestive of paraneoplastic syndrome, or localizing symptoms. Given the increased cancer risk associated with obesity, which is common in PWS, participation in national screening programs should be encouraged.

Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer

“…Additionally, a large study of 2561 British patients with constitutional autosomal deletions of chromosomal arms, confirmed the known association between deletion 11p and 13q with Wilms tumour and retinoblastoma, respectively, and identified that deletions of the genomic region 11q24 may predispose to anogenital cancer, in line with the recurrent somatic alterations described in these solid tumours [141][142][143]. Notably, several studies have reported cancer cases with other constitutional CNV such as Prader-Willi syndrome (deletion 15q11.2-q13) [144], DiGeorge syndrome (deletion 22q11.2) [145], Cri du Chat syndrome (deletion 5p) [146], and Williams-Beuren syndrome (deletion 7q11.23) [147], but their true incidence and any potential link with clinical outcomes remains unclear.…”