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

J Clin Endocrinol Metab. 2023 Nov 17;108(12):e1720-e1730. doi: 10.1210/clinem/dgad312.


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) 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.

Keywords: Prader-Willi syndrome; comorbidity; hypothalamo-hypophyseal system; neoplasms.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma*
  • Adolescent
  • Adult
  • Child
  • Fathers
  • Humans
  • Hyperphagia
  • Middle Aged
  • Prader-Willi Syndrome* / complications
  • Prader-Willi Syndrome* / diagnosis
  • Prader-Willi Syndrome* / epidemiology
  • Retrospective Studies
  • Young Adult