FMPP and Testicular Germ Cell Tumors - Supplementary Data

Objective: The purpose of this study is to report development of a malignant testicular<br> germ cell tumor (GCT) in two young adult males with Familial Male-limited Precocious<br> Puberty (FMPP) due to (LHCGR) pathogenic variants in two families. Secondary, to<br> study the possible relation between FMPP and testicular tumors and to investigate<br> whether FMPP might predispose to development of malignant testicular tumors in<br> adulthood a literature review is conducted. Methods: Data on six cases in two families<br> are obtained from the available medical records. In addition, a database search is<br> performed in Cochrane, Pubmed and Embase for studies that report on a possible link<br> between FMPP and testicular tumors. Results: The characteristics of six males with<br> FMPP based on activating luteinizing hormone receptor (LHCGR) germline pathogenic<br> variants are described, as well as details of the testicular GCTs. Furthermore, literature<br> review identified four more patients with signs of FMPP and a (precursor of a) testicular<br> GCT in adolescence or adulthood (age 15 to 35 years). Additionally, twelve patients<br> with signs of precocious puberty and, simultaneously, occurrence of a Leydig cell<br> adenoma or Leydig cell hyperplasia are reported. Conclusion: There is a strong<br> suggestion that FMPP might increase the risk of development of testicular GCTs in<br> early adulthood compared to the risk in the general population. Therefore, prolonged<br> patient monitoring from mid-pubertal age onwards including instruction for selfexamination<br> and periodic testicular ultrasound investigation in patients with a<br> germline LHCGRpathogenic variants might contribute to early detection and thus early<br> treatment of testicular GCT. This files contains the supplementary data.