FMPP and Testicular Germ Cell Tumors - Supplementary Data

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

This files contains the supplementary data.