title: Leydig-cell tumour in children: variable clinical presentation, diagnostic features, follow-up and genetic analysis of four cases.
abstract: BACKGROUND
  Testicular tumours are relatively uncommon in infants and children, accounting for only 1-2% of all paediatric solid tumours. Of these approximately 1.5% are Leydig-cell tumours. Further, activating mutations of the luteinizing hormone receptor gene (LHR), as well as of the G protein genes, such as Gsalpha (gsp) and Gialpha (gip2) subunits, and cyclin-dependent kinase gene 4(CDK4) have been associated with the development of several endocrine neoplasms.
  
  
  OBJECTIVE
  In this report, the clinical variability of Leydig-cell tumours in four children is described. The LHR-, gsp-, gip2- and CDK4 genes were investigated to establish the possible molecular pathogenesis of the variable phenotype of the Leydig-cell tumours.
  
  
  RESULTS
  No activating mutations in these genes were found in the four Leydig-cell tumours studied. Therefore, the absence of activating mutations in LHR, as well as in both the 'hot spot' regions for activating mutations within the G-alpha subunits and in the regulatory 'hot spot' on the CDK4 genes in these tumours indicates molecular heterogeneity among Leydig-cell tumours.
  
  
  CONCLUSIONS
  Four children with a variable phenotype caused by Leydig-cell tumours are described. A molecular analysis of all the 'activating' genes and mutational regions known so far was performed, but no abnormalities were found. The lessons learnt from these clinically variable cases are: perform ultrasound early and most importantly, consider discrepancies between testicular swelling, tumour size and androgen production.
authors.affiliation: Paediatric Endocrinology, University Children's Hospital, Inselspital, Bern, Switzerland.
authors.forename: Vibor
authors.initials: V
authors.lastname: Petkovic
authors.forename: Souzan
authors.initials: S
authors.lastname: Salemi
authors.forename: Erik
authors.initials: E
authors.lastname: Vassella
authors.forename: Evanthia
authors.initials: E
authors.lastname: Karamitopoulou-Diamantis
authors.forename: Udo J
authors.initials: UJ
authors.lastname: Meinhardt
authors.forename: Christa E
authors.initials: CE
authors.lastname: Flück
authors.forename: Primus E
authors.initials: PE
authors.lastname: Mullis
mesh_terms: D000728:Androgens / Q000097:blood; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007984:Leydig Cell Tumor / Q000235:genetics / Q000473:pathology; D008297:Male; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology; D013737:Testis / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography
chemical_list: D000728:Androgens