title: Familial testicular germ cell tumor: no associated syndromic pattern identified.
abstract: BACKGROUND
  Testicular germ cell tumor (TGCT) is the most common malignancy in young men. Familial clustering, epidemiologic evidence of increased risk with family or personal history, and the association of TGCT with genitourinary (GU) tract anomalies have suggested an underlying genetic predisposition. Linkage data have not identified a rare, highly-penetrant, single gene in familial TGCT (FTGCT) cases. Based on its association with congenital GU tract anomalies and suggestions that there is an intrauterine origin to TGCT, we hypothesized the existence of unrecognized dysmorphic features in FTGCT.
  
  
  METHODS
  We evaluated 38 FTGCT individuals and 41 first-degree relatives from 22 multiple-case families with detailed dysmorphology examinations, physician-based medical history and physical examination, laboratory testing, and genitourinary imaging studies.
  
  
  RESULTS
  The prevalence of major abnormalities and minor variants did not significantly differ between either FTGCT individuals or their first-degree relatives when compared with normal population controls, except for tall stature, macrocephaly, flat midface, and retro-/micrognathia. However, these four traits were not manifest as a constellation of features in any one individual or family. We did detect an excess prevalence of the genitourinary anomalies cryptorchidism and congenital inguinal hernia in our population, as previously described in sporadic TGCT, but no congenital renal, retroperitoneal or mediastinal anomalies were detected.
  
  
  CONCLUSIONS
  Overall, our study did not identify a constellation of dysmorphic features in FTGCT individuals, which is consistent with results of genetic studies suggesting that multiple low-penetrance genes are likely responsible for FTGCT susceptibility.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Mueller
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Korde
authors.forename: Mary L
authors.initials: ML
authors.lastname: McMaster
authors.forename: June A
authors.initials: JA
authors.lastname: Peters
authors.forename: Gennady
authors.initials: G
authors.lastname: Bratslavsky
authors.forename: Rissah J
authors.initials: RJ
authors.lastname: Watkins
authors.forename: Alex
authors.initials: A
authors.lastname: Ling
authors.forename: Christian P
authors.initials: CP
authors.lastname: Kratz
authors.forename: Eric A
authors.initials: EA
authors.lastname: Wulfsberg
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. greenem@mail.nih.gov.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Greene