ARTICLE Familial Coaggregation of Cryptorchidism, Hypospadias, and Testicular Germ Cell Cancer: A Nationwide Cohort Study

Cryptorchidism and hypospadias are the most common congenital malformations in boys, with prevalence at birth of 1 % – 9 % and 0.4 % – 0.8%, respectively ( 1 – 3). Testicular germ cell cancer (TGCC) is the most common cancer among young men, with a lifetime risk in Denmark of almost 1 % ( 4). Due to reports of in-creases in male urogenital disorders in the past 50 years, and research showing that these disorders share common risk factors ( 5 – 15), a testicular dysgenesis syndrome has been suggested for which hypospadias, cryptorchidism, and TGCC may all be symptoms ( 16 – 18). If these disorders share a common pathogenic pathway that is heritable, they would be expected to coaggregate within families. Indeed, it is well known that boys with cryptorchidism have a three- to eightfold increased risk of developing TGCC ( 19 – 22), and there is some weak evidence that a personal history of hypo-spadias may also be a risk factor for TGCC ( 21). However, knowledge of whether a family history of one disorder infl uences the risk of developing any of the other disorders in testicular dysgenesis syndrome is limited to a single study ( 13), showin