Undescended testis: current theories of etiology

Nonsyndromic cryptorchidism or undescended testis is a structural defect of infants and children whose etiology is unknown but likely related to a combination of genetic susceptibility and environmental factors. This review will focus on factors that may contribute to the etiology of this common and complex disease.

The incidence of cryptorchidism is estimated to be 2-4% or higher in some populations. Data suggesting increasing prevalence are conflicting, possibly related to problems with diagnostic accuracy. Increased risk of cryptorchidism in first-degree relatives suggests a significant genetic contribution to susceptibility. Sequence variants within key candidate genes, such as insulin-like 3 and relaxin/insulin-like family peptide receptor 2, in cases of nonsyndromic cryptorchidism are infrequent and of unclear significance. Epidemiological data suggest that fetal growth restriction, maternal factors such as smoking, alcohol use and gestational diabetes, and exposure to environmental chemicals may contribute to risk, although data are inconsistent.

The available evidence suggests a significant genetic contribution to cryptorchidism susceptibility that may be modulated by environmental risk factors. Additional studies are needed to define these factors, their complex interaction and their effects on testicular development and descent.