Ferlin A et al. (2008) Genetic alterations associated with cryptorchidism. JAMA 300: 2271–2276

Cryptorchidism is the most common congenital birth defect in boys. Testicular descent is regulated by testosterone and insulin-like factor 3 (INSL3). An Italian study investigated whether genetic defects affecting the function of these hormones were associated with cryptorchidism. The researchers found genetic defects in 5–8% of boys with persistent and/or bilateral cryptorchidism.

Ferlin et al. followed up 600 newborn boys with cryptorchidism for 2–3 years. Mutation analysis of the INSL3, RXFP2 (relaxin family peptide 2, the receptor for INSL3) and AR (androgen receptor) genes was performed; 300 boys without cryptorchidism were recruited as controls. Spontaneous descent occurred in 199 of 396 unilateral cases and 83 of 204 bilateral cases in the first 6 months of age; a further 14 unilateral cases and 1 bilateral case experienced spontaneous descent within 12 months. There were no instances of spontaneous descent after 12 months. Overall, 17 genetic abnormalities were found in the 600 boys with cryptorchidism. The rate of genetic abnormalities was 5.3% (16 of 303) in boys with persistent and 8.3% (10 of 120) in those with bilateral cryptorchidism, compared with 0.3% (1 of 300) in the control group. Eight of the defects discovered were chromosomal abnormalities of the Klinefelter type. Five boys with bilateral cryptorchidism had mutations in RXFP2, and there were two cases each of mutations in INSL3 and AR.

In a small percentage of the study population, there was a statistically significant association between bilateral and persistent cryptorchidism and genetic alterations, including Klinefelter syndrome and INSL3 receptor gene mutations.