Ferlin, A., Zuccarello, D., Zuccarello, B., Chirico, M. R., Zanon, G. F., & Foresta, C. (2008). Genetic alterations associated with cryptorchidism. JAMA. https://doi.org/10.1001/jama.2008.668
Ferlin A, Zuccarello D, Zuccarello B, Chirico MR, Zanon GF, Foresta C. Genetic alterations associated with cryptorchidism. JAMA. 2008. doi:10.1001/jama.2008.668
Ferlin, Alberto, et al. "Genetic alterations associated with cryptorchidism." JAMA, 2008.
Genetic alterations are uncommon in boys with cryptorchidism
A case-control study in Italy found genetic alterations in about 3 out of 100 boys with cryptorchidism (undescended testes). Boys with persistent cryptorchidism had far more genetic alterations than the 300 controls, boys aged 1 to 4 without the condition.
Key Findings
Genetic alterations occurred in 17/600 boys with cryptorchidism (2.8%; 95% confidence interval, 1.7%-4.5%), compared with 1/300 controls (0.3%; 95% confidence interval, 0.1%-0.8%).
Persistent cryptorchidism: 16/303 boys (5.3%; 95% confidence interval, 3.0%-8.4%; P = .001). Odds ratio for a genetic alteration in this group was 16.7 (95% confidence interval, 2.2-126.5).
Bilateral cryptorchidism: 10/120 boys (8.3%; 95% confidence interval, 4.1%-14.8%; P = .001), compared with 1/300 controls (0.3%).
Klinefelter syndrome accounted for 8 boys, and 5 boys carried mutations in the gene for the insulin-like factor 3 (INSL3) receptor.
No genetic alteration appeared among boys born with low birth weight or at a low gestational age. These boys had frequent spontaneous descent of the testes.
Interpretation
This synopsis rests on the published abstract of a case-control study, which compares boys with a condition against boys without it. The researchers worked in two pediatric surgery departments in Italy and followed the boys for 2 to 3 years. Boys who stayed cryptorchid had orchidopexy, surgery that brings the testis into the scrotum. The authors report a significant association between bilateral or persistent cryptorchidism and genetic alterations.
RRM Context
The abstract states that cryptorchidism represents an important risk factor for infertility and testicular cancer. Restorative reproductive medicine considers both partners, so undescended testes matter for the male partner. INSL3 and testosterone steer how the testes descend. The authors suggest that disrupting these pathways might cause the condition.
Our editorial summary of this paper, not the article's abstract.
Abstract
Context
Cryptorchidism is the most frequent congenital birth defect in male children and represents an important risk factor for infertility and testicular cancer. Major regulators of testicular descent are the hormones insulin-like factor 3 (INSL3) and testosterone, and disruption of these pathways might cause cryptorchidism.
Objective
To determine the frequency of genetic alterations in cryptorchidism.
Design and Setting
Case-control study in 2 departments of pediatric surgery in Italy between January 2003 and March 2005.
Patients
Six hundred male infants with cryptorchidism. Boys were followed up for 2 to 3 years (through January 2008) and orchidopexy was performed in those who were persistently cryptorchid. We analyzed 300 noncryptorchid male children aged 1 to 4 years as controls.
Main Outcome Measures
Karyotype anomalies and INSL3, INSL3 receptor, and androgen receptor gene mutations.
Results
The frequency of genetic alterations in boys with cryptorchidism was low (17/600 [2.8%; 95% confidence interval {CI}, 1.7%-4.5%]) and was significantly higher in participants with persistent cryptorchidism (16/303 [5.3%; 95% CI, 3.0%-8.4%]; P = .001) and those with bilateral cryptorchidism (10/120 [8.3%; 95% CI, 4.1%-14.8%]; P = .001) than in controls (1/300 [0.3%; 95% CI, 0.1%-0.8%]). Boys with persistent cryptorchidism had a 17-fold greater odds of having a genetic alteration (odds ratio, 16.7; 95% CI, 2.2-126.5). The most common genetic findings in those with cryptorchidism were 8 cases of Klinefelter syndrome and 5 cases of mutations in the INSL3 receptor gene. Genetic alterations were not found in boys with low birth weight or low gestational age, who had frequent spontaneous descent of the testes.
Conclusion
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.
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