Male Birth Defect May Be Linked To Genetic Mutations

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Main Category: Pediatrics / Children's Health
Also Included In: Pregnancy / Obstetrics;  Genetics;  Sexual Health / STDs
Article Date: 03 Dec 2008 - 0:00 PST

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Cryptorchidism, the congenital birth defect in which one or both testicles fail to descend into the scrotum, has been associated with certain genetic mutations, including a syndrome which is also a common cause of infertility, according to a study released on November 19, 2008 in JAMA.

As the most common congenital birth defect in male children, cryptorchidism may occur in 2-4% of all full-term male births. However, its cause is largely unknown, and the authors point out that,  "although cryptorchidism is often considered a mild malformation, it can seriously affect men's health, representing the best characterized risk factor for infertility and testicular cancer in adulthood."

To investigate the potential cause of cryptorchidism, Alberto Ferlin, Ph.D., of the University of Padova, Italy, and colleagues performed a case-control study evaluating the frequency of genetic alterations in 600 male children with and 300 male children without the disease. the children were followed up for 2 to 3 years for persistence of the malformation.

In the genetic examination, abnormalities were low even in the group of cases (2.8%), but statistically significantly higher than those of the controls. This was true in for children with persistent cryptochidism (5.3%) and bilateral cryptorchidism (8.3%) in which both testes fail to descend at once. The odds of a genetic alteration in children with persistent cryptorchidism was 17 times that of controls; the odds of a genetic alteration in children with bilateral persistent cryptorchidism was 27 times that of controls.

The types of genetic mutation were varied. In the small proportion of cases with genetic abnormalities, the most common was Klinefelter syndrome, the most common genetic cause of male infertility. Additionally, several cases had mutations in the INSL3 receptor gene, which affects descent of the testes. Genetic alterations were found exclusively in children with normal weights and gestational ages.

The authors point out the exclusive presence of Klinefelter syndrome: "We found that chromosomal aberrations represent the most frequent genetic alteration in participants with isolated cryptorchidism, particularly in those with persistent cryptorchidism (1.6 percent in the unilateral forms and 4.2 percent in the bilateral forms), and that chromosomal alterations were exclusively represented by Klinefelter syndrome."

They continue, summarizing the results of the study: "In this study, we found genetic alterations in a small percentage of boys with cryptorchidism. We found a significant association between bilateral and persistent cryptorchidism and genetic alterations, including mutations in the INSL3 receptor gene and Klinefelter syndrome. Genetic alterations were not found in participants with low birth weight or low gestational age ..."

However, the authors finally caution against strong generalization of these results, noting the limitations of their study. "Our findings have the limitations of a case-control study, and the main limitation is the small number of genetic abnormalities found. Future studies involving a higher number of participants are necessary to confirm our findings. This study should therefore be considered preliminary, and strong conclusions about association cannot be drawn," they write.

Genetic Alterations Associated With Cryptorchidism
Alberto Ferlin, PhD; Daniela Zuccarello, MD; Biagio Zuccarello, MD; Maria Rosaria Chirico, MD; Giovanni Franco Zanon, MD; Carlo Foresta, MD
JAMA. 2008;300(19):2271-2276.
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Written by Anna Sophia McKenney
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