Ferlin Alberto, Zuccarello Daniela, Zuccarello Biagio, Chirico Maria Rosaria, Zanon Giovanni Franco, Foresta Carlo
Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Via Gabelli 63, 35121 Padova, Italy.
JAMA. 2008 Nov 19;300(19):2271-6. doi: 10.1001/jama.2008.668.
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.
To determine the frequency of genetic alterations in cryptorchidism.
Case-control study in 2 departments of pediatric surgery in Italy between January 2003 and March 2005.
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.
Karyotype anomalies and INSL3, INSL3 receptor, and androgen receptor gene mutations.
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.
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.
隐睾症是男性儿童最常见的先天性出生缺陷，是不育和睾丸癌的重要危险因素。睾丸下降的主要调节因子是胰岛素样因子3（INSL3）和睾酮，这些途径的破坏可能导致隐睾症。
确定隐睾症中基因改变的频率。
2003年1月至2005年3月在意大利两个小儿外科部门进行的病例对照研究。
600名患有隐睾症的男婴。对男孩进行了2至3年的随访（至2008年1月），对持续隐睾的患儿进行了睾丸固定术。我们分析了300名1至4岁的非隐睾男性儿童作为对照。
核型异常以及INSL3、INSL3受体和雄激素受体基因突变。
隐睾症男孩的基因改变频率较低（17/600 [2.8%；95%置信区间{CI}，1.7%-4.5%]），持续隐睾的参与者（16/303 [5.3%；95% CI，3.0%-8.4%]；P = .001）和双侧隐睾的参与者（10/120 [8.3%；95% CI，4.1%-14.8%]；P = .001）的基因改变频率显著高于对照组（1/300 [0.3%；95% CI，0.1%-0.8%]）。持续隐睾的男孩发生基因改变的几率高17倍（优势比，16.7；95% CI，2.2-126.5）。隐睾症患者最常见的基因发现是8例克兰费尔特综合征和5例INSL3受体基因突变。低出生体重或低胎龄且睾丸经常自然下降的男孩未发现基因改变。
在一小部分研究人群中，双侧和持续隐睾症与基因改变（包括克兰费尔特综合征和INSL3受体基因突变）之间存在统计学上的显著关联。
