先天性睾丸发育不全

先天性睾丸发育不全主要表现为性染色体数目异常引起的以睾丸生精小管发育不良及间质细胞功能减退为主的综合症。别名：克兰费尔特综合征曲细精管发育不全先天性睾丸发育克氏征英文名：Klinefeltersyndrome发病部位：染色体就诊科室：内分泌科症状：小睾丸男性乳房发育多发人群：男性治疗手段：激素替代辅助生殖外科治疗是否遗传：不确定是否传染：否

症状<!--[ifgtemso9]><xml><w:WordDocument><w:BrowserLevel>MicrosoftInternetExplorer4</w:BrowserLevel><w:DisplayHorizontalDrawingGridEvery>0</w:DisplayHorizontalDrawingGridEvery><w:DisplayVerticalDrawingGridEvery>2</w:DisplayVerticalDrawingGridEvery><w:DocumentKind>DocumentNotSpecified</w:DocumentKind><w:DrawingGridVerticalSpacing>7.8磅</w:DrawingGridVerticalSpacing><w:PunctuationKerning></w:PunctuationKerning><w:View>Normal</w:View><w:Compatibility><w:DontGrowAutofit></w:DontGrowAutofit><w:BalanceSingleByteDoubleByteWidth></w:BalanceSingleByteDoubleByteWidth><w:DoNotExpandShiftReturn></w:DoNotExpandShiftReturn><w:UseFELayout></w:UseFELayout></w:Compatibility><w:Zoom>0</w:Zoom></w:WordDocument></xml><![endif]--><pclass="MsoNormal"style="mso-pagination:widow-orphan;text-align:left;">克氏征最重要的临床特点为小而质韧的睾丸和雄激素缺乏症的不同表现。<pclass="MsoNormal"style="mso-pagination:widow-orphan;text-align:left;">克氏征的特征性临床表现：<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">1.不育（无精症或少精症）<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">2.小而坚实的睾丸<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">3.高促性腺激素性性腺机能减退<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">4.男性乳房发育<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">5.身材瘦长，上部量小于下部量<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">6.骨质疏松（青年或中年患者）<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">7.肌肉运动迟缓或功能不全<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">8.言语、语言困难<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">9.注意力不集中<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">10.学习能力低<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">11.诵读困难或阅读不能<pclass="MsoNormal"style="margin-top:0.0000pt;margin-right:36.0000pt;margin-bottom:0.0000pt;padding:0pt0pt0pt0pt;mso-pagination:widow-orphan;text-align:left;">12.心理社会问题或行为异常<!--[ifgtemso9]><xml><w:LatentStylesDefLockedState="false"DefUnhideWhenUsed="true"DefSemiHidden="true"DefQFormat="false"DefPriority="99"LatentStyleCount="260"><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="Normal"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="heading1"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="heading2"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="heading3"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="heading4"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="heading5"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="heading6"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="heading7"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="heading8"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="heading9"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="index1"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="index2"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="index3"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="index4"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="index5"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="index6"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="index7"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="index8"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="index9"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="false"Name="toc1"></w:LsdException><w:LsdExceptionLocked="false"Priority="99"SemiHidden="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病因克氏征染色体数目异常主要是由于生殖细胞发育时，减数分裂性染色体不分离或合子有丝分裂性染色体不分离导致，减数分裂不分离为47,XXY形成的主要原因。另外，常染色体的非整倍体在克氏征中也较常见。目前认为，导致染色体异常的主要致病原因与父母生育时高龄有关，遗传因素对性染色体不分离可能也发挥重要作用，而放射照射和病毒感染等是否有致病作用，目前尚不确定。

检查1.激素测定患者青春期前的LH（黄体生成素）、FSH（卵泡刺激素）、T（睾酮）的基础水平、以及LH对GnRH兴奋试验的反应与同龄儿童相比无差异。青春期开始后，患者T开始升高。15岁左右，T开始逐渐下降。患者血清性激素结合球蛋白水平较高，并导致具有生物学活性的游离睾酮进一步降低。患者LH和FSH水平升高，此时GnRH兴奋试验可见促激素反应增强。LH水平增高，患者雄激素敏感度指数（LH浓度×睾酮浓度）增高。患者雌激素的水平正常或升高。B抑质素水平显著下降。患者可伴有甲状腺功能异常，TRH兴奋试验的反应减低，但一般无甲状腺机能减退的临床表现。约20%的患者伴有糖耐量减低，8%的患者有糖尿病。2.巴尔小体筛查颊黏膜拭子分析性染色质巴尔小体可成为快速、可靠的筛查手段，但不能代替染色体核型分析。3.染色体核型分析血淋巴细胞的染色体核型分析可明确诊断。罕见外周血淋巴细胞结果为正常或为标准核型，但睾丸组织为嵌合型，进一步皮肤成纤维细胞或睾丸活检组织的核型分析可明确。4.睾丸B超睾丸容积可通过触诊并与睾丸测量计比较获得，准确的容积可通过睾丸B超确定。5.精液分析几乎所有47,XXY核型患者的精液分析结果都为无精症，但也有罕见的病例报道克氏征患者可自行生育。部分患者睾丸组织内残余的精子生成区可有正常的精子发生，据报道仍有约8.4%的患者在精液中可观察到精子。6.睾丸活检显示典型的生精小管玻璃样变性、精原细胞丧失、睾丸间质Leydig细胞假瘤样增生。睾丸活检可行睾丸组织染色体核型分析，并可寻找睾丸组织中残余的精子生成区，行睾丸精子抽提术（TESE）。7.产前诊断：产前诊断可明确胎儿的染色体核型。8．INSL3胰岛素样因子3（Insulin-likeFactor3,INSL3），是Leydig细胞分泌的特异性激素以及男性青春期发育的新标志物。

诊断①睾丸小，少精症或无精症，血清睾酮降低或正常；②促性腺激素升高；③GnRH兴奋试验提示促性腺激素过度反应，HCG兴奋试验睾酮无反应；④染色体核型为47,XXY或其他变异型。

治疗一、雄激素替代治疗克氏征的早诊断早治疗可以明显地改善患者的生活质量并避免严重的并发症。当患者血清睾酮水平低于正常时，即可开始雄激素替代治疗，治疗目标为血睾酮达到正常中等水平。替代治疗应该尽早开始并持续终生，以避免出现雄激素缺乏的症状和后遗症。二、生育随着现代辅助生殖技术的开展，克氏征的不育已被攻克。1.卵胞浆内单精子注射术（ICSI）2.显微外科TEST术3.冷冻技术三、男性乳腺发育不会因为睾酮替代治疗而消退，患者心理压力较重者宜施行切除腺体的乳腺成形术。此外本病增生的乳腺发生恶变的机率比正常人群高18倍，为此，有人主张尽早施行乳腺成形术。

预后克氏征患者的期望寿命与健康人相比存在显著缩短，但两者只相差2.1年。虽然雄激素缺乏不会影响寿命，长期雄激素缺乏甚至可降低缺血性心脏病、前列腺癌的死亡率，但其他类型的心血管（如脑血管、外周血管）疾病、深静脉血栓、肺栓塞、髋关节骨折和其他肿瘤（如肺癌、乳腺癌、非霍奇金淋巴瘤）的死亡率增高。

预防辅助生殖术后患者子代染色体数目异常，特别是21、18、13三体综合征、克氏征的发生率增高，产前诊断可明确胎儿的染色体核型。快速检测染色体异常技术，可在1～2天内予以诊断，并已为许多大规模的临床研究所应用。但与核型分析不同的是，这些技术只用于特异的染色体数目异常（21、18、13号常染色体和X、Y性染色体异常）的检出。

男性不育