The genetic factors contributing to hypospadias and their clinical utility in its diagnosis

Hypospadias is among the most common congenital malformations in male neonates. It results from abnormal penile and urethral development, but is a multifactorial disorder that is highly heterogeneous, with several genetic and environmental determinants. Monogenic and chromosomal abnormalities are present in approximately 30% of cases, although the genetic factors contributing to hypospadias remain unknown in 70% of cases. While defects in androgen synthesis can lead to this malformation, mutational analyses have shown several genes, such as sonic hedgehog, fibroblast growth factors, bone morphogenetic proteins, homeobox genes, and the Wnt family, are involved in the normal development of male external genitalia. Mutations in the genes of penile development (e.g., HOX, FGF, Shh) and testicular determination (e.g., WT1, SRY), luteinizing hormone receptor, and androgen receptor have also been proposed to be implicated in hypospadias. Here we review the recent advances in this field and discuss the potential genes that could determine the risk of hypospadias.     

先天性尿道下裂的矫治（附1000例报告）

目的：总结先天性尿道下裂的矫治经验。方法：尿道下裂患者1000例,年龄1～26岁,平均4岁。冠状沟型118例,阴茎体型593例,阴茎阴囊型189例,会阴型100例。791例采用尿道板切开卷管成形法（TIP）,117例采用Duckett＋Duplay术,92例采用二期手术,一期行阴茎伸直及皮瓣转移,二期行尿道成形术（TIP）。术中遵循微创原则,使用显微器械,尽量保留原有的正常组织结构。结果：随访6月至2年,TIP术741例手术一次成功,Duckett＋Duplay术99例一次成功,分期手术二期成功86例。并发尿道皮肤瘘51例,尿道狭窄17例,尿道憩室6例,均经再次手术治愈。结论：尿道下裂矫治手术中,首先保留尿道板手术,并发症少,成功率高,值得推广,阴茎严重弯曲者或重度尿道下裂患者可选Duckett＋Duplay术或者分期手术。     

Cellular and molecular mechanisms of development of the external genitalia

The limb and external genitalia are appendages of the body wall. Development of these structures differs fundamentally in that masculine development of the external genitalia is androgen dependent, whereas development of the limb is not. Despite this fundamental difference in developmental regulation, epithelial-mesenchymal interactions play key roles in the development of both structures, and similar regulatory molecules are utilized as mediators of morphogenetic cell-cell interactions during development of both the limb and external genitalia. Given the relatively high incidence of hypospadias, a malformation of penile development, it is appropriate and timely to review the morphological, endocrine, and molecular mechanisms of development of the genital tubercle (GT), the precursor of the penis in males and the clitoris in females. Morphological observations comparing development of the GT in humans and mouse emphasize the validity of the mouse as an animal model of GT development and validate the results of experimental studies. Accordingly, the use of mutant mice provides important insights into the roles of specific regulatory molecules in development of the external genitalia. While our current understanding of the morphological and molecular mechanisms of mammalian external genitalia development is still rudimentary, this review summarizes the current state of our knowledge and whenever possible draws from the rich experimental embryology literature on other relevant organs such as the developing limb. Future research on the hormonal and molecular mechanisms of GT development may yield strategies to prevent or reduce the incidence of hypospadias and to elucidate the molecular genetic mechanisms of GT morphogenesis, especially in relation to common organogenetic pathways utilized in other organ systems.     

200例先天性尿道下裂患儿的临床特征及其危险因素分析

目的:研究200例先天性尿道下裂患儿的临床特征及其危险因素.方法:选择2016年1月?2019年12月我院收治的先天性尿道下裂患儿200例进行研究,记作观察组,另取同期于我院接受体检的健康儿童200例作为对照组,分析观察组患儿的临床分型情况,比较两组儿童父母的一般情况、儿童出生情况,并采用多因素Logistic回归分析...     

A proposed mechanism for intermediate atresia ani (AA), based on a porcine case of AA and hypospadias

BACKGROUND: Atresia Ani (AA) is one of the most common malformations of the lower gastrointestinal tract. It occurs in 1 in 1500 to 1 in 5000 human births. These patients suffer physically and psychologically from this disorder, and thus there is a research interest in the condition. There are 3 subcategories of AA: high, intermediate, and low. Each of these forms is likely related to separate etiological processes. METHODS: An anatomical study was performed on a porcine case of AA with a urorectal fistula and malformed urethra. RESULTS: This animal was found to have the intermediate form of AA. CONCLUSIONS: A new mechanism is hypothesized, distinct from that described for the high and low forms of AA. This proposed mechanism involves the persistence of the cloacal membrane. Evidence to support this hypothesis includes: location of the urorectal fistula in the region of the embryonic cloacal duct, the lack of anomalies usually seen in conjunction with AA associated with mutations of the Sonic Hedgehog gene, and the presence of a malformed urethra, which is significantly correlated to intermediate AA. This form of AA could be related to a failure of the cloacal membrane to break down at the appropriate time during urorectal separation.