Molecular epidemiology of hypospadias: Review of genetic and environmental risk factors
Article first published online: 8 OCT 2003
Copyright © 2003 Wiley-Liss, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 67, Issue 10, pages 825–836, October 2003
How to Cite
Manson, J. M. and Carr, M. C. (2003), Molecular epidemiology of hypospadias: Review of genetic and environmental risk factors. Birth Defects Research Part A: Clinical and Molecular Teratology, 67: 825–836. doi: 10.1002/bdra.10084
- Issue published online: 14 OCT 2003
- Article first published online: 8 OCT 2003
- Manuscript Accepted: 21 MAY 2003
- Manuscript Received: 16 SEP 2002
- EPA. Grant Numbers: K01 ES00352, R-82859901
Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 125 live male births. It is characterized by altered development of the urethra, foreskin, and ventral surface of the penis. In this review, the embryology, epidemiology, risk factors, genetic predisposition, and likely candidate genes for hypospadias are described. Recent reports have identified increases in the birth prevalence of mild and severe forms of hypospadias in the United States from the 1960s to the present. Studies in consanguineous families and small case series have identified allelic variants in genes controlling androgen action and metabolism that cause hypospadias, but the relevance of these findings to the general population is unknown. Concern has also focused on whether exposure to endocrine disrupting chemicals (EDC) with antiandrogenic activity is the cause of this increase. Hypospadias is believed to have a multifactorial etiology in which allelic variants in genes controlling androgen action and metabolism predispose individuals to develop this condition. When genetic susceptibility is combined with exposure to antiandrogenic agents, a threshold is surpassed, resulting in the manifestation of this birth defect. A clear role for exposure to antiandrogenic environmental chemicals has yet to be established in the etiology of hypospadias, although results from laboratory animal models indicate that a number of environmental chemicals could be implicated. Molecular epidemiology studies that simultaneously examine the roles of allelic variants in genes controlling androgen action and metabolism, and environmental exposures are needed to elucidate the risk factors for these anomalies and the causes of the increased rate of hypospadias. Birth Defects Research (Part A), 2003. © 2003 Wiley-Liss, Inc.