Society for Fetal Urology panel discussion: prenatal diagnosis and treatment of genital anomalies.

T focus of this panel discussion was the prenatal diagnosis and treatment of genital anomalies. The role of prenatal ultrasound in the management of urologic anomalies remains controversial. Hydronephrosis secondary to obstruction, vesicoureteral reflux, and posterior urethral valves are routinely diagnosed in utero, yet it remains unproven as to whether prenatal intervention is warranted. More recently it has become possible to diagnose genital anomalies in utero.1 In respect to hypospadias, the advantage of prenatal diagnosis remains speculative. Female fetuses with a diagnosis of congenital adrenal hyperplasia, however, can theoretically be diagnosed early in gestation and treated by the administration of maternal steroidal agents, thereby reducing the severity of in utero androgen expsoure. Since the most common form of congenital adrenal hyperplasia is 21-hydroxylase deficiency, which is transmitted in an autosomal recessive inheritance pattern, an unborn female sibling in a family with congenital adrenal hyperplasia has a 1 in 8 chance of being affected. The Society of Fetal Urology devoted a morning session to the diagnosis of congenital anomalies in utero followed by a point-counterpoint discussion concerning the risks and benefits of treating a fetus with a presumed diagnosis of congenital adrenal hyperplasia. Felix Conte, Professor of Pediatric Endocrinology at the University of California, San Francisco, started the morning panel discussion by reviewing the latest data on the molecular biology of sexual determination.1 Sexual determination and differentiation are sequential processes that begin at fertilization with establishment of the chromosomal sex, followed by development of gonadal sex which then regulates the ultimate phenotypic sex. Failure at any of the sequential stages of development can have profound effects on the phenotype and lead to sexual ambiguity or to more subtle abnormalities in function or reproduction. Multiple genes on multiple chromosomes act through a variety of mechanisms that involve hormones, growth factors, and receptors. Early embryos possess indifferent, common primordia that have a tendency to feminize without the action of masculinizing factors. In humans, genes on the Y chromosome induce testis formation and thus male sexual development. An evolutionary conserved gene isolated from the Y chromosome, SRY, is now accepted to be the testis-determining factor.2 SRY, as well as autosomal and X-linked genes, is necessary for testicular development and spermatogenesis. Unlike somatic cells, which have one X chromosome inactivated, female germ cells and oocoytes depend upon the contribution of both X chromosomes. Ovarian differentiation is dependent upon germ cell presence and thus both X chromosomes. In contrast, testicular differentiation can occur in the absence of germ cells, demonstrating that germ cells play no role in male sex determination. In males, spermatogenesis is quiescent during childhood, followed by active mitosis and meiosis. In contrast, the female has a maximal number of germ cells at birth, arrested in the first meiotic division until ovulation. The next presentation reviewed the genital anatomy of the developing male and female (Fig. 1). Genital specimens obtained between weeks 8 and 33 of gestation were serially sectioned and stained for epithelial, smooth muscle, and nerve structures using immunocyotochemical techniques. Selected specimens were reconstructed in three dimensions to better understand the relationship between the nerves, corporal bodies, and urethral spongiosum using NIH imaging and Adobe Photoshop.3 CareThis update reports on a Panel Discussion that took place on October 16, 1998 in San Francisco, California. From the Department of Urology, University of California San Francisco, UCSF Children’s Medical Center, San Francisco, California Reprint requests: Laurence S. Baskin, M.D., Department of Urology, Box 0738, UCSF Children’s Medical Center, 533 Parnassus Avenue, San Francisco, CA 94141 Submitted: December 1, 1998, accepted (with revisions): February 1, 1999 PEDIATRIC UROLOGY UPDATE