Turner syndrome and Klinefelter syndrome and their mosaic variants are classified as sex chromosome DSD. Mixed gonadal dysgenesis (45,X; 46,XY) often may present with genital ambiguity, asymmetric external genitalia, and inguinal hernias. There may be virilization on one side and none on the other. Similar findings may be seen with ovotesticular DSD, another classification of DSD.
Available @ StudentConsult.com
Ambiguous genitalia in a newborn must be attended to with as little delay as possible and with informed sensitivity to the psychosocial context as required. The laboratory evaluations required might take days or weeks to complete, delaying a sex assignment and naming of the infant, such that choice often precedes diagnosis. Beyond infancy and childhood, and to offset any gender uncertainty in the patient and confusion in the parents, health care providers must help families come to an appropriate closure and gender choice.
On physical examination, it is essential to note where the urethral opening lies and whether there is fusion of the anterior portion of the labioscrotal folds. Endogenous excessive production of androgen (as in congenital adrenal hyperplasia [CAH]) in a female fetus between 9 and 13 weeks of gestation leads to ambiguous genitalia. If the vaginal opening is normal, and there is no fusion, but the clitoris is enlarged without ventral fusion of the ventral urethra, the patient had later exposure to androgens. A patient with a fully formed scrotum, even if small, and a normally formed but small penis, termed a microphallus, must have had normal exposure to and action of androgen during 9 to 13 weeks of gestation.
The major goal is a rapid identification of any life-threatening disorders (salt loss and shock caused by the salt-losing form of CAH). Although the classic approach to sex assignment has been based on the feasibility of genital reconstruction and potential fertility rather than on karyotypeor gonadal histology, the effects of prenatal androgen mustbe considered. Yet it may be inappropriate to raise a femaleinfant who is severely virilized from virilizing CAH as amale; nonetheless in most reported cases, sex assignment andadult gender role remain female, and fertility can be retainedbecause the internal organs are female. A 46,XY male withambiguous genitalia and an extremely small phallus that doesnot increase in size with androgen therapy (partial androgen resistance) traditionally has been raised as a female becausesurgical construction of a fully functional phallus is difficult. Some of these patients frequently revert spontaneouslyto a male gender identity. Present management of ambiguous genitalia involves extensive open discussion with parentsinvolving the biology of the infant and the likely prognosis.Treatment should be individualized and managed by a team,including an experienced pediatric endocrinologist, urologistor gynecologist, psychologist, geneticist, and the primary carephysician.
The first step toward diagnosis is to determine whether thedisorder represents virilization of a genetic female (androgen excess) or underdevelopment of a genetic male (androgen deficiency) (see Fig. 177-2). Inguinal gonads that areevident on palpation usually are testes and indicate thatincomplete development of a male phenotype has occurred;this pattern is not consistent, and ovaries and ovotestes mayfeel similar. Similarly absence of female internal genitalia(detected by ultrasound) implies that müllerian-inhibitingsubstance was present and secreted by fetal testes. Karyotype determination is only one of many factors in decidingthe sexual identity for purposes of rearing; the SRY gene may be found on chromosomes other than the Y chromosome, and, conversely, a Y chromosome may lack an SRY gene (it may have been translocated to an X chromosome,leading to the development of a 46,XX maleXX sex reversal, testicular DSD).