Gonadal Dysgenesis
by Nichole E. Justus
Gonadal dysgenesis also known as Swyer syndrome is characterized by "streak gonads" is a phenotypic female with a 46,XY karyotype. This condition is due to a mutation which inhibits the function of the Y-borne determinant that would normally cause the indifferent embryonic gonad to differentiate into a testis. The streak gonad is incapable of ovulation or estrogen secretion. The syndrome is sometimes called "pure gonadal dysgenesis", however, this designation may also refer to the presence of streak gonads with a 46,XX karyotype. Mixed gonadal dysgenesis has extreme variability, which may extend from a Turner-like syndrome to a male phenotype. (J.Med. Genet, HMG box of the SRY gene leads to XY gonadal dysgenesis. Aug. 1993) This paper will reflect the mixed form resulting in the 46,XY female that lack the SRY gene responsible along with other genes for turning on the development of maleness. Individuals with this condition are often intelligent masculine females with heights below statistically determined norms.
Some patients have no evidence of masculinization and have a female phenotype with the somatic signs of Turner syndrome. The presence of unilateral testis, a contralateral streak gonad and chromosomal mosaicism with both XO and XY cell lines indicate the mixed gonadal condition. It has been suggested that mixed gonadal dysgenesis may be an extreme variant of true hermaphroditism and has been regarded as the main form of manifestation of 45,X / 46,XY mosaicism. (Al-Awadi, Sadika. "Mixed Gonadal Dysgenesis with Structural Anomalies of the Y-Chromosome." 1994.) The 46,XY female karyotype is often discovered prepubertally when chromosomal studies are made in short girls, or later when sexual maturation fails to occur. The fallopian tubes and uterus are present as well as gonads of intra-abdominal undifferentiated streaks. Gonadal tumors, usually gonadoblastomas, occur in about 25% of these patients particularly in those with the more female phenotypes. It is often recommended as a precaution to remove the gonadal tissue in patients reared as girls. (Microsoft Encarta 1996 Encyclopedia. Genital Disorders.)
One case of interest relates to two individuals named Stella and Ewa who won Olympic medals more than thirty years apart as females. It was later discovered that the women were 46,XY females with the mixed gonadal dysgenesis condition. Not much other than their phenotypically female status is known although it could be assumed the women were not able to bare children. There condition was not hereditary nor can it be predicted by individuals wishing to have children. The condition is thought to occur because the SRY gene normally located on one arm of the Y-chromosome is translocated to an X-chromosome or it is not functional at the normal location on the Y-chromosome. This gene is thought to be the testis determining factor that somehow triggers the undifferentiated gonadal tissue of the embryo to form testis. Research with transgenic mice has proven that in the absence of the SRY gene female development occurs. (Klug and Cummings. "Concepts of Genetics", 4th edition. The Y-Chromosome and Male Development.) This SRY gene is thought to be responsible for the sex reversal in 46,XY females and to date there have been nineteen mutations identified in the SRY gene associated with the mixed gonadal dysgenesis syndrome. (Olson, GP. Sex Differentiation Disorders. American Journal of Primary Health Care, 1998.)
The presence of immature testicular tubules had been observed in female patients that have karyotype 46,XX with the normal SRY gene translocated to the X-chromosome. Stella and Ewa could possibly have been the result of this SRY gene translocation although it more likely they received a Y-chromosome with a mutation of the SRY gene along the way. These two women were perhaps fortunate to have competed prior to 1968 when the Olympic committee began requiring a "buccal smear test" which resulted in XX representing only females and XY representing only males. This surely resulted in individuals not being able to compete or lead athletes to compete with individuals who shared their karyotype. In 1992 the International Olympic committee replaced the buccal smear test with the polymerase chain reaction (PCR) to identify the SRY gene. This is a method by which DNA segments are amplified, cycles of denaturation are used, along with annealing to primers, and DNA polymerase directed DNA synthesis. ( Klug and Cummings, "Concepts of Genetics", 4th edition. PCR testing.) This test enables fair representation of the individual and would not penalize anyone for a condition they were born with.
Another condition of the mixed gonadal dysgenesis is the OX/XY male. The mechanism underlying this masochism is probably the result of a mitotic nondysjunction in an originally XY embryo causing XO/XY and XYY cell lines. Mixed gonadal dysgenesis cases with structural anomalies of the Y-chromosome and associated structural damage is not well understood.

Al-Awadi, Sadika A. MD. "Mixed Gonadal Dysgenesis with Structural Anomalies of the Y-Chromosome. Kuwait Medical Genetics Center, Maternity Hospital, 1994.

Berhrman, Richard E. MD. Nelson textbook of Pediatrics, W.B. Saunders London, 14th edition, 1992. "45,X/46,XY Gonadal Dysgenesis."

Klug, William S. and Cummings, Michael R. Concepts of Genetics, 4th edition, Prentice Hall NJ. 1994. "The Y-Chromosome and Male Development"

Olson, GP. "Testicular feminization Syndrome", American Journal of Primary Health Care. Feb.1988.

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