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Objectives In most cases, XX or XY gonadal dysgenesis remains genetically unexplained. In this pilot study we searched for sex-chromosomal mosaicism in gonads of patients with XX or XY gonadal dysgenesis of undetermined origin. Study Design Gonadal tissues were analyzed by cytogenetic and interphase fluorescence in-situ hybridization (FISH) analyses in four patients with gonadal dysgenesis and normal female (46,XX) or male (46,XY) karyotypes in lymphocytes. Results Cytogenetic and FISH analyses of the gonads demonstrated in three patients a sex-chromosomal mosaicism. Cytogenetic analysis of gonadal tissue of the fourth patient confirmed the result of the lymphocytes with 46,XX, but FISH analysis revealed in 17% of nuclei only one X-chromosome. Conclusion Our data indicate that sex-chromosomal mosaicism in gonads may be a frequent cause of gonadal dysgenesis despite of normal karyotypes in lymphocytes. Therefore, cytogenetic and FISH analyses of gonadal tissue can provide important information in unexplained cases of gonadal dysgenesis.

OBJECTIVES: The purpose of our study was to discover whether the testicular determining factor gene SAY (sex-determining region on Y) is present or absent in XX true hermaphrodites and in subjects with gonadal dysgenesis caused by Y aneuploidy. STUDY DESIGN: We screened five XX true hermaphrodites and 24 subjects with gonadal dysgenesis caused by Y aneuploidy for the presence or absence of SAY. With the polymerase chain reaction technique, the sequence coding the 80 amino acid-conserved motif was amplified. The 0.9 kb Hin cll pY53.3 subclone, which covers the open reading frame of SAY, serves as a probe for Southern blot analysis. RESULTS: Test results for all five XX true hermaphrodites were negative for SAY. Conversely, 22 of the 24 individuals with 45,X/46,XY gonadal dysgenesis were positive for SAY, including the 10 subjects with only bilateral streak gonads. CONCLUSIONS: The absence of SAY in XX true hermaphrodites and the presence of SAY in 10 subjects with 45,X/46,XY constitution who harbored only bilateral streak gonads seem to indicate that multiple genes are involved in gonadal differentiation. (AM J OBSTET GYNECOL 1992;167: 1794-802.)

Three tall, phenotypic female siblings with XY gonadal dysgenesis were found to have short fourth metacarpal bones (bilateral in two and unilateral in the other). Clitoromegaly was observed in the two older siblings, without hirsutism. Bilateral streak gonads were found in all three. A gonadoblastoma was present in the left streak gonad of the youngest, and an adenomatoid tumor in the left streak gonad of the oldest, who was diabetic. Determination of androgens from peripheral and gonadal venous plasma revealed androgen secretion by the streak gonads. On the basis of clinical findings, familial tendency, and androgen secretion from the streak gonads in these patients, it is proposed that the XY gonadal dysgenesis represents a severe from of male pseudohermaphroditism.

Two patients with XY gonadal dysgenesis who developed dysgerminoma are presented. These two patients are sisters, and the article emphasizes the importance of investigation of all siblings once a single sister is found with gonadal dysgenesis, particularly if a tumor has developed in the gonadal tissue.

A case of a unilateral gonadoblastoma occurring in a chromatin-negative phenotypic female with 45, XO/46, XY fragment mosaic chromosome constitution is presented. The gonadoblastoma presumably arose in a testis-determined rudimentary gonad and the contralateral streak was undifferentiated, giving a typical picture of XY gonadal dysgenesis with neoplastic transformation. The condition may be gene determined and maternally transmitted either by an X-linked recessive or autosomal dominant gene with expression only in chromosomal males. Current hypotheses concerning the development of dysgenetic gonads and their potential malignant transformation are reviewed and discussed.

A twin pregnancy was established in a patient with XY gonadal dysgenesis. The pregnancy was supported with exogenously administered hormones for the initial 100 days. The infants were delivered by emergency cesarean section at 35 weeks' gestation when severe preeclampsia developed in the mother.