1990 Volume 81 Issue 3 Pages 359-366
In order to clarify the clinical aspects of sex chromosomal mosaicism, we evaluated the karyotypes, the anatomy of external genitalia and internal ductal system, the pituitary-gonadal function, and the histopathology of the gonads by immuno-staining for glutathion S-transferase (GST) in 5 patients who had been all raised as female.
Three patients have the 45, X/46, XYq- karyotype in the initial lymphocyte culture or the subsequent culture of skin fibroblasts. Another two karyotypes were 45, X/46, XYq-/47, XYq-, Yq- and 45, X/46, XdicY. Thus, Y chromosome of all patients retained short arms in which the testis determining factor is encoded.
Three prepubertal patients were referred to us for their ambigious external genitalia and two postpubertal patients were for the short statures. Although the vaginal orfice was separated from the urethral meatus in all of them, the phallic enlargement was noted in 4 patients and the posterior labial fusion in 2 patients. The oldest patient had a normal female appearance of external genitalia except the vaginal septum.
Serum gonadotrophin (GnH) levels were basically high in the postopubertal patients and the responses of GnH to LH-RH were significantly increased in the prepubertal patients. Serum testosterone levels to hCG stimulation ranged from no response to low normal response.
All patients underwent the exploratory laparotomy together with the feminizing genitoplasty. The gonads in 3 patients, diagnosed as mixed gonadal dysgenesis (MGD), consisted of a unilateral testis and a contralateral streak gonad. Two patients had variants, including one with bilateral dysgenetic testis and another with bilateral streak gonads. Development of müllerian structures, a fallopian tube and uterus, was recognized in all of associated gonads. Epididymal tissue as wolffian structure was recognized in 2 of 5 testes and in 2 of 5 streak gonads. Histopathological examination of gonads, especially by the immunostaining for GST, revealed various extents of gonadal dysgenesis. The testicular tissue in prepubertal patients, composed of positive immunostained immature seminiferous tubules and the sparsely distributed interstitial Leydig cells, resembled that in the cryptorchid in prepubertal boys. Postpubertally Leyding cells, which were few in the absolute number, became hyperplastic and the deterioration of seminiferous tubules were in progress. The positive staining for GST in some cell lumps suggested the existence of ovarian granulosa cells in the streak gonad.
In MGD and its variants with sex chromosomal mosaicism, the dysgenetic variation of primordial germ cells is mainly resulted from the disarrangement of sex chromosomal constitution including testis determining factor and mosaicism, and this primary gonadal dysgenesis with its deficient müllerian inhibition and androgen production makes the ambigious external genitalia and the various degrees of wolffian development without the suppresion of müllerian development. Though the positive increase of serum testosterone to hCG stimulation implies the existence of testicular tissue, no change of serum testosterone to hCG stimulation does not contradict the testicular element. These dysgenetic gonads are further going to be deteriorated in accordance with high GnH stimulation.
