An Unusual Presentation of 46,XY Pure Gonadal Dysgenesis: Spontaneous Breast Development and Menstruation

Abstract

46,XY pure gonadal dysgenesis (Swyer syndrome) is characterized by normal female genitalia at birth. It usually first becomes apparent in adolescence with delayed puberty and amenorrhea. Rarely, patients can present with spontaneous breast development and/or menstruation. A fifteen-year-old girl presented to our clinic with the complaint of primary amenorrhea. On physical examination, her external genitals were completely female. Breast development and pubic hair were compatible with Tanner stage V. Hormonal evaluation revealed a hypergonadotropic state despite a normal estrogen level. Chromosome analysis revealed a 46,XY karyotype. Pelvic ultrasonography showed small gonads and a normal sized uterus for age. SRY gene expression was confirmed by multiplex polymerase chain reaction. Direct sequencing on genomic DNA did not reveal a mutation in the SRY, SF1 and WT1 genes. After the diagnosis of Swyer syndrome was made, the patient started to have spontaneous menstrual cycles and therefore failed to attend her follow-up visits. After nine months, the patient underwent diagnostic laparoscopy. Frozen examination of multiple biopsies from gonad tissues revealed gonadoblastoma. With this report, we emphasize the importance of performing karyotype analysis, which is diagnostic for Swyer syndrome, in all cases with primary or secondary amenorrhea even in the presence of normal breast development. We also suggest that normal pubertal development in patients with Swyer syndrome may be associated with the presence of a hormonally active tumor.

Genetic, Genomic and Biophysical Case Study: Familial 46, XY Sex Reversal due to a Novel Inherited Mutation in Human Testis-Determining Factor SRY

“…Gonadal tumors were found in the probands (gonadoblastoma in P1 and dysgerminoma/gonadoblastomain P2). In accordance with other reports 70–72 , the presence of positive steroidogenic markers (such as CYP11A1 and CYP19) may rationalize the observed breast development and pubertal uterus size. Tumor steroid production might also have increased skeletal bone maturation, accounting for the heights of the sisters (shorter than expected in patients with 46, XY CGD 68 ).The presence of pluripotential aberrant germ cells was revealed by high nuclear OCT3/4 immuno-expression.…”

Disorder of sex development with germ cell tumors: Which is uncovered first?

“…Despite complete GD, the normal breast development observed in the current series needs to be pointed out, and it could explain the delay before diagnosis. This is not typically reported in Swyer syndrome (unlike in complete androgen insensitivity syndrome, where aromatization of androgen leads to breast growth), although it has been reported occasionally . Breast growth could be related to hormone activity of the tumor.…”

A rare case of primary amenorrhoea and breast development in a 46,XY 15-year-old girl

“…However, the breast development was not adequate in all the reports and did not achieve Tanner stage V, as in our patient. Catli et al reported a case of a 46,XY CGD teenager with adequate breast development and irregular menstrual periods [6]. There has also been a case of Swyer syndrome reported with adequate development of secondary sexual features and secondary amenorrhoea [10].…”