Case ReportDysgerminoma in a Prepubertal Girl with Complete 46XY Gonadal Dysgenesis: Case Report and Review of the Literature
Introduction
Complete 46XY gonadal dysgenesis was first described by Gim Swyer in 1955 as “male pseudohermaphroditism.”1 He reported 2 phenotypically female patients with a male karyotype presenting with primary amenorrhea. Both patients were tall with a normal amount of pubic and axillary hair and underdeveloped breasts. The external genitalia and vagina were found to be normal, although the uterus was small and the adnexa were not palpable. This syndrome was later associated with disorders of sex development (DSD) in which the development of anatomical, gonadal, and chromosomal sex is disrupted.
Swyer syndrome, so-called pure or complete gonadal dysgenesis, occurs in approximately 1 of 80,000 births. Normally, the expression of the Y sex chromosome determining the region Y (SRY) gene initiates the development of the undifferentiated gonad into a testis. Anti-Müllerian hormone (AMH) secreted by the Sertoli cells of the developing testis induces the regression of the Müllerian ducts in the fetus. From 10% to 20% of patients with Swyer syndrome have a deletion in the DNA-binding region of the SRY gene, whereas the remaining 80% to 90% of patients with a wild-type SRY gene have mutations in alternative testis-regulating factors.2
Individuals with complete 46XY gonadal dysgenesis typically present as phenotypically female with normal external genitalia and Müllerian structures. The symptoms manifest mostly in adolescence with delayed puberty and amenorrhea, as hormonal production is absent in the gonads. Exogenous estrogen is administered to induce secondary sex characteristics and puberty, followed by long-term combined estrogen and progesterone replacement therapy.3 Prophylactic bilateral gonadectomy is recommended, as the dysgenetic streak gonads contain a 30% risk of developing a gonadoblastoma, with a 50%-60% chance of malignancy, usually a dysgerminoma.4 Unfortunately, most girls experience a delayed diagnosis because the prepubertal phenotype appears as normal female.
Section snippets
Case
A 6-year-old phenotypical girl with dextrocardia and situs viscerum inversus diagnosed in infancy was referred for gynecological evaluation. Her karyotype from peripheral blood leukocytes was found to be 46XY in the absence of the SRY gene mutation. The patient's external genitalia were female, with moderate clitoral hypertrophy. Ultrasound examination revealed prepubertal uterine size; gonads fit the biological age: right gonad volume was 0.5 cm3 and left gonad 0.3 cm3. Following discussion
Discussion and Review of the Literature
Complete 46 XY gonadal dysgenesis (Swyer syndrome) is rare and thus challenging to diagnose. Ovarian insufficiency in young girls manifests as primary amenorrhea and/or delayed puberty; therefore prepubertal diagnosis is exceedingly rare. Complete 46XY gonadal dysgenesis elevates the risk of a gonadal tumor more than any of the other DSD.5 The lifetime risk of a gonadal tumor, generally a gonadoblastoma, in girls with Swyer syndrome is estimated to be 30%. Gonadoblastoma frequently appears
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