SAT-302 A Rare Diagnosis in a Female Adolescent Presenting with Primary Amenorrhea

Abstract

Background Primary amenorrhea (PA) occurs in about 2% of women in the reproductive age group. Evaluation of PA can be challenging, due to the multiple possible etiologies. In patients with PA secondary to hypergonadotropic hypogonadism, chromosomal anomalies are common. Clinical Case A 16 9/12 years old female with early kidney failure and delayed puberty with primary amenorrhea, in whom phenotypic sex and gender identity were not consistent with genotypic sex. Physical exam revealed a normal phenotypic female with no dysmorphic features. She has Tanner II-III for breast development, normal female external genitalia, Tanner V for pubic hair, no clitoromegaly and no galactorrhea. Workup demonstrated hypergonadotropic hypogonadism with a 46,XY karyotype. The SRY gene was present on FISH analysis. Patient had low levels of estradiol, testosterone, AMH and Inhibin, and normal prolactin, thyroid and adrenal function. MRI revealed duplicated internal female genital organs and unilateral streak gonad. DEXA scan showed severe osteopenia. The gender identity was female and consistent with the sex of rearing. The patient was started on weekly 0.050 mg Estradiol transdermal patch with gradual titration and will be followed with cyclical estrogen-progesterone replacement therapy. Bilateral gonadectomy was done. Surgical pathology report consistent with bilateral streak gonads. Conclusion Clinical and biological evaluation corroborated with the significant past medical history led to the highly suspected diagnosis of Denys-Drash Syndrome (DDS), a very rare genetic syndrome with approximately 150 cases reported worldwide. It is important to consider DDS and test for WT1 gene mutations in any patient with early onset kidney failure caused by diffuse mesangial sclerosis. Karyotype should be obtained in all patients at diagnosis of DDS, even in the absence of ambiguous genitalia. In 46, XY patients, performing gonadectomy at the time of nephrectomy is best, in order to prevent malignancy of streak gonads. Early institution of hormonal therapy is essential to induce puberty and prevent osteoporosis. If not evaluated for early, patients who present with normal female phenotypes, despite non-functional gonads, will not present until adolescence with a chief complaint of primary amenorrhea. Reference: Day YL, Fu JF et al. WT1 mutation as a cause of 46 XY DSD and Wilm's tumor: a case report and literature review. Acta Pediatr 2011. Jul: 100(7): e 39-42. Ostrer H. Disorders of sex development (DSDs): an update. J Clin Endocrinol Metab. 2014 May;99(5): 1503-9