SUN-163 45,X/46,X,Idic(Y)(q11.21) Mosaicism in a Nonbinary Individual Receiving Gender-Affirming Hormone Therapy Before Orchiectomy

Abstract Disclosure: S. Thota-Kammili: None. J.A. McNeil: None. S.J. Peres: None. M.A. Edgar: None. J.P. Reynolds: None. J. Eleazer: None. A.Y. Chang: None. Introduction: 45,X/46,X,psrY mosaicism has been reported in the context of prenatal diagnosis with few reports on the developmental phenotype through adulthood. The 45,X/46,XY karyotype is well-studied and linked to ambiguous genitalia, dysgenetic gonads, and increased gonadal tumor risk. Less is known about 45,X/46,X,psrY mosaicism, characterized by partial Y chromosome retention. Phenotypic variability with a broad spectrum of phenotypes including Turner syndrome features, delayed puberty, hypogonadism and infertility depends on the extent and functionality of preserved Y chromosome material. We present a case of 45,X/46,X,idic(Y)(q11.21) mosaicism in an individual assigned male at birth, with a nonbinary intersex gender identity who received gender affirming feminizing hormone therapy (GAHT) before orchiectomy. Clinical Case: This is a case of a 36 y.o. patient who was found to have 45,X/46,X +mar chromosomal abnormality prenatally and initially diagnosed with Turner’s syndrome. At birth, patient had male genitalia, descended testes, and only slight hypospadias. Subsequent Y-DNA studies determined the unknown marker to be the sex determining region of the Y chromosome. Early evaluations showed appropriate responses to LHRH and ACTH, and developmental milestones were met without major health or behavioral concerns aside from a delay in puberty. The patient experienced early gender incongruence and faced questioning for gender expression. Delayed puberty led to testosterone therapy, worsening distress. Parents did not share the medical history with the patient until adulthood, when they notified them about the potential for infertility. During infertility evaluation, semen analysis revealed azoospermia. Testosterone therapy was re-attempted for hypogonadism but resulted in increased distress and patient began GAHT. Patient sought a second opinion on previous diagnosis of differences of sexual development (DSD). Chromosomal analysis revealed the 45,X/46,X,idic(Y)(q11.21) mosaicism, with duplication of Yp and deletion of the Yq. Pt was referred to urology for bilateral orchiectomy to reduce gonadal tumor risk and gender dysphoria. Pathology revealed atrophic seminiferous tubules with complete absence of spermatogenesis which were populated by Sertoli cells only and surrounded by thickened basal lamina. Leydig cells were markedly depleted. These changes are seen in transgender patients treated with estrogen prior to orchiectomy. Conclusion: Our case expands the phenotypic characterization of 45,X/46,X,idic(Y)(q11.21) mosaicism by detailing clinical features and previously unreported testicular pathology. This patient had minimal developmental concerns, and testicular pathology reflected changes associated with GAHT, highlighting the variability in phenotypic expression of 45,X/45,X,psrY mosaicism. Presentation: Sunday, July 13, 2025