(764) 46,XX Testicular Disorder of Sex Development (DSD): A Rare SRY-Positive Male Case

Introduction 46,XX testicular disorder of sex development (DSD) is a rare condition characterized by discordance between genetic and phenotypic sex, most often caused by translocation of the sex-determining region Y (SRY) gene onto the X chromosome. Here, we present a phenotypically normal male patient with 46,XX karyotype and SRY positivity, diagnosed during infertility evaluation. Objective To present a rare case of SRY-positive 46,XX testicular DSD in a phenotypically normal male and to highlight its clinical, hormonal, imaging, and genetic characteristics. Methods A 26-year-old male presented with primary infertility after three years of unprotected intercourse. His partner, aged 19, had no detectable gynecologic pathology. The patient had undergone bilateral orchiopexy in 2007 due to cryptorchidism. Physical examination revealed normal male external genitalia with normal penile length, no hypospadias, and no gynecomastia. Pubertal development was normal, and he reported normal libido and morning erections (IIEF score: 22). Scrotal ultrasonography showed small-sized testes (right: 12×15×25 mm, left: 12×15×24 mm; estimated volume ~2.2 mL each) with heterogeneous parenchyma consistent with testicular atrophy/hypoplasia. Mild left pampiniform plexus dilatation (2.1 mm) with reflux during the Valsalva maneuver was observed. Pelvic MRI demonstrated normal appearance of the testes and prostate. Laboratory findings indicated hypergonadotropic hypogonadism (FSH: 32.9 mIU/mL, LH: 20.6 mIU/mL, testosterone: 3.77 ng/mL, prolactin: 18.8 ng/mL). Repeated semen analyses revealed azoospermia (volume: 2.0 mL). Genetic testing confirmed a 46,XX karyotype and presence of the SRY gene, supporting a diagnosis of SRY-positive 46,XX testicular DSD. The patient received genetic counseling. SRY translocation onto the X chromosome explains the male phenotype despite the absence of a Y chromosome. Results SRY-positive 46,XX DSD accounts for approximately 80% of 46,XX male cases and typically presents with a normal male phenotype but infertility due to absence of azoospermia factor (AZF) regions on the Y chromosome. In contrast, SRY-negative cases often exhibit varying degrees of genital ambiguity depending on other testis-determining or ovary-suppressing gene activity. Literature indicates that these patients frequently present in adulthood for infertility evaluation, with preserved erectile function, normal libido, and small, atrophic testes. This case aligns with the classical form of SRY-positive 46,XX testicular DSD: a phenotypically normal male presenting with primary infertility and hypergonadotropic hypogonadism. Conclusions A multidisciplinary approach combining clinical, hormonal, imaging, and genetic evaluation is crucial for accurate diagnosis. Given the absence of spermatogenesis from AZF deletion, testicular sperm extraction is futile. Fertility counseling should emphasize alternative options such as donor sperm or adoption. Detecting SRY translocation is key for confirming the diagnosis and guiding prognosis and reproductive decisions. Disclosure No