SRY-negative 46,XX testicular disorder of sex development (de la Chapelle syndrome) presenting with primary infertility: a case report.

Abstract

De la Chapelle syndrome describes phenotypic males with a 46,XX karyotype, most commonly caused by translocation of the SRY gene. The SRY-negative variant is exceptionally rare and invariably associated with non-obstructive azoospermia. Awareness of this condition is important for infertility specialists, as genetic evaluation can establish an accurate diagnosis early in the workup and guide appropriate counselling. We report the case of a 30-year-old man who presented with primary infertility. Clinical examination revealed small testes with an otherwise normal male phenotype. Semen analysis confirmed azoospermia, and hormonal testing showed elevated gonadotropins with borderline testosterone levels. Imaging demonstrated reduced testicular volume without malignant features. Karyotype analysis revealed a 46,XX constitution, and molecular testing confirmed the absence of the SRY gene, establishing the diagnosis of SRY-negative de la Chapelle syndrome. Based on these findings, the patient was counselled regarding the futility of autologous sperm retrieval and was advised on donor-assisted reproductive options. Written informed consent was obtained for publication. This case highlights the value of incorporating genetic testing into the evaluation of non-obstructive azoospermia. Early recognition avoids unnecessary invasive interventions such as testicular sperm extraction and allows couples to receive timely counselling about realistic reproductive options. Although natural fertility cannot be achieved, assisted reproduction with donor sperm offers a viable pathway to parenthood. Comprehensive care, including endocrine monitoring, psychosocial support, and multidisciplinary management, ensures optimal outcomes for affected individuals.