SRY -positive 46,XX testicular disorder of sex development in adult monozygotic twins

Abstract 46,XX testicular disorder of sex development (DSD), also known as De la Chapelle syndrome, is a rare condition characterized by a male phenotype in individuals with a 46,XX karyotype, most commonly caused by translocation of the sex-determining region Y (SRY) gene. Diagnosis is frequently delayed until adulthood because external genitalia are typically unambiguous. We report adult monozygotic twins referred for infertility evaluation who were found to have azoospermia and markedly reduced testicular volume. Cytogenetic analysis revealed a 46,XX karyotype in both individuals, and molecular testing confirmed the presence of the SRY gene and complete absence of all azoospermia factor regions. Endocrine evaluation demonstrated low serum testosterone concentrations with normal to mildly elevated gonadotropins, consistent with primary testicular failure. Imaging revealed no residual Müllerian duct structures. This exceptionally rare twin presentation highlights the importance of genetic testing in men presenting with azoospermia, provides insight into the timing of sex-determining genetic events, and underscores the need for long-term endocrine follow-up in individuals with 46,XX testicular DSD.