Case Report: 46, XX Testicular Disorder of Sex Development in A15-Year-Old Male

Abstract

Background: 46,XX testicular disorder of sex development (DSD), also known as de la Chapelle syndrome, is a rare condition in which an individual with a 46,XX karyotype develops as a phenotypic male. This typically results from translocation of the sex-determining region Y (SRY) gene onto an X chromosome during paternal meiosis. Affected individuals usually present in adolescence with hypergonadotropic hypogonadism and infertility, despite having male genitalia.

Case Presentation: We report a 15-year-old phenotypic male evaluated for delayed puberty and gynecomastia. He was short for his age and had minimal facial hair, underdeveloped musculature, and bilaterally small testes. Laboratory testing revealed elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) with low testosterone levels, suggesting primary testicular failure. Karyotype analysis unexpectedly showed 46,XX. Fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) confirmed the presence of the SRY gene on one X chromosome, consistent with SRY-positive 46,XX testicular DSD.

Management: The patient was started on low-dose testosterone replacement therapy to induce puberty, with gradual dose escalation. Hormone therapy led to development of secondary male characteristics and halted progression of gynecomastia. Psychological counseling and patient education were provided to address the discordance between chromosomal sex and gender identity. The patient was counseled about infertility and future options.

Conclusion: This case illustrates the diagnostic challenge of 46,XX testicular DSD in an adolescent male with delayed puberty. It highlights the importance of cytogenetic analysis in cases of hypergonadotropic hypogonadism, as well as the need for molecular testing to detect SRY gene translocation. Early identification and management with hormone therapy are critical for normal pubertal development. The report also underscores genotype–phenotype discordance and recommends confirming SRY involvement to guide appropriate counseling and genetic consultation.