SRY-positive 46, XX testicular disorder of sex development presenting as klinefelter-like hypogonadism and infertility: Cytogenetic diagnosis and genetic counselling
Year: 2026
Type: article
Study design: Case Report
Abstract: Background: 46, XX testicular disorder of sex development (DSD), historically described as 46, XX male syndrome or De la Chapelle syndrome, is a rare cause of primary testicular failure, hypergonadotropic hypogonadism and infertility in phenotypic males.In most SRY-positive cases, aberrant paternal meiotic X-Y recombination transfers the SRY locus onto an X chromosome, initiating testicular differentiation despite a 46, XX chromosomal constitution.Because the endocrine and reproductive phenotype may closely resemble Klinefelter syndrome, cytogenetic confirmation is essential for accurate diagnosis, fertility counselling and reproductive planning.Case presentation: A 30-year-old phenotypic male was evaluated for bilateral gynecomastia, poor pubertal progression, bilateral testicular atrophy and infertility.Semen analysis demonstrated azoospermia.Hormonal assessment revealed severe hypergonadotropic hypogonadism, with markedly elevated FSH and LH, markedly reduced testosterone, normal estradiol and prolactin levels.Bone mineral density was below the expected range for age.Following cytogenetic confirmation and counselling, testosterone replacement therapy was initiated for symptomatic hypogonadism and bone-health protection.Cytogenetic findings: GTG-banded karyotyping of peripheral blood lymphocyte metaphases revealed a uniform 46, XX chromosomal complement.Fluorescence in situ hybridization confirmed SRY positivity in an XX background, establishing SRY-positive 46, XX testicular DSD and excluding classic 47, XXY Klinefelter syndrome.Conclusion: This case highlights a clinically important diagnostic trap in male infertility practice: a Klinefelter-like phenotype may arise from an SRY-bearing XX genome rather than sex-chromosome aneuploidy.The pathophysiology reflects a dissociation between testis determination, driven by ectopic SRY/SOX9 activation, and spermatogenesis, which fails because Yq azoospermia factor regions are absent.Early diagnosis enables testosterone-based endocrine management, avoidance of unrealistic fertility interventions, and identity-sensitive genetic counselling covering donor-sperm conception, recurrence risk and individualized prenatal testing.
Institution: Dr. Lal PathLabs Pvt Ltd (India)
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W7164032784