Endocrine Abstracts

JOINT3783

Introduction: 46,XY Disorders of Sex Development (DSD) encompass a spectrum of conditions characterized by atypical gonadal, hormonal, or phenotypic development in individuals with a 46,XY karyotype. The underlying etiologies of 46,XY DSD vary widely and may include genetic mutations affecting gonadal differentiation, steroid biosynthesis defects, or androgen insensitivity syndromes. Understanding the prevalence and diagnostic yield in specific populations is crucial for optimizing clinical management and genetic counseling. This study aims to evaluate the diagnostic outcomes and underlying causes of 46,XY DSD among patients in Saudi Arabia, providing insights into the regional distribution of these conditions.

Methodology: A retrospective review was conducted at King Faces Specialist Hospital Research Centre (KFSHRC), analyzing medical records of patients diagnosed with 46,XY Disorders of Sex Development (DSD) who were seen in the endocrine clinic between 2019 and 2024. Clinical, biochemical, and genetic data were systematically reviewed. The diagnostic yield was assessed based on the ability to establish a definitive diagnosis through genetic investigations. STATA version 18 was used for statistical analysis. Ethical approval was obtained from the ethics committee at KFSHRC (reference: 2231110).

Results: A total of 278 DSD patients were included. At birth, 24.4% were assigned female, while 75.6% were assigned male. Currently, 80.9% identify as male, and 19.1% identify as female. Genetic testing was conducted in 201 patients (72.30%), of which 168 (83.58%) yielded positive results with 42 distinct mutations. The most frequently identified genetic abnormality was SRD5A2 deficiency, found in 43 out of 168 cases (25.50%), Complete Androgen Insensitivity Syndrome (CAIS) in 21 (12.50%), Adrenogenital disorders 17 (10.11%), 17β-HSD deficiency in 15 (8.92%), Gonadal dysgenesis in 12 (7.14%), LHCGR in 7 (4.16%), CHARGE syndrome in 4 (2.38%) and 49 (29.16%) others.

Conclusion: This study highlights the high diagnostic yield (83.58%) of genetic testing in 46,XY DSD in the Saudi population, emphasizing its critical role in establishing definitive diagnoses. SRD5A2 deficiency (25.5%), Complete Androgen Insensitivity Syndrome (12.5%), and adrenogenital disorders (10.1%) were the most frequently identified genetic abnormalities among 42 distinct mutations. The findings underscore the genetic heterogeneity of 46,XY DSD and the importance of early genetic evaluation in guiding clinical management. Additionally, the observed discrepancies between assigned sex at birth and current gender identity reinforce the need for a multidisciplinary approach integrating genetic, endocrine, and psychosocial support to optimize patient outcomes.