Clinical, Hormonal, and Genetic Spectrum of 46 XY Disorders of Sexual Development (DSD) Patients

• Published in: Indian journal of pediatrics Vol. 92; no. 8; pp. 836 - 843
• Main Authors: Palui, Rajan, Ravichandran, Lavanya, Kamalanathan, Sadishkumar, Chapla, Aaron, Sahoo, Jayaprakash, Narayanan, Niya, Naik, Dukhabandhu, Thomas, Nihal
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.08.2025
• Subjects: 17-Hydroxysteroid Dehydrogenases - deficiency; 17-Hydroxysteroid Dehydrogenases - genetics; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - deficiency; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics; Adolescent; Androgen-Insensitivity Syndrome - diagnosis; Androgen-Insensitivity Syndrome - genetics; Child; Child, Preschool; Disorder of Sex Development, 46,XY - blood; Disorder of Sex Development, 46,XY - diagnosis; Disorder of Sex Development, 46,XY - genetics; Female; Gynecology; Gynecomastia; Humans; India; Infant; Male; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Mutation; Original Article; Pediatrics; Receptors, Androgen - genetics; Steroid Metabolism, Inborn Errors - genetics; Testosterone - blood; India; 17β-hydroxysteroid dehydrogenase 3 (17BHSD3) deficiency; Partial androgen insensitivity syndrome (PAIS); 5 alpha-reductase type 2 deficiency (5ARD2); 46XY DSD; Next-generation sequencing (NGS)
• ISSN: 0019-5456; 0973-7693; 0973-7693
• DOI: 10.1007/s12098-024-05144-8

Objectives To evaluate the clinical, hormonal and genetic characteristics of 46XY disorders of sexual development (DSD) patients from South India. Methods 46XY DSD patients with a provisional diagnosis of 17β-hydroxysteroid dehydrogenase 3 (17BHSD3) deficiency, 5 alpha-reductase type 2 deficiency (5ARD2) or partial androgen insensitivity syndrome (PAIS) based on clinical and hormonal analysis were included in this study. All the patients underwent detailed clinical and hormonal evaluations. Targeted next-generation sequencing for all three genes ( AR , HSD17B3 , and SRD5A2 ) in parallel was carried out for all the included patients and their parents. Results Based upon the clinical and hormonal analysis, among the 37 children with 46XY DSD in the present study, 21 children were diagnosed with 5ARD2, 10 with PAIS, and six with 17BHSD3 deficiency. However, genetic analysis revealed pathogenic mutations in nine patients – six in the AR gene, two in the SRD5A2 gene, and one in the HSD17B3 gene. The concordance rate between provisional hormonal and genetic diagnosis was only 22.2%. Two out of six subjects with AR gene variants were positive for somatic mosaicism. Conclusions In the present study, a positive genetic diagnosis was detected in nine patients (24%), including five novel variants. In this study, mutations in the AR gene was the most reported. The authors did not find the testosterone: dihydrotestosterone (T: DHT) ratio to be an accurate hormonal diagnostic tool.