Karyotype and Phenotypic Variability in Disorders of Sex Development Refining Diagnosis with a Novel Comprehensive DSD Classification Score CDCS

Abstract

Introduction: Disorders of Sex Development (DSD) encompass a heterogeneous group of congenital conditions affecting chromosomal, gonadal, and phenotypic sex, with an estimated incidence of 1 in 4,500 live births. Current DSD classification relies heavily on phenotypic and karyotypic categorization, often without a standardized grading system for clinical severity. The Comprehensive DSD Classification Score (CDCS) was developed as a novel scoring system integrating four key domains: external genitalia, internal reproductive structures, gonadal positioning/function, and chromosomal assessment. Methods: This study was designed as a retrospective cohort analysis. The cohort consisted of 70 pediatric patients diagnosed with Disorders of Sex Development (DSD), who underwent comprehensive clinical, laboratory, and imaging evaluations. The Comprehensive DSD Classification Score (CDCS) was designed as a quantitative, standardized scoring system   (0–30 scale) integrating external genitalia appearance, internal reproductive structures, gonadal positioning/function, and chromosomal findings. Data were analyzed using SPSS (version 26.0) and GraphPad Prism (version 9.0). Predictive Accuracy of CDCS (ROC Curve Analysis): Receiver Operating Characteristic (ROC) curves evaluated CDCS as a predictor for surgical/hormonal interventions. Area Under the Curve (AUC) interpretation: AUC > 0.8 = Strong predictive ability. AUC 0.7–0.8 = Moderate predictive ability. AUC < 0.7 = Weak predictive ability. Results: The CDCS scoring system demonstrated strong inter-rater reliability, as measured by the Intraclass Correlation Coefficient (ICC = 0.82, 95% CI: 0.77–0.89). Independent scoring by two clinicians on 20 randomly selected cases showed high agreement, confirming CDCS as a reproducible classification tool. Conclusion: Most DSD scoring systems are static, focusing only on initial diagnosis. CDCS is dynamic, allowing tracking of disease progression, endocrine response, and surgical/hormonal outcomes over time, and reassessment at puberty, guiding future reproductive and endocrine management.