[Understanding pathogenesis and evolving strategies in the management of differences of sex development in children]

Area of Science:

• Genetics and Developmental Biology
• Pediatric Endocrinology
• Reproductive Medicine

Background:

• Disorders of Sex Development (DSD) encompass congenital conditions with discordance in chromosomal, gonadal, and phenotypic sex.
• These disorders present significant clinical and molecular heterogeneity, impacting pediatric and adolescent care.
• Management has evolved from isolated interventions to integrated, multidisciplinary approaches across the lifespan.

Purpose of the Study:

• To systematically review the pathogenesis of DSD, focusing on gene networks, hormonal signaling, and developmental timing.
• To delineate the molecular etiology and phenotypic spectrum of major genetic subtypes (46,XY DSD, 46,XX DSD, sex chromosome DSD).
• To outline current diagnostic pathways and treatment principles for DSD, emphasizing long-term care and support.

Main Methods:

• Systematic review of DSD pathogenesis, molecular etiology, and clinical management.
• Emphasis on genetic and hormonal dysregulation during sex determination and differentiation.
• Summary of multidisciplinary diagnostic and screening pathways, including genetic testing and biochemical profiling.

Main Results:

• DSD pathogenesis involves dysregulation of gene networks, hormonal signaling, and developmental timing.
• Major genetic subtypes (46,XY DSD, 46,XX DSD, sex chromosome DSD) exhibit distinct molecular etiologies and phenotypic spectra.
• Multidisciplinary approaches, including genetic testing and timely evaluation, are crucial for early detection and classification.

Conclusions:

• Integrated, multidisciplinary care is essential for optimizing long-term outcomes in DSD.
• Individualized decision-making, hormone therapy, and psychosocial support are key components of DSD management.
• Future directions include precision medicine, AI-assisted genomics, and enhanced patient/family support systems.