Differences of Sex Development: A Study of 420 Patients from a Single Tertiary Pediatric Endocrinology Center.

Background

Differences of sex development (DSD) are a group of congenital conditions characterized by atypical development of genital structures. The diagnosis is complex and involves clinical, hormonal, and genetic evaluations.

Objective

To describe the clinical profile, diagnosis, and management of patients with DSD, with particular attention to genetic diagnosis. Study design: Retrospective study from a tertiary care pediatric hospital in Italy.

Methods

420 patients with DSD referred to the Endocrine Unit of Bambino Gesù Children's Hospital in Rome, Italy, between 2016 and 2023 were included.

Results

75 patients had a 46,XY karyotype, 135 had a 46,XX karyotype, and 210 had chromosomal mosaicism. In our group of pediatric DSD patients, 21/420 patients were born from pregnancies induced with assisted reproduction techniques (ICSI/FIVET). Of these 21 patients, 5 had sex chromosome mosaicism. Using next-generation sequencing (NGS), we identified three new genetic variants: one in the AR gene, one in the NR5A1 gene, and one in the SRY gene. The use of NGS significantly improved the diagnostic yield, and a definitive diagnosis was reached in 84.76% of the entire cohort.

Conclusions

This study highlights the challenges in the management of patients with DSD from early recognition to treatment and follow-up. A multidisciplinary approach is essential for a comprehensive evaluation of these conditions and to understand the role and clinical significance of the genetic variants.