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ORIGINAL RESEARCH article

Front. Pediatr.
Sec. Pediatric Urology
Volume 13 - 2025 | doi: 10.3389/fped.2025.1456227

Molecular genetic diagnosis and surgical management in a cohort of children with 46,XY disorders/differences of sex development

Provisionally accepted
Yuenshan Sammi Wong Yuenshan Sammi Wong 1Ho Ming Luk Ho Ming Luk 2Ho Chung Yau Ho Chung Yau 3Lap Ming Wong Lap Ming Wong 4Sarah Wing-Yiu Poon Sarah Wing-Yiu Poon 2Joanna Yuet-Ling Tung Joanna Yuet-Ling Tung 2Yuk Him Tam Yuk Him Tam 1*
  • 1 The Chinese University of Hong Kong, Shatin, China
  • 2 Hong Kong Children's Hospital, Kowloon, Hong Kong, SAR China
  • 3 Prince of Wales Hospital, Shatin, Hong Kong Region, China
  • 4 Tuen Mun Hospital, Tuen Mun, Hong Kong, SAR China

The final, formatted version of the article will be published soon.

    Objective: A firm diagnosis revealing the etiology of disorders/differences of sex development(DSD) is most helpful in guiding clinical management. The aim of this study was to investigate the molecular genetic diagnoses and surgical treatment in a cohort of children with 46,XY DSD.A retrospective study was conducted on 46,XY DSD children who were referred to a tertiary surgical centre over the period of 2011 to 2022, and were found to have genetic alterations which were considered etiologies for their DSD. Data on clinical presentations, sex of rearing, genetic findings, surgical treatment and co-morbidities were collected and reviewed.Results: 21 patients were included in the study. 11 and 10 were reared as male and female respectively. Genetic alterations were found as the causes for androgen insensitivity syndrome(n=4), 5-alpha reductase type II deficiency(n=5), 17-beta hydroxysteroid dehydrogenase III deficiency(n=1), 17-alpha hydroxylase deficiency(n=1), gonadal dysgenesis(n=10). Of those with gonadal dysgenesis, the genetic alterations were NR5A1 mutation/deletion(n=3), DMRT1 deletion(n=4), WT1 mutation(n=2), and DAX1 duplication(n=1). 20/21 patients underwent one or more surgical procedures including hypospadias repairs(n=10), gonadectomy(n=11), gonadal biopsy(n=4), hernia repair(n=4), orchidopexy(n=1), feminizing genitoplasty(n=1). 5/21 had germ cell neoplasms in one or both gonads. 8/10 patients with gonadal dysgenesis had co-morbidities involving other systems. Of the whole group, 7 patients were found to inherit the genetic alterations from their parents.Conclusions: Molecular genetic diagnosis enhances the understanding of etiology, improves diagnostic accuracy, and provides precise guidance in the counselling and surgical management of children with 46,XY DSD.

    Keywords: Disorders/Differences of Sex Development, 46,XY, genetic diagnosis, Surgery, Gonadal Dysgenesis

    Received: 28 Jun 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Wong, Luk, Yau, Wong, Poon, Tung and Tam. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yuk Him Tam, The Chinese University of Hong Kong, Shatin, China

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