Mixed Gonadal Dysgenesis - A Comprehensive Review of Clinical Spectrum, Diagnostic Strategies, and Management Approaches

Sep 28, 2026

Uploaded by Callum

Mixed gonadal dysgenesis (MGD) is a rare form of differences in sex development (DSD) usually linked to 45,X/46,XY mosaicism, presenting from atypical genitalia to typical male or female appearances often with Turner stigmata. Clinical management is complex due to gonadal malignancy risk, decisions about gonadectomy, fertility, and sex of rearing. Narrative review evidence summarizes epidemiology, manifestations, diagnostics, malignancy risk, management, psychosocial factors, and long-term care strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

Epidemiology

Clinical Features

Diagnostic Evaluation

Malignancy Risk

Management Approaches

Psychosocial Considerations

Long-Term Care and Future Directions

Clinical Endocrinology REVIEW ARTICLE Paediatric Endocrinology Mixed Gonadal Dysgenesis: A Comprehensive Review of Clinical Spectrum, Diagnostic Strategies, and Management Approaches Dinesh Giri1,2 | Sushil Yewale3 | Hannah Hickingbotham4 | Cara Williams3 | Mohamed Shalaby1 | Julie Alderson1 | Julie Park3,5 1Bristol Royal Hospital for Children, Bristol, UK | 2University of Bristol, Bristol, UK | 3Alder Hey Children's Hospital, Liverpool, UK | 4Croydon University Hospital, London, UK | 5University of Liverpool, Liverpool, UK Correspondence: Dinesh Giri ([Dinesh.Giri@bristol.ac.uk](Dinesh.Giri@bristol.ac.uk)) Received: 25 July 2025 | Revised: 10 September 2025 | Accepted: 17 October 2025 Funding: The authors received no specific funding for this work. Keywords: differences in sex development | gonadal tumour | mixed gonadal dysgenesis ABSTRACT Background: Mixed gonadal dysgenesis (MGD) is a rare form of differences in sex development (DSD) typically associated with 45,X/46,XY mosaicism. The phenotypic presentation of MGD varies from atypical genitalia to typical male or female appearances often associated with Turner stigmata. Some of the challenges in the clinical management of patients with MGD include gonadal malignancy risk, decisions on gonadectomy, fertility and sex of rearing. The management is predominantly multidisciplinary with a focus on patient and family centred care. Methods: This article was prepared as a narrative review based on a comprehensive search of the literature. A systematic search of the PubMed, Embase, Scopus, and Google Scholar databases was performed using the key terms “mixed gonadal dysgenesis,” “45,X/46,XY mosaicism,” “differences in sex development,” and “gonadal tumour risk” to identify relevant articles published between 2000 and 2024 . References from the identified papers were further screened to capture additional relevant literature. We gathered the findings to provide an updated overview of MGD, focusing on epidemiology, clinical manifestations, diagnostic evaluation, malignancy risk, approaches to management, psychosocial considerations, and evolving strategies in the long‐term care of patients with MGD. Results: MGD accounts for 5%–15% of cases of atypical genitalia and carries a 15%–25% risk of gonadal tumour, with the highest malignancy rates in intra‐abdominal gonads. Approximately 12%–15% of patients with MGD may experience gender incongruence later in life. Management has shifted from early surgical intervention to a multidisciplinary, patient‐centred, and shared decision making approach. Conclusions: The future care of patients with MGD is likely to include biomarker‐driven surveillance, along with advanced fertility preservation techniques. Long‐term outcome data for patients with MGD along with patient‐reported outcomes, are limited in the literature, underscoring the need for further research. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Author(s) . Clinical Endocrinology published by John Wiley & Sons Ltd. Clinical Endocrinology, 2026; 104:92–102 92 [https://doi.org/10.1111/cen.70053](https://doi.org/10.1111/cen.70053) 1 | Introduction Mixed gonadal dysgenesis (MGD), first described in 1963 [1], represents a rare form of differences in sex development (DSD) resulting from 45,X/46,XY mosaicism and is typically characterised by the presence of a dysgenetic testis at various levels of descent on one side and a streak gonad on the other [2] . The most common karyotype reported is 45,X/46,XY mosaicism. Other rare karyotypes described include 45,X/47,XXY, and 45,X/47,XYY [3] . Rarely, cases with clinical features resembling MGD have been reported despite a normal 46, XX or 46, XY karyotype, often attributed to low‐level mosaicism detectable only with advanced genetic techniq

FAQs

What causes mixed gonadal dysgenesis and how is it usually linked to karyotypes?

MGD results from 45,X/46,XY mosaicism and is characterized by a dysgenetic testis on one side and a streak gonad on the other. The most common karyotype reported is 45,X/46,XY mosaicism, with other rare variants described.

What are the main clinical challenges in managing patients with MGD?

Key challenges include assessing gonadal malignancy risk, deciding whether and when to perform gonadectomy, addressing fertility preservation, and determining sex of rearing. Care is commonly multidisciplinary and emphasizes patient- and family-centred decision making.

How is management shifting over time for children with MGD?

Management has moved away from early surgical intervention toward a multidisciplinary, patient-centred approach with shared decision making. Irreversible surgery is typically delayed until a comprehensive MDT plan is agreed with the family.

Sep 28, 2026

Uploaded by Callum