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

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.