Clinical heterogeneity in children with gonadal dysgenesis associated with non-mosaic 46, XY karyotype

Introduction Gonadal dysgenesis is unique in disorders of sex development (DSD), in that it can be associated with 46, XX, 46, XY or mosaic 45, X/46, XY karyotypes. Gonadal dysgenesis can be partial or complete. Gonadal dysgenesis associated with the Y-chromosome has increased risk of gonadal germ cell neoplasms. Most of the literature focus on 45, X/46, XY gonadal dysgenesis, while there are scanty data on the condition when the karyotype is non-mosaic 46, XY. Objective To investigate the diversity of clinical pictures of children presenting with 46, XY DSD due to gonadal dysgenesis. Methods A retrospective study on consecutive patients diagnosed with 46, XY gonadal dysgenesis at age <= 18 years in a tertiary center from 1985 to 2015. The clinical presentations, phenotypes, gonadal features and associated anomalies were investigated. Results Twenty-eight patients with Y-chromosome gonadal dysgenesis were identified during the study period and six (21.4%) had non-mosaic 46, XY karyotype. Three had complete gonadal dysgenesis (CGD) with normal female phenotype, while the other three had partial gonadal dysgenesis (PGD). Of the three patients with CGD, two presented with the classical Swyer syndrome at adolescence, while the third presented at birth with multiple congenital anomalies. The three PGD patients presented with ambiguous genitalia at birth (n = 2), and isolated hypospadias (n = 1), which was associated with Frasier syndrome. Three patients had germ cell neoplasms: bilateral gonadoblastoma (n = 1), bilateral intratubular germ cell neoplasia unclassified (n = 1), and dysgerminoma + gonadoblastoma (n = 1). Two patients had global developmental delay with other congenital anomalies, and another patient had learning difficulties with borderline intelligence (Table). Discussion The findings suggest that 46, XY gonadal dysgenesis is much rarer than 45, X/46, XY gonadal dysgenesis. Patients differed in their clinical presentations and well-established syndromes happened in half of them. Overall, the risk of germ cell neoplasms and the association with other somatic anomalies appeared to be high. The study was limited by: its small number, single-center experience, and the possibility of missing the diagnosis in some male patients with mild undervirilization. Conclusion Heterogeneity was noted in the clinical, phenotypic and gonadal features among pediatric patients with 46, XY gonadal dysgenesis.