Endocrine Abstracts

Background: Patients with sex chromosome mosaicism (SCM) such as patients with Turner syndrome with Y chromosome material (45,X/46,XY), can vary widely on external genital appearance, ranging from typical female to typical male genitalia. Virilization may also progress with puberty. Advances in noninvasive prenatal testing have allowed for earlier identification of patients with SCM, however the potential for gonadal hormone production and additional virilization with puberty is unknown, which complicates the discussion regarding gender assignment and timing of gonadectomy. It is unknown whether percentage of mosaicism affects phenotype, potential for additional virilization with puberty, or gender identity. This study aims to evaluate the association between level of mosaicism of Y chromosome material, genital appearance, and gender identity.

Methods: This is a retrospective cohort study of patients with 45,X/46,XY mosaicism who had at least one visit at a urology or endocrinology outpatient clinic in a tertiary care pediatric hospital between 2001-2026. Information gathered from the charts included karyotype, including percent of Y chromosome material, phenotype, and gender identity. Patients were considered virilized if they presented with a phenotype other than typical female.

Results: Forty-seven patients (26 female and 21 male) were included in the study. With regards to genital appearance, 19 patients presented as typical female (42.2%); 5 patients presented as typical male (11.1%); 5 patients presented with clitoromegally (11.1%); and 16 presented with hypospadias (34%). Two patients (4.3%) did not have a phenotype recorded in their charts. Mean percent of Y chromsome material was 35.68±24.73%. Patients assigned male at birth were more likely to have a a larger percent of Y chromosome material (50.39±18.92%) than their female counterparts (20.98±5.45%; P<.001). The average percentage of Y chromosome mosaicism was significanly higher in oatients with virilization (47.33±21.99%) than patients with typical female appearance (22.38±21.19%; P<0.01).

Conclusions: Patients with 45X, 46XY mosaicism vary greatly in phenotypic appearance. There is a positive association between percentage of Y chromsome material and phenotype, with patients with a higher proportion of Y chromosome material more likely to have a virilized appearance and male gender identity. Future studies are needed to identify any relationship between level of sex chromosome mosaicism, gonadal hormone production with puberty, and risk of gonadoblastoma.