45, X/46, XY mosaicism and gender incongruence: ethical, medical, and psychological considerations

Objectives 45, X/46, XY mosaicism is a complex chromosomal difference of sexual development, commonly associated with 45, X/46, XY karyotype. It presents a broad phenotypic spectrum, creating challenges in gender assignment. This report examines the management of a child with 45, X/46, XY mosaicism diagnosed in middle childhood, assigned female at birth but later exhibiting gender incongruence, highlighting dilemmas in pubertal induction after prophylactic gonadectomy. Case presentation An 8-year-old female presented with differences in sexual development (DSD) following maternal concerns regarding genital appearance. Genetic investigations confirmed a 45, X/46, XY karyotype, leading to bilateral gonadectomy due to malignancy risk. By age 11, the child expressed alignment with being a boy while reluctantly being perceived as a girl. The absence of endogenous sex hormones following gonadectomy will complicate pubertal induction as there is incongruency between the child’s gender preference and the sex of rearing. Conclusions Limited guidance exists on managing gender incongruence in DSD, particularly regarding pubertal induction. In the UK, while sex assignment at birth is mandated, there is no specific guidance regarding the revision of sex assignment in childhood. A non-coercive environment is essential to support gender exploration whilst balancing medical, psychological, and ethical considerations in decision-making regarding pubertal induction.