Long-term outcomes in 45,X/46,XY mosaicism: a 30-year retrospective study in Hong Kong

45,X/46,XY mosaicism is a rare subset of sex chromosome abnormalities within the spectrum of differences of sex development. This study aimed to evaluate the long-term outcomes in a group of individuals with 45,X/46,XY mosaicism over a 30-year period.

A retrospective review was performed including 68 patients diagnosed from January 1990 to December 2023 at a tertiary unit. Cytogenetic analysis, patient demographics and various health outcomes were examined.

Thirty-five patients were raised as females and 33 were raised as males. Fifteen patients were found to have 45,X/46,XY mosaicism prenatally. The prevalence of gonadal tumor was 17.6% among phenotypic females and 38.5% in males with abnormal genitalia, whereas no tumors were detected in males with normal genitalia. The mean external genitalia score was significantly lower in males with gonadal tumors compared to those without (6.6 vs 10.4, P=0.002). For females, while most gonadal tumors were identified in those who had gonadectomy at pubertal age (5 of 6, 83.3%), gonadal tumors were also detected in very young children (1.3 years old). There was no significant improvement in height in those treated with growth hormone therapy and final adult height remained suboptimal (overall final adult height z-score -2.6±1.2). Adherence to surveillance for associated systemic comorbidities was inconsistent.

Gonadal tumor risk is higher in less masculinized males, while females may develop tumors across a wide age range. The long-term efficacy of growth hormone therapy in these patients remains unclear. Our findings emphasized the need for individualized surveillance in this population.