ESPE Abstracts

Background: Differences in sex development (DSD) comprise a large group of rare, mostly genetic disorders along the path of human sexual development. Since the Chicago Consensus, health care providers group them in sex chromosome DSD, 46,XY and 46,XX DSD with subgroups regarding their effect on sex hormone synthesis, action or excess, on gonadal development, and others. Incidence of rare DSD is not well established despite public interest.

Aim: The aim of this study was to estimate the nation-wide incidence of DSD in Switzerland.

Methods: This retrospective observational study included children with a DSD according to the Chicago Consensus classification who were born between January 1, 2000 and December 31, 2019 in Switzerland, except in the canton of Ticino. Endocrine care centers from all ten Children’s Hospitals in Switzerland and the eight largest private endocrine practices collected data on DSD diagnosis through the DSD registry or case report forms. An independent institution identified duplicate entries through record linkage. Population-based data on live births came from the Swiss Federal Office of Statistics (SFSO).

Results: Over the 20-year study period, we identified a total of 563 children with DSD born between 2000-2019, annually on average 28 new cases of DSD. Almost half (n=267, 47%) had sex chromosome DSD, 179 (32%) had 46,XY DSD and 118 (21%) had 46,XX DSD. Causes for 46,XY DSD were disturbed androgen synthesis or action (37/179, 21%), followed by atypical gonadal development (29/179, 16%), and other reasons (113/179, 63%). The main cause for 46,XX DSD was androgen excess (99/118, 84%), followed by atypical gonadal development (8/118, 7%), and other reasons (11/118, 9%). We found an incidence of sex chromosome DSD of 1 per 5,700 live births. One per 7,500 newborn girls had 46,XX congenital adrenal hypoplasia (CAH). Incidence for 46,XY DSD was 1 per 4,400 newborn boys, and incidence for 46,XX DSD (excluding CAH) was 1 per 37,000 newborn girls.

Conclusion: We found that incidence of sex chromosome DSD was lower than those reported by other studies because of underreporting. We probably missed milder DSD cases, which manifest late or do not require specialist care. For complex cases of 46,XY DSD and 46,XX DSD, we expect nation-wide coverage. Incidence of 46,XX CAH was comparable to national screening data, suggesting good completeness of cases. This study provides a valuable resource for policy-making and (inter)national research on DSD.