6777 Exploring the comorbidity in males with 45,X/46,XY mosaicism unveils a pattern mirroring that of Turner syndrome

Abstract Disclosure: K. Stochholm: None. C.H. Gravholt: None. A. Berglund: None. Background: Males with 45,X/46,XY mosaicism are rare with an apparent prevalence of 6 per 100,000 newborn males. Knowledge about associated health outcomes are limited. Females with 45,X/46,XY fall under the Turner syndrome diagnosis but males do not. Aim: To investigate the comorbidity pattern in a national cohort of males with 45,X/46,XY. Methods: Morbidity were investigated using Cox regression analysis on administratively longitudinally collected registry data regarding hospital diagnoses, prescribed medication, and surgery codes. Data were retrieved for all males diagnosed with 45,X/46,XY from 1960 to 2018 (n=135) and for 13,500 age-matched males from the general population, who served as comparator. Results: 45,X/46,XY was associated an increased overall risk of receiving a hospital diagnosis (HR: 1.6, CI: 1.3-1.9), being prescribed medication (HR: 1.2, CI: 1.03-1.5), and undergoing a surgical procedure (HR: 1.8, CI: 1.4-2.1). Dividing hospital diagnoses into 18 chapters according to the International Classification of Diseases (ICD-10), 45,X/46,XY had a significantly increased risk of diagnoses in all but three chapters. Among diagnoses with a significantly increased risk were gonadal dysfunction (HR=63.7, CI: 34.8-116.9), short stature (HR=24.7, CI: 10.0-60.6), pubertal disorders (HR=25.8, CI:7.2-92.6), type 1 (HR=4.1, CI: 1.8-9.4) and type 2 diabetes mellitus (HR=3.4, CI: 1.7-6.6), thyroid disorders (HR=3.8, CI: 1.4-10.4), obesity (HR=4.4, CI: 2.3-8.2), osteoporosis and osteopenia (HR=5.4, CI: 2.4-12.3), hearing loss (HR=2.2, CI: 1.3-3.8), otitis media (HR=1.6, CI: 1.3-1.9), ischemic heart disease (HR=2.4, CI: 1.3-4.4), hypertension (HR=2.3, CI: 1.4-3.9), inflammatory bowel disease (HR=2.5, CI: 1.2-5.4), cryptorchidism (HR=11.9, CI: 7.8-17.8), hypospadias (25.9, CI: 14.0-47.8), testis cancer (HR=6.4, CI: 2.0-20.6), infertility (HR=23.5, CI: 16.0-34.4), gynecomastia (HR=4.6, CI: 1.7-12.5), horse shoe kidney (HR=177,8, CI: 16.1-1968.8), coarctation of the aortae (HR=66.0, CI: 11.0-394.9), and bicuspid aortic valve (HR=53.4, CI: 12.7-223.7). Conclusion: Males with 45,X/46,XY mosaicism exhibit heightened morbidity, evidenced by a notable surge in hospital diagnoses, prescribed medications, and surgical interventions. This increased morbidity is linked to a broad spectrum of diseases, showcasing a comorbidity pattern reminiscent of Turner syndrome. This study emphasizes the need for systematic follow-up in individuals with 45,X/46,XY mosaicism, highlighting the imperative for proactive healthcare management in this population. Presentation: 6/1/2024