Cardiovascular Pathology in Males and Females with 45,X/46,XY Mosaicism

Context: The phenotype of 45,X/46,XY mosaicism is heterogeneous ranging from females with Turner syndrome (TS) to apparently normal males. Males with 45,X/46,XY frequently show stigmata typically associated with TS. We hypothesised that males with 45,X/46,XY have similar cardiovascular pathology as females with 45,X/46,XY. Objective: To investigate cardiovascular abnormalities in 45,X/46,XY males and to compare them with 45,X/46,XY females. Design: Patients with 45,X/46,XY mosaicism were selected from the Belgian Registry for Growth and Puberty problems and via the multidisciplinary clinic for disorders of sexual development. Patients: Eighteen patients were included: 8 raised as females (F) and 10 as males (M). Intervention: Complete cardiac examination with blood pressure measurement, ECG, echocardiography and MRI. Main Outcome Measurement: Cardiac parameters were registered for both groups. In a second phase, clinical features and external masculinisation score (EMS) were retrospectively collected from the medical files. Results: A structural heart defect was diagnosed before inclusion in 1 F with coarctation and 1 M with spontaneously closed VSD. A bicuspid aortic valve was found in 8 (3 F, 5 M). Dilation of the ascending aorta was present in 4 M and was severe in 2 young boys. QTc was prolonged in 3 F and 2 M. Conclusion: Males with 45, X/46, XY mosaicism have similar cardiovascular pathology as 45, X/46, XY females. Dilation of the ascending aorta can be important, also in males. We advise cardiac screening and life-long monitoring in all males with 45, X/46, XY mosaicism according to the existing guidelines for Turner syndrome.